Clinicopathological outcomes of preoperative chemoradiotherapy using S-1 plus Irinotecan for T4 lower rectal cancer.

PubMed

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

2016-07-01

To investigate the clinicopathological outcomes of patients with T4 lower rectal cancer treated using preoperative chemoradiotherapy with S-1 plus Irinotecan. Between 2005 and 2011, 35 patients with T4M0 lower rectal cancer, diagnosed initially as T4a in 12 and as T4b in 23, were treated with 45 Gy of radiotherapy concomitantly with S-1 plus Irinotecan. The median follow-up period was 50.6 months (range 2-123 months). A total of 32 patients (91.4 %) completed the radiotherapy and 26 (74.3 %) completed the full chemotherapy regimen. Radical surgery was then performed in 33 (94.3 %) of the 35 patients after the exclusion of two patients, who had macroscopic residual disease. The pathological diagnosis was downstaged from T4a to ypT0-3 in all 12 of those patients (100 %) and from T4b to ypT0-4a in 20 of those 23 patients (87.0 %). The tumor regression grade of 1a/1b/2/3 (complete response) was 10/8/15/2, respectively. In terms of long-term survival, the 5-year local relapse-free survival rate was 74.8 % and the recurrence-free survival rate was 52.0 %. This regimen may result in favorable downstaging. Moreover, in this series, pathological evidence of involvement of adjacent organs was rare following preoperative chemoradiotherapy, in the patients with disease diagnosed as T4b at the initial staging.

Comparison of non-Gaussian and Gaussian diffusion models of diffusion weighted imaging of rectal cancer at 3.0 T MRI.

PubMed

Zhang, Guangwen; Wang, Shuangshuang; Wen, Didi; Zhang, Jing; Wei, Xiaocheng; Ma, Wanling; Zhao, Weiwei; Wang, Mian; Wu, Guosheng; Zhang, Jinsong

2016-12-09

Water molecular diffusion in vivo tissue is much more complicated. We aimed to compare non-Gaussian diffusion models of diffusion-weighted imaging (DWI) including intra-voxel incoherent motion (IVIM), stretched-exponential model (SEM) and Gaussian diffusion model at 3.0 T MRI in patients with rectal cancer, and to determine the optimal model for investigating the water diffusion properties and characterization of rectal carcinoma. Fifty-nine consecutive patients with pathologically confirmed rectal adenocarcinoma underwent DWI with 16 b-values at a 3.0 T MRI system. DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models (IVIM-mono, IVIM-bi and SEM) on primary tumor and adjacent normal rectal tissue. Parameters of standard apparent diffusion coefficient (ADC), slow- and fast-ADC, fraction of fast ADC (f), α value and distributed diffusion coefficient (DDC) were generated and compared between the tumor and normal tissues. The SEM exhibited the best fitting results of actual DWI signal in rectal cancer and the normal rectal wall (R 2  = 0.998, 0.999 respectively). The DDC achieved relatively high area under the curve (AUC = 0.980) in differentiating tumor from normal rectal wall. Non-Gaussian diffusion models could assess tissue properties more accurately than the ADC derived Gaussian diffusion model. SEM may be used as a potential optimal model for characterization of rectal cancer.

Utility approach to decision-making in extended T1 and limited T2 glottic carcinoma.

PubMed

van Loon, Yda; Stiggelbout, Anne M; Hakkesteegt, Marieke M; Langeveld, Ton P M; de Jong, Rob J Baatenburg; Sjögren, Elisabeth V

2017-04-01

It is still undecided if endoscopic laser surgery or radiotherapy is the preferable treatment in extended T1 and limited T2 glottic tumors. Health utilities assessed from patients can aid in decision-making. Patients treated for extended T1 or limited T2 glottic carcinoma by laser surgery (n = 12) or radiotherapy (n = 14) assigned health utilities using a visual analog scale (VAS), time tradeoff (TTO) technique and scored their voice handicap using the Voice Handicap Index (VHI). VAS and TTO scores were slightly lower for the laser group compared to the radiotherapy group, however, not significantly so. The VHI showed a correlation with the VAS score, which was very low in both groups and can be considered (near) normal. Patients show no clear preference for the outcomes of laser surgery or radiotherapy from a quality of life (QOL) or voice handicap point of view. These data can now be incorporated into decision-making models. © 2017 Wiley Periodicals, Inc. Head Neck, 2017 © 2016 Wiley Periodicals, Inc. Head Neck 39: 779-785, 2017. © 2017 Wiley Periodicals, Inc.

Fusobacterium nucleatum and T Cells in Colorectal Carcinoma.

PubMed

Mima, Kosuke; Sukawa, Yasutaka; Nishihara, Reiko; Qian, Zhi Rong; Yamauchi, Mai; Inamura, Kentaro; Kim, Sun A; Masuda, Atsuhiro; Nowak, Jonathan A; Nosho, Katsuhiko; Kostic, Aleksandar D; Giannakis, Marios; Watanabe, Hideo; Bullman, Susan; Milner, Danny A; Harris, Curtis C; Giovannucci, Edward; Garraway, Levi A; Freeman, Gordon J; Dranoff, Glenn; Chan, Andrew T; Garrett, Wendy S; Huttenhower, Curtis; Fuchs, Charles S; Ogino, Shuji

2015-08-01

Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by downregulating antitumor T cell-mediated adaptive immunity. To test the hypothesis that a greater amount of F nucleatum in colorectal carcinoma tissue is associated with a lower density of T cells in tumor tissue. A cross-sectional analysis was conducted on 598 rectal and colon carcinoma cases in 2 US nationwide prospective cohort studies with follow-up through 2006, the Nurses' Health Study (participants enrolled in 1976) and the Health Professionals Follow-up Study (participants enrolled in 1986). Tissue collection and processing were performed from 2002 through 2008, and immunity assessment, 2008 through 2009. From 2013 through 2014, the amount of F nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high vs low). Multivariable ordinal logistic regression analysis was conducted in 2014 to assess associations of the amount of F nucleatum with densities (quartiles) of T cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted the 2-sided α level to .013 for multiple hypothesis testing. Densities of CD3+, CD8+, CD45RO (protein tyrosine phosphatase receptor type C [PTPRC])+, and FOXP3+ T cells in tumor tissue, determined by means of tissue microarray immunohistochemical analysis and computer-assisted image analysis. F nucleatum was detected in colorectal carcinoma

Rectal Carcinoma Model: A Novel Simulation in Pathology Training.

PubMed

Pongpaibul, Ananya; Chiravirakul, Prattana; Leksrisakul, Piyawadee; Silakorn, Phadungsak; Chumtap, Wangcha; Chongpipatchaipron, Somchai; Jaitrong, Peerasak; Jitvichai, Ekachai

2017-06-01

Until now, the apprenticeship training model is used to train pathology residents. Pathology residents are trained using patient specimens that are received during the course of normal daily pathology service. However, this training method could result in inconsistency in knowledge and experience among trainees because of variation in specimens that are received for analysis. The use of simulated specimens in pathology residency training could help ensure that all pathology residents receive consistent knowledge and experience. The aim of this study was to develop prototype rectal carcinoma model to be used as a simulation tool and to evaluate its effectiveness in pathology training. Five units of a prototype rectal carcinoma model were produced in latex rubber. The model was used as a simulation tool for training in 12 pathology residents and 7 pathologist assistants. Pretesting and posttesting of each participant was conducted by multiple choice question test. A questionnaire was also given to study participants to elicit their views regarding the fidelity of the model and the model's efficacy and usefulness relative to the gross examination technique. Among the 19 participants, the mean pretest score was 79.24% and the mean posttest score was 88.54% (P = 0.045). The fidelity of the model was rated as moderate to marked by all participants. Most participants (94.74%) rated the models efficacy and usefulness relative to the gross examination technique as being moderate to marked. The rectal carcinoma model introduced in this study was found to be an effective simulation tool for pathology training. The model had good fidelity on appearance and good efficacy as well as usefulness relative to the gross examination technique.

Does perineural invasion of the myenteric plexus have a key role in annular rectal invasion and digestive system symptoms of prostate carcinoma patients?

PubMed

Hashimoto, Hirotsugu; Kurata, Atsushi; Nashiro, Tamaki; Kuroda, Masahiko; Horiuchi, Hajime

2015-12-01

Prostate carcinoma is one of the most common cancers globally. It relatively rarely invades the rectum, accounting for only about 4% of resected cases. About half of these cases of rectal invasion show an annular rectal stricture pattern. It has been hypothesized that anatomical structures, namely Denonvilliers fascia, may play an important role in annular rectal involvement of prostate carcinoma. Here, we propose another hypothesis: the reason for annular rectal invasion by prostate carcinoma is its extension along the myenteric plexus (Auerbach's plexus). We illustrate this using a case presentation and description of the symptoms of such cases. From a review of the literature, autonomic digestive system symptoms of rectal invasion of prostatic carcinoma, such as diarrhea, tenesmus, or fecal incontinence is seen in about half of cases, coinciding with the frequency of annular rectal invasion. Thus, by modifying the long-established hypothesis, our suggestion that prostate carcinoma spreads along the myenteric plexus when cancer cells invade beyond the Denonvilliers fascia to the rectum could explain the cause and frequency not only of the annular rectal invasion but also the digestive system symptoms related to this disease. The prognosis of prostate carcinoma invading the rectum is very poor; however, this new hypothesis might shed light on the digestive system symptoms associated with prostate carcinoma and might lead to recognition and treatment of these cases at a relatively early stage of rectal invasion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Basaloid large cell lung carcinoma presenting as cutaneous metastasis at the colostomy site after abdominoperineal resection for rectal carcinoma.

PubMed

Sabater-Marco, Vicente; García-García, José Angel; Roig-Vila, José Vicente

2013-08-01

The occurrence of a tumor at the colostomy site after abdominoperineal resection for rectal carcinoma is rare and it may be related to a previously resected carcinoma or another primary tumor. We report a 61-year-old man who developed an ulcerated skin nodule at her colostomy site 6 years after resection of a rectal adenocarcinoma. Histopathologically, the skin nodule was composed of atypical large and pleomorphic cells with high mitotic rate and they were arranged in nests and within lymphatic channels in the dermis. The neoplastic cells were immunoreactive for cytokeratin (CK) AE1/3, CK7, CK34ßE12, epithelial membrane antigen and vimentin while detection of human papillomavirus and Epstein-Barr virus DNA was negative. A diagnosis of basaloid large cell carcinoma of pulmonary origin was suggested and it was confirmed by computed tomography-guided fine needle aspiration of a right subpleural mass. A metastatic tumor at the colostomy site is an exceptional finding and may be the first manifestation of lung cancer, especially if it consist of pleomorphic large cells with high mitotic rate and basaloid immunophenotype. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aneuploidy-dependent massive deregulation of the cellular transcriptome and apparent divergence of the Wnt/beta-catenin signaling pathway in human rectal carcinomas.

PubMed

Grade, Marian; Ghadimi, B Michael; Varma, Sudhir; Simon, Richard; Wangsa, Danny; Barenboim-Stapleton, Linda; Liersch, Torsten; Becker, Heinz; Ried, Thomas; Difilippantonio, Michael J

2006-01-01

To identify genetic alterations underlying rectal carcinogenesis, we used global gene expression profiling of a series of 17 locally advanced rectal adenocarcinomas and 20 normal rectal mucosa biopsies on oligonucleotide arrays. A total of 351 genes were differentially expressed (P < 1.0e-7) between normal rectal mucosa and rectal carcinomas, 77 genes had a >5-fold difference, and 85 genes always had at least a 2-fold change in all of the matched samples. Twelve genes satisfied all three of these criteria. Altered expression of genes such as PTGS2 (COX-2), WNT1, TGFB1, VEGF, and MYC was confirmed, whereas our data for other genes, like PPARD and LEF1, were inconsistent with previous reports. In addition, we found deregulated expression of many genes whose involvement in rectal carcinogenesis has not been reported. By mapping the genomic imbalances in the tumors using comparative genomic hybridization, we could show that DNA copy number gains of recurrently aneuploid chromosome arms 7p, 8q, 13q, 18q, 20p, and 20q correlated significantly with their average chromosome arm expression profile. Taken together, our results show that both the high-level, significant transcriptional deregulation of specific genes and general modification of the average transcriptional activity of genes residing on aneuploid chromosomes coexist in rectal adenocarcinomas.

Aneuploidy-Dependent Massive Deregulation of the Cellular Transcriptome and Apparent Divergence of the Wnt/β-catenin Signaling Pathway in Human Rectal Carcinomas

PubMed Central

Grade, Marian; Ghadimi, B. Michael; Varma, Sudhir; Simon, Richard; Wangsa, Danny; Barenboim-Stapleton, Linda; Liersch, Torsten; Becker, Heinz; Ried, Thomas; Difilippantonio, Michael J.

2016-01-01

To identify genetic alterations underlying rectal carcinogenesis, we used global gene expression profiling of a series of 17 locally advanced rectal adenocarcinomas and 20 normal rectal mucosa biopsies on oligonucleotide arrays. A total of 351 genes were differentially expressed (P < 1.0e–7) between normal rectal mucosa and rectal carcinomas, 77 genes had a >5-fold difference, and 85 genes always had at least a 2-fold change in all of the matched samples. Twelve genes satisfied all three of these criteria. Altered expression of genes such as PTGS2 (COX-2), WNT1, TGFB1, VEGF, and MYC was confirmed, whereas our data for other genes, like PPARD and LEF1, were inconsistent with previous reports. In addition, we found deregulated expression of many genes whose involvement in rectal carcinogenesis has not been reported. By mapping the genomic imbalances in the tumors using comparative genomic hybridization, we could show that DNA copy number gains of recurrently aneuploid chromosome arms 7p, 8q, 13q, 18q, 20p, and 20q correlated significantly with their average chromosome arm expression profile. Taken together, our results show that both the high-level, significant transcriptional deregulation of specific genes and general modification of the average transcriptional activity of genes residing on aneuploid chromosomes coexist in rectal adenocarcinomas. PMID:16397240

A 1.5 T transverse magnetic field in radiotherapy of rectal cancer: Impact on the dose distribution

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

Uilkema, Sander, E-mail: s.uilkema@nki.nl; Heide, Uulke van der; Sonke, Jan-Jakob

2015-12-15

Purpose: MRI guidance during radiotherapy has the potential to enable more accurate dose delivery, optimizing the balance between local control and treatment related toxicity. However, the presence of a permanent magnetic field influences the dose delivery, especially around air cavities. Here, electrons are able to return to the surface through which they entered the air cavity (electron return effect, ERE) locally resulting in dose hot- and cold-spots. Where RT of rectal cancer patients might benefit from MRI guidance for margin reduction, air cavities in and around the target volume are frequently present. The purpose of this research is to evaluatemore » the impact of the presence of a 1.5 T transverse magnetic field on dose delivery in patients with rectal cancer. Methods: Ten patients treated with 5 × 5 Gy RT having large changes in pelvic air content were selected out of a cohort of 33 patients. On the planning CT, a 1.5 T, 6 MV, 7-field intensity modulated radiotherapy (IMRT) plan was created. This plan was subsequently recalculated on daily CT scans. For each daily CT, the CTV V{sub 95%} and V{sub 107%} and bowel area V{sub 5Gy}, V{sub 10Gy}, V{sub 15Gy}, V{sub 20Gy}, and V{sub 25Gy} were calculated to evaluate the changes in dose distribution from fraction to fraction. For comparison, the authors repeated this procedure for the 0 T situation. To study the effect of changing air cavities separate from other anatomical changes, the authors also generated artificial air cavities in the CTV of one patient (2 and 5 cm diameter), in the high dose gradient region (2 cm), and in the low dose area (2 cm). Treatment plans were optimized without and with each simulated air cavity. For appearing and disappearing air cavities, the CTV V{sub 95%} and V{sub 107%} were evaluated. The authors also evaluated the ERE separate from attenuation changes locally around appearing gas pockets. Results: For the ten patients, at 1.5 T, the V{sub 95%} was influenced by both

Rectal cancer confined to the bowel wall: the role of 3 Tesla phased-array MR imaging in T categorization.

PubMed

Çolakoğlu Er, Hale; Peker, Elif; Erden, Ayşe; Erden, İlhan; Geçim, Ethem; Savaş, Berna

2018-02-01

To determine the diagnostic value of 3 Tesla MR imaging in detection of mucosal (Tis), submucosal (T 1 ) and muscularis propria (T 2 ) invasion in patients with early rectal cancer. A total of 50 consecutive patients who underwent 3 Tesla MR imaging and curative-intent intervention for MRI-staged Tis/T 1 /T 2 rectal cancer from March 2012 to December 2016 were included. The radiological T category of each rectal tumour was compared retrospectively with histopathological results assessed according to the tumor, node, metastasis (TNM) classification. The sensitivities, specificities, and overall accuracy rates of 3 Tesla MR imaging for Tis, T 1 , and T 2 cases were calculated using MedCalc statistical software v. 16. The sensitivity, specificity, PPV, NPV of 3 Tesla MR imaging in T categorization for T 2 were: 93.7% [95% CI (0.79-0.99)], 77.7% [95% CI (0.52-0.93)], 88.2% [95% CI (0.75-0.94)] and 87.5% [95% CI (0.64-0.96)]; for T 1 were 92% [95% CI (0.63-0.99)], 91.8% [95% CI (0.78-0.98)], 80% [95% CI (0.57-0.92)] and 97.1% [95% CI (0.83-0.99)]; for Tis were: 20% [95% CI (0.51-0.71)], 100% [95% CI (0.92-1)], 100%, 91.8% [95% CI (0.87-0.94)], respectively. MR categorization accuracy rates for T 2 , T 1 and Tis were calculated as 88, 92 and 92%, respectively. 3 Tesla MR imaging seems to be useful for accurate categorization of T-stage in early rectal cancer, especially for T 1 cancers. The method is not a reliable tool to detect Tis cases. The potential for overstaging and understaging of the technique should be realized and taken into consideration when tailoring the treatment protocol for each patient. Advances in knowledge: High-resolution MR with phased-array coil is being increasingly used in the pre-operative assessment of rectal cancer. 3 Tesla high-resolution MR imaging allows improved definition of bowel wall and tumour infiltration.

Spectral presaturation inversion recovery MR imaging sequence after gadolinium injection to differentiate fibrotic scar tissue and neoplastic strands in the mesorectal fat in patients undergoing restaging of rectal carcinoma after neoadjuvant chemo- and radiation therapy.

PubMed

Quaia, Emilio; Ulcigrai, Veronica; Coss, Matteo; De Paoli, Luca; Ukmar, Maja; Zanconati, Fabrizio; De Pellegrin, Alessandro; De Manzini, Nicolò; Cova, Maria Assunta

2011-11-01

To retrospectively assess the value of spectral presaturation by inversion-recovery (SPIR) magnetic resonance (MR) imaging sequence after gadolinium injection to differentiate fibrotic scar tissue and tumoral infiltration within the mesorectal fat in patients with rectal carcinoma undergoing MR restaging after neoadjuvant chemo- and radiation therapy (CRT). Forty-three consecutive patients (mean age, 65.8 years; range, 46-85 years; male:female, 29:14) with locally advanced rectal carcinoma underwent CRT followed by surgery. MR imaging was performed before and after completion of CRT by using T2-weighted turbo spin-echo and T1-weighted SPIR sequences before and after gadolinium injection, and MR images were assessed by two radiologists in consensus. Logistic regression was conducted to test the significance of the MR image findings with histology. After CRT the disease was either limited to the rectal wall (n = 18 patients) or presented perirectal infiltration (n = 25) on histology. In 21 patients, mesorectal enhancing strands were observed. Reticular-shaped enhancing strands reaching the mesorectal fascia presented the highest correlation with tumor infiltration of the mesorectal fat (OR 130.33, 95% CI: 4.1-4220.29; logistic regression), whereas linear-shaped enhancing strands either reaching or not reaching the mesorectal fascia (OR 0.25 or 0.1, 95% CI: 0.024-2.6 or 0.01-1.07) revealed the lowest correlation. Reticular-shaped enhancing strands on SPIR MR imaging after gadolinium injection are associated with tumor infiltration of the mesorectal fat. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

MRI in T staging of rectal cancer: How effective is it?

PubMed Central

Mulla, MG; Deb, R; Singh, R

2010-01-01

Background: Rectal cancer constitutes about one-third of all gastrointestinal (GI) tract tumors. Because of the high recurrence rates (30%) in rectal cancer, it is vitally important to accurately stage these tumours preoperatively so that appropriate surgical resection can be undertaken. MRI is the ideal technique for the preoperative staging of these tumours. Aim: To determine the accuracy of local T staging of rectal cancer with MRI, using histopathological staging as the gold. Materials and Methods: Forty consecutive patients admitted with rectal cancer over a period of 18 months were included in this retrospective study. MRI scans were performed prior to surgery in all patients, on 1.5T scanners. Two radiologists, with a special interest in gastrointestinal imaging reported all images. Two dedicated histopathologists reported the histology slides. The accuracy of preoperative local MRI T staging was assessed by comparison with postoperative histopathological staging. Results: There was agreement between MRI and histopathology (TNM) staging in 12 patients (30%). The sensitivity and specificity of MRI for T staging was 89% and 67% respectively. The circumferential resection margin (CRM) status was accurately staged in 94.1% of the patients. Conclusions: Preoperative staging with MRI is sensitive in identifying CRM involvement, which is the main factor affecting the outcome of surgery. PMID:20607023

Argon Plasma Coagulation Therapy Versus Topical Formalin for Intractable Rectal Bleeding and Anorectal Dysfunction After Radiation Therapy for Prostate Carcinoma

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

Yeoh, Eric, E-mail: eric.yeoh@health.sa.gov.au; School of Medicine, University of Adelaide, Adelaide; Tam, William

Purpose: To evaluate and compare the effect of argon plasma coagulation (APC) and topical formalin for intractable rectal bleeding and anorectal dysfunction associated with chronic radiation proctitis. Methods and Materials: Thirty men (median age, 72 years; range, 49-87 years) with intractable rectal bleeding (defined as ≥1× per week and/or requiring blood transfusions) after radiation therapy for prostate carcinoma were randomized to treatment with APC (n=17) or topical formalin (n=13). Each patient underwent evaluations of (1) anorectal symptoms (validated questionnaires, including modified Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic and visual analogue scales for rectal bleeding); (2) anorectal motormore » and sensory function (manometry and graded rectal balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before and after the treatment endpoint (defined as reduction in rectal bleeding to 1× per month or better, reduction in visual analogue scales to ≤25 mm, and no longer needing blood transfusions). Results: The treatment endpoint was achieved in 94% of the APC group and 100% of the topical formalin group after a median (range) of 2 (1-5) sessions of either treatment. After a follow-up duration of 111 (29-170) months, only 1 patient in each group needed further treatment. Reductions in rectal compliance and volumes of sensory perception occurred after APC, but no effect on anorectal symptoms other than rectal bleeding was observed. There were no differences between APC and topical formalin for anorectal symptoms and function, nor for anal sphincteric morphology. Conclusions: Argon plasma coagulation and topical formalin had comparable efficacy in the durable control of rectal bleeding associated with chronic radiation proctitis but had no beneficial effect on anorectal dysfunction.« less

A worldwide comparison of the management of T1 and T2 anterior floor of the mouth and tongue squamous cell carcinoma - Extent of surgical resection and reconstructive measures.

PubMed

Kansy, Katinka; Mueller, Andreas Albert; Mücke, Thomas; Koersgen, Friederike; Wolff, Klaus Dietrich; Zeilhofer, Hans-Florian; Hölzle, Frank; Pradel, Winnie; Schneider, Matthias; Kolk, Andreas; Smeets, Ralf; Acero, Julio; Haers, Piet; Ghali, G E; Hoffmann, Jürgen

2017-12-01

Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the results on general aspects of current reconstructive practice in German-speaking countries, Europe and worldwide, this paper presents specific concepts for the management of resection and reconstruction of T1/T2 squamous cell carcinoma (SCC) of the anterior floor of the mouth and tongue. The DOESAK questionnaire was distributed in three different phases to a growing number of maxillofacial units worldwide. Within this survey, clinical patient settings were presented to participants and center-specific treatment strategies were evaluated. A total of 188 OMFS units from 36 different countries documented their treatment strategies for T1/T2 anterior floor of the mouth squamous cell carcinoma and tongue carcinoma. For floor of mouth carcinoma close to the mandible, a wide variety of concepts are presented: subperiosteal removal of the tumor versus continuity resection of the mandible and reconstruction ranging from locoregional closure to microvascular bony reconstruction. For T2 tongue carcinoma, concepts are more uniform. These results demonstrate the lack of evidence and the controversy of different guidelines for the extent of safety margins and underline the crucial need of global prospective randomized trials on this topic to finally obtain evidence for a common guideline based on a strong community of OMFS units. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. All rights reserved.

Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

PubMed Central

2010-01-01

The incidence of oral squamous cell carcinoma remains high. Oral and oro-pharyngeal carcinomas are the sixth most common cancer in the world. Several clinicopathological parameters have been implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma. In this retrospective analysis, clinicopathological parameters of 115 T1/T2 OSCC were studied and compared to recurrence and death from tumour-related causes. The study protocol was approved by the Joint UCL/UCLH committees of the ethics for human research. The patients' data was entered onto proformas, which were validated and checked by interval sampling. The fields included a range of clinical, operative and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death and last clinic review. Causes of death were collated in 4 categories (1) death from locoregional spread, (2) death from distant metastasis, (3) death from bronchopulmonary pneumonia, and (4) death from any non-tumour event that lead to cardiorespiratory failure. The patients' population comprised 65 males and 50 females. Their mean age at the 1st diagnosis of OSCC was 61.7 years. Two-thirds of the patients were Caucasians. Primary sites were mainly identified in the tongue, floor of mouth (FOM), buccal mucosa and alveolus. Most of the identified OSCCs were low-risk (T1N0 and T2N0). All patients underwent primary resection ± neck dissection and reconstruction when necessary. Twenty-two patients needed adjuvant radiotherapy. Pathological analysis revealed that half of the patients had moderately differentiated OSCC. pTNM slightly differed from the cTNM and showed that 70.4% of the patients had low-risk OSCC. Tumour clearance was ultimately achieved in 107 patients. Follow-up resulted in a 3-year survival of 74.8% and a 5-year survival of 72.2%. Recurrence was identified in 23 males and 20 females. The mean age of 1st diagnosis of the

Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo

PubMed Central

de Bruin, Elza C.; van de Pas, Simone; van de Velde, Cornelis J. H.; van Krieken, J. Han J. M.; Peltenburg, Lucy T. C.; Marijnen, Corrie A. M.

2007-01-01

The level of apoptosis in rectal carcinomas of patients treated by surgery only predicts local failure; patients with intrinsically high-apoptotic tumors develop less local recurrences than patients with low levels of apoptosis. To identify genes involved in this intrinsic apoptotic process in vivo, 47 rectal tumors with known apoptotic phenotype (24 low- and 23 high-apoptotic) were analyzed by oligonucleotide microarray technology. We identified several genes differentially expressed between low- and high-apoptotic tumors. Unsupervised clustering of the tumors based on expression levels of these genes separated the low-apoptotic from the high-apoptotic tumors, indicating a gene expression-dependent regulation. In addition, this clustering revealed two subgroups of high-apoptotic tumors. One high-apoptotic subgroup showed subtle differences in mRNA and protein expression of the known apoptotic regulators BAX, cIAP2 and ARC compared to the low-apoptotic tumors. The other subgroup of high-apoptotic tumors showed high expression of immune-related genes; predominantly HLA class II and chemokines, but also HLA class I and interferon-inducible genes were highly expressed. Immunohistochemistry revealed HLA-DR expression in epithelial tumor cells in 70% of these high-apoptotic tumors. The expression data suggest that high levels of apoptosis in rectal carcinoma patients can be the result of either slightly altered expression of known pro- and anti-apoptotic genes or high expression of immune-related genes. Electronic supplementary material The online version of this article (doi: 10.1007/s10495-007-0088-2) contains supplementary material, which is available to authorized users. PMID:17610066

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

PubMed Central

Chateau, Morgan L.; Denton, Paul W.; Swanson, Michael D.; McGowan, Ian; Garcia, J. Victor

2013-01-01

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1JRCSF or the MSM-derived transmitted/founder (T/F) virus HIV-1THRO within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1JRCSF and HIV-1THRO, respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1JRCSF and 0% (0/6; log rank p = 0.02) for HIV-1THRO. This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides. PMID:23527295

[Surgical treatment of pulmonary metastases from colon and rectal cancer].

PubMed

Togashi, Ken-ichi; Aoki, K; Hirahara, H; Sugawara, M; Oguma, F

2004-09-01

We retrospectively studied the surgical treatment for pulmonary metastases from colon and rectal cancer. A total of 24 patients (9 males and 15 females; mean age 61 years) underwent 29 thoracotomies for metastatic colon carcinoma, while 22 patients (16 males and 6 females; mean age 63 years) underwent 29 thoracotomies for metastatic rectal cancer. The median interval between the primary procedure and lung resection for metastases was 26 months in the patients with colon carcinoma and 32 months in the patients with rectal cancer. In the patients with colon carcinoma, 16 underwent wedge resection or segmentectomy (including 4 video-assisted procedures) and 13 (54%) underwent lobectomy or pneumonectomy. In the patients with rectal cancer, 15 underwent wedge or segmentectomy (including 1 video-assisted procedure), 13 (59%) underwent lobectomy or pneumonectomy, and 1 underwent exploratory thoracotomy. All procedures except exploratory thoracotomy were curative operations. There was no mortality. Overall 5-year survival was 56% (n=46). Five-year survival was 65% for patients with colon metastases (n=24) and 45% for patients with rectal metastases (n=22), and there was no significant difference. Recurrent sites were 4 lungs (36%), 4 livers (36%), 1 bone, 1 uterus, and 1 peritoneum in patients with colon carcimoma, and 10 lungs (43%), 5 brains (22%), 3 livers (13%), 1 bone, and 1 vagina in patients with rectal cancer. Pulmonary resection for metastases from colon carcinoma may have better prognosis than that from rectal cancer. However, further investigation may be required to obtain convincing conclusions.

Esophageal carcinoma: Ex vivo evaluation by high-spatial-resolution T2 -mapping MRI compared with histopathological findings at 3.0T.

PubMed

Wei, Yi; Wu, Sen; Gao, Feifei; Sun, Tingyi; Zheng, Dandan; Ning, Peigang; Zhao, Cuihua; Li, Ziyuan; Li, Xiaodong; Li, Linlin; Zhu, Shaocheng

2017-06-01

To prospectively determine the feasibility of T 2 -mapping magnetic resonance imaging (MRI) to quantitatively describe the signal characteristics of the normal esophageal wall and assess the depth of esophageal wall invasion by carcinoma at 3.0T. Thirty-two patient specimens, each having foci of carcinoma, were studied using 3.0T MR. Freehand regions of interest were placed to measure the T 2 value of the normal esophageal layers and were compared with the regions of carcinoma. Three independent readers reviewed the MR images to evaluate the depth of carcinoma invasion; when the three radiologists could not fully agree with each other, the final stage was determined by consensus. The Games-Howell test was used to compare the difference between the normal esophageal layers and carcinoma. Spearman correlation coefficient analysis was used to compare the stage at MRI with that at histopathological analysis. The interobserver agreement was compared with Cohen's kappa. The sensitivity, specificity, and accuracy for detecting carcinoma invasion were calculated. The T 2 values between the carcinoma and normal esophageal layers were different (all P < 0.01), except for the inner circular muscle (P = 0.511). The T 2 value of each layer of the normal esophageal wall was also different from that of the adjacent layer (all P < 0.01). In 29 of 32 lesions, the depth of the esophageal wall invasion determined by MR was consistent with the histopathological stage (r = 0.969, P < 0.001). The sensitivity, specificity, and accuracy were 80%, 96.3%, and 93.8%, respectively, for invasion into the mucosa; 77.8%, 95.7%, and 90.6%, respectively, for invasion into submucosa; 100%, 95.8%, and 96.9%, respectively, for invasion into muscularis propria; and 100%, 100%, and 100%, respectively, for invasion into the adventitia. T 2 -mapping MR images obtained using a 3.0T MR scanner can be used to depict the precise histopathological layers of the esophageal wall clearly and provide

Dose Constraint for Minimizing Grade 2 Rectal Bleeding Following Brachytherapy Combined With External Beam Radiotherapy for Localized Prostate Cancer: Rectal Dose-Volume Histogram Analysis of 457 Patients

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

Shiraishi, Yutaka; Yorozu, Atsunori; Ohashi, Toshio, E-mail: ohashi@rad.med.keio.ac.jp

2011-11-01

Purpose: To determine the rectal tolerance to Grade 2 rectal bleeding after I-125 seed brachytherapy combined with external beam radiotherapy (EBRT), based on the rectal dose-volume histogram. Methods and Materials: A total of 458 consecutive patients with stages T1 to T3 prostate cancer received combined modality treatment consisting of I-125 seed implantation followed by EBRT to the prostate and seminal vesicles. The prescribed doses of brachytherapy and EBRT were 100 Gy and 45 Gy in 25 fractions, respectively. The rectal dosimetric factors were analyzed for rectal volumes receiving >100 Gy and >150 Gy (R100 and R150) during brachytherapy and formore » rectal volumes receiving >30 Gy to 40 Gy (V30-V40) during EBRT therapy in 373 patients for whom datasets were available. The patients were followed from 21 to 72 months (median, 45 months) after the I-125 seed implantation. Results: Forty-four patients (9.7%) developed Grade 2 rectal bleeding. On multivariate analysis, age (p = 0.014), R100 (p = 0.002), and V30 (p = 0.001) were identified as risk factors for Grade 2 rectal bleeding. The rectal bleeding rate increased as the R100 increased: 5.0% (2/40 patients) for 0 ml; 7.5% (20/267 patients) for >0 to 0.5 ml; 11.0% (11/100 patients) for >0.5 to 1 ml; 17.9% (5/28 patients) for >1 to 1.5 ml; and 27.3% (6/22 patients) for >1.5 ml (p = 0.014). Grade 2 rectal bleeding developed in 6.4% (12/188) of patients with a V30 {<=}35% and in 14.1% (26/185) of patients with a V30 >35% (p = 0.02). When these dose-volume parameters were considered in combination, the Grade 2 rectal bleeding rate was 4.2% (5/120 patients) for a R100 {<=}0.5 ml and a V30 {<=}35%, whereas it was 22.4% (13/58 patients) for R100 of >0.5 ml and V30 of >35%. Conclusion: The risk of rectal bleeding was found to be significantly volume-dependent in patients with prostate cancer who received combined modality treatment. Rectal dose-volume analysis is a practical method for predicting the risk of

Predictive value of MRI-detected extramural vascular invasion in stage T3 rectal cancer patients before neoadjuvant chemoradiation.

PubMed

Sun, Yiqun; Li, Jianwen; Shen, Lijun; Wang, Xiaolin; Tong, Tong; Gu, Yajia

2018-01-01

We set out to explore the probability of MRI-detected extramural vascular invasion (mr-EMVI) before chemoradiation to predict responses to chemoradiation and survival in stage T3 rectal cancer patients. A total of 100 patients with T3 rectal cancer who underwent MRI examination and received neoadjuvant chemoradiation and surgery were enrolled. The correlation between mr-EMVI and other clinical factors were analyzed by chi-square. Logistic regression model was performed to select the potential factors influencing tumor responses to neoadjuvant chemoradiation. A Cox proportional hazards regression model was performed to explore potential predictors of survival. The positive mr-EMVI result was more likely to be present in patients with a higher T3 subgroup (T3a+b = 7.1% vs. T3c+d = 90.1%, P < 0.001) and more likely in patients with mesorectal fascia involvement than in those without MRF (65% vs. 38.8%, P = 0.034). Compared with mr-EMVI (+) patients, more mr-EMVI (-) patients showed a good response (staged ≤ ypT2N0) (odds ratio [OR], 3.020; 95% confidence interval [CI], 1.071-8.517; P = 0.037). In univariate analysis, mr-EMVI (+) (hazard ratio [HR], 5.374; 95% CI, 1.210-23.872; P = 0.027) and lower rectal cancers (HR, 3.326; 95% CI, 1.135-9.743; P = 0.028) were significantly associated with decreased disease-free survival. A positive mr-EMVI status (HR, 5.727; 95% CI, 1.286-25.594; P = 0.022) and lower rectal cancers (HR, 3.137; 95% CI, 1.127-8.729; P = 0.029) also served as prognostic factors related to decreased disease-free survival in multivariate analysis. The mr-EMVI status before chemoradiation is a significant prognostic factor and could be used for identifying T3 rectal cancer patients who might benefit from neoadjuvant chemoradiation.

Image Quality Assessment of 2D versus 3D T2WI and Evaluation of Ultra-high b-Value (b=2,000 mm/s2) DWI for Response Assessment in Rectal Cancer.

PubMed

Hausmann, Daniel; Liu, Jing; Budjan, Johannes; Reichert, Miriam; Ong, Melissa; Meyer, Mathias; Smakic, Arman; Grimm, Robert; Strecker, Ralph; Schoenberg, Stefan O; Wang, Xiaoying; Attenberger, Ulrike I

2018-02-01

The purpose of this IRB-approved, retrospective study was to compare image quality between 2D and high-resolution 3D, T2-weighted (T2WI) magnetic resonance imaging (MRI) sequences and to investigate the additional value of ultra-high b-value diffusion-weighted imaging (DWI; b=2,000 mm/s 2 ) for both rectal cancer staging and evaluating treatment response. From 12 February to 24 August 2016, 26 consecutive patients (22 males, four females; mean age: 61.9±14.0 years) with histologically-proven rectal cancer. In total 31 examinations [12 prior to and 19 after chemoradiation (CRT)] were included. The patients underwent pelvic MRI on a 3.0-T scanner (Magnetom Skyra, Erlangen, Germany). Three radiologists (3, 4, and 5 years of experience in MRI, respectively) independently assessed all images and rated the image quality of DWI (b=800 mm/s 2 ), apparent diffusion coefficient map, DWI (b=2,000 mm/s 2 ), 3D sagittal T2WI, 3D axial T2WI, 2D sagittal T2WI, and 2D axial T2WI of each patient, respectively. In addition, signal intensity ratios (SIR) were calculated between rectal cancer and obturator internus muscle (background) in all patients after CRT on DWI (b=2,000 mm/s 2 ) and correlated with histopathological regression grade (RG). Tumor delineation was significantly better by 2D T2WI than 3D T2WI both before and after CRT (before CRT: Z=-3.2, p=0.02; after CRT: Z=-4.408, p<0.001; all: Z=-5.192; p<0.001) and was the preferred method, although image quality ratings were not significantly different (3D sagittal: 4.00±0.48; 2D sagittal: 4.03±0.34, p=0.713; 3D axial: 3.85±0.61, 2D axial: 3.78±0.64, p=0.537). Independent t-test showed significantly higher SIR between those with RG 1 or 2 (moderate response: mean score=2.02) and those with RG 3+4 (good response: mean score=0.8) (t=3.044, p=0.011). In those with RG 4 (complete response), SIR of b2000 was 0.946 compared to a 1.41 average of the whole cohort. In two patients, tumor was invisible on b2000 following CRT (RG 3

Positive Margins by Oropharyngeal Subsite in Transoral Robotic Surgery for T1/T2 Squamous Cell Carcinoma.

PubMed

Persky, Michael J; Albergotti, William G; Rath, Tanya J; Kubik, Mark W; Abberbock, Shira; Geltzeiler, Mathew; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L

2018-04-01

Objective To compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins. Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods We compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results. Results Between January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status. Conclusion Positive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate.

Influence of Preoperative Chemoradiotherapy on the Surgical Strategy According to the Clinical T Stage of Patients With Rectal Cancer

PubMed Central

Park, In Ja; Lee, Jong Lyul; Yoon, Yong Sik; Kim, Chan Wook; Lim, Seok-Byung; Lee, Jong Seok; Park, Seong Ho; Park, Jin Hong; Kim, Jong Hoon; Yu, Chang Sik; Kim, Jin Cheon

2015-01-01

Abstract The aim of this study was to evaluate the pathologic responses and changes to surgical strategies following preoperative chemoradiotherapy (PCRT) in rectal cancer patients according to their clinical T stage (cT). The use of PCRT has recently been extended to less advanced disease. The authors enrolled 650 patients with cT2 to 4 mid and low rectal cancer who received both PCRT and surgical resection. The rate of total regression and the proportion of local excision were compared according to the cT category. The 3-year recurrence-free survival (RFS) rate was compared using the log-rank test according to patient cT category, pathologic stage, and type of surgical treatment. Patients with cT2 were older (P = 0.001), predominately female (P = 0.028), and had low-lying rectal cancer (P = 0.008). Pathologic total regression was achieved most frequently in cT2 patients (54% of cT2 versus 17.6% of cT3 versus 8.2% of cT4; P < 0.001). Local excision was performed on 42 cT2 (42%) and 24 cT3 (5.2%) patients (P < 0.001). The 3-year RFS rates differed according to both cT (P < 0.001) and ypT stage (P < 0.001). Among patients with ypT0 to 1 disease, the 3-year RFS did not differ according to the type of surgical treatment received (P = 0.5). Total regression of the primary tumor and a change in the surgical strategy after PCRT are most commonly seen in cT2 disease. Although PCRT is not generally indicated for cT2 rectal cancer, optimal surgical treatment may be achieved with the tailored use of PCRT. PMID:26717384

Intensity modulated radiation therapy (IMRT): differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma.

