Response assessment in neuro-oncology.

PubMed

Quant, Eudocia C; Wen, Patrick Y

2011-02-01

Accuracy and reproducibility in determining response to therapy and tumor progression can be difficult to achieve for nervous system tumors. Current response criteria vary depending on the pathology and have several limitations. Until recently, the most widely used criteria for gliomas were "Macdonald criteria," based on two-dimensional tumor measurements on neuroimaging studies. However, the Response Assessment in Neuro-Oncology (RANO) Working Group has published new recommendations in high-grade gliomas and is working on recommendations for other nervous system tumors. This article reviews current response criteria for high-grade glioma, low-grade glioma, brain metastasis, meningioma, and schwannoma.

Gene expression levels of gamma-glutamyl hydrolase in tumor tissues may be a useful biomarker for the proper use of S-1 and tegafur-uracil/leucovorin in preoperative chemoradiotherapy for patients with rectal cancer.

PubMed

Sadahiro, Sotaro; Suzuki, T; Tanaka, A; Okada, K; Saito, G; Miyakita, H; Ogimi, T; Nagase, H

2017-06-01

Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV). The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay. A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%. Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, J; Gong, G; Cui, Y

Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitativemore » Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.« less

Contrast-Enhanced Spectral Mammography is Comparable to MRI in the Assessment of Residual Breast Cancer Following Neoadjuvant Systemic Therapy.

PubMed

Patel, Bhavika K; Hilal, Talal; Covington, Matthew; Zhang, Nan; Kosiorek, Heidi E; Lobbes, Marc; Northfelt, Donald W; Pockaj, Barbara A

2018-05-01

To evaluate the performance of contrast-enhanced spectral mammography (CESM) compared to MRI in the assessment of tumor response in breast cancer patients undergoing neoadjuvant systemic therapy (NST). The institutional review board approved this study. From September 2014 to June 2017, we identified patients with pathologically confirmed invasive breast cancer who underwent NST. All patients had both CESM and MRI performed pre- and post-NST with pathological assessment after surgical management. Size of residual malignancy on post-NST CESM and MRI was compared with surgical pathology. Lin concordance and Pearson correlation coefficient were used to assess agreement. Bland-Altman plots were used to visualize the differences between tumor size on imaging and pathology. Sixty-five patients were identified. Mean age was 52.7 (range 30-76) years. Type of NST included chemotherapy in 53 (82%) and endocrine therapy in 12 (18%). Mean tumor size after NST was 14.6 (range 0-105) mm for CESM and 14.2 mm (range 0-75 mm) for MRI compared with 19.6 (range 0-100) mm on final surgical pathology. Equivalence tests demonstrated that mean tumor size measured by CESM (p = 0.009) or by MRI (p = 0.01) was equivalent to the mean tumor size measured by pathology within - 1 and 1-cm range. Comparing CESM versus MRI for assessment of complete response, the sensitivity was 95% versus 95%, specificity 66.7% versus 68.9%, positive predictive value 55.9% versus 57.6%, and negative predictive value 96.7% versus 96.9% respectively. CESM was comparable to MRI in assessing residual malignancy after completion of NST.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Miller, Marian; Ottesen, Rebecca A; Niland, Joyce C; Kruper, Laura; Chen, Steven L; Vito, Courtney

2014-10-01

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

Challenges in Pathologic Staging of Renal Cell Carcinoma: A Study of Interobserver Variability Among Urologic Pathologists.

PubMed

Williamson, Sean R; Rao, Priya; Hes, Ondrej; Epstein, Jonathan I; Smith, Steven C; Picken, Maria M; Zhou, Ming; Tretiakova, Maria S; Tickoo, Satish K; Chen, Ying-Bei; Reuter, Victor E; Fleming, Stewart; Maclean, Fiona M; Gupta, Nilesh S; Kuroda, Naoto; Delahunt, Brett; Mehra, Rohit; Przybycin, Christopher G; Cheng, Liang; Eble, John N; Grignon, David J; Moch, Holger; Lopez, Jose I; Kunju, Lakshmi P; Tamboli, Pheroze; Srigley, John R; Amin, Mahul B; Martignoni, Guido; Hirsch, Michelle S; Bonsib, Stephen M; Trpkov, Kiril

2018-06-06

Staging criteria for renal cell carcinoma differ from many other cancers, in that renal tumors are often spherical with subtle, finger-like extensions into veins, renal sinus, or perinephric tissue. We sought to study interobserver agreement in pathologic stage categories for challenging cases. An online survey was circulated to urologic pathologists interested in kidney tumors, yielding 89% response (31/35). Most questions included 1 to 4 images, focusing on: vascular and renal sinus invasion (n=24), perinephric invasion (n=9), and gross pathology/specimen handling (n=17). Responses were collapsed for analysis into positive and negative/equivocal for upstaging. Consensus was regarded as an agreement of 67% (2/3) of participants, which was reached in 20/33 (61%) evaluable scenarios regarding renal sinus, perinephric, or vein invasion, of which 13/33 (39%) had ≥80% consensus. Lack of agreement was especially encountered regarding small tumor protrusions into a possible vascular lumen, close to the tumor leading edge. For gross photographs, most were interpreted as suspicious but requiring histologic confirmation. Most participants (61%) rarely used special stains to evaluate vascular invasion, usually endothelial markers (81%). Most agreed that a spherical mass bulging well beyond the kidney parenchyma into the renal sinus (71%) or perinephric fat (90%) did not necessarily indicate invasion. Interobserver agreement in pathologic staging of renal cancer is relatively good among urologic pathologists interested in kidney tumors, even when selecting cases that test the earliest and borderline thresholds for extrarenal extension. Disagreements remain, however, particularly for tumors with small, finger-like protrusions, closely juxtaposed to the main mass.

Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal {sup 18}F-FDG PET Features, Clinical Parameters, and Demographics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hao; Tan, Shan; Department of Control Science and Engineering, Huazhong University of Science and Technology, Wuhan

2014-01-01

Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]{sub max}, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changesmore » resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than did the LR model. Conclusions: The SVM model that used all features including spatial-temporal PET features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer.« less

Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis

PubMed Central

Pecori, Biagio; Lastoria, Secondo; Caracò, Corradina; Celentani, Marco; Tatangelo, Fabiana; Avallone, Antonio; Rega, Daniela; De Palma, Giampaolo; Mormile, Maria; Budillon, Alfredo; Muto, Paolo; Bianco, Francesco; Aloj, Luigi; Petrillo, Antonella; Delrio, Paolo

2017-01-01

Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. Methods: Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. Results: We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. Conclusions: This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS. PMID:28060889

Sequential PET/CT with [18F]-FDG Predicts Pathological Tumor Response to Preoperative Short Course Radiotherapy with Delayed Surgery in Patients with Locally Advanced Rectal Cancer Using Logistic Regression Analysis.

PubMed

Pecori, Biagio; Lastoria, Secondo; Caracò, Corradina; Celentani, Marco; Tatangelo, Fabiana; Avallone, Antonio; Rega, Daniela; De Palma, Giampaolo; Mormile, Maria; Budillon, Alfredo; Muto, Paolo; Bianco, Francesco; Aloj, Luigi; Petrillo, Antonella; Delrio, Paolo

2017-01-01

Previous studies indicate that FDG PET/CT may predict pathological response in patients undergoing neoadjuvant chemo-radiotherapy for locally advanced rectal cancer (LARC). Aim of the current study is evaluate if pathological response can be similarly predicted in LARC patients after short course radiation therapy alone. Thirty-three patients with cT2-3, N0-2, M0 rectal adenocarcinoma treated with hypo fractionated short course neoadjuvant RT (5x5 Gy) with delayed surgery (SCRTDS) were prospectively studied. All patients underwent 3 PET/CT studies at baseline, 10 days from RT end (early), and 53 days from RT end (delayed). Maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and total lesion glycolysis (TLG) of the primary tumor were measured and recorded at each PET/CT study. We use logistic regression analysis to aggregate different measures of metabolic response to predict the pathological response in the course of SCRTDS. We provide straightforward formulas to classify response and estimate the probability of being a major responder (TRG1-2) or a complete responder (TRG1) for each individual. The formulas are based on the level of TLG at the early PET and on the overall proportional reduction of TLG between baseline and delayed PET studies. This study demonstrates that in the course of SCRTDS it is possible to estimate the probabilities of pathological tumor responses on the basis of PET/CT with FDG. Our formulas make it possible to assess the risks associated to LARC borne by a patient in the course of SCRTDS. These risk assessments can be balanced against other health risks associated with further treatments and can therefore be used to make informed therapy adjustments during SCRTDS.

Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography.

PubMed

Lowe, V J; Dunphy, F R; Varvares, M; Kim, H; Wittry, M; Dunphy, C H; Dunleavy, T; McDonough, E; Minster, J; Fletcher, J W; Boyd, J H

1997-12-01

[F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable.

Radiologic-Pathologic Analysis of Contrast-enhanced and Diffusion-weighted MR Imaging in Patients with HCC after TACE: Diagnostic Accuracy of 3D Quantitative Image Analysis

PubMed Central

Chapiro, Julius; Wood, Laura D.; Lin, MingDe; Duran, Rafael; Cornish, Toby; Lesage, David; Charu, Vivek; Schernthaner, Rüdiger; Wang, Zhijun; Tacher, Vania; Savic, Lynn Jeanette; Kamel, Ihab R.

2014-01-01

Purpose To evaluate the diagnostic performance of three-dimensional (3Dthree-dimensional) quantitative enhancement-based and diffusion-weighted volumetric magnetic resonance (MR) imaging assessment of hepatocellular carcinoma (HCChepatocellular carcinoma) lesions in determining the extent of pathologic tumor necrosis after transarterial chemoembolization (TACEtransarterial chemoembolization). Materials and Methods This institutional review board–approved retrospective study included 17 patients with HCChepatocellular carcinoma who underwent TACEtransarterial chemoembolization before surgery. Semiautomatic 3Dthree-dimensional volumetric segmentation of target lesions was performed at the last MR examination before orthotopic liver transplantation or surgical resection. The amount of necrotic tumor tissue on contrast material–enhanced arterial phase MR images and the amount of diffusion-restricted tumor tissue on apparent diffusion coefficient (ADCapparent diffusion coefficient) maps were expressed as a percentage of the total tumor volume. Visual assessment of the extent of tumor necrosis and tumor response according to European Association for the Study of the Liver (EASLEuropean Association for the Study of the Liver) criteria was performed. Pathologic tumor necrosis was quantified by using slide-by-slide segmentation. Correlation analysis was performed to evaluate the predictive values of the radiologic techniques. Results At histopathologic examination, the mean percentage of tumor necrosis was 70% (range, 10%–100%). Both 3Dthree-dimensional quantitative techniques demonstrated a strong correlation with tumor necrosis at pathologic examination (R2 = 0.9657 and R2 = 0.9662 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively) and a strong intermethod agreement (R2 = 0.9585). Both methods showed a significantly lower discrepancy with pathologically measured necrosis (residual standard error [RSEresidual standard error] = 6.38 and 6.33 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively), when compared with non-3Dthree-dimensional techniques (RSEresidual standard error = 12.18 for visual assessment). Conclusion This radiologic-pathologic correlation study demonstrates the diagnostic accuracy of 3Dthree-dimensional quantitative MR imaging techniques in identifying pathologically measured tumor necrosis in HCChepatocellular carcinoma lesions treated with TACEtransarterial chemoembolization. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028783

Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

PubMed

Sada, Yvonne H; Tran Cao, Hop S; Chang, George J; Artinyan, Avo; Musher, Benjamin L; Smaglo, Brandon G; Massarweh, Nader N

2018-06-01

For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment. Published by Elsevier Inc.

Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Sam S., E-mail: syoon@partners.org; Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, PA; Duda, Dan G.

Purpose: Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials: Patients with {>=}5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results: The 20 patients had a median tumor sizemore » of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in {>=}80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73%, apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62-72% (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence. Conclusions: The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.« less

SU-F-R-48: Early Prediction of Pathological Response of Locally Advanced Rectal Cancer Using Perfusion CT:A Prospective Clinical Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nie, K; Yue, N; Jabbour, S

Purpose: To prospectively evaluate the tumor vascularity assessed by perfusion CT for prediction of chemo-radiation treatment (CRT) response in locally advanced rectal cancer (LARC). Methods: Eighteen consecutive patients (61.9±8.8 years, from March–June 2015) diagnosed with LARC who underwent 6–8 weeks CRT followed by surgery were included. The pre-treatment perfusion CT was acquired after a 5s delay of contrast agent injection for 45s with 1s interval. A total of 7-cm craniocaudal range covered the tumor region with 3-mm slice thickness. The effective radiation dose is around 15mSv, which is about 1.5 the conventional abdomen/pelvis CT dose. The parametric map of bloodmore » flow (BF), blood volume (BV), mean transit time (MTT), permeability (PMB), and maximum intensity map (MIP) were obtained from commercial software (Syngo-CT 2011A, Siemens). An experienced radiation oncologist outlined the tumor based on the pre-operative MR and pathologic residual region, but was blinded with regards to pathological tumor stage. The perfusion parameters were compared to histopathological response quantified by tumor regression grade as good-responder (GR, TRG 0-1) vs. non-good responder (non-GR). Furthermore, the predictive value for pathological complete response (pCR) was also investigated. Results: Both BV (p=0.02) and MTT (P=0.02) was significantly higher and permeambility was lower (p=0.004) in the good responders. The BF was higher in GR group but not statistically significant. Regarding the discrimination of pCR vs non-pCR, the BF was higher in the pCR group (p=0.08) but none of those parameters showed statistically significant differences. Conclusion: BV and MTT can discriminate patients with a favorable response from those that fail to respond well, potentially selecting high-risk patients with resistant tumors that may benefit from an aggressive preoperative treatment approach. However, future studies with more patient data are needed to verify the prognostic value of perfusion CT especially for pCR prediction. This work is supported by the National High-tech R&D program for Young Scientists by the Ministry of Science and Technology of China (Grant No. 2015AA020917), Natural Science Foundation of China (NSFC Grant No. 81201091).« less

Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages

PubMed Central

Stout, Robert D.; Watkins, Stephanie K.; Suttles, Jill

2009-01-01

The extent to which the functional heterogeneity of Mϕs is dependent on the differentiation of functional sublineages remains unresolved. One alternative hypothesis proposes that Mϕs are functionally plastic cells, which are capable of altering their functional activities progressively in response to progressively changing signaling molecules generated in their microenvironment. This “functional plasticity” hypothesis predicts that the functionally polarized Mϕs in chronic pathologies do not represent Mϕ sublineages but rather, are mutable phenotypes sustained by chronic signaling from the pathological environment. Solid TAMϕs are chronically polarized to provide activities that support tumor growth and metastasis and suppress adaptive immune responses. In support of the functional plasticity hypothesis, administration of slow-release microsphere-encapsulated IL-12 successfully reprogrammed TAMϕs in situ, reducing Mϕ support of tumor growth and metastasis and enhancing Mϕ proimmunogenic activities. Increased knowledge of how Mϕ function is regulated and how polarized Mϕs can be reprogrammed in situ will increase our ability to control Mϕ function in a variety of pathological states, including cancer and chronic inflammatory disease. PMID:19605698

Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions.

PubMed

Machairas, Nikolaos; Kostakis, Ioannis D; Prodromidou, Anastasia; Stamopoulos, Paraskevas; Feretis, Themistoklis; Garoufalia, Zoe; Damaskos, Christos; Tsourouflis, Gerasimos; Kouraklis, Gregory

2017-11-01

Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features

PubMed Central

Gangeh, Mehrdad; Tadayyon, Hadi; Sadeghi-Naini, Ali; Gandhi, Sonal; Wright, Frances C.; Slodkowska, Elzbieta; Curpen, Belinda; Tran, William; Czarnota, Gregory J.

2018-01-01

Background Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC) settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS), textural analysis and molecular features in patients with locally advanced breast cancer. Methods The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF) data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR), partial responders (PR), and non-responders (NR). Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times. Results Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the three response groups with accuracies less than 60% at all scan time points. Recurrence free survival (RFS) of response groups determined based on combined features followed similar trend as determined based on clinical and pathology. Conclusions This work demonstrates the potential of using QUS, texture and molecular features for predicting the response of primary breast tumors to chemotherapy early, and guiding the treatment planning of refractory patients. PMID:29298305

Applications of DNA-Based Liquid Biopsy for Central Nervous System Neoplasms.

PubMed

Wang, Joanna; Bettegowda, Chetan

2017-01-01

The management of central nervous system malignancies remains reliant on histopathological analysis and neuroimaging, despite their complex genetic profile. The intratumoral heterogeneity displayed by these tumors necessitates a more sophisticated method of tumor analysis and monitoring, with the ability to assess tumors over space and time. Circulating biomarkers, including circulating tumor cells, circulating tumor DNA, and extracellular vesicles, hold promise as a type of real-time liquid biopsy able to provide dynamic information not only regarding tumor burden to monitor disease progression and treatment response, but also regarding genetic profile to enable changes in management to match a constantly evolving tumor. In numerous cancer types, including glioma, they have demonstrated their clinical utility as a minimally invasive means for diagnosis, prognostication, and prediction. In addition, they can be used in the laboratory to probe mechanisms of acquired drug resistance and tumor invasion and dissemination. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Simulation of brain tumors in MR images for evaluation of segmentation efficacy.

PubMed

Prastawa, Marcel; Bullitt, Elizabeth; Gerig, Guido

2009-04-01

Obtaining validation data and comparison metrics for segmentation of magnetic resonance images (MRI) are difficult tasks due to the lack of reliable ground truth. This problem is even more evident for images presenting pathology, which can both alter tissue appearance through infiltration and cause geometric distortions. Systems for generating synthetic images with user-defined degradation by noise and intensity inhomogeneity offer the possibility for testing and comparison of segmentation methods. Such systems do not yet offer simulation of sufficiently realistic looking pathology. This paper presents a system that combines physical and statistical modeling to generate synthetic multi-modal 3D brain MRI with tumor and edema, along with the underlying anatomical ground truth, Main emphasis is placed on simulation of the major effects known for tumor MRI, such as contrast enhancement, local distortion of healthy tissue, infiltrating edema adjacent to tumors, destruction and deformation of fiber tracts, and multi-modal MRI contrast of healthy tissue and pathology. The new method synthesizes pathology in multi-modal MRI and diffusion tensor imaging (DTI) by simulating mass effect, warping and destruction of white matter fibers, and infiltration of brain tissues by tumor cells. We generate synthetic contrast enhanced MR images by simulating the accumulation of contrast agent within the brain. The appearance of the the brain tissue and tumor in MRI is simulated by synthesizing texture images from real MR images. The proposed method is able to generate synthetic ground truth and synthesized MR images with tumor and edema that exhibit comparable segmentation challenges to real tumor MRI. Such image data sets will find use in segmentation reliability studies, comparison and validation of different segmentation methods, training and teaching, or even in evaluating standards for tumor size like the RECIST criteria (response evaluation criteria in solid tumors).

T2-weighted signal intensity-selected volumetry for prediction of pathological complete response after preoperative chemoradiotherapy in locally advanced rectal cancer.

PubMed

Kim, Sungwon; Han, Kyunghwa; Seo, Nieun; Kim, Hye Jin; Kim, Myeong-Jin; Koom, Woong Sub; Ahn, Joong Bae; Lim, Joon Seok

2018-06-01

To evaluate the diagnostic value of signal intensity (SI)-selected volumetry findings in T2-weighted magnetic resonance imaging (MRI) as a potential biomarker for predicting pathological complete response (pCR) to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Forty consecutive patients with pCR after preoperative CRT were compared with 80 age- and sex-matched non-pCR patients in a case-control study. SI-selected tumor volume was measured on post-CRT T2-weighted MRI, which included voxels of the treated tumor exceeding the SI (obturator internus muscle SI + [ischiorectal fossa fat SI - obturator internus muscle SI] × 0.2). Three blinded readers independently rated five-point pCR confidence scores and compared the diagnostic outcome with SI-selected volumetry findings. The SI-selected volumetry protocol was validated in 30 additional rectal cancer patients. The area under the receiver-operating characteristic curve (AUC) of SI-selected volumetry for pCR prediction was 0.831, with an optimal cutoff value of 649.6 mm 3 (sensitivity 0.850, specificity 0.725). The AUC of the SI-selected tumor volume was significantly greater than the pooled AUC of readers (0.707, p < 0.001). At this cutoff, the validation trial yielded an accuracy of 0.87. SI-selected volumetry in post-CRT T2-weighted MRI can help predict pCR after preoperative CRT in patients with rectal cancer. • Fibrosis and viable tumor MRI signal intensities (SIs) are difficult to distinguish. • T2 SI-selected volumetry yields high diagnostic performance for assessing pathological complete response. • T2 SI-selected volumetry is significantly more accurate than readers and non-SI-selected volumetry. • Post-chemoradiation therapy T2-weighted MRI SI-selected volumetry facilitates prediction of pathological complete response.

Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases.

PubMed

Lucidi, Valerio; Hendlisz, Alain; Van Laethem, Jean-Luc; Donckier, Vincent

2016-04-21

In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.

Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer

PubMed Central

HASEGAWA, SHINICHIRO; EGUCHI, HIDETOSHI; TOMOKUNI, AKIRA; TOMIMARU, YOSHITO; ASAOKA, TADAFUMI; WADA, HIROSHI; HAMA, NAOKI; KAWAMOTO, KOICHI; KOBAYASHI, SHOGO; MARUBASHI, SHIGERU; KONNNO, MASAMITSU; ISHII, HIDESHI; MORI, MASAKI; DOKI, YUICHIRO; NAGANO, HIROAKI

2016-01-01

An elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with the pathological response to neoadjuvant therapies in numerous types of cancer. The aim of the current study was to clarify the association between pre-treatment NLR and the pathological response to preoperative chemoradiotherapy in pancreatic cancer patients. This retrospective analysis included data from 56 consecutive patients whose tumors were completely surgically resected. All patients received preoperative therapy, consisting of gemcitabine-based chemotherapy (alone or in combination with S-1) combined with 40 or 50.4 Gy irradiation, prior to surgery. Predictive factors, including NLR, platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score and prognostic nutrition index, were measured prior to treatment. A comparison was made between those who responded well pathologically (good response group, Evans classification IIb/III) and those with a poor response (Evans I/IIa). NLR was determined to be significantly higher in the poor response group. Multivariate analysis identified an elevated NLR as an independent risk factor for the poor pathological response [odds ratio (OR), 5.35; P=0.0257]. The pre-treatment NLR (≥2.2/<2.2) was found to be a statistically significant predictive indicator of pathological response (P=0.00699). The results demonstrate that pre-treatment NLR may be a useful predictive marker for the pathological response to preoperative therapy in pancreatic cancer patients. PMID:26893780

Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy

PubMed Central

Joseph, Richard W.; Peddareddigari, Vijay R.; Liu, Ping; Miller, Priscilla W.; Overwijk, Willem W.; Bekele, Nebiyou B.; Ross, Merrick I.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Lucci, Anthony; Prieto, Victor G.; McMannis, John D.; Papadopoulos, Nicholas; Kim, Kevin; Homsi, Jade; Bedikian, Agop; Hwu, Wen-Jen; Hwu, Patrick; Radvanyi, Laszlo G.

2011-01-01

Purpose Clinical trials on adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) have shown response rates of over 50% in refractory melanoma. However, little is known how clinical and pathologic features impact TIL outgrowth isolated from metastatic melanoma tumors. Experimental Design We analyzed the impact of clinical and pathologic features on initial TIL outgrowth in 226 consecutive patients undergoing tumor resection. Successful initial TIL outgrowth was defined as ≥40 million viable lymphocytes harvested from all tumor fragments in a 5-week culture. To normalize for the different size of resected tumors and thus available tumor fragments, we divided the number of expanded TIL by the starting number of tumor fragments (TIL/fragment). Results Overall, initial TIL outgrowth was successful in 62% of patients, with patients ≤30 years of age (94%; p=0.01) and female patients (71% vs. 57% for males; p=0.04) having the highest rate of success. Systemic therapy 30 days prior to tumor harvest negatively impacted initial TIL outgrowth compared to patients who never received systemic therapy (47% versus 71%, p=0.02). Biochemotherapy within 0–60 days of tumor harvest negatively impacted the initial TIL outgrowth with a success rate of only 16% (p<0.0001). Conclusion Parameters such as age, sex, and the type and timing of prior systemic therapy significantly affect the success rate of the initial TIL outgrowth from tumor fragments for ACT; these parameters may be helpful in selecting patients for melanoma ACT. PMID:21632855

TU-G-BRA-06: PET-Based Treatment Response Assessement for Neoadjuvent Chemoradiation for Pancreatic Adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dalah, E; Tai, A; Oshima, K

Purpose: To address the limitations of the conventional response evaluation criteria in solid tumors (RECIST), and validate PET response criteria in solid tumors (PERCIST1.0). We analyze the relationship between the pathological treatment response (PTR) and PERCIST1.0 for patients treated with neoadjuvent chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The pre- and post-nCR CT and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade1, 2 or 3 (G1, G2 or G3)more » for good, moderate, and poor responses, respectively. RECIST-based PET (RECISTPET), and PERCIST1.0 were defined using lean body mass normalized SUV (nSUVlb). RECIST-based CT (RECISTCT) was defined by contouring the whole pancreas head (CTPH). Pre- and post-nSUVlb and SUVbw, PERCIST 1.0, were correlated with PTR using Pearson’s correlation coefficient test. Results: The average mean and SD in nSUVlb for all 8 patients analyzed were lower in post-nCR (1.35±0.34) compared to those at pre-nCR (1.38±0.20). Using PERCIST1.0, 5/8 patients showed stable metabolic disease (SMD), 2/8 partial metabolic response (PMR), and 1/8 progressive metabolic disease (PMD). Using RECISTPET 4/8 showed stable disease (STD), 4/8 partial response (PR), whereas 8/8 showed stable disease (STD) using RECISTCT. PTR were correlated with PERCIST1.0 (R=0.3780/P=0.6071). Pathological tumor size was correlated with RECISTCT (R=0.0727/P=0.8679), and RECISTPET, R=−0.3333/P=0.3798. Conclusion: Chemoradiation treatment response assessment based on metabolic tumor activities using PRECIST1.0 and RECISTPET appears to provide better agreement with pathological assessment as compared to the conventional CT-based assessment using RECISTCT. The integration of these additional radiographic metrics in assessing treatment response to nCR for pancreatic adenocarcinoma may provide a promising strategy to better select those patients most suitable for therapeutic intensification.« less

Predicting pathologic tumor response to chemoradiotherapy with histogram distances characterizing longitudinal changes in 18F-FDG uptake patterns

PubMed Central

Tan, Shan; Zhang, Hao; Zhang, Yongxue; Chen, Wengen; D’Souza, Warren D.; Lu, Wei

2013-01-01

Purpose: A family of fluorine-18 (18F)-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) features based on histogram distances is proposed for predicting pathologic tumor response to neoadjuvant chemoradiotherapy (CRT). These features describe the longitudinal change of FDG uptake distribution within a tumor. Methods: Twenty patients with esophageal cancer treated with CRT plus surgery were included in this study. All patients underwent PET/CT scans before (pre-) and after (post-) CRT. The two scans were first rigidly registered, and the original tumor sites were then manually delineated on the pre-PET/CT by an experienced nuclear medicine physician. Two histograms representing the FDG uptake distribution were extracted from the pre- and the registered post-PET images, respectively, both within the delineated tumor. Distances between the two histograms quantify longitudinal changes in FDG uptake distribution resulting from CRT, and thus are potential predictors of tumor response. A total of 19 histogram distances were examined and compared to both traditional PET response measures and Haralick texture features. Receiver operating characteristic analyses and Mann-Whitney U test were performed to assess their predictive ability. Results: Among all tested histogram distances, seven bin-to-bin and seven crossbin distances outperformed traditional PET response measures using maximum standardized uptake value (AUC = 0.70) or total lesion glycolysis (AUC = 0.80). The seven bin-to-bin distances were: L2 distance (AUC = 0.84), χ2 distance (AUC = 0.83), intersection distance (AUC = 0.82), cosine distance (AUC = 0.83), squared Euclidean distance (AUC = 0.83), L1 distance (AUC = 0.82), and Jeffrey distance (AUC = 0.82). The seven crossbin distances were: quadratic-chi distance (AUC = 0.89), earth mover distance (AUC = 0.86), fast earth mover distance (AUC = 0.86), diffusion distance (AUC = 0.88), Kolmogorov-Smirnov distance (AUC = 0.88), quadratic form distance (AUC = 0.87), and match distance (AUC = 0.84). These crossbin histogram distance features showed slightly higher prediction accuracy than texture features on post-PET images. Conclusions: The results suggest that longitudinal patterns in 18F-FDG uptake characterized using histogram distances provide useful information for predicting the pathologic response of esophageal cancer to CRT. PMID:24089897

Thymidine phosphorylase and hypoxia-inducible factor 1-α expression in clinical stage II/III rectal cancer: association with response to neoadjuvant chemoradiation therapy and prognosis.

PubMed

Lin, Shuhan; Lai, Hao; Qin, Yuzhou; Chen, Jiansi; Lin, Yuan

2015-01-01

The aim of this study was to determine whether pretreatment status of thymidine phosphorylase (TP), and hypoxia-inducible factor alpha (HIF-1α) could predict pathologic response to neoadjuvant chemoradiation therapy with oxaliplatin and capecitabine (XELOXART) and outcomes for clinical stage II/III rectal cancer patients. A total of 180 patients diagnosed with clinical stage II/III rectal cancer received XELOXART. The status of TP, and HIF-1α were determined in pretreatment biopsies by immunohistochemistry (IHC). Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. 5-year disease free survival (DFS) and 5-year overall survival (OS) were evaluated with the Kaplan-Meier method and were compared by the log-rank test. Over expression of TP and low expression of HIF-1α were associated with pathologic response to XELOXART and better outcomes (DFS and OS) in clinical stage II/III rectal cancer patients (P < 0.05). Our result suggested that pretreatment status of TP and HIF-1α were found to predict pathologic response and outcomes in clinical stage II/III rectal cancer received XELOXART. Additional well-designed, large sample, multicenter, prospective studies are needed to confirm the result of this study.

Biopsy Specimens Obtained 7 Days After Starting Chemoradiotherapy (CRT) Provide Reliable Predictors of Response to CRT for Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Toshiyuki; Sadahiro, Sotaro, E-mail: sadahiro@is.icc.u-tokai.ac.jp; Tanaka, Akira

2013-04-01

Purpose: Preoperative chemoradiation therapy (CRT) significantly decreases local recurrence in locally advanced rectal cancer. Various biomarkers in biopsy specimens obtained before CRT have been proposed as predictors of response. However, reliable biomarkers remain to be established. Methods and Materials: The study group comprised 101 consecutive patients with locally advanced rectal cancer who received preoperative CRT with oral uracil/tegafur (UFT) or S-1. We evaluated histologic findings on hematoxylin and eosin (H and E) staining and immunohistochemical expressions of Ki67, p53, p21, and apoptosis in biopsy specimens obtained before CRT and 7 days after starting CRT. These findings were contrasted with themore » histologic response and the degree of tumor shrinkage. Results: In biopsy specimens obtained before CRT, histologic marked regression according to the Japanese Classification of Colorectal Carcinoma (JCCC) criteria and the degree of tumor shrinkage on barium enema examination (BE) were significantly greater in patients with p21-positive tumors than in those with p21-negative tumors (P=.04 and P<.01, respectively). In biopsy specimens obtained 7 days after starting CRT, pathologic complete response, histologic marked regression according to both the tumor regression criteria and JCCC criteria, and T downstaging were significantly greater in patients with apoptosis-positive and p21-positive tumors than in those with apoptosis-negative (P<.01, P=.02, P=.01, and P<.01, respectively) or p21-negative tumors (P=.03, P<.01, P<.01, and P=.02, respectively). The degree of tumor shrinkage on both BE as well as MRI was significantly greater in patients with apoptosis-positive and with p21-positive tumors than in those with apoptosis-negative or p21-negative tumors, respectively. Histologic changes in H and E-stained biopsy specimens 7 days after starting CRT significantly correlated with pathologic complete response and marked regression on both JCCC and tumor regression criteria, as well as with tumor shrinkage on BE and MRI (P<.01, P<.01, P<.01, P<.01, and P=.03, respectively). Conclusions: Immunohistochemical expressions of p21 and apoptosis together with histologic changes on H and E-stained biopsy specimens obtained 7 days after starting CRT are strong predictors of the response to CRT.« less

Ex vivo MR spectroscopic measure differentiates tumor from treatment effects in GBM

PubMed Central

Srinivasan, Radhika; Phillips, Joanna J.; VandenBerg, Scott R.; Polley, Mei-Yin C.; Bourne, Gabriela; Au, Alvin; Pirzkall, Andrea; Cha, Soonmee; Chang, Susan M.; Nelson, Sarah J.

2010-01-01

The motivation of this study was to address the urgent clinical problem related to the inability of magnetic resonance (MR) imaging measures to differentiate tumor progression from treatment effects in patients with glioblastoma multiforme (GBM). While contrast enhancement on MR imaging (MRI) is routinely used for assessment of tumor burden, therapy response, and progression-free survival in GBM, it is well known that changes in enhancement following treatment are nonspecific to tumor. To address this issue, the objective of this study was to investigate whether MR spectroscopy can provide improved biomarker surrogates for tumor following treatment. High-resolution metabolic profiles of tissue samples obtained from patients with GBM were directly correlated with their pathological assessment to determine metabolic markers that correspond to pathological indications of tumor or treatment effects. Acquisition of tissue samples with image guidance enabled the association of ex vivo biochemical and pathological properties of the tissue samples with in vivo MR anatomical and structural properties derived from presurgical MR images. Using this approach, we found that metabolic concentration levels of [Myo-inositol/total choline (MCI)] in tissue samples are able to differentiate tumor from nontumor and treatment-induced reactive astrocytosis with high significance (P < .001) in newly diagnosed and recurrent GBM. The MCI index has a sensitivity of 93% to tumor in recurrent GBM and delineates the contribution of cellularity that originates from tumor and astrocytic proliferation following treatment. Low levels of MCI for tumor were associated with a reduced apparent diffusion coefficient and elevated choline-N-acetyl-aspartate index derived from in vivo MR images. PMID:20647244

Predicting neo-adjuvant chemotherapy response and progression-free survival of locally advanced breast cancer using textural features of intratumoral heterogeneity on F-18 FDG PET/CT and diffusion-weighted MR imaging.

PubMed

Yoon, Hai-Jeon; Kim, Yemi; Chung, Jin; Kim, Bom Sahn

2018-03-30

Predicting response to neo-adjuvant chemotherapy (NAC) and survival in locally advanced breast cancer (LABC) is important. This study investigated the prognostic value of tumor heterogeneity evaluated with textural analysis through F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and diffusion-weighted imaging (DWI). We enrolled 83 patients with LABC who had completed NAC and curative surgery. Tumor texture indices from pretreatment FDG PET and DWI were extracted from histogram analysis and 7 different parent matrices: co-occurrence matrix, the voxel-alignment matrix, neighborhood intensity difference matrix, intensity size-zone matrix (ISZM), normalized gray-level co-occurrence matrix (NGLCM), neighboring gray-level dependence matrix (NGLDM), and texture spectrum matrix. The predictive values of textural features were tested regarding both pathologic NAC response and progression-free survival. Among 83 patients, 46 were pathologic responders, while 37 were nonresponders. The PET texture indices from 7 parent matrices, DWI texture indices from histogram, and 1 parent matrix (NGLCM) showed significant differences according to NAC response. On multivariable analysis, number nonuniformity of PET extracted from the NGLDM was an independent predictor of pathologic response (P = .009). During a median follow-up period of 17.3 months, 14 patients experienced recurrence. High-intensity zone emphasis (HIZE) and high-intensity short-zone emphasis (HISZE) from PET extracted from ISZM were significant textural predictors (P = .011 and P = .033). On Cox regression analysis, only HIZE was a significant predictor of recurrence (P = .027), while HISZE showed borderline significance (P = .107). Tumor texture indices are useful for NAC response prediction in LABC. Moreover, PET texture indices can help to predict disease recurrence. © 2018 Wiley Periodicals, Inc.

Early PET/CT scan is more effective than RECIST in predicting outcome of patients with liver metastases from colorectal cancer treated with preoperative chemotherapy plus bevacizumab.

PubMed

Lastoria, Secondo; Piccirillo, Maria Carmela; Caracò, Corradina; Nasti, Guglielmo; Aloj, Luigi; Arrichiello, Cecilia; de Lutio di Castelguidone, Elisabetta; Tatangelo, Fabiana; Ottaiano, Alessandro; Iaffaioli, Rosario Vincenzo; Izzo, Francesco; Romano, Giovanni; Giordano, Pasqualina; Signoriello, Simona; Gallo, Ciro; Perrone, Francesco

2013-12-01

Markers predictive of treatment effect might be useful to improve the treatment of patients with metastatic solid tumors. Particularly, early changes in tumor metabolism measured by PET/CT with (18)F-FDG could predict the efficacy of treatment better than standard dimensional Response Evaluation Criteria In Solid Tumors (RECIST) response. We performed PET/CT evaluation before and after 1 cycle of treatment in patients with resectable liver metastases from colorectal cancer, within a phase 2 trial of preoperative FOLFIRI plus bevacizumab. For each lesion, the maximum standardized uptake value (SUV) and the total lesion glycolysis (TLG) were determined. On the basis of previous studies, a ≤ -50% change from baseline was used as a threshold for significant metabolic response for maximum SUV and, exploratively, for TLG. Standard RECIST response was assessed with CT after 3 mo of treatment. Pathologic response was assessed in patients undergoing resection. The association between metabolic and CT/RECIST and pathologic response was tested with the McNemar test; the ability to predict progression-free survival (PFS) and overall survival (OS) was tested with the Log-rank test and a multivariable Cox model. Thirty-three patients were analyzed. After treatment, there was a notable decrease of all the parameters measured by PET/CT. Early metabolic PET/CT response (either SUV- or TLG-based) had a stronger, independent and statistically significant predictive value for PFS and OS than both CT/RECIST and pathologic response at multivariate analysis, although with different degrees of statistical significance. The predictive value of CT/RECIST response was not significant at multivariate analysis. PET/CT response was significantly predictive of long-term outcomes during preoperative treatment of patients with liver metastases from colorectal cancer, and its predictive ability was higher than that of CT/RECIST response after 3 mo of treatment. Such findings need to be confirmed by larger prospective trials.

Clinical outcome and prognosis of carbon ion radiotherapy on thoracic malignant tumors

NASA Astrophysics Data System (ADS)

Li, Sha

Objective To evaluate the therapeutic efficacy and side-response of high-LET carbon ion radiotherapy on thoracic malignant tumors. Methods Ten patients with pathological confirmed thoracic malignant tumors received treatment using heavy ion accelerator, which included 6 cases with non-small lung cancer, one case with small lung cancer, 2 cases with metastatic sarcomas and one case with invasive thymoma. The applied regimen included fractioned dose (5.5-6.8GyE/Fraction), one faction/day, and 7 fractions/week. The total dose ranged from 55 to 70 GyE. Results The short-term results showed that the response rate (the complete response (CR) rate +the partial response (PR) rate) was 10% at the first month, 40% at the third month and 90% at the sixth month. The overall response rate was 90% and the rate of stable disease was 10%. There was no relation between the response rate and tumor pathology (P>0.05) while significance between the response rate and the tumor volume.At median follow-up of 27 months (range, 6 to 36 months), the local control rate and free-disease rate were respectively 100% an 90% at the first year, 90% and 80% at the secondary year, 80% and 70% at the third year. The death rate due to disease progression was 20% and the non-specific death rate was 10%. Side and toxicity effects: Grade I skin effect occurred in three cases and Grade I lung effect occurred in two cases. The blood counts didn’t reach significance among pre-radiation course, peri-radiation course and post-radiation course (P>0.05). The subgoups of T cells detected in humoral immunity and cytoimmunity didn’t change between pre-radiation and post radiation(P>0.05). Conclusions Carbon ion radiotherapy is effective and safe in the management of patients with thoracic malignant tumors. There were no obvious side effects. The long term of clinical outcome and the late effect need to be further observed.

Pathophysiology of Tumor Neovascularization

PubMed Central

Furuya, Mitsuko; Nishiyama, Mariko; Kasuya, Yoshitoshi; Kimura, Sadao; Ishikura, Hiroshi

2005-01-01

Neovascularization is essential to the process of development and differentiation of tissues in the vertebrate embryo, and is also involved in a wide variety of physiological and pathological conditions in adults, including wound repair, metabolic diseases, inflammation, cardiovascular disorders, and tumor progression. Thanks to cumulative studies on vasculature, new therapeutic approaches have been opened for us to some life-threatening diseases by controlling angiogenesis in the affected organs. In cancer therapy, for example, modulation of factors responsible for tumor angiogenesis may be beneficial in inhibiting of tumor progression. Several antiangiogenic approaches are currently under preclinical trial. However, the mechanisms of neovascularization in tumors are complicated and each tumor shows unique features in its vasculature, depending on tissue specificity, angiogenic micromilieu, grades and stages, host immunity, and so on. For better understanding and effective therapeutic approaches, it is important to clarify both the general mechanism of angiogenic events and the disease-specific mechanism of neovascularization. This review discusses the general features of angiogenesis under physiological and pathological conditions, mainly in tumor progression. In addition, recent topics such as contribution of the endothelial progenitor cells, tumor vasculogenic mimicry, markers for tumor-derived endothelial cells and pericytes, and angiogenic/angiostatic chemokines are summarized. PMID:17315600

TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, H; Chen, W; Kligerman, S

2014-06-15

Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associatedmore » changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features including quantitative PET/CT features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer. This work was supported in part by National Cancer Institute Grant R21 CA131979 and R01 CA172638. Shan Tan was supported in part by the National Natural Science Foundation of China 60971112 and 61375018, and by Fundamental Research Funds for the Central Universities 2012QN086.« less

[A Case of Liver Metastasis from Esophageal Cancer Successfully Treated by Surgical Resection after Chemotherapy with Weekly-Paclitaxel].

PubMed

Nozawa, Akinori; Kubo, Naoshi; Shimizu, Sadatoshi; Murata, Akihiro; Kanazawa, Akishige; Kodai, Shintaro; Urata, Yorihisa; Miura, Kotaro; Tauchi, Jun; Sakurai, Katsunori; Tachimori, Akiko; Tamamori, Yutaka; Inoue, Toru; Yamashita, Yoshito; Nishiguchi, Yukio

2017-11-01

A 58-year-old man complaining of dysphagia was admitted to our hospital and diagnosed with esophageal cancer.He underwent thoracoscopic subtotal esophagectomy with 3-field lymph node dissection and reconstruction with a gastric tube created by hand-assisted laparoscopy.The pathological diagnosis was classified as AeLtG, pT3N2M0, pStage III .He was subsequently treated with systemic chemotherapy with 5-fluorouracil and cisplatin.After 2 courses, a single liver metastatic tumor appeared at segment 5.As chemotherapy against the recurrence, weekly-paclitaxel was administered.After 2 courses, the metastatic liver tumor reduced in size.Subsequently, laparoscopic partial liver resection was performed 11 months after first surgery.The pathological finding was negative for malignancy(pathological complete response).

Molecular cross-talk of IL-6 in tumors and new progress in combined therapy.

PubMed

Song, Zuoqing; Ren, Dian; Xu, Xiaohong; Wang, Yuxin

2018-06-01

IL-6, a cytokine activated by type I interferons (IFNs), is encoded by the IL-6 gene, and secreted by T cells and macrophages. It serves many purposes in the human body and is significant to pathological and physiological activities, such as acute inflammatory responses, autoimmune diseases, and tumor formation. The wide range of IL-6 actions on tumors rely on more than one specific pathway. Advances in modern research have determined that to fulfill its complex physiological functions, IL-6 must be involved in cross-talk with a number of other molecular pathways. Therefore, it is important to clarify the comprehensive pathway network associated with IL-6 activity and to explore the mechanisms to inhibit its pathological activity in order to develop corresponding treatment plans. This study is a simple review of the pathological and physiological actions of IL-6 on the human body. It explains in detail the molecular pathways involved in cross-talk between IL-6 and tumors, summarizing and discussing the latest progress made in IL-6-related internal medicine treatments in recent years, including chemotherapies, targeted therapies, and immunotherapies. Our results provide new insight into the treatment of tumors. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial

PubMed Central

Smyth, Elizabeth C.; Fassan, Matteo; Cunningham, David; Allum, William H.; Okines, Alicia F.C.; Lampis, Andrea; Hahne, Jens C.; Rugge, Massimo; Peckitt, Clare; Nankivell, Matthew; Langley, Ruth; Ghidini, Michele; Braconi, Chiara; Wotherspoon, Andrew; Grabsch, Heike I.

2016-01-01

Purpose The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable esophagogastric cancer. However, identification of patients at risk for relapse remains challenging. We evaluated whether pathologic response and lymph node status after neoadjuvant chemotherapy are prognostic in patients treated in the MAGIC trial. Materials and Methods Pathologic regression was assessed in resection specimens by two independent pathologists using the Mandard tumor regression grading system (TRG). Differences in overall survival (OS) according to TRG were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards method established the relationships among TRG, clinical-pathologic variables, and OS. Results Three hundred thirty resection specimens were analyzed. In chemotherapy-treated patients with a TRG of 1 or 2, median OS was not reached, whereas for patients with a TRG of 3, 4, or 5, median OS was 20.47 months. On univariate analysis, high TRG and lymph node metastases were negatively related to survival (Mandard TRG 3, 4, or 5: hazard ratio [HR], 1.94; 95% CI, 1.11 to 3.39; P = .0209; lymph node metastases: HR, 3.63; 95% CI, 1.88 to 7.0; P < .001). On multivariate analysis, only lymph node status was independently predictive of OS (HR, 3.36; 95% CI, 1.70 to 6.63; P < .001). Conclusion Lymph node metastases and not pathologic response to chemotherapy was the only independent predictor of survival after chemotherapy plus resection in the MAGIC trial. Prospective evaluation of whether omitting postoperative chemotherapy and/or switching to a noncross-resistant regimen in patients with lymph node-positive disease whose tumor did not respond to preoperative epirubicin, cisplatin, and fluorouracil may be appropriate. PMID:27298411

[A Case of Pathological Complete Response after Neoadjuvant Chemotherapy(S-1 plus Oxaliplatin)and Laparoscopic Low Anterior Resection for Rectal Cancer].

PubMed

Ichinohe, Daichi; Morohashi, Hajime; Umetsu, Satoko; Yoshida, Tatsuya; Wakasa, Yusuke; Odagiri, Tadashi; Kimura, Toshirou; Suto, Akiko; Saito, Takeshi; Yoshida, Eri; Akasaka, Harue; Jin, Hiroyuki; Miura, Takuya; Sakamoto, Yoshiyuki; Hakamada, Kenichi

2016-11-01

We report a case of pathological complete response after neoadjuvant chemotherapy(NAC)(S-1 plus oxaliplatin)for rectal cancer. The patient was a 50-year-old man who had type 3 circumferential rectal cancer. An abdominal CT scan revealed locally advanced rectal cancer(cT3N2H0P0M0, cStage III b)with severe stenosis and oral-side intestinal dilatation. The patient was treated with NAC after loop-ileostomy. After 3 courses of chemotherapy, a CT scan revealed significant tumor reduction. Laparoscopic low anterior resection and bilateral lymph node dissection were performed 5 weeks after the last course of chemotherapy. The pathological diagnosis was a pathological complete response(no residual cancer cells). This case suggests that laparoscopic low anterior resection after NAC with S-1 plus oxaliplatin for locally advanced rectal cancer is a potentially effective procedure.

Phase II study of capecitabine (Xeloda (registered) ) and concomitant boost radiotherapy in patients with locally advanced rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Sunil; Janjan, Nora A.; Skibber, John M.

2006-11-01

Purpose: The aim of this study was to determine the efficacy of capecitabine (Xeloda (registered) ), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant treatment of locally advanced rectal cancer (LARC). Methods and Materials: We conducted a phase II study of capecitabine (825 mg/m{sup 2} orally, twice daily continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and perirectal nodes) in 54 patients with LARC (node-negative {>=}T3 or any node-positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was pathologic response rate; secondary endpoints included toxicity profiles and survival parameters. Results: Of the 54 patients (median age,more » 56.7 years; range, 21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS. Surgery was not performed in 3 patients; 2 of these patients had metastatic disease, and the third patient refused after a complete clinical response. Of the 51 patients evaluable for pathologic response, 9 patients (18%) achieved complete response, and 12 patients (24%) had microscopic residual disease (<10% viable cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging, and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for tumor {<=}5 cm from the anal verge was 67% (18/27). Conclusion: This regimen of radiotherapy plus capecitabine is well tolerated and is more convenient than protracted venous infusion of 5-FU. The pathologic response rate is comparable to our previous experience using protracted venous infusion 5-FU for LARC.« less

Opportunities for Improvement in Pathology Reporting of Childhood Nonrhabdomyosarcoma Soft Tissue Sarcomas:  A Report From Children's Oncology Group (COG) Study ARST0332.

PubMed

Black, Jennifer O; Coffin, Cheryl M; Parham, David M; Hawkins, Douglas S; Speights, Rose A; Spunt, Sheri L

2016-09-01

Treatment of soft tissue tumors in young patients relies on the diagnostic information conveyed in the pathology report. We examined pathology reports from Children's Oncology Group ARST0332 for inclusion of data elements required in published guidelines. Pathology reports for 551 eligible patients were examined for required data elements defined by the College of American Pathologists, including tissue type, procedure, tumor site, tumor maximum diameter, macroscopic extent of tumor, histologic type, mitotic rate, extent of necrosis, tumor grade, margin status, use of ancillary studies, and pathologic stage. Only 65 (12%) of 551 reports included all required data elements. Of reports containing synoptic templates, 57% were complete. This study reveals significant opportunity to improve the quality of pathology reports in young patients with soft tissue tumors. Use of templates or checklists improves completeness of reports. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pineal region tumors: computed tomographic-pathologic spectrum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Futrell, N.N.; Osborn, A.G.; Cheson. B.D.

While several computed tomographic (CT) studies of posterior third ventricular neoplasms have included descriptions of pineal tumors, few reports have concentrated on these uncommon lesions. Some authors have asserted that the CT appearance of many pineal tumors is virtually pathognomonic. A series of nine biopsy-proved pineal gland and eight other presumed tumors is presented that illustrates their remarkable heterogeneity in both histopathologic and CT appearance. These tumors included germinomas, teratocarcinomas, hamartomas, and other varieties. They had variable margination, attentuation, calcification, and suprasellar extension. Germinomas have the best response to radiation therapy. Biopsy of pineal region tumors is now feasible andmore » is recommended for treatment planning.« less

Quantitative Imaging of Scattering Changes Associated With Epithelial Proliferation, Necrosis and Fibrosis in Tumors Using Microsampling Reflectance Spectroscopy

PubMed Central

Krishnaswamy, Venkataramanan; Hoopes, P. Jack; Samkoe, Kimberley S.; O'Hara, Julia A.; Hasan, Tayyaba; Pogue, Brian W.

2010-01-01

Highly localized reflectance measurements can be used to directly quantify scatter changes in tissues. This study presents a microsampling approach that is used to raster scan tumors to extract parameters believed to be related to the tissue ultra-structure. A confocal reflectance imager was developed to examine scatter changes across pathologically distinct regions within tumor tissues. Tissue sections from two murine tumors, AsPC-1 pancreas tumor and the Mat-LyLu Dunning prostate tumor, were imaged. After imaging, histopathology-guided region-of-interest studies of the images allowed analysis of the variations in scattering resulting from differences in tissue ultra-structure. On average, the median scatter power of tumor cells with high proliferation index was about 26% less compared to tumor cells with low proliferation index (LPI). Necrosis exhibited the lowest scatter power signature across all the tissue types considered, with about 55% lower median scatter power than LPI tumor cells. Additionally, the level and maturity of the tumor's fibroplastic response was found to influence the scatter signal. This approach to scatter visualization of tissue ultra-structure in situ could provide a unique tool for guiding surgical resection, but this kind of interpretation into what the signal means relative to the pathology is required before proceeding to clinical studies. PMID:19256692

Perioperative BRAF inhibitors in locally advanced stage III melanoma.

PubMed

Zippel, Douglas; Markel, Gal; Shapira-Frommer, Roni; Ben-Betzalel, Guy; Goitein, David; Ben-Ami, Eytan; Nissan, Aviram; Schachter, Jacob; Schneebaum, Schlomo

2017-12-01

Stage III malignant melanoma is a heterogeneous disease where those cases deemed marginally resectable or irresecatble are frequently incurable by surgery alone. Targeted therapy takes advantage of the high incidence of BRAF mutations in melanomas, most notably the V600E mutation. These agents have rarely been used in a neoadjuvant setting prior to surgery. Thirteen consecutive patients with confirmed BRAF V600E regionally advanced melanoma deemed marginally resectable or irrresectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The primary outcome measures were a successful resection and pathological response. Disease-free survival was a secondary outcome measure. Overall, 12/13 patients showed a marked clinical responsiveness to medical treatment, enabling a macroscopically successful resection in all cases. Four patients had a complete pathological response with no viable tumor evident in the resected specimens and eight patients showed evidence of minimally residual tumor with extensive tumoral necrosis and fibrosis. One patient progressed and died before surgery. At a median follow up of 20 months, 10 patients remain free of disease. Perioperative treatment with BRAF inhibiting agents in BRAFV600E mutated Stage III melanoma patients facilitates surgical resection and affords satisfactory disease free survival. © 2017 Wiley Periodicals, Inc.

Pancreatic Cancer Tumor Size on CT Scan Versus Pathologic Specimen: Implications for Radiation Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arvold, Nils D.; Niemierko, Andrzej; Mamon, Harvey J.

2011-08-01

Purpose: Pancreatic cancer primary tumor size measurements are often discordant between computed tomography (CT) and pathologic specimen after resection. Dimensions of the primary tumor are increasingly relevant in an era of highly conformal radiotherapy. Methods and Materials: We retrospectively evaluated 97 consecutive patients with resected pancreatic cancer at two Boston hospitals. All patients had CT scans before surgical resection. Primary endpoints were maximum dimension (in millimeters) of the primary tumor in any direction as reported by the radiologist on CT and by the pathologist for the resected gross fresh specimen. Endoscopic ultrasound (EUS) findings were analyzed if available. Results: Ofmore » the patients, 87 (90%) had preoperative CT scans available for review and 46 (47%) had EUS. Among proximal tumors (n = 69), 40 (58%) had pathologic duodenal invasion, which was seen on CT in only 3 cases. The pathologic tumor size was a median of 7 mm larger compared with CT size for the same patient (range, -15 to 43 mm; p < 0.0001), with 73 patients (84%) having a primary tumor larger on pathology than CT. Endoscopic ultrasound was somewhat more accurate, with pathologic tumor size being a median of only 5 mm larger compared with EUS size (range, -15 to 35 mm; p = 0.0003). Conclusions: Computed tomography scans significantly under-represent pancreatic cancer tumor size compared with pathologic specimens in resectable cases. We propose a clinical target volume expansion formula for the primary tumor based on our data. The high rate of pathologic duodenal invasion suggests a risk of duodenal undercoverage with highly conformal radiotherapy.« less

Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy.

PubMed

Litviakov, Nikolai; Tsyganov, Matvey; Larionova, Irina; Ibragimova, Marina; Deryusheva, Irina; Kazantseva, Polina; Slonimskaya, Elena; Frolova, Irina; Choinzonov, Eugeniy; Cherdyntseva, Nadezhda; Kzhyshkowska, Julia

2018-05-04

High activity of enzyme TOP2a in tumor cells is known to be associated with sensitivity to anthracycline chemotherapy, but 20% of such patients do not show clinical response. Tumor microenvironment, including tumor-associated macrophages (TAM), is an essential factor defining the efficiency of chemotherapy. In the present study, we analyzed the expression of M2 macrophage markers, YKL-39 and CCL18, in tumors of breast cancer patients received anthracycline-based NAC. Patients were divided into two groups according to the level of doxorubicin sensitivity marker TOP2a: DOX-Sense and DOX-Res groups. Expression levels of TOR2a, CD68, YKL-39 and CCL18 genes were analyzed by qPCR, the amplification of TOR2a gene locus was assessed by the microarray assay. Clinical and pathological responses to neoadjuvant chemotherapy were assessed. We found that the average level of TOP2a expression in patients of DOX-Sense group was almost 10 times higher than in patients of DOX-Res group, and the expression of CD68 was 3 times higher in the DOX-Sense group compared to DOX-Res group. We demonstrated that expression levels of M2-derived cytokines but not the amount of TAM is indicative for clinical and pathological chemotherapy efficacy in breast cancer patients. Out of 8 patients from DOX-Sense group who did not respond to neoadjuvant chemotherapy (NAC), 7 patients had M2+ macrophage phenotype (YKL-39 + CCL18 - or YKL-39 - CCL18 + ) and only one patient had M2- macrophage phenotype (YKL-39 - CCL18 - ). In DOX-Res group, out of 14 patients who clinically responded to NAC 9 patients had M2- phenotype and only 5 patients had M2+ macrophage phenotype. Among pathological non-responders in DOX-Sense group, 19 (82%) patients had M2+ tumor phenotype and only 4 (18%) patients had M2- phenotype. In DOX-Res group, all 5 patients who pathologically responded to NAC had M2 phenotype (YKL-39 - CCL18 - ). Unlike the clinical response to NAC, the differences in the frequency of M2+ and M2- phenotypes between pathologically responding and non-responding patients within DOX-Sense and DOX-Res groups were statistically significant. Thus, we showed that in patients with breast cancer who received anthracycline-containing NAC the absence of clinical response is associated with the presence of M2+ macrophage phenotype (YKL-39-CCL18 + or YKL-39 + CCL18-) based on TOP2a overexpression data.

Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

PubMed

Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

2018-06-01

To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

Pathologic fracture in childhood and adolescent osteosarcoma: A single-institution experience.

PubMed

Haynes, Lindsay; Kaste, Sue C; Ness, Kirsten K; Wu, Jianrong; Ortega-Laureano, Lucia; Bishop, Michael; Neel, Michael; Rao, Bhaskar; Fernandez-Pineda, Israel

2017-04-01

Pathologic fractures occur in 5-10% of pediatric osteosarcoma (OS) cases and have historically been considered a contraindication to limb salvage. Our purpose was to describe the radiographic features of pathologic fracture and examine its impact on local recurrence rates, functional outcomes, and overall survival. We retrospectively analyzed patients at our institution from 1990 to 2015 with pathologic fracture at diagnosis or during neoadjuvant chemotherapy. We selected a control group of 50 OS patients of similar age and gender without pathologic fracture from 1990 to 2015. Functional outcomes were scored using Musculoskeletal Tumor Society criteria. Chi-square test was used for comparative analysis of groups. Thirty-six patients with 37 pathologic fractures form the study cohort. Of patients who received surgery, 18 of 34 patients with fracture underwent amputation compared to 8 of 48 patients in the nonfracture group (P = 0.007). Indications for amputation in fracture patients were tumor size (n = 7), neurovascular involvement (n = 6), and tumor progression during neoadjuvant chemotherapy (n = 5). Only one patient (2.9%) in the fracture group who underwent limb salvage suffered local recurrence. Of patients who received neoadjuvant chemotherapy, 25 of 34 fracture patients showed poor histological response compared to 24 of 47 nonfracture patients (P = 0.044). There was no statistically significant difference in overall survival (P = 0.96). Functional outcomes were significantly lower in fracture patients (median = 17.5) than nonfracture patients (median = 24) (P = 0.023). Radiographic features of pathologic fractures were highly variable in this population. Limb salvage surgery can be performed without increased risk of local recurrence. Patients with pathologic fracture suffer worse functional outcomes but no decrease in overall survival. © 2016 Wiley Periodicals, Inc.

Tumor Size on Abdominal MRI Versus Pathologic Specimen in Resected Pancreatic Adenocarcinoma: Implications for Radiation Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hall, William A., E-mail: whall4@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; Mikell, John L.

2013-05-01

Purpose: We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. Methods and Materials: The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions ofmore » tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. Results: The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, −34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. Conclusions: Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before routine integration into the treatment planning process.« less

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity.

PubMed

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G; Helland, Aslaug; Rye, Inga H; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-02-13

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of cellular diversity for genetic and phenotypic features

PubMed Central

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-01-01

SUMMARY Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor subtype-specific and it did not change during treatment in tumors with partial or no response. However, lower pre-treatment genetic diversity was significantly associated with complete pathologic response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution. PMID:24462293

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

DOE PAGES

Almendro, Vanessa; Cheng, Yu -Kang; Randles, Amanda; ...

2014-02-01

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatialmore » distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.« less

[Diagnostic accuracy research of needle puncture biopsy during operation for pulmonary single nodules].

PubMed

Chen, Jin-feng; Liu, Yi-nan; Wu, Nan; Feng, Yuan; Wang, Jia; Lü, Chao; Wang, Yu-zhao; Pei, Yu-quan; Yan, Shi; Zheng, Qing-feng; Zhang, Li-jian; Yang, Yue

2012-04-01

To investigate the diagnostic accuracy of needle puncture biopsy and pathological examination of frozen during operation for pulmonary nodules, and whether this diagnostic method can replace tumor resection examination. Totally 50 patients (28 males and 22 females, average age was 59 years) who had the single nodule after imaging examination without any pathological diagnostic from January to October 2010 were selected in this research work. During open operation or video assisted thoracic surgery, needle (14 G model) was used to puncture biopsy for pathological examination of frozen. All the adverse events during puncture biopsy would be recorded. The resection specimens would be accepted paraffin pathological examination. The relationship between puncture frozen pathological and paraffin pathological examination was analyzed. All tumor sizes were ranged from 1.0 cm × 0.6 cm to 5.6 cm × 9.0 cm. The paraffin pathological examination after operation as the golden standard, there were 7 cases of benign tumor and 43 cases of malignant tumor. The diagnostic sensitivity of puncture biopsy was 90.7%, the specificity was 100%, the positive predictive value was 100% and the negative predictive value was 63.6%. There were 11 cases of benign tumor diagnosed by needle puncture biopsy, among which 4 cases were proved as malignant tumor by paraffin pathology, and the false negative rate was 9.3%. The main risk of puncture biopsy was bleeding after puncture immediately, and the rate was 4.0% (2/50). The puncture biopsy during operation had a high specificity for malignant lung tumor, and there was a certain false negative rate for benign tumor. Puncture biopsy and pathological examination of frozen tissue can replace tumor section biopsy in a way.

Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01).

PubMed

Charehbili, A; van de Ven, S; Smit, V T H B M; Meershoek-Klein Kranenbarg, E; Hamdy, N A T; Putter, H; Heijns, J B; van Warmerdam, L J C; Kessels, L; Dercksen, M; Pepels, M J; Maartense, E; van Laarhoven, H W M; Vriens, B; Wasser, M N; van Leeuwen-Stok, A E; Liefers, G J; van de Velde, C J H; Nortier, J W R; Kroep, J R

2014-05-01

The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.

TU-AB-BRA-12: Impact of Image Registration Algorithms On the Prediction of Pathological Response with Radiomic Textures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yip, S; Coroller, T; Niu, N

2015-06-15

Purpose: Tumor regions-of-interest (ROI) can be propagated from the pre-onto the post-treatment PET/CT images using image registration of their CT counterparts, providing an automatic way to compute texture features on longitudinal scans. This exploratory study assessed the impact of image registration algorithms on textures to predict pathological response. Methods: Forty-six esophageal cancer patients (1 tumor/patient) underwent PET/CT scans before and after chemoradiotherapy. Patients were classified into responders and non-responders after the surgery. Physician-defined tumor ROIs on pre-treatment PET were propagated onto the post-treatment PET using rigid and ten deformable registration algorithms. One co-occurrence, two run-length and size zone matrix texturesmore » were computed within all ROIs. The relative difference of each texture at different treatment time-points was used to predict the pathologic responders. Their predictive value was assessed using the area under the receiver-operating-characteristic curve (AUC). Propagated ROIs and texture quantification resulting from different algorithms were compared using overlap volume (OV) and coefficient of variation (CoV), respectively. Results: Tumor volumes were better captured by ROIs propagated by deformable rather than the rigid registration. The OV between rigidly and deformably propagated ROIs were 69%. The deformably propagated ROIs were found to be similar (OV∼80%) except for fast-demons (OV∼60%). Rigidly propagated ROIs with run-length matrix textures failed to significantly differentiate between responders and non-responders (AUC=0.65, p=0.07), while the differentiation was significant with other textures (AUC=0.69–0.72, p<0.03). Among the deformable algorithms, fast-demons was the least predictive (AUC=0.68–0.71, p<0.04). ROIs propagated by all other deformable algorithms with any texture significantly predicted pathologic responders (AUC=0.71–0.78, p<0.01) despite substantial variation in texture quantification (CoV>70%). Conclusion: Propagated ROIs using deformable registration for all textures can lead to accurate prediction of pathologic response, potentially expediting the temporal texture analysis process. However, rigid and fast-demons deformable algorithms are not recommended due to their inferior performance compared to other algorithms. The project was supported in part by a Kaye Scholar Award.« less

DCE-MRI Parameters Have Potential to Predict Response of Locally Advanced Breast Cancer Patients to Neoadjuvant Chemotherapy and Hyperthermia: A Pilot Study

PubMed Central

Craciunescu, Oana I.; Blackwell, Kimberly L.; Jones, Ellen L.; MacFall, James R.; Yu, Daohai; Vujaskovic, Zeljko; Wong, Terence Z.; Liotcheva, Vlayka; Rosen, Eric L.; Prosnitz, Leonard R.; Samulski, Thaddeus V.; Dewhirst, Mark W.

2009-01-01

Purpose To use a novel Morpho-Physiological Tumor Score (MPTS) generated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict response to treatment. Materials and Methods A protocol was designed to acquire DCE-MRI images of 20 locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NA ChT) and hyperthermia (HT). Imaging was done over 30 minutes following bolus injection of Gd-based contrast agent. Parametric maps were generated by fitting the signal intensity to a double exponential curve and were used to derive a morphological characterization of the lesions. Enhancement-variance dynamics parameters, washin and washout parameters (WiP, WoP) were extracted. The morphological characterization and the WiP and WoP were combined into a MPTS with the intent of achieving better prognostic efficacy. The MPTS was correlated with response to NA therapy as determined by pathologic residual tumor and MRI imaging. Results The contrast agent in all tumors typically peaked in the first 1–4 minutes. The tumors WiP and WoP varied considerably. The MPTS was highly correlated with whether the patients had a pathologic response. This scoring system has a specificity of 78% and a sensitivity of 91% for predicting response to NA chemotherapy. The kappa was 0.69 with a 95% confidence interval of [0.38, 1.0] and a p-value of 0.002. Conclusions This pilot study shows that the MPTS derived using pre-treatment MRI images has the potential to predict response to NA ChT and HT in LABC patients. Further prospective studies are needed to confirm the validity of these results. PMID:19657852

Immunosignature: Serum Antibody Profiling for Cancer Diagnostics.

PubMed

Chapoval, Andrei I; Legutki, J Bart; Stafford, Philip; Trebukhov, Andrey V; Johnston, Stephen A; Shoikhet, Yakov N; Lazarev, Alexander F

2015-01-01

Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at early stages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment of cancer. However the complexity of the body's response to the pathological processes makes it virtually impossible to evaluate this response to the development of the disease using a single biomarker that is present in the serum at low concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Instead of going after biomarkers themselves this approach rely on the analysis of the humoral immune response to molecular changes associated with the development of pathological processes. It is known that antibodies are produced in response to proteins expressed during cancer development. Accordingly, the changes in antibody repertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highly sensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the present review we discuss modern methods for antibody detection, as well as describe the principles and applications of immunosignature in research and clinical practice.

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakobsen, Anders, E-mail: anders.jakobsen@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2012-11-15

Purpose: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation. Methods and Materials: The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of {<=}5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; armmore » B). Concomitant chemotherapy, uftoral 300 mg/m{sup 2} and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0). Results: The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). Conclusions: This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.« less

Pre-operative assessment of residual disease in locally advanced breast cancer patients: A sequential study by quantitative diffusion weighted MRI as a function of therapy.

PubMed

Agarwal, Khushbu; Sharma, Uma; Sah, Rani G; Mathur, Sandeep; Hari, Smriti; Seenu, Vurthaluru; Parshad, Rajinder; Jagannathan, Naranamangalam R

2017-10-01

The potential of diffusion weighted imaging (DWI) in assessing pathologic response and surgical margins in locally advanced breast cancer patients (n=38) undergoing neoadjuvant chemotherapy was investigated. DWI was performed at pre-therapy (Tp0), after I (Tp1) and III (Tp3) NACT at 1.5T. Apparent diffusion coefficient (ADC) of whole tumor (ADC WT ), solid tumor (ADC ST ), intra-tumoral necrosis (ADC Nec ) was determined. Further, ADC of 6 consecutive shells (5mm thickness each) including tumor margin to outside tumor margins (OM1 to OM5) was calculated and the data analyzed to define surgical margins. Of 38 patients, 6 were pathological complete responders (pCR), 19 partial responders (pPR) and 13 were non-responders (pNR). Significant increase was observed in ADC ST and ADC WT in pCR and pPR following therapy. Pre-therapy ADC was significantly lower in pCR compared to pPR and pNR indicating the heterogeneous nature of tumor which may affect drug perfusion and consequently the response. ADC of outside margins (OM1, OM2, and OM3) was significantly different among pCR, pPR and pNR at Tp3 which may serve as response predictive parameter. Further, at Tp3, ADC of outside margins (OM1, OM2, and OM3) was significantly lower compared to that seen at Tp0 in pCR, indicating the presence of residual disease in these shells. Pre-surgery information may serve as a guide to define cancer free margins and the extent of residual disease which may be useful in planning breast conservation surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer.

PubMed

Hannemann, Juliane; Oosterkamp, Hendrika M; Bosch, Cathy A J; Velds, Arno; Wessels, Lodewyk F A; Loo, Claudette; Rutgers, Emiel J; Rodenhuis, Sjoerd; van de Vijver, Marc J

2005-05-20

At present, clinically useful markers predicting response of primary breast carcinomas to either doxorubicin-cyclophosphamide (AC) or doxorubicin-docetaxel (AD) are lacking. We investigated whether gene expression profiles of the primary tumor could be used to predict treatment response to either of those chemotherapy regimens. Within a single-institution, randomized, phase II trial, patients with locally advanced breast cancer received six courses of either AC (n = 24) or AD (n = 24) neoadjuvant chemotherapy. Gene expression profiles were generated from core-needle biopsies obtained before treatment and correlated with the response of the primary tumor to the chemotherapy administered. Additionally, pretreatment gene expression profiles were compared with those in tumors remaining after chemotherapy. Ten (20%) of 48 patients showed a (near) pathologic complete remission of the primary tumor after treatment. No gene expression pattern correlating with response could be identified for all patients or for the AC or AD groups separately. The comparison of the pretreatment biopsy and the tumor excised after chemotherapy revealed differences in gene expression in tumors that showed a partial remission but not in tumors that did not respond to chemotherapy. No gene expression profile predicting the response of primary breast carcinomas to AC- or AD-based neoadjuvant chemotherapy could be detected in this interim analysis. More subtle differences in gene expression are likely to be present but can only be reliably identified by studying a larger group of patients. Response of a breast tumor to neoadjuvant chemotherapy results in alterations in gene expression.

Expression of p53 protein in advanced head and neck squamous cell carcinoma before and after chemotherapy.

PubMed

Dunphy, C H; Dunphy, F R; Boyd, J H; Varvares, M A; Kim, H J; Lowe, V; Dunleavy, T L; Rodriguez, J; McDonough, E M; Minster, J

1997-11-01

The expression of p53 protein has been reported to be in the range of 35% to 67% in head and neck squamous cell carcinoma (HNSCC). Mutations of the gene for p53 protein have been associated with rapidly proliferating tumors, and p53 protein expression has been shown to be a significant predictor of worse survival in surgically resected HNSCC. To determine whether p53 protein expression in advanced (stages III and IV) HNSCC has any impact on tumor response to 2 to 3 courses of paclitaxel (Taxol) and carboplatin, we prospectively studied prechemotherapy specimens from patients with previously untreated, advanced-stage HNSCC. We also attempted to study residual tumors after chemotherapy to determine if the p53 status of the tumor changed. The expression of p53 protein was evaluated by immunohistochemical analysis (clone BP53-12-1; Bio-Genex, San Ramon, Calif). Tertiary university medical center. Two to 3 courses of chemotherapy with paclitaxel and carboplatin. Pathologic complete remission or residual tumor. The results of p53 immunostaining were positive in 24 (67%) of 36 HNSCC specimens before chemotherapy. After chemotherapy, 8 patients achieved pathologic complete remission. Before chemotherapy, the tumor was p53 negative in 2 patients and positive in 6 patients. No correlation of p53 protein expression with response to chemotherapy was noted. The expression of p53 protein converted from positive to negative in 5 (42%) of 12 specimens from patients with residual tumor after chemotherapy, with no impact on clinical outcome.

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

PubMed Central

Esserman, Laura J.; Berry, Donald A.; DeMichele, Angela; Carey, Lisa; Davis, Sarah E.; Buxton, Meredith; Hudis, Cliff; Gray, Joe W.; Perou, Charles; Yau, Christina; Livasy, Chad; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debasish; Lehman, Constance; Liu, Minetta C.; Olopade, Olufunmilayo I.; Rugo, Hope S.; Carpenter, John T.; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunn-Yi; Giri, Dilip; van 't Veer, Laura; Hylton, Nola

2012-01-01

Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. Conclusion In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology. PMID:22649152

Dysphagia is not a Valuable Indicator of Tumor Response after Preoperative Chemotherapy for R0 Resected Patients with Adenocarcinoma of the Gastroesophageal Junction.

PubMed

Strandby, R B; Svendsen, L B; Bæksgaard, L; Egeland, C; Achiam, M P

2016-06-01

Monitoring treatment response to preoperative chemotherapy is of utmost importance to avoid treatment toxicity, especially in non-responding patients. Currently, no reliable methods exist for tumor response assessment after preoperative chemotherapy. Therefore, the aim of this study was to evaluate dysphagia as a predictor of tumor response after preoperative chemotherapy and as a predictor of recurrence and survival. Patients with adenocarcinoma of the gastroesophageal junction, treated between 2010 and 2012, were retrospectively reviewed. Dysphagia scores (Mellow-Pinkas) were obtained before and after three cycles of perioperative chemotherapy together with clinicopathological patient characteristics. A clinical response was defined as improvement of dysphagia by at least 1 score from the baseline. The tumor response was defined as down staging of T-stage from initial computer tomography (CT) scan (cT-stage) to pathologic staging of surgical specimen (pT-stage). Patients were followed until death or censored on June 27th, 2014. Of the 110 included patients, 59.1% had improvement of dysphagia after three cycles of perioperative chemotherapy, and 31.8% had a chemotherapy-induced tumor response after radical resection of tumor. Improvement of dysphagia was not correlated with the tumor response in the multivariate analysis (p = 0.23). Moreover, the presence of dysphagia was not correlated with recurrence (p = 0.92) or survival (p = 0.94) in the multivariate analysis. In our study, improvement of dysphagia was not valid for tumor response evaluation after preoperative chemotherapy and was not correlated with the tumor response. The presence of dysphagia does not seem to be a predictor of recurrence or survival. © The Finnish Surgical Society 2015.

