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Sample records for adenocarcinoma eac methods

  1. Macrophage subtype predicts lymph node metastasis in oesophageal adenocarcinoma and promotes cancer cell invasion in vitro

    PubMed Central

    Cao, Wenqing; Peters, Jeffrey H; Nieman, Dylan; Sharma, Meenal; Watson, Thomas; Yu, JiangZhou

    2015-01-01

    Background: Currently, there is a lack of ideal biomarkers for predicting nodal status in preoperative stage of oesophageal adenocarcinoma (EAC) to aid optimising therapeutic options. We studied the potential of applying subtype macrophages to predict lymph node metastasis and prognosis in EAC. Material and Methods: Fifty-three EAC resection specimens were immunostained with CD68, CD40 (M1), and CD163 (M2). Lymphatic vessel density (LVD) was estimated with the staining of D2-40. Subsequently, we tested if M2d macrophage could promote EAC cell migration and invasion. Results: In EAC without neoadjuvant treatment, an increase in M2-like macrophage was associated with poor patient survival, independent of the locations of macrophages in tumour. The M2/M1 ratio that represented the balance between M2- and M1-like macrophages was significantly higher in nodal-positive EACs than that in nodal-negative EACs, and inversely correlated with patient overall survival. The M2/M1 ratio was not related to LVD. EAC cell polarised THP1 cell into M2d-like macrophage, which promoted EAC cell migration and invasion. Neoadjuvant therapy appeared to diminish the correlation between the M2/M1 ratio and survival. Conclusions: The ratio of M2/M1 macrophage may serve as a sensitive marker to predict lymph node metastasis and poor prognosis in EAC without neoadjuvant therapy. M2d macrophage may have important roles in EAC metastasis. PMID:26263481

  2. Incidence of Esophageal Adenocarcinoma and Causes of Mortality in Barrett's Esophagus after Radiofrequency Ablation

    PubMed Central

    Wolf, W. Asher; Pasricha, Sarina; Cotton, Cary; Li, Nan; Triadafilopoulos, George; Muthusamy, V. Raman; Chmielewski, Gary W.; Corbett, F. Scott; Camara, Daniel S.; Lightdale, Charles J.; Wolfsen, Herbert; Chang, Kenneth J.; Overholt, Bergein F.; Pruitt, Ron E.; Ertan, Atilla; Komanduri, Srinadh; Infantolino, Anthony; Rothstein, Richard I.; Shaheen, Nicholas J.

    2016-01-01

    Background & Aims Radiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, predictors of EAC, and EAC-specific and all-cause mortality rates. Methods We assessed outcomes in a multicenter study of RFA for BE. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (both all-cause and EAC-specific) rates were calculated, and adjusted all-cause mortality rates were assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. Results Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years (PY)), and 9 (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in non-dysplastic BE (NDBE) was 0.5/1000 PY. Overall, 157 (3%) patients died during follow-up (all-cause mortality 11.2/1000 PY). On multivariate logistic regression, baseline BE length (OR 1.1 per cm) and baseline histology (ORs of 5.8 and 50.3 for low grade dysplasia and high grade dysplasia (HGD) respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extra-esophageal cancers (15%). No deaths were associated with RFA. Conclusion In this multicenter registry of RFA for BE, death from EAC was rare. The incidence of EAC was markedly lower than natural history studies, with the greatest absolute benefit seen in HGD. PMID:26327132

  3. A global assessment of the male predominance in esophageal adenocarcinoma

    PubMed Central

    Xie, Shao-Hua; Lagergren, Jesper

    2016-01-01

    Background Esophageal adenocarcinoma (EAC) is characterized by a male predominance. However, variations in the sex difference across populations and over time have not previously been thoroughly investigated. Results The male-to-female ratio in EAC incidence varied greatly across continents, ranging from 1.03 in Africa to 7.64 in Northern America during 2003– 2007. The ratio was high in Europe (6.04) and Oceania (6.24), and lower in Asia (4.37) and Latin America and the Caribbean (3.94). The sex ratio remained relatively stable over time in most populations. In absolute terms, the sex difference in EAC incidence increased over time in populations of higher incidence, while it remained stable or slightly decreased in low-incidence populations. Materials and Methods We used data from the Cancer Incidence in Five Continents series to compute sex-specific age-standardized rates of EAC by population. The sex difference in incidence was evaluated on both absolute and relative scales, measured by the absolute difference and ratio between sexes, respectively. Conclusions This first global assessment of the sex ratio in EAC shows that the male predominance is particularly strong in developed countries. The underlying reasons remain to be identified, but the emerging EAC burden in men merits consideration for targeted prevention and early detection. PMID:27145283

  4. Risk of Esophageal Adenocarcinoma Decreases With Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization

    PubMed Central

    Thrift, Aaron P.; Risch, Harvey A.; Onstad, Lynn; Shaheen, Nicholas J.; Casson, Alan G.; Bernstein, Leslie; Corley, Douglas A.; Levine, David M.; Chow, Wong–Ho; Reid, Brian J.; Romero, Yvonne; Hardie, Laura J.; Liu, Geoffrey; Wu, Anna H.; Bird, Nigel C.; Gammon, Marilie D.; Ye, Weimin; Whiteman, David C.; Vaughan, Thomas L.

    2014-01-01

    BACKGROUND & AIMS Risks for some cancers increase with height. We investigated the relationship between height and risk of esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE). METHODS We analyzed epidemiologic and genome-wide genomic data from individuals of European ancestry in the Barrett’s and Esophageal Adenocarcinoma Consortium, from 999 cases of EAC, 2061 cases of BE, and 2168 population controls. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height and risks of EAC and BE. We performed a Mendelian randomization analysis to estimate an unconfounded effect of height on EAC and BE using a genetic risk score derived from 243 genetic variants associated with height as an instrumental variable. RESULTS Height was associated inversely with EAC (per 10-cm increase in height: OR, 0.70; 95% CI, 0.62–0.79 for men and OR, 0.57; 95% CI 0.40–0.80 for women) and BE (per 10-cm increase in height: OR, 0.69; 95% CI, 0.62–0.77 for men and OR, 0.61; 95% CI, 0.48–0.77 for women). The risk estimates were consistent across strata of age, education level, smoking, gastroesophageal reflux symptoms, body mass index, and weight. Mendelian randomization analysis yielded results quantitatively similar to those from the conventional epidemiologic analysis. CONCLUSIONS Height is associated inversely with risks of EAC and BE. Results from the Mendelian randomization study showed that the inverse association observed did not result from confounding factors. Mechanistic studies of the effect of height on EAC and BE are warranted; height could have utility in clinical risk stratification. PMID:24530603

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

    DTIC Science & Technology

    2009-03-01

    Composite Index methods. Our study uses the Gompertz growth curve to produce three EAC Models based on contract phase: A Production Model, a...31 9. Regression Error Results ...............................................................................................33 10. Gompertz ...36 12. Gompertz Parameter Estimates, Development

  6. 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.

  7. Exploring the Recent Trend in Esophageal Adenocarcinoma Incidence and Mortality Using Comparative Simulation Modeling

    PubMed Central

    Kong, Chung Yin; Kroep, Sonja; Curtius, Kit; Hazelton, William D.; Jeon, Jihyoun; Meza, Rafael; Heberle, Curtis R.; Miller, Melecia C.; Choi, Sung Eun; Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Feuer, Eric J.; Inadomi, John M.; Hur, Chin; Luebeck, E. Georg

    2014-01-01

    Background The incidence of esophageal adenocarcinoma (EAC) has increased five-fold in the United States since 1975. The aim of our study was to estimate future U.S. EAC incidence and mortality and to shed light on the potential drivers in the disease process that are conduits for the dramatic increase in EAC incidence. Methods A consortium of three research groups calibrated independent mathematical models to clinical and epidemiologic data including EAC incidence from the Surveillance, Epidemiology, and End Results (SEER 9) registry from 1975–2010. We then used a comparative modeling approach to project EAC incidence and mortality to year 2030. Results Importantly, all three models identified birth cohort trends affecting cancer progression as a major driver of the observed increases in EAC incidence and mortality. All models predict that incidence and mortality rates will continue to increase until 2030 but with a plateauing trend for recent male cohorts. The predicted ranges of incidence and mortality rates (cases per 100,000 person years) in 2030 are 8.4–10.1 and 5.4–7.4 respectively for males, and 1.3–1.8 and 0.9–1.2 for females. Estimates of cumulative cause-specific EAC deaths among both sexes for years 2011–2030 range between 142,300 and 186,298, almost double the number of deaths in the past 20 years. Conclusions Through comparative modeling, the projected increases in EAC cases and deaths represent a critical public health concern that warrants attention from cancer control planners to prepare potential interventions. Impact Quantifying this burden of disease will aid health policy makers to plan appropriate cancer control measures. PMID:24692500

  8. A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome.

    PubMed

    Lanuti, Michael; Liu, Geoffrey; Goodwin, Jonathan M; Zhai, Rihong; Fuchs, Bryan C; Asomaning, Kofi; Su, Li; Nishioka, Norman S; Tanabe, Kenneth K; Christiani, David C

    2008-05-15

    The epidermal growth factor (EGF) pathway is important in esophageal adenocarcinoma (EAC) tumorigenesis. We hypothesized that the EGF A61G homozygous variant genotype (GG) is (a) both a risk and poor prognostic factor for EAC and (b) associated with higher EGF serum levels in individuals with gastroesophageal reflux disease (GERD). Using unconditional logistic regression, we compared EGF A61G in 312 EAC cases and 447 GERD-free controls, adjusting for age, gender, smoking history, and healthy adult body mass index. Using the method of Kaplan and Meier, log-rank tests, and Cox proportional hazard models, we correlated EGF A61G with overall and failure-free survival in the EAC cases. Serum EGF levels and EGF genotype (G/G versus others) were correlated in 144 GERD patients using Wilcoxon rank sum tests. The EGF A61G G/G genotype conferred increased EAC risk, with an adjusted odds ratio of 1.81 (95% confidence interval, 1.2-2.7), and was even higher in the subgroup of EAC patients with concurrent Barrett's esophagus (adjusted odds ratio, 2.18; 95% confidence interval, 1.3-3.7). However, EGF A61G was not associated with a more aggressive phenotype or prognosis in EAC patients. Higher serum EGF levels were found in GERD patients carrying G/G compared with A/A or A/G (P = 0.03, Wilcoxon rank sum test). The EGF A61G G/G genotype is associated with a near 2-fold greater risk of EAC. The G/G allele was also associated with higher EGF levels in tumor-free patients with GERD. EGF genotyping can potentially identify high-risk patients with GERD and Barrett's metaplasia who might benefit from increased surveillance.