PubMed

Mok, Henry; Crane, Christopher H; Palmer, Matthew B; Briere, Tina M; Beddar, Sam; Delclos, Marc E; Krishnan, Sunil; Das, Prajnan

2011-06-08

A strong dose-volume relationship exists between the amount of small bowel receiving low- to intermediate-doses of radiation and the rates of acute, severe gastrointestinal toxicity, principally diarrhea. There is considerable interest in the application of highly conformal treatment approaches, such as intensity-modulated radiation therapy (IMRT), to reduce dose to adjacent organs-at-risk in the treatment of carcinoma of the rectum. Therefore, we performed a comprehensive dosimetric evaluation of IMRT compared to 3-dimensional conformal radiation therapy (3DCRT) in standard, preoperative treatment for rectal cancer. Using RTOG consensus anorectal contouring guidelines, treatment volumes were generated for ten patients treated preoperatively at our institution for rectal carcinoma, with IMRT plans compared to plans derived from classic anatomic landmarks, as well as 3DCRT plans treating the RTOG consensus volume. The patients were all T3, were node-negative (N = 1) or node-positive (N = 9), and were planned to a total dose of 45-Gy. Pairwise comparisons were made between IMRT and 3DCRT plans with respect to dose-volume histogram parameters. IMRT plans had superior PTV coverage, dose homogeneity, and conformality in treatment of the gross disease and at-risk nodal volume, in comparison to 3DCRT. Additionally, in comparison to the 3DCRT plans, IMRT achieved a concomitant reduction in doses to the bowel (small bowel mean dose: 18.6-Gy IMRT versus 25.2-Gy 3DCRT; p = 0.005), bladder (V40Gy: 56.8% IMRT versus 75.4% 3DCRT; p = 0.005), pelvic bones (V40Gy: 47.0% IMRT versus 56.9% 3DCRT; p = 0.005), and femoral heads (V40Gy: 3.4% IMRT versus 9.1% 3DCRT; p = 0.005), with an improvement in absolute volumes of small bowel receiving dose levels known to induce clinically-relevant acute toxicity (small bowel V15Gy: 138-cc IMRT versus 157-cc 3DCRT; p = 0.005). We found that the IMRT treatment volumes were typically larger than that covered by classic bony landmark-derived fields

Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven

PubMed Central

Holman, Fabian A.; Haddock, Michael G.; Gunderson, Leonard L.; Kusters, Miranda; Nieuwenhuijzen, Grard A. P.; van den Berg, Hetty A.; Nelson, Heidi

2016-01-01

Background The aim of this study is to analyse the pooled results of intraoperative electron beam radiotherapy (IOERT) containing multimodality treatment of locally advanced T4 rectal cancer, initially unresectable for cure, from the Mayo Clinic, Rochester, USA (MCR) and Catharina Hospital, Eindhoven, The Netherlands (CHE), both major referral centers for locally advanced rectal cancer. A rectal tumor is called locally unresectable for cure if after full clinical work-up infiltration into the surrounding structures or organs has been demonstrated, which would result in positive surgical margins if resection was the initial component of treatment. This was the reason to refer these patients to the IOERT program of one of the centers. Methods In the period from 1981 to 2010, 417 patients with locally unresectable T4 rectal carcinomas at initial presentation were treated with multimodality treatment including IOERT at either one of the two centres. The preferred treatment approach was preoperative (chemo) radiation and intended radical surgery combined with IOERT. Risk factors for local recurrence (LR), cancer specific survival, disease free survival and distant metastases (DM) were assessed. Results A total of 306 patients (73%) underwent a R0 resection. LRs and metastases occurred more frequently after an R1-2 resection (P<0.001 and P<0.001 respectively). Preoperative chemoradiation (preop CRT) was associated with a higher probability of having a R0 resection. Waiting time after preoperative treatment was inversely related with the chance of developing a LR, especially after R+ resection. In 16% of all cases a LR developed. Five-year disease free survival and overall survival (OS) were 55% and 56% respectively. Conclusions An acceptable survival can be achieved in treatment of patients with initially unresectable T4 rectal cancer with combined modality therapy that includes preop CRT and IOERT. Completeness of the resection is the most important predictive and

Rectal Dose and Source Strength of the High-Dose-Rate Iridium-192 Both Affect Late Rectal Bleeding After Intracavitary Radiation Therapy for Uterine Cervical Carcinoma

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

Isohashi, Fumiaki, E-mail: isohashi@radonc.med.osaka-u.ac.j; Yoshioka, Yasuo; Koizumi, Masahiko

2010-07-01

Purpose: The purpose of this study was to reconfirm our previous findings that the rectal dose and source strength both affect late rectal bleeding after high-dose-rate intracavitary brachytherapy (HDR-ICBT), by using a rectal dose calculated in accordance with the definitions of the International Commission on Radiation Units and Measurements Report 38 (ICRU{sub RP}) or of dose-volume histogram (DVH) parameters by the Groupe Europeen de Curietherapie of the European Society for Therapeutic Radiology and Oncology. Methods and Materials: Sixty-two patients who underwent HDR-ICBT and were followed up for 1 year or more were studied. The rectal dose for ICBT was calculatedmore » by using the ICRP{sub RP} based on orthogonal radiographs or the DVH parameters based on computed tomography (CT). The total dose was calculated as the biologically equivalent dose expressed in 2-Gy fractions (EQD{sub 2}). The relationship between averaged source strength or the EQD{sub 2} and late rectal bleeding was then analyzed. Results: When patients were divided into four groups according to rectal EQD{sub 2} ({>=} or =} or <2.4 cGy.m{sup 2}.h{sup -1}), the group with both a high EQD{sub 2} and a high source strength showed a significantly greater probability of rectal bleeding for ICRU{sub RP}, D{sub 2cc}, and D{sub 1cc}. The patients with a median rectal dose above the threshold level did not show a greater frequency of rectal bleeding unless the source strength exceeded 2.4 cGy.m{sup 2}.h{sup -1}. Conclusions: Our results obtained with data based on ICRU{sub RP} and CT-based DVH parameters indicate that rectal dose and source strength both affect rectal bleeding after HDR-ICBT.« less

Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung.

PubMed

Pavanello, Sofia; B'chir, Fatma; Pulliero, Alessandra; Saguem, Saâd; Ben Fraj, Radhia; El Aziz Hayouni, Abed; Clonfero, Erminio; Mastrangelo, Giuseppe

2007-09-01

This study aimed to identify new genetic characteristics contributing to individual susceptibility to smoke-induced lung cancer. Despite functional evidence of a possible role of cytochrome P450 1A2 (CYP1A2) in lung cancer susceptibility, no studies have evaluated the influence of CYP1A2 genotypes on lung cancer risk. We investigated the interaction between CYP1A2-T2467delT (allele*1D) polymorphism and smoking in Tunisian lung cancer cases (n=101 male smokers) separately for the histological types squamous cell carcinoma (SCC) (n=60) and adenocarcinoma (n=41), and in controls (n=98 male smokers) using a case-only study design. A significant interaction between CYP1A2-T/delT or delT/delT genotypes and tobacco consumption (pack-years) adjusted for age was evident (OR (95% CI) 7.78 (1.52-42.8)) in the SCC cases who smoked relatively less (< or =33 pack-years, I quartile value), but not in adenocarcinoma and controls. Our results suggest that CYP1A2-T2467delT polymorphism has an important role in lung carcinogenesis, especially SCC, among smokers.

Relapsed cervicomediastinal lymph node carcinoma with an unknown primary site treated with TS-1 alone: a case report.

PubMed

Yajima, Toshiki; Onozato, Ryoichi; Shitara, Yoshinori; Mogi, Akira; Tanaka, Shigebumi; Kuwano, Hiroyuki

2013-12-27

Cervicomediastinal lymph node carcinoma with an unknown primary site is quite rare, and useful treatment of these diseases has not been established. We report here the case of a patient successfully treated with TS-1 alone after the relapse of cervicomediastinal lymph node carcinoma with an unknown primary site. A 62-year-old man was referred to our hospital because of cervicomediastinal lymph node swelling and high serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen. Fluorodeoxyglucose-positron emission tomography/computed tomography revealed an accumulation of fluorodeoxyglucose in the left supraclavicular lymph nodes, mediastinal lymph nodes, and the pelvic cavity. Colonoscopy revealed rectal cancer, which was diagnosed by biopsy as a tubular adenocarcinoma. Because metastases from rectal cancer to the cervicomediastinal lymph nodes are rare, the patient underwent thoracoscopic mediastinal lymphadenectomy. A biopsy specimen from the paraaortic lymph nodes demonstrated papillary adenocarcinoma that was pathologically different from the rectal cancer; therefore, a diagnosis of mediastinal carcinoma with an unknown primary site was established. The patient underwent low anterior resection of the rectum for the rectal cancer, and no abdominal lymph node metastasis (pMP, N0/stage I) was found. Although radiotherapy was performed for the cervicomediastinal lymph nodes, the mediastinal carcinoma relapsed after 6 months. Because the patient desired oral chemotherapy on an outpatient basis, TS-1 was administered at a dosage of 80 mg/day for 2 weeks, followed by a 1-week rest. TS-1 treatment resulted in a decrease in the size of the cervicomediastinal lymph nodes, and the serum tumor marker levels decreased to normal after the fourth course. The patient continued TS-1 treatment without adverse events and is currently alive without recurrence or identification of the primary site at the 32nd month after TS-1 treatment. This is the first reported case of

Comorbidity between HTLV-1-associated adult T-cell lymphoma/leukemia and verrucous carcinoma: a case report

PubMed Central

Moreno, Luis

2017-01-01

Abstract Background: Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described. Case report: We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2. Treatment and outcome: The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle. Clinical relevance: Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV). PMID:28559645

SU-E-T-571: Prostate IMRT QA: Prediction of the Range of Rectal NTCP Using a 2D Field Approach Based on Variations of the Rectal Wall Motion and Thickness.

PubMed

Grigorov, G; Chow, J; Foster, K

2012-06-01

The aims of this study is to (1) introduce a 2D field of possible rectal normal tissue complication probability (NTCP) in prostate intensity modulated radiotherapy (IMRT) plan, so that based on a given prescribed dose the rectal NTCP is merely a function of the rectal wall thickness and rectal motion; and (2) separate the 2D field of rectal NTCP into area of low risk and area of high risk for rectal toxicity < Grade II, based on the threshold rectal NTCP. The 2D field of NTCP model was developed using ten randomly selected prostate IMRT plans. The clinical rectal geometry was initially represented by the cylindrical contour in the treatment planning system. Different combinations of rectal motions, rectal wall thicknesses, planning target volume margins and prescribed doses were used to determine the NTCP in prostate IMRT plans. It was found that the functions bordering the 2D field for the given AP, LR and SI direction can be described as exponential, quadratic and linear equations, respectively. A ratio of the area of 2D field containing data of the low risk NTCP to the entire area of the field was introduced and calculated. Although our method is based on the Kutcher's dose response model and published tissue parameters, other mathematical models can be used in our approach. The 2D field of rectal NTCP is useful to estimate the rectal NTCP range in the prostate pre-treatment and treatment QA. Our method can determine the patient's threshold immobilization for a given rectal wall thickness so that prescribed dose can be delivered to the prostate to avoid rectal complication. Our method is also applicable to multi-phase prostate IMRT, and can be adapted to any treatment planning systems. © 2012 American Association of Physicists in Medicine.

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.

Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.

PubMed

Abraham, Shaji; Knapp, Deborah W; Cheng, Liang; Snyder, Paul W; Mittal, Suresh K; Bangari, Dinesh S; Kinch, Michael; Wu, Lan; Dhariwal, Jay; Mohammed, Sulma I

2006-01-15

The EphA2 receptor tyrosine kinase is believed to play a role in tumor growth and metastasis. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers. The purpose of this work was to determine the expression of EphA2 and its ligand, Ephrin A-1, and E-cadherin in carcinoma of the urinary bladder, and determine EphA2 as a new target for therapy in bladder cancer. EphA2 mRNA and protein expression was investigated by reverse transcription-PCR and Western blot, respectively, in bladder cancer cell lines. In addition, the expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with different stages of urinary bladder cancer was determined by immunohistochemistry. Furthermore, the ability of Ephrin A-1 to inhibit growth of bladder cancer cells was also investigated using an adenoviral delivery system. Western blot analysis showed high EphA2 expression in TCCSUP, T24, and UMUC-3 cell lines. In tissues, the staining intensity of EphA2 was less in normal urothelium but increased greatly in advancing stages of urothelial carcinoma (P < 0.05). Similarly, the staining intensity of Ephrin A-1 was low in normal tissues and high in cancerous tissues, but it was similar across the various stages of urothelial carcinoma (T(a)-T(4)). E-cadherin immunoreactivity decreased in urothelial cancer. Association of EphA2 and Ephrin A-1 expression was found to be significant between T(a) stage and T(1)-T(2) (P < 0.04) and T(a) and T(3)-T(4) stages (P < 0.0001). Adenovirus delivery of Ephrin A-1 inhibited proliferation of TCCSUP cells. EphA2 may serve as a novel target for bladder cancer therapy.

Prophylactic central neck lymphadenectomy in high risk patients with T1 or T2 papillary thyroid carcinoma: is it useful?

PubMed

Delogu, Daniele; Pisano, Ilia Patrizia; Pala, Carlo; Pulighe, Fabio; Denti, Salvatore; Cossu, Antonio; Trignano, Mario

2014-01-01

The aim of this study was to evaluate the role of prophylactic central neck lymph node dissection in high risk patients with T1 or T2 papillary thyroid cancer. Seventy-three patients who had undergone total thyroidectomy for papillary thyroid cancer smaller than 4cm, without cervical lymphadenopathy and prophylactic central neck lymph node dissection were included. Patients were divided in two groups: low risk patients (group A) and high risk patients (group B). High risk patients were considered those with at least one of the followings: male sex, age ≥ 45 years, and extracapsular or extrathyroid disease. Statistical significant differences in persistent disease, recurrence and complications rates between the two groups were studied. Persistence of the disease was observed in one case in group A (5.9%) and in three cases in group B (5.4%), while thyroid cancer recurrence was registered in zero and two (3.6%) cases respectively. One single case (5.9%) of transitory recurrent laryngeal nerve damage was reported in group A and none in group B, while transitory hypoparathyroidism was observed in 2 (3.6%) patients in group A, and 1 (1.8%) patient in group B. Permanent recurrent laryngeal nerve damage was observed in one patient in group A, while permanent hypoparathyroidism was registered in one case in group B. Logistic regression evidenced that multifocality was the only risk factor significantly related to persistence of disease and recurrence. Our results suggests that prophylactic central neck lymph node dissection can be safely avoided in patients with T1 or T2 papillary thyroid cancer, except in those with multifocal disease. Cancer, Central neck, Cervical, Lymphadenectomy, Lymph nodes, Papillary carcinoma, Thyroid.

Mesorectal Invasion Depth in Rectal Carcinoma Is Associated With Low Survival.

PubMed

Lino-Silva, Leonardo S; Loaeza-Belmont, Reynaldo; Gómez Álvarez, Miguel A; Vela-Sarmiento, Itzel; Aguilar-Romero, José M; Domínguez-Rodríguez, Jorge A; Salcedo-Hernández, Rosa A; Ruiz-García, Erika B; Maldonado-Martínez, Héctor A; Herrera-Gómez, Ángel

2017-03-01

Most cases of rectal cancer (RC) in our institution are in pathologic stage T3. They are a heterogeneous group but have been classified in a single-stage category. We performed the present study to validate the prognostic significance of the mesorectal extension depth (MED) in T3 RC measured in millimeters beyond the muscularis propria plane. We performed a retrospective analysis of 104 patients with T3 RC who had undergone curative surgery after a course of preoperative chemoradiotherapy at a tertiary referral cancer hospital. The patients were grouped by MED (T3a, < 1 mm; T3b, 1-5 mm; T3c > 5-10 mm; and T3d > 10 mm). The clinicopathologic data and disease-free survival were analyzed. The 5-year disease-free survival rate according to the T3 subclassification was 87.5% for those with T3a, 57.9% for T3b, 38.7% for T3c, and 40.3% for those with T3d tumors (P = .050). On univariate and multivariate analysis, the prognostic factors affecting survival were overall recurrence (hazard ratio [HR], 3.670; 95% confidence interval [CI], 1.710-7.837; P = .001), histologic grade (HR, 2.204; 95% CI, 1.156-4.199; P = .016), mesorectal invasion depth (HR, 1.885; 95% CI, 1.164-3.052; P = .010), and lymph node metastasis (HR, 1.211; 95% CI, 1.015-1.444; P = .033). MED is a significant prognostic factor in patients with T3 RC who have undergone neoadjuvant chemoradiotherapy, especially when the MED is > 5 mm. The MED could be as important as other clinicopathologic factors in predicting disease-specific survival. Copyright © 2016 Elsevier Inc. All rights reserved.

Toward automatic segmentation and quantification of tumor and stroma in whole-slide images of H and E stained rectal carcinomas

NASA Astrophysics Data System (ADS)

Geessink, Oscar G. F.; Baidoshvili, Alexi; Freling, Gerard; Klaase, Joost M.; Slump, Cornelis H.; van der Heijden, Ferdinand

2015-03-01

Visual estimation of tumor and stroma proportions in microscopy images yields a strong, Tumor-(lymph)Node- Metastasis (TNM) classification-independent predictor for patient survival in colorectal cancer. Therefore, it is also a potent (contra)indicator for adjuvant chemotherapy. However, quantification of tumor and stroma through visual estimation is highly subject to intra- and inter-observer variability. The aim of this study is to develop and clinically validate a method for objective quantification of tumor and stroma in standard hematoxylin and eosin (H and E) stained microscopy slides of rectal carcinomas. A tissue segmentation algorithm, based on supervised machine learning and pixel classification, was developed, trained and validated using histological slides that were prepared from surgically excised rectal carcinomas in patients who had not received neoadjuvant chemotherapy and/or radiotherapy. Whole-slide scanning was performed at 20× magnification. A total of 40 images (4 million pixels each) were extracted from 20 whole-slide images at sites showing various relative proportions of tumor and stroma. Experienced pathologists provided detailed annotations for every extracted image. The performance of the algorithm was evaluated using cross-validation by testing on 1 image at a time while using the other 39 images for training. The total classification error of the algorithm was 9.4% (SD = 3.2%). Compared to visual estimation by pathologists, the algorithm was 7.3 times (P = 0.033) more accurate in quantifying tissues, also showing 60% less variability. Automatic tissue quantification was shown to be both reliable and practicable. We ultimately intend to facilitate refined prognostic stratification of (colo)rectal cancer patients and enable better personalized treatment.

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

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

Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol

2015-07-01

Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A totalmore » of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.« less

Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer.

PubMed

Park, In Ja; Kim, Dae Yong; Kim, Hee Cheol; Kim, Nam Kyu; Kim, Hyeong-Rok; Kang, Sung-Bum; Choi, Gyu-Seog; Lee, Kang Young; Kim, Seon-Hahn; Oh, Seung Taek; Lim, Seok-Byung; Kim, Jin Cheon; Oh, Jae Hwan; Kim, Sun Young; Lee, Woo Yong; Lee, Jung Bok; Yu, Chang Sik

2015-07-01

To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost

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

Jakobsen, Anders; Mortensen, John P.; Bisgaard, Claus

2006-02-01

Purpose: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal cancer with complete pathologic remission as end point. Methods and Materials: The study included 50 patients with rectal adenocarcinoma. All patients had T3 tumor with a circumferential margin 0-5 mm on a magnetic resonance imaging scan. The radiotherapy was delivered by a technique including two planning target volumes. Clinical target volume 1 (CTV1) received 60 Gy/30 fractions, and CTV2 received 48.6 Gy/27 fractions. The tumor dose was raised to 65 Gy with endorectal brachytherapy 5 Gy/1 fraction to the tumor bed.more » On treatment days, the patients received uracil and tegafur 300 mg/m2 concurrently with radiotherapy. Results: Forty-eight patients underwent operation. Histopathologic tumor regression was assessed by the Tumor Regression Grade (TRG) system. TRG1 was recorded in 27% of the patients, and a further 27% were classified as TRG2. TRG3 was found in 40%, and 6% had TRG4. The toxicity was low. Conclusion: The results indicate that high-dose radiation with concurrent chemotherapy and endorectal brachytherapy is feasible with a high rate of complete response, but further trials are needed to define its possible role as treatment option.« less

Comparative differences between T1a/b and T1e/m as substages in T1 urothelial carcinoma of the bladder.

PubMed

Turan, Turgay; Efiloğlu, Özgür; Günaydin, Bilal; Özkanli, Şeyma; Nikerel, Emrah; Atiş, Gökhan; Çaşkurlu, Turhan; Yildirim, Asif

2018-01-01

To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer and to display comparative differences between the T1a/b and T1e/m substaging systems. This study included 106 patients with primary stage T1 urothelial bladder tumours who underwent surgery between January 2009 and December 2014. Pathologic specimens were re-evaluated to confirm the diagnosis of T1 and substaging by the same pathologist using two systems: T1a and T1b, and T1m and T1e. Age, tumour size, multiplicity, associated carcinoma in situ, tumour grade, and T1 substaging system were investigated to detect the relation between disease progression and recurrence. The recurrence rate was 52% for T1a (n=42) vs. 76% for T1b (n=20) (p=0.028) and 55% for T1m (n=32) vs. 62% for T1e (n=30), respectively (p=0.446). There was no significant difference between the substaging groups for disease progression: T1a (n=12, 15%) vs. T1b (n=7, 27%), and T1m (n=8, 13.8%) vs. T1e (n=11, 23%) (p>0.05). In the multivariate analysis, tumour size >3 cm (p=0.008), multiplicity (p=0.049), and substaging T1b (p=0.043) were independent predictive factors for tumour recurrence. According to the Kaplan-Meier actuarial method, recurrence-free survival was significantly different in patients with pT1a tumours compared with those with pT1b tumours (p=0.033). Substaging T1 provides a prediction of disease recurrence. Regarding recurrence, T1a/b substaging can provide better knowledge of disease behaviour because it is predicted as more superior than T1 m/e, and it can help in determining the requirement for early cystectomy. Copyright® by the International Brazilian Journal of Urology.

Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase 3 trial.

PubMed

Fokas, E; Fietkau, R; Hartmann, A; Hohenberger, W; Grützmann, R; Ghadimi, M; Liersch, T; Ströbel, P; Grabenbauer, G G; Graeven, U; Hofheinz, R-D; Köhne, C-H; Wittekind, C; Sauer, R; Kaufmann, M; Hothorn, T; Rödel, C

2018-04-27

Surrogate endpoints in rectal cancer after preoperative chemoradiation are lacking as their statistical validation poses major challenges, including confirmation based on large phase 3 trials. We examined the prognostic role and individual-level surrogacy of neoadjuvant rectal (NAR) score that incorporates weighted cT, ypT and ypN categories for disease-free survival (DFS) in 1191 patients with rectal carcinoma treated within the CAO/ARO/AIO-04 phase 3 trial. Cox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1-4) were used to assess individual-level surrogacy of NAR for DFS. After a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based chemoradiotherapy (CRT) significantly improved 3-year DFS (75.9% [95% CI 72.30-79.50] vs 71.3% [95% CI 67.60-74.90]; P = 0.034; PC 1) and resulted in a shift towards lower NAR groups (P = 0.034, PC 2) compared to fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI, 88.2 95.2), 81.8% (95% CI, 78.4-85.1) and 58.1 (95% CI 52.4-63.9) for low, intermediate and high NAR score, respectively (P < 0.001; PC 3). NAR score remained an independent prognostic factor for DFS (low vs high NAR: HR 4.670; 95% CI 3.106-7.020; P < 0.001; low vs intermediate NAR: HR 1.971; 95% CI 1.303-2.98; P = 0.001) in multivariable analysis. Notwithstanding the inherent methodological difficulty in interpretation of PC 4 to establish surrogacy, the treatment effect on DFS was captured by NAR, supporting satisfaction of individual-level PC4. Our study validates the prognostic role and individual-level surrogacy of NAR score for DFS within a large randomized phase 3 trial. NAR score could help oncologists to speed up response-adapted therapeutic decision, and further large phase 3 trial datasets should aim to confirm trial-level surrogacy.

Cervical node metastasis in T1 squamous cell carcinoma of oral tongue- pattern and the predictive factors.

PubMed

S, Vishak; Rohan, Vinayak

2014-06-01

The squamous cell carcinoma (SCC) of the oral tongue is a common cancer in India. Elective lymphadenectomy is generally performed in all patients with T2-T4 tumors. In this study we have tried to analyze the pattern and risk factors associated with lymph node metastasis in T1 tongue cancers. A retrospective review of the records of 57 patients undergoing surgery for treatment of T1 sqamous cell carcinoma of oral tongue was carried out. The clinicopatological features of the tumor, pattern of nodal metastasis and the risk factors associated with lymph node metastasis were studied. Totally 57 patients with T1 tumor underwent excision of the primary and modified neck dissection (MND). Lymph node metastasis was found in 36.8 % of the patients. Level I to Level II was the commonest site of metastasis. Skip metastasis at level III and IV was found in 8.5 % of the patients and isolated skip metastasis at level IV in 1.5 % of the patients. The risk factors associated with the lymph node metastasis on univariete analysis were; higher grade, tumor size >1 cm and tumor thickness >3 mm. On multivariate analysis only the tumor thickness was found to be a risk factor for the lymph node metastasis (hazard ratio of 21.59). T1 sqamous cell carcinoma of tongue is associated with a high incidence of lymph node metastasis. Elective neck dissection should be considered in all patients with tumors more than 3 mm in thickness.

Correlation Between Magnetic Resonance Imaging-Based Evaluation of Extramural Vascular Invasion and Prognostic Parameters of T3 Stage Rectal Cancer.

PubMed

Yu, Jing; Huang, Dong-Ya; Xu, Hui-Xin; Li, Yang; Xu, Qing

2016-01-01

The aim of this study was to analyze the correlation between magnetic resonance imaging-based extramural vascular invasion (EMVI) and the prognostic clinical and histological parameters of stage T3 rectal cancers. Eighty-six patients with T3 stage rectal cancer who received surgical resection without neoadjuvant therapy were included. Magnetic resonance imaging-based EMVI scores were determined. Correlations between the scores and pretreatment carcinoembryonic antigen levels, tumor differentiation grade, nodal stage, and vascular endothelial growth factor expression were analyzed using Spearman rank coefficient analysis. Magnetic resonance imaging-based EMVI scores were statistically different (P = 0.001) between histological nodal stages (N0 vs N1 vs N2). Correlations were found between magnetic resonance imaging-based EMVI scores and tumor histological grade (rs = 0.227, P = 0.035), histological nodal stage (rs = 0.524, P < 0.001), and vascular endothelial growth factor expression (rs = 0.422; P = 0.016). Magnetic resonance imaging-based EMVI score is correlated with prognostic parameters of T3 stage rectal cancers and has the potential to become an imaging biomarker of tumor aggressiveness. Magnetic resonance imaging-based EMVI may be useful in helping the multidisciplinary team to stratify T3 rectal cancer patients for neoadjuvant therapies.

Exclusive low-dose-rate brachytherapy in 279 patients with T2N0 mobile tongue carcinoma

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

Bourgier, Celine; Coche-Dequeant, Bernard; Fournier, Charles

2005-10-01

Purpose: To evaluate the therapeutic results obtained with {sup 192}Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma. Patients and Methods: Between December 1979 and January 1998, 279 patients with T2N0 mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. {sup 192}Ir brachytherapy was performed according to the 'Paris system' with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h). Results: Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meiermore » method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus). Conclusion: Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.« less

Efficacy and safety of neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate for T3 or T4 stage II/III rectal cancer: the FACT trial.

PubMed

Koike, Junichi; Funahashi, Kimihiko; Yoshimatsu, Kazuhiko; Yokomizo, Hajime; Kan, Hayato; Yamada, Takeshi; Ishida, Hideyuki; Ishibashi, Keiichiro; Saida, Yoshihisa; Enomoto, Toshiyuki; Katsumata, Kenji; Hisada, Masayuki; Hasegawa, Hirotoshi; Koda, Keiji; Ochiai, Takumi; Sakamoto, Kazuhiro; Shiokawa, Hiroyuki; Ogawa, Shimpei; Itabashi, Michio; Kameoka, Shingo

2017-03-01

A multicenter phase II clinical study was performed in patients with T3 or T4 stage II/III rectal cancer to evaluate the efficacy and safety of neoadjuvant chemotherapy with 5-fluorouracil, levofolinate, and oxaliplatin (mFOLFOX6). Patients received four 2-week cycles of mFOLFOX6 therapy (oxaliplatin at 85 mg/m 2  + leucovorin at 200 mg/m 2  + fluorouracil as a 400 mg/m 2 bolus followed by infusion of 2400 mg/m 2 over 46 h, all on Day 1). They were evaluated by computed tomography after completion of the fourth cycle. If there was no disease progression, two additional cycles were administered and then surgery was performed. Adjuvant chemotherapy was generally administered for 6 months using appropriate regimens at the discretion of the physician. mFOLFOX6 therapy was given to 52 patients with locally advanced rectal cancer. The preoperative response rate was 48.8% and the operation rate was 80.8%. Serious adverse events of Grade 3-4 were neutropenia (n = 5), leukopenia (n = 1), thrombocytopenia (n = 1), febrile neutropenia (n = 1), nausea (n = 1), vomiting (n = 1), and peripheral neuropathy (n = 2). The R0 resection rate, pathologic complete response rate, and sphincter preservation rate were 91.0, 11.9, and 73.8%, respectively. Postoperative complications were tolerable. The present results suggested that neoadjuvant therapy with mFOLFOX6 is safe and effective, representing a reasonable treatment option for locally advanced rectal cancer.

Genetic variation in RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 and risk of colon or rectal cancer

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Wolff, Roger K.

2010-01-01

RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 are involved in several pathways central to the carcinogenic process, including regulation of cell growth, insulin, and inflammation. We evaluated genetic variation in their candidate genes to obtain a better understanding of their association with colon and rectal cancer. We used data from two population-based case-control studies of colon (n=1574 cases, 1940 controls) and rectal (n=791 cases, 999 controls) cancer. We observed genetic variation in RPS6KA1, RPS6KA2, and PRS6KB2 were associated with risk of developing colon cancer while only genetic variation in RPS6KA2 was associated with altering risk of rectal cancer. These genes also interacted significantly with other genes operating in similar mechanisms, including Akt1, FRAP1, NFκB1, and PIK3CA. Assessment of tumor markers indicated that these genes and this pathway may importantly contributed to CIMP+ tumors and tumors with KRAS2 mutations. Our findings implicate these candidate genes in the etiology of colon and rectal cancer and provide information on how these genes operate with other genes in the pathway. Our data further suggest that this pathway may lead to CIMP+ and KRAS2-mutated tumors. PMID:21035469

Laparoscopic approach to suspected T1 and T2 gallbladder carcinoma

PubMed Central

Ome, Yusuke; Hashida, Kazuki; Yokota, Mitsuru; Nagahisa, Yoshio; Okabe, Michio; Kawamoto, Kazuyuki

2017-01-01

AIM To evaluate a laparoscopic approach to gallbladder lesions including polyps, wall-thickening lesions, and suspected T1 and T2 gallbladder cancer (GBC). METHODS We performed 50 cases of laparoscopic whole-layer cholecystectomy (LCWL) and 13 cases of laparoscopic gallbladder bed resection (LCGB) for those gallbladder lesions from April 2010 to November 2016. We analyzed the short-term and long-term results of our laparoscopic approach. RESULTS The median operation time was 108 min for LCWL and 211 min for LCGB. The median blood loss was minimal for LCWL and 28 ml for LCGB. No severe morbidity occurred in either procedure. Nine patients who underwent LCWL and 7 who underwent LCGB were postoperatively diagnosed with GBC. One of these patients had undergone LCGB for pathologically diagnosed T2 GBC after LCWL. All of the final surgical margins were negative. Three of these 15 patients underwent additional open surgery. The mean follow-up period was 26 mo, and only one patient developed recurrence. CONCLUSION LCWL and LCGB are safe and useful procedures that allow complete resection of highly suspected or early-stage cancer and achieve good short-term and long-term results. PMID:28465640

Laparoscopic approach to suspected T1 and T2 gallbladder carcinoma.

PubMed

Ome, Yusuke; Hashida, Kazuki; Yokota, Mitsuru; Nagahisa, Yoshio; Okabe, Michio; Kawamoto, Kazuyuki

2017-04-14

To evaluate a laparoscopic approach to gallbladder lesions including polyps, wall-thickening lesions, and suspected T1 and T2 gallbladder cancer (GBC). We performed 50 cases of laparoscopic whole-layer cholecystectomy (LCWL) and 13 cases of laparoscopic gallbladder bed resection (LCGB) for those gallbladder lesions from April 2010 to November 2016. We analyzed the short-term and long-term results of our laparoscopic approach. The median operation time was 108 min for LCWL and 211 min for LCGB. The median blood loss was minimal for LCWL and 28 ml for LCGB. No severe morbidity occurred in either procedure. Nine patients who underwent LCWL and 7 who underwent LCGB were postoperatively diagnosed with GBC. One of these patients had undergone LCGB for pathologically diagnosed T2 GBC after LCWL. All of the final surgical margins were negative. Three of these 15 patients underwent additional open surgery. The mean follow-up period was 26 mo, and only one patient developed recurrence. LCWL and LCGB are safe and useful procedures that allow complete resection of highly suspected or early-stage cancer and achieve good short-term and long-term results.

Kinetics of absorption and elimination of ofloxacin in humans after oral and rectal administrations.

PubMed

Eboka, C J; Okor, R S; Akerele, J O; Aigbavboa, S O

1997-06-01

Ofloxacin pharmacokinetics have been studied in four healthy subjects after a single oral or rectal dose, each of 200 mg. For the oral dose tmax was about 2 h, Cmax 1.96 +/- 0.56 micrograms/ml and AUC1-15 15.22 micrograms/ml.h. Two-phase elimination pharmacol kinetics were observed for the oral dose, t1/2 for the rapid elimination phase was 3.3 h and for the slow phase 10 h. With the rectal dose tmax was 6 h, Cmax 0.71 +/- 0.44 microgram/ml and AUC0-15 7.58 micrograms/ml.h. The relative rectal bioavailability (AUC rectal/AUC oral) was 49.8%. Elimination rate of the rectal dose was generally slow (t1/2 = 9 h), an observation attributable to the sustained-release effect of the rectal suppository base, PEG 6000. The indication is that the rectal formulation cannot be substituted totally for the oral without first increasing the rectal dose; the 200 mg suppository can however be employed as a follow-up therapy to the oral dose in certain situations.

Colorectal carcinoma: Ex vivo evaluation using 3-T high-spatial-resolution quantitative T2 mapping and its correlation with histopathologic findings.

PubMed

Yamada, Ichiro; Yoshino, Norio; Hikishima, Keigo; Miyasaka, Naoyuki; Yamauchi, Shinichi; Uetake, Hiroyuki; Yasuno, Masamichi; Saida, Yukihisa; Tateishi, Ukihide; Kobayashi, Daisuke; Eishi, Yoshinobu

2017-05-01

In this study, we aimed to evaluate the feasibility of determining the mural invasion depths of colorectal carcinomas using high-spatial-resolution (HSR) quantitative T2 mapping on a 3-T magnetic resonance (MR) scanner. Twenty colorectal specimens containing adenocarcinomas were imaged on a 3-T MR system equipped with a 4-channel phased-array surface coil. HSR quantitative T2 maps were acquired using a spin-echo sequence with a repetition time/echo time of 7650/22.6-361.6ms (16 echoes), 87×43.5-mm field of view, 2-mm section thickness, 448×224 matrix, and average of 1. HSR fast-spin-echo T2-weighted images were also acquired. Differences between the T2 values (ms) of the tumor tissue, colorectal wall layers, and fibrosis were measured, and the MR images and histopathologic findings were compared. In all specimens (20/20, 100%), the HSR quantitative T2 maps clearly depicted an 8-layer normal colorectal wall in which the T2 values of each layer differed from those of the adjacent layer(s) (P<0.001). Using this technique, fibrosis (73.6±9.4ms) and tumor tissue (104.2±6.4ms) could also be clearly differentiated (P<0.001). In 19 samples (95%), the HSR quantitative T2 maps and histopathologic data yielded the same findings regarding the tumor invasion depth. Our results indicate that 3-T HSR quantitative T2 mapping is useful for distinguishing colorectal wall layers and differentiating tumor and fibrotic tissues. Accordingly, this technique could be used to determine mural invasion by colorectal carcinomas with a high level of accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status.

PubMed

Strassburg, Joachim; Junginger, Theo; Trinh, Trong; Püttcher, Olaf; Oberholzer, Katja; Heald, Richard J; Hermanek, Paul

2008-11-01

Is it possible to reduce the frequency of neoadjuvant therapy for rectal carcinoma and nevertheless achieve a rate of more than 90% circumferential resection margin (CRM)-negative resection specimens by a novel concept of magnetic resonance imaging (MRI)-based therapy planning? One hundred eighty-one patients from Berlin and Mainz, Germany, with primary rectal carcinoma, without distant metastasis, underwent radical surgery with curative intention. Surgical procedures applied were anterior resection with total mesorectal excision (TME) or partial mesorectal excision (PME; PME for tumours of the upper rectum) or abdominoperineal excision with TME. With MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62 of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170 of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was CRM-positive. Patients selected for primary surgery had CRM-negative specimens on histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a lower rate of clear margin: 56 of 62 (90%). By applying a MRI-based indication, the frequency of neoadjuvant treatment with its acute and late adverse effects can be reduced to 30-35% without reduction of pathologically CRM-negative resection specimens and, thus, without the danger of worsening the oncological long-term results. This concept should be confirmed in prospective multicentre observation studies with quality assurance of MRI, surgery and pathology.

Growth hormone 1 (GH1) gene and performance and post‐race rectal temperature during the South African Ironman triathlon

PubMed Central

Walpole, B; Noakes, T D; Collins, M

2006-01-01

Background Some studies have suggested that the insertion allele of the ACE gene is associated with endurance performance, including the Ironman triathlon. It is possible that this association is due to genetic linkage between the ACE I/D locus and the T/A variant in intron 4 of the neighbouring GH1 gene. The A variant is associated with lower levels of growth hormone production. Growth hormone has multiple effects, especially on metabolism during exercise and recovery from exercise. Its production during exercise has also been shown to stimulate sweat rate and heat loss. Objective To determine whether the GH1 gene is associated with the performance and/or post‐race rectal temperatures of competitors in the South African Ironman triathlon. Methods A total of 169 of the fastest finishing white male triathletes who completed the 2000 and/or 2001 South African Ironman triathlon and 155 control subjects were genotyped for the T/A variant in the GH1 gene. Post‐race rectal temperature was also determined in 103 of these triathletes. Results There was no significant difference in the frequency of this polymorphism in the GH1 gene when the fastest finishing triathletes were compared with the control subjects. Post‐race rectal temperatures were, however, significantly higher in those triathletes with an AA genotype (mean (SD) 37.7 (0.8)°C) compared with those with a TT genotype (37.2 (0.8)°C) (p  =  0.019). Conclusions The T/A polymorphism in intron 4 of the GH1 gene was not associated with performance of the fastest finishers of the South African Ironman triathlon. Post‐race rectal temperatures were, however, significantly higher in the fastest finishing athletes, who were homozygous for a GH1 genotype associated with lower growth hormone production. PMID:16432002

Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

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

Peterson, Jennifer L., E-mail: peterson.jennifer2@mayo.edu; Buskirk, Steven J.; Heckman, Michael G.

2014-04-01

Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminologymore » Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.« less

[Parametrial infiltration of cervix carcinoma: diagnostic value of contrast-enhanced fat-suppressed T1-weighted SE sequences at 1.5 tesla].

PubMed

Scheidler, J; Heuck, A; Wencke, K; Kimmig, R; Müller-Lisse, U; Reiser, M

1997-04-01

To determine whether contrast-enhanced and fat-suppressed sequences contribute to the MR imaging diagnosis of parametrial invasion. 21 patients with carcinoma of the cervix were prospectively examined with a phased-array coil and a 1.5T MR-scanner using the following sequences: transverse T2-weighted turbo spin echo (T2-TSE), T1-weighted spin echo (T1-SE) and fat suppressed T1-weighted SE sequences before and after Gd-DTPA. The sequences were evaluated separately for the presence of parametrial invasion. Image quality and diagnostic confidence were classified on a scale of 0-10 (nondiagnostic-excellent). Findings were compared to the results of the pathohistological examination. Sensitivity, specificity and diagnostic accuracy were highest for T2-TSE sequences (100%, 79% and 86%, respectively). Contrast-enhanced T1-SE sequences with fat-suppression (71%, 79%, and 76%) showed no improvement compared to T2-TSE. Unenhanced fat-suppressed T1-SE (100%, 30%, and 56%) and unenhanced T1-SE (100%, 7%, and 38%) as well as contrast-enhanced T1-SE (86%, 20%, and 47%) were significantly worse than T2-TSE. With similar image quality (p < 0.05) diagnostic confidence was higher on T2-TSE than on any of the other sequences (p < 0.001). Considering the cost-effectiveness of the examination, for the MR diagnosis of parametrial invasion the use of fat-suppressed contrast-enhanced sequences can be abandoned in favour of T2-weighted TSE sequences.

