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Sample records for adenocarcinoma eac methods

  1. Esophageal adenocarcinoma and Barrett esophagus in a neurologically impaired teenager.

    PubMed

    Hwang, Jae-Yeon; Lee, Yeoun Joo; Chun, Peter; Shin, Dong Hoon; Park, Jae Hong

    2016-11-01

    Esophageal adenocarcinoma (EAC) accompanied by Barrett esophagus (BE) is rare in patients younger than 20 years old. EAC in the upper esophagus is also rare. We report a rare case of EAC with BE that developed in the upper esophagus after chronic, untreated gastroesophageal reflux disease in a neurologically impaired teenager. A 19-year-old neurologically impaired man underwent endoscopy for evaluation of dysphagia and vomiting, and was diagnosed with EAC with BE. He underwent transthoracic esophagectomy, extensive lymph node dissection, and cervical esophagogastric anastomosis, but the prognosis was poor. Pathology indicated poorly differentiated adenocarcinoma with BE. © 2016 Japan Pediatric Society.

  2. Low risk of adenocarcinoma and high-grade dysplasia in patients with non-dysplastic Barrett’s esophagus: Results from a cohort from a country with low esophageal adenocarcinoma incidence

    PubMed Central

    Chaves, Paula

    2015-01-01

    Background The risk of esophageal adenocarcinoma (EAC) in non-dysplastic Barrett’s esophagus (NDBE) is considered to be approximately 0.3% per year or even lower, according to population-based studies. Data from countries with low EAC incidence are scarce. Our principal aim was to determine the incidence of high-grade dysplasia (HGD) and EAC in NDBE. Our secondary aims were to identify the predictors of progression and to calculate the incidence of HGD/EAC, by using the calculation method for surveillance time in population-based studies. Materials and methods A cohort of NDBE patients was prospectively followed up. Cases of HGD and EAC (study end points) diagnosed during the first year of follow-up were considered as prevalent. Only cases with an endoscopic surveillance time > 1 year were included in our analysis. Results We enrolled 331 patients (251 men) in the surveillance program. Their median age was 59 years (interquartile range (IQR): 47–67 years). Their median NDBE length was 3 cm (IQR: 2–4 cm). Of these patients, 80 died during the follow-up (one from EAC) and two were lost to follow-up. After 2284 patient-years of endoscopic follow-up (median surveillance time, 5 years (IQR: 2–10 years)), we found that five cases of HGD and two cases of EAC were diagnosed. The incidence of HGD/EAC was 3.1 cases per 1000 patient-years (95% CI: 1.3–6.0) and that of EAC was 0.9 (95% CI: 0.2–2.9). The incidence of HGD/EAC in short segments (≤ 3 cm) was 0.7 cases per 1000 patient-years (95% CI: 0.3–3.4). The sole variable that we found associated with progression was NDBE length. If the total surveillance time was considered (3537 patient-years), the incidence of HGD and EAC was only slight lower. Conclusions The incidence of HGD and EAC was very low in NDBE. Therefore, current surveillance guidelines must be reassessed, at least for short-segment BE. PMID:27403300

  3. Obesity and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: A Mendelian Randomization Study

    PubMed Central

    Shaheen, Nicholas J.; Gammon, Marilie D.; Bernstein, Leslie; Reid, Brian J.; Onstad, Lynn; Risch, Harvey A.; Liu, Geoffrey; Bird, Nigel C.; Wu, Anna H.; Corley, Douglas A.; Romero, Yvonne; Chanock, Stephen J.; Chow, Wong-Ho; Casson, Alan G.; Levine, David M.; Zhang, Rui; Ek, Weronica E.; MacGregor, Stuart; Ye, Weimin; Hardie, Laura J.; Vaughan, Thomas L.; Whiteman, David C.

    2014-01-01

    Background Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE). However, the relationships may be affected by bias and confounding. Methods We used data from the Barrett’s and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided. Results The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m2 increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses. Conclusions People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses. PMID:25269698

  4. Outcomes of submucosal (T1b) esophageal adenocarcinomas removed by endoscopic mucosal resection

    PubMed Central

    Ballard, Darren D; Choksi, Neel; Lin, Jingmei; Choi, Eun-Young; Elmunzer, B Joseph; Appelman, Henry; Rex, Douglas K; Fatima, Hala; Kessler, William; DeWitt, John M

    2016-01-01

    AIM To investigate the outcomes and recurrences of pT1b esophageal adenocarcinoma (EAC) following endoscopic mucosal resection (EMR) and associated treatments. METHODS Patients undergoing EMR with pathologically confirmed T1b EAC at two academic referral centers were retrospectively identified. Patients were divided into 4 groups based on treatment following EMR: Endoscopic therapy alone (group A), endoscopic therapy with either chemotherapy, radiation or both (group B), surgical resection (group C) or no further treatment/lost to follow-up (< 12 mo) (group D). Pathology specimens were reviewed by a central pathologist. Follow-up data was obtained from the academic centers, primary care physicians and/or referring physicians. Univariate analysis was performed to identify factors predicting recurrence of EAC. RESULTS Fifty-three patients with T1b EAC underwent EMR, of which 32 (60%) had adequate follow-up ≥ 12 mo (median 34 mo, range 12-103). There were 16 patients in group A, 9 in group B, 7 in group C and 21 in group D. Median follow-up in groups A to C was 34 mo (range 12-103). Recurrent EAC developed overall in 9 patients (28%) including 6 (38%) in group A (median: 21 mo, range: 6-73), 1 (11%) in group B (median: 30 mo, range: 30-30) and 2 (29%) in group C (median 21 mo, range: 7-35. Six of 9 recurrences were local; of the 6 recurrences, 5 were treated with endoscopy alone. No predictors of recurrence of EAC were identified. CONCLUSION Endoscopic therapy of T1b EAC may be a reasonable strategy for a subset of patients including those either refusing or medically unfit for esophagectomy. PMID:28042390

  5. Human Exploration Initiatives at EAC: Spaceship EAC and the Development of Large-Volume Lunar Regolith Simulant for LUNA

    NASA Astrophysics Data System (ADS)

    Nash, V. E.; Cowley, A.; Fateri, M.; Coene, S.; Siarov, S.; Cristoforetti, S.

    2017-09-01

    In order to address analogue capability gaps previously identified by ESA GSP studies, EAC has embarked on a number of exploration enabling initiatives at the centre in Cologne, Germany. Herein, preliminary results of two of these projects are presented; the Spaceship EAC initiative and EAC-1, a large-volume lunar regolith simulant for the LUNA facility.

  6. EAC trains its first international astronaut class.

    PubMed

    Bolender, Hans; Bessone, Loredana; Schoen, Andreas; Stevenin, Herve

    2002-11-01

    After several years of planning and preparation, ESA's ISS training programme has become operational. Between 26 August and 6 September, the European Astronaut Centre (EAC) near Cologne gave the first ESA advanced training course for an international ISS astronaut class. The ten astronauts who took part--two from NASA, four from Japan and four from ESA--had begun their advanced training programme back in 2001 with sessions at the Johnson Space Center (JSC) in Houston and at the Japanese Training Centre in Tsukuba. During their stay in Cologne, the ten astronauts participated in a total of 33 classroom lessons and hands-on training sessions, which gave them a detailed overview of the systems and subsystems of the Columbus module, the Automated Transfer Vehicle (ATV), and the related crew operations tasks. They were also introduced to the four ESA experiment facilities to be operated inside the Columbus module. After their first week of training at EAC, the astronauts were given the opportunity to see the flight model of the Columbus module being integrated at the site of ESA's ISS prime contractor, Astrium in Bremen. The second week of training at EAC included hands-on instruction on the Columbus Data Management System (DMS) using the recently installed Columbus Crew Training Facility. In preparation for the first advanced crew training session at EAC, two Training Readiness Reviews (TRR) were conducted there in June and August. These reviews were supported by training experts and astronauts from NASA, NASDA and CSA (Canada), who were introduced to ESA's advanced training concept and the development process, and then analysed and evaluated the training flow, content and instructional soundness of lessons and courses, as well as the fidelity of the training facilities and the skills of the ESA training instructors. The International Training Control Board (ITCB), made up of representatives from all of the ISS International Partners and mandated to control and

  7. Whole Genome Expression Array Profiling Highlights Differences in Mucosal Defense Genes in Barrett's Esophagus and Esophageal Adenocarcinoma

    PubMed Central

    Nancarrow, Derek J.; Clouston, Andrew D.; Smithers, B. Mark; Gotley, David C.; Drew, Paul A.; Watson, David I.; Tyagi, Sonika; Hayward, Nicholas K.; Whiteman, David C.

    2011-01-01

    Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC. PMID:21829465

  8. Volatile organic compounds in plasma for the diagnosis of esophageal adenocarcinoma: a pilot study.

    PubMed

    Bhatt, Amit; Parsi, Mansour A; Stevens, Tyler; Gabbard, Scott; Kumaravel, Arthi; Jang, Sunguk; Grove, David; Lopez, Rocio; Murthy, Sudish; Vargo, John J; Dweik, Raed

    2016-10-01

    A noninvasive screening test that can detect esophageal adenocarcinoma (EAC) at an earlier stage could improve the prognosis associated with EAC. The role of plasma volatile organic compounds (VOCs) for the diagnosis of EAC has not been previously studied. Plasma samples were collected from subjects with EAC and GERD before endoscopy. Twenty-two preselected VOCs were analyzed with selected ion flow tube mass spectrometry. The headspaces from 39 plasma samples (20 EAC, 19 GERD) were analyzed. The levels of 9 VOCs (acetonitrile, acrylonitrile, carbon disulfide, isoprene, 1-heptene, 3-methylhexane, [E]-2-nonene, hydrogen sulfide, and triethylamine) were significantly altered in EAC patients compared with GERD patients. A multivariable logistic regression analysis was performed to build a model for the prediction of EAC. The model identified patients with EAC with an area under the curve of 0.83 (95% confidence interval, 0.67-0.98). Plasma VOCs may be useful in diagnosing EAC. Larger studies are needed to confirm our pilot study observations. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  9. The role of gastroesophageal reflux and other factors during progression to esophageal adenocarcinoma

    PubMed Central

    Hazelton, William D.; Curtius, Kit; Inadomi, John M.; Vaughan, Thomas L.; Meza, Rafael; Rubenstein, Joel H.; Hur, Chin; Luebeck, E. Georg

    2015-01-01

    Background US esophageal adenocarcinoma (EAC) incidence increased over five-fold between 1975 and 2009. Symptomatic gastroesophageal reflux disease (sGERD) elevates the risk for EAC. However, a simple calculation suggests that changes in sGERD prevalence can explain at most ~16% of this trend. Importantly, a mechanistic understanding of the influence of sGERD and other factors (OF) on EAC is lacking. Methods A multiscale model was developed to estimate temporal trends for sGERD and OF, and their mechanistic role during carcinogenesis. Model calibration was to Surveillance, Epidemiology, and End Results (SEER) incidence and age-dependent sGERD data using maximum likelihood and Markov chain Monte Carlo (MCMC) methods. Results Among men, 77.8% [95% Credibility Interval (CI) = 64.9 – 85.6%] of the incidence trend is attributable to OF, 13.4% [95% CI = 11.4 – 17.3%] to sGERD, and 8.8% [95% CI = 4.2 – 13.7%] to sGERD-OF interactions. Among women, 32.6% [95% CI = 27.0 – 39.9%] of the trend is attributable to OF, 13.6% [95% CI = 12.5 – 15.9%] to sGERD, and 47.4% [95% CI = 30.7 – 64.6%] to interactions. The predicted trends were compared with historical trends for obesity, smoking, and proton pump inhibitor use. Interestingly, predicted OF cohort trends correlated most highly with median body mass index (BMI) at age 50, (r = 0.988 for men; r = 0.998 for women). Conclusions sGERD and OF mechanistically increase premalignant cell promotion, which increases EAC risk exponentially with exposure duration. Impact Surveillance should target individuals with long-duration sGERD and OF exposures. PMID:25931440

  10. Mucoepidermoid carcinoma of the external auditory canal (EAC).

    PubMed

    Bared, Anthony; Dave, Sandeep P; Garcia, Monica; Angeli, Simon I

    2007-03-01

    We present the third case of mucoepidermoid carcinoma of the external auditory canal (EAC) in the English literature, and discuss the management of this lesion. The patient underwent a wide local resection, superficial parotidectomy, and selective neck dissection. Although intraoperative frozen section margins were negative, permanent histopathologic examination demonstrated tumor in the medial margin, and the tumor was upgraded to a high-grade mucoepidermoid carcinoma. The patient returned to the operating room for a wider local resection, and EAC reconstruction with a temporoparietal pedicled flap and split thickness skin graft. All margins were negative on final histopathologic examination. Radiotherapy was deferred in the event of a recurrence. The patient is currently disease-free 29 months after the final excision. Most authors advocate an aggressive surgical approach, which includes a form of a temporal bone resection, for the treatment of EAC carcinoma. Although this may be warranted in cases of squamous cell carcinoma, mucoepidermoid carcinoma of the EAC may be amenable to a conservative step-by-step approach for local control with less postoperative morbidity. Given the difficulty in detecting mucoepidermoid carcinoma in surgical margins by frozen section analysis, patients should be informed of the possibility of further surgery (re-resection) when a conservative approach is used.

  11. Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma.

    PubMed

    Reed, Michelle A C; Singhal, Rishi; Ludwig, Christian; Carrigan, John B; Ward, Douglas G; Taniere, Phillipe; Alderson, Derek; Günther, Ulrich L

    2017-03-01

    Patients with Barrett's esophagus (BO) are at increased risk of developing esophageal adenocarcinoma (EAC). Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using 1 H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO. The study included 46 patients with EAC, 7 patients with BO, and 68 controls who underwent endoscopy for dyspeptic symptoms with normal appearances. Within the cancer cohort, 9 patients had nonneoplastic Barrett's adjacent to the cancer suitable for biopsy. It was possible to distinguish between histologically normal, BO, and EAC tissue in EAC patients [area under the receiver operator curve (AUROC) 1.00, 0.86, and 0.91] and between histologically benign BO in the presence and absence of EAC (AUROC 0.79). In both these cases, sample numbers limited the power of the models. Comparison of histologically normal tissue proximal to EAC versus that from controls (AUROC 1.00) suggests a strong field effect which may develop prior to overt EAC and hence be useful for identifying patients at high risk of developing EAC. Excellent sensitivity and specificity were found for this model to distinguish histologically normal squamous esophageal mucosa in EAC patients and healthy controls, with 8 metabolites being very significantly altered. This may have potential diagnostic value if a molecular signature can detect tissue from which neoplasms subsequently arise. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. 75 FR 18189 - Notice: Request for Substantive Comments on the EAC's Procedural Manual for the Election...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... provisions of the Administrative Procedures Act (APA). It is a voluntary effort by the EAC to gather input... the APA's rulemaking provisions applicable to development of this or future EAC procedural programs...

  13. Fucan-coated silver nanoparticles synthesized by a green method induce human renal adenocarcinoma cell death.

    PubMed

    Rocha Amorim, Monica Oliveira; Lopes Gomes, Dayanne; Dantas, Larisse Araujo; Silva Viana, Rony Lucas; Chiquetti, Samanta Cristina; Almeida-Lima, Jailma; Silva Costa, Leandro; Oliveira Rocha, Hugo Alexandre

    2016-12-01

    Polysaccharides containing sulfated L-fucose are often called fucans. The seaweed Spatoglossum schröederi synthesizes three fucans, among which fucan A is the most abundant. This polymer is not cytotoxic against various normal cell lines and is non-toxic to rats when administered at high doses. In addition, it exhibits low toxicity against tumor cells. With the aim of increasing the toxicity of fucan A, silver nanoparticles containing this polysaccharide were synthesized using a green chemistry method. The mean size of these nanoparticles was 210nm. They exhibited a spherical shape and negative surface charge and were stable for 14 months. When incubated with cells, these nanoparticles did not show any toxic effects against various normal cell lines; however, they decreased the viability of various tumor cells, especially renal adenocarcinoma cells 786-0. Flow cytometry analyses showed that the nanoparticles induced cell death responses of 786-0 cells through necrosis. Assays performed with several renal cell lines (HEK, VERO, MDCK) showed that these nanoparticles only induce death of 786-0 cells. The data obtained herein leads to the conclusion that fucan A nanoparticles are promising agents against renal adenocarcinoma. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Helicobacter pylori infection and esophageal adenocarcinoma: a review and a personal view

    PubMed Central

    Polyzos, Stergios A.; Zeglinas, Christos; Artemaki, Fotini; Doulberis, Michael; Kazakos, Evangelos; Katsinelos, Panagiotis; Kountouras, Jannis

    2018-01-01

    Esophageal adenocarcinoma (EAC) is etiologically associated with gastroesophageal reflux disease (GERD). There is evidence to support the sequence GERD, Barrett’s esophagus (BE), dysplasia, and finally EAC, with Helicobacter pylori (H. pylori) being implicated in each step to EAC. On the other side of this relation stands the hypothesis of the protective role of H. pylori against EAC. Based on this controversy, our aim was to review the literature, specifically original clinical studies and meta-analyses linking H. pylori infection with EAC, but also to provide our personal and others’ relative views on this topic. From a total of 827 articles retrieved, 10 original clinical studies and 6 meta-analyses met the inclusion criteria. Original studies provided inconclusive data on an inverse or a neutral association between H. pylori infection and EAC, whereas meta-analyses of observational studies favor an inverse association. Despite these data, we consider that the positive association between H. pylori infection and GERD or BE, but not EAC, is seemingly a paradox. Likewise, the oncogenic effect of H. pylori infection on gastric and colon cancer, but not on EAC, also seems to be a paradox. In this regard, well-designed prospective cohort studies with a powered sample size are required, in which potential confounders should be taken into consideration since their design. PMID:29333062

  15. 75 FR 4053 - Sunshine Act; Notice of Virtual Public Forum for EAC Standards Board; Notice of Virtual Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ... used by the EAC and NIST in their work with the Voluntary Voting System Guidelines. The EAC Standards... ELECTION ASSISTANCE COMMISSION Sunshine Act; Notice of Virtual Public Forum for EAC Standards Board; Notice of Virtual Public Forum for EAC Standards Board DATE & TIME: Monday, February 8, 2010, 9 a...

  16. Comparative Multi-Epitope-Ligand-Cartography reveals essential immunological alterations in Barrett's metaplasia and esophageal adenocarcinoma

    PubMed Central

    2010-01-01

    Background Barrett's esophagus (BE) is caused by gastroesophageal reflux with consecutive mucosal inflammation, predisposing patients to the development of esophageal adenocarcinoma (EAC). We investigated changes in T cell-related mucosal combinatorial molecular protein patterns in both diseases using the novel Multi-Epitope-Ligand-Cartography, a unique robotic whole-cell imaging technology that simultaneously visualizes dozens of proteins in structurally intact tissues and correlates cellular localization of proteins with function. Results Biopsies were taken during endoscopy from BE, EAC, and normal control tissue, and proteomic microscopy was performed on 32 different epitopes. When the significance level was set to p < 0.0005 and the search depth to five antibody combinations, controls and BE can be differentiated by 63, controls and EAC by 3222, and BE from EAC by 1521 distinct protein combinations. For example, the number of activated apoptotic naïve and memory T cells was significantly increased only in BE, whereas the number of activated apoptotic helper and regulatory T cells was significantly elevated in BE and EAC. In contrast, the number of activated apoptotic cytotoxic T cells was significantly elevated only in EAC. Confirming different pathways in BE and EAC, the number of T lymphocytes with p53 expression and downregulation of bcl2 expression (CD3+p53+Bcl2-NfkB-) was significantly increased in EAC compared to BE and controls. Interestingly, the number of precursor T cells (CD7+) was significantly elevated only in EAC. These cells lack Bax and caspase-8, suggesting impaired apoptosis in the early stages of T cell differentiation. Conclusion Proteomic analysis showed for the first time that proteins, which are critically involved in the mucosal immune system of the esophagus, are distinctly expressed in BE and EAC, whereas others are comparably altered in both diseases, suggesting that many pathogenic events might be shared by both diseases

  17. Comparative Multi-Epitope-Ligand-Cartography reveals essential immunological alterations in Barrett's metaplasia and esophageal adenocarcinoma.

    PubMed

    Berndt, Uta; Philipsen, Lars; Bartsch, Sebastian; Hu, Yuqin; Röcken, Christoph; Bertram, Wiedenmann; Hämmerle, Marcus; Rösch, Thomas; Sturm, Andreas

    2010-07-06

    Barrett's esophagus (BE) is caused by gastroesophageal reflux with consecutive mucosal inflammation, predisposing patients to the development of esophageal adenocarcinoma (EAC). We investigated changes in T cell-related mucosal combinatorial molecular protein patterns in both diseases using the novel Multi-Epitope-Ligand-Cartography, a unique robotic whole-cell imaging technology that simultaneously visualizes dozens of proteins in structurally intact tissues and correlates cellular localization of proteins with function. Biopsies were taken during endoscopy from BE, EAC, and normal control tissue, and proteomic microscopy was performed on 32 different epitopes. When the significance level was set to p < 0.0005 and the search depth to five antibody combinations, controls and BE can be differentiated by 63, controls and EAC by 3222, and BE from EAC by 1521 distinct protein combinations.For example, the number of activated apoptotic naïve and memory T cells was significantly increased only in BE, whereas the number of activated apoptotic helper and regulatory T cells was significantly elevated in BE and EAC. In contrast, the number of activated apoptotic cytotoxic T cells was significantly elevated only in EAC. Confirming different pathways in BE and EAC, the number of T lymphocytes with p53 expression and downregulation of bcl2 expression (CD3+p53+Bcl2-NfkB-) was significantly increased in EAC compared to BE and controls. Interestingly, the number of precursor T cells (CD7+) was significantly elevated only in EAC. These cells lack Bax and caspase-8, suggesting impaired apoptosis in the early stages of T cell differentiation. Proteomic analysis showed for the first time that proteins, which are critically involved in the mucosal immune system of the esophagus, are distinctly expressed in BE and EAC, whereas others are comparably altered in both diseases, suggesting that many pathogenic events might be shared by both diseases. Topological proteomic analysis

  18. Identification of suitable genes contributes to lung adenocarcinoma clustering by multiple meta-analysis methods.

    PubMed

    Yang, Ze-Hui; Zheng, Rui; Gao, Yuan; Zhang, Qiang

    2016-09-01

    With the widespread application of high-throughput technology, numerous meta-analysis methods have been proposed for differential expression profiling across multiple studies. We identified the suitable differentially expressed (DE) genes that contributed to lung adenocarcinoma (ADC) clustering based on seven popular multiple meta-analysis methods. Seven microarray expression profiles of ADC and normal controls were extracted from the ArrayExpress database. The Bioconductor was used to perform the data preliminary preprocessing. Then, DE genes across multiple studies were identified. Hierarchical clustering was applied to compare the classification performance for microarray data samples. The classification efficiency was compared based on accuracy, sensitivity and specificity. Across seven datasets, 573 ADC cases and 222 normal controls were collected. After filtering out unexpressed and noninformative genes, 3688 genes were remained for further analysis. The classification efficiency analysis showed that DE genes identified by sum of ranks method separated ADC from normal controls with the best accuracy, sensitivity and specificity of 0.953, 0.969 and 0.932, respectively. The gene set with the highest classification accuracy mainly participated in the regulation of response to external stimulus (P = 7.97E-04), cyclic nucleotide-mediated signaling (P = 0.01), regulation of cell morphogenesis (P = 0.01) and regulation of cell proliferation (P = 0.01). Evaluation of DE genes identified by different meta-analysis methods in classification efficiency provided a new perspective to the choice of the suitable method in a given application. Varying meta-analysis methods always present varying abilities, so synthetic consideration should be taken when providing meta-analysis methods for particular research. © 2015 John Wiley & Sons Ltd.

  19. [Change in cryolability of tumor stem cells depending on growth phase of Ehrlich adenocarcinoma in vivo].

    PubMed

    Hol'tsev, A M; Safranchuk, O V; Bondarovych, M O; Ostankov, M V

    2011-01-01

    Cancer stem cells (CSC) are the main structural unit in initia tion, support of in situ growth, as well as tumor metastasis during malignant development of various origin. Observed chemo- and radio-resistance of CSC make them a potential target cell to perform cryoeradication. We have performed a comparative study of changes in functional activity after cryopreservation of CSC of two differentiation levels from Erlich adenocarcinoma (EAC) of various culture terms (EAC-7, EAC-14). It was found that in the case of EAC-7 the expression of cryosuppression in terms of cell functional state at the initial stages of development was bigger in high potency CD44hi cells comparing to more differentiated cells, forming general pool of cells in peritoneal cavity. And vice versa, in the "eldering" EAC-14 this effect was bigger in more differentiated cells comparing to less differentiated ones, even causing in latter (CD44hi) the growth stimulation. Moreover, the minimal proliferative activity of general population cells cEAC- 14 during the first weeks was alternated at the next stage to its maximal expression among all the studied types of EAC cells of both culture terms. These data confirm again the fact, that during assessment of bioobject cryolability (cryostability) it is significant to determine not only cryopreservation conditions, but the initial state of the bioobject as well.

  20. Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma

    PubMed Central

    Stachler, Matthew D.; Taylor-Weiner, Amaro; Peng, Shouyong; McKenna, Aaron; Agoston, Agoston T.; Odze, Robert D.; Davison, Jon M.; Nason, Katie S.; Loda, Massimo; Leshchiner, Ignaty; Stewart, Chip; Stojanov, Petar; Seepo, Sara; Lawrence, Michael S.; Ferrer-Torres, Daysha; Lin, Jules; Chang, Andrew C.; Gabriel, Stacey B.; Lander, Eric S.; Beer, David G.; Getz, Gad; Carter, Scott L.; Bass, Adam J.

    2015-01-01

    Barrett’s esophagus, is thought to progress to esophageal adenocarcinoma (EAC) through a step-wise progression with loss of CDKN2A followed by p53 inactivation and aneuploidy. Here, we present whole exome sequencing from 25 pairs of EAC and Barrett’s and five patients whose Barrett’s and tumor were extensively sampled. Our analysis revealed that oncogene amplification typically occurred as a late event and that TP53 mutations often occur early in Barrett’s progression, including in non-dysplastic epithelium. Reanalysis of additional EAC exome data revealed that the majority (62.5%) of EACs emerged following genome doubling and that tumors with genomic doubling had different patterns of genomic alterations with more frequent oncogenic amplifications and less frequent inactivation of tumor suppressors, including CDKN2A. These data suggest that many EACs emerge not through gradual accumulation of tumor suppressor alterations but rather through a more direct path whereby a TP53-mutant cell undergoes genome doubling, followed by acquisition of oncogenic amplifications. PMID:26192918

  1. Central Adiposity Is Associated With Increased Risk of Esophageal Inflammation, Metaplasia, and Adenocarcinoma: A Systematic Review and Meta-analysis

    PubMed Central

    Singh, Siddharth; Sharma, Anamay N.; Murad, Mohammad Hassan; Buttar, Navtej S.; El-Serag, Hashem B.; Katzka, David A.; Iyer, Prasad G.

    2013-01-01

    BACKGROUND & AIMS Central adiposity has been implicated as a risk factor for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), possibly promoting the progression from inflammation to metaplasia and neoplasia. We performed a systematic review and meta-analysis of studies to evaluate the association between central adiposity and erosive esophagitis (EE), BE, and EAC, specifically exploring body mass index (BMI)–independent and gastroesophageal reflux (GERD)–independent effects of central adiposity on the risk of these outcomes. METHODS We performed a systematic search of multiple databases through March 2013. Studies were included if they reported effect of central adiposity (visceral adipose tissue area, waist-hip ratio, and/or waist circumference) on the risk of EE, BE, and EAC. Summary adjusted odds ratio (aOR) estimates with 95% confidence intervals (CIs), comparing highest category of adiposity with the lowest category of adiposity, were calculated by using randomeffects model. RESULTS Forty relevant articles were identified. Compared with patients with normal body habitus, patients with central adiposity had a higher risk of EE (19 studies; aOR, 1.87; 95% CI, 1.51–2.31) and BE (17 studies; aOR, 1.98; 95% CI, 1.52–2.57). The association between central adiposity and BE persisted after adjusting for BMI (5 studies; aOR, 1.88; 95% CI, 1.20–2.95). Refluxindependent association of central adiposity and BE was observed in studies that used GERD patients as controls or adjusted for GERD symptoms (11 studies; aOR, 2.04; 95% CI, 1.44–2.90). In 6 studies, central adiposity was associated with higher risk of EAC (aOR, 2.51; 95% CI, 1.54–4.06), compared with normal body habitus. CONCLUSIONS On the basis of a meta-analysis, central adiposity, independent of BMI, is associated with esophageal inflammation (EE), metaplasia (BE), and neoplasia (EAC). Its effects are mediated by reflux-dependent and reflux-independent mechanisms. PMID:23707461

  2. MicroRNA-17 is downregulated in esophageal adenocarcinoma cancer stem-like cells and promotes a radioresistant phenotype

    PubMed Central

    Lynam-Lennon, Niamh; Heavey, Susan; Sommerville, Gary; Bibby, Becky A.S.; Ffrench, Brendan; Quinn, Jennifer; Gasch, Claudia; O’Leary, John J; Gallagher, Michael F; Reynolds, John V; Maher, Stephen G

    2017-01-01

    Resistance to neoadjuvant chemoradiation therapy (CRT) remains a critical barrier to the effective treatment of esophageal adenocarcinoma (EAC). Cancer stem-like cells (CSCs) are a distinct subpopulation of cells implicated in the resistance of tumors to anti-cancer therapy. However, their role in the resistance of EAC to CRT is largely unknown. In this study, using a novel in vitro isogenic model of radioresistant EAC, we demonstrate that radioresistant EAC cells have enhanced tumorigenicity in vivo, increased expression of CSC-associated markers and enhanced holoclone forming ability. Further investigation identified a subpopulation of cells that are characterised by high aldehyde dehydrogenase (ALDH) activity, enhanced radioresistance and decreased expression of miR-17-5p. In vitro, miR-17-5p was demonstrated to significantly sensitise radioresistant cells to X-ray radiation and promoted the repression of genes with miR-17-5p binding sites, such as C6orf120. In vivo, miR-17-5p was significantly decreased, whilst C6orf120 was significantly increased, in pre-treatment EAC tumour samples from patients who demonstrated a poor response to neoadjuvant CRT. This study sheds novel insights into the role of CSCs in the resistance of EAC to CRT and highlights miR-17-5p as a potential biomarker of CRT sensitivity and novel therapeutic target in treatment resistant EAC. PMID:28002789

  3. General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Steffen, Annika; Huerta, José-Maria; Weiderpass, Elisabete; Bueno-de-Mesquita, H B As; May, Anne M; Siersema, Peter D; Kaaks, Rudolf; Neamat-Allah, Jasmine; Pala, Valeria; Panico, Salvatore; Saieva, Calogero; Tumino, Rosario; Naccarati, Alessio; Dorronsoro, Miren; Sánchez-Cantalejo, Emilio; Ardanaz, Eva; Quirós, J Ramón; Ohlsson, Bodil; Johansson, Mattias; Wallner, Bengt; Overvad, Kim; Halkjaer, Jytte; Tjønneland, Anne; Fagherazzi, Guy; Racine, Antoine; Clavel-Chapelon, Françoise; Key, Tim J; Khaw, Kay-Tee; Wareham, Nick; Lagiou, Pagona; Bamia, Christina; Trichopoulou, Antonia; Ferrari, Pietro; Freisling, Heinz; Lu, Yunxia; Riboli, Elio; Cross, Amanda J; Gonzalez, Carlos A; Boeing, Heiner

    2015-08-01

    General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation. © 2015 UICC.

  4. Delineation of disease phenotypes associated with esophageal adenocarcinoma by MALDI-IMS-MS analysis of serum N-linked glycans.

    PubMed

    Gaye, M M; Ding, T; Shion, H; Hussein, A; Hu, Y; Zhou, S; Hammoud, Z T; Lavine, B K; Mechref, Y; Gebler, J C; Clemmer, D E

    2017-05-02

    N-Linked glycans, extracted from patient sera and healthy control individuals, are analyzed by Matrix-assisted laser desorption ionization (MALDI) in combination with ion mobility spectrometry (IMS), mass spectrometry (MS) and pattern recognition methods. MALDI-IMS-MS data were collected in duplicate for 58 serum samples obtained from individuals diagnosed with Barrett's esophagus (BE, 14 patients), high-grade dysplasia (HGD, 7 patients), esophageal adenocarcinoma (EAC, 20 patients) and disease-free control (NC, 17 individuals). A combined mobility distribution of 9 N-linked glycans is established for 90 MALDI-IMS-MS spectra (training set) and analyzed using a genetic algorithm for feature selection and classification. Two models for phenotype delineation are subsequently developed and as a result, the four phenotypes (BE, HGD, EAC and NC) are unequivocally differentiated. Next, the two models are tested against 26 blind measurements. Interestingly, these models allowed for the correct phenotype prediction of as many as 20 blinds. Although applied to a limited number of blind samples, this methodology appears promising as a means of discovering molecules from serum that may have capabilities as markers of disease.

  5. Autocrine Extra-Pancreatic Trypsin 3 Secretion Promotes Cell Proliferation and Survival in Esophageal Adenocarcinoma

    PubMed Central

    Han, Song; Lee, Constance W.; Trevino, Jose G.; Hughes, Steven J.; Sarosi, George A.

    2013-01-01

    Trypsin or Tumor associated trypsin (TAT) activation of Protease-activated receptor 2 (PAR-2) promotes tumor cell proliferation in gastrointestinal cancers. The role of the trypsin/PAR-2 network in esophageal adenocarcinoma (EA) development has not yet been investigated. The aim of this study is to investigate the role of trypsin/PAR-2 activation in EA tumorogenesis and therapy. We found that esophageal adenocarcinoma cells (EACs) and Barrett’s Metaplasia (BART) expressed high levels of type 3 extra-pancreatic trypsinogen (PRSS3), a novel type of TAT. Activity of secreted trypsin was detected in cultured media from EA OE19 and OE33 cultures but not from BART culture. Surface PAR-2 expression in BART and EACs was confirmed by both flow cytometry and immunofluorescence. Trypsin induced cell proliferation (∼ 2 fold; P<0.01) in all tested cell lines at a concentration of 10 nM. Inhibition of PAR-2 activity in EACs via the PAR-2 antagonist ENMD (500 µM), anti-PAR2 antibody SAM-11 (2 µg/ml), or siRNA PAR-2 knockdown, reduced cell proliferation and increased apoptosis by up to 4 fold (P<0.01). Trypsin stimulation led to phosphorylation of ERK1/2, suggesting involvement of MAPK pathway in PAR-2 signal transduction. Inhibition of PAR-2 activation or siRNA PAR-2 knockdown in EACs prior to treatment with 5 FU reduced cell viability of EACs by an additional 30% (P<0.01) compared to chemotherapy alone. Our data suggest that extra-pancreatic trypsinogen 3 is produced by EACs and activates PAR-2 in an autocrine manner. PAR-2 activation increases cancer cell proliferation, and promotes cancer cell survival. Targeting the trypsin activated PAR-2 pathway in conjunction with current chemotherapeutic agents may be a viable therapeutic strategy in EA. PMID:24146905

  6. Impact of EGFR Mutation Detection Methods on the Efficacy of Erlotinib in Patients with Advanced EGFR-Wild Type Lung Adenocarcinoma

    PubMed Central

    Huang, Ming-Shyan; Chen, Chung-Yu; Chang, Cheng-Yu; Yang, Tsung-Ying; Tsai, Chi-Ren; Chen, Kun-Chieh; Hsu, Kuo-Hsuan; Tsai, Meen-Hsin; Yu, Sung-Liang; Su, Kang-Yi; Wu, Chih-Wei; Yang, Cheng-Ta; Chen, Yuh-Min; Chang, Gee-Chen

    2014-01-01

    Introduction Methods used for epidermal growth factor receptor (EGFR) mutation testing vary widely. The impact of detection methods on the rates of response to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-wild type (wt) lung adenocarcinoma patients is unknown. Methods We recruited the Group-I patients to evaluate the efficacy of erlotinib in patients with EGFR-wt lung adenocarcinoma by either direct sequencing (DS) or mutant type-specific sensitive (MtS) methods in six medical centers in Taiwan. Cross recheck of EGFR mutations was performed in patients who achieved objective response to erlotinib and had adequate specimens. The independent Group-II lung adenocarcinoma patients whose EGFR mutation status determined by DS were recruited to evaluate the potential limitations of three MtS methods. Results In Group-I analysis, 38 of 261 EGFR-wt patients (14.6%) achieved partial response to erlotinib treatment. Nineteen patients (50.0%) had adequate specimens for cross recheck of EGFR mutations and 10 of them (52.6%) had changes in EGFR mutation status, 5 in 10 by DS and 5 in 9 by MtS methods originally. In Group-II analysis, 598 of 996 lung adenocarcinoma patients (60.0%) had detectable EGFR mutations. The accuracy rates of the three MtS methods, MALDI-TOF MS, Scorpions ARMS and Cobas, were 87.8%, 86.8% and 85.8%, respectively. Conclusions A significant portion of the erlotinib responses in EGFR-wt lung adenocarcinoma patients were related to the limitations of detection methods, not only DS but also MtS methods with similar percentages. Prospective studies are needed to define the proper strategy for EGFR mutation testing. PMID:25215536

  7. Development, calibration, and validation of a U.S. white male population-based simulation model of esophageal adenocarcinoma.

    PubMed

    Hur, Chin; Hayeck, Tristan J; Yeh, Jennifer M; Richards, Ethan M; Richards, Ethan B; Spechler, Stuart J; Gazelle, G Scott; Kong, Chung Yin

    2010-03-01

    The incidence of esophageal adenocarcinoma (EAC) has risen rapidly in the U.S. and western world. The aim of the study was to begin the investigation of this rapid rise by developing, calibrating, and validating a mathematical disease simulation model of EAC using available epidemiologic data. The model represents the natural history of EAC, including the essential biologic health states from normal mucosa to detected cancer. Progression rates between health states were estimated via calibration, which identified distinct parameter sets producing model outputs that fit epidemiologic data; specifically, the prevalence of pre-cancerous lesions and EAC cancer incidence from the published literature and Surveillance, Epidemiology, and End Results (SEER) data. As an illustrative example of a clinical and policy application, the calibrated and validated model retrospectively analyzed the potential benefit of an aspirin chemoprevention program. Model outcomes approximated calibration targets; results of the model's fit and validation are presented. Approximately 7,000 cases of EAC could have been prevented over a 30-year period if all white males started aspirin chemoprevention at age 40 in 1965. The model serves as the foundation for future analyses to determine a cost-effective screening and management strategy to prevent EAC morbidity and mortality.

  8. Effects of galectin-9 on apoptosis, cell cycle and autophagy in human esophageal adenocarcinoma cells.

    PubMed

    Akashi, Emiko; Fujihara, Shintaro; Morishita, Asahiro; Tadokoro, Tomoko; Chiyo, Taiga; Fujikawa, Keiko; Kobara, Hideki; Mori, Hirohito; Iwama, Hisakazu; Okano, Keiichi; Suzuki, Yasuyuki; Niki, Toshiro; Hirashima, Mitsuomi; Masaki, Tsutomu

    2017-07-01

    The incidence of esophageal adenocarcinoma (EAC) is rapidly increasing in western countries. The overall mortality of this disease remains high with a 5-year survival rate of less than 20%, despite remarkable advances in the care of patients with EAC. Galectin-9 (Gal-9) is a tandem-repeat type galectin that exerts anti-proliferative effects on various cancer cell types. The aim of the present study was to evaluate the effects of Gal-9 on human EAC cells and to assess the expression of microRNAs (miRNAs) associated with the antitumor effects of Gal-9 in vitro. Gal-9 suppressed the proliferation of the EAC cell lines OE19, OE33, SK-GT4, and OACM 5.1C. Additionally, Gal-9 treatment induced apoptosis and increased the expression levels of caspase-cleaved cytokeratin 18, activated caspase-3 and activated caspase-9. However, it did not promote cell cycle arrest by reducing cell cycle-related protein levels. Furthermore, Gal-9 increased the level of the angiogenesis-related protein interleukin-8 (IL-8) and markedly altered miRNA expression. Based on these findings, Gal-9 may be of clinical use for the treatment of EAC.

  9. EAC: A program for the error analysis of STAGS results for plates

    NASA Technical Reports Server (NTRS)

    Sistla, Rajaram; Thurston, Gaylen A.; Bains, Nancy Jane C.

    1989-01-01

    A computer code is now available for estimating the error in results from the STAGS finite element code for a shell unit consisting of a rectangular orthotropic plate. This memorandum contains basic information about the computer code EAC (Error Analysis and Correction) and describes the connection between the input data for the STAGS shell units and the input data necessary to run the error analysis code. The STAGS code returns a set of nodal displacements and a discrete set of stress resultants; the EAC code returns a continuous solution for displacements and stress resultants. The continuous solution is defined by a set of generalized coordinates computed in EAC. The theory and the assumptions that determine the continuous solution are also outlined in this memorandum. An example of application of the code is presented and instructions on its usage on the Cyber and the VAX machines have been provided.

  10. Germline Mutations in MSR1, ASCC1, and CTHRC1 in Patients With Barrett Esophagus and Esophageal Adenocarcinoma

    PubMed Central

    Orloff, Mohammed; Peterson, Charissa; He, Xin; Heald, Shireen Ganapathi Brandie; Yang, Yi-ran; Bebek, Gurkan; Romigh, Todd; Song, Mess Jee Hoon; Wu, Mess Wenjing; David, Stefan; Cheng, Yulan; Meltzer, Stephen J.; Eng, Charis

    2013-01-01

    Context Barrett esophagus (BE) occurs in 1% to 10% of the general population and is believed to be the precursor of esophageal adenocarcinoma (EAC). The incidence of EAC has increased 350% in the last 3 decades without clear etiology. Finding predisposition genes may improve premorbid risk assessment, genetic counseling, and management. Genome-wide multiplatform approaches may lead to the identification of genes important in BE/EAC development. Objective To identify risk alleles or mutated genes associated with BE/EAC. Design, Setting, and Patients Model-free linkage analyses of 21 concordant-affected sibling pairs with BE/EAC and 11 discordant sibling pairs (2005–2006). Significant germline genomic regions in independent prospectively accrued series of 176 white patients with BE/EAC and 200 ancestry-matched controls (2007–2010) were validated and fine mapped. Integrating data from these significant genomic regions with somatic gene expression data from 19 BE/EAC tissues yielded 12 “priority” candidate genes for mutation analysis (2010). Genes that showed mutations in cases but not in controls were further screened in an independent prospectively accrued validation series of 58 cases (2010). Main Outcome Measures Identification of germline mutations in genes associated with BE/EAC cases. Functional interrogation of the most commonly mutated gene. Results Three major genes, MSR1, ASCC1, and CTHRC1 were associated with BE/EAC (all P<.001). In addition, 13 patients (11.2%) with BE/EAC carried germline mutations in MSR1, ASCC1, or CTHRC1. MSR1 was the most frequently mutated, with 8 of 116 (proportion, 0.069; 95% confidence interval [CI], 0.030–0.130; P<.001) cases with c.877C>T (p.R293X). An independent validation series confirmed germline MSR1 mutations in 2 of 58 cases (proportion, 0.035; 95% CI, 0.004–0.120; P=.09). MSR1 mutation resulted in CCND1 up-regulation in peripheral-protein lysate. Immunohistochemistry of BE tissues in MSR1-mutation carriers

  11. 77 FR 59914 - Amended Notice: Request for Substantive Comments on the EAC's Proposed Requirements for Version 1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... and Certification Program. As the EAC has worked to test and certify voting systems it observed and... test laboratory and across test campaigns at different laboratories. The EAC also received feedback from the National Institute of Standards and Technology (NIST) that the creation of formalized test...

  12. 75 FR 4054 - Sunshine Act; Notice of Virtual Public Forum for EAC Board of Advisors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ... COMMISSION Sunshine Act; Notice of Virtual Public Forum for EAC Board of Advisors DATE & TIME: Monday... efficient manner in a public forum, including being able to review and discuss draft documents, when it is... any resolutions during the 12-day forum of February 8-February 19, 2010. Members will post comments...

  13. 75 FR 17913 - Sunshine Act; Notice of Virtual Public Forum for EAC Standards Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... COMMISSION Sunshine Act; Notice of Virtual Public Forum for EAC Standards Board Date & Time: Monday, May 3... Standards Board to conduct business in an efficient manner in a public forum, including being able to review... Board will not take any votes or propose any resolutions during the 12-day forum of May 3-May 14, 2010...

  14. 75 FR 17912 - Sunshine Act; Notice of Virtual Public Forum for EAC Board of Advisors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... COMMISSION Sunshine Act; Notice of Virtual Public Forum for EAC Board of Advisors Date & Time: Monday, April... conduct business in an efficient manner in a public forum, including being able to review and comment on... take any votes or propose any resolutions during the 5-day forum of April 26-April 30, 2010. Members...

  15. Malignant mesothelioma: ultrastructural distinction from adenocarcinoma.

    PubMed

    Warhol, M J; Hickey, W F; Corson, J M

    1982-06-01

    Mesotheliomas and metastatic adenocarcinomas involving the pleura are frequently difficult to distinguish by light-microscopic and histochemical methods. In a double-blind study, we have compared ultrastructural features of 10 mesotheliomas of epithelial type and 10 adenocarcinomas from the lung, breast, and upper GI tract, i.e., sites known to give rise to metastases which mimic mesothelioma. Mesotheliomas were observed to have a significantly greater microvillus length/diameter ratio (LDR) than adenocarcinomas (p less than 0.01) and more abundant intermediate filaments (p less than 0.001). Mesotheliomas had more complex microvilli than adenocarcinomas, whereas adenocarcinomas had rootlets (2/10 cases) and lamellar inclusion bodies (2/10 cases), both of which were absent in the mesotheliomas. This study provides quantitative and qualitative ultrastructural features of potential utility in the differential diagnosis of pleural mesotheliomas and adenocarcinomas.

  16. Low MiR-187 Expression Promotes Resistance to Chemoradiation Therapy In Vitro and Correlates with Treatment Failure in Patients with Esophageal Adenocarcinoma

    PubMed Central

    Lynam-Lennon, Niamh; Bibby, Becky A S; Mongan, Ann Marie; Marignol, Laure; Paxton, Christian N; Geiersbach, Katherine; Bronner, Mary P; O’Sullivan, Jacintha; Reynolds, John V; Maher, Stephen G

    2016-01-01

    Esophageal adenocarcinoma (EAC) has a poor prognosis and is increasing in incidence in many Western populations. Neoadjuvant chemoradiation therapy (CRT) followed by surgery is increasingly the standard of care for locally advanced EAC; however, resistance to treatment is a significant clinical problem. The identification of both novel biomarkers predicting response to treatment and novel therapeutic targets to enhance the efficacy of CRT is key to improving survival rates in EAC. In this study, we performed global microRNA (miRNA) profiling of pretreatment EAC biopsies and identified 67 miRNAs significantly altered in patients who are resistant to CRT. One of these miRNAs, miR-187, was significantly decreased in pretreatment EAC tumors from patients having a poor response to neoadjuvant CRT, highlighting downregulation of miR-187 as a potential mediator of treatment resistance in EAC. In vitro, miR-187 was demonstrated to play a functional role in modulating sensitivity to X-ray radiation and cisplatin in EAC and its dysregulation was demonstrated to be due to chromosomal alterations. In vitro, miR-187 altered expression of a diverse array of pathways, including the immune regulator complement component 3 (C3), serum levels of which we have previously demonstrated to predict patient response to CRT. In vivo, expression of C3 was significantly increased in tumors from patients having a poor response to CRT. This study highlights for the first time a role for miR-187 as a novel biomarker of response to CRT and a potential therapeutic target for enhancing the efficacy of CRT in EAC. PMID:27254108

  17. Antitumor Activity of Prosopis glandulosa Torr. on Ehrlich Ascites Carcinoma (EAC) Tumor Bearing Mice

    PubMed Central

    Senthil Kumar, Raju; Rajkapoor, Balasubramanian; Perumal, Perumal; Dhanasekaran, Thangavel; Alvin Jose, Manonmani; Jothimanivannan, Chennakesavalu

    2011-01-01

    The antitumor activity of ethanol extract of Prosopis glandulosa Torr. (EPG) was evaluated against Ehrlich ascites carcinoma (EAC) tumor model in Swiss albino mice on dose dependent manner. The activity was assessed using survival time, average increase in body weight, hematological parameters and solid tumor volume. Oral administration of EPG at the dose of 100, 200 and 400 mg/Kg, significantly (p < 0.001) increased the survival time and decreased the average body weight of the tumor bearing mice. After 14 days of inoculation, EPG was able to reverse the changes in the hematological parameters, protein and PCV consequent to tumor inoculation. Oral administration of EPG was effective in reducing solid tumor mass development induced by EAC cells. The results indicate that EPG possess significant antitumor activity on dose dependent manner. PMID:24250382

  18. Antitumor Activity of Prosopis glandulosa Torr. on Ehrlich Ascites Carcinoma (EAC) Tumor Bearing Mice.

    PubMed

    Senthil Kumar, Raju; Rajkapoor, Balasubramanian; Perumal, Perumal; Dhanasekaran, Thangavel; Alvin Jose, Manonmani; Jothimanivannan, Chennakesavalu

    2011-01-01

    The antitumor activity of ethanol extract of Prosopis glandulosa Torr. (EPG) was evaluated against Ehrlich ascites carcinoma (EAC) tumor model in Swiss albino mice on dose dependent manner. The activity was assessed using survival time, average increase in body weight, hematological parameters and solid tumor volume. Oral administration of EPG at the dose of 100, 200 and 400 mg/Kg, significantly (p < 0.001) increased the survival time and decreased the average body weight of the tumor bearing mice. After 14 days of inoculation, EPG was able to reverse the changes in the hematological parameters, protein and PCV consequent to tumor inoculation. Oral administration of EPG was effective in reducing solid tumor mass development induced by EAC cells. The results indicate that EPG possess significant antitumor activity on dose dependent manner.

  19. [Detection of serum proteins in the patients of lung adenocarcinoma by the method of magnetic bead based sample fractionation and MALDI-TOF-MS].

    PubMed

    Liu, Dan; Liu, Lun-Xu; Yuan, Quan; Li, Xiao-Liang; Huang, Na; Yang, Xiao-Dong

    2010-05-01

    To screen the serum proteins related to human lung adenocarcinoma using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) technology. The blood samples were collected from 10 patients of lung adenocarcinoma before and one week after the surgery, while 10 healthy subjects were used as control. The differential protein expression between the two groups and the change of those proteins after surgery were studied by ClinProt magnetic bead enrichment and MALDI-TOF-MS. Six protein peaks were identified, 2 of them were highly expressed protein biomarkers with relative molecular weights of 2661, 2991, and increased after the surgery, 4 of them were lowly expressed protein biomarkers with relative molecular weights of 4091, 4210, 4644, 5336, which continuously decreased after the surgery. ClinProt magnetic bead enrichment and MALDI-TOF-MS is a quick, easy and sensitive method of proteomics. The differential expressed proteins may be the latent tumor marker of lung adenocarcinoma. The alteration of those proteins after surgery might be helpful to assess the therapeutic effect and prognosis.

  20. Extratumoral PD-1 blockade does not perpetuate obesity-associated inflammation in esophageal adenocarcinoma.

    PubMed

    Galvin, Karen C; Conroy, Melissa J; Doyle, Suzanne L; Dunne, Margaret R; Fahey, Ronan; Foley, Emma; O'Sullivan, Katie E; Doherty, Derek G; Geoghegan, Justin G; Ravi, Narayanasamy; O'Farrelly, Cliona; Reynolds, John V; Lysaght, Joanne

    2018-04-01

    Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continues to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells with anti-PD-1 (clone EH12.2H7) did not enhance inflammatory cytokine expression or proliferation, but transiently increased CD107a expression by CD8 + T cells. Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post neoadjuvant chemoradiotherapy, suggesting that combination with specific conventional treatments may severely impair the efficacy of anti-PD-1 immunotherapy. This study provides evidence that systemically administered anti-PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated inflammation outside the tumor in obesity-associated cancers, such as EAC. Furthermore, our data suggests that studies are required to identify the negative impact of concomitant therapies on PD-1 expression in order to boost overall response rates. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.

    PubMed

    Secrier, Maria; Li, Xiaodun; de Silva, Nadeera; Eldridge, Matthew D; Contino, Gianmarco; Bornschein, Jan; MacRae, Shona; Grehan, Nicola; O'Donovan, Maria; Miremadi, Ahmad; Yang, Tsun-Po; Bower, Lawrence; Chettouh, Hamza; Crawte, Jason; Galeano-Dalmau, Núria; Grabowska, Anna; Saunders, John; Underwood, Tim; Waddell, Nicola; Barbour, Andrew P; Nutzinger, Barbara; Achilleos, Achilleas; Edwards, Paul A W; Lynch, Andy G; Tavaré, Simon; Fitzgerald, Rebecca C

    2016-10-01

    Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

  2. Gastroesophageal reflux does not alter effects of body mass index on risk of esophageal adenocarcinoma.

    PubMed

    Lagergren, Jesper; Mattsson, Fredrik; Nyrén, Olof

    2014-01-01

    A history of high body mass index (BMI) is associated strongly with a risk of esophageal adenocarcinoma (EAC). We investigated whether gastroesophageal reflux is involved in this association. We analyzed data from a population-based Swedish nationwide study of patients with a new diagnosis of EAC (n = 189) or gastroesophageal junction adenocarcinoma (n = 262), and matched controls (n = 816), from 1995 through 1997. Our analysis included data on BMI 20 years before study inclusion; maximum adult BMI; frequency, severity, and duration of gastroesophageal reflux symptoms; tumor features; and covariates (sex, age, smoking, alcohol, fruit and vegetable intake, and socioeconomic status). We conducted stratified analyses and synergy tests, adjusting for covariates. Odds ratios (ORs) for EAC among subjects with a BMI of 25 or higher 20 years before inclusion, compared with those with a BMI less than 25, did not differ significantly, without or with adjustment for gastroesophageal reflux frequency (OR, 3.1; 95% confidence interval [CI], 2.2-4.4; and OR, 3.3; 95% CI, 2.2-4.8, respectively), severity (OR, 3.3; 95% CI, 2.2-4.8), or duration (OR, 3.2; 95% CI, 2.2-4.7). However, there were interactions between BMI and categories of gastroesophageal reflux. BMI appeared to have the largest effect on gastroesophageal reflux frequency (synergy index, 8.9; 95% CI, 2.3-34.1 for maximum BMI; and gastroesophageal reflux >3 times/wk). Based on a population-based study, the association between BMI and EAC does not appear to be affected by symptomatic gastroesophageal reflux, although there appears to be synergy between BMI and reflux. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma*

    PubMed Central

    Shah, Alok K.; Cao, Kim-Anh Lê; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C.; Saunders, Nicholas A.; Barbour, Andrew P.; Joshi, Virendra; Hill, Michelle M.

    2015-01-01

    We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di.uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates

  4. Adenocarcinoma of the Esophagogastric Junction

    PubMed Central

    Rüdiger Siewert, J.; Feith, Marcus; Werner, M.; Stein, Hubert J.

    2000-01-01

    Objective To assess the outcome of surgical therapy based on a topographic/anatomical classification of adenocarcinoma of the esophagogastric junction. Summary Background Data Because of its borderline location between the stomach and esophagus, the choice of surgical strategy for patients with adenocarcinoma of the esophagogastric junction is controversial. Methods In a large single-center series of 1,002 consecutive patients with adenocarcinoma of the esophagogastric junction, the choice of surgical approach was based on the location of the tumor center or tumor mass. Treatment of choice was esophagectomy for type I tumors (adenocarcinoma of the distal esophagus) and extended gastrectomy for type II tumors (true carcinoma of the cardia) and type III tumors (subcardial gastric cancer infiltrating the distal esophagus). Demographic data, morphologic and histopathologic tumor characteristics, and long-term survival rates were compared among the three tumor types, focusing on the pattern of lymphatic spread, the outcome of surgery, and prognostic factors in patients with type II tumors. Results There were marked differences in sex distribution, associated intestinal metaplasia in the esophagus, tumor grading, tumor growth pattern, and stage distribution between the three tumor types. The postoperative death rate was higher after esophagectomy than extended total gastrectomy. On multivariate analysis, a complete tumor resection (R0 resection) and the lymph node status (pN0) were the dominating independent prognostic factors for the entire patient population and in the three tumor types, irrespective of the surgical approach. In patients with type II tumors, the pattern of lymphatic spread was primarily directed toward the paracardial, lesser curvature, and left gastric artery nodes; esophagectomy offered no survival benefit over extended gastrectomy in these patients. Conclusion The classification of adenocarcinomas of the esophagogastric junction into type I, II, and

  5. Nanoparticle engineering enhances anticancer efficacy of andrographolide in MCF-7 cells and mice bearing EAC.

    PubMed

    Roy, Partha; Das, Suvadra; Mondal, Anushree; Chatterji, Urmi; Mukherjee, Arup

    2012-12-01

    Success in cancer chemotherapy relies on efficient delivery of anti-neoplastic drugs, with minimal side-effects on non-cancerous cells. Nanoparticulation of prospective anti-cancer drugs, that were deemed unsuitable due to short biological half life, poor water solubility and low cellular permeability, has been hypothesized to generate superior chemotherapeutic agents, leading to reduced non-specific action and fewer side-effects. In lieu of the above, different synthetic modulations on the putative anti-cancer compound andrographolide (AG) were explored to improve its therapeutic efficiency. Our results indicated that PLGA-nanoparticulation of andrographolide diterpenoid enhanced its anti-cancer properties three fold. Chitosan coating of AG nanoparticles further accentuated cellular localization, induced G1 cell cycle arrest and increased cellular toxicity and apoptosis in MCF-7 cells. The charge modulated nanoparticles were seen to traverse more efficiently through the cytoplasm and accumulate in the nucleus, thus enhancing their anti-proliferative efficacy. In vivo studies confirm that the nanoparticles reduced tumor weight by 68.21% as compared to 24.7% by AG, and increased the life span of mice infected with Ehrlich ascites carcinoma (EAC) by 78.08% as compared to 23.5% for AG alone. This was achieved through development of slow release-type nanoparticle cargo delivery devices, and enhanced the efficiency of AGnps for targeting cancer cells. AG nanoparticles also showed sufficient promise as safe anti-cancer drugs since they had minimal impact on animal hematology. Hence, we successfully prepared non-toxic and delivery-efficient andrographolide nanoparticles, and established for the first time that PLGA-nanoparticulation of andrographolide and additional chitosan coating increased its anti-cancer efficacy in human breast cancer cells and mouse EAC model.

  6. Prevalence of extra-esophageal cancers in patients with Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    Talukdar, Anjan; Chak, Amitabh; Lee, Tommy; Fang, Xiang; Watson, Patrice; Lynch, Henry; Mittal, Sumeet

    2012-01-01

    To compare the prevalence of extra-esophageal cancers in patients diagnosed with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with SEER database. Patients with BE and EAC are part of a NIH supported Familial Barrett's investigation involving personal and family history and pathology correlation recorded in the database. Data pertaining to extra-esophageal cancers in the proband was extracted into an excel datasheet for analysis. Expected prevalence obtained from SEER (Surveillance, Epidemiology and End Results) NIH database (1973-2006) for the general population, matched for age, was compared with our cohort. Chi-square test was used for statistical analysis. There were 1091 probands in the database of whom 876 had complete personal history. The mean age was 57.6 (5-84 years) with 807 Caucasians and 710 males. Overall incidence of extra-esophageal cancers was higher in our cohort when compared with the general population. There is a strong association of certain cancer types in patients with BE and EAC. However, further epidemiologic and genetic research is needed for investigation and development of genetic fingerprints.

  7. Ion Mobility-Mass Spectrometry Analysis of Serum N-linked Glycans from Esophageal Adenocarcinoma Phenotypes

    PubMed Central

    Gaye, M. M.; Valentine, S. J.; Hu, Y.; Mirjankar, N.; Hammoud, Z. T.; Mechref, Y.; Lavine, B. K.; Clemmer, D. E.

    2012-01-01

    Three disease phenotypes, Barrett’s esophagus (BE), high-grade dysplasia (HGD), esophageal adenocarcinoma (EAC), and a set of normal control (NC) serum samples are examined using a combination of ion mobility spectrometry (IMS), mass spectrometry (MS) and principal component analysis (PCA) techniques. Samples from a total of 136 individuals were examined, including: 7 characterized as BE, 12 as HGD, 56 as EAC and 61 as NC. In typical datasets it was possible to assign ~20 to 30 glycan ions based on MS measurements. Ion mobility distributions for these ions show multiple features. In some cases, such as the [S1H5N4+3Na]3+ and [S1F1H5N4+3Na]3+ glycan ions, the ratio of intensities of high-mobility features to low-mobility features vary significantly for different groups. The degree to which such variations in mobility profiles can be used to distinguish phenotypes is evaluated for eleven N-linked glycan ions. An outlier analysis on each sample class followed by an unsupervised PCA using a genetic algorithm for pattern recognition reveals that EAC samples are separated from NC samples based on 46 features originating from the 11-glycan composite IMS distribution. PMID:23126309

  8. Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium

    PubMed Central

    Lawrenson, Kate; Pakzamir, Elham; Liu, Biao; Lee, Janet M.; Delgado, Melissa K.; Duncan, Kara; Gayther, Simon A.; Liu, Song; Roman, Lynda; Mhawech-Fauceglia, Paulette

    2015-01-01

    Background The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses. Methodology/Principal Findings We studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035). Conclusion Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future. PMID:26132201

  9. The Antioxidative Fraction of White Mulberry Induces Apoptosis through Regulation of p53 and NFκB in EAC Cells

    PubMed Central

    Khan, Muhammad Ali; Kabir, Syed Rashel; Reza, Md Abu; Rahman, Md Mahbubur; Islam, Mohammad Saiful; Rahman, Md Aziz Abdur; Rashid, Mamunur; Sadik, Md Golam

    2016-01-01

    In this study, the antioxidative fraction of white mulberry (Morus alba) was found to have an apotogenic effect on Ehrlich’s ascites carcinoma cell-induced mice (EAC mice) that correlate with upregulated p53 and downregulated NFκB signaling. The antioxidant activities and polyphenolic contents of various mulberry fractions were evaluated by spectrophotometry and the ethyl acetate fraction (EAF) was selected for further analysis. Strikingly, the EAF caused 70.20% tumor growth inhibition with S-phase cell cycle arrest, normalized blood parameters including red/white blood cell counts and suppressed the tumor weight of EAC mice compared with untreated controls. Fluorescence microscopy analysis of EAF-treated EAC cells revealed DNA fragmentation, cell shrinkage, and plasma membrane blebbing. These characteristic morphological features of apoptosis influenced us to further investigate pro- and anti-apoptotic signals in EAF-treated EAC mice. Interestingly, apoptosis correlated with the upregulation of p53 and its target genes PARP-1 and Bax, and also with the down-regulation of NFκB and its target genes Bcl-2 and Bcl-xL. Our results suggest that the tumor- suppressive effect of the antioxidative fraction of white mulberry is likely due to apoptosis mediated by p53 and NFκB signaling. PMID:27936037

  10. 75 FR 21285 - Request for Substantive Comments on the EAC's Proposed Requirements for the Testing of Pilot...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... ELECTION ASSISTANCE COMMISSION Request for Substantive Comments on the EAC's Proposed Requirements for the Testing of Pilot Voting Systems To Serve UOCAVA Voters; Correction AGENCY: United States... publishing for public comment a set of proposed requirements for the testing of pilot voting systems to be...

  11. A Strategic Plan of Academic Management System as Preparation for EAC Accreditation Visit--From UKM Perspective

    ERIC Educational Resources Information Center

    Ab-Rahman, Mohammad Syuhaimi; Yusoff, Abdul Rahman Mohd; Abdul, Nasrul Amir; Hipni, Afiq

    2015-01-01

    Development of a robust platform is important to ensure that the engineering accreditation process can run smoothly, completely and the most important is to fulfill the criteria requirements. In case of Malaysia, the preparation for EAC (Engineering Accreditation Committee) assessment required a good strategic plan of academic management system…

  12. The French Translation of the EAC DTD: A Few Thoughts on Interoperability with Reference to Authority Data

    ERIC Educational Resources Information Center

    Bourdon, Francoise

    2005-01-01

    The translation into French of the Encoded Archival Context (EAC) DTD tag library has been in progress for a few months. It is being carried out by a group of experts gathered by AFNOR, the French national standards agency. The main goal of this group is to foster the interoperability of authority data between archives, libraries and museums, and…

  13. Prognostic significance of IgG4+ plasma cell infiltrates following neoadjuvant chemoradiation therapy for esophageal adenocarcinoma.

    PubMed

    Yakirevich, Evgeny; Lu, Shaolei; Allen, Danisha; Mangray, Shamlal; Fanion, Jacqueline R; Lombardo, Kara A; Safran, Howard; Resnick, Murray B

    2017-08-01

    Lymphoplasmacytic infiltrates in esophageal adenocarcinoma (EAC) tissue following chemoradiotherapy (CRT) reflect alterations in the tumor immunoenvironment. The presence and role of plasma cells in this process are poorly understood. Our aim was to characterize the IgG4+ plasma cell population in EAC following CRT. Seventy-one esophagectomy specimens post-CRT were compared with a surgery-only group of 31 EACs. The distribution, density, and ratio of IgG4+ and IgG+ plasma cells were evaluated by immunohistochemistry and correlated with clinicopathologic features, treatment response, and survival. In the CRT group, the presence of higher numbers of IgG4+ (≥ median of 94/high-power field) and IgG+ (≥ median of 225/high-power field) plasma cells and increased IgG4+/IgG+ ratio (≥ median of 41%) within ulcers was associated with complete or near-complete treatment response (P = .0077, P = .0503, and P = .0063, respectively). Lower tumor grade, smaller tumor size, and higher levels of IgG4+ plasma cells in posttherapy ulcers significantly correlated with better overall survival, whereas pretherapy clinical stage, posttherapy pathologic stage, smaller tumor size, and lower tumor grade were associated with longer recurrence-free survival. Multivariate analysis revealed that both posttherapy pathologic stage and high IgG4+ plasma cells in ulcers were independent predictors of overall survival (P = .05 and P = .01), whereas only posttherapy pathologic stage was associated with recurrence-free survival (P < .01). This is the first study describing a dense IgG4+ plasma cell infiltrate in EAC following CRT. The presence of increased IgG4+ plasma cells may be a novel reliable factor to predict prognosis of EAC patients following CRT. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Genomic regions associated with susceptibility to Barrett's esophagus and esophageal adenocarcinoma in African Americans: The cross BETRNet admixture study.

    PubMed

    Sun, Xiangqing; Chandar, Apoorva K; Canto, Marcia I; Thota, Prashanthi N; Brock, Malcom; Shaheen, Nicholas J; Beer, David G; Wang, Jean S; Falk, Gary W; Iyer, Prasad G; Abrams, Julian A; Venkat-Ramani, Medha; Veigl, Martina; Miron, Alexander; Willis, Joseph; Patil, Deepa T; Nalbantoglu, Ilke; Guda, Kishore; Markowitz, Sanford D; Zhu, Xiaofeng; Elston, Robert; Chak, Amitabh

    2017-01-01

    Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) are far more prevalent in European Americans than in African Americans. Hypothesizing that this racial disparity in prevalence might represent a genetic susceptibility, we used an admixture mapping approach to interrogate disease association with genomic differences between European and African ancestry. Formalin fixed paraffin embedded samples were identified from 54 African Americans with BE or EAC through review of surgical pathology databases at participating Barrett's Esophagus Translational Research Network (BETRNet) institutions. DNA was extracted from normal tissue, and genotyped on the Illumina OmniQuad SNP chip. Case-only admixture mapping analysis was performed on the data from both all 54 cases and also on a subset of 28 cases with high genotyping quality. Haplotype phases were inferred with Beagle 3.3.2, and local African and European ancestries were inferred with SABER plus. Disease association was tested by estimating and testing excess European ancestry and contrasting it to excess African ancestry. Both datasets, the 54 cases and the 28 cases, identified two admixture regions. An association of excess European ancestry on chromosome 11p reached a 5% genome-wide significance threshold, corresponding to -log10(P) = 4.28. A second peak on chromosome 8q reached -log10(P) = 2.73. The converse analysis examining excess African ancestry found no genetic regions with significant excess African ancestry associated with BE and EAC. On average, the regions on chromosomes 8q and 11p showed excess European ancestry of 15% and 20%, respectively. Chromosomal regions on 11p15 and 8q22-24 are associated with excess European ancestry in African Americans with BE and EAC. Because GWAS have not reported any variants in these two regions, low frequency and/or rare disease associated variants that confer susceptibility to developing BE and EAC may be driving the observed European ancestry association evidence.

  15. Adenocarcinoma of the urinary bladder

    PubMed Central

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma. PMID:26309895

  16. P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy.

    PubMed

    van Olphen, Sophie H; Biermann, Katharina; Shapiro, Joel; Wijnhoven, Bas P L; Toxopeus, Eelke L A; van der Gaast, Ate; Stoop, Hans A; van Lanschot, Jan J B; Spaander, Manon C W; Bruno, Marco J; Looijenga, Leendert H J

    2017-02-01

    The aim of the study was to investigate the association between p53, SOX2, and CD44 protein expression and tumor response, and to validate potential predictive biomarker(s) in an independent cohort. Neoadjuvant chemoradiotherapy (nCRT) followed by surgery has become a standard of care for esophageal adenocarcinoma (EAC). However, the response to nCRT is highly variable among patients. EAC patients who underwent nCRT and surgery, between January 2003 and December 2014 at the Erasmus University Medical Center, were included and divided into a primary (n = 77) and a validation cohort (n = 70). P53, SOX2, and CD44 expression was detected by immunohistochemistry in pretreatment tumor biopsies, and scored independently by 2 investigators. Response to nCRT was assessed based on tumor regression grade (TRG) in the resection specimen. Forty-one (53%) patients in the primary cohort and 33 (47%) patients in the validation cohort showed major response (TRG1 or TRG2) in the resection specimen. Aberrant p53 and absence of SOX2 were associated with major response in the primary cohort: adjusted odds ratio (OR) 6.3 [95% confidence interval (CI), 1.3-30.1) and adjusted OR 4.1 (95% CI, 1.4-12.4), respectively. The same was true for the validation cohort (p53: adjusted OR 8.6; 95% CI, 0.93-80.9 and SOX2: adjusted OR 6.1; 95% CI, 1.6-23.4). The highest probability of a major response was seen in patients with concurrent aberrant p53 and absence of SOX2 expression, with an OR of 6.7 (95% CI, 2.1-21.4) and 6.2 (95% CI, 1.8-21.2) in the primary and validation cohort. Pattern of p53 and particularly SOX2 protein expression in EAC predicts response to nCRT. These biomarkers may help to individualize treatment in EAC patients.

  17. Comparison of different automated lesion delineation methods for metabolic tumor volume of 18F-FDG PET/CT in patients with stage I lung adenocarcinoma.