  9. A functional EGF polymorphism, EGF serum levels and esophageal adenocarcinoma risk and outcome

    PubMed Central

    Lanuti, Michael; Liu, Geoffrey; Goodwin, Jonathan M.; Zhai, Rihong; Fuchs, Bryan C.; Asomaning, Kofi; Su, Li; Nishioka, Norman S.; Tanabe, Kenneth K.; Christiani, David C.

    2008-01-01

    Purpose: The epidermal growth factor (EGF) pathway is important in esophageal adenocarcinoma (EAC) tumorigenesis. We hypothesized that the EGF A61G homozygous variant genotype (GG) (i) is both a risk and poor prognostic factor for EAC; and (ii) is associated with higher EGF serum levels in individuals with gastroesophageal reflux disease (GERD). Experimental Design: Using unconditional logistic regression, we compared EGF A61G in 312 EAC cases and 447 GERD-free controls, adjusting for age, gender, smoking history and healthy adult body mass index. Using the method of Kaplan&Meier, log rank tests, and Cox proportional hazard models, we correlated EGF A61G with overall and failure-free survival in the EAC cases. Serum EGF levels and EGF genotype (G/G vs. others) were correlated in 144 GERD patients using Wilcoxon rank sum tests. Results: The EGF A61G G/G genotype conferred increased EAC risk with an adjusted odds ratio (AOR) of 1.81 (95% CI, 1.2-2.7), and was even higher in the subgroup of EAC patients with concurrent Barrett's esophagus (BE): AOR 2.18 (95%CI 1.3-3.7). However, EGF A61G was not associated with a more aggressive phenotype or prognosis in EAC patients. Higher serum EGF levels were found in GERD patients carrying G/G compared with A/A or A/G (p=0.03, Wilcoxon rank test). Conclusion: The EGF A61G G/G genotype is associated with a near 2-fold greater risk of EAC. The G/G allele was also associated with higher EGF levels in tumor free patients with GERD. EGF genotyping can potentially identify high risk patients with GERD and Barrett's metaplasia who might benefit from increased surveillance. PMID:18483390

  10. Magnitude of Missed Esophageal Adenocarcinoma After Barrett's Esophagus Diagnosis: A Systematic Review and Meta-analysis

    PubMed Central

    Visrodia, Kavel; Singh, Siddharth; Krishnamoorthi, Rajesh; Ahlquist, David A.; Wang, Kenneth K.; Iyer, Prasad G.; Katzka, David A.

    2016-01-01

    Background & Aims A proportion of patients with Barrett's esophagus (BE) are diagnosed with esophageal adenocarcinoma (EAC) within 1 year of an endoscopic examination that produced negative findings. These cases of missed cancers have not been well studied, despite current surveillance strategies for BE. We performed a systematic review and meta-analysis to determine the magnitude of missed EAC in cohorts of patients with BE. Methods We searched MEDLINE, EMBASE, and Web of Science from their inception to May 31, 2015 to identify cohort studies of adults with BE (baseline nondysplastic BE ± BE with low-grade dysplasia) and at least a 3-year follow-up period, providing data on missed and incident EACs (diagnosed within 1 year and diagnosed more than 1 year after the initial endoscopy in which BE was diagnosed, respectively). The main outcome measure was pooled proportion of missed and incident EACs (of all EACs detected after initial endoscopy) among BE cohorts, using a random effects model. Results In a metaanalysis of 24 studies reporting on 820 missed and incident EACs, 25.3% were classified as missed (95% confidence interval: 16.4%–36.8%) and 74.7% as incident EACs (95% CI: 63.2%–83.6%), although there was substantial heterogeneity among studies (I2 = 74%). When the analysis was restricted to nondysplastic BE cohorts (15 studies), 23.9% of EACs were classified as missed (95% confidence interval: 15.3%–35.4%; I2 = 0%). In a meta-analysis of 10 studies with follow-up periods of ≥5 years (a total of 239 EACs), 22.0% were classified as missed (95% confidence interval: 8.7%–45.5%), with substantial heterogeneity (I2 = 68%). Conclusions Among adults with nondysplastic BE (or BE with low-grade dysplasia) at their index endoscopy and at least a 3-year follow-up period, 25% of EACs are diagnosed within 1 year after the index endoscopy. Additional resources should be allocated to detect missed EAC. PMID:26619962

  11. Development, Calibration, and Validation of a U.S. White Male Population-Based Simulation Model of Esophageal Adenocarcinoma

    PubMed Central

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

    2010-01-01

    Background 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. Methods 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. Results 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. Conclusions The model serves as the foundation for future analyses to determine a cost-effective screening and management strategy to prevent EAC morbidity and mortality. PMID:20208996

  12. 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

  13. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy.

    PubMed

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008-2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC.

  14. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

    PubMed Central

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

  15. 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

  16. Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a Mendelian randomization study.

    PubMed

    Thrift, Aaron P; 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

    2014-11-01

    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. 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. 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/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses. 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

    PubMed Central

    Kuick, Rork; Thomas, Dafydd G.; Nadal, Ernest; Lin, Jules; Chang, Andrew C.; Reddy, Rishindra M.; Orringer, Mark B.; Taylor, Jeremy M. G.; Wang, Thomas D.; Beer, David G.

    2016-01-01

    The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies. PMID:27363029

  18. 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

  19. Preference of Endoscopic Ablation Over Medical Prevention of Esophageal Adenocarcinoma by Patients with Barrett's Esophagus

    PubMed Central

    Yachimski, Patrick; Wani, Sachin; Givens, Tonya; Howard, Eric; Higginbotham, Tina; Price, Angie; Berman, Kenneth; Hosford, Lindsay; Katcher, Paul Menard; Ozanne, Elissa; Perzan, Katherine; Hur, Chin

    2014-01-01

    Background & Aims Endoscopic intervention or pharmacologic inhibition of cyclooxygenase might be used to prevent progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC). We investigated whether patients with BE prefer endoscopic therapy or chemoprevention of EAC. Methods Eighty-one subjects with nondysplastic BE were given a survey that described 2 scenarios. The survey explained that treatment A (ablation), endoscopy, reduced lifetime risk of EAC by 50%, with a 5% risk for esophageal stricture, whereas treatment B (aspirin) reduced lifetime risk of EAC by 50% and the risk of heart attack by 30%, yet increased the risk for ulcer by 75%. Subjects indicated their willingness to undergo either treatment A and/or treatment B if endoscopic surveillance was required every 3–5 years, every 10 years, or was not required. Visual aids were included to represent risk and benefit percentages. Results When surveillance was required every 3–5 years, more subjects were willing to undergo treatment A than treatment B (78% [63/81] vs 53% [43/81], P<.01). There were no differences in age, sex, education level, or history of cancer, heart disease, or ulcer between patients willing to undergo treatment A and those willing to undergo treatment B. Altering the frequency of surveillance did not affect patients’ willingness to undergo either treatment. Conclusion In a simulated scenario, patients with BE preferred endoscopic intervention over chemoprevention for EAC. Further investigation may be warranted of the shared decision making process regarding preventive strategies for patients with BE. PMID:24681073

  20. GERD—Barrett—Adenocarcinoma: Do We Have Suitable Prognostic and Predictive Molecular Markers?

    PubMed Central

    Illig, Romana; Klieser, Eckhard; Kiesslich, Tobias; Neureiter, Daniel

    2013-01-01

    Due to unfavorable lifestyle habits (unhealthy diet and tobacco abuse) the incidence of gastroesophageal reflux disease (GERD) in western countries is increasing. The GERD-Barrett-Adenocarcinoma sequence currently lacks well-defined diagnostic, progressive, predictive, and prognostic biomarkers (i) providing an appropriate screening method identifying the presence of the disease, (ii) estimating the risk of evolving cancer, that is, the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC), (iii) predicting the response to therapy, and (iv) indicating an overall survival—prognosis for EAC patients. Based on histomorphological findings, detailed screening and therapeutic guidelines have been elaborated, although epidemiological studies could not support the postulated increasing progression rates of GERD to BE and EAC. Additionally, proposed predictive and prognostic markers are rather heterogeneous by nature, lack substantial proofs, and currently do not allow stratification of GERD patients for progression, outcome, and therapeutic effectiveness in clinical practice. The aim of this paper is to discuss the current knowledge regarding the GERD-BE-EAC sequence mainly focusing on the disputable and ambiguous status of proposed biomarkers to identify promising and reliable markers in order to provide more detailed insights into pathophysiological mechanisms and thus to improve prognostic and predictive therapeutic approaches. PMID:23573078

  1. Emotion regulation in patients with rheumatic diseases: validity and responsiveness of the Emotional Approach Coping Scale (EAC)

    PubMed Central

    Zangi, Heidi A; Garratt, Andrew; Hagen, Kåre Birger; Stanton, Annette L; Mowinckel, Petter; Finset, Arnstein

    2009-01-01

    Background Chronic rheumatic diseases are painful conditions which are not entirely controllable and can place high emotional demands on individuals. Increasing evidence has shown that emotion regulation in terms of actively processing and expressing disease-related emotions are likely to promote positive adjustment in patients with chronic diseases. The Emotional Approach Coping Scale (EAC) measures active attempts to acknowledge, understand, and express emotions. Although tested in other clinical samples, the EAC has not been validated for patients with rheumatic diseases. This study evaluated the data quality, internal consistency reliability, validity and responsiveness of the Norwegian version of the EAC for this group of patients. Methods 220 patients with different rheumatic diseases were included in a cross-sectional study in which data quality and internal consistency were assessed. Construct validity was assessed through comparisons with the Brief Approach/Avoidance Coping Questionnaire (BACQ) and the General Health Questionnaire (GHQ-20). Responsiveness was tested in a longitudinal pretest-posttest study of two different coping interventions, the Vitality Training Program (VTP) and a Self-Management Program (SMP). Results The EAC had low levels of missing data. Results from principal component analysis supported two subscales, Emotional Expression and Emotional Processing, which had high Cronbach's alphas of 0.90 and 0.92, respectively. The EAC had correlations with approach-oriented items in the BACQ in the range 0.17-0.50. The EAC Expression scale had a significant negative correlation with the GHQ-20 of -0.13. As hypothesized, participation in the VTP significantly improved EAC scores, indicating responsiveness to change. Conclusion The EAC is an acceptable and valid instrument for measuring emotional processing and expression in patients with rheumatic diseases. The EAC scales were responsive to change in an intervention designed to promote emotion