Free-breathing diffusion-weighted single-shot echo-planar MR imaging using parallel imaging (GRAPPA 2) and high b value for the detection of primary rectal adenocarcinoma.

PubMed

Soyer, Philippe; Lagadec, Matthieu; Sirol, Marc; Dray, Xavier; Duchat, Florent; Vignaud, Alexandre; Fargeaudou, Yann; Placé, Vinciane; Gault, Valérie; Hamzi, Lounis; Pocard, Marc; Boudiaf, Mourad

2010-02-11

Our objective was to determine the diagnostic accuracy of a free-breathing diffusion-weighted single-shot echo-planar magnetic resonance imaging (FBDW-SSEPI) technique with parallel imaging and high diffusion factor value (b = 1000 s/mm2) in the detection of primary rectal adenocarcinomas. Thirty-one patients (14M and 17F; mean age 67 years) with histopathologically proven primary rectal adenocarcinomas and 31 patients without rectal malignancies (14M and 17F; mean age 63.6 years) were examined with FBDW-SSEPI (repetition time (TR/echo time (TE) 3900/91 ms, gradient strength 45 mT/m, acquisition time 2 min) at 1.5 T using generalized autocalibrating partially parallel acquisitions (GRAPPA, acceleration factor 2) and a b value of 1000 s/mm2. Apparent diffusion coefficients (ADCs) of rectal adenocarcinomas and normal rectal wall were measured. FBDW-SSEPI images were evaluated for tumour detection by 2 readers. Sensitivity, specificity, accuracy and Youden score for rectal adenocarcinoma detection were calculated with their 95% confidence intervals (CI) for ADC value measurement and visual image analysis. Rectal adenocarcinomas had significantly lower ADCs (mean 1.036 x 10(-3)+/- 0.107 x 10(-3) mm2/s; median 1.015 x 10(-3) mm2/s; range (0.827-1.239) x 10(-3) mm2/s) compared with the rectal wall of control subjects (mean 1.387 x 10(-3)+/- 0.106 x 10(-3) mm2/s; median 1.385 x 10(-3) mm2/s; range (1.176-1.612) x 10(-3) mm2/s) (p < 0.0001). Using a threshold value < or = 1.240 x 10(-3) mm2/s, all rectal adenocarcinomas were correctly categorized and 100% sensitivity (31/31; 95% CI 95-100%), 94% specificity (31/33; 95% CI 88-100%), 97% accuracy (60/62; 95% CI 92-100%) and Youden index 0.94 were obtained for the diagnosis of rectal adenocarcinoma. FBDW-SSEPI image analysis allowed depiction of all rectal adenocarcinomas but resulted in 2 false-positive findings, yielding 100% sensitivity (31/31; 95% CI 95-100%), 94% specificity (31/33; 95% CI 88-100%), 97% accuracy (60

Application value of biplane transrectal ultrasonography plus ultrasonic elastosonography and contrast-enhanced ultrasonography in preoperative T staging after neoadjuvant chemoradiotherapy for rectal cancer.

PubMed

Xiao, Ying; Xu, Dong; Ju, Haixing; Yang, Chen; Wang, Liping; Wang, Jinming; Hazle, John D; Wang, Dongguo

2018-07-01

To determine the accuracy of biplane transrectal ultrasonography (TRUS) plus ultrasonic elastosonography (UE) and contrast-enhanced ultrasonography (CEUS) in preoperative T staging after neoadjuvant chemoradiotherapy for rectal cancer. Fifty-three patients with advanced lower rectal cancer were examined before and after neoadjuvant chemoradiotherapy with use of TRUS plus UE and CEUS and were diagnosed as having T stage disease. We compared ultrasonic T stages before and after neoadjuvant chemoradiotherapy and analyzed any changes. Also, with postoperative pathological stages as the gold standard, we compared ultrasonic and pathological T stages and determined their consistency by the kappa statistic. For patients with rectal cancer, ultrasonic T stages were lower after neoadjuvant chemoradiotherapy than before, with a statistically significant difference (P < 0.05). The posttreatment downstaging rate was 39.6% (21/53). A total of 84.9% received correct staging with use of biplane TRUS plus UE and CEUS in the evaluation of preoperative T staging after neoadjuvant chemoradiotherapy for rectal cancer, which was highly consistent with that of pathological staging (κ = 0.768, P < 0.05). Its sensitivities were 80.0%, 50.0%, 75.0%, 96.3%, and 100% in the diagnoses of stages T0 to T4 rectal cancers, respectively; the specificities were 95.4%, 97.9%, 95.1%, 88.5%, and 100% at stages T0 to T4, respectively. Biplane TRUS plus UE and CEUS can be used to accurately perform preoperative T staging in rectal cancer after neoadjuvant chemoradiotherapy; in addition, this procedure well reflects changes in depth of rectal cancer invasion into the intestinal wall before and after neoadjuvant chemoradiotherapy. It is of great value in clinically evaluating the efficacy of neoadjuvant chemoradiotherapy, in selecting therapeutic regimens, and in avoiding overtreatment. Copyright © 2018 Elsevier B.V. All rights reserved.

T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

PubMed Central

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-01-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. PMID:24890382

Preoperative neo-adjuvant therapy for curable rectal cancer--reaching a consensus 2008.

PubMed

Scott, N A; Susnerwala, S; Gollins, S; Myint, A Sun; Levine, E

2009-03-01

Our aim was to determine the range of neo-adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M(0)) rectal cancer. A senior oncologist from each of the four oncology centres in north Wales and the north-west of England (approximate target population 8 million - Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her understanding of the current evidence of neo-adjuvant therapy in rectal cancer. Then a representative from each centre was asked to identify which of three neo-adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions and long-course chemoradiotherapy) he/she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by magnetic resonance imaging as being T(2)-T(4) and/or N(0)-N(2). In all cases of locally advanced rectal cancer (T(3a) N(1)-T(4)), oncologists from the four oncology centres recommended long-course chemoradiotherapy before rectal resection. This consensus was maintained for cases of lower third T(3a) N(0) cancers. Thereafter, the majority of patients with rectal cancer are offered adjuvant short-course radiotherapy. Neo-adjuvant therapy is less likely to be offered if the tumour is early (T(2), N(0)) and/or situated in the upper third of the rectum.

Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

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

Mohiuddin, Mohammed, E-mail: asemuddin@gmail.com; Paulus, Rebecca; Mitchell, Edith

2013-07-01

Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m{sup 2} per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m{sup 2} per day, Monday to Friday, plus irinotecan, 50 mg/m{sup 2} once weeklymore » × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.« less

Obtaining T1-T2 distribution functions from 1-dimensional T1 and T2 measurements: The pseudo 2-D relaxation model

NASA Astrophysics Data System (ADS)

Williamson, Nathan H.; Röding, Magnus; Galvosas, Petrik; Miklavcic, Stanley J.; Nydén, Magnus

2016-08-01

We present the pseudo 2-D relaxation model (P2DRM), a method to estimate multidimensional probability distributions of material parameters from independent 1-D measurements. We illustrate its use on 1-D T1 and T2 relaxation measurements of saturated rock and evaluate it on both simulated and experimental T1-T2 correlation measurement data sets. Results were in excellent agreement with the actual, known 2-D distribution in the case of the simulated data set. In both the simulated and experimental case, the functional relationships between T1 and T2 were in good agreement with the T1-T2 correlation maps from the 2-D inverse Laplace transform of the full 2-D data sets. When a 1-D CPMG experiment is combined with a rapid T1 measurement, the P2DRM provides a double-shot method for obtaining a T1-T2 relationship, with significantly decreased experimental time in comparison to the full T1-T2 correlation measurement.

The Molecular Basis of Rectal Cancer

PubMed Central

Shiller, Michelle; Boostrom, Sarah

2015-01-01

The majority of rectal carcinomas are sporadic in nature, and relevant testing for driver mutations to guide therapy is important. A thorough family history is necessary and helpful in elucidating a potential hereditary predilection for a patient's carcinoma. The adequate diagnosis of a heritable tendency toward colorectal carcinoma alters the management of a patient disease and permits the implementation of various surveillance algorithms as preventive measures. PMID:25733974

Preoperative detection of malignant liver tumors: Comparison of 3D-T2-weighted sequences with T2-weighted turbo spin-echo and single shot T2 at 1.5 T.

PubMed

Barat, Maxime; Soyer, Philippe; Dautry, Raphael; Pocard, Marc; Lo-Dico, Rea; Najah, Haythem; Eveno, Clarisse; Cassinotto, Christophe; Dohan, Anthony

2018-03-01

To assess the performances of three-dimensional (3D)-T2-weighted sequences compared to standard T2-weighted turbo spin echo (T2-TSE), T2-half-Fourier acquisition single-shot turbo spin-echo (T2-HASTE), diffusion weighted imaging (DWI) and 3D-T1-weighted VIBE sequences in the preoperative detection of malignant liver tumors. From 2012 to 2015, all patients of our institution undergoing magnetic resonance imaging (MRI) examination for suspected malignant liver tumors were prospectively included. Patients had contrast-enhanced 3D-T1-weighted, DWI, 3D-T2-SPACE, T2-HASTE and T2-TSE sequences. Imaging findings were compared with those obtained at follow-up, surgery and histopathological analysis. Sensitivities for the detection of malignant liver tumors were compared for each sequence using McNemar test. A subgroup analysis was conducted for HCCs. Image artifacts were analyzed and compared using Wilcoxon paired signed rank-test. Thirty-three patients were included: 13 patients had 40 hepatocellular carcinomas (HCC) and 20 had 54 liver metastases. 3D-T2-weighted sequences had a higher sensitivity than T2-weighted TSE sequences for the detection of malignant liver tumors (79.8% versus 68.1%; P < 0.001). The difference did not reach significance for HCC. T1-weighted VIBE and DWI had a higher sensitivity than T2-weighted sequences. 3D-T2-weighted-SPACE sequences showed significantly less artifacts than T2-weitghted TSE. 3D-T2-weighted sequences show very promising performances for the detection of liver malignant tumors compared to T2-weighted TSE sequences. Copyright © 2018 Elsevier B.V. All rights reserved.

Pediatric renal cell carcinomas with Xp11.2 rearrangements are immunoreactive for hMLH1 and hMSH2 proteins.

PubMed

Rakheja, Dinesh; Kapur, Payal; Tomlinson, Gail E; Margraf, Linda R

2005-01-01

Alveolar soft part sarcoma and pediatric renal cell carcinoma share a similar chromosomal abnormality, t(X;17)(p11.2;q25). Recently, it has been suggested that the inactivation of DNA mismatch repair genes hMLH1 and hMSH2 may play an additional role in the pathogenesis of alveolar soft part sarcoma. Immunohistochemical expression of the proteins hMLH1 and hMSH2 is indicative of the activation status of the corresponding genes. We performed immunohistochemistry for hMLH1 and hMSH2 in 4 cases of pediatric renal cell carcinomas with Xp11.2 rearrangements. All cases showed nuclear immunoreactivity for both proteins, although the staining was patchy. Our study demonstrates that inactivation of the DNA mismatch repair genes hMLH1 and hMSH2 does not appear to play a role in the tumorigenesis of pediatric renal cell carcinomas with Xp11.2 rearrangements.

T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

PubMed

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-10-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients

PubMed Central

Napolitano, Maria; D'Alterio, Crescenzo; Cardone, Eleonora; Trotta, Anna Maria; Pecori, Biagio; Rega, Daniela; Pace, Ugo; Scala, Dario; Scognamiglio, Giosuè; Tatangelo, Fabiana; Cacciapuoti, Carmela; Pacelli, Roberto; Delrio, Paolo; Scala, Stefania

2015-01-01

Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN−/HLA-DR−/CD11b+/CD14−/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR−/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD). Peripheral MDSC and Tregs were evaluated at time 0 (T0), after 2 and 5 weeks (T2-T5) from radiotherapy; before surgery (T8) and 6–12 months after surgery (T9, T10). G-MDSC decreased at T5 and further at T8 while M-MDSC cells decreased at T5; Tregs reached the lowest value at T5. LARC poor responder patients displayed a major decrease in M-MDSC after SC-RT and an increase of Treg-PD-1. In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients. Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5–8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT. PMID:25823653

Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

PubMed Central

Stitzenberg, Karyn B.; Sanoff, Hanna K.; Penn, Dolly C.; Meyers, Michael O.; Tepper, Joel E.

2013-01-01

Purpose Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. Methods All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. Results LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Conclusion Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE. PMID:24166526

Practice patterns and long-term survival for early-stage rectal cancer.

PubMed

Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

2013-12-01

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

PubMed Central

Zaporowska-Stachowiak, Iwona; Kowalski, Grzegorz; Łuczak, Jacek; Kosicka, Katarzyna; Kotlinska-Lemieszek, Aleksandra; Sopata, Maciej; Główka, Franciszek

2014-01-01

slower after rectal than after intrathecal administration (t½= 5.50 versus 2.02 hours, respectively). Limitations This study reports two cases only, and there could be inter-patient variation. Conclusion Bupivacaine in boluses administered intrathecally (0.25%, 2 mL) provided effective, safe analgesia in advanced cancer patients. Bupivacaine enema (100 mg·100 mL−1) was shown to be a valuable option for control of end-of-life tenesmoid cancer pain. PMID:25336967

The Role of Transanal Surgery in the Management of T1 Rectal Cancers.

PubMed

Hassan, Imran; Wise, Paul E; Margolin, David A; Fleshman, James W

2015-09-01

The management of T1 rectal cancers is based on finding the balance between optimal oncologic outcomes and acceptable functional results for the patient. While radical resection involving a proctectomy is considered the most oncologically adequate option, its adverse effects on patient reported outcomes makes this a less than ideal choice in certain circumstances. While local excision can circumvent some of the adverse functional outcomes, its inadequacy in assessing metastatic lymph node disease and the subsequent negative impact of untreated positive lymph nodes on patient prognosis is a cause for concern. As a result, the therapeutic strategy has to be based on patient and disease-related factors in order to identify the best treatment choice that maximizes survival benefit and preserves health-related quality of life. After adequate preoperative staging work up, in selected patients with favorable pathological features, local excision can be considered. These cancers can be removed by transanal local excision or transanal endoscopic microsurgery, depending on the location of the cancer and expertise available. While perioperative morbidity is minimal, close postoperative follow-up is essential.

Protein phosphatase 2A (PP2A) inhibitor CIP2A indicates resistance to radiotherapy in rectal cancer.

PubMed

Birkman, Eva-Maria; Elzagheid, Adam; Jokilehto, Terhi; Avoranta, Tuulia; Korkeila, Eija; Kulmala, Jarmo; Syrjänen, Kari; Westermarck, Jukka; Sundström, Jari

2018-03-01

Preoperative (chemo)radiotherapy, (C)RT, is an essential part of the treatment of rectal cancer patients, but tumor response to this therapy among patients is variable. Thus far, there are no clinical biomarkers that could be used to predict response to (C)RT or to stratify patients into different preoperative treatment groups according to their prognosis. Overexpression of cancerous inhibitor of protein phosphatase 2A (CIP2A) has been demonstrated in several cancers and is frequently associated with reduced survival. Recently, high CIP2A expression has also been indicated to contribute to radioresistance in head and neck squamous cell carcinoma, but few studies have examined the connection between CIP2A and radiation response regarding other malignancies. We have evaluated CIP2A protein expression levels in relation to tumor regression after preoperative (C)RT and survival of rectal adenocarcinoma patients. The effects of CIP2A knockdown by siRNA on cell survival were further investigated in colorectal cancer cells exposed to radiation. Patients with low-CIP2A-expressing tumors had more frequently moderate or excellent response to long-course (C)RT than patients with high-CIP2A-expressing tumors. They also had higher 36-month disease-specific survival (DSS) rate in categorical analysis. In the multivariate analysis, low CIP2A expression level remained as an independent predictive factor for increased DSS. Suppression of CIP2A transcription by siRNA was found to sensitize colorectal cancer cells to irradiation and decrease their survival in vitro. In conclusion, these results suggest that by contributing to radiosensitivity of cancer cells, low CIP2A protein expression level associates with a favorable response to long-course (C)RT in rectal cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Ghrelin inhibits proliferation and increases T-type Ca{sup 2+} channel expression in PC-3 human prostate carcinoma cells

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

Diaz-Lezama, Nundehui; Hernandez-Elvira, Mariana; Sandoval, Alejandro

Research highlights: {yields} Ghrelin decreases prostate carcinoma PC-3 cells proliferation. {yields} Ghrelin favors apoptosis in PC-3 cells. {yields} Ghrelin increase in intracellular free Ca{sup 2+} levels in PC-3 cells. {yields} Grelin up-regulates expression of T-type Ca{sup 2+} channels in PC-3 cells. {yields} PC-3 cells express T-channels of the Ca{sub V}3.1 and Ca{sub V}3.2 subtype. -- Abstract: Ghrelin is a multifunctional peptide hormone with roles in growth hormone release, food intake and cell proliferation. With ghrelin now recognized as important in neoplastic processes, the aim of this report is to present findings from a series of in vitro studies evaluating themore » cellular mechanisms involved in ghrelin regulation of proliferation in the PC-3 human prostate carcinoma cells. The results showed that ghrelin significantly decreased proliferation and induced apoptosis. Consistent with a role in apoptosis, an increase in intracellular free Ca{sup 2+} levels was observed in the ghrelin-treated cells, which was accompanied by up-regulated expression of T-type voltage-gated Ca{sup 2+} channels. Interestingly, T-channel antagonists were able to prevent the effects of ghrelin on cell proliferation. These results suggest that ghrelin inhibits proliferation and may promote apoptosis by regulating T-type Ca{sup 2+} channel expression.« less

[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.

Breast cancer detection using double reading of unenhanced MRI including T1-weighted, T2-weighted STIR, and diffusion-weighted imaging: a proof of concept study.

PubMed

Trimboli, Rubina M; Verardi, Nicola; Cartia, Francesco; Carbonaro, Luca A; Sardanelli, Francesco

2014-09-01

The purpose of this study was to investigate the diagnostic performance of unenhanced MRI in detecting breast cancer and to assess the impact of double reading. A total of 116 breasts of 67 women who were 36-89 years old were studied at 1.5 T using an unenhanced protocol including axial T1-weighted gradient-echo, T2-weighted STIR, and echo-planar diffusion-weighted imaging (DWI). Two blinded readers (R1 and R2) independently evaluated unenhanced images using the BIRADS scale. A combination of pathology and negative follow-up served as the reference standard. McNemar and kappa statistics were used. Per-breast cancer prevalence was 37 of 116 (32%): 30 of 37 (81%) invasive ductal carcinoma, five of 37 (13%) ductal carcinoma in situ, and two of 37 (6%) invasive lobular carcinoma. Per-breast sensitivity of unenhanced MRI was 29 of 37 (78%) for R1, 28 of 37 (76%) for R2, and 29 of 37 (78%) for double reading. Specificity was 71 of 79 (90%) for both R1 and R2 and 69 of 79 (87%) for double reading. Double reading did not provide a significant increase in sensitivity. Interobserver agreement was almost perfect (Cohen κ = 0.873). An unenhanced breast MRI protocol composed of T1-weighted gradient echo, T2-weighted STIR, and echo-planar DWI enabled breast cancer detection with sensitivity of 76-78% and specificity of 90% without a gain in sensitivity from double reading.

Case-matched study of short-term effects of 3D vs 2D laparoscopic radical resection of rectal cancer.

PubMed

Zeng, QingMin; Lei, Fuming; Gao, ZhaoYa; Wang, YanZhao; Gao, Qing Kun

2017-09-22

The purpose of this study is to compare and evaluate the security and efficacy of 3D vs 2D laparoscopy in rectal cancer treatment. Forty-six patients who suffered from rectal cancer and went on laparoscopic radical resection of rectal carcinoma in Peking University Shougang Hospital from Feb. 2015 to Mar. 2016 were included in the study. They were randomly divided into two groups. The 23 patients operated with the 3D system were compared with 23 patients operated with the 2D system by perioperative data. There were no significant differences in age, sex, pathological type, tumor differentiation, TNM staging, and surgical procedures (P > 0.05). The average operating time of 3D laparoscopic surgery group (172.2 ± 27.5 min) was shorter than that of 2D group (192.6 ± 22.3) (P < 0.05); the rate of transfer to laparotomy is lower in 2D group (72.7%) than in 3D group (86.4%), but they have no significant difference; and the intraoperative blood loss (247.0 ± 173.6 ml vs 282.6 ± 195.6 ml), postoperative passage of flatus (2.8 ± 0.8 days vs 3.1 ± 1.0 days), and indwelling catheter time (5.6 ± 1.9 days vs 6.3 ± 2.0 days) in 3D group and 2D group (P > 0.05) were not significantly different. There were no differences in other complications between the two groups. No significantly different recrudescence and death rates were found between the two groups (P > 0.05). The 3D laparoscopy shortens the operation time of rectum cancer. 3D laparoscopic surgery is more efficient in treatment of rectal cancer than 2D laparoscopy and is worth of being generalized.

Expression of cyclooxygenase-1 and -2 in canine nasal carcinomas.

PubMed

Borzacchiello, G; Paciello, O; Papparella, S

2004-07-01

Cyclooxygenase-1 (COX-1) and cyclooxygenase -2 (COX-2) are known to play a role in the carcinogenesis of many human and animal primary epithelial tumours. However, expression of COX-1 and -2 has not been investigated in canine nasal epithelial carcinoma, a rare form of neoplasia. COX-1 immunolabelling was demonstrated in normal canine nasal mucosa and in a minority of neoplastic specimens. Cytoplasmic COX-2, however, was strongly expressed in the majority of canine nasal carcinomas. In addition, COX-2 expression was demonstrated in dysplastic epithelium and in a proportion of stromal cells. Co-expression of both enzyme isoforms was revealed by confocal laser scanning microscopy. The results indicate that COX-2 is overexpressed in a proportion of naturally occurring canine nasal carcinomas, suggesting its possible role in canine nasal tumorigenesis. Copyright 2004 Elsevier Ltd.

[Expression and correlation of Fra-1 and HMGA1 in laryngeal squamous cell carcinoma].

PubMed

Zhang, Y L; Song, X F; Duan, Y J; Zhao, R L

2017-12-07

Objective: To investigate the expressions of Fra -1 and HMGA 1 in laryngeal squamous cell carcinoma and their correlation . Methods: Immunohistochemistry and reverse transcription-polymer chain reaction (RT-PCR) were used to detect the expressions of HMGA 1 and Fra -1 in laryngeal squamous carcinoma tissues in 47 cases and para - carcinoma tissues in 21 cases ( the First Hospital of Shijiazhuang ). The relationship between the gene expressions in carcinoma tissues and clinopathological parameters such as pathological grade, clinical stage, lymph metastasis, age and anatomic site and the relevance of the two gene expressions were analyzed . SPSS 13.0 software was used to analyze the data . Results: The positive expression rates of Fra-1 and HMGA1 proteins in laryngeal squamous cancer tissue were 48.9% and 53.2%, which were respectively higher than the rates of 19.0% for Fra-1 (χ(2)=5.416, P <0.05) and of 23.8% for HMGA1 (χ(2)=5.083, P <0.05) in adjacent tissues. The expression of Fra -1 gene was correlation with pathological grade, clinical stage and lymph metastasis (t values were -1.079, -1.066 and -1.067, all P<0.05), but not with age and anatomic site (t values were -1.068 and -1.054, both P>0.05). The expression of HMGA 1 gene was correlation with pathological grade, clinical stage, lymph metastasis and age (t values were -1.112, -1.065, -1.009 and -1.066, all P<0.05), but not with anatomic site (t=-1.036, P>0.05). The expressions of Fra -1 and HMGA 1 gene were positively correlation (r=0.672, P<0.05). Conclusions: In laryngeal squamous cancer, Fra -1 and HMGA 1 are excessive expression, with a positive correlation between the expressions of both genes .

Renaissance of contact x-ray therapy for treating rectal cancer.

PubMed

Gérard, Jean-Pierre; Myint, Arthur Sun; Croce, Olivier; Lindegaard, Jacob; Jensen, Anie; Myerson, Robert; Hannoun-Lévi, Jean-Michel; Marcie, Serge

2011-07-01

Contact x-ray therapy (CXRT) with 50 kV has proven to be an efficient radiation therapy technique to achieve local control and rectal preservation for early rectal adenocarcinoma. Despite these results, CXRT has not been used due to the shortage of the no longer manufactured Philips RT 50™ unit. Recently, a new CXRT machine (Papillon 50™) became available on the market. This machine delivers a beam of 50 kV with a dose rate close to 15 Gy/min and has a percentage depth dose of 50% at 6-7 mm. The applicator size varies from 2-3 cm in diameter. Due to the original design of the main tube, treatment delivery is quick and more comfortable for the patients. An online viewing system incorporated in the tube allows a good visualization of the tumor with improved accuracy of radiation delivery. An international collaborative trial (Contact Endoscopic Microsurgery [CONTEM]) was set up to accrue approximately 300 cases of rectal adenocarcinoma staged T1, T2 or early T3 tumors in the UK, France, Denmark and Sweden. This trial should confirm the role of CXRT in curative treatment with organ preservation for early rectal cancers.

Polyethylene glycol hydrogel rectal spacer implantation in patients with prostate cancer undergoing combination high-dose-rate brachytherapy and external beam radiotherapy.

PubMed

Yeh, Jekwon; Lehrich, Brandon; Tran, Carolyn; Mesa, Albert; Baghdassarian, Ruben; Yoshida, Jeffrey; Torrey, Robert; Gazzaniga, Michael; Weinberg, Alan; Chalfin, Stuart; Ravera, John; Tokita, Kenneth

2016-01-01

To present rectal toxicity rates in patients administered a polyethylene glycol (PEG) hydrogel rectal spacer in conjunction with combination high-dose-rate brachytherapy and external beam radiotherapy. Between February 2010 and April 2015, 326 prostate carcinoma patients underwent combination high-dose-rate brachytherapy of 16 Gy (average dose 15.5 Gy; standard deviation [SD] = 1.6 Gy) and external beam radiotherapy of 59.4 Gy (average dose 60.2 Gy; SD = 2.9 Gy). In conjunction with the radiation therapy regimen, each patient was injected with 10 mL of a PEG hydrogel in the anterior perirectal fat space. The injectable spacer (rectal spacer) creates a gap between the prostate and the rectum. The rectum is displaced from the radiation field, and rectal dose is substantially reduced. The goal is a reduction in rectal radiation toxicity. Clinical efficacy was determined by measuring acute and chronic rectal toxicity using the National Cancer Center Institute Common Terminology Criteria for Adverse Events v4.0 grading scheme. Median followup was 16 months. The mean anterior-posterior separation achieved was 1.6 cm (SD = 0.4 cm). Rates of acute Grade 1 and 2 rectal toxicity were 37.4% and 2.8%, respectively. There were no acute Grade 3/4 toxicities. Rates of late Grade 1, 2, and 3 rectal toxicity were 12.7%, 1.4%, and 0.7%, respectively. There were no late Grade 4 toxicities. PEG rectal spacer implantation is safe and well tolerated. Acute and chronic rectal toxicities are low despite aggressive dose escalation. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Is there a role for neck dissection in T1 oral tongue squamous cell carcinoma? The UCLA experience.

PubMed

Peng, Kevin A; Chu, Alan C; Lai, Chi; Grogan, Tristan; Elashoff, David; Abemayor, Elliot; St John, Maie A

2014-01-01

We sought to examine prognostic and therapeutic implications, including cost-effectiveness, of elective neck dissection in the management of patients with clinically-determined T1N0 oral tongue carcinoma. A retrospective review of patients with cT1N0 oral tongue squamous cell carcinoma who underwent surgical extirpation of primary tumor, with or without elective neck dissection, at UCLA Medical Center from 1990 to 2009 was performed. Cox proportional hazards regression was used to assess effects of variables on time to first loco-regional recurrence. A healthcare costs analysis of elective neck dissection was performed by querying the SEER-Medicare linked database. Of the 123 patients identified with cT1N0 squamous cell carcinoma of the oral tongue, 88 underwent elective neck dissection at the time of tumor resection while 35 did not. For all patients, disease-free survival at 3, 5, and 10 years was 93%, 82%, and 79%. Of the 88 patients undergoing elective neck dissection, 20 (23%) demonstrated occult metastatic disease. Male gender, tumor size, perineural invasion, and occult metastatic disease were individually associated with higher rates of loco-regional recurrence. There was no significant difference in loco-regional recurrence between those who underwent elective neck dissection and those who did not (HR=0.76, p=0.52). On cost analysis, neck dissection was not associated with any significant difference in Medicare payments. The high rate of occult metastasis (23%) following elective neck dissection, which did not confer additional healthcare costs, leads to the recommendation of elective neck dissection in patients with cT1N0 oral tongue squamous cell carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

PubMed

Tharavichtikul, Ekkasit; Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-06-01

To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University

PubMed Central

Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-01-01

Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale. PMID:25061573

The novel WHO 2010 classification for gastrointestinal neuroendocrine tumours correlates well with the metastatic potential of rectal neuroendocrine tumours.

PubMed

Jernman, Juha; Välimäki, Matti J; Louhimo, Johanna; Haglund, Caj; Arola, Johanna

2012-01-01

Approximately 10-15% of gastroenteropancreatic neuroendocrine tumours (NETs, carcinoids) occur in the rectum, some of which are potentially able to metastasize. The new WHO 2010 classification of NETs applies to all gastroenteropancreatic NETs, but no reports have studied its correlation with the prognosis of rectal NETs. We retrospectively classified 73 rectal NETs according to the novel WHO 2010 and the previous WHO 2000 classifications. The aim was to assess the validity of the classifications in distinguishing indolent rectal NETs from metastasising tumours. Using the WHO 2010 criteria, we identified 61 G1 tumours, none of which had metastasised during follow-up. Of 11 G2 tumours, 9 had shown distant metastases. The only G3 neuroendocrine carcinoma that occurred had been disseminated at initial presentation. Our results show that rectal NETs classified as G1 according to the WHO 2010 classification have an indolent clinical course, whereas G2 NETs often metastasise. The WHO 2010 classification of NETs predicts the metastatic potential of rectal NETs better than the WHO 2000 classification. Copyright © 2011 S. Karger AG, Basel.

Hepatocellular carcinomas of the albumin SV40 T-antigen transgenic rat display fetal-like re-expression of lgf2 and deregulation of H19.

PubMed

Czarny, Matthew J; Babcock, Karlee; Baus, Rebecca M; Manoharan, Herbert; Pitot, Henry C

2007-09-01

Previous studies in our laboratory have shown that one of the earliest events during hepatocarcinogenesis in the albumin SV40 T antigen (Alb SV40 T Ag) transgenic rat is the duplication of chromosome 1q3.7-4.3, a region which contains the imprinted and coordinately regulated genes Igf2 and H19. We have also shown that this duplication is associated with the biallelic expression of the normally monoallelically-expressed H19. These results, however, are seemingly at odds with studies in the mouse that have shown a conservation of fetal regulatory patterns of these two genes in hepatic neoplasms. We therefore aimed in this study to determine the allelic origin of Igf2 expression in hepatocellular carcinomas of the Alb SV40 T Ag transgenic rat. Sprague-Dawley Alb SV40 T Ag transgenic rats and Brown Norway rats were reciprocally mated and the expression of Igf2 in hepatocellular carcinomas of the resulting F(1) transgene-positive female rats was analyzed by Northern blotting and RT-PCR. We determined that Igf2 was expressed exclusively from the paternal allele, which prompted the study (by the same methods) of the allelic origin of H19 in the same hepatocellular carcinomas in order to determine if the two genes remained coordinately regulated. Our results demonstrate fetal-like re-expression of Igf2 and deregulation of H19 in singular hepatocellular carcinomas of the rat. These results imply that another regulatory mechanism other than the generally accepted ICR/CTCF mechanism may play a role in the control of Igf2 and H19 expression. (c) 2007 Wiley-Liss, Inc.

Hilar location is an independent prognostic factor for recurrence in T1 renal cell carcinoma after nephrectomy.

PubMed

Shim, Myungsun; Song, Cheryn; Park, Sejun; Kim, Aram; Choi, Seung-Kwon; Kim, Choung-Soo; Ahn, Hanjong

2015-01-01

We investigated the prognostic significance of tumor location at the renal hilum near the sinus structure on the recurrence in T1 renal cell carcinoma (RCC). A total of 1,818 T1 RCC patients who underwent radical (RN) or partial nephrectomy (PN) from 1997 to 2011 were retrospectively reviewed. A hilar tumor was defined as a tumor abutting the main renal artery and/or vein or its segmental branches, without invasion. We compared the recurrence-free survival (RFS) rates between hilar and nonhilar T1 RCC and analyzed predictors of RFS after nephrectomy. Patients with hilar tumors showed a poorer 5-year RFS compared with nonhilar tumors both in T1a (89.7 vs. 98.5 %, p < 0.001) and T1b (81.6 vs. 95.1 %, p < 0.001) RCCs. Among patients who underwent RN and PN, hilar tumors were associated with lower 5-year RFS (87.6 vs. 97.2 % for RN, 78.1 vs. 98.2 % for PN, both p < 0.001). In T1a hilar tumor, PN was associated with poorer 5-year RFS than RN (79.5 vs. 93.0 %, p < 0.001). In multivariate analysis, a hilar location remained as an independent predictor of recurrence in both T1a and T1b tumors (both p = 0.001). Hilar tumors show a higher recurrence rate than nonhilar counterparts in T1 RCC. In T1a hilar tumors, PN demonstrated poorer RFS than RN. Potential intrinsic renal anatomical or lymphovascular structural differences as well as differences in cancer characteristics need further investigations.

Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

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

Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher

2014-07-01

Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% ofmore » patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.« less

Low Rectal Cancer Study (MERCURY II)

ClinicalTrials.gov

2016-03-11

Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

PTGS1, PTGS2, ALOX5, ALOX12, ALOX15, and FLAP SNPs: interaction with fatty acids in colon cancer and rectal cancer.

PubMed

Habermann, Nina; Ulrich, Cornelia M; Lundgreen, Abbie; Makar, Karen W; Poole, Elizabeth M; Caan, Bette; Kulmacz, Richard; Whitton, John; Galbraith, Rachel; Potter, John D; Slattery, Martha L

2013-01-01

Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated n-3 PUFA intakes from fish are associated with lower risk of colorectal cancer among those with genetic variants that result in higher levels of pro-inflammatory mediators. In population-based case-control studies of colon (case n = 1,574) and rectal cancer (case n = 791) and disease-free controls (n = 2,969), we investigated interactions between dietary fatty acid intake and 107 candidate polymorphisms and tagSNPs in PTGS1, PTGS2, ALOX12, ALOX5, ALOX15, and FLAP. The two studies used an identical genotyping protocol. We observed interactions and statistically significant increases in colon cancer risk for low docosahexaenoic acid intake among those with the PTGS1 rs10306110 (-1,053 A > G) variant genotypes (OR = 1.6, 95 % confidence interval = 1.1-2.3, adj. p = 0.06) and rectal cancer risk for low total fat intake among those with the variant PTGS1 rs10306122 (7,135 A > G) (OR(vs.wt) = 1.80, 1.02-2.99; adj. p = 0.08). The ALOX15 rs11568131 (10,339 C > T) wild type in combination with a high inflammation score (low EPA intake, high AA intake, no regular NSAID use, high BMI, smoking) was associated with increased colon cancer risk (OR = 2.28, 1.7-3.07). Rectal cancer risk was inversely associated with a low inflammation score among PTGS2 rs4648276 (3,934 T > C) variant allele carriers (OR = 0.49, 0.25-0.75). Overall, these data provide some modest evidence for interactions between dietary fat intake and genetic variation in genes involved in eicosanoid metabolism and colorectal cancer risk.

Randomized Trial of Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the Vocal Cord (RTOG 9512)

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

Trotti, Andy, E-mail: andy.trotti@moffitt.org; Zhang, Qiang; Bentzen, Søren M.

2014-08-01

Purpose: To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial. Methods and Materials: Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power. Results: Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239more » patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX. Conclusions: The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.« less

Transoral bisected resection for T1-2 oral tongue squamous cell carcinoma to secure adequate deep margin.

PubMed

Choi, Nayeon; Cho, Jae-Keun; Lee, Eun Kyu; Won, Sung Jun; Kim, Bo Young; Baek, Chung-Hwan

2017-10-01

To investigate the clinical usefulness of transoral bisected resection (TBR) asa new method to secure adequate deep resection margin in T1-2 oral tongue squamous cell carcinomas (SCC). Among 75 patients with cT1-2N0 oral tongue SCCs, 45 (60%) received transoral en-bloc resection (TER) while 30 (40%) received patients underwent TBR. Primary tumor resection was performed with 1.5-cm surgical resection margin for both groups. Mucosal and deep resection margins, adjuvant treatments including re-resection of the tongue and cheomoradiotherapy, local and regional recurrence free survival, and overall survival were compared between the two groups. Mean deep resection margin in the TBR group was 9.9mm (95% CI: 8.4-11.4mm), which was significantly (P<0.001) wider than that of the TER group (mean: 5.4mm, 95% CI: 4.5-6.3mm). However, mucosal resection margins were not significantly (P=0.153) different between the two groups. Re-resection of tongue was performed for 6 (13.3%) of 17 (37.8%) patients with inadequate deep resection margin in the TER group and none (0%) in 4 (13.3%) patients with inadequate deep resection margin in the TBR group. Adjuvant radiation due to inadequate deep resection margin was performed for 6.7% of patients in both groups. The TBR group had better local recurrence free survival than the TER group. However, regional recurrence free survival and overall survival were not significantly different between the two groups. TBR could provide adequate deep resection margin for early stage tongue cancers with better local tumor control than TER. It can decrease the necessity of adjuvant treatment for re-resection of the tongue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

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

Fogg, Mark; Murphy, John R.; Lorch, Jochen

Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, asmore » well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients.« less

MTN-017: A Rectal Phase 2 Extended Safety and Acceptability Study of Tenofovir Reduced-Glycerin 1% Gel

PubMed Central

Lama, Javier R.; Richardson, Barbra A.; Carballo-Diéguez, Alex; Kunjara Na Ayudhya, Ratiya Pamela; Liu, Karen; Patterson, Karen B.; Leu, Cheng-Shiun; Galaska, Beth; Jacobson, Cindy E.; Parikh, Urvi M.; Marzinke, Mark A.; Hendrix, Craig W.; Johnson, Sherri; Piper, Jeanna M.; Grossman, Cynthia; Ho, Ken S.; Lucas, Jonathan; Pickett, Jim; Bekker, Linda-Gail; Chariyalertsak, Suwat; Chitwarakorn, Anupong; Gonzales, Pedro; Holtz, Timothy H.; Liu, Albert Y.; Mayer, Kenneth H.; Zorrilla, Carmen; Schwartz, Jill L.; Rooney, James; McGowan, Ian

2017-01-01

Abstract Background. Human immunodeficiency virus (HIV) disproportionately affects men who have sex with men (MSM) and transgender women (TGW). Safe and acceptable topical HIV prevention methods that target the rectum are needed. Methods. MTN-017 was a phase 2, 3-period, randomized sequence, open-label, expanded safety and acceptability crossover study comparing rectally applied reduced-glycerin (RG) 1% tenofovir (TFV) and oral emtricitabine/TFV disoproxil fumarate (FTC/TDF). In each 8-week study period participants were randomized to RG-TFV rectal gel daily, or RG-TFV rectal gel before and after receptive anal intercourse (RAI; or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. Results. MSM and TGW (n = 195) were enrolled from 8 sites in the United States, Thailand, Peru, and South Africa with mean age of 31.1 years (range 18-64). There were no differences in ≥grade 2 adverse event rates between daily gel (incidence rate ratio [IRR], 1.09; P = .59) or RAI gel (IRR, 0.90; P = .51) compared to FTC/TDF. High adherence (≥80% of prescribed doses assessed by unused product return and Short Message System reports) was less likely in the daily gel regimen (odds ratio [OR], 0.35; P < .001), and participants reported less likelihood of future daily gel use for HIV protection compared to FTC/TDF (OR, 0.38; P < .001). Conclusions. Rectal application of RG TFV gel was safe in MSM and TGW. Adherence and product use likelihood were similar for the intermittent gel and daily oral FTC/TDF regimens, but lower for the daily gel regimen. Clinical Trials Registration: NCT01687218. PMID:27986684

Transanal total mesorectal excision: pathological results of 186 patients with mid and low rectal cancer.