The Lymphatic System and Pancreatic Cancer

PubMed Central

Fink, Darci M.; Steele, Maria M.; Hollingsworth, Michael A.

2016-01-01

This review summarizes current knowledge of the biology, pathology and clinical understanding of lymphatic invasion and metastasis in pancreatic cancer. We discuss the clinical and biological consequences of lymphatic invasion and metastasis, including paraneoplastic effects on immune responses and consider the possible benefit of therapies to treat tumors that are localized to lymphatics. A review of current techniques and methods to study interactions between tumors and lymphatics is presented. PMID:26742462

Correlation of tumor response on computed tomography with pathological necrosis in hepatocellular carcinoma treated by chemoembolization before liver transplantation.

PubMed

Dioguardi Burgio, Marco; Ronot, Maxime; Bruno, Onorina; Francoz, Claire; Paradis, Valérie; Castera, Laurent; Durand, François; Soubrane, Olivier; Vilgrain, Valérie

2016-11-01

The purpose of this article was to compare the results of Response Evaluation Criteria in Solid Tumors (RECIST), modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria for the evaluation of tumor necrosis in patients treated with transarterial chemoembolization before liver transplantation (LT) for hepatocellular carcinoma. Response to treatment was evaluated on computed tomography scan by 2 independent readers based on RECIST, mRECIST, and EASL criteria, and compared with tumor necrosis assessed by explant pathology. Necrosis was defined as major when >90%. Factors associated with major necrosis were tested by multivariate analysis. Fifty-eight patients (53 males; mean age, 54 years; range, 31-64 years) were included with 88 nodules. Fifty-one (58%) nodules were shown to have major necrosis. Among them readers 1 and 2 identified a complete response (CR) according to RECIST, mRECIST, and EASL criteria in 2 (4%), 47 (92%), and 47 (92%), and 1 (2%), 45 (88%), and 45 (88%) nodules, respectively. However, 12-14 of 59 nodules classified as CR on mRECIST or EASL criteria were found to have intermediate or minor necrosis (overestimation in 20%-24% of the patients). Combining the classification of CR by mRECIST and EASL criteria and complete lipiodol deposition reduced the overestimation to 11%. Among 59 nodules classified with a CR according to mRECIST or EASL, those with complete lipiodol deposition (n = 36, 61%) had a higher rate of necrosis than those with incomplete lipiodol deposition (n = 23, 39%): 95% versus 68% and 95% versus 63% for reader 1 and 2, respectively. In conclusion, CR based on mRECIST/EASL combined with complete lipiodol deposition was better for identification of major tumor necrosis. Even in the presence of CR according to mRECIST/EASL, incomplete lipiodol deposition should be considered indicative of substantial viable tumor remnant. Liver Transplantation 22 1491-1500 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma.

PubMed

Hao, Yoshiteru; Numata, Kazushi; Ishii, Tomohiro; Fukuda, Hiroyuki; Maeda, Shin; Nakano, Masayuki; Tanaka, Katsuaki

2017-05-07

To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test ( P = 0.002). The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs.

Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma

PubMed Central

Hao, Yoshiteru; Numata, Kazushi; Ishii, Tomohiro; Fukuda, Hiroyuki; Maeda, Shin; Nakano, Masayuki; Tanaka, Katsuaki

2017-01-01

AIM To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. METHODS Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. RESULTS During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test (P = 0.002). CONCLUSION The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs. PMID:28533668

Tumor size measured by preoperative ultrasonography and postoperative pathologic examination in papillary thyroid carcinoma: relative differences according to size, calcification and coexisting thyroiditis.

PubMed

Yoon, Young Hoon; Kwon, Ki Ryun; Kwak, Seo Young; Ryu, Kyeung A; Choi, Bobae; Kim, Jin-Man; Koo, Bon Seok

2014-05-01

Ultrasonography (US) is a useful diagnostic modality for evaluation of the size and features of thyroid nodules. Tumor size is a key indicator of the surgical extent of thyroid cancer. We evaluated the difference in tumor sizes measured by preoperative US and postoperative pathologic examination in papillary thyroid carcinoma (PTC). We reviewed the medical records of 172 consecutive patients, who underwent thyroidectomy for PTC treatment. We compared tumor size, as measured by preoperative US, with that in postoperative specimens. And we analyzed a number of factors potentially influencing the size measurement, including cancer size, calcification and coexisting thyroiditis. The mean size of the tumor measured by preoperative US was 11.4, and 10.2 mm by postoperative pathologic examination. The mean percentage difference (US-pathology/US) of tumor sizes measured by preoperative US and postoperative pathologic examination was 9.9 ± 19.3%, which was statistically significant (p < 0.001). When the effect of tumor size (≤10.0 vs. 10.1-20.0 vs. >20.0 mm) and the presence of calcification or coexisting thyroiditis on the tumor size discrepancy between the two measurements was analyzed, the mean percentage differences according to tumor size (9.1 vs. 11.2% vs. 9.8%, p = 0.842), calcification (9.2 vs. 10.2%, p = 0.756) and coexisting thyroiditis (17.6 vs. 9.5%, p = 0.223) did not show statistical significance. Tumor sizes measured in postoperative pathology were ~90% of those measured by preoperative US in PTC; this was not affected by tumor size, the presence of calcification or coexisting thyroiditis. When the surgical extent of PTC treatment according to tumor size measured by US is determined, the relative difference between tumor sizes measured by preoperative US and postoperative pathologic examination should be considered.

Major pathologic response to alectinib in ALK-rearranged adenocarcinoma of the lung.

PubMed

Imanishi, Naoko; Yoneda, Kazue; Taira, Akihiro; Ichiki, Yoshinobu; Sato, Naoko; Hisaoka, Masanori; Tanaka, Fumihiro

2018-03-09

Alectinib is a highly selective tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) and provided a significantly prolonged progression-free survival compared with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) harboring rearrangements of the ALK gene. Here, we present the first surgical case of ALK-rearranged lung adenocarcinoma with major pathological response in resected specimens after treatment with alectinib. A 65-year-old female with clinical stage IIIA-N2 ALK-rearranged adenocarcinoma originating from the left lower lobe presented. Involvement of lower para-tracheal node was pathologically confirmed by endobronchial ultrasound-guided biopsy. Alectinib was prescribed, as the patient may not tolerate radiotherapy due to a mental illness. After 3 months' treatment with alectinib, a remarkable radiological and metabolic response was achieved. The patient did not tolerate further continuation of alectinib treatment, and surgery was performed without any morbidity. Only < 10% tumor cells were viable in all resected specimens, indicating major pathological response to alectinib. Salvage surgery after alectinib treatment may be safe and effective for initially unresectable NSCLC harboring ALK-rearrangements.

Comparison of Macroscopic Pathology Measurements With Magnetic Resonance Imaging and Assessment of Microscopic Pathology Extension for Colorectal Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendez Romero, Alejandra, E-mail: a.mendezromero@erasmusmc.nl; Verheij, Joanne; Dwarkasing, Roy S.

2012-01-01

Purpose: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. Methods and Materials: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapymore » treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. Results: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (r{sub s} = 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r{sub s} = 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r{sub s} = 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r{sub s} = 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. Conclusions: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.« less

RNA-based determination of ESR1 and HER2 expression and response to neoadjuvant chemotherapy.

PubMed

Denkert, C; Loibl, S; Kronenwett, R; Budczies, J; von Törne, C; Nekljudova, V; Darb-Esfahani, S; Solbach, C; Sinn, B V; Petry, C; Müller, B M; Hilfrich, J; Altmann, G; Staebler, A; Roth, C; Ataseven, B; Kirchner, T; Dietel, M; Untch, M; von Minckwitz, G

2013-03-01

Hormone and human epidermal growth factor receptor 2 (HER2) receptors are the most important breast cancer biomarkers, and additional objective and quantitative test methods such as messenger RNA (mRNA)-based quantitative analysis are urgently needed. In this study, we investigated the clinical validity of RT-PCR-based evaluation of estrogen receptor (ESR1) and HER2 mRNA expression. A total of 1050 core biopsies from two retrospective (GeparTrio, GeparQuattro) and one prospective (PREDICT) neoadjuvant studies were evaluated by quantitative RT-PCR for ESR1 and HER2. ESR1 mRNA was significantly predictive for reduced response to neoadjuvant chemotherapy in univariate and multivariate analysis in all three cohorts. The complete pathologically documented response (pathological complete response, pCR) rate for ESR1+/HER2- tumors was 7.3%, 8.0% and 8.6%; for ESR1-/HER2- tumors it was 34.4%, 33.7% and 37.3% in GeparTrio, GeparQuattro and PREDICT, respectively (P < 0.001 in each cohort). In the Kaplan-Meier analysis in GeparTrio patients with ESR1+/HER2- tumors had the best prognosis, compared with ESR1-/HER2- and ESR1-/HER2+ tumors [disease-free survival (DFS): P < 0.0005, overall survival (OS): P < 0.0005]. Our results suggest that mRNA levels of ESR1 and HER2 predict response to neoadjuvant chemotherapy and are significantly associated with long-term outcome. As an additional option to standard immunohistochemistry and gene-array-based analysis, quantitative RT-PCR analysis might be useful for determination of the receptor status in breast cancer.

Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score.

PubMed

Kutikov, Alexander; Smaldone, Marc C; Egleston, Brian L; Manley, Brandon J; Canter, Daniel J; Simhan, Jay; Boorjian, Stephen A; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2011-08-01

Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available. All patients in the cohort underwent either partial or radical nephrectomy. The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Clinically Significant Prostate Cancer Local Recurrence After Radiation Therapy Occurs at the Site of Primary Tumor: Magnetic Resonance Imaging and Step-Section Pathology Evidence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pucar, Darko; Hricak, Hedvig; Shukla-Dave, Amita

2007-09-01

Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm{sup 3} and/or resulting inmore » extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm{sup 3}) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci ({<=}0.06 cm{sup 3}) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment.« less

Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

PubMed

Tsutsumi, Soichi; Tabe, Yuichi; Fujii, Takaaki; Yamaguchi, Satoru; Suto, Toshinaga; Yajima, Reina; Morita, Hiroki; Kato, Toshihide; Shioya, Mariko; Saito, Jun-Ichi; Asao, Takayuki; Nakano, Takashi; Kuwano, Hiroyuki

2011-11-01

The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

Constrained clusters of gene expression profiles with pathological features.

PubMed

Sese, Jun; Kurokawa, Yukinori; Monden, Morito; Kato, Kikuya; Morishita, Shinichi

2004-11-22

Gene expression profiles should be useful in distinguishing variations in disease, since they reflect accurately the status of cells. The primary clustering of gene expression reveals the genotypes that are responsible for the proximity of members within each cluster, while further clustering elucidates the pathological features of the individual members of each cluster. However, since the first clustering process and the second classification step, in which the features are associated with clusters, are performed independently, the initial set of clusters may omit genes that are associated with pathologically meaningful features. Therefore, it is important to devise a way of identifying gene expression clusters that are associated with pathological features. We present the novel technique of 'itemset constrained clustering' (IC-Clustering), which computes the optimal cluster that maximizes the interclass variance of gene expression between groups, which are divided according to the restriction that only divisions that can be expressed using common features are allowed. This constraint automatically labels each cluster with a set of pathological features which characterize that cluster. When applied to liver cancer datasets, IC-Clustering revealed informative gene expression clusters, which could be annotated with various pathological features, such as 'tumor' and 'man', or 'except tumor' and 'normal liver function'. In contrast, the k-means method overlooked these clusters.

BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

PubMed

Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

2018-05-03

BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Herrada, J; Iyer, R B; Atkinson, E N; Sneige, N; Buzdar, A U; Hortobagyi, G N

1997-09-01

The purpose of this study was to correlate physical examination and sonographic and mammographic measurements of breast tumors and regional lymph nodes with pathological findings and to evaluate the effect of neoadjuvant chemotherapy on clinical Tumor-Node-Metastasis stage by noninvasive methods. This was a retrospective analysis of 100 patients with locally advanced breast cancer registered and treated in prospective trials of neoadjuvant chemotherapy. All patients received four cycles of a doxorubicin-containing regimen and had noninvasive evaluation of the primary tumor and regional lymph nodes before and after neoadjuvant chemotherapy by physical examination, sonography, and mammography and underwent breast surgery and axillary dissection within 5 weeks after completion of neoadjuvant chemotherapy. The correlations between clinical and pathological measurements were determined by Spearman rank correlation analysis. A proportional odds model was used to examine predictive values. Eighty-three patients had both a clinically detectable primary tumor and lymph node metastases. Sixty-four patients had a decrease in Tumor-Node-Metastasis stage after chemotherapy. For 54% of patients, there was concordance in clinical response between the primary tumor and lymph node compartment; for the rest, results were discordant. Physical examination correlated best with pathological findings in the measurement of the primary tumor (P = 0.0003), whereas sonography was the most accurate predictor of size for axillary lymph nodes (P = 0.0005). The combination of physical examination and mammography worked best for assessment of the primary tumor (P = 0.003), whereas combining physical examination with sonography gave optimal evaluation of regional lymph nodes (P = 0.0001). In conclusion, physical examination is the best noninvasive predictor of the real size of locally advanced primary breast cancer, whereas sonography correlates better with the real dimensions of axillary lymph nodes. The combination of physical examination with either mammography or sonography significantly improves the accuracy of noninvasive assessment of tumor dimensions.

Analysis of vestibular testing in patients with vestibular schwannoma based on the nerve of origin, the localization, and the size of the tumor.

PubMed

Suzuki, Mitsuya; Yamada, Chikako; Inoue, Rika; Kashio, Akinori; Saito, Yuki; Nakanishi, Wakako

2008-10-01

We aimed to analyze the factors influencing caloric response and vestibular evoked myogenic potential (VEMP) in vestibular schwannoma. The subjects comprised 130 patients with unilateral vestibular schwannoma pathologically diagnosed by surgery. Caloric response and the amplitude and latency of VEMP were measured and analyzed based on the nerve of origin, localization, and size of the tumor. The tumors were classified into 3 types based on localization: intracanalicular, intermediate, and medial; and into 4 grades based on size: 9 mm or less, 10 to 19 mm, 20 to 29 mm, and 30 mm or greater. : Abnormal rates of caloric response and VEMP in patients with tumors arising from the superior vestibular nerve were not significantly different from those in patients with tumors of the inferior vestibular nerve. In the intermediate and medial type-but not in the intracanalicular type-a significant difference in tumor size was observed between patients with normal caloric response and those with canal paresis as also between patients with normal VEMP and those with abnormal VEMP. In patients with tumors that maximally measured 10 to 19 mm or of the intermediate type, the p- and n-wave latencies of VEMP were significantly prolonged compared with those in the normal opposite ear. 1) The nerve of origin of tumors cannot be predicted based on caloric response and VEMP. 2) In the intermediate and medial types, caloric response and the VEMP amplitude are significantly diminished in association with an increase in tumor size. 3) Prolonged VEMP latencies seem to be not only caused by tumor compression to the brainstem or vestibular spinal tract but also by tumor compression isolated to the inferior vestibular nerve.

[Clear cell carcinoma of the ovary simulating a yolk sac tumor].

PubMed

Bahri, Ibticem; Boudawara, Tahya; Khabir, Abdelmajid; Beyrouti, Mohamed Issam; Frikha, Mounir; Jlidi, Rachid

2003-04-01

Clear cell carcinoma (CCC) of the ovary is uncommon. In young patients, this tumor may simulate a yolk sac tumor. In this case, the morphologic distinction between these tumors is often difficult but the immunohistochemical staining for CA125 and alpha foeto protein (AFP) and the response to chemotherapy are particularly helpful to resolve this problem of differential diagnosis. We report a case of a 17 year old patient who was operated for a tumor of the right ovary. The diagnosis of a yolk sac tumor was first suggested. However, because of the non response to chemotherapy, a second laparotomy was performed; the definitive pathologic examination concluded to the diagnosis of a CCC of the ovary. The young age and the immunohistochemical staining for AFP are unusual and misleading features for a CCC. Our objective about this particular case is to discuss the anatomoclinical aspects of the CCC of the ovary and to prove the role of immunohistochemistry in the differential diagnosis.

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

PubMed

Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

2015-08-01

In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

Quantitative image variables reflect the intratumoral pathologic heterogeneity of lung adenocarcinoma.

PubMed

Choi, E-Ryung; Lee, Ho Yun; Jeong, Ji Yun; Choi, Yoon-La; Kim, Jhingook; Bae, Jungmin; Lee, Kyung Soo; Shim, Young Mog

2016-10-11

We aimed to compare quantitative radiomic parameters from dual-energy computed tomography (DECT) of lung adenocarcinoma and pathologic complexity.A total 89 tumors with clinical stage I/II lung adenocarcinoma were prospectively included. Fifty one radiomic features were assessed both from iodine images and non-contrast images of DECT datasets. Comprehensive histologic subtyping was evaluated with all surgically resected tumors. The degree of pathologic heterogeneity was assessed using pathologic index and the number of mixture histologic subtypes in a tumor. Radiomic parameters were correlated with pathologic index. Tumors were classified as three groups according to the number of mixture histologic subtypes and radiomic parameters were compared between the three groups.Tumor density and 50th through 97.5th percentile Hounsfield units (HU) of histogram on non-contrast images showed strong correlation with the pathologic heterogeneity. Radiomic parameters including 75th and 97.5th percentile HU of histogram, entropy, and inertia on 1-, 2- and 3 voxel distance on non-contrast images showed incremental changes while homogeneity showed detrimental change according to the number of mixture histologic subtypes (all Ps < 0.05).Radiomic variables from DECT of lung adenocarcinoma reflect pathologic intratumoral heterogeneity, which may help in the prediction of intratumoral heterogeneity of the whole tumor.

Low-tar and high-tar cigarettes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holt, P.G.; Chalmer, J.E.; Roberts, L.M.

Mice were exposed for 7 to 8 minutes on weekdays to fresh smoke from high-tar (HT) or low-tar (LT) cigarettes for varying periods of up to 36 weeks. Mice exposed to HT cigarettes exhibited more marked alterations in humoral immune responsiveness, hematological profiles, and pulmonary pathologic findings than those exposed to LT cigarettes. However, cell-mediated immune responsiveness to both bacterial and tumor-specific antigens was depressed similarly in animals exposed to HT or LT cigarettes. Furthermore, the growth rates of subcutaneously established tumors were enhanced similarly in the two groups, with respect to those in control animals.

Impact of Race, Ethnicity and BMI on Achievement of Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer: A Pooled Analysis of Four Prospective Alliance Clinical Trials (A151426)

PubMed Central

Warner, Erica T.; Ballman, Karla V.; Strand, Carrie; Boughey, Judy; Buzdar, Aman U.; Carey, Lisa A.; Sikov, William M.; Partridge, H.

2016-01-01

Purpose Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese but this may be due to chemotherapy under dosing. We assessed associations of race, ethnicity and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. Methods 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95% confidence intervals (CI) for the associations of race, ethnicity, and BMI with pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. Results 253 (14.1%) were black, 199 (11.1%) Hispanic, 520 (28.9%) overweight, and 743 (41.4%) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs. white: OR: 1.18, 95% CI: 0.85–1.62) nor ethnicity (Hispanic vs. non-Hispanic: OR: 1.30, 95% CI: 0.67–2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER−/HER2+ cancers. Conclusions There was no difference in breast pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology. PMID:27449492

Impact of race, ethnicity, and BMI on achievement of pathologic complete response following neoadjuvant chemotherapy for breast cancer: a pooled analysis of four prospective Alliance clinical trials (A151426).

PubMed

Warner, Erica T; Ballman, Karla V; Strand, Carrie; Boughey, Judy C; Buzdar, Aman U; Carey, Lisa A; Sikov, William M; Partridge, Ann H

2016-08-01

Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese, but this may be due to chemotherapy underdosing. We assessed associations of race, ethnicity, and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95 % confidence intervals (CI) for the associations of race, ethnicity, and BMI with in-breast pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. 253 (14.1 %) were black, 199 (11.1 %) Hispanic, 520 (28.9 %) overweight, and 743 (41.4 %) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs white: OR 1.18, 95 % CI 0.85-1.62) nor ethnicity (Hispanic vs non-Hispanic; OR 1.30, 95 % CI 0.67-2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER-/HER2+ cancers. There was no difference in pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology.

Preoperative Capecitabine and Pelvic Radiation in Locally Advanced Rectal Cancer-Is it Equivalent to 5-FU Infusion Plus Leucovorin and Radiotherapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Alexander K., E-mail: alexc@cancerboard.ab.c; Wong, Alfred O.; Jenken, Daryl A.

2010-04-15

Purpose: The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy (RT) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil (5-FU) infusion, leucovorin, and mitomycin C in rectal cancer. Methods and Materials: We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage (T3 or T4) and the tumor location (<=7 cm or >7 cm from the anal verge) with another 68 patients who were treated with preoperative intermittent 5-FU infusion, leucovorin, mitomycin C, and 50 Gy of RT for amore » comparison of the pathologic tumor response, local control, distant failure, and survival rates. Results: The pathologic complete response rate was 21% with capecitabine and 18% with 5-FU and leucovorin (p = 0.72). The rate of T downstaging after chemoradiation was 59% for both groups. The rate of sphincter-sparing resection was 38% after capecitabine plus RT and 43% after 5-FU plus RT (p = 0.67). At 3 years, there was no significant difference in the local control rate (93% for capecitabine and 92% for 5-FU and leucovorin), relapse-free rate (74% for capecitabine and 73% for 5-FU and leucovorin), or disease-specific survival rate (86% for capecitabine and 77% for 5-FU and leucovorin). The acute toxicity profile was comparable, with little Grade 3 and 4 toxicity. Conclusions: When administered with concurrent preoperative RT, both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response, local control, relapse-free survival, and disease-specific survival rates in rectal cancer.« less

Metabolic response of rectal cancer assessed by 18-FDG PET following chemoradiotherapy is prognostic for patient outcome.

PubMed

Yeung, J M C; Kalff, V; Hicks, R J; Drummond, E; Link, E; Taouk, Y; Michael, M; Ngan, S; Lynch, A C; Heriot, A G

2011-05-01

Complete pathological response has proven prognostic benefits in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Sequential 18-FDG PET may be an early surrogate for pathological response to chemoradiotherapy. The aim of this study was to identify whether metabolic response measured by FDG PET following chemoradiotherapy is prognostic for tumor recurrence and survival following neoadjuvant therapy and surgical treatment for primary rectal cancer. Patients with primary rectal cancer treated by long-course neoadjuvant chemoradiotherapy followed by surgery had FDG PET performed before and 4 weeks after treatment, before surgical resection was performed. Retrospective chart review was undertaken for patient demographics, tumor staging, recurrence rates, and survival. : Between 2000 and 2007, 78 patients were identified (53 male, 25 female; median age, 64 y). After chemoradiotherapy, 37 patients (47%) had a complete metabolic response, 26 (33%) had a partial metabolic response, and 14 (18%) had no metabolic response as assessed by FDG PET (1 patient had missing data). However, only 4 patients (5%) had a complete pathological response. The median postoperative follow-up period was 3.1 years during which 14 patients (19%) had a recurrence: 2 local, 9 distant, and 3 with both local and distant. The estimated percentage without recurrence was 77% at 5 years (95% CI 66%-89%). There was an inverse relationship between FDG PET metabolic response and the incidence of recurrence within 3 years (P = .04). Kaplan-Meier analysis of FDG PET metabolic response and overall survival demonstrated a significant difference in survival among patients in the 3 arms: complete, partial, and no metabolic response (P = .04); the patients with complete metabolic response had the best prognosis. Complete or partial metabolic response on PET following neoadjuvant chemoradiotherapy and surgery predicts a lower local recurrence rate and improved survival compared with patients with no metabolic response. Metabolic response may be used to stratify prognosis in patients with rectal cancer.

Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: development of a specific predictor and study of its utilities using decision curve analysis.

PubMed

Jankowski, Clémentine; Guiu, S; Cortet, M; Charon-Barra, C; Desmoulins, I; Lorgis, V; Arnould, L; Fumoleau, P; Coudert, B; Rouzier, R; Coutant, C; Reyal, F

2017-01-01

The aim of this study was to assess the Institut Gustave Roussy/M.D. Anderson Cancer Center (IGR/MDACC) nomogram in predicting pathologic complete response (pCR) to preoperative chemotherapy in a cohort of human epidermal growth factor receptor 2 (HER2)-positive tumors treated with preoperative chemotherapy with trastuzumab. We then combine clinical and pathological variables associated with pCR into a new nomogram specific to HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. Data from 270 patients with HER2-positive tumors treated with preoperative chemotherapy with trastuzumab at the Institut Curie and at the Georges François Leclerc Cancer Center were used to assess the IGR/MDACC nomogram and to subsequently develop a new nomogram for pCR based on multivariate logistic regression. Model performance was quantified in terms of calibration and discrimination. We studied the utility of the new nomogram using decision curve analysis. The IGR/MDACC nomogram was not accurate for the prediction of pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab, with poor discrimination (AUC = 0.54, 95% CI 0.51-0.58) and poor calibration (p = 0.01). After uni- and multivariate analysis, a new pCR nomogram was built based on T stage (TNM), hormone receptor status, and Ki67 (%). The model had good discrimination with an area under the curve (AUC) at 0.74 (95% CI 0.70-0.79) and adequate calibration (p = 0.93). By decision curve analysis, the model was shown to be relevant between thresholds of 0.3 and 0.7. To the best of our knowledge, ours is the first nomogram to predict pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. To ensure generalizability, this model needs to be externally validated.

Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

PubMed

Glaser, Rebecca L; York, Anne E; Dimitrakakis, Constantine

2017-07-01

Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

PubMed

Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

2018-05-08

Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer.

PubMed

García-Cabezas, Sonia; Rodríguez-Liñán, Milagrosa; Otero-Romero, Ana M; Bueno-Serrano, Carmen M; Gómez-Barbadillo, José; Palacios-Eito, Amalia

2016-10-01

Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P=.016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI=(0.691-13.328), P=.06. After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Pathology and Epidemiology of Ceruminous Gland Tumors among Endangered Santa Catalina Island Foxes (Urocyon littoralis catalinae) in the Channel Islands, USA

PubMed Central

Vickers, T. Winston; Clifford, Deana L.; Garcelon, David K.; King, Julie L.; Duncan, Calvin L.; Gaffney, Patricia M.; Boyce, Walter M.

2015-01-01

In this study, we examined the prevalence, pathology, and epidemiology of tumors in free-ranging island foxes occurring on three islands in the California Channel Islands, USA. We found a remarkably high prevalence of ceruminous gland tumors in endangered foxes (Urocyon littoralis catalinae) occurring on Santa Catalina Island (SCA)—48.9% of the dead foxes examined from 2001–2008 had tumors in their ears, and tumors were found in 52.2% of randomly-selected mature (≥ 4 years) foxes captured in 2007–2008, representing one of the highest prevalences of tumors ever documented in a wildlife population. In contrast, no tumors were detected in foxes from San Nicolas Island or San Clemente Island, although ear mites (Otodectes cynotis), a predisposing factor for ceruminous gland tumors in dogs and cats, were highly prevalent on all three islands. On SCA, otitis externa secondary to ear mite infection was highly correlated with ceruminous gland hyperplasia (CGH), and tumors were significantly associated with the severity of CGH, ceruminous gland dysplasia, and age group (older foxes). We propose a conceptual model for the formation of ceruminous gland tumors in foxes on SCA that is based on persistent, ubiquitous infection with ear mites, and an innate, over exuberant inflammatory and hyperplastic response of SCA foxes to these mites. Foxes on SCA are now opportunistically treated with acaricides in an attempt to reduce mite infections and the morbidity and mortality associated with this highly prevalent tumor. PMID:26618759

Yttrium-90 radioembolization as a bridge to liver transplantation: a single-institution experience.

PubMed

Tohme, Samer; Sukato, Daniel; Chen, Hui-Wei; Amesur, Nikhil; Zajko, Albert B; Humar, Abhinav; Geller, David A; Marsh, James W; Tsung, Allan

2013-11-01

To evaluate our experience with the use of yttrium-90 ((90)Y) radioembolization in maintaining potential candidacy and, in some instances, downstaging hepatocellular carcinoma (HCC) that does not meet Milan criteria for liver transplantation. A retrospective review of 20 consecutive patients with HCC who were listed to receive a liver transplant and were treated with (90)Y radioembolization as a sole modality for locoregional "bridge" therapy was performed. Demographics, radiographic and pathologic response, survival, and recurrences were examined. Twenty-two (90)Y treatments were performed in 20 patients before transplantation. Median time from first treatment to transplantation was 3.5 months. HCC in 14 patients met the Milan criteria at the time of the first (90)Y treatment, and HCC in six did not. All cases that originally met the Milan criteria remained within the criteria before transplantation, and two of six patients whose disease did not meet the criteria (33%) had their disease successfully downstaged to meet the criteria. Overall, nine patients (45%) had complete or partial radiologic response to (90)Y radioembolization according to modified Response Evaluation Criteria In Solid Tumors. Complete necrosis of tumor with no evidence of viable tumor on pathologic examination was observed in five patients (36%) whose disease met the Milan criteria. Particularly in regions with long wait list times, (90)Y treatment is effective in maintaining tumor size in potential liver transplantation candidates with HCC. In addition, it can also be considered as a downstaging therapy in select patients before transplantation. © SIR, 2013.

Less than 12 lymph nodes in the surgical specimen after neoadjuvant chemo-radiotherapy: an indicator of tumor regression in locally advanced rectal cancer?

PubMed Central

Gurawalia, Jaiprakash; Nayak, Sandeep P.; Kurpad, Vishnu; Pandey, Arun

2016-01-01

Background The number of lymph node retrieved in the surgical specimen is important for tumor staging and has paramount impact on prognosis in colorectal cancer and imitates the adequacy of lymph node surgical clearance. The paucity of lymph node yields in patients undergoing resection after preoperative chemo radiotherapy (CRT) in rectal cancer has seen. Lower total number of lymph nodes in the total mesoractal excision (TME) specimen after CRT, could a marker of better tumor response. Methods We retrospectively reviewed the prospectively managed data of patients underwent excision for rectal cancer, who treated by neoadjuvant radiotherapy with or without chemotherapy in locally advanced rectal cancer. From 2010 to 2014, 364 patients underwent rectal cancer surgery, of which ninety-one treated with neoadjuvant treatment. Standard surgical and pathological protocols were followed. Patients were categorized into two groups based on the number of total harvested lymph nodes with group 1, having 12 or more nodes harvested, and group 2 including patients who had <12 lymph nodes harvested. The total number of lymph nodes retrieved from the surgical specimen was correlated with grade of tumor regression with neoadjuvant treatment. Results Out of 91 patients, 38 patients (42%) had less than 12 lymph nodes examined in specimen. The difference in median number of lymph nodes was observed significantly as 9 (range, 2–11) versus 16 (range, 12–32), in group 2 and 1, respectively (P<0.01). Patients with fewer lymph node group were comparable with respect to age, BMI, pre-operative staging, neoadjuvant treatment. Pathological complete response in tumor pCR was seen with significantly higher rate (40% vs. 26%, P<0.05) in group 2. As per Mandard criteria, there was significant difference in tumor regression grade (TRG) between both the groups (P<0.05). Among patients with metastatic lymph nodes, median LNR was lower in <12 lymph nodes group at 0.167 (range, 0.09–0.45) versus 0.187 (range, 0.05–0.54), difference was not statistically significant (P=0.81). Conclusions Retrieval of fewer than 12 lymph nodes in surgical specimen of rectal cancer who had received neo-adjuvant radiotherapy with or without chemotherapy should be considered as a good indicator of tumor response with better local disease control, and a good prognostic factor, rather than as a pointer of poor diligence of the surgical and pathological assessment. PMID:28078118

YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study.

PubMed

Senetta, Rebecca; Duregon, Eleonora; Sonetto, Cristina; Spadi, Rossella; Mistrangelo, Massimiliano; Racca, Patrizia; Chiusa, Luigi; Munoz, Fernando H; Ricardi, Umberto; Arezzo, Alberto; Cassenti, Adele; Castellano, Isabella; Papotti, Mauro; Morino, Mario; Risio, Mauro; Cassoni, Paola

2015-01-01

Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome. c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

Role of Nonsteroidal Anti-inflammatory Drug in Treatment of Extra-abdominal Desmoid Tumors.

PubMed

Cho, Ja Young; Gupta, Sanjay; Cho, Hwan Seong; Park, Min Suk; Mok, Su Jung; Han, Ilkyu; Kim, Han-Soo

2018-06-01

We retrospectively reviewed the outcomes of patients who had been treated with meloxicam for the extra-abdominal desmoid tumors and evaluated the correlation between clinical outcome and clinic pathological variables. Twenty patients treated with meloxicam were followed up every 3 to 6 months. Meloxicam administration was planned at 15 mg/day orally for 6 months. Of the 20 patients evaluated, according to Response Evaluation Criteria in Solid Tumors criteria, there were five patients with partial response (25.0%), eight with stable disease (40.0%), and seven with tumor progression (35.0%). The cumulative probability of dropping out from our nonsurgical strategy using meloxicam was 35.0% at 1 year and 35.0% at 5 years. The present study suggests that conservative treatment would be a primary treatment option for this perplexing disease even though we were not able to determine that the use of a cyclooxygenase-2 inhibitor would have an additional influence on the natural course of a desmoid tumor.

Imaging Intratumor Heterogeneity: Role in Therapy Response, Resistance, and Clinical Outcome

PubMed Central

O’Connor, James P.B.; Rose, Chris J.; Waterton, John C.; Carano, Richard A.D.; Parker, Geoff J.M.; Jackson, Alan

2014-01-01

Tumors exhibit genomic and phenotypic heterogeneity which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks. These methods can establish whether one tumor is more or less heterogeneous than another and can identify sub-regions with differing biology. In this article we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, rather than be developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. PMID:25421725

The Production of lnterleukin-1 Receptor Antagonist by Human Bronchogenic Carcinoma

PubMed Central

Smith, Daniel R.; Kunkel, Steven L.; Standiford, Theodore J.; Chensue, Stephen W.; Rolfe, Mark W.; Orringer, Mark B.; Whyte, Richard I.; Burdick, Marie D.; Danforth, Jean M.; Gilbert, Andrew R.; Strieter, Robert M.

1993-01-01

Bronchogenic carcinoma displays an aggressive clinical course that may reflect a capacity to evade host defenses. We postulated that tumors may elaborate interleukin-1 receptor antagonist protein (IRAP) to escape host interleukin-1-dependent responses. Homogenates of human bronchogenic lung tumors demonstrated significant increases of IRAP compared with normal lung tissue controls (n = 48). There was no significant difference in interleukin-1 β levels between tumor and normal lung tissue. Immunohistochemical staining localized IRAP to tumor cells. Semiquantitative pathological analysis demonstrated a modest inflammatory cell infiltrate with qualitative differences between tumors of different histology. Western blot analysis of tumor homogenates demonstrated several molecular weight forms of IRAP. Finally, antigenic IRAP was detected in supernatants of the human bronchogenic carcinoma cell line (A549) maintained in vitro. These findings illustrate the capacity of bronchogenic tumors to produce and secrete IRAP that may be important in tumor evasion of host defenses. ImagesFigure 3Figure 4 PMID:8362978

Parameterizing the Logistic Model of Tumor Growth by DW-MRI and DCE-MRI Data to Predict Treatment Response and Changes in Breast Cancer Cellularity during Neoadjuvant Chemotherapy1

PubMed Central

Atuegwu, Nkiruka C; Arlinghaus, Lori R; Li, Xia; Chakravarthy, A Bapsi; Abramson, Vandana G; Sanders, Melinda E; Yankeelov, Thomas E

2013-01-01

Diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging (MRI) data of 28 patients were obtained pretreatment, after one cycle, and after completion of all cycles of neoadjuvant chemotherapy (NAC). For each patient at each time point, the tumor cell number was estimated using the apparent diffusion coefficient and the extravascular extracellular (ve) and plasma volume (vp) fractions. The proliferation/death rate was obtained using the number of tumor cells from the first two time points in conjunction with the logistic model of tumor growth, which was then used to predict tumor cellularity at the conclusion of NAC. The Pearson correlation coefficient between the predicted and the experimental number of tumor cells measured at the end of NAC was 0.81 (P = .0043). The proliferation rate estimated after the first cycle of therapy was able to separate patients who went on to achieve pathologic complete response from those who did not (P = .021) with a sensitivity and specificity of 82.4% and 72.7%, respectively. These data provide preliminary results indicating that incorporating readily available quantitative MRI data into a simple model of tumor growth can lead to potentially clinically relevant information for predicting an individual patient's response to NAC. PMID:23730404

Baseline blood immunological profiling differentiates between Her2-breast cancer molecular subtypes: implications for immunomediated mechanisms of treatment response.

PubMed

Tudoran, Oana; Virtic, Oana; Balacescu, Loredana; Lisencu, Carmen; Fetica, Bogdan; Gherman, Claudia; Balacescu, Ovidiu; Berindan-Neagoe, Ioana

2015-01-01

Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients' clinicopathological characteristics. Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2- primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status. We observed that more patients with estrogen (ER)/progesterone (PR)-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL26; and cytokines: CSF2, IFNA2, OSM, TNSF13. The expression levels of these genes have been previously shown to be associated with reduced immunological status; indeed, the triple-negative breast cancer patients presented with lower counts of lymphocytes and eosinophils than the ER/PR-positive ones. These results contribute to a better understanding of the possible role of antitumor immune responses in mediating the clinical outcome.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature.

PubMed

Hu, Fang-Ke; Yuan, Fang; Jiang, Cheng-Ying; Lv, Da-Wei; Mao, Bei-Bei; Zhang, Qiang; Yuan, Zeng-Qiang; Wang, Yan

2011-11-01

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Shrink pattern of breast cancer after neoadjuvant chemotherapy and its correlation with clinical pathological factors.

PubMed

Wang, Shushu; Zhang, Yi; Yang, Xinhua; Fan, Linjun; Qi, Xiaowei; Chen, Qingqiu; Jiang, Jun

2013-07-24

Breast conservation therapy (BCS) after neoadjuvant chemotherapy (NCT) can improve patients' quality of life. Currently used intraoperative examination for negative margins may not be sufficient to detect microresidual foci, which are a risk factor for local recurrence. This study was conducted to investigate the shrinking pattern of breast cancer and residual tumors as a risk factor for BCS after NCT. Ninety women with stage II or III invasive ductal carcinoma who achieved partial response after NCT with paclitaxel and epirubicin were enrolled. All patients had undergone modified radical mastectomy. One-half of the surgical specimens were subjected to subserial sectioning. Pathological changes of tumor bed and pericancerous tissues were examined with an optical microscope. The levels of estrogen receptors, progesterone receptors and HER2 were analyzed by immnohistochemical staining. The residual tumors were classified into three types according to their microscopic morphology: solitary lesion, multifocal and patchlike lesions, and main residual tumor with satellite lesions. Type I residual tumors were found in 55 patients (61%), type II in 30 patients (33%) and type III in 5 patients (6%). Types II and III were often associated with larger primary tumors. The types of residual tumors were not correlated with the status of hormone receptors or HER2. Three types of residual tumors were observed after NCT. The solitary residual tumor is most common, but main residual tumors with satellite lesions are most likely to cause local recurrence after BCS. Subserial sectioning would improve the identification of microfoci and patient survival after BCS.

Blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: a pilot study.

PubMed

Jiang, Lan; Weatherall, Paul T; McColl, Roderick W; Tripathy, Debu; Mason, Ralph P

2013-05-01

To determine whether a simple noninvasive method of assessing tumor oxygenation is feasible in the clinical setting and can provide useful, potentially predictive information. Tumor microcirculation and oxygenation play critical roles in tumor growth and responsiveness to cytotoxic treatment and may provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic and can serve as an endogenous contrast agent causing signal loss in echo planar magnetic resonance imaging (MRI) (blood oxygenation level-dependent [BOLD]-MRI). We used BOLD-MRI to provide early evaluation of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MRI was performed on 11 patients with biopsy-proven malignancy. MRI exams were scheduled before, during, and after chemotherapy. The BOLD study applied a 6-minute oxygen breathing challenge. Seven patients successfully completed the exams. Before chemotherapy, BOLD contrast enhancement was observed in all tumors, but the patients, who ultimately had complete pathological response, exhibited a significantly higher BOLD response to oxygen breathing. We have successfully implemented an oxygen-breathing challenge BOLD contrast technique as part of the standard breast MRI exam in patients with locally advanced breast cancer. The preliminary observation that a large BOLD response correlated with better treatment response suggests a predictive capability for BOLD MRI. Copyright © 2012 Wiley Periodicals, Inc.

The roles of pathology in targeted therapy of women with gynecologic cancers.

PubMed

Murali, Rajmohan; Grisham, Rachel N; Soslow, Robert A

2018-01-01

The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor. Therefore, expanding the arsenal of available systemic therapies with targeted therapeutic agents is appealing. Anti-angiogenic therapies, immunotherapy and poly ADP ribose polymerase (PARP) inhibitors are now routinely used for the treatment of advanced gynecologic cancer, and many more are under investigation. Pathologists remain important in the clinical management of patients with targeted therapy, by identifying potentially targetable tumors on the basis of their pathologic phenotype, by assessing biomarkers that are predictive of response to targeted therapy (e.g. microsatellite instability, PD1/PDL1 expression), and by monitoring treatment response and resistance. Pathologists are also vital to research efforts exploring novel targeted therapies by identifying homogenous subsets of tumors for more reliable and meaningful analyses, and by confirming expression in tumor tissues of novel targets identified in genomic, epigenetic or other screening studies. In the era of precision gynecologic oncology, the roles of pathologists in the discovery, development and implementation of targeted therapeutic strategies remain as central as they are for traditional (surgery-chemotherapy-radiotherapy) management of women with gynecologic cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

A deep learning classifier for prediction of pathological complete response to neoadjuvant chemotherapy from baseline breast DCE-MRI

NASA Astrophysics Data System (ADS)

Ravichandran, Kavya; Braman, Nathaniel; Janowczyk, Andrew; Madabhushi, Anant

2018-02-01

Neoadjuvant chemotherapy (NAC) is routinely used to treat breast tumors before surgery to reduce tumor size and improve outcome. However, no current clinical or imaging metrics can effectively predict before treatment which NAC recipients will achieve pathological complete response (pCR), the absence of residual invasive disease in the breast or lymph nodes following surgical resection. In this work, we developed and applied a convolu- tional neural network (CNN) to predict pCR from pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans on a per-voxel basis. In this study, DCE-MRI data for a total of 166 breast cancer pa- tients from the ISPY1 Clinical Trial were split into a training set of 133 patients and a testing set of 33 patients. A CNN consisting of 6 convolutional blocks was trained over 30 epochs. The pre-contrast and post-contrast DCE-MRI phases were considered in isolation and conjunction. A CNN utilizing a combination of both pre- and post-contrast images best distinguished responders, with an AUC of 0.77; 82% of the patients in the testing set were correctly classified based on their treatment response. Within the testing set, the CNN was able to produce probability heatmaps that visualized tumor regions that most strongly predicted therapeutic response. Multi- variate analysis with prognostic clinical variables (age, largest diameter, hormone receptor and HER2 status), revealed that the network was an independent predictor of response (p=0.05), and that the inclusion of HER2 status could further improve capability to predict response (AUC = 0.85, accuracy = 85%).

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

PubMed

Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

2017-05-01

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUV max ). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Heme oxygenase-1 in tumor biology and therapy.

PubMed

Was, Halina; Dulak, Jozef; Jozkowicz, Alicja

2010-12-01

Heme oxygenase-1 (HO-1) degrades heme to carbon monoxide (CO), biliverdin, and ferrous iron. As HO-1 expression is highly increased by stressful conditions, the major role of the enzyme is the protection against oxidative injury. Additionally, it regulates cell proliferation, modulates inflammatory response and facilitates angiogenesis. Beneficial activities of HO-1 have been recognized in many pathological states e.g. atherosclerosis, diabetes, ischemia/reperfusion injury or organ transplantation. Interestingly HO-1 expression is very often boosted in tumor tissues and could be further elevated in response to radio-, chemo-, or photodynamic therapy. A growing body of evidence suggests that HO-1 may play a role in tumor induction and can potently improve the growth and spread of tumors. This review discusses the implications of HO-1 properties for tumor proliferation and cell death, differentiation, angiogenesis and metastasis, and tumor-related inflammation. Finally, it suggests that pharmacological agents that regulate HO activity or HO-1 gene silencing may become powerful tools for preventing the onset or progression of various cancers and sensitize them to anticancer therapies.

Diffusion-weighted imaging: Apparent diffusion coefficient histogram analysis for detecting pathologic complete response to chemoradiotherapy in locally advanced rectal cancer.

PubMed

Choi, Moon Hyung; Oh, Soon Nam; Rha, Sung Eun; Choi, Joon-Il; Lee, Sung Hak; Jang, Hong Seok; Kim, Jun-Gi; Grimm, Robert; Son, Yohan

2016-07-01

To investigate the usefulness of apparent diffusion coefficient (ADC) values derived from histogram analysis of the whole rectal cancer as a quantitative parameter to evaluate pathologic complete response (pCR) on preoperative magnetic resonance imaging (MRI). We enrolled a total of 86 consecutive patients who had undergone surgery for rectal cancer after neoadjuvant chemoradiotherapy (CRT) at our institution between July 2012 and November 2014. Two radiologists who were blinded to the final pathological results reviewed post-CRT MRI to evaluate tumor stage. Quantitative image analysis was performed using T2 -weighted and diffusion-weighted images independently by two radiologists using dedicated software that performed histogram analysis to assess the distribution of ADC in the whole tumor. After surgery, 16 patients were confirmed to have achieved pCR (18.6%). All parameters from pre- and post-CRT ADC histogram showed good or excellent agreement between two readers. The minimum, 10th, 25th, 50th, and 75th percentile and mean ADC from post-CRT ADC histogram were significantly higher in the pCR group than in the non-pCR group for both readers. The 25th percentile value from ADC histogram in post-CRT MRI had the best diagnostic performance for detecting pCR, with an area under the receiver operating characteristic curve of 0.796. Low percentile values derived from the ADC histogram analysis of rectal cancer on MRI after CRT showed a significant difference between pCR and non-pCR groups, demonstrating the utility of the ADC value as a quantitative and objective marker to evaluate complete pathologic response to preoperative CRT in rectal cancer. J. Magn. Reson. Imaging 2016;44:212-220. © 2015 Wiley Periodicals, Inc.

Renal and adrenal tumors: Pathology, radiology, ultrasonography, therapy, immunology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lohr, E.; Leder, L.D.

1987-01-01

Aspects as diverse as radiology, pathology, urology, pediatrics and immunology have been brought together in one book. The most up-do-date methods of tumor diagnosis by CT, NMR, and ultrasound are covered, as are methods of catheter embolization and radiation techniques in case of primarily inoperable tumors. Contents: Pathology of Renal and Adrenal Neoplasms; Ultrasound Diagnosis of Renal and Pararenal Tumors; Computed-Body-Tomography of Renal Carcinoma and Perirenal Masses; Magnetic Resonance Imaging of Renal Mass Lesions; I-125 Embolotherapy of Renal Tumors; Adrenal Mass Lesions in Infants and Children; Computed Tomography of the Adrenal Glands; Scintigraphic Studies of Renal and Adrenal Function; Surgicalmore » Management of Renal Cell Carcinoma; Operative Therapy of Nephroblastoma; Nonoperative Treatment of Renal Cell Carcinoma; Prenatal Wilms' Tumor; Congenital Neuroblastoma; Nonsurgical Management of Wilms' Tumor; Immunologic Aspects of Malignant Renal Disease.« less

The short-term outcomes of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy in patients with poor-risk locally advanced rectal cancer.

PubMed

Beppu, Naohito; Yoshie, Hidenori; Kimura, Fumihiko; Aihara, Tsukasa; Doi, Hiroshi; Kamikonya, Norihiko; Matsubara, Nagahide; Tomita, Naohiro; Yanagi, Hidenori; Yamanaka, Naoki

2016-10-01

To evaluate the safety and efficacy of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy and surgery in patients with poor-risk locally advanced rectal cancer. We enrolled eligible patients with poor-risk rectal cancer defined as T3 lower rectal cancer with mesorectal fascia involvement, T4a or T4b tumors or cases with lateral lymph node swelling. The primary endpoint was a pathological complete response (pCR), and the secondary endpoints were the objective response rate (ORR) and the pathological high response rate (Grade 2 plus 3). Twenty eligible patients were enrolled. The majority (75.0 %, 15/20) of the patients completed four cycles of induction chemotherapy, and all patients completed the radiotherapy (25 Gy/10 fractions/5 days). The global rate of Grade 3-4 toxicities was 30.0 % (6/20 patients). The ORRs were 85.0 % (17/20) and 95.0 % (19/20) in the patients who underwent R0 and R1 resection, respectively. The pathological high response rate was 70.0 % (14/20) and the pCR was 10.0 % (2/20). The regimen of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy is safe and is associated with good tumor regression in patients with poor-risk locally advanced rectal cancer.

Early Detection of Ovarian Cancer by Tumor Epithelium-Targeted Molecular Ultrasound

DTIC Science & Technology

2014-10-01

successful pregnancy outcome. *PIF Proprietary G-12 IL-33-responsive group 2 innate lymphoid cells are present in mouse uterine tissue and may play roles in... innate lymphoid cells (ILC2s) that are responsive to IL-33 drive helminth immunity, type 2 immune responses, and tissue pathology and homeostasis in...16 (IL-16) secreted by immune cells . Inflammation of the ovary and tubal epithelium due to frequent ovulation leads to the development of oxidative

Detecting brain tumor in pathological slides using hyperspectral imaging

PubMed Central

Ortega, Samuel; Fabelo, Himar; Camacho, Rafael; de la Luz Plaza, María; Callicó, Gustavo M.; Sarmiento, Roberto

2018-01-01

Hyperspectral imaging (HSI) is an emerging technology for medical diagnosis. This research work presents a proof-of-concept on the use of HSI data to automatically detect human brain tumor tissue in pathological slides. The samples, consisting of hyperspectral cubes collected from 400 nm to 1000 nm, were acquired from ten different patients diagnosed with high-grade glioma. Based on the diagnosis provided by pathologists, a spectral library of normal and tumor tissues was created and processed using three different supervised classification algorithms. Results prove that HSI is a suitable technique to automatically detect high-grade tumors from pathological slides. PMID:29552415

Detecting brain tumor in pathological slides using hyperspectral imaging.

PubMed

Ortega, Samuel; Fabelo, Himar; Camacho, Rafael; de la Luz Plaza, María; Callicó, Gustavo M; Sarmiento, Roberto

2018-02-01

Hyperspectral imaging (HSI) is an emerging technology for medical diagnosis. This research work presents a proof-of-concept on the use of HSI data to automatically detect human brain tumor tissue in pathological slides. The samples, consisting of hyperspectral cubes collected from 400 nm to 1000 nm, were acquired from ten different patients diagnosed with high-grade glioma. Based on the diagnosis provided by pathologists, a spectral library of normal and tumor tissues was created and processed using three different supervised classification algorithms. Results prove that HSI is a suitable technique to automatically detect high-grade tumors from pathological slides.

Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

PubMed

Qin, Si-Yong; Feng, Jun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Liu, Xiang-Ji; Luo, Guo-Feng; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2014-02-12

Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical significance of MYCN amplification in patients with high-risk neuroblastoma.

PubMed

Lee, Ji Won; Son, Meong Hi; Cho, Hee Won; Ma, Young Eun; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe

2018-05-24

This study investigated the clinical significance of MYCN amplification within high-risk neuroblastoma (NB). Medical records of 135 patients who were diagnosed with high-risk NB from 2004 to 2016 were reviewed. Fifty-one (38%) patients had MYCN amplified tumors, and the remaining 84 (62%) had nonamplified tumors. MYCN amplification was associated with abdominal primary site, less differentiated pathology, higher levels of lactate dehydrogenase and neuron-specific enolase (NSE), lower vanillylmandelic acid level, and larger primary tumor volume at diagnosis. MYCN amplification was associated with a better early response (faster reduction of primary tumor volume and NSE level). The proportion of patients in complete response or very good partial response after induction treatment was relatively higher in MYCN amplified tumors than in nonamplified tumors; however, all progressions during induction treatment occurred only in MYCN amplified tumors (P = 0.007). The time to progression was shorter (median 1.5 years vs. 1.9 years, P = 0.037) and survival after relapse/progression was worse in MYCN amplified tumors (3 year overall survival: 7.7 ± 7.4% vs. 20.5 ± 8.8%, P = 0.046). There was no difference in event-free survival and overall survival between MYCN amplified and nonamplified tumors. MYCN amplification was associated with more aggressive features at diagnosis and a better early response, but a higher progression rate during induction treatment and lower chance of survival after relapse/progression. There was no difference in survival rates according to MYCN amplification in patients with high-risk NB. © 2018 Wiley Periodicals, Inc.

Two-phase computed tomography study of warthin tumor of parotid gland: differentiation from other parotid gland tumors and its pathologic explanation.

PubMed

Woo, Seung Hoon; Choi, Dae-Seob; Kim, Jin-pyeong; Park, Jung Je; Joo, Yeon Hee; Chung, Phil-Sang; Kim, Bo-Young; Ko, Young-Hyeh; Jeong, Han-Sin; Kim, Hyung-Jin

2013-01-01

The objective of this study was to define the radiological characteristics of 2-phase computed tomography (CT) of parotid gland Warthin tumors (WTs) with a pathologic basis for these findings. We prospectively enrolled 116 patients with parotid gland tumor who underwent preoperative 2-phase CT scans(scanning delays of 30 and 120 seconds). The attenuation changes and enhancement patterns were analyzed according to pathology. We also evaluated size-matched samples of WTs and pleomorphic adenoma by staining CD31, vascular endothelial growth factor-receptor 2, collagen IV, and smooth muscle actin. Computed tomography numbers in WTs were significantly higher than those in other tumors in early-phase scans and lower in delayed scans. Pathologically, CD31(+) blood vessel area was significantly higher in WTs than in pleomorphic adenomas. In addition, WTs had an extensive capillary network and many leaky blood vessels. The enhancement pattern of early fill-in and early washout is the typical finding of WTs on 2-phase CT scans, which may be attributed pathologically to abundant blood vessel and extensive capillary network.

Feasibility of using negative ultrasonography results of axillary lymph nodes to predict sentinel lymph node metastasis in breast cancer patients.

PubMed

Chen, Xue; He, Yingjian; Wang, Jiwei; Huo, Ling; Fan, Zhaoqing; Li, Jinfeng; Xie, Yuntao; Wang, Tianfeng; Ouyang, Tao

2018-06-14

Knowledge of the pathology of axillary lymph nodes (ALN) in breast cancer patients is critical for determining their treatment. Ultrasound is the best noninvasive evaluation for the ALN status. However, the correlation between negative ultrasound results and the sentinel lymph nodes (SLN) pathology remains unknown. To test the hypothesis that negative ultrasound results of ALN predict the negative pathology results of SLN in breast cancer patients, we assessed the association between ALN ultrasonography-negative results and the SLN pathology in 3115 patients with breast cancer recruited between October 2010 and April 2016 from a single cancer center, prospective database. Of these patients who met the inclusion criteria, 2317 (74.4%) had no SLN pathological metastasis. In the univariate analysis, other 798 patient with positive SLN tended to be under age 40 and premenopausal, having large tumor sizes (>2 cm), higher histological grade of primary tumor, positive hormone receptors, and negative HER-2 status (P < .05 for all). In the multivariate analysis, menstrual status, tumor size, ER status and histological types of primary tumor remained to be independent predictors for SLN pathological metastasis. The area under curve (AUC) was 0.658 (95% CI = 0.637-0.679), P > .05. In conclusion, only a 74.4% consistency between ALN ultrasonography-negative results and negative pathological SLN results, although menstrual status, tumor size, histologic subtypes of primary tumor and ER status were found to be statistically independent predictors of positive SLN among patients negative for ALN ultrasonography. Therefore, the present study suggests that negative ultrasound results of ALN do not adequately predict the negative pathology results of SLN in breast cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Multimodal treatment with primary single-agent epirubicin in operable breast cancer: 5-year experience of the Michelangelo Cooperative Group.

PubMed

Bonadonna, G; Zambetti, M; Bumma, C; Donadio, M; Bolognesi, A; Robustelli Della Cuna, G; Ambrosini, G; Lelli, G; Mansutti, M; Verderio, P; Valagussa, P

2002-07-01

To assess the efficacy of primary single-agent epirubicin (120 mg/m(2) every 3 weeks for three cycles) in reducing tumor burden in operable breast cancer >or=2.5 cm in largest diameter at diagnosis and its effect on the rate of conservative surgery. A total of 319 eligible patients, who were all candidates for mastectomy, were enrolled on to a multicenter prospective non-randomized study. Tumor response was assessed clinically and pathologically. Relapse-free and overall survival were assessed on major prognostic variables. After primary epirubicin, complete disappearance of invasive neoplastic cells accounted for only 2.6% of patients, but 40% of patients had their primary tumor downstaged to

[Necroscopic findings in patients with acquired immunodeficiency syndrome].

PubMed

Netto, J G; Collarile, D C; Borges, A F; Biancalana, M L; Stefano, H N

1990-01-01

The summaries of clinical data and the autopsy materials of 58 patients who died of acquired immunodeficiency syndrome were reviewed to study the spectrum of the pathologic features of this disease in a general hospital. Histologic sections of all organs were routinely obtained. The most affected organs were the lungs and encephalo, those responsible for the immediate cause of death. There were 11 types of microorganisms and 3 types of tumors. Among the microorganisms, the most frequent was the cytomegalovirus and, among tumors, Kaposi's sarcoma. The microorganisms were frequently associated, mainly in the central nervous system. There was also an association of microorganisms with tumors. Many patients presented with suppurative inflammation. Besides these lesions, a lymphocytic depletion of lymphoid organs was observed. The spectrum of pathologic changes in AIDS is vast, and pathologists should be aware of this fact to accurately diagnose the lesions they find. The morphologic lesions are neither unique nor specific for this syndrome, but in this clinical and immunologic setting they are characteristic. It became clear that several microorganisms and tumors sometimes can only be discovered by autopsy, which is an irrefutable proof that despite the modern technology, autopsy is unavoidable for the knowledge of the pathogeny of a disease.

Comprehensive Computational Pathological Image Analysis Predicts Lung Cancer Prognosis.

PubMed

Luo, Xin; Zang, Xiao; Yang, Lin; Huang, Junzhou; Liang, Faming; Rodriguez-Canales, Jaime; Wistuba, Ignacio I; Gazdar, Adi; Xie, Yang; Xiao, Guanghua

2017-03-01

Pathological examination of histopathological slides is a routine clinical procedure for lung cancer diagnosis and prognosis. Although the classification of lung cancer has been updated to become more specific, only a small subset of the total morphological features are taken into consideration. The vast majority of the detailed morphological features of tumor tissues, particularly tumor cells' surrounding microenvironment, are not fully analyzed. The heterogeneity of tumor cells and close interactions between tumor cells and their microenvironments are closely related to tumor development and progression. The goal of this study is to develop morphological feature-based prediction models for the prognosis of patients with lung cancer. We developed objective and quantitative computational approaches to analyze the morphological features of pathological images for patients with NSCLC. Tissue pathological images were analyzed for 523 patients with adenocarcinoma (ADC) and 511 patients with squamous cell carcinoma (SCC) from The Cancer Genome Atlas lung cancer cohorts. The features extracted from the pathological images were used to develop statistical models that predict patients' survival outcomes in ADC and SCC, respectively. We extracted 943 morphological features from pathological images of hematoxylin and eosin-stained tissue and identified morphological features that are significantly associated with prognosis in ADC and SCC, respectively. Statistical models based on these extracted features stratified NSCLC patients into high-risk and low-risk groups. The models were developed from training sets and validated in independent testing sets: a predicted high-risk group versus a predicted low-risk group (for patients with ADC: hazard ratio = 2.34, 95% confidence interval: 1.12-4.91, p = 0.024; for patients with SCC: hazard ratio = 2.22, 95% confidence interval: 1.15-4.27, p = 0.017) after adjustment for age, sex, smoking status, and pathologic tumor stage. The results suggest that the quantitative morphological features of tumor pathological images predict prognosis in patients with lung cancer. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Tumor Metabolism and Blood Flow as Assessed by PET Varies by Tumor Subtype in Locally Advanced Breast Cancer

PubMed Central

Specht, Jennifer M.; Kurland, Brenda F.; Montgomery, Susan K.; Dunnwald, Lisa K.; Doot, Robert K.; Gralow, Julie R.; Ellis, Georgina K.; Linden, Hannah M.; Livingston, Robert B.; Allison, Kimberly H.; Schubert, Erin K.; Mankoff, David A.

2010-01-01

Purpose Dynamic PET imaging can identify patterns of breast cancer metabolism and perfusion in patients receiving neoadjuvant chemotherapy (NC) that are predictive of response. This analysis examines tumor metabolism and perfusion by tumor subtype. Experimental Design Tumor subtype was defined by immunohistochemistry (IHC) in 71 patients with LABC undergoing NC. Subtype was defined as luminal (ER/PR positive), triple-negative (TN; ER/PR negative, HER2 negative) and HER2 (ER/PR negative, HER2 over-expressing). Metabolic rate (MRFDG) and blood flow (BF) were calculated from PET imaging prior to NC. Pathologic complete response (pCR) to NC was classified as pCR versus other. Results Twenty-five (35%) of 71 patients had TN tumors, 6 (8%) were HER2 and 40 (56%) were luminal. MRFDG for TN tumors was on average 67% greater than for luminal tumors (95% CI 9% – 156%), and average MRFDG/BF ratio was 53% greater in TN compared to luminal tumors (95% CI 9% – 114%) (p < 0.05 for both). Average blood flow levels did not differ by subtype (p = 0.73). Most luminal tumors showed relatively low MRFDG and BF (and did not achieve pCR); high MRFDG was generally matched with high BF in luminal tumors, and predicted pCR. This was not true in TN tumors. Conclusions The relationship between breast tumor metabolism and perfusion differed by subtype. The high MRFDG/BF ratio that predicts poor response to NC was more common in TN tumors. Metabolism and perfusion measures may identify subsets of tumors susceptible and resistant to NC and may help direct targeted therapy. PMID:20460489

In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy

NASA Astrophysics Data System (ADS)

Laufer, Jan; Johnson, Peter; Zhang, Edward; Treeby, Bradley; Cox, Ben; Pedley, Barbara; Beard, Paul

2012-05-01

The use of a novel all-optical photoacoustic scanner for imaging the development of tumor vasculature and its response to a therapeutic vascular disrupting agent is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor for mapping the photoacoustic waves and an image reconstruction algorithm based upon attenuation-compensated acoustic time reversal. The system was used to noninvasively image human colorectal tumor xenografts implanted subcutaneously in mice. Label-free three-dimensional in vivo images of whole tumors to depths of almost 10 mm with sub-100-micron spatial resolution were acquired in a longitudinal manner. This enabled the development of tumor-related vascular features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to be visualized over time. The system was also used to study the temporal evolution of the response of the tumor vasculature following the administration of a therapeutic vascular disrupting agent (OXi4503). This revealed the well-known destruction and recovery phases associated with this agent. These studies illustrate the broader potential of this technology as an imaging tool for the preclinical and clinical study of tumors and other pathologies characterized by changes in the vasculature.

Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: a prospective, multi-center cohort study

PubMed Central

De Martini, Paolo; Ceresoli, Marco; Mari, Giulio M.; Costanzi, Andrea; Maggioni, Dario; Pugliese, Raffaele; Ferrari, Giovanni

2017-01-01

Background To verify the prognostic value of the pathologic and radiological tumor response after neoadjuvant chemotherapy in the treatment of locally advanced gastric adenocarcinoma. Methods A total of 67 patients with locally advanced gastric cancer (clinical ≥ T2 or nodal disease and without evidence of distant metastases) underwent perioperative chemotherapy (ECF or ECX regimen) from December 2009 through June 2015 in two surgical units. Histopathological and radiological response to chemotherapy were evaluated by using tumor regression grade (TRG) (Becker’s criteria) and volume change assessed by CT. Results Fifty-one (86%) patients completed all chemotherapy scheduled cycles successfully and surgery was curative (R0) in 64 (97%) subjects. The histopathological analysis showed 19 (29%) specimens with TRG1 (less than 10% of vital tumor left) and 25 (37%) patients had partial or complete response (CR) assessed by CT scan. Median disease free survival (DFS) and overall survival (OS) were 25.70 months (range, 14.52–36.80 months) and 36.60 months (range, 24.3–52.9 months), respectively. The median follow up was 27 months (range, 5.00–68.00 months). Radiological response and TRG were found to be a prognostic factor for OS and DFS, while tumor histology was not significantly related to survival. Conclusions Both radiological response and TRG have been shown as promising survival markers in patients treated with perioperative chemotherapy for locally advanced gastric cancer. Other predictive markers of response to chemotherapy are strongly required. PMID:29299362

Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.

PubMed

Rugo, Hope S; Olopade, Olufunmilayo I; DeMichele, Angela; Yau, Christina; van 't Veer, Laura J; Buxton, Meredith B; Hogarth, Michael; Hylton, Nola M; Paoloni, Melissa; Perlmutter, Jane; Symmans, W Fraser; Yee, Douglas; Chien, A Jo; Wallace, Anne M; Kaplan, Henry G; Boughey, Judy C; Haddad, Tufia C; Albain, Kathy S; Liu, Minetta C; Isaacs, Claudine; Khan, Qamar J; Lang, Julie E; Viscusi, Rebecca K; Pusztai, Lajos; Moulder, Stacy L; Chui, Stephen Y; Kemmer, Kathleen A; Elias, Anthony D; Edmiston, Kirsten K; Euhus, David M; Haley, Barbara B; Nanda, Rita; Northfelt, Donald W; Tripathy, Debasish; Wood, William C; Ewing, Cheryl; Schwab, Richard; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Berry, Donald A; Esserman, Laura J

2016-07-07

The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

Concurrent Chemoradiation with Concomitant Boost in Locally Advanced Rectal Cancer: A Phase II Study.

PubMed

Picardi, Vincenzo; Deodato, Francesco; Guido, Alessandra; Giaccherini, Lucia; Macchia, Gabriella; Gambacorta, Maria A; Arcelli, Alessandra; Farioli, Andrea; Cellini, Francesco; Cuicchi, Dajana; DI Fabio, Francesca; Poggioli, Gilberto; Ardizzoni, Andrea; Frezza, Giovanni; Cilla, Savino; Caravatta, Luciana; Valentini, Vincenzo; Fuccio, Lorenzo; Morganti, Alessio G

2016-08-01

The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost. Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered to Gross Tumor Volume (GTV) 2 cm margin to a total dose of 55 Gy (2.2 Gy/fraction). The following concurrent chemotherapy was administered: Raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) on days 1, 17, and 35 of RT. Pathological response was evaluated according to the Mandard classification. Toxicities were scored according to the Common Terminology Criteria for Adverse Events v3.0 scale. Eighteen patients (median age=64.5 years) were enrolled. The median follow-up was 22 months (range=2-36 months). After chemoradiation treatment, 16 patients underwent surgical resection (seven anterior resections and nine abdominal-perineal amputation); two patients did not undergo surgery due to early metastatic progression or refusal. R0 resection was achieved in all patients who underwent surgery. Five patients had pathological complete response [27.7%; 95% confidence interval (CI)=9.7-53.5%] and two patients showed only microscopic residual disease (11.1%; 95% CI=0.1-34.7%). Mandard grades 1 and 2 were detected in seven patients (38.9%; 95% CI=17.3-64.3%). Acute grade 3 or more toxicity was found in eight patients (44.4%; 95% CI=21.5-69.2%): one leucopenia-neutropenia, one liver, one skin and five cases of gastrointestinal toxicities. No patient had local tumor recurrence. One-, 2- and 3-year cumulative disease-free survival were 93.8%. One-, 2- and 3-year cumulative overall survival were 92.3%. Concurrent chemoradiation with concomitant boost in patients with advanced rectal cancer allows complete or near-complete pathological response in more than 38% of patients. However, severe acute toxicity was reported in more than one-third of patients. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the Future

PubMed Central

van de Stolpe, Anja; den Toonder, Jaap M. J.

2014-01-01

Knowledge on cellular signal transduction pathways as drivers of cancer growth and metastasis has fuelled development of “targeted therapy” which “targets” aberrant oncogenic signal transduction pathways. These drugs require nearly invariably companion diagnostic tests to identify the tumor-driving pathway and the cause of the abnormal pathway activity in a tumor sample, both for therapy response prediction as well as for monitoring of therapy response and emerging secondary drug resistance. Obtaining sufficient tumor material for this analysis in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may provide an attractive alternative to biopsy on the premise that they can be captured from blood and the companion diagnostic test results are correctly interpreted. We discuss novel companion diagnostic directions, including the challenges, to identify the tumor driving pathway in CTCs, which in combination with a digital pathology platform and algorithms to quantitatively interpret complex CTC diagnostic results may enable optimized therapy response prediction and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration is envisioned to be largely replaced by cell free tumor DNA measurements in blood for therapy response and recurrence monitoring. The recent emergence of novel in vitro human model systems in the form of cancer-on-a-chip may enable elucidation of some of the so far elusive characteristics of CTCs, and is expected to contribute to more efficient CTC capture and CTC-based diagnostics. PMID:24879438

Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

PubMed

Bidard, François-Clément; Michiels, Stefan; Riethdorf, Sabine; Mueller, Volkmar; Esserman, Laura J; Lucci, Anthony; Naume, Bjørn; Horiguchi, Jun; Gisbert-Criado, Rafael; Sleijfer, Stefan; Toi, Masakazu; Garcia-Saenz, Jose A; Hartkopf, Andreas; Generali, Daniele; Rothé, Françoise; Smerage, Jeffrey; Muinelo-Romay, Laura; Stebbing, Justin; Viens, Patrice; Magbanua, Mark Jesus M; Hall, Carolyn S; Engebraaten, Olav; Takata, Daisuke; Vidal-Martínez, José; Onstenk, Wendy; Fujisawa, Noriyoshi; Diaz-Rubio, Eduardo; Taran, Florin-Andrei; Cappelletti, Maria Rosa; Ignatiadis, Michail; Proudhon, Charlotte; Wolf, Denise M; Bauldry, Jessica B; Borgen, Elin; Nagaoka, Rin; Carañana, Vicente; Kraan, Jaco; Maestro, Marisa; Brucker, Sara Yvonne; Weber, Karsten; Reyal, Fabien; Amara, Dominic; Karhade, Mandar G; Mathiesen, Randi R; Tokiniwa, Hideaki; Llombart-Cussac, Antonio; Meddis, Alessandra; Blanche, Paul; d'Hollander, Koenraad; Cottu, Paul; Park, John W; Loibl, Sibylle; Latouche, Aurélien; Pierga, Jean-Yves; Pantel, Klaus

2018-04-12

We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Data from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008). CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

Using Computer-extracted Image Phenotypes from Tumors on Breast MRI to Predict Breast Cancer Pathologic Stage

PubMed Central

Burnside, Elizabeth S.; Drukker, Karen; Li, Hui; Bonaccio, Ermelinda; Zuley, Margarita; Ganott, Marie; Net, Jose M.; Sutton, Elizabeth; Brandt, Kathleen R.; Whitman, Gary; Conzen, Suzanne; Lan, Li; Ji, Yuan; Zhu, Yitan; Jaffe, Carl; Huang, Erich; Freymann, John; Kirby, Justin; Morris, Elizabeth; Giger, Maryellen

2015-01-01

Background To demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on MRI can accurately predict pathologic stage. Methods We used a dataset of de-identified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. We analyzed 91 biopsy-proven breast cancer cases with pathologic stage (stage I = 22; stage II = 58; stage III = 11) and surgically proven nodal status (negative nodes = 46, ≥ 1 positive node = 44, no nodes examined = 1). We characterized tumors by (a) radiologist measured size, and (b) CEIP. We built models combining two CEIPs to predict tumor pathologic stage and lymph node involvement, evaluated them in leave-one-out cross-validation with area under the ROC curve (AUC) as figure of merit. Results Tumor size was the most powerful predictor of pathologic stage but CEIPs capturing biologic behavior also emerged as predictive (e.g. stage I+II vs. III demonstrated AUC = 0.83). No size measure was successful in the prediction of positive lymph nodes but adding a CEIP describing tumor “homogeneity,” significantly improved this discrimination (AUC = 0.62, p=.003) over chance. Conclusions Our results indicate that MRI phenotypes show promise for predicting breast cancer pathologic stage and lymph node status. PMID:26619259

p53 in breast cancer subtypes and new insights into response to chemotherapy.

PubMed

Bertheau, Philippe; Lehmann-Che, Jacqueline; Varna, Mariana; Dumay, Anne; Poirot, Brigitte; Porcher, Raphaël; Turpin, Elisabeth; Plassa, Louis-François; de Roquancourt, Anne; Bourstyn, Edwige; de Cremoux, Patricia; Janin, Anne; Giacchetti, Sylvie; Espié, Marc; de Thé, Hugues

2013-08-01

Despite an obvious central role of p53 in the hallmarks of cancer, TP53 status is not yet used for the management of breast cancer. Recent findings may lead to reconsider the role of p53 in breast cancer. TP53 mutations are the most frequent genetic alterations in breast cancer, observed in 30% of breast carcinomas. Their distribution is highly linked to molecular tumor subtypes found in 26% of luminal tumors (17% of luminal A, 41% of luminal B), in 50% of HER2 amplified tumors, in 69% of molecular apocrine breast carcinomas and in 88% of basal-like carcinomas. The type of mutation is linked to the tumor subtype with higher frequency of base-pair substitutions in luminal tumors, whereas molecular apocrine and basal-like tumors present much higher frequency of complex mutations (deletions/insertions). The timing of TP53 mutation also depends on the tumor subtype, being the first important event in luminal tumors but occurring after PTEN loss in basal-like tumors. Regarding response to cytotoxic chemotherapy, the situation is far from the p53-dependent apoptosis paradigm with subsequent clinical response. We reported that TP53 mutated non inflammatory locally advanced breast carcinomas had a high rate of complete pathological response to dose-dense doxorubicin-cyclophosphamide chemotherapy, while TP53 wild-type (WT) tumors never achieved complete response. Using human breast cancer xenograft models, we suggested that this could be due to the induction of senescence in TP53 WT tumor cells. A recent work confirmed these findings in MMTV-Wnt1 mammary tumors, showing that growth arrest and senescent phenotype, not apoptosis, were induced in TP53 WT tumors following doxorubicin treatment, while lack of arrest in mutant tumors resulted in aberrant mitoses, cell death and a superior clinical response. Furthermore, in ER positive (ER(+)) breast tumors, it has been recently reported that ER represses the p53-mediated apoptotic response induced by DNA damage. Taken together, these data can help to better understand p53-mediated response to doxorubicin-based chemotherapy in breast cancer: in ER(+) TP53 WT breast cancers, ER-induced inhibition of p53 apoptotic response would lead preferentially to tumor cell senescence and subsequent resistance to treatment. Conversely, in ER negative (ER(-)) TP53 mutated breast cancers, accumulation of genetic abnormalities would lead to mitotic catastrophe and subsequent better response. In view of these recent results, p53 impact in breast cancer should be reconsidered. Copyright © 2013 Elsevier Ltd. All rights reserved.