  2. D-mannose: a novel prognostic biomarker for patients with esophageal adenocarcinoma.

    PubMed

    Gu, Jianchun; Liang, Dong; Pierzynski, Jeanne A; Zheng, Leizhen; Ye, Yuanqing; Zhang, Jinhua; Ajani, Jaffer A; Wu, Xifeng

    2017-02-01

    Metabolomic profiling is a promising approach to identify new biomarkers for cancer prognosis. However, the role of circulating metabolites as prognostic indicators in esophageal adenocarcinoma (EAC) has not been well explored. In this study, we aimed to evaluate the prognostic value of three serum metabolites, d-mannose, l-proline (LP), and 3-hydroxybutyrate (BHBA), which were significantly different between EAC patients and controls, identified through a global and targeted metabolite profiling. We measured the levels of d-mannose, LP, and BHBA in pretreatment serum from 159 EAC patients, using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) methods. A multivariable Cox model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of these metabolites with recurrence and overall survival. We found that serum levels of d-mannose were significantly associated with recurrence and overall survival in EAC patients, whereas levels of LP and BHBA were not. Compared with patients with a low (first tertile) level of d-mannose, those with a high (second plus third tertiles) level had 49% reduced risk of recurrence (HR = 0.51; 95% CI: 0.29-0.91; P = 0.02), and 56% reduced risk of death (HR = 0.44; 95% CI: 0.25-0.77, P < 0.01). The significant association of high d-mannose levels with better prognosis was consistent among patients with early-stage and advanced-stage EAC. Our results suggest that serum level of d-mannose may be used as a novel prognostic biomarker for patients with EAC. Further studies in independent populations are warranted to confirm our findings. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. An immunofluorescent method for characterization of Barrett's esophagus cells.

    PubMed

    Inge, Landon J; Fowler, Aaron J; Bremner, Ross M

    2014-07-20

    Esophageal adenocarcinoma (EAC) has an overall survival rate of less than 17% and incidence of EAC has risen dramatically over the past two decades. One of the primary risk factors of EAC is Barrett's esophagus (BE), a metaplastic change of the normal squamous esophagus in response to chronic heartburn. Despite the well-established connection between EAC and BE, interrogation of the molecular events, particularly altered signaling pathways involving progression of BE to EAC, are poorly understood. Much of this is due to the lack of suitable in vitro models available to study these diseases. Recently, immortalized BE cell lines have become commercially available allowing for in vitro studies of BE. Here, we present a method for immunofluorescent staining of immortalized BE cell lines, allowing in vitro characterization of cell signaling and structure after exposure to therapeutic compounds. Application of these techniques will help develop insight into the mechanisms involved in BE to EAC progression and provide potential avenues for treatment and prevention of EAC.

  4. Geographic Distribution of Regional Metastatic Nodes Affects Outcome of Trimodality-Eligible Patients with Esophageal Adenocarcinoma

    PubMed Central

    Shiozaki, Hironori; Slack, Rebecca; Sudo, Kazuki; Elimova, Elena; Wadhwa, Roopma; Chen, Hsiang-Chun; Skinner, Heath D.; Komaki, Ritsuko; Lee, Jeffrey H.; Weston, Brian; Bhutani, Manoop S.; Blum, Mariela A.; Rogers, Jane E.; Maru, Dipen M.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2014-01-01

    Background Malignant nodes in patients with localized esophageal adenocarcinoma (L-EAC) portend a poor prognosis. We assessed the distribution of nodes to correlate with outcome of patients undergoing chemoradiation/surgery (trimodality). Methods We studied 209 L-EAC patients who had confirmed or suspicious nodes at baseline staging. All patients had trimodality therapy. Patients were grouped by nodal geography: above the diaphragm (AD), below the diaphragm (BD), or above and below the diaphragm (ABD). Survival estimates were calculated using the Kaplan-Meier method. The outcomes in subgroups were assessed by the log-rank test. Results Patients were primarily Caucasians (91%), men (93%), and had baseline stage III L-EAC (89%). The median follow-up was 2.8 years (range, 0.4 to 11.7 years). Of the 209 patients, 35% (n=73) had nodes AD, 20% (n=41) had nodes BD, and 45% (n=95) had nodes ABD. ABD patients had the 5-year overall survival rate of 33% compared to AD patients (55%) and BD (60%; P=0.02). Patients with higher histology grade were also at higher risk of relapse and had poor survival (P<0.01 for both). Conclusions L-EAC patients in the ABD group had worst outcome after trimodality compared to those in the AD or BD group. Novel strategies are needed for ABD patients. PMID:25765098

  5. Emerging therapeutic targets in esophageal adenocarcinoma

    PubMed Central

    Gaur, Puja; Hunt, Clayton R.; Pandita, Tej K.

    2016-01-01

    The incidence of gastro-esophageal disease and associated rate of esophageal adenocarcinoma (EAC) is rising at an exponential rate in the United States. However, research targeting EAC is lagging behind, and much research is needed in the field to identify ways to diagnose EAC early as well as to improve the rate of pathologic complete response (pCR) to systemic therapies. Esophagectomy with subsequent reconstruction is known to be a morbid procedure that significantly impacts a patient's quality of life. If indeed the pCR rate of patients can be improved and those patients destined to be pCR can be identified ahead of time, they may be able to avoid this life-altering procedure. While cancer-specific biological pathways have been thoroughly investigated in other solid malignancies, much remains unexplored in EAC. In this review, we will highlight some of the latest research in the field in regards with EAC, along with new therapeutic targets that are currently being explored. After reviewing conventional treatment and current changes in medical therapy for EAC, we will focus on unchartered grounds such as cancer stem cells, genetics and epigenetics, immunotherapy, and chemoradio-resistant pathways as we simultaneously propose some investigational possibilities that could be applicable to EAC. PMID:27102294

  6. A Quantitative Investigation of Fucosylated Serum Glycoproteins with Application to Esophageal Adenocarcinoma

    PubMed Central

    Mann, Benjamin; Madera, Milan; Klouckova, Iveta; Mechref, Yehia; Dobrolecki, Lacey E.; Hickey, Robert J.; Hammoud, Zane T.; Novotny, Milos V.

    2011-01-01

    Whereas glycoproteomic studies provide unique opportunities for cancer research, it has been necessary to develop specific methods for analysis of oncologically interesting glycoproteins. We describe a general, multimethodological approach for quantitative glycoproteomic analysis of fucosylated glycoproteins in human blood serum. A total of 136 putative fucosylated glycoproteins were identified with very high confidence in three clinically relevant sample pools (N=5 for each), with a mean coefficient of variation of 3.1% observed for replicate analyses. Two samples were collected from subjects diagnosed with esophagus disease states, high-grade dysplasia (HGD) plus esophageal adenocarcinoma (EAC), while the third sample was representative of a disease-free (DF) condition. Some glycoproteins, observed to be significantly upregulated in EAC, i.e. more than 2-fold higher than in the DF condition, are briefly discussed. Further investigation will be necessary to validate these findings; however, the method itself is demonstrated to be an effective tool for quantitative glycoproteomics of clinical samples. PMID:20446296

  7. Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk

    PubMed Central

    Cheung, Winson Y.; Zhai, Rihong; Kulke, Matthew H.; Heist, Rebecca S.; Asomaning, Kofi; Ma, Clement; Wang, Zhaoxi; Su, Li; Lanuti, Michael; Tanabe, Kenneth K.; Christiani, David C.

    2009-01-01

    Background: Single-nucleotide polymorphisms of key cancer genes, such as EGF A61G, are associated with an elevated risk of esophageal adenocarcinoma (EAC). As gastroesophageal reflux disease (GERD) is an established risk factor for EAC, we evaluated whether the association between epidermal growth factor (EGF) polymorphism and EAC development is altered by the presence of GERD. Methods: EGF genotyping of DNA samples was performed and GERD history was collected for 309 EAC patients and 275 matched healthy controls. Associations between genotypes and EAC risk were evaluated using adjusted logistic regression. Genotype–GERD relationships were explored using analyses stratified by GERD history and joint effects models that considered severity and duration of GERD symptoms. Results: EGF variants (A/G or G/G) were more common (P = 0.02) and GERD was more prevalent (P < 0.001) in cases than in controls. When compared with the EGF wild-type A/A genotype, the G/G variant was associated with a substantial increase in EAC risk among individuals with GERD [Odds ratio 9.7; 95% confidence interval (CI), 3.8–25.0; P < 0.001] and a slight decrease in risk for GERD-free individuals (odds ratio 0.4; 95% CI = 0.22–0.90; P = 0.02). In the joint effects models, the odds of EAC was also highest for G/G patients (when compared with A/A) who either experienced frequent GERD of more than once per week (odds ratio 21.8; 95% CI = 5.1–94.0; P < 0.001) or suffered GERD for longer than 15 years (odds ratio 22.4; 95% CI = 6.5–77.6; P < 0.001). There was a highly significant interaction between the G/G genotype and the presence of GERD (P < 0.001). Conclusions: EGF A61G polymorphism may alter EAC susceptibility through an interaction with GERD. PMID:19520791

  8. Incidence of Esophageal Adenocarcinoma and Causes of Mortality After Radiofrequency Ablation of Barrett's Esophagus.

    PubMed

    Wolf, W Asher; Pasricha, Sarina; Cotton, Cary; Li, Nan; Triadafilopoulos, George; Muthusamy, V Raman; Chmielewski, Gary W; Corbett, F Scott; Camara, Daniel S; Lightdale, Charles J; Wolfsen, Herbert; Chang, Kenneth J; Overholt, Bergein F; Pruitt, Ron E; Ertan, Atilla; Komanduri, Srinadh; Infantolino, Anthony; Rothstein, Richard I; Shaheen, Nicholas J

    2015-12-01

    Radiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Review: Experimental models for Barrett's esophagus and esophageal adenocarcinoma

    PubMed Central

    Orlando, Roy C.; Chen, Xiaoxin

    2012-01-01

    Several different cell culture systems and laboratory animal models have been used over the years to study Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Most of the existing models have key differences with the human esophagus and complex pathogenesis of disease. None of the models offers an ideal system for the complex study of environmental exposure, genetic risk, and prevention strategies. In fact, different model systems may be required to answer different specific research questions about the pathogenesis of BE and EAC. Given the high mortality associated with EAC and the fact that current screening strategies miss most cases of EAC, advances in basic and translational science related to esophageal injury, repair, and carcinogenesis are clearly needed. This review describes several of the existing and potential model systems for BE and EAC with their benefits and disadvantages. PMID:22421618

  10. A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study.

    PubMed

    O'Doherty, Mark G; Freedman, Neal D; Hollenbeck, Albert R; Schatzkin, Arthur; Abnet, Christian C

    2012-09-01

    The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma. Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIH-AARP cohort. 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric cardia adenocarcinoma risk (highest (≥35 kg/m(2)) vs referent (18.5-<25 kg/m(2)); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5-<25 kg/m(2)). Mutual adjustment of WHR and BMI attenuated both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia. Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI.