PubMed

de Lacy, F Borja; van Laarhoven, Jacqueline J E M; Pena, Romina; Arroyave, María Clara; Bravo, Raquel; Cuatrecasas, Miriam; Lacy, Antonio M

2018-05-01

Transanal total mesorectal excision (TaTME) seems to be a valid alternative to the open or laparoscopic TME. Quality of the TME specimen is the most important prognostic factor in rectal cancer. This study shows the pathological results of the largest single-institution series published on TaTME in patients with mid and low rectal cancer. We conducted a retrospective cohort study of all consecutive patients with rectal cancer, treated by TaTME between November 2011 and June 2016. Patient data were prospectively included in a standardized database. Patients with all TNM stages of mid (5-10 cm from the anal verge) and low (0-5 cm from the anal verge) rectal cancer were included. A total of 186 patients were included. Tumor was in the mid and low rectum in, respectively, 62.9 and 37.1%. Neoadjuvant chemoradiotherapy was given in 62.4%, only radiotherapy in 3.2%, and only chemotherapy in 2.2%. Preoperative staging showed T1 in 3.2%, T2 in 20.4%, T3 in 67.7%, and T4 in 7.5%. Mesorectal resection quality was complete in 95.7% (n = 178), almost complete in 1.6% (n = 3), and incomplete in 1.1% (n = 2). Overall positive CRM (≤ 1 mm) and DRM (≤ 1 mm) were 8.1% (n = 15) and 3.2% (n = 6), respectively. The composite of complete mesorectal excision, negative CRM, and negative DRM was achieved in 88.1% (n = 155) of the patients. The median number of lymph nodes found per specimen was 14.0 (IQR 11-18). The present study showed good rates regarding total mesorectal excision, negative circumferential, and distal resection margins. As the specimen quality is a surrogate marker for survival, TaTME can be regarded as a safe method to treat patients with rectal cancer, from an oncological point of view.

Rectal Microbicide Development

PubMed Central

Dezzutti, Charlene

2014-01-01

The last few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention as effective strategies for reducing the risk of acquiring or transmitting HIV infection. There has also been significant progress in the development of rectal microbicides. Preclinical non-human primate studies have demonstrated that antiretroviral microbicides can provide significant protection from rectal challenge with SIV or SHIV. Recent Phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics (PK), and pharmaco-dynamics (PD) of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in Phase 1 studies. The PK/PD data generated in these Phase 1 studies may reduce the risk of advancing ineffective candidate rectal microbicides into late stage development. Tenofovir gel is currently poised to move into Phase 2 evaluation and it is possible that a Phase 2B/3 effectiveness study with this product could be initiated in the next 2–3 years. PMID:23612991

Rectal microbicide development.

PubMed

McGowan, Ian

2012-11-01

Individuals practicing unprotected receptive anal intercourse are at particularly high risk of HIV infection. Men who have sex with men (MSM) in the developed and developing world continue to have disproportionate and increasing levels of HIV infection. The past few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis (PrEP), vaginal microbicides, and treatment as prevention, but there has also been significant progress in the development of rectal microbicides. The purpose of this review is to summarize the status of rectal microbicide research and to identify opportunities, challenges, and future directions in this important field of HIV prevention. Recent phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics, and pharmacodynamics of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in phase 1 studies. Complex phase 1 studies have provided important data on candidate rectal microbicides. Tenofovir gel is poised to move into phase 2 evaluation and it is possible that a phase 2B/3 effectiveness study could be initiated in the next 2-3 years.

WE-G-17A-07: Investigation of the Influence of the Electron Return Effect (ERE) On the Dose Distribution in Rectal Cancer Patients On a 1.5T MR-Linac

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

Uilkema, S; Heide, U; Nijkamp, J

Purpose: The purpose of this planning study is to investigate the influence of the ERE on the day-to-day dose distribution in rectal cancer patients, where changes in gas-pockets frequently occur. Methods: Daily CT scans of 5 patients treated neo-adjuvant with 5x5Gy for rectal cancer were used. We optimized two plans on the planning CT (Monaco, 1 mm3 dosegrid), a conventional 7-field 6MV IMRT plan (Dconv) and a plan in the presence of a 1.5T field (Dmrl). We recalculated the plans on all repeat-CT scans and evaluated under/over-dosage of the daily CTVs. Changes of more than 1% were considered significant. Inmore » the bowel area, we investigated the relative dose changes due to the ERE, where the contribution of the ERE was separated from other effects such as attenuation. Results: Both plans were comparable and compliant with ICRU 62 for all patients. For 2 fractions in one patient under-dosage in the CTV was significant, due to a disappearing gas-pocket. Here the V95 was 96.82 and 97.36% in in Dmrl compared to 98.85 and 98.66% in Dconv, respectively. For 3 fractions in another patient appearing gas-pockets resulted in significant over-dosage of the CTV. In these fractions the V107 was 1.88–2.68% in Dmrl compared to 0.33–1.27% in Dconv. In the bowel area the dose changes attributable to the ERE were approximately ± 5% in 1cc, at low dose levels. Conclusion: We were able to calculate acceptable treatment plans with and without a magnetic field. The ERE was present in the Dmrl, but the volumetric effect within the CTV was limited. Outside the CTV relative dose differences were similar, but on small volumes at lower, less relevant dose levels. This suggests that there is no clinical relevant ERE on dose distributions in rectal cancer patients on a 1.5T MR-Linac.« less

MiT translocation renal cell carcinomas: two subgroups of tumours with translocations involving 6p21 [t (6; 11)] and Xp11.2 [t (X;1 or X or 17)].

PubMed

Hora, Milan; Urge, Tomáš; Trávníček, Ivan; Ferda, Jiří; Chudáček, Zdeněk; Vaněček, Tomáš; Michal, Michal; Petersson, Fredrik; Kuroda, Naoto; Hes, Ondřej

2014-01-01

MiT translocation renal cell carcinomas (TRCC) predominantly occur in younger patients with only 25% of patients being over 40 years. TRCC contains two main subgroups with translocations involving 6p21 or Xp11.2. Herein we present 10 cases. Eight cases were treated at main author's institution (identified among 1653 (0.48%) cases of kidney tumours in adults). Two cases were retrieved from the Pilsen (CZ) Tumour Registry. Six cases were type Xp11.2 and four 6p21; 7 female, 3 male patients; Xp11.2 4:2, 6p21 3:1. The mean age 49 years (range: 21-80), 5 patients (50%) over 40 years. The mean age of the group with Xp11.2 TRCCs was 55 (median 51) and 6p21 41 (32) years. One female with a 6p21 tumour (24 years) underwent nephrectomy at 4 months of pregnancy. Stage (UICC, 7th ed. 2009) was 5xI, 3xIII, 2xIV. The mean size of tumour was 80 (40-165) mm. The mean follow-up was 33.2 (1-92) months. In patients with 6p21 tumours, one (25%) died after 3 months due to widely metastatic disease. In patients with Xp11.2 tumours, 3 (50%) succumbed due to metastatic disease (range 1-8 months). Three patients with Xp11.2 are alive at 7, 52 and 92 months of follow-up, were diagnosed at early stage (T1a). TRCCs were more common in females. Patient with 6p21 tumours were younger than those with Xp11.2. Both types have definitive malignant potential Type Xp11.2 seems to be a more aggressive neoplasm than 6p21. The case with metastatic 6p21 tumour is the 4th case described in the English literature.

Evaluation of MR imaging with T1 and T2* mapping for the determination of hepatic iron overload.

PubMed

Henninger, B; Kremser, C; Rauch, S; Eder, R; Zoller, H; Finkenstedt, A; Michaely, H J; Schocke, M

2012-11-01

To evaluate MRI using T1 and T2* mapping sequences in patients with suspected hepatic iron overload (HIO). Twenty-five consecutive patients with clinically suspected HIO were retrospectively studied. All underwent MRI and liver biopsy. For the quantification of liver T2* values we used a fat-saturated multi-echo gradient echo sequence with 12 echoes (TR = 200 ms, TE = 0.99 ms +  n × 1.41 ms, flip angle 20°). T1 values were obtained using a fast T1 mapping sequence based on an inversion recovery snapshot FLASH sequence. Parameter maps were analysed using regions of interest. ROC analysis calculated cut-off points at 10.07 ms and 15.47 ms for T2* in the determination of HIO with accuracy 88 %/88 %, sensitivity 84 %/89.5 % and specificity 100 %/83 %. MRI correctly classified 20 patients (80 %). All patients with HIO only had decreased T1 and T2* relaxation times. There was a significant difference in T1 between patients with HIO only and patients with HIO and steatohepatitis (P = 0.018). MRI-based T2* relaxation diagnoses HIO very accurately, even at low iron concentrations. Important additional information may be obtained by the combination of T1 and T2* mapping. It is a rapid, non-invasive, accurate and reproducible technique for validating the evidence of even low hepatic iron concentrations. • Hepatic iron overload causes fibrosis, cirrhosis and increases hepatocellular carcinoma risk. • MRI detects iron because of the field heterogeneity generated by haemosiderin. • T2* relaxation is very accurate in diagnosing hepatic iron overload. • Additional information may be obtained by T1 and T2* mapping.

Trans-rectal interventional MRI: initial prostate biopsy experience

NASA Astrophysics Data System (ADS)

Greenwood, Bernadette M.; Behluli, Meliha R.; Feller, John F.; May, Stuart T.; Princenthal, Robert; Winkel, Alex; Kaminsky, David B.

2010-02-01

Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of the prostate gland when evaluated along with T2-weighted images, diffusion-weighted images (DWI) and their corresponding apparent diffusion coefficient (ADC) maps can yield valuable information in patients with rising or elevated serum prostate-specific antigen (PSA) levels1. In some cases, patients present with multiple negative trans-rectal ultrasound (TRUS) biopsies, often placing the patient into a cycle of active surveillance. Recently, more patients are undergoing TRIM for targeted biopsy of suspicious findings with a cancer yield of ~59% compared to 15% for second TRUS biopsy2 to solve this diagnostic dilemma and plan treatment. Patients were imaged in two separate sessions on a 1.5T magnet using a cardiac phased array parallel imaging coil. Automated CAD software was used to identify areas of wash-out. If a suspicious finding was identified on all sequences it was followed by a second imaging session. Under MRI-guidance, cores were acquired from each target region3. In one case the microscopic diagnosis was prostatic intraepithelial neoplasia (PIN), in the other it was invasive adenocarcinoma. Patient 1 had two negative TRUS biopsies and a PSA level of 9ng/mL. Patient 2 had a PSA of 7.2ng/mL. He underwent TRUS biopsy which was negative for malignancy. He was able to go on to treatment for his prostate carcinoma (PCa)4. MRI may have an important role in a subset of patients with multiple negative TRUS biopsies and elevated or rising PSA.

Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

PubMed

Naiken, Surennaidoo P; Toso, Christian; Rubbia-Brandt, Laura; Thomopoulos, Theodoros; Roth, Arnaud; Mentha, Gilles; Morel, Philippe; Gervaz, Pascal

2014-01-17

Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy

Rectal bleeding after high-dose-rate brachytherapy combined with hypofractionated external-beam radiotherapy for localized prostate cancer: Impact of rectal dose in high-dose-rate brachytherapy on occurrence of grade 2 or worse rectal bleeding

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

Akimoto, Tetsuo; Katoh, Hiroyuki; Kitamoto, Yoshizumi

2006-06-01

Purpose: To evaluate the incidence of Grade 2 or worse rectal bleeding after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiotherapy (EBRT), with special emphasis on the relationship between the incidence of rectal bleeding and the rectal dose from HDR brachytherapy. Methods and Materials: The records of 100 patients who were treated by HDR brachytherapy combined with EBRT for {>=}12 months were analyzed. The fractionation schema for HDR brachytherapy was prospectively changed, and the total radiation dose for EBRT was fixed at 51 Gy. The distribution of the fractionation schema used in the patients was as follows: 5 Gy xmore » 5 in 13 patients; 7 Gy x 3 in 19 patients; and 9 Gy x 2 in 68 patients. Results: Ten patients (10%) developed Grade 2 or worse rectal bleeding. Regarding the correlation with dosimetric factors, no significant differences were found in the average percentage of the entire rectal volume receiving 30%, 50%, 80%, and 90% of the prescribed radiation dose from EBRT between those with bleeding and those without. The average percentage of the entire rectal volume receiving 10%, 30%, 50%, 80%, and 90% of the prescribed radiation dose from HDR brachytherapy in those who developed rectal bleeding was 77.9%, 28.6%, 9.0%, 1.5%, and 0.3%, respectively, and was 69.2%, 22.2%, 6.6%, 0.9%, and 0.4%, respectively, in those without bleeding. The differences in the percentages of the entire rectal volume receiving 10%, 30%, and 50% between those with and without bleeding were statistically significant. Conclusions: The rectal dose from HDR brachytherapy for patients with prostate cancer may have a significant impact on the incidence of Grade 2 or worse rectal bleeding.« less

Vaccine-induced T cells Provide Partial Protection Against High-dose Rectal SIVmac239 Challenge of Rhesus Macaques

PubMed Central

Lasaro, Marcio O; Haut, Larissa H; Zhou, Xiangyang; Xiang, Zhiquan; Zhou, Dongming; Li, Yan; Giles-Davis, Wynetta; Li, Hua; Engram, Jessica C; DiMenna, Lauren J; Bian, Ang; Sazanovich, Marina; Parzych, Elizabeth M; Kurupati, Raj; Small, Juliana C; Wu, Te-Lang; Leskowitz, Rachel M; Klatt, Nicole R; Brenchley, Jason M; Garber, David A; Lewis, Mark; Ratcliffe, Sarah J; Betts, Michael R; Silvestri, Guido; Ertl, Hildegund C

2011-01-01

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4+ T cells. In addition, the two vaccinated Mamu-A*01+ macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1. PMID:21081905

Vaccine-induced T cells provide partial protection against high-dose rectal SIVmac239 challenge of rhesus macaques.

PubMed

Lasaro, Marcio O; Haut, Larissa H; Zhou, Xiangyang; Xiang, Zhiquan; Zhou, Dongming; Li, Yan; Giles-Davis, Wynetta; Li, Hua; Engram, Jessica C; Dimenna, Lauren J; Bian, Ang; Sazanovich, Marina; Parzych, Elizabeth M; Kurupati, Raj; Small, Juliana C; Wu, Te-Lang; Leskowitz, Rachel M; Klatt, Nicole R; Brenchley, Jason M; Garber, David A; Lewis, Mark; Ratcliffe, Sarah J; Betts, Michael R; Silvestri, Guido; Ertl, Hildegund C

2011-02-01

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4(+) T cells. In addition, the two vaccinated Mamu-A*01(+) macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1.

A study on rectal dose measurement in phantom and in vivo using Gafchromic EBT3 film in IMRT and CyberKnife treatments of carcinoma of prostate

PubMed Central

Ganapathy, K.; Kurup, P. G. G.; Murali, V.; Muthukumaran, M.; Subramanian, S. Balaji; Velmurugan, J.

2013-01-01

The objective of this study is to check the feasibility of in vivo rectal dose measurement in intensity-modulated radiotherapy (IMRT) and CyberKnife treatments for carcinoma prostate. An in-house pelvis phantom made with bee's wax was used in this study. Two cylindrical bone equivalent materials were used to simulate the femur. Target and other critical structures associated with carcinoma prostate were delineated on the treatment planning images by the radiation oncologist. IMRT treatment plan was generated in Oncentra Master Plan treatment planning system and CyberKnife treatment plan was generated in Multiplan treatment planning system. Dose measurements were carried out in phantom and in patient using Gafchromic EBT3 films. RIT software was used to analyze the dose measured by EBT3 films. The measured doses using EBT3 films were compared with the TPS-calculated dose along the anterior rectal wall at multiple points. From the in-phantom measurements, it is observed that the difference between calculated and measured dose was mostly within 5%, except for a few measurement points. The difference between calculated and measured dose in the in-patient measurements was higher than 5% in regions which were away from the target. Gafchromic EBT3 film is a suitable detector for in vivo rectal dose measurements as it offers the possibility of analyzing the dose at multiple points. In addition, the method of extending this in vivo rectal dose measurement technique as a tool for patient-specific quality assurance check is also analyzed. PMID:24049320

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

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

Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo

2014-07-01

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months,more » the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.« less

Rectal metastasis from lobular breast carcinoma 15 years after primary diagnosis.

PubMed

López Deogracias, Maite; Flores Jaime, Laura; Arias-Camisón, Iñaki; Zamacola, Ilde; Murillo Guibert, Jesús; Suescun García, Rosa; Querejeta Usabiaga, Juan; Martínez García, Francisco

2010-02-01

Lobular breast carcinoma represents 2-20% of infiltrative carcinomas of the breast. The incidence of extrahepatic gastrointestinal (GI) tract metastases observed in necropsy studies varies from 6% to 18% and the most commonly affected organ is the stomach, followed by colon and rectum [1-4]. Reported herein is the case of a 67-year-old woman who was primarily diagnosed and surgically treated for a lobular carcinoma of the breast 15 years ago and is now referred with back pain and right hydronephrosis caused by a metastasis in rectum. Frequently, the absence of specific symptoms of digestive metastases of breast cancer leads to a misdiagnosis of this pathology [5-7]. The treatment will be based on a detailed clinical history and histopathological findings. Metastases from breast cancer in GI tract tumours must be excluded in a patient with previous history of breast carcinoma, as in the case reported herein.

Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors.

PubMed

Ye, Xuying; Yin, Huijuan; Lu, Yu; Zhang, Haixia; Wang, Han

2016-10-12

We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3-6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

Simultaneous acquisition for T2 -T2 Exchange and T1 -T2 correlation NMR experiments

NASA Astrophysics Data System (ADS)

Montrazi, Elton T.; Lucas-Oliveira, Everton; Araujo-Ferreira, Arthur G.; Barsi-Andreeta, Mariane; Bonagamba, Tito J.

2018-04-01

The NMR measurements of longitudinal and transverse relaxation times and its multidimensional correlations provide useful information about molecular dynamics. However, these experiments are very time-consuming, and many researchers proposed faster experiments to reduce this issue. This paper presents a new way to simultaneously perform T2 -T2 Exchange and T1 -T2 correlation experiments by taking the advantage of the storage time and the two steps phase cycling used for running the relaxation exchange experiment. The data corresponding to each step is either summed or subtracted to produce the T2 -T2 and T1 -T2 data, enhancing the information obtained while maintaining the experiment duration. Comparing the results from this technique with traditional NMR experiments it was possible to validate the method.

Phase I/II study of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma.

PubMed

Song, Y-P; Ma, J-B; Hu, L-K; Zhou, W; Chen, E-C; Zhang, W

2011-02-01

Compared to conventional fractionated-dose radiotherapy, high hypofractionated-dose radiotherapy could yield tumoricidal effects. However, few clinical trials of hypofractionated radiotherapy in loco-regionally advanced incurable esophageal cancer at present have yet been performed. The purpose of the current study was to evaluate the efficacy and toxicity of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma. From September 2003 to December 2005, 45 patients with locally advanced esophageal carcinoma were grouped and received three-dimensional conformal hypofractioned radiotherapy (3D-CRT) whose fractionated dose was gradually increase per group. Radiotherapy was administered to a total dose of from 50 to 54 Gy (fractionated dose of from 3.0 to 6.0 Gy, 3 times weekly), over a 3-4 week period. And patients received 4 cycles chemotherapy. The median follow-up period for survivors was 38 months. Treatment tolerance rate was 78.8% with daily dose of from 3 to 5 Gy. There are 21.2% patients occurring Grade ≥ 3 acute toxicities. But patients couldn't tolerate daily dose of 6 Gy (55.6%). The 1-year, 2-year and 3-year local control rates were 62%, 49% and 39% respectively. And the 1-year, 2-year and 3-year overall survival rates were 34%, 21% and 9% respectively. The median overall survival time was 17 months. At the time of following up, 13 patients (31.0%) had occurred esophageal late complications, with mainly esophageal perforation, hemorrhage or stenosis, including initial stenosis aggravation. Therefore hypofractionated irradiation was thought to be feasible for clinical T3-4N0-1M0 stage esophageal carcinoma. And daily dose of ≤5 Gy was comparatively suitable in hypofractionated irradiation for esophageal carcinoma, and the patients tolerated well. But further research was in need also.

The consistency of Fletcher-Suit applicator geometry and of the rectal probe’s position in high dose rate brachytherapy treatment fraction of cervix carcinoma

PubMed Central

2009-01-01

Purpose The dose values computed with the treatment planning system and the in vivo dose measurements with semiconductor detectors in rectum during the high dose rate brachytherapy treatment fraction of the cervix carcinoma are occasionally significantly different. We’ve investigated the consistency of the Fletcher-Suit applicator geometry and the in vivo rectal probe’s position stability during the high dose rate brachytherapy treatment fraction. Material and methods The patient lied in a lithotomic position during a biplane reconstruction images, throughout the treatment planning and dose administration. We obtained post-treatment reconstruction images and prepared a post-treatment plan. The amount of 14 treatment fractions of 10 patients were considered in the study. Two methods were applied: evaluation of the difference of reconstructed pre-treatment and post-treatment applicator points and rectal probe’s detectors being relevant to the co-ordinate system fixed to the applicator, and estimation of applicators and rectal probe’s reallocation with respect to the pelvic bones with registration of pre- and post-treatment reconstruction images. Results We’ve experienced good consistency in the Fletcher-Suit applicator geometry in all treatment fractions. 70% of them presented small variation in the rectal probe’s position, while the rest showed significant shift in the applicator or rectal probe’s position with regard to the pelvic bones. PMID:27807458

p53 predictive value for pT1-2 N0 disease at radical cystectomy.

PubMed

Shariat, Shahrokh F; Lotan, Yair; Karakiewicz, Pierre I; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J; Nielsen, Matthew E; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C; Karam, Jose A; Heukamp, Lukas C; Netto, George; Lerner, Seth P; Sagalowsky, Arthur I; Cote, Richard J

2009-09-01

Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

Phospho-T356RB1 predicts survival in HPV-negative squamous cell carcinoma of the head and neck

PubMed Central

Handorf, Elizabeth; Nikonova, Anna; Dubyk, Cara; Peri, Suraj; Lango, Miriam; Ridge, John A.; Serebriiskii, Ilya G.; Burtness, Barbara; Golemis, Erica A.; Mehra, Ranee

2015-01-01

Locally advanced squamous cell carcinoma of the head and neck (SCCHN) that is not associated with human papillomavirus (HPV) has a poor prognosis in contrast to HPV-positive disease. To better understand the importance of RB1 activity in HPV-negative SCCHN, we investigated the prognostic value of inhibitory CDK4/6 phosphorylation of RB1 on threonine 356 (T356) in archival HPV-negative tumor specimens from patients who underwent surgical resection and adjuvant radiation. We benchmarked pT356RB1 to total RB1, Ki67, pT202/Y204ERK1/2, and TP53, as quantified by automatic quantitative analysis (AQUA), and correlated protein expression with tumor stage and grade. High expression of pT356RB1 but not total RB1 predicted reduced overall survival (OS; P = 0.0295), indicating the potential relevance of post-translational phosphorylation. Paired analysis of The Cancer Genome Atlas (TCGA) data for regulators of this RB1 phosphorylation identified loss or truncating mutation of negative regulator CDKN2A (p16) and elevated expression of the CDK4/6 activator CCND1 (cyclin D) as also predicting poor survival. Given that CDK4/6 inhibitors have been most effective in the context of functional RB1 and low expression or deletion of p16 in other tumor types, these data suggest such agents may merit evaluation in HPV-negative SCCHN, specifically in cases associated with high pT356RB1. PMID:26265441

Variation in the CYP19A1 gene and risk of colon and rectal cancer

PubMed Central

Slattery, Martha L.; Lundgreen, Abbie; Herrick, Jennifer S.; Kadlubar, Susan; Caan, Bette J.; Potter, John D.; Wolff, Roger K.

2011-01-01

CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case–control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer. After adjustment for multiple comparisons, the AA genotype of rs12591359 was associated with an increased risk of colon cancer (OR 1.44 95% CI 1.16–1.80) and the AA genotype of rs2470144 was associated with a reduced risk of rectal cancer (OR 0.65 95% CI 0.50–0.84). Variants of CYP19A1 were associated with CIMP+ and CIMP+/KRAS2-mutated tumors. CT/TT genotypes of rs1961177 were significantly associated with an increased likelihood of a MSI+ colon tumor (OR 1.77 95% CI 1.26–2.37). We observed statistically significant interactions between genetic variation in NFκB1 and CYP19A1 for both colon and rectal cancer. Our data suggest the importance of CYP19A1 in the development of colon and rectal cancer and that estrogen may influence risk through an inflammation-related mechanism. PMID:21479914

Expression of MLH1 and MSH2 in urothelial carcinoma of the renal pelvis.

PubMed

Ehsani, Laleh; Osunkoya, Adeboye O

2014-09-01

In this study, we investigated microsatellite instability in urothelial carcinoma of the renal pelvis by lack of immunohistochemical staining for MLH1 and MSH2. The study included 44 cases of urothelial carcinoma of the renal pelvis obtained from radical nephroureterectomy specimens at our institution. We evaluated the loss of nuclear immunohistochemical staining of MLH1 and MSH2. Eight of 44 (18 %) patients had negative MLH1 expression and 25/44 (57 %) patients had negative MSH2 expression. Six of 8 (75 %) patients with negative MLH1 expression were male and 2/8 (25 %) patients were female. Nineteen of 25 (75 %) patients with negative MSH2 expression were male, and 6/25 (24 %) patients were female. Seven of 8 (88 %) cases with negative MLH1 expression were high-grade urothelial carcinoma, and 21/25 (84 %) cases with negative MSH2 expression were high-grade urothelial carcinoma. Twenty-one of 44 (48 %) cases had an inverted growth pattern, of which 3/21 (14 %) cases had negative MLH1 expression and 14/21 (67 %) cases had negative MSH2 expression. Our study showed that microsatellite instability based on negative expression of MLH1 and MSH2 was more common in male patients with high-grade urothelial carcinoma. There is a strong correlation between inverted growth pattern and negative MSH2 expression. Microsatellite instability testing should be performed in patients with upper urinary tract carcinoma and may have prognostic value.

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

PubMed Central

Rampazzo, Enrica; Del Bianco, Paola; Bertorelle, Roberta; Boso, Caterina; Perin, Alessandro; Spiro, Giovanna; Bergamo, Francesca; Belluco, Claudio; Buonadonna, Angela; Palazzari, Elisa; Leonardi, Sara; De Paoli, Antonino; Pucciarelli, Salvatore; De Rossi, Anita

2018-01-01

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT=T0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4–8 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (P<0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73–0.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10–4.11)-fold and 4.55 (95% CI 1.48–13.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy. PMID:29449673

Potential of DNA methylation in rectal cancer as diagnostic and prognostic biomarkers

PubMed Central

Exner, Ruth; Pulverer, Walter; Diem, Martina; Spaller, Lisa; Woltering, Laura; Schreiber, Martin; Wolf, Brigitte; Sonntagbauer, Markus; Schröder, Fabian; Stift, Judith; Wrba, Fritz; Bergmann, Michael; Weinhäusel, Andreas; Egger, Gerda

2015-01-01

Background: Aberrant DNA methylation is more prominent in proximal compared with distal colorectal cancers. Although a number of methylation markers were identified for colon cancer, yet few are available for rectal cancer. Methods: DNA methylation differences were assessed by a targeted DNA microarray for 360 marker candidates between 22 fresh frozen rectal tumour samples and 8 controls and validated by microfluidic high-throughput and methylation-sensitive qPCR in fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples, respectively. The CpG island methylator phenotype (CIMP) was assessed by MethyLight in FFPE material from 78 patients with pT2 and pT3 rectal adenocarcinoma. Results: We identified and confirmed two novel three-gene signatures in fresh frozen samples that can distinguish tumours from adjacent tissue as well as from blood with a high sensitivity and specificity of up to 1 and an AUC of 1. In addition, methylation of individual CIMP markers was associated with specific clinical parameters such as tumour stage, therapy or patients' age. Methylation of CDKN2A was a negative prognostic factor for overall survival of patients. Conclusions: The newly defined methylation markers will be suitable for early disease detection and monitoring of rectal cancer. PMID:26335606

Defining the rectal dose constraint for permanent radioactive seed implantation of the prostate.

PubMed

Albert, Michele; Song, Jun S; Schultz, Delray; Cormack, Robert A; Tempany, Clare M; Haker, Steve; Devlin, Phillip M; Beard, Clair; Hurwitz, Mark D; Suh, Wonsuk W; Jolesz, Ferenc; D'Amico, Anthony V

2008-01-01

This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy. Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent I(125) radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test. There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment. Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I(125) permanent prostate brachy mono-therapy.

Disturbed Colonic Motility Contributes to Anorectal Symptoms and Dysfunction After Radiotherapy for Carcinoma of the Prostate

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

Yeoh, Eric K., E-mail: eric.yeoh@health.sa.gov.a; Bartholomeusz, Dylan L.; Holloway, Richard H.

2010-11-01

Purpose: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. Patients and Methods: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. Results: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgencymore » of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. Conclusion: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.« less

Manometric characterization of rectal dysfunction following radical hysterectomy.

PubMed

Barnes, W; Waggoner, S; Delgado, G; Maher, K; Potkul, R; Barter, J; Benjamin, S

1991-08-01

Bladder dysfunction thought to be due to partial denervation has been described following radical hysterectomy. Some patients experience acute and chronic rectal dysfunction characterized by difficulty with defecation and loss of defecatory urge. To define this abnormality, anorectal pressure profiles were examined in 15 patients with Stage I carcinoma of the cervix before and after radical hysterectomy. Profiles were done using standard anorectal manometry with a water-infused system. In all patients preoperative manometric profiles were normal; postoperative studies were abnormal in all patients. Features seen include altered relaxation of the internal sphincter, increased distension needed to trigger relaxation, and decreased rectal sensation; external sphincters and resting internal sphincters were unchanged. Postoperatively, 12 patients reported problems with rectal function. A physiologic defect is definable in patients undergoing radical hysterectomy; this suggests disruption of the spinal reflex arcs controlling rectal emptying. These physiologic abnormalities correlate with the clinical symptomatology experienced by some patients. Continuing definition and evaluation of management options in this situation should be useful in developing effective therapy for rectal dysfunction following radical hysterectomy.

Impact of concomitant chemoradiation on survival for patients with T1-2N1 head and neck cancer.

PubMed

Zumsteg, Zachary S; Kim, Sungjin; David, John M; Yoshida, Emi J; Tighiouart, Mourad; Shiao, Stephen L; Scher, Kevin; Mita, Alain; Sherman, Eric J; Lee, Nancy Y; Ho, Allen S

2017-05-01

Single-modality radiotherapy is considered a standard-of-care option for certain stage III, T1-2N1 head and neck squamous cell carcinomas (HNSCCs). The role of concomitant chemoradiation is not well established because there have been no studies comparing chemoradiation with radiation alone in this population. This study analyzed patients in the National Cancer Data Base with cT1-2N1M0 invasive squamous cell carcinomas of the oropharynx, larynx, and hypopharynx who were diagnosed between 2004 and 2012 and were undergoing definitive radiation. Patients who were undergoing surgery before radiation with unknown follow-up or for whom either the receipt or timing of chemotherapy was unknown were excluded. In all, 5030 patients with T1-2N1 oropharyngeal, laryngeal, or hypopharyngeal cancer were included. The median follow-up was 56.8 months (95% confidence interval [CI], 55.7-58.6 months). Overall, 68% of the patients received concomitant chemoradiation (CCRT). The use of CCRT significantly increased during the time period of this study from 53% in 2004 to 78% in 2012 (P < .001). CCRT was associated with improved overall survival (OS) in comparison with radiation alone in a multivariate analysis (hazard ratio [HR], 0.80; 95% CI, 0.72-0.88; P < .001). In propensity score-adjusted analyses, CCRT remained significantly associated with improved OS, with 5-year OS rates of 63.5% (95% CI, 60.7%-66.2%) and 55.6% (95% CI, 52.7%-58.4%; P < .001) with CCRT and radiation alone, respectively. Subgroup analyses showed a benefit across the majority of subgroups, including patients with oropharyngeal cancer (HR, 0.74; 95% CI, 0.65-0.85; P < .001). Concomitant chemoradiation is associated with improved survival for patients with T1-2N1 HNSCC. Prospective trials in this population should be pursued. Cancer 2017;123:1555-1565. © 2017 American Cancer Society. © 2016 American Cancer Society.

Exclusive radiotherapy for stage T1-T2N0M0 lanryngeal cancer: retrospective study of 59 patients at CFB and CHU de Caen.

PubMed

Cuny, F; Géry, B; Florescu, C; Clarisse, B; Blanchard, D; Rame, J-P; Babin, E; De Raucourt, D

2013-11-01

Study of patients with stage T1N0M0 or T2N0M0 glottic cancer treated by exclusive radiotherapy and comparison of the survival and functional results of this series with those of the literature. Retrospective study of stage T1N0M0 or T2N0M0 glottic cancers diagnosed between 1st January 2000 and 31st December 2010 and treated by exclusive radiotherapy. Evaluation of survival, recurrence and larynx preservation rates. CLCC François-Baclesse and CHU de Caen. Fifty-nine patients (53 men and sixwomen) treated for glottic cancer (57 squamous cell carcinomas, two verrucous carcinomas) comprising 51 T1N0M0 and eight T2N0M0 tumours. Treatment with exclusive radiotherapy (mean dose of 70 Grays limited to the thyroid cartilage for 57 patients, with lymph node irradiation for two patients). In this series, five (9.8%) patients with stage T1N0M0 glottic cancer and three patients (37.5%) with stage T2N0M0 glottic cancer relapsed, corresponding to a global recurrence rate of 13.6%. Three of the eight recurrences involved lymph nodes exclusively (N), two patients relapsed exclusively at the primary tumour site (T) and three patients presented local and lymph node recurrence (T and N). Treatment consisted of salvage total laryngectomy with bilateral cervical lymph node dissection in three cases, bilateral cervical lymph node dissection and sensitized radiotherapy in two cases, exclusive chemotherapy in one case, cervical lymph node dissection and cervical radiotherapy in one case. The last patient with recurrence died prior to salvage therapy. The larynx preservation rate was 94.9%. In comparison with the literature, treatment of stage T1-T2N0M0 glottic cancer by exclusive radiotherapy gives very good results, with a larynx preservation rate of 95%. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Programmed Death-ligand 1 Expression in Upper Tract Urothelial Carcinoma.

PubMed

Skala, Stephanie L; Liu, Tzu-Ying; Udager, Aaron M; Weizer, Alon Z; Montgomery, Jeffrey S; Palapattu, Ganesh S; Siddiqui, Javed; Cao, Xuhong; Fields, Kristina; Abugharib, Ahmed E; Soliman, Moaaz; Hafez, Khaled S; Miller, David; Lee, Cheryl T; Alva, Ajjai; Chinnaiyan, Arul M; Morgan, Todd M; Spratt, Daniel E; Jiang, Hui; Mehra, Rohit

2017-10-01

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. Upper tract (renal pelvis and ureter) urothelial carcinomas (UTUC) account for approximately 5% of UCs but a significant subset are invasive and associated with poor clinical outcomes. To evaluate programmed death-ligand 1 (PD-L1) expression in UTUC. UTUC cases from 1997-2016 were retrospectively identified from the surgical pathology database at a single large academic institution. The cohort included 149 cases: 27 low-grade and 24 high-grade pathologic T (pT)a, 29 pT1, 23 pT2, 38 pT3, and eight pT4. PD-L1 immunohistochemistry (IHC) was performed on representative whole tumor sections using anti-PD-L1 primary antibody clone 5H1. PD-L1 expression was evaluated using a previously established cut-off for positivity (≥ 5% membranous staining). Association between PD-L1 IHC expression and clinicopathologic parameters was examined with Fisher's exact test; the effect of PD-L1 expression on cancer-specific mortality was assessed using the Cox proportional hazard model. Approximately one-third (32.7%) of invasive primary UTUC and 23.5% of all primary UTUC (invasive and noninvasive tumors) demonstrated positive PD-L1 expression. Positive PD-L1 expression was associated with high histologic grade, high pathologic stage, and angiolymphatic invasion. Cancer-specific survival was not significantly associated with positive PD-L1 expression using a 5% cut-off. Study limitations include the retrospective nature and the fact that PD-L1 expression by IHC is an imperfect surrogate for response to therapy. Positive PD-L1 expression in approximately one-third of primary invasive UTUC and association with high-risk clinicopathologic features provide a rational basis for further investigation of PD-L1-based immunotherapeutics in these patients. Upper tract urothelial carcinoma is often associated with poor clinical outcome. While current treatment options for advanced upper tract urothelial carcinoma are

[Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and its related mechanism].

PubMed

Zhang, Shao-nan; Yong, Qun; Wu, Xin-li; Liu, Xiao-ping

2014-11-01

To investigate the synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and the down-regulating effect of curcumin on the Keapl-Nrf2 pathway, a well recognized anti-drug pathway in almost drugged tumor cells. T24 cells were cultured and treated with increasing concentrations of curcumin(5 ,10 and 20 µmol/mL) combined with cisplatin(30 µg/mL) for 24 hours. The inhibitory effects on T24 cells were tested with MTI colorimetric assay. Nuclear Nrf2 and Keapl , cytoplasmic Keapl and two typical phase II enzymes (GSTP1 and NQOl) were checked with Western blotting. The proliferation of T24 cells was significantly inhibited by different concentrations of curcumin combined with cisplatin. After the treatment with different concentrations of curcumin, Nuclear Nrf2 was decreased but Keapl was increased, and GSTP1 and NQO1 were decreased. Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells is observed in this research. The Keapl-Nrf2 pathway in T24 cells is down-regulated by curcumin. The expression of typical phase I enzymes (GSTP1 and NQO1) mediated by Nrf2 are decreased by curcumin. The sensitivity of tumor cells to chemotherapeutic drugs is then enhanced. These may be the mechanism of synergism effect of curcumin combined with cisplatin.

New technique of transanal proctectomy with completely robotic total mesorrectal excision for rectal cancer.

PubMed

Gómez Ruiz, Marcos; Palazuelos, Carlos Manuel; Martín Parra, José Ignacio; Alonso Martín, Joaquín; Cagigas Fernández, Carmen; del Castillo Diego, Julio; Gómez Fleitas, Manuel

2014-05-01

Anterior resection with total mesorectal excision is the standard method of rectal cancer resection. However, this procedure remains technically difficult in mid and low rectal cancer. A robotic transanal proctectomy with total mesorectal excision and laparoscopic assistance is reported in a 57 year old male with BMI 32 kg/m2 and rectal adenocarcinoma T2N1M0 at 5 cm from the dentate line. Operating time was 420 min. Postoperative hospital stay was 6 days and no complications were observed. Pathological report showed a 33 cm specimen with ypT2N0 adenocarcinoma at 2 cm from the distal margin, complete TME and non affected circumferential resection margin. Robotic technology might reduce some technical difficulties associated with TEM/TEO or SILS platforms in transanal total mesorectal excision. Further clinical trials will be necessary to assess this technique. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

Warburg phenotype in renal cell carcinoma: high expression of glucose-transporter 1 (GLUT-1) correlates with low CD8(+) T-cell infiltration in the tumor.

PubMed

Singer, Katrin; Kastenberger, Michael; Gottfried, Eva; Hammerschmied, Christine G; Büttner, Maike; Aigner, Michael; Seliger, Barbara; Walter, Bernhard; Schlösser, Hans; Hartmann, Arndt; Andreesen, Reinhard; Mackensen, Andreas; Kreutz, Marina

2011-05-01

Many tumor cells are characterized by a dysregulated glucose metabolism associated with increased glycolysis in the presence of oxygen ("Warburg Effect"). Here, we analyzed for the first time a possible link between glucose metabolism and immune cell infiltration in renal cell carcinoma (RCC). RCC specimens revealed a highly significant increase in the expression of lactate dehydrogenase A (LDHA) and glucose-transporter 1 (GLUT-1) compared to the corresponding normal kidney tissue on mRNA level. Accordingly, tumor cell lines of different origin such as RCC, melanoma and hepatocellular carcinoma strongly expressed LDHA and GLUT-1 compared to their nonmalignant counterparts. In line with this finding, tumor cells secreted high amounts of lactate. High expression of GLUT-1 and LDH5, a tetramer of 4 LDHA subunits, was confirmed by tissue microarray analysis of 249 RCC specimens. Overall, 55/79 (69.6%) and 46/71 (64.7%) cases of clear cell carcinoma showed a constitutive, but heterogeneous expression of GLUT-1 and LDH5, respectively. The number of CD3(+), CD8(+) and FOXP3(+) T cells was significantly elevated in RCC lesions compared to normal kidney epithelium, but effector molecules such as granzyme B and perforin were decreased in tumor infiltrating T cells. Of interest, further analysis revealed an inverse correlation between GLUT-1 expression and the number of CD8(+) T cells in RCC lesions. Together, our data suggest that an accelerated glucose metabolism in RCC tissue is associated with a low infiltration of CD8(+) effector T cells. Targeting the glucose metabolism may represent an interesting tool to improve the efficacy of specific immunotherapeutic approaches in RCC. Copyright © 2010 UICC.

Relative Value of Restaging MRI, CT, and FDG-PET Scan After Preoperative Chemoradiation for Rectal Cancer.