The role of quantitative estrogen receptor status in predicting tumor response at surgery in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Raphael, Jacques; Gandhi, Sonal; Li, Nim; Lu, Fang-I; Trudeau, Maureen

2017-07-01

Estrogen receptor (ER) negative (-) breast cancer (BC) patients have better tumor response rates than ER-positive (+) patients after neoadjuvant chemotherapy (NCT). We conducted a retrospective review using the institutional database "Biomatrix" to assess the value of quantitative ER status in predicting tumor response at surgery and to identify potential predictors of survival outcomes. Univariate followed by multivariable regression analyses were conducted to assess the association between quantitative ER and tumor response assessed as tumor size reduction and pathologic complete response (pCR). Predictors of recurrence-free survival (RFS) were identified using a cox proportional hazards model (CPH). A log-rank test was used to compare RFS between groups if a significant predictor was identified. 304 patients were included with a median follow-up of 43.3 months (Q1-Q3 28.7-61.1) and a mean age of 49.7 years (SD 10.9). Quantitative ER was inversely associated with tumor size reduction and pCR (OR 0.99, 95% CI 0.99-1.00, p = 0.027 and 0.98 95% CI 0.97-0.99, p < 0.0001, respectively). A cut-off of 60 and 80% predicted best the association with tumor size reduction and pCR, respectively. pCR was shown to be an independent predictor of RFS (HR 0.17, 95% CI 0.07-0.43, p = 0.0002) in all patients. At 5 years, 93% of patients with pCR and 72% of patients with residual tumor were recurrence-free, respectively (p = 0.0012). Quantitative ER status is inversely associated with tumor response in BC patients treated with NCT. A cut-off of 60 and 80% predicts best the association with tumor size reduction and pCR, respectively. Therefore, patients with an ER status higher than the cut-off might benefit from a neoadjuvant endocrine therapy approach. Patients with pCR had better survival outcomes independently of their tumor phenotype. Further prospective studies are needed to validate the clinical utility of quantitative ER as a predictive marker of tumor response.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature

PubMed Central

Hu, Fang-Ke; Yuan, Fang; Jiang, Cheng-Ying; Lv, Da-Wei; Mao, Bei-Bei; Zhang, Qiang; Yuan, Zeng-Qiang; Wang, Yan

2011-01-01

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired Paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as “glomangioma” based upon a biopsy sample, “proliferative giant cell tumor of tendon sheath” based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively. PMID:22035861

The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

PubMed

Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

2014-08-21

Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response slows down as the tumor shrinks due to the heterogeneity and low concentration of agents in the tumor interior compared with the cases where other pathological effects may combine to flatten the IFP and thus reduce the heterogeneity. We conclude that dual normalizations of the micronevironment - both the vasculature and the interstitium - are needed to maximize the effects of chemotherapy, while normalization of only one of these may be insufficient to overcome the physical resistance and may thus lead to sub-optimal outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems

PubMed Central

Wu, Min; Frieboes, Hermann B.; Chaplain, Mark A.J.; McDougall, Steven R.; Cristini, Vittorio; Lowengrub, John

2014-01-01

Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but leads to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response slows down as the tumor shrinks due to the heterogeneity and low concentration of agents in the tumor interior compared with the cases where other pathological effects may combine to flatten the IFP and thus reduce the heterogeneity. We conclude that dual normalizations of the micronevironment - both the vasculature and the interstitium - are needed to maximize the effects of chemotherapy, while normalization of only one of these may be insufficient to overcome the physical resistance and thus leads to sub-optimal outcomes. PMID:24751927

[A prospective study of adenosine triphosphate-tumor chemosensitivity assay directed chemotherapy in patients with recurrent ovarian cancer].

PubMed

Gao, Yu-tao; Wu, Ling-ying; Zhang, Wei; Zhao, Dan; Li, Ning; Tian, Hai-mei; Wang, Xiao-bing; Li, Mo; Sun, Yang-chun; Li, Nan; Li, Xiao-guang

2013-05-01

To investigate the efficacy of adenosine triphosphate (ATP)-tumor chemosensitivity assay (TCA) directed chemotherapy in patients with recurrent epithelial ovarian cancer. From August 2010 to June 2012, recurrent epithelial ovarian cancer patients were prospectively enrollmented in Cancer Hospital, Peking Union Medical College,Chinese Academy of Medical Sciences.The entry criteria are as follows: (1) Histologically proven to be epithelial ovarian cancer. (2) Patients of recurrent ovarian cancer with bidimensionally measurable tumor, or ascitic or pleural fluid for testing. (3) Karnofsky performance status > 60. (4) A life expectancy of at least more than 6 months.According to patients desires, they were assigned into two groups: assay-directed therapy group and physician's-choice therapy group, patients' clinical and pathological characteristics, response rate to chemotherapy and progression-free survival (PFS) were compared between two groups. A total of 113 patients with recurrent epithelial ovarian cancer were prospectively enrollmented to assay-directed chemotherapy (n = 56) or physician's-choice chemotherapy (n = 57).There was no difference in median age,types of recurrence, surgical-pathological stage, pathological type, tumor grade, times of recurrence, residual disease at secondary cytoreductive surgery between assay-directed group and physician's-choice group. The overall response rate (ORR) and median PFS in the ATP-TCA group was 66% (37/56) and 7 months, while the ORR in the control group was 46% (26/57, P = 0.037), the median PFS was 4 months (P = 0.040). For platinum-resistant patients, the ORR between ATP-TCA directed chemotherapy 59% (16/27) and control group 25% (7/28) were significantly different (P = 0.010), and the median PFS between two groups were also significantly different (5 months and 2 months, respectively, P = 0.003). ATP-TCA directed chemotherapy could improve ORR and PFS in patients with recurrent epithelial ovarian cancer, especially in platinum-resistant patients.

Microvascular Decompression for Treatment of Trigeminal Neuralgia in Patient with Facial Nerve Schwannoma.

PubMed

Marinelli, John P; Van Gompel, Jamie J; Link, Michael J; Carlson, Matthew L

2018-05-01

Secondary trigeminal neuralgia (TN) is uncommon. When a space-occupying lesion with mass effect is identified, the associated TN is often exclusively attributed to the tumor. This report illustrates the importance of considering coexistent actionable pathology when surgically treating secondary TN. A 51-year-old woman presented with abrupt-onset TN of the V2 and V3 nerve divisions with hypesthesia. She denied changes in hearing, balance, or facial nerve dysfunction. Magnetic resonance imaging revealed a 1.6-cm contrast-enhancing cerebellopontine angle tumor that effaced the trigeminal nerve, consistent with a vestibular schwannoma. In addition, a branch of the superior cerebellar artery abutted the cisternal segment of the trigeminal nerve on T2-weighted thin-slice magnetic resonance imaging. Intraoperative electrical stimulation of the tumor elicited a response from the facial nerve at low threshold over the entire accessible tumor surface, indicating that the tumor was a facial nerve schwannoma. Considering the patient's lack of facial nerve deficit and that the tumor exhibited no safe entry point for intracapsular debulking, tumor resection was not performed. Working between the tumor and tentorium, a branch of the superior cerebellar artery was identified and decompressed with a Teflon pad. At last follow-up, the patient exhibited resolution of her TN. Her hearing and facial nerve function remained intact. Despite obstruction from a medium-sized tumor, it is still possible to achieve microvascular decompression of the fifth cranial nerve. This emphasizes the importance of considering other actionable pathology during surgical management of presumed tumor-induced TN. Further, TN is relatively uncommon with medium-sized vestibular schwannomas and coexistent causes should be considered. Copyright © 2018 Elsevier Inc. All rights reserved.

The Significance of the Discordant Occurrence of Lens Tumors in Humans versus Other Species

PubMed Central

Albert, Daniel M.; Phelps, Paul O.; Surapaneni, Krishna R.; Thuro, Bradley A.; Potter, Heather D.; Ikeda, Akihiro; Teixeira, Leandro B. C.; Dubielzig, Richard R.

2015-01-01

Purpose The purpose of this study was to determine in which species and under what conditions lens tumors occur. Design A review of data bases of available human and veterinary ocular pathological material and the previously reported literature. Participants Approximately 18,000 patients who had ocular surgical specimens submitted and studied at the University of Wisconsin School of Medicine and Public Health (UWSMPH) between 1920 and 2014 and 45,000 ocular veterinary cases from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) between 1983 and 2014. Methods Material in two major archived collections at the University of Wisconsin medical and veterinary schools were studied for occurrence of lens tumors. Tumor was defined as “a new growth of tissue characterized by progressive, uncontrolled proliferation of cells.” In addition, cases presented at 3 major eye pathology societies (Verhoeff-Zimmerman Ophthalmic Pathology Society, Eastern Ophthalmic Pathology Society, and The Armed Forces Institute of Pathology Ophthalmic Alumni Society) from 1975 through 2014 were reviewed. Finally, a careful search of the literature was carried out. Approval from the IRB to carry out this study was obtained. Main Outcome Measures The presence of tumors of the lens. Results The database search and literature review failed to find an example of a lens tumor in humans. In contrast, examples of naturally occurring lens tumors were found in cats, dogs, rabbits, and birds. 4.5% of feline intraocular and adnexal neoplasms (234/5153) in the veterinary school database were designated as feline ocular post-traumatic sarcoma (FOPTS), a tumor previously demonstrated to be of lens epithelial origin. Similar tumors were seen in rabbit eyes, a bird, and in a dog. All four species with lens tumors had a history of either ocular trauma or protracted uveitis. The literature search also revealed cases where lens tumors were induced in zebrafish, rainbow trout, hamsters, and mice, by carcinogenic agents (methylcholanthrene, thioacetamide), oncogenic viruses (SV40, HPV-16), and genetic manipulation. Conclusions Our results suggest that lens tumors do not occur in humans. In contrast, following lens capsule rupture, a lens tumor can occur in other species. We hypothesize that a genetic mechanism exists which prevents lens tumors in humans. PMID:26130328

Multicenter Study of Staging and Therapeutic Predictors of Hepatocellular Carcinoma Recurrence following Transplantation.

PubMed

Welling, Theodore H; Eddinger, Kevin; Carrier, Kristen; Zhu, Danting; Kleaveland, Tyler; Moore, Derek E; Schaubel, Douglas E; Abt, Peter L

2018-05-05

Orthotopic liver transplantation (OLT) and resection are effective treatments for hepatocellular carcinoma (HCC). However, optimizing OLT and limiting HCC recurrence remains a vexing problem. New HCC MELD and allocation algorithms provide greater observation of HCC patients, many while receiving local-regional treatments. Potential benefits of local-regional treatment for limiting HCC recurrence post-OLT remain incompletely understood. Therefore we aimed to define HCC specific prognostic factors affecting recurrence in a contemporary, multi-center cohort of HCC patients undergoing OLT and specifically whether local-regional therapies limited recurrence. We identified 441 patients undergoing OLT for HCC at three major transplant centers from 2008-2013. Cox regression was used to analyze covariate-adjusted recurrence and mortality rates post-OLT. "Bridging" or "down-staging" therapy was used in 238 patients (54%) with transarterial chemoembolization (TACE) being used in 170 (71%) of treated patients. The survival rate post-OLT was 88% and 78% at 1 and 3 years, respectively, with HCC recurrence (28% of deaths) significantly increasing mortality rate (HR=19.87, p<0.0001). Tumor size, not tumor number, either at presentation or on explant independently predicted HCC recurrence (HR 1.36 and 1.73, respectively, p<0.05) with a threshold effect noted at 4.0 cm size. Local-regional therapy (TACE) reduced HCC recurrence by 64% when adjusting for presenting tumor size (HR 0.36, p<0.05). Explant tumor size and microvascular invasion predicted mortality (HR 1.19 and 1.51, respectively, p<0.05) and pathologic response to therapy (TACE or RFA) significantly decreased explant tumor size (0.56-1.62 cm diameter reduction, p<0.05). HCC tumor size at presentation or explant is the most important predictor for HCC recurrence post-OLT. Local-regional therapy to achieve a pathologic response (decreasing tumor size) can limit HCC recurrences post-OLT. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

The Molecular Pathology of Cushing Disease: Are We Nearly There?

PubMed

Grossman, Ashley B

2017-02-01

The molecular pathology of corticotroph tumors is surveyed in the light of recent work showing the induction of aggressive corticotroph tumors by the transgenic expression of epidermal growth factor receptors.

Accuracy of Physical Examination, Ultrasonography, and Mammography in Predicting Residual Pathologic Tumor Size in Patients Treated With Neoadjuvant Chemotherapy

PubMed Central

Chagpar, Anees B.; Middleton, Lavinia P.; Sahin, Aysegul A.; Dempsey, Peter; Buzdar, Aman U.; Mirza, Attiqa N.; Ames, Fredrick C.; Babiera, Gildy V.; Feig, Barry W.; Hunt, Kelly K.; Kuerer, Henry M.; Meric-Bernstam, Funda; Ross, Merrick I.; Singletary, S Eva

2006-01-01

Objective: To assess the accuracy of physical examination, ultrasonography, and mammography in predicting residual size of breast tumors following neoadjuvant chemotherapy. Background: Neoadjuvant chemotherapy is an accepted part of the management of stage II and III breast cancer. Accurate prediction of residual pathologic tumor size after neoadjuvant chemotherapy is critical in guiding surgical therapy. Although physical examination, ultrasonography, and mammography have all been used to predict residual tumor size, there have been conflicting reports about the accuracy of these methods in the neoadjuvant setting. Methods: We reviewed the records of 189 patients who participated in 1 of 2 protocols using doxorubicin-containing neoadjuvant chemotherapy, and who had assessment by physical examination, ultrasonography, and/or mammography no more than 60 days before their surgical resection. Size correlations were performed using Spearman rho analysis. Clinical and pathologic measurements were also compared categorically using the weighted kappa statistic. Results: Size estimates by physical examination, ultrasonography, and mammography were only moderately correlated with residual pathologic tumor size after neoadjuvant chemotherapy (correlation coefficients: 0.42, 0.42, and 0.41, respectively), with an accuracy of ±1 cm in 66% of patients by physical examination, 75% by ultrasonography, and 70% by mammography. Kappa values (0.24–0.35) indicated poor agreement between clinical and pathologic measurements. Conclusion: Physical examination, ultrasonography, and mammography were only moderately useful for predicting residual pathologic tumor size after neoadjuvant chemotherapy. PMID:16432360

Long term results of a randomized trial in locally advanced rectal cancer: No benefit from adding a brachytherapy boost

PubMed Central

Appelt, Ane L; Vogelius, Ivan R; Pløen, John; Rafaelsen, Søren R; Lindebjerg, Jan; Havelund, Birgitte M; Bentzen, Søren M; Jakobsen, Anders

2014-01-01

Purpose/Objective(s) Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer. Methods and Materials Between March 2005 and November 2008, 248 patients withT3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4Gy in 28 fractions, peroral UFT and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10Gy in 2 fractions). Primary trial endpoint was pathological complete response (pCR) at time of surgery; secondary endpoints included overall survival (OS), progression-free survival (PFS) and freedom from locoregional failure. Results Results for the primary endpoint have previously been reported. This analysis presents survival data for the 224 patients in the Danish part of the trial. 221 patients (111 control arm, 110 brachytherapy boost arm) had data available for analysis, with a median follow-up of 5.4 years. Despite a significant increase in tumor response at the time of surgery, no differences in 5-year OS (70.6% vs 63.6%, HR=1.24, p=0.34) and PFS (63.9% vs 52.0%, HR=1.22, p=0.32) were observed. Freedom from locoregional failure at 5 years were 93.9% and 85.7% (HR=2.60, 1.00–6.73, p=0.06) in the standard and in the brachytherapy arm, respectively. There was no difference in the prevalence of stoma. Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration. Conclusions Despite increased pathological tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery. PMID:25015203

BRAF V600E mutations in papillary craniopharyngioma

PubMed Central

Brastianos, Priscilla K.; Santagata, Sandro

2016-01-01

Papillary craniopharyngioma is an intracranial tumor that results in high levels of morbidity. We recently demonstrated that the vast majority of these tumors harbor the oncogenic BRAF V600E mutation. The pathologic diagnosis of papillary craniopharyngioma can now be confirmed using mutation specific immunohistochemistry and targeted genetic testing. Treatment with targeted agents is now also a possibility in select situations. We recently reported a patient with a multiply recurrent papillary craniopharyngioma in whom targeting both BRAF and MEK resulted in a dramatic therapeutic response with a marked anti-tumor immune response. This work shows that activation of the MAPK pathway is the likely principal oncogenic driver of these tumors. We will now investigate the efficacy of this approach in a multicenter phase II clinical trial. Post-treatment resection samples will be monitored for the emergence of resistance mechanisms. Further advances in the non-invasive diagnosis of papillary craniopharyngioma by radiologic criteria and by cell-free DNA testing could someday allow neo-adjuvant therapy for this disease in select patient populations. PMID:26563980

Role of microglia in glioma biology.

PubMed

Badie, B; Schartner, J

2001-07-15

Microglia, a type of differentiated tissue macrophage, are considered to be the most plastic cell population of the central nervous system (CNS). In response to pathological conditions, resting microglia undergo a stereotypic activation process and become capable of phagocytosis, antigen presentation, and lymphocyte activation. Considering their immune effector function, it is not surprising to see microglia accumulation in almost every CNS disease process, including malignant brain tumors or malignant gliomas. Although the function of these cells in CNS inflammatory processes is being studied, their role in malignant glioma biology remains unclear. On one hand, microglia may represent a CNS anti-tumor response, which is inactivated by local secretion of immunosuppressive factors by glioma cells. On the other hand, taking into account that microglia are capable of secreting a variety of immunomodulatory cytokines, it is possible that they are attracted by gliomas to promote tumor growth. A better understanding of microglia-glioma interaction will be helpful in designing novel immune-based therapies against these fatal tumors. Copyright 2001 Wiley-Liss, Inc.

In vitro terahertz spectroscopy of gelatin-embedded human brain tumors: a pilot study

NASA Astrophysics Data System (ADS)

Chernomyrdin, N. V.; Gavdush, A. A.; Beshplav, S.-I. T.; Malakhov, K. M.; Kucheryavenko, A. S.; Katyba, G. M.; Dolganova, I. N.; Goryaynov, S. A.; Karasik, V. E.; Spektor, I. E.; Kurlov, V. N.; Yurchenko, S. O.; Komandin, G. A.; Potapov, A. A.; Tuchin, V. V.; Zaytsev, K. I.

2018-04-01

We have performed the in vitro terahertz (THz) spectroscopy of human brain tumors. In order to fix tissues for the THz measurements, we have applied the gelatin embedding. It allows for preserving tissues from hydration/dehydration and sustaining their THz response similar to that of the freshly-excised tissues for a long time after resection. We have assembled an experimental setup for the reflection-mode measurements of human brain tissues based on the THz pulsed spectrometer. We have used this setup to study in vitro the refractive index and the amplitude absorption coefficient of 2 samples of malignant glioma (grade IV), 1 sample of meningioma (grade I), and samples of intact tissues. We have observed significant differences between the THz responses of normal and pathological tissues of the brain. The results of this paper highlight the potential of the THz technology in the intraoperative neurodiagnosis of tumors relying on the endogenous labels of tumorous tissues.

Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts.

PubMed

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; Deweese, Theodore L; Herman, Joseph M

2012-04-01

We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response.

Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts1

PubMed Central

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; DeWeese, Theodore L; Herman, Joseph M

2012-01-01

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. RESULTS: Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. CONCLUSIONS: We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response. PMID:22496923

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaefer, Inga-Marie; Hornick, Jason L.; Barysauskas, Constance M.

Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportionalmore » hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.« less

Predictive value of magnetic resonance imaging determined tumor contact length for extracapsular extension of prostate cancer.

PubMed

Baco, Eduard; Rud, Erik; Vlatkovic, Ljiljana; Svindland, Aud; Eggesbø, Heidi B; Hung, Andrew J; Matsugasumi, Toru; Bernhard, Jean-Christophe; Gill, Inderbir S; Ukimura, Osamu

2015-02-01

Tumor contact length is defined as the amount of prostate cancer in contact with the prostatic capsule. We evaluated the ability of magnetic resonance imaging determined tumor contact length to predict microscopic extracapsular extension compared to existing predictors of extracapsular extension. We retrospectively analyzed the records of 111 consecutive patients with magnetic resonance imaging/ultrasound fusion targeted, biopsy proven prostate cancer who underwent radical prostatectomy from January 2010 to July 2013. Median patient age was 64 years and median prostate specific antigen was 8.9 ng/ml. Clinical stage was cT1 in 93 cases (84%) and cT2 in 18 (16%). Postoperative pathological analysis confirmed pT2 in 71 patients (64%) and pT3 in 40 (36%). We evaluated 1) in the radical prostatectomy specimen the correlation of microscopic extracapsular extension with pathological cancer volume, pathological tumor contact length and Gleason score, 2) the correlation between microscopic extracapsular extension and magnetic resonance imaging tumor contact length, and 3) the ability of preoperative variables to predict microscopic extracapsular extension. Logistic regression analysis revealed that pathological tumor contact length correlated better with microscopic extracapsular extension than the predictive power of pathological cancer volume (0.821 vs 0.685). The Spearman correlation between pathological and magnetic resonance imaging tumor contact length was r = 0.839 (p <0.0001). ROC AUC analysis revealed that magnetic resonance imaging tumor contact length outperformed cancer core involvement on targeted biopsy and the Partin tables to predict microscopic extracapsular extension (0.88 vs 0.70 and 0.63, respectively). At a magnetic resonance imaging tumor contact length threshold of 20 mm the accuracy for diagnosing microscopic extracapsular extension was superior to that of conventional magnetic resonance imaging criteria (82% vs 67%, p = 0.015). We developed a predicted probability plot curve of extracapsular extension according to magnetic resonance imaging tumor contact length. Magnetic resonance imaging determined tumor contact length could be a promising quantitative predictor of microscopic extracapsular extension. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Using Flow Characteristics in Three-Dimensional Power Doppler Ultrasound Imaging to Predict Complete Responses in Patients Undergoing Neoadjuvant Chemotherapy.

PubMed

Shia, Wei-Chung; Huang, Yu-Len; Wu, Hwa-Koon; Chen, Dar-Ren

2017-05-01

Strategies are needed for the identification of a poor response to treatment and determination of appropriate chemotherapy strategies for patients in the early stages of neoadjuvant chemotherapy for breast cancer. We hypothesize that power Doppler ultrasound imaging can provide useful information on predicting response to neoadjuvant chemotherapy. The solid directional flow of vessels in breast tumors was used as a marker of pathologic complete responses (pCR) in patients undergoing neoadjuvant chemotherapy. Thirty-one breast cancer patients who received neoadjuvant chemotherapy and had tumors of 2 to 5 cm were recruited. Three-dimensional power Doppler ultrasound with high-definition flow imaging technology was used to acquire the indices of tumor blood flow/volume, and the chemotherapy response prediction was established, followed by support vector machine classification. The accuracy of pCR prediction before the first chemotherapy treatment was 83.87% (area under the ROC curve [AUC] = 0.6957). After the second chemotherapy treatment, the accuracy of was 87.9% (AUC = 0.756). Trend analysis showed that good and poor responders exhibited different trends in vascular flow during chemotherapy. This preliminary study demonstrates the feasibility of using the vascular flow in breast tumors to predict chemotherapeutic efficacy. © 2017 by the American Institute of Ultrasound in Medicine.

Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome.

PubMed

O'Connor, James P B; Rose, Chris J; Waterton, John C; Carano, Richard A D; Parker, Geoff J M; Jackson, Alan

2015-01-15

Tumors exhibit genomic and phenotypic heterogeneity, which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as CT density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks using PET, MRI, and other emerging molecular imaging techniques. These methods can establish whether one tumor is more or less heterogeneous than another and can identify subregions with differing biology. In this article, we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, instead of being developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. ©2014 American Association for Cancer Research.

Comparison of EGFR signaling pathway somatic DNA mutations derived from peripheral blood and corresponding tumor tissue of patients with advanced non-small-cell lung cancer using liquidchip technology.

PubMed

Zhang, Hui; Liu, Deruo; Li, Shanqing; Zheng, Yongqing; Yang, Xinjie; Li, Xi; Zhang, Quan; Qin, Na; Lu, Jialin; Ren-Heidenreich, Lifen; Yang, Huiyi; Wu, Yuhua; Zhang, Xinyong; Nong, Jingying; Sun, Yifen; Zhang, Shucai

2013-11-01

Somatic DNA mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway are known to predict responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. We evaluated a sensitive liquidchip platform for detecting EGFR, KRAS (alias Ki-ras), proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations in plasma samples, which were highly correlated with matched tumor tissues from 86 patients with advanced non-small-cell lung cancers. Either EGFR exon 19 or 21 mutations were detected in 36 patients: 23 of whom had identical mutations in both their blood and tissue samples; whereas mutations in the remaining 13 were found only in their tumor samples. These EGFR mutations occurred at a significantly higher frequency in females, never-smokers, and in patients with adenocarcinomas (P ≤ 0.001). The EGFR exon 20 T790M mutation was detected in only one of the paired samples [100% (95% CI, 96% to 100%) agreement]. For KRAS, proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations, the overall agreements were 97% (95% CI, 90% to 99%), 98% (95% CI, 92% to 99%), and 97% (95% CI, 90% to 99%), respectively, and these were not associated with age, sex, smoking history, or histopathologic type. In conclusion, mutations detected in plasma correlated strongly with mutation profiles in each respective tumor sample, suggesting that this liquidchip platform may offer a rapid and noninvasive method for predicting tumor responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival.

PubMed

Falcão, Daniela; Alexandrino, Henrique; Caetano Oliveira, Rui; Martins, João; Ferreira, Luís; Martins, Ricardo; Serôdio, Marco; Martins, Mónica; Tralhão, José Guilherme; Cipriano, Maria Augusta; Castro E Sousa, Francisco

2018-04-11

Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer.

PubMed

Han, Kyung Su; Sohn, Dae Kyung; Kim, Dae Yong; Kim, Byung Chang; Hong, Chang Won; Chang, Hee Jin; Kim, Sun Young; Baek, Ji Yeon; Park, Sung Chan; Kim, Min Ju; Oh, Jae Hwan

2016-04-01

Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

Biological Image-Guided Radiotherapy in Rectal Cancer: Challenges and Pitfalls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roels, Sarah; Slagmolen, Pieter; Nuyts, Johan

2009-11-01

Purpose: To investigate the feasibility of integrating multiple imaging modalities for image-guided radiotherapy in rectal cancer. Patients and Methods: Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) were performed before, during, and after preoperative chemoradiotherapy (CRT) in patients with resectable rectal cancer. The FDG-PET signals were segmented with an adaptive threshold-based and a gradient-based method. Magnetic resonance tumor volumes (TVs) were manually delineated. A nonrigid registration algorithm was applied to register the images, and mismatch analyses were carried out between MR and FDG-PET TVs and between TVs over time. Tumor volumes delineated on the images after CRTmore » were compared with the pathologic TV. Results: Forty-five FDG-PET/CT and 45 MR images were analyzed from 15 patients. The mean MRI and FDG-PET TVs showed a tendency to shrink during and after CRT. In general, MRI showed larger TVs than FDG-PET. There was an approximately 50% mismatch between the FDG-PET TV and the MRI TV at baseline and during CRT. Sixty-one percent of the FDG-PET TV and 76% of the MRI TV obtained after 10 fractions of CRT remained inside the corresponding baseline TV. On MRI, residual tumor was still suspected in all 6 patients with a pathologic complete response, whereas FDG-PET showed a metabolic complete response in 3 of them. The FDG-PET TVs delineated with the gradient-based method matched closest with pathologic findings. Conclusions: Integration of MRI and FDG-PET into radiotherapy seems feasible. Gradient-based segmentation is recommended for FDG-PET. Spatial variance between MRI and FDG-PET TVs should be taken into account for target definition.« less

Effect of PDT-treated apoptotic cells on macrophages

NASA Astrophysics Data System (ADS)

Song, Sheng; Xing, Da; Zhou, Fei-fan; Chen, Wei R.

2009-02-01

Recently, the long-term immunological effects of photodynamic therapy have attracted much attention. PDT induced immune response was mainly initiated through necrotic cells and apoptotic cells, as well as immune cells such as macrophages. Nitric oxide (NO) as an important regulatory factor in signal transfer between cells has been wildly studied for generation, development, and metastasis of tumors. NO synthase is a key enzyme in nitric oxide synthesis. However, inducible nitric oxide synthase (iNOS) is usually activated under pathological conditions, such as stress and cancer, which can produce high levels of nitric oxide and contribute to tumor cytotoxicity. In addition, increased NO production by iNOS has been associated with the host immune response and cell apoptosis, which play an important role in many carcinogenesis and anti-carcinoma mechanisms. This study focuses on the NO production in macrophages, induced by mouse breast carcinoma apoptotic cells treated by PDT in vitro, and on the effects of immune response induced by apoptotic cells in tumor cells growth.

Lack of relevant information for tumor staging in pathology reports of primary cutaneous melanoma.

PubMed

Busam, K J

2001-05-01

For the T classification of primary cutaneous melanoma, the current American Joint Committee on Cancer staging (AJCC) system relies on tumor thickness and level of invasion. A new T classification has been proposed based on thickness and ulceration. The slides and reports of 135 departmental pathology consultations of patients referred to a major cancer center with a diagnosis of primary cutaneous invasive malignant melanoma were examined. Whether the outside pathology reports contained information on tumor thickness, level of invasion, and ulceration was recorded. Dermatopathologists had issued 76.3% of the reports and general surgical pathologists, 24.3%. Information provided was as follows: tumor thickness, 97.8%; Clark level, 71.9%; and presence or absence of ulceration, 28.1%. Of the 97 melanomas with no comment on ulceration, 17 were indeed ulcerated. Thus, the lack of a comment on ulceration cannot be equated with the absence of ulceration. The present study documents that many pathology reports on melanomas lack sufficient information for AJCC staging. Therefore, review of outside pathology material is necessary not only to confirm or revise the tumor diagnosis but also to provide clinicians with histologic parameters required for AJCC staging.

Can computerized tomography accurately stage childhood renal tumors?

PubMed

Abdelhalim, Ahmed; Helmy, Tamer E; Harraz, Ahmed M; Abou-El-Ghar, Mohamed E; Dawaba, Mohamed E; Hafez, Ashraf T

2014-07-01

Staging of childhood renal tumors is crucial for treatment planning and outcome prediction. We sought to identify whether computerized tomography could accurately predict the local stage of childhood renal tumors. We retrospectively reviewed our database for patients diagnosed with childhood renal tumors and treated surgically between 1990 and 2013. Inability to retrieve preoperative computerized tomography, intraoperative tumor spillage and nonWilms childhood renal tumors were exclusion criteria. Local computerized tomography stage was assigned by a single experienced pediatric radiologist blinded to the pathological stage, using a consensus similar to the Children's Oncology Group Wilms tumor staging system. Tumors were stratified into up-front surgery and preoperative chemotherapy groups. The radiological stage of each tumor was compared to the pathological stage. A total of 189 tumors in 179 patients met inclusion criteria. Computerized tomography staging matched pathological staging in 68% of up-front surgery (70 of 103), 31.8% of pre-chemotherapy (21 of 66) and 48.8% of post-chemotherapy scans (42 of 86). Computerized tomography over staged 21.4%, 65.2% and 46.5% of tumors in the up-front surgery, pre-chemotherapy and post-chemotherapy scans, respectively, and under staged 10.7%, 3% and 4.7%. Computerized tomography staging was more accurate in tumors managed by up-front surgery (p <0.001) and those without extracapsular extension (p <0.001). The validity of computerized tomography staging of childhood renal tumors remains doubtful. This staging is more accurate for tumors treated with up-front surgery and those without extracapsular extension. Preoperative computerized tomography can help to exclude capsular breach. Treatment strategy should be based on surgical and pathological staging to avoid the hazards of inaccurate staging. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Hepatic perivascular epithelioid cell tumor (PEComa): dynamic CT, MRI, ultrasonography, and pathologic features--analysis of 7 cases and review of the literature.

PubMed

Tan, Yan; Xiao, En-hua

2012-10-01

To evaluate the dynamic CT, MRI, ultrasonography, and pathologic features of hepatic perivascular epithelioid cell tumor (PEComa), improving the understanding and diagnosis of the tumor. A retrospective analysis of CT, MRI, ultrasonography, and pathologic features of 7 hepatic PEComas diagnosed by pathology during 1st January 2005 to 1st September 2011 in our hospital. The performance of dynamic CT, MRI, and ultrasonography revealed that lesions were regular masses with well-defined borders, the maximum diameters were 2.5-8.5 cm (mean = 4 cm), density was homogeneous, contrast-enhanced CT and MRI showed the lesions were significantly and heterogeneously enhanced on arterial phase, less enhanced on portal venous phase, and slightly hypodense on delayed phase. One patient had multiple hepatic lesions and had delayed enhancement. There were no backgrounds of hepatitis and cirrhosis, enlarged lymph nodes, or distant metastases. Pathology showed the gross appearance of the tumor was smooth. Tumor cells were round or polygonal, with clear boundaries and clear membranes, and had abundant translucent cytoplasm. Nuclei were round, with medium size. Tumor cells were epithelial-like cells and arranged in dense sheets. Immunohistochemistry showed that most of them were positive in HMB45 and MelanA, S-100, SMA, while negative in CgA, Syn, CK, CD117, CD10, and CD34. Dynamic CT, MRI, ultrasonography, and pathology of PEComa had some characteristics of benign tumor's performance. Enhanced scan showed PEComa quickly enhanced on arterial phase and enhanced less on portal venous phase. Knowing these characteristics could help to improve the understanding and diagnosis of hepatic PEComa.

Preoperative Transcatheter Selective Arterial Chemoembolization in Treatment of Unresectable Hepatoblastoma in Infants and Children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Jiaping; Chu Jianping, E-mail: truechu@hotmail.com; Yang Jianyong

2008-11-15

The purpose of this study was to evaluate the clinical feasibility and efficacy of transcatheter selective arterial chemoembolization (TACE) for unresectable hepatoblastoma in infants and children. The study was performed with the approval of our institutional review board. Sixteen patients (13 boys, 3 girls) with unresectable hepatoblastoma were treated one to three times with preoperative TACE in an effort to improve the surgical and clinical outcome. Their ages ranged from 50 days to 60 months, with a mean age of 20.4 months. All cases were pathologically proved hepatoblastoma by fine-needle biopsy. After an intra-arterial catheter was selectively inserted into themore » main feeding artery of the tumor, cycles of cisplatin (40 to 50 mg/m{sup 2}) and adriamycin (20 to 30 mg/m{sup 2}) mixed with lipiodol were given, followed by gelatin foam particles or stainless-steel coils. Tumor response was evaluated according to tumor shrinkage, {alpha}-fetoprotein (AFP) levels, and pathological findings. TACE procedure was performed one to three times, depending on the patient's response. Surgical resection was carried out when the tumor volume appeared sufficiently reduced to allow safe resection by either lobectomy or extended lobectomy. A marked reduction in tumor size associated with decreased AFP level occurred after treatment. According to paired-samples test, tumor shrinkage ranged from 19.0% to 82.0%, with a mean value of 59.2%. AFP levels decreased 99.0% to 29.0% from initial levels, with a mean decrease of 60.0%. TACE allowed subsequent complete surgical resection in 13 cases and the other 3 cases underwent partial resection. One patient underwent successful orthotopic liver transplantation after receiving TACE therapy. Pathological examination showed that the mean percentage of necrotic area in the surgical specimens was 87%. Overall survival rate at 1, 3, and 5 years was 87.5%, 68.7%, and 50%, respectively. Correspondingly, event-free survival rate was 75%, 62.5%, and 43.7%, respectively. In addition, there was no marked chemotherapeutic agent-induced toxicity noted during the observation period. We conclude that TACE is feasible, well tolerated, and effective in inducing surgical resectability of hepatoblastoma in pediatric patients, which has become an independent palliative or curative therapeutic option, especially for patients without distant metastasis.« less

p53 Mediates Vast Gene Expression Changes That Contribute to Poor Chemotherapeutic Response in a Mouse Model of Breast Cancer.

PubMed

Tonnessen-Murray, Crystal; Ungerleider, Nathan A; Rao, Sonia G; Wasylishen, Amanda R; Frey, Wesley D; Jackson, James G

2018-05-28

p53 is a transcription factor that regulates expression of genes involved in cell cycle arrest, senescence, and apoptosis. TP53 harbors mutations that inactivate its transcriptional activity in roughly 30% of breast cancers, and these tumors are much more likely to undergo a pathological complete response to chemotherapy. Thus, the gene expression program activated by wild-type p53 contributes to a poor response. We used an in vivo genetic model system to comprehensively define the p53- and p21-dependent genes and pathways modulated in tumors following doxorubicin treatment. We identified genes differentially expressed in spontaneous mammary tumors harvested from treated MMTV-Wnt1 mice that respond poorly (Trp53+/+) or favorably (Trp53-null) and those that lack the critical senescence/arrest p53 target gene Cdkn1a. Trp53 wild-type tumors differentially expressed nearly 10-fold more genes than Trp53-null tumors after treatment. Pathway analyses showed that genes involved in cell cycle, senescence, and inflammation were enriched in treated Trp53 wild-type tumors; however, no genes/pathways were identified that adequately explain the superior cell death/tumor regression observed in Trp53-null tumors. Cdkn1a-null tumors that retained arrest capacity (responded poorly) and those that proliferated (responded well) after treatment had remarkably different gene regulation. For instance, Cdkn1a-null tumors that arrested upregulated Cdkn2a (p16), suggesting an alternative, p21-independent route to arrest. Live animal imaging of longitudinal gene expression of a senescence/inflammation gene reporter in Trp53+/+ tumors showed induction during and after chemotherapy treatment, while tumors were arrested, but expression rapidly diminished immediately upon relapse. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Sequential pathological changes during malignant transformation of a craniopharyngioma: A case report and review of the literature

PubMed Central

Negoto, Tetsuya; Sakata, Kiyohiko; Aoki, Takachika; Orito, Kimihiko; Nakashima, Shinji; Hirohata, Masaru; Sugita, Yasuo; Morioka, Motohiro

2015-01-01

Background: Malignant transformation of craniopharyngiomas is quite rare, and the etiology of transformation remains unclear. The prognosis of malignantly transformed craniopharyngiomas is very poor. Case Description: A 36-year-old male had five craniotomies, five transsphenoidal surgeries, and two radiation treatments until 31 years of age after diagnosis of craniopharyngioma at 12 years of age. All serial pathological findings indicated adamantinomatous craniopharyngioma including those of a surgery performed for tumor regrowth at 31 years of age. However, when the tumor recurred approximately 5 years later, the pathological findings showed squamous metaplasia. The patient received CyberKnife surgery, but the tumor rapidly regrew within 4 months. The tumor was resected with the cavernous sinus via a dual approach: Transcranial and transsphenoidal surgery with an extracranial-intracranial bypass using the radial artery. Pathologic examination of a surgical specimen showed that it consisted primarily of squamous cells; the lamina propria was collapsed, and the tumor cells had enlarged nuclei and clarification of the nucleolus. The tumor was ultimately diagnosed as malignant transformation of craniopharyngioma. After surgery, he received combination chemotherapy (docetaxel, cisplatin, and fluorouracil). The tumor has been well controlled for more than 12 months. Conclusion: Serial pathological changes of the craniopharyngioma and a review of the 20 cases reported in the literature suggest that radiation of the squamous epithelial cell component of the craniopharyngioma led to malignant transformation via squamous metaplasia. We recommend aggressive surgical removal of craniopharyngiomas and avoidance of radiotherapy if possible. PMID:25883842

Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spindler, Karen-Lise Garm; Nielsen, Jens Nederby; Lindebjerg, Jan

2006-10-01

Purpose: Epidermal growth factor receptor (EGFR) has been associated with radioresistance in solid tumors. Recently a polymorphism in the Sp1 recognition site of the EGFR promoter region was identified. The present study investigated the predictive value of this polymorphism for the outcome of chemoradiation in locally advanced rectal cancer. Methods and Materials: The study included 77 patients with locally advanced T3 rectal tumors. Treatment consisted of preoperative radiation therapy at a total tumor dose of 65 Gy and concomitant chemotherapy with Uftoral. Blood samples from 63 patients were evaluated for Sp1 -216 G/T polymorphism by polymerase chain reaction analysis. Forty-eightmore » primary tumor biopsies were available for EGFR immunostaining. Patients underwent surgery 8 weeks after treatment. Pathologic response evaluation was performed according to the tumor regression grade (TRG) system. Results: Forty-nine percent had major response (TRG1-2) and 51% moderate response (TRG 3-4) to chemoradiation. The rates of major response were 34% (10/29) in GG homozygote patients compared with 65% (22/34) in patients with T containing variants (p = 0.023). Fifty-eight percent of biopsies were positive for EGFR expression (28/48). The major response rates with regard to EGFR immunostaining were not significantly different. EGFR-positive tumors were found in 83% of the GG homozygote patients compared with 38% of patients with TT or GT variants (p = 0.008). Conclusions: There was a significant correlation between EGFR Sp1 -216 G/T polymorphism and treatment response to chemoradiation in locally advanced rectal cancer. Further investigations of a second set of patient and other treatment schedules are warranted.« less

Dusting off another shelf: further comments on classic gynecologic pathology books of yesteryear.

PubMed

Young, Robert H

2005-01-01

Selected outstanding books from the older literature on gynecologic pathology are reviewed with emphasis on drawing attention to the abundant helpful information and often outstanding illustrations that are worthy of review by present-day pathologists. This represents a follow up to a previous similar essay that appeared in Volume 19:67-84, 2000. The first three books cover general gynecological pathology: Gynecological Pathology by Carl Abel; Gynecological and Obstetrical Pathology by Robert T. Frank; and Haines and Taylor's Gynaecological Pathology by Magnus Haines and Claud W. Taylor. Each of them emphasizes the time-honored problem of mimicry of malignancy by diverse benign lesions or even aspects of normal histology. Awareness of the clinical background and cooperation between the clinician and pathologist are emphasized. The other three books considered are all devoted largely or exclusively to the ovary: Ovarian Tumors by Hans Selye, Ovarian Neoplasms, Morphology, and Classification by Karel Motlik, and Special Tumors of Ovary and Testis and Related Extragonadal Lesions by Gunnar Teilum. The book of Selye has a truly remarkable encyclopedic coverage of the older literature, the references being so comprehensive that they are presented in a separate volume. A number of aspects of the histopathology of ovarian tumors that have been emphasized in recent years are noted in Selye's book. Dr. Motlik's book presents a very high quality consideration of the differential diagnosis of ovarian tumors. Teilum's book contains a masterful account of the histopathology of germ cell tumors emphasizing a neoplasm with which his name will always be associated, the yolk sac tumor (endodermal sinus tumor). Numerous beautiful and refreshingly large illustrations are provided, and Dr. Teilum's interest in comparative pathology is evident in the pages, his linking of the famous Schiller-Duval bodies with the endodermal sinuses of the rat placenta, being the most notable example.

The Immune System in the Pathogenesis of Ovarian Cancer

PubMed Central

Charbonneau, Bridget; Goode, Ellen L.; Kalli, Kimberly R.; Knutson, Keith L.; DeRycke, Melissa S.

2014-01-01

Clinical outcomes in ovarian cancer are heterogeneous even when considering common features such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling host characteristic is the immune response to ovarian cancer. While several studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease, recent genetic and protein analyses also suggest a role in disease incidence. Recent studies also show that anti-tumor immunity is often negated by immune suppressive cells present in the tumor microenvironment. These suppressive immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, future research into immunotherapy targeting ovarian cancer will likely become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression or by disrupting critical cytokine networks. PMID:23582060

Two- versus four-handed techniques for endonasal resection of orbital apex tumors.

PubMed

Craig, John R; Lee, John Y K; Petrov, Dmitriy; Mehta, Sonul; Palmer, James N; Adappa, Nithin D

2015-01-01

Open versus endonasal resection of orbital apex (OA) tumors is generally based on tumor size, location, and pathology. For endonasal resection, two- and four-handed techniques have been reported, but whether one technique is more optimal based on these tumor features has not been evaluated. To determine whether two- versus four-handed techniques result in better outcomes after endoscopic resection of OA tumors, and whether either technique is better suited for intra- versus extraconal location and for benign versus malignant pathology. A retrospective review of all expanded endonasal approaches for OA tumors was performed at a single institution from 2009 to 2013. A PubMed database search was also performed to review series published on endonasal OA tumor resection. Across all the cases reviewed, the following data were recorded: two- versus four-handed techniques, intra- versus extraconal tumor location, and benign versus malignant pathology. The relationship between these variables and resection extent was analyzed by the Fisher exact test. Postoperative visual status and complications were also reviewed. Ten cases from the institution and 94 cases from 17 publications were reviewed. Both two- and four-handed techniques were used to resect extra- and intraconal OA tumors, for both benign and malignant pathology. Four-handed techniques included a purely endonasal approach and a combined endonasal-orbital approach. On univariate analysis, the strongest predictor of complete resection was benign pathology (p = 0.005). No significant difference was found between the extent of resection and a two- versus a four-handed technique. Visual status was improved or unchanged in 94% of cases, and other complications were rare. Benign tumors that involve the medial extraconal and posterior inferomedial intraconal OA can be treated by either two- or four-handed endonasal techniques. Selecting two- versus four-handed techniques and endonasal versus endonasal-orbital four-handed techniques depends mainly on surgeons' experience. Endonasal approaches for malignant OA tumors are less likely to result in complete resection.

WE-FG-202-11: Longitudinal Diffusion MRI for Treatment Assessment of Sarcoma Patients with Pre-Operative Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Y; Cao, M; Kamrava, M

Purpose: Diffusion weighted MRI (DWI) is a promising imaging technique for early prediction of tumor response to radiation therapy. A recently proposed longitudinal DWI strategy using a Co-60 MRI guided RT system (MRIgRT) may bring functional MRI guided adaptive radiation therapy closer to clinical utility. We report our preliminary results of using this longitudinal DWI approach performed on the MRIgRT system for predicting the response of sarcoma patient to preop RT. Methods: Three sarcoma patients who underwent fractionated IMRT were recruited in this study. For all three patients DWI images were acquired immediately following his/her treatment. For each imaging session,more » ten slices were acquired interleaved with the b values covering the gross tumor volume (GTV). The diffusion images were processed to obtain the ADC maps using standard exponential fitting for each voxel. Regions of interest were drawn in the tumor on the diffusion images based on each patient’s clinical GTV contours. Each patient subsequently underwent surgery and the tumor necrosis score was available from standard pathology. The ADC values for each patient were compared to the necrosis scores to assess the predictive value of our longitudinal DWI for tumor response. Results: Each patient underwent 3 to 5 diffusion MRI scans depending on their treatment length. Patient 1 had a relatively unchanged ADC during the course of RT and a necrosis score of 30% at surgery. For patient 2, the mean ADC values decreased from 1.56 × 10-3 to 1.12 × 10-3 mm2/s and the patient’s necrosis score was less than 10%. Patient 3 had a slight increase in the ADC values from 0.59 × 10-3 to 0.71 × 10-3 mm2/s and patient’s necrosis score was 50%. Conclusion: Based on limited data from 3 patients, our longitudinal changes in tumor ADC assessed using the MRIgRT system correlated well with pathology results.« less

Pharmacogenomics of Breast Cancer Therapy: An Update

PubMed Central

Westbrook, Kelly

2013-01-01

Clinical and histopathologic characteristics of breast cancer have long played an important role in treatment decision-making. Well-recognized prognostic factors include tumor size, node status, presence or absence of metastases, tumor grade, and hormone receptor expression. High tumor grade, presence of hormone receptors, and HER2-positivity are a few predictive markers of response to chemotherapy, endocrine manipulations, and anti-HER2 agents, respectively. However, there is much heterogeneity of outcomes in patients with similar clinical and pathologic features despite equivalent treatment regimens. Some of the difference in response to specific therapies can be attributed to somatic tumor characteristics, such as degree of estrogen receptor expression and HER2 status. In recent years, there has been great interest in evaluating the role that pharmacogenetics/pharmacogenomics, or variations in germline DNA, play in alteration of drug metabolism and activity, thus leading to disparate outcomes among patients with similar tumor characteristics. The utility of these variations in treatment decision-making remains debated. Here we review the data available to date on genomic variants that may influence response to drugs commonly used to treat breast cancer. While none of the variants reported to date have demonstrated clinical utility, ongoing prospective studies and increasing understanding of pharmacogenetics will allow us to better predict risk of toxicity or likelihood of response to specific treatments and to provide a more personalized therapy. PMID:23500718

Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Oh, Jae Hwan

Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologicmore » downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.« less

Predicting response before initiation of neoadjuvant chemotherapy in breast cancer using new methods for the analysis of dynamic contrast enhanced MRI (DCE MRI) data

NASA Astrophysics Data System (ADS)

DeGrandchamp, Joseph B.; Whisenant, Jennifer G.; Arlinghaus, Lori R.; Abramson, V. G.; Yankeelov, Thomas E.; Cárdenas-Rodríguez, Julio

2016-03-01

The pharmacokinetic parameters derived from dynamic contrast enhanced (DCE) MRI have shown promise as biomarkers for tumor response to therapy. However, standard methods of analyzing DCE MRI data (Tofts model) require high temporal resolution, high signal-to-noise ratio (SNR), and the Arterial Input Function (AIF). Such models produce reliable biomarkers of response only when a therapy has a large effect on the parameters. We recently reported a method that solves the limitations, the Linear Reference Region Model (LRRM). Similar to other reference region models, the LRRM needs no AIF. Additionally, the LRRM is more accurate and precise than standard methods at low SNR and slow temporal resolution, suggesting LRRM-derived biomarkers could be better predictors. Here, the LRRM, Non-linear Reference Region Model (NRRM), Linear Tofts model (LTM), and Non-linear Tofts Model (NLTM) were used to estimate the RKtrans between muscle and tumor (or the Ktrans for Tofts) and the tumor kep,TOI for 39 breast cancer patients who received neoadjuvant chemotherapy (NAC). These parameters and the receptor statuses of each patient were used to construct cross-validated predictive models to classify patients as complete pathological responders (pCR) or non-complete pathological responders (non-pCR) to NAC. Model performance was evaluated using area under the ROC curve (AUC). The AUC for receptor status alone was 0.62, while the best performance using predictors from the LRRM, NRRM, LTM, and NLTM were AUCs of 0.79, 0.55, 0.60, and 0.59 respectively. This suggests that the LRRM can be used to predict response to NAC in breast cancer.

A pancreatic tumor-specific biomarker characterized in humans and mice as an immunogenic onco-glycoprotein is efficient in dendritic cell vaccination

PubMed Central

Collignon, Aurélie; Perles-Barbacaru, Adriana Teodora; Robert, Stéphane; Silvy, Françoise; Martinez, Emmanuelle; Crenon, Isabelle; Germain, Sébastien; Garcia, Stéphane; Viola, Angèle; Lombardo, Dominique

2015-01-01

Oncofetal fucose-rich glycovariants of the pathological bile salt-dependent lipase (pBSDL) appear during human pancreatic oncogenesis and are detected by themonoclonal antibody J28 (mAbJ28). We aimed to identify murine counterparts onpancreatic ductal adenocarcinoma (PDAC) cells and tissue and investigate the potential of dendritic cells (DC) loaded with this unique pancreatic tumor antigen to promote immunotherapy in preclinical trials. Pathological BSDLs purified from pancreatic juices of patients with PDAC were cleaved to generate glycosylated C-terminal moieties (C-ter) containing mAbJ28-reactive glycoepitopes. Immunoreactivity of the murine PDAC line Panc02 and tumor tissue to mAbJ28 was detected by immunohistochemistry and flow cytometry. C-ter-J28+ immunization promoted Th1-dominated immune responses. In vitro C-ter-J28+-loaded DCskewed CD3+ T-cells toward Th1 polarization. C-ter-J28+-DC-vaccinations selectively enhanced cell immunoreactivity to Panc02, as demonstrated by CD4+- and CD8+-T-cell activation, increased percentages of CD4+- and CD8+-T-cells and NK1.1+ cells expressing granzyme B, and T-cell cytotoxicity. Prophylactic and therapeutic C-ter-J28+-DC-vaccinations reduced ectopic Panc02-tumor growth, provided long-lasting protection from Panc02-tumor development in 100% of micebut not from melanoma, and attenuated progression of orthotopic tumors as revealed by MRI. Thusmurine DC loaded with pancreatic tumor-specific glycoepitope C-ter-J28+ induce efficient anticancer adaptive immunity and represent a potential adjuvant therapy for patients afflicted with PDAC. PMID:26405163

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck.

PubMed

Weiss, Jared M; Grilley-Olson, Juneko E; Deal, Allison Mary; Zevallos, Jose P; Chera, Bhishamjit S; Paul, Jennifer; Knowles, Mary Fleming; Usenko, Dmitriy; Weissler, Mark C; Patel, Samip; Hayes, David N; Hackman, Trevor

2018-05-09

The objective of this study was to demonstrate the feasibility and efficacy of induction chemotherapy, surgery, and pathology-guided adjuvant therapy to treat transorally resectable squamous head and neck cancer. Patients had squamous head and neck cancer that was resectable by the transoral route and advanced-stage disease (American Joint Committee on Cancer stage III-IV, T3-T4 tumors, and/or positive lymph nodes). They received treatment with weekly carboplatin at an area under the curve of 2, plus paclitaxel 135 mg/m 2 , and daily lapatinib 1000mg for 6 weeks followed by surgical resection. Pathology that revealed margins <5 mm, extracapsular extension, N2a of N2b lymph node status, perineural invasion, or lymphovascular space invasion resulted in adjuvant radiotherapy concurrent with weekly cisplatin. Pathology with N2c/N3 lymph node status or positive margins resulted in radiation with bolus cisplatin. The primary endpoint was the clinical response rate to induction chemotherapy, and a key secondary endpoint was feasibility. Toxicity was modest, and 37 of 40 patients completed study procedures as planned. The clinical response rate was 93%, the pathologic complete response rate was 36%, and the clinical response did not predict for a pathologic complete response. No patient on study follow-up has recurred or died. Twenty-nine of 39 patients who underwent surgery avoided radiation. Speech and swallowing function were well preserved. The study met both its primary efficacy endpoint and the secondary feasibility endpoint. Neoadjuvant, systemic therapy and surgical resection followed by risk-adapted adjuvant therapy resulted in high response rates and excellent long-term outcomes and should be further studied. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Malignant odontogenic tumors. A retrospective and collaborative study of seven cases.

PubMed

Mosqueda Taylor, Adalberto; Meneses García, Abelardo; Ruíz Godoy Rivera, Luz María; Suárez Roa, María de Lourdes; Luna Ortiz, Kuauhyama

2003-01-01

The frequency, clinico-pathologic features and outcome of malignant odontogenic tumors diagnosed according to the current WHO classification in three pathology services in Mexico City are presented. There were seven cases (5 male and 2 female patients), which represent less than 4% of all odontogenic tumors diagnosed in these services. There were six odontogenic carcinomas (two malignant ameloblastomas, two clear cell odontogenic carcinomas, one primary intraosseous carcinoma and one carcinoma arising in an odontogenic cyst) and one ameloblastic fibrosarcoma. Age ranged from 25 to 72 years (mean: 43.8). Clear cell odontogenic carcinomas occurred in the canine-premolar region, one in the maxilla and one in the mandible (one ia a man and one in a woman), while the remaining lesions affected the posterior region of the mandible, with a male predominance (4:1), which agrees with previously reported cases. Surgical resection was the treatment employed in all carcinomas, while the ameloblastic fibrosarcoma was treated with chemotherapy due to its large extension, but without favorable response. The patient with primary intraosseous carcinoma had submaxillary and cervical metastases and the neoplasm was the cause of death. In spite of their extremely low frequency, malignant odontogenic tumors are an important cause of extensive surgical procedures in the oral and maxillofacial region.

Tumor exosomes: cellular postmen of cancer diagnosis and personalized therapy.

PubMed

Sharma, Aman; Khatun, Zamila; Shiras, Anjali

2016-02-01

Nanosized (30-150 nm) extracellular vesicles 'exosomes' are secreted by cells for intercellular communication during normal and pathological conditions. Exosomes carry biomacromolecules from cell-of-origin and, therefore, represent molecular bioprint of the cell. Tumor-derived exosomes or TDEx modulate tumor microenvironment by transfer of macromolecules locally as well as at distant metastatic sites. Due to their biological stability, TDEx are rich source of biomarkers in cancer patients. TDEx focused cancer diagnosis allows liquid biopsy-based tumor typing and may facilitate therapy response monitoring by developing novel exosomes diagnostics. Therefore, efficient and specific capturing of exosomes for subsequent amplification of the biomessages; for example, DNA, RNA, miRNA can reinvent cancer diagnosis. Here, in this review, we discuss advancements in exosomes isolation strategies, presence of exosomes biomarkers and importance of TDEx in gauging tumor heterogeneity for their potential use in cancer diagnosis, therapy.

Pathological Location of Cranial Nerves in Petroclival Lesions: How to Avoid Their Injury during Anterior Petrosal Approach.

PubMed

Borghei-Razavi, Hamid; Tomio, Ryosuke; Fereshtehnejad, Seyed-Mohammad; Shibao, Shunsuke; Schick, Uta; Toda, Masahiro; Yoshida, Kazunari; Kawase, Takeshi

2016-02-01

Objectives  Numerous surgical approaches have been developed to access the petroclival region. The Kawase approach, through the middle fossa, is a well-described option for addressing cranial base lesions of the petroclival region. Our aim was to gather data about the variation of cranial nerve locations in diverse petroclival pathologies and clarify the most common pathologic variations confirmed during the anterior petrosal approach. Method  A retrospective analysis was made of both videos and operative and histologic records of 40 petroclival tumors from January 2009 to September 2013 in which the Kawase approach was used. The anatomical variations of cranial nerves IV-VI related to the tumor were divided into several location categories: superior lateral (SL), inferior lateral (IL), superior medial (SM), inferior medial (IM), and encased (E). These data were then analyzed taking into consideration pathologic subgroups of meningioma, epidermoid, and schwannoma. Results  In 41% of meningiomas, the trigeminal nerve is encased by the tumor. In 38% of the meningiomas, the trigeminal nerve is in the SL part of the tumor, and it is in 20% of the IL portion of the tumor. In 38% of the meningiomas, the trochlear nerve is encased by the tumor. The abducens nerve is not always visible (35%). The pathologic nerve pattern differs from that of meningiomas for epidermoid and trigeminal schwannomas. Conclusion  The pattern of cranial nerves IV-VI is linked to the type of petroclival tumor. In a meningioma, tumor origin (cavernous, upper clival, tentorial, and petrous apex) is the most important predictor of the location of cranial nerves IV-VI. Classification of four subtypes of petroclival meningiomas using magnetic resonance imaging is very useful to predict the location of deviated cranial nerves IV-VI intraoperatively.

Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients

PubMed Central

Vidal, J; Muinelo, L; Dalmases, A; Jones, F; Edelstein, D; Iglesias, M; Orrillo, M; Abalo, A; Rodríguez, C; Brozos, E; Vidal, Y; Candamio, S; Vázquez, F; Ruiz, J; Guix, M; Visa, L; Sikri, V; Albanell, J; Bellosillo, B; López, R; Montagut, C

2017-01-01

Abstract Background RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. Patients and methods RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. Results Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. Conclusion The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments. PMID:28419195

Immunohistochemical analysis of immune response in breast cancer and melanoma patients after laser immunotherapy

NASA Astrophysics Data System (ADS)

Nordquist, Robert E.; Bishop, Shelly L.; Ferguson, Halie; Vaughan, Melville B.; Jose, Jessnie; Kastl, Katherine; Nguyen, Long; Li, Xiaosong; Liu, Hong; Chen, Wei R.

2011-03-01

Laser immunotherapy (LIT) has shown great promise in pre-clinical studies and preliminary clinical trials. It could not only eradicate treated local tumors but also cause regression and elimination of untreated metastases at distant sites. Combining a selective photothermal therapy with an active immunological stimulation, LIT can induce systemic anti-tumor immune responses. Imiquimod (IMQ), a toll-like receptor agonist, was used for the treatment of late-stage melanoma patients and glycated chitosan (GC), a biological immunological modulator, was used for the treatment of late-stage breast cancer patients, in combination of irradiation of a near-infrared laser light. To observe the immunological changes before and after LIT treatment, the pathological tissues of melanoma and breast cancer patients were processed for immunohistochemical analysis. Our results show that LIT changed the expressions of several crucial T cell types. Specifically, we observed significant decreases of CD3+ T-cells and a significant increase of CD4+,CD8+, and CD68+ T-cells in the tumor samples after LIT treatment. While not conclusive, our study could shed light on one the possible mechanisms of anti-tumor immune responses induced by LIT. Further studies will be conducted to identify immunological biomarkers associated with LIT-induced clinical response.

Bilateral Wilms' tumor with anaplasia: lessons from the National Wilms' Tumor Study.

PubMed

Hamilton, Thomas E; Green, Daniel M; Perlman, Elizabeth J; Argani, Pedram; Grundy, Paul; Ritchey, Michael L; Shamberger, Robert C

2006-10-01

The purpose of this study was to evaluate whether initial diagnostic technique influenced the ability to identify anaplastic histology, to determine the time interval to diagnosis of anaplasia, and to delineate the incidence of discordant pathology in bilateral Wilms' tumor. We hypothesized that delay in diagnosis of anaplasia could affect time to appropriate surgery and intensive multimodality therapy. One hundred eight-nine children were enrolled in the fourth National Wilms' Tumor Study with synchronous bilateral tumors, 27 of whom were eventually shown to have anaplastic histology. Initial diagnostic technique, time interval to diagnosis of anaplasia, and the incidence of discordant pathology were determined. Anaplasia was identified in 0 of 7 tumors by core needle biopsy, 3 of 9 tumors by open wedge biopsy, and in 7 of 9 cases by partial or complete nephrectomy. The mean duration of first chemotherapy regimen (DD or EE) was 20, 39, and 36 weeks, respectively, before anaplasia was identified at second surgery. Discordant pathology between bilateral tumors was identified on final tissue diagnosis in 20 patients. Only 4 patients had anaplastic tumors in both kidneys. Core needle biopsy did not identify anaplasia in 7 of 7 children. Open biopsy or partial/complete nephrectomy identified anaplasia at initial diagnostic procedure in 10 of 18 children. Twenty of 24 patients at final tissue diagnosis had discordant pathology between the 2 kidneys. Earlier interval incisional biopsy or resection may identify anaplastic histology and limit the duration of chemotherapy targeted to favorable histology for children with bilateral Wilms' tumor and anaplasia.

Frozen section pathology for decision making in parotid surgery.

PubMed

Olsen, Kerry D; Moore, Eric J; Lewis, Jean E

2013-12-01

For parotid lesions, the high accuracy and utility of intraoperative frozen section (FS) pathology, compared with permanent section pathology, facilitates intraoperative decision making about the extent of surgery required. To demonstrate the accuracy and utility of FS pathology of parotid lesions as one factor in intraoperative decision making. Retrospective review of patients undergoing parotidectomy at a tertiary care center. Evaluation of the accuracy of FS pathology for parotid surgery by comparing FS pathology results with those of permanent section. Documented changes from FS to permanent section in 1339 parotidectomy pathology reports conducted from January 1, 2000, through December 31, 2009, included 693 benign and 268 primary and metastatic malignant tumors. Changes in diagnosis were found from benign to malignant (n = 11) and malignant to benign (n = 2). Sensitivity and specificity of a malignant diagnosis were 98.5% and 99.0%, respectively. Other changes were for lymphoma vs inflammation or lymphoma typing (n = 89) and for confirmation of or change in tumor type for benign (n = 36) or malignant (n = 69) tumors. No case changed from low- to high-grade malignant tumor. Only 4 cases that changed from FS to permanent section would have affected intraoperative decision making. Three patients underwent additional surgery 2 to 3 weeks later. Overall, only 1 patient was overtreated (lymphoma initially deemed carcinoma). Frozen section pathology for parotid lesions has high accuracy and utility in intraoperative decision making, facilitating timely complete procedures.

Is target oriented surgery sufficient with borderline ovarian tumors? - Role of accompanying pathologies.

PubMed

Gungor, Tayfun; Cetinkaya, Nilufer; Yalcin, Hakan; Ozdal, Bulent; Ozgu, Emre; Baser, Eralp; Yilmaz, Nafiye; Caglar, Mete; Zergeroglu, Sema; Erkaya, Salim

2014-01-01

There are limited data in the literature related to concomitant genital or extra-genital organ pathologies in patients with borderline ovarian tumors (BOTs). The aim of this study was to evaluate our experience with 183 patients to draw attention to the accompanying organ pathologies with BOTs. One hundred eighty-three patients with BOTs, diagnosed and/or treated in our center between January of 2000 and March of 2013 were evaluated retrospectively. Data related to age, tumor histology, lesion side, disease stage, accompanying incidental ipsilateral and/or contralateral ovarian pathologies, treatment approaches, and follow-up periods were investigated. Incidental gynecologic and non-gynecologic concomitant organ pathologies were also recorded. The mean age at diagnosis was 40.6 years (range: 17-78). Ninety- five patients (51%) were ≤40 years. A hundred and forty-seven patients (80%) were at stage IA of the disease. The most common type of BOT was serous in histology. Non-invasive tumor implants were diagnosed in 4% and uterine involvement was found 2% among patients who underwent hysterectomies. There were 12 patients with positive peritoneal washings. Only 17 and 84 patients respectively had concomitant ipsilateral and concomitant contralateral incidental ovarian pathologies. The most common type of uterine, appendicular and omental pathologies were chronic cervicitis, lymphoid hyperplasia and chronic inflammatory reaction. According to our findings most of accompanying pathologies for BOT are benign in nature. Nevertheless, there were additional malignant diseases necessitating further therapy. We emphasize the importance of the evaluation of all abdominal organs during surgery.

Choroid plexus adenoma in a child: expanding the clinical and pathological spectrum.

PubMed

Prendergast, Nicole; Goldstein, Jeffrey D; Beier, Alexandra D

2018-04-01

Primary choroid plexus tumors encompass a variety of tumors, with choroid plexus papilloma and carcinoma being the most common. Also in the differential diagnosis is the rare benign choroid plexus adenoma. As these tumors are infrequently described, the histological profile continues to evolve. The authors present a case with unusual characteristics that will broaden the pathological spectrum for choroid plexus adenomas.

Prognostic Effect of Carcinoma In Situ in Muscle-invasive Urothelial Carcinoma Patients Receiving Neoadjuvant Chemotherapy

PubMed Central

Thomas, Derek E.; Kaimakliotis, Hristos Z.; Rice, Kevin R.; Pereira, Jose A.; Johnston, Paul; Moore, Marietta L.; Reed, Angela; Cregar, Dylan M.; Franklin, Cindy; Loman, Rhoda L.; Koch, Michael O.; Bihrle, Richard; Foster, Richard S.; Masterson, Timothy A.; Gardner, Thomas A.; Sundaram, Chandru P.; Powell, Charles R.; Beck, Stephen D.W.; Grignon, David J.; Cheng, Liang; Albany, Costantine; Hahn, Noah M.

2017-01-01

We performed a single-institution retrospective analysis of 137 patients with muscle-invasive urothelial carcinoma who underwent neoadjuvant chemotherapy and radical cystectomy to assess the prognostic significance of carcinoma in situ (CIS). The pathologic complete response rates were significantly decreased for patients with CIS identified on transurethral resection of the bladder tumor before treatment. The long-term follow-up data from patients with isolated CIS at cystectomy revealed prolonged progression-free and overall survival. Background Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Materials and Methods Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. Results A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19–13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. Conclusion The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. PMID:28040424

Expression and clinical value of the soluble major histocompatibility complex class I-related chain A molecule in the serum of patients with renal tumors.

PubMed

Zhao, Y-K; Jia, C-M; Yuan, G-J; Liu, W; Qiu, Y; Zhu, Q-G

2015-06-29

We investigated the expression and clinical value of the soluble major histocompatibility complex class I-related chain A (sMICA) molecule in the serum of patients with renal tumors. Sixty patients diagnosed with renal tumors were enrolled in the experimental group, whereas 20 healthy volunteers served as the control group. The sMICA levels were measured via enzyme-linked immunosorbent assay, and the results were analyzed in combination with data from pathol-ogy examination. The experimental group had a statistically significant higher sMICA level (P < 0.05) than the control group. The sMICA level was higher in patients with malignant tumors than in those with be-nign tumors. We also observed a positive relationship among different tumor-node-metastasis (TNM) pathological stages with more advanced diseases exhibiting higher sMICA levels. As a tumor-associated antigen, MICA has a close relationship with renal tumorigenesis and immune es-cape. Our results indicated that sMICA levels were related to tumor pathol-ogy, TNM stage, and metastasis. Therefore, sMICA might be a potential marker for tumor characteristics, prognosis, and recurrence prediction.

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study.

PubMed

Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

2017-01-01

To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

ACE Over Expression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer's Disease

PubMed Central

Koronyo-Hamaoui, Maya; Shah, Kandarp; Koronyo, Yosef; Bernstein, Ellen; Giani, Jorge F.; Janjulia, Tea; Black, Keith L.; Shi, Peng D.; Gonzalez-Villalobos, Romer A.; Fuchs, Sebastien; Shen, Xiao Z.; Bernstein, Kenneth E.

2014-01-01

While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice over express ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer's disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD. PMID:24792094

Telomere length variation in tumor cells and cancer-associated fibroblasts: potential biomarker for hepatocellular carcinoma.

PubMed

Ma, Li-Jie; Wang, Xiao-Ying; Duan, Meng; Liu, Long-Zi; Shi, Jie-Yi; Dong, Liang-Qing; Yang, Liu-Xiao; Wang, Zhi-Chao; Ding, Zhen-Bin; Ke, Ai-Wu; Cao, Ya; Zhang, Xiao-Ming; Zhou, Jian; Fan, Jia; Gao, Qiang

2017-12-01

The role of telomere dysfunction and aberrant telomerase activities in hepatocellular carcinoma (HCC) has been overlooked for many years. This study aimed to delineate the variation and prognostic value of telomere length in HCC. Telomere-specific fluorescence in situ hybridization (FISH) and qPCR were used to evaluate telomere length in HCC cell lines, tumor tissues, and isolated non-tumor cells within the tumor. Significant telomere attrition was found in tumor cells and cancer-associated fibroblasts (CAFs) compared to their normal counterparts, but not in intratumor leukocytes or bile duct epithelial cells. Clinical relevance and prognostic value of telomere length were investigated on tissue microarrays of 257 surgically treated HCC patients. Reduced intensity of telomere signals in tumor cells or CAFs correlated with larger tumor size and the presence of vascular invasion (p < 0.05). Shortened telomeres in tumor cells or CAFs associated with reduced survival and increased recurrence, and were identified as independent prognosticators for HCC patients (p < 0.05). These findings were validated in an independent HCC cohort of 371 HCC patients from The Cancer Genome Atlas (TCGA) database, confirming telomere attrition and its prognostic value in HCC. We also showed that telomerase reverse transcriptase promoter (TERTp) mutation correlated with telomere shortening in HCC. Telomere variation in tumor cells and non-tumor cells within the tumor microenvironment of HCC was a valuable prognostic biomarker for this fatal malignancy. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

PubMed

Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

2015-07-25

CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable analysis.

Neuroblastoma in children: Update on clinicopathologic and genetic prognostic factors.

PubMed

Ahmed, Atif A; Zhang, Lei; Reddivalla, Naresh; Hetherington, Maxine

2017-04-01

Neuroblastoma is the most common extracranial solid tumor in childhood accounting for 8-10% of all childhood malignancies. The tumor is characterized by a spectrum of histopathologic features and a heterogeneous clinical phenotype. Modern multimodality therapy results in variable clinical response ranging from cure in localized tumors to limited response in aggressive metastatic disease. Accurate clinical staging and risk assessment based on clinical, surgical, biologic and pathologic criteria are of pivotal importance in assigning prognosis and planning effective treatment approaches. Numerous studies have analyzed the presence of several clinicopathologic and biologic factors in association with the patient's prognosis and outcome. Although patient's age, tumor stage, histopathologic classification, and MYCN amplification are the most commonly validated prognostic markers, several new gene mutations have been identified in sporadic and familial neuroblastoma cases that show association with an adverse outcome. Novel molecular studies have also added data on chromosomal segmental aberrations in MYCN nonamplified tumors. In this review, we provide an updated summary of the clinical, serologic and genetic prognostic indicators in neuroblastoma including classic factors that have consistently played a role in risk stratification of patients as well as newly discovered biomarkers that may show a potential significance in patients' management.

The Intricate Expression of CC Chemokines in Glial Tumors: Evidence for Involvement of CCL2 and CCL5 but Not CCL11.

PubMed

Moogooei, Mozhgan; Shamaei, Masoud; Khorramdelazad, Hossein; Fattahpour, Shirin; Seyedmehdi, Seyed Mohammad; Moogooei, Maryam; Hassanshahi, Gholamhossein; Kalantari Khandani, Behjat

2015-12-01

Chemokines are biologically active peptides involved in the pathogenesis of various pathologies including brain malignancies. They are amongst primitive regulators of the development of immune responses against malignant glial tumors. The present study aimed to examine the expression of CC chemokines in anaplastic astrocytoma and glioblastoma multiform patients at both mRNA and protein levels. Blood specimens in parallel with stereotactic biopsy specimens were obtained from 123 patients suffering from glial tumors and 100 healthy participants as a control. The serum levels of CCL2, CCL5, and CCL11 were measured by ELISA and stereotactic samples subjected to western and northern blotting methods for protein and mRNA, respectively. Demographic characteristics were also collected by a researcher-designed questionnaire. Results of the present study indicated that, however,CCL2 and CCL5 are elevated in serum and tumor tissues of patients suffering from a glial tumor at both mRNA and protein levels, the CCL11 was almost undetectable. According to the findings of the present investigation, it could presumably be reasonable to conclude that chemokines are good predictive molecules for expecting disease severity, metastasis, and response to treatment.

Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience.