    PubMed

    Wang, Xiao-Yi; Zhao, Yan-Feng; Liu, Ying; Yang, Yi-Kun; Zhu, Zheng; Wu, Ning

    2017-12-01

    The aim of the study was to investigate the suitable segmentation method in small, low uptake and heterogeneous nodules of stage I lung adenocarcinoma.133 stage I lung adenocarcinoma patients with F-FDG PET/CT scans were enrolled in this retrospective study. All lesions were divided into different groups according to nodule density, nodule size, and the maximum standard uptake value (SUVmax) level. Four different PET segmentation methods were performed, including percentage threshold of SUVmax (T42% and T42% × RC), gradient-based threshold (adaptive iterative algorithm, AT-AIA), and background-related threshold (adaptive thresholding at 40% SUVmax, AT40%) approaches. The MTVs were evaluated and compared with CT volume (CTV). Percentage volume error (%VE) compared to CTV was calculated and the correlations between MTVs and CTV were analyzed.AT-AIA had the highest accuracy in large, high uptake, and solid nodules (72.5%, 72.4%, and 65.6%, respectively). AT40% had the highest accuracy in small, low uptake and nonsolid nodules (56.6%, 56.1%, and 62.6%, respectively). In part-solid nodules, the accuracy of AT-AIA (60.0%) and AT40% (56.7%) were higher than that of T42% and T42% × RC. The MTV of AT-AIA was in excellent correlation with the CTV in solid nodules (R = 0.831, P < .001) and in high uptake nodules (R = 0.830, P < .001). The MTV of AT40% was in good correlation with the CTV in nonsolid nodules (R = 0.686, P = .003) and in part-solid nodules (R = 0.731, P < .001).AT40% showed best performance in small, low uptake, nonsolid and part-solid lesions. AT-AIA was suitable for large, high uptake, and solid lesions. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  18. Management of patients with T1b esophageal adenocarcinoma: a retrospective cohort study on patient management and risk of metastatic disease.

    PubMed

    Schölvinck, Dirk; Künzli, Hannah; Meijer, Sybren; Seldenrijk, Kees; van Berge Henegouwen, Mark; Bergman, Jacques; Weusten, Bas

    2016-09-01

    Esophagectomy for submucosal (T1b) esophageal adenocarcinoma (EAC) is performed in order to optimize patient outcomes given the risk of concurrent lymph node metastases (LNM). However, not seldom, comorbidity precludes these patients from surgery. Therefore, the aim of our study was to assess the course of follow-up after treatment in submucosal EAC patients undergoing surgery versus conservative therapy and to evaluate the incidence of metastatic disease. Between 2001 and 2012, all patients undergoing diagnostic endoscopic resection for EAC in two centers were reviewed. Only patients with histopathologically proven submucosal tumor invasion were included. Submucosal EACs were divided into tumors that were removed radically (R0) and irradically (R1). Subsequently, in the R0 group, EACs were classified as either low risk (LR; submucosal invasion <500 nm, G1-G2, no LVI) or high risk (HR; deep submucosal invasion >500 nm, G3-G4 and/or LVI). Metastatic disease was defined as LNM in surgical resection specimen and/or evidence of malignant disease during follow-up (FU). Sixty-nine patients with a submucosal EAC were included [23 R1-resections and 46 R0-resection (14 R0-LR and 32 R0-HR)]. Twenty-six patients underwent surgical treatment (1 R0-LR, 12 R0-HR and 13 R1). None of the 14 R0-LR patients developed metastatic disease after a median FU of 60 months. In the R0-HR group and R1 group, metastatic disease was diagnosed in 16 and 30 % of patients, respectively. Surgical patients tended to have a better overall survival than non-surgical patients (p = 0.09). Tumor-related deaths, however, were 12 % in both groups. In LR submucosal EAC, the risk of metastatic disease appears to be very low. In deep submucosal EAC (either R0- or R1-resection), the rate of metastatic disease is lower than reported in earlier surgical series. Given the reasonable disease-free survival and high background mortality, conservative management of these patients seems to be a valid

  19. HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma

    PubMed Central

    Hu, Yingchuan; Bandla, Santhoshi; Godfrey, Tony E.; Tan, Dongfeng; Luketich, James D.; Pennathur, Arjun; Qiu, Xing; Hicks, David G.; Peters, Jeffrey; Zhou, Zhongren

    2011-01-01

    The HER2 oncogene was recently reported to be amplified and overexpressed in esophageal adenocarcinoma. However, the relationship of HER2 amplification in esophageal adenocarcinoma with prognosis has not been well defined. The scoring systems for clinically evaluating HER2 in esophageal adenocarcinoma are not established. The aims of the study were to establish a HER2 scoring system and comprehensively investigate HER2 amplification and overexpression in esophageal adenocarcinoma and its precursor lesion. Using a tissue microarray, containing 116 cases of esophageal adenocarcinoma, 34 cases of BE, 18 cases of low grade dysplasia and 15 cases of high grade dysplasia, HER2 amplification and overexpression were analyzed by HercepTest and CISH methods. The amplification frequency in an independent series of 116 esophageal adenocarcinoma samples was also analyzed using Affymetrix SNP 6.0 microarrays. In our studies, we have found that HER2 amplification does not associate with poor prognosis in total 232 esophageal adenocarcinoma patients by CISH and high density microarrays. We further confirm the similar frequency of HER2 amplification by CISH (18.10%; 21/116) and SNP 6.0 microarrays (16.4%, 19/116) in esophageal adenocarcinoma. HER2 protein overexpression was observed in 12.1 % (14/116) of esophageal adenocarcinoma and 6.67% (1/15) of HGD. No HER2 amplification or overexpression was identified in BE or LGD. All HER2 protein overexpression cases showed HER2 gene amplification. Gene amplification was found to be more frequent by CISH than protein overexpression in esophageal adenocarcinoma (18.10% vs 12.9%). A modified two-step model for esophageal adenocarcinoma HER-2 testing is recommend for clinical esophageal adenocarcinoma HER-2 trial. PMID:21460800

  20. [Clinical stages of patients with Alzheimer disease treated in specialist clinics in Spain. The EACE study].

    PubMed

    Alom Poveda, J; Baquero, M; González-Adalid Guerreiro, M

    2013-10-01

    The diagnostic paradigm of Alzheimer disease (AD) is changing; there is a trend toward diagnosing the disease in its early stages, even before the complete syndrome of dementia is apparent. The clinical stage at which AD is usually diagnosed in our area is unknown. Therefore, the purpose of this study is to describe the clinical stages of AD patients at time of diagnosis. Multicentre, observational and cross-sectional study. Patients with probable AD according to NINCDS-ARDRA criteria, attended in specialist clinics in Spain, were included in the study. We recorded the symptom onset to evaluation and symptom onset to diagnosis intervals and clinical status of AD (based on MMSE, NPI questionnaire, and CDR scale). Participants in this study included 437 specialists representing all of Spain's autonomous communities and a total of 1,707 patients, of whom 1,694 were included in the analysis. Mean MMSE score was 17.6±4.8 (95% CI:17.4-17.9). Moderate cognitive impairment (MMSE between 10 and 20) was detected in 64% of the patients, and severe cognitive impairment (MMSE<10) in 6%. The mean interval between symptom onset and the initial primary care visit was 10.9±17.2 months (95% CI:9.9-11.8), and the interval between symptom onset and diagnosis with AD was 28.4±21.3 months. Results from the EACE show that most AD patients in our area have reached a moderate clinical stage by the time they are evaluated in a specialist clinic. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  1. Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids.

    PubMed

    Mukaisho, Ken-Ichi; Nakayama, Takahisa; Hagiwara, Tadashi; Hattori, Takanori; Sugihara, Hiroyuki

    2015-01-01

    Gastric cancer can be classified as cardia and non-cardia subtypes according to the anatomic site. Although the gastric cancer incidence has decreased steadily in several countries over the past 50 years, the incidence of cardia cancers and esophageal adenocarcinoma (EAC) continue to increase. The etiological factors involved in the development of both cardia cancers and EACs are associated with high animal fat intake, which causes severe obesity. Central obesity plays roles in cardiac-type mucosa lengthening and partial hiatus hernia development. There are two distinct etiologies of cardia cancer subtypes: one associated with gastroesophageal reflux (GER), which predominantly occurs in patients without Helicobacter pylori (H. pylori) infection and resembles EAC, and the other associated with H. pylori atrophic gastritis, which resembles non-cardia cancer. The former can be developed in the environment of high volume duodenal content reflux, including bile acids and a higher acid production in H. pylori-negative patients. N-nitroso compounds, which are generated from the refluxate that includes a large volume of bile acids and are stabilized in the stomach (which has high levels of gastric acid), play a pivotal role in this carcinogenesis. The latter can be associated with the changing colonization of H. pylori from the distal to the proximal stomach with atrophic gastritis because a high concentration of soluble bile acids in an environment of low acid production is likely to act as a bactericide or chemorepellent for H. pylori in the distal stomach. The manuscript introduces new insights in causative factors of adenocarcinoma of the cardia about the role of bile acids in gastro-esophageal refluxate based upon robust evidences supporting interactions among pH, H. pylori, and bile acids.

  2. Acetylsalicylic Acid Exhibits Antitumor Effects in Esophageal Adenocarcinoma Cells In Vitro and In Vivo.

    PubMed

    Piazuelo, Elena; Esquivias, Paula; De Martino, Alba; Cebrián, Carmelo; Conde, Blanca; Santander, Sonia; Emperador, Sonia; García-González, María Asunción; Carrera-Lasfuentes, Patricia; Lanas, Angel

    2016-10-01

    Recent observational studies have shown therapeutic benefits of acetylsalicylic acid (ASA) in several types of cancer. We examined whether ASA exerts antitumor activity in esophageal adenocarcinoma (EAC). Human EAC cells (OE33) were treated with ASA (0-5 mM) to evaluate proliferation, apoptosis, and migration. In vivo model: OE33-derived tumors were subcutaneously implanted into athymic mice which were allocated to ASA (5 or 50 mg/kg/day)/vehicle (5-6 animals/group). Tumor growth was assessed every 2-3 days, and after 40 days, mice were euthanized. Plasma drug levels were determined by high-performance liquid chromatography. Histological and immunohistochemical (Ki67, activated caspase-3) analysis of tumors were performed. The effect of ASA on tumor prostaglandin E2 (PGE2) levels was also evaluated. In vitro cell proliferation and migration were significantly inhibited while apoptosis increased (p < 0.05) by ASA. Although ASA did not induce tumor remission, tumor progression was significantly lower in ASA-treated mice when compared to non-treated animals (478 % in mice treated with 5 mg/kg/day ASA vs. 2696 % control; 748 % in mice treated with 50 mg/kg/day ASA vs. 2670 % control). Maximum tumor inhibition was 92 and 85 %, respectively. This effect was associated with a significant decrease of proliferation index in tumors. ASA 5 mg/kg/day did not modify tumor PGE2 levels. Whereas tumor PGE2 content in mice treated with ASA 50 mg/kg was lower than in control mice, the difference was not significant. Although these results need to be confirmed in other EAC cells, our data suggest a role for ASA in the treatment of this tumor.

  3. FRY site-specific methylation differentiates pancreatic ductal adenocarcinoma from other adenocarcinomas.

    PubMed

    Srisuttee, Ratakorn; Ota, Jun; Muangsub, Tachapol; Keelawat, Somboon; Trirattanachat, Surang; Kitkumthorn, Nakarin; Mutirangura, Apiwat

    2016-06-01

    Adenocarcinoma is a type of cancer that occurs in the glandular cells throughout the body. There are several metastatic adenocarcinoma of unknown primary origin. Currently, there is no highly effective method to differentiate pancreatic ductal adenocarcinoma (PDAC) from other adenocarcinomas. Here, we identified pancreas tissue by site-specific methylation at FRY and found that it can also detect PDAC. The establishment of Combined Bisulphite Restriction Analysis (COBRA) and quantitative real-time PCR techniques of FRY revealed FRY hypermethylation in 21 out of 24 normal pancreatic tissue samples, whereas all other normal tissue samples from thirteen other organs (80 samples) remained totally unmethylated. Similarly in application to PDAC, this marker effectively indicated 25 PDAC among 151 other common adenocarcinomas with values of 100%, 98.7%, 92.6%, and 100% in sensitivity, specificity, positive predictive value and negative predictive value, respectively. In summary, we have demonstrated that this epigenetic site-specific marker has high potential for pancreatic tissue identification and can be applied in PDAC diagnosis. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  4. Primary duodenal adenocarcinoma.

    PubMed

    Solej, Mario; D'Amico, Silvia; Brondino, Gabriele; Ferronato, Marco; Nano, Mario

    2008-01-01

    Primary duodenal adenocarcinoma is a rare tumor with a poorly defined natural history and prognostic factors. It presents with nonspecific symptoms, and for this reason the diagnosis is often delayed. It is a serious problem for the surgeon because of the difficulty in obtaining an early diagnosis and standardizing basic tenets for an appropriate surgical approach. The aim of this work was to conduct a review of the literature analyzing the points most frequently debated about this pathology. A bibliographic search was carried out on the main search engines to find studies regarding duodenal adenocarcinoma, published in English, from January 1992 to January 2007. A total of 19 articles was selected. Results concerning symptoms, location of the tumor, diagnostic examinations, surgical treatment, histopathology of the tumor, survival and follow-up were obtained and discussed. All patients who are medically fit to undergo surgery should be given the option of aggressive resection regardless of tumor size, tumor invasion or appearance of positive lymph nodes. Hopefully, an early diagnosis will correlate with improved long-term survival.

  5. Effect of normalization methods on the performance of supervised learning algorithms applied to HTSeq-FPKM-UQ data sets: 7SK RNA expression as a predictor of survival in patients with colon adenocarcinoma.

    PubMed

    Shahriyari, Leili

    2017-11-03

    One of the main challenges in machine learning (ML) is choosing an appropriate normalization method. Here, we examine the effect of various normalization methods on analyzing FPKM upper quartile (FPKM-UQ) RNA sequencing data sets. We collect the HTSeq-FPKM-UQ files of patients with colon adenocarcinoma from TCGA-COAD project. We compare three most common normalization methods: scaling, standardizing using z-score and vector normalization by visualizing the normalized data set and evaluating the performance of 12 supervised learning algorithms on the normalized data set. Additionally, for each of these normalization methods, we use two different normalization strategies: normalizing samples (files) or normalizing features (genes). Regardless of normalization methods, a support vector machine (SVM) model with the radial basis function kernel had the maximum accuracy (78%) in predicting the vital status of the patients. However, the fitting time of SVM depended on the normalization methods, and it reached its minimum fitting time when files were normalized to the unit length. Furthermore, among all 12 learning algorithms and 6 different normalization techniques, the Bernoulli naive Bayes model after standardizing files had the best performance in terms of maximizing the accuracy as well as minimizing the fitting time. We also investigated the effect of dimensionality reduction methods on the performance of the supervised ML algorithms. Reducing the dimension of the data set did not increase the maximum accuracy of 78%. However, it leaded to discovery of the 7SK RNA gene expression as a predictor of survival in patients with colon adenocarcinoma with accuracy of 78%. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/mTOR inactivation

    PubMed Central

    Kresty, Laura A.; Weh, Katherine M.; Zeyzus-Johns, Bree; Perez, Laura N.; Howell, Amy B.

    2015-01-01

    Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) were investigated utilizing acid-sensitive and acid-resistant human esophageal adenocarcinoma (EAC) cell lines and esophageal tumor xenografts in athymic NU/NU mice. C-PAC induced caspase-independent cell death mainly via autophagy and low levels of apoptosis in acid-sensitive JHAD1 and OE33 cells, but resulted in cellular necrosis in acid-resistant OE19 cells. Similarly, C-PAC induced necrosis in JHAD1 cells pushed to acid-resistance via repeated exposures to an acidified bile cocktail. C-PAC associated cell death involved PI3K/AKT/mTOR inactivation, pro-apoptotic protein induction (BAX, BAK1, deamidated BCL-xL, Cytochrome C, PARP), modulation of MAPKs (P-P38/P-JNK) and G2-M cell cycle arrest in vitro. Importantly, oral delivery of C-PAC significantly inhibited OE19 tumor xenograft growth via modulation of AKT/mTOR/MAPK signaling and induction of the autophagic form of LC3B supporting in vivo efficacy against EAC for the first time. C-PAC is a potent inducer of EAC cell death and is efficacious in vivo at non-toxic behaviorally achievable concentrations, holding promise for preventive or therapeutic interventions in cohorts at increased risk for EAC, a rapidly rising and extremely deadly malignancy. PMID:26378019

  7. Gene expression profiling in sinonasal adenocarcinoma

    PubMed Central

    2009-01-01

    Background Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers. Methods To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors. Results Among the genes with significant differential expression we selected LGALS4, ACS5, CLU, SRI and CCT5 for further exploration. The overexpression of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type. Conclusion Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers. PMID:19903339

  8. [Adenocarcinoma of the duodenum].

    PubMed

    Siqueira, Pablo Rodrigo De; Nadal, Sidney Roberto; Rodrigues, Francisco Cesar Martins; Malheiros, Carlos Alberto

    2002-01-01

    To revise literature data about adenocarcinoma of the duodenum comparing to our results. Six patients with this kind of cancer, excluding periampullary lesions, were treated from 1991 to 1999 in the Department of Surgery, Santa Casa of São Paulo Medical School. Five of them were males in theirs fifties. The commonest signs and symptoms were those of gastrointestinal obstruction and weight loss. All patients were evaluated by duodenoscopy. Ultrasonography and CT scans played an important role with regard to preoperative staging. Three patients underwent a segmental resection and the others were submitted to a palliative duodenal bypass. Post-operative hospitalization varied from 5 to 9 days (7,3 days average). The operative mortality was 16.6% (one patient). Patients were not submitted to chemo or radiotherapy. Follow-up has been done. Patients with curative resection were free from recurrence. Two patients submitted to palliative operations were lost to follow-up. Rarity of duodenum carcinomas and few patients in the literature did not permit conclusions.

  9. New Pattern-Based Personalized Risk Stratification for Endocervical Adenocarcinoma with Important Clinical Implications and Surgical Outcome

    PubMed Central

    Roma, Andres A.; Mistretta, Toni-Ann; De Vivar, Andrea Diaz; Park, Kay J.; Alvarado-Cabrero, Isabel; Rasty, Golnar; Chanona-Vilchis, Jose G.; Mikami, Yoshiki; Hong, Sung R.; Teramoto, Norihiro; Ali-Fehmi, Rouba; Barbuto, Denise; Rutgers, Joanne K.L.; Silva, Elvio G.

    2016-01-01

    We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphvascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.8 months. Seventy-three patients (21%) had pattern A tumors; all were stage I and there were no LN metastases or recurrences. Pattern B was seen in 90 tumors (26%); all were stage I and LVI was seen in 24 cases (26.6%). Nodal disease was found in only 4 (4.4%) pattern B tumors (one IA2, two IB1, one IB not further specified (NOS)), each of which showed LVI. Pattern C was found in 189 cases (54%), 117 had LVI (61.9%) and 17% were stage II or greater. Forty-five (23.8%) patients showed LN metastases (one IA1, 14 IB1, 5 IB2, 5 IB NOS, 11 II, 5 III and 4 IV) and recurrences were recorded in 41 (21.7%) patients. This new risk stratification system identifies a subset of stage I patients with essentially no risk of nodal disease, suggesting that patients with pattern A tumors can be spared lymphadenectomy. Patients with pattern B tumors rarely present with LN metastases, and sentinel LN examination could potentially identify these patients. Surgical treatment with nodal resection is justified in patients with pattern C tumors. PMID:27016227

  10. Endometrial adenocarcinoma: beliefs and scepticism.

    PubMed

    Sivridis, Efthimios; Giatromanolaki, Alexandra

    2004-04-01

    The incidence of endometrial adenocarcinoma is high in North America and northern Europe, and low in Asia and Africa. This variance in frequency rates occurred in the late 1970s and its real cause has remained in question since. There is a widespread belief that endometrial adenocarcinomas associated with endometrial hyperplasia have a much better prognosis than those related to endometrial atrophy. This view is, in general terms, true but only because a high proportion of tumors arising from an atrophic endometrium are of serous/papillary, clear cell, or Grade 2-3 endometrioid carcinomas, in contrast to those developing from a hyperplastic endometrium, which are nearly all G1 endometrioid adenocarcinomas. These adenocarcinomas have, however, an excellent prognosis, no matter whether they are related to hyperplasia or atrophy, and taxonomically they form a single tumor group. In this regard, it is most reasonable to separate endometrial carcinomas into low- and high-grade tumors. The first are formed solely of G1 or "authentic" endometrioid adenocarcinomas, i.e., endometrioid neoplasms composed in their entirety of glandular elements without having traces of nonsquamous solid components. The high-grade tumors are formed of both endometrioid Grade 2-3 adenocarcinomas and nonendometrioid carcinomas-all of particularly aggressive behavior. The question of grading endometrioid adenocarcinomas in a precise and reproducible way becomes obvious. It is also believed that endometrial adenocarcinomas associated with endometrial hyperplasia are estrogen-primed, while those related to endometrial atrophy are deprived of hormonal stimulation. However, as we have shown in this laboratory recently, estrogen stimulation may be very common in endometrial neoplasms developing in an atrophic endometrium. For indeed most, if not all, postmenopausal atrophic endometria harboring adenocarcinomas contain actively proliferating glands, with high Ki-67 proliferation index, high epidermal

  11. Specific gene expression profiles are associated with a pathologic complete response to neoadjuvant therapy in esophageal adenocarcinoma.

    PubMed

    McLaren, Patrick J; Barnes, Anthony P; Terrell, Willy Z; Vaccaro, Gina M; Wiedrick, Jack; Hunter, John G; Dolan, James P

    2017-05-01

    Predicting treatment response to chemo-radiotherapy (CRT) in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to prognosis. We aimed to determine if specific expression profiles are associated with pathologic complete response (pCR) after neoadjuvant CRT. Eleven genes previously associated with esophageal cancer prognosis were identified. Esophageal adenocarcinoma (EAC) patients treated with neoadjuvant CRT and esophagectomy were included. Patients were classified into two groups: pCR and no-or-incomplete response (NR). Polymerase chain reaction was used to evaluate gene expression. Omnibus testing was applied to overall gene expression differences between groups, and log-rank tests compared individual genes. Eleven pCR and eighteen NR patients were analyzed. Combined expression profiles were significantly different between pCR and NR groups (p < 0.01). The gene CCL28 was over-expressed in pCR patients (Log-HR: 1.53, 95%CI: 0.46-2.59, p = 0.005), and DKK3 was under-expressed in pCR (Log-HR: -1.03 95%CI: -1.97, -0.10, p = 0.031). EAC tumors that demonstrated a pCR have genetic profiles that are significantly different from typical NR profiles. The genes CCL28 and DKK3 are potential predictors of treatment response. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. An Evaluation of Growth Models as Predictive Tools for Estimates at Completion (EAC)

    DTIC Science & Technology

    2009-03-01

    8 Political Influences ........................................................................................................11 Factor Methods...Limitations Past political influences and assumptions combine with data accessibility to limit our research two fold. Past studies and practices are based...cancelling a contract or program. Political Influences An overarching theme found in the literature limits effective data handling by political influences

  13. Genome-wide analysis of esophageal adenocarcinoma yields specific copy number aberrations that correlate with prognosis.

    PubMed

    Frankel, Adam; Armour, Nicola; Nancarrow, Derek; Krause, Lutz; Hayward, Nicholas; Lampe, Guy; Smithers, B Mark; Barbour, Andrew

    2014-04-01

    The incidence of esophageal adenocarcinoma (EAC) has been increasing rapidly for the past 3 decades in Western (Caucasian) populations. Curative treatment is based around esophagectomy, which has a major impact on quality of life. For those suitable for treatment with curative intent, 5-year survival is ∼30%. More accurate prognostic tools are therefore needed, and copy number aberrations (CNAs) may offer the ability to act as prospective biomarkers in this regard. We performed a genome-wide examination of CNAs in 54 samples of EAC using single-nucleotide polymorphism (SNP) arrays. Our aims were to describe frequent regions of CNA, to define driver CNAs, and to identify CNAs that correlated with survival. Regions of frequent amplification included oncogenes such as EGFR, MYC, KLF12, and ERBB2, while frequently deleted regions included tumor suppressor genes such as CDKN2A/B, PTPRD, FHIT, and SMAD4. The genomic identification of significant targets in cancer (GISTIC) algorithm identified 24 regions of gain and 28 regions of loss that were likely to contain driver changes. We discovered 61 genes in five regions that, when stratified by CNA type (gain or loss), correlated with a statistically significant difference in survival. Pathway analysis of the genes residing in both the GISTIC and prognostic regions showed they were significantly enriched for cancer-related networks. Finally, we discovered that copy-neutral loss of heterozygosity is a frequent mechanism of CNA in genes currently targetable by chemotherapy, potentially leading to under-reporting of cases suitable for such treatment. Copyright © 2014 Wiley Periodicals, Inc.

  14. The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKα/mTOR pathway in vitro and in vivo.

    PubMed

    Fujihara, Shintaro; Morishita, Asahiro; Ogawa, Kana; Tadokoro, Tomoko; Chiyo, Taiga; Kato, Kiyohito; Kobara, Hideki; Mori, Hirohito; Iwama, Hisakazu; Masaki, Tsutomu

    2017-01-31

    Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). This drug inhibits cancer cell proliferation, but the underlying mechanisms in various cancers, including esophageal cancer, remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human esophageal cancer cell proliferation in vitro and in vivo. We assessed the effects of telmisartan on human esophageal adenocarcinoma (EAC) cells using the cell lines OE19, OE33, and SKGT-4. Telmisartan inhibited the proliferation of these three cell lines via blockade of the G0 to G1 cell cycle transition. This blockade was accompanied by a strong decrease in cyclin D1, cyclin E, and other cell cycle-related proteins. Notably, the AMP-activated protein kinase (AMPK) pathway, a fuel sensor signaling pathway, was enhanced by telmisartan. Compound C, which inhibits the two catalytic subunits of AMPK, enhanced the expression of cyclin E, leading to G0/G1 arrest in human EAC cells. In addition, telmisartan reduced the phosphorylation of epidermal growth factor receptor (p-EGFR) and ERBB2 in vitro. In our in vivo study, intraperitoneal injection of telmisartan led to a 73.2% reduction in tumor growth in mice bearing xenografts derived from OE19 cells. Furthermore, miRNA expression was significantly altered by telmisartan in vitro and in vivo. In conclusion, telmisartan suppressed human EAC cell proliferation and tumor growth by inducing cell cycle arrest via the AMPK/mTOR pathway.

  15. The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKa/mTOR pathway in vitro and in vivo

    PubMed Central

    Fujihara, Shintaro; Morishita, Asahiro; Ogawa, Kana; Tadokoro, Tomoko; Chiyo, Taiga; Kato, Kiyohito; Kobara, Hideki; Mori, Hirohito; Iwama, Hisakazu; Masaki, Tsutomu

    2017-01-01

    Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). This drug inhibits cancer cell proliferation, but the underlying mechanisms in various cancers, including esophageal cancer, remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human esophageal cancer cell proliferation in vitro and in vivo. We assessed the effects of telmisartan on human esophageal adenocarcinoma (EAC) cells using the cell lines OE19, OE33, and SKGT-4. Telmisartan inhibited the proliferation of these three cell lines via blockade of the G0 to G1 cell cycle transition. This blockade was accompanied by a strong decrease in cyclin D1, cyclin E, and other cell cycle-related proteins. Notably, the AMP-activated protein kinase (AMPK) pathway, a fuel sensor signaling pathway, was enhanced by telmisartan. Compound C, which inhibits the two catalytic subunits of AMPK, enhanced the expression of cyclin E, leading to G0/G1 arrest in human EAC cells. In addition, telmisartan reduced the phosphorylation of epidermal growth factor receptor (p-EGFR) and ERBB2 in vitro. In our in vivo study, intraperitoneal injection of telmisartan led to a 73.2% reduction in tumor growth in mice bearing xenografts derived from OE19 cells. Furthermore, miRNA expression was significantly altered by telmisartan in vitro and in vivo. In conclusion, telmisartan suppressed human EAC cell proliferation and tumor growth by inducing cell cycle arrest via the AMPK/mTOR pathway. PMID:28052030

  16. A Model Based on Pathologic Features of Superficial Esophageal Adenocarcinoma Complements Clinical Node Staging in Determining Risk of Metastasis to Lymph Nodes.

    PubMed

    Davison, Jon M; Landau, Michael S; Luketich, James D; McGrath, Kevin M; Foxwell, Tyler J; Landsittel, Douglas P; Gibson, Michael K; Nason, Katie S

    2016-03-01

    It is important to identify superficial (T1) gastroesophageal adenocarcinomas (EAC) that are most or least likely to metastasize to lymph nodes, to select appropriate therapy. We aimed to develop a risk stratification model for metastasis of superficial EAC to lymph nodes using pathologic features of the primary tumor. We collected pathology data from 210 patients with T1 EAC who underwent esophagectomy from 1996 through 2012 on factors associated with metastasis to lymph nodes (tumor size, grade, angiolymphatic invasion, and submucosal invasion). Using these variables, we developed a multivariable logistic model to generate 4 categories for estimated risk of metastasis (<5% risk, 5%-10% risk, 15%-20% risk, or >20% risk). The model was validated in a separate cohort of 39 patients who underwent endoscopic resection of superficial EAC and subsequent esophagectomy, with node stage analysis. We developed a model based on 4 pathologic factors that determined risk of metastasis to range from 2.9% to 60% for patients in the first cohort. In the endoscopic resection validation cohort, higher risk scores were associated with increased detection of lymph node metastases at esophagectomy (P = .021). Among patients in the first cohort who did not have lymph node metastases detected before surgery (cN0), those with high risk scores (>20% risk) had 11-fold greater odds for having lymph node metastases at esophagectomy compared with patients with low risk scores (95% confidence interval, 2.3-52 fold). Increasing risk scores were associated with reduced patient survival time (P < .001) and shorter time to tumor recurrence (P < .001). Patients without lymph node metastases (pT1N0) but high risk scores had reduced times of survival (P < .001) and time to tumor recurrence (P = .001) after esophagectomy than patients with pT1N0 tumors and lower risk scores. Pathologic features of primary superficial EACs can be used, along with the conventional node staging system, to identify

  17. Absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissues

    NASA Astrophysics Data System (ADS)

    Ivashko, Pavlo; Peresunko, Olexander; Zelinska, Natalia; Alonova, Marina

    2014-08-01

    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  18. Factors that affect life expectancy of patients with gastric adenocarcinoma.

    PubMed

    Chen, Wei-Ying; Cheng, Hsiu-Chi; Wang, Jung-Der; Sheu, Bor-Shyang

    2013-12-01

    We used a new, semi-parametric method to estimate life expectancy and expected years of life lost (EYLL) after diagnosis of gastric cancer and assess whether patients' sex or tumor type or location had any effects. We performed a nationwide retrospective cohort study of 35,576 patients with gastric cancer who were registered in the Taiwan Cancer Registry from 1998 through 2007; data were collected until the end of 2010. The Monte Carlo method and tables in Taiwan National Vital Statistics database were matched to the cohort reference populations on the basis of age and sex. The estimated regression line and the survival curve of reference populations were used to extrapolate the survival curve beyond 2010. We compared patients' age at diagnosis, life expectancy, and EYLL based on sex, tumor type, and location. In Taiwan, gastric cancer is more prevalent among men, and 88.6% of tumors are adenocarcinomas. Patients with adenocarcinoma of the gastric cardia have shorter life expectancies and greater EYLL than those with noncardia tumors (P < .05). Women with gastric adenocarcinoma are diagnosed at a younger age and have longer life expectancies but more EYLL than men with such tumors (P < .05). The estimated years of life saved if gastric adenocarcinoma is diagnosed at an early stage and cured are 22,827 years (2.62 years/case) for women and 33,700 years (1.97 years/case) for men. Among patients with gastric cancer, men and patients with adenocarcinomas of the cardia have shorter life expectancies and more EYLL. Early detection of gastric adenocarcinoma can increase life expectancy. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. An esophageal adenocarcinoma susceptibility locus at 9q22 also confers risk to esophageal squamous cell carcinoma by regulating the function of BARX1.

    PubMed

    Yan, Caiwang; Ji, Yong; Huang, Tongtong; Yu, Fei; Gao, Yong; Gu, Yayun; Qi, Qi; Du, Jiangbo; Dai, Juncheng; Ma, Hongxia; Jin, Guangfu

    2018-05-01

    Genome wide association studies (GWAS) have identified a series of genetic variants associated with the risk of esophageal adenocarcinoma (EAC)/Barrett's esophagus (BE), which was different from those loci for esophageal squamous cell carcinoma (ESCC). It is important to evaluate whether these susceptibility loci for EAC/BE are also implicated in ESCC development. In the current study, we analyzed genetic variants at 3p13, 9q22, 16q24 and 19p13 in a case-control study including 2139 ESCC patients and 2463 cancer-free controls in a Chinese population, and further characterized the biological relevance of genetic variants by functional assays. We found that the G allele of rs11789015 at 9q22, as compared with the A allele, was significantly associated with a decreased risk of ESCC with a per-allele odds ratio of 0.77 (95%CI, 0.65-0.90; P = 1.38 × 10 -3 ), whereas the other three loci were not associated with ESCC risk. We further found that rs11789015-G allele correlated with decreased mRNA and protein levels of BARX1. Dual-luciferase reporter gene assay revealed that the A > G change at rs11789015 significantly decreased the promoter activity of BARX1. Both the mRNA and protein levels of BARX1 were significantly higher in ESCC tumor tissues compared with the corresponding normal tissues. Moreover, the deletion of BARX1 substantially reduced ESCC cells growth, migration and invasion. In conclusion, these results suggest that genetic variants at 9q22 are associated with the risk of both EAC/BE and ESCC, possibly by regulating the function of BARX1. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Agricultural pesticide use and adenocarcinomas of the stomach and oesophagus

    PubMed Central

    Lee, W; Lijinsky, W; Heineman, E; Markin, R; Weisenburger, D; Ward, M

    2004-01-01

    Aims: To evaluate the risk of the stomach and oesophageal adenocarcinomas associated with farming and agricultural pesticide use. Methods: Population based case-control study in eastern Nebraska. Telephone interviews were conducted with men and women diagnosed with adenocarcinoma of the stomach (n = 170) or oesophagus (n = 137) between 1988 and 1993, and controls (n = 502) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds on reaction with nitrite). Non-farmers were used as the reference category for all analyses. Results: Ever living or working on a farm, duration of farming, and size of the farm were not associated with stomach or oesophageal adenocarcinomas. There was no association for either cancer with ever-use of insecticides (stomach OR 0.9, 95% CI 0.6 to 1.4; oesophagus OR 0.7, 95% CI 0.4 to 1.1) or herbicides (stomach OR 0.9, 95% CI 0.5 to 1.4; oesophagus OR 0.7, 95% CI 0.4 to 1.2). Likewise, individual pesticides, including individual nitrosatable pesticides, were not significantly associated with risk. Conclusions: No significant associations were found between specific agricultural pesticide exposures and the risk of stomach or oesophageal adenocarcinomas among Nebraska farmers. PMID:15317914

  1. Novel Therapeutics for Pancreatic Adenocarcinoma.

    PubMed

    Lowery, Maeve A; O'Reilly, Eileen M

    2015-08-01

    The last decade has seen significant developments in the use of combination systemic therapy for advanced pancreatic ductal adenocarcinoma (PDAC), with median survival approaching 1 year for select patients treated with FOLFIRINOX in the metastatic setting. However, it is sobering that these developments have been achieved with the use of traditional cytotoxics rather than from successes in the more modern fields of molecularly targeted therapies or immunotherapy. This article highlights several promising therapeutic approaches to PDAC currently under clinical evaluation, including immune therapies, molecularly targeted therapies, strategies for stromal depletion, and targeted therapy for genetically selected patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. New diagnostic technique for rapid fluorescence immunocytochemical staining of adenocarcinoma and mesothelial cells using liquid-based cytology.

    PubMed

    Morimoto, Ayumi; Ito, Akihiro; Hashimoto, Katsunori; Nakano, Akinobu; Nagasaka, Tetsuro; Yokoi, Toyoharu

    2014-01-01

    To evaluate the expression of antibodies against calretinin, cytokeratin 5/6, desmin, D2-40, HBME-1, mesothelin, thrombomodulin, WT1, Ber-EP4, CEA, EMA and MOC-31 individually and to compare it with a new rapid procedure for fluorescence immunocytochemistry (ICC) using liquid-based cytology (LBC). Sixty-four peritoneal cell specimens prepared with the LBC method were stained with these markers to evaluate their usefulness and develop a rapid fluorescence immunostaining method using Ber-EP4 that is applicable to intraoperative cancer cytodiagnosis. The adenocarcinoma markers were positive in 92% of adenocarcinoma cases, 57% of cases with suspicion of adenocarcinoma, and 5% of negative cases (reactive mesothelial cells). On the other hand, the mesothelial cell markers were positive in 8-15% of adenocarcinoma cases, 43-57% of cases with suspicion of adenocarcinoma, and 93-95% of negative cases. The rapid new fluorescence ICC procedure clearly stained only the adenocarcinoma cells within 20 min. Immunocytochemical examination with the LBC method is a powerful ancillary technique for discriminating adenocarcinoma cells from mesothelial cells. This rapid new fluorescence ICC procedure can be used as an ancillary technique for accurate detection of adenocarcinoma cells in the intraoperative cytological examination of peritoneal or pleural washing fluid. © 2014 S. Karger AG, Basel.

  3. Reappraisal of the diagnostic and prognostic value of morning stiffness in arthralgia and early arthritis: results from the Groningen EARC, Leiden EARC, ESPOIR, Leiden EAC and REACH.

    PubMed

    van Nies, Jessica A B; Alves, Celina; Radix-Bloemen, Audrey L S; Gaujoux-Viala, Cécile; Huizinga, Tom W J; Hazes, Johanna M W; Brouwer, Elisabeth; Fautrel, Bruno; van der Helm-van Mil, Annette H M

    2015-04-23

    Morning stiffness is assessed daily in the diagnostic process of arthralgia and arthritis, but large-scale studies on the discriminative ability are absent. This study explored the diagnostic value of morning stiffness in 5,202 arthralgia and arthritis patients and the prognostic value in early rheumatoid arthritis (RA). In arthralgia patients referred to the Early Arthritis Recognition Clinics (EARC) of Leiden (n = 807) and Groningen (n = 481) or included in the Rotterdam Early Arthritis Cohort (REACH) study (n = 353), the associations (cross-sectional analyses) between morning stiffness and presence of arthritis at physical examination were studied. In early arthritis patients, included in the Leiden Early Arthritis Clinic (EAC) (n = 2,748) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n = 813), associations with fulfilling the 2010-RA criteria after one year were assessed. In 2010-RA patients included in the EAC (n = 1,140) and ESPOIR (n = 677), association with the long-term outcomes of disease-modifying antirheumatic drug (DMARD)-free sustained remission and radiological progression were determined. Morning stiffness was defined as a duration ≥60 minutes; sensitivity analyses were performed for other definitions. In arthralgia, morning stiffness (≥60 minutes) associated with the presence of arthritis; Leiden EARC odds ratio (OR) 1.49 (95% CI 1.001 to 2.20), Groningen EARC OR 2.21 (1.33 to 3.69) and REACH OR 1.55 (0.97 to 2.47) but the areas under the receiver operating characteristic curve (AUCs) were low (0.52, 0.57, 0.54). In early arthritis, morning stiffness was associated with 2010-RA independent of other predictors (Leiden EAC OR 1.72 (95% CI 1.31 to 2.25, AUC 0.68), ESPOIR OR 1.68 (1.03 to 2.74, AUC 0.64)). Duration of ≥30 minutes provided optimal discrimination for RA in early arthritis. Morning stiffness was not associated with radiological progression or DMARD-free sustained

  4. New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome.

    PubMed

    Roma, Andres A; Mistretta, Toni-Ann; Diaz De Vivar, Andrea; Park, Kay J; Alvarado-Cabrero, Isabel; Rasty, Golnar; Chanona-Vilchis, Jose G; Mikami, Yoshiki; Hong, Sung R; Teramoto, Norihiro; Ali-Fehmi, Rouba; Barbuto, Denise; Rutgers, Joanne K L; Silva, Elvio G

    2016-04-01

    We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphovascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.8 months. Seventy-three patients (21%) had pattern A tumors; all were stage I and there were no LN metastases or recurrences. Pattern B was seen in 90 tumors (26%); all were stage I and LVI was seen in 24 cases (26.6%). Nodal disease was found in only 4 (4.4%) pattern B tumors (one IA2, two IB1, one IB not further specified (NOS)), each of which showed LVI. Pattern C was found in 189 cases (54%), 117 had LVI (61.9%) and 17% were stage II or greater. Forty-five (23.8%) patients showed LN metastases (one IA1, 14 IB1, 5 IB2, 5 IB NOS, 11 II, 5 III and 4 IV) and recurrences were recorded in 41 (21.7%) patients. This new risk stratification system identifies a subset of stage I patients with essentially no risk of nodal disease, suggesting that patients with pattern A tumors can be spared lymphadenectomy. Patients with pattern B tumors rarely present with LN metastases, and sentinel LN examination could potentially identify these patients. Surgical treatment with nodal resection is justified in patients with pattern C tumors. Copyright © 2016 Elsevier Inc. All rights

  5. "Ductal adenocarcinoma in anular pancreas".

    PubMed

    Benassai, Giacomo; Perrotta, Stefano; Furino, Ermenegildo; De Werra, Carlo; Aloia, Sergio; Del Giudice, Roberto; Amato, Bruno; Vigliotti, Gabriele; Limite, Gennaro; Quarto, Gennaro

    2015-09-01

    The annular pancreas is a congenital anomaly in which pancreatic tissue partially or completely surrounds the second portion of the duodenum. Its often located above of papilla of Vater (85%), rarely below (15%). This pancreatic tissue is often easily dissociable to the duodenum but there is same cases where it the tissue is into the muscolaris wall of the duodenum. We describe three case of annular pancreas hospitalized in our facility between January 2004 and January 2009. There were 2 male 65 and 69 years old respectively and 1 female of 60 years old, presented complaining of repeated episodes of mild epigastric pain. Laboratory tests (including tumor markers), a direct abdomen X-ray with enema, EGDS and total body CT scan were performed to study to better define the diagnosis. EUS showed the presence of tissue infiltrating the muscle layer all around the first part of duodenum. Biopsies performed found the presence of pancreatic tissue with focal areas of adenocarcinoma. Subtotal gastrectomy with Roux was performed. The histological examinations shows an annular pancreas of D1 with multiple focal area of adenocarcinoma. (T1aN0M0). We performed a follow up at 5 years. One patients died after 36 months for cardiovascular hit. Two patients, one male and one female, was 5-years disease-free. Annular pancreas is an uncommon congenital anomaly which usually presents itself in infants and newborn. Rarely it can present in late adult life with wide range of clinical severities thereby making its diagnosis difficult. Pre-operative diagnosis is often difficult. CT scan can illustrate the pancreatic tissue encircling the duodenum. ERCP and MRCP are useful in outlining the annular pancreatic duct. Surgery still remains necessary to confirm diagnosis and bypassing the obstructed segment. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  6. MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2017-02-08

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  7. Airborne occupational exposures and risk of oesophageal and cardia adenocarcinoma

    PubMed Central

    Jansson, C; Plato, N; Johansson, A L V; Nyrén, O; Lagergren, J

    2006-01-01

    Background The reasons for the increasing incidence of and strong male predominance in patients with oesophageal and cardia adenocarcinoma remain unclear. The authors hypothesised that airborne occupational exposures in male dominated industries might contribute. Methods In a nationwide Swedish population based case control study, 189 and 262 cases of oesophageal and cardia adenocarcinoma respectively, 167 cases of oesophageal squamous cell carcinoma, and 820 frequency matched controls underwent personal interviews. Based on each study participant's lifetime occupational history the authors assessed cumulative airborne occupational exposure for 10 agents, analysed individually and combined, by a deterministic additive model including probability, frequency, and intensity. Furthermore, occupations and industries of longest duration were analysed. Relative risks were estimated by odds ratios (OR), with 95% confidence intervals (CI), using conditional logistic regression, adjusted for potential confounders. Results Tendencies of positive associations were found between high exposure to pesticides and risk of oesophageal (OR 2.3 (95% CI 0.9 to 5.7)) and cardia adenocarcinoma (OR 2.1 (95% CI 1.0 to 4.6)). Among workers highly exposed to particular agents, a tendency of an increased risk of oesophageal squamous cell carcinoma was found. There was a twofold increased risk of oesophageal squamous cell carcinoma among concrete and construction workers (OR 2.2 (95% CI 1.1 to 4.2)) and a nearly fourfold increased risk of cardia adenocarcinoma among workers within the motor vehicle industry (OR 3.9 (95% CI 1.5 to 10.4)). An increased risk of oesophageal squamous cell carcinoma (OR 3.9 (95% CI 1.2 to 12.5)), and a tendency of an increased risk of cardia adenocarcinoma (OR 2.8 (95% CI 0.9 to 8.5)), were identified among hotel and restaurant workers. Conclusions Specific airborne occupational exposures do not seem to be of major importance in the aetiology of oesophageal or

  8. Detection of in situ and invasive endocervical adenocarcinoma on ThinPrep Pap Test: Morphologic analysis of false negative cases.

    PubMed

    Chaump, Michael; Pirog, Edyta C; Panico, Vinicius J A; D Meritens, Alexandre Buckley; Holcomb, Kevin; Hoda, Rana

    2016-01-01

    The goal of this study was to calculate the sensitivity and false negative (FN) rate of ThinPrep Pap Test (TPPT) and carefully analyze missed cases for educational purposes. Patients with histologically proven adenocarcinoma in-situ (AIS) or invasive endocervical adenocarcinoma (EAC) over a 17-year-period (1998-2015) were identified. The TPPT immediately preceding the histological diagnosis of AIS/ECA was designated as index Pap (IP). Paps up to 122 months before histologic diagnosis of AIS/ECA were considered for this study. All available negative and unsatisfactory TPPT were re-reviewed. There were 78 patients with histologically-proven AIS (56) or ECA (22) with 184 TPPTs, and 95 of these TPPTs were abnormal. Of the abnormal cases, 55.7% TPPTs were diagnosed as endocervical cell abnormality (atypical endocervical cells/AIS/ECA). Notably, 44.2% of abnormal TPPTs were diagnosed as squamous cell abnormality (atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion/high grade squamous intraepithelial lesion). Including the diagnoses of squamous cell abnormality, the sensitivity of index TPPT for histologically-confirmed AIS/ECA was 88%. Eighty-eight of 184 TPPT, including 10 IP, were negative = 87, or unsatisfactory = 1. Forty-two of these slides were available for re-review. Upon review, 21 TPPT (50%) were confirmed negative and 21 TPPT (50%) were reclassified as abnormal = 20, or unsatisfactory = 1. Of the FN cases, the main difficulty in correct diagnosis was the presence of few diagnostic cell clusters which had less feathering, and consisted of smaller, rounder cells in small and tighter clusters, with nuclear overlap. In particular, nuclear overlap in three-dimensional groups precluded the accurate diagnosis. Rare FN cases showed squamous cell abnormality on re-review, and rare cases showed obscuring blood or inflammation. A significant proportion of AIS/EAC is discovered after Pap showing squamous cell abnormality. FN

  9. Oesophageal adenocarcinoma: the new epidemic in men?

    PubMed

    Rutegård, Martin; Lagergren, Pernilla; Nordenstedt, Helena; Lagergren, Jesper

    2011-07-01

    The last decades have witnessed an unprecedented rise in the incidence of oesophageal adenocarcinoma. This rise has mainly affected men, and current male-to-female sex ratio estimates range from 7-10 to 1. Major risk factors for oesophageal adenocarcinoma are gastro-oesophageal reflux disease and obesity, especially in combination. The prevalence of these risk factors has increased during the last decades, but there does not seem to be a marked differential distribution among men and women. However, reflux among men is more often associated with erosive reflux disease than it is among women. There is also evidence that male-type obesity, with a prominent abdominal distribution of fat, confers a greater risk increase for oesophageal adenocarcinoma than the female equivalent. Due to the marked male predominance and the finding that women tend to develop specialized intestinal metaplasia (Barrett's oesophagus) and adenocarcinoma at a later age than men, interest has been directed towards a potential aetiological role of reproductive factors and sex hormones. Breastfeeding has been found to be a protective factor for the development of adenocarcinoma, while no association has hitherto been established with other reproductive factors. Taken together, the male predominance in the incidence of oesophageal adenocarcinoma may partly be explained by the differential effect of the major risk factors reflux disease and obesity, but the mechanisms whereby this occurs need to be elucidated. Moreover, the association with breastfeeding indicates a need for extensive epidemiological studies to clarify a possible role of sex hormonal influence in the aetiology of oesophageal adenocarcinoma. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. A human gallbladder adenocarcinoma cell line.

    PubMed

    Johzaki, H; Iwasaki, H; Nishida, T; Isayama, T; Kikuchi, M

    1989-12-01

    A cell strain (FU-GBC-1) was established from cancerous ascites of a 68-year-old male patient with well-differentiated adenocarcinoma of the gallbladder. By light and electron microscopy, the cultured cells showed the morphologic features of adenocarcinoma characterized by gland-like structures, intracellular microcystic spaces, and mucous production. Immunoperoxidase stains showed that FU-GBC-1 cells expressed several epithelial tumor antigens including CA 19-9, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA). The cell strain has been in continuous culture up to passage 44 for 1 1/2 years, with the population doubling time of 120 hours. The cytogenetic analysis by a G-band technique showed a constant loss of chromosome Y in FU-GBC-1 cells. The modal chromosome number at passage 12 was 82 with a range of 77 to 85. Flow cytometry with an ethidium bromide technique additionally confirmed aneuploid DNA content (4C) in the cultured cells at passage 12 and 35. Inoculation of FU-GBC-1 cells into the dermis of BALB/c nude mice produced transplantable adenocarcinoma identical to the original tumor. Because no continuous cell lines of the well-differentiated type of gallbladder adenocarcinoma have been reported in the literature currently, the newly established cell strain we report may yield a useful system for studying the morphologic and biologic characteristics of gallbladder adenocarcinoma.

  11. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas.

    PubMed

    Liu, Yang; Sethi, Nilay S; Hinoue, Toshinori; Schneider, Barbara G; Cherniack, Andrew D; Sanchez-Vega, Francisco; Seoane, Jose A; Farshidfar, Farshad; Bowlby, Reanne; Islam, Mirazul; Kim, Jaegil; Chatila, Walid; Akbani, Rehan; Kanchi, Rupa S; Rabkin, Charles S; Willis, Joseph E; Wang, Kenneth K; McCall, Shannon J; Mishra, Lopa; Ojesina, Akinyemi I; Bullman, Susan; Pedamallu, Chandra Sekhar; Lazar, Alexander J; Sakai, Ryo; Thorsson, Vésteinn; Bass, Adam J; Laird, Peter W

    2018-04-09

    We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Distribution of gastric adenocarcinoma subtypes in different ethnicities in Kuala Lumpur, Malaysia.

    PubMed

    Sukri, A; Hanafiah, A; Kosai, N R; Taher, M M; Mohamed Rose, I

    2017-12-01

    The multiracial population in Malaysia has lived together for almost a century, however, the risk of gastric cancer among them varies. This study aimed to determine the distribution of different gastric adenocarcinoma subtypes and Helicobacter pylori infection status among gastric adenocarcinoma patients. Patients with gastric adenocarcinoma were enrolled from November 2013 to June 2015. Blood samples were collected for detection of H. pylori using ELISA method. Gastric adenocarcinoma cases were more prevalent in the Chinese (52.8%), followed by the Malays (41.7%) and least prevalent in the Indians (5.6%). Gastric adenocarcinoma located in the cardia was significantly more prevalent in the Malays (66.7%) compared to the Chinese (26.3%), whereas non-cardia cancer was diagnosed more in the Chinese (73.7%) compared to the Malays (33.3%) [P = 0.019; OR = 5.6, 95 CI: 1.27 to 24.64]. The Malays also had significantly higher prevalence of gastric tumour located at the cardia or fundus than other gastric sites compared to the Chinese (P = 0.002; OR: 11.2, 95% CI: 2.2 to 56.9). Among the cardia gastric cancer patients, 55.6% of the Malays showed intestinal histological subtype, whereas all the Chinese had the diffuse subtype. More than half of the patients (55.3%) with gastric adenocarcinoma were positive for H. pylori infection and among them, 66.7% were Chinese patients. The risk of gastric adenocarcinoma in our population is different among ethnicities. Further studies on host factors are needed as it might play an important role in gastric cancer susceptibility in our population.

  13. Pulmonary Signet-Ring Cell Adenocarcinoma Metastatic to the Skin.

    PubMed

    Boyd, Alan S

    2017-05-01

    Internal malignancies occasionally metastasize to the skin, usually imparting a poor prognosis. In men, pulmonary malignancies are the second most common offending tumor. Roughly, half such lesions are adenocarcinomas. A small subset of pulmonary adenocarcinomas exhibits signet-ring morphology. To date, a cutaneous metastasis arising from a pulmonary signet-ring cell adenocarcinoma has not been reported.

  14. The prognosis of invasive adenocarcinoma presenting as ground-glass opacity on chest computed tomography after sublobar resection

    PubMed Central

    Moon, Youngkyu; Lee, Kyo Young

    2017-01-01

    Background Ground-glass opacity (GGO) on chest computed tomography (CT) is generally associated with non-invasive or minimally invasive adenocarcinoma (MIA). However, many instances of GGO are diagnosed as invasive adenocarcinoma. The purpose of this study is to analyse the histopathologic characteristics of invasive adenocarcinoma presenting as GGO and the prognosis after sublobar resection. Methods We conducted a retrospective chart review of 191 patients who were treated for stage I non-small cell lung cancer presenting as a GGO-predominant tumour upon CT and who underwent curative resection. We analysed the histologic subtypes and components of invasive adenocarcinomas presenting as GGO-predominant tumours. We also compared the 5-year recurrence-free survival (RFS) of invasive adenocarcinomas presenting as GGO-predominant in patients undergoing sublobar resection or lobectomy. Results Of 191 GGO-predominant tumour patients, 97 patients had adenocarcinoma in situ (AIS) or MIA, and 94 patients had invasive adenocarcinoma. In the analysis of the histologic component of invasive adenocarcinoma presenting as GGO, the mean rate of the lepidic component was 47.4%, that of the acinar component was 42.1%, and that of the papillary component was 7.3%. Micropapillary and solid components were nearly absent. The 5-year RFS rates of sublobar resection and lobectomy were both 100%. Conclusions Invasive components such as acinar and papillary components can also be seen as GGO tumours on chest CT. After the sublobar resection of GGO-predominant tumours, a good prognosis can be expected, even if the tumour is an invasive adenocarcinoma such as the acinar or papillary subtypes. PMID:29268386

  15. Pulmonary Adenocarcinoma Occurring 5 Years after Resection of a Primary Pancreatic Adenocarcinoma: A Relevant Differential Diagnosis

    PubMed Central

    Falkenstern-Ge, R. F.; Wohlleber, M.; Kimmich, M.; Huettl, K.; Friedel, G.; Ott, G.; Kohlhäufl, M.

    2014-01-01

    Ductal adenocarcinoma of the pancreas is a lethal disease. Surgical extirpation only offers the slim chance for long-term survival in localized disease. We report on a 73 year old female patient who initially underwent successful resection of pancreatic adenocarcinoma in May 2005. She was treated with adjuvant chemotherapy with gemcitabine. In October 2010 the patient noticed increasing dyspnea with haemoptysis. She was soon referred to our center. After the diagnosis of pulmonary adenocarcinoma with widespread metastasis, she was treated with systemic chemotherapy. For a period of next three years, she was treated with different chemotherapy regimens due to repeated episodes of tumor progression. To the best of our knowledge after reviewing the literature, this case represents an unusually clinical course with metachronous pulmonary adenocarcinoma arising after treatment of a primary pancreatic cancer after a long latency period. PMID:24716048

  16. Naked Cuticle Drosophila 1 Expression in Histologic Subtypes of Small Adenocarcinoma of the Lung

    PubMed Central

    Ahn, Sangjeong; Hwangbo, Won; Kim, Hyunchul

    2013-01-01

    Background Naked cuticle Drosophila 1 (NKD1) has been related to non-small cell lung cancer in that decreased NKD1 levels have been associated with both poor prognosis and increased invasive quality. Methods Forty cases of lung adenocarcinoma staged as Tis or T1a were selected. Cases were subclassified into adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and small adenocarcinoma (SAD). Immunohistochemical studies for NKD1 were performed. Results Forty samples comprised five cases of AIS (12.5%), eight of MIA (20.0%), and 27 of SAD (67.5%). AIS and MIA showed no lymph node metastasis and 100% disease-free survival, whereas among 27 patients with SAD, 2 (7.4%) had lymph node metastasis, and 3 (11.1%) died from the disease. Among the 40 cases, NKD1-reduced expression was detected in 8 (20%) samples, whereas normal expression was found in 15 (37.5%) and overexpression in 17 (42.5%). Loss of NKD1 expression was significantly associated with lymph node metastasis (p=0.001). All cases with predominant papillary pattern showed overexpression of NKD1 (p=0.026). Conclusions Among MIA and SAD, MIA had better outcomes than SAD. Down-regulated NKD1 expression was closely associated with nodal metastasis, and overexpression was associated with papillary predominant adenocarcinoma. PMID:23837013

  17. Ex vivo characterization of normal and adenocarcinoma colon samples by Mueller matrix polarimetry.

    PubMed

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ashraf, Sumara; Ahmad, Shakil; Ikram, Masroor

    2015-05-01

    Mueller matrix polarimetry along with polar decomposition algorithm was employed for the characterization of ex vivo normal and adenocarcinoma human colon tissues by polarized light in the visible spectral range (425-725 nm). Six derived polarization metrics [total diattenuation (DT ), retardance (RT ), depolarization(ΔT ), linear diattenuation (DL), retardance (δ), and depolarization (ΔL)] were compared for normal and adenocarcinoma colon tissue samples. The results show that all six polarimetric properties for adenocarcinoma samples were significantly higher as compared to the normal samples for all wavelengths. The Wilcoxon rank sum test illustrated that total retardance is a good candidate for the discrimination of normal and adenocarcinoma colon samples. Support vector machine classification for normal and adenocarcinoma based on the four polarization properties spectra (ΔT , ΔL, RT ,and δ) yielded 100% accuracy, sensitivity, and specificity, while both DTa nd DL showed 66.6%, 33.3%, and 83.3% accuracy, sensitivity, and specificity, respectively. The combination of polarization analysis and given classification methods provides a framework to distinguish the normal and cancerous tissues.

  18. Adenocarcinoma arising in urinary bladder endocervicosis.

    PubMed

    Nakaguro, Masato; Tsuzuki, Toyonori; Shimada, Satoko; Taki, Tetsuro; Tsuchiyama, Mari; Kitamura, Atsuko; Suzuki, Yasuhiko; Nakano, Yojiro; Ono, Kenzo

    2016-02-01

    Endocervicosis is a rare benign condition characterized by the presence of endocervical-type mucinous glands. Urinary bladder endocervicosis forms an elevated lesion in the posterior wall of the urinary bladder and is sometimes misdiagnosed as a malignant tumor clinically and pathologically. Herein we describe the first case of adenocarcinoma arising in urinary bladder endocervicosis. The patient, a 58-year-old woman, presented with asymptomatic hematuria. Cystoscopy revealed a nodular mass measuring 4 cm in diameter in the posterior wall, and total cystectomy was performed. Histology revealed that the elevated lesion of the bladder wall was composed of haphazard proliferation of cystic glands lined by benign endocervical-type epithelium. An adenocarcinoma arose at the center of this endocervicosis. Mucin histochemistry revealed the presence of sulfomucin in both the endocervicosis and adenocarcinoma components. Immunohistochemically, the endocervicosis was positive for cytokeratin (CK) 7, AE1/AE3, CAM5.2, HBME1, CA19-9, and estrogen receptor (ER), and negative for CK20, CDX2, progesterone receptor (PR), MUC5AC, and β-catenin. The adenocarcinoma showed similar immunohistochemical results, except for loss of ER expression and a slight increase in the ratio of Ki-67-positive cells. This case indicates that endocervicosis, known as a benign lesion, harbors the possibility of malignant transformation. © 2016 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  19. Adenocarcinoma - chest x-ray (image)

    MedlinePlus

    This chest x-ray shows adenocarcinoma of the lung. There is a rounded light spot in the right upper lung (left side ... density. Diseases that may cause this type of x-ray result would be tuberculous or fungal granuloma, and ...

  20. Urethral adenocarcinoma in a mental deficiency patient.

    PubMed

    Ramírez-Sevilla, Cristóbal; Llopis-Manzanera, Juan; Romero-Martín, José Antonio; García-Vidal, Olga

    2014-12-01

    To report the case of a urethral tumour in a patient with mental deficiency. Complete resection of the tumour was performed and the pathologic examination informed the presence of urethral adenocarcinoma. The patient is disease-free twelve months after surgery. Bibliographic review for diagnosis and treatment was performed.

  1. Comparison of absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissue

    NASA Astrophysics Data System (ADS)

    Peresunko, O. P.; Zelinska, N. V.; Prydij, O. G.; Zymnyakov, D. A.; Ushakova, O. V.

    2013-12-01

    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  2. The Significance of Serum Carcinoembryonic Antigen in Lung Adenocarcinoma

    PubMed Central

    Kim, Jae Jun; Hyun, Kwanyong; Park, Jae Kil; Moon, Seok Whan

    2015-01-01

    Background A raised carcinoembryonic antigen (CEA) may be associated with significant pathology during the postoperative follow-up of lung adenocarcinoma. Methods We reviewed the medical records of 305 patients who underwent surgical resections for primary lung adenocarcinoma at a single institution between April 2006 and February 2013. Results Preoperative CEA levels were significantly associated with age, smoking history, pathologic stage including pT (pathologic tumor stge), pN (pathologic nodal stage) and overall pathological stage, tumor size and differentiation, pathologically positive total lymph node, N1 and N2 lymph node, N2 nodal station (0/1/2=1.83/2.94/7.21 ng/mL, p=0.019), and 5-year disease-free survival (0.591 in group with normal preoperative CEA levels vs. 0.40 in group with high preoperative CEA levels, p=0.001). Preoperative CEA levels were significantly higher than postoperative CEA levels (p<0.001, Wilcoxon signed-rank test). Postoperative CEA level was also significantly associated with disease-free survival (p<0.001). A follow-up serum CEA value of >2.57 ng/mL was found to be the appropriate cutoff value for the prediction of cancer recurrence with sensitivity and specificity of 71.4% and 72.3%, respectively. Twenty percent of patients who had recurrence of disease had a CEA level elevated above this cutoff value prior to radiographic evidence of recurrence. Postoperative CEA, pathologic stage, differentiation, vascular invasion, and neoadjuvant therapy were identified as independent predictors of 5-year disease-free survival in a multivariate analysis. Conclusion The follow-up CEA level can be a useful tool for detecting early recurrence undetected by postoperative imaging studies. The perioperative follow-up CEA levels may be helpful for providing personalized evaluation of lung adenocarcinoma. PMID:26509127

  3. Possible pathways used to predict different stages of lung adenocarcinoma.

    PubMed

    Chen, Xiaodong; Duan, Qiongyu; Xuan, Ying; Sun, Yunan; Wu, Rong

    2017-04-01

    We aimed to find some specific pathways that can be used to predict the stage of lung adenocarcinoma.RNA-Seq expression profile data and clinical data of lung adenocarcinoma (stage I [37], stage II 161], stage III [75], and stage IV [45]) were obtained from the TCGA dataset. The differentially expressed genes were merged, correlation coefficient matrix between genes was constructed with correlation analysis, and unsupervised clustering was carried out with hierarchical clustering method. The specific coexpression network in every stage was constructed with cytoscape software. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed with KOBAS database and Fisher exact test. Euclidean distance algorithm was used to calculate total deviation score. The diagnostic model was constructed with SVM algorithm.Eighteen specific genes were obtained by getting intersection of 4 group differentially expressed genes. Ten significantly enriched pathways were obtained. In the distribution map of 10 pathways score in different groups, degrees that sample groups deviated from the normal level were as follows: stage I < stage II < stage III < stage IV. The pathway score of 4 stages exhibited linear change in some pathways, and the score of 1 or 2 stages were significantly different from the rest stages in some pathways. There was significant difference between dead and alive for these pathways except thyroid hormone signaling pathway.Those 10 pathways are associated with the development of lung adenocarcinoma and may be able to predict different stages of it. Furthermore, these pathways except thyroid hormone signaling pathway may be able to predict the prognosis.

  4. Composite protective lifestyle factors and risk of developing gastric adenocarcinoma: the Singapore Chinese Health Study

    PubMed Central

    Wang, Zhensheng; Koh, Woon-Puay; Jin, Aizhen; Wang, Renwei; Yuan, Jian-Min

    2017-01-01

    Background: Incidence of gastric cancer is the highest in Eastern Asia. Multiple modifiable lifestyle factors have been identified as risk factors for gastric cancer. However, their aggregated effect on the risk of gastric cancer has not been examined among populations with high prevalence of Helicobacter pylori. Methods: A study was conducted to examine the association between multiple lifestyle factors together and the risk of developing gastric adenocarcinoma in the Singapore Chinese Health Study, a prospective cohort of 63 257 men and women between 45 and 74 years enroled during 1993–1998. Composite score of cigarette smoking, alcohol consumption, obesity, dietary pattern, and sodium intake at baseline was assessed with hazard ratio (HR) and 95% confidence interval (CI) of gastric adenocarcinoma using Cox regression method. Results: Higher healthy composite lifestyle scores were significantly associated with reduced risk of gastric adenocarcinoma in a dose-dependent manner. Hazard ratios (95% CIs) for total, cardia, and non-cardia gastric adenocarcinoma for the highest (score 5) vs lowest composite score (score 0/1/2) were 0.42 (0.31–0.57), 0.22 (0.10–0.47), and 0.55 (0.39–0.78), respectively (all Ptrend<0.001). These lifestyles together accounted for 48% of total gastric adenocarcinoma cases in the study population. The inverse association was observed in both genders, and remained after exclusion of first 5 years of follow-up. Conclusions: The inverse association between the aggregated healthy lifestyle factors and the risk of gastric adenocarcinoma is in dose-dependent manner in this highly H. pylori-exposed population. These lifestyle factors together may account for up to half of disease burden in this study population. PMID:28125822

  5. Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade

    PubMed Central

    Overman, Michael J.; Fournier, Keith; Hu, Chung-Yuan; Eng, Cathy; Taggart, Melissa; Royal, Richard; Mansfield, Paul; Chang, George J.

    2013-01-01

    Purpose Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas; the prognostic impact of grade in localized disease, and the validity of the AJCC Cancer Staging Manual 7th edition decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known. Methods Patients with adenocarcinoma of the appendix diagnosed between 1988-2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage and grade were calculated; and Cox proportional hazards regression analyses were performed. Results We analyzed a total of 2,469 appendiceal adenocarcinomas, of which 1,375 had mucinous histology and 860 had non-mucinous histology. Though overall CSS was similar for mucinous and nonmucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female gender, stage IV disease, and well differentiated histology were more common for mucinous adenocarcinomas. Histological grade had a strong prognostic impact, especially in patients with stage IV mucinous adenocarcinoma. The adjusted hazard ratios for stage IV moderately and poorly differentiated histological grade were 1.63 (95%CI: 1.14-2.34) and 4.94 (95%CI: 3.32-7.35) for mucinous histology, in comparison to 1.44 (95%CI: 0.82-2.52) and 1.90 (95%CI: 0.95-3.80) for non-mucinous histology, respectively. Conclusion The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and this data does not support the combination of these two histological grades in the recent AJCC 7th edition. PMID:23001080

  6. Multidriver mutation analysis in pulmonary mucinous adenocarcinoma in Taiwan: identification of a rare CD74-NRG1 translocation case.

    PubMed

    Gow, Chien-Hung; Wu, Shang-Gin; Chang, Yih-Leong; Shih, Jin-Yuan

    2014-07-01

    Several new chromosomal translocations resulting in driver fusion mutations have recently been discovered in non-small-cell lung cancer. The driver mutational patterns in pulmonary mucinous adenocarcinoma, a rare subtype of non-small-cell lung cancer, have not been well studied. A single-institute cohort study in Taiwan was performed to determine the mutations of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), fusions of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and neuregulin 1 (NRG1) in patients diagnosed with pulmonary mucinous adenocarcinoma. We also examined NRG1 translocation in patients diagnosed as adenocarcinoma of other subtypes with wild-type EGFR, KRAS, ALK, and ROS1 genes. Surgical or biopsy specimens were collected from 13 patients with mucinous adenocarcinoma. Using the direct RNA sequencing method, we discovered a rare CD74-NRG1 fusion (8 %), an echinoderm microtubule-associated protein like 4 (EML4)-ALK fusion (17 %), and three KRAS mutations (25 %). No EGFR mutations or ROS1 rearrangements were detected. The rare CD74-NRG1 fusion positive patient presented with uncommon radiological features. We did not detect any CD74-NRG1 fusion in the 109 adenocarcinoma of other subtypes, which were all negative for EGFR, KRAS, ALK, and ROS1. The CD74-NRG1 fusion mutation is rare and may be exclusively present in patients with pulmonary mucinous adenocarcinoma. Patients harboring CD74-NRG1 positive tumors may present with uncommon imaging features.

  7. Genomic Alteration During Metastasis of Lung Adenocarcinoma.

    PubMed

    Tan, Qiang; Cui, Jian; Huang, Jia; Ding, Zhengping; Lin, Hao; Niu, Xiaomin; Li, Zhiming; Wang, Guan; Luo, Qingquan; Lu, Shun

    2016-01-01

    Recurrent gene mutation has been identified by the analysis of exonic DNA from lung adenocarcinoma, but its progression has not been extensively profiled. The investigation of the mutational landscape of tumors provides new insights into cancer genome evolution and further discovers the interplay of somatic mutation, adaptation of clones to their environment and natural selection. Cancer development involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype. Comparative whole exome sequencing of both primary and metastatic tumor tissues from four patients of stage IV lung adenocarcinoma patients with chest wall metastasis was performed. Both primary and metastatic tumors were diagnosed through biopsy followed by surgical resection. All tumor specimens were cut into several pieces to assess potential heterogenic clones within the tumor tissue. Adjacent normal lung tissue was also obtained to provide germline mutation background. By modeling and analyzing progression of the cancer metastasis based on non-synonymous variants, we defined the extent of heterogeneity of cancer genomes and identified similar cancer evolution pattern in the four patients: metastasis was an early event occurring right after the primary cancer formation and evolution in the metastatic tumor was continuously and simultaneously in progression with that in the primary tumor. By characterizing the clonal hierarchy of genetic lesions, we further charted a pathway of oncogenic events along which genes may drive lung adenocarcinoma metastasis, such as TAS2R31 and UMODL1, involving in G-protein coupled receptor protein signaling pathway. The candidate genes identified in this study may become targets for the treatment of lung adenocarcinoma metastasis. © 2016 S. Karger AG, Basel.

  8. ALDH1B1 as a Modulator of Pancreatic Adenocarcinoma

    PubMed Central

    Singh, Surendra; Arcaroli, John J.; Orlicky, David J.; Chen, Ying; Messersmith, Wells A.; Bagby, Stacey; Purkey, Alicia; Quackenbush, Kevin S.; Thompson, David C.; Vasiliou, Vasilis

    2016-01-01

    Objectives The aim of the current study was to examine expression and the role, if any, of ALDH1B1 in pancreatic adenocarcinoma. Methods A tissue microarray of 61 pancreatic cancer patients were evaluated for protein expression of ALDH1B1 by immunohistochemistry. ALDH1B1 siRNA was used to assess the contribution of ALDH1B1 on proliferation of pancreatic cancer cells. Results In normal human pancreas, ALDH1B1 is abundantly expressed in glandular cells, but sparsely in the ducts (ALDH1B1 immunopositivity = 16.7 ± 1.7). In pancreatic ductal carcinoma, we found high ALDH1B1 expression in ductal cancerous tissues (ALDH1B1 immunopositivity = 197.2 ± 29.4). Analysis of ALDH1B1 expression in a human pancreatic adenocarcinoma tissue microarray showed the greatest expression in tumors that were more invasive. A variation in ALDH1B1 expression was also observed in 16 human pancreatic cancer cell lines. Knockdown of ALDH1B1 caused a 35% reduction in cell growth in the high ALDH1B1-expressing cell lines. Conclusion Our data show for the first time that ALDH1B1 is expressed at very high levels in human pancreatic cancer and it contributes to proliferation in these tumor cells. These data suggest a potential modulatory role for ALDH1B1 in pancreatic cancer. PMID:26566217

  9. Randomized Placebo-Controlled Trial of a Gastrin Receptor Antagonist in Barretts Esophagus | Division of Cancer Prevention

    Cancer.gov

    The incidence of esophageal adenocarcinoma (EAC) has risen five-fold over the past several decades, yet the prognosis for EAC remains extremely poor. As such, EAC represents a very attractive target for chemoprevention. Barrett's esophagus (BE) is the precursor lesion for EAC, and acid reflux is a major risk factor for both BE and EAC. Virtually all patients with BE,

  10. Comprehensive molecular profiling of lung adenocarcinoma.

    PubMed

    2014-07-31

    Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

  11. [Multicystic presentation of a lepidic mucinous adenocarcinoma].