PubMed

Schneider, Daniel A; Akhurst, Timothy J; Ngan, Samuel Y; Warrier, Satish K; Michael, Michael; Lynch, Andrew C; Te Marvelde, Luc; Heriot, Alexander G

2016-03-01

Management of rectal cancer has become multidisciplinary and is driven by the stage of the disease, with increased focus on restaging rectal cancer after neoadjuvant therapy. The purpose of this study was to assess the relative impact of restaging after preoperative chemoradiation with FDG-PET scan, CT, and MRI in the management of patients with rectal cancer. This was a retrospective study from a single institution. This study was conducted at a tertiary cancer center. A total of 199 patients met the inclusion criteria: patients with rectal adenocarcinoma; staged with positron emission tomography, CT, and MRI; T2 to T4, N0 to N2, M0 to M1; treated with neoadjuvant chemoradiation 50.4 Gy and infusional 5-fluorouracil; and restaged 4 weeks after chemoradiation before surgery between 2003 and 2013. Comparisons of the tumor stage among different imaging modalities before and after neoadjuvant chemoradiation were performed. The impact of restaging on the management plan was assessed. The stage at presentation was T2, 8.04%; T3, 65.33%; T4, 26.63%; N0, 17.09%; N1, 47.74%; N2, 34.67%; M0, 81.91%; and M1, 18.09%. Changes in disease stage postneoadjuvant chemoradiation were observed in 99 patients (50%). The management plans of 29 patients (15%) were changed. The impact of each restaging modality on management for all of the patients was positron emission tomography, 11%; CT, 4%; and MRI, 4%. In patients with metastatic disease at primary staging, the relative impact of each restaging modality in changing management was positron emission tomography, 32%; CT, 18%; and MRI, 6%. This study was limited by its single-center and retrospective design. Operations were performed 4 weeks after restaging. Changes in the extent of disease after long-course chemoradiotherapy result in changes of management in a significant percentage of patients. Positron emission tomography has the most significant impact in the change of management overall, and its use in restaging advanced rectal

Pathophysiology and Natural History of Anorectal Sequelae Following Radiation Therapy for Carcinoma of the Prostate

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

Yeoh, Eric K., E-mail: eric.yeoh@health.sa.gov.au; Discipline of Medicine, University of Adelaide, Adelaide; Holloway, Richard H.

2012-12-01

Purpose: To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. Methods and Materials: Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activitiesmore » of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. Results: Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. Conclusions: Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.« less

Stapled haemorrhoidopexy transiently decreases rectal compliance and sensitivity.

PubMed

Filho, F L A; Macedo, G M; Dos Santos, A A; Rodrigues, L V; Oliveira, R B; Nobre E Souza, M A

2011-02-01

Stapled haemorrhoidopexy may damage the anorectal musculature and its sensorimotor function. Most studies have not used a barostat for the measurement of compliance. This study aimed to investigate the effect of stapled haemorrhoidopexy on rectal compliance and sensitivity. After Ethical Committee approval, we studied 10 male patients (mean age 33.8 years) with third- or fourth-degree haemorrhoids. Rectal compliance and sensitivity were measured with a 600-ml bag and an electronic barostat. Volunteers were submitted to two consecutive rectal distension protocols, including continuous distension at 2, 4 and 6 months after stapled haemorrhoidopexy. Intraluminal volume and pressure were recorded, including the first rectal sensation, desire to defecate and onset of rectal pain. Another group of 10 male control patients (mean age 24.9 years) with pilonidal sinus and no haemorrhoids was also included in the study. Two months after stapled haemorrhoidopexy, rectal compliance decreased (7.1 ± 0.2 vs 5.3 ± 0.1, 6.4 ± 0.1 vs 5.1 ± 0.1 and 5.6 ± 0.2 vs 4.7 ± 0.1 ml/mmHg for first rectal sensation, desire to defecate and rectal pain, respectively; P < 0.05). The sensitivity threshold volume did not change for the first sensation but decreased significantly for the desier to defecate and pain (p <0.05) (116.8 ± 13.8 vs 148.4 ± 14.61, 251.1 ± 8.9 vs 185.8 ± 8.6 and 293.3 ± 16.6 vs 221.2 ± 6.0 ml for first rectal sensation, desire to defecate and rectal pain, respectively). Four and 6 months after surgery, rectal compliance and sensitivity returned to levels similar to those in the basal period. Muscle tissue was found in only three of the 10 resected doughnuts. Controls remained without any change in rectal compliance and sensitivity. Stapled haemorrhoidopexy transiently decreases rectal compliance and sensitivity threshold in young male patients. © 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland.

Validity of Core Temperature Measurements at 3 Rectal Depths During Rest, Exercise, Cold-Water Immersion, and Recovery.

PubMed

Miller, Kevin C; Hughes, Lexie E; Long, Blaine C; Adams, William M; Casa, Douglas J

2017-04-01

  No evidence-based recommendation exists regarding how far clinicians should insert a rectal thermistor to obtain the most valid estimate of core temperature. Knowing the validity of temperatures at different rectal depths has implications for exertional heat-stroke (EHS) management.   To determine whether rectal temperature (T rec ) taken at 4 cm, 10 cm, or 15 cm from the anal sphincter provides the most valid estimate of core temperature (as determined by esophageal temperature [T eso ]) during similar stressors an athlete with EHS may experience.   Cross-sectional study.   Laboratory.   Seventeen individuals (14 men, 3 women: age = 23 ± 2 years, mass = 79.7 ± 12.4 kg, height = 177.8 ± 9.8 cm, body fat = 9.4% ± 4.1%, body surface area = 1.97 ± 0.19 m 2 ).   Rectal temperatures taken at 4 cm, 10 cm, and 15 cm from the anal sphincter were compared with T eso during a 10-minute rest period; exercise until the participant's T eso reached 39.5°C; cold-water immersion (∼10°C) until all temperatures were ≤38°C; and a 30-minute postimmersion recovery period. The T eso and T rec were compared every minute during rest and recovery. Because exercise and cooling times varied, we compared temperatures at 10% intervals of total exercise and cooling durations for these periods.   The T eso and T rec were used to calculate bias (ie, the difference in temperatures between sites).   Rectal depth affected bias (F 2,24 = 6.8, P = .008). Bias at 4 cm (0.85°C ± 0.78°C) was higher than at 15 cm (0.65°C ± 0.68°C, P < .05) but not higher than at 10 cm (0.75°C ± 0.76°C, P > .05). Bias varied over time (F 2,34 = 79.5, P < .001). Bias during rest (0.42°C ± 0.27°C), exercise (0.23°C ± 0.53°C), and recovery (0.65°C ± 0.35°C) was less than during cooling (1.72°C ± 0.65°C, P < .05). Bias during exercise was less than during postimmersion recovery (0.65°C ± 0.35°C, P < .05).   When EHS is suspected, clinicians should insert the flexible

A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk.

PubMed

Wang, Dan; Qi, Xiaoying; Liu, Fang; Yang, Chuanhua; Jiang, Wenguo; Wei, Xiaodan; Li, Xuri; Mi, Jia; Tian, Geng

2017-07-25

Based on 540 hepatocellular carcinoma patients and 540 age- and gender-matched controls, we tested the hypothesis that high mobility group protein box1 (HMGB1) and the receptor for advanced glycation end products (RAGE) genes are two potential candidate susceptibility genes for hepatocellular carcinoma in a multicenter hospital-based case-control analysis. The genotypes of seven widely-studied polymorphisms were determined, and their distributions respected the Hardy-Weinberg equilibrium. The mutant alleles of two polymorphisms, rs1045411 in HMGB1 gene and rs2070600 in RAGE gene, had significantly higher frequencies in patients than in controls (P < 0.001), with the power to detect this significance of being over 99.9%. Moreover, the above two polymorphisms increased the risk of developing hepatocellular carcinoma significantly, particularly for rs2070600 under the additive (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.34-2.32; P < 0.001) and dominant (OR = 1.75; 95% CI: 1.23-2.50; P = 0.002) models after adjusting for body mass index, smoking and drinking. Haplotype analysis showed that the T-C-T haplotype (rs1045411-rs2249825-rs1415125) in HMGB1 gene was associated with a 2.47-fold (95% CI: 1.41-4.34; P = 0.002) increased risk of hepatocellular carcinoma compared with the commonest C-C-T haplotype after adjustment. In RAGE gene, the T-T-A-G (rs1800625-rs1800624-rs2070600-rs184003) (adjusted OR; 95% CI; P: 1.75; 1.02-3.03; 0.045) and T-T-A-T (adjusted OR; 95% CI; P: 1.95; 1.01-3.76; 0.048) haplotypes were associated with a marginally increased risk of hepatocellular carcinoma compared with the commonest T-T-G-G haplotype. In summary, we identified two risk-associated polymorphisms (rs1045411 and rs2070600), and more importantly a joint impact of seven polymorphisms from the HMGB1/RAGE axis in susceptibility to hepatocellular carcinoma.

Unique mutational profile associated with a loss of TDG expression in the rectal cancer of a patient with a constitutional PMS2 deficiency.

PubMed

Vasovcak, P; Krepelova, A; Menigatti, M; Puchmajerova, A; Skapa, P; Augustinakova, A; Amann, G; Wernstedt, A; Jiricny, J; Marra, G; Wimmer, K

2012-07-01

Cells with DNA repair defects have increased genomic instability and are more likely to acquire secondary mutations that bring about cellular transformation. We describe the frequency and spectrum of somatic mutations involving several tumor suppressor genes in the rectal carcinoma of a 13-year-old girl harboring biallelic, germline mutations in the DNA mismatch repair gene PMS2. Apart from microsatellite instability, the tumor DNA contained a number of C:G→T:A or G:C→A:T transitions in CpG dinucleotides, which often result through spontaneous deamination of cytosine or 5-methylcytosine. Four DNA glycosylases, UNG2, SMUG1, MBD4 and TDG, are involved in the repair of these deamination events. We identified a heterozygous missense mutation in TDG, which was associated with TDG protein loss in the tumor. The CpGs mutated in this patient's tumor are generally methylated in normal colonic mucosa. Thus, it is highly likely that loss of TDG contributed to the supermutator phenotype and that most of the point mutations were caused by deamination of 5-methylcytosine to thymine, which remained uncorrected owing to the TDG deficiency. This case provides the first in vivo evidence of the key role of TDG in protecting the human genome against the deleterious effects of 5-methylcytosine deamination. Copyright © 2012 Elsevier B.V. All rights reserved.

Unique mutational profile associated with a loss of TDG expression in the rectal cancer of a patient with a constitutional PMS2 deficiency

PubMed Central

Vasovcak, P.; Krepelova, A.; Menigatti, M.; Puchmajerova, A.; Skapa, P.; Augustinakova, A.; Amann, G.; Wernstedt, A.; Jiricny, J.; Marra, G.; Wimmer, K.

2012-01-01

Cells with DNA repair defects have increased genomic instability and are more likely to acquire secondary mutations that bring about cellular transformation. We describe the frequency and spectrum of somatic mutations involving several tumor suppressor genes in the rectal carcinoma of a 13-year-old girl harboring biallelic, germline mutations in the DNA mismatch repair gene PMS2. Apart from microsatellite instability, the tumor DNA contained a number of C:G → T:A or G:C → A:T transitions in CpG dinucleotides, which often result through spontaneous deamination of cytosine or 5-methylcytosine. Four DNA glycosylases, UNG2, SMUG1, MBD4 and TDG, are involved in the repair of these deamination events. We identified a heterozygous missense mutation in TDG, which was associated with TDG protein loss in the tumor. The CpGs mutated in this patient's tumor are generally methylated in normal colonic mucosa. Thus, it is highly likely that loss of TDG contributed to the supermutator phenotype and that most of the point mutations were caused by deamination of 5-methylcytosine to thymine, which remained uncorrected owing to the TDG deficiency. This case provides the first in vivo evidence of the key role of TDG in protecting the human genome against the deleterious effects of 5-methylcytosine deamination. PMID:22608206

Carcinoma of the larynx: role of laser surgery

NASA Astrophysics Data System (ADS)

Inouye, Tetsuzo; Tanabe, Tetsuya; Nakanoboh, Manabu; Ohmae, Yukio; Ogura, Masami

1995-05-01

68 cases of glottic carcinomas (T1 53 and T2 15 cases) treated with CO2 laser or KTP/532 laser April 1982 through March 1992 were reviewed. The patients were followed up from 13 to 130 months (mean 60 months). The 3-year determinate survival rate was 100% and 5-year determinate survival rate was 100% for T1 and 80% for T2. The voice conservation rate was 97% for T1a, 83% for T1b, and 80% for T2 and vocal function was satisfactorily preserved for daily life. The results led to the following conclusions: (1) Glottic T1 carcinomas can be treated by laser surgery alone. (2) Lesions involving the anterior commissure can be treated by laser excision and vaporization. (3) Laser surgery followed by external radiation therapy for glottic T2 carcinomas improves the voice conservation rate.

Effect of preoperative treatment strategies on the outcome of patients with clinical T3, non-metastasized rectal cancer: A comparison between Dutch and Canadian expert centers.

PubMed

Breugom, A J; Vermeer, T A; van den Broek, C B M; Vuong, T; Bastiaannet, E; Azoulay, L; Dekkers, O M; Niazi, T; van den Berg, H A; Rutten, H J T; van de Velde, C J H

2015-08-01

High-dose-rate brachytherapy (HDRBT) appears to be associated with less treatment-related toxicity compared with external beam radiotherapy in patients with rectal cancer. The present study compared the effect of preoperative treatment strategies on overall survival, cancer-specific deaths, and local recurrences between a Dutch and Canadian expert center with different preoperative treatment strategies. We included 145 Dutch and 141 Canadian patients with cT3, non-metastasized rectal cancer. All patients from Canada were preoperatively treated with HDRBT. The preoperative treatment strategy for Dutch patients consisted of either no preoperative treatment, short-course radiotherapy, or chemoradiotherapy. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) comparing overall survival. We adjusted for age, cN stage, (y)pT stage, comorbidity, and type of surgery. Primary endpoint was overall survival. Secondary endpoints were cancer-specific deaths and local recurrences. Five-year overall survival was 70.9% (95% CI 62.6%-77.7%) in Dutch patients compared with 86.9% (80.1%-91.6%) in Canadian patients, resulting in an adjusted HR of 0.70 (95% CI 0.39-1.26; p = 0.233). Of 145 Dutch patients, 6.9% (95% CI 2.8%-11.0%) had a local recurrence and 17.9% (95% CI 11.7%-24.2%) patients died of rectal cancer, compared with 4.3% (95% CI 0.9%-7.5%) local recurrences and 10.6% (95% CI 5.5%-15.7%) rectal cancer deaths out of 141 Canadian patients. We did not detect statistically significant differences in overall survival between a Dutch and Canadian expert center with different treatment strategies. This finding needs to be further investigated in a randomized controlled trial. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electronic properties of in-plane phase engineered 1T'/2H/1T' MoS2

NASA Astrophysics Data System (ADS)

Thakur, Rajesh; Sharma, Munish; Ahluwalia, P. K.; Sharma, Raman

2018-04-01

We present the first principles studies of semi-infinite phase engineered MoS2 along zigzag direction. The semiconducting (2H) and semi-metallic (1T') phases are known to be stable in thin-film MoS2. We described the electronic and structural properties of the infinite array of 1T'/2H/1T'. It has been found that 1T'phase induced semi-metallic character in 2H phase beyond interface but, only Mo atoms in 2H phase domain contribute to the semi-metallic nature and S atoms towards semiconducting state. 1T'/2H/1T' system can act as a typical n-p-n structure. Also high holes concentration at the interface of Mo layer provides further positive potential barriers.

SU-F-T-358: Is Auto-Planning Useful for Volumetric-Modulated Arc Therapy Planning in Rectal Cancer Radiotherapy?

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

Li, K; Chang, X; Wang, J

Purpose: To evaluate whether Auto-Planning based volumetric-modulated radiotherapy (auto-VMAT) can reduce manual interaction time during treatment planning and improve plan quality for rectal cancer radiotherapy. Methods: Ten rectal cancer patients (stage II and III) after radical resection using Dixon surgery were enrolled. All patients were treated with VMAT technique. The manual VMAT plans (man-VMAT) were designed in the Pinnacle treatment planning system (Version 9.10) following the standard treatment planning procedure developed in our department. Clinical plans were manually designed by our experienced dosimetrists. Additionally, an auto-VMAT plan was created for each patient using Auto-Planning module. However, manual interaction was stillmore » applied to meet the clinical requirements. The treatment planning time and plan quality surrogated by the DVH parameters were compared between manual and automated plans. Results: The total planning time and manual interaction time were 50.38 and 4.47 min for the auto-VMAT and 36.81 and 16.94 min for the man-VMAT (t=60.14,−23.86; p=0.000, 0.000). In terms of plan quality, both plans meet the clinical requirements. The PTV homogeneity index (HI) and conformity index (CI) were 0.054 and 0.822 for the auto-VMAT and 0.059 and 0.815 for the man-VMAT (t=−1.72, 0.36;p=0.119,0.730).Compared to the man-VMAT, the auto-VMAT showed reduction of 11.9% and 0.7% in V40 and V50 of the bladder, respectively.The V30 and D mean were reduced by 14.0% and 5.1Gy in the left femur and 12.2% and 3.8Gy in the right femur. Conclusion: The Auto-Planning based VMAT plans not only shows similar or superior plan quality to the manual ones in the rectal cancer radiotherapy, but also improve the planning efficiency significantly. However, manual interactions are still required to achieve a clinically acceptable plan based on our experiences.« less

A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.

PubMed

Pelletier, Daniel J; Czeczok, Thomas W; Bellizzi, Andrew M

2018-07-01

Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus-associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross-reacted with MCPyV, that would be advantageous from a resource-utilisation perspective. Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small-cell lung carcinomas, and 18 extrapulmonary visceral small-cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches. The PAb416 antibody against the SV40 large T antigen does not cross-react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma. © 2018 John Wiley & Sons Ltd.

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.

PubMed

Szabó, J; Hegedûs, G; Bartók, K; Kerényi, T; Végh, A; Romics, I; Szende, B

2000-01-01

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.

Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

PubMed Central

Fogg, Mark; Murphy, John R.; Lorch, Jochen; Posner, Marshall; Wang, Fred

2013-01-01

Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. PMID:23601786

Oral versus rectal ibuprofen in healthy volunteers.

PubMed

Vilenchik, Rolanda; Berkovitch, Matitiahu; Jossifoff, Azaria; Ben-Zvi, Zvi; Kozer, Eran

2012-01-01

Ibuprofen is a safe and effective non steroidal anti-inflammatory drug (NSAID). Ibuprofen suppositories are marketed in Europe; but data regarding pharmacokinetics of rectal vs. oral ibuprofen in humans is scarce. The objective of this study is to compare the pharmacokinetics of single-dose rectal vs. oral ibuprofen in healthy adult volunteers. Ten healthy adult male volunteers, aged 20-37 years, received in a non-blind, cross-over setting, two formulations of ibuprofen. First, a 400 mg (about 5 mg/kg) of racemic ibuprofen suppository; second (after a three week washout period) the same dosage of ibuprofen syrup. Blood samples were collected before dosing and for 12 hours after administration. Pharmacokinetics analysis was preformed. Mean peak plasma concentration (Cmax) of rectal ibuprofen was considerably lower, and the mean time to peak (Tmax) considerably longer, compared to oral ibuprofen. Absorption of rectal ibuprofen was considerably lower than oral ibuprofen, with a relative bioequivalence of 63%. Rectal ibuprofen reached therapeutic plasma concentration (>10 µg/ml) 45 minutes after dosing and remained in that range for four hours. The values of Vd/F and CL/F also differ significantly after rectal and oral administration, while no difference was found in the elimination rate constant (Kel) or half-life elimination (t1/2). Racemic ibuprofen suppository has lower bioavailability compared with ibuprofen syrup. Therapeutic plasma concentrations of ibuprofen were reached 45 minutes after dosing and remained in that range for 4 hours. Ibuprofen suppositories can contribute to the management of fever and pain when the oral route is not available.

Rectal adenocarcinoma infiltrating the bulbar urethra and metastasising to the penis

PubMed Central

James, Mathews; Amaranathan, Anandhi; Nelamangala Ramakrishnaiah, Vishnu Prasad; Toi, Pampa Chakrabarty

2016-01-01

Secondary penile tumours from rectal carcinoma is a known clinical entity but can be missed unless carefully evaluated. We report a case of rectal adenocarcinoma with synchronous painless penile nodules. A patient presented with constipation and rectal bleeding. He had an anorectal growth as well as palpable nodules on his penis. Rectal biopsy yielded adenocarcinoma. Imaging revealed direct infiltration of tumour into the bulb of the penis as well as distal shaft lesions. Fine-needle aspiration cytology of the penile nodule showed metastatic adenocarcinoma. Diversion colostomy was performed and the patient referred for chemoradiation. Since he did not have any urinary symptoms, the penile lesions were left unaltered. Repeat imaging after concurrent chemoradiotherapy showed no response. The prognosis was explained and the patient was given palliative clinic care. PMID:27312852

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.

Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas.

PubMed

Almeida, Raquel; Silva, Elisabete; Santos-Silva, Filipe; Silberg, Debra G; Wang, Jiangfu; De Bolós, Carmen; David, Leonor

2003-01-01

Intestinal metaplasia (IM) is part of a stepwise sequence of alterations of the gastric mucosa, leading ultimately to gastric cancer, and is strongly associated with chronic Helicobacter pylori infection. The molecular mechanisms underlying the onset of IM remain elusive. The aim of this study was to assess the putative involvement of two intestine-specific transcription factors, CDX1 and CDX2, in the pathogenesis of gastric IM and gastric carcinoma. Eighteen foci of IM and 46 cases of gastric carcinoma were evaluated by immunohistochemistry for CDX1 and CDX2 expression. CDX1 was expressed in all foci of IM and in 41% of gastric carcinomas; CDX2 was expressed in 17/18 foci of IM and in 54% of gastric carcinomas. In gastric carcinomas, a strong association was observed between the expression of CDX1 and CDX2, as well as between the intestinal mucin MUC2 and CDX1 and CDX2. No association was observed between the expression of CDX1 and CDX2 and the histological type of gastric carcinoma. In conclusion, these results show that aberrant expression of CDX1 and CDX2 is consistently observed in IM and in a subset of gastric carcinomas. The association of CDX1 and CDX2 with expression of the intestinal mucin MUC2, both in IM and in gastric carcinoma, indirectly implies that CDX1 and CDX2 may be involved in intestinal differentiation along the gastric carcinogenesis pathway. Copyright 2002 John Wiley & Sons, Ltd.

CRTC1/MAML2 fusion transcript in central mucoepidermoid carcinoma of mandible--diagnostic and histogenetic implications.

PubMed

Bell, Diana; Holsinger, Christopher F; El-Naggar, Adel K

2010-12-01

Intraosseous salivary gland carcinomas are extremely rare, comprising only 2% to 3% of all mucoepidermoid carcinomas (MECs) reported. The t(11;19) translocation and its CRTC1/MAML1 fusion transcript have been identified in MEC at different sites and are believed to be associated with the development of a subset of these tumors. However, the status of the fusion transcript has not been reported in intraosseous MEC. Here, we report 3 examples of central MEC of the mandible, including a case with a history of primary retromolar MEC. Reverse transcriptase-polymerase chain reaction and DNA sequencing analyses of the microdissected components of these tumors were used for the detection and verification of the fusion transcript. We identified, for the first time, the t(11;19) fusion gene transcript in central MEC, including in the previous primary retromolar MEC. No fusion transcript was detected in the second primary noncentral MEC or in another central MEC. The results indicate that central MEC can manifest the fusion transcript. This finding may have diagnostic and histogenetic roles in the future analysis of this entity. Published by Elsevier Inc.

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn's Disease.

PubMed

Beaugerie, Laurent; Carrat, Fabrice; Nahon, Stéphane; Zeitoun, Jean-David; Sabaté, Jean-Marc; Peyrin-Biroulet, Laurent; Colombel, Jean-Frédéric; Allez, Matthieu; Fléjou, Jean-François; Kirchgesner, Julien; Svrcek, Magali

2018-06-01

Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29-40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula-related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula-related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1

[Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers].

PubMed

Wang, Fu-long; Wan, De-sen; Lu, Zhen-hai; Fang, Yu-jing; Li, Li-ren; Chen, Gong; Wu, Xiao-jun; Ding, Pei-rong; Kong, Ling-heng; Lin, Jun-zhong; Pan, Zhi-zhong

2013-04-01

To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques. Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis. The positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis. VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.

Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

PubMed

Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

2014-06-01

The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

Infiltrating T cells promote renal cell carcinoma (RCC) progression via altering the estrogen receptor β-DAB2IP signals.

PubMed

Yeh, Chiuan-Ren; Ou, Zheng-Yu; Xiao, Guang-Qian; Guancial, Elizabeth; Yeh, Shuyuan

2015-12-29

Previous studies indicated the T cells, one of the most common types of immune cells existing in the microenvironment of renal cell carcinoma (RCC), may influence the progression of RCC. The potential linkage of T cells and the estrogen receptor beta (ERβ), a key player to impact RCC progression, however, remains unclear. Our results demonstrate that RCC cells can recruit more T cells than non-malignant kidney cells. Using an in vitro matrigel invasion system, we found infiltrating T cells could promote RCC cells invasion via increasing ERβ expression and transcriptional activity. Mechanism dissection suggested that co-culturing T cells with RCC cells released more T cell attraction factors, including IFN-γ, CCL3 and CCL5, suggesting a positive regulatory feed-back mechanism. Meanwhile, infiltrating T cells may also promote RCC cell invasion via increased ERβ and decreased DAB2IP expressions, and knocking down DAB2IP can then reverse the T cells-promoted RCC cell invasion. Together, our results suggest that infiltrating T cells may promote RCC cell invasion via increasing the RCC cell ERβ expression to inhibit the tumor suppressor DAB2IP signals. Further mechanism dissection showed that co-culturing T cells with RCC cells could produce more IGF-1 and FGF-7, which may enhance the ERβ transcriptional activity. The newly identified relationship between infiltrating T cells/ERβ/DAB2IP signals may provide a novel therapeutic target in the development of agents against RCC.

TNF-alpha induction of GM2 expression on renal cell carcinomas promotes T cell dysfunction.

PubMed

Raval, Gira; Biswas, Soumika; Rayman, Patricia; Biswas, Kaushik; Sa, Gaurisankar; Ghosh, Sankar; Thornton, Mark; Hilston, Cynthia; Das, Tanya; Bukowski, Ronald; Finke, James; Tannenbaum, Charles S

2007-05-15

Previous studies from our laboratory demonstrated the role of tumor-derived gangliosides as important mediators of T cell apoptosis, and hence, as one mechanism by which tumors evade immune destruction. In this study, we report that TNF-alpha secreted by infiltrating inflammatory cells and/or genetically modified tumors augments tumor-associated GM2 levels, which leads to T cell death and immune dysfunction. The conversion of weakly apoptogenic renal cell carcinoma (RCC) clones to lines that can induce T cell death requires 3-5 days of TNF-alpha pretreatment, a time frame paralleling that needed for TNF-alpha to stimulate GM2 accumulation by SK-RC-45, SK-RC-54, and SK-RC-13. RCC tumor cell lines permanently transfected with the TNF-alpha transgene are similarly toxic for T lymphocytes, which correlates with their constitutively elevated levels of GM2. TNF-alpha increases GM2 ganglioside expression by enhancing the mRNA levels encoding its synthetic enzyme, GM2 synthase, as demonstrated by both RT-PCR and Southern analysis. The contribution of GM2 gangliosides to tumor-induced T cell death was supported by the finding that anti-GM2 Abs significantly blocked T cell apoptosis mediated by TNF-alpha-treated tumor cells, and by the observation that small interfering RNA directed against TNF-alpha abrogated GM2 synthase expression by TNF-transfected SK-RC-45, diminished its GM2 accumulation, and inhibited its apoptogenicity for T lymphocytes. Our results indicate that TNF-alpha signaling promotes RCC-induced killing of T cells by stimulating the acquisition of a distinct ganglioside assembly in RCC tumor cells.

NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

PubMed

Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

2016-08-01

Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

Adjuvant chemoradiotherapy instead of revision radical resection after local excision for high-risk early rectal cancer.

PubMed

Jeong, Jae-Uk; Nam, Taek-Keun; Kim, Hyeong-Rok; Shim, Hyun-Jeong; Kim, Yong-Hyub; Yoon, Mee Sun; Song, Ju-Young; Ahn, Sung-Ja; Chung, Woong-Ki

2016-09-05

After local excision of early rectal cancer, revision radical resection is recommended for patients with high-risk pathologic stage T1 (pT1) or pT2 cancer, but the revision procedure has high morbidity rates. We evaluated the efficacy of adjuvant concurrent chemoradiotherapy (CCRT) for reducing recurrence after local excision in these patients. Eighty-three patients with high-risk pT1 or pT2 rectal cancer underwent postoperative adjuvant CCRT after local excision. We defined high-risk features as pT1 having tumor size ≤3 cm, and/or resection margin (RM) ≤3 mm, and/or lymphovascular invasion (LVI), and/or non-full thickness excision such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), or unknown records regarding those features, or pT2 cancer. Radiotherapy was administered with a median dose of 50.4 Gy in 1.8 Gy fraction size over 5-7 weeks. Concurrent 5-fluorouracil and leucovorin were administered for 4 days in the first and fifth weeks of radiotherapy. The median interval between local excision and radiotherapy was 34 (range, 11-104) days. Fifteen patients (18.1 %) had stage pT2 tumors, 22 (26.5 %) had RM of ≥3 mm, and 21 (25.3 %) had tumors of ≥3 cm in size. Thirteen patients (15.7 %) had LVI. Transanal excision was performed in 58 patients (69.9 %) and 25 patients (30.1 %) underwent EMR or ESD. The median follow-up was 61 months. The 5-year overall survival (OS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS) rates for all patients were 94.9, 91.0, and 89.8 %, respectively. Multivariate analysis did not identify any significant factors for OS or LRFS, but the only significant factor affecting DFS was the pT stage (p = 0.027). In patients with high-risk pT1 rectal cancer, adjuvant CCRT after local excision could be an effective alternative treatment instead of revision radical resection. However, patients with pT2 stage showed inferior DFS compared to pT1.

[Effectiveness of Irinotecan, S-1, and Bevacizumab for Rectal Cancer with Lung and Skin Metastases after Adjuvant Chemotherapy].

PubMed

Hagihara, Kiyotaka; Ikeda, Masataka; Maeda, Sakae; Uemura, Mamoru; Yamamoto, Kazuyoshi; Miyake, Masakazu; Hama, Naoki; Nishikawa, Kazuhiro; Miyamoto, Atsushi; Omiya, Hideyasu; Miyazaki, Michihiko; Hirao, Motohiro; Takami, Koji; Nakamori, Shoji; Sekimoto, Mitsugu

2016-11-01

A 50-year-old woman with a chief complaint of bloody stools was diagnosed with rectal cancer via colonoscopy. Laparoscopic rectal anterior resection with D3 lymph node dissection was performed in June 2014. The pathological diagnosis was pStage III a(Ra, pT3, N1)cancer, and the patient received 8 courses of XELOX as postoperative adjuvant chemotherapy. During follow-up at 12 months after surgery, chest computed tomography revealed a mass in the left lingular segment measuring 25mm in diameter and multiple small nodules in both the lungs, indicating lung metastases. We found several subcutaneous nodules with a maximum diameter of 10mm in her abdomen and the back of head. We removed 3 subcutaneous nodules for the purpose of diagnosis and treatment in June of 2015. The pathological findings were consistent with cutaneous metastases of rectal cancer. The patient received a 1 course of IRIS and 5 courses of IRIS plus bevacizumab. Subsequently, the lung metastases disappeared and no new skin lesions were detected. We suggest that this case could be a good reference in determining the appropriate treatment for rectal cancer having lung or cutaneous metastases.

Laparoscopic versus open total mesorectal excision for rectal cancer.

PubMed

Breukink, S; Pierie, J; Wiggers, T

2006-10-18

Because definitive long-term results are not yet available, the oncological safety of laparoscopic surgery for treatment of rectal cancer remains controversial. However, laparoscopic total mesorectal excision (LTME) for rectal cancer has been proposed to have several short-term advantages in comparison with open total mesorectal excision (OTME). To evaluate whether there are any relevant differences in safety and efficacy after elective LTME, for the resection of rectal cancer, compared with OTME. We searched MEDLINE, EMBASE, Cochrane Central register of Controlled Trials (CENTRAL), and Current Contents from 1990 to December 2005. Searches were conducted using MESH terms: "laparoscopy", "minimally invasive","colorectal neoplasms". Furthermore we used the following text words: laparoscopy, surgical procedures, minimally invasive, rectal cancer, rectal carcinoma, rectal adenocarcinoma, rectal neoplasms, anterior resection, abdominoperineal resection, total mesorectal excision. We included randomised controlled trials (RCTs), controlled clinical trials and case series comparing LTME versus OTME. Furthermore case reports which describe LTME were also included. Two reviewers independently assessed study quality. All relevant studies have been categorized according to the evidence they provide according to the guidelines for "Levels of Evidence and Grades of Recommendation" supplied by the "Oxford Centre for Evidence-based Medicine". Disagreements were solved by discussion. 80 studies were identified of which 48 studies, representing 4224 patients, met the inclusion criteria. Methodological quality of most of the included studies was poor; three studies were grade 1b (individual randomised trial), 12 grade 2b (individual cohort study), 5 grade 3b (individual case-control study) and 28 grade 4 (case-series). As only one RCT described primary outcome, 3-year and 5-year disease-free survival rates, no meta-analyses could be performed. No significant differences in terms of

The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin.

PubMed

Cazzaniga, Alessandra; Moscheni, Claudia; Trapani, Valentina; Wolf, Federica I; Farruggia, Giovanna; Sargenti, Azzurra; Iotti, Stefano; Maier, Jeanette A M; Castiglioni, Sara

2017-01-17

The processes leading to anticancer drug resistance are not completely unraveled. To get insights into the underlying mechanisms, we compared colon carcinoma cells sensitive to doxorubicin with their resistant counterpart. We found that resistant cells are growth retarded, and show staminal and ultrastructural features profoundly different from sensitive cells. The resistant phenotype is accompanied by the upregulation of the magnesium transporter MagT1 and the downregulation of the ion channel kinase TRPM7. We demonstrate that the different amounts of TRPM7 and MagT1 account for the different proliferation rate of sensitive and resistant colon carcinoma cells. It remains to be verified whether they are also involved in the control of other "staminal" traits.

Genetic variation in C-reactive protein (CRP) in relation to colon and rectal cancer risk and survival

PubMed Central

Slattery, Martha L.; Curtin, Karen; Poole, Elizabeth M.; Duggan, David J.; Samowitz, Wade S.; Peters, Ulrike; Caan, Bette J.; Potter, John D.; Ulrich, Cornelia M.

2011-01-01

Background C-reactive protein (CRP), a biomarker of inflammation has been shown to be influenced by genetic variation in the CRP gene. Methods In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and rectal cancer and survival. Two population-based studies of colon cancer (n=1574 cases, 1970 controls) and rectal (n=791 cases, 999 controls) were conducted. We evaluated four CRP tagSNPs: rs1205 (G>A, 3’ UTR); rs1417938 (T>A, intron); rs1800947 (G>C, L184L); and rs3093075 (C>A, 3’ flanking). Results The CRP rs1205 AA genotype was associated with an increased risk of colon cancer (OR 1.3, 95%CI 1.1-1.7), whereas the rs3093075 A allele was associated with a reduced risk of rectal cancer (OR 0.7, 95%CI 0.5-0.9). The strongest association for the rs1205 polymorphism and colon cancer was observed among those with KRAS2 mutations (OR 1.5, 95%CI 1.1-2.0). The CRP rs1205 AA genotype also was associated with an increased risk of CIMP+ rectal tumors (OR 2.5, 95% CI 1.2-5.3); conversely, the rs1417938 A allele was associated with a reduced risk of CIMP+ rectal tumors (OR 0.5, 95%CI 0.3-0.9). We observed interactions between CRP rs1800947 and BMI and family history of CRC in modifying risk of both colon and rectal cancer. Conclusions These data suggest that genetic variation in the CRP gene influences risk of both colon and rectal cancer development. PMID:20949557

Rectal balloon use limits vaginal displacement, rectal dose, and rectal toxicity in patients receiving IMRT for postoperative gynecological malignancies.

PubMed

Wu, Cheng-Chia; Wuu, Yen-Ruh; Yanagihara, Theodore; Jani, Ashish; Xanthopoulos, Eric P; Tiwari, Akhil; Wright, Jason D; Burke, William M; Hou, June Y; Tergas, Ana I; Deutsch, Israel

2018-01-01

Pelvic radiotherapy for gynecologic malignancies traditionally used a 4-field box technique. Later trials have shown the feasibility of using intensity-modulated radiotherapy (IMRT) instead. But vaginal movement between fractions is concerning when using IMRT due to greater conformality of the isodose curves to the target and the resulting possibility of missing the target while the vagina is displaced. In this study, we showed that the use of a rectal balloon during treatment can decrease vaginal displacement, limit rectal dose, and limit acute and late toxicities. Little is known regarding the use of a rectal balloon (RB) in treating patients with IMRT in the posthysterectomy setting. We hypothesize that the use of an RB during treatment can limit rectal dose and acute and long-term toxicities, as well as decrease vaginal cuff displacement between fractions. We performed a retrospective review of patients with gynecological malignancies who received postoperative IMRT with the use of an RB from January 1, 2012 to January 1, 2015. Rectal dose constraint was examined as per Radiation Therapy Oncology Group (RTOG) 1203 and 0418. Daily cone beam computed tomography (CT) was performed, and the average (avg) displacement, avg magnitude, and avg magnitude of vector were calculated. Toxicity was reported according to RTOG acute radiation morbidity scoring criteria. Acute toxicity was defined as less than 90 days from the end of radiation treatment. Late toxicity was defined as at least 90 days after completing radiation. Twenty-eight patients with postoperative IMRT with the use of an RB were examined and 23 treatment plans were reviewed. The avg rectal V40 was 39.3% ± 9.0%. V30 was65.1% ± 10.0%. V50 was 0%. Separate cone beam computed tomography (CBCT) images (n = 663) were reviewed. The avg displacement was as follows: superior 0.4 + 2.99 mm, left 0.23 ± 4.97 mm, and anterior 0.16 ± 5.18 mm. The avg magnitude of displacement was superior

Cardiac Iron Determines Cardiac T2*, T2, and T1 in the Gerbil Model of Iron Cardiomyopathy

PubMed Central

Wood, John C.; Otto-Duessel, Maya; Aguilar, Michelle; Nick, Hanspeter; Nelson, Marvin D.; Coates, Thomas D.; Pollack, Harvey; Moats, Rex

2010-01-01

Background Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver using a gerbil iron-overload model. Methods and Results Twelve gerbils underwent iron dextran loading (200 mg · kg−1 · wk−1) from 2 to 14 weeks; 5 age-matched controls were studied as well. Animals had in vivo assessment of cardiac T2* and hepatic T2 and T2* and postmortem assessment of cardiac and hepatic T1 and T2. Relaxation measurements were performed in a clinical 1.5-T magnet and a 60-MHz nuclear magnetic resonance relaxometer. Cardiac and liver iron concentrations rose linearly with administered dose. Cardiac 1/T2*, 1/T2, and 1/T1 rose linearly with cardiac iron concentration. Liver 1/T2*, 1/T2, and 1/T1 also rose linearly, proportional to hepatic iron concentration. Liver and heart calibrations were similar on a dry-weight basis. Conclusions MRI measurements of cardiac T2 and T2* can be used to quantify cardiac iron. The similarity of liver and cardiac iron calibration curves in the gerbil suggests that extrapolation of human liver calibration curves to heart may be a rational approximation in humans. PMID:16027257

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.

Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients

PubMed Central

Soliman, A S; Bondy, M L; El-Badawy, S A; Mokhtar, N; Eissa, S; Bayoumy, S; Seifeldin, I A; Houlihan, P S; Lukish, J R; Watanabe, T; Chan, A On On; Zhu, D; Amos, C I; Levin, B; Hamilton, S R

2001-01-01

Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs before age 40 years and in the rectum. We compared the molecular pathology of 59 representative Egyptian patients aged 10–72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)-associated carcinoma and found significant differences. Most Egyptian cancers were rectal (51%) and poorly differentiated (58%). High levels of microsatellite instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair gene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis identified 2 groups: predominantly young men with poorly differentiated mucinous and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras mutation and schistosomiasis. Our findings show that the molecular pathology of colorectal cancer in older as well as younger Egyptians has unique differences from Western patients, and schistosomiasis influences the molecular pathogenesis of some tumours. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11592777

Postoperative radiation therapy of pT2-3N0M0 esophageal carcinoma-a review.