  11. The importance of delivery rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett’s and Esophageal Adenocarcinoma Consortium

    PubMed Central

    Lubin, Jay H.; Cook, Michael B.; Pandeya, Nirmala; Vaughan, Thomas L.; Abnet, Christian C.; Giffen, Carol; Webb, Penelope M.; Murray, Liam J.; Casson, Alan G.; Risch, Harvey A.; Ye, Weimin; Kamangar, Farin; Bernstein, Leslie; Sharp, Linda; Nyrén, Olof; Gammon, Marilie D.; Corley, Douglas A.; Wu, Anna H.; Brown, Linda M.; Chow, Wong-Ho; Ward, Mary H.; Freedman, Neal D.; Whiteman, David C.

    2012-01-01

    Background Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. Methods The authors pooled data from 12 case-control studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1,242 (EAC), 1,263 (EGJA) and 954 (ESCC) cases and 7,053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. Results For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01). Conclusions Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases. PMID:22504051

  12. Bioassay of Eucalyptus extracts for anticancer activity against Ehrlich ascites carcinoma (eac) cells in Swiss albino mice

    PubMed Central

    Islam, Farhadul; Khatun, Hasina; Ghosh, Soby; Ali, MM; Khanam, JA

    2012-01-01

    Objective To evaluate the antineoplastic activity of Eucalyptus extract (EuE) against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Methods Preliminary examination of four plant extracts (namely Eucalyptus, Costus, Azadirachta, Feronia) has been done by observing the reduction ability of number of EAC cells in previously inoculated Swiss albino mice. Among them as EuE showed maximum capability, the whole study has been conducted with EuE only. Important parameters viz. enhancement of life span, reduction of average tumor weight etc. have been studied. In addition the effects of EuE on hematological parameters in both normal and EAC inoculated mice have been measured. Effect of EuE on normal peritoneal cells has also been studied. Results : EuE reduced tumor burden remarkably. It reduced the tumor growth rate and enhanced the life span of EAC bearing mice noticeably. It reversed back the hematological parameters towards normal, reduced the trasplantability of EAC cells and enhanced the immunomodulatory effects in mice. The host toxic effect of EuE in mice is minimum and mostly reversible with time. All such data have been compared with those obtained by running parallel experiments with bleomycin at dose 0.3 mg/kg (i.p.). Conclusions The Eucalyptus extract may be considered as a potent anticancer agent for advanced researches. PMID:23569937

  13. Local synthesis of pepsin in Barrett’s esophagus and the role of pepsin in esophageal adenocarcinoma

    PubMed Central

    Samuels, Tina; Hoekzema, Craig; Gould, Jon; Goldblatt, Matthew; Frelich, Matthew; Bosler, Matthew; Lee, Sang-Hyuk; Johnston, Nikki

    2016-01-01

    Objective Despite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated. Methods Normal and Barrett’s biopsies from eight Barrett’s esophagus patients were collected for pepsin analysis via Western blot and RT-PCR. Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1mg/ml; 1-20hours), acid (pH4) +/− pepsin (5minutes); real-time RT-PCR, ELISA and cell migration were assayed. Results Pepsin was detected in all eight Barrett’s, and four of eight adjacent normal specimens. Pepsinogen mRNA was observed in two Barrett’s, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL1β expression and cell migration in vitro. Conclusions Pepsin is synthesized by metaplastic, Barrett’s esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in prevention of EAC. PMID:26077392

  14. MicroRNA Signature Characterizes Primary Tumors That Metastasize in an Esophageal Adenocarcinoma Rat Model

    PubMed Central

    Zaidi, Ali H.; Saldin, Lindsey T.; Kelly, Lori A.; Bergal, Linda; Londono, Ricardo; Kosovec, Juliann E.; Komatsu, Yoshihiro; Kasi, Pashtoon M.; Shetty, Amit A.; Keane, Timothy J.; Thakkar, Shyam J.; Huleihel, Luai; Landreneau, Rodney J.; Badylak, Stephen F.; Jobe, Blair A.

    2015-01-01

    Objective To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC). Background The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies. Methods The modified Levrat’s surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors. Results The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2. Conclusion In vivo metastasis was confirmed in the modified Levrat’s model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized. PMID:25826212

  15. MicroRNAs in Barrett’s esophagus and esophageal adenocarcinoma

    PubMed Central

    Kan, Takatsugu

    2009-01-01

    Summary The molecular genetics of Barrett’s Esophagus (BE) and its evolution to esophageal adenocarcinoma (EAC) have been widely studied, however, the molecular mechanism of BE-EAC carcinogenesis has not been completely understood. MicroRNA (miRNA) is now essential to understanding the molecular mechanism of cancer progression. Recent findings include the following: (1) miRNA expression profiles can distinguish between BE and EAC; (2) miR-196a is upregulated in EAC tissues targeting annexin A1, thereby exerting anti-apoptotic effects and contributing to EAC cell survival; miR-196a may also constitute a good biomarker of progression during BE-EAC carcinogenesis; and (3) The miR-106b-25 polycistron is activated by genomic amplification and is involved in esophageal neoplastic progression and proliferation via suppression of two target genes, p21 and Bim. PMID:19773200

  16. A Classification Method Based on Principal Components of SELDI Spectra to Diagnose of Lung Adenocarcinoma

    PubMed Central

    Xiong, Li-Wen; Wang, Yi; Geng, Jun-Feng; Feng, Jiu-Xian; Han, Bao-Hui; Bao, Guo-Liang; Yang, Yu; Wang, Xiaotian; Jin, Li; Guo, Wensheng; Wang, Jiu-Cun

    2012-01-01

    Purpose Lung cancer is the leading cause of cancer death worldwide, but techniques for effective early diagnosis are still lacking. Proteomics technology has been applied extensively to the study of the proteins involved in carcinogenesis. In this paper, a classification method was developed based on principal components of surface-enhanced laser desorption/ionization (SELDI) spectral data. This method was applied to SELDI spectral data from 71 lung adenocarcinoma patients and 24 healthy individuals. Unlike other peak-selection-based methods, this method takes each spectrum as a unity. The aim of this paper was to demonstrate that this unity-based classification method is more robust and powerful as a method of diagnosis than peak-selection-based methods. Results The results showed that this classification method, which is based on principal components, has outstanding performance with respect to distinguishing lung adenocarcinoma patients from normal individuals. Through leaving-one-out, 19-fold, 5-fold and 2-fold cross-validation studies, we found that this classification method based on principal components completely outperforms peak-selection-based methods, such as decision tree, classification and regression tree, support vector machine, and linear discriminant analysis. Conclusions and Clinical Relevance The classification method based on principal components of SELDI spectral data is a robust and powerful means of diagnosing lung adenocarcinoma. We assert that the high efficiency of this classification method renders it feasible for large-scale clinical use. PMID:22461913

  17. 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... Virtual Meeting Room at http://www.eac.gov . Once at the main page of EAC's Web site, viewers should click the link to the Board of Advisors Virtual Meeting Room. The virtual meeting room will open on...

  18. Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy

    PubMed Central

    Kumar, Sacheen; Abbassi-Ghadi, Nima; Salm, Max; Mitter, Richard; Horswell, Stuart; Rowan, Andrew; Phillimore, Benjamin; Biggs, Jennifer; Begum, Sharmin; Matthews, Nik; Hochhauser, Daniel; Hanna, George B; Swanton, Charles

    2015-01-01

    Esophageal adenocarcinomas (EACs) are associated with dismal prognosis. Deciphering the evolutionary histories of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable EACs, before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of EACs with the presence of heterogeneous driver mutations, parallel evolution, early genome doubling events and an association between high intratumor heterogeneity and poor response to NAC. Multi-region sequencing demonstrated a significant reduction in T>G mutations within a CTT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of C>A mutations within a CpC context following NAC. EACs are characterized by early chromosomal instability leading to amplifications containing targetable oncogenes persisting through chemotherapy, providing a rationale for future therapeutic approaches. PMID:26003801

  19. Overview of major molecular alterations during progression from Barrett's esophagus to esophageal adenocarcinoma.

    PubMed

    Kalatskaya, Irina

    2016-10-01

    Esophageal adenocarcinoma (EAC) develops in the sequential transformation of normal epithelium into metaplastic epithelium, called Barrett's esophagus (BE), then to dysplasia, and finally cancer. BE is a common condition in which normal stratified squamous epithelium of the esophagus is replaced with an intestine-like columnar epithelium, and it is the most prominent risk factor for EAC. This review aims to impartially systemize the knowledge from a large number of publications that describe the molecular and biochemical alterations occurring over this progression sequence. In order to provide an unbiased extraction of the knowledge from the literature, a text-mining methodology was used to select genes that are involved in the BE progression, with the top candidate genes found to be TP53, CDKN2A, CTNNB1, CDH1, GPX3, and NOX5. In addition, sample frequencies across analyzed patient cohorts at each stage of disease progression are summarized. All six genes are altered in the majority of EAC patients, and accumulation of alterations correlates well with the sequential progression of BE to cancer, indicating that the text-mining method is a valid approach for gene prioritization. This review discusses how, besides being cancer drivers, these genes are functionally interconnected and might collectively be considered a central hub of BE progression. © 2016 New York Academy of Sciences.