    PubMed

    Beurton, A; Gomez, E; Mandry, D; Champigneulle, J; Perez, P; Chaouat, A; Chabot, F

    2016-11-01

    The pneumonic form is very characteristic of lepidic pattern adenocarcinoma of the lung. However, the diagnosis and treatment of the disease when it presents in this way may be delayed by atypical radiological findings and severity of hypoxemia. A 48-year-old female, non-smoker, asthmatic since the age of 20 years, was hospitalized for a diffuse infiltrative pneumonia complicated by severe respiratory failure. The history included chronic cough, gradually increasing dyspnoea on exertion lasting for 14 months and the onset of haemoptysis of low abundance associated with arthralgia in the previous month. She had no professional or domestic exposure to any risk factors. Chest CT scan revealed bilateral alveolar condensations, ground glass areas with thickened septa creating a crazy paving pattern, and numerous large cysts of various sizes and locations, often with irregular thin walls. Microbiological and immunological tests were negative. She required early invasive ventilation and then venovenous ECMO together with broad-spectrum empiric antibiotic therapy, but died after 39 days in intensive care. The autopsy revealed lesions consistent with mucinous lepedic adenocarcinoma with no EGFR mutation and KRAS mutation. There was also associated pulmonary suppuration. Mucinous lepidic adenocarcinoma is an alternative diagnosis for pneumonic consolidation associated with multiple cysts. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  12. Pre-existing Pulmonary Diseases and Survival in Patients With Stage-dependent Lung Adenocarcinoma

    PubMed Central

    Jian, Zhi-Hong; Huang, Jing-Yang; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Wu, Ming-Fang; Liaw, Yung-Po

    2016-01-01

    Abstract Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common lung diseases associated with lung cancer mortality. This study evaluated sex disparities in pre-existing pulmonary diseases and stage-dependent lung adenocarcinoma survival. Patients newly diagnosed with lung adenocarcinoma between 2003 and 2008 were identified using the National Health Insurance Research Database and Cancer Registry. Cases with lung adenocarcinoma were followed until the end of 2010. Survival curves were estimated by the Kaplan–Meier method. Cox proportional-hazard regression was used to calculate the hazard ratio (HR) of pre-existing asthma, COPD, and/or TB, and to estimate all-cause mortality risk in patients with different stages of lung adenocarcinoma. A total of 14,518 cases were identified with lung adenocarcinoma. Specifically, among men, the HRs for TB were 1.69 (95% confidence interval [CI], 1.10–2.58), 1.48 (95% CI, 1.14–1.93), and 1.27 (95% CI, 1.08–1.49) for individuals with stage I + II, III, and IV diseases, respectively. The HRs for asthma were 1.41 (95% CI, 1.00–1.99) in women with stage I + II and 1.14 (95% CI, 1.04–1.26) in men with stage IV disease. For pulmonary disease combinations in men, the HRs were 1.45 (95% CI, 1.12–1.89) for asthma + COPD + TB, 1.35 (95% CI, 1.12–1.63) for COPD + TB, 1.28 (95% CI, 1.01–1.63) for TB, and 1.15 (95%CI, 1.04–1.27) for asthma + COPD, respectively. For women with stage I + II disease, the HR was 6.94 (95% CI, 2.72–17.71) for asthma + COPD + TB. Coexistence of pre-existing pulmonary diseases increased mortality risk in men with adenocarcinoma. TB is at elevated risk of mortality among men with different stages of adenocarcinoma. Asthmatic women with early-stage adenocarcinoma had increased risk of mortality. PMID:26962806

  13. Screening Methods for Metal-Containing Nanoparticles in Water

    EPA Science Inventory

    Screening-level analysis of water for metal-containing nanoparticles is achieved with single particle-inductively coupled plasma mass spectrometry (SP-ICPMS). This method measures both the concentration of nanoparticles containing an analyte metal and the mass of the metal in eac...

  14. Distinct metaplastic and inflammatory phenotypes in autoimmune and adenocarcinoma-associated chronic atrophic gastritis

    PubMed Central

    Jeong, Sangho; Choi, Eunyoung; Petersen, Christine P; Roland, Joseph T; Federico, Alessandro; Ippolito, Rossana; D'Armiento, Francesco P; Nardone, Gerardo; Nagano, Osamu; Saya, Hideyuki; Romano, Marco

    2016-01-01

    Background Autoimmune gastritis (AIG) and adenocarcinoma-associated chronic atrophic gastritis (CAG) are both associated with oxyntic atrophy, but AIG patients demonstrate an increased risk of carcinoid tumors rather than the elevated risk of adenocarcinoma observed with CAG. We therefore sought to compare the characteristics of the metaplastic mucosa in AIG and CAG patients. Methods We examined markers for metaplasia (spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia) as well as proliferation (Ki67) and immune cell populations (neutrophils, macrophages, and eosinophils) in gastric sections from 16 female patients with autoimmune thyroiditis and AIG and 17 patients with CAG associated with gastric adenocarcinoma. Results Both AIG and CAG patients demonstrated prominent SPEM and intestinal metaplasia. However, AIG patients displayed significantly lower numbers of infiltrating macrophages and significantly reduced mucosal cell proliferation as compared to CAG patients. Conclusions These findings indicate that, while both AIG and CAG patients display prominent oxyntic atrophy and metaplasia, the AIG patients do not show proliferative metaplastic lineages that would predispose to adenocarcinoma. PMID:28405320

  15. Metformin Inhibits the IL-6-Induced Epithelial-Mesenchymal Transition and Lung Adenocarcinoma Growth and Metastasis

    PubMed Central

    Wang, Yubo; Han, Rui; Li, Li; Xiang, Tong; He, Luhang; Long, Haixia; Zhu, Bo; He, Yong

    2014-01-01

    Objective Epithelial-mesenchymal transition (EMT) plays an important role in cancer tumorigenesis. However, the underlying mechanisms of EMT in lung adenocarcinoma, and how this process might be inhibited, remain to be explored. This study investigated the role of IL-6 in lung adenocarcinoma cell EMT and explored the potential effects of metformin on this process. Methods Invasion assay and MTT assay was performed to determine cell invasion and cell proliferation. Western blotting, immunofluorescence, real-time PCR, ELISA, and immunohistochemistry were performed to detect the expression of IL-6, E-cadherin, Vimentin, and p-STAT3. Results We discovered that IL-6, via STAT3 phosphorylation, could promote lung adenocarcinoma cell invasion via EMT in vitro. This was supported by the inverse correlation between E-cadherin and IL-6 expression, positive correlation between IL-6 and vimentin mRNA expression and between STAT3 phosphorylation and IL-6 expression in tumor tissues. Importantly, metformin inhibited tumor growth and distant metastases in tumor-bearing nude mice and reversed IL-6-induced EMT both in vitro and in vivo. Furthermore, we found that blockade of STAT3 phosphorylation might be the underlying mechanism of metformin inhibition of IL-6-induced EMT. Conclusions Collectively, our present results show that enhanced IL-6 expression, via STAT3 phosphorylation, is a mechanism of EMT in lung adenocarcinoma. We found that metformin could inhibit IL-6-induced EMT possibly by blocking STAT3 phosphorylation. PMID:24789104

  16. Slug regulates E-cadherin expression in metastatic adenocarcinoma cells isolated from pleural fluid.

    PubMed

    Li, Xiang-Nan; Fang, Chang-Qing; Wang, Ye-Lin; Wang, Xiu-Ru; Wang, En-Hua; Li, Jian-Hua

    2013-01-01

    Slug protein is a key regulator of epithelial-mesenchymal transition, but its expression in cancer is less well studied. To evaluate the expression of slug, E-cadherin and vimentin in adenocarcinoma cells from malignant pleural effusions, we analyzed 121 malignant pleural fluid specimens. Twenty-eight nonmalignant pleural fluid specimens were analyzed as control. Besides clinical cytological diagnosis tests, immunofluorescence, immunocytochemistry and Western blotting methods were used. Results showed strong membrane staining of E-cadherin in adenocarcinoma cells from pleural fluid. Slug mainly showed nucleus staining. Cytoplasma positive of vimentin was found in adenocarcinoma cells isolated from pleural fluid. Slug, E-cadherin and vimentin expression was found in 43/121 (36%), 87/121 (72%) and 102/121 (84%) cases, respectively. Our data showed elevated levels of slug were accompanied by down regulation of E-cadherin and the expression of vimentin in adenocarcinoma cells. In addition, there was no relationship between slug expression and patient's age or gender or tumor site. Hyperplasia epithelium cells from nonmalignant pleural fluid were uniformly negative for E-cadherin and slug. In conclusion, the results demonstrated the inverse expression of slug and E-cadherin in the majority of malignant pleural fluid cases compared with nonmalignant pleural fluid. The slug protein may be helpful to access the prognosis of patients with pleural fluid. Copyright © 2011 Wiley Periodicals, Inc.

  17. Treatment and Survival of Small-bowel Adenocarcinoma in the United States: A Comparison With Colon Cancer.

    PubMed

    Young, John I; Mongoue-Tchokote, Solange; Wieghard, Nicole; Mori, Motomi; Vaccaro, Gina M; Sheppard, Brett C; Tsikitis, Vassilki L

    2016-04-01

    Small-bowel adenocarcinoma is rare and fatal. Because of data paucity, there is a tendency to extrapolate treatment from colon cancer, particularly in the adjuvant stetting. The purpose of this study was to evaluate the current surgical and adjuvant treatments of small-bowel adenocarcinoma and compare with colon cancer. This was a retrospective cohort study. The linked Surveillance, Epidemiology, and End Results and Medicare database was used at a tertiary referral hospital. Patients with small-bowel adenocarcinoma and colon cancer identified from 1992 to 2010, using International Classification of Diseases for Oncology, 3 Revision, site, behavior, and histology codes were included. Overall survival and cancer-specific survival were estimated using the Kaplan-Meier method and competing risk analysis. A total of 2123 patients with small-bowel adenocarcinoma and 248,862 patients with colon cancer were identified. Five-year overall survival rates for patients with small-bowel adenocarcinoma and colon cancer were 34.9% and 51.5% (p < 0.0001). A total of 1550 patients with small-bowel adenocarcinoma (73.0%) underwent surgery, compared with 177,017 patients with colon cancer (71.1%). The proportion of patients who received chemotherapy was similar, at 21.3% for small bowel and 20.0% for colon. In contrast to colon cancer, chemotherapy did not improve overall or cancer-specific survival for patients with small-bowel adenocarcinoma, regardless of stage. Predictors of poor survival for small-bowel adenocarcinoma on multivariate analysis included advanced age, black race, advanced stage, poor tumor differentiation, high comorbidity index, and distal location. Chemotherapy did not confer additional survival benefit compared with surgery alone (HR, 1.04 (95% CI, 0.90-1.22)). This was a retrospective review. The reliance on Medicare data limited granularity and may have affected the generalizability of the results. The prognosis for small-bowel adenocarcinoma is worse than that

  18. KRAS Mutation is a Significant Prognostic Factor in Early Stage Lung Adenocarcinoma

    PubMed Central

    Kadota, Kyuichi; Sima, Camelia S.; Arcila, Maria E.; Hedvat, Cyrus; Kris, Mark G.; Jones, David R.; Adusumilli, Prasad S.; Travis, William D.

    2016-01-01

    Background The potential clinical impact of KRAS and epidermal growth factor receptor (EGFR) mutations has been investigated in lung adenocarcinomas; however, their prognostic value remains controversial. In our study, we sought to investigate the prognostic significance of driver mutations using a large cohort of early-stage lung adenocarcinomas. Methods We reviewed patients with pathologic early-stage, lymph node-negative, solitary lung adenocarcinoma who had undergone surgical resection (1995–2005; stage I/II = 463/19). Tumors were classified according to the IASLC/ATS/ERS classification and genotyped by Sequenom MassARRAY system and polymerase chain reaction-based assays. In stage I disease, the Kaplan-Meier method and cumulative incidence of recurrence (CIR) analyses were used to estimate the probability of overall survival (OS) and recurrence, respectively. Results Of all, 129 (27%) patients had mutations in KRAS, 86 (18%) in EGFR, 8 (2%) in BRAF, 8 (2%) in PIK3CA, 4 (1%) in NRAS, and 1 (0.2%) in AKT1. EGFR L858R mutation correlated with lepidic predominant histology (P = 0.006) while exon 19 deletion correlated with acinar predominant histology (P < 0.001). EGFR mutations were not detected in invasive mucinous adenocarcinomas (P = 0.033). The 5-year OS of patients with KRAS mutant tumors was significantly worse (n = 124; 5-year OS, 63%) than those with KRAS wild-type (n = 339; 77%; P < 0.001). In solid predominant tumors, KRAS mutations correlated with worse OS (P = 0.008) and increased risk of recurrence (P = 0.005). On multivariate analysis, KRAS mutation was an independent prognosticator of OS in all patients (hazard ratio, 1.87; P < 0.001) and recurrence in solid predominant tumors (hazard ratio, 4.73; P = 0.012). Conclusion In patients with resected stage I lung adenocarcinomas, KRAS mutation was an independent prognostic factor for OS and recurrence, especially in solid predominant tumors. PMID:27740967

  19. Intramucosal esophageal adenocarcinoma: primum non nocere.

    PubMed

    Li, Zhigang; Rice, Thomas W; Liu, Xiuli; Goldblum, John R; Williams, Sarah J; Rybicki, Lisa A; Murthy, Sudish C; Mason, David P; Raymond, Daniel P; Blackstone, Eugene H

    2013-06-01

    Intramucosal esophageal cancer treatment is evolving. Less-invasive therapies have emerged, necessitating review of safety, effectiveness, and determinants of long-term outcome after esophagectomy to clarify the role of this traditional, maximally invasive, and potentially harmful therapy. From January 1983 to January 2011, 164 patients underwent esophagectomy alone for intramucosal adenocarcinoma. Cancers were subdivided by depth of invasion: lamina propria 50 (30%) and muscularis mucosa 114 (70%; inner 42 [26%], middle 16 [10%], and outer 56 [34%]). We assessed complications and esophagectomy-related mortality (safety) and cancer recurrence (effectiveness), and identified determinants of long-term outcomes. Barrett esophagus (P = .005), larger cancers (P < .001), worse histologic grade (P < .001), lymphovascular invasion (P < .001), and overstaging (P = .02) were associated with deeper cancers. One patient had regional lymph node metastases (0.6%). Seventy-five patients (46%) had complications. Seven of 9 deaths within 6 months were esophagectomy related, 6 from respiratory failure. Seven patients had recurrence, all within 4 years. Five-, 10-, and 15-year survivals were 82%, 69%, and 60%, respectively, which were similar to those of a matched general population. Determinants of late mortality were older age (P = .004), poorer lung function (P < .0001), longer cancer (P = .04), postoperative pneumonia (P = .06), cancer recurrence (P < .0001), and second cancers (P < .0001). Survival after esophagectomy for intramucosal adenocarcinoma is excellent, determined more by patient than cancer characteristics. Patient selection and respiratory function are crucial to minimize harm. Considering the outcome of emerging therapies, esophagectomy should be reserved for patients with a long intramucosal adenocarcinoma or those in whom endoscopic therapies fail or are inappropriate. Copyright © 2013 The American Association for Thoracic Surgery. Published

  20. Unresectable Pancreatic Adenocarcinoma: Eight Years Later

    PubMed Central

    Smiley, Kate; Malhotra, Reetu; Peche, William; Langell, John T.

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, and is considered uniformly fatal when patients present with unresectable, advanced-stage disease at the time of diagnosis. Long-term survival of patients with advanced-stage pancreatic adenocarcinoma remains rare, despite advances in adjuvant chemoradiation protocols. A 73-year-old male presented to our emergency department with abdominal pain and a history of biopsy-proven, stage III pancreatic adenocarcinoma. His initial staging CT scan and trans-duodenal ultrasound had demonstrated a stage IIa (T3, N0, Mx) lesion. On surgical exploration, he was up-staged to stage III (T4, N0, Mx), noting encasement of the superior mesenteric vessels and involvement of the portal vein. He underwent palliative choledochojejunostomy and was treated with 4 months of oxaliplatin and capecitabine, with concurrent radiation therapy (50.4 Gy), followed by 4 months of gemcitabine. After 7 months, the patient withdrew from therapy due to treatment intolerance. He then turned to self-medication with non-traditional herbal therapies. After 3 years of surveillance, he was lost to follow-up until presenting to our facility with abdominal pain 8 years after his initial diagnosis. On diagnostic CT scan during his current presentation for abdominal pain, he was found to have no evidence of pancreatic cancer. Based on our review of the literature, we present the longest known survival of a patient with surgically unresectable pancreatic adenocarcinoma. Further study of this patient’s phenotypic or genotypic characteristics may provide insight into better therapeutic agents, or a predictive subset of patients who will benefit from specific chemotherapeutic options. PMID:28983358

  1. Comparison of a radiomic biomarker with volumetric analysis for decoding tumour phenotypes of lung adenocarcinoma with different disease-specific survival.

    PubMed

    Yuan, Mei; Zhang, Yu-Dong; Pu, Xue-Hui; Zhong, Yan; Li, Hai; Wu, Jiang-Fen; Yu, Tong-Fu

    2017-11-01

    To compare a multi-feature-based radiomic biomarker with volumetric analysis in discriminating lung adenocarcinomas with different disease-specific survival on computed tomography (CT) scans. This retrospective study obtained institutional review board approval and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Pathologically confirmed lung adenocarcinoma (n = 431) manifested as subsolid nodules on CT were identified. Volume and percentage solid volume were measured by using a computer-assisted segmentation method. Radiomic features quantifying intensity, texture and wavelet were extracted from the segmented volume of interest (VOI). Twenty best features were chosen by using the Relief method and subsequently fed to a support vector machine (SVM) for discriminating adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC). Performance of the radiomic signatures was compared with volumetric analysis via receiver-operating curve (ROC) analysis and logistic regression analysis. The accuracy of proposed radiomic signatures for predicting AIS/MIA from IAC achieved 80.5% with ROC analysis (Az value, 0.829; sensitivity, 72.1%; specificity, 80.9%), which showed significantly higher accuracy than volumetric analysis (69.5%, P = 0.049). Regression analysis showed that radiomic signatures had superior prognostic performance to volumetric analysis, with AIC values of 81.2% versus 70.8%, respectively. The radiomic tumour-phenotypes biomarker exhibited better diagnostic accuracy than traditional volumetric analysis in discriminating lung adenocarcinoma with different disease-specific survival. • Radiomic biomarker on CT was designed to identify phenotypes of lung adenocarcinoma • Built up radiomic signature for lung adenocarcinoma manifested as subsolid nodules • Retrospective study showed radiomic signature had greater diagnostic accuracy than volumetric analysis • Radiomics help to

  2. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Jaffe, J. S.; Chambers, J. T.

    2005-01-01

    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  3. Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.

    PubMed Central

    Wooldridge, A A; Gill, M S; Lemarchand, T; Eilts, B; Taylor, H W; Otterson, T

    1999-01-01

    A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed. Images Figure 1. PMID:10495911

  4. Hepatoid Adenocarcinoma of Unknown Primary Masquerading as a Pancreatic Tumor.

    PubMed

    Dogeas, Epameinondas; Peng, Lan; Choti, Michael A

    2017-12-01

    Hepatoid adenocarcinoma is a rare type of extrahepatic cancer characterized by hepatocellular carcinoma-like histology. We present a case of a large solitary mass in the peripancreatic region found to be an isolated lymph node metastasis from an unknown primary hepatoid adenocarcinoma masquerading as an acinar carcinoma of the pancreas.

  5. Comparison of glycoprotein expression between ovarian and colon adenocarcinomas.

    PubMed

    Multhaupt, H A; Arenas-Elliott, C P; Warhol, M J

    1999-10-01

    Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens. We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas. CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use in distinguishing between these 2 entities. A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot be distinguished from colonic adenocarcinomas using immunohistochemistry.

  6. Laparoscopic treatment of mucinous urachal adenocarcinoma with mucocele.

    PubMed

    Oberndoerfer, Marine; Bucher, Pascal; Caviezel, Alessandro; Platon, Alexandra; Ott, Vincent; Egger, Jean-François; Morel, Philippe

    2009-02-01

    We present a case of an asymptomatic 76-year-old woman treated laparoscopically for an urachal mucocele owing to a nonmetastatic urachal mucinous adenocarcinoma. Since laparoscopic en bloc resection of the urachus and partial cystectomy, the patient has been healthy and disease-free for 12 months. Modern surgical treatment of urachal adenocarcinoma is discussed in the light of this case.

  7. Frequent Overexpression of Aurora Kinase A in Upper Gastrointestinal Adenocarcinomas Correlates With Potent Antiapoptotic Functions

    PubMed Central

    Dar, Altaf A.; Zaika, Alexander; Piazuelo, Maria B.; Correa, Pelayo; Koyama, Tatsuki; Belkhiri, Abbes; Washington, Kay; Castells, Antoni; Pera, Manuel; El-Rifai, Wael

    2014-01-01

    BACKGROUND Upper gastrointestinal adenocarcinomas are a common cause of cancer-related deaths. In this study, the authors investigated the prevalence and biological significance of Aurora Kinase A (AURKA) overexpression in upper gastrointestinal adenocarcinomas. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining on tumor tissue microarrays (TMA) were used to study the expression of AURKA in upper gastrointestinal adenocarcinomas. To investigate the biological and signaling impact of AURKA, the authors used multiple in vitro assays that included 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), TUNEL (terminal deoxynucleotidyl transferase–mediated nick-end labeling), cytochrome C release, flow cytometry, luciferase reporter, and Western blot analysis. RESULTS Frequent overexpression of AURKA transcript in upper gastrointestinal adenocarcinomas was detected compared with normal samples (47%; P = .001). The immunohistochemical analysis of 130 tumors demonstrated moderate-to-strong immunostaining of AURKA in >50% of upper gastrointestinal adenocarcinomas. By using camptothecin as a drug-induced apoptosis in vitro model, the authors demonstrated that the expression of AURKA provided protection against apoptosis to gastrointestinal cancer cells (AGS and RKO) (P =.006) and RIE-1 primary intestinal epithelial cells (P =.001). The AURKA overexpression mediated an increase in phosphorylation of AKTSer473 with an increase in HDM2 level. The shRNA-knockdown of AKT in AURKA-overexpressing cells reversed this effect and showed a significant increase in the p53 protein level, indicating a possible nexus of AURKA/AKT/p53. Indeed, overexpression of AURKA led to a remarkable reduction in the transcription activity of p53, with subsequent reductions in transcript and protein levels of its downstream proapoptotic transcription targets (p21, BAX, NOXA, and PUMA). CONCLUSIONS Study results indicated that AURKA provides

  8. CT-based Radiomics Signature to Discriminate High-grade From Low-grade Colorectal Adenocarcinoma.

    PubMed

    Huang, Xiaomei; Cheng, Zixuan; Huang, Yanqi; Liang, Cuishan; He, Lan; Ma, Zelan; Chen, Xin; Wu, Xiaomei; Li, Yexing; Liang, Changhong; Liu, Zaiyi

    2018-03-01

    To develop and validate a computed tomography-based radiomics signature for preoperatively discriminating high-grade from low-grade colorectal adenocarcinoma (CRAC). This retrospective study was approved by our institutional review board, and the informed consent requirement was waived. This study enrolled 366 patients with CRAC (training dataset: n = 222, validation dataset: n = 144) from January 2008 to August 2015. A radiomics signature was developed with the least absolute shrinkage and selection operator method in training dataset. Mann-Whitney U test was applied to explore the correlation between radiomics signature and histologic grade. The discriminative power of radiomics signature was investigated with the receiver operating characteristics curve. An independent validation dataset was used to confirm the predictive performance. We further performed a stratified analysis to validate the predictive performance of radiomics signature in colon adenocarcinoma and rectal adenocarcinoma. The radiomics signature demonstrated discriminative performance for high-grade and low-grade CRAC, with an area under the curve of 0.812 (95% confidence interval [CI]: 0.749-0.874) in training dataset and 0.735 (95%CI: 0.644-0.826) in validation dataset. Stratified analysis demonstrated that radiomics signature also showed distinguishing ability for histologic grade in both colon adenocarcinoma and rectal adenocarcinoma, with area under the curve of 0.725 (95%CI: 0.653-0.797) and 0.895 (95%CI: 0.838-0.952), respectively. We developed and validated a radiomics signature as a complementary tool to differentiate high-grade from low-grade CRAC preoperatively, which may make contribution to personalized treatment. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  9. Adenocarcinoma metastasis causing discrete extraocular muscle enlargement.

    PubMed

    Slagle, William Scott; Eckermann, Daniel R; Musick, Angela N; Slagle, Amber M

    2009-07-01

    Discrete extraocular muscle (EOM) metastasis is rarely reported. Clinical signs and symptoms of EOM metastasis can often be indistinguishable from primary idiopathic orbital myositis, posing a significant clinical challenge. A case of a 61-year-old man with acute-onset unilateral periorbital pain and diplopia is presented. Magnetic resonance imaging showed an isolated edematous superior rectus/levator muscle complex with an isointense T2-weighted signal, supporting a diagnosis of orbital myositis. He was started on corticosteroids, with resolution of pain and improved motilities. Subsequently, his condition worsened. Repeat imaging results suggested the possibility of neoplastic infiltration of the muscle because of the newly demonstrated hyperintensity of the T2-weighted signal and perineural extension along the trigeminal nerve. Fine-needle aspiration biopsy showed adenocarcinoma cytology in the muscle. This case illustrates discrete adenocarcinoma metastasis of an EOM, initially displaying characteristics predominantly consistent with orbital myositis. There is a paucity of epidemiologic data on EOM cancer, and clinical characteristics are derived only from a selection of case reports in the literature. Thus, the predominant features of global orbital metastatic cancer versus primary inflammation are highlighted in this presentation. This case shows that the variable characteristics of each process prohibit identification of any clinical feature that would prove pathognomonic for either disorder. The varied practice philosophies and standard of care regarding the proper time to biopsy are reviewed. This case shows the importance of early referral for orbital biopsy, even in the presentation of isolated, discretely edematous, and painful EOM enlargement.

  10. Incidental adenocarcinoma in patients undergoing surgery for stricturing Crohn's disease

    PubMed Central

    Kristo, Ivan; Riss, Stefan; Argeny, Stanislaus; Maschke, Svenja; Chitsabesan, Praminthra; Stift, Anton

    2017-01-01

    AIM To evaluate frequency and clinical course of incidental adenocarcinoma in patients with stricturing Crohn's disease (CD). METHODS In this study, consecutive patients, who were operated on for stricturing CD between 1997-2012, were included at an academic tertiary referral center. Demographic data and clinical course were obtained by an institutional database and individual chart review. Besides baseline characteristics, intraoperative findings and CD related history were also recorded. Colorectal cancer was classified and staged according to the Union for International Cancer Control (UICC). RESULTS During the study period 484 patients underwent resections due to stricturing CD. Incidental adenocarcinoma was histologically confirmed in 6 (1.2%) patients (4 males, 2 females). Patients diagnosed with colorectal cancer had a median age of 43 (27-66) years and a median history of CD of 16 (7-36) years. Malignant lesions were found in the rectum (n = 4, 66.7%), descending colon (n = 1, 16.7%) and ileocolon (n = 1, 16.7%). According to the UICC classification two patients were stages as I (33.3%), whereas the other patients were classified as stage IIA (16.7%), stage IIIB (16.7%), stage IIIC (16.7%) and stage IV (16.7%), respectively. After a median follow-up of 2 (0.03-8) years only 1 patient is still alive. CONCLUSION The frequency of incidental colorectal cancer in patients, who undergo surgery for stenotic CD, is low but associated with poor prognosis. However, surgeons need to be aware about the possibility of malignancy in stricturing CD, especially if localized in the rectum. PMID:28210083

  11. Epidermal growth factor receptor mutations in adenocarcinoma in situ and minimally invasive adenocarcinoma detected using mutation-specific monoclonal antibodies.

    PubMed

    Nakamura, Haruhiko; Koizumi, Hirotaka; Kimura, Hiroyuki; Marushima, Hideki; Saji, Hisashi; Takagi, Masayuki

    2016-09-01

    Epidermal growth factor receptor (EGFR) mutation rates in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) were studied using both DNA analysis and mutation-specific immunohistochemistry. The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used to detect mutations in exons 18, 19, 20, and 21 of the EGFR gene in DNA samples extracted from paraffin-embedded tissue sections. Simultaneously, immunohistochemical analysis with two EGFR mutation-specific monoclonal antibodies was used to identify proteins resulting from an in-frame deletion in exon 19 (E746_A750del) and a point mutation replacing leucine with arginine at codon 858 of exon 21 (L858R). Forty-three tumors (22 AIS and 21 MIA) were examined. The EGFR mutation rate in AIS detected by DNA analysis was 27.3% (L858R, 5/22; exon 19 deletion,1/22), whereas that detected in MIA was 42.9% (L858R,4/21; exon 19 deletion,5/21). Mutations detected by immunohistochemical analysis included 22.7% (L858R, 4/22; exon 19 deletion, 1/22) in AIS and 42.9% (L858R, 4/21; exon 19 deletion, 5/21) in MIA. Although some results were contradictory, concordant results were obtained using both assays in 38 of 43 cases (88.4%). DNA and immunohistochemical analyses revealed similar EGFR mutation rates in both MIA and AIS, suggesting that mutation-specific monoclonal antibodies are useful to confirm DNA assay results. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Molecular profiling identifies prognostic markers of stage IA lung adenocarcinoma.

    PubMed

    Zhang, Jie; Shao, Jinchen; Zhu, Lei; Zhao, Ruiying; Xing, Jie; Wang, Jun; Guo, Xiaohui; Tu, Shichun; Han, Baohui; Yu, Keke

    2017-09-26

    We previously showed that different pathologic subtypes were associated with different prognostic values in patients with stage IA lung adenocarcinoma (AC). We hypothesize that differential gene expression profiles of different subtypes may be valuable factors for prognosis in stage IA lung adenocarcinoma. We performed microarray gene expression profiling on tumor tissues micro-dissected from patients with acinar and solid predominant subtypes of stage IA lung adenocarcinoma. These patients had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China in 2012. No patient had preoperative treatment. We performed the Gene Set Enrichment Analysis (GSEA) analysis to look for gene expression signatures associated with tumor subtypes. The histologic subtypes of all patients were classified according to the 2015 WHO lung Adenocarcinoma classification. We found that patients with the solid predominant subtype are enriched for genes involved in RNA polymerase activity as well as inactivation of the p53 pathway. Further, we identified a list of genes that may serve as prognostic markers for stage IA lung adenocarcinoma. Validation in the TCGA database shows that these genes are correlated with survival, suggesting that they are novel prognostic factors for stage IA lung adenocarcinoma. In conclusion, we have uncovered novel prognostic factors for stage IA lung adenocarcinoma using gene expression profiling in combination with histopathology subtyping.

  13. Secondhand Tobacco Smoke Exposure and Lung Adenocarcinoma In Situ/Minimally Invasive Adenocarcinoma (AIS/MIA).

    PubMed

    Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; Boffetta, Paolo; Xie, Dong; Wampfler, Jason A; Cote, Michele L; Chang, Shen-Chih; Ugolini, Donatella; Neri, Monica; Le Marchand, Loic; Schwartz, Ann G; Morgenstern, Hal; Christiani, David C; Yang, Ping; Zhang, Zuo-Feng

    2015-12-01

    The aim of this study was to estimate the effect of exposure to secondhand tobacco smoke on the incidence of lung adenocarcinoma in situ/minimally invasive adenocarcinoma (AIS/MIA). Data from seven case-control studies participating in the International Lung Cancer Consortium (ILCCO) were pooled, resulting in 625 cases of AIS/MIA and 7,403 controls, of whom 170 cases and 3,035 controls were never smokers. Unconditional logistic regression was used to estimate adjusted ORs (ORadj) and 95% confidence intervals (CI), controlling for age, sex, race, smoking status (ever/never), and pack-years of smoking. Study center was included in the models as a random-effects intercept term. Ever versus never exposure to secondhand tobacco smoke was positively associated with AIS/MIA incidence in all subjects (ORadj = 1.48; 95% CI, 1.14-1.93) and in never smokers (ORadj = 1.45; 95% CI, 1.00-2.12). There was, however, appreciable heterogeneity of ORadj across studies (P = 0.01), and the pooled estimates were largely influenced by one large study (40% of all cases and 30% of all controls). These findings provide weak evidence for an effect of secondhand tobacco smoke exposure on AIS/MIA incidence. Further studies are needed to assess the impact of secondhand tobacco smoke exposure using the newly recommended classification of subtypes of lung adenocarcinoma. ©2015 American Association for Cancer Research.

  14. Optic nerve metastasis caused by lung adenocarcinoma.

    PubMed

    Hernández Pardines, F; Molina Martín, J C; Fernández Montalvo, L; Juárez Marroquí, A

    2017-11-01

    Isolated optic nerve metastases are extremely uncommon. Many cases are associated with involvement from locations such as the choroid, orbit, or central nervous system. Optic nerve metastases often have their origin in primary tumours of the breast, lung, and stomach, in adults. The case is presented of a 57 year-old woman with a diagnosis of lung adenocarcinoma. Her first complaint was a sudden loss of visual acuity in her right eye. The diagnosis of optic nerve metastases was made based on her history, and the results of the MRI scan. Isolated optic nerve metastases are an uncommon condition, but should be suspected in any patient with a history of oncology who has deteriorated visual acuity. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    NASA Astrophysics Data System (ADS)

    Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.

    2014-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.

  16. Biomarkers in pancreatic adenocarcinoma: current perspectives

    PubMed Central

    Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. PMID:28003762

  17. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.

    PubMed

    2017-08-14

    We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The Troublesome Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma.

    PubMed

    Schneider, Jennifer L; Corley, Douglas A

    2017-07-01

    Barrett's esophagus and esophageal adenocarcinoma diagnoses have increased markedly in recent decades. Recent research with patients diagnosed with Barrett's esophagus (the only known precursor for esophageal adenocarcinoma) and esophageal adenocarcinoma has identified several modifiable and nonmodifiable potential risk factors. Consistent risk factors for both disorders include increasing age, male sex, white non-Hispanic race/ethnicity, gastroesophageal reflux disease, lack of infection with Helicobacter pylori, smoking, abdominal obesity, and a Western diet. The authors present detailed discussions of these risk factors along with possible explanations for some apparent discrepancies and ideas for future study. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Gene Expression-Based Survival Prediction in Lung Adenocarcinoma: A Multi-Site, Blinded Validation Study

    PubMed Central

    Shedden, Kerby; Taylor, Jeremy M.G.; Enkemann, Steve A.; Tsao, Ming S.; Yeatman, Timothy J.; Gerald, William L.; Eschrich, Steve; Jurisica, Igor; Venkatraman, Seshan E.; Meyerson, Matthew; Kuick, Rork; Dobbin, Kevin K.; Lively, Tracy; Jacobson, James W.; Beer, David G.; Giordano, Thomas J.; Misek, David E.; Chang, Andrew C.; Zhu, Chang Qi; Strumpf, Dan; Hanash, Samir; Shepherd, Francis A.; Ding, Kuyue; Seymour, Lesley; Naoki, Katsuhiko; Pennell, Nathan; Weir, Barbara; Verhaak, Roel; Ladd-Acosta, Christine; Golub, Todd; Gruidl, Mike; Szoke, Janos; Zakowski, Maureen; Rusch, Valerie; Kris, Mark; Viale, Agnes; Motoi, Noriko; Travis, William; Sharma, Anupama

    2009-01-01

    Although prognostic gene expression signatures for survival in early stage lung cancer have been proposed, for clinical application it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) can be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas. PMID:18641660

  20. Duodenal Bulb Adenocarcinoma Benefitted from Neoadjuvant Chemotherapy: A Case Report.

    PubMed

    Zhang, Geng-Yuan; Mao, Jie; Zhao, Bin; Long, Bo; Zhan, Hao; Zhang, Jun-Qiang; Zhou, Hui-Nian; Guo, Ling-Yun; Jiao, Zuo-Yi

    2017-01-01

    Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary tract which has a low incidence rate and nonspecific symptoms. It is difficult to diagnose early, and the misdiagnosis rate is high. CT, MRI, upper gastrointestinal endoscopy, and other advanced imaging modalities should be combined to make a comprehensive evaluation. The diagnostic confirmation of this tumor type mainly depends on the pathological examination. The combination of surgery with other treatment modalities is effective. A review of reports on duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990. However, there are few reports on neoadjuvant chemotherapy for the disease. In this report, preoperative S-1 in combination with oxaliplatin neoadjuvant chemotherapy achieved a complete pathological response in the treatment of duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to be further verified. © 2017 S. Karger AG, Basel.

  1. Adenocarcinoma of the Minor Duodenal Papilla: Report of a Case

    PubMed Central

    Takami, Kazuhiro; Moriya, Takuya; Kamiga, Takahiro; Abe, Tomoya; Miseki, Tetsuya; Oku, Takatomi; Aoki, Yasutaka; Tominaga, Tsuyoshi

    2011-01-01

    An 81-year-old male was found to have a duodenal tumor by screening upper gastrointestinal endoscopy. The tumor was located in the minor duodenal papilla. Pathological examination of the biopsy specimen revealed adenocarcinoma, and endoscopic ultrasound showed an elevated hypoechoic mass in the minor duodenal papilla. The preoperative diagnosis was therefore considered to be either adenocarcinoma of the minor duodenal papilla or duodenal cancer. We performed a subtotal stomach-preserving pancreaticoduodenectomy. Histopathological examination of the resected specimen showed the tumor cells to be primarily located in the submucosa of the minor duodenal papilla, with slight invasion into the pancreatic parenchyma through the accessory pancreatic duct. We therefore diagnosed a primary adenocarcima of the minor duodenal papilla. Adenocarcinoma of the minor duodenal papilla is considered to be a rare disease, but it may be underestimated because of the difficulty in distinguishing advanced adenocarcinoma of the minor duodenal papilla from primary duodenal cancer and cancer of the pancreatic head. PMID:21552440

  2. Radiomics Approach to Prediction of Occult Mediastinal Lymph Node Metastasis of Lung Adenocarcinoma.

    PubMed

    Zhong, Yan; Yuan, Mei; Zhang, Teng; Zhang, Yu-Dong; Li, Hai; Yu, Tong-Fu

    2018-04-18

    The purpose of this study was to evaluate the prognostic impact of radiomic features from CT scans in predicting occult mediastinal lymph node (LN) metastasis of lung adenocarcinoma. A total of 492 patients with lung adenocarcinoma who underwent preoperative unenhanced chest CT were enrolled in the study. A total of 300 radiomics features quantifying tumor intensity, texture, and wavelet were extracted from the segmented entire-tumor volume of interest of the primary tumor. A radiomics signature was generated by use of the relief-based feature method and the support vector machine classification method. A ROC regression curve was drawn for the predictive performance of radiomics features. Multivariate logistic regression models based on clinicopathologic and radiomics features were compared for discriminating mediastinal LN metastasis. Clinical variables (sex, tumor diameter, tumor location) and predominant subtype were risk factors for pathologic mediastinal LN metastasis. The accuracy of radiomics signature for predicting mediastinal LN metastasis was 91.1% in ROC analysis (AUC, 0.972; sensitivity, 94.8%; specificity, 92%). Radiomics signature (Akaike information criterion [AIC] value, 80.9%) showed model fit superior to that of the clinicohistopathologic model (AIC value, 61.1%) for predicting mediastinal LN metastasis. The radiomics signature of a primary tumor based on CT scans can be used for quantitative and noninvasive prediction of occult mediastinal LN metastasis of lung adenocarcinoma.

  3. HER3 expression is enhanced during progression of lung adenocarcinoma without EGFR mutation from stage 0 to IA1.

    PubMed

    Kumagai, Toru; Tomita, Yasuhiko; Nakatsuka, Shin-Ichi; Kimura, Madoka; Kunimasa, Kei; Inoue, Takako; Tamiya, Motohiro; Nishino, Kazumi; Susaki, Yoshiyuki; Kusu, Takashi; Tokunaga, Toshiteru; Okami, Jiro; Higashiyama, Masahiko; Imamura, Fumio

    2018-04-01

    Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood. In this paper, we focused on which receptor is correlated with lung adenocarcinoma progression in the presence or absence of EGFR mutation from stage 0 to IA1. HER2 and HER3 expression and activating EGFR mutations in surgically resected lung adenocarcinoma exhibiting ground glass nodules on chest computed tomography and re-classified to stage 0 and IA1 were examined by immunohistochemistry and peptide nucleic acid-locked nucleic acid PCR clamp method, respectively. HER2 and HER3 expression was detected in 22.2% and 86.1% of samples, respectively. The frequency of EGFR mutation was 45.7% and was not significantly different between stage 0 and IA1 (40.0% and 48.0%, respectively), suggesting that EGFR mutation does not correlate with cancer progression from stage 0 to IA1. HER2 expression also did not correlate to progression. However, not only the frequency, but also the intensity of HER3 expression was increased in stage IA1 lung adenocarcinoma, particularly in lung adenocarcinoma without EGFR mutation. HER3 tends to be intensively expressed during the progression of lung adenocarcinoma without EGFR mutation from carcinoma in situ to invasive carcinoma. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  4. Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium

    PubMed Central

    Villaruz, Liza C.; Socinski, Mark A.; Abberbock, Shira; Berry, Lynne D.; Johnson, Bruce E.; Kwiatkowski, David J; Iafrate, A. John; Varella-Garcia, Marileila; Franklin, Wilbur A.; Camidge, D. Ross; Sequist, Lecia V.; Haura, Eric B.; Ladanyi, Mark; Kurland, Brenda F.; Kugler, Kelly; Minna, John D; Bunn, Paul A.; Kris, Mark G.

    2014-01-01

    (1) PURPOSE The advent of effective targeted therapy in BRAFV600E mutant lung adenocarcinomas necessitates further exploration of the unique clinical features and behavior of advanced stage BRAF mutant lung adenocarcinomas. (2) PATIENTS AND METHODS We reviewed data from patients with advanced lung adenocarcinomas enrolled in the Lung Cancer Mutation Consortium whose tumors underwent testing for mutations in EGFR, KRAS, HER2, AKT1, BRAF, MEK1, NRAS, PIK3CA, ALK translocations, and MET amplification. (3) RESULTS Twenty-one BRAF mutations were identified in 951 patients with adenocarcinomas (2.2%: 95% CI 1.4 to 3.4%); 17 (81%: 95% CI 60 to 92%) were BRAFV600E and 4 were non-BRAFV600E mutations. Among the 733 cases tested for all 10 genes, BRAF mutations were more likely to occur in current or former smokers than most other genotypic abnormalities (BRAF versus sensitizing EGFR: 82% versus 36%, mid-P<0.001; versus ALK: 39%, mid-P=0.003; versus other mutations: 49%, mid-P=0.02; versus patients with more than one oncogenic driver (doubleton): 46%, mid-P=0.04.) The double mutation rate among patients with BRAF mutations was 16%, compared with 5% in patients with other genomic abnormalities (mid-P=0.045). Differences were not found in survival between patients with BRAF mutations and those with other genomic abnormalities (P>0.20). (4) CONCLUSIONS We demonstrate BRAF mutations occur in 2.2% of advanced stage lung adenocarcinomas, were most commonly V600E, were associated with distinct clinicopathologic features compared with other genomic subtypes and a high mutation rate in more than one gene, underscoring the importance of comprehensive genomic profiling in assessing patients with advanced lung adenocarcinomas. PMID:25273224

  5. Clinicopathological Significance of Micropapillary Pattern in Lung Adenocarcinoma.

    PubMed

    Pyo, Jung-Soo; Kim, Joo Heon

    2017-07-06

    The aim of this study was to elucidate the clinicopathological characteristics of the micropapillary (MP) subtype and its correlation with survival in lung adenocarcinoma. We investigated the clinicopathological characteristics, including the incidence, sex, smoking history, tumor size, lymph node metastasis, lymphovascular invasion, distant metastasis, genetic alteration, and prognosis in lung adenocarcinoma with the MP pattern through a meta-analysis. From 48 eligible studies, 19,502 lung adenocarcinomas were included. The incidence rate of the MP pattern was 0.101 [95% confidence interval (CI) 0.075-0.136]. There was no significant difference between stage I and III tumors. Lung adenocarcinoma with the MP pattern showed higher rates of lymphatic invasion (0.526, 95% CI 0.403-0.645). MP pattern was found in 0.150 (95% CI 0.008-0.790) of lung adenocarcinoma with distant metastasis. In lung adenocarcinoma with the MP pattern, the estimated rates of ALK, EGFR, and KRAS mutations were 0.102 (95% CI 0.027-0.322), 0.620 (95% CI 0.444-0.769), and 0.118 (95% CI 0.027-0.393), respectively. The MP pattern of lung adenocarcinoma was significantly correlated with worse overall and disease-free survival rates (hazard ratio 1.704, 95% CI 1.216-2.387, and 2.082, 95% CI 1.541-2.813, respectively). Taken together, identification of the MP pattern in lung adenocarcinoma is useful for prediction of clinicopathological characteristics and prognosis of patients.

  6. Differential N-glycan patterns identified in lung adenocarcinoma by N-glycan profiling of formalin-fixed paraffin-embedded (FFPE) tissue sections.

    PubMed

    Wang, Xiaoning; Deng, Zaian; Huang, Chuncui; Zhu, Tong; Lou, Jiatao; Wang, Lin; Li, Yan

    2018-02-10

    N-glycan profiling is a powerful approach for analyzing the functional relationship between N-glycosylation and cancer. Current methods rely on either serum or fresh tissue samples; however, N-glycan patterns may differ between serum and tissue, as the proteins of serum originate from a variety of tissues. Furthermore, fresh tissue samples are difficult to ship and store. Here, we used a profiling method based on formalin-fixed paraffin-embedded (FFPE) tissue sections from lung adenocarcinoma patients. We found that our method was highly reproducible. We identified 58 N-glycan compositions from lung adenocarcinoma FFPE samples, 51 of which were further used for MS n -based structure prediction. We show that high mannose type N-glycans are upregulated, while sialylated N-glycans are downregulated in our FFPE lung adenocarcinoma samples, compared to the control samples. Our receiver operating characteristic (ROC) curve analysis shows that high mannose type and sialylated N-glycans are useful discriminators to distinguish between lung adenocarcinoma and control tissue. Together, our results indicate that expression levels of specific N-glycans correlate well with lung adenocarcinoma, and strongly suggest that our FFPE-based method will be useful for N-glycan profiling of cancer tissues. Glycosylation is one of the most important post-translational protein modifications, and is associated with several physiopathological processes, including carcinogenesis. In this study, we tested the feasibility of using formalin-fixed paraffin-embedded (FFPE) tissue sections to identify changes in N-glycan patterns and identified the differentially expressed N-glycans of lung adenocarcinoma. Our study shows that the FFPE-based N-glycan profiling method is useful for clinical diagnosis as well as identification of potential biomarkers, and our data expand current knowledge of differential N-glycan patterns of lung adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Conservative management of rectal adenocarcinoma by radiotherapy.

    PubMed

    Maingon, P; Guerif, S; Darsouni, R; Salas, S; Barillot, I; d'Hombres, A; Bône-Lepinoy, M C; Fraisse, J; Horiot, J C

    1998-03-15

    The aim of this study was to analyze the experience of Centre GF Leclerc for conservative and curative treatment by radiotherapy of low rectal cancer. A total of 151 patients received radiotherapy alone for rectal adenocarcinoma with curative intent. They were clinically staged according to size (T1 < 3 cm, and T2 > 3 cm) and depth of infiltration (A=superficial, and B=impaired mobility and T3 fixed). Over the past 6 years, rectal ultrasound (US) has been used systematically, compared with computed tomographic scan and magnetic resonance imaging when needed. Intracavitary contact X ray was given to 129 patients (69%), and brachytherapy in 45 of 151. External radiotherapy was used in 34 cases (22.5%). Complete response was obtained in 93%. Local failures were observed in 50 cases (28%); two occurred in pelvic nodes after intracavitary X rays. Size (tumors > 3 cm) and alteration of mobility significantly influenced the rate of local failure (p=0.009 and 0.007). The addition of external radiotherapy in patients with poor prognostic factors improved the local control rate. A total of 39 patients with recurrence were amenable to salvage surgery. After salvage treatment, the local control rate was 82% with unlimited follow-up. The 5-year actuarial survival rate was 57%, with a specific survival of 66%. There was no difference in local control or survival according to differentiation of the tumors and distance between anal margin and the inferior level of the lesion. Severe late effect (grade 3) was 3.8%. The sphincter preservation was obtained in 104 of 124 cases (84%). The sphincter function was judged to normal in 102 of 104 patients (98%). Intracavitary contact X ray is the treatment of choice for clinical Stage T1A rectal tumors. External radiotherapy significantly improved the results of treatment of tumors > 3 cm. Clinical staging and transrectal ultrasound allows a safe selection of indications. Radiotherapy alone may be proposed for selected cases as an

  8. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

    PubMed Central

    Travis, William D.; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G.; Geisinger, Kim R.; Yatabe, Yasushi; Beer, David G.; Powell, Charles A.; Riely, Gregory J.; Van Schil, Paul E.; Garg, Kavita; Austin, John H. M.; Asamura, Hisao; Rusch, Valerie W.; Hirsch, Fred R.; Scagliotti, Giorgio; Mitsudomi, Tetsuya; Huber, Rudolf M.; Ishikawa, Yuichi; Jett, James; Sanchez-Cespedes, Montserrat; Sculier, Jean-Paul; Takahashi, Takashi; Tsuboi, Masahiro; Vansteenkiste, Johan; Wistuba, Ignacio; Yang, Pan-Chyr; Aberle, Denise; Brambilla, Christian; Flieder, Douglas; Franklin, Wilbur; Gazdar, Adi; Gould, Michael; Hasleton, Philip; Henderson, Douglas; Johnson, Bruce; Johnson, David; Kerr, Keith; Kuriyama, Keiko; Lee, Jin Soo; Miller, Vincent A.; Petersen, Iver; Roggli, Victor; Rosell, Rafael; Saijo, Nagahiro; Thunnissen, Erik; Tsao, Ming; Yankelewitz, David

    2015-01-01

    Introduction Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection

  9. Prognostic Significance of Adenocarcinoma in situ, Minimally Invasive Adenocarcinoma, and Nonmucinous Lepidic Predominant Invasive Adenocarcinoma of the Lung in Patients with Stage I Disease

    PubMed Central

    Kadota, Kyuichi; Villena-Vargas, Jonathan; Yoshizawa, Akihiko; Motoi, Noriko; Sima, Camelia S.; Riely, Gregory J.; Rusch, Valerie W.; Adusumilli, Prasad S.; Travis, William D.

    2014-01-01

    According to the IASLC/ATS/ERS classification, the lepidic predominant pattern consists of 3 subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and nonmucinous lepidic predominant invasive adenocarcinoma. We reviewed tumor slides from 1038 patients with stage I lung adenocarcinoma, recording the percentage of each histologic pattern and measuring invasive tumor size. Tumors were classified according to the IASLC/ATS/ERS classification: 2 were AIS, 34 MIA, and 103 lepidic predominant invasive. Cumulative incidence of recurrence (CIR) was used to estimate the probability of recurrence. Patients with AIS and MIA experienced no recurrences. Patients with lepidic predominant invasive tumors had a lower risk of recurrence (5-year CIR, 8%) than non-lepidic predominant tumors (n=899; 19%; P=0.003). Patients with >50% lepidic pattern tumors experienced no recurrences (n=84), those with >10%–50% lepidic pattern tumors had an intermediate risk of recurrence (n=344; 5-year CIR, 12%), and those with ≤10% lepidic pattern tumors had the highest risk (n=610; 22%; P<0.001). CIR was lower for patients with ≤2 cm tumors than for those with >2–3 cm tumors (for both total and invasive tumor size), with the difference more pronounced for invasive tumor size (5-year CIR, 13% vs. 21% [total size; P=0.022] and 12% vs. 27% [invasive size; P<0.001]). Most patients with lepidic predominant adenocarcinoma who experienced a recurrence had potential risk factors, including sublobar resection with close margins (≤0.5 cm; n=2), 20%–30% micropapillary component (n=2), and lymphatic or vascular invasion (n=2). It therefore may be possible to identify lepidic predominant adenocarcinomas that carry a low or high risk of recurrence. PMID:24472852

  10. Pre-existing Pulmonary Diseases and Survival in Patients With Stage-dependent Lung Adenocarcinoma: A STROBE-compliant Article.

    PubMed

    Jian, Zhi-Hong; Huang, Jing-Yang; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Wu, Ming-Fang; Liaw, Yung-Po

    2016-03-01

    Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common lung diseases associated with lung cancer mortality. This study evaluated sex disparities in pre-existing pulmonary diseases and stage-dependent lung adenocarcinoma survival.Patients newly diagnosed with lung adenocarcinoma between 2003 and 2008 were identified using the National Health Insurance Research Database and Cancer Registry. Cases with lung adenocarcinoma were followed until the end of 2010. Survival curves were estimated by the Kaplan-Meier method. Cox proportional-hazard regression was used to calculate the hazard ratio (HR) of pre-existing asthma, COPD, and/or TB, and to estimate all-cause mortality risk in patients with different stages of lung adenocarcinoma.A total of 14,518 cases were identified with lung adenocarcinoma. Specifically, among men, the HRs for TB were 1.69 (95% confidence interval [CI], 1.10-2.58), 1.48 (95% CI, 1.14-1.93), and 1.27 (95% CI, 1.08-1.49) for individuals with stage I + II, III, and IV diseases, respectively. The HRs for asthma were 1.41 (95% CI, 1.00-1.99) in women with stage I + II and 1.14 (95% CI, 1.04-1.26) in men with stage IV disease. For pulmonary disease combinations in men, the HRs were 1.45 (95% CI, 1.12-1.89) for asthma + COPD + TB, 1.35 (95% CI, 1.12-1.63) for COPD + TB, 1.28 (95% CI, 1.01-1.63) for TB, and 1.15 (95%CI, 1.04-1.27) for asthma + COPD, respectively. For women with stage I + II disease, the HR was 6.94 (95% CI, 2.72-17.71) for asthma + COPD + TB.Coexistence of pre-existing pulmonary diseases increased mortality risk in men with adenocarcinoma. TB is at elevated risk of mortality among men with different stages of adenocarcinoma. Asthmatic women with early-stage adenocarcinoma had increased risk of mortality.

  11. Hepatoid adenocarcinoma of the stomach - a different histology for not so different gastric adenocarcinoma: a case report.

    PubMed

    Gálvez-Muñoz, Elisa; Gallego-Plazas, Javier; Gonzalez-Orozco, Verónica; Menarguez-Pina, Francisco; Ruiz-Maciá, José A; Morcillo, Miguel A

    2009-08-12

    Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.

  12. [Expression of MADD in lung adenocarcinoma tissues and its effects on proliferation and apoptosis of lung adenocarcinoma A549 cells].

    PubMed

    Wei, Yu-Ping; Wu, Jin-Xiang; Guo, Yuan-Fang; Sun, Gao-Ying; Zhang, Qiang; Bi, Wen-Xiang; Dong, Liang

    2012-04-01

    To investigate the expression of MAPK-activating death domain protein (MADD) in lung adenocarcinoma tissues and its effects on proliferation and apoptosis of lung adenocarcinoma A549 cells. Immunohistochemistry was used to detect the expression of MADD in lung normal and tumor tissues. The expression of IG20 gene in A549 cells was measured by reverse transcription polymerase chain reaction. A549 cells were transfected with pEYFP-MADD plasmids carrying MADD gene or pNL-SIN-GFP-MID lentiviral vectors used for RNA interference. MADD expression and cell proliferation and apoptosis were determined by Western blot, MTT assay, and flow cytometry. The expression levels of MADD were higher in lung adenocarcinoma and squamous cell carcinoma tissues than that in lung normal tissues, and lung adenocarcinoma tissues expressed more MADD than lung squamous cell carcinoma tissues. The transcript encoding MADD was expressed in A549 cells. The transfection of pEYFP-MADD plasmids could increase MADD expression and cell proliferation of A549 cells, while the A549 cells transfected with pNL-SIN-GFP-MID lentiviral vectors showed significantly decreases in the MADD level and proliferation. It is shown that MADD overexpression could inhibit A549 cell apoptosis, and knock down of MADD could promote apoptosis of them. The expression of MADD increases obviously in lung adenocarcinoma, and MADD can promote survival of lung adenocarcinoma cells by inhibiting apoptosis.

  13. Assessment of cytotoxicity of Portulaca oleracea Linn. against human colon adenocarcinoma and vero cell line

    PubMed Central

    Mali, Prashant Y.

    2015-01-01

    Background: Portulaca oleracea Linn. (Portulacaceae) is commonly known as purslane in English. In traditional system it is used to cure diarrhea, dysentery, leprosy, ulcers, asthma, and piles, reduce small tumors and inflammations. Aim: To assess cytotoxic potential of chloroform extract of P. oleracea whole plant against human colon adenocarcinoma (HCT-15) and normal (Vero) cell line. Materials and Methods: Characterization of chloroform extract of P. oleracea by Fourier transform infrared (FTIR) spectroscopy was performed. Cytotoxicity (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay was used for assessment of cytotoxic potential of chloroform extract of P. oleracea. The concentrations of 1000–0.05 μg/ml were used in the experiment. Doxorubicin was considered as standard reference drug. Results: FTIR spectrum showed the peak at 1019.52 and 1396.21 center. The 50% cell growth inhibition (IC50) of chloroform extract of P. oleracea and doxorubicin was 1132.02 μg/ml and 460.13 μg/ml against human colon adenocarcinoma and 767.60 μg/ml and 2392.71 μg/ml against Vero cell line, respectively. Conclusion: Chloroform extract of P. oleracea whole plant was less efficient or does not have cytotoxic activity against human colon adenocarcinoma cell line. It was not safe to normal Vero cell line. But, there is a need to isolate, identify, and confirm the phytoconstituents present in extract by sophisticated analytical techniques. PMID:27833374

  14. Usefulness of carcinoembryonic antigen in the diagnosis of small cell lung cancer combined with adenocarcinoma.

    PubMed

    Lei, Lei; Chen, Qixun; Wang, Zeng; Han, Na; Chen, Bo; Qin, Jing; Lu, Hong-Yang

    2017-10-01

    Small cell lung cancer (SCLC) includes pure SCLC and SCLC combined with other pathologies (C-SCLC). C-SCLC accounts for about 28% of all SCLCs subjected to surgical resection, but only about 1%-3% of C-SCLCs are detected by biopsy. Since less than 5% of SCLC patients are eligible for surgery, it is necessary to develop alternative methods for the detection of C-SCLC. We determined whether serum carcinoembryonic antigen (CEA) levels, which are usually elevated in lung adenocarcinomas, could be used to differentiate between pure SCLC and SCLC combined with adenocarcinoma. We reviewed the records of 41 SCLC patients (35 with pure SCLC, 6 with C-SCLC) who underwent surgical resection between 2000 and 2014 in Zhejiang Cancer Hospital. Their preoperative serum CEA levels were noted, and the relationship between CEA level and the type of SCLC was analyzed. Serum CEA levels >6ng/mL were found more frequently in C-SCLC patients than in pure SCLC patients (p = 0.031). No such difference was observed when a CEA cut-off of 5ng/mL was used (p = 0.316). A preoperative serum CEA of >6ng/mL may be used as a reference in the diagnosis of SCLC combined with adenocarcinoma.

  15. Comprehensive molecular characterization of gastric adenocarcinoma

    PubMed Central

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Penny, Robert; Gardner, Johanna; Kemkes, Ariane; Mallery, David; Morris, Scott; Shelton, Troy; Shelton, Candace; Curley, Erin; Alexopoulou, Iakovina; Engel, Jay; Bartlett, John; Albert, Monique; Park, Do-Youn; Dhir, Rajiv; Luketich, James; Landreneau, Rodney; Janjigian, Yelena Y.; Kelsen, David P.; Cho, Eunjung; Ladanyi, Marc; Tang, Laura; McCall, Shannon J.; Park, Young S.; Cheong, Jae-Ho; Ajani, Jaffer; Camargo, M. Constanza; Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu; Demchok, John A.; Eley, Greg; Mills Shaw, Kenna R.; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Davidsen, Tanja; Hutter, Carolyn M.; Sofia, Heidi J.; Burton, Robert; Chudamani, Sudha; Liu, Jia

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  16. Comprehensive molecular characterization of gastric adenocarcinoma.

    PubMed

    2014-09-11

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

  17. Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

    PubMed

    Coveler, Andrew L; Rossi, Gabriela R; Vahanian, Nicholas N; Link, Charles; Chiorean, E Gabriela

    2016-02-01

    Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

  18. Neoadjuvant chemotherapy in locally advanced duodenal adenocarcinoma

    PubMed Central

    Velandia, Carlos; Morales, Rafael Delgado; Coello, Carlos; Mendoza, Armando Gil; Pérez, Gabriel; Aguero, Emperatriz

    2018-01-01

    Duodenal adenocarcinoma (ADC) represents only 0.3% of gastrointestinal neoplasms. With the frequency being higher between the ages of 40 and 60, it is predominantly located in the second part of the duodenum and around the periampullary region. Symptoms are nonspecific, so the majority of patients present with advanced disease. Neoadjuvant chemotherapy is a therapeutic option that has not been well studied. The global literature includes only isolated reports on this subject. This is why we are presenting the following case: a 60-year-old female patient with a locally advanced, inoperable duodenal ADC received neoadjuvant chemotherapy. Having presented a favourable response as observed in the post-neoadjuvant extension studies, a pancreaticoduodenectomy was performed without any perioperative complications and with satisfactory progress. The final biopsy reported a complete pathological response. After being monitored for 34 months, the patient was free from locoregional and distant metastatic disease. During the last weeks of monitoring, she developed a second primary breast tumour, which has been corroborated by immunohistochemistry. PMID:29662529

  19. Genetics and biology of pancreatic ductal adenocarcinoma

    PubMed Central

    Ying, Haoqiang; Dey, Prasenjit; Yao, Wantong; Kimmelman, Alec C.; Draetta, Giulio F.; Maitra, Anirban; DePinho, Ronald A.

    2016-01-01

    With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses. A deeper understanding of cancer cell biology, particularly altered cancer cell metabolism and impaired DNA repair processes, is providing novel therapeutic strategies that show strong preclinical activity. Elucidation of tumor biology principles, most notably a deeper understanding of the complexity of immune regulation in the tumor microenvironment, has provided an exciting framework to reawaken the immune system to attack PDAC cancer cells. While the long road of translation lies ahead, the path to meaningful clinical progress has never been clearer to improve PDAC patient survival. PMID:26883357

  20. Impact of Sarcopenia on Outcomes Following Resection of Pancreatic Adenocarcinoma

    PubMed Central

    Peng, Peter; Hyder, Omar; Firoozmand, Amin; Kneuertz, Peter; Schulick, Richard D.; Huang, Donghang; Makary, Martin; Hirose, Kenzo; Edil, Barish; Choti, Michael A.; Herman, Joseph; Cameron, John L.; Wolfgang, Christopher L.

    2013-01-01

    Introduction Assessing patient-specific risk factors for long-term mortality following resection of pancreatic adenocarcinoma can be difficult. Sarcopenia—the measurement of muscle wasting—may be a more objective and comprehensive patient-specific factor associated with long-term survival. Methods Total psoas area (TPA) was measured on preoperative cross-sectional imaging in 557 patients undergoing resection of pancreatic adenocarcinoma between 1996 and 2010. Sarcopenia was defined as the presence of a TPA in the lowest sex-specific quartile. The impact of sarcopenia on 90-day, 1-year, and 3-year mortality was assessed relative to other clinicopathological factors. Results Mean patient age was 65.7 years and 53.1 % was male. Mean TPA among men (611 mm2/m2) was greater than among women (454 mm2/m2). Surgery involved pancreaticoduodenectomy (86.0 %) or distal pancreatectomy (14.0 %). Mean tumor size was 3.4 cm; 49.9 % and 88.5 % of patients had vascular and perineural invasion, respectively. Margin status was R0 (59.0 %) and 77.7 % patients had lymph node metastasis. Overall 90-day mortality was 3.1 % and overall 1- and 3-year survival was 67.9 % and 35.7 %, respectively. Sarcopenia was associated with increased risk of 3-year mortality (HR=1.68; P<0.001). Tumor-specific factors such as poor differentiation on histology (HR=1.75), margin status (HR=1.66), and lymph node metastasis (HR=2.06) were associated with risk of death at 3-years (all P<0.001). After controlling for these factors, sarcopenia remained independently associated with an increased risk of death at 3 years (HR=1.63; P<0.001). Conclusions Sarcopenia was a predictor of survival following pancreatic surgery, with sarcopenic patients having a 63 % increased risk of death at 3 years. Sarcopenia was an objective measure of patient frailty that was strongly associated with long-term outcome independent of tumor-specific factors. PMID:22692586

  1. Laparoscopic distal pancreatectomy for adenocarcinoma: safe and reasonable?

    PubMed Central

    Postlewait, Lauren M.

    2015-01-01

    As a result of technological advances during the past two decades, surgeons now use minimally invasive surgery (MIS) approaches to pancreatic resection more frequently, yet the role of these approaches for pancreatic ductal adenocarcinoma resections remains uncertain, given the aggressive nature of this malignancy. Although there are no controlled trials comparing MIS technique to open surgical technique, laparoscopic distal pancreatectomy for pancreatic adenocarcinoma is performed with increasing frequency. Data from retrospective studies suggest that perioperative complication profiles between open and laparoscopic distal pancreatectomy are similar, with perhaps lower blood loss and fewer wound infections in the MIS group. Concerning oncologic outcomes, there appear to be no differences in the rate of achieving negative margins or in the number of lymph nodes (LNs) resected when compared to open surgery. There are limited recurrence and survival data on laparoscopic compared to open distal pancreatectomy for pancreatic adenocarcinoma, but in the few studies that assess long term outcomes, recurrence rates and survival outcomes appear similar. Recent studies show that though laparoscopic distal pancreatectomy entails a greater operative cost, the associated shorter length of hospital stay leads to decreased overall cost compared to open procedures. Multiple new technologies are emerging to improve resection of pancreatic cancer. Robotic pancreatectomy is feasible, but there are limited data on robotic resection of pancreatic adenocarcinoma, and outcomes appear similar to laparoscopic approaches. Additionally fluorescence-guided surgery represents a new technology on the horizon that could improve oncologic outcomes after resection of pancreatic adenocarcinoma, though published data thus far are limited to animal models. Overall, MIS distal pancreatectomy appears to be a safe and reasonable approach to treating selected patients with pancreatic ductal

  2. Prognostic significance of PINCH signalling in human pancreatic ductal adenocarcinoma

    PubMed Central

    Scaife, Courtney L; Shea, Jill; Emerson, Lyska; Boucher, Kenneth; Firpo, Matthew A; Beckerle, Mary C; Mulvihill, Sean J

    2010-01-01

    Objective: Prognostic markers for pancreatic ductal adenocarcinoma (PDA) have failed to accurately predict patient prognosis. Recently, interest has developed in the accuracy of integrin-associated PINCH protein expression in human cancers as a predictive marker of tumour status. The goal of this study was to define the expression of PINCH protein in PDA. Methods: Human PDA samples and orthotopic tumours from a murine model were analysed by immunohistochemistry for PINCH expression. In the animal model, PINCH expression was compared between primary and metastatic tumours. In the human samples, PINCH expression was correlated with stage, nodal involvement, margin status and overall survival. Results: In the murine model, there was greater PINCH expression in metastatic tumours than in primary tumours. In the human PDA samples, greater staining for PINCH in the tumour cells was correlated with higher T status. Additionally, high PINCH expression in the stroma was associated with decreased overall survival. Conclusions: Findings of increased PINCH protein in more advanced stages of human PDA, as well as in metastatic tumours in the animal model, support the hypothesis that PINCH is an important controller of cell survival and migration. Additionally, the importance of the differential expression of PINCH in the human tumour and stroma warrants further evaluation. PMID:20590912

  3. Quantitative changes in adenosine deaminase isoenzymes in human colorectal adenocarcinomas.

    PubMed

    ten Kate, J; Wijnen, J T; van der Goes, R G; Quadt, R; Griffioen, G; Bosman, F T; Khan, P M

    1984-10-01

    Several reports have suggested that a decrease or absence of adenosine deaminase complexing protein (ADCP) is consistently associated with cancer. However, in other studies, decreased as well as increased ADCP levels were found. In the present study, we investigated ADCP levels in 37 colorectal adenocarcinomas and correlated the results with clinicopathological characteristics in individual carcinomas. The levels of adenosine deaminase (EC 3.5.4.4) and soluble ADCP were determined in tissue samples by, respectively, a spectrophotometric assay and an ADCP specific radioimmunoassay. The values in the individual tumors were compared with their histological characteristics, such as degree of differentiation, nuclear grading, and the preoperative plasma carcinoembryonic antigen levels in the patients. It was found that ADCP was decreased in about a third of the tumors but unaltered or even increased in others. However, there was an overall 40% increase of the adenosine deaminase activity in the tumors compared to normal tissue. There seems to be no simple correlation between any of the clinicopathological parameters and the ADCP or adenosine deaminase levels. Methods detecting ADCP at single cell level might be helpful in exploring its potential use as a cancer-associated marker.