PubMed

Luo, Yijun; Wang, Xiaoli; Yu, Jinming; Zhang, Bin; Li, Minghuan

2016-11-01

Esophageal cancer is one of the most malignant gastrointestinal cancers worldwide. Despite advances in surgical technique, 5-year survival in pathologic stage T2-3N0M0 esophageal squamous cell carcinoma patients who are treated with surgery alone is still poor. The addition of adjuvant radiotherapy may confer a benefit for these patients. However, not all patients could get a benefit from radiotherapy and patients with esophageal squamous cell carcinoma receiving radiotherapy seem to have a disparity in treatment response. Thus, identifying effective prognostic indicator to complement current clinical staging approaches is extremely important. Those prognostic factors could give rise to a novel prognostic stratification system, which serve as criteria for selecting patients for adjuvant therapy. Consequently, it may help to define the subgroups who are more likely to benefit from postoperative radiation therapy.

BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma.

PubMed

Pennington, Kathryn P; Walsh, Tom; Lee, Ming; Pennil, Christopher; Novetsky, Akiva P; Agnew, Kathy J; Thornton, Anne; Garcia, Rochelle; Mutch, David; King, Mary-Claire; Goodfellow, Paul; Swisher, Elizabeth M

2013-01-15

Uterine serous carcinoma (USC) is not recognized as part of any defined hereditary cancer syndrome, and its association with hereditary breast and ovarian carcinoma and Lynch syndrome are uncertain. Using targeted capture and massively parallel genomic sequencing, 151 subjects with USC were assessed for germline mutations in 30 tumor suppressor genes, including BRCA1 (breast cancer 1, early onset), BRCA2, the DNA mismatch repair genes (MLH1 [mutL homolog 1], MSH2 [mutS homolog 2], MSH6, PMS2 [postmeiotic segregation increased 2]), TP53 (tumor protein p53), and 10 other genes in the Fanconi anemia-BRCA pathway. Ten cases with < 10% serous histology were also assessed. Seven subjects (4.6%) carried germline loss-of-function mutations: 3 subjects (2.0%) with mutations in BRCA1, 2 subjects (1.3%) with mutations in TP53, and 2 subjects (1.3%) with mutations in CHEK2 (checkpoint kinase 2). One subject with < 10% serous histology had an MSH6 mutation. Subjects with MSH6 and TP53 mutations had neither personal nor family histories suggestive of Lynch or Li-Fraumeni syndromes. Of the 22 women with USC and a personal history of breast carcinoma, the frequency of BRCA1 mutations was 9%, compared to 0.9% in 119 women with no such history. Approximately 5% of women with USC have germline mutations in 3 different tumor suppressor genes: BRCA1, CHEK2, and TP53. Mutations in DNA mismatch repair genes that cause Lynch syndrome are rare in USC. The germline BRCA1 mutation rate in USC subjects of 2% is higher than expected in a nonfounder population, suggesting that USC is associated with hereditary breast and ovarian carcinoma in a small proportion of cases. Women with USC and breast cancer should be offered genetic testing for BRCA1 and BRCA2 mutations. Copyright © 2012 American Cancer Society.

Outpatient application of formalin for chronic rectal bleeding after prostate irradiation: a quasi-experimental study.

PubMed

Viani, Gustavo Arruda; Sakamoto, Aline

2017-07-01

The aim of this quasi-experimental study is to evaluate a novel technique for an outpatient application of formalin for chronic rectal bleeding after prostate irradiation. This is a quasi- experimental clinical trial developed between January 2010 and July 2015, including 35 patients with chronic radiation rectitis (CRP) due to a previous prostate radiation course. The study's eligibility was (1) completed external beam radiation therapy for prostate carcinoma >6 months previously, (2) rectal bleeding, defined as a frequency of >1× per week and/or needing of blood transfusions, and (3) diagnosis of chronic proctitis at colonoscopy. The 5% formalin application was performed by a custom applicator, which requires neither anesthesia nor sigmoidoscopy. The endpoint of the study was bleeding cessation and hemoglobin level. The onset of bleeding due to chronic rectitis was 12 months (6-36). During a median follow-up of 24 months, the rate of overall efficacy was 94%. The sustained complete response in 1 and 2 years was 80% and 73%, respectively. The Hb mean pre- and post-treatment differed significantly (12.2 vs 14.4, p = 0.0001). The rates of blood transfusion differed significantly, pre- and post-treatment (17% vs 5.7%, p = 0.031). The technique is very effective and safe, resulting to a significant improvement of hemoglobin levels and quality of life scores. Further studies are warranted to compare this technique with other treatment options for chronic radiation-induced rectal bleeding.

Glottic and supraglottic pT3 squamous cell carcinoma: outcomes with transoral laser microsurgery.

PubMed

Pantazis, Dimitrios; Liapi, Georgia; Kostarelos, Dimitrios; Kyriazis, Georgios; Pantazis, Theodoros-Leonidas; Riga, Maria

2015-08-01

Patients diagnosed with T3 squamous cell laryngeal carcinomas are nowadays offered either organ-preserving surgical or non-surgical treatment, with the optimum approach remaining undefined. No direct comparison of organ-preserving therapeutical options, stratified by anatomical subsites is available in the literature. The aim of this study is to present institutional treatment outcomes for laser-assisted microsurgery (TLM) of laryngeal T3 squamous cell carcinomas and review the relevant literature. Sixty-four consecutive, previously untreated patients were evaluated. Twenty-four supraglottic and 19 glottic patients were treated with TLM and neck dissection, tumor exposure and postoperative upstaging of the tumors through pathology evaluation of the specimens being the only exclusion criteria. Five-year disease-specific survival and organ preservation rates for supraglottic carcinomas were both 91.7 %. The respective values for glottic carcinomas were 63.2 and 73.3 %. TLM-treated T3 supraglottic tumors seem to attribute better outcomes than T3 glottic tumors in terms of recurrence-free survival, organ preservation and local control (p = 0.01, <0.0001 and 0.01, respectively). The results of this study suggest that TLM-treated T3 supraglottic tumors have a good prognosis, substantially better than that of glottic tumors. A literature review, on the other hand, attributes to chemo-radiation-treated T3 supraglottic tumors a considerably poorer prognosis. Further studies of homogenous populations in terms of anatomical subsites are needed in order to reach a consensus regarding treatment of T3 laryngeal tumors.

Exercise and cancer: return to work as a firefighter with ostomy after rectal carcinoma - a case report.

PubMed

Wiskemann, Joachim; Schommer, Kai; Jaeger, Dirk; Scharhag-Rosenberger, Friederike

2016-07-01

Colorectal cancer survivors are deconditioned through anticancer therapy. Furthermore, about 10% of them have a permanent ostomy which is associated with weakened abdominal muscles and an increased risk of a hernia. This case study reports on how a firefighter with rectal carcinoma and ostomy was trained to regain operational fitness. A 44-year-old firefighter (178 cm, 82 kg) with an adenocarcinoma of the rectum (diagnosed 24 months prior) had been treated with neoadjuvant radiochemotherapy and surgery. After 2 temporary ileostomies, a permanent colostomy was performed 14 weeks before the start of a 9-months training program. The program included sensorimotor, endurance, and strength training of increasing volume and intensity. Endurance, strength, and patient reported outcomes were assessed every 2 to 3 months. Training frequency varied from 1 to 3 sessions/week, although 3 to 5 sessions/week were prescribed. Peak power output was 150, 158, 167, 192, and 175 watts at baseline, 2, 4, 6, and 9 months. Maximal oxygen uptake increased from 1.56 L/min (19.0 mL/min/kg) to 2.39 L/min (28.8 mL/min/kg) after 6 months. Maximal isokinetic peak torque (MIPT) of the knee extensors were 138.0 and 196.5 Nm (Newton meter) at baseline and 6 months. MIPT of the elbow and hip flexors increased from 51.8 to 66.0 Nm and 213.8 to 239.7 Nm, respectively, after 6 months. Physical fatigue decreased by 65% and distress by about 50% after 9 months. The firefighter passed a test for occupational fitness after 6 months and was permitted to work with an exterior crew on a pump truck. It is possible for colorectal cancer survivors with ostomy to regain occupational fitness for physically demanding tasks like firefighting through an individually tailored and supervised training program.

Response of glutathione S-transferase Pi (GSTP1) to neoadjuvant therapy in rectal adenocarcinoma.

PubMed

Bedford, M R; Anathhanam, S; Saleh, D; Hickson, A; McGregor, A K; Boyle, K; Burke, D

2012-12-01

The response of rectal adenocarcinoma to neoadjuvant therapy is variable. Accurate prediction of response would enable selective administration of therapy. The enzyme glutathione S-transferase Pi (GSTP1) has been shown to influence response to therapy in some solid tumours. Few data are available for rectal cancer. The GSTP1 levels in rectal adenocarcinoma and adjacent normal mucosa were quantified before and after exposure to neoadjuvant therapy. Venous blood samples and biopsies of normal rectal mucosa and tumour were prospectively obtained from patients with primary rectal cancer. Patients were stratified by exposure to neoadjuvant therapy or surgery alone. GSTP1 was quantitatively measured using an enzyme-linked immunosorbent assay. Ninety-two patients (54 men; median age 68 years) were recruited. The median GSTP1 level was significantly higher in rectal adenocarcinoma than in matched normal mucosa [6.59 μg/mg vs 4.57 μg/mg; P < 0.001]. The median tumour GSTP1 level was significantly lower in the therapy group compared with unmatched samples from the no-therapy group [4.47 μg/mg vs 7.76 μg/mg; P < 0.001]. The GSTP1 level is increased in rectal adenocarcinoma compared with adjacent normal mucosa. It decreases following neoadjuvant therapy. Future studies correlating pre-therapy GSTP1 levels with pathological response would be of interest. © 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

Local T1-T2 distribution measurements in porous media

NASA Astrophysics Data System (ADS)

Vashaee, S.; Li, M.; Newling, B.; MacMillan, B.; Marica, F.; Kwak, H. T.; Gao, J.; Al-harbi, A. M.; Balcom, B. J.

2018-02-01

A novel slice-selective T1-T2 measurement is proposed to measure spatially resolved T1-T2 distributions. An adiabatic inversion pulse is employed for slice-selection. The slice-selective pulse is able to select a quasi-rectangular slice, on the order of 1 mm, at an arbitrary position within the sample. The method does not employ conventional selective excitation in which selective excitation is often accomplished by rotation of the longitudinal magnetization in the slice of interest into the transverse plane, but rather a subtraction based on CPMG data acquired with and without adiabatic inversion slice selection. T1 weighting is introduced during recovery from the inversion associated with slice selection. The local T1-T2 distributions measured are of similar quality to bulk T1-T2 measurements. The new method can be employed to characterize oil-water mixtures and other fluids in porous media. The method is beneficial when a coarse spatial distribution of the components is of interest.

Role of postoperative radiation therapy (PORT) in pT1-T2 N0 deep tongue cancers.

PubMed

Gokavarapu, Sandhya; Parvataneni, Nagendra; Rao S, L M Chandrasekhara; Reddy, Rammohan; Raju, K V V N; Chander, Ravi

2015-12-01

Carcinoma of tongue is associated with a high risk of occult metastasis and mortality despite early-stage detection and therapy; the critical tumor thickness at which this risk increases has been demonstrated as 4 mm or greater. There are no sufficient data in the published literature to evaluate the role of postoperative radiation therapy (PORT) in the treatment of pT1-T2 N0 oral tongue cancers with depth of invasion 4 mm or greater. Historical cohorts of patients with primary pT1-T2 N0 oral tongue cancer of depth of invasion 4 mm or greater treated surgically from January 2010 to December 2012 were included in the study, and negative margins on initial resection were filtered. Locoregional recurrence and death were analyzed among the patients who received PORT and those who did not. A total of 103 patients fulfilled the above-mentioned criteria, with 62 patients receiving PORT and 41 patients not receiving PORT; median period of follow-up was 41.3 months. Logistic and Cox regression models showed no significant difference in locoregional recurrences (P = .078) and survival (P = .339) between patients who received PORT and those who did not receive PORT. PORT did not influence survival of patients with stage I and stage II deep tongue cancers, with 4 mm or greater tumor invasion depth. Copyright © 2015 Elsevier Inc. All rights reserved.

The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin

PubMed Central

Cazzaniga, Alessandra; Moscheni, Claudia; Trapani, Valentina; Wolf, Federica I.; Farruggia, Giovanna; Sargenti, Azzurra; Iotti, Stefano; Maier, Jeanette A. M.; Castiglioni, Sara

2017-01-01

The processes leading to anticancer drug resistance are not completely unraveled. To get insights into the underlying mechanisms, we compared colon carcinoma cells sensitive to doxorubicin with their resistant counterpart. We found that resistant cells are growth retarded, and show staminal and ultrastructural features profoundly different from sensitive cells. The resistant phenotype is accompanied by the upregulation of the magnesium transporter MagT1 and the downregulation of the ion channel kinase TRPM7. We demonstrate that the different amounts of TRPM7 and MagT1 account for the different proliferation rate of sensitive and resistant colon carcinoma cells. It remains to be verified whether they are also involved in the control of other “staminal” traits. PMID:28094304

Risk Factors Associated With Circumferential Resection Margin Positivity in Rectal Cancer: A Binational Registry Study.

PubMed

Warrier, Satish K; Kong, Joseph Cherng; Guerra, Glen R; Chittleborough, Timothy J; Naik, Arun; Ramsay, Robert G; Lynch, A Craig; Heriot, Alexander G

2018-04-01

Rectal cancer outcomes have improved with the adoption of a multidisciplinary model of care. However, there is a spectrum of quality when viewed from a national perspective, as highlighted by the Consortium for Optimizing the Treatment of Rectal Cancer data on rectal cancer care in the United States. The aim of this study was to assess and identify predictors of circumferential resection margin involvement for rectal cancer across Australasia. A retrospective study from a prospectively maintained binational colorectal cancer database was interrogated. This study is based on a binational colorectal cancer audit database. Clinical information on all consecutive resected rectal cancer cases recorded in the registry from 2007 to 2016 was retrieved, collated, and analyzed. The primary outcome measure was positive circumferential resection margin, measured as a resection margin ≤1 mm. A total of 3367 patients were included, with 261 (7.5%) having a positive circumferential resection margin. After adjusting for hospital and surgeon volume, hierarchical logistic regression analysis identified a 6-variable model encompassing the independent predictors, including urgent operation, abdominoperineal resection, open technique, low rectal cancer, T3 to T4, and N1 to N2. The accuracy of the model was 92.3%, with an receiver operating characteristic of 0.783 (p < 0.0001). The quantitative risk associated with circumferential resection margin positivity ranged from <1% (no risk factors) to 43% (6 risk factors). This study was limited by the lack of recorded long-term outcomes associated with circumferential resection margin positivity. The rate of circumferential resection margin involvement in patients undergoing rectal cancer resection in Australasia is low and is influenced by a number of factors. Risk stratification of outcome is important with the increasing demand for publicly accessible quality data. See Video Abstract at http://links.lww.com/DCR/A512.

Adoption of Preoperative Radiation Therapy for Rectal Cancer From 2000 to 2006: A Surveillance, Epidemiology, and End Results Patterns-of-Care Study

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

Mak, Raymond H.; McCarthy, Ellen P.; Das, Prajnan

2011-07-15

Purpose: The German rectal study determined that preoperative radiation therapy (RT) as a component of combined-modality therapy decreased local tumor recurrence, increased sphincter preservation, and decreased treatment toxicity compared with postoperative RT for rectal cancer. We evaluated the use of preoperative RT after the presentation of the landmark German rectal study results and examined the impact of tumor and sociodemographic factors on receiving preoperative RT. Methods and Materials: In total, 20,982 patients who underwent surgical resection for T3-T4 and/or node-positive rectal adenocarcinoma diagnosed from 2000 through 2006 were identified from the Surveillance, Epidemiology, and End Results tumor registries. We analyzedmore » trends in preoperative RT use before and after publication of the findings from the German rectal study. We also performed multivariate logistic regression to identify factors associated with receiving preoperative RT. Results: Among those treated with RT, the proportion of patients treated with preoperative RT increased from 33.3% in 2000 to 63.8% in 2006. After adjustment for age; gender; race/ethnicity; marital status; Surveillance, Epidemiology, and End Results registry; county-level education; T stage; N stage; tumor size; and tumor grade, there was a significant association between later year of diagnosis and an increase in preoperative RT use (adjusted odds ratio, 1.26/y increase; 95% confidence interval, 1.23-1.29). When we compared the years before and after publication of the German rectal study (2000-2003 vs. 2004-2006), patients were more likely to receive preoperative RT than postoperative RT in 2004-2006 (adjusted odds ratio, 2.35; 95% confidence interval, 2.13-2.59). On multivariate analysis, patients who were older, who were female, and who resided in counties with lower educational levels had significantly decreased odds of receiving preoperative RT. Conclusions: After the publication of the landmark German

[Transanal total mesorectal excision for rectal cancer - just a fashion trend?].

PubMed

Kala, Z; Skrovina, M; Procházka, V; Grolich, T; Klos, K

2014-12-01

Transanal total mesorectal excision performed using equipment for transanal minimally invasive surgery is an innovative surgical technique introduced to facilitate this procedure and to reach better oncosurgical outcomes in patients with low rectal cancer. This article presents a brief summary of guidelines for treatment of patients with low rectal carcinoma. Up-to-date information about the principles of this new method, its modifications and contemporary indications is presented. Based on their own experience and literature resources, the authors inform about the advantages, limitations and unresolved issues of minimally invasive transanal mesorectal excision.

Spontaneous rupture of the renal pelvis presenting as an urinoma in locally advanced rectal cancer

PubMed Central

Garg, Pankaj Kumar; Mohanty, Debajyoti; Rathi, Vinita; Jain, Bhupendra Kumar

2014-01-01

A 29-year-old gentleman underwent a transverse colostomy for intestinal obstruction caused by advanced rectal carcinoma. On the 5th postoperative day, the patient developed a painful swelling on the right side of the abdomen. The contrast enhanced computed tomography of the abdomen revealed a right sided hydronephrosis, a large rent in the renal pelvis, and a large retroperitoneal fluid collection on the right side. Percutaneous nephrostomy and pigtail catheter drainage of the urinoma led to resolution of abdominal swelling. Development of a urinoma as a consequence of rectal carcinoma is highly unusual. Prompt imaging for confirmation of diagnosis, decompression of the renal pelvicalyceal system, and drainage of the urinoma limits morbidity. PMID:24749123

Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma.

PubMed Central

Starzynska, T.; Marsh, P. J.; Schofield, P. F.; Roberts, S. A.; Myers, K. A.; Stern, P. L.

1994-01-01

The 5T4 oncofetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumour cells and metastatic spread. The 5T4 antigen phenotype of 72 colorectal cancers has been compared with the clinical outcome of the patients in order to assess its relationship with prognosis. Forty per cent of tumours were 5T4 positive; the remainder were either unlabelled or exhibited stroma-associated labelling only. There was a significant correlation between 5T4 expression in the malignant cells and unfavourable course of disease (P < 0.001). The 5 year survival with 5T4-positive tumours was 22% compared with 75% for patients with 5T4-negative tumours; median survival was 24 versus > 90 months respectively. Stratified analysis showed that 5T4 antigen tumour positivity was acting independently of each of stage, site of tumour, age or sex. There were significant differences in survival for patients with Dukes' B and C stage carcinomas (P = 0.001 and P = 0.034). The results suggest that in colorectal cancer immunohistochemical assessment of 5T4 expression may be useful in identifying patients at high risk for tumour recurrence and for whom additional treatment strategies might be most appropriate. Images Figure 1 PMID:8180020

Hybridized 1T/2H MoS2 Having Controlled 1T Concentrations and its use in Supercapacitors.

PubMed

Thi Xuyen, Nguyen; Ting, Jyh-Ming

2017-12-06

Molybdenum disulfide (MoS 2 ) nanoflowers consisting of hybridized 1T/2H phases have been synthesized by using a microwave-assisted hydrothermal (MTH) method. The concentration of the 1T phase, ranging from 40 % to 73 %, is controlled by simply adjusting the ratio of the Mo and S precursors. By using the hybridized 1T/2H MoS 2 as an electrode material, it was demonstrated that the resulting supercapacitor performance is dominated by the 1T phase concentration. It was found that a supercapacitor with 73 % 1T phase exhibits excellent capacitance of 259 F g -1 and great cyclic stability after 1000 cycles. The formation mechanism of the MHT-synthesized hybridized 1T/2H MoS 2 is also reported. More importantly, the mechanism also explains the observed relationship between the 1T phase concentration and the ratio of the Mo and S precursors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prostate Postbrachytherapy Seed Distribution: Comparison of High-Resolution, Contrast-Enhanced, T1- and T2-Weighted Endorectal Magnetic Resonance Imaging Versus Computed Tomography: Initial Experience

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

Bloch, B. Nicolas; Department of Radiology, General Hospital Vienna, Medical University Vienna, Vienna; Lenkinski, Robert E.

2007-09-01

Purpose: To compare contrast-enhanced, T1-weighted, three-dimensional magnetic resonance imaging (CEMR) and T2-weighted magnetic resonance imaging (T2MR) with computed tomography (CT) for prostate brachytherapy seed location for dosimetric calculations. Methods and Materials: Postbrachytherapy prostate MRI was performed on a 1.5 Tesla unit with combined surface and endorectal coils in 13 patients. Both CEMR and T2MR used a section thickness of 3 mm. Spiral CT used a section thickness of 5 mm with a pitch factor of 1.5. All images were obtained in the transverse plane. Two readers using CT and MR imaging assessed brachytherapy seed distribution independently. The dependency of datamore » read by both readers for a specific subject was assessed with a linear mixed effects model. Results: The mean percentage ({+-} standard deviation) values of the readers for seed detection and location are presented. Of 1205 implanted seeds, CEMR, T2MR, and CT detected 91.5% {+-} 4.8%, 78.5% {+-} 8.5%, and 96.1% {+-} 2.3%, respectively, with 11.8% {+-} 4.5%, 8.5% {+-} 3.5%, 1.9% {+-} 1.0% extracapsular, respectively. Assignment to periprostatic structures was not possible with CT. Periprostatic seed assignments for CEMR and T2MR, respectively, were as follows: neurovascular bundle, 3.5% {+-} 1.6% and 2.1% {+-} 0.9%; seminal vesicles, 0.9% {+-} 1.8% and 0.3% {+-} 0.7%; periurethral, 7.1% {+-} 3.3% and 5.8% {+-} 2.9%; penile bulb, 0.6% {+-} 0.8% and 0.3% {+-} 0.6%; Denonvillier's Fascia/rectal wall, 0.5% {+-} 0.6% and 0%; and urinary bladder, 0.1% {+-} 0.3% and 0%. Data dependency analysis showed statistical significance for the type of imaging but not for reader identification. Conclusion: Both enumeration and localization of implanted seeds are readily accomplished with CEMR. Calculations with MRI dosimetry do not require CT data. Dose determinations to specific extracapsular sites can be obtained with MRI but not with CT.« less

Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma

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

Nakamura, Tomoyuki; Sato, Yuko; Watanabe, Daisuke

2010-03-15

To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal inmore » any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.« less

Formulation and Evaluation of Irinotecan Suppository for Rectal Administration

PubMed Central

Feng, Haiyang; Zhu, Yuping; Li, Dechuan

2014-01-01

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. Cmax, t1/2, AUC0–30h and AUC0-∞ were 16.1 ± 2.7 g/ml, 7.6 ± 1.2 h, 71.3 ± 8.8 μg·h/ml and 82.3 ± 9.5 μg·h/ml, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of 5.3 ± 2.5 μg/ml at 4 h. The AUC0–30h and AUC0-∞ were 32.2 ± 6.2 μg·h/ml and 41.6 ± 7.2 μg·h/ml, respectively. It representing ∼50.6% of the absolute bioavailability. PMID:24596626

Formulation and evaluation of irinotecan suppository for rectal administration.

PubMed

Feng, Haiyang; Zhu, Yuping; Li, Dechuan

2014-01-01

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. Cmax, t1/2, AUC0-30h and AUC0-∞ were 16.1 ± 2.7 g/ml, 7.6 ± 1.2 h, 71.3 ± 8.8 μg·h/ml and 82.3 ± 9.5 μg·h/ml, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of 5.3 ± 2.5 μg/ml at 4 h. The AUC0-30h and AUC0-∞ were 32.2 ± 6.2 μg·h/ml and 41.6 ± 7.2 μg·h/ml, respectively. It representing ∼50.6% of the absolute bioavailability.

Phase I Trial of Neoadjuvant Preoperative Chemotherapy With S-1 and Irinotecan Plus Radiation in Patients With Locally Advanced Rectal Cancer

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

Sato, Takeo; Kokuba, Yukihito; Koizumi, Wasaburo

Purpose: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with preoperative chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. Patients and Methods: We gave preoperative radiotherapy (total dose, 45 Gy) to 23 patients with locally advanced (T3/T4) rectal cancer. Concurrently, S-1 was given orally at a fixed dose of 80 mg/m{sup 2}/day on Days 1-5, 8-12, 22-26, and 29-33, and irinotecan was given as a 90-min continuous i.v. infusion on Days 1, 8, 22, and 29. The dose of irinotecan was initially 40 mg/m{sup 2}/day and gradually increased to determine the MTDmore » and RD of this regimen. Results: Among the 4 patients who received 90 mg/m{sup 2} irinotecan, 2 had Grade 4 neutropenia and 1 had Grade 3 diarrhea. Because dose-limiting toxicity (DLT) occurred in 3 of the 4 patients, 90 mg/m{sup 2} irinotecan was designated as the MTD. Consequently, 80 mg/m{sup 2} irinotecan was given to 7 additional patients, with no DLT, and this was considered the RD. Of the patients who received irinotecan at the RD or lower doses, 6 (31.6%) had a complete pathologic response (Grade 3) and 9 (47.4%) underwent sphincter-preserving surgery. Conclusions: With our new regimen, the MTD of irinotecan was 90 mg/m{sup 2}, and the RD of irinotecan for Phase II studies was 80 mg/m{sup 2}. Although our results are preliminary, this new neoadjuvant chemoradiotherapy was considered safe and active, meriting further investigation in Phase II studies.« less

RMP-02/MTN-006: A Phase 1 Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Tenofovir 1% Gel Compared with Oral Tenofovir Disoproxil Fumarate

PubMed Central

Cranston, Ross D.; Kashuba, Angela; Hendrix, Craig W.; Bumpus, Namandjé N.; Richardson-Harman, Nicola; Elliott, Julie; Janocko, Laura; Khanukhova, Elena; Dennis, Robert; Cumberland, William G.; Ju, Chuan; Carballo-Diéguez, Alex; Mauck, Christine; McGowan, Ian

2012-01-01

Abstract This study was designed to assess the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic (PD) responses to rectal administration of tenofovir (TFV) 1% vaginally formulated gel and oral tenofovir disoproxil fumarate (TDF). This study was designed as a phase 1, randomized, two-site (United States), double-blind, placebo-controlled study of sexually abstinent men and women. Eighteen participants received a single 300-mg exposure of oral TDF and were then randomized 2:1 to receive a single and then seven daily exposures of rectal TFV or hydroxyethyl cellulose (HEC) placebo gel. Safety endpoints included clinical adverse events (AEs) and mucosal safety parameters. Blood and colonic biopsies were collected for PK analyses and ex vivo HIV-1 challenge. No serious AEs were reported. However, AEs were significantly increased with 7-day TFV gel use, most prominently with gastrointestinal AEs (p=0.002). Only 25% of participants liked the TFV gel. Likelihood of use “if somewhat protective” was ∼75% in both groups. Indices of mucosal damage showed minimal changes. Tissue TFV diphosphate (TFV-DP) Cmax 30 min after single rectal exposure was 6–10 times greater than single oral exposure; tissue TFV-DP was 5.7 times greater following 7-day versus single rectal exposure. In vivo exposure correlated with significant ex vivo tissue infectibility suppression [single-rectal: p=0.12, analysis of covariance (ANCOVA) p=0.006; 7-day rectal: p=0.02, ANCOVA p=0.005]. Tissue PK–PD was significantly correlated (p=0.002). We conclude that rectal dosing with TFV 1% gel resulted in greater TFV-DP tissue detection than oral dosing with reduced ex vivo biopsy infectibility, enabling PK–PD correlations. On the basis of increased gastrointestinal AEs, rectally applied, vaginally formulated TFV was not entirely safe or acceptable, suggesting the need for alternative rectal-specific formulations. PMID:22943559

FGFR2 alterations in endometrial carcinoma.

PubMed

Gatius, Sonia; Velasco, Ana; Azueta, Ainara; Santacana, Maria; Pallares, Judit; Valls, Joan; Dolcet, Xavier; Prat, Jaime; Matias-Guiu, Xavier

2011-11-01

Fibroblast growth factor receptor 2 (FGFR2) is a tyrosine kinase receptor involved in many biological processes such as embryogenesis, adult tissue homeostasis and cell proliferation. Mutations in FGFR2 have been reported in up to 10-12% of endometrial carcinomas identical to those found in congenital craniofacial disorders. Inhibition of FGFR2 could be a new therapeutic target in endometrial carcinoma. FGFR2 immunostaining was assessed in three tissue microarrays: one constructed from paraffin-embedded blocks of 60 samples of normal endometrium in different phases of menstrual cycle, and two tissue microarrays containing endometrial carcinoma samples (95 and 62 cases). FGFR2 expression was correlated with stage, histological type and grade as well as with immunostaining of PTEN, RASSF1A, estrogen and progesterone receptors, KI67, Cyclin D1, STAT-3 and SPRY2. FGFR2 mutations were assessed by PCR and direct sequencing, with DNA obtained from 31 paraffin-embedded endometrial carcinoma samples. In normal endometrium, FGFR2 expression was higher in the secretory than in the proliferative phase (P=0.001), with an inverse correlation with Ki67 (P=0.00032), suggesting a tumor-suppressor role for FGFR2 in normal endometrium. Cytoplasmic expression of FGFR2 was higher in endometrial carcinoma when compared with the atrophic endometrium from the same patients (P=0.0283), but was lower in comparison with normal endometrium from women in the menstrual cycle. Interestingly, nuclear staining was observed in some cases, and it was less frequent in endometrial carcinoma when compared with the adjacent atrophic endometrium (P=0.0465). There were no statistical differences when comparing superficial and myoinvasive endometrial carcinoma samples. Endometrioid endometrial carcinomas showed higher expression of FGFR2 than nonendometrioid endometrial carcinomas (fold change 2.56; P=0.0015). Grade III endometrioid endometrial carcinomas showed decreased FGFR2 expression when compared

Methylenetetrahydrofolate reductase gene polymorphisms and the risk of colorectal carcinoma in a sample of Egyptian individuals.

PubMed

El Awady, Mostafa K; Karim, Amr M; Hanna, Laila S; El Husseiny, Lamia A; El Sahar, Medhat; Menem, Hanan A Abdel; Meguid, Nagwa A

2009-01-01

The study was planned as a pilot study to investigate two common polymorphisms in the MTHFR gene c.677C > T and c.1298A > C and their association with enhanced risk of colorectal cancer (CRC) in a sample of Egyptian individuals. Venous blood samples were withdrawn from 35 cases of CRC and 68 healthy controls. Specimens from colonic and rectal carcinoma tissues in addition to cancer free tissues were obtained from all cases. Frequencies of MTHFR677T and 1298C alleles were significantly higher among cases of CRC tumor tissues (50% and 56%, respectively) than germ line alleles in CRC patients (33% and 41%, respectively) and healthy controls (21% and 35%, respectively). Frequencies of heterozygous and homoyzgous polymorphisms of MTHFR at positions 677 and 1298 in carcinoma tissues were always the highest. At position 677, TT and CT genotype frequencies were 17% and 66% with an odds ratio {OR} of 11 [95% confidence interval {CI} 2.39-50.59] and OR 8.34 [95%CI 2.97-23.92], respectively, in carcinoma tissues. While in the germ line of patients the genotype frequencies of 677TT and CT were 6% and 54% with OR 1.57 [95%CI 0.26-9.51] and 2.99 [95%CI 1.25-7.12], respectively, compared to controls (6% and 29%, respectively). The combined genotype MTHFR 1298CC + AC frequencies were 86% with OR 3.71 [95%CI 1.28-10.78] in carcinoma tissues, 69% with OR 1.35 [95%CI 0.57-3.21] in germ line of patients and 62% in controls. The combined genotype 677CT plus any of the following genotypes 1298AA, AC or CC enhanced risk of CRC, when comparing germ line DNA polymorphism of patients versus peripheral blood DNA of control subjects with OR 4.5 [95%CI 0.94-21.56], OR 3.12 [95%CI 0.79-12.36] and OR 18 [95%CI 1.56-207.5], respectively, suggesting strong genetic predisposition of certain Egyptian population to CRC. These results suggested that at least one C to T polymorphism at 677MTHFR gene is required to significantly increase the risk for CRC development. Further large scale studies are

Chemoradiotherapy response in recurrent rectal cancer.

PubMed

Yu, Stanley K T; Bhangu, Aneel; Tait, Diana M; Tekkis, Paris; Wotherspoon, Andrew; Brown, Gina

2014-02-01

The efficacy of response to preoperative chemoradiotherapy (CRT) in recurrent versus primary rectal cancer has not been investigated. We compared radiological downsizing between primary and recurrent rectal cancers following CRT and determined the optimal size reduction threshold for response validated by survival outcomes. The proportional change in tumor length for primary and recurrent rectal cancers following CRT was compared using the independent sample t-test. Overall survival (OS) was calculated using the Kaplan-Meier product limit method and differences between survival for tumor size reduction thresholds of 30% (response evaluation criteria in solid tumors [RECIST]), 40%, and 50% after CRT in primary and recurrent rectal cancer groups. A total of 385 patients undergoing CRT were analyzed, 99 with recurrent rectal cancer and 286 with primary rectal cancer. The mean proportional reduction in maximum craniocaudal length was significantly higher for primary rectal tumors (33%) compared with recurrent rectal cancer (11%) (P < 0.01). There was no difference in OS for either primary or recurrent rectal cancer when ≤30% or ≤40% definitions were used. However, for both primary and recurrent tumors, significant differences in median 3-year OS were observed when a RECIST cut-off of 50% was used. OS was 99% versus 77% in primary and 100% versus 42% in recurrent rectal cancer (P = 0.002 and P = 0.03, respectively). Only patients that demonstrated >50% size reduction showed a survival benefit. Recurrent rectal cancer appears radioresistant compared with primary tumors for tumor size after CRT. Further investigation into improving/intensifying chemotherapy and radiotherapy for locally recurrent rectal cancer is justified. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

PubMed

Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

2016-10-11

The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca 2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca 2+ -ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

A suppository kit for metronomic photodynamic therapy: The elimination of rectal cancer in situ.

PubMed

Shi, X F; Jin, W D; Gao, H; Yin, H J; Li, Y X; Huang, H; Ma, H; Dong, H J

2018-04-01

Metronomic photodynamic therapy (mPDT) was developed to improve tumor-specific responses through cell death by apoptosis. We developed an mPDT suppository kit including ALA and LED suppositories and analyzed its killing effect on rectal tumors in rabbits. The ALA (10 wt%) suppository was prepared using ALA powder, type 36 semi-synthetic fatty acid glyceride, and azone. The LED suppository was constructed by encapsulating LED units and a circuit in transparent epoxy resin. VX2 cells were injected into the rectal submucosa of rabbits to establish a carcinoma model in situ. The ALA suppository was inserted into the rectal cavity for 30 min of uptake and activated for 1 h by the LED suppository at a power density of 20 mW/cm 2 . The mPDT process was repeated three times once a day. MRI was used to monitor tumor growth, histopathology and TUNEL staining were performed at 14 days after mPDT. The overall response rate was 60% in the mPDT group using the kit in which the tumor size was decreased up to about 50% at 7 days post-mPDT and almost eliminated at 14 days. HE staining showed that only 6.16% of the tumor tissue remained after mPDT treatment. TUNEL detection showed that the apoptosis rate was 18.9%. We verified the killing effect of the mPDT suppository kit on rectal tumors in rabbits based on mPDT that induced tumor cell apoptosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of self-collected rectal swabs for the detection of bacteria responsible for sexually transmitted infections in a cohort of HIV-1-infected patients.

PubMed

Edouard, Sophie; Tamalet, Catherine; Tissot-Dupont, Hervé; Colson, Philippe; Ménard, Amélie; Ravaux, Isabelle; Dhiver, Catherine; Tomei, Christelle; Stein, Andreas; Raoult, Didier

2017-06-08

The standard approach to screening sexually transmitted infections (STIs) has often been restricted to urogenital specimens. Most current guidelines, however, also recommend testing extra-genital sites, including rectal locations, because asymptomatic rectal carriage of pathogens has often been reported. The aim of our study was to evaluate self-collected rectal swabs to screen bacterial STIs in HIV-infected patients in Marseille, France. Between January 2014 and December 2015, 118 HIV-infected patients (93 males and 25 females) agreed to self-sample anal swabs for detection of bacterial STI. Detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Mycoplasma genitalium and Haemophilus ducreyi was performed using in-house qPCR assay.Results/Key findings. Bacterial STIs were found in 8 % (9/118) of the patients. C. trachomatis was the most commonly detected bacterium (4.2 %) followed by N. gonorrhoeae (2.5 %), M. genitalium (1.7 %) and T. pallidum (0.8 %). All the positive patients were males. The rectal carriage of pathogenic bacteria was fortuitously discovered for seven men (78 %) who did not present rectal signs of STIs and was suspected for two men who presented proctitis (22 %). In conclusion, testing extra-genital sites is crucial for the diagnosis of STIs in men and women presenting or not concomitant urogenital infections in order to detect asymptomatic carriage with the aim of controlling and preventing transmission to their sexual partners.

Umbilical metastasis derived from early stage rectal cancer: a case report

PubMed Central

2014-01-01

Background Umbilical metastasis, also called Sister Mary Joseph’s nodule (SMJN), is defined as the umbilical nodule associated with advanced metastatic intra-abdominal and pelvic malignancies. A patient with umbilical metastasis has been deemed to have a poor prognosis. Rectal cancer presenting with a SMJN is a rare phenomenon, especially in the early stage and in middle-low rectal cancer. Case presentation We report a case of a 70-year-old male presenting with umbilical metastasis derived from rectal cancer (10 cm from the anal verge, T2N0). Discussion and conclusion For rectal cancer with umbilical metastasis, the exact metastatic routes as well as the criterion of diagnosis and treatments are not very clear. Here we review the literature on rectal cancer and SMJN to deepen the understanding of this disease. PMID:24708697

Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma.

PubMed

Moriyama, Shingo; Yoshida, Soichiro; Tanaka, Hajime; Tanaka, Hiroshi; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Kihara, Kazunori; Fujii, Yasuhisa

2018-03-25

To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma. T2-weighted images from 121 solid small renal masses (<4 cm) without visible fat (14 fat-poor angiomyolipomas, 92 clear cell renal cell carcinomas, six chromophobe renal cell carcinomas and nine papillary renal cell carcinomas) were retrospectively evaluated. An intensity ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2-weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated. The tumors were classified into three types: intensity ratio fat-poor angiomyolipoma (n = 19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014). Our novel semiquantitative model for combined assessment of key features of fat-poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor angiomyolipoma more accurate. © 2018 The Japanese Urological Association.

Definitive radiotherapy for locally advanced squamous cell carcinoma of the vulva and technical issues: a case report

NASA Astrophysics Data System (ADS)

Kumar, Gokula; Norhafizah, I.; Shazril, I.; Nursyatina, AR; Aziz, MZ Abdul; Zin, Hafiz M.; Zakir, MK; Norjayadi; Norliza, AS; Ismail, A.; Khairun, N.

2017-05-01

This case report describes a complex radical 3D-Conformal Radiotherapy treatment planning, dosimetric issues and outcome of definitive treatment of un-resectable carcinoma of the vulvar in a 42-year old lady. The patient presented with large fungating mass of the vulva which was biopsy confirmed as Keratinizing Squamous Cell Carcinoma. Further staging investigation revealed locally advanced disease (T4), with bilateral inguinal lymph nodes involvement. There is no systemic metastasis or intra-pelvic nodes. The patient was seen by Gynae-Oncology team and the disease was deemed un-resectable without significant morbidity. She was treated to a total dose of 64.8Gy in 36 fractions over 7 weeks with concurrent weekly Cisplatinum in 2 phases. 3D-Conformal radiotherapy technique using the modified segmental boost technique (MSBT, large PA and small AP photon fields with inguinal electron matching) was used. TLD chips were used for in-vivo dose verification in phase 1 and 2 of the treatment. At completion of planned radiotherapy, patient had a complete clinical response, grade 2-3 skin toxicity, grade 2 rectal toxicity, and grade 2 dysuria Vulval Squamous Cell Carcinomas are very radiosensitive tumours and the skills of the treating Radiation Oncologist, Dosimetrists, Physicist, Radiation Therapist and also nurses is of foremost importance is ensuring good clinical outcomes.

Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

PubMed

Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

2012-03-14

Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

Comparison of rectal and axillary temperatures in dogs and cats.