  20. The Resistance of Esophageal Adenocarcinoma to Bile Salt Insult is Associated with Manganese Superoxide Dismutase Expression

    PubMed Central

    Schiffman, Suzanne C.; Li, Yan; Xiao, Deyi; Li, Xuanshe; Aiyer, Harini S.; Martin, Robert C.G.

    2010-01-01

    BACKGROUND Bile acids are implicated as etiologic agents in esophageal cancer. We sought to analyze the impact of bile acid exposure on esophageal epithelial cells, Barrett’s metaplastic cells (BE), esophageal adenocarcinoma cells (EAC) and esophageal squamous carcinoma cell (ESC). We sought to determine if cellular resistance is related to manganese superoxide dismutase expression. METHODS Cells were exposed to sodium choleate (CA), sodium deoxycholate (DCA), sodium glycocholate (GCA), sodium taurocholate (TCA) or a 1:1 mixture (MIX) of reagents at concentrations ranging 0.2 – 0.8 mM. Cell viability was evaluated by MTT assay. MnSOD expression was analyzed by Western Blot. Statistical analysis was performed using SPSS 17.0. RESULTS Bile salt exposure inhibited cell viability in esophageal squamous cells in time and growth dependent manner. There was a 50% decrease in cell viability from four to 24 hours. BE, EAC and ESC cell lines were more resistant to bile insult. In untreated cell lines, MnSOD expression was significantly decreased in EAC and ESC cell lines as compared to esophageal squamous epithelial cells and BE cells (p=0.002). Exposure of ESC cells to bile salt increased MnSOD expression. DISCUSSION The confirmation of the role of ROS and bile acids in esophageal carcinogenesis has interesting implications for chemoprevention in patients with reflux esophagitis and Barrett’s esophagus. Further studies are necessary to assess the preventative role of antioxidant supplementation PMID:20638682

  1. 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

    ... COMMISSION Sunshine Act; Notice of Virtual Public Forum for EAC Standards Board; Notice of Virtual Public... 19, 2010, 9 p.m. EST. PLACE: EAC Standards Board Virtual Meeting Room at www.eac.gov . Once at ] the main page of EAC's Web site, viewers should click the link to the Standards Board Virtual Meeting...

  2. Targeting chemokine pathways in esophageal adenocarcinoma

    PubMed Central

    Shrivastava, Makardhwaj S; Hussain, Zulfiqar; Giricz, Orsolya; Shenoy, Niraj; Polineni, Rahul; Maitra, Anirban; Verma, Amit

    2014-01-01

    Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets. PMID:25485576

  3. Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

    PubMed

    Kauttu, T; Mustonen, H; Vainionpää, S; Krogerus, L; Ilonen, I; Räsänen, J; Salo, J; Puolakkainen, P

    2017-01-01

    Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

  4. Locoregional Failure Rate After Preoperative Chemoradiation of Esophageal Adenocarcinoma and the Outcomes of Salvage Strategies

    PubMed Central

    Sudo, Kazuki; Taketa, Takashi; Correa, Arlene M.; Campagna, Maria-Claudia; Wadhwa, Roopma; Blum, Mariela A.; Komaki, Ritsuko; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Skinner, Heath D.; Maru, Dipen M.; Rice, David C.; Swisher, Stephen G.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2013-01-01

    Purpose The primary purpose of surveillance of patients with esophageal adenocarcinoma (EAC) and/or esophagogastric junction adenocarcinoma after local therapy (eg, chemoradiotherapy followed by surgery or trimodality therapy [TMT]) is to implement a potentially beneficial salvage therapy to overcome possible morbidity/mortality caused by locoregional failure (LRF). However, the benefits of surveillance are not well understood. We report on LRFs and salvage strategies in a large cohort. Patients and Methods Between 2000 and 2010, 518 patients with EAC who completed TMT were analyzed for the frequency of LRF over time and salvage therapy outcomes. Standard statistical techniques were used. Results For 518 patients, the median follow-up time was 29.3 months (range, 1 to 149 months). Distant metastases (with or without LRF) occurred in 188 patients (36%), and LRF only occurred in 27 patients (5%). Eleven of 27 patients had lumen-only LRF. Most LRFs (89%) occurred within 36 months of surgery. Twelve patients had salvage chemoradiotherapy, but only five survived more than 2 years. Four patients needed salvage surgery, and three who survived more than 2 years developed distant metastases. The median overall survival of 27 patients with LRF was 17 months, and 10 patients (37%) survived more than 2 years. Thus, only 2% of all 518 patients benefited from surveillance/salvage strategies. Conclusion Our surveillance strategy, which is representative of many others currently being used, raises doubts about its effectiveness and benefits (along with concerns regarding types and times of studies and costs implications) to patients with EAC who have LRF only after TMT. Fortunately, LRFs are rare after TMT, but the salvage strategies are not highly beneficial. Our data can help develop an evidence-based surveillance strategy. PMID:24145339

  5. Proton Pump Inhibitors Do Not Reduce the Risk of Esophageal Adenocarcinoma in Patients with Barrett’s Esophagus: A Systematic Review and Meta-Analysis

    PubMed Central

    Hu, Qiang; Sun, Tian-Tian; Hong, Jie; Fang, Jing-Yuan; Xiong, Hua; Meltzer, Stephen J.

    2017-01-01

    Objectives Proton pump inhibitors (PPIs) have been used for treatment of Barrett's esophagus (BE) for many years. However, the connection between PPIs and esophageal adenocarcinoma (EAC) in patients with BE has still been controversial. The current systematic review and meta-analysis was designed to evaluate the association between PPIs and the risk of EAC or high-grade dysplasia (HGD) in patients with BE. Methods A systematic literature search of studies reporting the association between PPIs and the risk of EAC and/or HGD in patients with BE was conducted in PubMed, Embase, Web of Science and the Cochrane Library. Next, literature was screened using previously established criteria and relevant data were extracted from included studies. Finally, the software program Review Manage 5.2 was applied to aggregate data and analyze the results. Results Nine observational studies, comprising five cohort and four case-control studies (including a total of 5712 patients with BE), were identified. Upon meta-analysis, PPIs were found to have no association with the risk of EAC and/or HGD in patients with BE (unadjusted OR 0.43, 95% CI 0.17–1.08). Analysis for duration response relationship revealed no significant trend toward protection against EAC or HGD with PPIs usage for >2~3 years (one study using 7-year cutoff) when compared to usage for shorter time periods (PPIs usage >2~3 years vs. <2~3 years: OR 0.91 (95% CI 0.25–3.31) vs. 0.91 (0.40–2.07)).There also was considerable heterogeneity between studies. Conclusion No dysplasia- or cancer-protective effects of PPIs usage in patients with BE were identified by our analysis. Therefore, we conclude that clinicians who discuss the potential chemopreventive effects of PPIs with their patients, should be aware that such an effect, if exists, has not been proven with statistical significance. PMID:28072858

  6. Results from an ensemble prediction study of the East Australian Current (EAC)

    NASA Astrophysics Data System (ADS)

    O'Kane, Terence

    2010-05-01

    We present results from an ensemble prediction study of the East Australian Current (EAC) with a specific focus on the examination of the role of dynamical instabilities and flow dependent errors of the day. We frame our experiment in an operational setting utilizing the Australian Bureau of Meteorology's Ocean Model Analysis and Prediction System (OceanMAPS) comprising both global and nested regional ocean forecast models based on MOM4p1 initialized by the Bluelink Ocean Data Assimilation System (BODAS). The forecast ensemble perturbations are generated using the method of bred vectors allowing the identification of those perturbations to a given initial state which grow most rapidly. We consider a 6 month period spanning the Australian summer beginning in mid November through to mid May which corresponds to the period of maximum eddy variability. We find that the bred vector structures align with and anticorrelate with the forecast errors and that these structures typically occur in known areas of instability and in particular where the EAC boundary current separates. The forecast error for the ensemble average are substantially reduced, even for very small numbers of realizations, and in many cases the vertical extent of the forecast error is reduced by an order of magnitude. Our results suggest that one may augment the static background error covariances typically used in operational ocean data assimilation systems with flow dependent background errors from a relatively cheap ensemble prediction system.

  7. 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.

  8. 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 26, 2010, 9 a.m. EDT through Friday, April 30, 2010, 9 p.m. EDT. Place: EAC Board of Advisors Virtual... link to the Board of Advisors Virtual Meeting Room. The virtual meeting room will open on Monday,...

  9. 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, 2010, 9 a.m. EDT through Friday, May 14, 2010, 9 p.m. EDT. Place: EAC Standards Board Virtual Meeting... the Standards Board Virtual Meeting Room. The virtual meeting room will open on Monday, May 3,...

  10. 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

    ... COMMISSION Notice: Request for Substantive Comments on the EAC's Procedural Manual for the Election Assistance Commission's Pilot Voting System Testing and Certification Program Manual AGENCY: United States.... Election Assistance Commission (EAC) is publishing a procedural manual for its Pilot Voting System Testing...

  11. A Structure Standard for Archival Context: EAC-CPF Is Here

    ERIC Educational Resources Information Center

    Dryden, Jean

    2010-01-01

    The archival community's new descriptive standard, "Encoded Archival Context" for Corporate Bodies, Persons, and Families (EAC-CPF), supports the sharing of descriptions of records creators and is a significant addition to the suite of standards for archival description. EAC-CPF is a data structure standard similar to its older sibling EAD…

  12. A Structure Standard for Archival Context: EAC-CPF Is Here

    ERIC Educational Resources Information Center

    Dryden, Jean

    2010-01-01

    The archival community's new descriptive standard, "Encoded Archival Context" for Corporate Bodies, Persons, and Families (EAC-CPF), supports the sharing of descriptions of records creators and is a significant addition to the suite of standards for archival description. EAC-CPF is a data structure standard similar to its older sibling EAD…

  13. Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma

    PubMed Central

    Rubenstein, Joel H.; Shaheen, Nicholas J.