  4. Visceral Thromboses in Pancreas Adenocarcinoma: Systematic Review.

    PubMed

    Hicks, Angel Mier; DeRosa, Antonio; Raj, Micheal; Do, Richard; Yu, Kenneth H; Lowery, Maeve A; Varghese, Anna; O'Reilly, Eileen M

    2017-12-12

    Within gastrointestinal malignancies, primary hepatocellular carcinoma and pancreatic ductal adenocarcinoma (PDAC) are frequently associated with visceral thromboses (VT). Thrombus formation in the portal (PVT), mesenteric (MVT), or splenic vein (SVT) system leads to portal hypertension and intestinal ischemia. VT in PDAC may convey a risk of increased distal thrombosis and poses therapeutic uncertainty regarding the role of anticoagulation. An increasing number of reports describe VT associated with PDAC. It is possible that early diagnosis of these events may help reduce morbidity and speculatively improve oncologic outcomes. To perform a systematic review to study PVT, MVT, and SVT associated with PDAC, and to provide a comprehensive review. Medline/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library. Data Extraction and Assessment: Two blinded independent observers extracted and assessed the studies for diagnosis of PVT, MVT, and SVT in PDAC. Studies were restricted to English-language literature published between 2007 and 2016. Eleven articles were identified. Five case reports and 7 retrospective studies were found, with a total of 127 patients meeting the inclusion criteria. The mean age at diagnosis was 64 years. PVT was found in 35% (n = 46), SVT in 52% (n = 65), and MVT in 13% (n = 15). Mean follow-up time was 26 months. Only 3 of the selected articles studied the impact of anticoagulation in VT. All patients with nonvisceral thrombosis (eg, deep-vein thrombosis, pulmonary emboli) were therapeutically treated; in contrast, patients with VT only rarely received treatment. VT in PDAC is a frequent finding at diagnosis or during disease progression. Evidence to guide treatment choices is limited, and current management is based on inferred experience from nononcologic settings. Anticoagulation appears to be safe in VT, with most of the large studies recommending a careful assessment for patients at a high risk of bleeding. Copyright © 2017

  5. Prognostic factors in adenocarcinoma of the salivary glands.

    PubMed

    Huang, Andrew T; Tang, Chad; Bell, Diana; Yener, Murat; Izquierdo, Luis; Frank, Steven J; El-Naggar, Adel K; Hanna, Ehab Y; Weber, Randal S; Kupferman, Michael E

    2015-06-01

    We aimed to characterize prognostic factors and outcomes in adenocarcinomas of the salivary glands. Patients were identified and retrospectively reviewed for clinical and pathologic tumor characteristics. Low and high grade adenocarcinoma histologies were separated and analyzed. Treatment regimens and patient-related outcomes were recorded and measured. A total of 51 adenocarcinomas of the salivary glands were reviewed. The most common locations of disease were the superficial lobe of the parotid gland, followed by the deep lobe. Five-year overall and disease free survival rates were 43% and 37%. Univariate analysis identified the following as negative prognostic factors: symptoms of a fixed mass or rapid growth, advanced tumor or nodal stage, and perineural or lymphovascular invasion. Facial nerve paralysis was not found to be a significant prognostic variable. Multivariate analysis confirmed the independent negative prognostic importance of the following characteristics: presentation with a fixed mass or rapid growth, diagnosis of adenocarcinoma not otherwise specified, and positive surgical margins. Our results identify several important prognostic factors associated with overall survival in adenocarcinoma of the salivary glands. These prognostic variables encompass symptoms on presentation, clinical and pathologic tumor stage characteristics, and treatment-related factors; all of which are important in patient counseling and may provide impetus for determining treatment escalation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing

    PubMed Central

    Imielinski, Marcin; Berger, Alice H.; Hammerman, Peter S.; Hernandez, Bryan; Pugh, Trevor J.; Hodis, Eran; Cho, Jeonghee; Suh, James; Capelletti, Marzia; Sivachenko, Andrey; Sougnez, Carrie; Auclair, Daniel; Lawrence, Michael; Stojanov, Petar; Cibulskis, Kristian; Choi, Kyusam; de Waal, Luc; Sharifnia, Tanaz; Brooks, Angela; Greulich, Heidi; Banerji, Shantanu; Zander, Thomas; Seidel, Danila; Leenders, Frauke; Ansén, Sascha; Ludwig, Corinna; Engel-Riedel, Walburga; Stoelben, Erich; Wolf, Jürgen; Goparju, Chandra; Thompson, Kristin; Winckler, Wendy; Kwiatkowski, David; Johnson, Bruce E.; Jänne, Pasi A.; Miller, Vincent A.; Pao, William; Travis, William D.; Pass, Harvey; Gabriel, Stacey; Lander, Eric; Thomas, Roman K.; Garraway, Levi A.; Getz, Gad; Meyerson, Matthew

    2012-01-01

    SUMMARY Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, is responsible for over 500,000 deaths per year worldwide. Here, we report exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history and alterations of reported lung adenocarcinoma genes. Whole genome sequence analysis revealed frequent structural re-arrangements, including in-frame exonic alterations within EGFR and SIK2 kinases. The candidate genes identified in this study are attractive targets for biological characterization and therapeutic targeting of lung adenocarcinoma. PMID:22980975

  7. Lung adenocarcinoma mimicking pulmonary fibrosis-a case report.

    PubMed

    Mehić, Bakir; Duranović Rayan, Lina; Bilalović, Nurija; Dohranović Tafro, Danina; Pilav, Ilijaz

    2016-09-13

    Lung cancer is usually presented with cough, dyspnea, pain and weight loss, which is overlapping with symptoms of other lung diseases such as pulmonary fibrosis. Pulmonary fibrosis shows characteristic reticular and nodular pattern, while lung cancers are mostly presented with infiltrative mass, thick-walled cavitations or a solitary nodule with spiculated borders. If the diagnosis is established based on clinical symptoms and CT findings, it would be a misapprehension. We report a case of lung adenocarcinoma whose symptoms as well as clinical images overlapped strongly with pulmonary fibrosis. The patient's non-productive cough, progressive dyspnea, restrictive pattern of pulmonary function test and CT scans (showing reticular interstitial opacities) were all indicative of pulmonary fibrosis. The patient underwent a treatment consisting of corticosteroids and antibiotics, to no avail. Histopathology of the lung showed that the patient suffered from mucinous adenocarcinoma. Albeit the immunohistochemical staining was not consistent with lung adenocarcinoma, tumor's morphological characteristics were consistent, and were used to make the definitive diagnosis. Given the fact that radiography cannot always make a clear-cut difference between pulmonary fibrosis and lung adenocarcinomas, and that clinical symptoms often overlap, histological examination should be considered as gold standard for diagnosis of lung adenocarcinoma.

  8. Next-generation sequencing for molecular diagnosis of lung adenocarcinoma specimens obtained by fine needle aspiration cytology

    NASA Astrophysics Data System (ADS)

    Qiu, Tian; Guo, Huiqin; Zhao, Huan; Wang, Luhua; Zhang, Zhihui

    2015-06-01

    Identification of multi-gene variations has led to the development of new targeted therapies in lung adenocarcinoma patients, and identification of an appropriate patient population with a reliable screening method is the key to the overall success of tumor targeted therapies. In this study, we used the Ion Torrent next-generation sequencing (NGS) technique to screen for mutations in 89 cases of lung adenocarcinoma metastatic lymph node specimens obtained by fine-needle aspiration cytology (FNAC). Of the 89 specimens, 30 (34%) were found to harbor epidermal growth factor receptor (EGFR) kinase domain mutations. Seven (8%) samples harbored KRAS mutations, and three (3%) samples had BRAF mutations involving exon 11 (G469A) and exon 15 (V600E). Eight (9%) samples harbored PIK3CA mutations. One (1%) sample had a HRAS G12C mutation. Thirty-two (36%) samples (36%) harbored TP53 mutations. Other genes including APC, ATM, MET, PTPN11, GNAS, HRAS, RB1, SMAD4 and STK11 were found each in one case. Our study has demonstrated that NGS using the Ion Torrent technology is a useful tool for gene mutation screening in lung adenocarcinoma metastatic lymph node specimens obtained by FNAC, and may promote the development of new targeted therapies in lung adenocarcinoma patients.

  9. Triple-layer dissection of the lung adenocarcinoma transcriptome: regulation at the gene, transcript, and exon levels.

    PubMed

    Hsu, Min-Kung; Wu, I-Ching; Cheng, Ching-Chia; Su, Jen-Liang; Hsieh, Chang-Huain; Lin, Yeong-Shin; Chen, Feng-Chi

    2015-10-06

    Lung adenocarcinoma is one of the most deadly human diseases. However, the molecular mechanisms underlying this disease, particularly RNA splicing, have remained underexplored. Here, we report a triple-level (gene-, transcript-, and exon-level) analysis of lung adenocarcinoma transcriptomes from 77 paired tumor and normal tissues, as well as an analysis pipeline to overcome genetic variability for accurate differentiation between tumor and normal tissues. We report three major results. First, more than 5,000 differentially expressed transcripts/exonic regions occur repeatedly in lung adenocarcinoma patients. These transcripts/exonic regions are enriched in nicotine metabolism and ribosomal functions in addition to the pathways enriched for differentially expressed genes (cell cycle, extracellular matrix receptor interaction, and axon guidance). Second, classification models based on rationally selected transcripts or exonic regions can reach accuracies of 0.93 to 1.00 in differentiating tumor from normal tissues. Of the 28 selected exonic regions, 26 regions correspond to alternative exons located in such regulators as tumor suppressor (GDF10), signal receptor (LYVE1), vascular-specific regulator (RASIP1), ubiquitination mediator (RNF5), and transcriptional repressor (TRIM27). Third, classification systems based on 13 to 14 differentially expressed genes yield accuracies near 100%. Genes selected by both detection methods include C16orf59, DAP3, ETV4, GABARAPL1, PPAR, RADIL, RSPO1, SERTM1, SRPK1, ST6GALNAC6, and TNXB. Our findings imply a multilayered lung adenocarcinoma regulome in which transcript-/exon-level regulation may be dissociated from gene-level regulation. Our described method may be used to identify potentially important genes/transcripts/exonic regions for the tumorigenesis of lung adenocarcinoma and to construct accurate tumor vs. normal classification systems for this disease.

  10. Numb chin syndrome secondary to leptomeningeal carcinomatosis from gastric adenocarcinoma.

    PubMed

    Riesgo, Vincent J; Delgado, Silvia R; Poveda, Julio; Rammohan, Kottil

    2015-04-01

    Numb chin syndrome (NCS) can be a sign of malignancy. Its association with gastric adenocarcinoma is rare. We report a case of a 27-year-old Hispanic female that presented with complaint of left sided headache associated with numbness of the left side of chin and lower gingiva. Initial brain MRI, whole body gallium scan, high resolution CT of chest and elevated protein in the CSF were suggestive of sarcoidosis. She was treated with IV steroids with transient clinical improvement. Two weeks later, her symptoms worsened and further evaluation revealed the diagnosis of a poorly differentiated metastatic gastric adenocarcinoma with leptomeningeal involvement. This case report aims to emphasize the importance of identifying NCS as a possible indication of an underlying malignant condition. Reported cases of NCS associated with metastatic gastric adenocarcinoma are very rare.

  11. Numb chin syndrome secondary to leptomeningeal carcinomatosis from gastric adenocarcinoma

    PubMed Central

    Riesgo, Vincent J.; Poveda, Julio; Rammohan, Kottil

    2015-01-01

    Numb chin syndrome (NCS) can be a sign of malignancy. Its association with gastric adenocarcinoma is rare. We report a case of a 27-year-old Hispanic female that presented with complaint of left sided headache associated with numbness of the left side of chin and lower gingiva. Initial brain MRI, whole body gallium scan, high resolution CT of chest and elevated protein in the CSF were suggestive of sarcoidosis. She was treated with IV steroids with transient clinical improvement. Two weeks later, her symptoms worsened and further evaluation revealed the diagnosis of a poorly differentiated metastatic gastric adenocarcinoma with leptomeningeal involvement. This case report aims to emphasize the importance of identifying NCS as a possible indication of an underlying malignant condition. Reported cases of NCS associated with metastatic gastric adenocarcinoma are very rare. PMID:25830044

  12. Duodenal Adenocarcinoma of Brunner Gland Origin: A Case Report.

    PubMed

    Moon, Ji Hye; Lee, Kyoungbun; Yang, Han-Kwang; Kim, Woo Ho

    2017-12-27

    We report a case of adenocarcinoma originating from the duodenal Brunner glands in a 47-year-old female patient. The lesion was 0.8 cm in extent and located at the posterior wall of the first part of the duodenum. Histologically, the tumor showed transition from non-neoplastic Brunner glands through dysplastic epithelimmnto adenocarcinoma. The carcinoma cells were strongly positive for MUC6 protein, which is an epithelial marker for the Brunner glands. Tumor protein p53 was overexpressed in the carcinoma cells, but not in the non-neoplastic or dysplastic epithelium. Dystrophic calcification was predominant. This is the first case report of duodenal adenocarcinoma of Brunner gland origin in Korea.

  13. Duodenal adenocarcinoma presenting as a mass with aneurismal dilatation.

    PubMed

    Mama, Nadia; Ben Slama, Aïda; Arifa, Nadia; Kadri, Khaled; Sriha, Badreddine; Ksiaa, Mehdi; Jemni, Hela; Tlili-Graiess, Kalthoum

    2014-01-01

    Duodenal adenocarcinoma is frequent. Aneurysmal dilatation of the small bowel is reported to be a lymphoma characteristic imaging finding. A 57-year-old male was found to have a duodenal adenocarcinoma with aneurismal dilatation on imaging which is an exceptional feature. On laparotomy, the wall thickening of the dilated duodenum extended to the first jejunal loop, with multiple mesenteric lymph nodes and ascites. Segmental palliative resection with gastro-entero-anastomosis was done. Histopathology revealed a moderately differentiated adenocarcinoma with neuro-endocrine differentiation foci. Wide areas of necrosis and vascular emboli were responsible for the radiological feature of the dilated duodenum with wall thickening. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. [Extensive tumor of the skull base: sphenoid sinus adenocarcinoma].

    PubMed

    Kallel, Souha; Sellami, Moncef

    2017-01-01

    We report a rare case of adenocarcinoma of the sphenoid sinus manifesting as extended skull base tumor. The patient included in the study was a 42-year old woman presenting with unilateral right symptomatology consisting of nasal obstruction, diplopia and hemifacial neuralgias. Clinical examination showed paralysis of the cranial nerve pairs V and VI. Brain scanner showed voluminous heterogeneous sphenoid and clival mass reaching the right cavernous sinus, with a peripheral tissue component at the level of the sphenoid sinus. Biopsy was performed under general anesthesia, through endonasal sphenoidotomy approach. Histological examination showed non-intestinal adenocarcinoma. The patient died due to impaired general condition occurred during examinations. Skull base adenocarcinomas mainly occur in the ethmoid bone. Sphenoid origin is exceptional. Radiological appearance is not specific and suggests malignancy. Diagnosis should be suspected in patients with aggressive tumor, even when it occurs in the midline skull base.

  15. Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

    ClinicalTrials.gov

    2016-03-17

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

  16. Different histological status of gastritis in superficial adenocarcinoma of the esophagogastric junction.

    PubMed

    Yamada, Masayoshi; Kushima, Ryoji; Oda, Ichiro; Mojtahed, Kaveh; Nonaka, Satoru; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Matsubara, Akiko; Taniguchi, Hirokazu; Sekine, Shigeki; Saito, Yutaka; Shimoda, Tadakazu

    2014-01-01

    Although many gastric cancers arise in chronic gastritis, the association between adenocarcinoma of the esophagogastric junction and the status of background gastritis remains unclear. We aim to investigate the histological status of gastritis in the background fundic gland mucosa of adenocarcinoma of the esophagogastric junction. The present study included 121 consecutive patients with superficial adenocarcinoma of the esophagogastric junction obtained by surgical and/or endoscopic resection. We re-evaluated the histogenesis of adenocarcinoma of the esophagogastric junction, including the background fundic gland mucosa using the Updated Sydney System. The prevalence of histologic atrophic gastric mucosa with gastritis (positive gastritis), non-atrophic gastric mucosa without gastritis (negative gastritis) and Barrett's adenocarcinoma was examined. Histologic-positive gastritis was found in 67 (55%) of all patients, in 24 (38%) of 63 Barrett's adenocarcinoma patients and in 43 (74%) of 58 non-Barrett's adenocarcinoma patients (P < 0.01). A higher female ratio in non-Barrett's adenocarcinoma with gastritis patients `and younger age in non-Barrett's adenocarcinoma without gastritis patients were shown. There were no differences in clinicopathological features related to the gastritis status in Barrett's adenocarcinoma patients. Reflux esophagitis was observed in most (81%) of all patients, and 32 (74%) of the non-Barrett's adenocarcinoma with gastritis patients. In the 67 positive gastritis patients, the mean Updated Sydney System scores of glandular atrophy and intestinal metaplasia were 1.45 and 1.10, respectively, and these scores were higher in the non-Barrett's adenocarcinoma patients than in the Barrett's adenocarcinoma patients. This study suggests that about half of the patients with adenocarcinoma of the esophagogastric junction harbor histological gastritis. Adenocarcinoma of the esophagogastric junction is considered to be a heterogeneous entity, including

  17. Metastatic ampullary adenocarcinoma presenting as a hydrocele: a case report.

    PubMed

    Lane, Whitney O; Bentley, Rex C; Hurwitz, Herbert I; Howard, Leigh A; Polascik, Thomas J; Anderson, Mark R; Blazer, Dan G

    2014-05-27

    Metastases from ampullary malignancies are common, but spread to the testicle and paratesticular tissue is exceedingly rare with only 2 reported cases in the literature. We report a case of a 70 year-old male with a history of ampullary adenocarcinoma status post pancreaticoduodenectomy who presented with a symptomatic right-sided hydrocele. Subsequent pathology revealed metastatic ampullary adenocarcinoma. Metastasis to the testicle and paratesticular tissue from ampullary malignancies is rare, but must be considered in the evaluation of scrotal masses in patients with a history of ampullary malignancy.

  18. Collision tumors: pancreatic adenocarcinoma and mantle cell lymphoma.

    PubMed

    Dasanu, Constantin A; Shimanovsky, Alexei; Rotundo, Edyta K; Posteraro, Anthony F; Cooper, Dennis L; Atienza, Jonessa A

    2013-07-10

    Collision tumors are very rare entities composed of two or more distinct tumor components, each separated by normal tissue. Perhaps due to technical advances in the last decade, the incidence of collision tumors has been on the rise. To the best of our knowledge, collision tumors featuring mantle cell lymphoma and pancreatic adenocarcinoma have not been previously described in the scientific literature. For the first time, we describe herein the clinical course of a collision tumor between pancreatic adenocarcinoma and mantle cell lymphoma. We hypothesize several aspects in the pathogenesis of a such event and review the existing literature on collision tumors.

  19. Napsin A is a useful marker for metastatic adenocarcinomas of pulmonary origin.

    PubMed

    Kim, Moon-Young; Go, Heounjeong; Koh, Jaemoon; Lee, Kyoungbun; Min, Hye-Sook; Kim, Min-A; Jeon, Yoon Kyung; Lee, Hye-Seung; Moon, Kyung-Chul; Park, So Yeon; Kim, Woo-Ho; Chung, Doo Hyun

    2014-08-01

    To address whether napsin A is useful for identifying metastatic adenocarcinomas of pulmonary origin. Fifty-four cases of adenocarcinoma that metastasized from the lungs to various sites and 1762 cases of carcinoma from various organs were immunostained for napsin A, TTF-1, CK7, CK20 and CDX2 using tissue microarray. The expression patterns of napsin A and TTF-1 in metastatic pulmonary adenocarcinomas were compared with matched primary lung tumours. Napsin A and TTF-1 were expressed in 87.0% and 81.5% of the metastatic pulmonary adenocarcinomas, respectively. Although there was no significant difference in the positivity of napsin A and TTF-1 as a single marker in metastatic pulmonary adenocarcinomas, the expression scores for napsin A were much higher than those for TTF-1 (P < 0.001). Moreover, the positivity and expression scores of napsin A in primary pulmonary adenocarcinomas were maintained in metastatic adenocarcinomas better than TTF-1. Most non-pulmonary adenocarcinomas were negative for napsin A, except for renal cell carcinomas (13.4%), ovarian adenocarcinomas (7.1%) and uterine endometrial adenocarcinomas (14.5%). In particular, clear cell adenocarcinomas of ovary (68.8%) and uterus (66.7%) frequently expressed napsin A. These data suggest that napsin A may be a useful marker for identifying metastatic adenocarcinomas of pulmonary origin in combination with TTF-1. © 2014 John Wiley & Sons Ltd.

  20. An ultrastructural comparison of mesotheliomas and adenocarcinomas of the ovary and endometrium.

    PubMed

    Warhol, M J; Hunter, N J; Corson, J M

    1982-01-01

    The ultrastructural features of 16 malignant mesotheliomas were compared qualitatively and quantitatively with nine ovarian adenocarcinomas and 11 endometrial adenocarcinomas. The mesotheliomas could be distinguished ultrastructurally by their significantly greater content of tonofilaments (p less than 0.001) and their lack of structures found in both ovarian and endometrial adenocarcinomas, specifically abundant mucin, numerous cilia, and dense core granules of the neurosecretory type.

  1. [Clinicopathological features of low-grade nasopharyngeal papillary adenocarcinoma].

    PubMed

    Wu, Ruochen; Liu, Honggang

    2014-09-01

    To study the clinicopathological features, immunophenotype, differential diagnosis and prognosis of low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA). The histopathological features and clinical and pathological data of nine cases of LGNPPA were retrospectively analyzed. Immunohistochemistry (Two-step EnVision methods) was used to evaluate the expression of CKpan, vimentin, CK7, CK19, TTF-1 and TG; in situ hybridization was used to detect Epstein-Barr virus mRNA (EBER); and flow-through hybridization was used to evaluate the presence of human papilloma virus (HPV). The mean age for the nine patients (eight males, one female) was 45.3 years (range 23 to 62 years). Microscopically the tumors were characterized by lobulated, papillary and glandular structures with patchy distribution of spindle cells. The papillary interstitial tissue was edematous, myxoid or hyalinized. The tumors were unencapsulated and infiltrated into the surrounding stroma. Four cases displayed transition between normal nasopharyngeal epithelium to neoplastic cells; and one case contained psammoma bodies. Five cases were strongly positive for CKpan, vimentin, CK7, CK19, TTF-1, and were focally positive for EMA and CD117. These five cases were all negative for TG, CK5/6, CK20, S-100 protein, p63, Calponin and SMA. In situ hybridization for EBER and flow-through hybridization for HPV were negative in all five cases. Follow-up data showed no post-operative recurrence of the LGNPPA. LGNPPA is a rare low-grade neoplasm with distinct morphological characteristics. Its diagnosis is primarily based on the site of lesions and the histological features. The diagnosis and differential diagnosis of LGNPPA could be aided by immunohistochemical staining. LGNPPA may originate from nasopharyngeal epithelium; and the prognosis is good with simple and complete resection.

  2. DEK protein overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

    PubMed

    Sun, Jie; Bi, Fangfang; Yang, Yang; Zhang, Yuan; Jin, Aihua; Li, Jinzi; Lin, Zhenhua

    2017-02-01

    DEK, a transcription factor, is involved in mRNA splicing, transcriptional control, cell division and differentiation. Recent studies suggest that DEK overexpression can promote tumorigenesis in a wide range of cancer cell types. However, little is known concerning the status of DEK in pancreatic ductal adenocarcinoma (PDAC). Based on the microarray data from Gene Expression Omnibus (GEO), the expression levels of DEK mRNA in PDAC tissues were significantly higher than levels in the adjacent non-tumor tissues. To explore the clinical features of DEK overexpression in PDAC, 87 PDAC and 52 normal pancreas tissues were selected for immunoenzyme staining of the DEK protein. Localization of the DEK protein was detected in PANC-1 pancreatic cancer cells using immunofluorescence (IF) staining. The correlations between DEK overexpression and the clinical features of PDAC were evaluated using the Chi-squared (χ2) and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. The expression levels of DEK mRNA in PDAC tissues were significantly higher than that in the adjacent non‑tumor tissues. The DEK protein showed a primarily nuclear staining pattern in PDAC. The positive rate of the DEK protein was 52.9% (46/87) in PDAC, which was significantly higher than that in the adjacent normal pancreatic tissues (7.7%, 4/52). DEK overexpression in PDAC was correlated with tumor size, histological grade, tumor‑node‑metastasis (TNM) stage and overall survival (OS) rates. In addition, multivariate analysis demonstrated that DEK overexpression was an independent prognostic factor along with histological grade and TNM stage in patients with PDAC. In conclusion, DEK overexpression is associated with PDAC progression and may be a potential biomarker for poor prognostic evaluation in PDAC.

  3. IMP3 Predicts Invasion and Prognosis in Human Lung Adenocarcinoma.

    PubMed

    Yan, Jinhai; Wei, Qingzhu; Jian, Wenjing; Qiu, Bo; Wen, Jing; Liu, Jianghuan; Fu, Bo; Zhou, Xinhua; Zhao, Tong

    2016-02-01

    Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with several aggressive and advanced cancers. Whether IMP3 can predict invasion, and prognosis in patients with human lung adenocarcinoma (LAC) remains unclear. Ninety-five LAC and 75 non-tumor lung tissue samples were included in a tissue microarray. IMP3 expression was assessed by immunohistochemical examination. Correlation between IMP3 expression levels, clinicopathological characteristics, and overall prognosis was evaluated. In a separate in vitro study, RNA interference method was applied for knockdown of IMP3 gene in human LAC cell lines. Invasive potential of LAC cells was then evaluated by transwell migration assay. IMP3 immunoreactivity was observed in 39 out of 95 (41.1 %) LAC patients, but not in non-tumor lung tissues. IMP3 expression levels were closely associated with histological grade (P = 0.037), TNM stage (P = 0.034), and lymph node metastasis (P = 0.011). Patients presenting with positive IMP3 expression (P = 0.000), an advanced TNM stage (P = 0.000), and lymph node metastasis (P = 0.001) had a worse overall survival, compared to those lacking these characteristics. Both IMP3 expression (hazard ratio [HR], 2.310; 95 % confidence interval [CI] 1.192-4.476; P = 0.013) and TNM stage (HR 2.338; 95 % CI 1.393-3.925; P = 0.001) were independent predictors of poor prognosis. The invasive potential of LAC cells was significantly inhibited by IMP3 knockdown. IMP3 appears to play an important role in tumor invasion in patients with LAC and may serve as a useful prognostic biomarker in these patients.

  4. FOLFIRINOX induction therapy for stage III pancreatic adenocarcinoma

    PubMed Central

    Sadot, Eran; Doussot, Alexandre; O’Reilly, Eileen M.; Lowery, Maeve A.; Goodman, Karyn A.; Do, Richard Kinh Gian; Tang, Laura H.; Gönen, Mithat; D’Angelica, Michael I.; DeMatteo, Ronald P.; Kingham, T. Peter; Jarnagin, William R.; Allen, Peter J.

    2016-01-01

    Background FOLFIRINOX therapy for pancreatic ductal adenocarcinoma (PDAC) has been reported to result in objective response rates that are 2–3 fold higher than other regimens. Our goal was to assess response rates and resection rates in locally unresectable (stage III) patients initially treated with induction FOLFIRINOX. Methods The institutional cancer database was queried for patients treated with induction FOLFIRINOX therapy between 2010–2013. Patients were included if they were treated at our institution for stage III PDAC (locally unresectable) that had been adjudicated at a weekly multidisciplinary tumor board. Results One hundred and one patients were identified. The median age was 64 years (range:37–81) and the median follow-up was 12 months (range:3–37). Patients received a median of six cycles of induction FOLFIRINOX(range:1–20). No grade 4–5 toxicity was recorded. At initial restaging(median of 3 months following diagnosis), 23 patients(23%) had developed distant metastases, 15 patients(15%) underwent resection, and 63 patients(63%) proceeded to chemoradiation. Within the group of 63patients who proceeded to chemoradiation(median of 9 months following diagnosis), an additional 16 patients(16%) underwent resection and 5(5%) developed metastases. A partial radiographic response was observed in 29% of all patients, which was associated with the ability to perform resection(p=0.004). The median overall survival within the group who progressed on FOLFIRINOX and the group who did not progress were 11 and 26months, respectively. Conclusion Nearly a third of patients who had been initially identified to have stage III pancreatic carcinoma and had been treated with FOLFIRINOX responded radiographically and underwent tumor resection. PMID:26065868

  5. Evaluating Mismatch Repair Deficiency in Pancreatic Adenocarcinoma: Challenges and Recommendations.

    PubMed

    Hu, Zishuo I; Shia, Jinru; Stadler, Zsofia K; Varghese, Anna M; Capanu, Marinela; Salo-Mullen, Erin; Lowery, Maeve A; Diaz, Luis A; Mandelker, Diana; Yu, Kenneth H; Zervoudakis, Alice; Kelsen, David P; Iacobuzio-Donahue, Christine A; Klimstra, David S; Saltz, Leonard B; Sahin, Ibrahim H; O'Reilly, Eileen M

    2018-03-15

    Purpose: Immune checkpoint inhibition has been shown to generate profound and durable responses in mismatch repair deficient (MMR-D) solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D pancreatic ductal adenocarcinoma (PDAC) and assess the utility of next-generation sequencing (NGS) in providing additional prognostic and predictive information for MMR-D PDAC. Experimental Design: Archival and prospectively acquired samples and matched normal DNA from N = 833 PDAC cases were analyzed using a hybridization capture-based, NGS assay designed to perform targeted deep sequencing of all exons and selected introns of 341 to 468 cancer-associated genes. A computational program using NGS data derived the MSI status from the tumor-normal paired genome sequencing data. Available germline testing, IHC, and microsatellite instability (MSI) PCR results were reviewed to assess and confirm MMR-D and MSI status. Results: MMR-D in PDAC is a rare event among PDAC patients (7/833), occurring at a frequency of 0.8%. Loss of MMR protein expression by IHC, high mutational load, and elevated MSIsensor scores were correlated with MMR-D PDAC. All 7 MMR-D PDAC patients in the study were found to have Lynch syndrome. Four (57%) of the MMR-D patients treated with immune checkpoint blockade had treatment benefit (1 complete response, 2 partial responses, 1 stable disease). Conclusions: An integrated approach of germline testing and somatic analyses of tumor tissues in advanced PDAC using NGS may help guide future development of immune and molecularly directed therapies in PDAC patients. Clin Cancer Res; 24(6); 1326-36. ©2018 AACR . ©2018 American Association for Cancer Research.

  6. Irreversible electroporation of locally advanced pancreatic neck/body adenocarcinoma

    PubMed Central

    2015-01-01

    Objective Irreversible electroporation (IRE) of locally advanced pancreatic adenocarcinoma of the neck has been used to palliate appropriate stage 3 pancreatic cancers without evidence of metastasis and who have undergone appropriate induction therapy. Currently there has not been a standardized reported technique for pancreatic mid-body tumors for patient selection and intra-operative technique. Patients Subjects are patients with locally advanced pancreatic adenocarcinoma of the body/neck who have undergone appropriate induction chemotherapy for a reasonable duration. Main outcome measures Technique of open IRE of locally advanced pancreatic adenocarcinoma of the neck/body is described, with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open IRE of the pancreatic neck/body with bracketing of the celiac axis and superior mesenteric artery with continuous intraoperative ultrasound imaging and consideration of intraoperative navigational system is described. Conclusions IRE of locally advanced pancreatic adenocarcinoma of the body/neck is feasible for appropriate patients with locally advanced unresectable pancreatic cancer. PMID:26029461

  7. Giant colonic mucocele following palliative surgery for metastatic adenocarcinoma.

    PubMed

    Ali, A; Krishnan, A; Rehman, S; Rao, Vsr; Pearson, H J

    2011-03-01

    We report an unusual case of a giant colonic mucocele following ileo-sigmoid bypass surgery in a patient with advanced adenocarcinoma of the splenic flexure. The formation of a giant colonic mucocele resulted from distal splenic flexure obstruction due to tumour relapse and proximal caecal obstruction due to peritoneal disease with subsequent accumulation of mucus in the closed loop. © JSCR.

  8. An unexpected digital papillary adenocarcinoma of the thumb *

    PubMed Central

    Nash, Mitchell; Burn, Juliet; Chan, Simon

    2016-01-01

    Abstract Digital papillary adenocarcinoma (DPAca) is an aggressive lesion with high metastatic potential, which is easily misdiagnosed. We present a 55-year-old male with a cystic lesion on his right thumb. Above all else, lesions of the digits should be sent for histopathology routinely, regardless of their history or appearance. PMID:27990456

  9. New cancer suppressor gene for colorectal adenocarcinoma: filamin A.

    PubMed

    Tian, Zi-Qiang; Shi, Jian-Wei; Wang, Xiao-Ran; Li, Zhong; Wang, Gui-Ying

    2015-02-21

    To determine the expression and significance of filamin A (FLNa) in colorectal adenocarcinoma tissue. The expression of FLNa in 46 colorectal cancer tissues and normal tissues was detected by immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, and its relationship with clinical parameters and prognosis was analyzed. The positive expression of FLNa in cancer tissues was lower than that in normal mucosa, and the difference was statistically significant. The expression of FLNa correlated with liver metastasis, lymph node metastasis and rectal invasion depth, regardless of sex, age, tumor location, tumor size, gross shape and histological type of colorectal carcinoma. Multivariate analysis showed that FLNa was an independent risk factor for postoperative survival of patients with colorectal adenocarcinoma. Moreover, survival analysis showed that the expression level of FLNa was closely related with survival of patients with colorectal adenocarcinoma. The results of RT-PCR and Western blotting were consistent with those of immunohistochemistry. FLNa showed low expression in colorectal adenocarcinoma, high correlation with the incidence and development of colorectal cancer, and was considered an indicator of prognosis.

  10. [Mucinous adenocarcinoma of the prostate: description of a case].

    PubMed

    Ferrero, G; Mastroberardino, E; Del Vino, A; Artese, L

    2000-04-01

    We report an occasional biopsy of primary mucinous adenocarcinoma of the prostate with review of the literature and discussion about all criteria used to classify this clinical-pathological entity. Histochemical (Alcian Blue and P.A.S.) and immunohistochemical (P.A.P. and P.S.A.) stainings were performed.

  11. Laparoscopic distal pancreatectomy for adenocarcinoma of the pancreas

    PubMed Central

    Björnsson, Bergthor; Sandström, Per

    2014-01-01

    Since the first report on laparoscopic distal pancreatectomy (LDP) appeared in the 1990s, the procedure has been performed increasingly frequently to treat both benign and malignant lesions of the pancreas. Many earlier publications have shown LDP to be a good alternative to open distal pancreatectomy for benign lesions, although this has never been studied in a prospective, randomized manner. The evidence for the use of LDP to treat adenocarcinoma of the pancreas is not as well established. The purpose of this review is to evaluate the current evidence for LDP in cases of pancreatic adenocarcinoma. We conducted a review of English language publications reporting LDP results between 1990 and 2013. All studies reporting results in patients with histologically proven pancreatic adenocarcinoma were included. Thirty-nine publications were found and included in the results for a total of 309 cases of pancreatic adenocarcinoma (potential double publications were not eliminated). Most LDP procedures are performed in selected cases and generally involve smaller tumors than open distal pancreatectomy (ODP) procedures. Some of the papers report unselected cases and include procedures on larger tumors. The number of lymph nodes harvested using LDP is comparable to the number obtained with ODP, as is the frequency of R0 resections. Current data suggest that similar short term oncological results can be obtained using LDP as those obtained using ODP. PMID:25309072

  12. Renal adenocarcinoma: prognostics and treatment reflected by survival.

    PubMed

    Katz, S A; Davis, J E

    1977-07-01

    A retrospective study of 164 patients with renal adenocarcinoma has reconfirmed the highly malignant potential of this neoplasm. Stage and size of the tumor appear to be the best prognostic parameters. Radical surgery appears to have improved survival statistics. Follow-up must be indefinite since late metastases are not uncommon.

  13. Duodenal adenocarcinoma in a 10-year-old boy.

    PubMed

    Mohamed, Zouari; Habib, Bouthour; Rabia, Ben Abdallah; Youssef, Hlel; Riath, Ben Malek; Youssef, Gharbi; Nejib, Kaabar

    2014-01-01

    Gastrointestinal malignancies are extremely rare in the paediatric population and duodenal cancers represent an even more unusual entity. It represents 0.3-1% of all gastrointestinal tumours. A case report of a 10-year-old boy with duodenal adenocarcinoma is reported and the difficulties of diagnosing and treating this rare tumour are discussed.

  14. Solitary splenic metastasis from lung adenocarcinoma: A case report

    PubMed Central

    Izumi, Nobuhiro; Tsukioka, Takuma; Komatsu, Hiroaki; Toda, Michihito; Miyamoto, Hikaru; Suzuki, Satoshi; Kimura, Takuya; Shibata, Toshihiko; Nishiyama, Noritoshi

    2017-01-01

    Solitary splenic metastasis is extremely rare, with only 27 reported cases in the literature. An 81‐year‐old woman was referred to our hospital for treatment of pulmonary and splenic lesions. Chest computed tomography showed a small lung nodule in the right upper lobe, abdominal computed tomography showed an 8 cm splenic mass with abnormal accumulation, and positron emission tomography revealed a maximum standardized uptake value of 7.9. She had elevated serum cancer antigen 19‐9 (1847 U/mL) and carcinoembryonic antigen concentrations (17.9 ng/mL). She underwent laparoscopic splenectomy. Pathological examination revealed poorly differentiated adenocarcinoma. We performed partial lung resection and diagnosed the small lung lesion as lung adenocarcinoma. Both lesions were positive for thyroid transcription factor 1. Thus, primary lung adenocarcinoma and solitary splenic metastasis were diagnosed. The patient was still alive without recurrence four years postoperatively. Herein, we report a rare case of lung adenocarcinoma with solitary splenic metastasis and review the literature. PMID:28731531

  15. Evaluation of the new IASLC/ATS/ERS proposed classification of adenocarcinoma based on lepidic pattern in patients with pathological stage IA pulmonary adenocarcinoma.

    PubMed

    Nakagiri, Tomoyuki; Sawabata, Noriyoshi; Morii, Eiichi; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Okumura, Meinoshin

    2014-11-01

    The International association for the study of cancer (IASLC)/American thoracic society (ATS)/European respiratory society (ERS) has established a new subclassification of lung adenocarcinoma, especially for the lepidic pattern component, formerly called bronchioloalveolar adenocarcinoma (BAC). According to the new classification, BAC has been classified into the following 4 main subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and variants of invasive adenocarcinoma (VIA). An observational study was conducted to validate this classification in patients with pathological stage IA pulmonary adenocarcinoma. 147 patients treated for pathological stage IA lung adenocarcinoma by complete resection at Osaka University Medical Hospital from January 1993 to December 2002 were assessed. The tumor specimens of the cohort were classified into the 4 subgroups. In addition, these groups were compared for various prognostic factors. Adenocarcinoma in situ was observed in 30 patients, MIA in 8, IA in 104, and VIA in 5 patients, with 5-year survival rates of 100, 100, 85.5, and 60.0 %, respectively. The relationship between the histological classification and K-ras mutation was significant (p < 0.001), especially when comparing the VIA group with the others (p ≪ 0.001). Ki67-labeling indices were significantly different between the AIS and IA groups (p = 0.040). This study validated the proposed IASLC/ATS/ERS classification for pulmonary adenocarcinoma in patients with pathological stage IA pulmonary adenocarcinoma. The difference between AIS and IA may depend on the proliferation of the carcinoma. In addition, the difference between VIA and the other adenocarcinoma types may depend on genetic factors, especially K-ras mutations.

  16. Simultaneous multifocal polymorphous low-grade adenocarcinoma. Report of two cases.

    PubMed

    Clayton, J R; Pogrel, M A; Regezi, J A

    1995-07-01

    The polymorphous low-grade adenocarcinoma is a recently described variant of salivary gland adenocarcinoma with a comparatively good prognosis. Polymorphous low-grade adenocarcinoma occurs most frequently in the palate with a peak incidence between 30 and 70 years of age. The female/male ratio is approximately 2:1, and the tumors exhibit slow growth with a low recurrence rate. The simultaneous occurrence of polymorphous low-grade adenocarcinoma has not been previously reported. This article reviews the existing literature and describes the first two reports of simultaneous intraoral polymorphous low-grade adenocarcinoma.

  17. Adenocarcinoma of the paraurethral glands: a case report.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Modena, Alessandra; Maines, Francesca; Segala, Diego; Luchini, Claudio; Marcolini, Lisa; Cavicchioli, Francesca; Cavalleri, Stefano; Bria, Emilio; Brunelli, Matteo; Martignoni, Guido; Artibani, Walter; Tortora, Giampaolo

    2014-10-01

    Adenocarcinoma of the paraurethral glands represents a very rare neoplasm of the urinary tract. Due to the rarity of this disease, there is no standard therapeutic approach. We report a case of adenocarcinoma of the paraurethral glands in a 56-year-old woman, presenting with abnormal serous vaginal discharges. The radiologic examination revealed a 5-cm mass around the urethra, which underwent surgical resection. After surgical resection, the histology revealed a moderately differentiated adenocarcinoma, probably arising from the paraurethral glands. One month later, a pelvic recurrent mass was radiologically diagnosed; consequently, an anterior pelvic exenteration with lymph node dissection was performed. Histological examination revealed a moderately differentiated adenocarcinoma, with glandular and micropapillary architecture, with multiple lymph node metastases. The absence of modifications such as urethritis cystic glandularis on the urethral mucosa, as well as the lack of a lesion in situ, associated with the immunohistochemical expression of PAX8 and negativity for GATA3 and S100p, suggested that the adenocarcinoma originated from the paraurethral glands rather than from the urethral mucosa. Post-surgery CT scans revealed no evidence of metastatic disease. The patient received 6 courses of adjuvant chemotherapy with carboplatin and paclitaxel. One year after the pelvic exenteration, because of inguinal lymph node progression, an inguinal lymphadenectomy was performed. Four months later, a TC-PET revealed a multidistrectual lymph node and a lung micronodule disease progression. Invasive micropapillary carcinomas have been characterized as a rare distinctive variant of carcinomas in several anatomic sites and are distinguished by a marked tendency to lymphovascular invasion, justifying the association with high-stage disease and poor prognosis. In the present case, both the poor prognosis connected with micropapillary structure and the lymph node involvement

  18. Vitamin D deficiency and prognostics among patients with pancreatic adenocarcinoma.

    PubMed

    Cho, May; Peddi, Parvin F; Ding, Kevin; Chen, Ling; Thomas, Denise; Wang, Jian; Lockhart, Albert C; Tan, Benjamin; Wang-Gillam, Andrea

    2013-09-08

    The prevalence of vitamin D deficiency among patients with cancer has been previously reported. Because vitamin D is fat soluble, patients with pancreatic adenocarcinoma may have an especially high risk of vitamin D deficiency in association with ongoing and varying degrees of malabsorption. However, little is known about the correlation between vitamin D status and prognosis in these patients. We conducted a retrospective review of vitamin D status in patients with pancreatic adenocarcinoma who were treated at Siteman Cancer Center. Patients' demographic information, clinical staging at the time of vitamin D assessment, vitamin D levels, and survival data were collected. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25[OH]D) level of less than 20 ng/mL, and vitamin D insufficiency was defined as a 25(OH)D level of between 20 ng/mL and 30 ng/mL. Between December 2007 and June 2011, 178 patients with pancreatic adenocarcinoma had their vitamin D levels checked at the time of initial visit at this center. Of these 178 patients, 87 (49%) had vitamin D deficiency, and 44 (25%) had vitamin D insufficiency. The median 25(OH)D level was significantly lower among nonwhite patients and among patients with stage I and II disease. A 25(OH)D level of less than 20 ng/mL was found to be associated with poor prognosis (p = 0.0019) in patients with stage III and IV disease. Vitamin D insufficiency and deficiency were prevalent among patients with pancreatic adenocarcinoma. The vitamin D level appears to be prognostic for patients with advanced pancreatic adenocarcinoma, and its effects should be further examined in a prospective study.

  19. [Down-expression of FOXA2 in gastric adenocarcinoma].

    PubMed

    Zhang, Zhengliang; Sun, Jiangli; Bai, Zhenghai; Li, Haijun; He, Shicai; Chen, Rui; Che, Xiangming

    2015-05-01

    To investigate the expression of FOXA2 in human gastric adenocarcinoma and its correlation with cell migration and invasion. Fifty-six pairs of gastric adenocarcinoma and matched tumor-adjacent tissues were freshly collected. The expressions of FOXA2 and epithelial cadherin (E-cadherin) in the gastric specimens were detected using immunohistochemistry. Western blotting was performed to test FOXA2 and E-cadherin expressions in different gastric cancer cell lines. FOXA2 was over-expressed in MKN-45 cells. TranswellTM assays were performed to observe gastric cancer cell migration and invasion in vitro. Spearman rank correlation coefficient was used for correlation analysis. The expressions of FOXA2 and E-cadherin in gastric adenocarcinoma were significantly lower than those in matched tumor-adjacent noncancerous tissues. FOXA2 was positively correlated with E-cadherin expression in gastric adenocarcinoma tissues. Clinical analysis suggested that FOXA2 expression was prominently associated with tumor differentiation, infiltration depth, lymph node metastasis and TNM stage, respectively. The lowest expressions of FOXA2 and E-cadherin were found in highly invasive gastric cancer MKN-45 cell line; the highest expressions of FOXA2 and E-cadherin were observed in low metastatic gastric cancer N-87 cell line. Over-expression of FOXA2 significantly increased the expression of E-cadherin protein and obviously inhibited cell migration and invasion in MKN-45 cells. Expression of FOXA2 is reduced in gastric adenocarcinoma tissues and its low-expression is correlated with malignant clinical pathological features. Over-expression of FOXA2 in MKN-45 cells up-regulates E-cadherin expression and inhibits gastric cancer cell migration and invasion.

  20. Opium: an emerging risk factor for gastric adenocarcinoma.

    PubMed

    Shakeri, Ramin; Malekzadeh, Reza; Etemadi, Arash; Nasrollahzadeh, Dariush; Aghcheli, Karim; Sotoudeh, Masoud; Islami, Farhad; Pourshams, Akram; Pawlita, Michael; Boffetta, Paolo; Dawsey, Sanford M; Abnet, Christian C; Kamangar, Farin

    2013-07-15

    Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9-5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.3-8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance. Copyright © 2013 UICC.

  1. Opium; an emerging risk factor for gastric adenocarcinoma

    PubMed Central

    Shakeri, Ramin; Malekzadeh, Reza; Etemadi, Arash; Nasrollahzadeh, Dariush; Aghcheli, Karim; Sotoudeh, Masoud; Islami, Farhad; Pourshams, Akram; Pawlita, Michael; Boffetta, Paolo; Dawsey, Sanford M.; Abnet, Christian C.; Kamangar, Farin

    2013-01-01

    Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia, and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products, and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9 – 5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95%CI: 2.3-8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance. PMID:23319416

  2. Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma

    PubMed Central

    Wang, Yiwei; Huang, Dan; Chen, Kai-Yuan; Cui, Min; Wang, Weihuan; Huang, Xiaoran; Awadellah, Amad; Li, Qing; Friedman, Ann; Xin, William W.; Di Martino, Luca; Cominelli, Fabio; Miron, Alex; Chan, Ricky; Fox, James; Xu, Yan; Shen, Xiling; Kalady, Mathew F.; Markowitz, Sanford; Maillard, Ivan; Lowe, John B.; Xin, Wei; Zhou, Lan

    2016-01-01

    Background & Aims De novo synthesis of GDP-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or TSTA3). GMDS deletions and mutations are found in 6%–13% of colorectal cancers; these mostly affect ascending and transverse colon. We investigated whether lack of fucosylation consequent to loss of GDP-fucose synthesis contributes to colon carcinogenesis. Methods FX deficiency and GMDS deletion produce the same biochemical phenotype of GDP-fucose deficiency. We studied a mouse model of fucosylation deficiency (Fx–/– mice) and mice with the full-length Fx gene (controls). Mice were placed on standard chow or fucose-containing diet (equivalent to a control fucosylglycan phenotype). Colon tissues were collected and analyzed histologically or by ELISAs to measure cytokine levels; T cells were also collected and analyzed. Fecal samples were analyzed by 16s rRNA sequencing. Mucosal barrier function was measured by uptake of fluorescent dextran. We transplanted bone marrow cells from Fx–/– or control mice (Ly5.2) into irradiated 8-week old Fx–/– or control mice (Ly5.1). We performed immunohistochemical analyses for expression of Notch and the hes family bHLH transcription factor (HES1) in colon tissues from mice and a panel of 60 human colorectal cancer specimens (27 left-sided, 33 right-sided). Results Fx–/– mice developed colitis and serrated-like lesions. The intestinal pathology of Fx–/– mice was reversed by addition of fucose to the diet, which restored fucosylation via a salvage pathway. In the absence of fucosylation, dysplasia appeared and progressed to adenocarcinoma in up to 40% of mice, affecting mainly the right colon and cecum. Notch was not activated in Fx–/– mice fed standard chow, leading to decreased expression of its target Hes1. Fucosylation deficiency altered the composition of the fecal microbiota, reduced

  3. [Laparoscopic radical antegrade modular pancreatosplenectomy for left-sided pancreatic adenocarcinoma: analysis of 12 cases].

    PubMed

    Xu, X W; Zhang, R C; Mou, Y P; Qian, Z Y; Huang, C J; Zhu, Q C; Jin, W W; Zhou, Y C

    2018-03-01

    Objective: To evaluate the safety and feasibility of laparoscopic radical antegrade modular pancreatosplenectomy(Lap-RAMPS) for left-sided pancreatic adenocarcinoma. Methods: Clinical data of total 12 patients underwent Lap-RAMPS for left-sided pancreatic adenocarcinoma at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital from March 2016 to August 2017 were reviewed retrospectively.There were 7 male patients and 5 female patients, with median age of 60.5 years old(47-68 years old). Abdominal enhanced CT, pancreatic MRI, PET-CT were performed on all patients to evaluate the lesion and exclude metastasis.Follow-up were done with out-patient clinic or telephone consultancy until October 2017. Results: All patients underwent pure Lap-RAMPS.The medium operative time was 250 minutes(180-445 minutes), and the blood loss was 150 ml(50-500 ml). The medium first flatus time and diet resumption time were 3.0 days(1-5 days) and 3.5 days(1-7 days) respectively.The medium postoperative hospital stay was 9 days(4-18 days). Morbidity occurred in 8 patients with gastric empty delay( n =1), bleeding( n =1), fluid collection( n =3). There was no mortality.The medium overall number of retrived lymph nodes was 15.6 and the positive rate was 41.7%. The R0 rate was 100%.The medium follow-up was 10 months.One patient was diagnosed as liver metastasis after 8 months and accepted chemotherapy.One patient died after 14 months for tumor recurrence and metastasis.Others survived without tumor recurrence or metasitasis. Conclusion: Lap-RAMPS is safe and feasible with accepted oncological outcomes for selected left side pancreatic adenocarcinoma under skilled hands.

  4. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    SciTech Connect

    Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomymore » in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to

  5. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    SciTech Connect

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), andmore » 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system

  6. The Prognostic Value of Tumor-Infiltrating Neutrophils in Gastric Adenocarcinoma after Resection

    PubMed Central

    Wang, Wei; Chen, Ju-gao; Wu, Yan-heng; Lv, Lin; Li, Jian-jun; Chen, Yi-bing; Wang, Dan-dan; Pan, Qiu-zhong; Li, Xiao-dong; Xia, Jian-chuan

    2012-01-01

    Background Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs. Patients and Methods The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis. Results Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00–115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients. Conclusions The presence of CD15+ TINs is an independent and

  7. Role of CT perfusion imaging in patients with variously differentiated gastric adenocarcinoma.

    PubMed

    Sun, Zong-Qiong; Cheng, Xiao-Fang; Ge, Yu-Xi; Chen, Lin; Yue, Jian-Guo; Jin, Lin-Fang; Xie, Zhi-Hui; Zhang, Han-Di; Xuan, Ying-Hua

    2015-01-01

    To explore the characteristics of variously differentiated gastric cancers on computed tomography (CT) perfusion imaging, including specific perfusion parameter values, and potential clinical applications in the prognosis assessment of gastric cancer. Fifty patients with gastric cancer confirmed by gastroscope pathology were studied prospectively using CT perfusion imaging examinations on a 64-slice spiral CT scanner. The acquired volume data were used for calculations, mapping, and analysis by using an abdominal tumor perfusion protocol (deconvolution method) in the CT perfusion software package to measure 4 parameters: blood flow (BF), blood volume (BV), mean transit time (MTT), and the permeability surface (PS) area product. The different differentiated Gastric cancers with CT perfusion values were divided into 3 groups: well-differentiated, moderately differentiated and poorly differentiated gastric adenocarcinoma, and compared statistically with one another by statistical software. The mean perfusion values of 10 patients with well-differentiated gastric adenocarcinoma were as follows: BF, 75.28 ± 6.81 mL/100 g/min; BV, 9.01 ± 0.94 mL/100 g; MTT, 9.89 ± 1.65 s; and PS, 10.05 ± 0.71 mL/100 g/min. The mean perfusion values of 24 patients with moderately differentiated gastric adenocarcinoma were as follows: BF, 110.01 ± 31.90 mL/100 g/min; BV, 18.18 ± 5.62 mL/100 g; MTT, 9.81 ± 3.69 s; and PS, 40.08 ± 15.82 mL/100 g/min. The mean perfusion values of 16 patients with poorly differentiated gastric adenocarcinoma were as follows: BF, 138.59 ± 38.09 mL/100 g/min; BV, 21.08 ± 4.11 mL/100 g; MTT, 9.47 ± 1.80 s; and PS, 57.50 ± 13.28 mL/100 g/min. Comparing the 3 groups, differences between the well-differentiated group and the moderate differentiation group were all statistically significant for BF, BV, and PS (p < 0.05, respectively), differences between the well-differentiated group and the poor differentiation group were all statistically significant

  8. Airborne occupational exposures and risk of oesophageal and cardia adenocarcinoma.

    PubMed

    Jansson, C; Plato, N; Johansson, A L V; Nyrén, O; Lagergren, J

    2006-02-01

    The reasons for the increasing incidence of and strong male predominance in patients with oesophageal and cardia adenocarcinoma remain unclear. The authors hypothesised that airborne occupational exposures in male dominated industries might contribute. In a nationwide Swedish population based case control study, 189 and 262 cases of oesophageal and cardia adenocarcinoma respectively, 167 cases of oesophageal squamous cell carcinoma, and 820 frequency matched controls underwent personal interviews. Based on each study participant's lifetime occupational history the authors assessed cumulative airborne occupational exposure for 10 agents, analysed individually and combined, by a deterministic additive model including probability, frequency, and intensity. Furthermore, occupations and industries of longest duration were analysed. Relative risks were estimated by odds ratios (OR), with 95% confidence intervals (CI), using conditional logistic regression, adjusted for potential confounders. Tendencies of positive associations were found between high exposure to pesticides and risk of oesophageal (OR 2.3 (95% CI 0.9 to 5.7)) and cardia adenocarcinoma (OR 2.1 (95% CI 1.0 to 4.6)). Among workers highly exposed to particular agents, a tendency of an increased risk of oesophageal squamous cell carcinoma was found. There was a twofold increased risk of oesophageal squamous cell carcinoma among concrete and construction workers (OR 2.2 (95% CI 1.1 to 4.2)) and a nearly fourfold increased risk of cardia adenocarcinoma among workers within the motor vehicle industry (OR 3.9 (95% CI 1.5 to 10.4)). An increased risk of oesophageal squamous cell carcinoma (OR 3.9 (95% CI 1.2 to 12.5)), and a tendency of an increased risk of cardia adenocarcinoma (OR 2.8 (95% CI 0.9 to 8.5)), were identified among hotel and restaurant workers. Specific airborne occupational exposures do not seem to be of major importance in the aetiology of oesophageal or cardia adenocarcinoma and are unlikely to

  9. Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis.

    PubMed

    Feng, Mei; Zhu, Jing; Liang, Liqun; Zeng, Ni; Wu, Yanqiu; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

    2017-04-01

    Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis. Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE. The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93. CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.

  10. Evaluation of different methods of cryopreservation of Ehrlich tumor cells.

    PubMed

    Santos, Kamilla M; Maciel, Fernanda P S; Souza, Cristina M; Cassali, Geovanne D; Thome, Ralph G; Santos, Hélio B; Ribeiro, Ribeiro I M A

    2015-01-01

    The Ehrlich Ascitic Carcinoma (EAC) is an experimental transplantable neoplasm that develops in several species of mice. The maintenance of the tumor occurs in vivo. Thus, freezing the cells would reduce the number of passages between animals, ensuring genetic stability and storage for longs period of experimentation. Search by EAC cryoprotectants. The combinations of nutrient medium (Tris, hen egg yolk, and DEMEN) and cryoprotective agent (Glicerol, Trehalose and DMSO) on freezing EAC cells and the transplantability after defrosting were evaluated. The cooling was conducted at 2 C/min. until -180 degree C and the thawing by immersion in water at 37 degree C. The transplantability was evaluated from cell inoculation in mice for 14 days. The best results were the associations IA (Cryoprotective agent Glycerol 6 % and medium containing 3.0 % Tris w / v, 1.8 % Citric acid w / v, 1.3 % D-fructose w / v and 20 % hen egg yolk v / v) and IIB (Cryoprotective agent Trehalose 100mM and medium containing 50 % coconut water v / v, 25 % sodium citrate 5 % v / v and 20 % hen egg yolk v / v) with 85.2 % and 55.1 % viable cells, respectively. These transplantable cells were efficient for tumor development, therefore demonstrating that this method of cryopreservation is simple and affordable.

  11. Proliferation index of different Gleason pattern 4 histomorphologies and associated pattern 3 adenocarcinoma of the prostate.

    PubMed

    Fu, Liying; Hwang, Michael; Adeniran, Adebowale J; Humphrey, Peter A

    2017-12-01

    Gleason grade is one of the most powerful prognostic indicators for adenocarcinoma of the prostate. A higher proliferation index of prostatic adenocarcinoma has been demonstrated in numerous studies to be significantly associated with more aggressive behavior. To date, the proliferation index of the different Gleason pattern 4 histomorphologies, including cribriform, fused glands, and poorly formed glands, has not been determined. The aim of this investigation was to quantitate and compare the proliferation index, as assessed by Ki67 labeling index, of different Gleason pattern 4 histomorphologies. We also analyzed the Ki67 labeling index of Gleason pattern 3 adenocarcinoma associated with and without cribriform adenocarcinoma. Among Gleason pattern 4 morphologies, cribriform adenocarcinoma exhibited a higher mean proliferation index at 5.3% compared to fused gland adenocarcinoma at 3.9% (P = .03) and poorly formed glands at 3.6% (P < .01). The mean Ki67 labeling index for Gleason pattern 3 associated with cribriform adenocarcinoma was higher at 4.1% compared to pure Gleason pattern 3 at 2.2% (P < .01) and Gleason pattern 3 associated with non-cribriform pattern 4 adenocarcinoma at 2.9% (P = .02). This higher proliferation index of Gleason pattern 3 adenocarcinoma associated with cribriform pattern 4 adenocarcinoma indicates that not all Gleason pattern 3 cells are identical and that cribriform adenocarcinoma may influence or be related to associated Gleason pattern 3. Gleason pattern 4 adenocarcinoma of the prostate with cribriform growth has a higher proliferation index than other grade 4 histomorphologies, consistent with the more clinically aggressive nature of cribriform adenocarcinoma of the prostate. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. A new classification of HLA-DRB1 alleles based on acid-base properties of the amino acids located at positions 13, 70 and 71: impact on ACPA status or structural progression, and meta-analysis on 1235 patients with rheumatoid from two cohorts (ESPOIR and EAC cohort).

    PubMed

    Ruyssen-Witrand, Adeline; van Steenbergen, Hanna W; van Heemst, Jurgen; Gourraud, Pierre-Antoine; Nigon, Delphine; Lukas, Cédric; Miceli-Richard, Corinne; Jamard, Bénédicte; Cambon-Thomsen, Anne; Cantagrel, Alain; Dieudé, Philippe; van der Helm-van Mil, Annette H M; Constantin, Arnaud

    2015-01-01

    To group HLA-DRB1 alleles based on acid-base properties of amino acids at positions 13, 70 and 71 and analyse their association with the presence of anticitrullinated peptide antibodies (ACPA) and structural progression in 2 cohorts of early rheumatoid arthritis (RA). Patients with RA (N=612) from ESPOIR cohort and from EAC cohort (n=624) were genotyped for HLA-DRB1 alleles. The alleles containing the RAA sequence at positions 72-74 were classified into 3 groups according to the amino acid at positions 13, 70 and 71: BB encoding basic amino acids at positions 13, 70 and 71; A encoding acidic amino acids at positions 70 and 71; and BN encoding either neutral amino acids at position 13 and basic amino acids at positions 70 and 71, or basic amino acid at position 13 and neutral amino acids at positions 70 and 71. The associations between the different alleles and (1) the ACPA presence, and (2) the structural progression were assessed by χ(2) test; a meta-analysis was performed on the 2 cohorts using the Mantel-Haenszel method. After meta-analysis, BB alleles were significantly associated with ACPA presence (OR (95% CI) 4.08 (3.14 to 5.31)) and structural progression (OR (95% CI) 2.33 (1.76 to 3.09)). The alleles protected significantly against ACPA presence (OR (95% CI) 0.37 (0.28 to 0.50)) and structural progression (OR (95% CI) 0.34 (0.23 to 0.50)). This acid-base classification allowed to separate another group BN with an intermediate risk of ACPA production (OR (95% CI) 1.14 (0.91 to 1.44)) and structural progression (OR (95% CI) 1.01 (0.77 to 1.33)). This new classification permitted to make a hierarchy of HLA-DRB1 alleles in terms of association with ACPA presence or structural progression in early RA.

  13. Polymorphous low grade adenocarcinoma presenting an uncommon radiographic aspect.

    PubMed

    de Magalhães, M H C G; de Magalhães, R P; de Araújo, V C; de Sousa, S O M

    2006-05-01

    The aim of this study was to present clinical, histological and immunohistochemical aspects of a polymorphous low grade adenocarcinoma occurring in the mandible. A radiolucent tumour, located in the right mandible, was removed from a 40-year-old woman. Radiographic and CT exams revealed that the lesion expanded bucco-lingual cortical plates and presented an irregular scalloping of the bone. The surrounding lining mucosa was intact. The patient underwent total surgical removal of the lesion with an intraoperative biopsy. Histological diagnosis was polymorphous low-grade adenocarcinoma confirmed by immunohistochemical study. One-year follow up was uneventful. The accurate diagnosis of lesions presenting unusual clinical aspects, as the one presented here, is critical for correctly handling treatment.

  14. Digital Papillary Adenocarcinoma: Presentation, Natural History and Management

    PubMed Central

    Carter, Kristen; Yao, Jie J.; Melton, Shelby D.; Lopez, Jorge; Huerta, Sergio

    2015-01-01

    Digital papillary adenocarcinoma (DPA) is a rare malignant tumor of the sweat glands that often presents as a solitary painless mass on the digits of the hands or feet. We present a rare case of DPA on the ankle in a 54 year-old African American man. Although the most common location for digital papillary adenocarcinoma is on the hands and feet, it can present in other locations. Treatment modalities and concerns such as the level of margin resection, degree of negative margins, and the need for a sentinel lymph node biopsy might be different if the tumor is encountered in locations other than the digits. In the following manuscript, we discuss the natural history of this rare tumor including a review of the current literature with emphasis on documented treatment strategies as well as the approach in treating patients with a unique presentation. PMID:26266016

  15. Aggressive digital papillary adenocarcinoma arising on the right great toe.

    PubMed

    Mori, Osamu; Nakama, Takekuni; Hashimoto, Takashi

    2002-01-01

    A 20-year-old Japanese man with aggressive digital papillary adenocarcinoma on the right great toe was presented. The tumor was comprised of multiple lobules of epithelial cells exhibiting solid areas, lacking cystic spaces. A pattern of fused back-to-back glands lined by cuboidal to low columnar epithelial cells with little evidence of papillary formations was observed. Apocrine-like decapitation secretion was not observed, and continuity of the tumor to the epidermis was evident. The neoplastic cells were immunohistochemically positive for S-100 protein, but negative for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and gross cystic disease fluid protein (GCDFP). Intraluminal contents, however, showed positive reactivity with CEA and EMA. On the basis of their histologic and immunohistochemical features, the tumor was diagnosed as aggressive digital papillary adenocarcinoma.

  16. MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

    PubMed

    Carpenter, Nancy A; Crook, Erika K

    2017-03-01

    An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

  17. Canine ovarian serous papillary adenocarcinoma with neoplastic hypercalcemia.

    PubMed

    Hori, Yasutomo; Uechi, Masami; Kanakubo, Kayo; Sano, Tadashi; Oyamada, Toshifumi

    2006-09-01

    A female golden retriever was referred to assess a history of a palpable abdominal mass. A serum chemistry analysis revealed elevated concentrations of blood urea nitrogen, creatinine, calcium, and parathyroid hormone-related protein (PTH-rP). Exploratory laparotomy revealed an ovoid mass within the right ovary. This mass was removed surgically by performing an ovariohysterectomy. The right ovarian mass was diagnosed as a serous papillary adenocarcinoma. Following surgery, the dog recovered, and the serum calcium and PTH-rP concentrations decreased. Therefore, concentrations of PTH-rP and calcium might be associated with serous papillary adenocarcinomas. Serial evaluation of the serum PTH-rP and calcium was useful for evaluating the prognosis.

  18. Indian file pattern of adenocarcinoma cells in effusions.

    PubMed

    Hemachandran, Manikkapurath; Dey, Pranab

    2004-01-01

    To determine the prevalence of the Indian file pattern of adenocarcinoma cells in malignant serous effusions. Twenty-five malignant and 10 benign effusion samples were selected. Clinical data, including the sites of the primary neoplasms, were noted. The presence or absence of Indian file arrangement of carcinoma cells and other patterns were recorded. Seven of the 25 positive cases showed Indian file arrangement, whereas none of the negative cases did. Their number did not show any correlation with the type and site of the primary neoplasms. In most of the 7 cases other patterns, such as 3-dimensional balls and papillations, were also present. Cells in Indian file in serous effusions are strongly suggestive of metastatic carcinoma. They are not specific to any particular site of the primary adenocarcinoma.

  19. Uterine adenocarcinoma in a Przewalski's wild horse (Equus ferus przewalskii).

    PubMed

    Thompson, Rachel; Armién, Aníbal G; Rasmussen, James M; Wolf, Tiffany M

    2014-06-01

    A 25-yr-old, nulliparous, female Przewalski's wild horse (Equus ferus przewalskii) with a history of pituitary pars intermedia dysfunction and recent onset of serosanguinous vaginal discharge was euthanized after a period of lethargy and inappetance. Postmortem examination confirmed an infiltrative uterine adenocarcinoma, which is an uncommon neoplasia in equids. Reproductive disease is significant in this species as they are considered endangered by IUCN. Reproductive soundness and success are paramount to conservation efforts.

  20. [Chicken pox recurrence revealing a renal adenocarcinoma in an adult].

    PubMed

    Thieulent, N; Grezard, P; Wolf, F; Barrut, D; Perrot, H

    2000-09-01

    A new episode of chicken pox in adults who had a well documented infection previously is usually observed in immunocompromised individuals. The principal immunodeficiency factors are hematology diseases, acquired immunodeficiency disease and old age. We report here the case of a young woman who after a contaminating contact presented a recurrence of typical chicken pox. Morphological investigations evidenced a right kidney tumor which pathology revealed to be a renal adenocarcinoma. We discuss this pathological association and review cases reported in the literature.

  1. Comprehensive Computed Tomography Radiomics Analysis of Lung Adenocarcinoma for Prognostication.

    PubMed

    Lee, Geewon; Park, Hyunjin; Sohn, Insuk; Lee, Seung-Hak; Song, So Hee; Kim, Hyeseung; Lee, Kyung Soo; Shim, Young Mog; Lee, Ho Yun

    2018-04-05

    In this era of personalized medicine, there is an expanded demand for advanced imaging biomarkers that reflect the biology of the whole tumor. Therefore, we investigated a large number of computed tomography-derived radiomics features along with demographics and pathology-related variables in patients with lung adenocarcinoma, correlating them with overall survival. Three hundred thirty-nine patients who underwent operation for lung adenocarcinoma were included. Analysis was performed using 161 radiomics features, demographic, and pathologic variables and correlated each with patient survival. Prognostic performance for survival was compared among three models: (a) using only clinicopathological data; (b) using only selected radiomics features; and (c) using both clinicopathological data and selected radiomics features. At multivariate analysis, age, pN, tumor size, type of operation, histologic grade, maximum value of the outer 1/3 of the tumor, and size zone variance were statistically significant variables. In particular, maximum value of outer 1/3 of the tumor reflected tumor microenvironment, and size zone variance represented intratumor heterogeneity. Integration of 31 selected radiomics features with clinicopathological variables led to better discrimination performance. Radiomics approach in lung adenocarcinoma enables utilization of the full potential of medical imaging and has potential to improve prognosis assessment in clinical oncology. Two radiomics features were prognostic for lung cancer survival at multivariate analysis: (a) maximum value of the outer one third of the tumor reflects the tumor microenvironment and (b) size zone variance represents the intratumor heterogeneity. Therefore, a radiomics approach in lung adenocarcinoma enables utilization of the full potential of medical imaging and could play a larger role in clinical oncology. © AlphaMed Press 2018.

  2. Poor Prognosis of Gastric Adenocarcinoma with Decreased Expression of AHRR

    PubMed Central

    Wang, Wei; Yuan, Shu-qiang; Huang, Chun-yu; Chen, Yong-ming; Zheng, Yan; Keshari, Rajiv Prasad; Xia, Jian-chuan; Zhou, Zhi-wei

    2012-01-01

    Background The aryl hydrocarbon receptor (AHR) repressor (AHRR), a member of growing superfamily, is a basic-helix-loop-helix/Per-AHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. Recently, AHRR has been proposed to function as a putative new tumor suppressor gene based on some relevant studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in primary gastric adenocarcinoma. Methodology/Principal Findings The expression level of AHRR was analyzed using real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining. It was clearly showed that the expression status of AHRR was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples by RT-qPCR (P = 0.0423) and western blotting analysis (P = 0.004). Moreover, data revealed that AHRR without exon 8 (the active isoform) was the predominant form either in tumor tissues (66.7%, 8/12) or in matched adjacent non-tumor tissues (100.0%, 12/12), and the mRNA level of this isoform was significantly reduced in tumor tissues (P = 0.006). Immunohistochemistry analysis indicated that AHRR expression was significantly decreased in 175 of 410 (42.7%) gastric adenocarcinoma cases. Kaplan-Meier survival curves and Multivariate Cox analysis revealed that decreased expression of AHRR was significantly associated with poor prognosis in gastric adenocarcinoma patients. Conclusions/Significance Our data suggests that, in primary gastric adenocarcinoma, AHRR may play as a suppressor gene and its expression status has the potential to be an independent prognostic factor. PMID:22952704

  3. Evaluation of microvessel density and p53 expression in pancreatic adenocarcinoma

    PubMed Central

    Jureidini, Ricardo; da Cunha, José Eduardo Monteiro; Takeda, Flavio; Namur, Guilherme Naccache; Ribeiro, Thiago Costa; Patzina, Rosely; Figueira, Estela RR; Ribeiro, Ulysses; Bacchella, Telesforo; Cecconello, Ivan

    2016-01-01

    OBJECTIVE: To evaluate the prognostic significance of microvessel density and p53 expression in pancreatic cancer. METHODS: Between 2008 and 2012, 49 patients with pancreatic adenocarcinoma underwent resection with curative intention. The resected specimens were immunohistochemically stained with anti-p53 and anti-CD34 antibodies. Microvessel density was assessed by counting vessels within ten areas of each tumoral section a highpower microscope. RESULTS: The microvessel density ranged from 21.2 to 54.2 vessels/mm2. Positive nuclear staining for p53 was found in 20 patients (40.6%). The overall median survival rate after resection was 24.1 months and there were no differences in survival rates related to microvessel density or p53 positivity. Microvessel density was associated with tumor diameter greater than 3.0 cm and with R0 resection failure. CONCLUSIONS: Microvessel density was associated with R1 resection and with larger tumors. p53 expression was not correlated with intratumoral microvessel density in pancreatic adenocarcinoma. PMID:27438564

  4. Generating a robust prediction model for stage I lung adenocarcinoma recurrence after surgical resection.

    PubMed

    Wu, Yu-Chung; Wei, Nien-Chih; Hung, Jung-Jyh; Yeh, Yi-Chen; Su, Li-Jen; Hsu, Wen-Hu; Chou, Teh-Ying

    2017-10-03

    Lung cancer mortality remains high even after successful resection. Adjuvant treatment benefits stage II and III patients, but not stage I patients, and most studies fail to predict recurrence in stage I patients. Our study included 211 lung adenocarcinoma patients (stages I-IIIA; 81% stage I) who received curative resections at Taipei Veterans General Hospital between January 2001 and December 2012. We generated a prediction model using 153 samples, with validation using an additional 58 clinical outcome-blinded samples. Gene expression profiles were generated using formalin-fixed, paraffin-embedded tissue samples and microarrays. Data analysis was performed using a supervised clustering method. The prediction model generated from mixed stage samples successfully separated patients at high vs. low risk for recurrence. The validation tests hazard ratio (HR = 4.38) was similar to that of the training tests (HR = 4.53), indicating a robust training process. Our prediction model successfully distinguished high- from low-risk stage IA and IB patients, with a difference in 5-year disease-free survival between high- and low-risk patients of 42% for stage IA and 45% for stage IB ( p < 0.05). We present a novel and effective model for identifying lung adenocarcinoma patients at high risk for recurrence who may benefit from adjuvant therapy. Our prediction performance of the difference in disease free survival between high risk and low risk groups demonstrates more than two fold improvement over earlier published results.