PubMed

Goic, Joana B; Reineke, Erica L; Drobatz, Kenneth J

2014-05-15

To compare rectal versus axillary temperatures in dogs and cats. Prospective observational study. 94 dogs and 31 cats. Paired axillary and rectal temperatures were measured in random order with a standardized method. Animal signalment, initial complaint, blood pressure, blood lactate concentration, and variables associated with vascular perfusion and coat were evaluated for associations with axillary and rectal temperatures. Axillary temperature was positively correlated with rectal temperature (ρ = 0.75 in both species). Median axillary temperature (38.4°C [101.1°F] in dogs, and 38.4°C [101.2°F] in cats) was significantly different from median rectal temperature in dogs (38.9°C [102.0°F]) but not in cats (38.6°C [101.5°F]). Median rectal-axillary gradient (difference) was 0.4°C (0.7°F; range, -1.3° to 2.3°C [-2.4° to 4.1°F]) in dogs and 0.17°C (0.3°F; range -1.1° to 1.6°C [-1.9° to 3°F]) in cats. Sensitivity and specificity for detection of hyperthermia with axillary temperature were 57% and 100%, respectively, in dogs and 33% and 100%, respectively, in cats; sensitivity and specificity for detection of hypothermia were 86% and 87%, respectively, in dogs and 80% and 96%, respectively, in cats. Body weight (ρ = 0.514) and body condition score (ρ = 0.431) were correlated with rectal-axillary gradient in cats. Although axillary and rectal temperatures were correlated in dogs and cats, a large gradient was present between rectal temperature and axillary temperature, suggesting that axillary temperature should not be used as a substitute for rectal temperature.

Relative bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension.

PubMed

Clemens, Pamela L; Cloyd, James C; Kriel, Robert L; Remmel, Rory P

2007-01-01

Maintenance of effective drug concentrations is essential for adequate treatment of epilepsy. Some antiepileptic drugs can be successfully administered rectally when the oral route of administration is temporarily unavailable. Oxcarbazepine is a newer antiepileptic drug that is rapidly converted to a monohydroxy derivative, the active compound. This study aimed to characterise the bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension using a randomised, crossover design in ten healthy volunteers. Two subjects received 300 mg doses of oxcarbazepine suspension via rectal and oral routes and eight received 450 mg doses. A washout period of at least 2 weeks elapsed between doses. The rectal dose was diluted 1:1 with water. Blood samples and urine were collected for 72 hours post-dose. Adverse effects were assessed at each blood collection time-point using a self-administered questionnaire. Plasma was assayed for oxcarbazepine and monohydroxy derivative; urine was assayed for monohydroxy derivative and monohydroxy derivative-glucuronide. Maximum plasma concentration (C(max)) and time to reach C(max) (t(max)) were obtained directly from the plasma concentration-time curves. The areas under the concentration-time curve (AUCs) were determined via non-compartmental analysis. Relative bioavailability was calculated and the C(max) and AUCs were compared using Wilcoxon signed-rank tests. Mean relative bioavailability calculated from plasma AUCs was 8.3% (SD 5.5%) for the monohydroxy derivative and 10.8% (SD 7.3%) for oxcarbazepine. Oxcarbazepine and monohydroxy derivative C(max) and AUC values were significantly lower following rectal administration (p < 0.01). The total amount of monohydroxy derivative excreted in the urine following rectal administration was 10 +/- 5% of the amount excreted following oral administration. Oral absorption was consistent with previous studies. The most common adverse effects were headache and fatigue

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in papillary thyroid carcinoma.

PubMed

Danilovic, Debora Lucia Seguro; de Mello, Evandro Sobroza; Frazzato, Eliana Salgado Turri; Wakamatsu, Alda; de Lima Jorge, Alexander Augusto; Hoff, Ana Oliveira; Marui, Suemi

2018-06-01

Nuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, transcription factor of antioxidative genes. In the presence of reactive oxygen species, Keap1 (Kelch-ECH-associating protein-1) inhibitor complex undergoes conformational changes disrupting Keap1-Nrf2 binding and Nrf2 translocates into nucleus. We evaluated the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) and correlated them with clinical presentation. Coding regions of NFE2L2 and KEAP1 were sequenced in 131 patients with PTC. Clinical and histopathological features were analyzed. Immunohistochemical analysis of Nrf2 expression was performed in mutated carcinomas. Although no mutations were found in NFE2L2, missense mutations in KEAP1 were observed in 6 patients with PTC (4.6%). Immunohistochemistry showed increased Nrf2 expression in nuclei of all mutated carcinomas, which presented poor prognostic features in histopathology. We identified mutations in KEAP1 associated with Nrf2 overexpression in PTC. Mutations favored disruption of inhibitory interaction Nrf2-Keap1 to enable increased antioxidant Nrf2 activity, possibly with prognostic consequences. © 2018 Wiley Periodicals, Inc.

Can T1 w/T2 w ratio be used as a myelin-specific measure in subcortical structures? Comparisons between FSE-based T1 w/T2 w ratios, GRASE-based T1 w/T2 w ratios and multi-echo GRASE-based myelin water fractions.

PubMed

Uddin, Md Nasir; Figley, Teresa D; Marrie, Ruth Ann; Figley, Chase R

2018-03-01

Given the growing popularity of T 1 -weighted/T 2 -weighted (T 1 w/T 2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T 1 w/T 2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T 2 w image acquisition, and to compare the resulting T 1 w/T 2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole-brain T 1 w magnetization prepared rapid acquisition gradient echo (MPRAGE), T 2 w FSE and three-dimensional multi-echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high-dimensional, non-linear warping, region of interest (ROI) analyses were performed to compare T 1 w/T 2 w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS 'Eve' atlas. Although the GRASE sequence systematically underestimated T 1 w/T 2 w values compared to the FSE sequence (revealed by Bland-Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r 2 = 0.62 for all ROIs, r 2 = 0.62 for WM structures and r 2 = 0.73 for SGM structures). However, correlations between either FSE-based or GRASE-based T 1 w/T 2 w ratios and MWFs were extremely low in WM structures (FSE-based, r 2 = 0.000020; GRASE-based, r 2 = 0.0014), low across all ROIs (FSE-based, r 2 = 0.053; GRASE-based, r 2 = 0.029) and moderate in SGM structures (FSE-based, r 2 = 0.20; GRASE-based, r 2 = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE-based and GRASE-based T 1 w/T 2 w ratios, and low correlations between T 1 w/T 2 w ratios and MWFs. This

GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas.

PubMed

Davis, Drew G; Siddiqui, Momin T; Oprea-Ilies, Gabriela; Stevens, Keith; Osunkoya, Adeboye O; Cohen, Cynthia; Li, Xiaoxian Bill

2016-01-01

GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor-positive, Her2/neu-positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor-positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

[Efficacy analysis of proximally extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy].

PubMed

Qin, Qiyuan; Kuang, Yingyi; Ma, Tenghui; Wu, Yali; Wang, Huaiming; Pi, Yanna; Wang, Hui; Wang, Lei

2017-11-25

To evaluate the short-term outcomes and perioperative safety of proximally extended resection for locally advanced rectal cancer after neoadjuvant chemoradiotherapy. From colorectal cancer database in The Sixth Affiliated Hospital of Sun Yat-sen University, a cohort of patients who underwent neoadjuvant chemoradiotherapy(1.8-2.0 Gy per day, 25-28 fractions, concurrent fluorouracil-based chemotherapy) followed by curative sphincter-preserving surgery for locally advanced rectal cancer between May 2016 and June 2017 were retrospectively identified. Exclusion criteria were synchronous colon cancer, intraoperatively confirmed distal metastasis, multiple visceral resection, and emergency operation. Thirty-one patients underwent proximal extended resection and two were excluded for incomplete extended resection, then 29 patients were enrolled as the extended group. Using propensity scores matching with 1/1 ration, 29 locally advanced rectal cancer patients who underwent conventional resection after neoadjuvant chemoradiotherapy at the same time were matched as the conventional group. Clinical data of two groups were analyzed, and the baseline characteristics and short-term outcomes were compared using the t test, χ 2 test, or Mann-Whitney U test. Two groups were well balanced with respect to the baseline characteristics after propensity score matching. As compared with conventional group, patients in extended group had longer surgical specimen [(18.8±5.1) cm vs.(11.6±3.4) cm, t=6.314, P=0.000] and longer proximal resection margin [(14.8±5.5) cm vs.(8.2±3.0) cm, t=5.725, P=0.000], but also had longer total operating time [(322.4±100.7) min vs.(254.6±70.3) min, t=2.975, P=0.004] and more intraoperative blood loss [100(225) ml vs. 100(50) ml, Z=-2.403, P=0.016]. No significant differences were observed in the length of distal resection margin, ratio of positive resection margin, number of retrieved lymph node, time of analgesic use, time of draining tube use, time to

A phase II study of preoperative chemoradiation with tegafur-uracil plus leucovorin for locally advanced rectal cancer with pharmacogenetic analysis.

PubMed

Kim, Sun Young; Baek, Ji Yeon; Oh, Jae Hwan; Park, Sung Chan; Sohn, Dae Kyung; Kim, Min Ju; Chang, Hee Jin; Kong, Sun-Young; Kim, Dae Yong

2017-03-27

This study aimed to evaluate the efficacy of a high dose of oral tegafur-uracil (400 mg/m 2 ) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 (CYP2A6), uridine monophosphate synthetase (UMPS), and ATP-binding cassette B1 (ABCB1) on clinical outcome. Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m 2 /day and leucovorin 90 mg/m 2 /day for 7 days a week during preoperative chemoradiation (50.4 Gy/28 fractions) in this phase II trial. Primary endpoint was pathologic complete response rate, and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 (*4, *7, *9 and *10), UMPS G638C, and three ABCB1 genotypes (C1236T, C3435T, and G2677T). Ninety-one patients were given study treatment, and 90 underwent surgery. Pathologic complete response was noted in 10 patients (11.1%). There was no grade 4 or 5 toxicity; 20 (22.0%) experienced grade 3 toxicities, including diarrhea (10, 11.0%), abdominal pain (2, 2.2%), and anemia (2, 2.2%). Relapse-free survival and overall survival at 5 years were 88.6% and 94.2%, respectively. Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea (p for trend = 0.018). Preoperative chemoradiation with tegafur-uracil 400 mg/m 2 /day with leucovorin was feasible, but did not meet the expected pathologic complete response rate. The UMPS 638 CC genotype might be a candidate biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer. ISRCTN11812525 , registered on 25 July 2016. Retrospectively registered.

Somatic alterations of the serine/threonine kinase LKB1 gene in squamous cell (SCC) and large cell (LCC) lung carcinoma.

PubMed

Strazisar, Mojca; Mlakar, Vid; Rott, Tomaz; Glavac, Damjan

2009-05-01

Somatic LKB1 serine/threonine kinase alterations are rare in sporadic cancers, with the exception lung adenocarcinoma, but no mutations in squamous cell or large cell primary carcinoma were discovered. We screened the LKB1 gene in 129 primary nonsmall cell lung carcinomas, adjacent healthy lung tissue, and control blood samples. Forty-five percent of nonsmall cell lung tumors harbored either intron or exon alterations. We identified R86G, F354L, Y272Y and three polymorphisms: 290+36G/T, 386+156G/T, and 862+145C/T (novel). R86G (novel) and F354L mutations were found in six squamous cell carcinomas and three large cell cancer carcinomas, but not in the adjacent healthy tissue or controls samples. The F354L mutation was found in advanced squamous cell carcinomas with elevated COX-2 expression, rare P53, and no K-RAS mutation. Results indicate that the LKB1 gene is changed in a certain proportion of nonsmall cell lung tumors, predominately in advanced squamous lung carcinoma. Inactivation of the gene takes place via the C-terminal domain and could be related to mechanisms influencing tumor initiation, differentiation, and metastasis.

A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC).

PubMed

Oki, E; Murata, A; Yoshida, K; Maeda, K; Ikejiri, K; Munemoto, Y; Sasaki, K; Matsuda, C; Kotake, M; Suenaga, T; Matsuda, H; Emi, Y; Kakeji, Y; Baba, H; Hamada, C; Saji, S; Maehara, Y

2016-07-01

Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur-uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer. The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20-80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500-600 mg/day on days 1-5, followed by 2 days rest) or S-1 (80-120 mg/day on days 1-28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events. In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63-0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm. One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

[Differential diagnosis between renal cell carcinoma associated with XP11.2 translocation/TFE gene fusion and papillary renal cell carcinoma based on CT and MRI findings].

PubMed

Zhu, Qingqiang; Zhu, Wenrong; Wu, Jingtao; Fu, Jianxiong; Chen, Wenxin; Wang, Zhongqiu

2014-05-20

To comparative study of CT and MRI appearances in renal cell carcinoma associated with XP11.2 translocation/TFE gene fusion (XP11.2 RCC) and papillary renal cell carcinoma (PRCC). 12 patients with XP11.2 RCC and 18 patients with PRCC were retrospectively studied, and the data was analyzed by AVONA and chi-square text. 12 patients with XP11.2 RCC and 18 patients with PRCC, cystic components (2 vs 11, P < 0.05), calcification (0 vs 6, P < 0.05), hemorrhage (9 vs 5, P < 0.05), homogeneous enhancement (10 vs 7, P < 0.05) and had lymph node (3 vs 0) or hepatic metastasis (1vs 0) (P < 0.05). On unenhanced CT, the density of XP11.2 RCC was greater than PRCC, normal renal cortex or medulla (P < 0.05). Their degree of enhancement were less than normal renal cortex on all enhanced phases (P < 0.05). The enhancement degree of XP11.2 RCC was higher than PRCC (on all phases) and renal medulla (on cortical and medullary phase) (P < 0.05), but less than normal renal medulla on the delayed phase (P < 0.05). The enhancement degree of PRCC was lower than renal medulla on all phases (P < 0.05). The XP11.2 RCC was isointense on T1-weighted imaging, hypointense on T2-weighted imaging. The PRCC was isointense or hypointense on T1-weighted imaging, isointense on T2-weighted imaging. The CT and MRI could show imagings features of XP11.2 RCC and PRCC, and these features were helpful in predicting a specific subtype of renal cell carcinoma.

Influence of multiple stapler firings used for rectal division on colorectal anastomotic leak rate.

PubMed

Braunschmid, Tamara; Hartig, Nikolaus; Baumann, Lukas; Dauser, Bernhard; Herbst, Friedrich

2017-12-01

Anastomotic leakage following colorectal resection remains one of the most significant complications with relevant morbidity and mortality. There is evidence that a higher number of stapler firings for rectal division can affect the leak rate in double stapling anastomosis. However, there are no data concerning compression anastomosis. We present our institutional experience addressing this issue. This is a retrospective review of a prospective institutional database of patients undergoing colonic and rectal resection for benign and malignant indications between January 2008 and December 2014 at the surgical department of the St. John of God Hospital, Vienna. Inclusion criteria were rectal division with linear stapling devices and construction of anastomosis to the rectal stump using a circular stapler or compression device. Three hundred eighty two (196 female; 51.3%) patients were included. Mean age was 65.8 years (range: 18-95) Indications for the operation included diverticular disease (44.8%), colorectal carcinoma (51.6%), inflammatory bowel disease (1.8%), and adenoma (1.8%). A laparoscopic approach was employed in 334 cases (87.4%); in 170 patients (44.9%), a compression anastomosis was created. One, two, and three or more stapler cartridges were used for rectal division in 58.4, 33.5, and 8.1%, respectively. Male gender, neoadjuvant therapy, rectal cancer as an underlying disease, laparoscopic surgical approach, and duration of operation longer than 200 min are leading causes for the usage of more than one stapler cartridge. Overall leak rate was 4.7% (18/382). The only factor associated with the occurrence of leakage was the use of three or more stapler cartridges for the closure of the rectal stump (p = 0.002). Our data support that multiple stapler firings for rectal division following colorectal resection has a major impact on anastomotic leak rate. Especially in laparoscopic surgery efforts should be made to minimize the number of stapler

Human papilloma virus status of penile squamous cell carcinoma is associated with differences in tumour-infiltrating T lymphocytes.

PubMed

Lohneis, Philipp; Boral, Sengül; Kaufmann, Andreas M; Lehmann, Annika; Schewe, Christiane; Dietel, Manfred; Anagnostopoulos, Ioannis; Jöhrens, Korinna

2015-03-01

Meta-analyses show that approximately half of all squamous cell carcinomas (SCCs) of the penis are associated with a human papillomavirus (HPV) infection. As data about the tumour microenvironment of HPV-positive and HPV-negative penile carcinomas is scarce and conflicting, we examined tumour-infiltrating lymphocyte populations in such cases. The HPV status of 28 penile SCCs was determined by polymerase chain reaction, while the number and distribution of different lymphocyte populations were analysed by immunohistochemistry on whole sections of paraffin-embedded tumour specimens. The average number of tumour-infiltrating T cells in HPV-associated SCC was higher than in HPV-negative SCC, and their phenotype showed strong polarization towards a T helper 1 and cytotoxic immune response. In addition, we identified more tumour-infiltrating regulatory T cells in HPV-positive carcinomas, which might represent a mechanism of immune evasion. The present study provides further evidence that the tumour microenvironment of HPV-positive carcinomas differs from that of HPV-negative carcinomas.

Meta-analysis of elective surgical complications related to defunctioning loop ileostomy compared with loop colostomy after low anterior resection for rectal carcinoma.

PubMed

Geng, Hong Zhi; Nasier, Dilidan; Liu, Bing; Gao, Hua; Xu, Yi Ke

2015-10-01

Introduction Defunctioning loop ileostomy (LI) and loop colostomy (LC) are used widely to protect/treat anastomotic leakage after colorectal surgery. However, it is not known which surgical approach has a lower prevalence of surgical complications after low anterior resection for rectal carcinoma (LARRC). Methods We conducted a literature search of PubMed, MEDLINE, Ovid, Embase and Cochrane databases to identify studies published between 1966 and 2013 focusing on elective surgical complications related to defunctioning LI and LC undertaken to protect a distal rectal anastomosis after LARRC. Results Five studies (two randomized controlled trials, one prospective non-randomized trial, and two retrospective trials) satisfied the inclusion criteria. Outcomes of 1,025 patients (652 LI and 373 LC) were analyzed. After the construction of a LI or LC, there was a significantly lower prevalence of sepsis (p=0.04), prolapse (p=0.03), and parastomal hernia (p=0.02) in LI patients than in LC patients. Also, the prevalence of overall complications was significantly lower in those who received LIs compared with those who received LCs (p<0.0001). After closure of defunctioning loops, there were significantly fewer wound infections (p=0.006) and incisional hernias (p=0.007) in LI patients than in LC patients, but there was no significant difference between the two groups in terms of overall complications. Conclusions The results of this meta-analysis show that a defunctioning LI may be superior to LC with respect to a lower prevalence of surgical complications after LARRC.

Pretreatment Evaluation of Microcirculation by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Predicts Survival in Primary Rectal Cancer Patients

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

DeVries, Alexander Friedrich; Piringer, Gudrun, E-mail: gudrun.piringer@hotmail.com; Kremser, Christian

2014-12-01

Purpose: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. Methods and Materials: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T{sub 1} mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration–time curve divided by the maximum of the arterial inputmore » function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. Results: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). Conclusions: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.« less

Locally advanced rectal cancer: diffusion-weighted MR tumour volumetry and the apparent diffusion coefficient for evaluating complete remission after preoperative chemoradiation therapy.

PubMed

Ha, Hong Il; Kim, Ah Young; Yu, Chang Sik; Park, Seong Ho; Ha, Hyun Kwon

2013-12-01

To evaluate DW MR tumour volumetry and post-CRT ADC in rectal cancer as predicting factors of CR using high b values to eliminate perfusion effects. One hundred rectal cancer patients who underwent 1.5-T rectal MR and DW imaging using three b factors (0, 150, and 1,000 s/mm(2)) were enrolled. The tumour volumes of T2-weighted MR and DW images and pre- and post-CRT ADC150-1000 were measured. The diagnostic accuracy of post-CRT ADC, T2-weighted MR, and DW tumour volumetry was compared using ROC analysis. DW MR tumour volumetry was superior to T2-weighted MR volumetry comparing the CR and non-CR groups (P < 0.001). Post-CRT ADC showed a significant difference between the CR and non-CR groups (P = 0.001). The accuracy of DW tumour volumetry (Az = 0.910) was superior to that of T2-weighed MR tumour volumetry (Az = 0.792) and post-CRT ADC (Az = 0.705) in determining CR (P = 0.015). Using a cutoff value for the tumour volume reduction rate of more than 86.8 % on DW MR images, the sensitivity and specificity for predicting CR were 91.4 % and 80 %, respectively. DW MR tumour volumetry after CRT showed significant superiority in predicting CR compared with T2-weighted MR images and post-CRT ADC.

Development of a rectal sexually transmitted infection (STI) Model in Rhesus macaques using Chlamydia trachomatis serovars E and L2.

PubMed

Henning, Tara R; Morris, Monica; Ellis, Shanon; Kelley, Kristen; Phillips, Christi; Ritter, Jana; Jones, Tara; Nachamkin, Eli; Chen, Cheng Y; Hong, Jaeyoung; Kang, Joseph; Patton, Dorothy; McNicholl, Janet; Papp, John; Kersh, Ellen N

2017-10-01

Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L 2 (CT-L 2 ); C. trachomatis serovar E (CT-E), followed by CT-L 2 ; or CT-E, treatment/clearance, then CT-L 2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L 2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L 2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes

NASA Astrophysics Data System (ADS)

Hu, Fengqin; Zhao, Yong Sheng

2012-09-01

Magnetic resonance imaging (MRI) yields high spatially resolved contrast with anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning. To improve imaging sensitivity, adding contrast agents accelerates the relaxation rate of water molecules, thereby greatly increasing the contrast between specific issues or organs of interest. Currently, the majority of T1 contrast agents are paramagnetic molecular complexes, typically Gd(iii) chelates. Various nanoparticulate T1 and T1/T2 contrast agents have recently been investigated as novel agents possessing the advantages of both the T1 contrast effect and nanostructural characteristics. In this minireview, we describe the recent progress of these inorganic nanoparticle-based MRI contrast agents. Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and ultrasmall iron oxide/ferrite nanoparticles.

Role of MR-DWI and MR-PWI in the radiotherapy of implanted pulmonary VX-2 carcinoma in rabbits.

PubMed

Zhang, Qiang; Zhang, Mingmin; Liu, Zhaoxin; Shi, Baoqi; Qi, Fuliang; Wang, Haijiang; Lv, Yuan; Jin, Haijiao; Zhang, Weijing

2014-10-01

To detect the activity of tumor cells and tumor blood flow before and after the radiotherapy of implanted pulmonary VX-2 carcinoma in rabbit models by using magnetic resonance diffusion-weighted imaging (MR-DWI) and magnetic resonance perfusion weighted imaging (MR-PWI), and to evaluate the effectiveness and safety of the radiotherapy based on the changes in the MR-DWI and MR-PWI parameters at different treatment stages. A total of 56 rabbit models with implanted pulmonary VX-2 carcinoma were established, and then equally divided into treatment group and control group. MR-DWI and MR-PWI were separately performed using a Philips Acheiva 1.5T MRI machine (Philips, Netherland). MRI image processing was performed using special perfusion software and the WORKSPACE advanced workstation for MRI. MR-DWI was applied for the observation of tumor signals and the measurement of apparent diffusion coefficient (ADC) values; whereas MR-PWI was used for the measurement of wash in rate (WIR), wash out rate (WOR), and maximum enhancement rate (MER). The radiation treatment was performed using Siemens PRIMUS linear accelerator. In the treatment group, the radiotherapy was performed 21 days later on a once weekly dosage of 1,000 cGy to yield a total dosage of 5,000 cGy. THE ADC PARAMETERS IN THE REGION OF INTEREST ON DWI WERE AS FOLLOWS: on the treatment day for the implanted pulmonary VX-2 carcinoma, the t values at the center and the edge of the lesions were 1.352 and 1.461 in the treatment group and control group (P>0.05). During weeks 0-1 after treatment, the t values at the center and the edge of the lesions were 1.336 and 1.137 (P>0.05). During weeks 1-2, the t values were 1.731 and 1.736 (P<0.05). During weeks 2-3, the t values were 1.742 and 1.749 (P<0.05). During weeks 3-4, the t values were 2.050 and 2.127 (P<0.05). During weeks 4-5, the t values were 2.764 and 2.985 (P<0.05). The ADC values in the treatment group were significantly higher than in the control group. After

RECTAL-SPECIFIC MICROBICIDE APPLICATOR: EVALUATION AND COMPARISON WITH A VAGINAL APPLICATOR USED RECTALLY

PubMed Central

Carballo-Diéguez, Alex; Giguere, Rebecca; Dolezal, Curtis; Bauermeister, José; Leu, Cheng-Shiun; Valladares, Juan; Rohan, Lisa C.; Anton, Peter A.; Cranston, Ross D.; Febo, Irma; Mayer, Kenneth; McGowan, Ian

2014-01-01

An applicator designed for rectal delivery of microbicides was tested for acceptability by 95 young men who have sex with men, who self-administered 4mL of placebo gel prior to receptive anal intercourse over 90 days. Subsequently, 24 of the participants self-administered rectally 4mL of tenofovir or placebo gel over 7 days using a vaginal applicator, and compared both applicators on a Likert scale of 1–10, with 10 the highest rating. Participants reported high likelihood to use either applicator in the future (mean scores 9.3 and 8.8 respectively, p= ns). Those who tested both liked the vaginal applicator significantly more than the rectal applicator (7.8 vs. 5.2, p=0.003). Improvements in portability, conspicuousness, aesthetics, tip comfort, product assembly and packaging were suggested for both. This rectal-specific applicator was not superior to a vaginal applicator. While likelihood of future use is reportedly high, factors that decrease acceptability may erode product use over time in clinical trials. Further attention is needed to develop user-friendly, quick-acting rectal microbicide delivery systems. PMID:24858481

The curative management of synchronous rectal and prostate cancer

PubMed Central

Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

2016-01-01

Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity

Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children.

PubMed

Sharif, Mohammad Reza; Haji Rezaei, Mostafa; Aalinezhad, Marzieh; Sarami, Golbahareh; Rangraz, Masoud

2016-01-01

Fever is the most common complaint in pediatric medicine and its treatment is recommended in some situations. Paracetamol is the most common antipyretic drug, which has serious side effects such as toxicity along with its positive effects. Diclofenac is one of the strongest non-steroidal anti-inflammatory (NSAID) drugs, which has received little attention as an antipyretic drug. This study was designed to compare the antipyretic effectiveness of the rectal form of Paracetamol and Diclofenac. This double-blind controlled clinical trial was conducted on 80 children aged six months to six years old. One group was treated with rectal Paracetamol suppositories at 15 mg/kg dose and the other group received Diclofenac at 1 mg/kg by rectal administration (n = 40). Rectal temperature was measured before and one hour after the intervention. Temperature changes in the two groups were compared. The average rectal temperature in the Paracetamol group was 39.6 ± 1.13°C, and 39.82 ± 1.07°C in the Diclofenac group (P = 0.37). The average rectal temperature, one hour after the intervention, in the Paracetamol and the Diclofenac group was 38.39 ± 0.89°C and 38.95 ± 1.09°C, respectively (P = 0.02). Average temperature changes were 0.65 ± 0.17°C in the Paracetamol group and 1.73 ± 0.69°C in the Diclofenac group (P < 0.001). In the first one hour, Diclofenac suppository is able to control the fever more efficient than Paracetamol suppositories.

Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

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

Nomura, Tomoko; Murakami, Ryuji, E-mail: murakami@kumamoto-u.ac.j; Toya, Ryo

Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m{sup 2}/day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%),more » anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.« less

T1 mapping combined with Gd-EOB-DTPA-enhanced magnetic resonance imaging in predicting the pathologic grading of hepatocellular carcinoma.

PubMed

Chen, C Y; Chen, J; Xia, C C; Huang, Z X; Song, B

2017-01-01

The aim of this study was to investigate the value of Gd-EOB-DTPA-enhanced MRI on hepatobiliary phase (HBP) imaging and T1 mapping sequence in the differentiation of hepatocellular carcinoma (HCC). A total of 45 patients with HCC who were to undergo a resection were enrolled in this study. Gd-EOB-DTPA-enhanced magnetic resonance examination was performed prior to resection. T1 mapping was performed before and 20 min after injection of Gd-EOB-DTPA. T1 values of the lesions were measured on pre-contrast (T1p) and during HBP (T1-HBP) on T1 maps. The signal intensity, the diameter and the margin of HCC lesions on HBP images were analyzed. The reduction in T1 value (T1d) and the reduction rate (ΔT1%) of T1 mapping between pre-contrast and HBP were calculated. The Edmondson-Steiner classification of each lesion was made after surgery. The SPSS software package was used for statistical analysis and the analysis of receiver operator characteristic (ROC) curve and area under the curve (AUC) were carried out by using MedCalc software package. Mean values of T1p and T1-HBP were 1935.4±730.8 ms and 1257.1±529.1 ms, respectively. T1p accuracy (AUC = 0.685, p = 0.037) in predicting pathological grading was similar to that of T1-HBP (AUC = 0.751, p = 0.005). A T1p of 1648.2 ms or greater had a sensitivity and specificity of 85.19% and 61.11%, respectively. A T1-HBP of 1006 ms or greater had a sensitivity and specificity of 81.84% and 61.11%, respectively. The number of HCCs with a non-smooth tumor margin was 20 (44.4%), and a non-smooth tumor margin correlated moderately with the Edmondson-Steiner grade (Spearman r = 0.491, p = 0.041). There was no significant correlation between T1d, ΔT1%, HCC signal intensity on HBP image and lesion diameter with pathologic grading. T1 mapping in pre-contrast and HBP of Gd-EOB-DTPA-enhanced MRI, a non-smooth tumor margin in the HBP of Gd-EOB-DTPA-enhanced MRI, are useful in predicting the pathologic grading of HCC.

CT-Guided Transgluteal Biopsy for Systematic Random Sampling of the Prostate in Patients Without Rectal Access.

PubMed

Goenka, Ajit H; Remer, Erick M; Veniero, Joseph C; Thupili, Chakradhar R; Klein, Eric A

2015-09-01

The objective of our study was to review our experience with CT-guided transgluteal prostate biopsy in patients without rectal access. Twenty-one CT-guided transgluteal prostate biopsy procedures were performed in 16 men (mean age, 68 years; age range, 60-78 years) who were under conscious sedation. The mean prostate-specific antigen (PSA) value was 11.4 ng/mL (range, 2.3-39.4 ng/mL). Six had seven prior unsuccessful transperineal or transurethral biopsies. Biopsy results, complications, sedation time, and radiation dose were recorded. The mean PSA values and number of core specimens were compared between patients with malignant results and patients with nonmalignant results using the Student t test. The average procedural sedation time was 50.6 minutes (range, 15-90 minutes) (n = 20), and the mean effective radiation dose was 8.2 mSv (median, 6.6 mSv; range 3.6-19.3 mSv) (n = 13). Twenty of the 21 (95%) procedures were technically successful. The only complication was a single episode of gross hematuria and penile pain in one patient, which resolved spontaneously. Of 20 successful biopsies, 8 (40%) yielded adenocarcinoma (Gleason score: mean, 8; range, 7-9). Twelve biopsies yielded nonmalignant results (60%): high-grade prostatic intraepithelial neoplasia (n = 3) or benign prostatic tissue with or without inflammation (n = 9). Three patients had carcinoma diagnosed on subsequent biopsies (second biopsy, n = 2 patients; third biopsy, n = 1 patient). A malignant biopsy result was not significantly associated with the number of core specimens (p = 0.3) or the mean PSA value (p = 0.1). CT-guided transgluteal prostate biopsy is a safe and reliable technique for the systematic random sampling of the prostate in patients without a rectal access. In patients with initial negative biopsy results, repeat biopsy should be considered if there is a persistent rise in the PSA value.

Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

PubMed

Linedale, Richard; Schmidt, Campbell; King, Brigid T; Ganko, Annabelle G; Simpson, Fiona; Panizza, Benedict J; Leggatt, Graham R

2017-01-01

Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.

Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

PubMed

Bensignor, T; Brouquet, A; Dariane, C; Thirot-Bidault, A; Lazure, T; Julié, C; Nordlinger, B; Penna, C; Benoist, S

2015-06-01

Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

[Correlations between serine hydroxymethyltransferase1 C1420T polymorphisms and susceptibilities to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].

PubMed

Wang, Yi-Min; Guo, Wei; Zhang, Xiu-Feng; Li, Yan; Wang, Na; Ge, Hui; Wei, Li-Zhen; Wen, Deng-Gui; Zhang, Jian-Hui

2006-03-01

Serine hydroxymethyltransferase (SHMT), a key enzyme in the folate metabolism, affects gene methylation and DNA synthesis through providing one-carbon units for purine, thymidylate, and methionine. It is closely related to the development and progression of tumors. This study was to investigate the correlations between SHMT1 C1420T single nucleotide polymorphisms (SNP) and susceptibilities to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). SHMT1 C1420T SNP was genotyped by polymerase chain reaction-confronting two-pair primers (PCR-CTPP) analysis in 584 ESCC patients, 467 GCA patients, and 540 healthy controls. The correlations between SHMT1 C1420T SNP polymorphisms and susceptibilities to ESCC and GCA were analyzed with Logistic regression model. Family history of upper gastrointestinal cancer (UGIC) significantly enhanced the risk of developing ESCC and GCA [the age, gender, smoking status, and family history of UGIC adjusted odds ratio (OR)=2.89, 95% confident interval (CI)=2.23-3.73; OR =1.68, 95% CI=1.28-2.23]. The frequency of 1420C/T genotype was significantly lower in ESCC and GCA patients than in healthy controls (12.0% vs. 16.5%, P<0.05; 10.9% vs. 16.5%, P<0.01). Compared with C/C genotype, C/T genotype significantly reduced susceptibilities to ESCC and GCA, with adjusted OR of 0.70 (95% CI=0.50-0.98) for ESCC and 0.55 (95% CI=0.38-0.81) for GCA. Stratification analysis showed that C/T genotype significantly reduced susceptibilities to ESCC and GCA among non-smokers, with adjusted OR of 0.54 (95% CI=0.33-0.90) for ESCC and 0.56 (95% CI=0.33-0.95) for GCA. In addition, C/T genotype significantly reduced susceptibility to GCA among individuals with or without UGIC history, with adjusted OR of 0.46 (95%CI=0.24-0.90) and 0.62 (95% CI=0.38-0.99) respectively, and reduced susceptibility to ESCC only among individuals with UGIC history, with adjusted OR of 0.51 (95% CI=0.29-0.89). SHMT1 1420C/T genotype could significantly

High phase-purity 1T'-MoS2- and 1T'-MoSe2-layered crystals

NASA Astrophysics Data System (ADS)

Yu, Yifu; Nam, Gwang-Hyeon; He, Qiyuan; Wu, Xue-Jun; Zhang, Kang; Yang, Zhenzhong; Chen, Junze; Ma, Qinglang; Zhao, Meiting; Liu, Zhengqing; Ran, Fei-Rong; Wang, Xingzhi; Li, Hai; Huang, Xiao; Li, Bing; Xiong, Qihua; Zhang, Qing; Liu, Zheng; Gu, Lin; Du, Yonghua; Huang, Wei; Zhang, Hua

2018-06-01

Phase control plays an important role in the precise synthesis of inorganic materials, as the phase structure has a profound influence on properties such as conductivity and chemical stability. Phase-controlled preparation has been challenging for the metallic-phase group-VI transition metal dichalcogenides (the transition metals are Mo and W, and the chalcogens are S, Se and Te), which show better performance in electrocatalysis than their semiconducting counterparts. Here, we report the large-scale preparation of micrometre-sized metallic-phase 1T'-MoX2 (X = S, Se)-layered bulk crystals in high purity. We reveal that 1T'-MoS2 crystals feature a distorted octahedral coordination structure and are convertible to 2H-MoS2 following thermal annealing or laser irradiation. Electrochemical measurements show that the basal plane of 1T'-MoS2 is much more active than that of 2H-MoS2 for the electrocatalytic hydrogen evolution reaction in an acidic medium.

Total mesorectal excision for the treatment of rectal cancer

PubMed Central

Zedan, Ali; Salah, Tareq

2015-01-01

Introduction In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. Methods This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan’s technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method. Results One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan’s technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was

Total mesorectal excision for the treatment of rectal cancer.

PubMed

Zedan, Ali; Salah, Tareq

2015-12-01

In the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer. This retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan's technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method. One hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan's technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was administered to 67.3% of the

Treatment outcomes in locally advanced colorectal carcinoma

PubMed Central

Harish, K; Narayanaswamy, YV; Nirmala, S

2004-01-01

Background Locally advanced colorectal cancers form a distinct subgroup where contiguous organs could be involved without distant metastases and so may be amenable to curative surgical resection. It was our objective to report our experience in treating six such patients with operable locally advanced colorectal carcinomas. Methods We retrospectively reviewed the case notes of 47 patients who were diagnosed with colorectal cancers at M S Ramaiah Medical Teaching Hospital between the years 1996 – 2001. Six patients were identified with T4 lesions, adjacent organ involvement and with no nodal involvement. The treatments and outcomes for these patients were then reviewed. Results Two of three patients with rectal malignancies who underwent pelvic exenteration succumbed to disease recurrence within the first 18 months. One of the three patients with colonic cancers died of non malignant causes. The other two are disease free till date. Conclusions Aggressive multivisceral resections for locally advanced colonic cancers might be appropriate. Rectal cancers when locally advanced may be considered for pelvic exenteration, but a more guarded prognosis may apply. PMID:15527504

Modeling T1 and T2 relaxation in bovine white matter

NASA Astrophysics Data System (ADS)

Barta, R.; Kalantari, S.; Laule, C.; Vavasour, I. M.; MacKay, A. L.; Michal, C. A.

2015-10-01

The fundamental basis of T1 and T2 contrast in brain MRI is not well understood; recent literature contains conflicting views on the nature of relaxation in white matter (WM). We investigated the effects of inversion pulse bandwidth on measurements of T1 and T2 in WM. Hybrid inversion-recovery/Carr-Purcell-Meiboom-Gill experiments with broad or narrow bandwidth inversion pulses were applied to bovine WM in vitro. Data were analysed with the commonly used 1D-non-negative least squares (NNLS) algorithm, a 2D-NNLS algorithm, and a four-pool model which was based upon microscopically distinguishable WM compartments (myelin non-aqueous protons, myelin water, non-myelin non-aqueous protons and intra/extracellular water) and incorporated magnetization exchange between adjacent compartments. 1D-NNLS showed that different T2 components had different T1 behaviours and yielded dissimilar results for the two inversion conditions. 2D-NNLS revealed significantly more complicated T1/T2 distributions for narrow bandwidth than for broad bandwidth inversion pulses. The four-pool model fits allow physical interpretation of the parameters, fit better than the NNLS techniques, and fits results from both inversion conditions using the same parameters. The results demonstrate that exchange cannot be neglected when analysing experimental inversion recovery data from WM, in part because it can introduce exponential components having negative amplitude coefficients that cannot be correctly modeled with nonnegative fitting techniques. While assignment of an individual T1 to one particular pool is not possible, the results suggest that under carefully controlled experimental conditions the amplitude of an apparent short T1 component might be used to quantify myelin water.

S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-04-09

Colon Adenocarcinoma; ERBB2 Gene Amplification; Rectal Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage III Colon Cancer AJCC v7; Stage III Rectal Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIA Rectal Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIB Rectal Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7; Stage IIIC Rectal Cancer AJCC v7; Stage IV Colon Cancer AJCC v7; Stage IV Rectal Cancer AJCC v7; Stage IVA Colon Cancer AJCC v7; Stage IVA Rectal Cancer AJCC v7; Stage IVB Colon Cancer AJCC v7; Stage IVB Rectal Cancer AJCC v7

Apex technique in the treatment of obstructed defecation syndrome associated with rectal intussusception and full rectal mucosa prolapse.