    2015-01-01

    Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence in Western cultures. Barrett’s esophagus (BE) is the presumed precursor lesion for this cancer. Several other risk factors for this cancer have been described, including chronic heartburn, tobacco use, Caucasian race, and obesity. Despite these known associations, most patients with EAC present with symptoms of dysphagia from late-stage tumors—only a small minority of patients are identified in screening and surveillance programs. Diagnostic analysis of EAC usually commences with upper endoscopy, followed by cross-sectional imaging. Endoscopic ultrasound is useful to assess local extent of disease as well as the involvement regional lymph nodes. T1a EAC may be treated endoscopically; some patients with T1b disease might also benefit from endoscopic therapy. Locally advanced disease is generally managed with esophagectomy, often accompanied by neoadjuvant chemoradiotherapy or chemotherapy. The prognosis is based on tumor stage: patients with T1a tumors have an excellent prognoses, whereas few patients with advanced disease have longterm survival. PMID:25957861

  14. Comprehensive Genomic Profiling of Advanced Esophageal Squamous Cell Carcinomas and Esophageal Adenocarcinomas Reveals Similarities and Differences.

    PubMed

    Wang, Kai; Johnson, Adrienne; Ali, Siraj M; Klempner, Samuel J; Bekaii-Saab, Tanios; Vacirca, Jeffrey L; Khaira, Depinder; Yelensky, Roman; Chmielecki, Juliann; Elvin, Julia A; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S

    2015-10-01

    Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations. Next-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of >650× for all coding exons of 315 cancer-related genes plus selected introns from 28 genes frequently rearranged in cancer. Results from a single sample were evaluated for all classes of genomic alterations (GAs) including point mutations, short insertions and deletions, gene amplifications, homozygous deletions, and fusions/rearrangements. Clinically relevant genomic alterations (CRGAs) were defined as alterations linked to approved drugs and those under evaluation in mechanism-driven clinical trials. There were no significant differences by sex for either tumor type, and the median age for all patients was 63 years. All ESCCs and EACs were at an advanced stage at the time of sequencing. All 71 ESCCs and 231 EACs featured GAs on profiling, with 522 GAs in ESCC (7.4 per sample) and 1,303 GAs in EAC (5.6 per sample). The frequency of clinically relevant GAs in ESCC was 94% (2.6 per sample) and 93% in EAC (2.7 per sample). CRGAs occurring more frequently in EAC included KRAS (23% EAC vs. 6% ESCC) and ERBB2 (23% EAC vs. 3% ESCC). ESCC samples were enriched for CRGA in PIK3CA (24% ESCC vs. 10% EAC), PTEN (11% ESCC vs. 4% EAC), and NOTCH1 (17% ESCC vs. 3% EAC). Other GAs that differed significantly between histologic tumor types included SMAD4 (14% EAC

  15. 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

  16. Post-trimodality expression levels of metadherin (MTDH) as a prognostic biomarker for esophageal adenocarcinoma patients.

    PubMed

    Mizrak Kaya, Dilsa; Dong, Xiaochuan; Nogueras-González, Graciela M; Xu, Yan; Estrella, Jeannelyn S; Harada, Kazuto; Lopez, Anthony; Amlashi, Fatemeh G; Hofstetter, Wayne L; Maru, Dipen M; Nguyen, Quynh-Nhu; Lee, Jeffrey H; Weston, Brian; Bhutani, Manoop S; Erasmus, Jeremy J; Thomas, Irene; Rogers, Jane E; Song, Shumei; Ajani, Jaffer A

    2017-08-01

    Resectable esophageal adenocarcinoma (EAC) patients often receive chemoradiation followed by surgery. However, most patients experience recurrences. Overexpression of MTDH, an oncoprotein with multiple functions, has been found to be associated with poor prognosis in breast cancer, glioblastoma, melanoma and various gastrointestinal malignancies, but not in EAC. We sought to establish its role in resistant EAC (post-treatment residual EAC). MTDH was assessed by immunohistochemistry in resected EAC, and results were correlated with clinical outcomes. MTDH expression was detectable in 72.5% (50/69) of patients, while expression levels were high (positive) in 50.7% (35/69). Of 69 patients analyzed, 25 had no relapse and 44 patients had a relapse (8 with local-regional and 36 with distant). The median follow-up duration was 3 years (0.4-11.6). The median overall survival was not associated with MTDH status (2.79 years for MTDH-negative and 3.60 years for MTDH-positive patients, p = 0.121). In addition, MTDH was not associated with either the type of relapse (local or distant), baseline clinical stage, tumor grade, presence of signet ring cells, surgical (yp) stage, percentage of residual EAC or presence of lymphovascular invasion. Our data reveal that MTDH is not a prognostic biomarker in resistant EAC after trimodality therapy.

  17. 75 FR 16088 - Notice: Request for Substantive Comments on the EAC's Proposed Requirements for the Testing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ...) Quality Assurance. (6) Configuration Management. (7) Technical Data Package. (8) Systems Users Manual... Procedures Act (APA). It is a voluntary effort by the EAC to gather input from the public on the EAC's... by the EAC for public comment is not intended to make any of the APA's rulemaking...

  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. Advances in the management of Barrett’s esophagus and early esophageal adenocarcinoma

    PubMed Central

    Singh, Ajaypal; Chak, Amitabh

    2015-01-01

    The incidence of esophageal adenocarcinoma (EAC) has markedly increased in the United States over the last few decades. Barrett’s esophagus (BE) is the most significant known risk factor for this malignancy. Theoretically, screening and treating early BE should help prevent EAC but the exact incidence of BE and its progression to EAC is not entirely known and cost-effectiveness studies for Barrett’s screening are lacking. Over the last few years, there have been major advances in our understanding of the epidemiology, pathogenesis and endoscopic management of BE. These developments focus on early recognition of advanced histology and endoscopic treatment of high-grade dysplasia. Advanced resection techniques now enable us to endoscopically treat early esophageal cancer. In this review, we will discuss these recent advances in diagnosis and treatment of Barrett’s esophagus and early esophageal adenocarcinoma. PMID:26486568

  20. Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.

    PubMed

    Schumacher, Sarah; Bartenhagen, Christoph; Hoffmann, Martin; Will, Daniel; Fischer, Johannes C; Baldus, Stephan E; Vay, Christian; Fluegen, Georg; Dizdar, Levent; Vallböhmer, Daniel; Klein, Christoph A; Knoefel, Wolfram T; Stoecklein, Nikolas H; Möhlendick, Birte

    2017-08-22

    Chromosomal instability (CIN) has repeatedly been identified as a prognostic marker. Here we evaluated the percentage of aberrant genome per cell (PAG) as a measure of CIN in single disseminated tumour cells (DTC) isolated from patients with operable oesophageal adenocarcinoma (EAC), to assess the impact of CIN(high) DTCs on prognosis. We isolated CK18(positive) DTCs from bone marrow (BM) or lymph node (LN) preparations of operable EAC patients. After whole-genome amplification, single DTCs were analysed for chromosomal gains and losses using metaphase-based comparative genomic hybridisation (mCGH). We calculated the PAG for each DTC and determined the critical threshold value that identifies high-risk patients by STEPP (Subpopulation Treatment Effect Pattern Plot) analysis in two independent EAC patient cohorts (cohort #1, n=44; cohort #2; n=29). The most common chromosomal alterations observed among the DTCs were typical for EAC, but the DTCs showed a varying PAG between individual patients. Generally, LNDTCs displayed a significantly higher PAG than BMDTCs. STEPP analysis revealed an increasing PAG of DTCs to be correlated with an increased risk for short survival in two independent EAC cohorts as well as in the corresponding pooled analysis. In all three data sets (cohort #1, cohort #2 and pooled cohort), PAG(high) DTCs conferred an independent risk for a significantly decreased survival. The analysis of PAG/CIN in solitary marker-positive DTCs identifies operable EAC patients with poor prognosis, indicating a more aggressive minimal residual disease.

  1. Proton Pump Inhibitors Display Antitumor Effects in Barrett's Adenocarcinoma Cells.

    PubMed

    Chueca, Eduardo; Apostolova, Nadezda; Esplugues, Juan V; García-González, María A; Lanas, Ángel; Piazuelo, Elena

    2016-01-01

    Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H(+)-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H(+)-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro. H(+)-VATPase expression was assessed by immunohistochemistry in paraffined-embedded samples or by immunofluorescence in cultured BE and EAC cell lines. Cells were treated with different concentrations of PPIs and parameters of citotoxicity, oxidative stress, and autophagy were evaluated. H(+)-VATPase expression was found in all biopsies and cell lines evaluated, showing differences in the location of the pump between the cell lines. Esomeprazole inhibited proliferation and cell invasion and induced apoptosis of EAC cells. Production of reactive oxygen species (ROS) seemed to be involved in the cytotoxic effects observed since the addition of N-acetylcysteine significantly reduced esomeprazole-induced apoptosis in EAC cells. Esomeprazole also reduced intracellular pH of tumor cells, whereas only disturbed the mitochondrial membrane potential in OE33 cells. Esomeprazole induced autophagy in both EAC cells, but also triggered a blockade in autophagic flux in the metastatic cell line. These data provide in vitro evidence supporting the potential use of PPIs as novel antineoplastic drugs for EAC and also shed some light on the mechanisms that trigger PPIs cytotoxic effects, which differ upon the cell line evaluated.

  2. Proton Pump Inhibitors Display Antitumor Effects in Barrett's Adenocarcinoma Cells

    PubMed Central

    Chueca, Eduardo; Apostolova, Nadezda; Esplugues, Juan V.; García-González, María A.; Lanas, Ángel; Piazuelo, Elena

    2016-01-01

    Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H+-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H+-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro. H+-VATPase expression was assessed by immunohistochemistry in paraffined-embedded samples or by immunofluorescence in cultured BE and EAC cell lines. Cells were treated with different concentrations of PPIs and parameters of citotoxicity, oxidative stress, and autophagy were evaluated. H+-VATPase expression was found in all biopsies and cell lines evaluated, showing differences in the location of the pump between the cell lines. Esomeprazole inhibited proliferation and cell invasion and induced apoptosis of EAC cells. Production of reactive oxygen species (ROS) seemed to be involved in the cytotoxic effects observed since the addition of N-acetylcysteine significantly reduced esomeprazole-induced apoptosis in EAC cells. Esomeprazole also reduced intracellular pH of tumor cells, whereas only disturbed the mitochondrial membrane potential in OE33 cells. Esomeprazole induced autophagy in both EAC cells, but also triggered a blockade in autophagic flux in the metastatic cell line. These data provide in vitro evidence supporting the potential use of PPIs as novel antineoplastic drugs for EAC and also shed some light on the mechanisms that trigger PPIs cytotoxic effects, which differ upon the cell line evaluated. PMID:27932981

  3. 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.