  5. French multicentric validation of ALK rearrangement diagnostic in 547 lung adenocarcinomas.

    PubMed

    Lantuejoul, Sylvie; Rouquette, Isabelle; Blons, Hélène; Le Stang, Nolwenn; Ilie, Marius; Begueret, Hugues; Grégoire, Valerie; Hofman, Paul; Gros, Audrey; Garcia, Stephane; Monhoven, Nathalie; Devouassoux-Shisheboran, Mojgan; Mansuet-Lupo, Audrey; Thivolet, Françoise; Antoine, Martine; Vignaud, Jean-Michel; Penault-Llorca, Frederique; Galateau-Sallé, Françoise; McLeer-Florin, Anne

    2015-07-01

    Anaplastic lymphoma kinase (ALK) gene rearrangements in lung adenocarcinoma result in kinase activity targetable by crizotinib. Although fluorescence in situ hybridisation (FISH) is the reference diagnostic technique, immunohistochemistry (IHC) could be useful for pre-screening. Diagnostic yields of ALK IHC, FISH and quantitative reverse transcriptase PCR performed in 14 French pathology/molecular genetics platforms were compared. 547 lung adenocarcinoma specimens were analysed using 5A4 and D5F3 antibodies, two break-apart FISH probes and TaqMan kits. Clinicopathological data were recorded. 140 tumours were ALK rearranged (FISH with ≥15% of rearranged cells) and 400 were ALK FISH negative (<15%). FISH was not interpretable for seven cases. ALK patients were young (p=0.003), mostly females (p=0.007) and light/nonsmokers (p<0.0001). 13 cases were IHC negative but FISH ≥15%, including six cases with FISH between 15% and 20%; eight were IHC positive with FISH between 10% and 14%. Sensitivity and specificity for 5A4 and D5F3 were 87% and 92%, and 89% and 76%, respectively. False-negative IHC, observed in 2.4% of cases, dropped to 1.3% for FISH >20%. Variants were undetected in 36% of ALK tumours. Discordances predominated with FISH ranging from 10% to 20% of rearranged cells and were centre dependent. IHC remains a reliable pre-screening method for ALK rearrangement detection. Copyright ©ERS 2015.

  6. Pressurized Intra Peritoneal Aerosol Chemotherapy in patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma

    PubMed Central

    Khosrawipour, Tanja; Khosrawipour, Veria

    2017-01-01

    Background Patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma were treated with Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC), initial clinical findings are presented. Methods Single institution, tertiary referral center certified for therapy of peritoneal disease. Prospective data collection of PIPAC therapy with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2 of body surface delivered at intervals of six weeks. The outcome criteria were microscopic pathological response, survival and adverse events (v4.0 CTCAE). Results A total of 20 patients (m/f = 3:1) with a mean age of 64.9 (range: 45.0 to 87.0) years underwent 41 PIPAC procedures without intraoperative complications. The mean number of PIPAC cycles was 2.1 (range: one to four). Ten patients with ≥ 2 PIPAC applications were eligible for histological analysis to assess carcinoma regression. Complete or high grade tumor regression was found in two (10%) and five (25%) patients, respectively. An overall median survival of 36.6 weeks after the first PIPAC application was observed. One patient died postoperatively due to small bowel obstruction. No CTCAE level 3 and 4 complications occurred. Conclusion In about one third of patients, repeated PIPAC therapy did induce histological regression of systemic chemo-resistant PC of pancreatic adenocarcinoma. Prospective randomized trials are needed to further clarify any clinical impact of such observations. PMID:29049340

  7. Gastric adenocarcinoma of fundic gland type: Endoscopic and clinicopathological features

    PubMed Central

    Tohda, Gen; Osawa, Takeshi; Asada, Yasuyuki; Dochin, Masaki; Terahata, Shintarou

    2016-01-01

    Gastric adenocarcinoma of fundic gland type (GA-FG) with chief cell differentiation was recently proposed as an extremely rare type of gastric adenocarcinoma. Here, we report 4 cases of GA-FG with chief cell differentiation. Endoscopic features included a submucosal tumor shape or a flat shape, whitish discoloration and dilated vessels on the surface. The tumors were located in the upper or middle third of the stomach. All cases were preoperatively diagnosed as GA-FG by biopsy, and endoscopic submucosal dissection was performed. Resected specimens revealed well-differentiated adenocarcinomas resembling chief cells. Tumor cells were diffusely positive for pepsinogen-I, but partially positive for H+/K+-ATPase in scattered locations around the tumor margin. Despite the presence of minimal invasion of the carcinoma into the submucosal layer, which was observed in two cases, neither lymphatic nor venous invasion was detected in any of the cases. Finally, all cases showed less aggressive clinical behavior with low grade malignancy. PMID:26962407

  8. Adenocarcinoma in Caroli's Disease Treated by Liver Transplantation

    PubMed Central

    Margarit, C.; Murio, E.; Lazaro, J. L.; Charco, R.; Vidal, M. T.; Bonnin, J.

    1993-01-01

    Caroli's disease is characterized by congenital cystic dilatation of the intrahepatic bile ducts. In 7% of casea a malignant tumor develops complicating the course of the disease. We report the case of a 25 year-old woman in whom Caroli's disease was diagnosed at the age of 11. From that time on, she had several episodes of cholangitis. In 1989, the abdominal ultrasound and CT scan showed dilatation of the intrahepatic bile ducts, intracystic lithiasis and a solid mass. FNA cytology showed a papillary adenocarcinoma. At laparotomy a tumor was found occupying both hepatic lobes, and intraoperative US showed another two nodules in the left lobe. The tumor was considered unresectable. Examination of the hilar lymph nodes was tumor-negative. Two weeks later, the patient underwent an ortothopic liver transplantation (OLT). The pathological examination confirmed Caroli's disease with adenocarcinoma. Two years after OLT, the patient is alive with normal liver function and no evidence of disease. To our knowledge this is the first case report of adenocarcinoma in Caroli's disease treated by OLT. PMID:8260439

  9. IL-17 induces EMT via Stat3 in lung adenocarcinoma.

    PubMed

    Huang, Qi; Han, Jieli; Fan, Jinshuo; Duan, Limin; Guo, Mengfei; Lv, Zhilei; Hu, Guorong; Chen, Lian; Wu, Feng; Tao, Xiaonan; Xu, Juanjuan; Jin, Yang

    2016-01-01

    Epithelial-mesenchymal transition (EMT) plays a vital role in lung inflammatory diseases, including lung cancer. However, the role and mechanism of action of the proinflammatory cytokine IL-17 in EMT in lung adenocarcinoma remain unresolved. In our study, we discovered that the expression of N-cadherin, Vimentin, Snail1, Snail2, and Twist1 was positively correlated with IL-17 expression, while E-cadherin expression was negatively correlated with IL-17 expression in human lung adenocarcinoma tissues. Moreover, we confirmed that IL-17 promoted EMT in A549 and Lewis lung carcinoma (LLC) cells in vitro by upregulating N-cadherin, Vimentin, Snail1, Snail2, and Twist1 expression and downregulating E-cadherin expression. Stat3 was activated in IL-17-treated A549 and LLC cells, and Stat3 inhibition or siRNA knockdown notably reduced IL-17-induced EMT in A549 and LLC cells. Thus, IL-17 promotes EMT in lung adenocarcinoma via Stat3 signaling; these observations suggest that targeting IL-17 and EMT are potential novel therapeutic strategies for lung cancer.

  10. Esophageal Adenocarcinoma Developing after Eradication of Helicobacter pylori

    PubMed Central

    Abe, Yasuhiko; Koike, Tomoyuki; Iijima, Katsunori; Imatani, Akira; Ishida, Kazuhiko; Yuki, Toyohiko; Miyata, Go; Shimosegawa, Tooru

    2011-01-01

    A 75-year-old man underwent endoscopic hemostatic therapy for hemorrhagic gastric ulcer in September 2002. After healing of the gastric ulcer, he underwent Helicobacter pylori eradication therapy in February 2003. In August 2007, an irregular tumor was detected in the lower esophagus at annual checkup for gastric cancer screening using X-ray. Endoscopic examination showed that the lower margin of the tumor almost coincided with the esophagogastric junction and that a short segment of Barrett's epithelium existed near the tumor. Biopsies of the tumor showed moderately to poorly differentiated adenocarcinoma. Mild reflux esophagitis and minor hiatal hernia was also observed, and the previously treated gastric ulcer was not recurrent. Absence of H. pylori was confirmed by serum antibody and urea breath test. Surgical resection of the lower esophagus and proximal stomach was performed. The tumor invaded into the muscularis propria of the esophageal wall but had no evidence of lymph node metastasis. Based on macroscopic and pathological findings, the tumor was recognized as esophageal adenocarcinoma. Previous endoscopic examination did not detect any apparent signs of tumor in the esophagogastric junction. As far as we know, this is the first report documenting a newly developed esophageal adenocarcinoma after the successful eradication of H. pylori. PMID:21769287

  11. Molecular biological analysis in a patient with multiple lung adenocarcinomas.

    PubMed

    Wakayama, Tomoshige; Hirata, Hirokuni; Suka, Shunsuke; Sato, Kozo; Tatewaki, Masamitsu; Souma, Ryosuke; Satoh, Hideyuki; Tamura, Motohiko; Matsumura, Yuji; Imada, Hiroki; Sugiyama, Kumiya; Arima, Masafumi; Kurasawa, Kazuhiro; Fukuda, Takeshi; Fukushima, Yasutsugu

    2018-05-01

    The utility of molecular biological analysis in lung adenocarcinoma has been demonstrated. Herein we report a rare case presenting as multiple lung adenocarcinomas with four different EGFR gene mutations detected in three lung tumors. After opacification was detected by routine chest X-ray, the patient, a 64-year-old woman, underwent chest computed tomography which revealed a right lung segment S4 ground-glass nodule (GGN). Follow-up computed tomography revealed a 42 mm GGN nodule with a 26 mm nodule (S6) and a 20 mm GGN (S10). Histopathology of resected specimens from the right middle and lower lobes revealed all three nodules were adenocarcinomas. Four EGFR mutations were detected; no three tumors had the same mutations. Molecular biological analysis is a promising tool for the diagnosis of primary tumors in patients with multiple lung carcinomas of the same histotype, enabling appropriate treatment. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  12. Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

    PubMed

    Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

    2017-07-01

    Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. [Adenocarcinoma of the uterine cervix: particularities in diagnosis and treatment].

    PubMed

    Vandenbroucke, L; Robert, A-L; Lavoué, V; Foucher, F; Henno, S; Levêque, J

    2013-05-01

    The adenocarcinoma of the uterine cervix accounts for 10 to 20% of the premalignant and malignant lesions and is different from the cervical intraepithelial neoplasia and invasive squamous cell carcinoma. Recent literature review (from 1985 to 2012) based on the literature available. Adenocarcinoma in situ is an induced HPV lesion (role of HPV 18) of the glandular epithelium: its preferential endocervical situation explains the difficulties in the diagnosis and follow-up after conservative treatment. If the hysterectomy remains the gold standard for treatment, the conservative treatments (resection in sano of the lesions with margins of more than 1cm, meticulous study of the operative specimen, compliance with the follow-up) are possible in the young patients who desire to preserve their fertility. The invasive adenocarcinoma is characterized by a more difficult diagnosis because of its endocervical development, and a prognosis less favorable when compared to squamous cell carcinoma with a greater frequency of the lymphatic node involvement and metastatic diffusion. Its treatment must take into account the particular gravity of the factors of worse prognosis (FIGO stage, tumor size, lymphatic node spreading, adenosquamous histological subtype) in particular in the advanced stages and includes beside the surgery, radiotherapy and chemotherapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. Outcomes of robotic surgery for pancreatic ductal adenocarcinoma

    PubMed Central

    Zhan, Qian; Deng, Xiaxing; Weng, Yuanchi; Jin, Jiabin; Wu, Zhichong; Li, Hongwei; Shen, Baiyong

    2015-01-01

    Background To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma (PDAC). Methods The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. Results Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy (DP), the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy (MP), the average operative time was 225 min and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula (n=11), bile leak (n=5), anastomotic bleeding (n=2), pancreatic fistula complicated with portal vein thrombosis (n=1), and anastomotic bleeding complicated with acute renal failure (n=1). Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 (15.6±5.8) months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. Conclusions Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and

  15. α-Mangostin suppresses human gastric adenocarcinoma cells in vitro via blockade of Stat3 signaling pathway

    PubMed Central

    Shan, Tao; Cui, Xi-juan; Li, Wei; Lin, Wan-run; Lu, Hong-wei; Li, Yi-ming; Chen, Xi; Wu, Tao

    2014-01-01

    Aim: To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen (Garcinia mangostana Linn), against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects. Methods: Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot. Results: Treatment with α-mangostin (3–10 μg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners. Furthermore, α-mangostin (7 μg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm. Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells. Conclusion: The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway. PMID:24976157

  16. The revised AJCC Staging System (7th Edition) improves prognostic stratification after minimally invasive esophagectomy for esophagogastric adenocarcinoma

    PubMed Central

    Zahoor, Haris; Luketich, James D.; Weksler, Benny; Winger, Daniel G.; Christie, Neil A.; Levy, Ryan M.; Gibson, Michael K.; Davison, Jon M.; Nason, Katie S.

    2015-01-01

    Background Staging for esophagogastric adenocarcinoma lacked sufficient prognostic accuracy and was revised. We compared survival prognostication between American Joint Commission on Cancer (AJCC) 6th- and 7th-editions. Methods We abstracted data for 836 patients who underwent minimally invasive esophagectomy (MIE) for esophagogastric adenocarcinoma (n=256 neoadjuvant). Monotonicity and strength of survival trends, by stage, were assessed (log-rank test of trend chi-squared statistic) and compared using permutation testing. Overall survival (Cox regression) and model fit (Akaike Information Criterion (AIC)) were determined. Results A greater log-rank test of trend statistic indicated stronger survival trends by stage in AJCC-7th (152.872 vs. 167.623; permutation test p<0.001). Greater Cox likelihood chi squared value (162.957 vs. 173.951) and lower AIC (4831.011 vs 4820.016) indicated better model fit. Superior performance was also shown after neoadjuvant therapy. Conclusion AJCC 7th-edition staging for esophagogastric adenocarcinoma provides superior prognostic stratification after MIE, overall and after neoadjuvant therapy compared to AJCC 6th-edition. PMID:26188709

  17. Helicobacter pylori vacA d1 genotype predicts risk of gastric adenocarcinoma and peptic ulcers in northwestern Iran.

    PubMed

    Basiri, Zeinab; Safaralizadeh, Reza; Bonyadi, Morteza Jabbarpour; Somi, Mohammad Hossein; Mahdavi, Majid; Latifi-Navid, Saeid

    2014-01-01

    There is a close relationship between Helicobacter pylori (H pylori)-specific factors and different gastroduodenal diseases. The present study aimed to investigate the prevalence of vacA d1, d2 genotypes in the H pylori isolates from patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and gastritis in East Azerbaijan region, where the incidence of gastric cancer (GC) is high. Strains isolated from this area are likely to be of European ancestry. In this study, genotyping of the vacA d region of 115 isolates obtained from patients with different gastrodoudenal diseases was accomplished by PCR methods. In addition to PCR amplification of H pylori 16S rDNA, rapid urease tests or histological examination were used to confirm the presence of H pylori in biopsy specimens. Data were collected and analyzed using SPSS version 19. Of the total of 83 H pylori isolates, 36 (43.4%) contained the d1 allele and 47 (56.6%) were subtype d2. The results of the multiple linear/logistic regression analysis showed high correlation between allele d1 and gastric adenocarcinoma or PUD. This study suggests that the H pylori vacA d1 genotype helps predict risk for gastric adenocarcinoma and PUD in East Azerbaijan, Iran.

  18. Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma.

    PubMed

    Kumar, Sacheen; Huang, Juzheng; Abbassi-Ghadi, Nima; Mackenzie, Hugh A; Veselkov, Kirill A; Hoare, Jonathan M; Lovat, Laurence B; Španěl, Patrik; Smith, David; Hanna, George B

    2015-12-01

    The present study assessed whether exhaled breath analysis using Selected Ion Flow Tube Mass Spectrometry could distinguish esophageal and gastric adenocarcinoma from noncancer controls. The majority of patients with upper gastrointestinal cancer present with advanced disease, resulting in poor long-term survival rates. Novel methods are needed to diagnose potentially curable upper gastrointestinal malignancies. A Profile-3 Selected Ion Flow Tube Mass Spectrometry instrument was used for analysis of volatile organic compounds (VOCs) within exhaled breath samples. All study participants had undergone upper gastrointestinal endoscopy on the day of breath sampling. Receiver operating characteristic analysis and a diagnostic risk prediction model were used to assess the discriminatory accuracy of the identified VOCs. Exhaled breath samples were analyzed from 81 patients with esophageal (N = 48) or gastric adenocarcinoma (N = 33) and 129 controls including Barrett's metaplasia (N = 16), benign upper gastrointestinal diseases (N = 62), or a normal upper gastrointestinal tract (N = 51). Twelve VOCs-pentanoic acid, hexanoic acid, phenol, methyl phenol, ethyl phenol, butanal, pentanal, hexanal, heptanal, octanal, nonanal, and decanal-were present at significantly higher concentrations (P < 0.05) in the cancer groups than in the noncancer controls. The area under the ROC curve using these significant VOCs to discriminate esophageal and gastric adenocarcinoma from those with normal upper gastrointestinal tracts was 0.97 and 0.98, respectively. The area under the ROC curve for the model and validation subsets of the diagnostic prediction model was 0.92 ± 0.01 and 0.87 ± 0.03, respectively. Distinct exhaled breath VOC profiles can distinguish patients with esophageal and gastric adenocarcinoma from noncancer controls.

  19. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis

    PubMed Central

    Reid, Brian J.; Li, Xiaohong; Galipeau, Patricia C.; Vaughan, Thomas

    2010-01-01

    The public health importance of Barrett’s oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world and there are indications that the incidence of this disease is on the rise in Asian populations where it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma and data indicate that patients with Barrett’s oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinoma arise in individuals without a prior diagnosis of Barrett’s oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma? PMID:20094044

  20. Viral expression associated with gastrointestinal adenocarcinomas in TCGA high-throughput sequencing data

    PubMed Central

    2013-01-01

    Background Up to 20% of cancers worldwide are thought to be associated with microbial pathogens, including bacteria and viruses. The widely used methods of viral infection detection are usually limited to a few a priori suspected viruses in one cancer type. To our knowledge, there have not been many broad screening approaches to address this problem more comprehensively. Methods In this study, we performed a comprehensive screening for viruses in nine common cancers using a multistep computational approach. Tumor transcriptome and genome sequencing data were available from The Cancer Genome Atlas (TCGA). Nine hundred fifty eight primary tumors in nine common cancers with poor prognosis were screened against a non-redundant database of virus sequences. DNA sequences from normal matched tissue specimens were used as controls to test whether each virus is associated with tumors. Results We identified human papilloma virus type 18 (HPV-18) and four human herpes viruses (HHV) types 4, 5, 6B, and 8, also known as EBV, CMV, roseola virus, and KSHV, in colon, rectal, and stomach adenocarcinomas. In total, 59% of screened gastrointestinal adenocarcinomas (GIA) were positive for at least one virus: 26% for EBV, 21% for CMV, 7% for HHV-6B, and 20% for HPV-18. Over 20% of tumors were co-infected with multiple viruses. Two viruses (EBV and CMV) were statistically significantly associated with colorectal cancers when compared to the matched healthy tissues from the same individuals (p = 0.02 and 0.03, respectively). HPV-18 was not detected in DNA, and thus, no association testing was possible. Nevertheless, HPV-18 expression patterns suggest viral integration in the host genome, consistent with the potentially oncogenic nature of HPV-18 in colorectal adenocarcinomas. The estimated counts of viral copies were below one per cell for all identified viruses and approached the detection limit. Conclusions Our comprehensive screening for viruses in multiple cancer types using next

  1. Expression of cyclooxygenase-2 and its relationship to p53 accumulation in ovarian adenocarcinomas.

    PubMed

    Shigemasa, Kazushi; Tian, Xiurong; Gu, Lijun; Shiroyama, Yuko; Nagai, Nobutaka; Ohama, Koso

    2003-01-01

    To investigate cyclooxygenase-2 (COX-2) expression and its relationship to p53 accumulation in ovarian adenocarcinomas, COX-2 and p53 protein expressions were examined by immunohistochemistry in 86 ovarian adenocarcinomas and six normal ovaries. In addition, COX-2 mRNA expression level was examined by semi-quantitative PCR in 36 ovarian adenocarcinomas. Neither COX-2 expression nor p53 accumulation were detected in normal ovarian surface epithelium or germinal inclusion cyst epithelial cells. In contrast, COX-2 protein expression was detected in 31.4% of adenocarcinomas, and p53 protein accumulation was found in 30.2% of adenocarcinomas. A significantly higher COX-2 expression rate was observed in endometrioid adenocarcinomas than in either mucinous (p=0.019) or clear cell (p=0.021) adenocarcinomas, and a significantly higher p53 accumulation rate was observed in serous adenocarcinomas compared to clear cell adenocarcinomas (p=0.015). p53 accumulation correlated with advanced clinical stage (stage I vs. stage II/III/IV: p=0.007), whereas no correlation was found between COX-2 expression and clinical stage. There was a significant positive correlation between COX-2 expression and p53 accumulation status (p=0.003). Log-rank testing showed that p53 accumulation was significantly correlated with poor patient survival (p=0.004), whereas no correlation was found between COX-2 expression and survival. COX-2 mRNA expression was detected in 72.2% of ovarian adenocarcinomas, and a significant correlation between COX-2 mRNA expression status and immunoreactivity (p=0.023) was observed. These results suggest that COX-2 expression might play an important role in ovarian cancer development and that COX-2 expression in ovarian adenocarcinomas is frequently associated with p53 protein accumulation. COX-2 overexpression in ovarian cancer cells might partly be caused by dysfunctional p53.

  2. Loss of RUNX1 is associated with aggressive lung adenocarcinomas.

    PubMed

    Ramsey, Jon; Butnor, Kelly; Peng, Zhihua; Leclair, Tim; van der Velden, Jos; Stein, Gary; Lian, Jane; Kinsey, C Matthew

    2018-04-01

    The mammalian runt-related factor 1 (RUNX1) is a master transcription factor that regulates lineage specification of hematopoietic stem cells. RUNX1 translocations result in the development of myeloid leukemias. Recently, RUNX1 has been implicated as a tumor suppressor in other cancers. We postulated RUNX1 expression may be associated with lung adenocarcinoma etiology and/or progression. We evaluated the association of RUNX1 mRNA expression with overall survival data from The Cancer Genome Atlas (TCGA), a publically available database. Compared to high expression levels, Low RUNX1 levels from lung adenocarcinomas were associated with a worse overall survival (Hazard Ratio = 2.014 (1.042-3.730 95% confidence interval), log-rank p = 0.035) compared to those that expressed high RUNX1 levels. Further immunohistochemical examination of 85 surgical specimens resected at the University of Vermont Medical Center identified that low RUNX1 protein expression was associated with larger tumors (p = 0.038). Gene expression network analysis was performed on the same subset of TCGA cases that demonstrated differential survival by RUNX1 expression. This analysis, which reveals regulatory relationships, showed that reduced RUNX1 levels were closely linked to upregulation of the transcription factor E2F1. To interrogate this relationship, RUNX1 was depleted in a lung cancer cell line that expresses high levels of RUNX1. Loss of RUNX1 resulted in enhanced proliferation, migration, and invasion. RUNX1 depletion also resulted in increased mRNA expression of E2F1 and multiple E2F1 target genes. Our data implicate loss of RUNX1 as driver of lung adenocarcinoma aggression, potentially through deregulation of the E2F1 pathway. © 2017 Wiley Periodicals, Inc.

  3. Gallic Acid Induces Apoptosis in Human Gastric Adenocarcinoma Cells.

    PubMed

    Tsai, Chung-Lin; Chiu, Ying-Ming; Ho, Tin-Yun; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Wu, Yi-Ying

    2018-04-01

    Gastric cancer is one of the most common malignant cancers with a poor prognosis and high mortality rate worldwide. Current treatment of gastric cancer includes surgery and chemotherapy as the main modalities, but the potentially severe side-effects of chemotherapy present a considerable challenge. Gallic acid is a trihydroxybenzoic acid found to exert an anticancer effect against a variety of cancer cells. The purpose of this study was to determine the anti-cancer activity of Galla chinensis and its main component gallic acid on human gastric adenocarcinoma cells. MTT assay and cell death ELISA were used to determine the apoptotic effect of Gallic Chinensis and gallic acid on human gastric adenocarcinoma cells. To determine the pathway and relevant components by which gallic acid-induced apoptosis is mediated through, cells were transfected with siRNA (Fas, FasL, DR5, p53) using Lipofectamine 2000. Reults: Gallic Chinensis and gallic acid induced apoptosis of human gastric adenocarcinoma cells. Gallic acid induced up-regulation of Fas, FasL, and DR5 expression in AGS cells. Transfection of cells with Fas, FasL, or DR5 siRNA reduced gallic acid-induced cell death. In addition, p53 was shown to be involved in gallic acid-mediated Fas, FasL, and DR5 expression as well as cell apoptosis in AGS cells. These results suggest that gallic acid has a potential role in the treatment of gastric cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. 184AA3: a xenograft model of ER+ breast adenocarcinoma

    DOE PAGES

    Hines, William C.; Kuhn, Irene; Thi, Kate; ...

    2015-12-12

    Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER+) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER+ adenocarcinomas that had a high proliferative rate and other features consistent withmore » “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44High subpopulation was discovered, yet their tumor forming ability was far less than CD44Low cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER+ cancers. This model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development.« less

  5. CK7/CK20 Double-Negative Pulmonary Enteric Adenocarcinoma With Histopathological Evaluation of Transformation Zone Between Enteric Adenocarcinoma and Conventional Pulmonary Adenocarcinoma.

    PubMed

    Miyaoka, Masashi; Hatanaka, Kazuhito; Iwazaki, Masayuki; Nakamura, Naoya

    2018-02-01

    We report a rare case of pulmonary enteric adenocarcinoma (PEA) exhibiting a immunohistochemical feature of CK7/CK20 double-negativity by evaluating the transformation zone between PEA and conventional pulmonary adenocarcinoma (CPA). A 75-year-old man was found to have a mass, 40 mm in diameter, in the right lower lobe on chest computed tomography, and underwent right lower lobectomy. Histologically, the tumor was composed of a PEA and CPA component. The dominant PEA component had medium to large complex glands with tall columnar cells with eosinophilic cytoplasm and brush-border. The CPA component comprised small to medium glands with cuboidal cells. Moreover, intermediate glands (INT), which had cuboidal to tall columnar cells, with morphological features between PEA and CPA, was also observed in the transformation area. Immunohistochemically, the PEA component was negative for CK7, CK20, and TTF-1, and positive for CDX2 and SATB2 (weak): the CPA component was negative for CK20, CDX2, and SATB2, and positive for CK7 and TTF-1: the INT were negative for SATB2, with intermingled positive signals for CK7, CK20, TTF-1, and CDX2. The final diagnosis was PEA based on the CPA component and not colorectal carcinoma. To distinguish CK7-negative PEA from metastatic colorectal carcinoma, careful examination for a CPA component is very useful along with clinical information. There are no reports that discuss about process of oncogenesis, de novo sequence or transformation from CPA of PEA. This is the first reported case of CK7/CK20 double-negative PEA, with analysis of the transformation zone between PEA and CPA components.

  6. [Vaginal metastasis revealing an adenocarcinoma of the transverse colon].

    PubMed

    Quaranta, D; Delotte, J; Bongain, A; François, E; Bereder, J-M; Bernard, J-L

    2014-09-01

    Secondary localization to vagina had a severe prognosis, suggesting a disseminated metatastic disease. We report the case of prevalent vaginal metastasis of adenocarcinoma of the transverse colon. A 65 years old patient has consulted for vaginal mass. After delayed diagnosis, she presented with disseminated metastatic disease with peritoneal carcinomatosis. After neoadjuvant chemotherapy, the following treatment consisted of complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and vaginal adjuvant radiotherapy. No recurrence occurred after one year. Vaginal metastasis of colon cancer are rare. The dark prognosis might justify a systematic gynecological examination of women presenting colorectal neoplasy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. Apocrine adenocarcinoma of the nipple: a case report.

    PubMed

    Alex, George

    2008-08-12

    Apocrine adenocarcinomas are rare malignant skin adnexal tumours. Apocrine carcinoma of the nipple is extremely rare and this case to the author's knowledge is only the third reported case worldwide and the first with associated ductal carcinoma in situ elsewhere in the breast. A seventy one year old caucasian female presented to the breast clinic with a growth on her nipple which proved on histopathological analysis to be an apocrine carcinoma. Recommended treatment for apocrine carcinoma includes surgery in the form of wide local excision.

  8. Pulmonar collision tumor: metastatic adenoid cystic carcinoma and lung adenocarcinoma.

    PubMed

    Blanco, M; García-Fontán, E; Ríos, J; Rivo, J E; Fernández-Martín, R; Cañizares, M A

    2012-01-01

    We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen. Copyright © 2010 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

  9. Invasive adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp and synchronous transverse colon cancer

    PubMed Central

    2013-01-01

    An admixture of hyperplastic and adenomatous components within the same polyp is unusual. Adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp (MHAP) occurs even more rarely. We report the first case of a 59-year-old male who presented with invasive adenocarcinoma originating from a MHAP at a sigmoid colon and synchronous transverse colon cancer. PMID:23984814

  10. Invasive adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp and synchronous transverse colon cancer.

    PubMed

    Chen, Chuang-Wei; Hsiao, Koung-Hong; Yue, Chung-Tai; Wang, Chia-Chi

    2013-08-28

    An admixture of hyperplastic and adenomatous components within the same polyp is unusual. Adenocarcinoma arising from a mixed hyperplastic/adenomatous polyp (MHAP) occurs even more rarely. We report the first case of a 59-year-old male who presented with invasive adenocarcinoma originating from a MHAP at a sigmoid colon and synchronous transverse colon cancer.

  11. L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett's adenocarcinoma.

    PubMed

    Lin, Jules; Raoof, Duna A; Thomas, Dafydd G; Greenson, Joel K; Giordano, Thomas J; Robinson, Gregory S; Bourner, Maureen J; Bauer, Christopher T; Orringer, Mark B; Beer, David G

    2004-01-01

    The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5% (24/64) of esophageal adenocarcinomas on tissue microarray. LAT-1 also transports the amino acid-related chemotherapeutic agent, melphalan. Two esophageal adenocarcinoma and one esophageal squamous cell line, expressing LAT-1 on Western blot analysis, were sensitive to therapeutic doses of melphalan (P <.001). Simultaneous treatment with the competitive inhibitor, BCH [2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid], decreased sensitivity to melphalan (P <.05). In addition, confluent esophageal squamous cultures were less sensitive to melphalan (P <.001) and had a decrease in LAT-1 protein expression. Tumors from two esophageal adenocarcinoma cell lines grown in nude mice retained LAT-1 mRNA expression. These results demonstrate that LAT-1 is highly expressed in a subset of esophageal adenocarcinomas and that Barrett's adenocarcinoma cell lines expressing LAT-1 are sensitive to melphalan. LAT-1 expression is also retained in cell lines grown in nude mice providing a model to evaluate melphalan as a chemotherapeutic agent against esophageal adenocarcinomas expressing LAT-1.

  12. ALK-rearranged pulmonary adenocarcinoma in Thai Patients: From diagnosis to treatment efficacy.

    PubMed

    Incharoen, Pimpin; Reungwetwattana, Thanyanan; Saowapa, Sakditad; Kamprerasart, Kaettipong; Pangpunyakulchai, Duangjai; Arsa, Lalida; Jinawath, Artit

    2016-05-03

    Anaplastic lymphoma kinase (ALK) gene rearrangement is detected in 3% to 13% of non-small cell lung carcinoma patients, and these patients benefit from ALK inhibitors. The aim of this study was to determine the prevalence, the clinical and histological characteristics and the treatment outcomes of ALK-rearranged lung adenocarcinoma using immunohistochemistry (IHC) IHC, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) methodologies. A total of 268 pulmonary adenocarcinoma patients were screened for ALK expression by ALK IHC, which was confirmed by FISH and/or RT-PCR for ALK gene rearrangement. The treatment outcomes of ALK-rearranged patients were retrospectively reviewed. ALK gene rearrangement was identified in 26 cases (9.7%) with no EGFR co-mutation, and it showed significant associations with younger age, female sex and non-smoker status (p < 0.05). A cribriform growth pattern was identified as the dominant histologic feature, and a solid signet ring cell component was focally present in a minority of the cases. Among 12 ALK-rearranged patients with conventional treatment, seven cases in the early stage of disease were cured and alive, and five patients in the late stage of the disease progressed and died, with a median overall survival (OS) at 14 months. Of the 14 patients receiving crizotinib, all of them had clinical benefit from crizotinib treatment, with one patient having a complete response (CR), 12 patients having a partial response (PR) and one patient having stable disease (SD). On the cutoff date, six of 14 patients were continuing crizotinib treatment with a median time of response of 7.5 (3-13) months, while eight patients had disease progression, and five of them died with a median OS at 8 months. ALK gene rearrangement tended to occur in younger, non-smoking, female patients. ALK IHC is a reliable screening method to detect ALK gene rearrangement. Crizotinib therapy provided treatment benefit

  13. Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients

    PubMed Central

    Wang, Wei; Pan, Ke; Huang, Chun-yu; Li, Yuan-fang; Wang, Qi-Jing; Yuan, Shu-qiang; Jiang, Shan-shan; Qiu, Hai-bo; Chen, Yong-ming; Zhang, Xiao-fei; Zhao, Bai-wei; mai, Cong; Xia, Jian-chuan; Zhou, Zhi-wei

    2014-01-01

    Background The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro. Methodology/Principal Findings Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion. Conclusions/Significance The reduced expression of UPK1A might play a role in the progression of gastric cancer. Thus, UPK1A could be a potential

  14. Subtype Classification of Lung Adenocarcinoma Predicts Benefit From Adjuvant Chemotherapy in Patients Undergoing Complete Resection

    PubMed Central

    Tsao, Ming-Sound; Marguet, Sophie; Le Teuff, Gwénaël; Lantuejoul, Sylvie; Shepherd, Frances A.; Seymour, Lesley; Kratzke, Robert; Graziano, Stephen L.; Popper, Helmut H.; Rosell, Rafael; Douillard, Jean-Yves; Le-Chevalier, Thierry; Pignon, Jean-Pierre; Soria, Jean-Charles; Brambilla, Elisabeth M.

    2015-01-01

    Purpose The classification for invasive lung adenocarcinoma by the International Association for the Study of Lung Cancer, American Thoracic Society, European Respiratory Society, and WHO is based on the predominant histologic pattern—lepidic (LEP), papillary (PAP), acinar (ACN), micropapillary (MIP), or solid (SOL)—present in the tumor. This classification has not been tested in multi-institutional cohorts or clinical trials or tested for its predictive value regarding survival from adjuvant chemotherapy (ACT). Patients and Methods Of 1,766 patients in the IALT, JBR.10, CALGB 9633 (Alliance), and ANITA ACT trials included in the LACE-Bio study, 725 had adenocarcinoma. Histologies were reclassified according to the new classification and then collapsed into three groups (LEP, ACN/PAP, and MIP/SOL). Primary end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs were estimated through multivariable Cox models stratified by trial. Prognostic value was estimated in the observation arm and predictive value by a treatment effect interaction with histologic subgroups. Significance level was set at .01 for pooled analysis. Results A total of 575 patients were included in this analysis. OS was not prognostically different between histologic subgroups, but univariable DFS and SDFS were worse for MIP/SOL compared with LEP or ACN/PAP subgroup (P < .01); this remained marginally significant after adjustment. MIP/SOL patients (but not ACN/PAP) derived DFS and SDFS but not OS benefit from ACT (OS: HR, 0.71; 95% CI, 0.51 to 0.99; interaction P = .18; DFS: HR, 0.60; 95% CI, 0.44 to 0.82; interaction P = < .01; and SDFS: HR, 0.59; 95% CI, 0.42 to 0.81; interaction P = .01). Conclusion The new lung adenocarcinoma classification based on predominant histologic pattern was not predictive for ACT benefit for OS, but it seems predictive for disease-specific outcomes. PMID:25918286

  15. An ultrastructural comparison of mesotheliomas with adenocarcinomas of the lung and breast.

    PubMed

    Warhol, M J; Corson, J M

    1985-01-01

    The ultrastructural features of 15 mesotheliomas were compared with those of equal numbers of adenocarcinomas of the lung and of the breast in a double-blind study. Combined quantitative and qualitative features were evaluated to provide criteria for distinguishing among these three tumors, which may present as either primary or metastatic pleural tumors. mesotheliomas could be distinguished from adenocarcinomas of the lung by length of microvilli (mean ratios of length to diameter [LDR], 15.7 and 8.7, respectively; P less than 0.01) and content of tonofilaments. Length of microvilli was also useful in distinguishing mesotheliomas from breast adenocarcinomas (mean LDR, 15.7 and 6.9, respectively; P less than 0.001). Adenocarcinomas of the lung could be distinguished from adenocarcinomas of the breast by tonofilament content and the presence of intracytoplasmic lumina. Combined quantitative and qualitative criteria are essential for maximal ultrastructural discrimination among these tumors.

  16. Endometrioid Adenocarcinoma Arising from Endometriosis of the Uterine Cervix: A Case Report

    PubMed Central

    Park, Han Moie; Lee, Sang Soo; Eom, Dae Woon; Kang, Gil Hyun; Yi, Sang Wook

    2009-01-01

    Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix is rare in premenopausal woman. We describe here a patient with this condition and review the clinical and pathological features of these tumors. A 48-yr-old woman complaining of severe dysmenorrhea was referred for investigation of a pelvic mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histological examination revealed an endometrioid adenocarcinoma directly adjacent to the endometriosis at the uterine cervix, with a transition observed between endometriosis and endometrioid adenocarcinoma. The patient was diagnosed as having endometrioid adenocarcinoma arising from endometriosis of the uterine cervix and underwent postoperative chemotherapy. Gynecologists and pathologists should be aware of the difficulties associated with a delay in diagnosis of endometrioid adenocarcinoma arising from endometriosis when the tumor presents as a benign looking endometrioma. PMID:19654969

  17. Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early, Extrathoracic, Multisite Recurrence and of Poor Postrecurrence Survival

    PubMed Central

    Ujiie, Hideki; Kadota, Kyuichi; Chaft, Jamie E.; Buitrago, Daniel; Sima, Camelia S.; Lee, Ming-Ching; Huang, James; Travis, William D.; Rizk, Nabil P.; Rudin, Charles M.; Jones, David R.; Adusumilli, Prasad S.

    2015-01-01

    Purpose To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS). Patients and Methods We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated. Results Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P < .001), and more multisite (P = .011) recurrences. Multivariable analysis of primary tumor factors revealed that, among patients who recurred, solid predominant histologic pattern in the primary tumor (hazard ratio [HR], 1.76; P = .016), age older than 65 years (HR, 1.63; P = .01), and sublobar resection (HR, 1.6; P = .01) were significantly associated with worse PRS. Presence of extrathoracic metastasis (HR, 1.76; P = .013) and age older than 65 years at the time of recurrence (HR, 1.7; P = .014) were also significantly associated with worse PRS. Conclusion In patients with stage I primary lung adenocarcinoma, solid predominant subtype is an independent predictor of early recurrence and, among those patients who recur, of worse PRS. Our findings provide a rationale for investigating adjuvant therapy and identify novel therapeutic targets for patients with solid predominant lung adenocarcinoma. PMID:26261257

  18. Gastric adenocarcinoma in a diamond python (Morelia spilota spilota).

    PubMed

    Baron, H R; Allavena, R; Melville, L M; Doneley, R J T

    2014-10-01

    A 5-year-old captive male diamond python (Morelia spilota spilota) was presented with a 1-month history of regurgitation and anorexia and discrete coelomic distention. Physical examination revealed a firm, immobile mass at approximately two-thirds of the snout-vent length from the front of the head. Ultrasound-guided fine needle aspirate biopsy of the mass in the region of the stomach showed necrosis with bacterial infiltration and possibly neoplastic changes. A gastroscopy was conducted, but showed grossly normal gastric mucosa, confirmed by biopsy. On exploratory coeliotomy, it was confirmed the mass involved most of the stomach wall and occluded the gastric lumen. The mass was completely excised and based on histopathology, a diagnosis of gastric adenocarcinoma was made. The snake was found dead 12 h postoperatively, but no specific cause of death was found on postmortem examination. Most cases of adenocarcinoma in snakes go undiagnosed. This case report illustrates that the architecture of gastric masses may lead to false-negative gastric biopsy results in snakes with neoplasia. © 2014 Australian Veterinary Association.

  19. Minimally Invasive Surgical Approaches for Pancreatic Adenocarcinoma: Recent Trends.

    PubMed

    Lianos, Georgios D; Christodoulou, Dimitrios K; Katsanos, Konstantinos H; Katsios, Christos; Glantzounis, Georgios K

    2017-06-01

    Pancreatic resection for cancer represents a real challenge for every surgeon. Recent improvements in laparoscopic experience, minimally invasive surgical techniques and instruments make now the minimally invasive approach a real "triumph." There is no doubt that minimally invasive surgery has replaced with great success conventional surgery in many fields, including surgical oncology. However, its progress in pancreatic resection for adenocarcinoma has been dramatically slow. Recent evidence supports the notion that minimally invasive distal pancreatectomy is safe and feasible and that is becoming the procedure of choice mainly for benign or low-grade malignant lesions in the distal pancreas. On the other side, minimally invasive pancreatoduodenectomy has not yet been widely accepted and there is enormous skepticism when applied for pancreatic head adenocarcinoma. In this review, we summarize the current evidence on the potential applications of minimally invasive surgical approaches for this aggressive, heterogeneous, and enigmatic type of cancer. Moreover, the potential future applications of these approaches are discussed with the hope to improve the quality of life as well as the survival rates of pancreatic cancer patients.

  20. Proteomic alteration in gastic adenocarcinomas from Japanese patients

    PubMed Central

    Yoshihara, Takahiro; Kadota, Yoshito; Yoshimura, Yoshiyuki; Tatano, Yutaka; Takeuchi, Naohiro; Okitsu, Hiroshi; Umemoto, Atsushi; Yamauchi, Takashi; Itoh, Kohji

    2006-01-01

    Background Gastric adenocarcinomas comprise one of the common types of cancers in Asian countries including Japan. Comprehensive protein profiling of paired surgical specimens of primary gastric adenocarcinomas and nontumor mucosae derived from Japanese patients was carried out by means of two-dimensional gel electrophoresis (2D-EP) and liquid chromatography-electrospray ionic tandem mass spectrometry (LC-ESI-MS) to establish gastric cancer-specific proteins as putative clinical biomarkers and molecular targets for chemotherapy. Results Relatively common alterations in protein expression were revealed in the tumor tissues. Increases in manganese dismutase and nonhistone chromosomal protein HMG-1 (HMG-1) were observed, while decreases in carbonic anhydrases I and II, glutatione-S-transferase and foveolin precursor (gastrokine-1) (FOV), an 18-kDa stomach-specific protein with putative tumor suppressor activity, were detected. RT-PCR analysis also revealed significant down-regulation of FOV mRNA expression in tumor tissues. Conclusion A possible pathological role for down-regulation of FOV in gastric carcinogenesis was demonstrated. Evaluation of the specific decreases in gene and protein expression of FOV in patients may be utilized as clinical biomarkers for effective diagnosis and assessment of gastric cancer. PMID:17187689

  1. Synchronous rectal adenocarcinoma and splenic marginal zone lymphoma.

    PubMed

    Srikumar, T; Markow, M; Centeno, B; Hoffe, S; Tao, J; Fernandez, H; Strosberg, J; Shibata, D

    2016-02-01

    Synchronous cancers of different primary origin are rare. Here, we describe the case of a patient with concomitant diagnoses of rectal adenocarcinoma and splenic marginal zone lymphoma (smzl). A 57-year-old woman initially presented with abdominal pain. Physical examination and computed tomography demonstrated massive splenomegaly, and a complete blood count revealed microcytic anemia and lymphopenia. During the subsequent evaluation, she presented with hematochezia, melena, and constipation, which prompted gastroenterology referral. Subsequent endoscopic rectal ultrasonography revealed a T3N1 moderately differentiated rectal adenocarcinoma, with computed tomography imaging of chest, abdomen, and pelvis confirming no metastasis. Thus, the cancer was classified as clinical stage T3N1M0, stage iii. Bone marrow biopsy confirmed co-existing marginal zone lymphoma, and with the clinical presentation of massive splenomegaly, a diagnosis of smzl was made. The patient's management was individually tailored for simultaneous optimal treatment of both conditions. Concurrent treatment with neoadjuvant rituximab and 5-fluorouracil chemotherapy, with external-beam radiation therapy to the pelvis, was administered, followed by surgery consisting of en bloc splenectomy and distal pancreatectomy, and low anterior resection. The patient completed a standard course of adjuvant folfox (fluorouracil-leucovorin-oxaliplatin) chemotherapy and has remained disease-free for 7 years. To our knowledge, this report is the first to specifically describe simultaneous diagnoses of locally advanced rectal cancer and smzl. We also describe the successful combined neoadjuvant treatment combination of 5-fluorouracil, rituximab, and pelvic radiation.

  2. Dedifferentiated endometrioid adenocarcinoma of the uterus: a case report.

    PubMed

    Soyama, H; Takano, M; Miyamoto, M; Kato, M; Goto, T; Furuya, K

    2016-01-01

    Dedifferentiated endometrioid adenocarcinoma (DEAC) of the uterus was first described by Silva et al. in 2006. The tumor has high-grade endometrial carcinoma component which abruptly emerged from low-grade areas. DEAC showed more aggressive phenotype than FIGO grade 3 endometrioid adenocarcinoma. However, there have been a few studies evaluating effectiveness of adjuvant therapy for the patients with DEC. A 41-year-old case with Stage IVB DEAC that clinically showed resistance to several regimens of chemotherapy is reported. The uterine corpus tumor with size of 120 x 100 mm, and the metastases were found in lung, liver, and pelvic lymph nodes. She underwent supra-vaginal hysterectomy, left salpingo-oophorectomy, and partial resection of ileum. Pathologically, the tumor had both well differentiated and undifferentiated carcinoma components, and it was diagnosed as DEAC. After primary surgery, the patient received four regimens of adjuvant chemotherapy, however all regimens were judged as progressive disease. Subsequently, the patient died of disease seven months after surgery. The present case of DEAC had an exceedingly poor prognosis, as was suggested in the several previous reports. The review of adjuvant therapeutic modalities revealed that there has been no effective therapy in the response-evaluable patients with DEAC. Further investigations for new strategy to treat the cases with DEAC are needed.

  3. Angiogenesis as a prognostic indicator in pancreatic ductal adenocarcinoma.

    PubMed

    Stipa, F; Lucandri, G; Limiti, M R; Bartolucci, P; Cavallini, M; Di Carlo, V; D'Amato, A; Ribotta, G; Stipa, S

    2002-01-01

    Angiogenesis has gained wide acceptance as a reliable prognostic factor in several solid tumors. However, to date, experience in pancreatic adenocarcinoma is limited. Specimens from 45 patients radically operated on at our departments from 1988 to 1997 were stained immunohistochemically with the antibodies anti-mutant p53, anti-bcl2, anti Ki67 and anti-CD31. All the slides were reviewed by the same pathologist without knowledge of the patients' outcome. Mutant p53, Ki67 index and vessel count were significantly related to tumoral behaviour and patients' outcome. Among patients with nodal involvement (Stage III), cumulative survival between hypovascular and hypervascular subgroups differed significantly (p = 0.03). Angiogenesis was independent from TNM in assessing the patients'prognosis at COX analysis (p = 0.02). In patients with pancreatic adenocarcinoma, angiogenesis is a reliable indicator of tumor extension, lymph node status and survival. Its evaluation as a common procedure may contribute to a further improvement in the management of these patients and to a proper selection of those who could benefit from different follow-up protocols or adjuvant treatment.

  4. PNMA1 promotes cell growth in human pancreatic ductal adenocarcinoma.

    PubMed

    Jiang, Shu-Heng; He, Ping; Ma, Ming-Ze; Wang, Yang; Li, Rong-Kun; Fang, Fang; Fu, Ying; Tian, Guang-Ang; Qin, Wen-Xin; Zhang, Zhi-Gang

    2014-01-01

    Paraneoplastic Ma1 (PNMA1) is a member of an expanding family of 'brain/testis' proteins involved in an autoimmune disorder defined as paraneoplastic neurological syndrome (PNS). Although it is widely studied in PNS, little is known about the underlying clinical significance and biological function of PNMA1 in tumors. Here, we find that elevated PNMA1 expression is more commonly observed in pancreatic ductal adenocarcinoma (PDAC) cell lines, compared with normal pancreatic cell and tissues from pancreatic ductal adenocarcinoma patient. Besides, higher PNMA1 expression is closely correlated with large tumor size. Suppression of endogenous PNMA1 expression decreases cell viability and promotes cell apoptosis. Subsequent studies reveal that the PI3K/AKT, MAPK/ERK pathway and members of the anti-apoptotic Bcl-2 family may be involved in the pro-survival and anti-apoptotic effect of PNMA1 on PDAC. Taken together, this study provides evidence that PNMA1 is involved in tumor growth of pancreatic carcinoma and PNMA1-related pathways might represent a new treatment strategy.

  5. Histologic and Outcome Study Supports Reclassifying Appendiceal Goblet Cell Carcinoids as Goblet Cell Adenocarcinomas, and Grading and Staging Similarly to Colonic Adenocarcinomas.

    PubMed

    Yozu, Masato; Johncilla, Melanie E; Srivastava, Amitabh; Ryan, David P; Cusack, James C; Doyle, Leona; Setia, Namrata; Yang, Michelle; Lauwers, Gregory Y; Odze, Robert D; Misdraji, Joseph

    2018-03-23

    Goblet cell carcinoid tumors are amphicrine tumors whose biological behavior ranges from indolent to highly aggressive, depending on tumor grade. Current grading systems for these tumors are based on identifying an adenocarcinoma arising in the setting of a goblet cell carcinoid tumor, which distinguishes this tumor from other gastrointestinal tract adenocarcinomas. Because goblet cell tumors are predominantly tumors of mucin secreting cells, we propose that they be classified as goblet cell adenocarcinomas, and graded using a methodology that has parallels in colorectal adenocarcinoma grading. We graded a large series of goblet cell adenocarcinomas by assessing the proportion of the tumor that demonstrates tubular or clustered growth. Histologic grade correlated with overall survival independent of stage, with median overall survival of 204, 86, and 29 months for low-grade, intermediate-grade, and high-grade goblet cell adenocarcinomas, respectively. Tumor stage also correlated with overall survival. We also graded the tumors according to previously proposed grading systems, and found that these systems are valid, in that they segregate patients according to prognosis.

  6. A Multiscale Model Evaluates Screening for Neoplasia in Barrett’s Esophagus

    PubMed Central

    Curtius, Kit; Hazelton, William D.; Jeon, Jihyoun; Luebeck, E. Georg

    2015-01-01

    Barrett’s esophagus (BE) patients are routinely screened for high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC) screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC) in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1) the probability that small cancers are missed during biopsy-based screening, (2) the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3) the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence. PMID:26001209

  7. A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus.

    PubMed

    Curtius, Kit; Hazelton, William D; Jeon, Jihyoun; Luebeck, E Georg

    2015-05-01

    Barrett's esophagus (BE) patients are routinely screened for high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC) screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC) in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1) the probability that small cancers are missed during biopsy-based screening, (2) the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3) the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence.

  8. Cancer-testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma.

    PubMed

    Xie, Kaipeng; Zhang, Kai; Kong, Jing; Wang, Cheng; Gu, Yayun; Liang, Cheng; Jiang, Tingting; Qin, Na; Liu, Jibin; Guo, Xuejiang; Huo, Ran; Liu, Mingxi; Ma, Hongxia; Dai, Juncheng; Hu, Zhibin

    2018-01-01

    Piwi-like RNA-mediated gene silencing 1 (PIWIL1) has been identified as a novel extremely highly expressed cancer-testis (CT) gene in lung adenocarcinoma. However, the exact function and mechanism of PIWIL1 in lung adenocarcinoma remains unclear. Herein, we sought to investigate the role of PIWIL1 in the occurrence and development of lung adenocarcinoma. We examined the expression pattern of PIWIL1 in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples, and validated it by Real-Time PCR (RT-PCR) in additional 21 paired lung adenocarcinoma tissues and 16 normal tissues. Subsequently, we explored the biological function of PIWIL1 in A549 and H1299 cell lines by gain and loss-of-function analyses. Using TCGA lung adenocarcinoma data, we further performed coexpression and Gene Ontology (GO) analyses, and analyzed the association of DNA methylation levels in PIWIL1 promoter region with its expression. Finally, we evaluated its expression in different mutation status of significantly mutated genes (SMGs) in TCGA lung adenocarcinoma data. We observed that PIWIL1 was expressed in testis and lung adenocarcinoma but not in other normal tissues, and its high expression was associated with shortened survival of lung cancer patients. Overexpression of PIWIL1 could facilitate the proliferation, invasion and migration of lung adenocarcinoma cells and vice versa. GO analysis revealed that PIWIL1 upregulated genes were enriched in embryonic development, cell proliferation and regulation of transcription. Moreover, promoter DNA hypomethylation of PIWIL1 could contribute to its aberrant expression in tumors. Interestingly, PIWIL1 expression was significantly higher in patients without hepatocyte growth factor (HGF) or serine/threonine kinase 11 (STK11) mutation (P = 0.006 and 0.005, respectively). PIWIL1 is an epidriver gene in lung adenocarcinoma, indicating a potential target for further therapy. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  9. Pulmonary Adenocarcinoma in Malignant Pleural Effusion Enriches Cancer Stem Cell Properties during Metastatic Cascade

    PubMed Central

    Chen, Su-Feng; Lin, Yaoh-Shiang; Jao, Shu-Wen; Chang, Yun-Ching; Liu, Chia-Lin; Lin, Yu-Ju; Nieh, Shin

    2013-01-01

    Background Metastasis occurs in a series of discrete steps involving invasion, angiogenesis, lymphovascular space permeation, and establishment of secondary tumors. Malignant pleural effusion (MPE), a type of tumor metastasis, is usually a poor prognostic sign for patients with pulmonary adenocarcinoma, although its underlying mechanism has received less attention than other types of metastases have. The objective of the current study was to confirm whether cancer stem cells (CSCs) in MPE contribute to the “metastatic cascade” through the epithelial – mesenchymal transition (EMT), anoikis, and adaptation in the microenvironment. Methods Pulmonary tissue and corresponding cell blocks of MPE samples from 20 patients with primary adenocarcinoma were analyzed by immunohistochemical staining with CSC-representative markers (CD133, Nanog, and OCT-4) and EMT-associated markers (E-cadherin and vimentin). Correlations between these variables and clinico-pathological parameters were analyzed. Primary cultures from eight cases of MPE were investigated to characterize the CSC properties, including marker expression, sphere formation, and differentiation. Results Expressions of CSC-representative markers for 20 cases of MPE cell blocks were quite diverse and variable ranging from 15% to 90%. Stronger expression of CSC-representative markers and alteration of EMT-associated markers were found at the invasive fronts and in MPEs compared with the expression in primary pulmonary tumor tissues. The expression of OCT-4 in MPEs significantly related to distant metastasis and stage, as well as inversely correlated with patient survival. Primary cultures confirmed the CSC properties in MPE. Five of eight cases of MPE yielded adequate cell clusters, which also showed variable expressions of CSC markers in addition to sphere formation and the ability for differentiation and metastasis. Conclusion This pilot study offers a better understanding of the metastatic cascade. Establishing

  10. Failure Patterns in Resected Pancreas Adenocarcinoma: Lack of Predicted Benefit to SMAD4 Expression

    PubMed Central

    Winter, Jordan M.; Tang, Laura H.; Klimstra, David S.; Liu, Weiguo; Linkov, Irena; Brennan, Murray F.; D'Angelica, Michael I.; DeMatteo, Ronald P.; Fong, Yuman; Jarnagin, William R.; O'Reilly, M.; Allen, Peter J.

    2015-01-01

    Objective To determine if SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA) Introduction SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection. Methods A tissue microarray was constructed including 127 patients with resected PDA and either short (<12 months) or long (>30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, tumor size) were recorded, and disease-specific outcomes (e.g. recurrence pattern and early cancer-specific mortality) determined. Results Loss of SMAD4 expression in pancreatic adenocarcinoma was identified in 40 of 127 patients (32 %). SMAD4 loss occurred in 27% of patients who experienced isolated local recurrence, 33% of patients with a distant recurrence, 33% of patients who recurred locally and at distant sites, and 25% of patients who were without evidence of recurrence (Fisher's exact, p=0.9). In a multivariate analysis, the presence of regional lymph node metastases was the only factor associated with the development of distant metastases (odds ratio, OR=4.7, p=0.02). SMAD4 was neither associated with recurrence pattern (OR=0.9, p=0.9), nor early death (OR=0.5, p=0.15). Conclusion Primary tumor SMAD4 expression status was not a predictor of recurrence pattern in a large cohort of patients with resected PDA. PMID:23360922

  11. Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

    SciTech Connect

    Horowitz, David P.; Hsu, Charles C.; Wang Jingya

    2011-08-01

    Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients {>=}75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age {>=}75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were {>=}75 years of age and 489 of 655 patients (74.7%) were <75 years of age.more » Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.« less

  12. P16-positive continuous minimal deviation adenocarcinoma and gastric type adenocarcinoma in a patient with Peutz-Jeghers syndrome.

    PubMed

    Peng, Wei-Xia; Kure, Shoko; Ishino, Kousuke; Kurose, Keisuke; Yoneyama, Koichi; Wada, Ryuichi; Naito, Zenya

    2015-01-01

    We report a case of Peutz-Jeghers syndrome (PJS) in a 33-year-old female patient with synchronous uterine cervical minimal deviation adenocarcinoma (MDA) and gastric type adenocarcinoma (GTA). The patient was diagnosed with PJS at the age of 10. At the time of consultation, she complained of watery discharge. Magnetic resonance imaging of the pelvis showed a poorly circumscribed mass in the uterine cervix. Histologically, both MDA and GTA components, as well as their transitional area, were observed. Both components were diffusely positive for MUC6, CK7 and, robustly, for p16. Moreover, the components were negative for ER, PgR and CEA, while HIK1083 and CK20 positive cells were found focally. Ki-67 labeling index in the MDA component was 5% while that in the GTA component was 50%. This case of GTA accompanied by MDA in a patient with PJS is distinct from the single previously-reported comparable case of which we are aware, with respect to the overexpression of p16 protein, an event considered rare in these tumors, and the continuity between the MDA and GTA components. This continuity favors the hypothesis that GTA arises from the dedifferentiation of MDA.

  13. P16-positive continuous minimal deviation adenocarcinoma and gastric type adenocarcinoma in a patient with Peutz-Jeghers syndrome

    PubMed Central

    Peng, Wei-Xia; Kure, Shoko; Ishino, Kousuke; Kurose, Keisuke; Yoneyama, Koichi; Wada, Ryuichi; Naito, Zenya

    2015-01-01

    We report a case of Peutz-Jeghers syndrome (PJS) in a 33-year-old female patient with synchronous uterine cervical minimal deviation adenocarcinoma (MDA) and gastric type adenocarcinoma (GTA). The patient was diagnosed with PJS at the age of 10. At the time of consultation, she complained of watery discharge. Magnetic resonance imaging of the pelvis showed a poorly circumscribed mass in the uterine cervix. Histologically, both MDA and GTA components, as well as their transitional area, were observed. Both components were diffusely positive for MUC6, CK7 and, robustly, for p16. Moreover, the components were negative for ER, PgR and CEA, while HIK1083 and CK20 positive cells were found focally. Ki-67 labeling index in the MDA component was 5% while that in the GTA component was 50%. This case of GTA accompanied by MDA in a patient with PJS is distinct from the single previously-reported comparable case of which we are aware, with respect to the overexpression of p16 protein, an event considered rare in these tumors, and the continuity between the MDA and GTA components. This continuity favors the hypothesis that GTA arises from the dedifferentiation of MDA. PMID:26191312

  14. The Significance of MMP-1 in EGFR-TKI-Resistant Lung Adenocarcinoma: Potential for Therapeutic Targeting.

    PubMed

    Saito, Ryoko; Miki, Yasuhiro; Ishida, Naoya; Inoue, Chihiro; Kobayashi, Masayuki; Hata, Shuko; Yamada-Okabe, Hisafumi; Okada, Yoshinori; Sasano, Hironobu

    2018-02-18

    Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance is one of the most important problems in lung cancer therapy. Lung adenocarcinoma with EGFR-TKI resistance was reported to have higher abilities of invasion and migration than cancers sensitive to EGFR-TKI, but the function of matrix metalloproteinases (MMPs) has not been explored in EGFR-TKI-resistant lung adenocarcinoma. This study aims to clarify the significance of MMP-1 in EGFR-TKI-resistant lung adenocarcinoma. From the results of in vitro studies of migration and invasion assays using EGFR-TKI-sensitive and -resistant cell lines and phosphorylation antibody arrays using EGF and rapamycin, we first demonstrate that overexpression of MMP-1, which might follow activation of a mammalian target of rapamycin (mTOR) pathway, plays an important role in the migration and invasion abilities of EGFR-TKI-resistant lung adenocarcinoma. Additionally, immunohistochemical studies using 89 cases of lung adenocarcinoma demonstrate that high expression of MMP-1 is significantly correlated with poor prognosis and factors such as smoking history and the subtype of invasive mucinous adenocarcinoma. These are consistent with the results of this in vitro study. To conclude, this study provides insights into the development of a possible alternative therapy manipulating MMP-1 and the mTOR signaling pathway in EGFR-TKI-resistant lung adenocarcinoma.

  15. Correlation between matrix metalloproteinase-9 and vascular endothelial growth factor expression in lung adenocarcinoma.

    PubMed

    Wen, Y L; Li, L

    2015-12-29

    The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) and clinicopathological features of lung adenocarcinoma. The expression of MMP-9 and VEGF was evaluated by immunohistochemistry of 30 samples from lung adenocarcinoma patients and 12 paratumoral (normal) tissue samples. In addition, the change in VEGF or MMP-9 expression after MMP-9 or VEGF blockade, respectively, was measured using western blot in lung adenocarcinoma A549 cells. High expression of MMP-9 was found in 63.3% of adenocarcinoma tissues versus 16.7% in normal tissues (P < 0.05). High expression of VEGF was found in 70% of adenocarcinoma tissues versus 25% in normal tissues (P < 0.05). A positive correlation was identified between MMP-9 and VEGF expression (correlation coefficient = 0.7094, P < 0.001), and their mutual overexpression was associated with clinical staging and lymph node status (P < 0.05). In addition, an decrease in VEGF protein expression was observed after MMP-9 blockade by an MMP-9-specific monoclonal antibody. Similarly, a decrease in MMP-9 protein expression was found after VEGF blockade by a VEGF-specific monoclonal antibody. In conclusion, VEGF and MMP-9 are overexpressed in lung adenocarcinoma tissues, and they have a synergistic effect on the invasion and metastasis of adenocarcinoma.

  16. p16INK4A overexpression and HPV infection in uterine cervix adenocarcinoma.

    PubMed

    Missaoui, Nabiha; Hmissa, Sihem; Frappart, Lucien; Trabelsi, Amel; Ben Abdelkader, Atef; Traore, Cheick; Mokni, Moncef; Yaacoubi, Mohamed Tahar; Korbi, Sadok

    2006-05-01

    Human papillomaviruses (HPVs) are causally involved in the genesis of cervical carcinomas and their precursors, and there is a strong relationship between the cyclin-dependant kinase inhibitor p16INK4A and HPV infection. This study was carried out to assess the correlations between p16INK4A expression as an early biomarker of the endocervical adenocarcinoma and HPV infection. p16INK4A expression and HPV typing were performed on 46 samples including 5 normal endocervix, 9 benign lesions of the endocervix, 25 endocervical adenocarcinomas, and 7 endometrioid adenocarcinomas of the uterine corpus. A semiquantification of the p16INK4A immunostaining was realized (using both the staining intensity and the percentage of positive cells) and was graded from 0 to 15. All of the 25 endocervical adenocarcinomas overexpressed p16INK4A; the adjacent epithelium and the connective tissue were strictly negative. No p16INK4A was detected in nine benign endocervical lesions and in five normal endocervix. Few endometrioid adenocarcinomas of the uterine corpus that infiltrate the endocervix exhibited a low immunoreactivity (score 0/15 or 1/15). This pattern of expression is significantly associated with HPV infection (p<10(-3)), mainly high-risk HPV types (p=0.02). Our results suggest that p16INK4A is a putative molecular biomarker that consistently discriminates uterine cervix adenocarcinomas from benign lesions and from endometrioid adenocarcinomas of the uterine corpus.

  17. ALK rearrangement in specific subtypes of lung adenocarcinoma: immunophenotypic and morphological features.

    PubMed

    Possidente, Luciana; Landriscina, Matteo; Patitucci, Giuseppe; Borgia, Ludovica; Lalinga, Vittoria; Vita, Giulia

    2017-05-01

    Lung adenocarcinomas are characterized by a variety of genetic and epigenetic changes that lead to activation of specific signaling pathways. This allowed the classification of lung adenocarcinomas according to genetic alterations and the clinical development of novel anticancer agents that affect the activity of specific oncoproteins. In such a context, chromosomal rearrangements that cause constitutive activation of ALK gene define a category of lung adenocarcinomas that is amenable to targeted therapy with ALK inhibitors. Thus, a major issue of current research is to define the morphological and immunophenotypic features of lung ALK-rearranged adenocarcinomas to improve the selection of tumors suitable for molecular genotyping. ALK status was determined, by immunohistochemistry and fluorescence in situ hybridization, in 94 surgically resected lung adenocarcinomas and correlated with histomorphological parameters. Indeed, ALK rearrangement was observed in 10/94 (11%) lung adenocarcinomas and enriched in tumors with a predominant mucinous (46%; p < 0.05) and solid (29%; p < 0.05) pattern. By contrast, it was lacking or sporadically observed in lung adenocarcinomas with predominant acinar, papillary or lepidic pattern. Moreover, the presence of signet-ring cells was predominantly observed in ALK-rearranged tumors (47%; p < 0.05). These data suggest that ALK rearrangement is associated with specific and distinct clinical-pathological characters compared to other genotypes. Thus, the knowledge of these characteristics can improve the diagnostic accuracy and lead to a better understanding of the behavior of ALK-rearranged NSCLC.

  18. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    SciTech Connect

    Guo, Kai, E-mail: gk161@163.com; Department of Respiration, 161th Hospital, PLA, Wuhan 430015; Jin, Faguang, E-mail: jinfag@fmmu.edu.cn

    2015-09-25

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5more » also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.« less

  19. Expression of VEGF, EGFR, and IL-6 in gastric adenomas and adenocarcinomas by endoscopic submucosal dissection.

    PubMed

    Lee, Shin-Ae; Choi, Seok-Reyol; Jang, Jin-Seok; Lee, Jong-Hun; Roh, Myung-Hwan; Kim, Sang Ock; Kim, Min-Chan; Kim, Su-Jin; Jeong, Jin-Sook

    2010-07-01

    The degree of intratumoral microvascular density is thought to affect tumor metastasis and prognosis in various human cancers, including gastric cancer. Despite recent medical advancements, gastric adenoma or adenocarcinoma remains a considerable therapeutic challenge. Endoscopic submucosal dissection (ESD) is a more recent approach that is now commonly used for radical resection of gastric adenoma and adenocarcinoma. The expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and interleukin-6 (IL-6) are related to the prognosis of gastric adenocarcinoma. However, the expression of these factors in gastric adenoma/adenocarcinoma following ESD has not been clearly evaluated. Here, we report on our study of the expression of VEGF, EGFR, and IL-6 by immunohistochemical staining in extracted tissue from adenoma or adenocarcinoma of the stomach by ESD and subsequent evaluation of the correlation of VEGF, EGFR, and IL-6 with other clinicopathological parameters. The patient cohort consisted of 102 patients with adenoma or adenocarcinoma of the stomach. Immunohistochemical staining for VEGF and IL-6 was significantly higher in both high grade dysplasia and adenocarcinoma than in low grade dysplasia (P < 0.05). There was significant correlation between histological grade and intensity of immunohistochemical staining of VEGF (P = 0.039). Histological differentiation of adenocarcinoma was related to IL-6 expression (P = 0.028). The immunoreactivity of VEGF and IL-6 increased significantly in lesions >2 cm compared to lesions <2 cm (P < 0.05). The immunohistochemical expression of IL-6 and VEGF can be considered to be useful for clinical diagnosis and follow-up of adenoma or adenocarcinoma of the stomach.

  20. Cytomorphological features of ALK-positive lung adenocarcinomas: psammoma bodies and signet ring cells.

    PubMed

    Pareja, Fresia; Crapanzano, John P; Mansukhani, Mahesh M; Bulman, William A; Saqi, Anjali

    2015-03-01

    Correlation between histology and genotype has been described in lung adenocarcinomas. For example, studies have demonstrated that adenocarcinomas with an anaplastic lymphoma kinase (ALK) gene rearrangement may have mucinous features. The objective of the current study was to determine whether a similar association can be identified in cytological specimens. A retrospective search for ALK-rearranged cytopathology (CP) and surgical pathology (SP) lung carcinomas was conducted. Additional ALK-negative (-) lung adenocarcinomas served as controls. For CP and SP cases, the clinical data (i.e., age, sex, and smoking history), architecture, nuclear features, presence of mucin-containing cells (including signet ring cells), and any additional salient characteristics were evaluated. The search yielded 20 ALK-positive (+) adenocarcinomas. Compared with patients with ALK(-) lung adenocarcinomas (33 patients; 12 with epidermal growth factor receptor [EGFR]-mutation, 11 with Kristen rat sarcoma [KRAS]-mutation, and 10 wild-type adenocarcinomas), patients with ALK(+) adenocarcinoma presented at a younger age; and there was no correlation noted with sex or smoking status. The most common histological pattern in SP was papillary/micropapillary. Mucinous features were associated with ALK rearrangement in SP specimens. Signet ring cells and psammoma bodies were evident in and significantly associated with ALK(+) SP and CP specimens. However, psammoma bodies were observed in rare adenocarcinomas with an EGFR mutation. Both the ALK(+) and ALK(-) groups had mostly high nuclear grade. Salient features, including signet ring cells and psammoma bodies, were found to be significantly associated with ALK(+) lung adenocarcinomas and are identifiable on CP specimens. Recognizing these may be especially helpful in the molecular triage of scant CP samples. © 2014 American Cancer Society.

  1. Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations.

    PubMed

    Zheng, Difan; Wang, Rui; Zhang, Yang; Pan, Yunjian; Cheng, Xinghua; Cheng, Chao; Zheng, Shanbo; Li, Hang; Gong, Ranxia; Li, Yuan; Shen, Xuxia; Sun, Yihua; Chen, Haiquan

    2016-04-01

    We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations. We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients. Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas. ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.

  2. Endometrial adenocarcinoma in a 13-year-old girl.

    PubMed

    Kim, Sung Mee; Shin, So Jin; Bae, Jin Gon; Kwon, Kun Young; Rhee, Jeong Ho

    2016-03-01

    Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature.

  3. pANCA-vasculitis associated with rectal adenocarcinoma.