PubMed

Patel, Uday B; Taylor, Fiona; Blomqvist, Lennart; George, Christopher; Evans, Hywel; Tekkis, Paris; Quirke, Philip; Sebag-Montefiore, David; Moran, Brendan; Heald, Richard; Guthrie, Ashley; Bees, Nicola; Swift, Ian; Pennert, Kjell; Brown, Gina

2011-10-01

To assess magnetic resonance imaging (MRI) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter study. In a prospective cohort study, 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T, N and circumferential resection margin (CRM) status. Tumor regression grade (TRG) was also assessed by MRI. Overall survival (OS) was estimated by using the Kaplan-Meier product-limit method, and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics. On multivariate analysis, the MRI-assessed TRG (mrTRG) hazard ratios (HRs) were independently significant for survival (HR, 4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI, 1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001), and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to 12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was 39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus 10% (P = .001). Pathology node status did not predict outcomes. MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome.

The contribution of Chlamydia-specific CD8⁺ T cells to upper genital tract pathology.

PubMed

Vlcek, Kelly R; Li, Weidang; Manam, Srikanth; Zanotti, Brian; Nicholson, Bruce J; Ramsey, Kyle H; Murthy, Ashlesh K

2016-02-01

Genital chlamydial infections lead to severe upper reproductive tract pathology in a subset of untreated women. We demonstrated previously that tumor necrosis factor (TNF)-α-producing CD8(+) T cells contribute significantly to chlamydial upper genital tract pathology in female mice. In addition, we observed that minimal chlamydial oviduct pathology develops in OT-1 transgenic (OT-1) mice, wherein the CD8(+) T-cell repertoire is restricted to recognition of the ovalbumin peptide Ova(257-264), suggesting that non-Chlamydia-specific CD8(+) T cells may not be responsible for chlamydial pathogenesis. In the current study, we evaluated whether antigen-specific CD8(+) T cells mediate chlamydial pathology. Groups of wild-type (WT) C57BL/6J, OT-1 mice, and OT-1 mice replete with WT CD8(+) T cells (1 × 10(6) cells per mouse intravenously) were infected intravaginally with C. muridarum (5 × 10(4) IFU/mouse). Serum total anti-Chlamydia antibody and total splenic anti-Chlamydia interferon (IFN)-γ and TNF-α responses were comparable among the three groups of animals. However, Chlamydia-specific IFN-γ and TNF-α production from purified splenic CD8(+) T cells of OT-1 mice was minimal, whereas responses in OT-1 mice replete with WT CD8(+) T cells were comparable to those in WT animals. Vaginal chlamydial clearance was comparable between the three groups of mice. Importantly, the incidence and severity of oviduct and uterine horn pathology was significantly reduced in OT-1 mice but reverted to WT levels in OT-1 mice replete with WT CD8(+) T cells. Collectively, these results demonstrate that Chlamydia-specific CD8(+) T cells contribute significantly to upper genital tract pathology.

Angiofibroma of soft tissue with fibrohistiocytic features and intratumor genetic heterogeneity of NCOA2 gene rearrangement revealed by chromogenic in situ hybridization: a case report.

PubMed

Fukuda, Yumiko; Motoi, Toru; Kato, Ikuma; Ikegami, Masachika; Funata, Nobuaki; Ohtomo, Rie; Horiguchi, Shinichiro; Goto, Takahiro; Hishima, Tsunekazu

2014-05-01

Angiofibroma of soft tissue is a recently described soft tissue tumor that is characterized by fibroblastic spindle tumor cells with arborizing capillary proliferation. Cytogenetically, it harbors a specific fusion gene involving the nuclear receptor coactivator 2 (NCOA2) gene. We report here additional new pathological and cytogenetic features. A soft tissue tumor in the left thigh of 73-year-old female was investigated. Microscopically, histiocytoid tumor cells were scattered in an edematous background with branching capillary proliferation. Immunohistochemically, we identified that the tumor cells were positive for histiocytic markers such as CD68 and CD163. Rearrangement of the NCOA2 gene was detected successfully by chromogenic in situ hybridization; however, abnormal signal patterns were observed in only a small subset of tumor cells. Unlike typical tumors with bland spindle cells, the present tumor needs to be distinguished from myxoid, dendritic and clear cell tumors. This case may suggest that angiofibroma of soft tissue is not in the center of the fibroblastic/myofibroblastic tumor group, but rather shows a fibrohistiocytic nature. We also found intratumor genetic heterogeneity, which is uncommon for a translocation-associated tumor. Therefore, careful evaluation is required to detect the gene rearrangement in this tumor entity. © 2014 The Authors. Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Positive surgical margins in robot-assisted partial nephrectomy: a multi-institutional analysis of oncologic outcomes (leave no tumor behind).

PubMed

Khalifeh, Ali; Kaouk, Jihad H; Bhayani, Sam; Rogers, Craig; Stifelman, Michael; Tanagho, Youssef S; Kumar, Ramesh; Gorin, Michael A; Sivarajan, Ganesh; Samarasekera, Dinesh; Allaf, Mohamad E

2013-11-01

Expanding indications for robot-assisted partial nephrectomy raise major oncologic concerns for positive surgical margins. Previous reports showed no correlation between positive surgical margins and oncologic outcomes. We report a multi-institutional experience with the oncologic outcomes of positive surgical margins on robot-assisted partial nephrectomy. Pathological and clinical followup data were reviewed from an institutional review board approved, prospectively maintained joint database from 5 institutions. Tumors with malignant pathology were isolated and statistically analyzed for demographics and oncologic followup. The log rank test was used to compare recurrence-free and metastasis-free survival between patients with positive and negative surgical margins. The proportional hazards method was used to assess the influence of multiple factors, including positive surgical margins, on recurrence and metastasis. A total of 943 robot-assisted partial nephrectomies for malignant tumors were successfully completed. Of the patients 21 (2.2%) had positive surgical margins on final pathological assessment, resulting in 2 groups, including the 21 with positive surgical margins and 922 with negative surgical margins. Positive surgical margin cases had higher recurrence and metastasis rates (p<0.001). As projected by the Kaplan-Meier method in the population as a whole at followup out to 63.6 months, 5-year recurrence-free and metastasis-free survival was 94.8% and 97.5%, respectively. There was a statistically significant difference in recurrence-free and metastasis-free survival between patients with positive and negative surgical margins (log rank test<0.001), which favored negative surgical margins. Positive surgical margins showed an 18.4-fold higher HR for recurrence when adjusted for multiple tumors, tumor size, tumor growth pattern and pathological stage. Positive surgical margins on final pathological evaluation increase the HR of recurrence and metastasis. In addition to pathological and molecular tumor characteristics, this should be considered to plan appropriate management. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Integrated Genomic Biomarkers to Identify Aggressive Disease in African Americans with Prostate Cancer

DTIC Science & Technology

2016-09-01

300 of these men; have completed pathology review of 70 of the discovery sample tumors; macrodissected and performed DNA extraction from 50 tumors...block, and sections cut and tumor areas marked by histopathologist. Target completion September 1st 2017; Discovery sample 35% completed Pathology ...African American population. Target completion March 2017; 50% completed. What was accomplished under these goals? In the current reporting

Intraoperative imaging during Mohs surgery with reflectance confocal microscopy: initial clinical experience

NASA Astrophysics Data System (ADS)

Flores, Eileen S.; Cordova, Miguel; Kose, Kivanc; Phillips, William; Rossi, Anthony; Nehal, Kishwer; Rajadhyaksha, Milind

2015-06-01

Mohs surgery for the removal of nonmelanoma skin cancers (NMSCs) is performed in stages, while being guided by the examination for residual tumor with frozen pathology. However, preparation of frozen pathology at each stage is time consuming and labor intensive. Real-time intraoperative reflectance confocal microscopy (RCM), combined with video mosaicking, may enable rapid detection of residual tumor directly in the surgical wounds on patients. We report our initial experience on 25 patients, using aluminum chloride for nuclear contrast. Imaging was performed in quadrants in the wound to simulate the Mohs surgeon's examination of pathology. Images and videos of the epidermal and dermal margins were found to be of clinically acceptable quality. Bright nuclear morphology was identified at the epidermal margin and detectable in residual NMSC tumors. The presence of residual tumor and normal skin features could be detected in the peripheral and deep dermal margins. Intraoperative RCM imaging may enable detection of residual tumor directly on patients during Mohs surgery, and may serve as an adjunct for frozen pathology. Ultimately, for routine clinical utility, a stronger tumor-to-dermis contrast may be necessary, and also a smaller microscope with an automated approach for imaging in the entire wound in a rapid and controlled manner.

Next generation diagnostic molecular pathology: critical appraisal of quality assurance in Europe.

PubMed

Dubbink, Hendrikus J; Deans, Zandra C; Tops, Bastiaan B J; van Kemenade, Folkert J; Koljenović, S; van Krieken, Han J M; Blokx, Willeke A M; Dinjens, Winand N M; Groenen, Patricia J T A

2014-06-01

Tumor evaluation in pathology is more and more based on a combination of traditional histopathology and molecular analysis. Due to the rapid development of new cancer treatments that specifically target aberrant proteins present in tumor cells, treatment decisions are increasingly based on the molecular features of the tumor. Not only the number of patients eligible for targeted precision medicine, but also the number of molecular targets per patient and tumor type is rising. Diagnostic molecular pathology, the discipline that determines the molecular aberrations present in tumors for diagnostic, prognostic or predictive purposes, is faced with true challenges. The laboratories have to meet the need of comprehensive molecular testing using only limited amount of tumor tissue, mostly fixed in formalin and embedded in paraffin (FFPE), in short turnaround time. Choices must be made for analytical methods that provide accurate, reliable and cost-effective results. Validation of the test procedures and results is essential. In addition, participation and good performance in internal (IQA) and external quality assurance (EQA) schemes is mandatory. In this review, we critically evaluate the validation procedure for comprehensive molecular tests as well as the organization of quality assurance and assessment of competence of diagnostic molecular pathology laboratories within Europe. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Hybridization-Induced Aggregation Technology for Practical Clinical Testing: KRAS Mutation Detection in Lung and Colorectal Tumors.

PubMed

Sloane, Hillary S; Landers, James P; Kelly, Kimberly A

2016-07-01

KRAS mutations have emerged as powerful predictors of response to targeted therapies in the treatment of lung and colorectal cancers; thus, prospective KRAS genotyping is essential for appropriate treatment stratification. Conventional mutation testing technologies are not ideal for routine clinical screening, as they often involve complex, time-consuming processes and/or costly instrumentation. In response, we recently introduced a unique analytical strategy for revealing KRAS mutations, based on the allele-specific hybridization-induced aggregation (HIA) of oligonucleotide probe-conjugated microbeads. Using simple, inexpensive instrumentation, this approach allows for the detection of any common KRAS mutation in <10 minutes after PCR. Here, we evaluate the clinical utility of the HIA method for mutation detection (HIAMD). In the analysis of 20 lung and colon tumor pathology specimens, we observed a 100% correlation between the KRAS mutation statuses determined by HIAMD and sequencing. In addition, we were able to detect KRAS mutations in a background of 75% wild-type DNA-a finding consistent with that reported for sequencing. With this, we show that HIAMD allows for the rapid and cost-effective detection of KRAS mutations, without compromising analytical performance. These results indicate the validity of HIAMD as a mutation-testing technology suitable for practical clinical testing. Further expansion of this platform may involve the detection of mutations in other key oncogenic pathways. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Adoptive cell therapy of prostate cancer using female mice-derived T cells that react with prostate antigens

PubMed Central

Yi, Huanfa; Yu, Xiaofei; Guo, Chunqing; Manjili, Masoud H.; Repasky, Elizabeth A.; Wang, Xiang-Yang

2011-01-01

In this study, we report a novel treatment strategy that could potentially be used to improve efficacy of adoptive cell therapy for patients with prostate cancer. We show that female C57BL/6 mice are able to effectively reject two syngeneic prostate tumors (TRAMP-C2 and RM1) in a T cell-dependent manner. The protective antitumor immunity appears to primarily involve T cell responses reactive against general prostate tumor/tissue antigens, rather than simply to male-specific H-Y antigen. For the first time we show that adoptive transfer of lymphocytes from TRAMP-C2-primed or naive female mice effectively control prostate tumor growth in male mice, when combined with host pre-conditioning (i.e., non-myeloablative lymphodepletion) and IL-2 administration. No pathological autoimmune response was observed in the treated tumor-bearing male mice. Our studies provide new insights regarding the immune-mediated recognition of male-specific tissue, such as the prostate, and may offer new immunotherapy treatment strategies for advanced prostate cancer. PMID:21088965

Roles of purinergic P2X7 receptor in glioma and microglia in brain tumors.

PubMed

McLarnon, James G

2017-08-28

This review considers evidence suggesting that activation of the ionotropic purinergic receptor P2X 7 (P2X 7 R) is a contributing factor in the growth of brain tumors. Importantly, expression of P2X 7 R may be upregulated in both glioma cells and in immune responding microglial cells with possible differential effects on tumor progression. The recruitment of immune cells into tumor regions may not only be involved in supporting an immunosuppressive environment aiding tumor growth but activated microglia could secrete inflammatory factors promoting neoangiogenesis in expanding tumors. The subtype P2X 7 R exhibits a number of unique properties including activation of the receptor in pathological conditions associated with developing brain tumors. In particular, the tumor microenvironment includes elevated levels of ATP required for activation of P2X 7 R and the sustained tumor and immune cell P2X 7 R-mediated responses which in total contribute to overall tumor growth and viability. Studies on cultured rat and human glioma show marked increases in expression of P2X 7 R and enhanced cell mobility relative to control. Glioma cell animal models demonstrate enhanced expression of P2X 7 R in both glioma and microglia with antagonism of receptor showing differential effects on tumor growth. Overall, P2X 7 R activation is associated with a complexity of modulatory actions on tumor growth in part due to ubiquitous expression of the receptor in glioma and immune responsive cells. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Decreased background parenchymal enhancement of the contralateral breast after two cycles of neoadjuvant chemotherapy is associated with tumor response in HER2-positive breast cancer.

PubMed

You, Chao; Gu, Yajia; Peng, Wen; Li, Jianwei; Shen, Xuxia; Liu, Guangyu; Peng, Weijun

2018-07-01

Background Several recent studies have focused on the association between background parenchymal enhancement (BPE) and tumor response to neoadjuvant chemotherapy (NAC), but early prediction of tumor response based on BPE has yet not been investigated. Purpose To retrospectively investigate whether changes in the BPE of the contralateral breast following NAC could help predict tumor response in early stage HER2-positive breast cancer. Material and Methods Data from 71 patients who were diagnosed with unilateral HER2 positive breast cancer and then underwent NAC with trastuzumab before surgery were analyzed retrospectively. Two experienced radiologists independently categorized the patients' levels of BPE of the contralateral breast into four categories (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) at baseline and after the second cycle of NAC. After undergoing surgery, 34 patients achieved pathologic complete response (pCR) and 37 patients had residual disease (non-pCR). The association between BPE and histopathologic tumor response was analyzed. Result The level of BPE was higher in premenopausal than post-menopausal women both at baseline and after the second cycle of NAC ( P < 0.005). A significant reduction in BPE ( P < 0.001) was observed after the second NAC cycle; however, a more obvious decrease in BPE was identified in premenopausal relative to post-menopausal women ( P = 0.041). No significant association was identified between pCR and baseline BPE ( P = 0.287). However, after the second NAC cycle, decreased BPE was significantly associated with pCR ( P = 0.003). Conclusion For HER2-positive patients, changes in BPE may serve as an additional imaging biomarker of treatment response at an early stage.

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.

PubMed

Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B; Galante, Pedro A F; Perez, Rodrigo O; Camargo, Anamaria A

2015-11-10

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.

Accuracy of Intraoperative Frozen Section Diagnosis of Borderline Ovarian Tumors by Hospital Type.

PubMed

Shah, Jaimin S; Mackelvie, Michael; Gershenson, David M; Ramalingam, Preetha; Kott, Marylee M; Brown, Jubilee; Gauthier, Polly; Nugent, Elizabeth; Ramondetta, Lois M; Frumovitz, Michael

2018-04-19

To compare the accuracy of frozen section diagnosis of borderline ovarian tumors among 3 distinct types of hospital-academic hospital with gynecologic pathologists, academic hospital with nongynecologic pathologists, and community hospital with nongynecologic pathologists-and to determine if surgical staging alters patient care or outcomes for women with a frozen section diagnosis of borderline ovarian tumor. Retrospective study (Canadian Task Force classification II-1). Tertiary care, academic, and community hospitals. Women with an intraoperative frozen section diagnosis of borderline ovarian tumor at 1 of 3 types of hospital from April 1998 through June 2016. Comparison of final pathology with intraoperative frozen section diagnosis. Two hundred twelve women met the inclusion criteria. The frozen section diagnosis of borderline ovarian tumor correlated with the final pathologic diagnosis in 192 of 212 cases (90.6%), and the rate of correlation did not differ among the 3 hospital types (p = .82). Seven tumors (3.3%) were downgraded to benign on final pathologic analysis and 13 (6.1%) upgraded to invasive carcinoma. The 3 hospital types did not differ with respect to the proportion of tumors upgraded to invasive carcinoma (p = .62). Mucinous (odds ratio, 7.1; 95% confidence interval, 2.1-23.7; p = .002) and endometrioid borderline ovarian tumors (odds ratio, 32.4; 95% confidence interval, 1.8-595.5; p = .02) were more likely than serous ovarian tumors to be upgraded to carcinoma. Only 88 patients (41.5%) underwent lymphadenectomy, and only 1 (1.1%) had invasive carcinoma in a lymph node. A frozen section diagnosis of borderline ovarian tumor correlates with the final pathologic diagnosis in a variety of hospital types. Copyright © 2018 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.

Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology.

PubMed

Gold, Bert; Cankovic, Milena; Furtado, Larissa V; Meier, Frederick; Gocke, Christopher D

2015-05-01

Diagnosing and screening for tumors through noninvasive means represent an important paradigm shift in precision medicine. In contrast to tissue biopsy, detection of circulating tumor cells (CTCs) and circulating tumor nucleic acids provides a minimally invasive method for predictive and prognostic marker detection. This allows early and serial assessment of metastatic disease, including follow-up during remission, characterization of treatment effects, and clonal evolution. Isolation and characterization of CTCs and circulating tumor DNA (ctDNA) are likely to improve cancer diagnosis, treatment, and minimal residual disease monitoring. However, more trials are required to validate the clinical utility of precise molecular markers for a variety of tumor types. This review focuses on the clinical utility of CTCs and ctDNA testing in patients with solid tumors, including somatic and epigenetic alterations that can be detected. A comparison of methods used to isolate and detect CTCs and some of the intricacies of the characterization of the ctDNA are also provided. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series.

PubMed

Yu, Run; Jih, Lily; Zhai, Jing; Nissen, Nicholas N; Colquhoun, Steven; Wolin, Edward; Dhall, Deepti

2013-04-01

The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients. Five patients were identified. The median age at presentation was 74 years (range, 59-89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9-16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to 30% of cells were truly amphicrine, whereas most were differentiated into either endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.

Phase II Trial of Induction Chemotherapy Followed by Surgery for Squamous Cell Carcinoma of the Oral Tongue in Young Adults

PubMed Central

Kies, Merrill S.; Boatright, Dowin H.; Li, Guojun; Blumenschein, George; El-Naggar, Adel K.; Lewin, Jan S.; Steinhaus, Ganene; Sturgis, Erich M.

2013-01-01

Background We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. Methods From September 2001 to October 2004, 23 patients aged 18–49 years with clinical T2-3N0-2M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. Results On final surgical pathology, 9 (39%) patients had a complete/major (2 complete) histologic response at the primary tumor site; 8 (35%) had no response or progression. Similarly, 9 (39%) patients had a complete response in the neck or remained node negative; 6 (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 (43%) patients developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (P = .029), poor histologic differentiation (P = .012), and multiple adverse features on final surgical pathology (P = .040). Conclusions Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. PMID:22009800

Phase II trial of induction chemotherapy followed by surgery for squamous cell carcinoma of the oral tongue in young adults.

PubMed

Kies, Merrill S; Boatright, Dowin H; Li, Guojun; Blumenschein, George; El-Naggar, Adel K; Brandon Gunn, G; Lewin, Jan S; Steinhaus, Ganene D; Sturgis, Erich M

2012-09-01

We conducted a phase II clinical trial of induction chemotherapy followed by surgery ± radiotherapy for squamous cell carcinoma of the oral tongue (SCCOT) in young adults. From September 2001 to October 2004, 23 patients aged 18 to 49 years with clinical T2-3 N0-2 M0 SCCOT and no prior radiotherapy, chemotherapy, or neck dissection underwent induction chemotherapy (paclitaxel, ifosfamide, and carboplatin) followed by glossectomy and neck dissection ± radiotherapy and chemotherapy. On final surgical pathology, 9 patients (39%) had a complete/major (2 complete) histologic response at the primary tumor site; 8 patients (35%) had no response or progression. Similarly, 9 patients (39%) had a complete response in the neck or remained node negative; 6 patients (26%) had an increase in nodal category. No treatment-associated deaths occurred, and toxicity was modest. At a median follow-up from the end of treatment of 52 months (minimum, 23 months), 10 patients (43%) developed recurrence, and all 10 died of cancer. Crude recurrence/cancer death rates were associated with ≤ a partial response at the tongue (p = .029), poor histologic differentiation (p = .012), and multiple adverse features on final surgical pathology (p = .040). Response rates and overall survival with this induction chemotherapy regimen were limited, but complete/major response at the tongue was associated with excellent prognosis. Additionally, improved patient selection and predictive tumor biomarkers will be needed for induction chemotherapy to be routinely incorporated into the treatment of oral tongue cancer in young adults. Copyright © 2011 Wiley Periodicals, Inc.

PDT-treated apoptotic cells induce macrophage synthesis NO

NASA Astrophysics Data System (ADS)

Song, S.; Xing, D.; Zhou, F. F.; Chen, W. R.

2009-11-01

Nitric oxide (NO) is a biologically active molecule which has multi-functional in different species. As a second messenger and neurotransmitter, NO is not only an important regulatory factor between cells' information transmission, but also an important messenger in cell-mediated immunity and cytotoxicity. On the other side, NO is involving in some diseases' pathological process. In pathological conditions, the macrophages are activated to produce a large quantity of nitric oxide synthase (iNOS), which can use L-arginine to produce an excessive amount of NO, thereby killing bacteria, viruses, parasites, fungi, tumor cells, as well as in other series of the immune process. In this paper, photofrin-based photodynamic therapy (PDT) was used to treat EMT6 mammary tumors in vitro to induce apoptotic cells, and then co-incubation both apoptotic cells and macrophages, which could activate macrophage to induce a series of cytotoxic factors, especially NO. This, in turn, utilizes macrophages to activate a cytotoxic response towards neighboring tumor cells. These results provided a new idea for us to further study the immunological mechanism involved in damaging effects of PDT, also revealed the important function of the immune effect of apoptotic cells in PDT.

Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial.

PubMed

Uppaluri, Ravindra; Winkler, Ashley E; Lin, Tianxiang; Law, Jonathan H; Haughey, Bruce H; Nussenbaum, Brian; Paniello, Randal C; Rich, Jason T; Diaz, Jason A; Michel, Loren P; Wildes, Tanya; Dunn, Gavin P; Zolkind, Paul; Kallogjeri, Dorina; Piccirillo, Jay F; Dehdashti, Farrokh; Siegel, Barry A; Chernock, Rebecca D; Lewis, James S; Adkins, Douglas R

2017-05-01

Purpose: Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK inhibition with trametinib. Experimental Design: Patients with stage II-IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity [maximum standardized uptake values (SUV max ) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated. Results: Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related ( n = 2: nausea, duodenal perforation) or unrelated ( n = 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%-74%). Partial metabolic response (≥25% reduction in SUV max ) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%-52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients. Conclusions: Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC. Clin Cancer Res; 23(9); 2186-94. ©2016 AACR . ©2016 American Association for Cancer Research.

Multi-channel MRI segmentation of eye structures and tumors using patient-specific features

PubMed Central

Ciller, Carlos; De Zanet, Sandro; Kamnitsas, Konstantinos; Maeder, Philippe; Glocker, Ben; Munier, Francis L.; Rueckert, Daniel; Thiran, Jean-Philippe

2017-01-01

Retinoblastoma and uveal melanoma are fast spreading eye tumors usually diagnosed by using 2D Fundus Image Photography (Fundus) and 2D Ultrasound (US). Diagnosis and treatment planning of such diseases often require additional complementary imaging to confirm the tumor extend via 3D Magnetic Resonance Imaging (MRI). In this context, having automatic segmentations to estimate the size and the distribution of the pathological tissue would be advantageous towards tumor characterization. Until now, the alternative has been the manual delineation of eye structures, a rather time consuming and error-prone task, to be conducted in multiple MRI sequences simultaneously. This situation, and the lack of tools for accurate eye MRI analysis, reduces the interest in MRI beyond the qualitative evaluation of the optic nerve invasion and the confirmation of recurrent malignancies below calcified tumors. In this manuscript, we propose a new framework for the automatic segmentation of eye structures and ocular tumors in multi-sequence MRI. Our key contribution is the introduction of a pathological eye model from which Eye Patient-Specific Features (EPSF) can be computed. These features combine intensity and shape information of pathological tissue while embedded in healthy structures of the eye. We assess our work on a dataset of pathological patient eyes by computing the Dice Similarity Coefficient (DSC) of the sclera, the cornea, the vitreous humor, the lens and the tumor. In addition, we quantitatively show the superior performance of our pathological eye model as compared to the segmentation obtained by using a healthy model (over 4% DSC) and demonstrate the relevance of our EPSF, which improve the final segmentation regardless of the classifier employed. PMID:28350816

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitera, Gunita, E-mail: Gunita.Mitera@Sunnybrook.ca; Probyn, Linda; Ford, Michael

Purpose: To correlate computed tomography (CT) imaging features of spinal metastases with pain relief after radiotherapy (RT). Methods and Materials: Thirty-three patients receiving computed tomography (CT)-simulated RT for spinal metastases in an outpatient palliative RT clinic from January 2007 to October 2008 were retrospectively reviewed. Forty spinal metastases were evaluated. Pain response was rated using the International Bone Metastases Consensus Working Party endpoints. Three musculoskeletal radiologists and two orthopaedic surgeons evaluated CT features, including osseous and soft tissue tumor extent, presence of a pathologic fracture, severity of vertebral height loss, and presence of kyphosis. Results: The mean patient age wasmore » 69 years; 24 were men and 9 were women. The mean worst pain score was 7/10, and the mean total daily oral morphine equivalent was 77.3 mg. Treatment doses included 8 Gy in one fraction (22/33), 20 Gy in five fractions (10/33), and 20 Gy in eight fractions (1/33). The CT imaging appearance of spinal metastases included vertebral body involvement (40/40), pedicle involvement (23/40), and lamina involvement (18/40). Soft tissue component (10/40) and nerve root compression (9/40) were less common. Pathologic fractures existed in 11/40 lesions, with resultant vertebral body height loss in 10/40 and kyphosis in 2/40 lesions. At months 1, 2, and 3 after RT, 18%, 69%, and 70% of patients experienced pain relief. Pain response was observed with various CT imaging features. Conclusions: Pain response after RT did not differ in patients with and without pathologic fracture, kyphosis, or any other CT features related to extent of tumor involvement. All patients with painful spinal metastases may benefit from palliative RT.« less

Tumors of the Testis: Morphologic Features and Molecular Alterations.

PubMed

Howitt, Brooke E; Berney, Daniel M

2015-12-01

This article reviews the most frequently encountered tumor of the testis; pure and mixed malignant testicular germ cell tumors (TGCT), with emphasis on adult (postpubertal) TGCTs and their differential diagnoses. We additionally review TGCT in the postchemotherapy setting, and findings to be integrated into the surgical pathology report, including staging of testicular tumors and other problematic issues. The clinical features, gross pathologic findings, key histologic features, common differential diagnoses, the use of immunohistochemistry, and molecular alterations in TGCTs are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Feasibility of intraoperative imaging during Mohs surgery with reflectance confocal microscopy

NASA Astrophysics Data System (ADS)

Flores, Eileen S.; Cordova, Miguel; Kose, Kivanc; Phillips, William; Nehal, Kishwer; Rajadhyaksha, Milind

2014-03-01

Mohs surgery for the removal of non-melanoma skin cancers (NMSCs) is performed in stages, while being guided by the examination for residual tumor with frozen pathology. However, preparation of frozen pathology at each stage is timeconsuming and labor-intensive. Real-time intraoperative reflectance confocal microscopy (RCM) may enable rapid detection of residual tumor directly in surgical wounds on patients. We report initial feasibility on twenty-one patients, using 35% AlCl3 for nuclear contrast. Imaging was performed in quadrants in the wound, to simulate the Mohs surgeon's examination of pathology. Images and videos of the epidermal and dermal margins were found to be of clinically acceptable quality. Bright nuclear morphology was identified at the epidermal margin. The presence of residual BCC/SCC tumor and normal skin features could be detected in the peripheral and deep dermal margins. Nuclear morphology was detectable in residual BCC/SCC tumors. Intraoperative RCM imaging may enable detection of residual tumor, directly on Mohs patients, and may serve as an adjunct for frozen pathology. However, a stronger source of contrast will be necessary, and also a smaller device with an automated approach for imaging in the entire wound in a rapid and controlled manner for clinical utility.

Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes.

PubMed

von Minckwitz, Gunter; Untch, Michael; Blohmer, Jens-Uwe; Costa, Serban D; Eidtmann, Holger; Fasching, Peter A; Gerber, Bernd; Eiermann, Wolfgang; Hilfrich, Jörn; Huober, Jens; Jackisch, Christian; Kaufmann, Manfred; Konecny, Gottfried E; Denkert, Carsten; Nekljudova, Valentina; Mehta, Keyur; Loibl, Sibylle

2012-05-20

The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain. Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane-based chemotherapy in seven randomized trials were analyzed. Disease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes (0.623), and focal-invasive disease (0.727) were included in the definition. pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 (HER2) -negative (P = .005), HER2-positive/nonluminal (P < .001), and triple-negative (P < .001) tumors but not in luminal A (P = .39) or luminal B/HER2-positive (P = .45) breast cancer. pCR in HER2-positive (nonluminal) and triple-negative tumors was associated with excellent prognosis. pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes. Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR. pCR is a suitable surrogate end point for patients with luminal B/HER2-negative, HER2-positive (nonluminal), and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors.

[Imaging manifestations and pathologic basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors].

PubMed

Ou, Youkuan; Xiao, Enhua; Shang, Quanliang; Chen, Juan

2015-10-01

To investigate the imaging manifestations of CT, MRI and pathological basis for hepatic capsular retraction syndrome caused by benign and malignant liver tumors.
 CT or MRI images and pathological features for hepatic capsular retraction syndrome were retrospectively analyzed in 50 patients with benign and malignant liver tumors. Picture archive and communication system (PACS) was used to observe and compare the morphology, size, width, depth, edge of the capsular retraction and the status of liquid under the liver capsule. The structure, differentiation and proliferation of the tumor were analyzed under the microscope.
 There were malignant liver tumors in 44 patients and benign tumor in 6 patients. The smooth or rough for the edge of capsular retraction was significant difference between the benign tumors and the malignant tumors with three differentiated grades (all P<0.05). There were significant difference in the width and depth for capsule retraction with different amount of fibrous tissues (all P<0.05). The width and depth of capsule retraction were positively correlated to the size of the tumors (r=0.557, 0.309 respectively, both P<0.05).
 Benign and malignant hepatic tumors may appear capsule retraction syndrome, but there are morphological differences between them. The differences are closely related with the lesion size, differentiated degree of tumor and fibrous tissue proliferation.

Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study.

PubMed

Barro, Ana M Bada; Rivero, Arianna Iglesias; Goñi, Avelina León; Navarro, Bárbara O González; Angarica, Meilis Mesa; Ramírez, Belinda Sánchez; Bedoya, Darel Martínez; Triana, Consuelo González; Rodríguez, Axel Mancebo; Parada, Ángel Casacó

2012-12-17

Human epidermal growth factor receptor (HER1) constitutes a tumor associated antigen. Its overexpression in many epithelial tumors has been associated with bad prognosis and poor survival. Cancer vaccine based on the extracellular domain (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and Montanide ISA 51-VG is a new and complementary approach for the treatment of epithelial tumors. The present study deals with the immunogenicity of this vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12 months. Twelve monkeys were randomized into two groups of 3 animals per sex: control and vaccinated. Treated monkeys received 9 doses of vaccination and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study. Humoral immune response, clinical pathology parameters and delayed type hypensensitivity were analyzed. Skin biopsy was performed at the end of the study in all animals. Animal's survival in the study was 100% (n=12). Local reactions were observed at the administration site of four treated animals (n=6), with two showing slight inflammatory cutaneous damage. Clinical pathology parameters were not affected. HER1 vaccine induced high IgG antibodies titers in the treated animals even when DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines, decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic effects in H125 cells. In general the present study showed that HER1 vaccine induced specific immune response in M. fascicularis monkeys and was well tolerated, suggesting it could be safely used in clinical studies in epithelial cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study

PubMed Central

Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

2017-01-01

Objective To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). Materials and methods In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. Results The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). Conclusion CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent. PMID:28894329

Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

PubMed Central

Ferrari, Linda; Fichera, Alessandro

2015-01-01

The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

Current Approaches and Challenges for Monitoring Treatment Response in Colon and Rectal Cancer

PubMed Central

McKeown, Elizabeth; Nelson, Daniel W.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alexander; Nissan, Aviram; Avital, Itzhak; Brücher, Björn LDM; Steele, Scott R.

2014-01-01

Introduction: With the advent of multidisciplinary and multimodality approaches to the management of colorectal cancer patients, there is an increasing need to define how we monitor response to novel therapies in these patients. Several factors ranging from the type of therapy used to the intrinsic biology of the tumor play a role in tumor response. All of these can aid in determining the ideal course of treatment, and may fluctuate over time, pending down-staging or progression of disease. Therefore, monitoring how disease responds to therapy requires standardization in order to ultimately optimize patient outcomes. Unfortunately, how best to do this remains a topic of debate among oncologists, pathologists, and colorectal surgeons. There may not be one single best approach. The goal of the present article is to shed some light on current approaches and challenges to monitoring treatment response for colorectal cancer. Methods: A literature search was conducted utilizing PubMed and the OVID library. Key-word combinations included colorectal cancer metastases, neoadjuvant therapy, rectal cancer, imaging modalities, CEA, down-staging, tumor response, and biomarkers. Directed searches of the embedded references from the primary articles were also performed in selected circumstances. Results: Pathologic examination of the post-treatment surgical specimen is the gold standard for monitoring response to therapy. Endoscopy is useful for evaluating local recurrence, but not in assessing tumor response outside of the limited information gained by direct examination of intra-lumenal lesions. Imaging is used to monitor tumors throughout the body for response, with CT, PET, and MRI employed in different circumstances. Overall, each has been validated in the monitoring of patients with colorectal cancer and residual tumors. Conclusion: Although there is no imaging or serum test to precisely correlate with a tumor's response to chemo- or radiation therapy, these modalities, when used in combination, can aid in allowing clinicians to adjust medical therapy, pursue operative intervention, or (in select cases) identify complete responders. Improvements are needed, however, as advances across multiple modalities could allow appropriate selection of patients for a close surveillance regimen in the absence of operative intervention. PMID:24396496

Pulsed terahertz imaging of breast cancer in freshly excised murine tumors

NASA Astrophysics Data System (ADS)

Bowman, Tyler; Chavez, Tanny; Khan, Kamrul; Wu, Jingxian; Chakraborty, Avishek; Rajaram, Narasimhan; Bailey, Keith; El-Shenawee, Magda

2018-02-01

This paper investigates terahertz (THz) imaging and classification of freshly excised murine xenograft breast cancer tumors. These tumors are grown via injection of E0771 breast adenocarcinoma cells into the flank of mice maintained on high-fat diet. Within 1 h of excision, the tumor and adjacent tissues are imaged using a pulsed THz system in the reflection mode. The THz images are classified using a statistical Bayesian mixture model with unsupervised and supervised approaches. Correlation with digitized pathology images is conducted using classification images assigned by a modal class decision rule. The corresponding receiver operating characteristic curves are obtained based on the classification results. A total of 13 tumor samples obtained from 9 tumors are investigated. The results show good correlation of THz images with pathology results in all samples of cancer and fat tissues. For tumor samples of cancer, fat, and muscle tissues, THz images show reasonable correlation with pathology where the primary challenge lies in the overlapping dielectric properties of cancer and muscle tissues. The use of a supervised regression approach shows improvement in the classification images although not consistently in all tissue regions. Advancing THz imaging of breast tumors from mice and the development of accurate statistical models will ultimately progress the technique for the assessment of human breast tumor margins.

Long-Term Results of a Randomized Trial in Locally Advanced Rectal Cancer: No Benefit From Adding a Brachytherapy Boost

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appelt, Ane L., E-mail: ane.lindegaard.appelt@rsyd.dk; Faculty of Health Sciences, University of Southern Denmark, Odense; Vogelius, Ivan R.

Purpose/Objective(s): Mature data on tumor control and survival are presented from a randomized trial of the addition of a brachytherapy boost to long-course neoadjuvant chemoradiation therapy (CRT) for locally advanced rectal cancer. Methods and Materials: Between March 2005 and November 2008, 248 patients with T3-4N0-2M0 rectal cancer were prospectively randomized to either long-course preoperative CRT (50.4 Gy in 28 fractions, per oral tegafur-uracil and L-leucovorin) alone or the same CRT schedule plus a brachytherapy boost (10 Gy in 2 fractions). The primary trial endpoint was pathologic complete response (pCR) at the time of surgery; secondary endpoints included overall survival (OS), progression-free survivalmore » (PFS), and freedom from locoregional failure. Results: Results for the primary endpoint have previously been reported. This analysis presents survival data for the 224 patients in the Danish part of the trial. In all, 221 patients (111 control arm, 110 brachytherapy boost arm) had data available for analysis, with a median follow-up time of 5.4 years. Despite a significant increase in tumor response at the time of surgery, no differences in 5-year OS (70.6% vs 63.6%, hazard ratio [HR] = 1.24, P=.34) and PFS (63.9% vs 52.0%, HR=1.22, P=.32) were observed. Freedom from locoregional failure at 5 years were 93.9% and 85.7% (HR=2.60, P=.06) in the standard and in the brachytherapy arms, respectively. There was no difference in the prevalence of stoma. Explorative analysis based on stratification for tumor regression grade and resection margin status indicated the presence of response migration. Conclusions: Despite increased pathologic tumor regression at the time of surgery, we observed no benefit on late outcome. Improved tumor regression does not necessarily lead to a relevant clinical benefit when the neoadjuvant treatment is followed by high-quality surgery.« less

Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors.

PubMed

Wagner, Andrew J; Malinowska-Kolodziej, Izabela; Morgan, Jeffrey A; Qin, Wei; Fletcher, Christopher D M; Vena, Natalie; Ligon, Azra H; Antonescu, Cristina R; Ramaiya, Nikhil H; Demetri, George D; Kwiatkowski, David J; Maki, Robert G

2010-02-10

PURPOSE Perivascular epithelioid cell tumors (PEComas) represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. There is no known effective therapy for PEComa, and the molecular pathophysiology of aberrant mTOR signaling provided us with a scientific rationale to target this pathway therapeutically. On this mechanistic basis, we treated three consecutive patients with metastatic PEComa with an oral mTOR inhibitor, sirolimus. PATIENTS AND METHODS Patients with advanced PEComa were treated with sirolimus and consented to retrospective collection of data from their medical records and analysis of archival tumor specimens. Tumor response was determined by computed tomography scans obtained at the clinical discretion of the treating physicians. Tumors were assessed for immunohistochemical evidence of mTORC1 activation and genetic evidence of alterations in TSC1 and TSC2. Results Radiographic responses to sirolimus were observed in all patients. PEComas demonstrated loss of TSC2 protein expression and evidence of baseline mTORC1 activation. Homozygous loss of TSC1 was identified in one PEComa. CONCLUSION Inhibition of mTORC1, pathologically activated by loss of the TSC1/TSC2 tumor suppressor complex, is a rational mechanistic target for therapy in PEComas. The clinical activity of sirolimus in PEComa additionally strengthens the pathobiologic similarities linking PEComas to other neoplasms related to the tuberous sclerosis complex.

CYR61 suppresses growth of human malignant melanoma.

PubMed

Chen, Jun; Liu, Yang; Sun, Qilin; Wang, Beiqing; Li, Ningli; Chen, Xiangdong

2016-11-01

Cysteine-rich protein 61 (CCN1/CYR61) is an important marker of proliferation and metastasis in malignant melanoma, making it a potential target for melanoma treatment. In this study, we compared the expression of CRY61 in Chinese patients with malignant melanoma with its expression in patients with other skin tumors or with no skin pathological conditions. We examined the effects of anti-human CYR61 monoclonal antibody on proliferation and evaluated the changes in CYR61 expression and cell proliferation in response to treatment with either epirubicin or interferon (IFN)-α. CYR61 was expressed at lower levels in patients with malignant melanoma than in patients with other skin tumors or with no pathology. Following the treatment of B16 cells with epirubicin and IFN-α, CYR61 levels increased, cell growth was inhibited, and proliferating cell nuclear antigen expression decreased. Thus, CYR61 could become a therapeutic target for malignant melanoma patients with high CYR61 expression.

Hereditary factors are unlikely behind unusual pattern of early - Onset colorectal cancer in Egyptians: A study of family history and pathology features in Egyptians with large bowel cancer (cross-sectional study).

PubMed

Abou-Zeid, Ahmed A; Jumuah, Wael A; Ebied, Essam F; Abd El Samee Atia, Karim Sabry; El Ghamrini, Yasser; Somaie, Dina A

2017-08-01

Colorectal cancer in Egypt has a higher incidence in young patients compared to western countries, where the disease is more prevalent in the old age group. This difference has been attributed to higher incidence of hereditary cancers in young Egyptian patients. The aim of this study is to compare the family history criteria and pathology features of tumors in young (≤40 years) and old (>40 years) Egyptian patients with adenocarcinoma of the colon and rectum. This is the analysis of our prospectively collected data on the pathology features of tumors in 313 consecutive patients (133 young, 180 old) with colorectal cancer presenting to the Department of Surgery within an eight-year period. A detailed family history was obtained from 258 patients (112 young, 146 old). 41 young and 48 old patients reported family history of cancer, the difference was not statistically significant. Ten young patients (9%) reported a family history of colorectal cancer in a first degree relative (3 fitting into Amsterdam criteria, 7 fitting into less strict criteria) which was not significantly different from the old age group. The pathologic features of tumors in both groups resembled sporadic rather than hereditary cancer and there was no significant difference between groups in tumor location, degree of differentiation, mucin production, synchronous and metachronous colorectal tumors or polyps and grossly stricturing or ulcerating tumors. Extracolonic tumors developed in one young and two old patients. The characteristics of large bowel cancer in young Egyptian patients do not differ significantly from those in older patients. Despite the high incidence of large bowel cancer in young Egyptian patients, family history and pathologic features of tumors do not support a hereditary origin of colorectal cancer in this age group in Egypt. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration

PubMed Central

Bossuyt, V.; Provenzano, E.; Symmans, W. F.; Boughey, J. C.; Coles, C.; Curigliano, G.; Dixon, J. M.; Esserman, L. J.; Fastner, G.; Kuehn, T.; Peintinger, F.; von Minckwitz, G.; White, J.; Yang, W.; Badve, S.; Denkert, C.; MacGrogan, G.; Penault-Llorca, F.; Viale, G.; Cameron, D.; Earl, Helena; Alba, Emilio; Lluch, Ana; Albanell, Joan; Amos, Keith; Biernat, Wojciech; Bonnefoi, Hervé; Buzdar, Aman; Cane, Paul; Pinder, Sarah; Carson, Lesley; Dickson-Witmer, Diana; Gong, Gyungyub; Green, Jimmy; Hsu, Chih-Yi; Tseng, Ling-Ming; Kroep, Judith; Leitch, A. Marilyn; Sarode, Venetia; Mamounas, Eleftherios; Marcom, Paul Kelly; Nuciforo, Paolo; Paik, Soonmyung; Peg, Vicente; Peston, David; Pierga, Jean-Yves; Quintela-Fandino, Miguel; Salgado, Roberto; Sikov, William; Thomas, Jeremy; Unzeitig, Gary; Wesseling, Jelle

2015-01-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. PMID:26019189

Programmed Death Cell Ligand 1 (PD-L1) Is Associated With Survival in Stage I Non-Small Cell Lung Cancer.

PubMed

Sepesi, Boris; Cuentas, Edwin Parra; Canales, Jaime Rodriguez; Behrens, Carmen; Correa, Arlene M; Vaporciyan, Ara; Weissferdt, Annikka; Kalhor, Neda; Moran, Cesar; Swisher, Stephen; Wistuba, Ignacio

2017-01-01

Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis. Statistics included recursive partitioning, univariable, multivariable, and Kaplan-Meier analyses. Patients whose tumors expressed <4.7% PD-L1 (N = 87) experienced significantly better overall survival (OS) (P = 0.001) than patients with PD-L1 >4.7% (N = 26). Patients with PD-L1 expression in macrophages <6.3% (N = 24) also experienced significantly better (P = 0.005) OS than patients with >6.3% (N = 89). The best outcomes were observed in patients with low PD-L1 expression in both tumor and macrophages with 5-year OS of 94% (N = 17). Contrarily, patients with high PD-L1 expression in both tumor and macrophages experienced 5-year OS of 20% (N = 19). Low PD-L1 expression in the tumor and in the TIMs was independently associated with survival in multivariable analysis (P = 0.000 and P = 0.030, respectively). Lower PD-L1 % expression in the tumor and in the TIMs seems to be associated with significantly better OS in surgically resected stage I lung cancer. Additional studies are needed to validate PD-L1 as a prognostic biomarker in lung cancer and to study the mechanisms of intratumoral immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

Low-dose chemotherapy with methotrexate and vinblastine for patients with desmoid tumors: relationship to CTNNB1 mutation status.

PubMed

Nishida, Yoshihiro; Tsukushi, Satoshi; Urakawa, Hiroshi; Hamada, Shunsuke; Kozawa, Eiji; Ikuta, Kunihiro; Ando, Yuichi; Ishiguro, Naoki

2015-12-01

This study was conducted to determine the efficacy and safety of low-dose chemotherapy with methotrexate (MTX) and vinblastine (VBL) for patients with desmoid tumors refractory to meloxicam treatment, focusing in particular on the relationship between the efficacy of this chemotherapy and catenin β-1 (CTNNB1) mutation status. Since March 2003, patients pathologically diagnosed with extraperitoneal desmoid tumors have been prospectively treated with meloxicam, a COX-2 inhibitor, at our institution. Patients with inoperable tumors who were resistant to meloxicam treatment underwent MTX and VBL therapy every other week. The responses of all patients were evaluated, and factors that were correlated with efficacy were analyzed, including CTNNB1 mutation status. Sixty-eight patients were prospectively treated with meloxicam. MTX + VBL therapy was administered in 15 patients. Six patients showed a partial response. Only one patient presented disease progression. A few patients showed grade 3-4 treatment-related toxicity with the administration of MTX and VBL every other week. Intriguingly, CTNNB1 status did not affect the efficacy of this treatment. MTX and VBL treatment every other week is well tolerated and achieved a favorable response in patients resistant to meloxicam treatment, regardless of CTNNB1 mutation status.

Etanercept Exacerbates Inflammation and Pathology in a Rabbit Model of Active Pulmonary Tuberculosis

PubMed Central

Tsenova, Liana; O'Brien, Paul; Holloway, Jennifer; Peixoto, Blas; Soteropoulos, Patricia; Fallows, Dorothy; Subbian, Selvakumar

2014-01-01

Treatment of chronic inflammatory diseases with tumor necrosis factor alpha (TNF-α) antagonists has been associated with increased risk of tuberculosis (TB). We examined the usefulness of the rabbit model of active pulmonary TB for studying the impact of the human immune modulatory reagent etanercept on the host immune response. Control of Mycobacterium tuberculosis (Mtb) infection, disease pathology, and the global transcriptional response in Mtb-infected lungs of rabbits were studied. Etanercept treatment exacerbated disease pathology and reduced bacillary control in the lungs, compared with infected untreated animals. Reduced collagen and fibrin deposition in the granulomas was associated with significant downregulation of the collagen metabolism and fibrosis network genes and upregulation of genes in the inflammatory response and cell recruitment networks in the lungs of etanercept treated, compared with untreated rabbits. Our results suggest that targeting the TNF-α signaling pathway disrupts the tissue remodeling process, which is required for the formation and maintenance of well-differentiated granulomas and for control of Mtb growth in the lungs. These results validate the use of the rabbit model for investigating the impact of selected human immune modulatory drugs, such as a TNF-α antagonist, on the host immune response and pathogenesis in TB. PMID:24831609

Survival benefit with proapoptotic molecular and pathologic responses from dual targeting of mammalian target of rapamycin and epidermal growth factor receptor in a preclinical model of pancreatic neuroendocrine carcinogenesis.

PubMed

Chiu, Christopher W; Nozawa, Hiroaki; Hanahan, Douglas

2010-10-10

Pancreatic neuroendocrine tumors (PNETs), although rare, often metastasize, such that surgery, the only potentially curative therapy, is not possible. There is no effective systemic therapy for patients with advanced PNETs. Therefore, new strategies are needed. Toward that end, we investigated the potential benefit of dual therapeutic targeting of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a preclinical mouse model of PNET. Rapamycin and erlotinib, inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic mice bearing advanced multifocal PNET. Tumor growth and survival were monitored, and tumors were surveyed for potential biomarkers of response to the therapeutics. Rapamycin monotherapy was notably efficacious, prolonging survival concomitant with tumor stasis (stable disease). However, the tumors developed resistance, as evidenced by eventual relapse to progressive tumor growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal survival benefit. In combination, there was an unprecedented survival benefit in the face of this aggressive multifocal cancer and, in contrast to either monotherapy, the development of adaptive resistance was not apparent. Additionally, the antiapoptotic protein survivin was implicated as a biomarker of sensitivity and beneficial responses to the dual targeted therapy. Preclinical trials in a mouse model of endogenous PNET suggest that combined targeting of the mTOR and EGFR signaling pathways could have potential clinical benefit in treating PNET. These results have encouraged development of an ongoing phase II clinical trial aimed to evaluate the efficacy of this treatment regimen in human neuroendocrine tumors.

Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

PubMed Central

Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

2011-01-01

Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulations vary among different neoplastic models. Thus, it is thought that the type and quantities of inflammatory mediators generated during neoplasia dictate the composition of the resultant MDSC response. Although much interest has been devoted to monocytic MDSC biology, a fundamental gap remains in our understanding of the derivation of granulocytic MDSC. In settings of heightened granulocytic MDSC responses, we hypothesized that inappropriate production of G-CSF is a key initiator of granulocytic MDSC accumulation. We observed abundant amounts of G-CSF in vivo, which correlated with robust granulocytic MDSC responses in multiple tumor models. Using G-CSF loss- and gain-of-function approaches, we demonstrated for the first time that: 1) abrogating G-CSF production significantly diminished granulocytic MDSC accumulation and tumor growth; 2) ectopically over-expressing G-CSF in G-CSF-negative tumors significantly augmented granulocytic MDSC accumulation and tumor growth; and 3) treatment of naïve healthy mice with recombinant G-CSF protein elicited granulocytic-like MDSC remarkably similar to those induced under tumor-bearing conditions. Collectively, we demonstrated that tumor-derived G-CSF enhances tumor growth through granulocytic MDSC-dependent mechanisms. These findings provide us with novel insights into MDSC subset development and potentially new biomarkers or targets for cancer therapy. PMID:22110722

The molecular mechanisms on glomangiopericytoma invasion

PubMed Central

2013-01-01

Purpose To observed the imaging and pathological features of the glomangiopericytoma. Experimental design In this paper we report a typical case of glomangiopericytoma arising in the skull base area and summarize the clinical manifestations, imaging and pathological features of such diseases. Results Immunohistochemical staining confirmed the tumor cells were strongly positive to Vim, SMA, MSA and negative to CD31, CD34. Partial cells were positive to FVIII. The imaging can’t confirm the diagnosis but indicate the the tumor has intact envelope.The cells in the tumor envelope is positive to Vim and negative SMA and FVIII. These findings were compatible with glomangiopericytoma and the cells in the tumor envelope is not glomangiopericytoma cells. Conclusion In view of the clinical and pathological features of the glomangiopericytoma, we believe that the surgery is the best treatment so far and the tumor can be resected completely. The above results can be preliminary reason to explain the low recurrence of such diseases. PMID:24074285

Serum Immunoproteomics Combined With Pathological Reassessment of Surgical Specimens Identifies TCP-1ζ Autoantibody as a Potential Biomarker in Thyroid Neoplasia.

PubMed

Belousov, Pavel V; Bogolyubova, Apollinariya V; Kim, Yan S; Abrosimov, Alexander Y; Kopylov, Arthur T; Tvardovskiy, Andrey A; Lanshchakov, Kirill V; Sazykin, Alexei Y; Dvinskikh, Nina Y; Bobrovskaya, Yana I; Selivanova, Lilia S; Shilov, Evgeniy S; Schwartz, Anton M; Shebzukhov, Yuriy V; Severskaia, Natalya V; Vanushko, Vladimir E; Moshkovskii, Sergei A; Nedospasov, Sergei A; Kuprash, Dmitry V

2015-09-01

Current methods of preoperative diagnostics frequently fail to discriminate between benign and malignant thyroid neoplasms. In encapsulated follicular-patterned tumors (EnFPT), this discrimination is challenging even using histopathological analysis. Autoantibody response against tumor-associated antigens is a well-documented phenomenon with prominent diagnostic potential; however, autoantigenicity of thyroid tumors remains poorly explored. Objectives were exploration of tumor-associated antigen repertoire of thyroid tumors and identification of candidate autoantibody biomarkers capable of discrimination between benign and malignant thyroid neoplasms. Proteins isolated from FTC-133 cells were subjected to two-dimensional Western blotting using pooled serum samples of patients originally diagnosed with either papillary thyroid carcinoma (PTC) or EnFPT represented by apparently benign follicular thyroid adenomas, as well as healthy individuals. Immunoreactive proteins were identified using liquid chromatography-tandem mass-spectrometry. Pathological reassessment of EnFPT was performed applying nonconservative criteria for capsular invasion and significance of focal PTC nuclear changes (PTC-NCs). Recombinant T-complex protein 1 subunitζ (TCP-1ζ) was used to examine an expanded serum sample set of patients with various thyroid neoplasms (n = 89) for TCP-1ζ autoantibodies. All patients were included in tertiary referral centers. A protein demonstrating a distinct pattern of EnFPT-specific seroreactivity was identified as TCP-1ζ protein. A subsequent search for clinicopathological correlates of TCP-1ζ seroreactivity revealed nonclassical capsular invasion or focal PTC-NC in all TCP-1ζ antibody-positive cases. Further studies in an expanded sample set confirmed the specificity of TCP-1ζ autoantibodies to malignant EnFPT. We identified TCP-1ζ autoantibodies as a potential biomarker for presurgical discrimination between benign and malignant encapsulated follicular-patterned thyroid tumors. Our results suggest the use of nonconservative morphological criteria for diagnosis of malignant EnFPT in biomarker identification studies and provide a peculiar example of uncovering the diagnostic potential of a candidate biomarker using incorporation of pathological reassessment in the pipeline of immunoproteomic research.

Primary ovarian leiomyoma in a premenarchal adolescent: first reported case.

PubMed

Blue, Nathan R; Felix, Juan C; Jaque, Jenny

2014-08-01

Primary ovarian leiomyoma is a rare benign ovarian tumor with only several reported cases in adolescents. Little is known about the origin or natural history of these rare tumors as they have occurred in a variety of presentations and were removed upon presentation without observation. A 14-year-old, premenarchal female was found to have a 4 cm mass which grew to 6.5 cm over two years. It appeared sonographically most consistent with a teratoma; however, during surgical resection it was found to be solid, and on pathologic evaluation was identified as an ovarian leiomyoma. The growth of this patient's tumor with the onset of puberty supports hormonal responsivity, but its presence prior to menarche suggests an alternate origin, independent of gonadal hormones. Published by Elsevier Inc.

MYC activation is a hallmark of cancer initiation and maintenance.

PubMed

Gabay, Meital; Li, Yulin; Felsher, Dean W

2014-06-02

The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors. MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence. When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark" features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation. Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis. Hence, tumors appear to be "addicted" to MYC because of both tumor cell-intrinsic, cell-autonomous and host-dependent, immune cell-dependent mechanisms. Both the trajectory and persistence of many human cancers require sustained MYC activation. Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC. MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Risk interrelationship among multiple primary tumors

PubMed Central

Safi, Mohammed; Sun, Xiuhua; Wang, Lifen; Zhang, Xinwei; Song, Jicheng; Ameen, Mohammed

2018-01-01

Abstract Rationale: Along with advanced management in oncology, great progress has been recently achieved in the studies of multiple primary tumors. Several reports have studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or Warthin tumor. However, the level of coexistence between these cases remains unclear due to the absence of a distinct link between them. Patient concerns: We present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin tumor) in an 80-year-old man and a review of the literature on the coexistence of RCC with lymphoma and lymphoma with Warthin tumor. Diagnosis: With a history of RCC, the patient had a freely movable lump under his left ear, and the pathological report indicated Hodgkin lymphoma and Warthin tumor. Intervention: RCC and Warthin tumor of the patient were surgically treated, followed by 2 cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1 for 7 cycles. Outcomes: After the last day of chemotherapy, the patient showed a complete response. Lessons: To the best of our knowledge, this paper is the first to report a case of multiple primary tumors with a complete response. For their early detection, favorable prognosis, and correlation identification, we suggest a transitive relation between these coexisting tumors. Therefore, similar studies should be conducted. PMID:29642151

Numeric pathologic lymph node classification shows prognostic superiority to topographic pN classification in esophageal squamous cell carcinoma.

PubMed

Sugawara, Kotaro; Yamashita, Hiroharu; Uemura, Yukari; Mitsui, Takashi; Yagi, Koichi; Nishida, Masato; Aikou, Susumu; Mori, Kazuhiko; Nomura, Sachiyo; Seto, Yasuyuki

2017-10-01

The current eighth tumor node metastasis lymph node category pathologic lymph node staging system for esophageal squamous cell carcinoma is based solely on the number of metastatic nodes and does not consider anatomic distribution. We aimed to assess the prognostic capability of the eighth tumor node metastasis pathologic lymph node staging system (numeric-based) compared with the 11th Japan Esophageal Society (topography-based) pathologic lymph node staging system in patients with esophageal squamous cell carcinoma. We retrospectively reviewed the clinical records of 289 patients with esophageal squamous cell carcinoma who underwent esophagectomy with extended lymph node dissection during the period from January 2006 through June 2016. We compared discrimination abilities for overall survival, recurrence-free survival, and cancer-specific survival between these 2 staging systems using C-statistics. The median number of dissected and metastatic nodes was 61 (25% to 75% quartile range, 45 to 79) and 1 (25% to 75% quartile range, 0 to 3), respectively. The eighth tumor node metastasis pathologic lymph node staging system had a greater ability to accurately determine overall survival (C-statistics: tumor node metastasis classification, 0.69, 95% confidence interval, 0.62-0.76; Japan Esophageal Society classification; 0.65, 95% confidence interval, 0.58-0.71; P = .014) and cancer-specific survival (C-statistics: tumor node metastasis classification, 0.78, 95% confidence interval, 0.70-0.87; Japan Esophageal Society classification; 0.72, 95% confidence interval, 0.64-0.80; P = .018). Rates of total recurrence rose as the eighth tumor node metastasis pathologic lymph node stage increased, while stratification of patients according to the topography-based node classification system was not feasible. Numeric nodal staging is an essential tool for stratifying the oncologic outcomes of patients with esophageal squamous cell carcinoma even in the cohort in which adequate numbers of lymph nodes were harvested. Copyright © 2017 Elsevier Inc. All rights reserved.

Continuous measurement of breast tumor hormone receptor expression: a comparison of two computational pathology platforms

PubMed Central

Ahern, Thomas P.; Beck, Andrew H.; Rosner, Bernard A.; Glass, Ben; Frieling, Gretchen; Collins, Laura C.; Tamimi, Rulla M.

2017-01-01

Background Computational pathology platforms incorporate digital microscopy with sophisticated image analysis to permit rapid, continuous measurement of protein expression. We compared two computational pathology platforms on their measurement of breast tumor estrogen receptor (ER) and progesterone receptor (PR) expression. Methods Breast tumor microarrays from the Nurses’ Health Study were stained for ER (n=592) and PR (n=187). One expert pathologist scored cases as positive if ≥1% of tumor nuclei exhibited stain. ER and PR were then measured with the Definiens Tissue Studio (automated) and Aperio Digital Pathology (user-supervised) platforms. Platform-specific measurements were compared using boxplots, scatter plots, and correlation statistics. Classification of ER and PR positivity by platform-specific measurements was evaluated with areas under receiver operating characteristic curves (AUC) from univariable logistic regression models, using expert pathologist classification as the standard. Results Both platforms showed considerable overlap in continuous measurements of ER and PR between positive and negative groups classified by expert pathologist. Platform-specific measurements were strongly and positively correlated with one another (rho≥0.77). The user-supervised Aperio workflow performed slightly better than the automated Definiens workflow at classifying ER positivity (AUCAperio=0.97; AUCDefiniens=0.90; difference=0.07, 95% CI: 0.05, 0.09) and PR positivity (AUCAperio=0.94; AUCDefiniens=0.87; difference=0.07, 95% CI: 0.03, 0.12). Conclusion Paired hormone receptor expression measurements from two different computational pathology platforms agreed well with one another. The user-supervised workflow yielded better classification accuracy than the automated workflow. Appropriately validated computational pathology algorithms enrich molecular epidemiology studies with continuous protein expression data and may accelerate tumor biomarker discovery. PMID:27729430

Thymidylate Synthase Gene Polymorphism Affects the Response to Preoperative 5-Fluorouracil Chemoradiation Therapy in Patients With Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hur, Hyuk; Kang, Jeonghyun; Kim, Nam Kyu, E-mail: namkyuk@yuhs.ac

2011-11-01

Purpose: This study aims to correlate thymidylate synthase (TS) gene polymorphisms with the tumor response to preoperative 5-fluorouracil (5-FU)-based chemoradiation therapy (CRT) in patients with rectal cancer. Methods and Materials: Forty-four patients with rectal cancer treated with 5-FU-based preoperative CRT were prospectively enrolled in this study. Thymidylate synthase expression and TS gene polymorphisms were evaluated in tumor obtained before preoperative CRT and were correlated with the pathologic response, as assessed by histopathologic staging (pTNM) and tumor regression grade. Results: Patients exhibited 2R/3R and 3R/3R tandem repeat polymorphisms in the TS gene. With regard to TS expression in these genotypes, 2R/3RCmore » and 3RC/3RC were defined as the low-expression group and 2R/3RG, 3RC/3RG, and 3RG/3RG as the high-expression group. There was no significant correlation between TS expression and tumor response. There was no significant difference in the tumor response between patients homozygous for 3R/3R and patients heterozygous for 2R/3R. However, 13 of 14 patients in the low-expression group with a G>C single-nucleotide polymorphism (SNP) (2R/3RC [n = 5] or 3RC/3RC [n = 9]) exhibited a significantly greater tumor downstaging rate, as compared with only 12 of 30 patients in the high-expression group without the SNP (2R/3RG [n = 10], 3RC/3RG [n = 9], or 3RG/3RG [n = 11]) (p = 0.001). The nodal downstaging rate was also significantly greater in this low-expression group, as compared with the high-expression group (12 of 14 vs. 14 of 30, p = 0.014). However, there was no significant difference in the tumor regression grade between these groups. Conclusions: This study suggests that SNPs within the TS enhancer region affect the tumor response to preoperative 5-FU-based CRT in rectal cancer.« less

Carotid body tumor imitator: An interesting case of Castleman's disease.

PubMed

Shakir, Hakeem J; Diletti, Sara M; Hart, Alexandra M; Meyers, Joshua E; Dumont, Travis M; Siddiqui, Adnan H

2015-01-01

There are very few reports in the literature of Castleman's disease affecting the carotid artery and a single previous report of a case of Castleman's disease of the neck originally mistaken as a carotid body tumor. We describe a rare case of Castleman's disease, manifesting with classic radiographic hallmarks of a carotid body tumor. The postoperative pathologic examination identified the resected mass as Castleman's lymphadenopathy. The management of this particular case is discussed, and the findings are highlighted. We present a unique case of a tumor initially and incorrectly diagnosed as a carotid body tumor. However, after comprehensive treatment with endovascular and surgical modalities and subsequent pathologic examination, the diagnosis of this rare entity was made.

Advance in diagnosis of female genital tract tumor with laser fluorescence

NASA Astrophysics Data System (ADS)

Ding, Ai-Hua; Tseng, Quen; Lian, Shao-Hui

1998-11-01

In order to improve the diagnostic accuracy of malignant tumors with laser fluorescence, in 1996, our group successfully created the computerized laser fluorescence spectrograph type II with more reliable images shown overshadowing the naked eye method before 74 cases of female genital tract diseases had been examined by the LFS II resulting in 10 positive cases which were also proven pathologically as malignant tumors, without nay false negative, 3 cases presented suspicious positive but all were proven pathologically as non-tumors lesions, the false positive rate was 4 percent. Our work showed that the method of LFS II can provide a more rapid and accurate diagnosis for the clinical malignant tumors.

Response evaluation of giant-cell tumor of bone treated by denosumab: Histogram and texture analysis of CT images.

PubMed

Yi, Jisook; Lee, Young Han; Kim, Sang Kyum; Kim, Seung Hyun; Song, Ho-Taek; Shin, Kyoo-Ho; Suh, Jin-Suck

2018-05-01

This study aimed to compare computed tomography (CT) features, including tumor size and textural and histogram measurements, of giant-cell tumors of bone (GCTBs) before and after denosumab treatment and determine their applicability in monitoring GCTB response to denosumab treatment. This retrospective study included eight patients (male, 3; female, 5; mean age, 33.4 years) diagnosed with GCTB, who had received treatment by denosumab and had undergone pre- and post-treatment non-contrast CT between January 2010 and December 2016. This study was approved by the institutional review board. Pre- and post-treatment size, histogram, and textural parameters of GCTBs were compared by the Wilcoxon signed-rank test. Pathological findings of five patients who underwent surgery after denosumab treatment were evaluated for assessment of treatment response. Relative to the baseline values, the tumor size had decreased, while the mean attenuation, standard deviation, entropy (all, P = 0.017), and skewness (P = 0.036) of the GCTBs had significantly increased post-treatment. Although the difference was statistically insignificant, the tumors also exhibited increased kurtosis, contrast, and inverse difference moment (P = 0.123, 0.327, and 0.575, respectively) post-treatment. Histologic findings revealed new bone formation and complete depletion or decrease in the number of osteoclast-like giant cells. The histogram and textural parameters of GCTBs changed significantly after denosumab treatment. Knowledge of the tendency towards increased mean attenuation and heterogeneity but increased local homogeneity in post-treatment CT histogram and textural features of GCTBs might aid in treatment planning and tumor response evaluation during denosumab treatment. Copyright © 2018. Published by Elsevier B.V.

Value of diffusion-weighted MRI and apparent diffusion coefficient measurements for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy.

PubMed

Iannicelli, Elsa; Di Pietropaolo, Marco; Pilozzi, Emanuela; Osti, Mattia Falchetto; Valentino, Maria; Masoni, Luigi; Ferri, Mario

2016-10-01

The aim of our study was to assess the performance value of magnetic resonance imaging (MRI) in the restaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) and in the identification of good vs. poor responders to neoadjuvant therapy. A total of 34 patients with locally advanced rectal cancer underwent MRI prior to and after CRT. T stage and tumor regression grade (TRG) on post-CRT MRI was compared with the pathological staging ypT and TRG. Tumor volume and the apparent diffusion coefficient (ADC) were measured using diffusion-weighted imaging (DWI) before and after neoadjuvant CRT; the percentage of tumor volume reduction and the change of ADC (ΔADC) was also calculated. ADC parameters and the percentage of tumor volume reduction were correlated to histopathological results. The diagnostic performance of ADC and volume reduction to assess tumor response was evaluated by calculating the area under the ROC curve and the optimal cut-off values. A significant correlation between the T stage and the TRG defined in DW-MRI after CRT and the ypT and the TRG observed on the surgical specimens was found (p = 0.001; p < 0.001). The mean post-CRT ADC and ΔADC in responder patients was significantly higher compared to non-responder ones (p = 0.001; p = 0.01). Furthermore, the mean post-CRT ADC values were significantly higher in tumors with T-downstage (p = 0.01). DW-MRI may have a significant role in the restaging and in the evaluation of post-CRT response of locally advanced rectal cancer. Quantitative analysis of DWI through ADC map may result in a promising noninvasive tool to evaluate the response to therapy.

Diagnostic Quality of Magnetic Resonance Imaging Interpretation for Peripheral Nerve Sheath Tumors: Can Malignancy Be Determined?

PubMed

Karsy, Michael; Guan, Jian; Ravindra, Vijay M; Stilwill, Sarah; Mahan, Mark A

2016-11-01

Background Optimal management of peripheral nerve sheath tumors including neurofibromas, schwannomas, and malignant peripheral sheath tumors (MPNSTs) is predicated on knowing the specific pathology. Magnetic resonance imagining (MRI) has the potential to provide insight in the tumor type, yet imprecision in diagnosis remains. We assessed the accuracy of preoperative imaging diagnoses by comparing them with postoperative histopathologic diagnoses. We specifically focus on erroneous diagnosis of MPNSTs. Methods We reviewed all pathologically confirmed cases of nerve sheath tumors treated at our institution retrospectively from 2007 to 2015. Pre- and postoperative imaging data were reviewed for imaging-based diagnosis and compared with postresection pathologic diagnosis. Results The study included 127 patients: 82 diagnosed with neurofibroma, 17 with schwannoma, 24 with MPNST, and 4 with other histology types. A mean age of 40.8 ± 20.4 years, mean tumor size of 4.3 ± 3.6 cm, and mean follow-up of 29.1 ± 21.6 months were recorded. A family history of neurofibromatosis type 1 (NF1) was seen in 58 patients (46%). A discordant diagnosis from preoperative imaging and postoperative pathology was found in 65 individuals (51%). Most discordant diagnoses ( n  = 34) were inconclusive interpretation of preoperative imaging; however, 10 patients were diagnosed with a benign or unknown lesion on preoperative imaging but had an MPNST on histopathology. Patients with MPNST were more likely than those with benign pathologies to have larger lesions (7.6 ± 4.8 cm versus 3.5 ± 3.3 cm; p  = 0.004); however, a statistically acceptable threshold value could not be found to separate benign from malignant lesions. Clinical factors, such as NF1 status, did not meaningfully improve preoperative diagnosis. Conclusions These results suggest that routine MRI is insufficient to guide surgical decision making reliably. Additional imaging techniques may be necessary to delineate the radiologic features of nerve sheath tumors to determine pathology more precisely. Georg Thieme Verlag KG Stuttgart · New York.

Diagnostic Ability of Percutaneous Needle Biopsy Immediately After Radiofrequency Ablation for Malignant Lung Tumors: An Initial Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasegawa, Takaaki, E-mail: t-hasegawa@aichi-cc.jp; Kondo, Chiaki; Sato, Yozo

PurposeTo evaluate the safety and diagnostic ability of percutaneous needle biopsy performed immediately after lung radiofrequency ablation (RFA).Materials and MethodsFrom May 2013 to April 2014, percutaneous needle biopsy was performed immediately after RFA for 3 patients (2 men and 1 woman, aged 57–76 years) who had lung tumors measuring 1.3–2.6 cm in diameter. All patients had prior history of malignancy, and all tumors were radiologically diagnosed as malignant. Obtained specimens were pathologically classified using standard hematoxylin and eosin staining.ResultsWe completed three planned sessions of RFA followed by percutaneous needle biopsy, all of which obtained tumor tissue that could be pathologically diagnosed. Twomore » tumors were metastatic from renal clear cell carcinoma and rectal adenocarcinoma, respectively; one tumor was primary lung adenocarcinoma. There was no death or major complication related to the procedures. Although pneumothorax occurred in two patients, these resolved without the need for aspiration or chest tube placement. Tumor seeding was not observed, but 21 months after the procedure, one case developed local tumor progression that was treated by additional RFA.ConclusionPathologic diagnosis was possible by needle biopsy immediately after RFA for lung tumors. This technique may reduce the risks and efforts of performing biopsy and RFA on separate occasions.« less

Prediction of Pathological Complete Response Using Endoscopic Findings and Outcomes of Patients Who Underwent Watchful Waiting After Chemoradiotherapy for Rectal Cancer.

PubMed

Kawai, Kazushige; Ishihara, Soichiro; Nozawa, Hiroaki; Hata, Keisuke; Kiyomatsu, Tomomichi; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

2017-04-01

Nonoperative management for patients with rectal cancer who have achieved a clinical complete response after chemoradiotherapy is becoming increasingly important in recent years. However, the definition of and modality used for patients with clinical complete response differ greatly between institutions, and the role of endoscopic assessment as a nonoperative approach has not been fully investigated. This study aimed to investigate the ability of endoscopic assessments to predict pathological regression of rectal cancer after chemoradiotherapy and the applicability of these assessments for the watchful waiting approach. This was a retrospective comparative study. This study was conducted at a single referral hospital. A total of 198 patients with rectal cancer underwent preoperative endoscopic assessments after chemoradiotherapy. Of them, 186 patients underwent radical surgery with lymph node dissection. The histopathological findings of resected tissues were compared with the preoperative endoscopic findings. Twelve patients refused radical surgery and chose watchful waiting; their outcomes were compared with the outcomes of patients who underwent radical surgery. The endoscopic criteria correlated well with tumor regression grading. The sensitivity and specificity for a pathological complete response were 65.0% to 87.1% and 39.1% to 78.3%. However, endoscopic assessment could not fully discriminate pathological complete responses, and the outcomes of patients who underwent watchful waiting were considerably poorer than the patients who underwent radical surgery. Eventually, 41.7% of the patients who underwent watchful waiting experienced uncontrollable local failure, and many of these occurrences were observed more than 3 years after chemoradiotherapy. The number of the patients treated with the watchful waiting strategy was limited, and the selection was not randomized. Although endoscopic assessment after chemoradiotherapy correlated with pathological response, it is unsuitable for surveillance of patients treated via a nonoperative approach. Incorporation of a "watchful waiting" strategy without establishing proper surveillance protocols and salvage strategies might result in poor local control.

Effects of letrozole on breast cancer micro-metastatic tumor growth in bone and lung in mice inoculated with murine 4T1 cells.