  4. 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.

  5. Exploring the recent trend in esophageal adenocarcinoma incidence and mortality using comparative simulation modeling.

    PubMed

    Kong, Chung Yin; Kroep, Sonja; Curtius, Kit; Hazelton, William D; Jeon, Jihyoun; Meza, Rafael; Heberle, Curtis R; Miller, Melecia C; Choi, Sung Eun; Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein; Feuer, Eric J; Inadomi, John M; Hur, Chin; Luebeck, E Georg

    2014-06-01

    The incidence of esophageal adenocarcinoma (EAC) has increased five-fold in the United States since 1975. The aim of our study was to estimate future U.S. EAC incidence and mortality and to shed light on the potential drivers in the disease process that are conduits for the dramatic increase in EAC incidence. A consortium of three research groups calibrated independent mathematical models to clinical and epidemiologic data including EAC incidence from the Surveillance, Epidemiology, and End Results (SEER 9) registry from 1975 to 2010. We then used a comparative modeling approach to project EAC incidence and mortality to year 2030. Importantly, all three models identified birth cohort trends affecting cancer progression as a major driver of the observed increases in EAC incidence and mortality. All models predict that incidence and mortality rates will continue to increase until 2030 but with a plateauing trend for recent male cohorts. The predicted ranges of incidence and mortality rates (cases per 100,000 person years) in 2030 are 8.4 to 10.1 and 5.4 to 7.4, respectively, for males, and 1.3 to 1.8 and 0.9 to 1.2 for females. Estimates of cumulative cause-specific EAC deaths between both sexes for years 2011 to 2030 range between 142,300 and 186,298, almost double the number of deaths in the past 20 years. Through comparative modeling, the projected increases in EAC cases and deaths represent a critical public health concern that warrants attention from cancer control planners to prepare potential interventions. Quantifying this burden of disease will aid health policy makers to plan appropriate cancer control measures. Cancer Epidemiol Biomarkers Prev; 23(6); 997-1006. ©2014 AACR. ©2014 American Association for Cancer Research.

  6. Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk.

    PubMed

    Cheung, Winson Y; Zhai, Rihong; Kulke, Matthew H; Heist, Rebecca S; Asomaning, Kofi; Ma, Clement; Wang, Zhaoxi; Su, Li; Lanuti, Michael; Tanabe, Kenneth K; Christiani, David C; Liu, Geoffrey

    2009-08-01

    Single-nucleotide polymorphisms of key cancer genes, such as EGF A61G, are associated with an elevated risk of esophageal adenocarcinoma (EAC). As gastroesophageal reflux disease (GERD) is an established risk factor for EAC, we evaluated whether the association between epidermal growth factor (EGF) polymorphism and EAC development is altered by the presence of GERD. EGF genotyping of DNA samples was performed and GERD history was collected for 309 EAC patients and 275 matched healthy controls. Associations between genotypes and EAC risk were evaluated using adjusted logistic regression. Genotype-GERD relationships were explored using analyses stratified by GERD history and joint effects models that considered severity and duration of GERD symptoms. EGF variants (A/G or G/G) were more common (P = 0.02) and GERD was more prevalent (P < 0.001) in cases than in controls. When compared with the EGF wild-type A/A genotype, the G/G variant was associated with a substantial increase in EAC risk among individuals with GERD [Odds ratio 9.7; 95% confidence interval (CI), 3.8-25.0; P < 0.001] and a slight decrease in risk for GERD-free individuals (odds ratio 0.4; 95% CI = 0.22-0.90; P = 0.02). In the joint effects models, the odds of EAC was also highest for G/G patients (when compared with A/A) who either experienced frequent GERD of more than once per week (odds ratio 21.8; 95% CI = 5.1-94.0; P < 0.001) or suffered GERD for longer than 15 years (odds ratio 22.4; 95% CI = 6.5-77.6; P < 0.001). There was a highly significant interaction between the G/G genotype and the presence of GERD (P < 0.001). EGF A61G polymorphism may alter EAC susceptibility through an interaction with GERD.

  7. Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

    PubMed Central

    Gallerani, Giulia; Fabbri, Francesco

    2016-01-01

    Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted. PMID:27527155

  8. Whole-genome sequencing of nine esophageal adenocarcinoma cell lines

    PubMed Central

    Contino, Gianmarco; Eldridge, Matthew D.; Secrier, Maria; Bower, Lawrence; Fels Elliott, Rachael; Weaver, Jamie; Lynch, Andy G.; Edwards, Paul A.W.; Fitzgerald, Rebecca C.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines—ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4—all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC. PMID:27594985

  9. Distribution of Resistant Esophageal Adenocarcinoma in the Resected Specimens of Clinical Stage III Patients After Chemoradiation: Its Clinical Implications

    PubMed Central

    Neishaboori, Nastaran; Wadhwa, Roopma; Nogueras-González, Graciela M.; Elimova, Elena; Shiozaki, Hironori; Sudo, Kazuki; Charalampakis, Nikolaos; Hiremath, Adarsh; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Blum, Mariela A.; Rogers, Jane E.; Garris, Jeana L.; Rice, David C.; Komaki, Ritsuko; Swisher, Stephen G.; Skinner, Heath D.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2015-01-01

    Background We have limited knowledge of the geographic distribution of resistant EAC in the resected specimen and its clinical importance can be enormous. Method We selected patients with baseline stage III EAC who had chemoradiation followed by surgery, and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (% of resistant EAC, anatomic distribution). Results 100 clinical stage III patients were studied. 90% had an R0 resection. 99% had either moderate or poorly differentiated EAC. 12% had >50% residual cancer, 31% had 11–50% residual cancer, 53% had 1–10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa=66%, muscularis propria=76%, serosa=62%, and all=35%. Lack of EAC (meaning response) was observed in mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery had no EAC in 79% of patients, in the surgical specimen, however, resistant EAC was frequent (66%) in mucosa/submucosa. Conclusion Contrary to our belief that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the post-chemoradiation biopsies are misleading and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients. PMID:25765719

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

    PubMed Central

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

    2016-01-01

    Background & Aims 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. Methods We collected pathology data from 210 patients with T1 EAC who underwent esophagectomy from1996 through 2012 on factors associated with metastatsis to lymph nodes (tumor size, grade, angio-lymphatic 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. Results 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=.025). 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 to 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. Conclusions Pathologic features of primary superficial EACs can be used, along with the

  11. Meat and heme iron intake and esophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study.

    PubMed

    Jakszyn, Paula; Luján-Barroso, Leila; Agudo, Antonio; Bueno-de-Mesquita, H Bas; Molina, Esther; Sánchez, Ma José; Fonseca-Nunes, Ana; Siersema, Peter D; Matiello, Amalia; Tumino, Rosario; Saieva, Calogero; Pala, Valeria; Vineis, Paolo; Boutron-Ruault, Marie-Christine; Racine, Antoine; Bastide, Nadie; Travis, Ruth C; Khaw, Kay-Tee; Riboli, Elio; Murphy, Neil; Vergnaud, Anne-Claire; Trichopoulou, Antonia; Valanou, Elissavet; Oikonomidou, Edespina; Weiderpass, Elisabete; Skeie, Guri; Johansen, Dorthe; Lindkvist, Björn; Johansson, Mattias; Duarte-Salles, Talita; Freisling, Heinz; Barricarte, Aurelio; Huerta, Jose Ma; Amiano, Pilar; Tjonneland, Anne; Overvad, Kim; Kuehn, Tilman; Grote, Verena; Boeing, Heiner; Peeters, Petra H M; González, Carlos A

    2013-12-01

    Although recent studies suggest that high intakes of meat and heme iron are risk factors for several types of cancer, studies in relation to esophageal adenocarcinoma (EAC) are scarce. Previous results in the European Prospective Investigation into Cancer and Nutrition (EPIC) based on a relatively small number of cases suggested a positive association between processed meat and EAC. In this study, we investigate the association between intake of different types of meats and heme iron intake and EAC risk in a larger number of cases from EPIC. The study included 481,419 individuals and 137 incident cases of EAC that occurred during an average of 11 years of follow-up. Dietary intake of meat (unprocessed/processed red and white meat) was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat. After adjusting for relevant confounders, we observed a statistically significant positive association of EAC risk with heme iron and processed meat intake, with HR: 1.67, 95% CI: 1.05-2.68 and HR: 2.27, 95% CI:1.33-3.89, respectively, for comparison of the highest vs. lowest tertile of intake. Our results suggest a potential association between higher intakes of processed meat and heme iron and risk of EAC.

  12. Mapping of homozygous deletions in verified esophageal adenocarcinoma cell lines and xenografts.

    PubMed

    Boonstra, Jurjen J; van Marion, Ronald; Douben, Hannie J C W; Lanchbury, Jerry S; Timms, Kirsten M; Abkevich, Victor; Tilanus, Hugo W; de Klein, Annelies; Dinjens, Winand N M

    2012-03-01

    Human esophageal adenocarcinoma (EAC) cell lines and xenografts are powerful tools in the search for genetic alterations because these models are composed of pure human cancer cell populations without admixture of normal human cells. In particular detection of homozygous deletions (HDs) is easier using these pure populations of cancer cells. Identification of HDs could potentially lead to the subsequent identification of new tumor suppressor genes (TSGs) involved in esophageal adenocarcinogenesis. Genome wide single nucleotide polymorphism (SNP) arrays were used to identify HDs in 10 verified EAC cell lines and nine EAC xenografts. In total, 61 HDs (range 1-6 per sample) were detected and confirmed by polymerase chain reaction. Besides HDs observed in common fragile genomic regions (n = 26), and gene deserts (n = 8), 27 HDs were located in gene-containing regions. HDs were noted for known TSGs, including CDKN2A, SMAD4 and CDH3/CDH1. Twenty-two new chromosomal regions were detected harboring potentially new TSGs involved in EAC carcinogenesis. Two of these regions of homozygous loss, encompassing the ITGAV and RUNX1 gene, were detected in multiple samples indicating a potential role in the carcinogenesis of EAC. To exclude culturing artifacts, these last two deletions were confirmed by fluorescent in situ hybridization in the primary tumors of which the involved cell lines and xenografts were derived. In summary, in this report we describe the identification of HDs in a series of verified EAC cell lines and xenografts. The deletions documented here are a step forward identifying the key genes involved in EAC development.