    PubMed

    Hommel, C; Rihova, Z; Mokaddem, F; Libotte, B

    2014-12-01

    We report the case of a 69-year-old male patient who was admitted for fever, dry cough, recurrent sinusitis with epistaxis, anorexia with weight loss of 20 kg over a 3-month period, myalgia, and mononeuritis multiplex. He was diagnosed with pANCA/anti-MPO associated vasculitis and rectal adenocarcinoma. The tumor was treated by surgical resection. Recurrence of vasculitis occurred during steroid tapering which prompted us to add Mycophenolate mofetyl. A complete remission was achieved. We conclude that in the present case the vasculitis was an independent disease, not a paraneoplastic phenomenon. We discuss the value of different ANCA serologies for diagnostics and follow-up, the epidemiology of vasculitis associated with malignancy, and the concept of vasculitis as a paraneoplastic syndrome.

  4. A retrospective study of 44 canine apocrine sweat gland adenocarcinomas.

    PubMed

    Simko, Elemir; Wilcock, Brian P; Yager, Julie A

    2003-01-01

    Apocrine sweat gland adenocarcinomas (AACs) are relatively uncommon skin tumors in dogs. Little prognostic or behavioral information has been published for these tumors. In this retrospective study, 44 AACs from diagnostic archives were reexamined and clinical postexcisional follow-ups for 25 of the 44 cases were obtained by a survey. There were 28 out of 44 (65.9%) AACs that invaded the capsule, stroma, or both, 5 of 44 (11.4%) invaded blood vessels and stroma, and 1 out of 25 (4%) had distant metastases. The presence or absence of stromal and vascular invasion was predicted by clinical examination with more than 80% accuracy. Postexcisional median survival of dogs with AACs was 30 mo at the time of survey. Determination of a correlation between histological features and malignant behavior of AACs was compromised by the low number of cases with clinical AAC-related problems; however, it appears that intravascular invasion is an important indicator of potential systemic metastases.

  5. Recent advances in preoperative management of esophageal adenocarcinoma

    PubMed Central

    Harada, Kazuto; Mizrak Kaya, Dilsa; Baba, Hideo; Ajani, Jaffer A.

    2017-01-01

    Esophageal cancer is an aggressive malignancy with increasing incidence, and the prognosis of patients treated by surgery alone remains dismal. Preoperative treatment can modestly prolong overall survival. Preoperative chemotherapy or chemoradiation is the standard of care for resectable esophageal cancer (greater than clinical stage I and less than clinical stage IV). One of the challenges is to predict complete response in the surgical specimen from preoperative therapy and to avoid surgery in some patients but also predict ineffectiveness of preoperative therapy if the tumor is resistant and avoid such therapies altogether. In-depth understanding of the molecular biology could lead to personalized therapy, and in the future, clinical trials designed according to molecular features are expected. Here, we summarize preoperative treatment for esophageal adenocarcinoma and their potential. PMID:28491289

  6. Bronchogenic adenocarcinoma in a hyacinth macaw (Anodorhynchus hyacinthinus).

    PubMed

    Baumgartner, Wes A; Guzman, David Sanchez-Migallon; Hollibush, Shawn; Gaschen, Lorrie; Hodgin, E Clay; Mitchell, Mark A

    2008-09-01

    An adult female hyacinth macaw (Anodorhynchus hyacinthinus) was presented for sudden onset of severe weakness in the legs. Neurologic examination revealed bilateral paresis of the pelvic limbs and decreased proprioception. Results of radiographs and computed tomography (CT) revealed variably sized soft tissue nodules throughout the lungs and invading into the spine and vertebral canal. Soon after the CT scan, the bird went into cardiorespiratory arrest and died. At necropsy, several yellow, coalescing nodules that were firm with a caseous component were present in the lungs, and a focus of similar tissue was attached to the vertebrae and invaded the spinal canal. On histologic examination, the diagnosis was primary pulmonary bronchial adenocarcinoma with spinal invasion.

  7. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma.

    PubMed

    Yetkin, Gurkan; Celayir, Fevzi; Akgun, Ismail Ethem; Ucak, Ramazan

    2017-01-01

    A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy.

  8. Synchronous Occurrence of Primary Breast Carcinoma and Primary Colon Adenocarcinoma

    PubMed Central

    Yetkin, Gurkan; Akgun, Ismail Ethem; Ucak, Ramazan

    2017-01-01

    A 65-year-old female patient presented to the emergency clinic with abdominal pain, meteorism, and intermittent rectal bleeding. Colonoscopy was performed, and a hepatic flexure tumor was detected. Histopathological examination of biopsy revealed adenocarcinoma. Thoracoabdominal CT was performed for staging, and a spiculated contour mass was found incidentally on the left breast. Mammography and ultrasonography were performed for the cause of these findings, and suspicious lesions of malignancy were seen in the left breast. Invasive ductal carcinoma was detected in core needle biopsy samples from lesions. In the multidisciplinary council consisting of oncologist, pathologist, radiologist, and general surgery specialist, it was decided to perform breast operation first and then colon operation, followed by adjuvant chemotherapy. In the first operation, left total mastectomy and sentinel lymph node biopsy were performed. One week after her initial operation, the patient underwent right hemicolectomy. After operations, the patient did not develop postoperative complications and was sent to medical oncology department for adjuvant chemotherapy. PMID:29209551

  9. A case of primary papillary disseminated adenocarcinoma of canine lung.

    PubMed

    Conti, Maria Beatrice; Marchesi, M C; Angeli, G; Lepri, E; Marinetti, C; Rueca, F

    2010-06-01

    Primary lung tumors are rare in dogs, whereas pulmonary metastatic neoplastic involvement is common. We describe a case of a 12-year-old male, mixed-breed dog with a 3-month history of coughing and dyspnea. The investigating protocol, which also includes transcutaneous pulmonary biopsy, allowed a diagnosis of lung adenocarcinoma that necroscopic findings confirmed as a primary neoplasia. The tumor exhibited a nodular-disseminated growth, mimicking the metastatic involvement of the lung, instead of the single-mass appearance that has been observed by other authors. The present report indicates that, although the incidence of canine primary lung neoplasms is markedly low, this condition must be considered in the differential diagnosis of lung diseases that cause coughing and dyspnea in older dogs.

  10. Cutaneous metastases of a bronchial adenocarcinoma in a cat.

    PubMed

    Favrot, Claude; Degorce-Rubiales, Frederique

    2005-06-01

    This case report describes a cat with metastasis of a bronchial adenocarcinoma to the abdominal skin. The cat had been treated with antibiotics and corticosteroids for several episodes of coughing when it acutely developed erythema, pustules and plaques on the abdominal skin. Diagnosis was based on cytological examination of fine-needle aspirates of cutaneous pustules, X-ray examination of the thorax and histological examination of skin biopsy samples. As the prognosis was poor, the cat was euthanased. Necropsy findings confirmed the diagnosis. Cutaneous metastases of lung carcinoma are rare in cats but have been reported in the digits with underlying bone involvement. To the authors' knowledge, this is the first report of metastasis of a feline bronchial carcinoma to the ventral skin.

  11. Serrated pathway adenocarcinomas: molecular and immunohistochemical insights into their recognition.

    PubMed

    Gurzu, Simona; Szentirmay, Zoltan; Toth, Erika; Bara, Tivadar; Bara, Tivadar; Jung, Ioan

    2013-01-01

    Colorectal adenocarcinomas (CRC) developed through serrated pathway seem to present particular behavior compared with the non-serrated ones, but recognition of them is difficult to do. The aim of our paper was to establish some criteria to facilitate their identification. In 170 consecutive CRCs, we performed immunohistochemical staining with Cytokeratin 7 (CK7) and Cytokeratin 20 (CK20) and also with p53 and MLH-1. At the same time, we analyzed BRAF and K-ras mutations and the microsatellite status of CRC. 26.47% of cases expressed CK7, and 16.47% were CK20-negative. Diffuse positivity for CK7 was associated in the proximal colon with CK20 negativity or weak positivity, BRAF mutations, lack of K-ras mutations, and p53 and MLH-1 negativity. All these cases were microsatellite-unstable and were diagnosed in stage II. Those cases from the distal colon and rectum that expressed CK7 were K-ras-mutated and had low p53 index and MLH-1 positivity, independent of the CK20 expression. CK7, associated with MLH-1 and p53 expression, and also with the microsatellite status, BRAF and K-ras pattern, might be used to identify the CRC potentially going through serrated pathway. The serrated pathway adenocarcinomas of the proximal colon that do not display the morphological features of this pattern are more frequent CK7+/p53-/MLH-1-/BRAF-mutated/K-ras-wt/MSI cases, but those located in the distal colorectal segments seem to be CK7+/CK20+/p53-/MLH-1+/BRAF wt/K-ras-mutated/MSS cases.

  12. [Lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement].

    PubMed

    Caliez, J; Monnet, I; Pujals, A; Rousseau-Bussac, G; Jabot, L; Boudjemaa, A; Leroy, K; Chouaid, C

    2017-05-01

    Among patients with non-small-cell lung cancer, coexistence of EGFR mutation and ALK rearrangement is rare. We describe the clinical features of two patients with this double anomaly. A 62-year-old Caucasian non-smoking woman was diagnosed with cT4N0M0 lung adenocarcinoma. Initial biopsy showed EGFR mutation and ALK rearrangement. She received cisplatin-gemcitabine, followed by 17 months of gemcitabine. Owing to progression, she received erlotinib for 14 months, then paclitaxel for 6 months and finally crizotinib. A partial response was achieved and maintained for 24 months. A 45-year-old Caucasian woman, light smoker, was diagnosed with cT2N3M0 lung adenocarcinoma. Only EGFR mutation was found on initial analysis. She underwent treatment with cisplatin-gemcitabine and thoracic radiotherapy. Progression occurred after 8 months and afatinbib was started. Eight months later, progression was observed with a neoplasic pleural effusion in which tumor cells expressing ALK rearrangement were found. A new FISH analysis was performed on the initial tumor but did not find this rearrangement. Despite a third line of crizotinib, the patient died one month later. The literature shows 45 other cases of these two abnormalities, observed either from the start or during follow-up. EGFR's TKI were almost always given before ALK's TKI. Therapeutic strategy needs to be clarified in cases of double alteration. With regard to the second patient, appearance of ALK rearrangement may constitute a resistance mechanism to EGFR's TKI. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  13. Prognostic Comparison Between Mucinous and Nonmucinous Adenocarcinoma in Colorectal Cancer

    PubMed Central

    Park, Jong Seob; Huh, Jung Wook; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong; Chun, Ho-Kyung

    2015-01-01

    Abstract Mucinous adenocarcinoma (MAC) is a histological subtype of colorectal cancer. The oncologic behavior of MAC differs from nonmucinous adenocarcinoma (non-MAC). Our aim in this study was to characterize patients with colorectal MAC through evaluation of a large, institutional-based cohort with long-term follow-up. A total of 6475 patients with stages I to III colorectal cancer who underwent radical surgery were enrolled from January 2000 to December 2010. Prognostic comparison between MAC (n = 274, 4.2%) and non-MAC was performed. The median follow-up period was 48.0 months. Patients with MAC were younger than those without MAC (P = 0.012) and had larger tumor size (P < 0.001), higher preoperative carcinoembryonic antigen (P < 0.001), higher pathologic T stage (P < 0.001), more right-sided colon cancer (49.3%, P < 0.001), and more frequent high-frequency microsatellite instability (10.2%, P < 0.001). Five-year disease-free survival (DFS) was 76.5% in the MAC group and 83.2% in the non-MAC group (P = 0.008), and 5-year overall survival was 81.4% versus 87.4%, respectively (P = 0.005). Mucinous histology (MAC vs non-MAC) in the entire cohort was not an independent prognostic factor of DFS but had a statistical tendency (P = 0.071). In subgroup analysis of colon cancer without rectal cancer, mucinous histology was an independent prognostic factor (P = 0.026). MAC was found at more advanced stage, located mainly at the right side and was an independent factor of survival in colon cancer. Because of the unique biological behavior of MAC, patients with MAC require special consideration during follow-up. PMID:25881840

  14. Pattern Classification of Endocervical Adenocarcinoma: Reproducibility and Review of Criteria

    PubMed Central

    Rutgers, Joanne K.L.; Roma, Andres; Park, Kay; Zaino, Richard J.; Johnson, Abbey; Alvarado, Isabel; Daya, Dean; Rasty, Golnar; Longacre, Teri; Ronnett, Brigitte; Silva, Elvio

    2017-01-01

    Previously, our international team proposed a 3-tiered pattern classification (Pattern Classification) system for endocervical adenocarcinoma of the usual type that correlates with nodal disease and recurrence. Pattern Classification- A have well demarcated glands lacking destructive stromal invasion or lymphovascular invasion (lymphovascular invasion), Pattern Classification- B show localized, limited destructive invasion arising from A-type glands, and Pattern Classification- C have diffuse destructive stromal invasion, significant (filling a 4× field) confluence, or solid architecture. 24 Pattern Classification-A, 22 Pattern Classification-B, 38 Pattern Classification-C from the tumor set used in the original description were chosen using the reference diagnosis (reference diagnosis) originally established. 1 H&E slide per case was reviewed by 7 gynecologic pathologists, 4 from the original study. Kappa statistics were prepared, and cases with discrepancies reviewed. We found a majority agreement with reference diagnosis in 81% of cases, with complete or near complete (6 of 7) agreement in 50%. Overall concordance was 74%. Overall Kappa (agreement among pathologists) was .488 (moderate agreement). Pattern Classification- B has lowest kappa, and agreement is not improved by combining B+C. 6 of 7 reviewers had substantial agreement by weighted kappas (>.6), with one reviewer accounting for the majority of cases under or overcalled by 2 tiers. Confluence filling a 4× field, labyrinthine glands, or solid architecture accounted for undercalling other reference diagnosis-C cases. Missing a few individually infiltrative cells was the most common cause of undercalling reference diagnosis- B. Small foci of inflamed, loose or desmoplastic stroma lacking infiltrative tumor cells in reference diagnosis-A appeared to account for those cases up-graded to Pattern Classification-B. In summary, an overall concordance of 74% indicates that the criteria can be reproducibly

  15. Microbiome and Potential Targets for Chemoprevention of Esophageal Adenocarcinoma

    PubMed Central

    Neto, Antonio Galvao; Whitaker, April; Pei, Zhiheng

    2015-01-01

    Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett’s esophagus- BE) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (i.e., changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia- EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel

  16. Primary adenocarcinoma of the rete testis: A case report and review of the literature.

    PubMed

    Tian, Ye; Yao, Wenqing; Yang, Lulu; Wang, Jianzhong; Wazir, Romel; Wang, Kunjie

    2014-02-01

    Primary adenocarcinoma of the rete testis is an extremely rare extratesticular neoplasm. Due to its low occurrence and the scarcity of data, sonographic characteristics of adenocarcinoma of the rete testis are still poorly defined. A 46-year-old male complained of swelling and pain in the right side of the scrotum. No associated symptoms were observed. Anti-tuberculosis chemotherapy yielded no response. Postoperative pathology revealed a diagnosis of poorly-differentiated adenocarcinoma of the rete testis. Using the ultrasonography features observed, combined with a review of current literature, the diagnosis and differential diagnosis of this neoplasm are presented.

  17. Primary mucinous adenocarcinoma of the larynx in female patient: a rare entity.

    PubMed

    Ebru, Tastekin; Omer, Yalcin; Fulya, Oz Puyan; Ufuk, Usta; Kemal, Kutlu

    2012-10-01

    Laryngeal malignant tumors are mainly composed of squamous cell carcinomas. Glandular carcinomas of the larynx are rare tumors that constitute less than 1% of all laryngeal malignancies where "adenocarcinoma not otherwise specified" is the most common histologic subtype. Here we report a case of a 70-year-old female patient with primary laryngeal mucinous adenocarcinoma. The rarity of the tumor type and the differential diagnosis of this tumor before reporting it as a primary adenocarcinoma of the larynx are discussed here with literature findings. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Is cervical screening preventing adenocarcinoma and adenosquamous carcinoma of the cervix?

    PubMed Central

    Landy, Rebecca; Sasieni, Peter D.

    2016-01-01

    While the incidence of squamous carcinoma of the cervix has declined in countries with organised screening, adenocarcinoma has become more common. Cervical screening by cytology often fails to prevent adenocarcinoma. Using prospectively recorded cervical screening data in England and Wales, we conducted a population‐based case–control study to examine whether cervical screening leads to early diagnosis and down‐staging of adenocarcinoma. Conditional logistic regression modelling was carried out to provide odds ratios (ORs) and 95% confidence intervals (CIs) on 12,418 women with cervical cancer diagnosed between ages 30 and 69 and 24,453 age‐matched controls. Of women with adenocarcinoma of the cervix, 44.3% were up to date with screening and 14.6% were non‐attenders. The overall OR comparing women up to date with screening with non‐attenders was 0.46 (95% CI: 0.39–0.55) for adenocarcinoma. The odds were significantly decreased (OR: 0.22, 95% CI: 0.15–0.33) in up to date women with Stage 2 or worse adenocarcinoma, but not for women with Stage1A adenocarcinoma 0.71 (95% CI: 0.46–1.09). The odds of Stage 1A adenocarcinoma was double among lapsed attenders (OR: 2.35, 95% CI: 1.52–3.62) compared to non‐attenders. Relative to women with no negative cytology within 7 years of diagnosis, women with Stage1A adenocarcinoma were very unlikely to be detected within 3 years of a negative cytology test (OR: 0.08, 95% CI: 0.05–0.13); however, the odds doubled 3–5 years after a negative test (OR: 2.30, 95% CI: 1.67–3.18). ORs associated with up to date screening were smaller for squamous and adenosquamous cervical carcinoma. Although cytology screening is inefficient at preventing adenocarcinomas, invasive adenocarcinomas are detected earlier than they would be in the absence of screening, substantially preventing Stage 2 and worse adenocarcinomas. PMID:27096255

  19. Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil

    PubMed Central

    Leal, Mariana Ferreira; Lima, Eleonidas Moura; Silva, Patrícia Natália Oliveira; Assumpção, Paulo Pimentel; Calcagno, Danielle Queiroz; Payão, Spencer Luiz Marques; Burbano, Rommel Rodríguez; Smith, Marília de Arruda Cardoso

    2007-01-01

    AIM: To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics. METHODS: Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic gastric adenocarcinoma, 30 intestinal-type gastric adenocarcinoma and 35 diffuse-type gastric adenocarcinoma samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher's exact test to assess associations between methylation status and clinico-pathological characteristics. RESULTS: Hypermethylation frequencies of CDH1, FHIT, MTAP and PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hypermethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hypermethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender. CONCLUSION: Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition. PMID:17552003

  20. [Value of immunocytochemistry in differential diagnosis of gastric adenocarcinoma, reactive mesothelial cells and malignant epithelial mesothelioma in metastatic effusion fluid].

    PubMed

    Lyu, M; Cha, N; Zou, Y F; Leng, J H; Xu, L; Sun, Y; Hao, Y Y

    2018-03-08

    Objective: To investigate the diagnostic value of some antibodies in peritoneal fluid of patients with gastric cancer and malignant epithelioid mesothelioma in serous effusion. Methods: One hundred and eighty-two cases of serous effusion were collected at Jilin Cancer Hospital, from July 2012 to July 2016. The expression of GLUT1, CDX2, Villin, calretinin and WT1 was evaluated using SP immunocytochemical technique in peritoneal fluid samples collected from 98 patients with gastric cancer and 74 patients with reactive mesothelial cells. The expression of GLUT1, calretinin and WT1 was also evaluated in serous effusion from 10 patients with mesothelioma. Results: The sensitivity of GLUT1, CDX2 and Villin in adenocarcinoma cells was 91.8%(90/98), 68.4% (67/98) and 88.8%(87/98), respectively. The specificity was 95.9% (71/74), 100.0%(74/74) and 100.0% (74/74), respectively. The sensitivity of calretinin and WT1 for reactive mesothelium was 93.2% (69/74) and 79.7% (59/74), respectively. The specificity was 96.9% (95/98) and 100.0% (98/98), respectively. The sensitivity of GLUT1, calretinin and WT1 for mesothelioma was 9/10, 9/10 and 7/10. The reactivity of GLUT1, CDX2, Villin, calretinin and WT1 showed a significant difference ( P <0.01) between adenocarcinoma cells and reactive mesothelium. The reactivity of GLUT1 showed a significant difference ( P <0.01) between mesothelioma and reactive mesothelium. Conclusions: The optimal combination is a panel of GLUT1, CDX2, Villin, calretinin and WT1 for differential diagnosis between adenocarcinoma cells and reactive mesothelium in peritoneal fluid of patients with gastric cancer. Whereas GLUT1, calretinin and WT1 is the best for differential diagnosis between reactive mesothelium and mesothelioma in serous effusions.

  1. Predictive factors for treatment response using dual-energy computed tomography in patients with advanced lung adenocarcinoma.

    PubMed

    Hong, Sae Rom; Hur, Jin; Moon, Yong Wha; Han, Kyunghwa; Chang, Suyon; Kim, Jin Young; Im, Dong Jin; Suh, Young Joo; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Choi, Byoung Wook

    2018-04-01

    This study aimed to investigate whether the quantitative parameters of dual-energy computed tomography (DECT) can predict the effects of chemotherapy in advanced adenocarcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. A total of 90 patients (59 males, 31 females, age 61.4 ± 12.3 (23-85)) with unresectable lung adenocarcinoma (TNM stage IIIB or IV) who underwent DECT before chemotherapy were prospectively included in this study. By comparing baseline studies with the best response achieved during 1 st line chemotherapy, patients were divided into two groups according to RECIST (version 1.1) guidelines as follows; responders (CR or PR) and non-responders (SD or PD). Quantitative measurements were performed on baseline DECT, and a logistic regression model was used to evaluate predictive factors for a response to chemotherapy. Among 90 patients, 38 were categorized as responders, while 52 patients were non-responders. The mean iodine concentration measurements were significantly higher in responders compared with non-responders (1.81 ± 0.51 vs 1.33 ± 0.76 mg/ml, p < 0.001). On multivariate analysis, EGFR mutation (odds ratio (OR): 3.116, 95% confidential interval (CI):1.182-8.213, p = .019) and iodine concentration (OR: 1.112, 95% CI:1.034-1.196, p = .006) were found to be significant for predicting a treatment response. Dual-energy CT using a quantitative analytic method based on iodine concentration measurements can be used to predict the effects of chemotherapy in patients with advanced adenocarcinoma. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Impact of neoadjuvant therapy in downstaging of lower rectal adenocarcinoma and the role of pelvic magnetic resonance in staging.

    PubMed

    Magri, Karina Dagre; Bin, Fang Chia; Formiga, Fernanda Bellotti; Manzione, Thiago da Silveira; Gomes, Caroline Merci Caliari de Neves; Candelári, Paulo de Azeredo Passos; Ortiz, Jorge Alberto; Klug, Wilmar Artur; Mandia, José; Capelhuchnik, Peretz

    2016-01-01

    to evaluate the effect of neoadjuvant therapy on the stage (TNM) of patients with rectal adenocarcinoma and validate the use of MRI as a method of determining locoregional stage. we conducted a retrospective study of 157 patients with lower rectum adenocarcinoma, whom we divided into two groups: Group 1, 81 patients (52%) who had undergone surgical treatment initially, with the purpose to analyze the accuracy of locoregional staging by pelvic magnetic resonance imaging throug the comparison of radiological findings with pathological ones; Group 2, 76 patients (48%), who had been submitted to neoadjuvant therapy (chemotherapy and radiation) prior to definitive surgical treatment, so as to evaluate its effects on the stage by comparing clinical and radiological findings with pathology. In group 1, the accuracy of determining tumor depth (T) and lymph node involvement (N) was 91.4% and 82.7%, respectively. In group 2, neoadjuvant therapy decreased the T stage, N stage and TNM stage in 51.3%, 21% and 48.4% of cases, respectively. neoadjuvant therapy in patients with rectal adenocarcinoma is effective in decreasing disease stage, and pelvic magnetic resonance imaging is effective for locoregional staging. avaliar o efeito da terapia neoadjuvante, nos pacientes portadores de adenocarcinoma de reto, sobre o estádio (TNM) e validar o emprego da ressonância magnética como método de determinação do estádio locorregional. estudo retrospectivo de 157 pacientes com diagnóstico de adenocarcinoma de reto baixo, que foram divididos em dois grupos: Grupo 1, 81 pacientes (52%), submetidos ao tratamento cirúrgico de princípio, cuja finalidade foi analisar a acurácia da determinação do estádio locorregional pela ressonância magnética da pelve, através da comparação entre os achados radiológicos e os achados anatomopatológicos; Grupo 2, 76 pacientes (48%), encaminhados à terapia neoadjuvante (quimioterapia e radioterapia), antes do tratamento cirúrgico definitivo

  3. QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    ClinicalTrials.gov

    2016-10-26

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  4. Thymic adenocarcinoma with sarcomatoid features characterized by intracaval tumor growth: report of a case.

    PubMed

    Ishiwata, Toshiji; Sekiya, Mitsuaki; Suzuki, Tsutomu; Matsuoka, Takashi; Kumasaka, Toshio; Takahashi, Kazuhisa

    2010-11-01

    Primary thymic adenocarcinoma is an extremely rare tumor. This report describes a case of thymic adenocarcinoma with a peculiar pathological feature and clinical course. A 54-year-old man complained of cough, dyspnea, and chest pain. Computed tomography scans revealed an anterior mediastinal mass with intracaval growth into the superior vena cava. No definitive diagnosis could be made after several examinations and palliative radiotherapy was performed. He passed away 56 days after the appearance of the initial symptoms. An autopsy revealed that the mediastinal tumor obstructed not only the superior vena cava but also the pulmonary arteries. The histological findings revealed the tumor to be an adenocarcinoma with sarcomatous features. The tumor was immunohistochemically positive for CD5 and negative for thyroid transcription factor-1. These results suggested the tumor to be a thymic adenocarcinoma with sarcomatoid features; furthermore, the tumor invaded the great vessels, thus resulting in a poor prognosis.

  5. Atypical Presentation of Skull Metastasis from Rectal Adenocarcinoma as an Initial Symptom of Recurrence

    PubMed Central

    Fırat, Cemal; Aytekin, Ahmet Hamdi; Erbatur, Serkan; Aydın, Nasuhi Engin; Selcuk, Engin Burak

    2012-01-01

    Most malignant rectal tumors are histopathologically characterized as adenocarcinoma and generally metastasize to distant organs such as the lungs or the liver. Metastasis of rectal carcinomas to the skull is extremely rare. This study reports the initial diagnosis of rectal adenocarcinoma recurrence in a 65-year-old female with scalp metastasis. The patient's history indicated a colorectal adenocarcinoma that was resected five years earlier. A skull metastasis from a rectal adenocarcinoma has not yet been reported in the literature as an initial symptom for recurrence. This paper suggests that skull metastasis from any part of the body must be considered in the differential diagnosis of soft tissue tumors in the skull even in the absence of intestinal symptoms. PMID:22811727

  6. Atypical presentation of skull metastasis from rectal adenocarcinoma as an initial symptom of recurrence.

    PubMed

    Fırat, Cemal; Aytekin, Ahmet Hamdi; Erbatur, Serkan; Aydın, Nasuhi Engin; Selcuk, Engin Burak

    2012-01-01

    Most malignant rectal tumors are histopathologically characterized as adenocarcinoma and generally metastasize to distant organs such as the lungs or the liver. Metastasis of rectal carcinomas to the skull is extremely rare. This study reports the initial diagnosis of rectal adenocarcinoma recurrence in a 65-year-old female with scalp metastasis. The patient's history indicated a colorectal adenocarcinoma that was resected five years earlier. A skull metastasis from a rectal adenocarcinoma has not yet been reported in the literature as an initial symptom for recurrence. This paper suggests that skull metastasis from any part of the body must be considered in the differential diagnosis of soft tissue tumors in the skull even in the absence of intestinal symptoms.

  7. Actinin-4 protein overexpression as a predictive biomarker in adjuvant chemotherapy for resected lung adenocarcinoma.

    PubMed

    Shiraishi, Hideaki; Fujiwara, Yutaka; Kakuya, Takanori; Tsuta, Koji; Motoi, Noriko; Miura, Nami; Watabe, Yukio; Watanabe, Shun-Ichi; Noro, Rintaro; Nagashima, Kengo; Huang, Wilber; Yamada, Tesshi; Asamura, Hisao; Ohe, Yuichiro; Honda, Kazufumi

    2017-06-29

    Although several clinical trials demonstrated the benefits of platinum-combination adjuvant chemotherapy for stage II-IIIA lung adenocarcinoma, predictive biomarkers for the efficacy of such therapy have not yet been identified. We evaluated protein overexpression of actinin-4 as a predictive biomarker of the efficacy of adjuvant chemotherapy in resected lung adenocarcinoma. We measured actinin-4 protein levels in patients with completely resected stage II-IIIA lung adenocarcinoma using immunohistochemistry and then retrospectively compared survival between adjuvant chemotherapy and observation groups. A total of 148 eligible patients were classified into actinin-4 positive or negative cases by immunohistochemistry. In the former, patients with adjuvant chemotherapy survived significantly longer than those with observation (hazard ratio [HR]: 0.307; p = 0.028). But, no significant survival benefit was noted with adjuvant chemotherapy (HR: 0.926; p = 0.876) in the latter. This marker could predict the efficacy of adjuvant chemotherapy for resected lung adenocarcinoma patients.

  8. Submandibular gland cystadenocarcinoma with mucinous adenocarcinoma-like areas: a case report.

    PubMed

    Zhang, Chun; Chen, Chunyan; Wang, Jianrong

    2014-04-28

    Cystadenocarcinoma is primarily characterized by cystic structures of varying sizes, that are lined by epithelial cells. As a rare neoplasm, only four cases of cystadenocarcinoma of submandibular glands have been previously reported. Herein, we reported a unique case of submandibular gland cystadenocarcinoma in a 44-year-old man. By in large, this case had typical morphologic cystadenocarcinoma features. However, mucinous adenocarcinoma-like areas were additionally observed in the tumor tissues. This case was initially misdiagnosed as mucinous adenocarcinoma due to the low incidence of submandibular gland cystadenocarcinoma and the presentation of mucinous adenocarcinoma-like areas in the tumor tissues. Histopathology of additional tumor tissues revealed that mucinous adenocarcinoma-like areas accounted for only a small percentage of the tumor tissues, confirming the submandibular gland cystadenocarcinoma diagnosis. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1387916949121142.

  9. A review of the epidemiology of Barrett’s oesophagus and oesophageal adenocarcinoma

    PubMed Central

    Schneider, Jennifer L.; Corley, Douglas A.

    2017-01-01

    While the incidence rates of many cancers have decreased in past decades, the incidence of oesophageal adenocarcinoma continues to increase. The only known precursor for oesophageal adenocarcinoma is Barrett’s oesophagus. Studies conducted have identified white race, male sex, GORD, cigarette smoking, obesity, and the absence of Helicobacter pylori status as risk factors for oesophageal adenocarcinoma. Other potential associations include dietary factors and the absence of non-steroidal anti-inflammatory drug use. Many individual studies have been limited by sample size and several meta-analyses have pooled data from studies to address this limitation. In this review we present a synthesis of these studies and summarize current knowledge of risk factors for both oesophageal adenocarcinoma and Barrett’s oesophagus. PMID:25743454

  10. A review of the epidemiology of Barrett's oesophagus and oesophageal adenocarcinoma.

    PubMed

    Schneider, Jennifer L; Corley, Douglas A

    2015-02-01

    While the incidence rates of many cancers have decreased in past decades, the incidence of oesophageal adenocarcinoma continues to increase. The only known precursor for oesophageal adenocarcinoma is Barrett's oesophagus. Studies conducted have identified white race, male sex, GORD, cigarette smoking, obesity, and the absence of Helicobacter pylori status as risk factors for oesophageal adenocarcinoma. Other potential associations include dietary factors and the absence of non-steroidal anti-inflammatory drug use. Many individual studies have been limited by sample size and several meta-analyses have pooled data from studies to address this limitation. In this review we present a synthesis of these studies and summarize current knowledge of risk factors for both oesophageal adenocarcinoma and Barrett's oesophagus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. The distinction of mesothelioma from adenocarcinoma in malignant effusions by electron microscopy.

    PubMed

    Kobzik, L; Antman, K H; Warhol, M J

    1985-01-01

    To determine the usefulness of the electron microscopic (EM) differential diagnosis between malignant mesothelioma and metastatic adenocarcinoma in cytologic specimens of serous fluids, we undertook a prospective study of 17 pleural and peritoneal effusions from 14 patients. In the nine effusions identified as malignant by routine cytologic examination, EM correctly diagnosed three mesotheliomas and six adenocarcinomas. EM resolved the differential diagnosis of mesothelioma versus adenocarcinoma in three cases in which routine cytologic examination could not. As with tissue specimens, EM cannot be used to diagnose the malignancy of cytologic specimens; it can, however, reliably identify the origin of cells diagnosed as malignant by routine cytologic examination. We conclude that, when EM is used to evaluate cytologically malignant effusions, it can accurately distinguish mesothelioma from adenocarcinoma. This technique will be diagnostically useful in selected cases and may be helpful in avoiding more invasive procedures as well as delays in diagnosis and therapy.

  12. Tumor Spread Through Air Spaces is an Important Pattern of Invasion and Impacts the Frequency and Location of Recurrences Following Limited Resection for Small Stage I Lung Adenocarcinomas

    PubMed Central

    Kadota, Kyuichi; Nitadori, Jun-ichi; Sima, Camelia S.; Ujiie, Hideki; Rizk, Nabil P.; Jones, David R.; Adusumilli, Prasad S.; Travis, William D.

    2015-01-01

    Introduction Tumor invasion in lung adenocarcinoma is defined as infiltration of stroma, blood vessels, or pleura. Based on observation of tumor spread through air spaces (STAS), we considered whether this could represent new patterns of invasion and investigated whether it correlated with locoregional versus distant recurrence according to limited resection versus lobectomy. Methods We reviewed resected small (≤2 cm) stage I lung adenocarcinomas (n=411; 1995–2006). Tumor STAS was defined as tumor cells—micropapillary structures, solid nests, or single cells—spreading within air spaces in the lung parenchyma beyond the edge of the main tumor. Competing risks methods were used to estimate risk of disease recurrence and its associations with clinicopathological risk factors. Results STAS was observed in 155 cases (38%). In the limited resection group (n=120), the risk of any recurrence was significantly higher in patients with STAS-positive tumors than that of patients with STAS-negative tumors (5-year cumulative incidence of recurrence [CIR], 42.6% vs. 10.9%; P<0.001); the presence of STAS correlated with higher risk of distant (P=0.035) and locoregional recurrence (P=0.001). However, in the lobectomy group (n=291), presence of STAS was not associated with either any (P=0.50) or distant recurrence (P=0.76). In a multivariate analysis, presence of tumor STAS remained independently associated with the risk of developing recurrence (hazard ratio, 3.08; P=0.014). Conclusion Presence of STAS is a significant risk factor of recurrence in small lung adenocarcinomas treated with limited resection. These findings support our proposal that STAS should formally be recognized as a pattern of invasion in lung adenocarcinoma. PMID:25629637

  13. [An experimental study on the Chinese lung adenocarcinoma cell clone CPA-Yang1-BR with brain metastasis potency in nude mice and in vivo imaging research].

    PubMed

    Lei, Bei; Cao, Jie; Shen, Jie; Zhao, Lanxiang; Liang, Sheng; Meng, Qinggang; Xie, Wenhui; Yang, Shunfang

    2013-08-20

    Lung cancer is the leading cause of cancer-related death in men and women. It is also the most common cause of brain metastases. A brain metastasis model is difficult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. Thus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great significance. CPA-Yang1 cells were obtained from a patient with human lung adenocarcinoma by lentiviral vector-mediated transfection of green fluorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro ¹⁸F FDG-PET/CT scanners, small animal in vivo imaging system for fluorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. The samples were divided into two parts for cell culture and histological diagnosis. The process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. The use of MRI for the detection of brain metastases has obvious advantages. An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeficient mice. The results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

  14. Cytokeratins and carcinoembryonic antigen in diagnosis, staging and prognosis of colorectal adenocarcinoma

    PubMed Central

    Fernandes, Luís C.; Kim, Su B.; Matos, Delcio

    2005-01-01

    AIM: To evaluate the serum levels of cytokeratins and carcinoembryonic antigen (CEA) in diagnosis, staging and prognosis of patients with colorectal adenocarcinoma. METHODS: The sample consisted of 169 patients. One hundred blood donors formed the control group. Radical surgery was performed on 120 patients, with an average follow-up duration of 22.3 mo. Relapses occurred in 23 individuals after an average of 18.09 mo. CEA was assayed via the Delfia® method with a limit of 5 ng/mL. Cytokeratins were assayed via the LIA-mat® TPA-M Prolifigen® method with a limit of 72 U/L. RESULTS: In the diagnosis of patients with colorectal adenocarcinoma, CEA showed a sensitivity of 56%, a specificity of 95%, a positive predictive value of 94%, a negative predictive value of 50% and an accuracy of 76.8%. TPA-M had a sensitivity of 70%, a specificity of 96%, a positive predictive value of 97%, a negative predictive value of 66% and an accuracy of 93.6%. The elevation of one of the markers was shown to have a sensitivity of 76.9%, a specificity of 91%, a positive predictive value of 93.5%, a negative predictive value of 70% and an accuracy of 83.6%. There was no variation in the levels of the markers according to the degree of cell differentiation while there was an elevation in their concentrations in accordance with the increase in neoplastic dissemination. There was a statistically significant difference between the patients with stage IV lesions and those with stages I, II and III tumors. With regard to CEA, the average level was 14.2 ng/mL in patients with stage I lesions, 8.5 ng/mL in patients with stage II lesions, 8.0 ng/mL in patients with stage III lesions and 87.7 ng/mL in patients with stage IV lesions. In relation to TPA-M, the levels were 153.1 U/L in patients with stage I tumors, 106.5 U/L in patients with stage II tumors, 136.3 U/L in patients with stage III tumors and 464.3 U/L in patients with stage IV tumors. There was a statistical difference in patients with

  15. Ovarian and endometrial endometrioid adenocarcinomas have distinct profiles of microsatellite instability, PTEN expression, and ARID1A expression.

    PubMed

    Huang, Hsien-Neng; Lin, Ming-Chieh; Tseng, Li-Hui; Chiang, Ying-Cheng; Lin, Liang-In; Lin, Yu-Feng; Huang, Hsin-Ying; Kuo, Kuan-Ting

    2015-03-01

    To understand the role of and differences in molecular alterations between endometrial and ovarian endometrioid adenocarcinomas. We investigated the microsatellite status of 26 ovarian endometrioid adenocarcinomas (OVEMs), 42 endometrial endometrioid adenocarcinomas (EMCAs), and 19 concurrent (endometrial and ovarian) endometrioid adenocarcinomas. We evaluated the expression of the mismatch repair proteins, PTEN and ARID1A, and mutations of PTEN, KRAS, CTNNB1, and PIK3CA. High levels of microsatellite instability (MSI-H) were present in one of 26 OVEMs, 12 of 42 EMCAs, and four of 19 concurrent endometrioid adenocarcinomas. Only four of 19 concurrent endometrioid adenocarcinomas showed identical molecular alterations in their endometrial and ovarian components. Loss of ARID1A or loss of PTEN expression, and MSI-H, were more common in EMCAs than OVEMs (P = 0.044, P = 0.004, and P = 0.012, respectively). MSI-H in endometrial endometrioid adenocarcinomas was also related to loss of ARID1A expression (P < 0.001). In the cohort of MSI-H endometrioid adenocarcinomas involving the endometrium (n = 16), MSH6-deficient cases showed higher frequencies of CTNNB1 and PIK3CA mutations (P = 0.008 and P = 0.036, respectively), but lower frequencies of KRAS mutation (P = 0.011), than PMS2-deficient cases. The different frequencies of molecular genetic alterations between endometrial endometrioid adenocarcinomas and ovarian endometrioid adenocarcinomas imply that distinct processes may be involved in their tumorigenesis or tumour progression. © 2014 John Wiley & Sons Ltd.

  16. Rac3 regulates cell proliferation through cell cycle pathway and predicts prognosis in lung adenocarcinoma.

    PubMed

    Wang, Gebang; Wang, Huan; Zhang, Chenlei; Liu, Tieqin; Li, Qingchang; Lin, Xuyong; Xie, Jingwei; Liu, Hongxu

    2016-09-01

    Lung cancer is still the leading cause of malignant deaths in the world. It is of great importance to find novel functional genes for the tumorigenesis of lung cancer. We demonstrated that Rac3 could promote cell proliferation and inhibit apoptosis in lung adenocarcinoma cell line A549 previously. The aim of this study was to investigate the function and mechanism of Rac3 in lung adenocarcinoma cell lines. Immunohistochemistry staining was performed in 107 lung adenocarcinoma tissues and matched non-tumor tissues. Multivariate analysis and Kaplan-Meier analysis were used to investigate the correlation between Rac3 expression and the clinical outcomes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and flow cytometry analysis were employed to determine the proliferative ability, cell cycle distribution, and apoptosis in H1299 and H1975 cell lines. Gene expression microarray and pathway analysis between the Rac3-siRNA group and the control group in A549 cells were performed to investigate the pathways and mechanism of Rac3 regulation. Rac3 was shown to be positively expressed in lung adenocarcinoma tissues, and the expression of Rac3 associates with longer survival in lung adenocarcinoma patients. Silencing of Rac3 significantly induced cell growth inhibition, colony formation decrease, cell cycle arrest, and apoptosis of lung adenocarcinoma cell lines, which accompanied by obvious downregulation of CCND1, MYC, and TFDP1 of cell cycle pathway involving in the tumorigenesis of lung adenocarcinoma based on the gene expression microarray. In conclusion, these findings suggest that Rac3 has the potential of being a therapeutic target for lung adenocarcinoma.

  17. The prognostic significance of growth factors and growth factor receptors in gastric adenocarcinoma.

    PubMed

    Kim, Jung Yeon; Jeon, Tae Joo; Bae, Byung-Noe; Kwon, Ji Eun; Kim, Hyun-Jung; Park, Kyeongmee; Shin, Eunah

    2013-02-01

    We evaluated growth factors/receptors expression in gastric adenocarcinoma. Immunohistochemistry was used to evaluate epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), VEGF-D, VEGF receptor (VEGFR)-2, VEGFR-3, transforming growth factor (TGF)-α, TGF-β1, and TGF-β-RII in tissue microarrays of adenocarcinoma, dysplasia, metaplasia, and gastritis. In adenocarcinoma, the expression rates of EGFR, VEGF, VEGF-D, VEGFR-2, VEGFR-3, TGF-α, TGF-β1, and TGF-β-RII were 2.0%, 0%, 10.7%, 4.4%, 11.2%, 26.3%, 9.4%, and 19.5%, respectively. VEGF-D, TGF-α, TGF-β1, and TGF-β-RII expression rate were higher in adenocarcinoma than in other groups. TGF-β-RII expression was correlated with VEGFR-3, VEGF-D, and TGF-α expression in adenocarcinomas. Tumor location, histologic type, stage, lymphatic invasion, perineural invasion, angioinvasion, VEGF-D, and VEGFR-2 expressions were associated with patient survival in a log rank test and advanced stage and positive expression of VEGF-D were poor prognostic factors using Cox analysis. VEGF-D expression may be of prognostic value in gastric adenocarcinoma, whereas EGFR and TGF family expression may only have a minor influence. © 2012 The Authors APMIS © 2012 APMIS.

  18. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

    PubMed

    Mok, Tony S; Wu, Yi-Long; Thongprasert, Sumitra; Yang, Chih-Hsin; Chu, Da-Tong; Saijo, Nagahiro; Sunpaweravong, Patrapim; Han, Baohui; Margono, Benjamin; Ichinose, Yukito; Nishiwaki, Yutaka; Ohe, Yuichiro; Yang, Jin-Ji; Chewaskulyong, Busyamas; Jiang, Haiyi; Duffield, Emma L; Watkins, Claire L; Armour, Alison A; Fukuoka, Masahiro

    2009-09-03

    Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for

  19. Pattern classification of endocervical adenocarcinoma: reproducibility and review of criteria.

    PubMed

    Rutgers, Joanne K L; Roma, Andres A; Park, Kay J; Zaino, Richard J; Johnson, Abbey; Alvarado, Isabel; Daya, Dean; Rasty, Golnar; Longacre, Teri A; Ronnett, Brigitte M; Silva, Elvio G

    2016-09-01

    Previously, our international team proposed a three-tiered pattern classification (Pattern Classification) system for endocervical adenocarcinoma of the usual type that correlates with nodal disease and recurrence. Pattern Classification-A tumors have well-demarcated glands lacking destructive stromal invasion or lymphovascular invasion, Pattern Classification-B tumors show localized, limited destructive invasion arising from A-type glands, and Pattern Classification-C tumors have diffuse destructive stromal invasion, significant (filling a 4 × field) confluence, or solid architecture. Twenty-four cases of Pattern Classification-A, 22 Pattern Classification-B, and 38 Pattern Classification-C from the tumor set used in the original description were chosen using the reference diagnosis originally established. One H&E slide per case was reviewed by seven gynecologic pathologists, four from the original study. Kappa statistics were prepared, and cases with discrepancies reviewed. We found a majority agreement with reference diagnosis in 81% of cases, with complete or near-complete (six of seven) agreement in 50%. Overall concordance was 74%. Overall kappa (agreement among pathologists) was 0.488 (moderate agreement). Pattern Classification-B has lowest kappa, and agreement was not improved by combining B+C. Six of seven reviewers had substantial agreement by weighted kappas (>0.6), with one reviewer accounting for the majority of cases under or overcalled by two tiers. Confluence filling a 4 × field, labyrinthine glands, or solid architecture accounted for undercalling other reference diagnosis-C cases. Missing a few individually infiltrative cells was the most common cause of undercalling reference diagnosis-B. Small foci of inflamed, loose or desmoplastic stroma lacking infiltrative tumor cells in reference diagnosis-A appeared to account for those cases up-graded to Pattern Classification-B. In summary, an overall concordance of 74% indicates that the criteria can

  20. Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma

    PubMed Central

    Calcagno, Danielle Queiroz; Leal, Mariana Ferreira; Seabra, Aline Damaceno; Khayat, André Salim; Chen, Elizabeth Suchi; Demachki, Samia; Assumpção, Paulo Pimentel; Faria, Mario Henrique Girão; Rabenhorst, Silvia Helena Barem; Ferreira, Márcia Valéria Pitombeira; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodríguez

    2006-01-01

    AIM: To investigate chromosome 8 numerical aberrations, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histopathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immunostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneuploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level of chromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal-type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic pathways. PMID:17036397

  1. Using Frozen Section to Identify Histologic Patterns in Stage I Lung Adenocarcinoma ≤3 cm: Accuracy and Interobserver Agreement

    PubMed Central

    Yeh, Yi-Chen; Nitadori, Jun-ichi; Kadota, Kyuichi; Yoshizawa, Akihiko; Rekhtman, Natasha; Moreira, Andre L.; Sima, Camelia S.; Rusch, Valerie W.; Adusumilli, Prasad S.; Travis, William D.

    2015-01-01

    Aims The IASLC/ATS/ERS classification of lung adenocarcinoma provides a prognostically significant histologic subclassification. The aim of this study is to investigate the accuracy, limitations, and interobserver agreement of frozen sections (FS) for predicting histologic subtype. Methods and results FS and permanent section slides from 361 resected stage I lung adenocarcinomas ≤ 3 cm were reviewed for predominant histologic subtype and presence or absence of lepidic, acinar, papillary, micropapillary, and solid patterns. Fifty cases were additionally reviewed by 3 pathologists to determine interobserver agreement. To test the accuracy of FS in judging degree of invasion, 5 pathologists reviewed FS slides from 35 cases with predominantly lepidic pattern. There was moderate agreement on predominant histologic subtype between FS and final diagnosis (κ = 0.565). FS had high specificity for micropapillary and solid patterns (94% and 96%, respectively), but sensitivity was low (37% and 69%, respectively). The interobserver agreement was satisfactory (κ > 0.6, except for acinar pattern). Conclusions FS can provide information on the presence of aggressive histologic patterns – micropapillary and solid – with high specificity but low sensitivity. It was difficult to predict the predominant pattern based on frozen section mostly due to sampling issues. PMID:24889415

  2. Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

    PubMed

    Wang, Hai-Jun; Liu, Yu; Zhou, Bao-Jun; Zhang, Zhan-Xue; Li, Ai-Ying; An, Ran; Yue, Bin; Fan, Li-Qiao; Li, Yong

    2018-01-01

    Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO 3 vehicle alone or CP dissolved in NaHCO 3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.

  3. Increased RCAS1 Expression Is Associated with Advanced Histopathological Stage and Poor Prognosis in Patients with Gastric Adenocarcinoma

    PubMed Central

    Giaginis, Constantinos; Efkarpidis, Themistoclis; Alexandrou, Paraskevi; Patsouris, Efstratios; Kouraklis, Gregory; Theocharis, Stamatios

    2013-01-01

    Background. The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that has been considered to play a crucial role in tumor progression by enabling cancer cells to evade immune surveillance. The present study aimed to evaluate the clinical significance of the RCAS1 expression in gastric adenocarcinoma. Material and Methods. RCAS1 protein expression was assessed immunohistochemically on 54 gastric adenocarcinoma tissue samples and was analyzed in relation to clinicopathological parameters, tumor proliferative capacity, and patients' survival. Results. Enhanced RCAS1 expression levels were significantly associated with advanced histopathological stage and presence of organ metastasis (P = 0.0084 and P = 0.0327). Gastric cancer patients with elevated RCAS1 expression levels showed significantly shorter survival times compared to those with low RCAS1 expression (log-rank test, P = 0.0168). In multivariate analysis, histopathological stage and grade of differentiation as well as the RCAS1 expression were identified as independent prognostic factors (Cox regression analysis, P = 0.0204, P = 0.0035, and P = 0.0081). Conclusions. Our data support the evidence that RCAS1 upregulation may contribute to gastric malignant progression, representing a useful biomarker to predict the biological behaviour and prognosis in gastric neoplasia. PMID:24167369

  4. Jaundice: an important, poorly recognized risk factor for diminished survival in patients with adenocarcinoma of the head of the pancreas

    PubMed Central

    Strasberg, Steven M; Gao, Feng; Sanford, Dominic; Linehan, David C; Hawkins, William G; Fields, Ryan; Carpenter, Danielle H; Brunt, Elizabeth M; Phillips, Carolyn

    2014-01-01

    Objectives: Jaundice impairs cellular immunity, an important defence against the dissemination of cancer. Jaundice is a common mode of presentation in pancreatic head adenocarcinoma. The purpose of this study was to determine whether there is an association between preoperative jaundice and survival in patients who have undergone resection of such tumours. Methods: Thirty possible survival risk factors were evaluated in a database of over 400 resected patients. Univariate analysis was used to determine odds ratio for death. All factors for which a P-value of <0.30 was obtained were entered into a multivariate analysis using the Cox model with backward selection. Results: Preoperative jaundice, age, positive node status, poor differentiation and lymphatic invasion were significant indicators of poor outcome in multivariate analysis. Absence of jaundice was a highly favourable prognostic factor. Interaction emerged between jaundice and nodal status. The benefit conferred by the absence of jaundice was restricted to patients in whom negative node status was present. Five-year overall survival in this group was 66%. Jaundiced patients who underwent preoperative stenting had a survival advantage. Conclusions: Preoperative jaundice is a negative risk factor in adenocarcinoma of the pancreas. Additional studies are required to determine the exact mechanism for this effect. PMID:23600768

  5. Evaluation of p53 codon 72 polymorphism in adenocarcinomas of the colon and rectum in La Plata, Argentina

    PubMed Central

    Pérez, Luis Orlando; Abba, Martin Carlos; Dulout, Fernando Noel; Golijow, Carlos Daniel

    2006-01-01

    AIM: To evaluate the potential association between p53 codon 72 polymorphism and sporadic colorectal adenocarcinoma development, and human papillomavirus (HPV) infection. METHODS: One-hundred and nine controls and 53 patients with colon cancer from the city of La Plata, Argentina were analyzed. p53 codon 72 genotypes and HPV infection were identified using allele-specific polymerase chain reaction and nested polymerase chain reaction, respectively. RESULTS: The differences in the distribution of p53 codon 72 polymorphism between the cases and controls were statistically significant. The arginine allele had a prevalence of 0.65 in controls and 0.77 in cases. The corresponding odds ratio for the homozygous arginine genotype was 2.08 (95% CI, 1.06-4.05; P<0.05). Lack of association was found between p53 polymorphism and HPV infection in the set of adenocarcinomas. CONCLUSION: The findings of the present study indicate that p53 codon 72 arginine homozygous genotype may represent a genetic predisposing factor for colon cancer development. However, further studies are needed in order to elucidate the role of p53 codon 72 polymorphism in colorectal cancer. PMID:16552814

  6. Hypoxia inducible BHLHB2 is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma

    SciTech Connect

    Wang, Weibin; Reiser-Erkan, Carolin; Michalski, Christoph W.

    2010-10-22

    Research highlights: {yields} The expression and function of BHLHB2 (DEC1/SHARP2) in pancreatic cancer is unknown. {yields} Hypoxia and serum starvation induces BHLHB2 expression in pancreatic ductal adenocarcinoma. {yields} BHLHB2 inhibition in pancreatic cancer cell line SU86.86 increases ED50 of gemcitabine 2.8-fold. {yields} BHLHB2 is an independent prognostic factor in multivariable cox analysis with a hazard ratio of 2:4. -- Abstract: Aims: The cyclic adenosine monophosphate-inducible basic helix-loop-helix (bHLH) domain containing class-B2 transcriptional factor BHLHB2 is differentially expressed in a number of human malignancies. In the present study, the expression, regulation, functions and prognostic impact of BHLHB2 in pancreatic cancer weremore » investigated. Methods: Expression analyses were carried out in tissues of the normal pancreas (n = 10) and pancreatic ductal adenocarcinoma (n = 77) as well as in eight pancreatic cancer cell lines using quantitative RT-PCR, semiquantitative immunohistochemistry, and immunoblot analyses. In vitro functional experiments were conducted using siRNA transfection, hypoxia, serum starvation, apoptosis induction with gemcitabine and actinomycin-D, and invasion assays. Survival analysis was performed using the Kaplan-Meier method. Prognostic factors were determined in a multivariable analysis using a Cox proportional hazards model. Results: BHLHB2 mRNA and protein expressions were strongly induced by hypoxia and by serum starvation in pancreatic cancer cell lines. BHLHB2 silencing with RNAi had no significant effects on growth and invasion but increased apoptosis resistance against gemcitabine by reducing caspace-3 cleavage. In BHLHB2 silenced cells the ED50 of gemcitabine increased from 13.95 {+-} 1.353 to 38.70 {+-} 5.262 nM (p < 0.05). Ex vivo, the weak/absent nuclear staining in normal pancreatic ducts and acinar cells was replaced by moderate to strong nuclear/cytoplasmic staining in PanIN lesions and

  7. [Comparison of laparoscopic distal pancreatectomy and open distal pancreatectomy in pancreatic ductal adenocarcinoma].

    PubMed

    Xu, K; Su, J J; Su, M; Yan, L; Feng, J; Xin, X L; Chen, Y L

    2017-10-23

    Objective: To compare and evaluate the curative effect of laparoscopic distal pancreatectomy(LDP) and traditional open distal pancreatectomy(ODP) in pancreatic ductal adenocarcinoma. Methods: The clinical data of 15 patients treated by LDP and 87 contemporaneous cases treated by ODP from January 2010 to November 2015 was collected, and the curative effect and prognosis of these patients were retrospectively analyzed. Results: The operation time of LDP group was (286.5±48.1) min, significantly longer than that of OPD group(226.6±56.8) min ( P <0.05). The operative hemorrhage, postoperative exhaust time, recovery eating time, the whole and postoperative hospitalization time of LDP group were (188.7±108.9) ml, (2.2±1.3) d, (2.9±1.1) d, (13.2±10.4) d and (9.3±8.1) d, respectively, dramatically shorter than those of ODP group (625.2±982.1) ml, (4.3±1.7) d, (5.2±1.8) d, (20.7±8.7) d and (14.9±7.8) d, respectively (all of P <0.05). There were no intraoperative blood transfusion case in LDP group, however, 13 patients in ODP group received intraoperative blood transfusion, without significant difference ( P =0.207). Alternatively, 6 cases occurred pancreatic fistula in LDP group, among them, 5 cases were grade A and 1 case was grade B; In ODP group, 17 cases occurred pancreatic fistula, among them 13 cases were grade A, 1 case was grade B and 3 cases were grade C, without significant differences ( P =0.130). There were 2 cases of delayed gastric empty, 1 case of pulmonary infection in LDP group. In ODP group, there were 5 cases of postoperative delayed gastric empty, 3 cases of pulmonary infection and 6 cases of intra-abdominal infection, without significant differences ( P >0.05). In both LDP group and ODP group, none occurred percutaneous drainage, re-admissions, second operation or perioperative death. Conclusions: Compared to ODP, LDP is much safer and more steady in perioperative periodand operation. Patients of pancreatic ductal adenocarcinoma received

  8. EGFR-RAD51 fusion variant in lung adenocarcinoma and response to erlotinib: A case report.

    PubMed

    Zhu, You-Cai; Wang, Wen-Xian; Xu, Chun-Wei; Song, Zheng-Bo; Du, Kai-Qi; Chen, Gang; Lv, Tang-Feng; Song, Yong

    2018-01-01

    The most frequent epidermal growth factor receptor (EGFR) mutations of lung cancer include exon 19 in deletion and the exon 21 L858R mutation. And EGFR-tyrosine kinase inhibitor (TKI) as the standard first line treatment show good response to classical/sensitizing EGFR mutations. With the development of detection methods, some uncommon genomic mutation events such as exon 18-25 kinase domain duplications (KDD) and EGFR rearrangements (EGFR-RAD51 or EGFR-PURB) are found. We reported a case of EGFR-RAD51 fusion in non-small-cell lung cancer(NSCLC) and the efficacy of erlotinib to this type fusion of NSCLC patients. A 48-year-old Chinese man with right lung tumor and multiple brain metastases NSCLC (T1N2M1, stage IV). Histological examination of surgical specimens from the brain tumor showed lung adenocarcinoma metastasis. By using next generation sequencing assay, we found that tumor had EGFR-RAD51 fusion rather than the most common kind of EGFR mutations. Then the patient experienced a remarkable tumor response to erlotinib. Considering this rare EGFR fusion and remarkable response to TKI treatment, we conclude that the incidence of EGFR fusions in NSCLC patients should be attentive. NSCLC patients with EGFR-RAD51 fusion gene response to treatment with EGFR inhibitor. With the guidance of precise diagnosis, it is important that we should realize other rare EGFR gene mutations and novel diagnostic method. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Phase II Trial of Bortezomib Alone or in Combination with Irinotecan in Patients with Adenocarcinoma of the Gastroesophageal Junction or Stomach

    PubMed Central

    Ocean, Allyson J.; Christos, Paul; Sparano, Joseph A.; Shah, Manish A.; Yantiss, Rhonda K.; Cheng, Jonathan; Lin, Juan; Papetti, Michael; Matulich, Dan; Schnoll-Sussman, Felice; Besanceney-Webler, Christen; Xiang, Jenny; Ward, Maureen; Dilts, Kaili Temple; Keresztes, Roger; Holloway, Shannon; Chen, Eric X.; Wright, John J.; Lane, Maureen E.

    2014-01-01

    Purpose To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods Forty-one patients with advanced GEJ (89%) or gastric (11%) adenocarcinoma received bortezomib (1.3 mg/m2 days 1, 4, 8, 11) plus irinotecan (125 mg/m2 days 1, 8) every 21 days as first line therapy (N=29), or bortezomib alone as second line therapy (N=12). The trial was designed to detect a 40% response rate for the combination, and 20% response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results Objective response occurred in 3 of 29 patients (10%, 95% confidence intervals [CI] 2%, 27%) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8%, 95% CI 0%, 39%) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 hours after therapy with bortezomib alone (N=2) or the combination (N=10). Conclusions We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population. PMID:24526575

  10. Fried meat intake is a risk factor for lung adenocarcinoma in a prospective cohort of Chinese men and women in Singapore

    PubMed Central

    Butler, Lesley M.; Yu, Mimi C.

    2013-01-01

    Probable human carcinogens are generated during Chinese-style high-temperature cooking of meat and have been detected in the ambient air and on the meat surface. Although the inhalation of these compounds is an established risk factor for lung cancer, exposure via fried meat consumption has not yet been prospectively evaluated as a risk factor. The relationship between fried meat intake and lung cancer risk was investigated using data from a prospective cohort study among Chinese in Singapore. Lung cancer cases (n = 1130) were identified from 61 321 men and women, 70% of whom were lifetime never smokers. Proportional hazards regression methods were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, there was no association between fried meat intake and risk of all lung cancers combined. For lung adenocarcinoma, fried meat intake had a statistically significant association with increased risk. The association between fried meat intake and risk of lung adenocarcinoma became stronger when analyses were restricted to lifetime never smokers. Compared with the lowest tertile of fried meat intake, the HRs (95% CIs) for the second and third tertiles were 1.43 (0.98, 2.08) and 1.51 (1.03, 2.22), respectively (P for trend = 0.04). The positive association was present among both men and women. There was no association between fried meat intake and risk of non-adenocarcinomas of the lung. Our prospective results for fried meat intake support consumption as an important route of exposure to compounds from Chinese-style high-temperature cooking for the development of lung adenocarcinoma. PMID:23568952

  11. A Prospective, Molecular Epidemiology Study of EGFR Mutations in Asian Patients with Advanced Non–Small-Cell Lung Cancer of Adenocarcinoma Histology (PIONEER)

    PubMed Central

    Shi, Yuankai; Au, Joseph Siu-Kie; Thongprasert, Sumitra; Srinivasan, Sankar; Tsai, Chun-Ming; Khoa, Mai Trong; Heeroma, Karin; Itoh, Yohji; Cornelio, Gerardo

    2014-01-01

    Introduction: PIONEER (NCT01185314) was a prospective, multinational, epidemiological study of epidermal growth factor receptor (EGFR) mutations in patients from Asia with newly diagnosed advanced lung adenocarcinoma. Methods: Eligible patients (aged ≥20 years) had untreated stage IIIB/IV adenocarcinoma. The EGFR mutation status (primary end point: positive, negative, or undetermined) of tumor samples (biopsy, surgical specimen, or cytology) was determined (Scorpion amplification refractory mutation system). EGFR mutation frequency was calculated and compared between demographic and clinical subgroups. Results: Of 1482 patients from seven Asian regions, 43.4% of patients were female, median age was 60 years (range, 17–94), and 52.6% of patients were never-smokers. EGFR mutation status was evaluable in tumors from 1450 patients (97.8%) (746 [51.4%] positive; 704 [48.6%] negative). Country, sex, ethnicity, smoking status, pack-years (all p < 0.001), disease stage (p = 0.009), and histology type (p = 0.016) correlated significantly with EGFR mutation frequency. Mutation frequency was 61.1% in females, 44.0% in males; lower in patients from India (22.2%) compared with other areas (47.2%–64.2%); highest among never-smokers (60.7%); and decreased as pack-year number increased (>0–10 pack-years, 57.9%; >50 pack-years, 31.4%) (similar trend by sex). Ethnic group (p < 0.001) and pack-years (p < 0.001) had statistically significant associations with mutation frequency (multivariate analysis); sex was not significant when adjusted for smoking status. Conclusion: PIONEER is the first prospective study to confirm high EGFR mutation frequency (51.4% overall) in tumors from Asian patients with adenocarcinoma. The observed high mutation frequency in demographic/clinical subgroups compared with white populations suggests that mutation testing should be considered for all patients with stage IIIB/IV adenocarcinoma, even males and regular smokers, among Asian populations

  12. Interplay Between Gemcitabine and Erlotinib Over Pancreatic Adenocarcinoma Cells.

    PubMed

    Torres, Carolina; Linares, Ana; Alejandre, Maria Jose; Palomino-Morales, Rogelio Jesus; Delgado, Juan Ramon; Perales, Sonia

    2016-02-01

    Pancreatic ductal adenocarcinoma remains as a chemoresistant disease with the poorest prognosis. Gemcitabine has been the standard treatment during the last decade. Erlotinib, a tyrosine kinase inhibitor, in combination with gemcitabine produces a small increase in survival. However, these results remain insufficient. The aim of this study was to investigate the molecular interplay in vitro between them regarding their effects over cytotoxicity, proliferation, apoptosis, and invasion. Using the human pancreatic cancer cell lines Panc-1 and BxPC-3 in vitro, the effects of gemcitabine and erlotinib therapy on growth, proliferation, and invasion were tested by cytotoxicity, cell cycle, and Annexin V-Fluorescein Isothiocyanate analysis, reverse transcription polymerase chain reaction, protein expression, and Chip assays. Therapy decreased cell proliferation causing G0/G1 phase cell cycle arrest with induction of apoptosis in the Panc-1 cell line. This blockade was associated with increased p27 expression. Besides, treatments enhanced the nuclear factor-κB (NF-κB) pathway and the binding of NF-κB to the promoters of genes related to the proliferation and the evasion of apoptosis. Our data suggest that, although gemcitabine and erlotinib exert antiproliferative effects over pancreatic cancer cell lines, the gemcitabine-induced activation of NF-κB expression and its DNA-binding activities are important drawbacks of this treatment against pancreatic cancer.

  13. Cell death in cancer therapy of lung adenocarcinoma.

    PubMed

    Zagryazhskaya, Anna; Gyuraszova, Katarina; Zhivotovsky, Boris

    2015-01-01

    Lung cancer is the main cause of all cancer-related deaths in the world, with lung adenocarcinoma (ADC) being the most common subtype of this fatal disease. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new cancer therapy approaches. The high resistance of lung ADC to conventional radio- and chemotherapies represents a major challenge to treatment effectiveness. Here we discuss recent progress in understanding the mechanisms of ADC's broad resistance to treatment and its possible therapeutic implications. A number of driving oncogenic alterations were identified in a subset of lung ADCs, making them suitable for targeted therapies directed towards specific cancer-associated molecular changes. In addition, we discuss the molecular aberrations common in lung ADC that are currently being exploited or are potentially important for targeted cancer therapy, as well as limitations of this type of therapy. Furthermore, we highlight possible treatment modalities that hold promise for overcoming resistance to targeted therapies as well as alternative treatment options such as immunotherapies that are potentially promising for improving the clinical outcome of lung ADC patients.

  14. Next generation sequencing of pancreatic ductal adenocarcinoma: right or wrong?

    PubMed

    Connor, Ashton A; Gallinger, Steven

    2017-07-01

    Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all epithelial malignancies and a paradoxically rising incidence rate. Clinical translation of next generation sequencing (NGS) of tumour and germline samples may ameliorate outcomes by identifying prognostic and predictive genomic and transcriptomic features in appreciable fractions of patients, facilitating enrolment in biomarker-matched trials. Areas covered: The literature on precision oncology is reviewed. It is found that outcomes may be improved across various malignancies, and it is suggested that current issues of adequate tissue acquisition, turnaround times, analytic expertise and clinical trial accessibility may lessen as experience accrues. Also reviewed are PDAC genomic and transcriptomic NGS studies, emphasizing discoveries of promising biomarkers, though these require validation, and the fraction of patients that will benefit from these outside of the research setting is currently unknown. Expert commentary: Clinical use of NGS with PDAC should be used in investigational contexts in centers with multidisciplinary expertise in cancer sequencing and pancreatic cancer management. Biomarker directed studies will improve our understanding of actionable genomic variation in PDAC, and improve outcomes for this challenging disease.

  15. Nox1-dependent superoxide production controls colon adenocarcinoma cell migration.

    PubMed

    Sadok, Amine; Bourgarel-Rey, Véronique; Gattacceca, Florence; Penel, Claude; Lehmann, Maxime; Kovacic, Hervé

    2008-01-01

    Reactive oxygen species are well-known mediators of various biological responses. Recently, new homologues of the catalytic subunit of NADPH oxidase have been discovered in non-phagocytic cells. These new homologues (Nox1-Nox5) produce low levels of superoxides compared to the phagocytic homologue Nox2/gp91phox. Using Nox1 siRNA, we show that Nox1-dependent superoxide production affects the migration of HT29-D4 colonic adenocarcinoma cells on collagen-I. Nox1 inhibition or down-regulation led to a decrease of superoxide production and alpha 2 beta 1 integrin membrane availability. An addition of arachidonic acid stimulated Nox1-dependent superoxide production and HT29-D4 cell migration. Pharmacological evidences using phospholipase A2, lipoxygenases and protein kinase C inhibitors show that upstream regulation of Nox1 relies on arachidonic acid metabolism. Inhibition of 12-lipoxygenase decreased basal and arachidonic acid induced Nox1-dependent superoxide production and cell migration. Migration and ROS production inhibited by a 12-lipoxygenase inhibitor were restored by the addition of 12(S)-HETE, a downstream product of 12-lipoxygenase. Protein kinase C delta inhibition by rottlerin (and also GO6983) prevented Nox1-dependent superoxide production and inhibited cell migration, while other protein kinase C inhibitors were ineffective. We conclude that Nox1 activation by arachidonic acid metabolism occurs through 12-lipoxygenase and protein kinase C delta, and controls cell migration by affecting integrin alpha 2 subunit turn-over.

  16. A retrospective study of 44 canine apocrine sweat gland adenocarcinomas

    PubMed Central

    Simko, Elemir; Wilcock, Brian P.; Yager, Julie A.

    2003-01-01

    Apocrine sweat gland adenocarcinomas (AACs) are relatively uncommon skin tumors in dogs. Little prognostic or behavioral information has been published for these tumors. In this retrospective study, 44 AACs from diagnostic archives were reexamined and clinical postexcisional follow-ups for 25 of the 44 cases were obtained by a survey. There were 28 out of 44 (65.9%) AACs that invaded the capsule, stroma, or both, 5 of 44 (11.4%) invaded blood vessels and stroma, and 1 out of 25 (4%) had distant metastases. The presence or absence of stromal and vascular invasion was predicted by clinical examination with more than 80% accuracy. Postexcisional median survival of dogs with AACs was 30 mo at the time of survey. Determination of a correlation between histological features and malignant behavior of AACs was compromised by the low number of cases with clinical AAC-related problems; however, it appears that intravascular invasion is an important indicator of potential systemic metastases. PMID:12619554

  17. Metastatic apocrine sweat gland adenocarcinoma in a terrier dog.

    PubMed

    Baharak, Akhtardanesh; Reza, Kheirandish; Shahriar, Dabiri; Omid, Azari; Daruoosh, Vosoogh; Nasrin, Askari

    2012-08-01

    This report describes the clinical and pathological aspects of an apocrine sweat gland carcinoma with distant metastasis in an aged dog. A 7-year-old male terrier dog was referred to small animal hospital of Shahid Bahonar University of Kerman with a 5.5×3.5 centimeter pedunculated mass on its head near left auricular region which had been progressively growing since three months ago. The radiography showed no local and distant metastasis. Surgical excision and histological evaluation was done. Histologically, the mass was composed of epithelial cells arranged in glandular and solid patterns. The morphologic findings suggested either a primary or metastatic apocrine-gland carcinoma. Immunohistochemically, the tumor cells were intensely positive for cytokeratin 7 and 20 and negative for S100 protein. On the basis of histopathological and clinical findings, the tumor was diagnosed as a malignant apocrine gland tumor, arising from apocrine sweat glands of the skin. Local tumor recurrence with anorexia and weight loss was reported by the owner nine month later. Severe submandibular and prescapular lymphadenomegaly was noted in clinical examination. Several large pulmonary nodules were noted in chest radiographs resembling mediastinal lymph node metastasis. Second surgery and chemotherapy was rejected by the owner due to grave prognosis of the patient. The animal was died 45 days later due to respiratory complications. Tumors of apocrine sweat glands are relatively uncommon in dogs whereas apocrine gland adenocarcinoma with distant metastasis is extremely rare.