PubMed

Regadas, F Sergio P; Abedrapo, Mario; Cruz, Jose Vinicius; Murad Regadas, Sthela M; Regadas Filho, F Sergio P

2014-11-01

The aim of the current study was to demonstrate the use of a modified stapling technique, called the apex technique, to treat rectal intussusception and full rectal mucosal prolapse. It was conducted as a retrospective study at 3 centers (2 in Brazil and 1 in Chile). The apex technique is performed by using a HEM/EEA-33 stapler. A pursestring suture is placed at the apex of the prolapse, on the 4 quadrants, independent of the distance to the dentate line. A second pursestring is then placed to define the band of rectal mucosa to be symmetrically resected. Outcome measures included width of the resected full-thickness rectal wall; the intensity of postoperative pain on a visual analog scale from 1 to 10; full mucosal prolapse and rectal intussusception assessed by physical examination, cinedefecography, or echodefecography; and change in the constipation scale. Forty-five patients (30 women/15 men; mean age, 59.5 years) with rectal intussusception and full mucosal prolapse were included. The median operative time was 17 (range, 15-30) minutes. Bleeding after stapler fire requiring manual suture occurred in 3 patients (6.7%); 25 (55.6%) patients reported having no postoperative pain. Hospital stay was 24 hours. The mean width of the resected rectal wall was 5.9 (range, 5.0-7.5) cm. Stricture at the staple line was seen in 4 patients, of whom 1 required dilation under anesthesia. The median follow-up time was 120 (range, 90-120) days. A small residual prolapse was identified in 6 (13.3%) patients. Imaging demonstrated complete disappearance of rectal intussusception in all patients, and the mean postoperative constipation score decreased from 13 (range, 8-15) to 5 (range, 3-7). The apex technique appears to be a safe, quickly performed, and low-cost method for the treatment of rectal intussusception. In this series, imaging examinations showed the disappearance of rectal intussusception, and a significant decrease in constipation score suggested improvement in

Imaging in rectal cancer with emphasis on local staging with MRI

PubMed Central

Arya, Supreeta; Das, Deepak; Engineer, Reena; Saklani, Avanish

2015-01-01

Imaging in rectal cancer has a vital role in staging disease, and in selecting and optimizing treatment planning. High-resolution MRI (HR-MRI) is the recommended method of first choice for local staging of rectal cancer for both primary staging and for restaging after preoperative chemoradiation (CT-RT). HR-MRI helps decide between upfront surgery and preoperative CT-RT. It provides high accuracy for prediction of circumferential resection margin at surgery, T category, and nodal status in that order. MRI also helps assess resectability after preoperative CT-RT and decide between sphincter saving or more radical surgery. Accurate technique is crucial for obtaining high-resolution images in the appropriate planes for correct staging. The phased array external coil has replaced the endorectal coil that is no longer recommended. Non-fat suppressed 2D T2-weighted (T2W) sequences in orthogonal planes to the tumor are sufficient for primary staging. Contrast-enhanced MRI is considered inappropriate for both primary staging and restaging. Diffusion-weighted sequence may be of value in restaging. Multidetector CT cannot replace MRI in local staging, but has an important role for evaluating distant metastases. Positron emission tomography-computed tomography (PET/CT) has a limited role in the initial staging of rectal cancer and is reserved for cases with resectable metastatic disease before contemplating surgery. This article briefly reviews the comprehensive role of imaging in rectal cancer, describes the role of MRI in local staging in detail, discusses the optimal MRI technique, and provides a synoptic report for both primary staging and restaging after CT-RT in routine practice. PMID:25969638

[Renal cell carcinoma with t(6;11)(p21.2;q13)/MALAT1-TFEB fusion: a clinical and pathological analysis].

PubMed

Xia, Qiuyuan; Shi, Shanshan; Shen, Qin; Wei, Xue; Wang, Xuan; Ma, Henghui; Lu, Zhenfeng; Zhou, Xiaojun; Rao, Qiu

2015-12-01

To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion. A total of 9 cases of such rare tumor were selected for clinicopathologic, immunohistochemical and molecular analysis, with review of literature. The age of the patients ranged from 21 to 42 years (mean=31.3 years). The patients included four men and five women. Histologically, 4 of the 9 cases studied showed classic morphologic features of TFEB RCC, with hyaline material, pigments and psammoma bodies frequently identified. The remaining 5 cases demonstrated uncommon morphology, mimicking perivascular epithelioid cell neoplasm, clear cell RCC, chromophobe RCC or papillary RCC. Immunohistochemical study showed that TFEB and vimentin were positive in all cases. Most of the tumors studied also expressed Ksp-cadherin, E-cadherin, CD117, HMB45, Melan A and Cathepsin K. CKpan showed immunostaining in only 1 case. The staining for TFE3, CD10 and CK7 were all negative. TFEB gene rearrangement was detected in all the 9 cases studied using fluorescence in-situ hybridization. MALAT1-TFEB fusion gene was identified in 2 cases by polymerase chain reaction and direct sequencing. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none developed tumor recurrence, progression, or metastasis. TFEB fusion-associated RCC is a rare neoplasm, tends to occur in young age group and carries an indolent behavior. Diagnosis relies on clinicopathologic findings and immunohistochemical analysis. TFEB break-apart FISH assay is a reliable tool in confirming the diagnosis.

HBV-specific CD4+ cytotoxic T cells in hepatocellular carcinoma are less cytolytic toward tumor cells and suppress CD8+ T cell-mediated antitumor immunity.

PubMed

Meng, Fanzhi; Zhen, Shoumei; Song, Bin

2017-08-01

In East Asia and sub-Saharan Africa, chronic infection is the main cause of the development of hepatocellular carcinoma, an aggressive cancer with low survival rate. Cytotoxic T cell-based immunotherapy is a promising treatment strategy. Here, we investigated the possibility of using HBV-specific CD4 + cytotoxic T cells to eliminate tumor cells. The naturally occurring HBV-specific cytotoxic CD4 + and CD8 + T cells were identified by HBV peptide pool stimulation. We found that in HBV-induced hepatocellular carcinoma patients, the HBV-specific cytotoxic CD4 + T cells and cytotoxic CD8 + T cells were present at similar numbers. But compared to the CD8 + cytotoxic T cells, the CD4 + cytotoxic T cells secreted less cytolytic factors granzyme A (GzmA) and granzyme B (GzmB), and were less effective at eliminating tumor cells. In addition, despite being able to secrete cytolytic factors, CD4 + T cells suppressed the cytotoxicity mediated by CD8 + T cells, even when CD4 + CD25 + regulator T cells were absent. Interestingly, we found that interleukin 10 (IL-10)-secreting Tr1 cells were enriched in the cytotoxic CD4 + T cells. Neutralization of IL-10 abrogated the suppression of CD8 + T cells by CD4 + CD25 - T cells. Neither the frequency nor the absolute number of HBV-specific CD4 + cytotoxic T cells were correlated with the clinical outcome of advanced stage hepatocellular carcinoma patients. Together, this study demonstrated that in HBV-related hepatocellular carcinoma, CD4 + T cell-mediated cytotoxicity was present naturally in the host and had the potential to exert antitumor immunity, but its capacity was limited and was associated with immunoregulatory properties. © 2017 APMIS. Published by John Wiley & Sons Ltd.

SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

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

Park, J; Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul; Park, H

Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from themore » whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of

Meta-analysis of elective surgical complications related to defunctioning loop ileostomy compared with loop colostomy after low anterior resection for rectal carcinoma

PubMed Central

Geng, Hong Zhi; Nasier, Dilidan; Liu, Bing; Gao, Hua; Xu, Yi Ke

2015-01-01

Introduction Defunctioning loop ileostomy (LI) and loop colostomy (LC) are used widely to protect/treat anastomotic leakage after colorectal surgery. However, it is not known which surgical approach has a lower prevalence of surgical complications after low anterior resection for rectal carcinoma (LARRC). Methods We conducted a literature search of PubMed, MEDLINE, Ovid, Embase and Cochrane databases to identify studies published between 1966 and 2013 focusing on elective surgical complications related to defunctioning LI and LC undertaken to protect a distal rectal anastomosis after LARRC. Results Five studies (two randomized controlled trials, one prospective non-randomized trial, and two retrospective trials) satisfied the inclusion criteria. Outcomes of 1,025 patients (652 LI and 373 LC) were analyzed. After the construction of a LI or LC, there was a significantly lower prevalence of sepsis (p=0.04), prolapse (p=0.03), and parastomal hernia (p=0.02) in LI patients than in LC patients. Also, the prevalence of overall complications was significantly lower in those who received LIs compared with those who received LCs (p<0.0001). After closure of defunctioning loops, there were significantly fewer wound infections (p=0.006) and incisional hernias (p=0.007) in LI patients than in LC patients, but there was no significant difference between the two groups in terms of overall complications. Conclusions The results of this meta-analysis show that a defunctioning LI may be superior to LC with respect to a lower prevalence of surgical complications after LARRC. PMID:26274752

Rectal bleeding and implications for surgical care in Nepal.

PubMed

Tessler, Robert; Gupta, Shailvi; Pathak, John; Ghimire, Pranita; Kingham, Thomas P; Kushner, Adam L; Amatya, Kapendra Shekhar; Nwomeh, Benedict C

2015-07-01

Because rectal bleeding is a cardinal symptom of many colorectal diseases including colorectal cancers, its presence alone could give insight into the prevalence of these conditions where direct population screening is lacking. In South Asia, which is home to over one fifth of the world's population, there is paucity of epidemiologic data on colorectal diseases, particularly in the lower-income countries such as Nepal. The aim of this study was to enumerate the prevalence of rectal bleeding in Nepal and increase understanding of colorectal diseases as a health problem in the South Asian region. A countrywide survey using the Surgeons OverSeas Assessment of Surgical Need tool was administered from May 25-June 12, 2014 in 15 of the 75 districts of Nepal, randomly selected proportional to population. In each district, three Village Development Committees were selected randomly, two rural and one urban based on the Demographic Health Survey methodology. Individuals were interviewed to determine the period and point prevalence of rectal bleeding and patterns of health-seeking behavior related to surgical care for this problem. Individuals aged >18 y were included in this analysis. A total of 1350 households and 2695 individuals were surveyed with a 97% response rate. Thirty-eight individuals (55% male) of the 1941 individuals ≥ 18 y stated they had experienced rectal bleeding (2.0%, 95% confidence interval 1.4%-2.7%), with a mean age of 45.5 (standard deviation 2.2). Of these 38 individuals, 30 stated they currently experience rectal bleeding. Health Care was sought in 18 participants with current rectal bleeding, with two major procedures performed, one an operation for an anal fistula. For those who sought health care but did not receive surgical care, reasons included no need (4), not available (6), fear and/or no trust (5), and no money for health care (1). For those with current rectal bleeding who did not seek health care, reasons included no need (1), not

[Robotic rectal resection in rectal cancer: short term results in a monocentric prospective study].

PubMed

Bianchi, P; Petz, W; Spinoglio, G; Belotti, D; Bertani, E; Zampino, M G; Crosta, C; Lazzari, R; Andreoni, B

2011-12-01

The aim of this study was to evaluate technical feasibility, oncological safety and short-term clinical results of robotic rectal resection for cancer. From January 2008 to July 2010, 46 patients (27 males and 19 females, median age 69 years, median BMI 24.6 kg/m2) with histologically-proven adenocarcinoma of medium and distal rectum were enrolled in a prospective database. Preoperative assessment was performed with colonoscopy with biopsies, thoraco-abdominal CT scan, pelvic MRI and endorectal-ultrasound (ERUS). In the case of locally advanced non metastatic disease (T3/4 or N1/2), patients received preoperative radiotherapy (45 Grays in 5 weeks) and chemotherapy (oral Capecitabine). The robotic system was a four-arms Da Vinci® (Intuitive Surgical, Sunnyvale, CA, USA); arms position is not modified during the entire surgical procedure. Twenty-five patients received a preoperative radio-chemotherapy. Surgical procedure was an abdomino-perineal amputation in nine patients and an anterior resection in the remaining 37, with temporary ileostomy in 16 cases and a laparoscopic mobilization of splenic flexure in 25. Median operative time was 251 minutes, median time of first bowel movements 1.7 days and median hospital stay 6.7 days. Major complications requiring reoperation verified in 2 patients, while overall complication rate is 15.2%. Median number of harvested lymph nodes per patient was 18; median distance of the tumour from distal resection margin was 2 cm; distance of the tumour from circumferential margin was superior to 1 mm in all of the patients. At a median follow up of 11 months, all patients are alive and disease-free. Robotic rectal resection is a feasible technique which can provide good oncological and short-term clinical results.

Minimal Rectal Toxicity in the Setting of Comorbid Crohn's Disease Following Prostate Cancer Radiotherapy with a Hydrogel Rectal Spacer.

PubMed

Singh, Raj; Jackson, Philip S; Blake, Mollie; Cutlip, James; Sharma, Sanjeev

2017-08-01

We present one of the first cases of a prostate cancer (PCa) patient with inflammatory bowel disease (IBD) treated with intensity-modulated radiotherapy (IMRT) and a hydrogel rectal spacer. A 73-year-old male with a past medical history significant for Crohn's disease (CD) and the recent diagnosis of T1cN0M0 high-risk PCa was referred for definitive radiotherapy. Given the patient's history of CD and the possible increased risk of gastrointestinal (GI) toxicity and disease exacerbation, prior to IMRT, a hydrogel spacer was placed between the prostate and the anterior rectal wall to further minimize irradiation to the rectum. The patient then received IMRT (78 Gy/2 Gy fractions at a 100 percent isodose line). Over the course of treatment, Radiation Therapy Oncology Group (RTOG) Grade 1 GI toxicities of mild diarrhea were noted during the fifth and sixth weeks of treatment as well as an RTOG Grade 1 genitourinary (GU) toxicity of a decrease in the urinary stream that resolved with tamsulosin. At the 3, 6, 9, and 12-month follow-ups, bowel movements and urinary stream were reported to be at baseline with prostate-specific antigen (PSA) levels of 0.18 ng/mL and 0.03 ng/mL at the three and nine-month follow-ups, respectively. As such, this case report suggests that IBD patients with localized PCa may be viable candidates for radiotherapy given the promising results of hydrogel spacers in combination with IMRT in limiting rectal toxicity.

Merkel cell polyomavirus small T antigen initiates Merkel cell carcinoma-like tumor development in mice

PubMed Central

Verhaegen, Monique E.; Mangelberger, Doris; Harms, Paul W.; Eberl, Markus; Wilbert, Dawn M.; Meireles, Julia; Bichakjian, Christopher K.; Saunders, Thomas L.; Wong, Sunny Y.; Dlugosz, Andrzej A.

2017-01-01

Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a non-proliferative population of neuroendocrine cells which arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor’s cell of origin, are unknown. Using a panel of pre-term transgenic mice, we show that epidermis-targeted co-expression of sT and the cell fate determinant atonal bHLH transcription factor 1 (Atoh1) leads to development of widespread cellular aggregates with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Co-expression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with Atoh1. MCPyV sT, when co-expressed with Atoh1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. PMID:28512245

Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice.

PubMed

Verhaegen, Monique E; Mangelberger, Doris; Harms, Paul W; Eberl, Markus; Wilbert, Dawn M; Meireles, Julia; Bichakjian, Christopher K; Saunders, Thomas L; Wong, Sunny Y; Dlugosz, Andrzej A

2017-06-15

Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151-7. ©2017 AACR . ©2017 American Association for Cancer Research.

Palliative Short-Course Radiation Therapy in Rectal Cancer: A Phase 2 Study

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

Picardi, Vincenzo; Deodato, Francesco; Guido, Alessandra

2016-07-15

Purpose: The management of patients with symptomatic rectal cancer not amenable to curative treatment may be challenging. The aim of this phase 2 study was to evaluate the efficacy of short-course radiation therapy in patients with obstructing rectal cancer. Methods and Materials: Patients who were not candidates for surgical resection because of synchronous metastases, age, and/or comorbidities were considered eligible. The sample size was calculated based on the 2-stage design of Simon. Short-course radiation therapy was delivered with an isocentric 4-field box technique (total, 25 Gy; 5 fractions in 5 days). Chemotherapy was suspended during radiation treatment. Clinical outcome measures were symptomaticmore » response rate, toxicity, colostomy-free survival, and overall survival. Results: From October 2003 to November 2012, 18 patients (median age, 77.5 years) were enrolled. The median follow-up was 11.5 months (range, 3-36 months). Four weeks after treatment, a complete response (ie, complete symptom resolution) was observed in 38.9% of patients and a partial response in 50.0% cases, whereas 11.1% had no response. The rates of reduction or resolution of pain and bleeding were 87.5% and 100%, respectively. The 1-, 2-, and 3-year colostomy-free survival rates were 100%, 71.4%, and 47.6%, respectively (median, 30 months). The 1-, 2-, and 3-year cumulative overall survival rates were 85.2%, 53%, and 39.8%, respectively (median, 25 months). No patients stopped treatment because of gastrointestinal or genitourinary toxicities: 38.9% of patients had grade 1 to 2 toxicity, and 16.7% had grade 3 toxicity. Only 1 patient had hematologic grade 2 toxicity, and 2 patients had grade 2 skin toxicity. Conclusions: Short-course radiation therapy may represent a safe and effective alternative treatment option in patients with obstructing rectal cancer not eligible for curative treatment, allowing colostomy to be avoided in a substantial proportion of patients.« less

Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

PubMed Central

Sgourakis, George; Gockel, Ines; Lang, Hauke

2013-01-01

.001]. A significantly greater number of SCC patients were submitted to surgery (log-odds, ADC: -2.1206 ± 0.6249 vs SCC: 4.1356 ± 0.4038, P < 0.05). The odds for re-classification of tumor stage after endoscopic resection were 53% and 39% for ADC and SCC, respectively. Local tumor recurrence was best predicted by grade 3 differentiation and piecemeal resection, metachronous cancer development by the carcinoma in situ component, and lymph node positivity by lymphovascular invasion. With regard to surgically resected patients: Significant differences in patients with positive lymph nodes were observed between ADC and SCC [coefficient: 1.889569, 95%CI: (0.3945146, 3.384624), P < 0.01). In contrast, lymphovascular and microvascular invasion and grade 3 patients between histologic types were comparable, the respective rank order of the predictors of lymph node positivity was: Grade 3, lymphovascular invasion (L+), microvascular invasion (V+), submucosal (Sm) 3 invasion, Sm2 invasion and Sm1 invasion. Histologic type (ADC/SCC) was not included in the model. The best predictors for SCC lymph node positivity were Sm3 invasion and (V+). For ADC, the most important predictor was (L+). CONCLUSION: Local tumor recurrence is predicted by grade 3, metachronous cancer by the carcinoma in-situ component, and lymph node positivity by L+. T1b cancer should be treated with surgical resection. PMID:23539431

Quantitative analysis of rectal cancer by spectral domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Zhang, Q. Q.; Wu, X. J.; Tang, T.; Zhu, S. W.; Yao, Q.; Gao, Bruce Z.; Yuan, X. C.

2012-08-01

To quantify OCT images of rectal tissue for clinic diagnosis, the scattering coefficient of the tissue is extracted by curve fitting the OCT signals to a confocal single model. A total of 1000 measurements (half and half of normal and malignant tissues) were obtained from 16 recta. The normal rectal tissue has a larger scattering coefficient ranging from 1.09 to 5.41 mm-1 with a mean value of 2.29 mm-1 (std:±0.32), while the malignant group shows lower scattering property and the values ranging from 0.25 to 2.69 mm-1 with a mean value of 1.41 mm-1 (std:±0.18). The peri-cancer of recta has also been investigated to distinguish the difference between normal and malignant rectal tissue. The results demonstrate that the quantitative analysis of the rectal tissue can be used as a promising diagnostic criterion of early rectal cancer, which has great value for clinical medical applications.

Role of CRTC1/MAML2 Translocation in the Prognosis and Clinical Outcomes of Mucoepidermoid Carcinoma.

PubMed

Saade, Rami E; Bell, Diana; Garcia, Joaquin; Roberts, Dianna; Weber, Randal

2016-03-01

The CRTC1/MAML2 fusion transcript, which arises from the CRTC1/MAML2 translocation, is a molecular marker unique to mucoepidermoid carcinoma (MEC), the most common malignant tumor of the salivary gland. The extent to which the transcript influences disease features and patient survival is unclear. To determine whether the CRTC1/MAML2 fusion transcript is associated with disease stage, tumor grade, or survival outcomes in patients with MEC. A retrospective medical record review was performed at a tertiary-care academic medical institution. The review included 90 patients with MEC who underwent treatment from January 1, 1995, to December 31, 2011, and for whom archived formalin-fixed, paraffin-embedded tumor specimens were available. Records were reviewed for clinical, demographic, and survival data. Tumor specimens underwent fluorescence in situ hybridization. Follow-up was completed on May 15, 2014, and data were analyzed from June 1 to July 1, 2014. CRTC1/MAML2 fusion transcript status. Statistical analysis determined whether transcript status was associated with disease stage, tumor grade, and/or overall and disease-free survival. Among the 90 eligible patients (median [range] age, 55.1 [7.8-89.2] years), 42 were female and 48 were male. Fluorescence in situ hybridization revealed a CRTC1/MAML2 translocation in 50 patients (56%). The translocations were more prevalent in intermediate-grade tumors (31 of 49 [63%]) than in high-grade (11 of 49 [22%]) and low-grade (7 of 49 [14%]) tumors; 1 tumor sample had no available grading. Similar proportions of patients with translocation-positive disease had T1 (13 of 49 [26%]), T2 (15 of 49 [31%]), T4a (14 of 49 [28%]), or T0 or Tx (8 of 49 [16%]) stages of disease. Thirty-eight of 49 patients with translocation-positive MEC (78%) had N0 stage of disease. Rates of 5-year overall survival were similar for patients with translocation-positive and translocation-negative disease (76.8% vs 75.5%, respectively; P = .17), as

Effects of sodium phenylbutyrate on differentiation and induction of the P21WAF1/CIP1 anti-oncogene in human liver carcinoma cell lines.

PubMed

Meng, Mei; Jiang, Jun Mei; Liu, Hui; In, Cheng Yong; Zhu, Ju Ren

2005-01-01

To explore the effects of sodium phenylbutyrate on the proliferation, differentiation, cell cycle arrest and induction of the P(21WAF1/CIP1) anti-oncogene in human liver carcinoma cell lines Bel-7402 and HepG2. Bel-7402 and HepG2 human liver carcinoma cells were treated with sodium phenylbutyrate at different concentrations. Light microscopy was used to observe morphological changes in the carcinoma cells. Effects on the cell cycle were detected by using flow cytometry. P(21WAF1/CIP1) expression was determined by both reverse transcription-polymerase chain reaction and western blotting. Statistical analysis was performed by using one-way anova and Student's t-test. Sodium phenylbutyrate treatment caused time- and dose-dependent growth inhibition of Bel-7402 and HepG2 cells. This treatment also caused a decline in the proportion of S-phase cells and an increase in the proportion of G(0)/G(1) cells. Sodium phenylbutyrate increased the expression of P(21WAF1/CIP1). Sodium phenylbutyrate inhibits the proliferation of human liver carcinoma cells Bel-7402 and HepG2, induces partial differentiation, and increases the expression of P(21WAF1/CIP1).

Prevention of SIV Rectal Transmission and Priming of T Cell Responses in Macaques after Local Pre-exposure Application of Tenofovir Gel

PubMed Central

Cranage, Martin; Sharpe, Sally; Herrera, Carolina; Cope, Alethea; Dennis, Mike; Berry, Neil; Ham, Claire; Heeney, Jonathan; Rezk, Naser; Kashuba, Angela; Anton, Peter; McGowan, Ian; Shattock, Robin

2008-01-01

Background The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV) drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT) inhibitor tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl] adenine monohydrate), a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV) in a well-established and standardised macaque model. Methods and Findings A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50) of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC), quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA) load by sensitive quantitative competitive (qc) RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test) wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from

SU-D-BRA-04: Fractal Dimension Analysis of Edge-Detected Rectal Cancer CTs for Outcome Prediction

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

Zhong, H; Wang, J; Hu, W

2015-06-15

Purpose: To extract the fractal dimension features from edge-detected rectal cancer CTs, and to examine the predictability of fractal dimensions to outcomes of primary rectal cancer patients. Methods: Ninety-seven rectal cancer patients treated with neo-adjuvant chemoradiation were enrolled in this study. CT images were obtained before chemoradiotherapy. The primary lesions of the rectal cancer were delineated by experienced radiation oncologists. These images were extracted and filtered by six different Laplacian of Gaussian (LoG) filters with different filter values (0.5–3.0: from fine to coarse) to achieve primary lesions in different anatomical scales. Edges of the original images were found at zero-crossingsmore » of the filtered images. Three different fractal dimensions (box-counting dimension, Minkowski dimension, mass dimension) were calculated upon the image slice with the largest cross-section of the primary lesion. The significance of these fractal dimensions in survival, recurrence and metastasis were examined by Student’s t-test. Results: For a follow-up time of two years, 18 of 97 patients had experienced recurrence, 24 had metastasis, and 18 were dead. Minkowski dimensions under large filter values (2.0, 2.5, 3.0) were significantly larger (p=0.014, 0.006, 0.015) in patients with recurrence than those without. For metastasis, only box-counting dimensions under a single filter value (2.5) showed differences (p=0.016) between patients with and without. For overall survival, box-counting dimensions (filter values = 0.5, 1.0, 1.5), Minkowski dimensions (filter values = 0.5, 1.5, 2.0, 2,5) and mass dimensions (filter values = 1.5, 2.0) were all significant (p<0.05). Conclusion: It is feasible to extract shape information by edge detection and fractal dimensions analysis in neo-adjuvant rectal cancer patients. This information can be used to prognosis prediction.« less

[Numbers of lymph nodes in large intestinal resections for colorectal carcinoma].

PubMed

Motycka, V; Ferko, A; Tycová, V; Nikolov, Hadzi; Sotona, O; Cecka, F; Dusek, T; Chobola, M; Pospísil, I

2010-03-01

Precise evaluation of lymph nodes in the surgical specimen is crucial for the staging and subsequent decision about the adjuvant therapy in colorectal cancer. Prognosis of the patients can be assessed only in cases when at least 12 lymph nodes in the surgical specimen are examined. To evaluate the radicalism of resections for colorectal carcinoma after introducing laparoscopic approach. We compared all resections for primary colorectal cancer and rectal cancer (C 18-C20) performed in the Department of Surgery in University Hospital Hradec Králové in the years 2005 and 2008 and we evaluated numbers of examined lymph nodes in the surgical specimens. The patients with recurrent tumours and the patients with complete pathological response (negative histology) after neoadjuvant therapy were excluded from the study. 117 patients were included in the study in 2005, 2 of them were operated laparoscopically. 155 patients (more by 32.5%) were included in the study in 2008, 53 of them (34.2%) were operated laparoscopically. In tumours of the right part of the colon (C180-C184) treated by right hemicolectomy: on an average 7.9 (+/- 5.3) lymph nodes were examined in the specimens in 2005, and 15.3 (+/- 7.0) lymph nodes in 2008. In tumours of the left part of the colon (C185-C186) treated by left hemicolectomy: 6.5 (+/- 5.1) lymph nodes were examined in 2005, and 19.6 (+/- 15.6) in 2008. In tumours of the sigmoid colon (C187) 9.1 (+/- 6.9) lymph nodes were examined in 2005,and 15.4 (+/- 7.9) in 2008. In tumours of the rectosigmoid junction (C19) 8.0 (+/- 6.9) lymph nodes were examined in 2005, and 17.8 (+/- 11.2) in 2008. In rectal cancer (C20) 5.2 (+/- 4.5) lymph nodes were examined in 2005, and 13.6 (+/- 12.5) in 2008. There is a significant difference in a number of examined lymph nodes in patients without neodadjuvant treatment compared to those with neoadjuvant chemoradiotherapy and neoadjuvant radiotherapy. In 2005, in an average 3.7 (+/- 3.3) lymph nodes were removed in

The effect of rectal Foley catheterization on rectal bleeding rates after transrectal ultrasound-guided prostate biopsy.

PubMed

Kilciler, Mete; Erdemir, Fikret; Demir, Erkan; Güven, Oğuz; Avci, Ali

2008-09-01

To assess whether Foley catheterization of the rectum after transrectal ultrasound (TRUS)-guided prostate biopsy decreases complication rates. Between June 2000 and September 2006, 275 consecutive patients were evaluated after undergoing TRUS-guided prostate biopsy. All procedures were performed on an outpatient basis. Patients were divided into two groups. In the first group (n = 134), a Foley catheter was inserted into the rectum and inflated to 50 cm(3) after TRUS-guided biopsy. In the second group (n = 141), catheterization was performed without balloon placement. Rectal bleeding, hematuria, hematospermia, infection, and acute urinary retention rates were compared between groups. The mean ages of the patients were 63.3 years +/- 5.6 and 62.1 years +/- 7.2 years in the Foley catheter group and control group, respectively (P = .112). Hematuria, hematospermia, infection, and rectal bleeding occurred in 31 (23.1%), 30 (22.4), nine (6.7%), and two patients (1.5%), respectively, in the Foley catheter group; and in 36 (25.5%), 36 (25.5%), 11 (7.8%), and 25 patients (17.7%), respectively, in the control group. The incidences of infection, hematuria, and hematospermia were not significantly different between groups (P > .05). In contrast, the rectal bleeding rate was significantly lower in the Foley catheter group (1.5%) than in the control group (17.7%; P = .001). Although it has no effect on other complications, TRUS-guided prostate biopsy with rectal Foley catheterization is a useful, practical method to decrease or prevent rectal bleeding.

WE-G-BRD-08: Motion Analysis for Rectal Cancer: Implications for Adaptive Radiotherapy On the MR-Linac

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

Kleijnen, J; Asselen, B van; Burbach, M

2015-06-15

Purpose: Purpose of this study is to find the optimal trade-off between adaptation interval and margin reduction and to define the implications of motion for rectal cancer boost radiotherapy on a MR-linac. Methods: Daily MRI scans were acquired of 16 patients, diagnosed with rectal cancer, prior to each radiotherapy fraction in one week (N=76). Each scan session consisted of T2-weighted and three 2D sagittal cine-MRI, at begin (t=0 min), middle (t=9:30 min) and end (t=18:00 min) of scan session, for 1 minute at 2 Hz temporal resolution. Tumor and clinical target volume (CTV) were delineated on each T2-weighted scan andmore » transferred to each cine-MRI. The start frame of the begin scan was used as reference and registered to frames at time-points 15, 30 and 60 seconds, 9:30 and 18:00 minutes and 1, 2, 3 and 4 days later. Per time-point, motion of delineated voxels was evaluated using the deformation vector fields of the registrations and the 95th percentile distance (dist95%) was calculated as measure of motion. Per time-point, the distance that includes 90% of all cases was taken as estimate of required planning target volume (PTV)-margin. Results: Highest motion reduction is observed going from 9:30 minutes to 60 seconds. We observe a reduction in margin estimates from 10.6 to 2.7 mm and 16.1 to 4.6 mm for tumor and CTV, respectively, when adapting every 60 seconds compared to not adapting treatment. A 75% and 71% reduction, respectively. Further reduction in adaptation time-interval yields only marginal motion reduction. For adaptation intervals longer than 18:00 minutes only small motion reductions are observed. Conclusion: The optimal adaptation interval for adaptive rectal cancer (boost) treatments on a MR-linac is 60 seconds. This results in substantial smaller PTV-margin estimates. Adaptation intervals of 18:00 minutes and higher, show little improvement in motion reduction.« less

Preoperative predictors of occult nodal disease in cT1N0 oral cavity squamous cell carcinoma: Review of 2623 cases.

PubMed

Zhan, Kevin Y; Morgan, Patrick F; Neskey, David M; Kim, Joanne J; Huang, Andrew T; Garrett-Mayer, Elizabeth; Day, Terry A

2018-05-14

Nodal disease predicts survival in oral cavity squamous cell carcinoma (SCC). Currently, no large studies on predictors of occult nodal disease in cT1N0 oral cavity SCC exist. The National Cancer Database (NCDB) review for cT1N0 oral cavity SCC with surgical resection and elective neck dissection (END). The number of patients found with occult nodal disease was 2623 (15.1%). In multivariable regression, female sex and tumor differentiation predict occult nodal disease. Occult nodal disease incidence was 5.9% in well-differentiated tumors, 17.4% in moderately differentiated tumors, and 28.5% in poorly differentiated tumor (P < .001). Women with oral tongue tumors had higher occult nodal disease (19.1%) than men (12%; P = .001). Adjusted odds ratios (aORs) for occult nodal disease in women were: aOR 1.26; 95% confidence interval (CI) 1.01-1.59; P = .045; moderately differentiated aOR 3.52; 95% CI 2.47-5.01; P < .001; and poorly differentiated aOR 6.25; 95% CI 4.17-9.38; P < .001. Sex and tumor differentiation significantly predict occult nodal disease. END is recommended for all moderately and poorly differentiated cT1N0 oral cavity SCC, regardless of the depth of invasion. One can consider not performing END in well-differentiated tumors. © 2018 Wiley Periodicals, Inc.

B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma

PubMed Central

Hua, Dong; Sun, Jing; Mao, Yong; Chen, Lu-Jun; Wu, Yu-Yu; Zhang, Xue-Guang

2012-01-01

AIM: To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment. METHODS: One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study. Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells. Data was analyzed with statistical software. RESULTS: Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found congregated in CRC tumor nest and stroma. Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P < 0.0001) and tumor stroma (P = 0.0200) of 102 cases of CRC tissues. Among the total T cells, a variable amount of regulatory T cells with a clear Foxp3+ (forkhead box P3) staining could be detected in CRC tissues and patients’ blood. Interestingly, in the 33 samples (15 cases of B7-H1high CRC tissues and 18 cases of B7-H1low CRC tissues) of freshly isolated mononuclear cells from CRC tissues, the percentages of CD4+Foxp3+ and CD8+Foxp3+ regulatory T cells were found remarkably higher in B7-H1high CRC tissues than in B7-H1low CRC tissues (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in proliferation of regulatory T cell. No significant difference was found in CRC peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell, which is expressed by activated T cell. Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells

B7-H1 expression is associated with expansion of regulatory T cells in colorectal carcinoma.

PubMed

Hua, Dong; Sun, Jing; Mao, Yong; Chen, Lu-Jun; Wu, Yu-Yu; Zhang, Xue-Guang

2012-03-07

To investigate the expression of B7-H1 in human colorectal carcinoma (CRC) to define its regulating effects on T cells in tumor microenvironment. One hundred and two paraffin blocks and 33 fresh samples of CRC tissues were subject to this study. Immunohistochemistry was performed for B7-H1 and CD3 staining in CRC tissues. Ficoll-Hypaque density gradient centrifugation was used to isolate peripheral blood mononuclear cells of fresh CRC tissues; flow cytometry and immunofluorescence staining were used for detection of regulatory T cells. Data was analyzed with statistical software. Costimulatory molecule B7-H1 was found strongly expressed in CRC tissues, localized in tumor cell membrane and cytoplasm, while weak or none expression of B7-H1 was detected in pared normal colorectal tissues. Meanwhile, CD3 positive T cells were found congregated in CRC tumor nest and stroma. Statistic analysis showed that B7-H1 expression level was negatively correlated to the total T cell density in tumor nest (P < 0.0001) and tumor stroma (P = 0.0200) of 102 cases of CRC tissues. Among the total T cells, a variable amount of regulatory T cells with a clear Foxp3⁺ (forkhead box P3) staining could be detected in CRC tissues and patients' blood. Interestingly, in the 33 samples (15 cases of B7-H1(high) CRC tissues and 18 cases of B7-H1(low) CRC tissues) of freshly isolated mononuclear cells from CRC tissues, the percentages of CD4⁺Foxp3⁺ and CD8⁺Foxp3⁺ regulatory T cells were found remarkably higher in B7-H1(high) CRC tissues than in B7-H1(low) CRC tissues (P = 0.0024, P = 0.0182), indicating that B7-H1 expression was involved in proliferation of regulatory T cell. No significant difference was found in CRC peripheral blood (P = 0.0863, P = 0.0678). PD-1 is the specific ligand for B7-H1 pathway transferring inhibitory signal to T cell, which is expressed by activated T cell. Our further analysis of PD-1 expression on T cells in CRC tissues showed that conventional T cells (CD4�

Enhanced circulating transforming growth factor beta 1 is causally associated with an increased risk of hepatocellular carcinoma: a mendelian randomization meta-analysis.

PubMed

Lu, Wei-Qun; Qiu, Ji-Liang; Huang, Zhi-Liang; Liu, Hai-Ying

2016-12-20

The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model. Overall, the association of C-509T polymorphism with hepatocellular carcinoma was negative, but its association with circulating TGF-β1 was statistically significant, with a higher concentration observed in carriers of the -509TT genotype (WMD, 95% CI, P: 1.72, 0.67-2.78, 0.001) and -509TT/-509TC genotypes (WMD, 95% CI, P: 0.98, 0.43-1.53, < 0.001). In subgroup analysis, C-509T polymorphism was significantly associated with hepatocellular carcinoma in population-based studies under homozygous-genotype (OR, 95% CI, P: 1.74, 1.08-2.80, 0.023) and dominant (OR, 95% CI, P: 1.48, 1.01-2.17, 0.047) models. Further MR analysis indicated that per unit increase in circulating TGF-β1 was significantly associated with a 38% (95% CI: 1.03-4.65) and 49% (95% CI: 1.01-6.06) increased risk of hepatocellular carcinoma under homozygous-genotype and dominant models, respectively. Conclusively, based on a MR meta-analysis, our findings suggest that enhanced circulating TGF-β1 is causally associated with an increased risk of hepatocellular carcinoma.

Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells

PubMed Central

Park, So Young; Kwon, Soo Jin; Lim, Soon Sung; Kim, Jin-Kyu; Lee, Ki Won; Park, Jung Han Yoon

2016-01-01

Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis. This study examined whether HEGU and licoricidin inhibit metastasis using the 4T1 mammary cancer model. Both HEGU and licoricidin treatment reduced pulmonary metastasis and the expression of CD45, CD31, HIF-1α, iNOS, COX-2, and VEGF-A in tumor tissues. Additionally, a decrease in protein expression of VEGF-R2, VEGF-C, VEGF-R3, and LYVE-1 was noted in tumor tissues of licoricidin-treated mice. Furthermore, the blood concentrations of MMP-9, ICAM-1, VCAM-1, and VEGF-A were decreased in HEGU-treated mice. In vitro 4T1 cell culture results showed that both HEGU and licoricidin inhibited cell migration, MMP-9 secretion, and VCAM expression. The present study demonstrates that the licoricidin in HEGU inhibits lung metastasis of 4T1 mammary carcinoma cells, which may be mediated via inhibition of cancer cell migration, tumor angiogenesis, and lymphangiogenesis. PMID:27314329

High Rate of Induction of Human Autologous Cytotoxic T Lymphocytes against Renal Carcinoma Cells Cultured with an Interleukin Cocktail

PubMed Central

Liu, Shu Qin; Kawai, Koji; Shiraiwa, Hiroshi; Hayashi, Hitoshi; Akaza, Hideyuki; Hashizaki, Kazuko; Shiba, Reiko; Saijo, Kaoru

1998-01-01

A high rate of induction (9 of 10 cases) of human autologous cytotoxic T lymphocytes (CTL) was achieved in vitro from peripheral blood mononuclear cells of renal carcinoma patients by applying an interleukin (IL)‐cocktail consisting of IL‐1, ‐2, ‐4, and ‐6. The CTL specifically lysed their own target carcinoma cells within 24 h but did not kill neighboring autologous normal kidney cells or allogeneic renal cancer cell lines. In the case of TUHR4TKB, for which autologous CTL were not induced, no expression of MHC class‐I molecules was observed on the surface of these carcinoma cells, although they were sensitive to autologous natural killer cells. The results imply that adoptive immunotherapy for metastasized renal carcinoma will be feasible with autologous CTL in combination with natural killer cells. PMID:9914789

Outcomes of Endoscopic Submucosal Dissection vs Esophagectomy for T1 Esophageal Squamous Cell Carcinoma in a Real-world Cohort.

PubMed

Zhang, Yiqun; Ding, Han; Chen, Tao; Zhang, Xiaocen; Chen, Wei-Feng; Li, Quanlin; Yao, Liqing; Korrapati, Praneet; Jin, Xue-Juan; Zhang, Yong-Xing; Xu, Mei-Dong; Zhou, Ping-Hong

2018-04-25

Esophagectomy is the standard treatment for early-stage esophageal squamous cell carcinoma (EESCC), but patients who undergo this procedure have high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a less-invasive procedure for treatment of EESCC, but is considered risky because this tumor frequently metastasizes to the lymph nodes. We aimed to directly compare outcomes of patients with EESCC treated with ESD vs esophagectomy. We performed a retrospective cohort study of patients with T1a-m2/m3, or T1b EESCCs who underwent ESD (n=322) or esophagectomy (n=274) from October 1, 2011 through September 31, 2016 at Zhongshan Hospital in Shanghai, China. The primary outcome was all-cause mortality at the end of follow up (minimum of 6 months). Secondary outcomes included operation time, hospital stay, cost, perioperative mortalities/severe non-fatal adverse events, requirement for adjuvant therapies, and disease-specific mortality and cancer recurrence or metastasis at the end of the follow up period. Patients who underwent ESD were older (mean 63.5 years vs 62.3 years for patients receiving esophagectomy; P=.006) and a greater proportion was male (80.1% vs 70.4%; P=.006) and had a T1a tumor (74.5% vs 27%; P=.001). A lower proportion of patients who underwent ESD had perioperative mortality (0.3% vs 1.5% of patients receiving esophagectomy; P=.186) and non-fatal severe adverse events (15.2% vs 27.7%; P=.001)-specifically lower proportions of esophageal fistula (0.3% of patients receiving ESD vs 16.4% for patients receiving esophagectomy; P=.001) and pulmonary complications (0.3% vs 3.6%; P=.004). After a median follow-up time of 21 months (range, 6-73 months), there were no significant differences between treatments in all-cause mortality (7.4% for ESD vs 10.9%; P=.209) or rate of cancer recurrence or metastasis (9.1% for ESD vs 8.9%; P=.948). Disease-specific mortality was lower among patients who received ESD (3.4%) vs patients who patients who

Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.

PubMed

Perez, Kimberly; Safran, Howard; Sikov, William; Vrees, Matthew; Klipfel, Adam; Shah, Nishit; Schechter, Steven; Oldenburg, Nicklas; Pricolo, Victor; Rosati, Kayla; Dipetrillo, Thomas