PubMed

Wang, Wendan; Belosay, Aashvini; Yang, Xujuan; Hartman, James A; Song, Huaxin; Iwaniec, Urszula T; Turner, Russell T; Churchwell, Mona I; Doerge, Daniel R; Helferich, William G

2016-06-01

Breast cancer (BC) is the leading cancer in women worldwide. Metastasis occurs in stage IV BC with bone and lung being common metastatic sites. Here we evaluate the effects of the aromatase inhibitor letrozole on BC micro-metastatic tumor growth in bone and lung metastasis in intact and ovariectomized (OVX) mice with murine estrogen receptor negative (ER-) BC cells inoculated in tibia. Forty-eight BALB/c mice were randomly assigned to one of four groups: OVX, OVX + Letrozole, Intact, and Intact + Letrozole, and injected with 4T1 cells intra-tibially. Letrozole was subcutaneously injected daily for 23 days at a dose of 1.75 µg/g body weight. Tumor progression was monitored by bioluminescence imaging (BLI). Following necropsy, inoculated tibiae were scanned via µCT and bone response to tumor was scored from 0 (no ectopic mineralization/osteolysis) to 5 (extensive ectopic mineralization/osteolysis). OVX mice had higher tibial pathology scores indicative of more extensive bone destruction than intact mice, irrespective of letrozole treatment. Letrozole decreased serum estradiol levels and reduced lung surface tumor numbers in intact animals. Furthermore, mice receiving letrozole had significantly fewer tumor colonies and fewer proliferative cells in the lung than OVX and intact controls based on H&E and Ki-67 staining, respectively. In conclusion, BC-inoculated OVX animals had higher tibia pathology scores than BC-inoculated intact animals and letrozole reduced BC metastases to lungs. These findings suggest that, by lowering systemic estrogen level and/or by interacting with the host organ, the aromatase inhibitor letrozole has the potential to reduce ER- BC metastasis to lung.

Assessing residual cancer cells using MRI and US after preoperative chemotherapy in primary breast cancer to omit surgery.

PubMed

Iwase, Madoka; Sawaki, Masataka; Hattori, Masaya; Yoshimura, Akiyo; Ishiguro, Junko; Kotani, Haruru; Gondo, Naomi; Adachi, Yayoi; Kataoka, Ayumi; Onishi, Sakura; Sugino, Kayoko; Iwata, Hiroji

2018-04-04

Enhanced magnetic resonance imaging (MRI) and ultrasonography (US) are used to assess residual lesions after preoperative chemotherapy before surgery. However, residual lesion assessments based on preoperative imaging often differ from postoperative pathologic diagnoses. We retrospectively reviewed the accuracy of preoperative residual lesion assessments, including ductal carcinoma in situ (DCIS) cases to find criteria for cases in which surgery can be omitted. We reviewed 201 patients who received preoperative chemotherapy and surgery in our hospital from January 2013 to November 2016. Presurgical evaluations regarding the possible existence of residual lesions, and clinical Complete Response (cCR) or non-cCR, were compared with postoperative pathological diagnoses. Of the 201 patients, 52 were diagnosed with cCR, and 39 with pathological complete response (pCR). Predictions for residual lesions were 86.4% sensitive, 76.9% specific, and 84.6% accurate. When patients were divided into 4 groups by estrogen receptor (ER) and HER2 status, sensitivity in each group was ER + /HER2 - : 91.4%; ER - /HER2 - : 94.1%; ER + /HER2 + : 78.6%; and ER - /HER2 + : 78.5%. Of the 22 patients preoperatively assessed with cCR, but diagnosed with non-pCR, the median invasive residual tumor size was 2 mm (range 0-46 mm); 5 patients (22.7%) had only DCIS. Predicting residual lesions after preoperative chemotherapy by using MRI and US is a reasonable strategy. However, current methods are inadequate for identifying patients who can omit surgery; therefore, a new strategy for detecting small tumors in these patients is needed.

Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zampino, Maria Giulia; Magni, Elena; Leonardi, Maria Cristina

2009-10-01

Purpose: To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). Methods and Materials: From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m{sup 2}, orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m{sup 2}, orally, twice daily, 14 days on 7 days off) up until 2 weeksmore » before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. Results: Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors {<=}6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). Conclusions: Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.« less

[Soft tissue sarcomas: the role of histology and molecular pathology for differential diagnosis].

PubMed

Poremba, C

2006-01-01

Soft tissue sarcomas include a wide spectrum of different entities. The so-called small round blue cell tumors and spindle cell tumors are difficult to classify based solely on conventional histology. To identify different subtypes of tumors special histochemical and immunohistochemical techniques are necessary. Analysis of protein expression by immunohistochemistry provides a helpful tool to investigate the histogenesis of tumors. A basic spectrum of antibodies should be included to study these tumors: Desmin and myogenin (or MyoD1) for skeletal differentiation; S-100, NSE, CD56, and synaptophysin for neural/neuroendocrine differentiation; CD3, CD20, and CD79 alpha for malignant lymphomas; CD34, sm-actin, and beta-catenin for spindle cell tumors; additional antigens, e. g. Ki-67 and p 53, for estimation of proliferation and tumor suppressor gene malfunctions. Nevertheless, the molecular analysis of soft tissue sarcomas is necessary for demonstration of specific translocations or gene defects to specify and proof a diagnosis. For this purpose, RT-PCR for RNA expression analysis of gene fusion transcripts and multi-color FISH for analysis of chromosomal rearrangements are used. Further investigations, using DNA microrrays may help to subclassify such tumors, with respect to prognosis or prediction of therapeutic response.

Cyclophosphamide dose intensification may circumvent anthracycline resistance of p53 mutant breast cancers.

PubMed

Lehmann-Che, Jacqueline; André, Fabrice; Desmedt, Christine; Mazouni, Chafika; Giacchetti, Sylvie; Turpin, Elisabeth; Espié, Marc; Plassa, Louis-François; Marty, Michel; Bertheau, Philippe; Sotiriou, Christos; Piccart, Martine; Symmans, W Fraser; Pusztai, Lajos; de Thé, Hugues

2010-01-01

The predictive value of p53 for the efficacy of front-line anthracycline-based chemotherapy regimens has been a matter of significant controversy. Anthracyclines are usually combined with widely different doses of alkylating agents, which may significantly modulate tumor response to these combinations. We analyzed three series of de novo stage II-III breast cancer patients treated front line with anthracycline-based regimens of various cyclophosphamide dose intensities: 65 patients with estrogen receptor (ER)(-) tumors treated with anthracyclines alone (Institut Jules Bordet, Brussels), 51 unselected breast cancer patients treated with intermediate doses of cyclophosphamide (MD Anderson Cancer Center, Houston, TX), and 128 others treated with a dose-dense anthracycline-cyclophosphamide combination (St. Louis, Paris). After chemotherapy and surgery, pathologic complete response (pCR) was evaluated. p53 status was determined by a yeast functional assay on the pretreatment tumor sample. In a multivariate analysis of the pooled results, a lack of ER expression and high-dose cyclophosphamide administration were associated with a higher likelihood of pCR. A sharp statistical interaction was detected between p53 status and cyclophosphamide dose intensity. Indeed, when restricting our analysis to patients with ER(-) tumors, we confirmed that a mutant p53 status was associated with anthracycline resistance, but found that p53 inactivation was required for response to the dose-intense alkylating regimen. The latter allowed very high levels of pCR in triple-negative tumors. Thus, our data strongly suggest that cyclophosphamide dose intensification in ER(-) p53-mutated breast cancer patients could significantly improve their response.

Favorable Prognosis in Patients With High-Grade Glioma With Radiation Necrosis: The University of Colorado Reoperation Series

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusthoven, Kyle E.; Olsen, Christine; Franklin, Wilbur

Purpose: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). Methods and Materials: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if {>=}80% of the specimen was necrotic and as tumor recurrence if {>=}20% was tumor. Predictors of survival were analyzed using log-rank comparisons andmore » Cox proportional hazards regression. Results: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p = 0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. Conclusions: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.« less

DTI fiber tracking to differentiate demyelinating diseases from diffuse brain stem glioma.

PubMed

Giussani, Carlo; Poliakov, Andrew; Ferri, Raymond T; Plawner, Lauren L; Browd, Samuel R; Shaw, Dennis W W; Filardi, Tanya Z; Hoeppner, Corrine; Geyer, J Russell; Olson, James M; Douglas, James G; Villavicencio, Elisabeth H; Ellenbogen, Richard G; Ojemann, Jeffrey G

2010-08-01

Intrinsic diffuse brainstem tumors and demyelinating diseases primarily affecting the brainstem can share common clinical and radiological features, sometimes making the diagnosis difficult especially at the time of first clinical presentation. To explore the potential usefulness of new MRI sequences in particular diffusion tensor imaging fiber tracking in differentiating these two pathological entities, we review a series of brainstem tumors and demyelinating diseases treated at our institution. The clinical history including signs and symptoms and MRI findings of three consecutive demyelinating diseases involving the brainstem that presented with diagnostic uncertainty and three diffuse intrinsic brainstem tumors were reviewed, along with a child with a supratentorial tumor for comparison. Fiber tracking of the pyramidal tracts was performed for each patient using a DTI study at the time of presentation. Additionally Fractional Anisotropy values were calculated for each patient in the pons and the medulla oblongata. Routine MR imaging was unhelpful in differentiating between intrinsic tumor and demyelination. In contrast, retrospective DTI fiber tracking clearly differentiated the pathology showing deflection of the pyramidal tracts posteriorly and laterally in the case of intrinsic brainstem tumors and, in the case of demyelinating disease, poorly represented and truncated fibers. Regionalized FA values were variable and of themselves were not predictive either pathology. DTI fiber tracking of the pyramid tracts in patients with suspected intrinsic brainstem tumor or demyelinating disease presents two clearly different patterns that may help in differentiating between these two pathologies when conventional MRI and clinical data are inconclusive. Copyright 2010 Elsevier Inc. All rights reserved.

Congenital renal rhabdoid tumor with placental metastases: immunohistochemistry, cytogenetic, and ultrastructural findings.

PubMed

de Tar, Michael; Sanford Biggerstaff, Julie

2006-01-01

Malignant congenital tumors of fetal origin are rare lesions, the most common type being congenital neuroblastoma. Although prenatal diagnosis is possible in large tumors, occasionally the tumor will be diagnosed first by its metastatic involvement of the placenta. Placental metastases can reflect either maternal or fetal primary sites, and each has relatively specific patterns of placental involvement. We describe the clinical and pathologic features of a widely metastatic congenital renal rhabdoid tumor with its placental and autopsy findings, and include the immunohistochemical, cytogenetic, and ultrastructural features. The pathologic features of the placenta in congenital renal rhabdoid tumor with placental metastasis have not been previously described. The examination of the placenta in this case led to the initial diagnosis and obviated the need for additional diagnostic procedures.

Tumor Size of Invasive Breast Cancer on Magnetic Resonance Imaging and Conventional Imaging (Mammogram/Ultrasound): Comparison with Pathological Size and Clinical Implications.

PubMed

Haraldsdóttir, K H; Jónsson, Þ; Halldórsdóttir, A B; Tranberg, K-G; Ásgeirsson, K S

2017-03-01

In Landspitali University Hospital, magnetic resonance imaging is used non-selectively in addition to mammogram and ultrasound in the preoperative assessment of breast cancer patients. The aim of this study was to assess invasive tumor size on imaging, compare with pathological size and evaluate the impact of magnetic resonance imaging on the type of surgery performed. All women with invasive breast cancer, diagnosed in Iceland, between 2007 and 2009 were reviewed retrospectively. In all, 438 of 641 (68%) patients diagnosed had preoperative magnetic resonance imaging. Twelve patients treated with neoadjuvant chemotherapy were excluded and 65 patients with multifocal or contralateral disease were assessed separately. Correlations between microscopic and radiologic tumor sizes were relatively weak. All imaging methods were inaccurate especially for large tumors, resulting in an overall underestimation of tumor size for these tumors. Magnetic resonance imaging under- and overestimated pathological tumor size by more than 10 mm in 16/348 (4.6%) and 26/348 patients (7.5%), respectively. In 19 patients (73%), overestimation of size was seen exclusively on magnetic resonance imaging. For tumors under- or overestimated by magnetic resonance imaging, the mastectomy rates were 56% and 65%, respectively, compared to an overall mastectomy rate of 43%. Of 51 patients diagnosed with multifocal disease on pathology, 19 (37%) were diagnosed by mammogram or ultrasound and 40 (78%) by magnetic resonance imaging resulting in a total detection rate of 84% (43 patients). Fourteen (3%) patients were diagnosed preoperatively with contralateral disease. Of those tumors, all were detected on magnetic resonance imaging but seven (50%) were also detected on mammogram or ultrasound or both. Our results suggest that routine use of magnetic resonance imaging may result in both under- and overestimation of tumor size and increase mastectomy rates in a small proportion of patients. Magnetic resonance imaging aids in the diagnosis of contralateral and multifocal disease.

Effect of long interval between hyperthermochemoradiation therapy and surgery for rectal cancer on apoptosis, proliferation and tumor response.

PubMed

Kato, Toshihide; Fujii, Takaaki; Ide, Munenori; Takada, Takahiro; Sutoh, Toshinaga; Morita, Hiroki; Yajima, Reina; Yamaguchi, Satoru; Tsutsumi, Soichi; Asao, Takayuki; Oyama, Tetsunari; Kuwano, Hiroyuki

2014-06-01

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

General pathologist-helper: The new medical app about general pathology.

PubMed

Fernández-Vega, Iván

2015-01-01

Smartphone applications (apps) have become increasingly prevalent in medicine. Due to most pathologists, pathology trainees, technicians, and medical students use smartphones; apps can be a different way for general pathology education. "General pathologist-helper (GP-HELPER)" is a novel app developed as a reference tool in general pathology and especially for general pathologists, developed for Android and iOS platforms. "GP-HELPER," was created using Mobincube website platform. This tool also integrates "FORUM GP-HELPER," an external website created using Miarroba website (http://forum-gp-helper.mboards.com) and "COMMUNITY GP-HELPER" a multichannel chat created using Chatango website platform. The application was released in July 2015, and it is been periodically updated since then. The app has permanent information (offline data) about different pathology protocols (TNM latest edition, protocols regarding management of tumors of unknown primary origin, and flowcharts for some of the most difficult tumors to diagnose) and a database with more than 5000 immunohistochemistry results from different tumors. Online data have links to more than 1100 reference pathology video lectures, 250 antibodies information, more than 70 pathology association websites, 46 pathology providers, and 78 outstanding pathology journal websites. Besides this information, the app has two interactive places such as "FORUM GP-HELPER" and "COMMUNITY GP-HELPER" that let users to stay in touch everywhere and every time. Expert consult section is also available. "GP-HELPER" pretends to integrate offline and online data about pathology with two interactive external places in order to represent a reference tool for general pathologists and associate members.

Functional Assessment of Synoptic Pathology Reporting for Ovarian Cancer.

PubMed

Słodkowska, Janina; Cierniak, Szczepan; Patera, Janusz; Kopik, Jarosław; Baranowski, Włodzimierz; Markiewicz, Tomasz; Murawski, Piotr; Buda, Irmina; Kozłowski, Wojciech

2016-01-01

Ovarian cancer has one of the highest death/incidence rates and is commonly diagnosed at an advanced stage. In the recent WHO classification, new histotypes were classified which respond differently to chemotherapy. The e-standardized synoptic cancer pathology reports offer the clinicians essential and reliable information. The aim of our project was to develop an e-template for the standardized synoptic pathology reporting of ovarian carcinoma [based on the checklist of the College of American Pathologists (CAP) and the recent WHO/FIGO classification] to introduce a uniform and improved quality of cancer pathology reports. A functional and qualitative evaluation of the synoptic reporting was performed. An indispensable module for e-synoptic reporting was developed and integrated into the Hospital Information System (HIS). The electronic pathology system used a standardized structure with drop-down lists of defined elements to ensure completeness and consistency of reporting practices with the required guidelines. All ovarian cancer pathology reports (partial and final) with the corresponding glass slides selected from a 1-year current workflow were revised for the standard structured reports, and 42 tumors [13 borderline tumors and 29 carcinomas (mainly serous)] were included in the study. Analysis of the reports for completeness against the CAP checklist standard showed a lack of pTNM staging in 80% of the partial or final unstructured reports; ICD-O coding was missing in 83%. Much less frequently missed or unstated data were: ovarian capsule infiltration, angioinvasion and implant evaluation. The e-records of ovarian tumors were supplemented with digital macro- and micro-images and whole-slide images. The e-module developed for synoptic ovarian cancer pathology reporting was easily incorporated into HIS.CGM CliniNet and facilitated comprehensive reporting; it also provided open access to the database for concerned recipients. The e-synoptic pathology reports appeared more accurate, clear and conclusive than traditional narrative reports. Standardizing structured reporting and electronic tools allows open access and downstream utilization of pathology data for clinicians and tumor registries. © 2016 S. Karger AG, Basel.

[Clinical analysis of 31 patients with gastric stromal tumors].

PubMed

Li, Junxia; Liu, Ping; Wang, Huahong; Yu, Jing; Xie, Pengyan; Liu, Xinguang

2002-11-01

To investigate the clinical manifestations, diagnosis and treatment of gastric stromal tumors. 31 patients with gastric stromal tumors treated from 1993, 1 - 2001, 9 were analyzed retrospectively. All cases were diagnosed by pathological and immunohistochemistry examinations. According to Levin's standard combining with Hurliman's and Goldbum's methods, the patients were classified. There are no significant difference between male and female patients. 50 - 60 years old patients have high incidence. The distribution of gastric tromal tumors is fundus > body > antrum. Diagnosis of this condition is sometimes difficult and treatment is often delayed because patients usually present with nonspecific abdominal symptoms. The main manifestations of gastric stromal tumors are upper gastrointestinal hemorrhage 61.3% (19/31), 7 patients with acute hemorrhage and 12 with chronic hemorrhage. Most of them were malignant. Abdominal malaises and/or distention 32.3% (10/31) and abdominal pain 22.6% (7/31). Gastroscopy, ultrasound gastroscopy, computed tomography, B type ultrasound and upper gastrointestinal X-ray series are helpful to diagnosis. But the final diagnosis is decided by pathological and immunohistochemistry examinations. Gastric stromal tumors exhibit consistent immunohistochemical expressions of CD(117) and/or CD(34). The operative treatment is thought of the first choice. Effect of the chemotherapy isn't satisfied. There is no standard chemotherapy for gastric stromal tumors. Gastric stromal tumor is a kind of separated submucosal tumor which is different from leiomyoma, leiomyosarcoma and neurogenic tumors. Pathological and immunohistochemistry inspectations are very important to make clear diagnosis. Early diagnosis and rational treatment are the keys to improve the prognosis.

Surgical pathology in sub-Saharan Africa--volunteering in Malawi.

PubMed

Berezowska, Sabina; Tomoka, Tamiwe; Kamiza, Steve; Milner, Danny A; Langer, Rupert

2012-04-01

The breadth of material found in surgical pathology services in African countries differs from the common spectrum of "the West". We report our experience of a voluntary work in the pathology departments of Blantyre and Lilongwe, Malawi. During a 6-week period, 405 cases (378 histology and 27 cytology cases) were processed. The vast majority showed significant pathological findings (n = 369; 91.1 %): 175 cases (47.4 %) were non-tumoral conditions with predominance of inflammatory lesions, e.g., schistosomiasis (n = 11) and tuberculosis (n = 11). There were 39 (10.6 %) benign tumors or tumor-like lesions. Intraepithelial neoplasia of the cervix uteri dominated among premalignant conditions (n = 15; 4.1 %). The large group of malignancies (n = 140; 37.9 %) comprised 11 pediatric tumors (e.g., rhabdomyosarcoma, small blue round cell tumors) and 129 adult tumors. Among women (n = 76), squamous cell carcinomas (SCCs) of the cervix uteri predominated (n = 25; 32.9 %), followed by breast carcinomas (n = 12; 15.8 %) and esophageal SCC (n = 9; 11.8 %). Males (n = 53) most often showed SCC of the esophagus (n = 9; 17.0 %) and of the urinary bladder (n = 7; 13.2 %). Lymphomas (n = 7) and Kaposi's sarcomas (n = 6) were less frequent. Differences compared to the western world include the character of the conditions in general, the spectrum of inflammatory lesions, and the young age of adult tumor patients (median 45 years; range 18-87 years). Providing pathology service in a low-resource country may be handicapped by lack of personnel, inadequate material resources, or insufficient infrastructure. Rotating volunteers offer a bridge for capacity building of both personnel and the local medical service; in addition, the volunteer's horizons are broadened professionally and personally.

Augmentation of Chemotherapeutic Infusion Effect by TSU-68, an Oral Targeted Antiangiogenic Agent, in a Rabbit VX2 Liver Tumor Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hyo-Cheol; Chung, Jin Wook, E-mail: chungjw@snu.ac.kr; Choi, Seung Hong

Purpose: This study was designed to investigate the in vivo effects of combination therapy with TSU-68 and chemotherapeutic infusion in a rabbit VX2 liver tumor model. Methods: This study was approved by the animal care committee at our institute. Three weeks before chemotherapeutic infusion, VX2 carcinoma was implanted into the livers of 32 rabbits. One week after chemotherapeutic infusion, vehicle was administered orally for 3 weeks in the control group (n = 16), and TSU-68 was administered orally at a daily dose of 200 mg/kg for 3 weeks in the treated group (n = 16). Computed tomography (CT) was performedmore » before and 1, 2, 3, and 4 weeks after chemotherapeutic infusion. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) on CT scan. The maximum thickness of viable tumor was measured on microscopic sections. Results: According to the RECIST, stable disease was observed in 9 (56%) rabbits and progressive disease in 7 (44%) in the control group, whereas partial response was observed in 1 (6%) rabbit and stable disease in 15 (94%) in the treated group. On pathologic examination, a viable lesion was present in 12 (75%) rabbits in the control group and in 6 (38%) rabbits in the treated group (P = 0.073). The mean maximum thickness of viable tumor in the treated group was significantly smaller than that in the control group (0.74 mm vs. 3.39 mm; P = 0.02). Conclusions: Oral administration of TSU-68 augmented the effect of chemotherapeutic infusion in a rabbit VX2 liver tumor model.« less

Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.

PubMed

Bertheau, Philippe; Turpin, Elisabeth; Rickman, David S; Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-03-01

In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.

Clinical Activity of mTOR Inhibition With Sirolimus in Malignant Perivascular Epithelioid Cell Tumors: Targeting the Pathogenic Activation of mTORC1 in Tumors

PubMed Central

Wagner, Andrew J.; Malinowska-Kolodziej, Izabela; Morgan, Jeffrey A.; Qin, Wei; Fletcher, Christopher D.M.; Vena, Natalie; Ligon, Azra H.; Antonescu, Cristina R.; Ramaiya, Nikhil H.; Demetri, George D.; Kwiatkowski, David J.; Maki, Robert G.

2010-01-01

Purpose Perivascular epithelioid cell tumors (PEComas) represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. There is no known effective therapy for PEComa, and the molecular pathophysiology of aberrant mTOR signaling provided us with a scientific rationale to target this pathway therapeutically. On this mechanistic basis, we treated three consecutive patients with metastatic PEComa with an oral mTOR inhibitor, sirolimus. Patients and Methods Patients with advanced PEComa were treated with sirolimus and consented to retrospective collection of data from their medical records and analysis of archival tumor specimens. Tumor response was determined by computed tomography scans obtained at the clinical discretion of the treating physicians. Tumors were assessed for immunohistochemical evidence of mTORC1 activation and genetic evidence of alterations in TSC1 and TSC2. Results Radiographic responses to sirolimus were observed in all patients. PEComas demonstrated loss of TSC2 protein expression and evidence of baseline mTORC1 activation. Homozygous loss of TSC1 was identified in one PEComa. Conclusion Inhibition of mTORC1, pathologically activated by loss of the TSC1/TSC2 tumor suppressor complex, is a rational mechanistic target for therapy in PEComas. The clinical activity of sirolimus in PEComa additionally strengthens the pathobiologic similarities linking PEComas to other neoplasms related to the tuberous sclerosis complex. PMID:20048174

The perioperative outcomes between renal hilar and non-hilar tumors following robotic-assisted partial nephrectomy (RAPN).

PubMed

Lu, Shih-Yen; Chung, Hsiao-Jen; Huang, Eric Yi-Hsiu; Lin, Tzu-Pin; Lin, Alex T L

2018-03-15

The aim of this study was to compare the perioperative outcomes between renal hilar tumors and non-hilar tumors after robotic-assisted partial nephrectomy (RAPN). A retrospective review of consecutive patients who underwent RAPN from December 2009 to September 2015 at our institution was recruited. Perioperative outcomes including demographic characteristics, perioperative, pathological and renal function outcomes were compared between the hilar group (n = 30) and non-hilar group (n = 170). In characteristics, hilar group was younger (52.4 vs. 58 years, p = 0.04) and had less body mass index (23.7 vs. 25.4 kg/m 2 , p = 0.018). Hilar group had larger tumor size (4.8 vs. 3.7 cm, p = 0.009), higher Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score (10.7 vs. 8.5, p < 0.001) and higher RENAL (radius, exophytic/endophytic properties of the tumor, nearness of tumor deepest portion to the collecting system or sinus, anterior/posterior description and the location relative to polar lines) score (9.0 vs. 7.4, p < 0.001). Hilar tumor was associated with longer operative time (293.6 vs. 240.5 min, p = 0.001) and warm ischemia time (39.9 vs. 21.8 min, p < 0.001). But there was no statistically difference in estimated blood loss (EBL), postoperative stay and complication rate. For pathological outcomes, there was no difference of positive margin rate and pathological T stage between these groups. For renal function outcomes, hilar tumor patients had no difference of the change of creatinine and estimated glomerular filtration rate (eGFR) at postoperative 6 and 12 month as compared with non-hilar tumor patients. For renal hilar tumor, RAPN could provide acceptable results of perioperative, pathological and renal function outcome as compared with non-hilar tumor group. Thus RAPN is a safe and effective nephron-sparing surgery technique for renal hilar tumors. Copyright © 2018. Published by Elsevier Taiwan LLC.

Correlation between Standardized Uptake Value of 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and Pathological Classification of Neuroendocrine Tumors.

PubMed

Kaewput, Chalermrat; Suppiah, Subapriya; Vinjamuri, Sobhan

2018-01-01

The aim of our study was to correlate tumor uptake of 68 Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68 Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUV max ) and averaged SUV SUV mean of "main tumor lesions" were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 <2, intermediate grade: Ki-67 3-20, and high grade: Ki-67 >20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUV max of tumor and Ki-67 index ( r = -0.241) and negatively poor agreement between SUV mean of tumor and Ki-67 index ( r = -0.094). SUV max of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUV mean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUV max and SUV mean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68 Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68 Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68 Ga-DOTA-NOC may be associated with aggressive behavior and may, therefore, result in poor prognosis.

Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.

PubMed

Viganò, Luca; Capussotti, Lorenzo; De Rosa, Giovanni; De Saussure, Wassila Oulhaci; Mentha, Gilles; Rubbia-Brandt, Laura

2013-11-01

We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival rate of 23.3% vs 45.7% if absent, P = 0.017; 0% vs 42.3%, P = 0.032, respectively). TRG was confirmed to be a crucial prognostic determinant. CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. Steatosis was found to have a protective effect on survival. Micrometastases significantly impacted prognosis assessment.

Colorectal tumors: the histology report.

PubMed

Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

2011-03-01

Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

[The Value of High Frequency Color Doppler Ultrasonography in the Diagnosis of Solid Skin Tumorsa-a Preliminary Study].

PubMed

Zhong, Lin; Tang, Yuan-Jiao; Yang, Yu-Jia; Qiu, Li

2017-01-01

To explore the value of high frequency color doppler ultrasonography in differentiating benign and malignant skin solid tumors. Clinical and ultrasonic data of cutaneous solid tumors confirmed by pathology in our hospital were collected. The differences in clinical and sonographic features between benign and malignant tumors were statistically analyzed. A total of 512 patients, involving 527 cases of skin solid tumors, were enrolled in this study. The ultrasonic detected 99.43% of the cases, with 99.02% accuracy in locating the lesions. The benign and malignant tumors showed differences in patient age, location, multiple occurance, location and depth, surface skin condition, tumor size, echo, morphology, uniformity, calcification, blood flow status, tumor rear area and peripheral echo, and pathological requests ( P <0.05). High frequency ultrasound has excellent detection rate of skin tumors, which can locate invasion depth of skin accurately. Benign and malignant skin tumors show differences in a number of clinical and ultrasound features.

Issues of diagnostic review in brain tumor studies: from the Brain Tumor Epidemiology Consortium.

PubMed

Davis, Faith G; Malmer, Beatrice S; Aldape, Ken; Barnholtz-Sloan, Jill S; Bondy, Melissa L; Brännström, Thomas; Bruner, Janet M; Burger, Peter C; Collins, V Peter; Inskip, Peter D; Kruchko, Carol; McCarthy, Bridget J; McLendon, Roger E; Sadetzki, Siegal; Tihan, Tarik; Wrensch, Margaret R; Buffler, Patricia A

2008-03-01

Epidemiologists routinely conduct centralized single pathology reviews to minimize interobserver diagnostic variability, but this practice does not facilitate the combination of studies across geographic regions and institutions where diagnostic practices differ. A meeting of neuropathologists and epidemiologists focused on brain tumor classification issues in the context of protocol needs for consortial studies (http://epi.grants.cancer.gov/btec/). It resulted in recommendations relevant to brain tumors and possibly other rare disease studies. Two categories of brain tumors have enough general agreement over time, across regions, and between individual pathologists that one can consider using existing diagnostic data without further review: glioblastomas and meningiomas (as long as uniform guidelines such as those provided by the WHO are used). Prospective studies of these tumors benefit from collection of pathology reports, at a minimum recording the pathology department and classification system used in the diagnosis. Other brain tumors, such as oligodendroglioma, are less distinct and require careful histopathologic review for consistent classification across study centers. Epidemiologic study protocols must consider the study specific aims, diagnostic changes that have taken place over time, and other issues unique to the type(s) of tumor being studied. As diagnostic changes are being made rapidly, there are no readily available answers on disease classification issues. It is essential that epidemiologists and neuropathologists collaborate to develop appropriate study designs and protocols for specific hypothesis and populations.

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach

PubMed Central

Blanco-Calvo, Moisés; Concha, Ángel; Figueroa, Angélica; Garrido, Federico; Valladares-Ayerbes, Manuel

2015-01-01

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice. PMID:26084042

Giant intrascrotal embryonal rhabdomyosarcoma in an adult: a case report and review of the literature.

PubMed

Gong, Wentao; Gao, Qingqiang; Xu, Zhipeng; Dai, Yutian

2018-05-28

Intrascrotal embryonal rhabdomyosarcoma in adults is a rare tumor with high aggression and a poor prognosis. We report our patient's case and review the relevant literature to improve the understanding of this rare disease. A 21-year-old Han Chinese man presented to our hospital with a right intrascrotal mass of 1 year's duration. His physical examination revealed an enlarged right scrotum containing a huge tender mass measuring about 10 × 7 cm. Ordinary and contrast-enhanced ultrasonography showed a solid mass in the right scrotum, which was suspected to be a malignant tumor. An abdominopelvic computed tomographic scan revealed metastases in the retroperitoneal lymph nodes. The patient was diagnosed with malignant testicular tumor and underwent a right radical orchiectomy by an inguinal approach. Postoperative pathological examination suggested an intrascrotal embryonal rhabdomyosarcoma. Intrascrotal embryonal rhabdomyosarcoma is a rare but highly aggressive tumor. Clinical and imaging manifestations of this tumor are nonspecific, so the definitive diagnosis depends on postoperative pathology and immunohistochemistry. Early suspicion, radical orchiectomy, accurate pathologic diagnosis, and adjuvant chemotherapy and/or radiotherapy are the keys to optimal prognosis.

Modern Soft Tissue Pathology | Center for Cancer Research

Cancer.gov

This book comprehensively covers modern soft tissue pathology and includes both tumors and non-neoplastic entities. Soft tissues make up a large bulk of the human body, and they are susceptible to a wide range of diseases. Many soft-tissue tumors are biologically very aggressive, and the chance of them metastasizing to vital organs is quite high. In recent years, the outlook

Effectiveness of Radiotherapy in Myxoid Sarcomas Is Associated With a Dense Vascular Pattern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vreeze, Ronald S.A. de; Jong, Daphne de; Haas, Rick L.

2008-12-01

Purpose: Surgery and adjuvant radiotherapy (RT) have long been the standard treatment for most deep-seated sarcomas; however, since the randomized trial from the National Cancer Institute of Canada, which described similar local control for pre- vs. postoperative RT, both modalities are now widely accepted. As a group, sarcomas are classified as radiation resistant. The subgroup of myxoid liposarcoma (MLS), a sarcoma with a typical vascular crow's feet pattern, is highly radiosensitive, but a mechanism for this phenomenon is unknown. Here we describe our results with preoperative RT and propose a mechanism explaining the high sensitivity based on the distinctive vascularizationmore » pattern of MLS. Methods and Materials: Between 2002 and 2006, 31 sarcoma patients, including 10 with MLS, underwent preoperative RT at our institute. Resected specimens were histologically evaluated, focusing on classification, grade, and vascularization patterns. Results: Twenty sarcomas showed more than 80% pathologic response after preoperative RT. A pathologic complete response was found in all 'pure' MLS specimens after preoperative RT (n = 8). There were no pathologic complete responses in the remaining sarcoma patients (n = 23), although 12 showed 80% to 90% pathologic response. In contrast to the remaining RT-resistant sarcomas, the highly responding specimens contained branching vasculature, partial thrombus formation and inflammation of medium sized arterioles, similar to the vascular changes in MLS. Conclusions: Both MLS and sarcomas with MLS-like vasculature are highly radiosensitive. Radiation sensitivity may be explained by changes in medium-sized arterioles, obstructing the specific crow's feet vascularization and inducing hypoxia with secondary tumor cell death.« less

The p53 breast cancer tissue biomarker in Indian women

PubMed Central

Patil, Vinayak W; Tayade, Mukund B; Pingale, Sangeeta A; Dalvi, Shubhangi M; Rajekar, Rajesh B; Deshmukh, Hemkant M; Patil, Shital D; Singhai, Rajeev

2011-01-01

Background Combination chemotherapy is highly effective in locally advanced breast cancer. A negative expression of biomarker p53 indicates a higher chance of responding to this regimen. Patients’ p53 status may be used as a biological cancer marker to identify those who would benefit from more aggressive treatments. Aims The role of p53 in modulating apoptosis has suggested that it may affect the efficacy of anticancer agents. p53 alterations in 80 patients with locally advanced breast cancer IIIB undergoing neoadjuvant chemotherapy were prospectively evaluated. Materials and methods Patients received three cycles of paclitaxel (175 mg/m2) and doxorubicin (60 mg/m2) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression, using immunohistochemistry and DNA sequencing. Results An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of 25 patients who obtained a complete clinical response, only two were classified as p53-positive (P = 0.004, χ2). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, χ2). Conclusion Immunohistochemical (IHC) analysis has been shown to be a prognostic factor for patients with breast cancer in India. Paclitaxel is one of the most promising anticancer agents for the therapy of breast cancer, where it has also shown activity in tumors resistant to doxorubicin. PMID:24367177

[Clinicopathologic characteristics of hemangiopericytoma/solitary fibrous tumor with giant cells].

PubMed

Wang, Hai-yan; Fan, Qin-he; Gong, Qi-xing; Wang, Zheng

2009-03-01

To study the pathological characteristics, diagnosis and differential diagnoses of hemangiopericytoma-solitary fibrous tumor with giant cells. Pathological characteristics of seven cases of orbital and extraorbital hemangiopericytoma-solitary fibrous tumors with giant cells were evaluated by HE and immunohistochemistry (EnVision method). Two cases were located in the orbit, one of which had recurred. Five cases were located in the extraorbital regions. Histologically, the tumors were well-circumscribed and composed of non-atypical, round to spindle cells with collagen deposition in the stroma. The tumors had prominent vasculatures and in areas, pseudovascular spaces lined by multinucleated giant cells lining which were also present in the stroma. Immunohistochemically, both neoplastic cells and multinucleate giant cells expressed CD34. Seven patients underwent tumor excision and were well and without tumor recurrence upon the clinical follow-up. Hemangiopericytoma-solitary fibrous tumor with giant cells is an intermediate soft tissue tumor. It typically involves the orbital or extraorbital regions. Histologically, the tumor should be distinguished from giant cell fibroblastoma, pleomorphic hyalinzing angiectatic tumor of soft part and angiomatoid fibrous histiocytoma.

Quantitative ultrasound assessment of breast tumor response to chemotherapy using a multi-parameter approach

PubMed Central

Tadayyon, Hadi; Sannachi, Lakshmanan; Gangeh, Mehrdad; Sadeghi-Naini, Ali; Tran, William; Trudeau, Maureen E.; Pritchard, Kathleen; Ghandi, Sonal; Verma, Sunil; Czarnota, Gregory J.

2016-01-01

Purpose This study demonstrated the ability of quantitative ultrasound (QUS) parameters in providing an early prediction of tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). Methods Using a 6-MHz array transducer, ultrasound radiofrequency (RF) data were collected from 58 LABC patients prior to NAC treatment and at weeks 1, 4, and 8 of their treatment, and prior to surgery. QUS parameters including midband fit (MBF), spectral slope (SS), spectral intercept (SI), spacing among scatterers (SAS), attenuation coefficient estimate (ACE), average scatterer diameter (ASD), and average acoustic concentration (AAC) were determined from the tumor region of interest. Ultrasound data were compared with the ultimate clinical and pathological response of the patient's tumor to treatment and patient recurrence-free survival. Results Multi-parameter discriminant analysis using the κ-nearest-neighbor classifier demonstrated that the best response classification could be achieved using the combination of MBF, SS, and SAS, with an accuracy of 60 ± 10% at week 1, 77 ± 8% at week 4 and 75 ± 6% at week 8. Furthermore, when the QUS measurements at each time (week) were combined with pre-treatment (week 0) QUS values, the classification accuracies improved (70 ± 9% at week 1, 80 ± 5% at week 4, and 81 ± 6% at week 8). Finally, the multi-parameter QUS model demonstrated a significant difference in survival rates of responding and non-responding patients at weeks 1 and 4 (p=0.035, and 0.027, respectively). Conclusion This study demonstrated for the first time, using new parameters tested on relatively large patient cohort and leave-one-out classifier evaluation, that a hybrid QUS biomarker including MBF, SS, and SAS could, with relatively high sensitivity and specificity, detect the response of LABC tumors to NAC as early as after 4 weeks of therapy. The findings of this study also suggested that incorporating pre-treatment QUS parameters of a tumor improved the classification results. This work demonstrated the potential of QUS and machine learning methods for the early assessment of breast tumor response to NAC and providing personalized medicine with regards to the treatment planning of refractory patients. PMID:27105515

Quantitative ultrasound assessment of breast tumor response to chemotherapy using a multi-parameter approach.

PubMed

Tadayyon, Hadi; Sannachi, Lakshmanan; Gangeh, Mehrdad; Sadeghi-Naini, Ali; Tran, William; Trudeau, Maureen E; Pritchard, Kathleen; Ghandi, Sonal; Verma, Sunil; Czarnota, Gregory J

2016-07-19

This study demonstrated the ability of quantitative ultrasound (QUS) parameters in providing an early prediction of tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC). Using a 6-MHz array transducer, ultrasound radiofrequency (RF) data were collected from 58 LABC patients prior to NAC treatment and at weeks 1, 4, and 8 of their treatment, and prior to surgery. QUS parameters including midband fit (MBF), spectral slope (SS), spectral intercept (SI), spacing among scatterers (SAS), attenuation coefficient estimate (ACE), average scatterer diameter (ASD), and average acoustic concentration (AAC) were determined from the tumor region of interest. Ultrasound data were compared with the ultimate clinical and pathological response of the patient's tumor to treatment and patient recurrence-free survival. Multi-parameter discriminant analysis using the κ-nearest-neighbor classifier demonstrated that the best response classification could be achieved using the combination of MBF, SS, and SAS, with an accuracy of 60 ± 10% at week 1, 77 ± 8% at week 4 and 75 ± 6% at week 8. Furthermore, when the QUS measurements at each time (week) were combined with pre-treatment (week 0) QUS values, the classification accuracies improved (70 ± 9% at week 1, 80 ± 5% at week 4, and 81 ± 6% at week 8). Finally, the multi-parameter QUS model demonstrated a significant difference in survival rates of responding and non-responding patients at weeks 1 and 4 (p=0.035, and 0.027, respectively). This study demonstrated for the first time, using new parameters tested on relatively large patient cohort and leave-one-out classifier evaluation, that a hybrid QUS biomarker including MBF, SS, and SAS could, with relatively high sensitivity and specificity, detect the response of LABC tumors to NAC as early as after 4 weeks of therapy. The findings of this study also suggested that incorporating pre-treatment QUS parameters of a tumor improved the classification results. This work demonstrated the potential of QUS and machine learning methods for the early assessment of breast tumor response to NAC and providing personalized medicine with regards to the treatment planning of refractory patients.

[Outstanding problems of normal and pathological morphology of the diffuse endocrine system].

PubMed

Iaglov, V V; Iaglova, N V

2011-01-01

The diffuse endocrine system (DES)--a mosaic-cellular endoepithelial gland--is the biggest part of the human endocrine system. Scientists used to consider cells of DES as neuroectodermal. According to modem data cells of DES are different cytogenetic types because they develop from the different embryonic blastophyllum. So that any hormone-active tumors originated from DES of the digestive, respiratory and urogenital system shouldn't be considered as neuroendocrinal tumors. The basic problems of DES morphology and pathology are the creation of scientifically substantiated histogenetic classification of DES tumors.

Pancreatic neuroendocrine tumors containing areas of iso- or hypoattenuation in dynamic contrast-enhanced computed tomography: Spectrum of imaging findings and pathological grading.

PubMed

Hyodo, Ryota; Suzuki, Kojiro; Ogawa, Hiroshi; Komada, Tomohiro; Naganawa, Shinji

2015-11-01

To evaluate dynamic contrast-enhanced computed tomography (CT) features of pancreatic neuroendocrine tumors (PNETs) containing areas of iso- or hypoattenuation and the relationship with pathological grading. Between June 2006 and March 2014, 61 PNETs in 58 consecutive patients (29 male, 29 female; median-age 55 years), which were surgically diagnosed, underwent preoperative dynamic contrast-enhanced CT. PNETs were classified based on contrast enhancement patterns in the pancreatic phase: iso/hypo-PNETs were defined as tumors containing areas of iso- or hypoattenuation except for cystic components, and hyper-PNETs were tumors showing hyperattenuation over the whole area. CT findings and contrast-enhancement patterns of the tumors were evaluated retrospectively by two radiologists and compared with the pathological grading. Iso/hypo-PNETs comprised 26 tumors, and hyper-PNETs comprised 35 tumors. Not only hyper-PNETs but also most iso/hypo-PNETs showed peak enhancement in the pancreatic phase and a washout from the portal venous phase to the delayed phase. Iso/hypo-PNETs showed larger tumor size than the hyper-PNETs (mean, 3.7 cm vs. 1.6 cm; P<0.001), and were significantly correlated with unclear tumor margins (n=4 vs. n=0; P=0.029), the existence of cystic components (n=10 vs. n=3; P=0.006), intratumoral blood vessels in the early arterial phase (n=13 vs. n=3; P<0.001), and a smooth rim enhancement in the delayed phase (n=12 vs. n=6; P=0.019). Iso/hypo-PNETs also showed significantly higher pathological grading (WHO 2010 classification; iso/hypo, G1=14, G2=11, G3=1; hyper, G1=34, G2=1; P<0.001). PNETs containing iso/hypo-areas showed a rapid enhancement pattern as well as hyper-PNETs, various radiological features and higher malignant potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PubMed Central

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan

2015-01-01

Purpose Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. Methods This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. Results The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. Conclusion A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID:26361613

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PubMed

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

[A patient with thyroid cancer evaluated according to Response Evaluation Criteria in Solid Tumors during treatment for breast cancer recurrence in hepatic and cervical lymph nodes].

PubMed

Hayashi, Keiko; Enomoto, Takumo; Oshida, Sayuri; Habiro, Takeyoshi; Hatate, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko

2013-11-01

We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials.

PubMed

von Minckwitz, Gunter; Untch, Michael; Nüesch, Eveline; Loibl, Sibylle; Kaufmann, Manfred; Kümmel, Sherko; Fasching, Peter A; Eiermann, Wolfgang; Blohmer, Jens-Uwe; Costa, Serban Dan; Mehta, Keyur; Hilfrich, Jörn; Jackisch, Christian; Gerber, Bernd; du Bois, Andreas; Huober, Jens; Hanusch, Claus; Konecny, Gottfried; Fett, Werner; Stickeler, Elmar; Harbeck, Nadia; Müller, Volkmar; Jüni, Peter

2011-01-01

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

[Study of susceptibility weighted imaging on MR and pathologic findings to distinguish benign or malignant soft tissue tumor].

PubMed

Liu, J; Chen, Y; Bao, X M; Ling, X L; Ding, J P; Zhang, Z K

2017-05-23

Objective: To explore the diagnostic performance of susceptibility weighted imaging (SWI)in distinguishing benign or malignant soft tissue tumor, and to study pathological observation. Methods: Sixty-eight patients with soft tissue tumor, who received no previous treatment or invasive examination, received routine preoperative MRI examination and SWI scanning. The graduation and distribution of intratumoral susceptibility signal intensity(ITSS) and proportion of tumor volume were observed.The pathological results were also included for comparative analysis. Results: Fourty of 68 patients were benign and 28 were malignant. 72.5% (29/40) patients with benign soft tissue tumors were ITSS grade 1 and ITSS grade 3 (hemangioma). 89.3%(25/28) patients with malignant soft tissue tumors were ITSS grade 2 and ITSS grade 3. The difference was statistically significant ( P <0.01). The distribution of ITSS in patients with benign soft tissue tumors was dominated by peripheral distribution and diffuse distribution (hemangioma), accounting for 90.0% (36/40). The distribution of ITSS in patients with malignant soft tissue tumors mainly distributed in the central region, accounting for 78.6% (22 /28). The difference was statistically significant ( P <0.01). The proportion of tumor volume occupied by ITSS in benign soft tissue tumors was <1/3 and> 2/3 (hemangioma), accounting for 90.0% (36/40). The volume of malignant soft tissue tumors were predominantly <1/3 , accounting for 82.1% (23/28). The difference was statistically significant ( P <0.01). Conclusion: SWI is sensitive in displaying the vein and blood metabolites in soft tissue lesions, which is helpful for the differential diagnosis of benign and malignant tumors in soft tissue.

Pathological findings of uterine tumors preoperatively diagnosed as red degeneration of leiomyoma by MRI.

PubMed

Nakai, Go; Yamada, Takashi; Hamada, Takamitsu; Atsukawa, Natsuko; Tanaka, Yoshikazu; Yamamoto, Kiyohito; Higashiyama, Akira; Juri, Hiroshi; Nakamoto, Atsushi; Yamamoto, Kazuhiro; Hirose, Yoshinobu; Ohmichi, Masahide; Narumi, Yoshifumi

2017-07-01

Venous infarction of a leiomyoma is known as red degeneration of leiomyoma (RDL) and can be a cause of acute abdomen. Although magnetic resonance imaging (MRI) is the only modality that can depict the inner condition of a leiomyoma, the typical MR findings of RDL are sometimes identified incidentally even in asymptomatic patients. The purpose of this study is to clarify common pathological findings of uterine tumors preoperatively diagnosed as RDL by MRI. We diagnosed 28 cases of RDL by MRI from March 2007 to April 2015. The ten lesions subjected to pathological analysis after resection were included in the study and reviewed by a gynecological pathologist. The average time from MRI to operation was 4.7 months. The typical beefy-red color was not observed on the cut surface of the tumor except in one tumor resected during the acute phase. All lesions diagnosed as RDL by MRI had common pathological findings consistent with red degeneration of leiomyoma, including coagulative necrosis. Other common pathological features of RDL besides extensive coagulative necrosis appear to be a lack of inflammatory cell infiltrate or hemorrhage in the entire lesion. Although RDL is known to cause acute abdomen, its typical MR findings can be observed even in asymptomatic patients in a condition that manifests long after red degeneration. The characteristic pathological findings in both the acute phase and the chronic phase that we found in this study, along with radiology reports, will be helpful references for gynecologists and pathologists in suspecting a history of red degeneration and confirming the diagnosis.

Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival.

PubMed

Okubo, K; Mark, E J; Flieder, D; Wain, J C; Wright, C D; Moncure, A C; Grillo, H C; Mathisen, D J

1999-10-01

The principal feature of bronchoalveolar carcinoma is that it spreads along airways or aerogenously with multifocality, but many issues are unresolved. We studied 119 patients with pathologically confirmed bronchoalveolar carcinoma. Symptoms, smoking status, radiologic findings, the size of tumor, operative procedures, and complications were reviewed. We studied the pathologic features: presence or absence of aerogenous spread, patterns of growth, cell type, nuclear grade, mitosis, rate of bronchoalveolar carcinoma in adenocarcinoma, and lymphocyte infiltration. The correlation among clinical, radiologic, and pathologic findings was examined, and the factors affecting survival were analyzed. Symptomatic patients had more infiltrative radiographic features, and asymptomatic patients tended to have more mass-like features (P <.0001). Tumors with radiographically infiltrating lesions tended to have mucinous histologic features (P =.006). Tumors with mass lesions by radiograph tended to have nonmucinous and sclerosing histologic features (P =.003). Aerogenous spread was seen in 94% of specimens. The presence of a variety of cell types suggested multiple clonal origin. The overall survival in those patients undergoing resection was 69.1% at 5 years and 56.5% at 10 years. The significant factors affecting survival were radiologic presence of a mass or infiltrate, pathologic findings of the presence of sclerosis, association with a scar, the rate of bronchoalveolar carcinoma in adenocarcinoma, lymphocyte infiltration grade, nodal involvement, and status of complete resection. Mitosis or nuclear grade of tumor cells did not correlate with survival. Bronchoalveolar carcinoma showed good overall survival with appropriate surgical procedures. Certain radiologic or pathologic findings correlated with survival. These findings may enhance the ability to predict long-term survival.

Correlation between response to neoadjuvant chemotherapy and survival in locally advanced breast cancer patients.

PubMed

Romero, A; García-Sáenz, J A; Fuentes-Ferrer, M; López Garcia-Asenjo, J A; Furió, V; Román, J M; Moreno, A; de la Hoya, M; Díaz-Rubio, E; Martín, M; Caldés, T

2013-03-01

Measurement of residual disease following neoadjuvant chemotherapy that accurately predicts long-term survival in locally advanced breast cancer (LABC) is an essential requirement for clinical trials development. Several methods to assess tumor response have been described. However, the agreement between methods and correlation with survival in independent cohorts has not been reported. We report survival and tumor response according to the measurement of residual breast cancer burden (RCB), the Miller and Payne classification and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in 151 LABC patients. Kappa Cohen's coefficient (К) was used to test the agreement between methods. We assessed the correlation between the treatment outcome and overall survival (OS) and relapse-free survival (RFS) by calculating Harrell's C-statistic (c). The agreement between Miller and Payne classification and RCB classes was very high (К = 0.82). In contrast, we found a moderate-to-fair agreement between the Miller and Payne classification and RECIST criteria (К = 0.52) and RCB classes and RECIST criteria (К = 0.38). The adjusted C-statistic to predict OS for RCB index (0.77) and RCB classes (0.75) was superior to that of RECIST criteria (0.69) (P = 0.007 and P = 0.035, respectively). Also, RCB index (c = 0.71), RCB classes (c = 0.71) and Miller and Payne classification (c = 0.67) predicted better RFS than RECIST criteria (c = 0.61) (P = 0.005, P = 0.006 and P = 0.028, respectively). The pathological assessment of tumor response might provide stronger prognostic information in LABC patients.

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration.

PubMed

Bossuyt, V; Provenzano, E; Symmans, W F; Boughey, J C; Coles, C; Curigliano, G; Dixon, J M; Esserman, L J; Fastner, G; Kuehn, T; Peintinger, F; von Minckwitz, G; White, J; Yang, W; Badve, S; Denkert, C; MacGrogan, G; Penault-Llorca, F; Viale, G; Cameron, D

2015-07-01

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Is It Important to Adapt Neoadjuvant Chemotherapy to the Visible Clinical Response? An Open Randomized Phase II Study Comparing Response-Guided and Standard Treatments in HER2-Negative Operable Breast Cancer

PubMed Central

Mouret-Reynier, Marie-Ange; Savoye, Aude-Marie; Abrial, Catherine; Kwiatkowski, Fabrice; Garbar, Christian; DuBray-Longeras, Pascale; Eymard, Jean-Christophe; Lebouedec, Guillaume; Vanpraagh, Isabelle; Penault-Llorca, Frederique; Chollet, Philippe; Cure, Hervé

2015-01-01

Background. Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment. Methods. Overall, 264 previously untreated stage II–III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m2, respectively, for 3 cycles) followed by docetaxel (100 mg/m2 for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by <30% after 2 cycles or <50% after 4 cycles of FEC100 (ultrasound assessments according to World Health Organization criteria). Otherwise, FEC100 was given for six cycles before surgery. Intent-to-treat analysis was performed. Results. Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses. Conclusion. Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected. PMID:25637380

Neoadjuvant oral vs. infusional chemoradiotherapy on locally advanced rectal cancer: Prognostic factors.

PubMed

Conde, Sofia; Borrego, Margarida; Teixeira, Tânia; Teixeira, Rubina; Sá, Anabela; Soares, Paula

2012-01-01

To evaluate the prognostic factors and impact on survival of neoadjuvant oral and infusional chemoradiotherapy in patients with locally advanced rectal cancer. There is still no definitive consensus about the prognostic factors and the impact of neoadjuvant chemoradiotherapy on survival. Some studies have pointed to an improvement in overall survival (OS) and progression-free survival (PFS) in patients with tumor downstaging (TD) and nodal downstaging (ND). A set of 159 patients with LARC were treated preoperatively. Group A - 112 patients underwent concomitant oral chemoradiotherapy: capecitabine or UFT + folinic acid. Group B - 47 patients submitted to concomitant chemoradiation with 5-FU in continuous infusion. 63.6% of patients were submitted to adjuvant chemotherapy. pathologic complete response (pCR) - 18.7%; TD - 55.1%; ND - 76%; loco-regional response - 74.8%. Group B: pCR - 11.4%; TD - 50%; ND - 55.8%; LRR - 54.5%. The loco-regional control was 95.6%. There was no difference in survival between both groups. Those with loco-regional response had better PFS. Tumor and nodal downstaging, loco-regional response and a normal CEA level turned out to be important prognostic factors in locally advanced rectal cancer. Nodal downstaging and loco-regional response were higher in Group A. Those with tumor downstaging and loco-regional response from Group A had better OS. Adjuvant chemotherapy had no impact on survival except in those patients with loco-regional response who achieved a higher PFS.

Etiologic Field Effect: Reappraisal of the Field Effect Concept in Cancer Predisposition and Progression

PubMed Central

Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Fuchs, Charles S; Beck, Andrew H; Giovannucci, Edward; Ogino, Shuji

2014-01-01

The term “field effect” (also known as field defect, field cancerization, or field carcinogenesis) has been used to describe a field of cellular and molecular alteration, which predisposes to the development of neoplasms within that territory. We explore an expanded, integrative concept, “etiologic field effect”, which asserts that various etiologic factors (the exposome including dietary, lifestyle, environmental, microbial, hormonal, and genetic factors) and their interactions (the interactome) contribute to a tissue microenvironmental milieu that constitutes a “field of susceptibility” to neoplasia initiation, evolution, and progression. Importantly, etiological fields predate the acquisition of molecular aberrations commonly considered to indicate presence of filed effect. Inspired by molecular pathological epidemiology (MPE) research, which examines the influence of etiologic factors on cellular and molecular alterations during disease course, an etiologically-focused approach to field effect can: 1) broaden the horizons of our inquiry into cancer susceptibility and progression at molecular, cellular, and environmental levels, during all stages of tumor evolution; 2) embrace host-environment-tumor interactions (including gene-environment interactions) occurring in the tumor microenvironment; and, 3) help explain intriguing observations, such as shared molecular features between bilateral primary breast carcinomas, and between synchronous colorectal cancers, where similar molecular changes are absent from intervening normal colon. MPE research has identified a number of endogenous and environmental exposures which can influence not only molecular signatures in the genome, epigenome, transcriptome, proteome, metabolome and interactome, but also host immunity and tumor behavior. We anticipate that future technological advances will allow the development of in vivo biosensors capable of detecting and quantifying “etiologic field effect” as abnormal network pathology patterns of cellular and microenvironmental responses to endogenous and exogenous exposures. Through an “etiologic field effect” paradigm, and holistic systems pathology (systems biology) approaches to cancer biology, we can improve personalized prevention and treatment strategies for precision medicine. PMID:24925058

Primary epidural hemangiopericytoma in the lumbar spine: a case report.

PubMed

Ijiri, Kosei; Yuasa, Shinya; Yone, Kazunori; Matsunaga, Shunji; Ryoki, Yoshihiro; Taniguchi, Noboru; Yonezawa, Suguru; Komiya, Setsuro

2002-04-01

A case report of primary epidural hemangiopericytoma in the lumbar spine and a review of the literature are presented. To present the result of pathologic diagnosis using immunohistochemical staining and the treatment of spinal hemangiopericytoma. Spinal hemangiopericytoma is a very rare soft tissue tumor with specific pathologic features and a clinical course featuring high rates of recurrence and metastasis. A 39-year-old woman reported numbness in both legs. Neither sensory abnormalities nor muscle weakness was present in her lower extremities. Magnetic resonance imaging showed a tumor dorsal to the thecal sac at L1-L2. After L1 and L2 laminectomy, the tumor with its dural base was resected en bloc. The patient's clinical and neurologic symptoms disappeared after surgery. Microscopic examination showed oval- or spindle-shaped cells with slightly acidic cytoplasm and oval nuclei. Silver staining emphasized fibers around tumor cells. The test results for the tumor cells were positive for vimentin staining, but negative for alpha-TM staining using thrombomodulin, a marker for endothelial cells. On the basis of these pathologic findings, the tumor was diagnosed as a hemangiopericytoma, a type of tumor composed of mesenchymal hemangiopericytes. Neither recurrence nor metastasis of the tumor was found during the 2-year follow-up period after surgery. Soft tissue hemangiopericytoma is a well-recognized entity considered to be an aggressive neoplasm with a high rate of recurrence and a propensity to metastasize. Immunohistochemical investigation was essential for the diagnosis of this tumor. Although hemangiopericytoma very rarely occurs in the spine, surgeons treating patients with this tumor should be aware of its metastatic potential.

A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

NASA Astrophysics Data System (ADS)

Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

2016-11-01

The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

[Leiomyoma of the bladder causing the destruction of a kidney].

PubMed

Kehila, Mehdi; Mekni, Karima; Abouda, Hassine Saber; Chtourou, Maher; Zeghal, Dorra; Chanoufi, Mohamed Badis

2016-01-01

Leiomyoma of the bladder is a rare benign tumor deemed to have a good prognosis after surgical treatment. This is unfortunately not always true. We report the case of a 33 year-old patient who consulted for lumbar pain on right side. Exploration of patient revealed bladder floor solid tumor with non-functioning right kidney and left urinary tract dilation. Cystoscopy objectified solid tumor of the right perimeatal bladder. Tumor biopsies were performed together with the insertion of a left double J stent. Anatomo-pathologic study showed leiomyoma of the bladder. The patient underwent laparoscopic myomectomy. The postoperative course was uneventful. Pathological effect and sequelae was complete distruction of kidney.

New laser technologies in the clinic of neurosurgery

NASA Astrophysics Data System (ADS)

Stupak, V. V.; Fomichev, N. G.; Tsvetovsky, S. B.; Dmitriev, A. B.; Kobosev, V. V.; Bagaev, S. N.; Mayorov, A. P.; Struts, S. G.

2005-08-01

In report summarized more then 10 experience of authors in Novosibirsk Traumatology and orthopedics research institute Neurosurgery clinic on usage of laser technologies in treatment of central nervous system tumors. On the basis of ND-YAG laser application original technologies have been developed and used in surgical treatment of patients with various neurosurgical pathology and protected by 8 Patents of the Russian Federation. 427 patients were operated on with the use of YAG:Nd3+ laser. Out of them 152 patients had extracerebral tumors of various volume and localization, 135 patients - spinal cord tumors, 74 patients - a pathology of cerebrospinal transition (Amold-Chiari syndrome of 1-2 types), and 66 patients - intramedullary tumors of deep localization. Results showed good results of laser technologies usage for central nervous system tumors removal.

Association between radiation dose and pathological complete response after preoperative radiochemotherapy in esophageal squamous cell cancer.

PubMed

Ordu, Arif Deniz; Nieder, Carsten; Geinitz, Hans; Scherer, Vera; Kup, Philipp Günther; Schuster, Tibor; Combs, Stephanie E; Fakhrian, Khashayar

2014-12-01

This study was undertaken to examine the impact of radiation dose on pathological complete response (pCR) rates following neoadjuvant radiochemotherapy (N-RCT) for squamous cell esophageal cancer (ESCC). From 1988 to 2011, 218 patients were treated with 30-30.6 Gy (1.8-2 Gy per fraction), 39.6-40 Gy (1.8-2 Gy per fraction) or 44-45 Gy (1.8-2 Gy per fraction) and concomitant cisplatin ± 5-fluorouracil (5-FU), oxaliplatin + 5-FU or 5-FU alone. The most commonly used concomitant chemotherapy was continuous infusion of 5-FU-alone with a dose of 300 mg/m(2)/day during the whole course of treatment (n=111). To eliminate the dispersing effect of potentially different efficacy levels of these drug regimens on pCR, we excluded patients with regimens other than 5-FU-alone. Histomorphological regression grade 1a (0% residual tumor), 1b (<10% residual tumor), 2 (10-50% residual tumor) and 3 (>50% residual tumor) was observed in 26 (23%), 24 (22%), 36 (32%) and 25 (23%) patients, respectively. pCR was observed in 9 out of 71 (13%) patients treated with 30 Gy-30.6 Gy, 13 of 34 (38%) patients treated with 39.6-40 Gy and 4 of 6 (67%) patients treated with 44-45 Gy (p=0.001). Median follow-up time from the start of N-RCT was 191 months (range=2-262 months). The estimated 5-year overall survival (OS) was 33% for the whole cohort. OS at 5 years was 58% for patients with pCR compared to 25% for patients with less favorable response to N-RCT (p=0.009), respectively. The dose of radiation correlates significantly with the likelihood of achieving a pCR in stage II/III squamous cell esophageal cancer patients. Prospective randomized trials are required to definitively evaluate the impact of application of higher radiation doses on efficacy and safety/tolerability in the context of N-RCT on the clinical outcomes. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[(99)Tc(m)N-NOET dual-phase SPECT in differential diagnosis of benign and malignant lung tumors].

PubMed

Liu, Haiyan; Li, Sijin; Yang, Suyun; Wu, Zhifang

2014-01-01

To investigate the value of (99)Tc(m)N-NOET dual-phase SPECT in differential diagnosis of benign and malignant lung tumors. CT scan, early (20 to 30 min) and delayed (2 h) imaging of NOET SPECT were performed on 61 patients suspected of lung lesions before operation. The results were compared with the pathological findings. All cases were not treated with radiotherapy, chemotherapy or surgery before checks. Moreover, all patients had pathological diagnosis. To determine the value in differential diagnosis of tumors by analyzing the tumor uptake and excretion of (99)Tc(m)N-NOET, and the results were compared with that of CT. The value of early T/N ratio (ER) in the malignant (G1) and benign (G2) groups was 1.25 ± 0.15 and 1.09 ± 0.11 (P < 0.001), respectively, and delayed T/N ratio (DR) was 1.40 ± 0.17 and 1.18 ± 0.21 (P < 0.001). The retention index (RI) of groups G1 was (12.22 ± 6.38)% and group G2 was (8.3 ± 10.91)%, with a non-significant difference between them (P > 0.05). The ER, DR and RI of NOET SPECT in the malignant patients were not significantly correlated with TNM staging, pathological types, tumor diameter, cavity in the lung tumor mass, history of smoking, tumor size and patient gender (P > 0.05). The sensitivity of NOET dual-phase SPECT and CT in the differential diagnosis of benign and malignant lung tumors was 94.1% vs. 90.2%, specificity was 70.0% vs. 80.0% , positive predictive value (PPV) was 94.1% vs. 95.8%, negative predictive value (NPV) was 70.0% vs. 61.5 %, and accuracy was 90.2%. vs. 88.5% (P > 0.05 for all). (99)Tc(m)N- NOET dual-phase SPECT could be used in differential diagnosis of benign and malignant lung tumors, with no significant differences compared with the efficacy of CT imaging. The semiquantitative indexes (ER, DR and RI) of NOET SPECT can also be used in differential diagnosis of benign and malignant lung tumors, and are not significantly correlated with TNM staging, pathological types, tumor diameter, cavity of the lung tumor mass, history of smoking, tumor size and patient gender.

Discordance between Ureteroscopic Biopsy and Final Pathology for Upper Tract Urothelial Carcinoma.

PubMed

Margolin, Ezra J; Matulay, Justin T; Li, Gen; Meng, Xiaosong; Chao, Brian; Vijay, Varun; Silver, Hayley; Clinton, Timothy N; Krabbe, Laura-Maria; Woldu, Solomon L; Singla, Nirmish; Bagrodia, Aditya; Margulis, Vitaly; Huang, William C; Bjurlin, Marc A; Shah, Ojas; Anderson, Christopher B

2018-06-01

We evaluated the discordance between ureteroscopic biopsy and surgical pathology findings for grading and staging upper tract urothelial carcinoma. We also sought to establish preoperative predictors of aggressive tumors. We retrospectively reviewed the records of 314 patients who underwent ureteroscopic biopsy followed by surgical management of upper tract urothelial carcinoma from 2000 to 2016 at a total of 3 institutions. Our primary outcomes were muscle invasive (pT2 or greater) disease at surgical pathology and upgrading of clinical low grade tumors to pathological high grade. At biopsy 61% of the patients had clinical high grade tumors and 21% had subepithelial connective tissue invasion (cT1+). On final pathology 79% of the patients had pathological high grade tumors and 45% had stage pT2 or greater. On multivariate analysis advanced patient age, clinical high grade and cT1+ were independently associated with pT2 or greater. The combined presence of clinical high grade and cT1+ had 86% positive predictive value for muscle invasion while the combined absence of clinical high grade and cT1+ had 80% negative predictive value. The likelihood of missing invasion on biopsy in patients with muscle invasive disease was increased when biopsy fragments were limited to 1 mm or less. Of clinical low grade cases on biopsy 51% were upgraded at surgery. The presence of positive urine cytology was associated with an increased risk of upgrading but this was not statistically significant. Clinical high grade, cT1+ on biopsy and advanced patient age are independent risk factors for muscle invasive upper tract urothelial carcinoma. There is a significant risk of upgrading in patients with clinical low grade tumors on biopsy, especially when urine cytology is positive. The predictive value of biopsy can likely be improved by more extensive ureteroscopic sampling. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Neoadjuvant therapy in the treatment of breast cancer

PubMed Central

Teshome, Mediget; Hunt, Kelly K.

2014-01-01

Synopsis Neoadjuvant systemic therapy in the treatment of breast cancer was initially employed for patients with inoperable disease. Over the past several decades this treatment approach has proved beneficial in many other patients including those with early-stage, operable breast cancer. Several randomized prospective studies have shown comparable survival rates when compared with adjuvant systemic therapy. Additionally, neoadjuvant chemotherapy can decrease the tumor burden facilitating breast conservation in selected patients without significant increases in local recurrence. Response to therapy has proven to be a strong predictor of outcome, with patients achieving pathologic complete response (pCR) demonstrating improved survival compared with those achieving less than a pCR. Furthermore, molecular subtype analysis has shown improved response following neoadjuvant chemotherapy in certain tumor types providing patients with the most aggressive subtypes a chance at cure with targeted therapies. In particular, targeting the HER2-positive subtype with trastuzumab and other HER2-directed therapies has markedly improved the outcome in these patients. Conversely, the early recognition of poor responders is important in limiting the toxicity of ineffective therapy and altering management. Neoadjuvant endocrine therapy in postmenopausal women with hormone receptor-positive tumors consistently decreases tumor size improving rates of breast conservation. Aromatase inhibitors have demonstrated superiority to tamoxifen with improved response and favorable toxicity profiles. Imaging modalities have shown promise in predicting patients with pCR, however they have not yet eliminated the need for surgical intervention. Less invasive surgical strategies such as breast conserving surgery and sentinel lymph node dissection have been shown to be safe following neoadjuvant chemotherapy in selected patients. A multidisciplinary approach with primary systemic therapy when indicated, improves the likelihood for breast conservation, provides a window into tumor biology and predicts patient outcomes. PMID:24882348

Mediastinal pathology and the contributions of Dr. Juan Rosai.

PubMed

Wick, Mark R

2016-09-01

Dr. Juan Rosai is one of the most prolific contributors to the literature on mediastinal pathology, and he has added steadily to that body of work over a 50-year period. Rosai has written several landmark articles in this topical area, including articles on thymic epithelial lesions, mediastinal neuroendocrine tumors, mediastinal lymphoma and other hematopoietic lesions, thymolipoma, thymoliposarcoma, mediastinal solitary fibrous tumor, intrathymic langerhans-cell histiocytosis, mediastinal germ cell neoplasms, and multilocular thymic cyst. This review recounts his role as one of the principal figures in the surgical pathology of mediastinal diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Early detection of chemotherapy-refractory patients by monitoring textural alterations in diffuse optical spectroscopic images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J., E-mail: Gregory.Czarnota@sunnybrook.ca

2015-11-15

Purpose: Changes in textural characteristics of diffuse optical spectroscopic (DOS) functional images, accompanied by alterations in their mean values, are demonstrated here for the first time as early surrogates of ultimate treatment response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). NAC, as a standard component of treatment for LABC patient, induces measurable heterogeneous changes in tumor metabolism which were evaluated using DOS-based metabolic maps. This study characterizes such inhomogeneous nature of response development, by determining alterations in textural properties of DOS images apparent at early stages of therapy, followed later by gross changes in mean valuesmore » of these functional metabolic maps. Methods: Twelve LABC patients undergoing NAC were scanned before and at four times after treatment initiation, and tomographic DOS images were reconstructed at each time. Ultimate responses of patients were determined clinically and pathologically, based on a reduction in tumor size and assessment of residual tumor cellularity. The mean-value parameters and textural features were extracted from volumetric DOS images for several functional and metabolic parameters prior to the treatment initiation. Changes in these DOS-based biomarkers were also monitored over the course of treatment. The measured biomarkers were applied to differentiate patient responses noninvasively and compared to clinical and pathologic responses. Results: Responding and nonresponding patients demonstrated different changes in DOS-based textural and mean-value parameters during chemotherapy. Whereas none of the biomarkers measured prior the start of therapy demonstrated a significant difference between the two patient populations, statistically significant differences were observed at week one after treatment initiation using the relative change in contrast/homogeneity of seven functional maps (0.001 < p < 0.049), and mean value of water content in tissue (p = 0.010). The cross-validated sensitivity and specificity of these parameters at week one of therapy ranged between 80%–100% and 67%–100%, respectively. Higher levels of statistically significant differences were exhibited at week four after start of treatment, with cross-validated sensitivities and specificities ranging between 80% and 100% for three textural and three mean-value parameters. The combination of the textural and mean-value parameters in a “hybrid” profile could better separate the two patient populations early on during a course of treatment, with cross-validated sensitivities and specificities of up to 100% (p = 0.001). Conclusions: The results of this study suggest that alterations in textural characteristics of DOS images, in conjunction with changes in their mean values, can classify noninvasively the ultimate clinical and pathologic response of LABC patients to chemotherapy, as early as one week after start of their treatment. This provides a basis for using DOS imaging as a tool for therapy personalization.« less

Early detection of chemotherapy-refractory patients by monitoring textural alterations in diffuse optical spectroscopic images.

PubMed

Sadeghi-Naini, Ali; Vorauer, Eric; Chin, Lee; Falou, Omar; Tran, William T; Wright, Frances C; Gandhi, Sonal; Yaffe, Martin J; Czarnota, Gregory J

2015-11-01

Changes in textural characteristics of diffuse optical spectroscopic (DOS) functional images, accompanied by alterations in their mean values, are demonstrated here for the first time as early surrogates of ultimate treatment response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). NAC, as a standard component of treatment for LABC patient, induces measurable heterogeneous changes in tumor metabolism which were evaluated using DOS-based metabolic maps. This study characterizes such inhomogeneous nature of response development, by determining alterations in textural properties of DOS images apparent at early stages of therapy, followed later by gross changes in mean values of these functional metabolic maps. Twelve LABC patients undergoing NAC were scanned before and at four times after treatment initiation, and tomographic DOS images were reconstructed at each time. Ultimate responses of patients were determined clinically and pathologically, based on a reduction in tumor size and assessment of residual tumor cellularity. The mean-value parameters and textural features were extracted from volumetric DOS images for several functional and metabolic parameters prior to the treatment initiation. Changes in these DOS-based biomarkers were also monitored over the course of treatment. The measured biomarkers were applied to differentiate patient responses noninvasively and compared to clinical and pathologic responses. Responding and nonresponding patients demonstrated different changes in DOS-based textural and mean-value parameters during chemotherapy. Whereas none of the biomarkers measured prior the start of therapy demonstrated a significant difference between the two patient populations, statistically significant differences were observed at week one after treatment initiation using the relative change in contrast/homogeneity of seven functional maps (0.001

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

PubMed

Hall, Matthew D; Schultheiss, Timothy E; Smith, David D; Fakih, Marwan G; Wong, Jeffrey Y C; Chen, Yi-Jen

2016-12-01

Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

Evaluation with 3.0-T MR imaging: predicting the pathological response of triple-negative breast cancer treated with anthracycline and taxane neoadjuvant chemotherapy.

PubMed

Kim, Min Jung; Kim, Eun-Kyung; Park, Seho; Moon, Hee Jung; Kim, Seung Il; Park, Byeong-Woo

2015-09-01

Triple-negative breast cancer (TNBC) which expresses neither hormonal receptors nor HER-2 is associated with poor prognosis and shorter survival. Several studies have suggested that TNBC patients attaining pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) show a longer survival than those without pCR. To assess the accuracy of 3.0-T breast magnetic resonance imaging (MRI) in predicting pCR and to evaluate the clinicoradiologic factors affecting the diagnostic accuracy of 3.0-T breast MRI in TNBC patients treated with anthracycline and taxane (ACD). This retrospective study was approved by the institutional review board; patient consent was not required. Between 2009 and 2012, 35 TNBC patients with 3.0-T breast MRI prior to (n = 26) or after (n = 35) NAC were included. MRI findings were reviewed according to pCR to chemotherapy. The diagnostic accuracy of 3.0-T breast MRI for predicting pCR and the clinicoradiological factors affecting MRI accuracy and response to NAC were analyzed. 3.0-T MRI following NAC with ACD accurately predicted pCR in 91.4% of TNBC patients. The residual tumor size between pathology and 3.0-T MRI in non-pCR cases showed a higher correlation in the Ki-67-positive TNBC group (r = 0.947) than in the Ki-67 negative group (r = 0.375) with statistical trends (P = 0.069). Pre-treatment MRI in the non-pCR group compared to the pCR group showed a larger tumor size (P = 0.030) and non-mass presentation (P = 0.015). 3.0-T MRI in TNBC patients following NAC with ACD showed a high accuracy for predicting pCR to NAC. Ki-67 can affect the diagnostic accuracy of 3.0-T MRI for pCR to NAC with ACD in TNBC patients. © The Foundation Acta Radiologica 2014.

Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

PubMed

Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

2015-12-01

Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P < .05). The tumor necrosis factor alpha and interleukin-8 levels in the BALF reached baseline levels when the humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P < .05). Moreover, humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway. Copyright © 2015 by Daedalus Enterprises.

[Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement].

PubMed

Jiménez-Ballvé, A; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Salsidua-Arroyo, O; Román-Santamaría, J M; Pelayo Alarcón, A; Fuentes Ferrer, M E; Carreras-Delgado, J L

2015-01-01

To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

AAV-dominant negative tumor necrosis factor (DN-TNF) gene transfer to the striatum does not rescue medium spiny neurons in the YAC128 mouse model of Huntington's disease.

PubMed

Alto, Laura Taylor; Chen, Xi; Ruhn, Kelly A; Treviño, Isaac; Tansey, Malú G

2014-01-01

CNS inflammation is a hallmark of neurodegenerative disease, and recent studies suggest that the inflammatory response may contribute to neuronal demise. In particular, increased tumor necrosis factor (TNF) signaling is implicated in the pathology of both Parkinson's disease (PD) and Alzheimer's disease (AD). We have previously shown that localized gene delivery of dominant negative TNF to the degenerating brain region can limit pathology in animal models of PD and AD. TNF is upregulated in Huntington's disease (HD), like in PD and AD, but it is unknown whether TNF signaling contributes to neuronal degeneration in HD. We used in vivo gene delivery to test whether selective reduction of soluble TNF signaling could attenuate medium spiny neuron (MSN) degeneration in the YAC128 transgenic (TG) mouse model of Huntington's disease (HD). AAV vectors encoding cDNA for dominant-negative tumor necrosis factor (DN-TNF) or GFP (control) were injected into the striatum of young adult wild type WT and YAC128 TG mice and achieved 30-50% target coverage. Expression of dominant negative TNF protein was confirmed immunohistologically and biochemically and was maintained as mice aged to one year, but declined significantly over time. However, the extent of striatal DN-TNF gene transfer achieved in our studies was not sufficient to achieve robust effects on neuroinflammation, rescue degenerating MSNs or improve motor function in treated mice. Our findings suggest that alternative drug delivery strategies should be explored to determine whether greater target coverage by DN-TNF protein might afford some level of neuroprotection against HD-like pathology and/or that soluble TNF signaling may not be the primary driver of striatal neuroinflammation and MSN loss in YAC128 TG mice.

HGNET-BCOR Tumors of the Cerebellum: Clinicopathologic and Molecular Characterization of 3 Cases.

PubMed

Appay, Romain; Macagno, Nicolas; Padovani, Laetitia; Korshunov, Andrey; Kool, Marcel; André, Nicolas; Scavarda, Didier; Pietsch, Torsten; Figarella-Branger, Dominique

2017-09-01

The central nervous system (CNS) high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR) is a recently described molecular entity. We report 3 new CNS HGNET-BCOR cases sharing common clinical presentation and pathologic features. The 3 cases concerned children aged 3 to 7 years who presented with a voluminous mass of the cerebellum. Pathologic features included proliferation of uniform spindle to ovoid cells with fine chromatin associated with a rich arborizing capillary network. Methylation profiling classified these cases as CNS HGNET-BCOR tumors. Polymerase chain reaction analysis confirmed the presence of internal tandem duplications in the C-terminus of BCOR (BCOR-ITD), a characteristic of these tumors, in all 3 cases. Immunohistochemistry showed a strong nuclear BCOR expression. In 2 cases, local recurrence occurred within 6 months. The third case, a patient who received a craniospinal irradiation after total surgical removal followed by a metronomics maintenance with irinotecan, temozolomide, and itraconazole, is still free of disease 14 months after diagnosis. In summary, CNS HGNET-BCOR represents a rare tumor occurring in young patients with dismal prognosis. BCOR nuclear immunoreactivity is highly suggestive of a BCOR-ITD. Whether CNS HGNET-BCOR should be classified among the category of "embryonal tumors" or within the category of "mesenchymal, nonmeningothelial tumors" remains to be clarified. Because CNS HGNET-BCOR share pathologic features and characteristic BCOR-ITD with clear cell sarcoma of the kidney, these tumors may represent local variants of the same entity.

The Significance of the Stromal Response in Breast Cancer: An Immunohistochemical Study of Myofibroblasts in Primary and Metastatic Breast Cancer.

PubMed

Roozdar, Alale; Hayes, Malcolm M; Pourseyedei, Bahram; Zeinalinejad, Hamid; Shamsi Meymandi, Manzumeh; Dabiri, Bahram; Dabiri, Shahriar

2018-05-01

Gene expression profiling of breast cancer has demonstrated the importance of stromal response in determining the prognosis of invasive breast cancer. The host response to breast cancer is of increasing interest to pathologists and may be a future focus for novel pharmacological treatments. This study describes the pattern of distribution of stromal myofibroblasts using immunostains for CD10 and smooth muscle actin (SMA) in 50 primary breast cancers and their matched nodal metastases (68.6% nodes positive and 31.4% nodes negative). The stroma within the tumor (intratumoral) and at the advancing tumor edge (peri-tumoral) was studied in both primary and nodal sites. A simple quantitative scoring system was employed for both immunostains. The correlation between expression of these markers by stromal cells and standard pathological prognostic factors of stage, grade, hormone receptor and Her-2 status was analysed. SMA-positive stromal cells were more abundant in peri-tumoral stroma compared with intratumoral stroma in both primary and metastatic lesions. SMA expression in the lymph node metastases showed a significant correlation with tumor stage. SMA expression in peri-tumoral stroma correlated with Her-2 status. The results of this study suggest that myofibroblasts, particularly those expressing SMA, might potentiate the progression of the carcinomatous process especially in nodal metastases. Thus these cells may be a potential therapeutic target. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Berberine inhibits colitis-associated tumorigenesis via suppressing inflammatory responses and the consequent EGFR signaling-involved tumor cell growth.

PubMed

Li, Dandan; Zhang, Youyu; Liu, Kun; Zhao, Yujie; Xu, Beibei; Xu, Liang; Tan, Li; Tian, Yuan; Li, Cunxi; Zhang, Wenqing; Cao, Hanwei; Zhan, Yan-Yan; Hu, Tianhui

2017-11-01

The anti-inflammatory and anti-tumor effects of berberine, a traditional Chinese medicine, were separately discovered in pathological intestinal tissues. However, whether the anti-inflammatory effect of berberine contributes to its anti-tumor effect on colitis-associated colorectal cancer (CACRC) remains unknown. In the present study, we found that berberine effectively inhibited colitis-associated tumorigenesis and colonic epithelium hyperproliferation in dextran sulfate sodium (DSS)-treated Apc Min/+ mice. A mechanistic study identified that these inhibitory effects of berberine occurred through blocking interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression in colonic macrophages. An in vitro study on cell lines identified that berberine treatment of Raw 264.7 macrophages resulted in conditioned media with fewer proliferative effects on a cell line with a heterozygous Apc mutation (Immorto-Min colonic epithelium, IMCE). EGFR-ERK signaling act downstream of berberine/pro-inflammatory cytokines axis to regulate CACRC cell proliferation. Furthermore, in vivo administration of IL-6 to DSS-treated Apc Min/+ mice effectively weakened the inhibitory effects of berberine on tumorigenesis and EGFR-ERK signaling in colon tissues. Altogether, the results of our studies have revealed that berberine inhibits the development of CACRC by interfering with inflammatory response-driven EGFR signaling in tumor cell growth. The findings of this study support the possibility that berberine and other anti-inflammatory drugs may be beneficial in the treatment of CACRC.

Interleukin-33 in tumorigenesis, tumor immune evasion, and cancer immunotherapy.

PubMed

Lu, Binfeng; Yang, Min; Wang, Qingqing

2016-05-01

Interleukin-33 (IL-33) is a member of the IL-1 gene family and mainly expressed in the nucleus of tissue lining cells, stromal cells, and activated myeloid cells. IL-33 is considered a damage-associated molecular pattern (DAMP) molecule and plays an important role in many physiological and pathological settings such as tissue repair, allergy, autoimmune disease, infectious disease, and cancer. The biological functions of IL-33 include maintaining tissue homeostasis, enhancing type 1 and 2 cellular immune responses, and mediating fibrosis during chronic inflammation. IL-33 exerts diverse functions through signaling via its receptor ST2, which is expressed in many types of cells including regulatory T cells (Treg), group 2 innate lymphoid cells (ILC2s), myeloid cells, cytotoxic NK cells, Th2 cells, Th1 cells, and CD8(+) T cells. Tumor development results in downregulation of IL-33 in epithelial cells but upregulation of IL-33 in the tumor stroma and serum. The current data suggest that IL-33 expression in tumor cells increases immunogenicity and promotes type 1 antitumor immune responses through CD8(+) T cells and NK cells, whereas IL-33 in tumor stroma and serum facilitates immune suppression via Treg and myeloid-derived suppressor cell (MDSC). Understanding the role of IL-33 in cancer immunobiology sheds lights on targeting this cytokine for cancer immunotherapy.

Genetic polymorphisms in 5-Fluorouracil-related enzymes predict pathologic response after neoadjuvant chemoradiation for rectal cancer.

PubMed

Nelson, Bailey; Carter, Jane V; Eichenberger, Maurice R; Netz, Uri; Galandiuk, Susan

2016-11-01

Many patients with rectal cancer undergo preoperative neoadjuvant chemoradiation, with approximately 70% exhibiting pathologic downstaging in response to treatment. Currently, there is no accurate test to predict patients who are likely to be complete responders to therapy. 5-Fluorouracil is used regularly in the neoadjuvant treatment of rectal cancer. Genetic polymorphisms affect the activity of thymidylate synthase, an enzyme involved in 5-Fluorouracil metabolism, which may account for observed differences in response to neoadjuvant treatment between patients. Detection of genetic polymorphisms might identify patients who are likely to have a complete response to neoadjuvant therapy and perhaps allow them to avoid operation. DNA was isolated from whole blood taken from patients with newly diagnosed rectal cancer who received neoadjuvant therapy (n = 50). Response to therapy was calculated with a tumor regression score based on histology from the time of operation. Polymerase chain reaction was performed targeting the promoter region of thymidylate synthase. Polymerase chain reaction products were separated using electrophoresis to determine whether patients were homozygous for a double-tandem repeat (2R), a triple-tandem repeat (3R), or were heterozygous (2R/3R). A single nucleotide polymorphism, 3G or 3C, also may be present in the second repeat unit of the triple-tandem repeat allele. Restriction fragment length polymorphism assays were performed in patients with at least one 3R allele using HaeIII. Patients with at least 1 thymidylate synthase 3G allele were more likely to have a complete or partial pathologic response to 5-Fluorouracil neoadjuvant therapy (odds ratio 10.4; 95% confidence interval, 1.3-81.6; P = .01) than those without at least one 3G allele. Identification of rectal cancer patients with specific genetic polymorphisms in enzymes involved in 5-Fluorouracil metabolism seems to predict the likelihood of complete or partial pathologic response to preoperative neoadjuvant therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Tumor Slice Culture: A New Avatar in Personalized Oncology

DTIC Science & Technology

2017-09-01

of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188...significantly correlated with pathologic assessment of tumor viability/necrosis. We continue to optimize the conditions for TSC by manipulating growth...following exposure to treatments. We are in the process of assessing the pathologic outcome using H&E staining of the treated slices and correlating the

Tumor Slice Culture: A New Avatar in Personalized Oncology

DTIC Science & Technology

2017-09-01

the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public... correlated with pathologic assessment of tumor viability/necrosis. We continue to optimize the conditions for TSC by manipulating growth factors...exposure to treatments. We are in the process of assessing the pathologic outcome using H&E staining of the treated slices and correlating the results

Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: two case studies.

PubMed

Koontz, Bridget F; Miles, Edward F; Rubio, Mary Ann D; Madden, John F; Fisher, Samuel R; Scher, Richard L; Brizel, David M

2008-02-01

Angiosarcoma of the face is a vascular tumor with poor local control and short median survival despite standard treatment. Bevacizumab is a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), which can inhibit tumor growth. It is synergistic with radiotherapy in gastrointestinal malignancies. Given the vascular nature of angiosarcoma and the need for better treatment of this disease, we investigated the concurrent use of bevacizumab with preoperative radiotherapy for head and neck angiosarcoma. Two patients diagnosed with angiosarcoma of the nose were treated preoperatively with bevacizumab (5-10 mg/kg) and concurrent radiotherapy (50 Gy), followed by resection of the tumor bed. Both patients had a complete pathologic response with no residual disease. Neither has developed recurrence, with follow-up of 8.5 months and 2.1 years. The neoadjuvant combination of bevacizumab and radiation therapy is promising and should be further studied in the setting of vascular malignancies.

Treatment of Pituitary Carcinomas and Atypical Pituitary Adenomas: A Review

PubMed Central

HIROHATA, Toshio; ISHII, Yudo; MATSUNO, Akira

2014-01-01

Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53 protein, according to the World Health Organization (WHO) classification in 2004. Pituitary carcinomas (PC) usually develop from progressive APAs and predominantly consist of hormone-generating tumors, defined by the presence of disseminations in the cerebrospinal system or systemic metastases. Most of the cases with these malignant pituitary adenomas underwent surgeries, irradiations and adjuvant medical treatments, nevertheless, the therapies are mainly palliative. Recently, the efficacy of temozolomide (TMZ), an orally administered alkylating agent, has been reported as an alternative medical treatment. However, some recent studies have demonstrated a significant recurrence rate after effective response to TMZ. Further clinical and pathological researches of malignant pituitary adenomas will be required to improve the outcome of patients with these tumors. PMID:25446382

Giant cell angiofibroma misdiagnosed as a vascular malformation and treated with absolute alcohol for one year: a case report and review of the literature.

PubMed

He, Yue; Zhang, Chenping; Liu, Guanglong; Tian, Zhuowei; Wang, Lizhen; Kalfarentzos, Evagelos

2014-04-24

To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA). In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease.After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA. GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate.

An active learning approach for rapid characterization of endothelial cells in human tumors.

PubMed

Padmanabhan, Raghav K; Somasundar, Vinay H; Griffith, Sandra D; Zhu, Jianliang; Samoyedny, Drew; Tan, Kay See; Hu, Jiahao; Liao, Xuejun; Carin, Lawrence; Yoon, Sam S; Flaherty, Keith T; Dipaola, Robert S; Heitjan, Daniel F; Lal, Priti; Feldman, Michael D; Roysam, Badrinath; Lee, William M F

2014-01-01

Currently, no available pathological or molecular measures of tumor angiogenesis predict response to antiangiogenic therapies used in clinical practice. Recognizing that tumor endothelial cells (EC) and EC activation and survival signaling are the direct targets of these therapies, we sought to develop an automated platform for quantifying activity of critical signaling pathways and other biological events in EC of patient tumors by histopathology. Computer image analysis of EC in highly heterogeneous human tumors by a statistical classifier trained using examples selected by human experts performed poorly due to subjectivity and selection bias. We hypothesized that the analysis can be optimized by a more active process to aid experts in identifying informative training examples. To test this hypothesis, we incorporated a novel active learning (AL) algorithm into FARSIGHT image analysis software that aids the expert by seeking out informative examples for the operator to label. The resulting FARSIGHT-AL system identified EC with specificity and sensitivity consistently greater than 0.9 and outperformed traditional supervised classification algorithms. The system modeled individual operator preferences and generated reproducible results. Using the results of EC classification, we also quantified proliferation (Ki67) and activity in important signal transduction pathways (MAP kinase, STAT3) in immunostained human clear cell renal cell carcinoma and other tumors. FARSIGHT-AL enables characterization of EC in conventionally preserved human tumors in a more automated process suitable for testing and validating in clinical trials. The results of our study support a unique opportunity for quantifying angiogenesis in a manner that can now be tested for its ability to identify novel predictive and response biomarkers.

Encephalitis and AMPA receptor antibodies

PubMed Central

Höftberger, Romana; van Sonderen, Agnes; Leypoldt, Frank; Houghton, David; Geschwind, Michael; Gelfand, Jeffrey; Paredes, Mercedes; Sabater, Lidia; Saiz, Albert; Titulaer, Maarten J.; Graus, Francesc

2015-01-01

Objective: We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Methods: This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic techniques have been reported previously. Results: Patients' median age was 62 years (range 23–81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5–266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome (p = 0.009). Conclusion: Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome. PMID:25979696

A Head and Neck Simulator for Radiology and Radiotherapy

NASA Astrophysics Data System (ADS)

Thompson, Larissa; Campos, Tarcísio P. R.

2013-06-01

Phantoms are suitable tools to simulate body tissues and organs in radiology and radiation therapy. This study presents the development of a physical head and neck phantom and its radiological response for simulating brain pathology. The following features on the phantom are addressed and compared to human data: mass density, chemical composition, anatomical shape, computerized tomography images and Hounsfield Units. Mass attenuation and kerma coefficients of the synthetic phantom and normal tissues, as well as their deviations, were also investigated. Radiological experiments were performed, including brain tumors and subarachnoid hemorrhage simulations. Computerized tomography images of such pathologies in phantom and human were obtained. The anthropometric dimensions of the phantom present anatomical conformation similar to a human head and neck. Elemental weight percentages of the equivalent tissues match the human ones. Hounsfield Unit values of the main developed structures are presented, approaching human data. Kerma and mass attenuation coefficients spectra from human and phantom are presented, demonstrating smaller deviations in the radiological X-ray spectral domain. In conclusion, the phantom presented suitable normal and pathological radiological responses relative to those observed in humans. It may improve radiological protocols and education in medical imaging.

Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment.

PubMed

Tateishi, Ukihide; Miyake, Mototaka; Nagaoka, Tomoaki; Terauchi, Takashi; Kubota, Kazunori; Kinoshita, Takayuki; Daisaki, Hiromitsu; Macapinlac, Homer A

2012-04-01

To clarify whether fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging performed after two cycles of neoadjuvant chemotherapy (NAC) can be used to predict pathologic response in breast cancer. Institutional human research committee approval and written informed consent were obtained. Accuracy after two cycles of NAC for predicting pathologic complete response (pCR) was examined in 142 women (mean age, 57 years: range, 43-72 years) with histologically proved breast cancer between December 2005 and February 2009. Quantitative PET/CT and DCE MR imaging were performed at baseline and after two cycles of NAC. Parameters of PET/CT and of blood flow and microvascular permeability at DCE MR were compared with pathologic response. Patients were also evaluated after NAC by using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on DCE MR measurements and European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Multiple logistic regression analyses were performed to examine continuous variables at PET/CT and DCE MR to predict pCR, and diagnostic accuracies were compared with the McNemar test. Significant decrease from baseline of all parameters at PET/CT and DCE MR was observed after NAC. Therapeutic response was obtained in 24 patients (17%) with pCR and 118 (83%) without pCR. Sensitivity, specificity, and accuracy to predict pCR were 45.5%, 85.5%, and 82.4%, respectively, with RECIST and 70.4%, 95.7%, and 90.8%, respectively, with EORTC and PERCIST. Multiple logistic regression revealed three significant independent predictors of pCR: percentage maximum standardized uptake value (%SUV(max)) (odds ratio [OR], 1.22; 95% confidence interval [CI]: 1.11, 1.34; P < .0001), percentage rate constant (%k(ep)) (OR, 1.07; CI: 1.03, 1.12; P = .002), and percentage area under the time-intensity curve over 90 seconds (%AUC(90)) (OR, 1.04; CI: 1.01, 1.07; P = .048). When diagnostic accuracies are compared, PET/CT is superior to DCE MR for the prediction of pCR (%SUV(max) [90.1%] vs %κ(ep) [83.8%] or %AUC(90) [76.8%]; P < .05). The sensitivities of %SUV(max) (66.7%), %k(ep) (51.7%), and %AUC(90) (50.0%) at (18)F-FDG PET/CT and DCE MR after two cycles of NAC are not acceptable, but the specificities (96.4%, 92.0%, and 95.2%, respectively) are high for stratification of pCR cases in breast cancer. © RSNA, 2012.

The role of regulatory T cells in the control of natural killer cells: relevance during tumor progression.

PubMed

Ghiringhelli, Francois; Ménard, Cédric; Martin, Francois; Zitvogel, Laurence

2006-12-01

Tumor immunosurveillance relies on cognate immune effectors [lymphocytes and interferon-gamma (IFN-gamma)] and innate immunity [natural killer (NK) cells, natural killer group 2, member D (NKG2D) ligands, perforin/granzyme, and tumor necrosis factor-related apoptosis-inducing ligand]. In parallel, tumor cells promote the expansion of CD4(+)CD25(+) regulatory T cells (Tregs) that counteract T-cell-based anti-tumor immunity. Moreover, accumulating evidence points to a critical role for Tregs in dampening NK cell immune responses. This review summarizes the findings showing that Tregs suppress NK cell effector functions in vitro and in vivo, i.e. homeostatic proliferation, cytotoxicity, and interleukin-12-mediated IFN-gamma production. The molecular mechanism involve selective expression of membrane-bound transforming growth factor-beta on Tregs, which downregulate NKG2D expression on NK cells in vitro and in vivo. The regulatory events dictating NK cell suppression by Tregs have been studied and are discussed. The pathological relevance of the Treg-NK cell interaction has been brought up in tumor models and in patients with cancer. Consequently, inhibition of Tregs through pharmacological interventions should be considered during NK-cell-based immunotherapy of cancer.

Exquisite Sensitivity of TP53 Mutant and Basal Breast Cancers to a Dose-Dense Epirubicin−Cyclophosphamide Regimen

PubMed Central

Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

2007-01-01

Background In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. Methods and Findings In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m2 epirubicin and 1,200 mg/m2 cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status. Conclusions This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin–cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features. PMID:17388661

Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S., E-mail: pajohnst@iupui.edu

Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally,more » stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.« less

Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: Evaluating the effect of race/ethnicity

PubMed Central

Chavez-MacGregor, Mariana; Litton, Jennifer; Chen, Huiqin; Giordano, Sharon H.; Hudis, Clifford A.; Wolff, Antonio C.; Valero, Vicente; Hortobagyi, Gabriel N.; Bondy, Melissa L.; Gonzalez-Angulo, Ana Maria

2010-01-01

Purpose To evaluate the influence of race/ethnicity and tumor subtype in pathological complete response (pCR) following treatment with neoadjuvant chemotherapy. Methods 2074 patients diagnosed with breast cancer between 1994 and 2008, treated with neoadjuvant anthracycline- and taxane-based chemotherapy, were included. pCR was defined as no residual invasive cancer in the breast and axilla. Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome. Results Median age was 50 years, 14.6% patients were black, 15.2% Hispanic, 64.3% White, and 5.9% other race. There were no differences in pCR rates among race/ethnicity: (12.3% in black, 14.2% in Hispanics, 12.3% in whites and 11.5% in others, p=.788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse RFS and OS (p≤.0001). Differences in RFS by race/ethnicity were seen in the patients with hormone receptor-positive disease, p=.007. In multivariate analysis, Hispanics had improved RFS (HR, 95% CI 0.69; 0.49-0.97) and OS (HR, 95% CI 0.63; 0.41-0.97); blacks had a trend to worse outcomes (RFS:HR, 95% CI 1.28; 0.97-1.68, OS:HR, 1.32; 95% CI; 0.97-1.81) when compared to whites. Conclusions In this cohort of patients, race/ethnicity was not significantly associated with pCR rates. In a multivariate analysis we observed improved outcomes in Hispanics and a trend towards worse outcomes in black patients, when compared to whites. Further research is needed to explore the potential differences in biology and outcomes. PMID:20564153

Quantifying the benefit of a pathologic complete response after neoadjuvant chemoradiotherapy in the treatment of esophageal cancer.

PubMed

Scheer, Richard V; Fakiris, Achilles J; Johnstone, Peter A S

2011-07-15

To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not. Copyright © 2011 Elsevier Inc. All rights reserved.

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

PubMed

Kamiya, T; Uehara, K; Nakayama, G; Ishigure, K; Kobayashi, S; Hiramatsu, K; Nakayama, H; Yamashita, K; Sakamoto, E; Tojima, Y; Kawai, S; Kodera, Y; Nagino, M

2016-06-01

Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option. Copyright © 2016 Elsevier Ltd. All rights reserved.

Importance of positron emission tomography for assessing the response of primary and metastatic lesions to induction treatments in T4 esophageal cancer.

PubMed

Makino, Tomoki; Yamasaki, Makoto; Tanaka, Koji; Tatsumi, Mitsuaki; Takiguchi, Shuji; Hatazawa, Jun; Mori, Masaki; Doki, Yuichiro

2017-10-01

There is no consensus strategy for treatment of T4 esophageal cancer, and because of this, a better evaluation of treatment response is crucial to establish personalized therapies. This study aimed to establish a useful system for evaluating treatment response in T4 esophageal cancer. This study included 130 patients with cT4 esophageal cancer without distant metastasis who underwent 18 F-fluorodeoxyglucose-positron emission tomography before and after a series of induction treatments comprising chemoradiation or chemotherapy. We evaluated the maximal standardized uptake value and treatment response. The mean ± standard deviation of standardized uptake value in the primary tumor before and after induction treatments were 13.8 ± 4.4 and 5.4 ± 4.1, respectively, and the mean standardized uptake value decrease was 58.4%. The most significant difference in survival between positron emission tomography-primary tumor responders and nonresponders was at a decrease of 60% standardized uptake value, based on every 10% stepwise cutoff analysis (2-year cause-specific survival: 60.2 vs 23.5%; hazard ratio = 2.705; P < .0001). With this cutoff value, the resectability (P = .0307), pathologic response (P = .0004), and pT stage (P < .0001) were associated with positron emission tomography-primary tumor response. Univariate analysis of 2-year cause-specific survival indicated a correlation between cause-specific survival and clinical stages according to TNM classification, esophageal perforation, positron emission tomography-primary tumor response, lymph node status evaluated by positron emission tomography before and after induction treatments, and operative resection. Multivariate analysis further identified positron emission tomography-primary tumor response (hazard ratio = 2.354; P = .0107), lymph node status evaluated by positron emission tomography after induction treatments (hazard ratio = 1.966; P = .0089), and operative resection (hazard ratio = 2.012; P = .0245) as independent prognostic predictors. Positron emission tomography evaluation of the response of primary and metastatic lesions to induction treatments is important to formulate treatment strategies for cT4 esophageal cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective pathologies of the head and neck in children: a developmental perspective.

PubMed

Ozolek, John A

2009-09-01

The range of pathology seen in the head and neck region is truly amazing and to a large extent probably mirrors the complex signaling pathways and careful orchestration of events that occurs between the primordial germ layers during the development of this region. As is true in general for the entire discipline of pediatric pathology, the head and neck pathology within this age group is as diverse and different as its adult counterpart. Cases that come across the pediatric head and neck surgical pathology bench are more heavily weighted toward developmental and congenital lesions such as branchial cleft anomalies, thyroglossal duct cysts, ectopias, heterotopias, choristomas, and primitive tumors. Many congenital "benign" lesions can cause significant morbidity and even mortality if they compress the airway or other vital structures. Exciting investigations into the molecular embryology of craniofacial development have begun to shed light on the pathogenesis of craniofacial developmental lesions and syndromes. Much more investigation is needed, however, to intertwine aberrations in the molecular ontogeny and development of the head and neck regions to the represented pathology. This review will integrate traditional morphologic embryology with some of the recent advances in the molecular pathways of head and neck development followed by a discussion of a variety of developmental lesions finishing with tumors presumed to be derived from pluripotent/progenitor cells and tumors that show anomalous or aborted development.

Clinical utility of pretreatment prediction of chemoradiotherapy response in rectal cancer: a review.

PubMed

Yoo, Byong Chul; Yeo, Seung-Gu

2017-03-01

Approximately 20% of all patients with locally advanced rectal cancer experience pathologically complete responses following neoadjuvant chemoradiotherapy (CRT) and standard surgery. The utility of radical surgery for patients exhibiting good CRT responses has been challenged. Organ-sparing strategies for selected patients exhibiting complete clinical responses include local excision or no immediate surgery. The subjects of this tailored management are patients whose presenting disease corresponds to current indications of neoadjuvant CRT, and their post-CRT tumor response is assessed by clinical and radiological examinations. However, a model predictive of the CRT response, applied before any treatment commenced, would be valuable to facilitate such a personalized approach. This would increase organ preservation, particularly in patients for whom upfront CRT is not generally prescribed. Molecular biomarkers hold the greatest promise for development of a pretreatment predictive model of CRT response. A combination of clinicopathological, radiological, and molecular markers will be necessary to render the model robust. Molecular research will also contribute to the development of drugs that can overcome the radioresistance of rectal tumors. Current treatments for rectal cancer are based on the expected prognosis given the presenting disease extent. In the future, treatment schemes may be modified by including the predicted CRT response evaluated at presentation.

Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma.

PubMed

Roos, Frederik C; Evans, Andrew J; Brenner, Walburgis; Wondergem, Bill; Klomp, Jeffery; Heir, Pardeep; Roche, Olga; Thomas, Christian; Schimmel, Heiko; Furge, Kyle A; Teh, Bin T; Thüroff, Joachim W; Hampel, Christian; Ohh, Michael

2011-02-01

Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Reduction-Responsive Polymeric Micelles and Vesicles for Triggered Intracellular Drug Release

PubMed Central

Sun, Huanli; Cheng, Ru; Deng, Chao

2014-01-01

Abstract Significance: The therapeutic effects of current micellar and vesicular drug formulations are restricted by slow and inefficient drug release at the pathological site. The development of smart polymeric nanocarriers that release drugs upon arriving at the target site has received a tremendous amount of attention for cancer therapy. Recent Advances: Taking advantage of a high reducing potential in the tumor tissues and in particular inside the tumor cells, various reduction-sensitive polymeric micelles and vesicles have been designed and explored for triggered anticancer drug release. These reduction-responsive nanosystems have demonstrated several unique features, such as good stability under physiological conditions, fast response to intracellular reducing environment, triggering drug release right in the cytosol and cell nucleus, and significantly improved antitumor activity, compared to traditional reduction-insensitive counterparts. Critical Issues: Although reduction-sensitive micelles and polymersomes have accomplished rapid intracellular drug release and enhanced in vitro antitumor effect, their fate inside the cells including the mechanism, site, and rate of reduction reaction remains unclear. Moreover, the systemic fate and performance of reduction-sensitive polymeric drug formulations have to be investigated. Future Directions: Biophysical studies should be carried out to gain insight into the degradation and drug release behaviors of reduction-responsive nanocarriers inside the tumor cells. Furthermore, novel ligand-decorated reduction-sensitive nanoparticulate drug formulations should be designed and explored for targeted cancer therapy in vivo. Antioxid. Redox Signal. 21, 755–767. PMID:24279980

Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome.

PubMed

Ferrandina, Gabriella; Martinelli, Enrica; Zannoni, Gian Franco; Distefano, Mariagrazia; Paglia, Amelia; Ferlini, Cristiano; Scambia, Giovanni

2007-02-01

Alterations of the beta subunit of tubulin have been reported to be predictive of resistance to radiation and antitubulin agents in several solid tumors. The aim of the study was to investigate the clinical role of beta III tubulin expression as prognostic factor for survival and as a predictive parameter of response to preoperative radiochemotherapy in a single institutional series of locally advanced cervical cancer (LACC) patients. The study included 98 LACC patients admitted to the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso between January 1998 and January 2005. Immunohistochemistry was performed by using the polyclonal rabbit anti-beta III tubulin antibody (Covance, Princeton, NJ, USA). The value of 10% immunostained tumor cells was arbitrarily chosen as cut-off value to distinguish cases with high versus low beta III tubulin content. In the whole series, beta III tubulin immunoreaction was detectable in 66/98 cases (67.3%), and the percentage of positively stained cells ranged from 0 to 100% (median=10%). The percentages of cases with high beta III tubulin expression were shown not to be differently distributed according to clinico-pathological characteristics. There was no statistically significant difference in the distribution of cases with high beta III tubulin expression according to clinical and pathological response to treatment. During the follow-up period, recurrence and death of disease occurred in 15 and 13 cases, respectively. There was no difference in disease-free and overall survival in cases with high versus low beta III tubulin expression. The assessment of class III beta tubulin status seems of little usefulness in order to identify LACC patients with poor chance of response to concomitant radiochemotherapy and unfavorable prognosis.

Pathological characteristics of spine metastases treated with high-dose single-fraction stereotactic radiosurgery.

PubMed

Katsoulakis, Evangelia; Laufer, Ilya; Bilsky, Mark; Agaram, Narasimhan P; Lovelock, Michael; Yamada, Yoshiya

2017-01-01

OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may makeit difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator-based single-fraction (18-24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36-80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6-50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7-86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2-70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered.

Pathological characteristics of spine metastases treated with high-dose single-fraction stereotactic radiosurgery

PubMed Central

Katsoulakis, Evangelia; Laufer, Ilya; Bilsky, Mark; Agaram, Narasimhan P.; Lovelock, Michael; Yamada, Yoshiya

2017-01-01

OBJECTIVE Spine radiosurgery is increasingly being used to treat spinal metastases. As patients are living longer because of the increasing efficacy of systemic agents, appropriate follow-up and posttreatment management for these patients is critical. Tumor progression after spine radiosurgery is rare; however, vertebral compression fractures are recognized as a more common posttreatment effect. The use of radiographic imaging alone posttreatment may make it difficult to distinguish tumor progression from postradiation changes such as fibrosis. This is the largest series from a prospective database in which the authors examine histopathology of samples obtained from patients who underwent surgical intervention for presumed tumor progression or mechanical pain secondary to compression fracture. The majority of patients had tumor ablation and resulting fibrosis rather than tumor progression. The aim of this study was to evaluate tumor histopathology and characteristics of patients who underwent pathological sampling because of radiographic tumor progression, fibrosis, or collapsed vertebrae after receiving high-dose single-fraction stereotactic radiosurgery. METHODS Between January 2005 and January 2014, a total of 582 patients were treated with linear accelerator–based single-fraction (18–24 Gy) stereotactic radiosurgery. The authors retrospectively identified 30 patients (5.1%) who underwent surgical intervention for 32 lesions with vertebral cement augmentation for either mechanical pain or instability secondary to vertebral compression fracture (n = 17) or instrumentation (n = 15) for radiographic tumor progression. Radiation and surgical treatment, histopathology, and long-term outcomes were reviewed. Survival and time to recurrence were calculated using the Kaplan-Meier method. RESULTS The mean age at the time of radiosurgery was 59 years (range 36–80 years). The initial pathological diagnoses were obtained for all patients and primarily included radioresistant tumor types, including renal cell carcinoma in 7 (22%), melanoma in 6 (19%), lung carcinoma in 4 (12%), and sarcoma in 3 (9%). The median time to surgical intervention was 24.7 months (range 1.6–50.8 months). The median follow-up and overall survival for all patients were 42.5 months and 41 months (overall survival range 7–86 months), respectively. The majority of assessed lesions showed no evidence of tumor on pathological review (25 of 32, 78%), while a minority of lesions revealed residual tumor (7 of 32, 22%). The median survival for patients after tumor recurrence was 5 months (range 2–70 months). CONCLUSIONS High-dose single-fraction radiosurgery is tumor ablative in the majority of instances. In a minority of cases, tumor persists and salvage treatments should be considered. PMID:28041326

The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study.

PubMed

Wang, Peng; Liang, Jianwei; Wang, Zheng; Hou, Huirong; Shi, Lei; Zhou, Zhixiang

2017-05-01

This retrospective cohort study aimed to discuss the prognostic value of p53 positive in colorectal cancer. A total of 124 consecutive patients diagnosed with colorectal cancer were evaluated at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 1 January 2009 to 31 December 2010. The expression of p53 in colorectal cancer was examined by immunohistochemistry. Based on the expression levels of p53, the 124 patients were divided into a p53 positive group and a p53 negative group. In this study, 72 patients were in the p53 positive group and 52 in the p53 negative group. The two groups were well balanced in gender, age, body mass index, American Society of Anesthesiologists scores, and number of lymph nodes harvested. p53 positive was associated with carcinoembryonic antigen ≥5 ng/mL ( p = 0.036), gross type ( p = 0.037), degree of tumor differentiation ( p = 0.026), pathological tumor stage ( p = 0.019), pathological node stage ( p = 0.004), pathological tumor-node-metastasis stage ( p = 0.017), nerve invasion ( p = 0.008), and vessel invasion ( p = 0.018). Tumor site, tumor size, and pathological pattern were not significantly different between these two groups. Disease-free survival and overall survival in the p53 positive group were significantly shorter than the p53 negative group ( p = 0.021 and 0.025, respectively). Colorectal cancer patients with p53 positive tended to be related to a higher degree of malignancy, advanced tumor-node-metastasis stage, and shorter disease-free survival and overall survival. p53 positive was independently an unfavorable prognostic marker for colorectal cancer patients.

Cancer Staging

MedlinePlus

... cancer described by this staging system in your pathology report, unless you have a cancer for which ... adult and childhood cancers. Related Resources Tumor Grade Pathology Reports Posted: March 9, 2015 Most text on ...

Pentameric procyanidins isolated from Theobroma cacao seeds selectively downregulate ErbB2 in human aortic endothelial cells.

PubMed

Kenny, Thomas P; Keen, Carl L; Jones, Paul; Kung, Hsing-Jien; Schmitz, Harold H; Gershwin, M Eric

2004-03-01

Flavonoids isolated from cocoa have biological activities relevant to oxidant defenses, vascular health, tumor suppression, and immune function. The intake of certain dietary flavonoids, along with other dietary substances such as tocopherols, ascorbate, and carotenoids, is epidemiologically associated with a reduced risk of cardiovascular disease. Flavonoids have also been shown to modulate tumor pathology in vitro and in animal models. We took advantage of the conserved sequences found in tyrosine kinases to study the influence of cocoa fractions and controls on gene expression. We report that the pentameric procyanidin (molecular weight of 1442 daltons) fraction isolated from cocoa was a potent inhibitor of tyrosine kinase ErbB2 expression, a receptor important in angiogenesis regulation. Consistent with this primary observation, the cocoa flavonoid fraction also suppressed human aortic endothelial cell (HAEC) growth and decreased expression of two tyrosine kinases responsive to ErbB2 modulation, namely VEGFR-2/KDR and MapK 11/p38beta2. These inhibitory effects were observed when HAECs were treated with the flavonol fraction (molecular weight 280 daltons) isolated from cocoa, which comprise the structural subunits from which the procyanidin flavonoid subclass is biosynthetically constructed. Down-regulation of ErbB2 and inhibition of HAEC growth by cocoa procyanidins may have several downstream implications, including reduced vascular endothelial growth factor (VEGF) activity and angiogenic activity associated with tumor pathology. These results suggest specific dietary flavonoids are capable of selectively inhibiting ErbB2 and therefore may offer important insight into the design of therapeutic agents that target tumors overexpressing ErbB2.

Brain Tumor Segmentation Using Deep Belief Networks and Pathological Knowledge.

PubMed

Zhan, Tianming; Chen, Yi; Hong, Xunning; Lu, Zhenyu; Chen, Yunjie

2017-01-01

In this paper, we propose an automatic brain tumor segmentation method based on Deep Belief Networks (DBNs) and pathological knowledge. The proposed method is targeted against gliomas (both low and high grade) obtained in multi-sequence magnetic resonance images (MRIs). Firstly, a novel deep architecture is proposed to combine the multi-sequences intensities feature extraction with classification to get the classification probabilities of each voxel. Then, graph cut based optimization is executed on the classification probabilities to strengthen the spatial relationships of voxels. At last, pathological knowledge of gliomas is applied to remove some false positives. Our method was validated in the Brain Tumor Segmentation Challenge 2012 and 2013 databases (BRATS 2012, 2013). The performance of segmentation results demonstrates our proposal providing a competitive solution with stateof- the-art methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Radionuclide bone scanning of osteosarcoma: falsely extended uptake patterns.

PubMed

Chew, F S; Hudson, T M

1982-07-01

The pathologic specimens of 18 osteosarcomas of long bones were examined to correlate histologic abnormalities with abnormalities seen on preoperative 99mTc pyrophosphate or methylene diphosphonate bone scans. Seven scans accurately represented the extent of the tumor. Eleven scans disclosed increased activity extending beyond the radiographic abnormalities. In eight of these, there was no occult tumor extension and in the other three, the scan activity did not accurately portray the skip metastases that were present. Therefore, these 11 scans demonstrated the falsely extended pattern of uptake beyond the true limits of the tumors. Pathologic slides were available for 10 of the 11 areas of bone that exhibited extended uptake. In two instances, there was no pathologic abnormality. In the other eight cases we found marrow hyperemia, medullary reactive bone, or periosteal new bone. This is the first description of these histologic abnormalities of medullary bone in areas of extended uptake on radionuclide bone scans.

Normal pelvic ultrasound or MRI does not rule out neoplasm in patients with gonadal dysgenesis and Y chromosome material.

PubMed

Ebert, Kristin M; Hewitt, Geri D; Indyk, Justin A; McCracken, Katherine A; Nahata, Leena; Jayanthi, Venkata R

2018-04-01

Patients with gonadal dysgenesis (GD) with a Y chromosome have an increased risk of gonadal neoplasm. Few data exist on the ability of imaging to detect malignancy in intra-abdominal gonads in these patients. We aimed to determine the correlation between preoperative imaging findings and gonadal pathology in GD patients with Y chromosome material. A retrospective review was performed of patients with XY or XO/XY GD who underwent gonadectomy at our institution from 2003 to 2017. Patients were assessed preoperatively with ultrasonography; some additionally underwent MRI. The series consisted of 10 patients, all with female gender and non-palpable gonads. Median age was 13.1 years (range 2.4-18.3 years). Overall, four of the ten patients (40%) had a tumor (gonadoblastoma or dysgerminoma) on final pathology. Four patients had a gonad or gonads that were definitively seen on ultrasonography. All visualized gonads were described as "normal" or "small" with the exception of one patient, who had a normal MRI. Three of the four patients in this group had a tumor on final pathology. The remaining six patients had a gonad or gonads that were not definitively visualized on ultrasound; one patient in this group had a tumor on final pathology. Overall, five of seven gonads (71%) definitively visualized on ultrasound had tumor on final pathology, and two of thirteen gonads (15%) not visualized on ultrasound had tumor on final pathology; this difference was statistically significant (p = 0.012). Three patients were imaged with MRI. Of the gonads that could be visualized on MRI, no definitive abnormalities were seen. All patients imaged with MRI had tumors on final pathology. Both ultrasound and MRI are relatively poor at identifying and characterizing intra-abdominal gonads in GD patients. The majority of patients who had a neoplasm had normal imaging findings. Gonads that were definitively visualized on ultrasound were more likely to contain neoplasms that could not be visualized, which perhaps because of tumor growth. No other consistent imaging findings of malignancy were found. Our study included ultrasound evaluations that were completed over 10 years ago and not performed by pediatric ultrasonographers, which may have biased the results. However, results suggest that when discussing gonadectomy with GD patients, one should not be reassured by "normal" imaging findings. Neither ultrasound nor MRI should be relied on for surveillance in GD patients who decide against gonadectomy. A normal ultrasound or MRI does not rule out neoplasm in GD patients with intra-abdominal gonads. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Jikuzono, Tomoo; Higashiyama, Takuya; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Ichihara, Kiyoshi; Kuma, Kanji

2007-04-01

In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors.

PubMed

Snuderl, Matija; Wirth, Dennis; Sheth, Sameer A; Bourne, Sarah K; Kwon, Churl-Su; Ancukiewicz, Marek; Curry, William T; Frosch, Matthew P; Yaroslavsky, Anna N

2013-01-01

Intraoperative diagnosis plays an important role in accurate sampling of brain tumors, limiting the number of biopsies required and improving the distinction between brain and tumor. The goal of this study was to evaluate dye-enhanced multimodal confocal imaging for discriminating gliomas from nonglial brain tumors and from normal brain tissue for diagnostic use. We investigated a total of 37 samples including glioma (13), meningioma (7), metastatic tumors (9) and normal brain removed for nontumoral indications (8). Tissue was stained in 0.05 mg/mL aqueous solution of methylene blue (MB) for 2-5 minutes and multimodal confocal images were acquired using a custom-built microscope. After imaging, tissue was formalin fixed and paraffin embedded for standard neuropathologic evaluation. Thirteen pathologists provided diagnoses based on the multimodal confocal images. The investigated tumor types exhibited distinctive and complimentary characteristics in both the reflectance and fluorescence responses. Images showed distinct morphological features similar to standard histology. Pathologists were able to distinguish gliomas from normal brain tissue and nonglial brain tumors, and to render diagnoses from the images in a manner comparable to haematoxylin and eosin (H&E) slides. These results confirm the feasibility of multimodal confocal imaging for intravital intraoperative diagnosis. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Anti- and pro-tumor functions of autophagy.

PubMed

Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Vicencio, José-Miguel; Criollo, Alfredo; Maiuri, Maria Chiara; Kroemer, Guido

2009-09-01

Autophagy constitutes one of the major responses to stress in eukaryotic cells, and is regulated by a complex network of signaling cascades. Not surprisingly, autophagy is implicated in multiple pathological processes, including infection by pathogens, inflammatory bowel disease, neurodegeneration and cancer. Both oncogenesis and tumor survival are influenced by perturbations of the molecular machinery that controls autophagy. Numerous oncoproteins, including phosphatidylinositol 3-kinase, Akt1 and anti-apoptotic members of the Bcl-2 family suppress autophagy. Conversely, several tumor suppressor proteins (e.g., Atg4c; beclin 1; Bif-1; BH3-only proteins; death-associated protein kinase 1; LKB1/STK11; PTEN; UVRAG) promote the autophagic pathway. This does not entirely apply to p53, one of the most important tumor suppressor proteins, which regulates autophagy in an ambiguous fashion, depending on its subcellular localization. Irrespective of the controversial role of p53, basal levels of autophagy appear to inhibit tumor development. On the contrary, chemotherapy- and metabolic stress-induced activation of the autophagic pathway reportedly contribute to the survival of formed tumors, thereby favoring resistance. In this context, autophagy inhibition would represent a major therapeutic target for chemosensitization. Here, we will review the current knowledge on the dual role of autophagy as an anti- and pro-tumor mechanism.

Computer aided detection of tumor and edema in brain FLAIR magnetic resonance image using ANN

NASA Astrophysics Data System (ADS)

Pradhan, Nandita; Sinha, A. K.

2008-03-01

This paper presents an efficient region based segmentation technique for detecting pathological tissues (Tumor & Edema) of brain using fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. This work segments FLAIR brain images for normal and pathological tissues based on statistical features and wavelet transform coefficients using k-means algorithm. The image is divided into small blocks of 4×4 pixels. The k-means algorithm is used to cluster the image based on the feature vectors of blocks forming different classes representing different regions in the whole image. With the knowledge of the feature vectors of different segmented regions, supervised technique is used to train Artificial Neural Network using fuzzy back propagation algorithm (FBPA). Segmentation for detecting healthy tissues and tumors has been reported by several researchers by using conventional MRI sequences like T1, T2 and PD weighted sequences. This work successfully presents segmentation of healthy and pathological tissues (both Tumors and Edema) using FLAIR images. At the end pseudo coloring of segmented and classified regions are done for better human visualization.

Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study.

PubMed

Schneider, Karolin; Marbaix, Etienne; Bouzin, Caroline; Hamoir, Marc; Mahy, Pierre; Bol, Vanesa; Grégoire, Vincent

2018-03-01

Human papillomavirus (HPV) prevalence in oropharynx squamous cell carcinoma (OPSCC) is on the rise. HPV-linked OPSCCs represent a distinct clinical entity with a better treatment response and patient survival compared to tumors not linked to HPV. An emerging role in treatment response has been attributed to immune cell infiltration in human tumors. In this study, we investigated immune cell infiltration in human SCC of the head and neck region and its relation to overall survival after treatment with surgery (with or without radiotherapy) or concomitant chemo (or cetuximab)-radiotherapy. Paraffin-embedded tumor samples of 136 patients with SCC of the larynx, hypopharynx, oral cavity and oropharynx were processed for immunohistochemical detection of CD3 + T-cells, CD8 + cytotoxic T-cells, CD20 + B-cells and CD163 + M2 macrophages within the tumor infiltrated area. Clinico-pathological data were analyzed as a function of tumor location and p16-status. Immune cell infiltration was represented as stained area on the whole tumor infiltrated area, compared for the different tumor locations and correlated to patient survival. Patients with oropharynx tumors expressing significant p16 levels (p16-sg) had a 5-year overall survival of 85% compared to 43% for patients with no significant p16 (p16-ns) expression (HR: 0.3 - 95% CI: 0.1-0.6). Median immune cell infiltration (T- and B-lymphocytes) was significantly elevated in p16-sg oropharyngeal tumors, compared to p16-ns oropharyngeal tumors and to all other head and neck tumor locations. No difference in CD163 + macrophage infiltration was observed across the different patient groups. In the whole population, a high infiltration by CD3 + T-lymphocytes was associated to a significantly (p = .03; HR: 0.6, 95% CI: 0.4-0.97) better overall survival. Oropharynx cancer with significant p16 expression showed an increased overall survival and elevated T- and B-lymphocyte infiltration, which suggests a prognostic relevance of immune cell infiltration.

NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial)

PubMed Central

2008-01-01

Background Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. Methods/design Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score). Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy). Discussion The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice. Trial registration ISRCTN45750457 PMID:18671847

[Sinonasal-type hemangiopericytoma: a clinicopathologic analysis of 6 cases].

PubMed

Wang, Shu-yi; Zhu, Xiong-zeng

2006-05-01

To study the clinicopathologic features, histologic diagnosis and differential diagnosis of sinonasal-type of hemangiopericytoma (SNTHPC). The clinical, radiographic and pathologic findings of 6 cases of SNTHPC were analyzed. Immunohistochemistry and electron microscopy were performed on selected examples. Amongst the 6 patients studied, 4 were males and 2 were females. The age of patients ranged from 56 to 71 years (mean = 60.5 years old). The commonest clinical presentation was nasal obstruction and/or epistaxis. Other symptoms could include increased nasal secretion, eyeball pain, decreased visual acuity, increased tear secretion and headache. The tumor involved nasal cavity and/or paranasal sinuses. Gross examination showed polypoid tumor masses, brownish fleshy tissue or whitish tumor tissue fragments. Histologically, the tumor showed a mixture of diffuse, fascicular, storiform, reticulated and whorled growth patterns. The tumor cells were spindle-shaped and possessed clear to eosinophilic cytoplasm. Mitotic figures were rarely seen. The intervening vasculature was characteristically thin-walled, with focal hyalinization changes and rarely the staghorn pattern. Immunohistochemical study showed that the tumor cells expressed vimentin (6/6), smooth muscle actin (5/6) and CD34 (3/6). Electron microscopy demonstrated the presence of intracytoplasmic myofilaments. The tumor cells were linked together by primitive cell junctions. In general, the histologic diagnosis of SNTHPC was difficult, and only 1 case had the correct initial pathologic diagnosis made. Follow-up data were available in 5 patients and 2 of them had local recurrences. SNTHPC is a low to intermediate grade soft tissue tumor with pericytes differentiation. Correct diagnosis relies on detailed pathologic assessment and application of ancillary investigations.

Value of the Strain Ratio on Ultrasonic Elastography for Differentiation of Benign and Malignant Soft Tissue Tumors.

PubMed

Hahn, Seok; Lee, Young Han; Lee, Seung Hyun; Suh, Jin-Suck

2017-01-01

The purpose of this study was to evaluate whether the strain ratio provides additional value to conventional visual elasticity scores in the differentiation of benign and malignant soft tissue tumors by ultrasonic elastography. The Institutional Review Board approved the protocol of this retrospective review. Seventy-three patients who underwent elastography and had a soft tissue mass pathologically confirmed by ultrasound-guided core biopsy or surgical excision were enrolled from April 2012 through October 2014. On elastography, elasticity scores were determined with a 5-point visual scale, and the strain ratio to adjacent soft tissue at the same depth was calculated. Tumors were divided into benign and malignant groups according to the pathologic diagnoses. Elasticity scores and strain ratios were compared between benign and malignant groups, and diagnostic performance was evaluated by receiver operating characteristic curves. Of the 73 patients, 40 had benign tumors, and 33 had malignant tumors. Strain ratios (P = .003) and elasticity scores (P = .048) were significantly different between pathologic results. The areas under the receiver operating characteristic curves were 0.700 (95% confidence interval, 0.581-0.802) for the strain ratio and 0.623 (95% confidence interval, 0.515-0.746) for elastography. The strain ratios of malignant soft tissue tumors were lower than those of benign tumors and showed better diagnostic performance than did elasticity scores. The strain ratio can be used as a diagnostic indicator to predict the malignant potential of soft tissue tumors. © 2016 by the American Institute of Ultrasound in Medicine.

Expression of receptor activator of nuclear factor kappa-B ligand (RANKL) in neoplasms of dogs and cats.

PubMed

Barger, Anne M; Fan, Timothy M; de Lorimier, Louis-Philippe; Sprandel, Ian T; O'Dell-Anderson, Kristen

2007-01-01

Receptor activator of nuclear factor kappa-B (RANK), RANK-ligand (RANKL), and the soluble decoy receptor osteoprotegerin (OPG) form a key axis modulating osteoclastogenesis. In health, RANKL-expressing bone stromal cells and osteoblasts activate osteoclasts through RANK ligation, resulting in homeostatic bone resorption. Skeletal tumors of dogs and cats, whether primary or metastatic, may express RANKL and directly induce malignant osteolysis. Bone malignancies of dogs and cats may express RANKL, thereby contributing to pathologic bone resorption and pain. Furthermore, relative RANKL expression in bone tumors may correlate with radiographic characteristics of bone pathology. Forty-two dogs and 6 cats with spontaneously-occurring tumors involving bones or soft tissues were evaluated. A polyclonal anti-human RANKL antibody was validated for use in canine and feline cells by flow cytometry and immunocytochemistry. Fifty cytologic specimens were collected from bone and soft tissue tumors of 48 tumor-bearing animals and assessed for RANKL expression. In 15 canine osteosarcoma (OSA) samples, relative RANKL expression was correlated with radiographic characteristics of bone pathology. Expression of RANKL by neoplastic cells was identified in 32/44 canine and 5/6 feline tumor samples. In 15 dogs with OSA, relative RANKL expression did not correlate with either radiographic osteolysis or bone mineral density as assessed by dual energy x-ray absorptiometry. In dogs and cats, tumors classically involving bone and causing pain, often may express RANKL. Confirming RANKL expression in tumors is a necessary step toward the rational institution of novel therapies targeting malignant osteolysis via RANKL antagonism.

Networking for ovarian rare tumors: a significant breakthrough improving disease management.

PubMed

Chiannilkulchai, N; Pautier, P; Genestie, C; Bats, A S; Vacher-Lavenu, M C; Devouassoux-Shisheboran, M; Treilleux, I; Floquet, A; Croce, S; Ferron, G; Mery, E; Pomel, C; Penault-Llorca, F; Lefeuvre-Plesse, C; Henno, S; Leblanc, E; Lemaire, A S; Averous, G; Kurtz, J E; Ray-Coquard, I

2017-06-01

Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pathological and clinical features of primary osseous tumours of the jaw.

PubMed

Sarkar, Reena

2014-11-01

Primary bone tumors of the jaw are rare. The neoplastic cells in these tumors are the osteoblasts and osteoclasts. The gnathic bone tumors have also been referred to as borderline. The clinicopathologic approach towards these bony lesions have been reviewed.

mRNA Expression of Platelet-Derived Growth Factor Receptor-{beta} and C-KIT: Correlation With Pathologic Response to Cetuximab-Based Chemoradiotherapy in Patients With Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Erben, Philipp; Horisberger, Karoline; Muessle, Benjamin

2008-12-01

Purpose: Deviant expression of platelet-derived growth factor receptor-{beta} (PDGFR{beta}) and c-kit was shown in patients with colorectal cancer. In the present study, mRNA expression of PDGFR{beta} and c-kit in 33 patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy with cetuximab/capecitabine/irinotecan in correlation with the tumor regression rate was investigated. Methods and Materials: Pretherapeutic biopsy cores and tumor material from the resected specimens were collected in parallel with normal rectal mucosa. The expression levels of PDGFR{beta} and c-kit were measured by quantitative polymerase chain reaction. Tumors were classified as good responders (tumor regression grade [TRG], 2-3) or poor responders (TRG,more » 0-1). Results: The TRG evaluation of the resected specimen was TRG 0-1 in 11 and TRG 2-3 in 22. The median normalized ratios in the pretreatment mucosa vs. tumor biopsy cores was as follows: PDGFR{beta} ratio of 15.2 vs. 49.5 (p <0.0001) and c-kit ratio of 0.94 vs. 0.67 (p = 0.014). The same tendency was observed for the median PDGFR{beta} ratios after chemoradiotherapy completion: 34.2 vs. 170.0 (p <0.0001). The PDGFR{beta} and c-kit mRNA expression values in the pretreatment tumor biopsy cores were lower than the values in the resected specimens: PDGFR{beta} ratio 49.5 vs. 170.0 (p = 0.0002) and c-kit ratio 0.67 vs. 1.1 (p = 0.0003). Nevertheless, no correlation was seen between the pretherapeutic PDGFR{beta} and c-kit mRNA expression and the pathologic regression rate. Conclusion: Cetuximab-based chemoradiotherapy increased PDGFR{beta} levels even further compared with the pretreatment samples and deserves further investigation.« less

Arterial spin labeling perfusion-weighted MR imaging: correlation of tumor blood flow with pathological degree of tumor differentiation, clinical stage and nodal metastasis of head and neck squamous cell carcinoma.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Nada, Nadia

2018-05-01

The prognostic parameters of head and neck squamous cell carcinoma (HNSCC) include the pathological degree of tumor differentiation, clinical staging, and presence of metastatic cervical lymph nodes. To correlate tumor blood flow (TBF) acquired from arterial spin labeling (ASL) perfusion-weighted MR imaging with pathological degree of tumor differentiation, clinical stage, and nodal metastasis of HNSCC. Retrospective analysis of 43 patients (31 male, 12 female with a mean age of 65 years) with HNSCC that underwent ASL of head and neck and TBF of HNSCC was calculated. Tumor staging and metastatic lymph nodes were determined. The stages of HNSCC were stage 1 (n = 7), stage II (n = 12), stage III (n = 11) and stage IV (n = 13). Metastatic cervical lymph nodes were seen in 24 patients. The degree of tumor differentiation was determined through pathological examination. The mean TBF of poorly and undifferentiated HNSCC (157.4 ± 6.7 mL/100 g/min) was significantly different (P = 0.001) than that of well-to-moderately differentiated (142.5 ± 5.7 mL/100 g/min) HNSCC. The cut-off TBF used to differentiate well-moderately differentiated from poorly and undifferentiated HNSCC was 152 mL/100 g/min with an area under the curve of 0.658 and accuracy of 88.4%. The mean TBF of stages I, II (146.10 ± 9.1 mL/100 g/min) was significantly different (P = 0.014) than that of stages III, IV (153.33 ± 9.3 mL/100 g/min) HNSCC. The cut-off TBF used to differentiate stages I, II from stages III and IV was 148 mL/100 g/min with an area under the curve of 0.701 and accuracy of 69.8%. The TBF was higher in patients with metastatic cervical lymph nodes. The cut-off TBF suspect metastatic node was 147 mL/100 g/min with an area under the curve of 0.671 and accuracy of 67.4%. TBF is a non-invasive imaging parameter that well correlated with pathological degree of tumor differentiation, clinical stage of tumor and nodal metastasis of HNSCC.

Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer

PubMed Central

Cuaron, John; Dunphy, Mark; Rimner, Andreas

2013-01-01

The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated 18F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. 18F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. 18F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on 18F-FDG-PET scan when CT criteria for malignant involvement are not met. 18F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. 18F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. 18F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3–6 months, using 18F-FDG-PET to evaluate equivocal CT findings. As high 18F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, 18F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable 18F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET. PMID:23316478

Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer.

PubMed

Cuaron, John; Dunphy, Mark; Rimner, Andreas

2012-01-01

The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated (18)F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. (18)F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. (18)F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on (18)F-FDG-PET scan when CT criteria for malignant involvement are not met. (18)F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. (18)F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. (18)F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3-6 months, using (18)F-FDG-PET to evaluate equivocal CT findings. As high (18)F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, (18)F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable (18)F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.

Value of Diffusion-Weighted Magnetic Resonance Imaging for Prediction and Early Assessment of Response to Neoadjuvant Radiochemotherapy in Rectal Cancer: Preliminary Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lambrecht, Maarten, E-mail: maarten.lambrecht@uzleuven.be; Vandecaveye, Vincent; De Keyzer, Frederik

2012-02-01

Purpose: To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). Methods and Materials: Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10-15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0-1000 s/mm{sup 2}) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change ( Increment ADC), and volume change ( Increment V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectalmore » excision (pathologic complete response [pCR] vs. no pCR, ypT0-2 vs. ypT3-4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, Increment ADC, and Increment V for the detection of pCR was compared with receiver operating characteristics analysis. Results: Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm{sup 2}/s: 0.94 {+-} 0.12 Multiplication-Sign 10{sup -3} vs. 1.19 {+-} 0.22 Multiplication-Sign 10{sup -3}, p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: {Delta}V{sub during}: -62 {+-} 16 vs. -33 {+-} 16, respectively, p = 0.015; and {Delta}V{sub post}: -86 {+-} 12 vs. -60 {+-} 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the {Delta}V{sub during} and, respectively, 83% and 86% for the {Delta}V{sub post}. The Increment ADC during ({Delta}ADC{sub during}) and after RCT ({Delta}ADC{sub post}) showed a significantly higher value in patients with pCR compared with patients without (in %: {Delta}ADC{sub during}: 72 {+-} 14 vs. 16 {+-} 12, p = 0.0006; and {Delta}ADC{sub post}: 88 {+-} 35 vs. 26 {+-} 19, p = 0.0011), yielding a sensitivity and specificity of 100% for the {Delta}ADC{sub during} and, respectively, 100% and 93% for the {Delta}ADC{sub post}. Conclusions: These initial findings indicate that DWI, using pretreatment ADC, {Delta}ADC{sub during}, and {Delta}ADC{sub post} may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements.« less

Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101

PubMed Central

Giakoustidis, Alex; Stamp, Gordon; Gaya, Andy; Mudan, Satvinder

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​ PMID:26870619

The Oral Pathology Related Articles Published in Iranian Journal of Pathology from 2006 to 2015.

PubMed

Shamim, Thorakkal

2016-01-01

There is a paucity of information about the oral pathology related articles published in a pathology journal. This study aimed to audit the oral pathology related articles published in Iranian Journal of Pathology (Iran J Pathol) from 2006 to 2015. Bibliometric analysis of issues of Iran J Pathol from 2006 to 2015 was performed using web-based search. The articles published were analyzed for type of article and individual topic of oral pathology. The articles published were also checked for authorship trends. Out of the total 49 published articles related to oral pathology, case reports (21) and original articles (18) contributed the major share. The highest number of oral pathology related articles was published in 2011, 2014 and 2015 with 8 articles each and the least published year was 2012 with 1 article. Among the oral pathology related articles published, spindle cell neoplasms (7) followed by salivary gland tumors (5), jaw tumors (4), oral granulomatous conditions (4), lymphomas (4), oral cancer (3) and odontogenic cysts (3) form the major attraction of the contributors. The largest numbers of published articles related to oral pathology were received from Tehran University of Medical Sciences; Tehran (7) followed by Mashhad University of Medical Sciences, Mashhad (6) and Shahid Beheshti University of Medical Sciences, Tehran (5). This paper may be considered as a baseline study for the bibliometric information regarding oral pathology related articles published in a pathology journal.

The Oral Pathology Related Articles Published in Iranian Journal of Pathology from 2006 to 2015

PubMed Central

Shamim, Thorakkal

2016-01-01

Background: There is a paucity of information about the oral pathology related articles published in a pathology journal. This study aimed to audit the oral pathology related articles published in Iranian Journal of Pathology (Iran J Pathol) from 2006 to 2015. Methods: Bibliometric analysis of issues of Iran J Pathol from 2006 to 2015 was performed using web-based search. The articles published were analyzed for type of article and individual topic of oral pathology. The articles published were also checked for authorship trends. Results: Out of the total 49 published articles related to oral pathology, case reports (21) and original articles (18) contributed the major share. The highest number of oral pathology related articles was published in 2011, 2014 and 2015 with 8 articles each and the least published year was 2012 with 1 article. Among the oral pathology related articles published, spindle cell neoplasms (7) followed by salivary gland tumors (5), jaw tumors (4), oral granulomatous conditions (4), lymphomas (4), oral cancer (3) and odontogenic cysts (3) form the major attraction of the contributors. The largest numbers of published articles related to oral pathology were received from Tehran University of Medical Sciences; Tehran (7) followed by Mashhad University of Medical Sciences, Mashhad (6) and Shahid Beheshti University of Medical Sciences, Tehran (5). Conclusion: This paper may be considered as a baseline study for the bibliometric information regarding oral pathology related articles published in a pathology journal. PMID:27799973

Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Ramsay, R G; Phillips, W A; Heriot, A G

2016-03-01

Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (pCR) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit. A systematic review of the English language literature was conducted to identify pathological factors, imaging modalities and molecular factors that predict pCR following chemoradiotherapy. PubMed, MEDLINE and Cochrane Database searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation', 'tumor response'. After review of title and abstracts, 85 articles addressing the prediction of pCR were selected. Clear methods to predict pCR before chemoradiotherapy have not been defined. Clinical and radiological features of the primary cancer have limited ability to predict response. Molecular profiling holds the greatest potential to predict pCR but adoption of this technology will require greater concordance between cohorts for the biomarkers currently under investigation. At present no robust markers of the prediction of pCR have been identified and the topic remains an area for future research. This review critically evaluates existing literature providing an overview of the methods currently available to predict pCR to nCRT for locally advanced rectal cancer. The review also provides a comprehensive comparison of the accuracy of each modality. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Margin Status Remains an Important Determinant of Survival after Surgical Resection of Colorectal Liver Metastases in the Era of Modern Chemotherapy

PubMed Central

Andreou, Andreas; Aloia, Thomas A.; Brouquet, Antoine; Dickson, Paxton V.; Zimmitti, Giuseppe; Maru, Dipen M.; Kopetz, Scott; Loyer, Evelyne M.; Curley, Steven A.; Abdalla, Eddie K.; Vauthey, Jean-Nicolas

2013-01-01

Objective To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases (CLM) after modern preoperative chemotherapy. Summary Background Data In the era of effective chemotherapy for CLM, the association between surgical margin status and survival has become controversial. Methods Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. Results Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin < 1 mm). The 5-year OS rates for patients with R0 resection (margin ≥ 1 mm) and R1 resection were 55% and 26%, respectively (P=0.017). Multivariate analysis identified R1 resection (P=0.03) and minor pathologic response to chemotherapy (P=0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs. R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs. 11%, P=0.007) than in patients with optimal response (3-year OS rate: 92% vs. 88%, P=0.917) and greater in patients with minor pathologic response (5-year OS rate: 46% vs. 0%, P=0.002) than in patients with major response (5-year OS rate: 63% vs. 67%, P=0.587). Conclusions In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy. PMID:23426338

Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy.

PubMed

Andreou, Andreas; Aloia, Thomas A; Brouquet, Antoine; Dickson, Paxton V; Zimmitti, Giuseppe; Maru, Dipen M; Kopetz, Scott; Loyer, Evelyne M; Curley, Steven A; Abdalla, Eddie K; Vauthey, Jean-Nicolas

2013-06-01

To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases after modern preoperative chemotherapy. In the era of effective chemotherapy for colorectal liver metastases, the association between surgical margin status and survival has become controversial. Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin <1 mm). The 5-year OS rates for patients with R0 resection (margin ≥1 mm) and R1 resection were 55% and 26%, respectively (P = 0.017). Multivariate analysis identified R1 resection (P = 0.03) and a minor pathologic response to chemotherapy (P = 0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs 11%; P = 0.007) than in patients with optimal response (3-year OS rate: 92% vs 88%; P = 0.917) and greater in patients with a minor pathologic response (5-year OS rate: 46% vs 0%; P = 0.002) than in patients with a major response (5-year OS rate: 63% vs 67%; P = 0.587). In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy.

MR Imaging of Uterine Epithelioid Trophoblastic Tumor: A Case Report

PubMed Central

KAGEYAMA, Sakiko; KANOTO, Masafumi; SUGAI, Yukio; SUTO, Takeshi; NAGASE, Satoru; OSAKABE, Mitsumasa; HOSOYA, Takaaki

2016-01-01

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic neoplasm of chorionic-type intermediate trophoblasts, and it is most frequently located in the lower uterine segment and endocervix. Due to the epithelial-growth pattern with geographic necrosis exhibited by the neoplastic cells, ETT is commonly confused, both clinically and pathologically, with squamous cell carcinoma. Although there have been no previous reports of ETT focusing on computed tomography (CT) or magnetic resonance imaging (MRI) findings, we report a case of uterine ETT with special attention to the MRI findings referring to the pathological findings and MR images of previous reports. A 42-year-old Japanese woman (gravid 1, para 1) presented with uterus enlargement during screening, and complained of recent-onset lower abdominal pain. The MRI showed a solid tumor throughout the entire myometrium of the lower uterine segment, with the hemorrhagic cystic portion extending to the posterior subserosal space. Following hysterectomy, the final pathological diagnosis was ETT. An ETT is essentially a solid tumor composed of intermediate trophoblasts that exhibit an epithelial-like growth pattern and contain geographic necrosis with calcification. In our case, MRI revealed a non-specific-intensity solid tumor in the lower uterine segment with massive necrosis and hemorrhage extending to the subserosa. While it is difficult to distinguish between ETT and uterine carcinomas, recognition of certain tumor shapes and necrosis could enable more accurate diagnosis before treatment. PMID:27001388

Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

PubMed

Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

2017-12-01

Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

[The value of high resolution diffusion weighted imaging in differentiating benign and malignant epithelial tumors of parotid gland].

PubMed

Wen, B H; Cheng, J L; Zhang, H X; Zhang, Z X; Wang, F F; Xue, K K

2018-05-08

Objective: To investigate the diagnostic value of RESOLVE DWI in the evaluation of benign and malignant epithelial tumors of parotid gland. Methods: A total of 106 patients in the First Affiliated Hospital of Zhengzhou University with epithelial tumors of parotid gland confirmed by pathology from July 2015 to October 2017 were retrospectively analyzed. All patients underwent preoperative routine MRI and RESOLVE DWI, the ADC average values were calculated, t test were used to compare the ADC values of benign and malignant epithelial tumors of parotid gland. Diagnostic performance of ADC value was compared using receiver operating characteristic (ROC)curves. Results: All lesions were solitary, including 69 benign epithelial tumors and 37 malignant epithelial tumors. The mean ADC values of pleomorphic adenoma and basal cell adenoma, adenolymphoma and malignant epithelial tumors were (1.47±0.16)×10(-3) mm(2)/s, (0.83±0.19)×10(-3) mm(2)/s and(1.14±0.14)×10(-3) mm(2)/s, the mean ADC value of adenolymphoma lower than the rest of the two groups, there were statistically significant differences among them ( P <0.05). Using 0.94×10(-3) mm(2)/s≤ADC value≤1.28×10(-3)mm(2)/s as the critical value for diagnosing malignant epithelial tumors of parotid gland and comparing with pathological results, the result obtained had a sensitivity of 81.1%, specificity of 88.9%. ADC value had high correlations compared with pathological results, kappa value was 0.600. Conclusion: RESOLVE DWI can be applied in differential diagnosis between benign and malignant epithelial tumors of parotid gland.

Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients

PubMed Central

Greene, Christopher J.; Attwood, Kristopher; Sharma, Nitika J.; Gross, Kenneth W.; Smith, Gary J.; Xu, Bo; Kauffman, Eric C.

2017-01-01

The central dysregulated pathway of clear cell (cc) renal cell carcinoma (RCC), the von Hippel Lindau/hypoxia inducible factor-α axis, is a key regulator of intracellular iron levels, however the role of iron uptake in human RCC tumorigenesis and progression remains unknown. We conducted a thorough, large-scale investigation of the expression and prognostic significance of the primary iron uptake protein, transferrin receptor 1 (TfR1/CD71/TFRC), in RCC patients. TfR1 immunohistochemistry was performed in over 1500 cores from 574 renal cell tumor patient tissues (primary tumors, matched benign kidneys, metastases) and non-neoplastic tissues from 36 different body sites. TfR1 levels in RCC tumors, particularly ccRCC, were significantly associated with adverse clinical prognostic features (anemia, lower body mass index, smoking), worse tumor pathology (size, stage, grade, multifocality, sarcomatoid dedifferentiation) and worse survival outcomes, including after adjustments for tumor pathology. Highest TfR1 tissue levels in the non-gravid body were detected in benign renal tubule epithelium. Opposite to TfR1 changes in the primary tumor, TfR1 levels in benign kidney dropped during tumor progression and were inversely associated with worse survival outcomes, independent of tumor pathology. Quantitative measurement of TfR1 subcellular localization in cell lines demonstrated mixed cytoplasmic and membranous expression with increased TfR1 in clusters in ccRCC versus benign renal cell lines. Results of this study support an important role for TfR1 in RCC progression and identify TfR1 as a novel RCC biomarker and therapeutic target. PMID:29291011

[Feasibility study of dynamic contrast enhanced magnetic resonance imaging qualitative diagnosis of musculoskeletal tumors].

PubMed

Zhang, J; Zuo, P L; Cheng, K B; Yu, A H; Cheng, X G

2016-04-18

To investigate the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in differentiating musculoskeletal tumors with different behaviours of pathological findings before therapy. A total of 34 subjects of musculoskeletal tumors were involved in this retrospective analysis. DCE-MRI was performed using a fat-saturated 3D VIBE (volumetric interpolated breath-hold exam) imaging sequence with following parameters: FA, 10 degree; TR/TE, 5.6/2.4 ms; slice thickness, 4.0 mm with no intersection gap; field of view, 310 mm×213 mm; matrix, 256×178; voxel size, 1.2 mm×1.2 mm×4.0 mm; parallel imaging acceleration factor. The actuation time for the DCE-MRI sequence was 255 s with a temporal resolution of 5 s and 40 image volumes. Using pathological results as a gold standard, tumors were divided into benign, borderline and malignant tumors. Toft's model was used for calculation of K(trans) (volume transfer constant), Ve (extravascular extracellular space distribute volume per unit tissue volume) and Kep (microvascular permeability reflux constant). Those parameters were compared between the lesions and the control tissues using paired t tests. The one-way analysis of variance was used to assess the difference among benign, borderline and malignant tumors. P values <0.05 difference was statistically significant. Based on the WHO Classification of Tumours of Soft Tissue and Bone(2012) criteria, 34 patients were divided into three groups: 11 for benign tumors, 12 for borderline tumors, and 11 for malignancies. Compared with control tissues, K(trans) and Kep showed no difference, but Ve was increased in benign tumors, Kep showed no difference, but K(trans) and Ve were increased in borderline tumors,K(trans), Kep and Ve were increased in malignant tumors. K(trans) (P<0.001) and Kep (P<0.01) were significantly higher in malignant tumors than in benign and borderline tumors, but did not show any difference between benign tumors and borderline tumors. Ve was significantly higher in malignant tumors than in benign (P<0.05), but did not show any difference between malignant and borderline tumors, benign tumors and borderline tumors (P>0.05). DCE-MRI technique is useful to evaluate the pathological behaviour of musculoskeletal tumors. The quantitative analysis of DCE parameters in conjunction with conventional MR images can improve the accuracy of musculoskeletal tumor qualitative analysis.