  18. Metastatic apocrine sweat gland adenocarcinoma in a terrier dog

    PubMed Central

    Baharak, Akhtardanesh; Reza, Kheirandish; Shahriar, Dabiri; Omid, Azari; Daruoosh, Vosoogh; Nasrin, Askari

    2012-01-01

    This report describes the clinical and pathological aspects of an apocrine sweat gland carcinoma with distant metastasis in an aged dog. A 7-year-old male terrier dog was referred to small animal hospital of Shahid Bahonar University of Kerman with a 5.5×3.5 centimeter pedunculated mass on its head near left auricular region which had been progressively growing since three months ago. The radiography showed no local and distant metastasis. Surgical excision and histological evaluation was done. Histologically, the mass was composed of epithelial cells arranged in glandular and solid patterns. The morphologic findings suggested either a primary or metastatic apocrine-gland carcinoma. Immunohistochemically, the tumor cells were intensely positive for cytokeratin 7 and 20 and negative for S100 protein. On the basis of histopathological and clinical findings, the tumor was diagnosed as a malignant apocrine gland tumor, arising from apocrine sweat glands of the skin. Local tumor recurrence with anorexia and weight loss was reported by the owner nine month later. Severe submandibular and prescapular lymphadenomegaly was noted in clinical examination. Several large pulmonary nodules were noted in chest radiographs resembling mediastinal lymph node metastasis. Second surgery and chemotherapy was rejected by the owner due to grave prognosis of the patient. The animal was died 45 days later due to respiratory complications. Tumors of apocrine sweat glands are relatively uncommon in dogs whereas apocrine gland adenocarcinoma with distant metastasis is extremely rare. PMID:23569992

  19. Expression and Significance of Cyclophilin J in Primary Gastric Adenocarcinoma.

    PubMed

    Gong, Zhaohua; Mu, Yuling; Chen, Jian; Chu, Hongjin; Lian, Peiwen; Wang, Congcong; Wang, Jiahui; Jiang, Lixin

    2017-08-01

    Biomarkers are essential in early diagnosis and understanding of the molecular mechanism of human cancer. The expression of cyclophilin J, a novel member of the cyclophilin family, was investigated in primary gastric adenocarcinoma. Western blot analysis was carried out on 36 paired tumor and normal tissue samples; immunohistochemical analysis was carried out on 120 gastric carcinoma tissues and normal adjacent tissue. Cyclophilin J protein was overexpressed in 72.2% of gastric carcinoma tissues compared to adjacent normal tissues. Immunohistochemical analysis revealed that cyclophilin J was overexpressed in 49.2% (59/120) and 23.3% (28/120) of gastric carcinoma tissues and adjacent tissues, respectively (p<0.05). Expression of cyclophilin J was associated with the degree of differentiation, but not with lymph node metastasis, gender or depth of tumor infiltration. The overall survival of patients showed no association with the overexpression of cyclophilin J protein. Cyclophilin J expression was up-regulated in gastric carcinoma compared to normal gastric tissues. However, in order to confirm its association with the survival of patients with gastric cancer, more cases need to be studied. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. Challenges and future directions in therapeutics for pancreatic ductal adenocarcinoma.

    PubMed

    Al Haddad, Amal H I; Adrian, Thomas E

    2014-11-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. The 5-year survival of < 5% has not changed in decades. In contrast to other major cancers, the incidence of PDAC is increasing. The aims of this paper are first to analyze why PDAC is so difficult to treat and, second, to suggest future directions for PDAC therapeutics. The authors provide an article that is based on a comprehensive search through MEDLINE and the clinicalTrials.gov website. Progress has been made recently. Notably, FOLFIRINOX or nab-paclitaxel plus gemcitabine provide survival benefit over gemcitabine alone, which was previously the mainstay of therapy for PDAC. Most of the current trials are testing combinations of repurposed drugs rather than addressing key targets in the PDAC pathogenesis. It is clear that to really make an impact on this disease, it will be necessary to address three different problems with targeted therapeutics. First, it is important to eradicate PDAC stem cells that result in recurrence. Second, it is important to reduce the peritumoral stroma that provides the tumors with growth support and provides a barrier to access of therapeutic agents. Finally, it is important to address the marked cachexia and metabolic derangement that contribute to morbidity and mortality and further complicate therapeutic intervention.

  1. Peutz-Jeghers syndrome and metastasising colonic adenocarcinoma.

    PubMed Central

    Tweedie, J H; McCann, B G

    1984-01-01

    A case of metastasising colonic carcinoma associated with Peutz-Jeghers syndrome in a 39 year old man is described. The caecal adenocarcinoma had metastasised widely to regional lymph nodes and was associated with several other colonic Peutz-Jeghers polyps, showing no evidence of dysplasia or malignancy. It was not possible to determine whether the carcinoma had arisen from a Peutz-Jeghers polyp. The patient also had gastric and small intestinal polyps. The serum carcinoembryonic antigen (CEA) was normal at presentation in this patient and in one other reported case. The use of this determination as a screening test for so-called high risk groups is, therefore, not supported by this report. The risk of malignancy is not known. It will only be determined by careful follow up of a defined Peutz-Jeghers syndrome population and comparison of carcinoma incidence with a matched sample of the general population. A national registry of Peutz-Jeghers syndrome patients in the United Kingdom would help to resolve this question. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:6479688

  2. Prognostic significance of PINCH signalling in human pancreatic ductal adenocarcinoma.

    PubMed

    Scaife, Courtney L; Shea, Jill; Emerson, Lyska; Boucher, Kenneth; Firpo, Matthew A; Beckerle, Mary C; Mulvihill, Sean J

    2010-06-01

    Prognostic markers for pancreatic ductal adenocarcinoma (PDA) have failed to accurately predict patient prognosis. Recently, interest has developed in the accuracy of integrin-associated PINCH protein expression in human cancers as a predictive marker of tumour status. The goal of this study was to define the expression of PINCH protein in PDA. Human PDA samples and orthotopic tumours from a murine model were analysed by immunohistochemistry for PINCH expression. In the animal model, PINCH expression was compared between primary and metastatic tumours. In the human samples, PINCH expression was correlated with stage, nodal involvement, margin status and overall survival. In the murine model, there was greater PINCH expression in metastatic tumours than in primary tumours. In the human PDA samples, greater staining for PINCH in the tumour cells was correlated with higher T status. Additionally, high PINCH expression in the stroma was associated with decreased overall survival. Findings of increased PINCH protein in more advanced stages of human PDA, as well as in metastatic tumours in the animal model, support the hypothesis that PINCH is an important controller of cell survival and migration. Additionally, the importance of the differential expression of PINCH in the human tumour and stroma warrants further evaluation.

  3. Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma.

    PubMed

    ten Kate, J; van den Ingh, H F; Khan, P M; Bosman, F T

    1986-04-15

    Immunoreactive adenosine deaminase complexing protein (ADCP) was studied in 91 human colorectal adenocarcinomas. The expression of ADCP was correlated with that of secretory component (SC) and carcinoembryonic antigen (CEA), with the histological grade and the Dukes' stage of the carcinomas. The histological grade was scored semi-quantitatively according to 5 structural and 4 cytological variables. ADCP expression was observed in 3 different staining patterns, namely: (1) diffuse cytoplasmic (77% of the carcinomas); (2) granular cytoplasmic (13%); and (3) membrane-associated (66%). These patterns were observed alone or in combination. Eleven percent of the carcinomas exhibited no ADCP immunoreactivity. Linear regression analysis showed that the expression of ADCP correlates with that of SC and CEA. However, no significant correlation emerged between the histological parameters or the Dukes' stage and any of the immunohistological parameters. Comparison of the histological characteristics of carcinomas exhibiting little or no ADCP immunoreactivity with those showing extensive immunoreactivity, showed that membranous ADCP immunoreactivity occurs more frequently in well-differentiated carcinomas. Structural parameters showed a better correlation with membranous ADCP expression than the cytological variables. It is concluded that membranous expression of ADCP and CEA are indicators of a high level of differentiation as reflected primarily in the structural characteristics of the tumor.

  4. Eradication of ovine pulmonary adenocarcinoma by motherless rearing of lambs.

    PubMed

    Voigt, K; Krämer, U; Brügmann, M; Dewar, P; Sharp, J M; Ganter, M

    2007-07-28

    The principles of maedi-visna eradication programmes were applied to a field trial for the eradication of ovine pulmonary adenocarcinoma (OPA). In two maternal flocks the prevalence of gross and histological lesions in slaughtered animals was 18.3 per cent and 29.8 per cent, respectively. The lambing period was supervised for three consecutive years from 1999 to 2001, during which the lambs were taken away from their mothers at birth, deprived of maternal colostrum, and hand-reared away from other sheep. Over the three-year period, 322 hand-reared animals, mainly male lambs between 10 and 14 months old, were slaughtered; their lungs were examined grossly, 52.5 per cent of them were examined histologically, and 105 samples of caudal mediastinal lymph nodes were examined by PCR. No OPA tumours were detected in the slaughter specimens from the derived flock, but one lamb had histological lesions in one lung location; intrauterine transmission was ruled out in this case. No clinical OPA has subsequently been observed in the hand-reared flock. Bronchoalveolar lavage samples from the breeding stock were examined by PCR in order to rule out further subclinical cases of OPA. No Jaagsiekte retrovirus was detected in any of the 488 samples.

  5. A novel fusion of TPR and ALK in lung adenocarcinoma.

    PubMed

    Choi, Yoon-La; Lira, Maruja E; Hong, Mineui; Kim, Ryong Nam; Choi, So-Jung; Song, Ji-Young; Pandy, Kinnari; Mann, Derrick L; Stahl, Joshua A; Peckham, Heather E; Zheng, Zongli; Han, Joungho; Mao, Mao; Kim, Jhingook

    2014-04-01

    Anaplastic lymphoma kinase (ALK) fusion is the most common mechanism for overexpression and activation in non-small-cell lung carcinoma. Several fusion partners of ALK have been reported, including echinoderm microtubule-associated protein-like 4, TRK-fused gene, kinesin family member 5B, kinesin light chain 1 (KLC1), protein tyrosine phosphatase and nonreceptor type 3, and huntingtin interacting protein 1 (HIP1). A 60-year-old Korean man had a lung mass which was a poorly differentiated adenocarcinoma with ALK overexpression. By using an Anchored Multiplex polymerase chain reaction assay and sequencing, we found that tumor had a novel translocated promoter region (TPR)-ALK fusion. The fusion transcript was generated from an intact, in-frame fusion of TPR exon 15 and ALK exon 20 (t(1;2)(q31.1;p23)). The TPR-ALK fusion encodes a predicted protein of 1192 amino acids with a coiled-coil domain encoded by the 5'-2 of the TPR and juxtamembrane and kinase domains encoded by the 3'-end of the ALK. The novel fusion gene and its protein TRP-ALK, harboring coiled-coil and kinase domains, could possess transforming potential and responses to treatment with ALK inhibitors. This case is the first report of TPR-ALK fusion transcript in clinical tumor samples and could provide a novel diagnostic and therapeutic candidate target for patients with cancer, including non-small-cell lung carcinoma.

  6. Identification of Targetable ALK Rearrangements in Pancreatic Ductal Adenocarcinoma.

    PubMed

    Singhi, Aatur D; Ali, Siraj M; Lacy, Jill; Hendifar, Andrew; Nguyen, Khanh; Koo, Jamie; Chung, Jon H; Greenbowe, Joel; Ross, Jeffrey S; Nikiforova, Marina N; Zeh, Herbert J; Sarkaria, Inderpal S; Dasyam, Anil; Bahary, Nathan

    2017-05-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival of 8%. Current therapeutic regimens are largely ineffective and underscore the need for novel treatment strategies. Chromosomal rearrangements involving the anaplastic lymphoma kinase ( ALK ) gene have been identified in several neoplasms. In addition, ALK protein inhibitors have proven efficacy in patients with ALK -rearranged tumors. However, ALK translocations in PDAC have not been described. Through comprehensive genomic profiling of 3,170 PDACs, we identified 5 cases (0.16%) that harbored an ALK fusion gene: an exon 6 EML4 -exon 20 ALK translocation (n=3), an exon 13 EML4- exon 20 ALK translocation (n=1), and an exon 3 STRN -exon 20 ALK translocation (n=1). Among the most prevalent PDAC-related genes, activating KRAS mutations were absent in all 5 cases, who were <50 years of age. Among patients aged <50 years in our study cohort, ALK translocations constituted 1.3% of PDACs. Four of 5 patients were treated with an ALK inhibitor, and 3 of these patients demonstrated stable disease, radiographic response, and/or normalization of serum CA 19-9. Although rare, ALK fusions occur in PDAC, and screening for ALK rearrangements should be considered in young patients with PDAC. Copyright © 2017 by the National Comprehensive Cancer Network.

  7. Stem cells as the root of pancreatic ductal adenocarcinoma

    SciTech Connect

    Balic, Anamaria; Dorado, Jorge; Alonso-Gomez, Mercedes

    2012-04-01

    Emerging evidence suggests that stem cells play a crucial role not only in the generation and maintenance of different tissues, but also in the development and progression of malignancies. For the many solid cancers, it has now been shown that they harbor a distinct subpopulation of cancer cells that bear stem cell features and therefore, these cells are termed cancer stem cells (CSC) or tumor-propagating cells. CSC are exclusively tumorigenic and essential drivers for tumor progression and metastasis. Moreover, it has been shown that pancreatic ductal adenocarcinoma does not only contain one homogeneous population of CSC rather than diverse subpopulationsmore » that may have evolved during tumor progression. One of these populations is called migrating CSC and can be characterized by CXCR4 co-expression. Only these cells are capable of evading the primary tumor and traveling to distant sites such as the liver as the preferred site of metastatic spread. Clinically even more important, however, is the observation that CSC are highly resistant to chemo- and radiotherapy resulting in their relative enrichment during treatment and rapid relapse of disease. Many laboratories are now working on the further in-depth characterization of these cells, which may eventually allow for the identification of their Achilles heal and lead to novel treatment modalities for fighting this deadly disease.« less

  8. Short versus long duration infusions of paclitaxel for any advanced adenocarcinoma

    PubMed Central

    Williams, Chris; Bryant, Andrew

    2014-01-01

    Background Paclitaxel has become a standard drug used in a number of common cancers. At first long infusions were used to reduce the rate of inflow of the drug and as a result reduce the occurrence of hypersensitivity types of allergic reactions. Trials with shorter durations of infusion, and using a cocktail of anti-allergic drugs to prevent hypersensitivity reactions, some randomised, were begun. These were interpreted as showing that effectiveness of treatment was not lessened by a short infusion time. These studies also appeared to show that some important toxicities were less common with short infusions and that they were more convenient for the patient and the hospital. Objectives To assess the effectiveness and toxicity of short versus long infusions of paclitaxel for any advanced adenocarcinoma. Search methods We searched the Cochrane Gynaecological Cancer Review Group Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2009, MEDLINE and EMBASE up to March 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included trials and contacted experts in the field, as well as drug companies. Selection criteria The review was restricted to randomised controlled trials (RCTs) of single agent paclitaxel or paclitaxel with other drugs, where the only variable was the duration of paclitaxel infusion. The review only includes patients with advanced adenocarcinoma. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in meta-analyses. Main results We identified six trials that met our inclusion criteria. The trials compared 3, 24 and 96 hour infusions and one trial examined different schedules (1 versus 3 day). From the included RCTs we found no evidence of a difference between short and long infusions in terms of overall and progression-free survival and tumour non-response. In most

  9. Expression of the "stem cell marker" CD133 in pancreas and pancreatic ductal adenocarcinomas

    PubMed Central

    Immervoll, Heike; Hoem, Dag; Sakariassen, Per Øystein; Steffensen, Ole Johnny; Molven, Anders

    2008-01-01

    Background It has been suggested that a small population of cells with unique self-renewal properties and malignant potential exists in solid tumors. Such "cancer stem cells" have been isolated by flow cytometry, followed by xenograft studies of their tumor-initiating properties. A frequently used sorting marker in these experiments is the cell surface protein CD133 (prominin-1). The aim of this work was to examine the distribution of CD133 in pancreatic exocrine cancer. Methods Fifty-one cases of pancreatic ductal adenocarcinomas were clinically and histopathologically evaluated, and immunohistochemically investigated for expression of CD133, cytokeratin 19 and chromogranin A. The results were interpreted on the background of CD133 expression in normal pancreas and other normal and malignant human tissues. Results CD133 positivity could not be related to a specific embryonic layer of organ origin and was seen mainly at the apical/endoluminal surface of non-squamous, glandular epithelia and of malignant cells in ductal arrangement. Cytoplasmic CD133 staining was observed in some non-epithelial malignancies. In the pancreas, we found CD133 expressed on the apical membrane of ductal cells. In a small subset of ductal cells and in cells in centroacinar position, we also observed expression in the cytoplasm. Pancreatic ductal adenocarcinomas showed a varying degree of apical cell surface CD133 expression, and cytoplasmic staining in a few tumor cells was noted. There was no correlation between the level of CD133 expression and patient survival. Conclusion Neither in the pancreas nor in the other investigated organs can CD133 membrane expression alone be a criterion for "stemness". However, there was an interesting difference in subcellular localization with a minor cell population in normal and malignant pancreatic tissue showing cytoplasmic expression. Moreover, since CD133 was expressed in shed ductal cells of pancreatic tumors and was found on the surface of tumor

  10. Decreased Expression of Transcription Elongation Factor A-Like 7 Is Associated with Gastric Adenocarcinoma Prognosis

    PubMed Central

    Chen, Yi-bing; Jiang, Shan-shan; Yan, Shu-mei; Zhao, Bai-wei; Pan, Ke; Wang, Dan-dan; Lv, Lin; Li, Yuan-fang; Wang, Wei; Zhou, Zhi-wei; Xia, Jian-chuan

    2013-01-01

    Background We sought to investigate the expression levels and prognosis value of TCEAL7 in primary gastric cancer. Methods and Results We investigated TCEAL7 and other homologous five members of the TCEAL family expression in normal gastricepithelial cell line and gastric cancer cell lines using real-time quantitative PCR. Furthermore, we examined the expression of TCEAL7 in 39 paired cancerous and matched adjacent noncancerous gastric mucosa tissues by real-time quantitative PCR and western blotting. Moreover, we analyzed TCEAL7 expression in 406 gastric cancer patients using immunohistochemistry. The relationships between the TCEAL7 expression levels, the clinicopathological factors, and patient survival were investigated. RT- qPCR data showed that mRNA expression level of TCEAL7 was significantly lower in the gastric cancer cell lines comparing with the levels of other five members of the TCEAL family. Results also revealed decreased TCEAL7 mRNA (P = 0.025) and protein (P = 0.012) expression in tumor tissue samples compared with matched adjacent non-tumor tissue samples. Immunohistochemical staining data showed that TCEAL7 expression was significantly decreased in 43.3% of gastric adenocarcinoma cases. The result also showed that the low TCEAL7 expression was significantly correlated with female, larger tumor size, higher histological grade and worse nodal status. Kaplan–Meier survival curves revealed that the reduced expression of TCEAL7 was associated with a poor prognosis in gastric adenocarcinoma patients (P<0.001). Based on a univariate analysis that included all 406 patients, TCEAL7 expression was found to have statistically significant associations with overall survival (P<0.001). Multivariate analysis also demonstrated that TCEAL7 expression (P = 0.009), age, tumor size, histological grade, lymphovascular invasion, T stage, N stage and M stage were independent risk factors in the prognosis of gastric cancer patients. Conclusions Our study

  11. A 65‑gene signature for prognostic prediction in colon adenocarcinoma.

    PubMed

    Jiang, Hui; Du, Jun; Gu, Jiming; Jin, Liugen; Pu, Yong; Fei, Bojian

    2018-04-01

    The aim of the present study was to examine the molecular factors associated with the prognosis of colon cancer. Gene expression datasets were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases to screen differentially expressed genes (DEGs) between colon cancer samples and normal samples. Survival‑related genes were selected from the DEGs using the Cox regression method. A co‑expression network of survival‑related genes was then constructed, and functional clusters were extracted from this network. The significantly enriched functions and pathways of the genes in the network were identified. Using Bayesian discriminant analysis, a prognostic prediction system was established to distinguish the positive from negative prognostic samples. The discrimination efficacy of the system was validated in the GSE17538 dataset using Kaplan‑Meier survival analysis. A total of 636 and 1,892 DEGs between the colon cancer samples and normal samples were screened from the TCGA and GSE44861 dataset, respectively. There were 155 survival‑related genes selected. The co‑expression network of survival‑related genes included 138 genes, 534 lines (connections) and five functional clusters, including the signaling pathway, cellular response to cAMP, and immune system process functional clusters. The molecular function, cellular components and biological processes were the significantly enriched functions. The peroxisome proliferator‑activated receptor signaling pathway, Wnt signaling pathway, B cell receptor signaling pathway, and cytokine‑cytokine receptor interactions were the significant pathways. A prognostic prediction system based on a 65‑gene signature was established using this co‑expression network. Its discriminatory effect was validated in the TCGA dataset (P=3.56e‑12) and the GSE17538 dataset (P=1.67e‑6). The 65‑gene signature included kallikrein‑related peptidase 6 (KLK6), collagen type XI α1 (COL11A1), cartilage

  12. Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine-needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations.

    PubMed

    Song, Dae Hyun; Lee, Boram; Shin, Yooju; Choi, In Ho; Ha, Sang Yun; Lee, Jae Jun; Hong, Min Eui; Choi, Yoon-La; Han, Joungho; Um, Sang-Won

    2015-07-01

    Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutation in pulmonary adenocarcinoma is clinically important due to its association with resistance to EGFR inhibitors and poor prognosis. To our knowledge, there has not been a comparative study focusing on cytological nuclear features of pulmonary adenocarcinoma harboring KRAS mutation (KRAS-AD). Hence, we compared the cytomorphology of metastatic KRAS-AD and EGFR-positive adenocarcinoma (EGFR-AD) in aspiration specimens from lymph nodes. Forty lymph node aspiration specimens from forty KRAS-AD patients were collected at Samsung Medical Center (Seoul, Korea) from 2009 to 2013. As a control group, 40 EBUS-FNA lymph node specimens from 20 EGFR-AD patients were collected. EGFR-AD specimens were evaluated at Samsung Medical Center (Seoul, Korea) from 2012 to 2013. All 80 specimens were histologically confirmed to metastatic adenocarcinoma. Two pathologists performed a blinded review of all specimens. Compared with EGFR-AD, KRAS-AD exhibited more severe nuclear pleomorphism (P < 0.001), coarse chromatin (P = 0.001), cherry-red nucleoli (P < 0.001) and naked tumor cells (P = 0.002) with necrotic (P < 0.001) and neutrophilic (P = 0.008) background. Our study provides the first demonstration of cytomorphologic differentiation between metastatic KRAS-AD and metastatic EGFR-AD in lymph node aspiration specimens. © 2014 Wiley Periodicals, Inc.

  13. Cytological features of hepatoid adenocarcinoma of the gallbladder: A case report with immunocytochemical analyzes.

    PubMed

    Yoshioka, Saya; Ishida, Mitsuaki; Okano, Kimiaki; Sandoh, Kaori; Ebisu, Yusuke; Miyasaka, Chika; Yamamoto, Tomohisa; Ryota, Hironori; Satoi, Sohei; Tsuta, Koji

    2018-04-10

    Hepatoid adenocarcinoma is defined as an extrahepatic malignant neoplasm showing morphological and immunohistochemical resemblance of hepatocellular carcinoma. The occurrence of this type of tumor in the gallbladder is extremely rare. In this study, we report the first cytological case of hepatoid adenocarcinoma of the gallbladder. An 80-year-old Japanese female was found to have a tumorous lesion in the gallbladder. Papanicolaou smear of the ascites demonstrated a few epithelial cell clusters composed of round to oval neoplastic cells with distinct cell border and large centrally-located nuclei. Tumor touch smear of the resected tumor revealed the presence of two distinct neoplastic components. The first component was composed of clusters or sheets of epithelial cells with distinct cell border, relatively rich clear cytoplasm, and centrally-located nuclei, as seen in the ascites specimen. The other component was composed of tall columnar cells with large basally-oriented nuclei, and glandular formation was noted as well. Immunocytochemical analyzes of the touch smear material demonstrated that the former component was positive for HepPar1, thus it was considered as a hepatoid adenocarcinoma, and the latter component deemed as a typical adenocarcinoma. Histopathological and immunohistochemical examination of the resected gallbladder tumor confirmed a diagnosis of hepatoid adenocarcinoma. The characteristic cytological features of hepatoid adenocarcinoma are the presence of sheets or clusters of neoplastic cells with distinct cell border and centrally-located nuclei. Immunocytochemical analysis for HepPar1 may help its diagnosis. Demonstration of hepatoid adenocarcinoma is important in the cytological specimen because this type of tumor shows an aggressive clinical course. © 2018 Wiley Periodicals, Inc.

  14. Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

    PubMed

    Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

    2017-07-24

    This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (p<0.05). AAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

  15. SIRT-1expression is associated with expression of NANOG in patients with colorectal adenocarcinoma.

    PubMed

    Osama, Amany; Sabry, Dina; Hassany, Sahar M; Abdelmoneim, Soha Saoud; Sabry, Abeer

    2016-06-24

    The study aimed to investigate the quantitative expression of NANOG, p38 α , NCF2, ELF and TGF-β genes in patients with colorectal adenocarcinoma, adenoma and normal colonic tissue and their correlation with SIRT-1 protein level expression. This study enrolled one hundred sixty seven patients; group A: 87 patients with colonoscopic findings of no adenoma or adenocarcinoma and group B: 80 patients with colorectal mass. Consecutive colonoscopic examinations were conducted, and tissue samples were taken from the colonic lesions/masses. Total RNA was isolated and mRNA expression level of NANOG, mitogen activated p38α , Neutrophil Cytosol Factor 2 (NCF2), Embryonic Liver Fodrin (ELF) and Transforming Growth Factor Beta (TGF-β) genes were quantified by qRT-PCR. Sirt-1 protein expression level was assessed by quantitative western blot. There were significantly high level of mRNA transcripts expression of the genes studied in patients with adenocarcinoma and adenoma compared with normal tissue (P value < 0.01), NANOG, NCF2, ELF and TGF-β at a cut of > 0.314, > 0.392, 0.349 and 0.333 respectively showed sensitivity (96.5%, 98.8%, 95.3%, 98.8%) and specificity of (95.3%, 92.6%, 89.5%, 93.8%) respectively in diagnosing colonic adenocarcinoma. Sirt-1 protein level was significantly highly expressed in colorectal adenocarcinoma compared to normal and adenoma colonic tissue and positively correlated with NANOG. Over expression of NANOG, p38α , NCF2, ELF and TGF-β genes in both cases of adenocarcinoma and adenoma could have a diagnostic value. SIRT-1 and NANOG are high correlated biological markers for diagnosis and prognosis follow up in patients with adenocarcinoma.

  16. Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma.

    PubMed

    Sawada, Akinari; Fujiwara, Yasuhiro; Nagami, Yasuaki; Tanaka, Fumio; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Tominaga, Kazunari; Watanabe, Toshio; Gi, Min; Wanibuchi, Hideki; Arakawa, Tetsuo

    2016-11-01

    Recent studies suggest that chronic inflammation-associated cancer is relevant to microbiome. Esophageal adenocarcinoma arises from an inflammatory condition called Barrett's esophagus, which is caused by gastroesophageal reflux. We hypothesized that esophageal microbiome plays a role in carcinogenesis of esophageal adenocarcinoma. We investigated whether alteration of microbiome using antibiotics affects the development of esophageal adenocarcinoma in a rat model. Seven-week-old male Wistar rats which had undergone esophagojejunostomy were divided into control (n = 21) and antibiotic groups (n = 22) at 21 weeks after surgery. Control animals were given drinking water, while the other group was given penicillin G and streptomycin in drinking water until rats were killed at 40 weeks after operation. Incidence rates of Barrett's esophagus and adenocarcinoma in each group were evaluated by histological analysis. DNA was extracted from a portion of the distal esophagus, and the microbiome was investigated using terminal restriction fragment length polymorphism (T-RFLP) analysis. All rats in both groups developed Barrett's esophagus. Incidence of esophageal adenocarcinoma was similar between both groups with a trend to reduced incidence in the antibiotics group (89 % in the control group, 71 % in the antibiotics group, P = 0.365). T-RFLP analysis showed that esophageal microbiome was different between two groups such as the proportion of Lactobacillales was lower in the antibiotics group and Clostridium cluster XIVa and XVIII was higher in the antibiotics group. Alteration of microbiome does not affect the incidence of esophageal adenocarcinoma. Microbiome may not contribute to the development of esophageal adenocarcinoma.

  17. Deregulation of 2 potassium channels in pancreas adenocarcinomas: implication of KV1.3 gene promoter methylation.

    PubMed

    Brevet, Marie; Fucks, David; Chatelain, Denis; Regimbeau, Jean-Marc; Delcenserie, Richard; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2009-08-01

    The aim of this study was to examine expression of 2 potassium (K) channels in pancreatic adenocarcinoma. The immunohistochemical and mRNA expression of GIRK1 (G-protein inwardly rectifying K channel 1) and KV1.3 channel (voltage-dependent K channel) was studied in 55 and 18 adenocarcinomas and 33 and 8 normal pancreas specimens, respectively. The methylation status of KV1.3 promoter was studied by methyl-specific polymerase chain reaction in 33 pancreatic adenocarcinomas. The results were correlated with the patients' prognosis. GIRK1 was highly expressed in 80% (44/55) of adenocarcinoma samples versus 57.6% (19/33) of normal samples (P=0.03), as confirmed by reverse transcriptase-polymerase chain reaction results (P=0.007). KV1.3 expression was decreased in pancreatic adenocarcinomas compared with normal tissue (7.3% vs 39.4%; P=0.0005). KV1.3 down-expression was associated with metastatic tumors (P=0.018). KV1.3 promoter methylation was observed in 69.7% (22/33) of adenocarcinomas. This is the first report of deregulation of 2 K channels in pancreatic adenocarcinoma. GIRK1 was highly expressed in pancreatic adenocarcinomas, corresponding to its role in cell proliferation. Methylation of KV1.3 gene promoter could explain the decrease of KV1.3 expression in adenocarcinomas. New therapeutic agents, such as DNA methylation inhibitors, could be useful against this dramatic cancer.

  18. Perioperative chemo(radio)therapy versus primary surgery for resectable adenocarcinoma of the stomach, gastroesophageal junction, and lower esophagus.

    PubMed

    Ronellenfitsch, Ulrich; Schwarzbach, Matthias; Hofheinz, Ralf; Kienle, Peter; Kieser, Meinhard; Slanger, Tracy E; Jensen, Katrin

    2013-05-31

    The outcome of patients with locally advanced gastroesophageal adenocarcinoma (adenocarcinoma of the esophagus, gastroesophageal (GE) junction, and stomach) is poor. There is conflicting evidence regarding the effects of perioperative chemotherapy on survival and other outcomes. To assess the effect of perioperative chemotherapy for gastroesophageal adenocarcinoma on survival and other clinically relevant outcomes in the overall population of participants in randomized controlled trials (RCTs) and in prespecified subgroups. We performed computerized searches in the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Review of Effectiveness (DARE), the Cochrane Database of Systematic Reviews (CDSR) from The Cochrane Library, MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), combining the Cochrane highly sensitive search strategy with specific search terms. Moreover, we handsearched several online databases, conference proceedings, and reference lists of retrieved papers. We included RCTs which randomized patients with gastroesophageal adenocarcinoma, in the absence of distant metastases, to receive either chemotherapy with or without radiotherapy followed by surgery, or surgery alone. Two independent review authors identified eligible trials. We solicited individual patient data (IPD) from all selected trials. We performed meta-analyses based on intention-to-treat populations using the two-stage method to combine IPD with aggregate data from RCTs for which IPD were unavailable. We combined data from all trials providing IPD in a Cox proportional hazards model to assess the effect of several covariables on overall survival. We identified 14 RCTs with 2422 eligible patients. For eight RCTs with 1049 patients (43.3%), we were able to obtain IPD. Perioperative chemotherapy was associated with significantly longer overall survival (hazard ratio (HR) 0.81; 95

  19. A novel messenger RNA signature as a prognostic biomarker for predicting relapse in pancreatic ductal adenocarcinoma

    PubMed Central

    Shi, Guodong; Zhang, Jingjing; Lu, Zipeng; Liu, Dongfang; Wu, Yang; Wu, Pengfei; Yin, Jie; Yuan, Hao; Zhu, Qicong; Chen, Lei; Fu, Yue; Peng, Yunpeng; Wang, Yan; Jiang, Kuirong; Miao, Yi

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) death rate and recurrence rate have remained obstinately high. Current methods can not satisfy the need of predicting cancer relapse accurately. Utilizing expression profiles of 10 GEO datasets (N = 774), we identified 154 differentially expressed genes (DEGs) between PDAC and normal pancreas tissue or paracancerous tissue. Next we built a 16-mRNA-based signature by means of the LASSO COX regression model. We also validated the prognostic value of the signature. Patients were classified into high-risk and low-risk group according to the signature risk score; 1 year RFS was 45% (95% CI: 31.6%–63.9%) for high-risk group in contrast to 92.5% (95% CI: 86.3%–99.1%) for low-risk group. Moreover, it could predict RFS well in cases with the receipt of different treatment modalities. The 16-mRNA-based signature was an independent and powerful prognostic biomarker for RFS for PDAC patients (HR = 7.74, 95% CI: 3.25–18.45, p < 0.0001). PMID:29340021

  20. Curcumin Induces Pancreatic Adenocarcinoma Cell Death via Reduction of the Inhibitors of Apoptosis

    PubMed Central

    Osterman, Carlos J. Díaz; Gonda, Amber; Stiff, TessaRae; Sigaran, Ulysses; Valenzuela, Malyn May Asuncion; Bennit, Heather R. Ferguson; Moyron, Ron B.; Khan, Salma; Wall, Nathan R.

    2015-01-01

    Objectives The inhibitor of apoptosis (IAP) proteins are critical modulators of chemotherapeutic resistance in various cancers. To address the alarming emergence of chemotherapeutic resistance in pancreatic cancer, we investigated the efficacy of the turmeric derivative curcumin in reducing IAP protein and mRNA expression resulting in pancreatic cancer cell death. Methods The pancreatic adenocarcinoma cell line PANC-1 was used to assess curcumin’s effects in pancreatic cancer. Curcumin uptake was measured by spectral analysis and fluorescence microscopy. AlamarBlue and Trypan blue exclusion assays were used to determine PANC-1 cell viability following curcumin treatment. Visualization of PANC-1 cell death was performed using Hoffman Modulation Contrast microscopy. Western blot and PCR analyses were used to evaluate curcumin’s effects on IAP protein and mRNA expression. Results Curcumin enters PANC-1 cells and is ubiquitously present within the cell following treatment. Furthermore, curcumin reduces cell viability and induces morphological changes characteristic of cell death. Additionally, curcumin decreases IAP protein and mRNA expression in PANC-1 cells. Conclusions These data demonstrate that PANC-1 cells are sensitive to curcumin treatment. Furthermore, curcumin as a potential therapeutic tool for overcoming chemotherapeutic resistance mediated by IAPs, supports a role for curcumin as part of the therapeutic approach for pancreatic cancer. PMID:26348467

  1. Quantitative Proteomic Analysis of Differentially Expressed Protein Profiles Involved in Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Kuo, Kung-Kai; Kuo, Chao-Jen; Chiu, Chiang-Yen; Liang, Shih-Shin; Huang, Chun-Hao; Chi, Shu-Wen; Tsai, Kun-Bow; Chen, Chiao-Yun; Hsi, Edward; Cheng, Kuang-Hung; Chiou, Shyh-Horng

    2016-01-01

    Objectives The aim of this study was to identify differentially expressed proteins among various stages of pancreatic ductal adenocarcinoma (PDAC) by shotgun proteomics using nano-liquid chromatography coupled tandem mass spectrometry and stable isotope dimethyl labeling. Methods Differentially expressed proteins were identified and compared based on the mass spectral differences of their isotope-labeled peptide fragments generated from protease digestion. Results Our quantitative proteomic analysis of the differentially expressed proteins with stable isotope (deuterium/hydrogen ratio, ≥2) identified a total of 353 proteins, with at least 5 protein biomarker proteins that were significantly differentially expressed between cancer and normal mice by at least a 2-fold alteration. These 5 protein biomarker candidates include α-enolase, α-catenin, 14-3-3 β, VDAC1, and calmodulin with high confidence levels. The expression levels were also found to be in agreement with those examined by Western blot and histochemical staining. Conclusions The systematic decrease or increase of these identified marker proteins may potentially reflect the morphological aberrations and diseased stages of pancreas carcinoma throughout progressive developments leading to PDAC. The results would form a firm foundation for future work concerning validation and clinical translation of some identified biomarkers into targeted diagnosis and therapy for various stages of PDAC. PMID:26262590

  2. A robust gene expression-based prognostic risk score predicts overall survival of lung adenocarcinoma patients.

    PubMed

    Chen, En-Guo; Wang, Pin; Lou, Haizhou; Wang, Yunshan; Yan, Hong; Bi, Lei; Liu, Liang; Li, Bin; Snijders, Antoine M; Mao, Jian-Hua; Hang, Bo

    2018-01-23

    Identification of reliable predictive biomarkers and new therapeutic targets is a critical step for significant improvement in patient outcomes. Here, we developed a multi-step bioinformatics analytic strategy to mine large omics and clinical data to build a prognostic scoring system for predicting the overall survival (OS) of lung adenocarcinoma (LuADC) patients. In latter we first identified 1327 significantly and robustly deregulated genes, 600 of which were significantly associated with the OS of LuADC patients. Gene co-expression network analysis revealed the biological functions of these 600 genes in normal lung and LuADCs, which were found to be enriched for cell cycle-related processes, blood vessel development, cell-matrix adhesion and metabolic processes. Finally, we implemented a multiple resampling method combined with Cox regression analysis to identify a 27-gene signature associated with OS, and then created a prognostic scoring system based on this signature. This scoring system robustly predicted OS of LuADC patients in 100 sampling test sets and was further validated in four independent LuADC cohorts. In addition, in comparison to other existing prognostic gene signatures published in the literature, our signature was significantly superior in predicting OS of LuADC patients. In summary, our multi-omics and clinical data integration study created a 27-gene prognostic risk score that can predict OS of LuADC patients independent of age, gender and clinical stage. This score could guide therapeutic selection and allow stratification in clinical trials.

  3. Genexol inhibits primary tumour growth and metastases in gemcitabine-resistant pancreatic ductal adenocarcinoma

    PubMed Central

    Shea, Jill E; Nam, Kweon-Ho; Rapoport, Natalya; Scaife, Courtney L

    2011-01-01

    Introduction Gemcitabine, the current standard of care for pancreatic ductal adenocarcinoma (PDA), has a less than 10% partial response rate. Genexol-PM, a modified form of paclitaxel, has been shown to have antitumour effects in clinical trials of metastatic breast and small-lung-cell carcinoma. The aim of the present study was to determine if Genexol would be a beneficial treatment for gemcitabine-resistant PDA. Materials and methods We measured the in vitro IC50s of gemcitabine and genexol in cell lines sensitive and resistant to gemcitabine. In vivo, animals with orthotopic pancreatic tumours, resistant to gemcitabine, were treated with phosphate-buffered saline (PBS), gemcitabine, Genexol or gemcitabine+Genexol. Tumour progression was monitored using red fluorescent protein imaging. Results We showed equivalent IC50s for gemcitabine-sensitive and gemcitabine-resistant cell lines when treated with genexol. In vivo treatment with genexol resulted in a greater per cent reduction in tumour size, less metastatic spread and longer survival compared with treatment with gemcitabine. Discussion Genexol proved to be an effective treatment for gemcitabine-resistant PDA. These data combined with the successful clinical use of genexol in Phase II trials of other malignancies suggests it maybe an effective treatment for pancreatic cancer, specifically for those patients resistant to gemcitabine. PMID:21309930

  4. Helicobacter Species Identified in Captive Sooty Mangabeys (Cercocebus atys) with Metastatic Gastric Adenocarcinoma

    PubMed Central

    Esmail, Michael Y.; Bacon, Rebecca; Swennes, Alton G.; Feng, Yan; Shen, Zeli; Garcia, AnaPatricia; Sharma, Prachi; Cohen, Joyce; Fox, James G.

    2016-01-01

    Background Of all human cancers, gastric carcinoma is the one of the leading causes of death. Helicobacter pylori is considered a major etiologic agent of this disease. Spontaneously occurring gastric carcinoma is a rare diagnosis in nonhuman primates. A 2011 case report documented a high incidence of gastric adenocarcinoma in a closed colony of captive sooty mangabeys (Cercebus atys). However, H. pylori infection was not detected in these animals. Materials and Methods In this study, using archived formalin-fixed, paraffin-embedded stomach sections of these animals alternative methodologies were used to identify H. pylori and other non-H. pylori Helicobacter species. In addition, two additional cases of sooty mangabeys with metastatic gastric carcinoma are characterized. Results Using fluorescent in situ hybridization, we identified gastric H. suis in 75% of archived and new gastric carcinoma cases. In the two newly reported cases, H. suis and a novel Helicobacter species were detected via PCR and sequence analysis of the 16S rRNA gene. H. pylori was not identified in any of the gastric carcinoma cases via FISH and/or PCR and sequence analysis of Helicobacter spp. in DNA from of available tissues. Conclusions This report is the first to characterize Helicobacter species infection in spontaneous gastric carcinoma with metastatic potential in nonhuman primates. PMID:26477442

  5. Delay of Lung Adenocarcinoma (LAC-1) Development in Mice by Dietary Oleic Acid.

    PubMed

    Piegari, Mariana; Soria, Elio A; Eynard, Aldo R; Valentich, Mirta A

    2017-10-01

    Lung cancer is the leading cause of death by cancer, and is a major sanitary concern worldwide. Some nutrients, such as ω-9 fatty acids, have been proposed as anticancer agents. Thus, an olein-enriched diet was assayed in a murine model of lung adenocarcinoma (LAC-1) to evaluate neoplastic and paraneoplastic evolution in BALB/c mice. The organic assimilation of dietary fatty acids was confirmed in liver by gas chromatography. This experimental oleic acid-containing diet increased animal survival and tumour latency (analysed by the Kaplan-Meier method), improving neoplastic evolution and general status, with weak effects on the paraneoplastic syndrome (thymus atrophy, splenomegaly, splenocyte response to mitogen, blood anaemia, and leucocytosis). Tumour lipid oxidation was not involved. Thus, diet enrichment with olein, a natural source of the ω-9 oleic acid, significantly delayed progression of LAC-1 and increased tumour latency and mice survival. These results support its use in nutritional management of cancer, with further studies being encouraged.

  6. ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability

    PubMed Central

    Teixido, Cristina; Michels, Sebastian; Morales-Espinosa, Daniela; Viteri, Santiago; Hartmann, Wolfgang; Merkelbach-Bruse, Sabine; Fischer, Rieke; Schildhaus, Hans-Ulrich; Fassunke, Jana; Sebastian, Martin; Serke, Monika; Kaminsky, Britta; Randerath, Winfried; Gerigk, Ulrich; Ko, Yon-Dschun; Krüger, Stefan; Schnell, Roland; Rothe, Achim; Kropf-Sanchen, Cornelia; Heukamp, Lukas; Rosell, Rafael

    2015-01-01

    Background While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. Patients and Methods 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. Results 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. Conclusion ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC. PMID:25868855

  7. Postoperative complications and overall survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

    PubMed Central

    Pugalenthi, Amudhan; Protic, Mladjan; Gonen, Mithat; Kingham, T. Peter; D’ Angelica, Michael I.; Dematteo, Ronald P.; Fong, Yuman; Jarnagin, William R.; Allen, Peter J.

    2016-01-01

    INTRODUCTION Pancreaticoduodenectomy (PD) performed for pancreatic ductal adenocarcinoma (PDA) has a postoperative morbidity of 40–50%. In this study, we analyzed the impact of high grade complications after PD for PDA on overall survival. METHODS 596 patients that underwent PD for PDA between 2001–2009 were identified from a prospective database. Complications were defined and graded (1–5) as per our Institutional Surgical Secondary Events Program. High grade complications were defined as ≥ grade 3. Postoperative mortality (≤ 90 days) was excluded. Univariate and multivariate analyses were performed to identify factors associated with overall survival. RESULTS Median survival was 24 months. Overall complication rate was 51% (301/596). Low grade complications were recorded in 266 patients (45%) and high grade complications in 22% (n= 129). Our 90 day mortality was 3.7% (n= 22). Anastomotic fistula/ leak/abscess rate was 14% (n= 82). Multivariate Cox-Regression analysis identified node positivity, estimated blood loss (EBL) > 600 ml, length of stay (LOS) > 10 days, margin positivity and vascular procedures as predictors of decreased overall survival (p < 0.05). High grade complications were not associated with overall survival (p = 0.948). CONCLUSION In this study, the occurrence of high grade postoperative complications was not associated with overall survival. PMID:26678349

  8. Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma

    PubMed Central

    Sharmab, Anup; Xie, Fei; Liu, Yanliang; Li, Kai; Wan, Weiwei; Baylin, Stephen B.; Wolfgang, Christopher L.; Ahuja, Nita

    2016-01-01

    Background O6-methylguanine-DNA methyltransferase (MGMT) methylation status has not been extensively investigated in duodenal adenocarcinoma (DA). The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA. Methods Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP), microsatellite instability (MSI), and KRAS mutations. Results MGMT methylation was detected in 17 of 64 (26.6%) patients, and was not correlated with sex, age, tumor differentiation, CIMP, MSI, or KRAS mutations. MGMT methylation was the only one factor associated with both overall survival (OS) and disease-free survival (DFS) on both univariate and multivariate analyses. In patients treated with surgery alone, MGMT-methylated group had worse OS and DFS when compared with MGMT-unmethylated group. However, in patients treated with chemotherapy/radiotherapy, outcomes became comparable between the two groups. Conclusions Our results demonstrate MGMT methylation is a reliable and independent prognostic factor in DAs. Methylation of MGMT is associated with poor prognosis in patients with stage III DAs. PMID:27643594

  9. Dynamic contrast-enhanced MRI of the microenvironment of pancreatic adenocarcinoma xenografts.

    PubMed

    Wegner, Catherine S; Hauge, Anette; Gaustad, Jon-Vidar; Andersen, Lise Mari K; Simonsen, Trude G; Galappathi, Kanthi; Rofstad, Einar K

    2017-12-01

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor outcome. Resistance to treatment is associated with impaired vascularity, extensive hypoxia, and interstitial hypertension. In this study, the potential of dynamic contrast-enhanced (DCE)-MRI as a method for assessing the microvascular density (MVD), the fraction of hypoxic tissue, and the interstitial fluid pressure (IFP) of PDACs was investigated. Intramuscular BxPC-3, Capan-2, MIAPaCa-2, and Panc-1 PDAC xenografts were used as preclinical models of human PDACs. DCE-MRI with Gd-DOTA as contrast agent was conducted with a 7.05-T scanner, and the DCE-MRI series were analyzed voxelwise by using the Tofts pharmacokinetic model. Tumor MVD and hypoxia were measured in histological preparations by using pimonidazole as a hypoxia marker and CD31 as a marker of endothelial cells. IFP was measured with a Millar catheter. K trans (the volume transfer constant of Gd-DOTA) increased with increasing MVD and decreased with increasing hypoxic fraction, but was not associated with IFP. Any association between v e (the fractional distribution volume of Gd-DOTA) and MVD, hypoxic fraction, or IFP could not be detected. This study shows that DCE-MRI is a useful modality for assessing important features of the microenvironment of PDAC xenografts and thus provides the basis for future preclinical and clinical DCE-MRI investigations of PDAC.

  10. A 76-year-old man with a right lung adenocarcinoma and invasive Aspergillosis.

    PubMed

    Dos Santos, Vitorino Modesto; da Trindade, Marcos Correa; de Souza, Diogo Wagner da Silva; de Menezes, Ana Isabel Costa; Oguma, Patricia Midori; Nascimento, Afonso Lucas Oliveira

    2013-08-01

    A 76-year-old male with adenocarcinoma on the right lung underwent five cycles of chemotherapy with pemetrexed disodium, cisplatin, and dexamethasone. Imaging studies of control showed a node in a cavitary lesion on the left lung, and the main hypothesis was Aspergillus infection. PCR was utilized and contributed to establish the early diagnosis in this patient with invasive aspergillosis. Furthermore, the species Aspergillus fumigatus was characterized by its growing at 50 °C but not at 10 °C, typical culture features, and presence of subclavate vesicles. Diagnosis criteria for Aspergillus pulmonary infection include characteristic clinical and imaging findings, elevated C-reactive protein and erythrocyte sedimentation rate, positive specific serological test, and isolation of Aspergillus from bronchoalveolar cultures. Molecular methods, as PCR, have been useful to complement the conventional microbiological investigations in immunocompromised people with invasive fungal infections. The patient was successfully treated with a schedule of voriconazole 4 mg/kg intravenous infusion every 12 h for 21 days and then switched to oral administration of 200 mg twice a day. He has been comfortable, maintaining normal vital signs, and the results of the periodical microbiologic tests of control are negative. Pathogenesis of invasive aspergillosis in patients with lung cancer is not completely understood. Case studies may contribute to a better knowledge about Aspergillus infection in this setting.

  11. Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy

    SciTech Connect

    Leeman, Jonathan E.; Rimner, Andreas; Montecalvo, Joseph

    2017-01-01

    Purpose: Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype. Methods and Materials: We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 Worldmore » Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non–high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score–weighted Cox regression models. Results: The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non–high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival. Conclusions: The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype

  12. Solitary ground-glass opacity nodules of stage IA pulmonary adenocarcinoma: combination of 18F-FDG PET/CT and high-resolution computed tomography features to predict invasive adenocarcinoma.

    PubMed

    Zhou, Jun; Li, Yanli; Zhang, Yiqiu; Liu, Guobing; Tan, Hui; Hu, Yan; Xiao, Jie; Shi, Hongcheng

    2017-04-04

    To investigate the performance of combined 18F-FDG Positron Emission Tomography/Computed Tomography with high-resolution CT for differentiating invasive adenocarcinoma from adenocarcinoma in situ (pre-invasive lesion) or minimally invasive adenocarcinoma in stage IA lung cancer patients with solitary ground-glass opacity nodules. This retrospective study enrolled 58 consecutive stage IA pulmonary adenocarcinoma patients with solitary ground-glass opacity nodules. The characteristics and measurements of the ground-glass opacity nodules as pure ground-glass opacity nodules and mixed ground-glass opacity nodules in the pre-invasive or minimally invasive adenocarcinoma and invasive adenocarcinoma groups on Positron Emission Tomography/Computed Tomography and high-resolution CT were compared and analyzed. Ground-glass opacity nodules in the pre-invasive or minimally invasive adenocarcinoma group preferentially manifested as pure ground-glass opacity nodule (p < 0.01) compared to the invasive adenocarcinoma group. While cystic appearance was more common in the invasive adenocarcinoma group (p < 0.05). Significant differences were found in the diameter of the ground-glass opacity nodule itself and its solid component, and consolidation/tumor ratio between the two groups. The sensitivity in predicting invasive adenocarcinoma was higher with a combined consolidation/tumor ratio > 0.38 and SUVmax > 1.46 in mixed ground-glass opacity nodule when compared to those of SUVmax > 0.95 alone or consolidation/tumor ratio> 0.39 alone (both p > 0.05). For a mixed ground-glass opacity nodule combined consolidation/tumor ratio > 0.38 and SUVmax > 1.46 appears to better predict invasive adenocarcinoma in stage IA lung cancer patients with solitary ground-glass opacity nodules.

  13. Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma.

    PubMed

    Bellezza, Guido; Vannucci, Jacopo; Bianconi, Fortunato; Metro, Giulio; Del Sordo, Rachele; Andolfi, Marco; Ferri, Ivana; Siccu, Paola; Ludovini, Vienna; Puma, Francesco; Sidoni, Angelo; Cagini, Lucio

    2017-12-01

    Aquaporins (AQPs) are a group of transmembrane water-selective channel proteins thought to play a role in the regulation of water permeability for plasma membranes. Indeed, high AQP levels have been suggested to promote the progression, invasion and metastasis of tumours. Specifically, AQP1 and AQP5 overexpression in lung adenocarcinoma (AC) have been suggested to be involved in molecular mechanisms in lung cancer. The aim of this retrospective cohort single-centre study was to assess both the levels of expression and therein the prognostic significance, regarding outcome of AQP1 and AQP5 in resected AC patients. Patients with histological diagnoses of lung AC submitted to pulmonary resection were included in this cohort study. Tissue microarrays containing cores from 185 ACs were prepared. AQP1 and AQP5 expressions were assessed by immunohistochemistry. Results were scored as either low (Score 0-2) or high (Score 3-9). Clinical data, pathological tumour-node-metastasis staging and follow-up were recorded. Multivariate Cox survival analysis and Fisher's t-test were performed. AQP1 overexpression was detected in 85 (46%) patients, while AQP5 overexpression was observed in 45 (24%) patients. AQP1 did not result being significantly correlated with clinical and pathological parameters, while AQP5 resulted more expressed in AC with mucinous and papillary predominant patterns. Patients with AQP1 overexpression had shorter disease-free survival (P = 0.001) compared with patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter disease-free survival (P = 0.001). Our results evidenced that AQP1 overexpression resulted in a shorter disease-free survival in lung AC patients. Being so, AQP1 overexpression might be an important prognostic marker in lung AC. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights

  14. [Opened vs. laparoscopic radical nephrectomy in renal adenocarcinoma cost comparison].

    PubMed

    Herranz Amo, F; Subirá Ríos, D; Hernández Fernández, C; Martínez Salamanca, J I; Monzó, J I; Cabello Benavente, R

    2006-10-01

    To undertake a cost comparison (cost minimization) between transperitoneal laparoscopic and opened nephrectomy in renal adenocarcinoma treatment. Retrospective study on the first 26 patients submitted to LN without intra or postoperative complications in the period 2002-2003, using as control 22 patients treated with ON with the same characteristics and in the same period. Demographic variables were evaluated (age, sex, tumor size, etc.), intraoperative (operative time and fungible material used) and postoperative (length of stay in Postanaesthesic Care Unit, Acute Pain Unit needs and hospital stay). Our Hospital costs plus those imputed during year 2003 to the Urology Service, as well as the cost of fungible material for the same year were applied, carrying out a comparison of costs between both groups. There were no differences between the demographic variables between both groups except in the tumor, bigger size in the opened nephrectomy (p=0,001). Transperitoneal laparoscopic was 29,4% globally more expensive than opened nephrectomy. The transperitoneal laparoscopic intraoperative cost (operating room, anesthesia and fungibles) the exceeded in 151,6% to that of the opened nephrectomy, whereas in the opened nephrectomy the postoperative cost was a 63 % higher than in the transperitoneal laparoscopic cases. Transperitoneal laparoscopic in our Center is more expensive than opened nephrectomy due to a major occupation of operating room and that the specific fungible material used at the surgical act has a very high cost. It would be necessary to drastically reduce surgical time and decrease fungible material expenses, thus transperitoneal laparoscopic procedure could be competitive in our Hospital.

  15. Modulation of prostaglandin biosynthesis in murine mammary adenocarcinoma tumor cells

    SciTech Connect

    Shalinsky, D.R.

    1988-01-01

    In efforts to exploit the differential oxygen levels within the subcompartments of solid neoplasms, this project has focused on modulating prostaglandin (PG) biosynthesis under aerobic and hypoxic conditions. Mammary adenocarcinoma tumor cells (Line 4526), either intact or sonicated, were incubated with either 2.0 uM {sup 14}C-arachidonic acid (AA) or 20.0 uM {sup 14}C-PGH{sub 2}, respectively. Following metabolism, products were extracted, separated by thin layer chromatography and analyzed by radiochromatographic scan. PGE{sub 2} was predominantly formed with minimal amounts of PGF{sub 2a} or PGD{sub 2}. Indomethacin and ibuprofen inhibited the PGE{sub 2} formation from AA with an IC{sub 50} value ofmore » 6.3 {times} 10{sup {minus}8} and 9.6 {times} 10{sup {minus}5}M, respectively. Suspended cells in glass vials were made hypoxic by flushing with N{sub 2} for varying time intervals to study AA metabolism. A time-dependent inhibition of PG biosynthesis was observed under hypoxia, and by 30 min, the PGE{sub 2} synthesis was reduced by 50% which was further inhibited by indomethacin. Misonidazole, a 2-nitroimidazole analogue, partially reversed the inhibition of PGE{sub 2} synthesis under hypoxia by 49% at 100 uM. However, misonidazole did not affect PG biosynthesis under aerobic conditions. The stimulation of PGE{sub 2} biosynthesis by misonidazole under hypoxia was blocked by indomethacin, suggesting that misonidazole can not act independently of the cyclooxygenase.« less

  16. Evaluation of Bevacizumab in Advanced Small Bowel Adenocarcinoma.

    PubMed

    Aydin, Dincer; Sendur, Mehmet Ali; Kefeli, Umut; Ustaalioglu, Basak Bala; Aydin, Ozhan; Yildirim, Emre; Isik, Deniz; Ozcelik, Melike; Surmeli, Heves; Oyman, Abdilkerim; Isik, Selver; Sener, Nur; Ercelep, Ozlem; Odabas, Hatice; Aliustaoglu, Mehmet; Gumus, Mahmut

    2017-03-01

    Small bowel adenocarcinomas (SBAs) are rarely seen tumors. Data regarding the use of chemotherapy together with bevacizumab in patients with advanced SBA are lacking. The aim of this study was the evaluation of treatment with bevacizumab in advanced SBA. Twenty-eight patients from 5 centers with a diagnosis of advanced SBA who received first-line treatments with modified FOLFOX6 (mFOLFOX6; oxaliplatin, leucovorin, and 5-fluorouracil) and FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan) chemotherapy regimens were involved in the study. All patients were divided into 2 groups; those who received bevacizumab together with these chemotherapy regimens (Chemo+Bev group) and those who did not receive bevacizumab (Chemo group). The median progression-free survival (PFS) and overall survival (OS) times of all population were 8.7 months and 16.9 months, respectively. The overall response rate was 43.7% in the Chemo group and 58.3% in the Chemo+Bev group. The median PFSs in the Chemo and Chemo+Bev groups were found to be 7.7 months and 9.6 months, respectively, and the median OSs were 14.8 months and 18.5 months, respectively. There was not a significant difference between the groups in terms of overall response rate, PFS, and OS. Although there was no significant difference in any of the outcomes, use of bevacizumab together with chemotherapy is a more effective treatment approach compared with chemotherapy alone, and it does not cause an excess of significant toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Robotic pancreaticoduodenectomy for pancreatic adenocarcinoma: role in 2014 and beyond

    PubMed Central

    Baker, Erin H.; Ross, Samuel W.; Seshadri, Ramanathan; Swan, Ryan Z.; Iannitti, David A.; Vrochides, Dionisios

    2015-01-01

    Minimally invasive surgery (MIS) for pancreatic adenocarcinoma has found new avenues for performing pancreaticoduodenectomy (PD) procedures, a historically technically challenging operation. Multiple studies have found laparoscopic PD to be safe, with equivalent oncologic outcomes as compared to open PD. In addition, several series have described potential benefits to minimally invasive PD including fewer postoperative complications, shorter hospital length of stay, and decreased postoperative pain. Yet, despite these promising initial results, laparoscopic PDs have not become widely adopted by the surgical community. In fact, the vast majority of pancreatic resections performed in the United States are still performed in an open fashion, and there are only a handful of surgeons who actually perform purely laparoscopic PDs. On the other hand, robotic assisted surgery offers many technical advantages over laparoscopic surgery including high-definition, 3-D optics, enhanced suturing ability, and more degrees of freedom of movement by means of fully-wristed instruments. Similar to laparoscopic PD, there are now several case series that have demonstrated the feasibility and safety of robotic PD with seemingly equivalent short-term oncologic outcomes as compared to open technique. In addition, having the surgeon seated for the procedure with padded arm-rests, there is an ergonomic advantage of robotics over both open and laparoscopic approaches, where one has to stand up for prolonged periods of time. Future technologic innovations will likely focus on enhanced robotic capabilities to improve ease of use in the operating room. Last but not least, robotic assisted surgery training will continue to be a part of surgical education curriculum ensuring the increased use of this technology by future generations of surgeons. PMID:26261726

  18. Preoperative radiotherapy for rectal adenocarcinoma: Which are strong prognostic factors?

    PubMed

    Chapet, Olivier; Romestaing, Pascale; Mornex, Francoise; Souquet, Jean-Christophe; Favrel, Veronique; Ardiet, Jean-Michel; d'Hombres, Anne; Gerard, Jean-Pierre

    2005-04-01

    This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors. Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by digital rectal examination and rigid proctoscopy. EUS was performed in 236 patients. Postoperative staging was performed by examination of the pathologic specimen. The median follow-up was 49 months. The overall 5-year survival rate was 67%, with a local failure rate of 9%. The rate of sphincter preservation was 65%. The clinical examination findings were strong prognostic factor for both cT stage (p < 0.001) and cN stage (p < 0.006) but had poor specificity for cN stage (only 25 lymph nodes detected). In both univariate and multivariate analyses, EUS had a statistically significant prognostic value for uT (p < 0.014) but not for uN (p < 0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p < 0.001 and p < 0.001, respectively). Pretreatment staging, including clinical examination and EUS, seemed accurate enough to present a high prognostic value for the T stage. EUS was insufficient to stage lymph node involvement. Owing to its lack of specificity, uN stage was not a reliable prognostic factor. An improvement in N staging is necessary and essential. Despite downstaging, postoperative staging remained a very strong prognostic factor for both T and N stages.

  19. Epigenetic regulation on the gene expression signature in esophagus adenocarcinoma.

    PubMed

    Xi, Ting; Zhang, Guizhi

    2017-02-01

    Understanding the molecular mechanisms represents an important step in the development of diagnostic and therapeutic measures of esophagus adenocarcinoma (NOS). The objective of this study is to identify the epigenetic regulation on gene expression in NOS, shedding light on the molecular mechanisms of NOS. In this study, 78 patients with NOS were included and the data of mRNA, miRNA and DNA methylation of were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis between NOS and controls was performed in terms of gene expression, miRNA expression, and DNA methylation. Bioinformatic analysis was followed to explore the regulation mechanisms of miRNA and DNA methylationon gene expression. Totally, up to 1320 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs were identified. 240 DEGs that were not only the target genes but also negatively correlated with the screened differentially expressed miRNAs. 101 DEGs were found to be highlymethylated in CpG islands. Then, 8 differentially methylated genes (DMGs) were selected, which showed down-regulated expression in NOS. Among of these genes, 6 genes including ADHFE1, DPP6, GRIA4, CNKSR2, RPS6KA6 and ZNF135 were target genes of differentially expressed miRNAs (hsa-mir-335, hsa-mir-18a, hsa-mir-93, hsa-mir-106b and hsa-mir-21). The identified altered miRNA, genes and DNA methylation site may be applied as biomarkers for diagnosis and prognosis of NOS. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function

    PubMed Central

    Osterman, Carlos J. Diaz; Lynch, James C.; Leaf, Patrick; Gonda, Amber; Ferguson Bennit, Heather R.; Griffiths, Duncan; Wall, Nathan R.

    2015-01-01

    Pancreatic cancer has the highest mortality rates of all cancer types. One potential explanation for the aggressiveness of this disease is that cancer cells have been found to communicate with one another using membrane-bound vesicles known as exosomes. These exosomes carry pro-survival molecules and increase the proliferation, survival, and metastatic potential of recipient cells, suggesting that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to successfully address and eradicate pancreatic cancer, it is imperative to develop therapeutic strategies that neutralize cancer cells and exosomes simultaneously. Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested that exosomal curcumin exerts anti-inflammatory properties on recipient cells. However, curcumin’s effects on exosomal pro-tumor function have yet to be determined. We hypothesize that curcumin will alter the pro-survival role of exosomes from pancreatic cancer cells toward a pro-death role, resulting in reduced cell viability of recipient pancreatic cancer cells. The main objective of this study was to determine the functional alterations of exosomes released by pancreatic cancer cells exposed to curcumin compared to exosomes from untreated pancreatic cancer cells. We demonstrate, using an in vitro cell culture model involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic cancer cells as observed by spectral studies and fluorescence microscopy. Furthermore, curcumin is delivered to recipient pancreatic cancer cells via exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively, these data suggest that the efficacy of curcumin may be enhanced in pancreatic cancer cells through

  1. Brain metastasis in gastroesophageal adenocarcinoma and HER2 status.

    PubMed

    Limon, Dror; Gal, Omer; Gordon, Noa; Katz, Lior; Perl, Gali; Purim, Ofer; Amit, Limor; Stemmer, Salomon M; Kundel, Yulia; Ben-Aharon, Irit; Brenner, Baruch; Siegal, Tali; Yust-Katz, Shlomit

    2018-02-10

    The increased survival of patients with gastroesophageal adenocarcinoma (GAD) following improvements in treatment has been accompanied by a rising incidence of secondary brain metastasis. HER2 amplification/overexpression, which has been associated with an increased risk of brain metastasis in breast cancer, is found in about 20% of patients with GAD. The aim of this study was to evaluate the effect of HER2 status on brain metastasis in GAD. The database of a tertiary cancer center was searched for patients with GAD diagnosed in 2011-2015, and data were collected on clinical characteristics, brain metastasis, HER2 status, and outcome. We identified 404 patients with a confirmed diagnosis of GAD. HER2 results were available for 298: 69 (23.2%) positive and 227 negative. Brain metastasis developed in 15 patients with GAD (3.7%); HER2 results, available in 13, were positive in 6, negative in 6, and equivocal in 1. The brain metastasis rate was significantly higher in HER2-positive than HER2-negative patients with GAD (6/69, 8.7% vs. 6/227, 2.6%; RR = 3.3, 95% CI 1.1-9.9, p = 0.034). Median overall survival from diagnosis of brain metastasis was 2.3 months, with no significant difference by HER2 status. HER2 positive GAD patients may be at increased risk to develop BM. Clinicians should maintain a lower threshold for performing brain imaging in patients with HER2-positive GAD given their increased risk of brain metastasis. The role of anti-HER2 agents in the development and treatment of brain metastasis in GAD warrants further study.

  2. Health Disparities Impact Expected Treatment of Pancreatic Ductal Adenocarcinoma Nationally.

    PubMed

    Lutfi, Waseem; Zenati, Mazen S; Zureikat, Amer H; Zeh, Herbert J; Hogg, Melissa E

    2018-04-24

    National adherence to treatment guidelines for pancreatic ductal adenocarcinoma (PDAC) is a concern. This study aims to evaluate national expected treatment (ET) adherence for all PDAC stages. We hypothesized that both patient and hospital demographics are associated with national ET disparities for PDAC. Clinical stage I through IV PDAC patients were evaluated using the National Cancer Data Base from 2004 to 2013. ET was defined as surgery for stage I/II, chemotherapy or radiation for stage III, and chemotherapy for stage IV. Unexpected treatment (UT) was defined as no surgery for stage I/II, surgery for stage III, and radiation or surgery for stage IV. No treatment is denoted by NT. 171,351 patients were identified, of whom 56,589 (33.0%) were stage I/II, 23,459 (13.7%) were stage III, and 91,303 (53.3%) were stage IV. Of patients, 48.4% received ET, 14.7% received UT, and 36.9% received NT. ET rates were 41.1% for stage I/II, 65.4% for stage III, and 48.5% for stage IV patients. On multivariable analysis, older age, non-White race, lower socioeconomic status, being uninsured or Medicaid, increased comorbidities, nonacademic centers, and low-volume hospitals were independent negative predictors of receiving ET (P < 0.01). On subgroup analysis, high-volume academic centers had similar negative predictors of ET despite higher ET adherence overall (P < 0.01). Patient and hospital factors impact ET of PDAC on a national level. These treatment disparities for PDAC are concerning, even at high-volume academic centers. Future studies need to identify the causes of treatment disparities for PDAC with intervention measures aimed to relieve treatment disparities.

  3. Latexin exhibits tumor-suppressor potential in pancreatic ductal adenocarcinoma

    PubMed Central

    XUE, ZHANXIONG; ZHOU, YUHUI; WANG, CHENG; ZHENG, JIHANG; ZHANG, PU; ZHOU, LINGLING; WU, LIANG; SHAN, YUNFENG; YE, MENGSI; HE, YUN; CAI, ZHENZHAI

    2016-01-01

    Recent studies suggest that latexin (Lxn) expression is involved in stem cell regulation and that it plays significant roles in tumor cell migration and invasion. The clinicopathological significance of Lxn expression and its possible correlation with CD133 expression in pancreatic ductal adenocarcinoma (PDAC) is currently unknown. In the present study, immunohistochemical analysis was performed to determine Lxn and CD133 expression in 43 PDAC patient samples and in 32 corresponding adjacent non-cancerous samples. The results were analyzed and compared with patient age, gender, tumor site and size, histological grade, clinical stage and overall mean survival time. Lxn expression was clearly decreased in the PDAC tissues compared with that in the adjacent non-cancerous tissues, while CD133 expression was increased. Low Lxn expression in the PDAC tissues was significantly correlated with tumor size (P=0.002), histological grade (P=0.000), metastasis (P=0.007) and clinical stage (P=0.018), but not with age (P=0.451), gender (P=0.395) or tumor site (P=0.697). Kaplan-Meier survival analysis revealed that low Lxn expression was significantly correlated with reduced overall survival time (P=0.000). Furthermore, Lxn expression was found to be inversely correlated with CD133 expression (r=−0.485, P=0.001). Furthermore, CD133-positive MIA PaCa-2 pancreatic tumor cells were sorted by magnetic-activated cell sorting (MACS), and those that overexpressed Lxn exhibited a significantly higher rate of apoptosis and lower proliferative activity. Our findings suggest that Lxn may function as a tumor suppressor that targets CD133-positive pancreatic cancer cells. PMID:26530530

  4. The role of the obestatin/GPR39 system in human gastric adenocarcinomas

    PubMed Central

    Alén, Begoña O.; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S.; Beiras, Andrés; Casanueva, Felipe F.; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P.; Pazos, Yolanda

    2016-01-01

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer. PMID:26716511

  5. The role of the obestatin/GPR39 system in human gastric adenocarcinomas.

    PubMed

    Alén, Begoña O; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S; Beiras, Andrés; Casanueva, Felipe F; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P; Pazos, Yolanda

    2016-02-02

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.

  6. The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma.

    PubMed

    Chung, Yumin; Wi, Young Chan; Kim, Yeseul; Bang, Seong Sik; Yang, Jung-Ho; Jang, Kiseok; Min, Kyueng-Whan; Paik, Seung Sam

    2018-01-01

    Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma. Combined expression patterns based on Smad4+/- and PTEN+/- status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed. Smad4-/PTEN- status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4-/PTEN- and Smad4+/PTEN+ groups were compared, Smad4-/PTEN- status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4-/PTEN+ or Smad4+/PTEN-, and Smad4-/PTEN-) (all p<.05). Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

  7. Coalescent pleural malignant mesothelioma and adenocarcinoma of the lung, involving only minor asbestos exposure.

    PubMed

    Tsuzuki, Toyonori; Ninomiya, Hironori; Natori, Yuji; Ishikawa, Yuichi

    2008-07-01

    Coexistence of pulmonary adenocarcinoma and pleural malignant mesothelioma is extremely rare, although both are asbestos-related. Herein is presented a rare case of coalescent lung tumor made up of a malignant mesothelioma and a pulmonary adenocarcinoma in a 62-year-old Japanese man, a high-school teacher with only minor asbestos exposure. Preoperative diagnosis of adenocarcinoma was made on transbronchial biopsy. At surgery, multiple small white nodules were observed on the parietal pleural surface, opposite to the lung tumor. They were confirmed to be malignant mesothelioma on histopathology of paraffin section. The pulmonary tumor mass itself consisted of two distinct portions. The major part contained papillary proliferation of hobnail and columnar cells. Peripherally, neoplastic cells grew in a lepidic fashion and micropapillary growth was also detected. The other component featured tubular structures. The former was positive for adenocarcinoma markers such as CEA, Ber-EP4, PE-10, thyroid transcription factor-1 and Napsin A, and negative for mesothelial markers including calretinin, D2-40, WT-1 and HBME, while the latter was the opposite, resulting in a diagnosis of coalescing malignant mesothelioma and adenocarcinoma. The panel of antibodies used for immunohistochemistry was useful to distinguish the two different components in the one tumor.

  8. Outcomes of unresected ground-glass nodules with cytology suspicious for adenocarcinoma.

    PubMed

    Gulati, Caroline M; Schreiner, Andrew M; Libby, Daniel M; Port, Jeffrey L; Altorki, Nasser K; Gelbman, Brian D

    2014-05-01

    Five-year survival rates for resected stage I adenocarcinoma approach 100%. Given previous studies describing the prolonged indolent natural history of ground-glass lesions suspicious for early adenocarcinoma, our purpose in this study was to determine if outcomes were different among patients who were observed for radiographic and biopsy suspected early adenocarcinoma compared with those who were resected immediately. We identified 63 patients with no prior history of lung adenocarcinoma who had undergone computer tomography-guided fine-needle aspiration of ground-glass opacities with cytology concerning for new early adenocarcinoma between January 2002 and December 2011. We compared the clinical outcomes of patients who were resected after abnormal cytology results and those who opted for watchful waiting. Sixteen patients elected to observe their ground-glass nodules despite having suspicious cytology results, whereas 47 opted for immediate resection. Of the 16 observed patients, six (37.5%) ultimately demonstrated growth or increase solid component of the ground-glass nodule. Five of these patients elected for definitive therapy by surgical resection or radiation. There were no occurrences of distant metastasis or lung cancer-associated deaths in the observed group. Of the 47 resected patients, two developed metastatic disease, five developed new cancers in remaining lung, and three developed progression in existing ground-glass nodules. Ground-glass lesions that were observed after biopsy did not demonstrate any increased rates of metastasis or cancer-related deaths and delayed resection does not seem to have a negative effect on outcomes.

  9. Inhibitory effect of Nodal on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma of uterus.

    PubMed

    Wang, Yi; Jiang, Yang; Tian, Tian; Hori, Yumiko; Wada, Naoki; Ikeda, Jun-ichiro; Morii, Eiichi

    2013-11-01

    Cancers consist of heterogeneous populations. Recently, it has been demonstrated that cells with tumorigenic potential are limited to a small population, called cancer-initiating cells (CICs). Aldehyde dehydrogenase 1 (ALDH1) is one of the markers of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and ALDH1-high population of endometrioid adenocarcinoma cell line was more tumorigenic, resistant to anti-cancer drugs, and invasive than ALDH1-low population. Here, the regulatory signaling for ALDH1 was examined. The inhibition of TGF-β signaling increased ALDH1-high population. Among TGF-β family members, Nodal expression and ALDH1 expression levels were mutually exclusive. Immunohistochemical analysis on clinical samples revealed Nodal-high tumor cells to be ALDH-low and vise versa, suggesting that Nodal may inhibit ALDH1 expression via stimulating TGF-β signaling in uterine endometrioid adenocarcinoma. In fact, the addition of Nodal to endometrioid adenocarcinoma cell line reduced ALDH1-high population. Although ALDH1 mRNA level was not affected, the amount of ALDH1 protein appeared to be reduce by Nodal through ubiquitine-proteasome pathway. The regulation of TGF-β signaling might be a novel therapeutic target of CICs in endometrioid adenocarcinoma. Copyright © 2013. Published by Elsevier Inc.

  10. Reflux-inducing dietary factors and risk of adenocarcinoma of the esophagus and gastric cardia.

    PubMed

    Terry, P; Lagergren, J; Wolk, A; Nyrén, O

    2000-01-01

    Gastroesophageal reflux (GER) is the strongest known risk factor for esophageal adenocarcinoma. For long-term sufferers with severe symptoms, the excess risk may exceed 40-fold. GER has also been shown to increase the risk of cancers of the gastric cardia more than fourfold. Several foods, including dietary fat, chocolate, mints, coffee, onions, citrus fruit, and tomatoes, have been associated with temporary symptoms of reflux, most likely through a relaxation of the lower esophageal sphincter (LES). Our aim was to determine whether these foods are associated with risk of adenocarcinoma of the esophagus or gastric cardia. We studied intakes of LES-relaxing foods and other dietary habits potentially associated with reflux in a nationwide population-based case-control study in Sweden, with 185 and 258 cases of esophageal adenocarcinoma and gastric cardia adenocarcinoma, respectively, and 815 controls. We found no association between LES-relaxing foods and symptoms of chronic reflux, although this might be due to avoidance of these foods among sufferers. In addition, we found no association between dietary factors known to cause LES relaxation and the risk of adenocarcinoma of the esophagus or gastric cardia. Our findings indicate that dietary factors associated with LES relaxation and transient GER (but perhaps not severe chronic reflux) are not associated with any important risk of esophageal malignancy.

  11. Significance of effector protease receptor-1 expression and its relationship with proliferation and apoptotic index in patients with primary advanced gastric adenocarcinoma

    PubMed Central

    Yao, Xue-Quan; Liu, Fu-Kun; Li, Jie-Shou; Qi, Xiao-Ping; Wu, Bo; Yin, Hong-Lin; Ma, Heng-Hui; Shi, Qun-Li; Zhou, Xiao-Jun

    2004-01-01

    AIM: To investigate the expression of effector protease receptor-1 (EPR-1), proliferative index ki-67 and apoptosis index in patients with primary advanced gastric adenocarcinoma and to clarify the significance of EPR-1 expression and its correlationship with the proliferation and apoptosis indexes. METHODS: Using immunohistochemical staining and terminal deoxynucleotidyl transferase mediated nick end labelling (TUNEL) technique, we determined the expression of EPR-1, proliferative index (Ki-67) and apoptotic index (AI) in 120 paraffin-embedded specimens of primary advanced gastric adenocarcinoma as well as lymph node metastasis and adjacent normal tissues. RESULTS: EPR-1 expression was distributed in the cytoplasm of normal gastric mycoderma, carcinoma cells and smooth muscle cells. The positive rate of EPR-1 expression in the primary gastric adenocarcinomas, invasion tumor node and lymph node metastasis was 65.83%, 55.29% and 68%, respectively. While the positive rate in normal gastric mycoderma and smooth muscle cells was 46.7% and 53.3%, respectively. The average positive rate of ki-67 in EPR-1-positive tumors was 7.00% which was significantly lower than that of 8.53% in EPR-1-negative tumors, but the average AI in EPR-1-positive tumors was 1.25%, which was significantly higher than that of 1.00% observed in EPR-1-negative tumors. On the other hand, the average positive labeling index for Ki-67 (ki-67) in EPR-1-positive lymph node metastasis was 7.65%, which was significantly lower than that of 9.44% observed in EPR-1-negative lymph node metastasis. However, the average AI in EPR-1-positive lymph node metastasis tumors was 0.99%, which was significantly higher than that of 0.67% observed in EPR-1-negative lymph node metastasis. CONCLUSION: The frequency of EPR-1 expression was significantly higher in primary gastric adenocarcinoma and in its lymph node metastasis than that in normal gastric mucosa. Expression of EPR-1 was significantly correlated with tumor

  12. Adenocarcinoma predominant pattern subtyping and nuclear grading in cytology: Is there a role in prognostication of advanced pulmonary adenocarcinomas?

    PubMed

    Nambirajan, A; Kaur, H; Jangra, K; Kaur, K; Madan, K; Mathur, S R; Iyer, V K; Jain, D

    2018-04-01

    Primary lung adenocarcinomas (ADs) show varied architectural patterns, and pattern-based subtyping of ADs is currently recommended due to prognostic implications. Predicting AD patterns on cytology is challenging; however, cytological nuclear features appear to correlate with histological grade and survival in early stage lung ADs. The feasibility and value of AD pattern prediction and nuclear grading on cytology in advanced lung ADs is not known. We aimed to predict patterns and analyse nuclear features on cytology and evaluate their role in prognostication. One-hundred patients of Stage III/IV lung AD with available matched cytology and histology samples were included. Cyto-patterns based on cell arrangement patterns (flat sheets vs three-dimensional clusters vs papillae) and cyto-nuclear score based on nuclear features (size, shape, contour), nucleoli (macronucleoli vs prominent vs inconspicuous), and nuclear chromatin were determined, and correlated with predominant histological-pattern observed on the matched small biopsy and outcome. Higher cyto-nuclear scores were observed with high-grade histo-patterns (solid, micropapillary and cribriform), while the predicted cyto-patterns did not correspond to the predominant pattern on histology in 77% cases. Highest cyto-histo agreement was observed for solid pattern (72%). High grade histo-patterns and cyto-nuclear scores > 3 showed a trend towards inferior survival (not significant). Nuclear grade scoring on cytology is simple to perform, and is predictive of high grade patterns. Its inclusion in routine reporting of cytology samples of lung ADs may be valuable. © 2018 John Wiley & Sons Ltd.

  13. Investigation of cell culture volatilomes using solid phase micro extraction: Options and pitfalls exemplified with adenocarcinoma cell lines.

    PubMed

    Schallschmidt, Kristin; Becker, Roland; Jung, Christian; Rolff, Jana; Fichtner, Iduna; Nehls, Irene

    2015-12-01

    Three strategies to sample volatile organic compounds (VOC) from lung cancer cell lines cultured in vitro were compared. Headspace solid phase microextraction was applied in situ to culture flasks and alternatively to subsamples of headspace gas or to nutrient solution subsamples followed by gas chromatography-mass spectrometry. The direct quantification of 55 VOC in the headspace of cell cultures was validated and is discussed with respect to reproducibility and system-related interferences. The role of the VOC background from culture media and usually employed polystyrene culture vessels is examined and was seen to invoke potentially misleading conclusions. The commercial A549 and two further adenocarcinoma cell lines displayed largely similar VOC profiles with distinct differences regarding certain individual substances. There is evidence for the inappropriateness of the standard cell culturing methods in the search for volatile cancer markers. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. [Three-dimensional spatial texture of adenocarcinoma of the prostate by a combination of stereology and digital image analysis].

    PubMed

    Mattfeldt, T; Vogel, U; Gottfried, H W

    1993-01-01

    Second-order stereology combines stereology with stochastic geometry and digital image analysis to obtain an insight into the spatial architecture (texture) of tissues. In twenty radical prostatectomy specimens from patients with invasive adenocarcinomas of the prostate gland, the pair correlation function of the epithelial tissue component was estimated both for the carcinomatous and the tumour-free domains. After interactive segmentation of the gray level images, the method works fully automatically. The mean pair correlation function of carcinomatous tissue shows less clustering of epithelium at short distances and less rhythmicity of epithelium at long distances as compared to tumour-free tissue. This loss of glandular integrity is higher in cribriform than in tubular carcinomas. The results suggest that second-order stereology is a powerful tool for the objective evaluation of glandular differentiation.

  15. Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of Pancreatic Adenocarcinoma.

    PubMed

    2015-10-01

    The SCAN pancreatic cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Cancer Comprehensive Network (2014), the European Society of Medical Oncology (2012), Cancer Care Ontario (2013), the Japan Pancreas Society (2013) and the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, and the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (2005). Recommendations on the management of resected, borderline resectable, locally advanced and metastatic pancreatic adenocarcinoma were developed. These adapted guidelines form the SCAN Guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore.

  16. [Establishment and characterization of a human lung adenocarcinoma cell line, Ch-Huang-1].

    PubMed

    Li, Bailing; Zhong, Keng; Jin, Lei; Yuan, Yang; Gong, Dejun; Liu, Xiaohong; Huang, Shengdong

    2012-05-01

    Lung cancer is a major worldwide health problem. The aim of this study is to establish a novel Chinese human lung adenocarcinoma cell line and examine its biological characteristics. Lung adenocarcinoma specimens were freshly resected during surgery. The tissues were incubated in vitro and the cell line was named Ch-Huang-1. The biological characteristics of the cells were investigated by light microscopy, chromosome analysis, and transplantation experiment. Light microscopy revealed that cells from the primary tumor, Ch-Huang-1 cell line, and transplanted tumor possessed the characteristics of a malignant glandular epithelial tumor. The cell growth curve, doubling time, and mitotic index were also observed in vitro. Nuclear chromosome analysis revealed that the tumor was a subtriploid with a mode of 35-44 per cell. Tumor nodes were observed under the skin of nude mice by heterogenic transplantation. The characteristics of the established cell line suggest that it is a newly established human adenocarcinoma cell line.

  17. Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma

    NASA Astrophysics Data System (ADS)

    Champanhac, Carole; Teng, I.-Ting; Cansiz, Sena; Zhang, Liqin; Wu, Xiaoqiu; Zhoa, Zilong; Fu, Ting; Tan, Weihong

    2015-11-01

    Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection.

  18. Intestinal adenocarcinoma in a herd of farmed Sika deer (Cervus nippon): a novel syndrome.

    PubMed

    Kelly, P A; Toolan, D; Jahns, H

    2015-01-01

    Intestinal adenocarcinomas were identified in 76 adult deer from a closed herd of 193 breeding animals grazing pasture heavily infested with bracken fern (Pteridium aquilinum). Tumors were observed postmortem in 32 animals with rapid weight loss, and similar neoplasms were detected in a further 44 clinically normal deer at "cull." Tumors were located in distal ileum, cecum, and proximal colon and presented as single (26%) or multiple (74%), variably sized, pale-gray, firm, poorly circumscribed neoplasms with associated intestinal strictures. Histopathologically tumors were well-differentiated, locally infiltrative, low-grade adenocarcinomas of tubular (51%), mucinous (33.5%), or mixed (15.5%) types. Extraintestinal metastases were not observed. The high incidence of intestinal adenocarcinoma within this herd suggests a specific and novel syndrome, and genetic and/or environmental factors may be involved in the pathogenesis. © The Author(s) 2014.

  19. Ground-glass opacity heralding invasive lung adenocarcinoma with prodromal dermatomyositis: a case report.

    PubMed

    Beel, Andrew J; Demos, David S; Chung, Alfred; Liao, Charles; Lui, Natalie S

    2018-02-07

    Dermatomyositis, an inflammatory myopathy with cutaneous involvement, is associated with malignancy and often manifests paraneoplastically. While co-occurrence with small cell carcinoma is well attested, primary lung adenocarcinoma, which may present as focal ground-glass opacification on computed tomography of the thorax, is less frequently coincident. We report the case of a 72-year-old female patient with dermatomyositis - treated with a combination of prednisone, methotrexate, and intravenous immunoglobulin - and an indolent, subsolid, non-hypermetabolic pulmonary lesion, which was determined to be invasive primary lung adenocarcinoma. Supporting a paraneoplastic basis, immunosuppressive therapy was discontinued following tumor excision without relapse of signs or symptoms of dermatomyositis. While dermatomyositis prodromal to lung adenocarcinoma is not without precedent, association with an indolent, subsolid lesion has, to the best of our knowledge, not been reported. The case described herein illustrates the importance of maintaining a high index of suspicion for malignancy in the setting of dermatomyositis.

  20. Gene expression profiling and its use in adenocarcinomas of unknown primary origin: A case report.

    PubMed

    DE Miguel, Ana Cebollero; Cid, Roberto Pazo; Trufero, Javier Martinez; Bernad, Isabel Pajares; Urquizu, Lourdes Calera; Cubero, Jorge Hernando; Torres, Antonio Anton

    2015-10-01

    Carcinomas of unknown primary origin account for 3-5% of all malignancies. The current literature suggests that metastatic dissemination is able to occur in the absence of primary tumor growth. In metastatic disease that is difficult to diagnose, the origin usually remains unknown even after an exhaustive evaluation of immunohistochemistry (IHC) markers. In the current study, a 49-year-old male presented with lymph nodes metastases of unknown origin. The excisional biopsy of an inguinal node revealed an adenocarcinoma growth pattern, but the IHC could not determine the primary origin. A gene profiling test was performed to complete the diagnosis and a salivary gland adenocarcinoma was diagnosed with 90% probability. Subsequently, the patient underwent appropriate chemotherapy for salivary gland adenocarcinoma, and exhibited an improved partial response. The present case study highlights the importance of an accurate diagnosis of the primary tumor and the use of all the current tools available in order to provide patients with the best treatment possible.

  1. [The Clinical and Molecular Characteristics of Adenocarcinoma Presented 
by Multi-focal GGO].

    PubMed

    Song, Yang; Liang, Naixin; Li, Shanqing

    2018-03-20

    Due to emphasis on early screening for lung cancer, the detection rate of multiple ground glass opacities (GGOs) on computed tomography (CT) image increases in recent years, and research on multifocal adenocarcinomas presented by GGOs has been thriving. It is more common in women and non-smokers and has excellent prognosis both in patients with natural history and after surgery. These clinical features suggest that it is likely to be a distinct disease entity. From the perspective of molecular genetics, lesions in the same individual are likely to have distinct clonal features. Therefore, genetic heterogeneity is the most prominent feature of multifocal pulmonary adenocarcinomas with GGOs. The genetic heterogeneity is expected to assist the diagnosis of multifocal pulmonary adenocarcinoma and intrapulmonary metastasis, and also suggests that genetic testing of the GGO lesions is of great therapeutic significance. Some GGO lesions may harvest the similar clonal feature, which provide new evidence for the theory of spread through air spaces (STAS).
.

  2. Chromogenic in situ hybridization is a reliable assay for detection of ALK rearrangements in adenocarcinomas of the lung.

    PubMed

    Schildhaus, Hans-Ulrich; Deml, Karl-Friedrich; Schmitz, Katja; Meiboom, Maren; Binot, Elke; Hauke, Sven; Merkelbach-Bruse, Sabine; Büttner, Reinhard

    2013-11-01

    Reliable detection of anaplastic lymphoma kinase (ALK) rearrangements is a prerequisite for personalized treatment of lung cancer patients, as ALK rearrangements represent a predictive biomarker for the therapy with specific tyrosine kinase inhibitors. Currently, fluorescent in situ hybridization (FISH) is considered to be the standard method for assessing formalin-fixed and paraffin-embedded tissue for ALK inversions and translocations. However, FISH requires a specialized equipment, the signals fade rapidly and it is difficult to detect overall morphology and tumor heterogeneity. Chromogenic in situ hybridization (CISH) has been successfully introduced as an alternative test for the detection of several genetic aberrations. This study validates a newly developed ALK CISH assay by comparing FISH and CISH signal patterns in lung cancer samples with and without ALK rearrangements. One hundred adenocarcinomas of the lung were included in this study, among them 17 with known ALK rearrangement. FISH and CISH were carried out and evaluated according to the manufacturers' recommendations. For both assays, tumors were considered positive if ≥15% of tumor cells showed either isolated 3' signals or break-apart patterns or a combination of both. A subset of tumors was exemplarily examined by using a novel EML4 (echinoderm microtubule-associated protein-like 4) CISH probe. Red, green and fusion CISH signals were clearcut and different signal patterns were easily recognized. The percentage of aberrant tumor cells was statistically highly correlated (P<0.001) between FISH and CISH. On the basis of 86 samples that were evaluable by ALK CISH, we found a 100% sensitivity and 100% specificity of this assay. Furthermore, EML4 rearrangements could be recognized by CISH. CISH is a highly reliable, sensitive and specific method for the detection of ALK gene rearrangements in pulmonary adenocarcinomas. Our results suggest that CISH might serve as a suitable alternative to FISH, which

  3. Contrast-harmonic endoscopic ultrasound for the diagnosis of pancreatic adenocarcinoma: a prospective multicenter trial.

    PubMed

    Gincul, Rodica; Palazzo, Maxime; Pujol, Bertrand; Tubach, Florence; Palazzo, Laurent; Lefort, Christine; Fumex, Fabien; Lombard, Alexandra; Ribeiro, Daniel; Fabre, Monique; Hervieu, Valerie; Labadie, Michel; Ponchon, Thierry; Napoléon, Bertrand

    2014-05-01

    Histology is the gold standard for the diagnosis of pancreatic adenocarcinoma. However, the negative predictive value of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis remains low. The aims of this prospective multicenter study were: (1) to compare the performance of contrast-harmonic EUS (CH-EUS) with that of EUS-FNA for the diagnosis of pancreatic adenocarcinoma; (2) to assess the intra- and interobserver concordances of CH-EUS. A total of 100 consecutive patients with a solid pancreatic mass of unknown origin were prospectively included at three centers (July 2009 - April 2010). All patients were examined by CH-EUS followed by EUS-FNA. Absence of vascular enhancement at CH-EUS was regarded as a sign for pancreatic adenocarcinoma. The final diagnosis (gold standard) was based on pathological examination (EUS-FNA, surgery) or 12-month follow-up.  The final diagnoses were: 69 adenocarcinoma, 10 neuroendocrine tumors, 13 chronic pancreatitis, and 8 other lesions. In diagnosing adenocarcinoma, CH-EUS and EUS-FNA had respective accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 95 %, 96 %, 94 %, 97 %, and 91 %, and of 95 %, 93 %, 100 %, 100 %, and 86 % without significant difference. Five false-negative cases with EUS-FNA were correctly classified by CH-EUS. Interobserver agreement (seven endosonographers) was good (kappa 0.66). Intraobserver agreement was good to excellent (kappa 0.76 for junior, 0.90 for senior). The performance of CH-EUS for the diagnosis of pancreatic adenocarcinoma was excellent. The good intra- and interobserver concordances suggest an excellent reproducibility. CH-EUS could help to guide the choice between surgery and follow-up when EUS-FNA is inconclusive. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Growth Hormone differentially modulates chemoresistance in human endometrial adenocarcinoma cell lines.

    PubMed

    Gentilin, Erica; Minoia, Mariella; Bondanelli, Marta; Tagliati, Federico; Degli Uberti, Ettore C; Zatelli, Maria Chiara

    2017-06-01

    Growth Hormone may influence neoplastic development of endometrial epithelium towards endometrial adenocarcinoma, which is one of the most occurring tumors in acromegalic patients. Since chemoresistance often develops in advanced endometrial adenocarcinoma, we investigated whether Growth Hormone might influence the development of chemoresistance to drugs routinely employed in endometrial adenocarcinoma treatment, such as Doxorubicin, Cisplatin, and Paclitaxel. Growth Hormone and Growth Hormone receptor expression was assessed by immunofluorescence in two endometrial adenocarcinoma cell lines, AN3 CA and HEC-1-A cells. Growth Hormone effects were assessed investigating cell viability, caspase3/7 activation, ERK1/2, and protein kinase C delta protein expression. AN3 CA and HEC-1-A cells display Growth Hormone and Growth Hormone receptor. Growth Hormone does not influence cell viability in both cells lines, but significantly reduces caspase 3/7 activation in AN3 CA cells, an effect blocked by a Growth Hormone receptor antagonist. Growth Hormone rescues AN3 CA cells from the inhibitory effects of Doxorubicin and Cisplatin on cell viability, while it has no effect on Paclitaxel. Growth Hormone does not influence the pro-apoptotic effects of Doxorubicin, but is capable of rescuing AN3 CA cells from the pro-apoptotic effects of Cisplatin. On the other hand, Growth Hormone did not influence the effects of Doxorubicin and Paclitaxel on HEC-1A cell viability. The protective action of Growth Hormone towards the effects of Doxorubicin may be mediated by ERK1/2 activation, while the pro-apoptotic effects of Cisplatin may be mediated by protein kinase C delta inhibition. All together our results indicate that Growth Hormone may differentially contribute to endometrial adenocarcinoma chemoresistance. This may provide new insights on novel therapies against endometrial adenocarcinoma chemoresistant aggressive tumors.

  5. Inflammation and focal atrophy in prostate needle biopsy cores and association to prostatic adenocarcinoma.

    PubMed

    Benedetti, Ines; Bettin, Alfonso; Reyes, Niradiz

    2016-10-01

    The possible origin of proliferative inflammatory atrophy in the regenerative proliferation of prostate epithelial cells in response to injury caused by inflammation, and their relation to prostate adenocarcinoma have not been defined. Inflammation and focal atrophy are common pathological findings in prostate biopsies, currently not routinely included in surgical pathology reports. The objective of the study was to determine the correlation between inflammation and focal atrophy with prostate adenocarcinoma. Prostate needle biopsies from 203 patients with clinical parameters suspicious for malignancy were evaluated for the presence and extent of chronic inflammation, type and grade of focal atrophy, high-grade intraepithelial neoplasia, and adenocarcinoma. Relations among them and with age were also analyzed. χ(2) tests and binary logistic regression were used to estimate associations. Chronic inflammation was observed in 77.3% of the biopsies, significantly associated to adenocarcinoma (P = .031). Moderate/severe inflammation in at least 1 biopsy core increased the risk of prostate adenocarcinoma (odds ratio, 2.94; 95% confidence interval, 1.27-6.8), whereas glandular localization of inflammation decreased the risk. Focal atrophy was present in 72.9% of the biopsies, proliferative inflammatory atrophy was the most common type, and its grade was significantly associated to inflammation (P < .0001) and inflammation intensity (P = .003). An association between prostate adenocarcinoma and inflammation was found, with higher odds in presence of moderate/severe inflammation in at least 1 biopsy core. Increasing grades of proliferative inflammatory atrophy were associated to high levels of inflammation, supporting its previously proposed inflammatory nature. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    SciTech Connect

    Dalah, E; Tai, A; Oshima, K

    2015-06-15

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

  7. Role of microRNA-33a in regulating the expression of PD-1 in lung adenocarcinoma.

    PubMed

    Boldrini, Laura; Giordano, Mirella; Niccoli, Cristina; Melfi, Franca; Lucchi, Marco; Mussi, Alfredo; Fontanini, Gabriella

    2017-01-01

    MiRNAs are vital in functioning as either oncogenes or tumor suppressors in the cell cycle. Target transcripts for immune checkpoint molecules such as PD-1/PD-L1 and (programmed cell death-1/its ligand and cytotoxic T-lymphocyte antigen 4) have proven to be beneficial against several solid tumors, including lung adenocarcinoma. Simultaneous quantification of the expression level of miR-33a and PD - 1 , PD - L1 and CTLA4 mRNAs with NanoString technology was performed in 88 lung adenocarcinoma specimens. A cohort of 323 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database was further analyzed, in order to test our hypothesis. Potential interference of PD - 1, PD - L1 and CTLA4 gene expression by miR-33a was predicted using the microRNA target prediction program RNA22. High miR-33a expression was significantly associated with younger (p = 0.005), female (p = 0.04), patients with low grade (p < 0.0001), early stage (p = 0.03) tumors, and better survival. The hypothesis of the involvement of miR-33a in PD-1/PD-L1/CTLA4 mechanisms was corroborated by the finding of putative miR-33a binding sites in all three genes using the RNA22 method. We found an inverse correlation between miR-33a and PD - 1 levels (p = 0.01), as well as for PD - L1 (p = 0.01) and CTLA4 (p = 0.03) expression, and a significant better prognosis for patients with high miR-33a/low PD - 1 . TCGA database analysis confirmed that miR-33a high levels were associated with low PD-1 expression and with longer survival on a larger population. Our study emphasizes the notion of a potential value of miR-33a as a favorable prognostic marker through PD - 1 regulation.

  8. [The mechanism of inhibition effect of adenovirus-mediated ING4 on human lung adenocarcinoma xenografts in nude mice].

    PubMed

    Huang, Jinhong; Yang, Jicheng; Ling, Chunhua; Zhao, Daguo; Xie, Yufeng; You, Zhenhua

    2014-02-01

    The inhibitor of growth 4 (ING4) is an important tumor suppressive gene.It has been proven that ING4 could inhibite the proliferation of many tumors. e aim of this study is to investigate the inhibitory effect and anti-cancer mechanism of adenovirus-mediated ING4 gene on SPC-A1 human lung adenocarcinoma in nude mice. A human lung adenocarcinoma xenograft model was established with SPC-A1 cells in nude mice. A total of 15 tumor-bearing nude mice were randomly divided into three groups, namely, PBS, Ad-GFP, and Ad-ING4. e mice in the three groups were intratumorally injected every other day. Their tumor volumes were continually recorded. The treatment tumors were then removed from the mice and weighed. Tumor inhibition rates were calculated. Cell apoptosis was examined by TUNEL method. Caspase-3, COX-2, Fas, and FasL expressions were investigated by immunohistochemistry SP assay. Both tumor weight and volume in the Ad-ING4 group were significantly decreased. The tumor inhibition rate of the mice in the Ad-ING4 group (33.17% ± 5.24%) was statistically different from that of the mice in the Ad-GFP group (1.31% ± 0.31%; P<0.05). The apoptotic index of the mice in the Ad-ING4 group (69.23% ± 6.53%) was also significantly different from those in PBS (17.04% ± 1.10%) and Ad-GFP groups (18.81% ± 1.93%; P<0.05). Based on immunohistochemistry SP assay, the results showed that Ad-ING4 may not only upregulate the expressions of caspase-3, Fas, and FasL but also downregulate the expression of COX-2. ING4 gene elicited a remarkable growth inhibitory e-ect on human lung adenocarcinoma xenografts in nude mice. e mechanism is possibly related to an increase in tumor cell apoptosis.

  9. Prognostic impact of serum CYFRA 21–1 in patients with advanced lung adenocarcinoma: a retrospective study

    PubMed Central

    2013-01-01

    Background Serum CYFRA 21–1 is one of the most important serum markers in the diagnosis of non-small cell lung cancer (NSCLC), especially squamous-cell carcinoma. However, it remains unknown whether pretreatment serum CYFRA 21–1 values (PCV) may also have prognostic implications in patients with advanced lung adenocarcinoma. Methods We retrospectively reviewed the data of 284 patients (pts) who were diagnosed as having advanced lung adenocarcinoma and had received initial therapy. Results Of the study subjects, 121 pts (43%) had activating epidermal growth factor receptor (EGFR) mutations (Mt+), while the remaining 163 pts (57%) had wild-type EGFR (Mt-). Univariate analysis identified gender (male/ female), ECOG performance status (PS) (0-1/ ≥2), PCV (<2.2 ng/ml/ ≥2.2 ng/ml), EGFR mutation status (Mt+/ Mt-), pretreatment serum CEA values (<5.0 ng/ml/ ≥5.0 ng/ml), smoking history (yes/ no) and EGFR-TKI treatment (yes/ no) as prognostic factors (p = .008, p < .0001, p < .0001, p < .0001, p = .036, p = .0012, p < .0001 respectively). Cox's multivariate regression analysis identified PCV < 2.2ng/ml as the only factor significantly associated with prolonged survival (p < .0001, hazard ratio: 0.43, 95% CI 0.31-0.59), after adjustments for PS (p < .0001), EGFR mutation status (p = .0069), date of start of initial therapy (p = .07), gender (p = .75), serum CEA level (p = .63), smoking history (p = .39) and EGFR-TKI treatment (p = .20). Furthermore, pts with Mt+ and PCV of <2.2 ng/ml had a more favorable prognosis than those with Mt+ and PCV of ≥2.2 ng/ml (MST: 67.0 vs. 21.0 months, p < .0001), and patients with Mt- and PCV of <2.2 ng/ml had a more favorable prognosis than those with Mt- and PCV of ≥2.2 ng/ml (MST: 24.1 vs. 10.2 months, p < .0001). Conclusion PCV may be a potential independent prognostic factor in both Mt+ and Mt- patients with advanced lung adenocarcinoma. PMID:23879483

  10. Lymphocyte to Monocyte Ratio and Modified Glasgow Prognostic Score Predict Prognosis of Lung Adenocarcinoma Without Driver Mutation

    PubMed Central

    Minami, Seigo; Ihara, Shouichi; Kim, Sung-Ho; Yamamoto, Suguru; Komuta, Kiyoshi

    2018-01-01

    Background Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR) and modified Glasgow prognostic score (mGPS) are useful prognostic markers based on host-related systemic inflammatory response. They have been shown as independent prognostic biomarkers in various cancers, including non-small cell lung cancer. However, there has been little evidence for a specific population of pulmonary adenocarcinoma without active epidermal growth factor receptor (EGFR) mutation. Methods We retrospectively reviewed 159 patients who met the following criteria: histologically or cytologically diagnosed adenocarcinoma, confirmed wild-type EGFR, started first-line cytotoxic chemotherapy between July 2007 and March 2017 at our hospital, and c-stage IIIB or IV. We compared overall survival (OS) between dichotomized groups by the optimal cut-off points of NLR and LMR, and mGPS 0 - 1 vs. 2. Univariate and multivariate Cox proportional hazard analyses also detected prognostic factors for OS. Results As favorable prognostic factors for OS, multivariate analysis detected Eastern Cooperative Oncology Group performance status (ECOG PS) 0 - 1 (hazard ratio (HR) 3.43, 95% confidence interval (CI): 2.12 - 5.53; P < 0.01), LMR ≥ 1.97 (HR 0.39, 95% CI: 0.21 - 0.72; P < 0.01) and mGPS 0 - 1 (HR 1.95, 95% CI: 1.20 - 3.16; P < 0.01). The OS of LMR ≥ 1.97 and mGPS 0 - 1 groups were significantly longer than those of LMR < 1.97 and mGPS 2 groups, respectively. We divided 159 patients into three groups, both LMR ≥ 1.97 and mGPS 0 - 1, either LMR ≥ 1.97 or mGPS 0 - 1 and both LMR < 1.97 and mGPS 2. The OS of both LMR < 1.97 and mGPS 2 was significantly shorter than the other two groups. After adjustment for age, sex, ECOG PS, sodium, alkaline phosphatase and NLR, multivariate analysis found both LMR < 1.97 and mGPS 2 as an independent poor prognostic combination in comparison with both LMR ≥ 1.97 and mGPS0-1 (HR 5.98, 95% CI: 2.64 - 13.5; P < 0.01). Conclusions LMR and m

  11. [Correlation between Serum Tumor Markers and Efficacy of First-line EGFR-TKIs in Patients with Advanced Lung Adenocarcinoma].

    PubMed

    Chen, Hanxiao; Yang, Xue; Liu, Huijun; Ma, Kun; Zhong, Jia; Dong, Zhi; Zhuo, Minglei; Wang, Yuyan; Li, Jianjie; An, Tongtong; Wu, Meina; Wang, Ziping; Zhao, Jun

    2017-09-20

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation. Limited to the standards of tumor tissue samples and detection methods, still some people can't receive target therapy following genetic guidance. This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs. We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation, who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital, analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs. The objective response rate (ORR) was 52.8% and the disease control rate (DCR) was 89.3%. The results showed that, patients with high CEA level before treatment responded better to TKIs (ORR 61.3% vs 35.9%, DCR 95.2% vs 74.4%, P<0.001). Similar phenomena was found in patients with CEA decreased 1 month later (61.5% vs 25%, P=0.002). Progression-free survival (PFS) significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo, P=0.027). To the opposite, PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo, P=0.029; 9.0 mo vs 11.5 mo, P=0.023, respectively). Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score of 0-1, normal baseline CYFRA21-1 and CEA decline predicted longer PFS. The overall survival (OS) was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo, P=0.003; 22.7 mo vs 55.0 mo, P<0.001, respectively), while independent of CEA. High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma. While high levels of baseline CYFRA21-1 and CA125 indicated shortened survival.

  12. Outcomes of robotic surgery for pancreatic ductal adenocarcinoma.

    PubMed

    Zhan, Qian; Deng, Xiaxing; Weng, Yuanchi; Jin, Jiabin; Wu, Zhichong; Li, Hongwei; Shen, Baiyong; Peng, Chenghong

    2015-12-01

    To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma (PDAC). The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy (DP), the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy (MP), the average operative time was 225 min and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula (n=11), bile leak (n=5), anastomotic bleeding (n=2), pancreatic fistula complicated with portal vein thrombosis (n=1), and anastomotic bleeding complicated with acute renal failure (n=1). Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 (15.6±5.8) months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and therefore can achieve the lymph node

  13. [Predictive value of optical coherence tomography on the outcome of lung adenocarcinoma with choroidal metastases].

    PubMed

    García-Fernández, M; Burgueño-Montañés, C

    2014-01-01

    A 59 year-old male, with the diagnosis of lung adenocarcinoma stage iv, following palliative systemic chemotherapy treatment. He was referred to our department due to bilateral blurred vision. In the eye-fundus we observed: bilateral choroidal metastases with macular involvement, and in optical coherence tomography (OCT): neurosensory detachment in both eyes. This neurosensory detachment showed improvement with chemotherapy before the clinical and radiologic improvement. OCT could be a great tool in order to predict the response to systemic treatment in cases of lung adenocarcinoma associated with choroidal metastases. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  14. Sixth cranial nerve palsy caused by gastric adenocarcinoma metastasis to the clivus.

    PubMed

    Lee, Aleum; Chang, Kee-Hyun; Hong, Hyunsook; Kim, Heekyung

    2015-03-01

    Tumors of the clivus and metastases to the clivus are very rare. Metastasis involving the clivus has previously been described in only two case reports. In skull metastasis, the breast and prostate are the most common primary foci, while metastasis from gastric carcinoma is extremely rare. A review of the English literature revealed only one published case of clivus metastases from gastric adenocarcinoma. There is no literature thoroughly explaining the differential diagnosis between chordoma and metastasis. Here we report a rare case of metastasis to the clivus from a gastric adenocarcinoma in a 42-year-old female patient with sudden blurry vision, presenting as bilateral cranial nerve VI palsy.

  15. Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.

    PubMed

    Tempero, Margaret A; Malafa, Mokenge P; Al-Hawary, Mahmoud; Asbun, Horacio; Bain, Andrew; Behrman, Stephen W; Benson, Al B; Binder, Ellen; Cardin, Dana B; Cha, Charles; Chiorean, E Gabriela; Chung, Vincent; Czito, Brian; Dillhoff, Mary; Dotan, Efrat; Ferrone, Cristina R; Hardacre, Jeffrey; Hawkins, William G; Herman, Joseph; Ko, Andrew H; Komanduri, Srinadh; Koong, Albert; LoConte, Noelle; Lowy, Andrew M; Moravek, Cassadie; Nakakura, Eric K; O'Reilly, Eileen M; Obando, Jorge; Reddy, Sushanth; Scaife, Courtney; Thayer, Sarah; Weekes, Colin D; Wolff, Robert A; Wolpin, Brian M; Burns, Jennifer; Darlow, Susan

    2017-08-01

    Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection. Copyright © 2017 by the National Comprehensive Cancer Network.

  16. SMALL INTESTINAL ADENOCARCINOMA WITH CARCINOMATOSIS IN A SWIFT FOX (VULPES VELOX).

    PubMed

    Choudhary, Shambhunath; Andrews, Gordon A; Carpenter, James W

    2015-09-01

    A 7-yr-old, intact, female swift fox (Vulpes velox) presented to the Veterinary Health Center at Kansas State University with a history of chronic weight loss, lethargy, inappetence, and myiasis. On physical examination, a firm mass was palpated in the mid- to cranial abdomen. The fox was euthanatized as a result of the grave prognosis. Gross necropsy and histologic findings included a small intestinal adenocarcinoma with diffuse transperitoneal spread throughout the abdominal cavity (carcinomatosis). To the authors' knowledge, this is the first report of intestinal adenocarcinoma with carcinomatosis in a swift fox.

  17. Choroidal metastasis secondary to prostatic adenocarcinoma: case report and review of literature.

    PubMed

    Albadainah, Faisal; Khader, Jamal; Salah, Samer; Salem, Ahmed

    2015-03-01

    Choroidal metastasis from prostate adenocarcinoma is exceedingly rare. Furthermore, data addressing the optimal therapeutic strategy is limited. A 62-year-old male patient with metastatic prostate cancer was found to have a choroidal metastasis after complaining of decreased vision in his left eye. Following treatment with external beam radiotherapy, complete response in the choroidal metastasis was demonstrated. A literature search was undertaken to highlight the therapeutic options for this rare presentation. Choroidal metastasis secondary to adenocarcinoma of the prostate is exceedingly rare, as only eight cases have been reported so far. External beam radiotherapy is an effective therapeutic modality. Copyright © 2015. Published by Elsevier B.V.

  18. Pancreatic adenocarcinoma presenting as acute pancreatitis during pregnancy: clinical and radiologic manifestations.

    PubMed

    Perera, Dinushi; Kandavar, Ramprasad; Palacios, Enrique

    2011-01-01

    Only seven cases of pancreatic adenocarcinoma diagnosed during pregnancy have been reported. In this article, we describe a case of pancreatic adenocarcinoma presenting clinically as acute pancreatitis in a pregnant patient. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) revealed a pancreatic mass with an inflammatory component and multiple hyperintense metastatic lesions in the liver. The patient was initially treated for biliary pancreatitis, and pancreatic cancer was not suspected given her young age and absence of risk factors. A diagnosis of pancreatic cancer in a pregnant patient requires a high index of suspicion, and pancreatitis can be a mode of presentation.

  19. Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery.

    PubMed

    de Geus, Susanna W L; Boogerd, Leonora S F; Swijnenburg, Rutger-Jan; Mieog, J Sven D; Tummers, Willemieke S F J; Prevoo, Hendrica A J M; Sier, Cornelis F M; Morreau, Hans; Bonsing, Bert A; van de Velde, Cornelis J H; Vahrmeijer, Alexander L; Kuppen, Peter J K

    2016-12-01

    The purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma. The expression of eight potential imaging targets was assessed by the target selection criteria (TASC)-score and immunohistochemical analysis in normal pancreatic tissue (n = 9), pancreatic (n = 137), and periampullary (n = 28) adenocarcinoma. Integrin α v β 6 , carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p < 0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients. The results of this study show that integrin α v β 6 , CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.

  20. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  1. Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett’s Esophagus, and Gastroesophageal Reflux

    PubMed Central

    2013-01-01

    Background Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett’s esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. Methods We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2 g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were two-sided, except in the case of variance-explained estimation where one-sided tests were used. Results We estimated a statistically significant genetic variance explained for BE (h2 g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10−9) and for EA (h2 g = 25 %; SE = 5%; one-sided P = 2 × 10−7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10−6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. Conclusions We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases. PMID:24168968

  2. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience

    PubMed Central

    Dias-Santagata, Dora; Wistuba, Ignacio I.; Chen, Heidi; Fujimoto, Junya; Kugler, Kelly; Franklin, Wilbur A.; Iafrate, A. John; Ladanyi, Marc; Kris, Mark G.; Johnson, Bruce E.; Bunn, Paul A.; Minna, John D.; Kwiatkowski, David J.

    2015-01-01

    Introduction Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing, and clinicopathologic correlations are presented. Methods Mutation testing in at least one of 8 genes (EGFR, KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing +/− PNA and/or sizing assays, along with ALK and/or MET FISH were performed in 6 labs on 1007 patients from 14 institutions. Results 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared to 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22, 25, 8.5, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never smoking status, and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK or MET. Conclusion Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations. PMID:25738220

  3. Efficiency Analysis of Competing Tests for Finding Differentially Expressed Genes in Lung Adenocarcinoma

    PubMed Central

    Jordan, Rick; Patel, Satish; Hu, Hai; Lyons-Weiler, James

    2008-01-01

    In this study, we introduce and use Efficiency Analysis to compare differences in the apparent internal and external consistency of competing normalization methods and tests for identifying differentially expressed genes. Using publicly available data, two lung adenocarcinoma datasets were analyzed using caGEDA (http://bioinformatics2.pitt.edu/GE2/GEDA.html) to measure the degree of differential expression of genes existing between two populations. The datasets were randomly split into at least two subsets, each analyzed for differentially expressed genes between the two sample groups, and the gene lists compared for overlapping genes. Efficiency Analysis is an intuitive method that compares the differences in the percentage of overlap of genes from two or more data subsets, found by the same test over a range of testing methods. Tests that yield consistent gene lists across independently analyzed splits are preferred to those that yield less consistent inferences. For example, a method that exhibits 50% overlap in the 100 top genes from two studies should be preferred to a method that exhibits 5% overlap in the top 100 genes. The same procedure was performed using all available normalization and transformation methods that are available through caGEDA. The ‘best’ test was then further evaluated using internal cross-validation to estimate generalizable sample classification errors using a Naïve Bayes classification algorithm. A novel test, termed D1 (a derivative of the J5 test) was found to be the most consistent, and to exhibit the lowest overall classification error, and highest sensitivity and specificity. The D1 test relaxes the assumption that few genes are differentially expressed. Efficiency Analysis can be misleading if the tests exhibit a bias in any particular dimension (e.g. expression intensity); we therefore explored intensity-scaled and segmented J5 tests using data in which all genes are scaled to share the same intensity distribution range

  4. Young investigator challenge: Cadherin-17 and SATB2 in cytology specimens: Do these new immunostains help in differentiating metastatic colorectal adenocarcinoma from adenocarcinomas of other origins?

    PubMed

    Brandler, Tamar C; Jelloul, Fatima-Zahra; Soto, Daniel; Das, Kasturi; Rosen, Lisa; Bhuiya, Tawfiqul A

    2015-12-01

    Cadherin-17 (intestinal peptide-associated transporter) and SATB2 (SATB homeobox 2) immunoexpression has recently been described in surgical pathology to have value in establishing the colorectal origin of metastatic adenocarcinoma. However, to the authors' knowledge, the role of these markers in metastatic colorectal adenocarcinoma (MCA) in cytology has not been addressed to date. In the current study, the authors evaluated the contribution of cadherin-17 and SATB2 to the diagnosis of MCA in cytology specimens and compared these two novel markers with the standard gastrointestinal immunohistochemistry panel in an attempt to identify the optimal panel. A total of 43 MCA cytology cases and 68 metastatic noncolorectal adenocarcinoma (non-MCA) cytology controls were stained for SATB2; cadherin-17; and the standard panel of cytokeratin (CK) 7, CK20, and Caudal-Type Homeobox Transcription Factor 2 (CDX2). Staining intensity and percentage of positive cells were recorded. Sensitivity and specificity values for immunostains individually and in combination were computed and compared. Despite specificities of 83.8% and 91.2%, respectively, for cadherin-17 and SATB2, when critically examining the new immunostains together with the standard panel, there was no significant difference noted with regard to prediction of MCA (vs non-MCA) compared with the standard panel alone (P < .6). The results of the current study reinforce that the standard gastrointestinal immunohistochemistry panel remains the gold standard for distinguishing MCA from non-MCA in cytology. © 2015 American Cancer Society.

  5. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    SciTech Connect

    Chen, Y.-J.; Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan

    2005-11-15

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses ofmore » CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.« less

  6. Optical metabolic imaging of colorectal adenocarcinoma derived organoids: assessing cellular-level resistance to therapy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    James, Haley M.; Prieto, Sandra P.; Greening, Gage J.; Muldoon, Timothy J.

    2017-02-01

    Locally advanced adenocarcinomas located in the distal rectum are commonly treated via 5-fluorouracil (5-FU)-based neoadjuvant chemoradiation therapy (CRT). The occurrence of pre-operative pathological complete response, or the absence of any histological evidence of residual cancer, is seen in 15-27% of rectal cancer cases. Response to chemotherapeutic agents varies between patients, introducing the need for a system to predict optimal drug combinations. We propose a method of utilizing optical metabolic imaging of in vitro, primary tumor-derived, three-dimensional organoid culture to create specific drug sensitivity profiles, and to rapidly assess a patient's potential response to drugs. Murine xenografts were developed in Swiss athymic nude mice, using human colorectal adenocarcinoma cell lines, implanted in the flank (RKO, ATCC). Tumors were excised upon reaching a volume of 500mm3 and processed for organoid culture. Organoids were subjected to longitudinal metabolic imaging of metabolic cofactors FAD and NADH for seven days. The resulting images were used to yield an optical redox value on a cell-by-cell basis, determined by the fluorescence intensity ratio of FAD/(FAD+NADH). This data infers proliferative index of the organoids. Beginning on day three, a control vehicle dimethyl sulfoxide, or the cytotoxic agent 5-FU, was added to the organoid growth media in wells, with metabolic imaging performed the same as previously stated. The optical redox values decreased due to the addition of 5-FU, which targets rapidly dividing cells and induces apoptosis. The changes in the optical redox histograms were correlated to markers of cell proliferation (Ki-67) and apoptosis (cleaved caspase-3).

  7. Outcomes of Adjuvant Chemoradiation After Pancreaticoduodenectomy With Mesenterico-Portal Vein Resection for Adenocarcinoma of the Pancreas

    SciTech Connect

    Hristov, Boris; Reddy, Sushanth; Lin, Steven H.

    2010-01-15

    Purpose: Surgery followed by chemotherapy and radiation (CRT) offers patients with pancreatic adenocarcinoma a chance for extended survival. In some patients, however, resection is difficult because of vascular involvement by the carcinoma, necessitating resection and grafting of the mesenterico-portal vessels. The purpose of this study was to compare outcomes between pancreaticoduodenectomy (PD) with and without mesenterico-portal vein resection (VR) in patients receiving adjuvant CRT for pancreatic adenocarcinoma. Methods and Materials: Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of the 160 underwent VR. Clinical outcomes,more » including median survival, overall survival, and complication rates were assessed for both groups. Results: Patients who underwent VR had significantly longer operative times (p = 0.009), greater intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p = 0.03). However, postoperative morbidity, median survival, and overall survival rates were similar between the two groups. Most patients (70%) from both groups were able to complete CRT, and a subgroup analysis demonstrated no appreciable differences in terms of complications. None of the VR patients who received adjuvant CRT developed veno-occlusive disease or graft failure/leakage. Conclusion: In a cohort of patients treated with adjuvant 5-FU-based CRT at the Johns Hopkins Hospital, having a VR at the time of PD resulted in similar complication rates and survival. These data support the feasibility and safety of adjuvant CRT in patients undergoing VR at the time of PD.« less

  8. MO-DE-207B-08: Radiomic CT Features Complement Semantic Annotations to Predict EGFR Mutations in Lung Adenocarcinomas

    SciTech Connect

    Rios Velazquez, E; Parmar, C; Narayan, V

    2016-06-15

    Purpose: To compare the complementary value of quantitative radiomic features to that of radiologist-annotated semantic features in predicting EGFR mutations in lung adenocarcinomas. Methods: Pre-operative CT images of 258 lung adenocarcinoma patients were available. Tumors were segmented using the sing-click ensemble segmentation algorithm. A set of radiomic features was extracted using 3D-Slicer. Test-retest reproducibility and unsupervised dimensionality reduction were applied to select a subset of reproducible and independent radiomic features. Twenty semantic annotations were scored by an expert radiologist, describing the tumor, surrounding tissue and associated findings. Minimum-redundancy-maximum-relevance (MRMR) was used to identify the most informative radiomic and semantic featuresmore » in 172 patients (training-set, temporal split). Radiomic, semantic and combined radiomic-semantic logistic regression models to predict EGFR mutations were evaluated in and independent validation dataset of 86 patients using the area under the receiver operating curve (AUC). Results: EGFR mutations were found in 77/172 (45%) and 39/86 (45%) of the training and validation sets, respectively. Univariate AUCs showed a similar range for both feature types: radiomics median AUC = 0.57 (range: 0.50 – 0.62); semantic median AUC = 0.53 (range: 0.50 – 0.64, Wilcoxon p = 0.55). After MRMR feature selection, the best-performing radiomic, semantic, and radiomic-semantic logistic regression models, for EGFR mutations, showed a validation AUC of 0.56 (p = 0.29), 0.63 (p = 0.063) and 0.67 (p = 0.004), respectively. Conclusion: Quantitative volumetric and textural Radiomic features complement the qualitative and semi-quantitative radiologist annotations. The prognostic value of informative qualitative semantic features such as cavitation and lobulation is increased with the addition of quantitative textural features from the tumor region.« less

  9. Diagnostic utility of C-kit protein (CD117) expression in differentiating adenoid cystic carcinoma and polymorphous low grade Adenocarcinoma

    PubMed Central

    Tariq, Hassan; Anjum, Saba; Din, Hafeez ud; Akhtar, Farhan

    2017-01-01

    Background & Objective: To evaluate usefulness of immunohistochemical marker C-kit (CD117) in differentiating Adenoid cystic carcinoma (AdCC) from Polymorphous low-grade adenocarcinoma (PLGA) in patients of salivary gland carcinomas. AdCC is a malignant salivary gland neoplasm with poor prognosis. PLGA is a salivary gland malignancy with indolent growth pattern. Differentiating between the two entities is a diagnostic challenge. We evaluated the role of C-kit in differentiating the two. Methods: This is a Cross sectional study. Samples of 19 tumors including 12 AdCC and 4 PLGA was evaluated at Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from December 2015 to August 2016. Immunohistochemical techniques were used to analyze the level of c-kit expression in AdCC (n = 12), polymorphous low-grade adenocarcinoma (PLGA) (n = 6). Samples were stained using monoclonal antibody against C-kit. Statistical analysis of the data was done using SPSS version 21. Results: Strong diffuse cytoplasmic reactivity was observed in more than 50% of the tumor cells of AdCC whereas less than 20% of cells showed negative to weak positivity in PLGA. Hence, the difference in the expression of c-kit between AdCC and PLGA was statistically significant (p value <0.002). Conclusions: CD117 expression itself can be used as a marker in differential diagnosis of salivary gland neoplasms. However, the percentage of the CD117 immunoreactive cells and the staining intensities appeared to be important factors in distinguishing AdCC from PLGA. PMID:29492062

  10. Tumor Budding Correlates With the Protumor Immune Microenvironment and Is an Independent Prognostic Factor for Recurrence of Stage I Lung Adenocarcinoma

    PubMed Central

    Kadota, Kyuichi; Yeh, Yi-Chen; Villena-Vargas, Jonathan; Cherkassky, Leonid; Drill, Esther N.; Sima, Camelia S.; Jones, David R.; Travis, William D.

    2015-01-01

    BACKGROUND: Immune cell infiltration associated with tumor capsule disruption and tumor budding has been shown to reflect invasiveness, metastasis, and unfavorable prognosis in colorectal cancer. We investigated the influence of tumor budding on prognosis and its association with the immune microenvironment in lung adenocarcinoma. METHODS: Tumor slides from resected stage I lung adenocarcinomas were reviewed (n = 524 and n = 514, for training and validation cohorts, respectively) for assessment of tumor budding. CD3+ and forkhead box P3+ (FoxP3+) lymphocytes, CD68+ macrophages, IL-7 receptor, and IL-12 receptor β2 were analyzed using tissue microarrays constructed from tumor and stroma. Probability of recurrence was calculated using the competing risks method. RESULTS: In the training cohort, risk of recurrence for high-grade tumor budding was higher than it was for low-grade tumor budding (32% vs 12%, P < .001), which was confirmed in the validation cohort (P = .005). Tumor budding stratified the risk of recurrence for acinar-predominant (22% vs 9%, P < .001), papillary-predominant (22% vs 13%, P = .045), and solid-predominant (39% vs 19%, P = .022) tumors. Tumor budding was associated with higher stromal FoxP3+ lymphocyte infiltration, higher stromal FoxP3/CD3 risk index, higher tumoral and stromal CD68+ macrophage infiltration, and IL-7 receptor overexpression (P < .001, all associations). Tumor budding remained independently associated with recurrence on multivariate analysis (hazard ratio, 1.61; P = .008). CONCLUSIONS: Tumor budding is an independent prognostic factor of stage I lung adenocarcinoma and correlates with the protumor immune microenvironment. Our findings advocate investigating tumor-immune cell interactions at the invading edge as a biologic driver of tumor aggressiveness. PMID:25836013

  11. [Radiosensitizing effect of erlotinib on human lung adenocarcinoma cell line A549].

    PubMed

    Liu, Xiao-qun; Qiao, Tian-kui

    2013-11-01

    To explore the radiosensitizing effect of erlotinib on human lung adenocarcinoma cell line A549 cells and the related mechanisms. The inhibitory effect of erlotinib on A549 cells was assessed by MTT assay, and its IC50 concentration was calculated. The radiosensitization was evaluated by the method of clone forming assay. Flow cytometry was used to analyze the effect of erlotinib on cell cycle and apoptosis. The growth of A549 cells was inhibited after the cells were exposed to erlotinib for 48 hours. Moreover, the inhibitory rates increased with the increase of erlotinib concentrations, and IC50 was 19.26 µmol/L. In contrast to the irradiation alone group, the survival rates of the cells in erlotinib plus irradiation groups decreased, and erlotinib enhanced the radiosensitivity of the A549 cells. This effect was further increased as cells were exposed to erlotinib for a longer time. In the irradiation alone group and the two groups exposed to erlotinib for 24 hours and 48 hours before irradiation, D0 values were 3.01 Gy, 2.58 Gy and 2.45 Gy respectively, and Dq values were 2.16 Gy, 1.94 Gy and 1.61 Gy, respectively. In the last two groups, SERD0 values were 1.17 and 1.23, respectively. The flow cytometry analysis showed that erlotinib induced G2/M phase arrest and increased the apoptosis rate in A549 cells. With the increase of exposure time, the effects were more significant. Erlotinib inhibits the A549 cell growth and enhances the radiosensitivity of A549 cells in vitro. The radiosensitizing mechanisms might be related to inhibiting repair of sublethal injury and inducing G2/M phase arrest and apoptosis.

  12. Mounting Pressure in the Microenvironment: Fluids, Solids, and Cells in Pancreatic Ductal Adenocarcinoma.

    PubMed

    DuFort, Christopher C; DelGiorno, Kathleen E; Hingorani, Sunil R

    2016-06-01

    The microenvironment influences the pathogenesis of solid tumors and plays an outsized role in some. Our understanding of the stromal response to cancers, particularly pancreatic ductal adenocarcinoma, has evolved from that of host defense to tumor offense. We know that most, although not all, of the factors and processes in the microenvironment support tumor epithelial cells. This reappraisal of the roles of stromal elements has also revealed potential vulnerabilities and therapeutic opportunities to exploit. The high concentration in the stroma of the glycosaminoglycan hyaluronan, together with the large gel-fluid phase and pressures it generates, were recently identified as primary sources of treatment resistance in pancreas cancer. Whereas the relatively minor role of free interstitial fluid in the fluid mechanics and perfusion of tumors has been long appreciated, the less mobile, gel-fluid phase has been largely ignored for historical and technical reasons. The inability of classic methods of fluid pressure measurement to capture the gel-fluid phase, together with a dependence on xenograft and allograft systems that inaccurately model tumor vascular biology, has led to an undue emphasis on the role of free fluid in impeding perfusion and drug delivery and an almost complete oversight of the predominant role of the gel-fluid phase. We propose that a hyaluronan-rich, relatively immobile gel-fluid phase induces vascular collapse and hypoperfusion as a primary mechanism of treatment resistance in pancreas cancers. Similar properties may be operant in other solid tumors as well, so revisiting and characterizing fluid mechanics with modern techniques in other autochthonous cancers may be warranted. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges.

    PubMed

    Root, Alex; Allen, Peter; Tempst, Paul; Yu, Kenneth

    2018-03-07

    Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community. The first set of challenges involves nominating and verifying biomarkers. Candidate biomarkers need to discriminate disease from benign controls with high sensitivity and specificity for an intended use, which we describe as a two-tiered strategy of identifying and screening high-risk patients. Community-wide efforts to share samples, data, and analysis methods have been beneficial and progress meeting this challenge has been achieved. The second set of challenges is assay optimization and validating biomarkers. After initial candidate validation, assays need to be refined into accurate, cost-effective, highly reproducible, and multiplexed targeted panels and then validated in large cohorts. To move the most promising candidates forward, ideally, biomarker panels, head-to-head comparisons, meta-analysis, and assessment in independent data sets might mitigate risk of failure. Much more investment is needed to overcome these challenges. The third challenge is achieving clinical translation. To moonshot an early detection test to the clinic requires a large clinical trial and organizational, regulatory, and entrepreneurial know-how. Additional factors, such as imaging technologies, will likely need to improve concomitant with molecular biomarker development. The magnitude of the clinical translational challenge is uncertain, but interdisciplinary

  14. A Comprehensive Peptidome Profiling Technology for the Identification of Early Detection Biomarkers for Lung Adenocarcinoma

    PubMed Central

    Ueda, Koji; Saichi, Naomi; Takami, Sachiko; Kang, Daechun; Toyama, Atsuhiko; Daigo, Yataro; Ishikawa, Nobuhisa; Kohno, Nobuoki; Tamura, Kenji; Shuin, Taro; Nakayama, Masato; Sato, Taka-Aki; Nakamura, Yusuke; Nakagawa, Hidewaki

    2011-01-01

    The mass spectrometry-based peptidomics approaches have proven its usefulness in several areas such as the discovery of physiologically active peptides or biomarker candidates derived from various biological fluids including blood and cerebrospinal fluid. However, to identify biomarkers that are reproducible and clinically applicable, development of a novel technology, which enables rapid, sensitive, and quantitative analysis using hundreds of clinical specimens, has been eagerly awaited. Here we report an integrative peptidomic approach for identification of lung cancer-specific serum peptide biomarkers. It is based on the one-step effective enrichment of peptidome fractions (molecular weight of 1,000–5,000) with size exclusion chromatography in combination with the precise label-free quantification analysis of nano-LC/MS/MS data set using Expressionist proteome server platform. We applied this method to 92 serum samples well-managed with our SOP (standard operating procedure) (30 healthy controls and 62 lung adenocarcinoma patients), and quantitatively assessed the detected 3,537 peptide signals. Among them, 118 peptides showed significantly altered serum levels between the control and lung cancer groups (p<0.01 and fold change >5.0). Subsequently we identified peptide sequences by MS/MS analysis and further assessed the reproducibility of Expressionist-based quantification results and their diagnostic powers by MRM-based relative-quantification analysis for 96 independently prepared serum samples and found that APOA4 273–283, FIBA 5–16, and LBN 306–313 should be clinically useful biomarkers for both early detection and tumor staging of lung cancer. Our peptidome profiling technology can provide simple, high-throughput, and reliable quantification of a large number of clinical samples, which is applicable for diverse peptidome-targeting biomarker discoveries using any types of biological specimens. PMID:21533267

  15. Oxidative stress mediated cytotoxicity of biologically synthesized silver nanoparticles in human lung epithelial adenocarcinoma cell line

    PubMed Central

    2014-01-01

    The goal of the present study was to investigate the toxicity of biologically prepared small size of silver nanoparticles in human lung epithelial adenocarcinoma cells A549. Herein, we describe a facile method for the synthesis of silver nanoparticles by treating the supernatant from a culture of Escherichia coli with silver nitrate. The formation of silver nanoparticles was characterized using various analytical techniques. The results from UV-visible (UV-vis) spectroscopy and X-ray diffraction analysis show a characteristic strong resonance centered at 420 nm and a single crystalline nature, respectively. Fourier transform infrared spectroscopy confirmed the possible bio-molecules responsible for the reduction of silver from silver nitrate into nanoparticles. The particle size analyzer and transmission electron microscopy results suggest that silver nanoparticles are spherical in shape with an average diameter of 15 nm. The results derived from in vitro studies showed a concentration-dependent decrease in cell viability when A549 cells were exposed to silver nanoparticles. This decrease in cell viability corresponded to increased leakage of lactate dehydrogenase (LDH), increased intracellular reactive oxygen species generation (ROS), and decreased mitochondrial transmembrane potential (MTP). Furthermore, uptake and intracellular localization of silver nanoparticles were observed and were accompanied by accumulation of autophagosomes and autolysosomes in A549 cells. The results indicate that silver nanoparticles play a significant role in apoptosis. Interestingly, biologically synthesized silver nanoparticles showed more potent cytotoxicity at the concentrations tested compared to that shown by chemically synthesized silver nanoparticles. Therefore, our results demonstrated that human lung epithelial A549 cells could provide a valuable model to assess the cytotoxicity of silver nanoparticles. PMID:25242904

  16. Oxidative stress mediated cytotoxicity of biologically synthesized silver nanoparticles in human lung epithelial adenocarcinoma cell line

    NASA Astrophysics Data System (ADS)

    Han, Jae Woong; Gurunathan, Sangiliyandi; Jeong, Jae-Kyo; Choi, Yun-Jung; Kwon, Deug-Nam; Park, Jin-Ki; Kim, Jin-Hoi

    2014-09-01

    The goal of the present study was to investigate the toxicity of biologically prepared small size of silver nanoparticles in human lung epithelial adenocarcinoma cells A549. Herein, we describe a facile method for the synthesis of silver nanoparticles by treating the supernatant from a culture of Escherichia coli with silver nitrate . The formation of silver nanoparticles was characterized using various analytical techniques. The results from UV-visible (UV-vis) spectroscopy and X-ray diffraction analysis show a characteristic strong resonance centered at 420 nm and a single crystalline nature, respectively. Fourier transform infrared spectroscopy confirmed the possible bio-molecules responsible for the reduction of silver from silver nitrate into nanoparticles. The particle size analyzer and transmission electron microscopy results suggest that silver nanoparticles are spherical in shape with an average diameter of 15 nm. The results derived from in vitro studies showed a concentration-dependent decrease in cell viability when A549 cells were exposed to silver nanoparticles. This decrease in cell viability corresponded to increased leakage of lactate dehydrogenase (LDH), increased intracellular reactive oxygen species generation (ROS), and decreased mitochondrial transmembrane potential (MTP). Furthermore, uptake and intracellular localization of silver nanoparticles were observed and were accompanied by accumulation of autophagosomes and autolysosomes in A549 cells. The results indicate that silver nanoparticles play a significant role in apoptosis. Interestingly, biologically synthesized silver nanoparticles showed more potent cytotoxicity at the concentrations tested compared to that shown by chemically synthesized silver nanoparticles. Therefore, our results demonstrated that human lung epithelial A549 cells could provide a valuable model to assess the cytotoxicity of silver nanoparticles.

  17. Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience.

    PubMed

    Sholl, Lynette M; Aisner, Dara L; Varella-Garcia, Marileila; Berry, Lynne D; Dias-Santagata, Dora; Wistuba, Ignacio I; Chen, Heidi; Fujimoto, Junya; Kugler, Kelly; Franklin, Wilbur A; Iafrate, A John; Ladanyi, Marc; Kris, Mark G; Johnson, Bruce E; Bunn, Paul A; Minna, John D; Kwiatkowski, David J

    2015-05-01

    Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing and clinicopathologic correlations are presented. Mutation testing in at least one of the eight genes (epidermal growth factor receptor [EGFR], KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, and PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing+/- peptide nucleic acid and/or sizing assays, along with anaplastic lymphoma kinase (ALK) and/or MET fluorescence in situ hybridization, were performed in six labs on 1007 patients from 14 institutions. In all, 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared with 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22%, 25%, 8.5%, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never-smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never-smoking status and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never-smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK, or MET. Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations.

  18. Targeted depletion of a MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity

    PubMed Central

    Stromnes, Ingunn M.; Brockenbrough, Scott; Izeradjene, Kamel; Carlson, Markus A.; Cuevas, Carlos; Simmons, Randi M.; Greenberg, Philip D.; Hingorani, Sunil R.

    2015-01-01

    Objective Pancreatic ductal adenocarcinoma (PDA) is characterized by a robust desmoplasia, including the notable accumulation of immunosuppressive cells that shield neoplastic cells from immune detection. Immune evasion may be further enhanced if the malignant cells fail to express high levels of antigens that are sufficiently immunogenic to engender an effector T cell response. In this report, we investigate the predominant subsets of immunosuppressive cancer-conditioned myeloid cells that chronicle and shape pancreas cancer progression. We show that selective depletion of one subset of myeloid-derived suppressor cells (MDSC) in an autochthonous, genetically engineered mouse model (GEMM) of PDA unmasks the ability of the adaptive immune response to engage and target tumor epithelial cells. Methods A combination of in vivo and in vitro studies were performed employing a GEMM that faithfully recapitulates the cardinal features of human PDA. The predominant cancer-conditioned myeloid cell subpopulation was specifically targeted in vivo and the biological outcomes determined. Results PDA orchestrates the induction of distinct subsets of cancer-associated myeloid cells through the production of factors known to influence myelopoeisis. These immature myeloid cells inhibit the proliferation and induce apoptosis of activated T cells. Targeted depletion of granulocytic MDSC (Gr-MDSC) in autochthonous PDA increases the intratumoral accumulation of activated CD8 T cells and apoptosis of tumor epithelial cells, and also remodels the tumor stroma. Conclusions Neoplastic ductal cells of the pancreas induce distinct myeloid cell subsets that promote tumor cell survival and accumulation. Targeted depletion of a single myeloid subset, the Gr-MDSC, can unmask an endogenous T cell response, revealing an unexpected latent immunity and invoking targeting of Gr-MDSC as a potential strategy to exploit for treating this highly lethal disease. PMID:24555999

  19. Role of CPS1 in Cell Growth, Metabolism, and Prognosis in LKB1-Inactivated Lung Adenocarcinoma

    PubMed Central

    Çeliktaş, Müge; Tanaka, Ichidai; Chandra Tripathi, Satyendra; Fahrmann, Johannes F.; Aguilar-Bonavides, Clemente; Villalobos, Pamela; Delgado, Oliver; Dhillon, Dilsher; Dennison, Jennifer B.; Ostrin, Edwin J.; Wang, Hong; Behrens, Carmen; Do, Kim-Anh; Gazdar, Adi F.

    2017-01-01

    Abstract Background: Liver kinase B1 (LKB1) is a tumor suppressor in lung adenocarcinoma (LADC). We investigated the proteomic profiles of 45 LADC cell lines with and without LKB1 inactivation. Carbamoyl phosphate synthetase 1 (CPS1), the first rate-limiting mitochondrial enzyme in the urea cycle, was distinctively overexpressed in LKB1-inactivated LADC cell lines. We therefore assessed the role of CPS1 and its clinical relevance in LKB1-inactivated LADC. Methods: Mass spectrometric profiling of proteome and metabolome and function of CPS1 were analyzed in LADC cell lines. CPS1 and LKB1 expression in tumors from 305 LADC and 160 lung squamous cell carcinoma patients was evaluated by immunohistochemistry. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and CPS1 and LKB1 expression. All statistical tests were two-sided. Results: CPS1 knockdown reduced cell growth, decreased metabolite levels associated with nucleic acid biosynthesis pathway, and contributed an additive effect when combined with gemcitabine, pemetrexed, or CHK1 inhibitor AZD7762. Tissue microarray analysis revealed that CPS1 was expressed in 65.7% of LKB1-negative LADC, and only 5.0% of LKB1-positive LADC. CPS1 expression showed statistically significant association with poor overall survival in LADC (hazard ratio = 3.03, 95% confidence interval = 1.74 to 5.25, P < .001). Conclusions: Our findings suggest functional relevance of CPS1 in LKB1-inactivated LADC and association with worse outcome of LADC. CPS1 is a promising therapeutic target in combination with other chemotherapy agents, as well as a prognostic biomarker, enabling a personalized approach to treatment of LADC. PMID:28376202

  20. Selective internal radiation therapy (SIRT) for liver metastases secondary to colorectal adenocarcinoma

    SciTech Connect

    Welsh, James S.; Kennedy, Andrew S.; Thomadsen, Bruce

    2006-10-01

    Introduction: Selective internal radiation therapy (SIRT) is a relatively new commercially available microbrachytherapy technique for treatment of malignant hepatic lesions using {sup 9}Y embedded in resin microspheres, which are infused directly into the hepatic arterial circulation. It is FDA approved for liver metastases secondary to colorectal carcinoma and is under investigation for treatment of other liver malignancies, such as hepatocellular carcinoma and neuroendocrine malignancies. Materials/Methods: A modest number of clinical trials, preclinical animal studies, and dosimetric studies have been reported. Here we review several of the more important results. Results: High doses of beta radiation can be selectively delivered tomore » tumors, resulting in impressive local control and survival rates. Ex vivo analyses have shown that microspheres preferentially cluster around the periphery of tumor nodules with a high tumor:normal tissue ratio of up to 200:1. Toxicity is usually mild, featuring fatigue, anorexia, nausea, abdominal discomfort, and slight elevations of liver function tests. Conclusions: Selective internal radiation therapy represents an effective means of controlling liver metastases from colorectal adenocarcinoma. Clinical trials have demonstrated improved local control of disease and survival with relatively low toxicity. Investigations of SIRT for other hepatic malignancies and in combination with newer chemotherapy agents and targeted biologic therapies are under way or in planning. A well-integrated team involving interventional radiology, nuclear medicine, medical oncology, surgical oncology, medical physics, and radiation oncology is essential for a successful program. Careful selection of patients through the combined expertise of the team can maximize therapeutic efficacy and reduce the potential for adverse effects.« less