Changes in jawbones of male patients with chronic renal failure on digital panoramic radiographs.

PubMed

Dagistan, Saadettin; Miloglu, Ozkan; Caglayan, Fatma

2016-01-01

To compare the existence of gonial cortical bone thickness, antegonial index, mandibular canal bone resorption and gonial angle values and pathologies like ground-glass appearance in jawbones and brown tumor in male patients undergoing dialysis due to chronic renal failure and men from the healthy control group on panoramic radiographs. Panoramic radiographs were taken from 80 male individuals in total (40 normal and 40 dialysis patients). Values obtained from the right and left sides of the mandible were summed and their means were calculated. Gonial cortical thickness, antegonial index and gonial angle values were assessed with the Student's t-test, mandibular canal wall resorption with the Chi-square test, and pathologies such as ground-glass appearance and Brown tumor as "available" or "not available." Statistically significant differences were observed among the antegonial index (P < 0.001), gonial cortical bone thickness (P < 0.001), and gonial angle (P < 0.001) values of study and control groups. Besides, mandibular canal wall resorption (P < 0.001) was also statistically significant. In the study group, pathologies with ground-glass appearance were encountered in mandible, but no radiographic findings were observed similar to brown tumor. Compared to the control group, decreases were found in gonial cortical bone thicknesses, antegonial index values, mandibular canal wall resorption, and gonial angle values of the patients receiving dialysis treatment due to chronic renal failure. Although it is not statistically significant, pathology with ground-glass appearance was detected in a patient, but no pathologies like brown tumor were observed. These findings from patients with chronic renal failure must be evaluated in panoramic radiography.

R.E.N.A.L. Nephrometry Score: A Preoperative Risk Factor Predicting the Fuhrman Grade of Clear-Cell Renal Carcinoma

PubMed Central

Chen, Shao-Hao; Wu, Yu-Peng; Li, Xiao-Dong; Lin, Tian; Guo, Qing-Yong; Chen, Ye-Hui; Huang, Jin-Bei; Wei, Yong; Xue, Xue-Yi; Zheng, Qing-Shui; Xu, Ning

2017-01-01

Objective: The purpose of this study was to evaluate the efficacy and feasibility of the R.E.N.A.L. Nephrometry Score to postoperatively predict high-grade clear-cell renal carcinoma (ccRCC). Methods: The study included 288 patients diagnosed with ccRCC who had complete CT/CTA data and R.E.N.A.L. Nephrometry Scores and underwent renal surgery at our center between January 2012 and December 2015. The relationship between the pathological grade of renal masses and R.E.N.A.L. Nephrometry Score was evaluated. Results: Univariate analysis indicated that diagnostic modality, cystic necrosis, enlargement of the regional lymph node, distant metastasis, clinical T stage, TNM stage, surgical modality, tumor size, nearness of the tumor to the collecting system or sinus, total Nephrometry Score and individual anatomic descriptor components were significantly associated with postoperative tumor grade (P < 0.05). Multivariate analysis showed that tumor size, the maximal diameter (R score), exophytic/endophytic properties (E score) and the location relative to the polar lines (L score) were independent prognostic factors to preoperatively predicting ccRCC pathological grade. The areas under the ROC curve with respect to the multi-parameter regression model (0.935, 95%CI: 0.904-0.966), tumor size (0.901, 95%CI: 0.866-0.937), R score (0.868, 95%CI: 0.825-0.911), E score (0.511, 95%CI: 0.442-0.581) and L score (0.842, 95%CI: 0.791-0.892) were calculated and compared. Conclusion: Tumor size, as well as R, E, and L scores were independent prognostic factors for high-grade pathology. Lager tumor sizes and higher R, E and L scores were more likely to be associated with high-grade pathological outcomes. Thus, the R.E.N.A.L. Score is of practical significance in facilitating urologists to make therapeutic decisions. PMID:29151960

Clinical values of (18) F-FDG PET/CT in oral cavity cancer with dental artifacts on CT or MRI.

PubMed

Hong, Hye Ran; Jin, Soyoung; Koo, Hyun Jung; Roh, Jong-Lyel; Kim, Jae Seung; Cho, Kyung-Ja; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2014-11-01

2a To investigate the role of (18) F-FDG PET/CT in tumor staging, extent, and volume measurements in oral cavity squamous cell carcinoma (OSCC) patients with/without dental artifacts on CT or MRI. This study was conducted in 63 consecutive patients with OSCC who received initial workups including (18) F-FDG PET/CT and MRI. The results of the imaging modalities were compared to those of pathology, using McNemar's test and the paired t-test. Thirty-seven patients (59%) had dental or metallic artifacts obscuring primary tumors. (18) F-FDG PET/CT scanning was superior to MRI in tumor staging (weighted κ = 0.870 vs. 0.518, P = 0.004) in patients with dental artifacts. In addition, (18) F-FDG PET/CT scans were more specific than MRI in detecting sublingual gland (P = 0.014) and mouth floor (P = 0.011) involvement. In patients with dental artifacts, there was a significant discrepancy between primary tumor volume (PTV) measured by pathology and MRI (P = 0.018), but not between PTV measured from pathology and (18) F-FDG PET/CT at SUV2.5 (P = 0.245), which showed the highest intraclass correlation coefficient value (0.860). (18) F-FDG PET/CT scans provide accurate tumor staging and volume measurements in OSCC patients with CR/MRI dental artifacts, leading to improved preoperative planning. 2b CONDENSED ABSTRACT This study evaluated the clinical value of (18) F-FDG PET/CT in 63 patients with oral cavity cancers. In 37 (59%) patients with dental artifacts on CT/MRI, (18) F-FDG PET/CT showed superior results compared to MRI in tumor staging and represented the highest intraclass correlation coefficient value to tumor volume determined by pathology. © 2014 Wiley Periodicals, Inc.

Coexistence of neurofibroma and meningioma at exactly the same level of the cervical spine.

PubMed

Chen, Kai-Yuan; Wu, Jau-Ching; Lin, Shih-Cheih; Huang, Wen-Cheng; Cheng, Henrich

2014-11-01

We report a case of the coexistence of different spinal tumors at the same level of the cervical spine, without neurofibromatosis (NF), which was successfully treated with surgery. A 72-year-old female presented with right upper-limb clumsiness and weakness. Magnetic resonance imaging revealed an intradural, extramedullary tumor mass at the right C3-4 level with extradural extension into the intervertebral foramen. The extradural tumor was removed, and the pathology showed neurofibroma. After incision of the dura, the intradural tumor was removed, and was identified as meningioma in the pathological report. The patient did not meet the criteria of NF. Coexistence of neurofibroma and meningioma at exactly the same level of the spine without NF is extremely rare. Exploration of the intradural space may be necessary after resection of an extradural tumor if the surgical finding does not correlate well with the preoperative images. Copyright © 2014. Published by Elsevier Taiwan.

Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.

PubMed

Iotti, Valentina; Ravaioli, Sara; Vacondio, Rita; Coriani, Chiara; Caffarri, Sabrina; Sghedoni, Roberto; Nitrosi, Andrea; Ragazzi, Moira; Gasparini, Elisa; Masini, Cristina; Bisagni, Giancarlo; Falco, Giuseppe; Ferrari, Guglielmo; Braglia, Luca; Del Prato, Alberto; Malavolti, Ivana; Ginocchi, Vladimiro; Pattacini, Pierpaolo

2017-09-11

Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin's coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin's coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and 84%, respectively, for CESM, and 87% and 60% for MRI. CESM and MRI lesion size measurements were highly correlated. CESM seems at least as reliable as MRI in assessing the response to NAC, and may be an alternative if MRI is contraindicated or its availability is limited.

Assessment of treatment response during chemoradiation therapy for pancreatic cancer based on quantitative radiomic analysis of daily CTs: An exploratory study.

PubMed

Chen, Xiaojian; Oshima, Kiyoko; Schott, Diane; Wu, Hui; Hall, William; Song, Yingqiu; Tao, Yalan; Li, Dingjie; Zheng, Cheng; Knechtges, Paul; Erickson, Beth; Li, X Allen

2017-01-01

In an effort for early assessment of treatment response, we investigate radiation induced changes in quantitative CT features of tumor during the delivery of chemoradiation therapy (CRT) for pancreatic cancer. Diagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. On each daily CT, the pancreatic head, the spinal cord and the aorta were delineated and the histograms of CT number (CTN) in these contours were extracted. Eight histogram-based radiomic metrics including the mean CTN (MCTN), peak position, volume, standard deviation (SD), skewness, kurtosis, energy and entropy were calculated for each fraction. Paired t-test was used to check the significance of the change of specific metric at specific time. GEE model was used to test the association between changes of metrics over time for different pathology responses. In general, CTN histogram in the pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the 1st to the 26th fraction in MCTN ranged from -15.8 to 3.9 HU with an average of -4.7 HU (p<0.001). Meanwhile the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less peaked). The changes of MCTN, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response is associated with the changes of MCTN, SD, and skewness. In cases of good response, patients tend to have large reductions in MCTN and skewness, and large increases in SD and kurtosis. Significant changes in CT radiomic features, such as the MCTN, skewness, and kurtosis in tumor were observed during the course of CRT for pancreas cancer based on quantitative analysis of daily CTs. These changes may be potentially used for early assessment of treatment response and stratification for therapeutic intensification.

Nitric Oxide in Mammary Tumor Progession

DTIC Science & Technology

1999-07-01

healing , embryonic development and endometrial proliferation. Numerous pathological conditions, such as diabetic retinopathy, rheumatoid arthritis and...serum NO levels have been observed in many cancer patients (26) indicating that tumor cells or host cells serve as the additional source of NO in these... patients . A high expression of active NOS enzymes in tumor cells (27,28,31-33), endothelial cells in tumor vasculature (28) or tumor-infiltrating

Pleural neoplastic pathology.

PubMed

Karpathiou, Georgia; Stefanou, Dimitrios; Froudarakis, Marios E

2015-08-01

Malignant pleural effusion is a frequent situation in pulmonary medicine. However, it is sometimes difficult to recognize the underlying etiology. The aim of this review is to provide the key characteristics of primary and metastatic pleural neoplasms. A review of the recent literature regarding pleural neoplasia is provided. Malignant pleural mesothelioma (MPM) is the commonest primary pleural epithelial tumor showing remarkable histological heterogeneity often with prognostic significance. Various genetic alterations like changes in INK4 locus, NF2, BAP1 but also epigenetic changes are present in MPM. It should be distinguished from atypical mesothelial hyperplasia, mainly through morphological and clinical criteria, and from other rare primary and metastatic tumors, for which immunohistochemistry is rather important. Solitary fibrous tumor, the commonest primary pleural mesenchymal tumor is characterized by STAT6 overexpression. Other primary tumors, like adenomatoid tumor, well-differentiated papillary mesothelioma, synovial sarcoma, vascular tumors, various other sarcomas, thymic tumors and tumors of uncertain histogenesis are rarely encountered in the pleura. In contrast, metastatic disease is the commonest neoplasia of the pleura, and especially lung, breast and lymphoid malignancies. The basic pathological, immunohistochemical and molecular characteristics of these entities are provided in the current review, along with their differential diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reporting and Staging of Testicular Germ Cell Tumors: The International Society of Urological Pathology (ISUP) Testicular Cancer Consultation Conference Recommendations.

PubMed

Verrill, Clare; Yilmaz, Asli; Srigley, John R; Amin, Mahul B; Compérat, Eva; Egevad, Lars; Ulbright, Thomas M; Tickoo, Satish K; Berney, Daniel M; Epstein, Jonathan I

2017-06-01

The International Society of Urological Pathology held a conference devoted to issues in testicular and penile pathology in Boston in March 2015, which included a presentation and discussion led by the testis microscopic features working group. This conference focused on controversies related to staging and reporting of testicular tumors and was preceded by an online survey of the International Society of Urological Pathology members. The survey results were used to initiate discussions, but decisions were made by expert consensus rather than voting. A number of recommendations emerged from the conference, including that lymphovascular invasion (LVI) should always be reported and no distinction need be made between lymphatic or blood invasion. If LVI is equivocal, then it should be regarded as negative to avoid triggering unnecessary therapy. LVI in the spermatic cord is considered as category pT2, not pT3, unless future studies provide contrary evidence. At the time of gross dissection, a block should be taken just superior to the epididymis to define the base of the spermatic cord, and direct invasion of tumor in this block indicates a category of pT3. Pagetoid involvement of the rete testis epithelium must be distinguished from rete testis stromal invasion, with only the latter being prognostically useful. Percentages of different tumor elements in mixed germ cell tumors should be reported. Although consensus was reached on many issues, there are still areas of practice that need further evidence on which to base firm recommendations.

Review at a multidisciplinary tumor board impacts critical management decisions of pediatric patients with cancer.

PubMed

Thenappan, Arun; Halaweish, Ihab; Mody, Rajen J; Smith, Ethan A; Geiger, James D; Ehrlich, Peter F; Jasty Rao, Rama; Hutchinson, Raymond; Yanik, Gregory; Rabah, Raja M; Heider, Amer; Stoll, Tammy; Newman, Erika A

2017-02-01

Optimal cancer care requires a multidisciplinary approach. The purpose of the current study was to evaluate the impact of a multidisciplinary tumor board on the treatment plans of children with solid tumors. The records of 158 consecutive patients discussed at a formal multidisciplinary pediatric tumor board between July 2012 and April 2014 were reviewed. Treatment plans were based on clinical practice guidelines and on current Children's Oncology Group protocols. Alterations in radiologic, pathologic, surgical, and medical interpretations were analyzed to determine the impact on changes in recommendations for clinical management. Overall, 55 of 158 children (35%) had alterations in radiologic, pathologic, medical, or surgical interpretation of clinical data following multidisciplinary discussion. Of these, 64% had changes to the initial recommendation for clinical management. Review of imaging studies resulted in interpretation changes in 30 of 158 patients studied (19%), with 12 clinical management changes. Six of 158 patients (3.9%) had changes in pathologic interpretation, with four patients (2.5%) requiring treatment changes. In eight patients (5%), a change in medical management was recommended, while in 11 patients (7%) there were changes in surgical management that were based solely on discussion and not on interpretation of imaging or pathology. Formal multidisciplinary review led to alterations in interpretation of clinical data in 35% of patients, and the majority led to changes in recommendations for treatment. Comprehensive multidisciplinary tumor board incorporated into the care of children with cancer provides additional perspectives for families and care providers when delineating optimal treatment plans. © 2016 Wiley Periodicals, Inc.

Differentiating invasive and pre-invasive lung cancer by quantitative analysis of histopathologic images

NASA Astrophysics Data System (ADS)

Zhou, Chuan; Sun, Hongliu; Chan, Heang-Ping; Chughtai, Aamer; Wei, Jun; Hadjiiski, Lubomir; Kazerooni, Ella

2018-02-01

We are developing automated radiopathomics method for diagnosis of lung nodule subtypes. In this study, we investigated the feasibility of using quantitative methods to analyze the tumor nuclei and cytoplasm in pathologic wholeslide images for the classification of pathologic subtypes of invasive nodules and pre-invasive nodules. We developed a multiscale blob detection method with watershed transform (MBD-WT) to segment the tumor cells. Pathomic features were extracted to characterize the size, morphology, sharpness, and gray level variation in each segmented nucleus and the heterogeneity patterns of tumor nuclei and cytoplasm. With permission of the National Lung Screening Trial (NLST) project, a data set containing 90 digital haematoxylin and eosin (HE) whole-slide images from 48 cases was used in this study. The 48 cases contain 77 regions of invasive subtypes and 43 regions of pre-invasive subtypes outlined by a pathologist on the HE images using the pathological tumor region description provided by NLST as reference. A logistic regression model (LRM) was built using leave-one-case-out resampling and receiver operating characteristic (ROC) analysis for classification of invasive and pre-invasive subtypes. With 11 selected features, the LRM achieved a test area under the ROC curve (AUC) value of 0.91+/-0.03. The results demonstrated that the pathologic invasiveness of lung adenocarcinomas could be categorized with high accuracy using pathomics analysis.

Giant cell angiofibroma misdiagnosed as a vascular malformation and treated with absolute alcohol for one year: a case report and review of the literature

PubMed Central

2014-01-01

Purpose To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA). Case presentation In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease. After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA. Conclusion GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate. PMID:24758544

Ga-68 DOTA-NOC uptake in the pancreas: pathological and physiological patterns.

PubMed

Krausz, Yodphat; Rubinstein, Rina; Appelbaum, Liat; Mishani, Eyal; Orevi, Marina; Fraenkel, Merav; Tshori, Sagi; Glaser, Benjamin; Bocher, Moshe; Salmon, Asher; Chisin, Roland; Gross, David J; Freedman, Nanette

2012-01-01

Gallium-68 (Ga-68) DOTA-1-NaI3-octreotide (DOTA-NOC) positron emission tomography (PET)/computed tomography (CT) is increasingly used for neuroendocrine tumors (NETs), often found primarily in the pancreas. However, physiologic uptake of DOTA-NOC has been described in the uncinate process of the pancreas. We studied DOTA-NOC uptake in this organ. Ninety-six patients underwent 103 DOTA-NOC scans, with pathology-proven pancreatic NET (n = 40) and nonpancreatic NET or biochemical suspicion of NET (n = 63). DOTA-NOC uptake was detected in 35 documented pancreatic tumor sites (SUV: 5.5-165; mean: 25.7 ± 28.8; median: 17.8). Among 63 cases without previous known pathology, uptake was suspicious for tumor in 24 sites (SUV: 4.7-35; mean 16.3 ± 8.0; median: 14.1), and in 38 sites, it was judged as physiological, generally lower relative to adjacent structures (SUV: 2.2-12.6; mean: 6.6 ± 2.2; median: 6.2). In 24 scans with suspected tumor and in 37 of 38 scans with physiological uptake, diagnostic computed tomography or magnetic resonance imaging or endoscopic ultrasonography failed to detect tumor. Pancreatic DOTA-NOC uptake must be interpreted with caution, and further studies are required.

Perivascular epithelioid cell neoplasms: pathology and pathogenesis.

PubMed

Folpe, Andrew L; Kwiatkowski, David J

2010-01-01

This review article summarizes our current understanding of the clinical, pathologic, immunohistochemical, and genetic aspects of perivascular epithelioid cell neoplasms, a rare group of related tumors defined by both morphologic and immunophenotypic criteria.

Transcriptional response of peripheral lymphocytes to early fibrosarcoma: a model system for cancer detection based on hybridization signatures.

PubMed

Marques, Márcia M C; Junta, Cristina M; Zárate-Blades, Carlos R; Sakamoto-Hojo, Elza Tiemi; Donadi, Eduardo A; Passos, Geraldo A S

2009-07-01

Since circulating leukocytes, mainly B and T cells, continuously maintain vigilant and comprehensive immune surveillance, these cells could be used as reporters for signs of infection or other pathologies, including cancer. Activated lymphocyte clones trigger a sensitive transcriptional response, which could be identified by gene expression profiling. To assess this hypothesis, we conducted microarray analysis of the gene expression profile of lymphocytes isolated from immunocompetent BALB/c mice subcutaneously injected with different numbers of tumorigenic B61 fibrosarcoma cells. Flow cytometry demonstrated that the number of circulating T (CD3(+)CD4(+) or CD3(+)CD8(+)) or B (CD19(+)) cells did not change. However, the lymphocytes isolated from tumor cell-injected animals expressed a unique transcriptional profile that was identifiable before the development of a palpable tumor mass. This finding demonstrates that the transcriptional response appears before alterations in the main lymphocyte subsets and that the gene expression profile of peripheral lymphocytes can serve as a sensitive and accurate method for the early detection of cancer.

Macrophage-mediated response to hypoxia in disease.

PubMed

Tazzyman, Simon; Murdoch, Craig; Yeomans, James; Harrison, Jack; Muthana, Munitta

2014-01-01

Hypoxia plays a critical role in the pathobiology of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of rheumatoid arthritic joints, healing wounds, and sites of bacterial infection. These areas of hypoxia form when the blood supply is occluded and/or the oxygen supply is unable to keep pace with cell growth and/or infiltration of inflammatory cells. Macrophages are ubiquitous in all tissues of the body and exhibit great plasticity, allowing them to perform divergent functions, including, among others, patrolling tissue, combating invading pathogens and tumor cells, orchestrating wound healing, and restoring homeostasis after an inflammatory response. The number of tissue macrophages increases markedly with the onset and progression of many pathological states, with many macrophages accumulating in avascular and necrotic areas, where they are exposed to hypoxia. Recent studies show that these highly versatile cells then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. Here we review the evidence for hypoxia-driven macrophage inflammatory responses in various disease states, and how this influences disease progression and treatment.

Nuclear magnetic resonance proton imaging of bone pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atlan, H.; Sigal, R.; Hadar, H.

Thirty-two patients with diversified pathology were examined with a supraconductive NMR imager using spin echo with different TR and TE to obtain T1 and T2 weighted images. They included 20 tumors (12 primary, eight metastasis), six osteomyelitis, three fractures, two osteonecrosis, and one diffuse metabolic (Gaucher) disease. In all cases except for the stress fractures, the bone pathology was clearly visualized in spite of the normal lack of signal from the compact cortical bone. Nuclear magnetic resonance (NMR) imaging proved to be at least as sensitive as radionuclide scintigraphy but much more accurate than all other imaging procedures including computedmore » tomography (CT) and angiography to assess the extension of the lesions, especially in tumors extended to soft tissue. This is due both to easy acquisition of sagittal and coronal sections and to different patterns of pathologic modifications of T1 and T2 which are beginning to be defined. It is hoped that more experience in clinical use of these patterns will help to discriminate between tumor extension and soft-tissue edema. We conclude that while radionuclide scintigraphy will probably remain the most sensitive and easy to perform screening test for bone pathology, NMR imaging, among noninvasive diagnostic procedures, appears to be at least as specific as CT. In addition, where the extension of the lesions is concerned, NMR imaging is much more informative than CT. In pathology of the spine, the easy visualization of the spinal cord should decrease the need for myelography.« less

What Is Cancer?

MedlinePlus

... myeloid). Our page on leukemia has more information. Lymphoma Lymphoma is cancer that begins in lymphocytes (T ... tumors has more information. Related Resources Tumor Grade Pathology Reports Metastatic Cancer Common Cancer Myths and Misconceptions ...

Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

PubMed

Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

2017-12-01

This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

Peripheral primitive neuroectodermal tumor of the vulva: report of a case with imprint cytology.

PubMed

Takeshima, N; Tabata, T; Nishida, H; Furuta, N; Tsuzuku, M; Hirai, Y; Hasumi, K

2001-01-01

Peripheral primitive neuroectodermal tumor (PNET) of the vulva is an extremely rare disease, and, to our knowledge, only two cases have been previously reported. A 45-year-old woman presented with a mass in the right labium major. Three years after removal of the tumor, she noticed a new lesion in the same place and underwent a partial vulvectomy. The imprint cytology of the recurrent tumor showed a monomorphic appearance, composed of small round cells with scant cytoplasm against a hemorrhagic background. These tumor cells were loosely connective, but rosettelike structures were observed focally. On pathologic examination, the neoplasm was composed of small round tumor cells showing sinusoidal, diffuse or micropapillary growth. Immunohistochemically, the neoplastic cells stained positively for neuron-specific enolase, vimentin and HBA 71 and negatively for cytokeratin, HBA 45 and muscle-specific actin. The morphologic characteristics of the disease were well expressed in the imprint cytology, and this influenced the selection of immunohistochemical studies. Cytologic examination for vulvar tumors, even imprint cytology, can be a useful tool in obtaining an accurate pathologic diagnosis of a rare disease, such as peripheral PNET.

Tumor Metabolism and Blood Flow Changes by Positron Emission Tomography: Relation to Survival in Patients Treated With Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer

PubMed Central

Dunnwald, Lisa K.; Gralow, Julie R.; Ellis, Georgiana K.; Livingston, Robert B.; Linden, Hannah M.; Specht, Jennifer M.; Doot, Robert K.; Lawton, Thomas J.; Barlow, William E.; Kurland, Brenda F.; Schubert, Erin K.; Mankoff, David A.

2008-01-01

Purpose Patients with locally advanced breast carcinoma (LABC) receive preoperative chemotherapy to provide early systemic treatment and assess in vivo tumor response. Serial positron emission tomography (PET) has been shown to predict pathologic response in this setting. We evaluated serial quantitative PET tumor blood flow (BF) and metabolism as in vivo measurements to predict patient outcome. Patients and Methods Fifty-three women with primary LABC underwent dynamic [18F]fluorodeoxyglucose (FDG) and [15O]water PET scans before and at midpoint of neoadjuvant chemotherapy. The FDG metabolic rate (MRFDG) and transport (FDG K1) parameters were calculated; BF was estimated from the [15O]water study. Associations between BF, MRFDG, FDG K1, and standardized uptake value and disease-free survival (DFS) and overall survival (OS) were evaluated using the Cox proportional hazards model. Results Patients with persistent or elevated BF and FDG K1 from baseline to midtherapy had higher recurrence and mortality risks than patients with reductions. In multivariable analyses, BF and FDG K1 changes remained independent prognosticators of DFS and OS. For example, in the association between BF and mortality, a patient with a 5% increase in tumor BF had a 67% higher mortality risk compared with a patient with a 5% decrease in tumor BF (hazard ratio = 1.67; 95% CI, 1.24 to 2.24; P < .001). Conclusion LABC patients with limited or no decline in BF and FDG K1 experienced higher recurrence and mortality risks that were greater than the effects of clinical tumor characteristics. Tumor perfusion changes over the course of neoadjuvant chemotherapy measured directly by [15O]water or indirectly by dynamic FDG predict DFS and OS. PMID:18626006

Clinico-pathological patterns of a rare presentation of abdominal neuroblastoma in children.

PubMed

Aldaqal, Saleh M; Turki, Ali M

2013-01-01

To study the diagnosis, management, and outcome of abdominal neuroblastoma (NBL) in infants and children and also the behavior of some rare types. This is a retrospective review of 46 infants and children having abdominal NBL at King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia and Tanta University Hospital, Tanta, Egypt (a joint study) between February 2008 and January 2012. The patients' medical records were reviewed for demographic details, clinical presentations, histopathology, radiological diagnosis, management, and outcome. Of the 46 patients, 5 (10.7%), three males and two females, aged 1.5-6.5 years (mean: 4.5 years) had rare types of NBL (one bilateral NBL, one pelvic NBL, one pelvic-abdominal, and there were two cases of ganglioneuroblastoma). Three patients (two ganglioneuroblastoma and one pelvic) underwent complete surgical removal of the tumor with a good disease survival, whereas the other two patients (two bilateral and one pelviabdominal) had advanced disease and received palliative chemoradiotherapy. The remaining 41 patients, 23 males (56.1%) and 18 females (43.9%), with mean age 3.9 years (range: 1-7 years), had unilateral abdominal NBL. Twelve of them had resectable tumor and underwent primary surgical removal of the tumor, whereas the remaining 29 patients had unresectable tumor and received pre-operative chemotherapy with good response of the tumor in seven patients and no response in the remaining 22 patients. Primary complete surgical removal of tumor is advisable in localized NBL with a good outcome, whereas in advanced cases, it is better to start with pre-operative chemotherapy to downsize the tumour mass and safe delayed surgical excision. An increase in patient's age is associated with advanced stage of NBL and poor prognosis except in ganglioneuroblastoma cases due to maturation of tumor cells.

Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

PubMed

Riva, Francesca; Bidard, Francois-Clement; Houy, Alexandre; Saliou, Adrien; Madic, Jordan; Rampanou, Aurore; Hego, Caroline; Milder, Maud; Cottu, Paul; Sablin, Marie-Paule; Vincent-Salomon, Anne; Lantz, Olivier; Stern, Marc-Henri; Proudhon, Charlotte; Pierga, Jean-Yves

2017-03-01

In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 ( TP53 ) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS ( r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index ( P = 0.003), tumor grade ( P = 0.003), and stage ( P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free ( P < 0.001) and overall ( P = 0.006) survival. Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival. © 2016 American Association for Clinical Chemistry.

FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer

PubMed Central

Andren, Ove; Ohlson, Anna‐Lena; Carlsson, Jessica; Andersson, Swen‐Olof; Giunchi, Francesca; Rider, Jennifer R.; Fiorentino, Michelangelo

2017-01-01

Background The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Methods Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. Results In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT‐stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart. Conclusions Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti‐tumor immune response may be initiated even before the primary tumor is established. PMID:29105795

Accumulation of FOXP3+T-cells in the tumor microenvironment is associated with an epithelial-mesenchymal-transition-type tumor budding phenotype and is an independent prognostic factor in surgically resected pancreatic ductal adenocarcinoma

PubMed Central

Wartenberg, Martin; Zlobec, Inti; Perren, Aurel; Koelzer, Viktor Hendrik; Gloor, Beat; Lugli, Alessandro; Eva, Karamitopoulou

2015-01-01

Here we explore the role of the interplay between host immune response and epithelial-mesenchymal-transition (EMT)-Type tumor-budding on the outcome of pancreatic adenocarcinoma (PDAC). CD4+, CD8+, and FOXP3+T-cells as well as iNOS+ (M1) and CD163+-macrophages (M2) were assessed on multipunch tissue-microarrays containing 120 well-characterized PDACs, precursor lesions (PanINs) and corresponding normal tissue. Counts were normalized for the percentage of tumor/spot and associated with the clinico-pathological features, including peritumoral (PTB) and intratumoral (ITB) EMT-Type tumor-budding and outcome. Increased FOXP3+T-cell-counts and CD163-macrophages and decreased CD8+T-cell-counts were observed in PDACs compared with normal tissues and PanINs (p < 0.0001). Increased peritumoral FOXP3+T-cell-counts correlated significantly with venous invasion, distant metastasis, R1-status, high-grade ITB, PTB and independently with reduced survival. Increased intratumoral FOXP3+T-cells correlated with lymphatic invasion, N1-stage, PTB and marginally with adverse outcome. High peritumoral CD163-counts correlated with venous invasion, PTB and ITB. High intratumoral CD163-counts correlated with higher T-stage and PTB. PDAC-microenvironment displays a tumor-favoring immune-cell composition especially in the immediate environment of the tumor-buds that promotes further growth and indicates a close interaction of the immune response with the EMT-process. Increased peritumoral FOXP3+T-cell density is identified as an independent adverse prognostic factor in PDAC. Patients with phenotypically aggressive PDACs may profit from targeted immunotherapy against FOXP3. PMID:25669968

Higher Numbers of T-Bet+ Tumor-Infiltrating Lymphocytes Associate with Better Survival in Human Epithelial Ovarian Cancer.

PubMed

Xu, Yun; Chen, Lujun; Xu, Bin; Xiong, Yuqi; Yang, Min; Rui, Xiaohui; Shi, Liangrong; Wu, Changping; Jiang, Jingting; Lu, Binfeng

2017-01-01

T-bet, a member of the T-box family of transcription factors, is a key marker of type I immune response within the tumor microenvironment, and has been previously reported by us to serve as an important prognostic indicator for human gastric cancer patients and a potential biomarker for immunotherapy. In the present study, we aimed to assess the clinical significance and prognostic value of T-bet+ tumor-infiltrating lymphocytes in human epithelial ovarian cancer. The immunohistochemistry was used to analyze the infiltration density of T-bet+ lymphoid cells in human epithelial ovarian cancer tissues, and the flow cytometry analysis was used to further analyze the presence of T-bet+ tumor-infiltrating lymphocytes subgroups in cancer tissues. Our immunohistochemistry analysis showed increased number of T-bet+ lymphoid cells in the human epithelial ovarian cancer tissues, and the flow cytometry analysis further demonstrated the presence of T-bet+ tumor-infiltrating lymphocytes subgroups including CD4+ , CD8+ T cells and NK cells. In addition, we also observed a significant association of T-bet+ tumor-infiltrating lymphocytes density in the tumor nest of cancer with not only serum CA125 levels but also with distant metastasis. However no association was observed with other characteristics like patients' age, pathological type, FIGO stage, tumor site and tumor size. Furthermore, the survival analysis showed that higher density of T-bet+ tumor-infiltrating lymphocytes both in tumor nest and tumor stroma of cancer tissues was significantly associated with better patient survival. In addition, the density of T-bet+ tumor-infiltrating lymphocytes in tumor nest appeared to be an independent risk factor for predicting patients' postoperative prognoses. Our data indicated that the key transcription factor T-bet might play an important role in the type I immune cells mediated antitumor response, and the density of T-bet+ lymphocytes in human epithelial ovarian cancer tissues could serve as a prognostic predictor for ovarian cancer patients. © 2017 The Author(s)Published by S. Karger AG, Basel.

Nodular hidradenocarcinoma over the parotid gland: a pathologic presentation.

PubMed

Verret, D J; Kabbani, Wareef; DeFatta, Robert J

2007-02-01

Nodular hidradenocarcinoma (NHAC), an eccrine carcinoma, has been reported in the dermatology and pathology literature, but few references have been made in the otolaryngology literature even though the head and neck is a common site of occurrence. A case report of a 37-year-old Hispanic man with a right-sided neck mass diagnosed preoperatively as a parotid mass by imaging and fine-needle aspiration is presented. After presentation at our multidisciplinary tumor board, excision of the mass was undertaken. Final pathology revealed a NHAC, which is presented in our report. NHAC is an aggressive malignant tumor that is often misdiagnosed preoperatively and that must be treated with aggressive multimodality therapy for increased survival.

Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer.

PubMed

Abdel-Fatah, Tarek M; Ball, Graham; Lee, Andrew H S; Pinder, Sarah; MacMilan, R Douglas; Cornford, Eleanor; Moseley, Paul M; Silverman, Rafael; Price, James; Latham, Bruce; Palmer, David; Chan, Arlene; Ellis, Ian O; Chan, Stephen Y T

2015-03-01

There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy. We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125). A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lymphovascular invasion, increasing number of lymph node metastases, and administration of hormone therapy were significantly associated with short breast cancer-specific survival (BCSS) and disease-free survival (DFS); Ps < 0.01, while reduction of tumor size was associated with DFS (P = 0.022). Nottingham Clinico-Pathological Response Indexes (NPRI) were calculated, and four prognostic groups (NPRI-PG) were identified. Patients in prognostic group 2 (NPRI-PG2) for BCSS (66 of 172; 38.4%) have the same prognosis as those who achieved pathologic complete response (pCR; NPRI-PG1; 15%). Receiver-operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding the NPRI improved their performance as a predictor for both BCSS (area under the curve [AUC], 0.88) and DFS (AUC, 0.87). The NPRI predicts BCSS and DFS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinicopathologic response as a study endpoint, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers. ©2014 American Association for Cancer Research.

Epidemiology, biology and treatment of sarcomatoid RCC: current state of the art.

PubMed

Lebacle, Cedric; Pooli, Aydin; Bessede, Thomas; Irani, Jacques; Pantuck, Allan J; Drakaki, Alexandra

2018-06-01

Long recognized to confer an extremely poor prognosis, sarcomatoid dedifferentiation of renal cell carcinoma (sRCC) is a tumor phenotype that is finally beginning to be better understood on the molecular and genetic levels. With an overall incidence that ranges from 1 to 32% depending on associated RCC subtype, the survival of sarcomatoid RCC patients rarely exceeds 2 years. The main reasons for its poor outcome include its aggressive biology, its tendency to present at an advanced or metastatic stage at the time of diagnosis, its high rate of tumor recurrence after nephrectomy, and its limited response to systemic therapies. Molecular pathology studies suggest that sarcomatoid dedifferentiation originates from a focal epithelial-mesenchymal transition (EMT) arising in the carcinomatous component of the tumor. It is hoped that the growing understanding of the molecular biology of sRCC will soon make it possible to adapt treatments based on the identification of actionable tumor alterations. The deliberate inclusion of these patients in the multicenter clinical trials of immune, targeted and combination therapies is a necessary next step in pioneering future treatment strategies.

Treatment-Related Predictive and Prognostic Factors in Trimodality Approach in Stage IIIA/N2 Non-Small Cell Lung Cancer.

PubMed

Jeremić, Branislav; Casas, Francesc; Dubinsky, Pavol; Gomez-Caamano, Antonio; Čihorić, Nikola; Videtic, Gregory; Igrutinovic, Ivan

2018-01-01

While there are no established pretreatment predictive and prognostic factors in patients with stage IIIA/pN2 non-small cell lung cancer (NSCLC) indicating a benefit to surgery as a part of trimodality approach, little is known about treatment-related predictive and prognostic factors in this setting. A literature search was conducted to identify possible treatment-related predictive and prognostic factors for patients for whom trimodality approach was reported on. Overall survival was the primary endpoint of this study. Of 30 identified studies, there were two phase II studies, 5 "prospective" studies, and 23 retrospective studies. No study was found which specifically looked at treatment-related predictive factors of improved outcomes in trimodality treatment. Of potential treatment-related prognostic factors, the least frequently analyzed factors among 30 available studies were overall pathologic stage after preoperative treatment and UICC downstaging. Evaluation of treatment response before surgery and by pathologic tumor stage after induction therapy were analyzed in slightly more than 40% of studies and found not to influence survival. More frequently studied factors-resection status, degree of tumor regression, and pathologic nodal stage after induction therapy as well as the most frequently studied factor, the treatment (in almost 75% studies)-showed no discernible impact on survival, due to conflicting results. Currently, it is impossible to identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/pN2 NSCLC.

"Ask The Pathologist": An Internet Forum Facilitating Communication Between Cancer Registrars and Pathologists.

PubMed

Strickland-Marmol, Leah B; Muro-Cacho, Carlos A; Washington, Kay; Foulis, Philip R

2018-05-30

- Cancer registrars should work closely with pathologists to ensure compliance with reporting standards. Many registrars, however, have little contact with pathologists, resulting in a lack of "real-time" interaction that is essential for their professional activities and development. - To facilitate registrars' case management, as cancer biology becomes more complex, we developed the ATP (Ask the Pathologist) forum as a place to ask pathology-related questions about neoplasms, such as terminology, biology, histologic classification, extent of disease, molecular markers, and prognostic factors. - Questions posted are reviewed by the ATP multidisciplinary oversight committee, which consists of 3 pathologists, 4 cancer registrars, 1 internal medicine physician, the pathology resident member of the College of American Pathologists Cancer Committee, and 2 medical technologists. The oversight committee may answer the question. Alternatively, the committee may forward the question to a content expert pathologist, determine that the question is better suited for another reference Web site, or both. - Since September 2013, when the ATP forum became available, users have posted 284 questions, of which 48 (17%) related to gastrointestinal tumors, 43 (15%) to breast tumors, and 37 (13%) to general pathology. The average turnaround time, from question posted to response, is 11.1 days. - The ATP forum has had a positive impact in the daily activities of cancer registrars. Of 440 registrars surveyed, more than 90% considered that questions were answered satisfactorily, and one-third reported that ATP answers affected how they managed a given case.

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer.

PubMed

Beukinga, Roelof J; Hulshoff, Jan Binne; Mul, Véronique E M; Noordzij, Walter; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Plukker, John T M

2018-06-01

Purpose To assess the value of baseline and restaging fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18 F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18 F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β.

PubMed

Alamino, Vanina A; Mascanfroni, Iván D; Montesinos, María M; Gigena, Nicolás; Donadio, Ana C; Blidner, Ada G; Milotich, Sonia I; Cheng, Sheue-Yann; Masini-Repiso, Ana M; Rabinovich, Gabriel A; Pellizas, Claudia G

2015-04-01

Bidirectional cross-talk between the neuroendocrine and immune systems orchestrates immune responses in both physiologic and pathologic settings. In this study, we provide in vivo evidence of a critical role for the thyroid hormone triiodothyronine (T3) in controlling the maturation and antitumor functions of dendritic cells (DC). We used a thyroid hormone receptor (TR) β mutant mouse (TRβPV) to establish the relevance of the T3-TRβ system in vivo. In this model, TRβ signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRβ increased DC viability and augmented DC migration to lymph nodes. Moreover, T3 stimulated the ability of DCs to cross-present antigens and to stimulate cytotoxic T-cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DCs inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFNγ-producing CD8(+) T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DCs, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy. ©2015 American Association for Cancer Research.

Warthin tumor: a potential source of diagnostic error.

PubMed

Colella, Giuseppe; Tozzi, Umberto; Pagliarulo, Valentina; Bove, Pierfrancesco

2010-11-01

Warthin tumor, also known as papillary cystadenoma lymphomatosum, is a fairly common tumor. It makes up 14% to 30% of parotid tumors. There has been much interest in this tumor because of its typical and intriguing morphologic features: the association of benign-looking lymphoid and epithelial components and its frequent occurrence in the intraparotid or periparotid lymph nodes. Moreover, multifocal and/or bilateral Warthin tumors have been reported, and malignant transformation of Warthin tumor and its association with other malignancies have been documented. Warthin tumor can sometimes be confused with other pathologic lesions because of symptoms and signs that accompany the disease, so it could be treated as other pathologic lesions. We present 3 patients. The first one had a differentiated squamous cell carcinoma, no lymph node metastasis, and a Warthin tumor of the left parotid gland. The other 2 patients presented monoclonal gammopathy and a high tracer uptake in the left parotid gland by the 18F-fluorodeoxyglucose positron emission tomography/computed tomography total body. The aim of this study was to evaluate the clinical and histopathologic features of 3 cases where clinical presentation of a Warthin tumor lies in the possible errors in diagnosis and decision making and not least in the management of the patient.

Ewing-like sarcomas with BCOR-CCNB3 fusion transcript: a clinical, radiological and pathological retrospective study from the Société Française des Cancers de L'Enfant.

PubMed

Cohen-Gogo, Sarah; Cellier, Cécile; Coindre, Jean-Michel; Mosseri, Véronique; Pierron, Gaëlle; Guillemet, Cécile; Italiano, Antoine; Brugières, Laurence; Orbach, Daniel; Laurence, Valérie; Delattre, Olivier; Michon, Jean

2014-12-01

This retrospective multicenter study assessed the clinical, radiological and pathological presentation, treatment and outcome of 26 patients with Ewing-like sarcoma harboring BCOR-CCNB3 gene fusion transcript. Tumor samples had been collected between 1994 and April 2012. Eligibility criteria included assessment of a BCOR-CCNB3 transcript-positive tumor after molecular analysis and availability of minimal clinical and pathological data. Radiological data were also retrieved when possible. Data were analyzed by descriptive statistics and methods for survival analysis. Median age at diagnosis was 13.1 years (5.9 to 25.6 years). Most patients (24/26) had localized tumors. All tumors but five were localized to bone. CCNB3 immunochemistry showed strong nuclear staining on all samples. No specific radiological features were found. Most patients received chemotherapy (15 according to protocols designed for Ewing tumors), before and/or after local treatment (surgery and/or radiotherapy, with 46.2% receiving both). Local and metastatic relapses were of poor prognosis. Induction chemotherapy and treatment according to an Ewing protocol might influence survival for patients with localized tumors. Sixteen patients are alive in complete remission with a median follow-up of 86 months. Five year overall survival and disease-free survival were respectively 76.5% (95% CI, 58%-95%) and 67.9% (95% CI, 48%-88%). BCOR-CCNB3 transcript-positive Ewing-like sarcoma diagnosis should be discussed for a transcript-negative small round cell sarcoma in a child, adolescent or young adult patient. Diagnosis needs to be stated through CCNB3 immunochemistry or transcript identification. The exquisite chemosensitivity of these tumors should encourage the use of polychemotherapy for appropriate care, associated with best local tumor control. © 2014 Wiley Periodicals, Inc.

Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy

PubMed Central

2017-01-01

Intercellular communications play a major role in tissue homeostasis and responses to external cues. Novel structures for this communication have recently been described. These tunneling nanotubes (TNTs) consist of thin-extended membrane protrusions that connect cells together. TNTs allow the cell-to-cell transfer of various cellular components, including proteins, RNAs, viruses, and organelles, such as mitochondria. Mesenchymal stem cells (MSCs) are both naturally present and recruited to many different tissues where their interaction with resident cells via secreted factors has been largely documented. Their immunosuppressive and repairing capacities constitute the basis for many current clinical trials. MSCs recruited to the tumor microenvironment also play an important role in tumor progression and resistance to therapy. MSCs are now the focus of intense scrutiny due to their capacity to form TNTs and transfer mitochondria to target cells, either in normal physiological or in pathological conditions, leading to changes in cell energy metabolism and functions, as described in this review. PMID:28659978

Development of Raman spectral markers to assess metastatic bone in breast cancer

PubMed Central

Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

2014-01-01

Abstract. Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk. PMID:24933683

Development of Raman spectral markers to assess metastatic bone in breast cancer

NASA Astrophysics Data System (ADS)

Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

2014-11-01

Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk.

Proceedings of the 2013 National Toxicology Program Satellite Symposium

PubMed Central

Elmore, Susan A.; Boyle, Michael C.; Boyle, Molly H.; Cora, Michelle C.; Crabbs, Torrie A.; Cummings, Connie A.; Gruebbel, Margarita M.; Johnson, Crystal L.; Malarkey, David E.; McInnes, Elizabeth F.; Nolte, Thomas; Shackelford, Cynthia C.; Ward, Jerrold M.

2014-01-01

The 2013 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri” was held in Portland, Oregon in advance of the Society of Toxicologic Pathology's 32nd annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a caudal tail vertebra duplication in mice; nephroblastematosis in rats; ectopic C cell tumor in a hamster; granular cell aggregates/tumor in the uterus of a hamster; Pneumocystis carinii in the lung of a rat; iatrogenic chronic inflammation in the lungs of control rats; hepatoblastoma arising within an adenoma in a mouse; humoral hypercalcemia of benignancy in a transgenic mouse; acetaminophen induced hepatoxicity in rats; electron microscopy images of iatrogenic intraerythrocytic inclusions in transgenic mice; questionable hepatocellular degeneration/cell death/artifact in rats; atypical endometrial hyperplasia in rats; malignant mixed Müllerian tumors/carcinosarcomas in rats; differential diagnoses of proliferative lesions the intestine of rodents; and finally obstructive nephropathy caused by melamine poisoning in a rat. PMID:24334674

Double-Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor-Depth Photothermal Therapy.

PubMed

Zhang, Ming-Kang; Wang, Xiao-Gang; Zhu, Jing-Yi; Liu, Miao-Deng; Li, Chu-Xin; Feng, Jun; Zhang, Xian-Zheng

2018-04-17

This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS-HA is specifically set within the optimal size window for passive tumor-targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size-dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS-HA due to HAase-catalyzed HA degradation, in turn activating the recovery of initially CuS-quenched luminescence of UCNP and also driving the tumor-depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor-ignited explosible firework. Together with the double-targeting functionality, the pathology-selective tumor ignition permits precise tumor detection and imaging-guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making.

PubMed

Ravindra, Vijay M; Eli, Ilyas M; Schmidt, Meic H; Brockmeyer, Douglas L

2016-08-01

Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making.

Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy.

PubMed

Sabir, Adeel; Schor-Bardach, Rachel; Wilcox, Carol J; Rahmanuddin, Syed; Atkins, Michael B; Kruskal, Jonathan B; Signoretti, Sabina; Raptopoulos, Vassilios D; Goldberg, S Nahum

2008-07-01

The objective of our study was to determine whether perfusion CT can be used to detect early changes in therapeutic response to antiangiogenic therapy in an animal tumor model. Twenty-five rats implanted with R3230 mammary adenocarcinoma (diameter, 1.2-2.0 cm) randomly received 7.5 or 30 mg/kg of an antiangiogenic agent, sorafenib, by daily gavage for 4 (n = 4), 9 (n = 9), or 14 (n = 5) days. Seven untreated animals served as a control group. Perfusion MDCT was performed at days 0, 4, 9, and 14 with 0.4 mL of ioversol (350 mg/mL) and included four 5-mm slices covering the entire tumor volume. Changes in tumor growth were determined by volumetric analysis of CT data. Serial changes in tumor volume and blood flow were assessed and correlated with pathology findings. All control tumors grew larger (from 2.0 +/- 0.7 cm(3) at day 0 to 5.9 +/- 1.0 cm(3) at day 14), whereas all treated tumors shrank (from 2.5 +/- 1.1 to 2.1 +/- 1.0 cm(3)), with a statistically significant rate of growth or shrinkage in both groups (p < 0.05). Although perfusion in the control tumors changed little from day 0 to day 14 (day 0, 18.1 +/- 9.2 mL/min/100 g; day 4, 15.8 +/- 5.6; day 9, 21.7 +/- 12.2; day 14, 27.7 +/- 34), in the sorafenib group, the mean blood flow was significantly lower at day 4 (5.2 +/- 3.2 mL/min/100 g, 77% decrease), day 9 (6.4 +/- 4.0 mL/min/100 g, 66% decrease), and day 14 (6.3 +/- 5.2 mL/min/100 g, 83% decrease) compared with day 0 (23.8 +/- 11.6 mL/min/100 g) (p < 0.05). Poor correlation was seen between changes in blood flow and tumor volume for days 0-9 (r(2) = 0.34), 4-9 (r(2) = 0.0004), and 9-14 (r(2) = 0.16). However, when comparing day 4 images with days 9 and 14 images, seven of 14 (50%) sorafenib-treated tumors had focal areas of new perfusion that correlated with areas of histopathologic viability despite the fact that these tumors were shrinking in size from day 4 onward (day 4, 2.18 +/- 0.8 cm(3); day 9, 1.98 +/- 0.8 cm(3)). Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

Multimodal fiber-probe spectroscopy for the diagnostics and classification of bladder tumors

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Fantechi, Riccardo; Gacci, Mauro; Nesi, Gabriella; Carini, Marco; Pavone, Francesco S.

2017-02-01

The gold standard for the detection of bladder cancer is white light cystoscopy, followed by an invasive biopsy and pathological examination. Tissue pathology is time consuming and often prone to sampling errors. Recently, optical spectroscopy techniques have evolved as promising techniques for the detection of neoplasia. The specific goal of this study is to evaluate the application of combined auto-fluorescence (excited using 378 nm and 445 nm wavelengths) and diffuse reflectance spectroscopy to discriminate normal bladder tissue from tumor at different grades. The fluorescence spectrum at both excitation wavelengths showed an increased spectral intensity in tumors with respect to normal tissues. Reflectance data indicated an increased reflectance in the wavelength range 610 nm - 700 nm for different grades of tumors, compared to normal tissues. The spectral data were further analyzed using principal component analysis for evaluating the sensitivity and specificity for diagnosing tumor. The spectral differences observed between various grades of tumors provides a strong genesis for the future evaluation on a larger patient population to achieve statistical significance. This study indicates that a combined spectroscopic strategy, incorporating fluorescence and reflectance spectroscopy, could improve the capability for diagnosing bladder tumor as well as for differentiating tumors in different grades.

Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

PubMed

Fontebasso, Adam M; Jabado, Nada

2015-01-01

Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

Cannabinoids receptor type 2, CB2, expression correlates with human colon cancer progression and predicts patient survival.

PubMed

Martínez-Martínez, Esther; Gómez, Irene; Martín, Paloma; Sánchez, Antonio; Román, Laura; Tejerina, Eva; Bonilla, Félix; Merino, Antonio García; de Herreros, Antonio García; Provencio, Mariano; García, Jose M

2015-01-01

Many studies have demonstrated that the endocannabinoid system (ECS) is altered in different tumor types, including colon cancer. However, little is known about the role of the ECS in tumor progression. Here we report the correlation between CB 2 expression and pathological data in a series of 175 colorectal cancer patients, as well as the response of the HT29 colon cancer-derived cell line upon CB 2 activation. CB 2 mRNA was detected in 28.6% of samples tested. It was more frequent in N+ patients and predicts disease free survival and overall survival in colon cancer. In positive samples, CB 2 was expressed with great intensity in tumor epithelial cells and correlated with tumor growth. Treatment of HT29 with CB 2 agonist revealed membrane loss of E-cadherin and SNAIL1 overexpression. A direct correlation between CB 2 and SNAIL1 expression was also found in human tumors. CB 2 receptor expression is a poor prognostic marker for colon cancer and the activation of this receptor, with non-apoptotic doses of agonists, could be collaborating with disease progression. These results raise the question whether the activation of CB 2 should be considered as anti-tumoral therapy.

Tumor Microenvironment and Immune Effects of Antineoplastic Therapy in Lymphoproliferative Syndromes

PubMed Central

Álvaro, Tomás; de la Cruz-Merino, Luis; Henao-Carrasco, Fernando; Villar Rodríguez, José Luis; Vicente Baz, David; Codes Manuel de Villena, Manuel; Provencio, Mariano

2010-01-01

Lymphomas represent a wide group of heterogenic diseases with different biological and clinical behavior. The underlying microenvironment-specific composition seems to play an essential role in this scenario, harboring the ability to develop successful immune responses or, on the contrary, leading to immune evasion and even promotion of tumor growth. Depending on surrounding lymphoid infiltrates, lymphomas may have different prognosis. Moreover, recent evidences have emerged that confer a significant impact of main lymphoma's treatment over microenvironment, with clinical consequences. In this review, we summarize these concepts from a pathological and clinical perspective. Also, the state of the art of lymphoma's anti-idiotype vaccine development is revised, highlighting the situations where this strategy has proven to be successful and eventual clues to obtain better results in the future. PMID:20814546

18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature?

PubMed

Taïeb, David; Sebag, Frederic; Barlier, Anne; Tessonnier, Laurent; Palazzo, Fausto F; Morange, Isabelle; Niccoli-Sire, Patricia; Fakhry, Nicolas; De Micco, Catherine; Cammilleri, Serge; Enjalbert, Alain; Henry, Jean-François; Mundler, Olivier

2009-05-01

Our objective was to evaluate (18)F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). (18)F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. All but 2 patients showed significantly increased (18)F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean +/- SD, 8.2 +/- 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean +/- SD, 9.7 +/- 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase-related tumors were notable in being the most (18)F-FDG-avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau-related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome-related tumors (P = 0.02). (18)F-FDG PET was superior to (131)I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, (18)F-FDG PET underestimated the extent of the disease, compared with 6-(18)F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain (18)F-FDG uptake since most tumors were highly avid for (18)F-FDG. (18)F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez, Rodrigo O.; Angelita and Joaquim Gama Institute, Sao Paulo; Habr-Gama, Angelita, E-mail: gamange@uol.com.br

Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([{sup 18}FDG]PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied ( (ClinicalTrials.org) identifier (NCT00254683)). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks from CRT completion). Clinical assessment was at 12 weeks. Maximal standard uptake value (SUVmax) of the primary tumor was measured and recorded at each PET/CT study aftermore » 1 h (early) and 3 h (late) from {sup 18}FDG injection. Patients with an increase in early SUVmax between 6 and 12 weeks were considered 'bad' responders and the others as 'good' responders. Results: Ninety-one patients were included; 46 patients (51%) were 'bad' responders, whereas 45 (49%) patients were 'good' responders. 'Bad' responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; P=.001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; P=.008) and exhibited greater final tumor dimension (4.3 cm vs. 3.3 cm; P=.03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CT was a significant predictor of 'good' response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients.« less

Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

PubMed Central

Judge, Meagan J.; Evans, Alan; Frishberg, David P.; Prieto, Victor G.; Thompson, John F.; Trotter, Martin J.; Walsh, Maureen Y.; Walsh, Noreen M.G.; Ellis, David W.

2013-01-01

An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may facilitate the development of protocols for other tumor types. Widespread utilization of an internationally agreed upon, structured pathology data set for melanoma will lead not only to improved patient management but is a prerequisite for research and for international benchmarking in health care. PMID:24061524

Stromal matrix metalloprotease-13 knockout alters Collagen I structure at the tumor-host interface and increases lung metastasis of C57BL/6 syngeneic E0771 mammary tumor cells.

PubMed

Perry, Seth W; Schueckler, Jill M; Burke, Kathleen; Arcuri, Giuseppe L; Brown, Edward B

2013-09-05

Matrix metalloproteases and collagen are key participants in breast cancer, but their precise roles in cancer etiology and progression remain unclear. MMP13 helps regulate collagen structure and has been ascribed largely harmful roles in cancer, but some studies demonstrate that MMP13 may also protect against tumor pathology. Other studies indicate that collagen's organizational patterns at the breast tumor-host interface influence metastatic potential. Therefore we investigated how MMP13 modulates collagen I, a principal collagen subtype in breast tissue, and affects tumor pathology and metastasis in a mouse model of breast cancer. Tumors were implanted into murine mammary tissues, and their growth analyzed in Wildtype and MMP13 KO mice. Following extraction, tumors were analyzed for collagen I levels and collagen I macro- and micro-structural properties at the tumor-host boundary using immunocytochemistry and two-photon and second harmonic generation microscopy. Lungs were analyzed for metastases counts, to correlate collagen I changes with a clinically significant functional parameter. Statistical analyses were performed by t-test, analysis of variance, or Wilcoxon-Mann-Whitney tests as appropriate. We found that genetic ablation of host stromal MMP13 led to: 1. Increased mammary tumor collagen I content, 2. Marked changes in collagen I spatial organization, and 3. Altered collagen I microstructure at the tumor-host boundary, as well as 4. Increased metastasis from the primary mammary tumor to lungs. These results implicate host MMP13 as a key regulator of collagen I structure and metastasis in mammary tumors, thus making it an attractive potential therapeutic target by which we might alter metastatic potential, one of the chief determinants of clinical outcome in breast cancer. In addition to identifying stromal MMP13 is an important regulator of the tumor microenvironment and metastasis, these results also suggest that stromal MMP13 may protect against breast cancer pathology under some conditions, a finding with important implications for development of chemotherapies directed against matrix metalloproteases.

Cardioprotective Role of Tumor Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and Necroptosis.

PubMed

Guo, Xiaoyun; Yin, Haifeng; Li, Lei; Chen, Yi; Li, Jing; Doan, Jessica; Steinmetz, Rachel; Liu, Qinghang

2017-08-22

Programmed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. We examined the role of tumor necrosis factor receptor-associated factor 2 (Traf2) in regulating myocardial necroptosis and remodeling using genetic mouse models. We also performed molecular and cellular biology studies to elucidate the mechanisms by which Traf2 regulates necroptosis signaling. We identified a critical role for Traf2 in myocardial survival and homeostasis by suppressing necroptosis. Cardiac-specific deletion of Traf2 in mice triggered necroptotic cardiac cell death, pathological remodeling, and heart failure. Plasma tumor necrosis factor α level was significantly elevated in Traf2 -deficient mice, and genetic ablation of TNFR1 largely abrogated pathological cardiac remodeling and dysfunction associated with Traf2 deletion. Mechanistically, Traf2 critically regulates receptor-interacting proteins 1 and 3 and mixed lineage kinase domain-like protein necroptotic signaling with the adaptor protein tumor necrosis factor receptor-associated protein with death domain as an upstream regulator and transforming growth factor β-activated kinase 1 as a downstream effector. It is important to note that genetic deletion of RIP3 largely rescued the cardiac phenotype triggered by Traf2 deletion, validating a critical role of necroptosis in regulating pathological remodeling and heart failure propensity. These results identify an important Traf2-mediated, NFκB-independent, prosurvival pathway in the heart by suppressing necroptotic signaling, which may serve as a new therapeutic target for pathological remodeling and heart failure. © 2017 American Heart Association, Inc.

Long non-coding RNA-CRNDE: a novel regulator of tumor growth and angiogenesis in hepatoblastoma.

PubMed

Dong, Rui; Liu, Xiang-Qi; Zhang, Bin-Bin; Liu, Bai-Hui; Zheng, Shan; Dong, Kui-Ran

2017-06-27

Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. They have emerged as key players in the pathology of several tumors, including hepatoblastoma. In this study, we elucidate the biological and clinical significance of CRNDE up-regulation in hepatoblastoma. CRNDE is significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. CRNDE knockdown reduces tumor growth and tumor angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, and angiogenic effect in vitro. Mechanistic studies show that CRNDE knockdown plays its anti-proliferation and anti-angiogenesis role via regulating mammalian target of rapamycin (mTOR) signaling. Taken together, this study reveals a crucial role of CRNDE in the pathology of hepatoblastoma. CRNDE may serve as a promising diagnostic marker and therapeutic target for hepatoblastoma.

Effective deactivation of A549 tumor cells in vitro and in vivo by RGD-decorated chitosan-functionalized single-walled carbon nanotube loading docetaxel.

PubMed

Li, Bin; Zhang, Xiao-Xue; Huang, Hao-Yan; Chen, Li-Qing; Cui, Jing-Hao; Liu, Yanli; Jin, Hehua; Lee, Beom-Jin; Cao, Qing-Ri

2018-05-30

This study aims to construct and evaluate RGD-decorated chitosan (CS)-functionalized pH-responsive single-walled carbon nanotube (SWCNT) carriers using docetaxel (DTX) as a model anticancer drug. DTX was loaded onto SWCNT via π-π stacking interaction (SWCNT-DTX), followed by the non-covalent conjugation of RGD-decorated CS to SWCNT-DTX to prepare RGD-CS-SWCNT-DTX. The RGD-CS-SWCNT-DTX showed significantly higher drug release than the pure drug, giving higher release rate at pH 5.0 (68%) than pH 7.4 (49%). The RGD-CS-SWCNT-DTX could significantly inhibit the growth of A549 tumor cells in vitro, and the uptake amount of A549 cells was obviously higher than that of MCF-7 cells. Meanwhile, the cellular uptake of RGD-CS-SWCNT-DTX was higher than that of CS-SWCNT-DTX in A549 cells, mainly through clathrin and caveolae-mediated endocytosis. The RGD-CS-SWCNT-DTX significantly inhibited tumor growth of A549 cell-bearing nude mice through active tumor-targeting ability. Furthermore, no pathological changes were found in tissues and organs. The result demonstrated that RGD-CS-SWCNT-DTX displayed high drug loading, pH-responsive drug release, remarkable antitumor effect in vitro and in vivo, and also good safety to animal body. Copyright © 2018 Elsevier B.V. All rights reserved.

Imaging features of carcinoid tumors metastatic to the breast.

PubMed

Glazebrook, Katrina N; Jones, Katie N; Dilaveri, Christina A; Perry, Kyle; Reynolds, Carol

2011-06-29

The objective of this study was to describe the imaging findings of carcinoid tumors metastatic to the breast, with pathologic and clinical correlations. We searched our surgical database for cases of pathologically proven carcinoid tumors metastatic to the breast from October 1, 2000, to May 31, 2010. Of the approximate 10,000 breast biopsies identified, 7000 had malignant findings. Ten cases of metastatic carcinoid (0.1% of all malignancies), all with imaging studies available for review, were included in the study. All patients were women and had their primary carcinoid in the gastrointestinal tract (n=9) or lung (n = 1). One patient presented with a palpable breast mass and no history of carcinoid tumor; an ileal carcinoid was discovered after the pathologic diagnosis of metastatic carcinoid was established. In the breast, tumors presented as solitary lesions in half the cases. Metastases to the breast typically presented as circumscribed masses mammographically and as hypoechoic circumscribed masses ultrasonographically; some showed increased through-transmission and increased vascularity with color Doppler evaluation. Five patients had octreotide scans; of these, 4 had increased focal activity in the region of metastasis within the breast. Six patients underwent computed tomography. Without contrast, nodular masses were observed; with contrast, the masses showed rapid enhancement during arterial phase imaging. Magnetic resonance imaging (n = 4) also showed rapid enhancement and washout kinetics after contrast administration. Recognition of carcinoid metastases to the breast in patients with known or occult primary carcinoid tumors is important to avoid unnecessary treatment for primary breast cancer.

A discriminative model-constrained graph cuts approach to fully automated pediatric brain tumor segmentation in 3-D MRI.

PubMed

Wels, Michael; Carneiro, Gustavo; Aplas, Alexander; Huber, Martin; Hornegger, Joachim; Comaniciu, Dorin

2008-01-01

In this paper we present a fully automated approach to the segmentation of pediatric brain tumors in multi-spectral 3-D magnetic resonance images. It is a top-down segmentation approach based on a Markov random field (MRF) model that combines probabilistic boosting trees (PBT) and lower-level segmentation via graph cuts. The PBT algorithm provides a strong discriminative observation model that classifies tumor appearance while a spatial prior takes into account the pair-wise homogeneity in terms of classification labels and multi-spectral voxel intensities. The discriminative model relies not only on observed local intensities but also on surrounding context for detecting candidate regions for pathology. A mathematically sound formulation for integrating the two approaches into a unified statistical framework is given. The proposed method is applied to the challenging task of detection and delineation of pediatric brain tumors. This segmentation task is characterized by a high non-uniformity of both the pathology and the surrounding non-pathologic brain tissue. A quantitative evaluation illustrates the robustness of the proposed method. Despite dealing with more complicated cases of pediatric brain tumors the results obtained are mostly better than those reported for current state-of-the-art approaches to 3-D MR brain tumor segmentation in adult patients. The entire processing of one multi-spectral data set does not require any user interaction, and takes less time than previously proposed methods.

Small-Animal Molecular Imaging for Preclinical Cancer Research: .μPET and μ.SPECT.

PubMed

Cuccurullo, Vincenzo; Di Stasio, Giuseppe D; Schillirò, Maria L; Mansi, Luigi

2016-01-01

Due to different sizes of humans and rodents, the performance of clinical imaging devices is not enough for a scientifically reliable evaluation in mice and rats; therefore dedicated small-animal systems with a much higher sensitivity and spatial resolution, compared to the ones used in humans, are required. Smallanimal imaging represents a cutting-edge research method able to approach an enormous variety of pathologies in which animal models of disease may be used to elucidate the mechanisms underlying the human condition and/or to allow a translational pharmacological (or other) evaluation of therapeutic tools. Molecular imaging, avoiding animal sacrifice, permits repetitive (i.e. longitudinal) studies on the same animal which becomes its own control. In this way also the over time evaluation of disease progression or of the treatment response is enabled. Many different rodent models have been applied to study almost all kind of human pathologies or to experiment a wide series of drugs and/or other therapeutic instruments. In particular, relevant information has been achieved in oncology by in vivo neoplastic phenotypes, obtained through procedures such as subcutaneous tumor grafts, surgical transplantation of solid tumor, orthotopic injection of tumor cells into specific organs/sites of interest, genetic modification of animals to promote tumor-genesis; in this way traditional or innovative treatments, also including gene therapy, of animals with a cancer induced by a known carcinogen may be experimented. Each model has its own disadvantage but, comparing different studies, it is possible to achieve a panoramic and therefore substantially reliable view on the specific subject. Small-animal molecular imaging has become an invaluable component of modern biomedical research that will gain probably an increasingly important role in the next few years.

Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer.

PubMed

Huang, Bao-Tian; Wu, Li-Li; Guo, Long-Jia; Xu, Liang-Yu; Huang, Rui-Hong; Lin, Pei-Xian; Chen, Jian-Zhou; Li, De-Rui; Chen, Chuang-Zhen

2017-01-01

To compare the radiobiological response between simultaneously dose-escalated and non-escalated intensity-modulated radiation therapy (DE-IMRT and NE-IMRT) for patients with upper thoracic esophageal cancer (UTEC) using radiobiological evaluation. Computed tomography simulation data sets for 25 patients pathologically diagnosed with primary UTEC were used in this study. DE-IMRT plan with an escalated dose of 64.8 Gy/28 fractions to the gross tumor volume (GTV) and involved lymph nodes from 25 patients pathologically diagnosed with primary UTEC, was compared to an NE-IMRT plan of 50.4 Gy/28 fractions. Dose-volume metrics, tumor control probability (TCP), and normal tissue complication probability for the lung and spinal cord were compared. In addition, the risk of acute esophageal toxicity (AET) and late esophageal toxicity (LET) were also analyzed. Compared with NE-IMRT plan, we found the DE-IMRT plan resulted in a 14.6 Gy dose escalation to the GTV. The tumor control was predicted to increase by 31.8%, 39.1%, and 40.9% for three independent TCP models. The predicted incidence of radiation pneumonitis was similar (3.9% versus 3.6%), and the estimated risk of radiation-induced spinal cord injury was extremely low (<0.13%) in both groups. Regarding the esophageal toxicities, the estimated grade ≥2 and grade ≥3 AET predicted by the Kwint model were increased by 2.5% and 3.8%. Grade ≥2 AET predicted using the Wijsman model was increased by 14.9%. The predicted incidence of LET was low (<0.51%) in both groups. Radiobiological evaluation reveals that the DE-IMRT dosing strategy is feasible for patients with UTEC, with significant gains in tumor control and minor or clinically acceptable increases in radiation-induced toxicities.

Sex Disparities After Induction Chemoradiotherapy and Esophagogastrectomy for Esophageal Cancer.

PubMed

Rowse, Phillip G; Jaroszewski, Dawn E; Thomas, Mathew; Harold, Kristi; Harmsen, William S; Shen, K Robert

2017-10-01

The impact of sex on the outcomes of treatment for locally advanced esophageal carcinoma is unclear. This study analyzed the impact of sex on response to neoadjuvant chemoradiotherapy (nCRT), tumor recurrence, and survival. From January 1990 through December 2013, female patients who received nCRT followed by esophagogastrectomy at 3 affiliated centers were compared with control male patients based on age, pretreatment clinical stage, histologic type, and surgical era. Only patients staged preoperatively with computed tomographic scans and endoscopic ultrasonography (EUS) were included. There were 366 patients (145 women and 221 men). The median female age was 64 years (range, 22-81 years), whereas male patients were 61 years (range, 33-82 years). The histologic type was adenocarcinoma in 105 (72%) women and 192 (87%) men, and it was squamous cell carcinoma in 40 (28%) women and 29 (13%) men (p = 0.005). Women were more likely to attain either a complete pathologic (CP) response or a nearly complete pathologic (NCP) response to induction therapy (84 [58%]) compared with men (103 [47%]; p = 0.034). Men had an 80% increased risk of recurrence (hazard ratio [HR], 1.80; 95% CI, 1.15-2.68; p = 0.008). There was no sex association with risk of death (p = 0.538). Irrespective of sex, a partial responder (relative to a complete or nearly complete responder) was 3 times more likely to have recurrence (HR, 2.96; 95% CI, 1.98-4.43; p < 0.001) and 2.5 times more likely to die (HR, 2.56; 95% CI, 1.88-3.48; p < 0.001). Female sex correlated with improved rates of achieving either a CP response or an NCP response after neoadjuvant chemotherapy and a smaller likelihood of experiencing tumor recurrence. Future efforts should be directed at understanding determinants of this sex disparity. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Papillary Microcarcinoma of the Thyroid among Atomic Bomb Survivors: Tumor Characteristics and Radiation Risk

PubMed Central

Hayashi, Yuzo; Lagarde, Frederic; Tsuda, Nobuo; Funamoto, Sachiyo; Preston, Dale L.; Koyama, Kojiro; Mabuchi, Kiyohiko; Ron, Elaine; Kodama, Kazunori; Tokuoka, Shoji

2009-01-01

Background Radiation exposure is an established cause of clinical thyroid cancer, but little is known about radiation effects on papillary microcarcinoma (PMC) of the thyroid, a relatively common subclinical thyroid malignancy. Because the incidence of these small thyroid cancers has been increasing, it is important to better understand them and their relationship to radiation. Methods PMCs were identified in a subset of 7659 members of the Life Span Study of atomic-bomb survivors who had archived autopsy or surgical materials. We conducted a pathology review of these specimens and evaluated the histological features of the tumors and the association between PMCs and thyroid radiation dose. Results From 1958 to1995, 458 PMCs were detected among 313 study subjects. The majority of cancers exhibited pathologic features of papillary thyroid cancers. Overall, 81% of the PMCs were of the sclerosing variant and 91% were nonencapsulated, psammoma bodies occurred in 13% and calcification was observed in 23%. Over 95% had papillary or papillary-follicular architecture and most displayed nuclear overlap, clear nuclei, and nuclear grooves. Several of these features increased with increasing tumor size, but no association was found with radiation dose. A significant radiation-dose response was found for the prevalence of PMCs (estimated excess odds ratio/Gy=0.57; 95% CI: 0.01-1.55), with the excess risk observed primarily among females. Conclusion Low-to-moderate doses of ionizing radiation appears to increase the risk of thyroid PMCs, even when exposure occurs during adulthood. PMID:20120034

Bone Sarcoma Pathology: Diagnostic Approach for Optimal Therapy.

PubMed

Rosenberg, Andrew E

2017-01-01

The pathologic interpretation of malignant bone tumors is one of the more challenging areas in surgical pathology. This is based on the reality that primary bone sarcomas are uncommon, demonstrate significant morphologic heterogeneity, and have a broad spectrum of biology. Accordingly, it is difficult for pathologists to acquire the necessary experience to confidently and accurately diagnose bone sarcomas. The task is further complicated by the fact that it requires the integration of clinical and radiologic information into the diagnostic process. Lastly, molecular aberrations in sarcomas are being newly discovered and their identification is often critical to make specific diagnoses. The pathologist's role in guiding optimal treatment in biopsy specimens is to make an accurate diagnosis and provide the grade and molecular aberrations when appropriate. The pathology report of resected tumors must confirm this information and assess the surgical resection margins and the percentage of necrosis if the sarcoma has been treated with neoadjuvant systemic therapy.

Standardized uptake value and apparent diffusion coefficient of endometrial cancer evaluated with integrated whole-body PET/MR: Correlation with pathological prognostic factors.

PubMed

Shih, I-Lun; Yen, Ruoh-Fang; Chen, Chi-An; Chen, Bang-Bin; Wei, Shwu-Yuan; Chang, Wen-Chun; Sheu, Bor-Ching; Cheng, Wen-Fang; Tseng, Yao-Hui; Chen, Xin-Jia; Chen, Chi-Hau; Wei, Lin-Hung; Chiang, Ying-Cheng; Torng, Pao-Ling; Yen, Men-Luh; Shih, Tiffany Ting-Fang

2015-12-01

To evaluate the correlation between maximum standardized uptake value (SUVmax ) and minimum apparent diffusion coefficient (ADCmin ) of endometrial cancer derived from an integrated positron emission tomography / magnetic resonance (PET/MR) system and to determine their correlation with pathological prognostic factors. This prospective study was approved by the Institutional Review Board of the hospital, and informed consent was obtained. Between April and December 2014, 47 consecutive patients with endometrial cancer were enrolled and underwent simultaneous PET/MR examinations before surgery. Thirty-six patients with measurable tumors on PET/MR were included for image analysis. Pearson's correlation coefficient was used to evaluate the correlation between SUVmax and ADCmin of the tumors. The Mann-Whitney U-test was utilized to evaluate relationships between these two imaging biomarkers and pathological prognostic factors. The mean SUVmax and ADCmin were 14.7 ± 7.1 and 0.48 ± 0.13 × 10(-3) mm(2) /s, respectively. A significant inverse correlation was found between SUVmax and ADCmin (r = -0.53; P = 0.001). SUVmax was significantly higher in tumors with advanced stage, deep myometrial invasion, cervical invasion, lymphovascular space involvement, and lymph node metastasis (P < 0.05). ADCmin was lower in tumors with higher grade, advanced stage, and cervical invasion (P < 0.05). The ratio of SUVmax to ADCmin was higher in tumors with higher grade, advanced stage, deep myometrial invasion, cervical invasion, lymphovascular space involvement, and lymph node metastasis (P < 0.05). SUVmax and ADCmin of endometrial cancer derived from integrated PET/MR are inversely correlated and are associated with pathological prognostic factors. © 2015 Wiley Periodicals, Inc.

Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

PubMed Central

Mavaddat, Nasim; Barrowdale, Daniel; Andrulis, Irene L.; Domchek, Susan M.; Eccles, Diana; Nevanlinna, Heli; Ramus, Susan J.; Spurdle, Amanda; Robson, Mark; Sherman, Mark; Mulligan, Anna Marie; Couch, Fergus J.; Engel, Christoph; McGuffog, Lesley; Healey, Sue; Sinilnikova, Olga M.; Southey, Melissa C.; Terry, Mary Beth; Goldgar, David; O’Malley, Frances; John, Esther M.; Janavicius, Ramunas; Tihomirova, Laima; Hansen, Thomas v O; Nielsen, Finn C.; Osorio, Ana; Stavropoulou, Alexandra; Benítez, Javier; Manoukian, Siranoush; Peissel, Bernard; Barile, Monica; Volorio, Sara; Pasini, Barbara; Dolcetti, Riccardo; Putignano, Anna Laura; Ottini, Laura; Radice, Paolo; Hamann, Ute; Rashid, Muhammad U.; Hogervorst, Frans B.; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Evans, D. Gareth; Brewer, Carole; Walker, Lisa; Rogers, Mark T.; Side, Lucy E.; Houghton, Catherine; Weaver, JoEllen; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Kast, Karin; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Doroteha; Preisler-Adams, Sabine; Varon-Mateeva, Raymonda; Schönbuchner, Ines; Gevensleben, Heidrun; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Barjhoux, Laure; Isaacs, Claudine; Peshkin, Beth N.; Caldes, Trinidad; de al Hoya, Miguel; Cañadas, Carmen; Heikkinen, Tuomas; Heikkilä, Päivi; Aittomäki, Kristiina; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Agnarsson, Bjarni A.; Arason, Adalgeir; Barkardottir, Rosa B.; Dumont, Martine; Simard, Jacques; Montagna, Marco; Agata, Simona; D’Andrea, Emma; Yan, Max; Fox, Stephen; Rebbeck, Timothy R.; Rubinstein, Wendy; Tung, Nadine; Garber, Judy E.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S.; Lindor, Noralane M.; Szabo, Csilla; Offit, Kenneth; Sakr, Rita; Gaudet, Mia M.; Singer, Christian F.; Tea, Muy-Kheng; Rappaport, Christine; Mai, Phuong L.; Greene, Mark H.; Sokolenko, Anna; Imyanitov, Evgeny; Toland, Amanda Ewart; Senter, Leigha; Sweet, Kevin; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben; Caligo, Maria; Aretini, Paolo; Rantala, Johanna; von Wachenfeld, Anna; Henriksson, Karin; Steele, Linda; Neuhausen, Susan L.; Nussbaum, Bob; Beattie, Mary; Odunsi, Kunle; Sucheston, Lara; Gayther, Simon A; Nathanson, Kate; Gross, Jenny; Walsh, Christine; Karlan, Beth; Chenevix-Trench, Georgia; Easton, Douglas F.; Antoniou, Antonis C.

2011-01-01

Background Previous small studies found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. Methods We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian and contralateral breast cancers. Results There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (p-trend=1.2×10−5) but increased with age at diagnosis among BRCA2 carriers (p-trend=6.8×10−6). The proportion of triple negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histological grade than ER-positive tumors (Grade 3 vs. Grade 1, p=1.2×10−13 for BRCA1 and p=0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status (ER-positive odds ratio (OR) for BRCA2=9.4, 95%CI:7.0-12.6 and PR-positive OR=1.7, 95%CI:1.3-2.3, under joint analysis). Lobular tumors were more likely to be BRCA2-related (OR for BRCA2=3.3, 95%CI:2.4-4.4, p=4.4×10−14), and medullary tumors BRCA1-related (OR for BRCA2=0.25, 95%CI:0.18-0.35, p=2.3×10−15). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (p=0.0004 for BRCA1; p=0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous:67%; mucinous:1%; endometriod:12%; clear-cell:2%). Conclusions/Impact Pathology characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk prediction algorithms and informing clinical strategies for screening and prophylaxis. PMID:22144499

Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.

PubMed

Otero, Jesse E; Stevens, Jeff W; Malandra, Allison E; Fredericks, Douglas C; Odgren, Paul R; Buckwalter, Joseph A; Morcuende, Jose

2014-12-01

Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A case of unresectable combined hepatocellular cholangiocarcinoma showing favorable response to LFP therapy.

PubMed

Kato, Sayuri; Takeuchi, Yasuto; Wada, Nozomu; Morimoto, Yuuki; Kuwaki, Kenji; Ohnishi, Hideki; Nakamura, Shinichiro; Shiraha, Hidenori; Takaki, Akinobu; Okada, Hiroyuki

2016-01-01

A woman in her 50s was admitted to our hospital because of multiple tumors detected in her liver. She was diagnosed with combined hepatocellular cholangiocarcinoma using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biopsy of the liver tumors. We judged the tumors to be unresectable because they were found in both lobes of the liver, with a tumor thrombus being found in the main left portal vein. The pathological findings showed that the tumors exhibited characteristics of hepatocellular carcinoma. Therefore, sorafenib was administered;however, 6 months later, the disease progressed. Consequently, she received second-line chemotherapy with a one-shot intra-arterial injection of cisplatin, but this too was ineffective, and her general condition worsened. As hence, we changed the regimen to 5-fluorouracil continuous infusion and consecutive low dose cisplatin (LFP) therapy. After one cycle of chemotherapy with LFP, Gd-EOB-DTPA-enhanced MRI showed markedly decreased sizes and numbers of tumors. To date, she has completed six cycles of LFP therapy, and almost all her tumors are no longer visible on MRI. She has recovered to a good state and has achieved long-term survival. Thus, this case indicates that although LFP therapy is generally selected for cases of advanced hepatocellular carcinoma, it also appears to be effective for long-term disease control in cases of hepatocellular cholangiocarcinoma.

Prognostic factors for keratocystic odontogenic tumor (odontogenic keratocyst): analysis of clinico-pathologic and immunohistochemical findings in cysts treated by enucleation.

PubMed

Kuroyanagi, Norio; Sakuma, Hidenori; Miyabe, Satoru; Machida, Junichiro; Kaetsu, Atsuo; Yokoi, Motoo; Maeda, Hatsuhiko; Warnakulasuriya, Saman; Nagao, Toru; Shimozato, Kazuo

2009-04-01

The purpose of this study was to determine prognostic factors for the recurrence of keratocystic odontogenic tumors (KCOTs) following simple enucleation by examining clinico-pathologic and immunohistochemical findings. Following enucleation, the frequency of recurrence among 32 subjects diagnosed with KCOT was analyzed for tumor site, radiographic and histologic features, and immunopositivity for Ki-67 and p53. Keratocystic odontogenic tumors in four out of 32 subjects (12.5%) recurred during the follow-up period (median: 33 months, range: 7-114 months). Three out of four subjects (75.0%) among recurrent group showed high expression of Ki-67 (LI >10%) in basal layer and four (4/28; 14.3%) among non-recurrence group (P = 0.025). Expression of p53 among non-recurrent group was observed in 11 subjects (11/28; 39.3%), and in three subjects (3/4; 75.0%) among the recurrent group (P = 0.295). Hazard risk for the recurrence of KCOT was 4.02 (95% CI 1.42-18.14) for high Ki-67 expression in the basal layer by the Cox proportional hazard model (P = 0.009). In our study, none of the other clinico-pathologic variables were associated with the recurrence of KCOT. The results suggested that the evaluation of Ki-67 expression in KCOT at the time of pathological diagnosis might be helpful for consideration of appropriate adjunctive surgical procedures to avoid a recurrence and may serve as a prognostic marker.

Unusual benign polypoid and papular neoplasms and tumor-like lesions of the vulva.

PubMed

AbdullGaffar, Badr; Keloth, Tasnim R; Raman, Lakshmiah G; Mahmood, Suaad; Almulla, Amal; AlMarzouqi, Mamoun; Al-Hasani, Salam

2014-04-01

We aimed to investigate the prevalence and spectrum of unusual benign neoplasms and tumor-like lesions presenting as vulvar polyps and papules, to study their clinical, pathologic, hormonal, and developmental features and whether they have important associations with other pathologic lesions or clinical diseases. We conducted a retrospective review study of 115 vulvar specimens over 7 years. Common lesions, for example, fibroepithelial polyps, skin tags, papillomas, abscesses, viral warts and common cysts, were excluded. We found 21 cases (18%) with uncommon benign vulvar lesions. They included 7 epithelial cysts, 3 vascular lesions, 3 glandular neoplasms, 3 endometrioses, 1 caruncle, 1 pilonidal sinus, 1 prolapsed urethra, 1 seborrheic keratosis, and 1 granular cell tumor. The age range was between 1 and 64 years with a mean age of 33 years. Most (86%) were 2.5 cm or less. Many were asymptomatic incidental pathologic findings that can be missed clinically. Nine cases have important clinical associations or coexisting incidental pathologic lesions. Some lesions demonstrated hormone receptors. Some were clinically confused with fibroepithelial polyps, abscesses, warts, melanocytic lesions, and tumors. In conclusion, although the vulva is a small compartment, its developmental and histologic complexity can result in a variety of unusual and rare benign polypoid and papular lesions, some unique to the vulva, which might present diagnostic challenges to the clinicians and pathologists. In addition, many bear controversy regarding their histogenesis and origin of development in the vulva. Copyright © 2014 Elsevier Inc. All rights reserved.

[The pathology of salivary glands. Tumors of the salivary glands].

PubMed

Mahy, P; Reychler, H

2006-01-01

The management of benign and malignant neoplasms of the salivary glands requires precise knowledge of tumor histogenesis and classification as well as surgical skills. Pleomorphic adenoma and Whartin's tumor are the most frequent tumors in parotid glands while the probability for malignant tumors is higher in other glands, especially in sublingual and minor salivary glands. Those malignant salivary glands tumors are rare and necessitate multidisciplinar staging and management in close collaboration with the pathologist and the radiation oncologist.

The potential usefulness of the Response Index in positron emission tomography assessing the therapeutic effect of pre-operative chemotherapy for advanced colorectal cancer.

PubMed

Nomura, Masatoshi; Takahashi, Hidekazu; Haraguchi, Naotsugu; Nishimura, Junichi; Hata, Taishi; Matsuda, Chu; Ikenaga, Masakazu; Yamamoto, Hirofumi; Murata, Kohei; Doki, Yuichiro; Mori, Masaki; Mizushima, Tsunekazu

2017-12-01

Pre-operative chemotherapy is an option for patients with local advanced rectal cancer, but the response rate to pre-operative chemotherapy with oxaliplatin is still low. If the therapeutic effect of pre-operative chemotherapy could be assessed, we may be able to convert to surgery early. The purpose of the present study was to validate the correlation between the maximum standardized uptake value (SUV max ) in 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) of the primary tumor and the therapeutic effect of pre-operative chemotherapy in advanced colorectal cancer. Retrospective cohort study from January 2011 to October 2015. We examined 28 patients with pathologically confirmed sigmoid or rectal cancer that underwent pre-operative chemotherapy and surgery. The correlation between Response Index (RI), calculated as (SUV max after chemotherapy)/(SUV max before chemotherapy), and the therapeutic effect on the primary tumor in advanced colorectal cancer. The degree of differentiation (p = 0.04), SUV max in the primary tumor after chemotherapy (p = 0.02), and RI (p = 0.008) were significant predictors of the therapeutic effect in univariate analysis. The areas under the ROC curve constructed with RI and therapeutic effect was 0.77. The optimal cut-off values for the RI in the responder group was < 0.32. RI calculated as (SUV max after chemotherapy)/(SUV max before chemotherapy) in the primary tumor significantly correlated with the therapeutic effect of chemotherapy on advanced colorectal cancer. Thus, RI is potentially useful for predicting the therapeutic effect in advanced colorectal cancer.

SRF selectively controls tip cell invasive behavior in angiogenesis.

PubMed

Franco, Claudio A; Blanc, Jocelyne; Parlakian, Ara; Blanco, Raquel; Aspalter, Irene M; Kazakova, Natalia; Diguet, Nicolas; Mylonas, Elena; Gao-Li, Jacqueline; Vaahtokari, Anne; Penard-Lacronique, Virgine; Fruttiger, Markus; Rosewell, Ian; Mericskay, Mathias; Gerhardt, Holger; Li, Zhenlin

2013-06-01

Efficient angiogenic sprouting is essential for embryonic, postnatal and tumor development. Serum response factor (SRF) is known to be important for embryonic vascular development. Here, we studied the effect of inducible endothelial-specific deletion of Srf in postnatal and adult mice. We find that endothelial SRF activity is vital for postnatal growth and survival, and is equally required for developmental and pathological angiogenesis, including during tumor growth. Our results demonstrate that SRF is selectively required for endothelial filopodia formation and cell contractility during sprouting angiogenesis, but seems dispensable for vascular remodeling. At the molecular level, we observe that vascular endothelial growth factor A induces nuclear accumulation of myocardin-related transcription factors (MRTFs) and regulates MRTF/SRF-dependent target genes including Myl9, which is important for endothelial cell migration in vitro. We conclude that SRF has a unique function in regulating migratory tip cell behavior during sprouting angiogenesis. We hypothesize that targeting the SRF pathway could provide an opportunity to selectively target tip cell filopodia-driven angiogenesis to restrict tumor growth.

Mortality following single-fraction stereotactic body radiation therapy for central pulmonary oligometastasis

PubMed Central

Ma, Sung Jun; Mix, Michael; Rivers, Charlotte; Hennon, Mark; Gomez, Jorge

2017-01-01

The case of a 56-year-old male who developed bronchopulmonary hemorrhage after a course of stereotactic body radiation therapy (SBRT) for centrally located squamous cell lung carcinoma is presented. The patient was previously treated with concurrent chemoradiation for stage IVA squamous cell carcinoma of the base of tongue. He showed no evidence of disease for 4 years until he developed a solitary metastasis of squamous cell carcinoma in the right hilum. He underwent a single fraction of 26 Gy with heterogeneity correction. He showed no evidence of disease for 13 months until he developed a sudden grade 4 bronchopulmonary hemorrhage. He underwent an urgent right pneumonectomy and later died of a post-operative complication. Pathologic analysis of the specimen revealed no evidence of tumor. Single-fraction SBRT of 26 Gy was sufficient to achieve complete response of his large central lung tumor. However, when treating patients with central lung tumors, some risk of mortality may be unavoidable with either SBRT or pneumonectomy. PMID:29296456

A universal fluorogenic switch for Fe(ii) ion based on N-oxide chemistry permits the visualization of intracellular redox equilibrium shift towards labile iron in hypoxic tumor cells.

PubMed

Hirayama, Tasuku; Tsuboi, Hitomi; Niwa, Masato; Miki, Ayaji; Kadota, Satoki; Ikeshita, Yukie; Okuda, Kensuke; Nagasawa, Hideko

2017-07-01

Iron (Fe) species play a number of biologically and pathologically important roles. In particular, iron is a key element in oxygen sensing in living tissue where its metabolism is intimately linked with oxygen metabolism. Regulation of redox balance of labile iron species to prevent the generation of iron-catalyzed reactive oxygen species (ROS) is critical to survival. However, studies on the redox homeostasis of iron species are challenging because of a lack of a redox-state-specific detection method for iron, in particular, labile Fe 2+ . In this study, a universal fluorogenic switching system is established, which is responsive to Fe 2+ ion based on a unique N-oxide chemistry in which dialkylarylamine N-oxide is selectively deoxygenized by Fe 2+ to generate various fluorescent probes of Fe 2+ -CoNox-1 (blue), FluNox-1 (green), and SiRhoNox-1 (red). All the probes exhibited fluorescence enhancement against Fe 2+ with high selectivity both in cuvette and in living cells. Among the probes, SiRhoNox-1 showed an excellent fluorescence response with respect to both reaction rate and off/on signal contrast. Imaging studies were performed showing the intracellular redox equilibrium shift towards labile iron in response to reduced oxygen tension in living cells and 3D tumor spheroids using SiRhoNox-1, and it was found that the hypoxia induction of labile Fe 2+ is independent of iron uptake, hypoxia-induced signaling, and hypoxia-activated enzymes. The present studies demonstrate the feasibility of developing sensitive and specific fluorescent probes for Fe 2+ with refined photophysical characteristics that enable their broad application in the study of iron in various physiological and pathological conditions.

Down-regulation of heat-shock protein 70 (HSP-70) correlated with responsiveness to neoadjuvant aromatase inhibitor therapy in breast cancer patients.

PubMed

Yiu, Christopher C P; Chanplakorn, Niramol; Chan, Monica S M; Loo, Wings T Y; Chow, Louis W C; Toi, Masakazu; Sasano, Hironobu

2010-09-01

Aromatase inhibitor (AI) has been established as an effective endocrine therapy in estrogen receptor (ER)-positive postmenopausal breast cancer patients. Our recent proteomic analysis demonstrated that ten proteins were significantly altered in their expression levels before and after the therapy in the patients receiving neoadjuvant AI. Among these newly identified proteins, heat-shock protein 70 (HSP-70) was the most significantly correlated with both clinical and pathological responses. Therefore, in this study, we further evaluated the significance of this HSP-70 alteration using immunohistochemistry. A total of 32 patients treated with neoadjuvant exemestane or letrozole in whom pre- and post-treatment tumor tissues were available were included. Immunohistochemical evaluation of ER, progesterone receptor (PgR), Her-2, Ki-67 and HSP-70 was performed. Results obtained were compared to both clinical and biological responses of the patients. The majority of the patients responded to treatment (16 patients with partial response, 14 with stable disease and 2 with progressive disease). The means of ER, Ki-67 and HSP-70 were significantly different between treatment responders and non-responders. Decrement of HSP-70 and Ki-67 after AI treatment and pretreatment Ki-67 labeling index of >10% tumor cells were significantly associated with clinical responsiveness to AI treatment (p<0.0001). There was a significant positive correlation between changes of HSP-70 and Ki-67 before and after the therapy. Decrement of HSP-70 in breast carcinoma cells plays important roles in therapeutic mechanisms of AIs through suppressing tumor cell proliferation in breast cancer patients.

[Analysis of the diagnosis and treatment of desmoplastic small round cell tumor].

PubMed

Lu, Baojian; Zhang, Wei; Shang, Zhiqun; Sun, Erlin; Nian, Xuewu; Gao, Jingda; Ma, Chengquan; Han, Ruifa

2015-09-01

To explore the clinical diagnostic features and treatment of desmoplastic small round cell tumor (DSRCT), and to improve the understanding and management of this tumor. The clinicopathological data of nine patients treated in our hospital from October 2004 to June 2014 were retrospectively analyzed and a review of the literature was made. The clinical manifestations, pathological characteristics, diagnosis and differential diagnosis, treatment and prognosis of this tumor were summarized and analyzed. Nine patients with DSRCT, 5 males and 4 females, with an average age of 21 years (range 8-56 years) were included in this study. Ultrasound examination revealed irregular low-density mass shadow in the abdominal cavity. CT examination found that 6 cases had abdominal and retroperitoneal multiple solid tumor nodules, uneven density, and visible low density fluid area. Postoperative pathological examination revealed that the tumor cells were small, mostly elliptic, gathered to form clear structure of nests with clear irregular boundaries. The central portion of large tumor nests often showed necrosis. Scattered fibroblasts and large amount of hyalinization of collagen fibers were seen in the interstitial tissue around the nests. Six patients received laparotomy surgery, however, all failed to resect the tumor completely. Three patients received postoperative chemotherapy, i. e. two cases had carboplatin and paclitaxel chemotherapy, and one case of chemotherapy regimen not specified. Two patients had radiation and chemotherapy (no concrete plan was available). Another case was lost to follow-up. Two of the three patients without surgery received chemotherapy with CAP (cyclophosphamide+adriamycin+carboplatin) and total rectal lesions, pelvic and inguinal lymph nodes, ilium metastases radiation therapy. Another one patient received EP regimen (DDP+VP16) which was then changed into a TP chemotherapy alone. Eight of the nine cases died shortly after surgery, and only one patient treated with chemotherapy alone was still alive after 11 months of follow-up. Desmoplastic small round cell tumor is a very rare, special type of soft tissue tumor, with very poor prognosis. This tumor may be preliminarily diagnosed according to the imaging characteristics and detection of tumor markers, however, final diagnosis is made by pathology. Surgery is the priority of treatment, combined with complementary radiation and chemotherapy.

Nonlinear cancer response at ultralow dose: a 40800-animal ED(001) tumor and biomarker study.

PubMed

Bailey, George S; Reddy, Ashok P; Pereira, Clifford B; Harttig, Ulrich; Baird, William; Spitsbergen, Jan M; Hendricks, Jerry D; Orner, Gayle A; Williams, David E; Swenberg, James A

2009-07-01

Assessment of human cancer risk from animal carcinogen studies is severely limited by inadequate experimental data at environmentally relevant exposures and by procedures requiring modeled extrapolations many orders of magnitude below observable data. We used rainbow trout, an animal model well-suited to ultralow-dose carcinogenesis research, to explore dose-response down to a targeted 10 excess liver tumors per 10000 animals (ED(001)). A total of 40800 trout were fed 0-225 ppm dibenzo[a,l]pyrene (DBP) for 4 weeks, sampled for biomarker analyses, and returned to control diet for 9 months prior to gross and histologic examination. Suspect tumors were confirmed by pathology, and resulting incidences were modeled and compared to the default EPA LED(10) linear extrapolation method. The study provided observed incidence data down to two above-background liver tumors per 10000 animals at the lowest dose (that is, an unmodeled ED(0002) measurement). Among nine statistical models explored, three were determined to fit the liver data well-linear probit, quadratic logit, and Ryzin-Rai. None of these fitted models is compatible with the LED(10) default assumption, and all fell increasingly below the default extrapolation with decreasing DBP dose. Low-dose tumor response was also not predictable from hepatic DBP-DNA adduct biomarkers, which accumulated as a power function of dose (adducts = 100 x DBP(1.31)). Two-order extrapolations below the modeled tumor data predicted DBP doses producing one excess cancer per million individuals (ED(10)(-6)) that were 500-1500-fold higher than that predicted by the five-order LED(10) extrapolation. These results are considered specific to the animal model, carcinogen, and protocol used. They provide the first experimental estimation in any model of the degree of conservatism that may exist for the EPA default linear assumption for a genotoxic carcinogen.

Ocular Response of Choroidal Melanoma With Monosomy 3 Versus Disomy 3 After Iodine-125 Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marathe, Omkar S.; Wu, Jeffrey; Lee, Steve P.

2011-11-15

Purpose: To report the ocular response of choroidal melanoma with monosomy 3 vs. disomy 3 after {sup 125}I brachytherapy. Methods and Materials: We evaluated patients with ciliochoroidal melanoma managed with fine needle aspiration biopsy immediately before plaque application for {sup 125}I brachytherapy between January 1, 2005 and December 31, 2008. Patients with (1) cytopathologic diagnosis of melanoma, (2) melanoma chromosome 3 status identified by fluorescence in situ hybridization, and (3) 6 or more months of follow-up after brachytherapy were sorted by monosomy 3 vs. disomy 3 and compared by Kruskal-Wallis test. Results: Among 40 ciliochoroidal melanomas (40 patients), 15 hadmore » monosomy 3 and 25 had disomy 3. Monosomy 3 melanomas had a median greatest basal diameter of 12.00 mm and a median tumor thickness of 6.69 mm before brachytherapy; at a median of 1.75 years after brachytherapy, median thickness was 3.10 mm. Median percentage decrease in tumor thickness was 48.3%. Disomy 3 melanomas had a median greatest basal diameter of 10.00 mm and median tumor thickness of 3.19 mm before brachytherapy; at a median of 2.00 years after brachytherapy, median tumor thickness was 2.37 mm. The median percentage decrease in tumor thickness was 22.7%. Monosomy 3 melanomas were statistically greater in size than disomy 3 melanomas (p < 0.001) and showed a greater decrease in tumor thickness after brachytherapy (p = 0.006). Conclusion: In this study, ciliochoroidal melanomas with monosomy 3 were significantly greater in size than disomy 3 melanoma and showed a significantly greater decrease in thickness at a median of 1.75 years after brachytherapy. The greater decrease in monosomy 3 melanoma thickness after brachytherapy is consistent with other malignancies in which more aggressive pathology has been shown to be associated with a greater initial response to radiotherapy.« less

Synoptic reporting in tumor pathology: advantages of a web-based system.

PubMed

Qu, Zhenhong; Ninan, Shibu; Almosa, Ahmed; Chang, K G; Kuruvilla, Supriya; Nguyen, Nghia

2007-06-01

The American College of Surgeons Commission on Cancer (ACS-CoC) mandates that pathology reports at ACS-CoC-approved cancer programs include all scientifically validated data elements for each site and tumor specimen. The College of American Pathologists (CAP) has produced cancer checklists in static text formats to assist reporting. To be inclusive, the CAP checklists are pages long, requiring extensive text editing and multiple intermediate steps. We created a set of dynamic tumor-reporting templates, using Microsoft Active Server Page (ASP.NET), with drop-down list and data-compile features, and added a reminder function to indicate missing information. Users can access this system on the Internet, prepare the tumor report by selecting relevant data from drop-down lists with an embedded tumor staging scheme, and directly transfer the final report into a laboratory information system by using the copy-and-paste function. By minimizing extensive text editing and eliminating intermediate steps, this system can reduce reporting errors, improve work efficiency, and increase compliance.

Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity.

PubMed

Maeda, Hiroshi

2015-08-30

The enhanced permeability and retention (EPR) effect of solid tumors as seen with nanomedicines and macromolecular drugs is well known. However, many researchers appear to lack a full understanding of this effect. The effect varies depending on a patient's pathological and physiological characteristics and clinical condition. When a patient's systolic blood pressure is low side of about 90mmHg instead of 120-130mmHg, the hydrodynamic force pushing blood from the luminal side of a vessel into tumor tissue becomes significantly low, which results in a low EPR. Also, a vascular embolism in a tumor may impede blood flow and the EPR. Here, I describe the background of the EPR effect, heterogeneity of this effect, physiological and pathological factors affecting the effect, the EPR effect in metastatic tumors, artifacts of the EPR effect with micellar and liposomal drugs, problems of macromolecular drug stability and drug release, and access to target sites. Copyright © 2015 Elsevier B.V. All rights reserved.

MALDI TOF imaging mass spectrometry in clinical pathology: a valuable tool for cancer diagnostics (review).

PubMed

Kriegsmann, Jörg; Kriegsmann, Mark; Casadonte, Rita

2015-03-01

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) is an evolving technique in cancer diagnostics and combines the advantages of mass spectrometry (proteomics), detection of numerous molecules, and spatial resolution in histological tissue sections and cytological preparations. This method allows the detection of proteins, peptides, lipids, carbohydrates or glycoconjugates and small molecules.Formalin-fixed paraffin-embedded tissue can also be investigated by IMS, thus, this method seems to be an ideal tool for cancer diagnostics and biomarker discovery. It may add information to the identification of tumor margins and tumor heterogeneity. The technique allows tumor typing, especially identification of the tumor of origin in metastatic tissue, as well as grading and may provide prognostic information. IMS is a valuable method for the identification of biomarkers and can complement histology, immunohistology and molecular pathology in various fields of histopathological diagnostics, especially with regard to identification and grading of tumors.

Disseminated Oligodendroglial-like Leptomeningeal Tumor in the Adult: Case Report and Review of the Literature.

PubMed

Fiaschi, Pietro; Badaloni, Filippo; Cagetti, Bernarda; Bruzzone, Luca; Marucci, Gianluca; Dellachà, Anna; Pavanello, Marco; Ganci, Giuseppe; Padolecchia, Riccardo; Valsania, Valtero

2018-06-01

Diffuse leptomeningeal glioneuronal tumor (DLGNT) was recently added to the World Health Organization classification of central nervous system tumors. DLGNT is a rare entity that occurs more commonly in pediatric patients, but occasional cases have been reported in adults. This tumor has been recognized as a distinct pathologic entity; however, its biologic behavior remains unclear. It is considered an indolent neoplasm, although considerable morbidity has been reported. For this reason, further characterization and collection of evidence are crucial. In this article, we reported a case of a 36-year-old woman with a DLGNT characterized by rapid, aggressive behavior. We also performed a review of the literature for reported cases of low-grade and high-grade forms involving adults and children. DLGNTs should no longer be considered only as low-grade tumors affecting pediatric patients. The spectrum of presentations also includes aggressive tumors affecting adults. Further clinical and pathologic data supported by cytogenetic and molecular investigations are mandatory to better characterize DLGNTs. Copyright © 2018 Elsevier Inc. All rights reserved.

A Specific miRNA Signature Correlates With Complete Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Della Vittoria Scarpati, Giuseppina; Falcetta, Francesca; Carlomagno, Chiara, E-mail: chiara.carlomagno@unina.it

2012-07-15

Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific 'signature' correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy. Methods and Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsiesmore » obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study. Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909 Asterisk-Operator , miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.« less

Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis by possible reduction of NLRP3 activation and up-regulation of NET expression.

PubMed

Li, Yong; Pan, Yiyuan; Gao, Lin; Lu, Guotao; Zhang, Jingzhu; Xie, Xiaochun; Tong, Zhihui; Li, Baiqiang; Li, Gang; Li, Weiqin

2018-01-22

Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms. Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 μg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1β, and interleukin (IL)-1β in pancreatic tissue was detected by Western blot and real-time PCR. Dexmedetomidine at 20 μg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 μg/kg significantly down-regulated the expression of NLRP3, pro-IL-1β, and IL-1β in pancreatic tissue, but up-regulated the expression of NET in both mouse models. Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression. Copyright © 2018 Elsevier Inc. All rights reserved.

DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu; Wang Xiaozhe; Niemierko, Andrzej

2012-05-01

Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, withmore » biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need confirmation in an independent data set.« less

Relationship between the Temporal Changes in Positron-Emission-Tomography-Imaging-Based Textural Features and Pathologic Response and Survival in Esophageal Cancer Patients.

PubMed

Yip, Stephen S F; Coroller, Thibaud P; Sanford, Nina N; Mamon, Harvey; Aerts, Hugo J W L; Berbeco, Ross I

2016-01-01

Although change in standardized uptake value (SUV) measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer. Fifty-four esophageal cancer patients received PET/CT scans before and after chemoradiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two cooccurrence matrix (Entropy and Homogeneity), two run-length matrix (RLM) (high-gray-run emphasis and Short-run high-gray-run emphasis), and two size-zone matrix (high-gray-zone emphasis and short-zone high-gray emphasis) textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC) and Kaplan-Meier statistics, respectively. All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC = 0.79, p = 1.7 × 10(-4)) and partial (AUC = 0.71, p = 0.01) responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run-length and size-zone matrix textures (AUC = 0.71-0.76, p ≤ 0.02). Homogeneity, SUVmax, and SUVmean failed to differentiate between any of the responders (AUC = 0.50-0.57, p ≥ 0.46). However, none of the measures were found to significantly distinguish between complete and partial responders with AUC <0.60 (p = 0.37). Median Entropy and RLM textures significantly discriminated patients with good and poor survival (log-rank p < 0.02), while all other textures and survival were poorly related (log-rank p > 0.25). For the patients studied, temporal changes in Entropy and all RLM were better correlated with pathological response and survival than the SUV measures. The hypothesis that these metrics can be used as clinical predictors of better patient outcomes will be tested in a larger patient dataset in the future.

Comparative analysis of whole mount processing and systematic sampling of radical prostatectomy specimens: pathological outcomes and risk of biochemical recurrence.

PubMed

Salem, Shady; Chang, Sam S; Clark, Peter E; Davis, Rodney; Herrell, S Duke; Kordan, Yakup; Wills, Marcia L; Shappell, Scott B; Baumgartner, Roxelyn; Phillips, Sharon; Smith, Joseph A; Cookson, Michael S; Barocas, Daniel A

2010-10-01

Whole mount processing is more resource intensive than routine systematic sampling of radical retropubic prostatectomy specimens. We compared whole mount and systematic sampling for detecting pathological outcomes, and compared the prognostic value of pathological findings across pathological methods. We included men (608 whole mount and 525 systematic sampling samples) with no prior treatment who underwent radical retropubic prostatectomy at Vanderbilt University Medical Center between January 2000 and June 2008. We used univariate and multivariate analysis to compare the pathological outcome detection rate between pathological methods. Kaplan-Meier curves and the log rank test were used to compare the prognostic value of pathological findings across pathological methods. There were no significant differences between the whole mount and the systematic sampling groups in detecting extraprostatic extension (25% vs 30%), positive surgical margins (31% vs 31%), pathological Gleason score less than 7 (49% vs 43%), 7 (39% vs 43%) or greater than 7 (12% vs 13%), seminal vesicle invasion (8% vs 10%) or lymph node involvement (3% vs 5%). Tumor volume was higher in the systematic sampling group and whole mount detected more multiple surgical margins (each p <0.01). There were no significant differences in the likelihood of biochemical recurrence between the pathological methods when patients were stratified by pathological outcome. Except for estimated tumor volume and multiple margins whole mount and systematic sampling yield similar pathological information. Each method stratifies patients into comparable risk groups for biochemical recurrence. Thus, while whole mount is more resource intensive, it does not appear to result in improved detection of clinically important pathological outcomes or prognostication. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Stromal p16 Overexpression in Adult Granulosa Cell Tumors of the Ovary.

PubMed

Na, Kiyong; Sung, Ji-Youn; Kim, Hyun-Soo

2017-05-01

Adult granulosa cell tumor of the ovary is usually diagnosed at an early stage. However, most patients with advanced or recurrent disease will die of the disease due to limited treatment options. Data on the stromal p16 expression of ovarian adult granulosa cell tumors are limited. The aim of this study was to analyze the immunohistochemical p16 expression in the peritumoral stroma of primary and recurrent adult granulosa cell tumors and investigate whether there were significant differences in stromal p16 expression among nonpathological ovaries, benign sex cord-stromal tumors, and adult granulosa cell tumors. This study included 13 and 11 cases of primary and recurrent adult granulosa cell tumors, respectively. Non-pathological ovaries and benign sex cord-stromal tumors showed negative or weak positive expression, whereas most of the adult granulosa cell tumors showed diffuse and moderate-to-strong immunostaining. Primary adult granulosa cell tumors had significantly higher stromal p16 expression levels than nonpathological ovaries and benign sex cord-stromal tumors (p<0.001). Moreover, recurrent adult granulosa cell tumors showed significantly elevated levels of stromal p16 expression compared to primary adult granulosa cell tumors (p=0.032). In contrast, the difference in stromal p16 expression between non-pathological ovaries and benign sex cord-stromal tumors was not statistically significant (p=0.522). Our observations suggest that stromal p16 expression may be involved in the development and progression of ovarian adult granulosa cell tumors. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer.

PubMed

Rodríguez, Marta; Silva, Javier; López-Alfonso, Ana; López-Muñiz, María Belen; Peña, Cristina; Domínguez, Gemma; García, Jose Miguel; López-Gónzalez, Ana; Méndez, Miriam; Provencio, Mariano; García, Vanesa; Bonilla, Félix

2014-09-01

Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the exosomes isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes isolated in plasma and BAL from 30 and 75 patients with tumor and nontumor pathology were quantified by acetylcholinesterase activity and characterized by Western Blot, Electron Microscopy, and Nanoparticle Tracking Analysis. Differences in exosome cargo were analyzed by miRNA quantitative PCR in pooled samples and validated in a second series of patients. More exosomes were detected in plasma than in BAL in both groups (P < 0.001). The most miRNAs evaluated by PCR array were detected in tumor plasma, tumor BAL, and nontumor BAL pools, but only 56% were detected in the nontumor plasma pool. Comparing the top miRNAs with the highest levels detected in each pool, we found close homology only between the BAL samples of the two pathologies. In tumor plasma, we found a higher percentage of miRNAs with increased levels than in tumor BAL or in nontumor plasma. The data reveal differences between BAL and plasma exosome amount and miRNA content. © 2014 Wiley Periodicals, Inc.

Automatic Brain Tumor Detection in T2-weighted Magnetic Resonance Images

NASA Astrophysics Data System (ADS)

Dvořák, P.; Kropatsch, W. G.; Bartušek, K.

2013-10-01

This work focuses on fully automatic detection of brain tumors. The first aim is to determine, whether the image contains a brain with a tumor, and if it does, localize it. The goal of this work is not the exact segmentation of tumors, but the localization of their approximate position. The test database contains 203 T2-weighted images of which 131 are images of healthy brain and the remaining 72 images contain brain with pathological area. The estimation, whether the image shows an afflicted brain and where a pathological area is, is done by multi resolution symmetry analysis. The first goal was tested by five-fold cross-validation technique with 100 repetitions to avoid the result dependency on sample order. This part of the proposed method reaches the true positive rate of 87.52% and the true negative rate of 93.14% for an afflicted brain detection. The evaluation of the second part of the algorithm was carried out by comparing the estimated location to the true tumor location. The detection of the tumor location reaches the rate of 95.83% of correct anomaly detection and the rate 87.5% of correct tumor location.

An evaluation of the anti-tumor efficacy of oleanolic acid-loaded PEGylated liposomes

NASA Astrophysics Data System (ADS)

Tang, Shengnan; Gao, Dawei; Zhao, Tingting; Zhou, Jing; Zhao, Xiaoning

2013-06-01

The effective delivery of oleanolic acid (OA) to the target site has several benefits in therapy for different pathologies. However, the delivery of OA is challenging due to its poor aqueous solubility. The study aims to evaluate the tumor inhibition effect of the PEGylated OA nanoliposome on the U14 cervical carcinoma cell line. In our previous study, OA was successfully encapsulated into PEGylated liposome with the modified ethanol injection method. Oral administration of PEGylated OA liposome was demonstrated to be more efficient in inhibiting xenograft tumors. The results of organ index indicated that PEG liposome exhibited higher anti-tumor activity and lower cytotoxicity. It was also found that OA and OA liposomes induced tumor cell apoptosis detected by flow cytometry. Furthermore, effects of OA on the morphology of tumor and other tissues were observed by hematoxylin and eosin staining. The histopathology sections did not show pathological changes in kidney or liver in tested mice. In contrast, there was a significant difference in tumor tissues between treatment groups and the negative control group. These observations imply that PEGylated liposomes seem to have advantages for cancer therapy in terms of effective delivery of OA.

Missed causative tumors in diagnosing tumor-induced osteomalacia with (18)F-FDG PET/CT: a potential pitfall of standard-field imaging.

PubMed

Kaneuchi, Yoichi; Hakozaki, Michiyuki; Yamada, Hitoshi; Hasegawa, Osamu; Tajino, Takahiro; Konno, Shinichi

2016-01-01

We describe herein two tumor-induced osteomalacia (TIO) cases for whom the causative lesions, located in their popliteal fossa, that were not identified in the standard field of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT), which usually images only the head, trunk, and proximal parts of the extremities. A 47 years old Japanese man with multiple pathological fractures due to osteomalacia, accompanied by muscle weakness, hypophosphatemia, and an elevation of alkaline phosphatase (ALP) was referred to our hospital. A (18)F-FDG PET/CT scan was performed, but no (18)F-FDG uptake was detected in the standard field of imaging. Magnetic resonance imaging revealed a small subcutaneous tumor (1.9×1.2×0.6cm) of the left posteriomedial knee, displaying uniform enhancement on gadolinium-enhanced T1-weighted fat-suppression imaging. The tumor was resected widely and diagnosed as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). The other patient was a 31 years old Japanese woman with multiple pathological fractures, hypophosphatemia and elevated of ALP and was referred to our hospital on suspicion of TIO. Although the causative lesion was not identified in the standard field of (18)F-FDG PET/CT, (18)F-FDG uptake (SUVmax 2.9) was detected on the right knee in the additional whole-body (18)F-FDG PET/CT. Magnetic resonance imaging revealed a soft-tissue tumor (6.4×4.1×2.9cm) in the right posterior knee. Following biopsy, the tumor was marginally resected, and was pathologically diagnosed as PMTMCT. Once patients are suspected to have TIO, a whole-body nuclear imaging study such as (18)F-FDG PET/CT should be performed, in order not to miss the hidden causative tumor, especially occurring in the distal extremities.

The Added Diagnostic Value of 18F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors.

PubMed

Addeo, Pietro; Poncet, Gilles; Goichot, Bernard; Leclerc, Loic; Brigand, Cécile; Mutter, Didier; Romain, Benoit; Namer, Izzie-Jacques; Bachellier, Philippe; Imperiale, Alessio

2018-04-01

The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs. Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative 18 F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and 18 F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology. There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, 18 F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, 18 F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0 ± 2.2 vs. 0.4 ± 0.7 vs. 0.6 ± 1.5, p = 0.0003). 18 F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. 18 F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

Seizure prognosis of patients with low-grade tumors.

PubMed

Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

2012-09-01

Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and radiation therapy have a favorable impact on seizure outcome. Additional epilepsy surgery is effective. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Commentary on "Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy."

PubMed

Thomas, D E; Kaimakliotis, H Z; Rice, K R; Pereira, J A; Johnston, P; Moore, M L; Reed, A; Cregar, D M; Franklin, C; Loman, R L; Koch, M O; Bihrle, R; Foster, R S; Masterson, T A; Gardner, T A; Sundaram, C P; Powell, C R; Beck, Sdw; Grignon, D J; Cheng, L; Albany, C; Hahn, N M

2018-07-01

Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Prognostic Effect of Carcinoma In Situ in Muscle-invasive Urothelial Carcinoma Patients Receiving Neoadjuvant Chemotherapy.

PubMed

Thomas, Derek E; Kaimakliotis, Hristos Z; Rice, Kevin R; Pereira, Jose A; Johnston, Paul; Moore, Marietta L; Reed, Angela; Cregar, Dylan M; Franklin, Cindy; Loman, Rhoda L; Koch, Michael O; Bihrle, Richard; Foster, Richard S; Masterson, Timothy A; Gardner, Thomas A; Sundaram, Chandru P; Powell, Charles R; Beck, Stephen D W; Grignon, David J; Cheng, Liang; Albany, Costantine; Hahn, Noah M

2017-08-01

Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19-13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Endoscopic photodynamic therapy with hematoporphyrin derivative in the treatment of malignant tumors: report of 120 cases

NASA Astrophysics Data System (ADS)

Tian, Mao-en; Liu, Fa-wen; Qian, Jia-ping; Ji, Qing; Feng, Yun-qiu

1993-03-01

One-hundred-twenty cases of malignant tumors treated by endoscopic photodynamic therapy with hematoporphyrin derivative from August 1982 - July 1990 are reported. Of the 120 cases, including 97 males and 23 females ages varying from 39 to 77 years old, 40 cases were primary tumors and 80 cases were local residual or recurrent after surgery or radiotherapy or chemotherapy. All cases were confirmed in pathological biopsy, including 58 squamous cell carcinoma, 28 various adenocarcinoma, and 34 transitional cell carcinoma. Twenty-four, 48 and/or 72 hours after intravenous injection of HpD 2.0 - 3.0 mg/kg, or DHE 1.5 - 2.0 mg/kg, or Y-HpD 5.0 mg/kg, the tumor was irradiated with 630 nm wavelength of argon dye laser via a quartz light fiber inserted through the forceps channel of the endoscope. Of the 120 cases treated, CR was obtained in 38 cases, PR in 25 cases, MR in 52 cases, and NR in 5 cases. Total response rate was 95.8%; significant response rate 52.5%; and tumor eradicated rate 31.7%. The 38 cases included: 14 cases of early esophageal carcinoma, 3 cases of early cardiac carcinoma, 1 case of early lung cancer, 1 case of early gastric carcinoma, 15 cases of superficial bladder carcinoma, 3 cases of local residual recurrent micro lung cancer, and 1 case of cardiac carcinoma. The longest cancer-free survival was over eight years. Endoscopic photodynamic therapy is, therefore, curative effective in the treatment of early and superficial carcinoma, and palliative effective in the treatment of advanced carcinoma. Standardized and controlled trials are required to assess its place in combined treatment of malignant tumors.

Effect of MR Imaging Contrast Thresholds on Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes: A Subgroup Analysis of the ACRIN 6657/I-SPY 1 TRIAL

PubMed Central

Li, Wen; Arasu, Vignesh; Newitt, David C.; Jones, Ella F.; Wilmes, Lisa; Gibbs, Jessica; Kornak, John; Joe, Bonnie N.; Esserman, Laura J.; Hylton, Nola M.

2016-01-01

Functional tumor volume (FTV) measurements by dynamic contrast-enhanced magnetic resonance imaging can predict treatment outcomes for women receiving neoadjuvant chemotherapy for breast cancer. Here, we explore whether the contrast thresholds used to define FTV could be adjusted by breast cancer subtype to improve predictive performance. Absolute FTV and percent change in FTV (ΔFTV) at sequential time-points during treatment were calculated and investigated as predictors of pathologic complete response at surgery. Early percent enhancement threshold (PEt) and signal enhancement ratio threshold (SERt) were varied. The predictive performance of resulting FTV predictors was evaluated using the area under the receiver operating characteristic curve. A total number of 116 patients were studied both as a full cohort and in the following groups defined by hormone receptor (HR) and HER2 receptor subtype: 45 HR+/HER2−, 39 HER2+, and 30 triple negatives. High AUCs were found at different ranges of PEt and SERt levels in different subtypes. Findings from this study suggest that the predictive performance to treatment response by MRI varies by contrast thresholds, and that pathologic complete response prediction may be improved through subtype-specific contrast enhancement thresholds. A validation study is underway with a larger patient population. PMID:28066808

Granular cell tumor of the esophagus. Report of three cases.

PubMed

Cohle, S D; McKechnie, J C; Truong, L; Jurco, S

1981-06-01

Granular cell tumors, (formerly called myoblastomas) involving the esophagus were encountered in three patients. In all three the tumors were asymptomatic and in two they were multiple. The first published endoscopic photographs of such a tumor are presented. The successful total removal of this neoplasm using the endoscope is described. The pathologic, radiologic and therapeutic aspects of previously reported cases of granular cell tumor of the esophagus are reviewed and compared with the three reported herein.

Infectious Angiogenesis-Different Pathways, the Same Goal.

PubMed

Urbanowicz, Maria; Kutzner, Heinz; Riveiro-Falkenbach, Erica; Rodriguez-Peralto, Jose L

2016-11-01

Infectious angiogenesis is the biological response of neoangiogenesis induced by infectious organisms. The authors present 3 exemplary entities which show paradigmatic clinico-pathological settings of infectious angiogenesis: Bacillary angiomatosis, Orf (ecthyma contagiosum), and Kaposi sarcoma. The authors review the literature and elucidate etiopathogenetic pathways leading to the phenomenon of neovascularization stimulated by infectious organisms. The authors describe the clinical and histological pictures, interactions between microorganisms and host cells, and changes that occur within cellular structures, as well as angiogenic factors that underpin infectious angiogenesis. The importance of chronic inflammation and tumor angiogenesis is emphasized.

Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webster, S.S.J.

1993-04-05

The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

Cell specific radiation dosimetry in skeleton from life-span carcinogenesis studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webster, S.S.J.

1993-04-05

The osteogenic sarcoma is the dominant life-threatening pathology in lifespan studies of beagles exposed to alpha-emitting bone-seeking radionuclides. It was deduced from these studies that certain skeletal sites are more prone to develop tumors. This project sought to determine the bone cells at risk and their cell-specific radiation dose. The cell-specific radiation dose values are related to loss and high Ra-226 and Pu-239 induced osteogenic sarcoma sites, to test different dose response hypothesis and predict the extent of effects in humans.

PORTR: Pre-Operative and Post-Recurrence Brain Tumor Registration

PubMed Central

Niethammer, Marc; Akbari, Hamed; Bilello, Michel; Davatzikos, Christos; Pohl, Kilian M.

2014-01-01

We propose a new method for deformable registration of pre-operative and post-recurrence brain MR scans of glioma patients. Performing this type of intra-subject registration is challenging as tumor, resection, recurrence, and edema cause large deformations, missing correspondences, and inconsistent intensity profiles between the scans. To address this challenging task, our method, called PORTR, explicitly accounts for pathological information. It segments tumor, resection cavity, and recurrence based on models specific to each scan. PORTR then uses the resulting maps to exclude pathological regions from the image-based correspondence term while simultaneously measuring the overlap between the aligned tumor and resection cavity. Embedded into a symmetric registration framework, we determine the optimal solution by taking advantage of both discrete and continuous search methods. We apply our method to scans of 24 glioma patients. Both quantitative and qualitative analysis of the results clearly show that our method is superior to other state-of-the-art approaches. PMID:24595340

Long non-coding RNA-CRNDE: a novel regulator of tumor growth and angiogenesis in hepatoblastoma

PubMed Central

Dong, Rui; Liu, Xiang-Qi; Zhang, Bin-Bin; Liu, Bai-Hui; Zheng, Shan; Dong, Kui-Ran

2017-01-01

Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. They have emerged as key players in the pathology of several tumors, including hepatoblastoma. In this study, we elucidate the biological and clinical significance of CRNDE up-regulation in hepatoblastoma. CRNDE is significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. CRNDE knockdown reduces tumor growth and tumor angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, and angiogenic effect in vitro. Mechanistic studies show that CRNDE knockdown plays its anti-proliferation and anti-angiogenesis role via regulating mammalian target of rapamycin (mTOR) signaling. Taken together, this study reveals a crucial role of CRNDE in the pathology of hepatoblastoma. CRNDE may serve as a promising diagnostic marker and therapeutic target for hepatoblastoma. PMID:28178668

Met synergizes with p53 loss to induce mammary tumors that possess features of claudin-low breast cancer

PubMed Central

Knight, Jennifer F.; Lesurf, Robert; Zhao, Hong; Pinnaduwage, Dushanthi; Davis, Ryan R.; Saleh, Sadiq M. I.; Zuo, Dongmei; Naujokas, Monica A.; Chughtai, Naila; Herschkowitz, Jason I.; Prat, Aleix; Mulligan, Anna Marie; Muller, William J.; Cardiff, Robert D.; Gregg, Jeff P.; Andrulis, Irene L.; Hallett, Michael T.; Park, Morag

2013-01-01

Triple-negative breast cancer (TNBC) accounts for ∼20% of cases and contributes to basal and claudin-low molecular subclasses of the disease. TNBCs have poor prognosis, display frequent mutations in tumor suppressor gene p53 (TP53), and lack targeted therapies. The MET receptor tyrosine kinase is elevated in TNBC and transgenic Met models (Metmt) develop basal-like tumors. To investigate collaborating events in the genesis of TNBC, we generated Metmt mice with conditional loss of murine p53 (Trp53) in mammary epithelia. Somatic Trp53 loss, in combination with Metmt, significantly increased tumor penetrance over Metmt or Trp53 loss alone. Unlike Metmt tumors, which are histologically diverse and enriched in a basal-like molecular signature, the majority of Metmt tumors with Trp53 loss displayed a spindloid pathology with a distinct molecular signature that resembles the human claudin-low subtype of TNBC, including diminished claudins, an epithelial-to-mesenchymal transition signature, and decreased expression of the microRNA-200 family. Moreover, although mammary specific loss of Trp53 promotes tumors with diverse pathologies, those with spindloid pathology and claudin-low signature display genomic Met amplification. In both models, MET activity is required for maintenance of the claudin-low morphological phenotype, in which MET inhibitors restore cell-cell junctions, rescue claudin 1 expression, and abrogate growth and dissemination of cells in vivo. Among human breast cancers, elevated levels of MET and stabilized TP53, indicative of mutation, correlate with highly proliferative TNBCs of poor outcome. This work shows synergy between MET and TP53 loss for claudin-low breast cancer, identifies a restricted claudin-low gene signature, and provides a rationale for anti-MET therapies in TNBC. PMID:23509284

Application of Ultrasound-Guided Core Biopsy to Minimal-Invasively Diagnose Supraclavicular Fossa Tumors and Minimize the Requirement of Invasive Diagnostic Surgery

PubMed Central

Chen, Chun-Nan; Lin, Che-Yi; Chi, Fan-Hsiang; Chou, Chen-Han; Hsu, Ya-Ching; Kuo, Yen-Lin; Lin, Chih-Feng; Chen, Tseng-Cheng; Wang, Cheng-Ping; Lou, Pei-Jen; Ko, Jenq-Yuh; Hsiao, Tzu-Yu; Yang, Tsung-Lin

2016-01-01

Abstract Tumors of the supraclavicular fossa (SC) is clinically challenging because of anatomical complexity and tumor pathological diversity. Because of varied diseases entities and treatment choices of SC tumors, making the accurate decision among numerous differential diagnoses is imperative. Sampling by open biopsy (OB) remains the standard procedure for pathological confirmation. However, complicated anatomical structures of SC always render surgical intervention difficult to perform. Ultrasound-guided core biopsy (USCB) is a minimally invasive and office-based procedure for tissue sampling widely applied in many diseases of head and neck. This study aims to evaluate the clinical efficacy and utility of using USCB as the sampling method of SC tumors. From 2009 to 2014, consecutive patients who presented clinical symptoms and signs of supraclavicular tumors and were scheduled to receive sampling procedures for diagnostic confirmation were recruited. The patients received USCB or OB respectively in the initial tissue sampling. The accurate diagnostic rate based on pathological results was 90.2% for USCB, and 93.6% for OB. No significant difference was noted between USCB and OB groups in terms of diagnostic accuracy and the percentage of inadequate specimens. All cases in the USCB group had the sampling procedure completed within 10 minutes, but not in the OB group. No scars larger than 1 cm were found in USCB. Only patients in the OB groups had the need to receive general anesthesia and hospitalization and had scars postoperatively. Accordingly, USCB can serve as the first-line sampling tool for SC tumors with high diagnostic accuracy, minimal invasiveness, and low medical cost. PMID:26825877

Diffusion-Weighted PROPELLER MRI for Quantitative Assessment of Liver Tumor Necrotic Fraction and Viable Tumor Volume in VX2 Rabbits

PubMed Central

Deng, Jie; Virmani, Sumeet; Young, Joseph; Harris, Kathleen; Yang, Guang-Yu; Rademaker, Alfred; Woloschak, Gayle; Omary, Reed A.; Larson, Andrew C.

2010-01-01

Purpose To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) MRI provides more accurate liver tumor necrotic fraction (NF) and viable tumor volume (VTV) measurements than conventional DW-SE-EPI (spin echo echo-planar imaging) methods. Materials and Methods Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 10 VX2 liver tumors, DW-PROPELLER and DW-SE-EPI scans were performed at contiguous axial slice positions covering each tumor volume. Apparent diffusion coefficient maps of each tumor were used to generate spatially resolved tumor viability maps for NF and VTV measurements. We compared NF, whole tumor volume (WTV), and VTV measurements to corresponding reference standard histological measurements based on correlation and concordance coefficients and the Bland–Altman analysis. Results DW-PROPELLER generally improved image quality with less distortion compared to DW-SE-EPI. DW-PROPELLER NF, WTV, and VTV measurements were strongly correlated and satisfactorily concordant with histological measurements. DW-SE-EPI NF measurements were weakly correlated and poorly concordant with histological measurements. Bland–Altman analysis demonstrated that DWPROPELLER WTV and VTV measurements were less biased from histological measurements than the corresponding DW-SE-EPI measurements. Conclusion DW-PROPELLER MRI can provide spatially resolved liver tumor viability maps for accurate NF and VTV measurements, superior to DW-SE-EPI approaches. DWPROPELLER measurements may serve as a noninvasive surrogate for pathology, offering the potential for more accurate assessments of therapy response than conventional anatomic size measurements. PMID:18407540

Tumors of the brain and nervous system after radiotherapy in childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ron, E.; Modan, B.; Boice, J.D. Jr.

1988-10-20

We investigated the relation between radiotherapy in childhood for tinea capitis and the later development of tumors of the brain and nervous system among 10,834 patients treated between 1948 and 1960 in Israel. Benign and malignant tumors were identified from the pathology records of all Israeli hospitals and from Israeli national cancer and death registries. Doses of radiation to the neural tissue were retrospectively estimated for each patient (mean, 1.5 Gy). Sixty neural tumors developed in the patients exposed as children, and the 30-year cumulative risk (+/- SE) was 0.8 +/- 0.2 percent. The incidence of tumors was 1.8 permore » 10,000 persons per year. The estimated relative risk as compared with that for 10,834 matched general-population controls and 5392 siblings who had not been irradiated was 6.9 (95 percent confidence interval, 4.1 to 11.6) for all tumors and 8.4 (confidence interval, 4.8 to 14.8) when the analysis was restricted to neural tumors of the head and neck. Increased risks were apparent for meningiomas (relative risk, 9.5; n = 19), gliomas (relative risk, 2.6; n = 7), nerve-sheath tumors (relative risk, 18.8; n = 25), and other neural tumors (relative risk, 3.4; n = 9). A strong dose--response relation was found, with the relative risk approaching 20 after estimated doses of approximately 2.5 Gy. Our study confirms that radiation doses on the order of 1 to 2 Gy can significantly increase the risk of neural tumors.« less

Computational pathology: Exploring the spatial dimension of tumor ecology.

PubMed

Nawaz, Sidra; Yuan, Yinyin

2016-09-28

Tumors are evolving ecosystems where cancer subclones and the microenvironment interact. This is analogous to interaction dynamics between species in their natural habitats, which is a prime area of study in ecology. Spatial statistics are frequently used in ecological studies to infer complex relations including predator-prey, resource dependency and co-evolution. Recently, the emerging field of computational pathology has enabled high-throughput spatial analysis by using image processing to identify different cell types and their locations within histological tumor samples. We discuss how these data may be analyzed with spatial statistics used in ecology to reveal patterns and advance our understanding of ecological interactions occurring among cancer cells and their microenvironment. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Pathology of orbital bones. The XXXII Edward Jackson Memorial Lecture.

PubMed

Blodi, F C

1976-01-01

The orbital bones may show nearly all the pathologic changes observed in the skull and in the face. The congenital anomalies in this area are numerous and involve various forms of craniostenoses. Among the benign osseous tumors the osteoma is most frequently encountered in the orbit. Fibrous dysplasia is a tumefaction of indeterminate behavior that often involves the orbit. Osteosarcoma or other malignant neoplasms are rarely seen in this area. Eosinophilic granuloma and Hand-Schüller-Christian disease are tumor-like lesions that may involve the orbit.

Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steel, Jason C.; Morrison, Brian J.; Mannan, Poonam

Oncolytic adenoviruses as a treatment for cancer have demonstrated limited clinical activity. Contributing to this may be the relevance of preclinical animal models used to study these agents. Syngeneic mouse tumor models are generally non-permissive for adenoviral replication, whereas human tumor xenograft models exhibit attenuated immune responses to the vector. The cotton rat (Sigmodon hispidus) is susceptible to human adenovirus infection, permissive for viral replication and exhibits similar inflammatory pathology to humans with adenovirus replicating in the lungs, respiratory passages and cornea. We evaluated three transplantable tumorigenic cotton rat cell lines, CCRT, LCRT and VCRT as models for the studymore » of oncolytic adenoviruses. All three cells lines were readily infected with adenovirus type-5-based vectors and exhibited high levels of transgene expression. The cell lines supported viral replication demonstrated by the induction of cytopathogenic effect (CPE) in tissue culture, increase in virus particle numbers and assembly of virions seen on transmission electron microscopy. In vivo, LCRT and VCRT tumors demonstrated delayed growth after injection with replicating adenovirus. No in vivo antitumor activity was seen in CCRT tumors despite in vitro oncolysis. Adenovirus was also rapidly cleared from the CCRT tumors compared to LCRT and VCRT tumors. The effect observed with the different cotton rat tumor cell lines mimics the variable results of human clinical trials highlighting the potential relevance of this model for assessing the activity and toxicity of oncolytic adenoviruses.« less

[Role and responsibility of multimodal imaging in head and neck cancer].

PubMed

Gõdény, Mária

2013-09-01

Hungary is first in head and neck cancer mortality in Europe in men and also in women. Head and neck (HN) is a difficult region, its anatomy and also pathology is very complex, various connection points exist between the sites which determine the extension of the disease. Diagnostic algorithms as well as imaging techniques have to be optimized to examine in standard manner. Like most other cancers, prognosis depends largely on the stage of the tumor. Accuracy of tumor detection and evaluation is very important because it affects treatment planning. As non-surgical organ-preserving therapeutic modalities (chemotherapy, chemoradiotherapy, targeted biological therapy) gain general acceptance, the importance of noninvasive diagnostic accuracy as well as radiologic evaluation of the extent of the tumor has increased. Clinical examinations including endoscopy should be combined with radiologic imaging to assess the precise local (T), regional nodal (N), and distant (M) extent of the tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) have become basic tools in the diagnosis of head and neck tumors. They are both useful for assessing deep tumor extensions, able to detect changes missed by endoscopy. It has been shown that the primary determined tumor stage increases in up to 90% of patients after the results of cross sectional imaging. MRI is being increasingly used and has become the gold standard in head and neck cancer for staging, assessing tumor response, finding recurrent tumor and also for treatment planning in radiotherapy. The field strength of MRI scanners has been increasing to 1.5 T and now 3 T with better signal-to-noise ratio, higher resolution images and better tissue diagnosis. Functional MR techniques such as dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted MRI (DW-MRI) may provide further characterization. PET/CT is beneficial in detecting unsuspected metastatic nodes, distant disease and second primary tumor. PET/CT and MRI both appeared almost similarly accurate in the detection of an occult primary tumor. The effective management of patients depends highly on the competece of radiologists and requires close collaboration between clinical and surgical oncologists, diagnostic and therapeutic radiologists as well as pathologists.

Effects of stress on immune function: the good, the bad, and the beautiful.

PubMed

Dhabhar, Firdaus S

2014-05-01

Although the concept of stress has earned a bad reputation, it is important to recognize that the adaptive purpose of a physiological stress response is to promote survival during fight or flight. While long-term stress is generally harmful, short-term stress can be protective as it prepares the organism to deal with challenges. This review discusses the immune effects of biological stress responses that can be induced by psychological, physiological, or physical (including exercise) stressors. We have proposed that short-term stress is one of the nature's fundamental but under-appreciated survival mechanisms that could be clinically harnessed to enhance immunoprotection. Short-term (i.e., lasting for minutes to hours) stress experienced during immune activation enhances innate/primary and adaptive/secondary immune responses. Mechanisms of immuno-enhancement include changes in dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and function as well as local and systemic production of cytokines. In contrast, long-term stress suppresses or dysregulates innate and adaptive immune responses by altering the Type 1-Type 2 cytokine balance, inducing low-grade chronic inflammation, and suppressing numbers, trafficking, and function of immunoprotective cells. Chronic stress may also increase susceptibility to some types of cancer by suppressing Type 1 cytokines and protective T cells and increasing regulatory/suppressor T cell function. Here, we classify immune responses as being protective, pathological, or regulatory, and discuss "good" versus "bad" effects of stress on health. Thus, short-term stress can enhance the acquisition and/or expression of immunoprotective (wound healing, vaccination, anti-infectious agent, anti-tumor) or immuno-pathological (pro-inflammatory, autoimmune) responses. In contrast, chronic stress can suppress protective immune responses and/or exacerbate pathological immune responses. Studies such as the ones discussed here could provide mechanistic targets and conceptual frameworks for pharmacological and/or biobehavioral interventions designed to enhance the effects of "good" stress, minimize the effects of "bad" stress, and maximally promote health and healing.

Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.

PubMed

Markkula, Andrea; Simonsson, Maria; Rosendahl, Ann H; Gaber, Alexander; Ingvar, Christian; Rose, Carsten; Jernström, Helena

2014-10-15

The COX2 rs5277 (306G>C) polymorphism has been associated with inflammation-associated cancers. In breast cancer, tumor COX-2 expression has been associated with increased estrogen levels in estrogen receptor (ER)-positive and activated Akt-pathway in ER-negative tumors. Our study investigated the impact of COX2 genotypes on early breast cancer events and treatment response in relation to tumor ER status and body constitution. In Sweden, between 2002 and 2008, 634 primary breast cancer patients, aged 25-99 years, were included. Disease-free survival was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained preoperatively. Clinical data, patient- and tumor-characteristics were obtained from questionnaires, patients' charts, population registries and pathology reports. Minor allele(C) frequency was 16.1%. Genotype was not linked to COX-2 tumor expression. Median follow-up was 5.1 years. G/G genotype was not associated with early events in patients with ER-positive tumors, adjusted HR 0.77 (0.46-1.29), but conferred an over 4-fold increased risk in patients with ER-negative tumors, adjusted HR 4.41 (1.21-16.02)(p(interaction) = 0.015). Chemotherapy-treated G/G-carriers with a breast volume ≥ 850 ml had an increased risk of early events irrespective of ER status, adjusted HR 8.99 (1.14-70.89). Endocrine-treated C-allele carriers with ER-positive tumors and a breast volume ≥ 850 ml had increased risk of early events, adjusted HR 2.30 (1.12-4.75). COX2 genotype, body constitution and ER status had a combined effect on the risk of early events and treatment response. The high risk for early events in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may identify patients in need of more personalized treatment. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Supradiaphragmatic ectopic liver: delayed traumatic hepatic hernia mimics pulmonary tumor.

PubMed

Huang, C-S; Hsu, W-H; Hsia, C-Y

2007-06-01

We present a rare case of a 63-year-old woman, the oldest one in the literature, with supradiaphragmatic ectopic liver that mimics a pulmonary nodule. The chest roentgenogram and chest computer tomography showed a lobulated tumor nearby the diaphragm. Pathological examination of the resected tumor disclosed only remarkable fatty liver change. Ectopic liver should be kept in mind to differentiate for the pulmonary tumor nearby the diaphragm.

Value of percutaneous needle biopsy of small renal tumors in patients referred for cryoablation.

PubMed

Iguchi, Toshihiro; Hiraki, Takao; Gobara, Hideo; Fujiwara, Hiroyasu; Sakurai, Jun; Matsui, Yusuke; Araki, Motoo; Nasu, Yasutomo; Kanazawa, Susumu

2017-04-01

To retrospectively evaluate the safety and diagnostic yield of needle biopsy of small renal tumors, and the clinical consequences of performing needle biopsy in patients referred for percutaneous cryoablation before their treatment. Biopsy was performed for 120 tumors (mean diameter, 2.2 cm) in 119 patients. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the two groups. All cryoablation procedures were divided into two groups: procedures with or without simultaneous biopsy. The rates of benign or non-diagnostic tumors in each group were compared. After performing 120 initial and eight repeat biopsies, Grade 1 bleedings occurred in 44 cases. Six tumors were non-diagnostic and 114 were pathologically diagnosed. There were no significant variables between the diagnostic and non-diagnostic biopsies. Unnecessary cryoablation was avoided in nine benign lesions by performing biopsy in advance. Cryoablation performed simultaneously with biopsy included significantly more benign or non-diagnostic tumors than cryoablation performed after biopsy (15.2% vs. 1.4%; p = .01). Percutaneous biopsy of small renal tumors referred for cryoablation was a safe procedure with high diagnostic yield. The confirmation of pathological diagnosis prior to cryoablation is necessary because patients with benign tumors can avoid unnecessary treatment.

Re-evaluating the concept of "dominant/index tumor nodule" in multifocal prostate cancer.

PubMed

Huang, Cheng Cheng; Deng, Fang-Ming; Kong, Max X; Ren, Qinhu; Melamed, Jonathan; Zhou, Ming

2014-05-01

Prostate cancer (PCa) often presents as a multifocal disease with heterogeneity in Gleason score (GS) and genetic alterations. Dominant/index tumor nodule (DN), the largest nodule in a multifocal disease, is presumed to harbor the most aggressive biological behavior and therefore dictate the overall clinical behavior of PCa. In this study, we examined the pathological features of DN and re-evaluated the validity of the "DN" concept in multifocal PCa. A total of 201 consecutive radical prostatectomy specimens were totally submitted and examined. All independent cancer foci were recorded with prognostically important pathological parameters. Unifocal and multifocal disease was present in 25 (12.4 %) and 176 (87.6 %) cases, respectively. In 20 (11.3 %) multifocal cases, the highest GS, the largest tumor volume (TV), and extraprostatic extension (EPE) did not concur in the same tumor nodules. Non-DNs had a higher GS and EPE in 13 cases each and had both the highest GS and EPE in 5 cases. In the majority of multifocal prostate cancer (88.7 %), DNs have the highest GS and EPE. In these cases, DN is still a valid concept and can be used for assigning overall GS and procuring tissue for research. However, in a significant number of cases (11.3 %), the largest TV, the highest GS, and EPE did not concur in the same tumor nodules. In these cases, pathologists should de-emphasize the concept of DN. Instead, they should place the emphasis on the multifocal nature of the disease and document the pathological features of all independent tumor foci that have the largest TV, the highest GS, and EPE.

The prognostic values of tumor-infiltrating neutrophils, lymphocytes and neutrophil/lymphocyte rates in bladder urothelial cancer.

PubMed

Liu, Kangkang; Zhao, Kun; Wang, Lining; Sun, Erlin

2018-05-20

Tumor-infiltrating neutrophils (TINs) and lymphocytes (TILs) are found to play essential roles in many tumors and associate with the prognosis of patients. But, the prognostic values of TINs, TILs and NLR (neutrophils-lymphocytes ratio) in bladder cancer (BC) are still undefined. The object of our study was to systematically interrogate the associations of these immune cells with clinical outcomes of BC patients. In our study, a total of 102 patients pathologically diagnosed with BC were included. CD66b + and CD8 + antibodies were used to mark neutrophils and CD8 + lymphocytes by immunohistochemistry. The results found that TINs and NLR were significantly associated with pathological T-stages of tumors (P < 0.01), but TILs were not. And TINs were also related to pathological tumor grades (P = 0.012). Regarding the prognostic values, TINs was related to the high risk of recurrence in non-muscle invasive BC (NMIBC) patients. Elevated TINs and NLR were associated with poor overall survivals of BC patients, whereas higher TILs were related to longer survivals (P < 0.01). Multivariate analysis showed that both of TINs (HR 2.427, 1.024-5.752, P = 0.044) and NLR (HR 3.529, 1.147-10.864, P = 0.028) were independent unfavorable prognosis markers. In conclusion, Tumor infiltrating immune cells, including TINs, TILs and NLR were important markers in predicting the prognosis of bladder cancer patients. TINs and NLR were more likely to be negative predictors, but TILs were favorable in patients with BC. Copyright © 2018 Elsevier GmbH. All rights reserved.

Recurrence in Uterine Tumors with Ovarian Sex-Cord Tumor Resemblance: A Case Report and Systematic Review.

PubMed

Cömert, Günsu Kimyon; Kiliç, Çiğdem; Çavuşoğlu, Deniz; Türkmen, Osman; Karalok, Alper; Turan, Taner; Başaran, Derman; Boran, Nurettin

2018-05-10

The aim of this study was to evaluate the prognostic factors of recurrence in uterine tumors resembling ovarian sex-cord tumors (UTROSCT) and to determine clinical-pathological characteristics, treatment options and outcome. An electronic literature search was conducted from 1976 to 2018. After the comprehensive evaluation and conjunction with our case, the study included 79 cases. The median age at initial diagnosis was 49 years (range; 16-86 years). The age was under 40 years in 21 (26.6%) patients. Whereas 68 patients underwent at least hysterectomy, 9 patients had organ sparing surgery. There was necrosis in 4 (5.1%) patients, atypia in 16 (20.3%) patients, and infiltrative tumor border in 34 (43%) patients. At least one mitosis per 10 high power fields was determined in 36 (45.5%) patients. The tumor involved at least part of the myometrium in 54 (68.3%) patients. Median follow-up time was 30 months (range; 3-296 months). Recurrence was determined in 5 (6.3%) patients. The disease free survival (DFS) was significantly related only to surgery type. None of the pathologic features were associated with DFS. The 5-year DFS was 86% and 96% in patients who underwent organ sparing surgery or not, respectively (p=0.038). The accurate pathologic diagnosis of UTROSCT has great value in shaping surgical management and management during the follow-up period. Organ sparing surgery was related to poor DFS. Although recurrence is rare, it should be kept in mind for patients with UTROSCT.

Pyogenic granuloma associated with periodontal abscess and bone loss - A rare case report

PubMed Central

Panseriya, Bhrugesh J.; Hungund, Shital

2011-01-01

A diverse group of the pathologic process can produce the enlargement of soft tissues in the oral cavity and often present a diagnostic challenge. This soft tissue enlargement may represent a variation of the normal anatomic structure, inflammatory reaction, cyst, neoplasm, and developmental anomalies. A group of reactive hyperplasias, which develop in response to chronic recurring tissue injury that stimulates an excessive tissue repair response. The pyogenic granuloma (PG) is a reactive enlargement that is an inflammatory response to local irritation such as calculus, a fractured tooth, rough dental restoration, and foreign materials or hormonal (pregnancy tumor) and rarely associated with bone loss. This paper presents a rare case of PG associated with periodontal abscess and bone loss in a 30-year-old male. PMID:22090773

Pyogenic granuloma associated with periodontal abscess and bone loss - A rare case report.

PubMed

Panseriya, Bhrugesh J; Hungund, Shital

2011-07-01

A diverse group of the pathologic process can produce the enlargement of soft tissues in the oral cavity and often present a diagnostic challenge. This soft tissue enlargement may represent a variation of the normal anatomic structure, inflammatory reaction, cyst, neoplasm, and developmental anomalies. A group of reactive hyperplasias, which develop in response to chronic recurring tissue injury that stimulates an excessive tissue repair response. The pyogenic granuloma (PG) is a reactive enlargement that is an inflammatory response to local irritation such as calculus, a fractured tooth, rough dental restoration, and foreign materials or hormonal (pregnancy tumor) and rarely associated with bone loss. This paper presents a rare case of PG associated with periodontal abscess and bone loss in a 30-year-old male.

[Benign tumors and pseudotumors of temporo-mandibular joint: radiologic aspects].

PubMed

Izzo, L; Caputo, M; Buffone, A; Casullo, A; Perrone, A; Sassi, S; Impara, L; Luppi, G; Mazza, D; Marini, Marina

2005-01-01

Benign tumors and tumor-like lesions that involve temporo mandibular joint are very rare. Those more frequent are osteochondroma, chondroma, osteoma, pigmented villonodular synovitis and synovial chondromatosis. The Authors report six cases of patients affected by these pathologies in which imaging, such as TC, MRI and/or ortopantomography have been useful to have a diagnosis.