  13. Polymorphisms in MGMT and DNA repair genes and the risk of esophageal adenocarcinoma.

    PubMed

    Doecke, James; Zhao, Zhen Zhen; Pandeya, Nirmala; Sadeghi, Shahram; Stark, Mitchell; Green, Adèle C; Hayward, Nicholas K; Webb, Penelope M; Whiteman, David C

    2008-07-01

    Rates of adenocarcinoma of the esophagus (EAC) and esophago-gastric junction (EGJAC) have increased rapidly in recent decades. The primary risk factors, gastro-esophageal acid reflux and smoking, are potentially genotoxic through the generation of N-nitroso compounds. The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is the major cellular defense against alkylating DNA damage. We compared patients with EAC (n = 263) or EGJAC (n = 303) with matched population controls (n = 1,337) for the frequency of 5 MGMT single nucleotide polymorphisms (SNPs) (rs12269324, rs12268840, L84F, I143V, K178R), as well as SNPs in DNA repair genes ERCC1 (N118N), XRCC1 (Q399R) and XPD (K751Q). Relative risks were estimated using multivariable logistic regression. Potential biological interaction was assessed through the synergy index S. Each MGMT SNP conferred increased risks of EAC but not EGJAC; strongest associations were found for the 2 variant MGMT alleles rs12268840 and I143V (p = 0.005 and p < 0.001, respectively). Homozygous carriers of MGMT rs12268840 with frequent acid reflux had significantly higher risks of EAC (OR 15.5, 95% CI 5.8-42) than expected under an additive model, consistent with biological interaction (S = 3.3, 95% CI 1.1-10). Modest, nonsignificant interactions with smoking were also observed. Homozygous variant ERCC1 genotype was associated with reduced risks of EAC (OR 0.6, 95% CI 0.4-1.1), while the homozygous variant XRCC1 genotype conferred higher risks of EGJAC (OR 1.6, 95% CI 1.1-2.4). No associations with EAC or EGJAC were observed with XPD (rs13181). In summary, MGMT SNPs are associated with increased risks of EAC. Exposure to acid reflux, and possibly smoking, confer markedly higher risks among homozygous variant genotype carriers.

  14. Curcumin promotes apoptosis, increases chemosensitivity, and inhibits nuclear factor kappaB in esophageal adenocarcinoma.

    PubMed

    Hartojo, Wibisono; Silvers, Amy L; Thomas, Dafydd G; Seder, Christopher W; Lin, Lin; Rao, Hyma; Wang, Zhuwen; Greenson, Joel K; Giordano, Thomas J; Orringer, Mark B; Rehemtulla, Alnawaz; Bhojani, Mahaveer S; Beer, David G; Chang, Andrew C

    2010-04-01

    The transcription factor, nuclear factor kappaB (NF-kappaB), plays a central role as a key mediator of cell survival and proliferation, and its activation may confer increased tumor chemoresistance. Curcumin, an orally available naturally occurring compound, has been shown to inhibit NF-kappaB and has a potential role in cancer chemoprevention. We investigated the effects of curcumin on NF-kappaB activity, on cell viability, and as a chemosensitizing agent with 5-fluorouracil (5-FU) or cisplatin (CDDP) in esophageal adenocarcinoma (EAC). Oligonucleotide microarray analysis of 46 cases, consisting of Barrett metaplasia, low-grade dysplasia, high-grade dysplasia and EAC, showed increased expression of NF-kappaB and IkappaB kinase subunits and decreased effector caspase expression in EAC compared with Barrett metaplasia. Stromal expression of both IkappaB and phospho-IkappaB was detected in several EAC samples by tissue microarray analysis. Curcumin alone inhibited NF-kappaB activity and induced apoptosis in both Flo-1 and OE33 EAC cell lines as determined by Western blot analysis, NF-kappaB reporter assays, and Caspase-Glo 3/7 assays. It also increased 5-FU- and CDDP-induced apoptosis in both cell lines. These data suggest that activation of NF-kappaB and inhibition of apoptosis may play a role in the progression from Barrett metaplasia to EAC. In addition, curcumin, a well-known inhibitor of NF-kappaB activity, was shown to increase apoptosis and enhance both 5-FU- and CDDP-mediated chemosensitivity, suggesting that it may have potential application in the therapy of patients with EAC.

  15. Curcumin Promotes Apoptosis, Increases Chemosensitivity, and Inhibits Nuclear Factor κB in Esophageal Adenocarcinoma1

    PubMed Central

    Hartojo, Wibisono; Silvers, Amy L; Thomas, Dafydd G; Seder, Christopher W; Lin, Lin; Rao, Hyma; Wang, Zhuwen; Greenson, Joel K; Giordano, Thomas J; Orringer, Mark B; Rehemtulla, Alnawaz; Bhojani, Mahaveer S; Beer, David G; Chang, Andrew C

    2010-01-01

    The transcription factor, nuclear factor κB (NF-κB), plays a central role as a key mediator of cell survival and proliferation, and its activation may confer increased tumor chemoresistance. Curcumin, an orally available naturally occurring compound, has been shown to inhibit NF-κB and has a potential role in cancer chemoprevention. We investigated the effects of curcumin on NF-κB activity, on cell viability, and as a chemosensitizing agent with 5-fluorouracil (5-FU) or cisplatin (CDDP) in esophageal adenocarcinoma (EAC). Oligonucleotide microarray analysis of 46 cases, consisting of Barrett metaplasia, low-grade dysplasia, high-grade dysplasia and EAC, showed increased expression of NF-κB and IκB kinase subunits and decreased effector caspase expression in EAC compared with Barrett metaplasia. Stromal expression of both IκB and phospho-IκB was detected in several EAC samples by tissue microarray analysis. Curcumin alone inhibited NF-κB activity and induced apoptosis in both Flo-1 and OE33 EAC cell lines as determined by Western blot analysis, NF-κB reporter assays, and Caspase-Glo 3/7 assays. It also increased 5-FU- and CDDP-induced apoptosis in both cell lines. These data suggest that activation of NF-κB and inhibition of apoptosis may play a role in the progression from Barrett metaplasia to EAC. In addition, curcumin, a well-known inhibitor of NF-κB activity, was shown to increase apoptosis and enhance both 5-FU- and CDDP-mediated chemosensitivity, suggesting that it may have potential application in the therapy of patients with EAC. PMID:20360934

  16. Dynamic changes in microRNA expression profiles reflect progression of Barrett's esophagus to esophageal adenocarcinoma.

    PubMed

    Slaby, Ondrej; Srovnal, Josef; Radova, Lenka; Gregar, Jan; Juracek, Jaroslav; Luzna, Pavla; Svoboda, Marek; Hajduch, Marian; Ehrmann, Jiri

    2015-05-01

    Esophageal adenocarcinoma (EAC) is highly aggressive malignancy that frequently develops from Barrett's esophagus (BE), a premalignant pathologic change occurring in the lower end of the esophagus. MicroRNAs (miRNAs) are small, non-coding RNAs that function as posttranscriptional regulators of gene expression and were repeatedly proved to play key roles in pathogenesis of BE as well as EAC. In our study, we used Affymetrix GeneChip miRNA arrays to obtain miRNA expression profiles in total of 119 tissue samples [24 normal esophageal mucosa (EM), 60 BE and 35 EAC]. We identified a number of miRNAs, that showed altered expression progressively in sequence EM, BE and EAC, including for instance miR-21, miR-25, miR-194 and miR-196a with increasing levels (P < 0.0015) and miR-203, miR-205, miR-210 and miR-378 with decreasing levels (P < 0.0001). The subsequent analysis revealed four diagnostic miRNA signatures enabling to distinguish EM and BE [12 miRNAs, area under curve (AUC) = 0.971], EM and EAC (13 miRNAs, AUC = 1.0), BE without and BE with dysplasia (21 miRNAs, AUC = 0.856) and BE without dysplastic changes and BE with dysplasia together with EAC (2 miRNAs, AUC = 0.886). We suggest that miRNA expression profiling expands current knowledge in molecular pathology of Barrett's-based carcinogenesis and enables identification of molecular biomarkers for early detection of BE dysplasia and progression to EAC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas

    PubMed Central

    Adams, Olivia; Dislich, Bastian; Berezowska, Sabina; Schläfli, Anna M.; Seiler, Christian A.; Kroell, Dino; Tschan, Mario P.; Langer, Rupert

    2016-01-01

    Esophageal adenocarcinomas (EAC) are aggressive tumors with considerable rates of chemoresistance. Autophagy is a lysosome-dependent degradation process, characterized by the formation of vesicles called autophagosomes, and has been implicated in cancer. Protein light chain 3 B (LC3B) and p62 are associated with autophagosomal membranes and degraded. We aimed to assess the impact of basal autophagy on EAC. In EAC cell lines, an increase in LC3B and p62 was observed with increasing concentrations of the autophagy inhibitor chloroquine, which indicates functional basal autophagy. LC3B and p62 immunohistochemistry was performed on primary resected EAC. High LC3B and p62 expression was associated with earlier tumor stages (p < 0.05). High nuclear and cytoplasmic p62 staining were associated with a better prognosis (p = 0.006; p = 0.028). Various combinations of p62 expression with or without LC3B expression identified different prognostic groups. Tumors with low total p62 (p = 0.007) or low LC3B/low p62 expression had the worst outcome (p = 0.007; p = 0.005). A combination score of dot-like/cytoplasmic p62 and nuclear p62 staining was an independent prognostic parameter (p = 0.033; HR = 0.6). This study highlights the potential significance of basal autophagy in EAC biology. Tumors with low LC3B and p62 expression show the most aggressive behavior and may be candidates for autophagy regulating therapeutics. PMID:27250034

  18. Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

    PubMed Central

    Peng, DunFa; Guo, Yan; Chen, Heidi; Zhao, Shilin; Washington, Kay; Hu, TianLing; Shyr, Yu; El-Rifai, Wael

    2017-01-01

    The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC. PMID:28102292

  19. Alpha-fetoprotein-producing esophageal adenocarcinoma: a mimicker of hepatocellular carcinoma.

    PubMed

    Wang, Jeremy; Liu, Wendy; Parikh, Keyur; Post, Anthony Benjamin

    2017-02-01

    Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but rarely with esophageal carcinoma. Here, we report a rare case of AFP-producing EAC. A 51-year-old man presented with two weeks of acid reflux and a 35-lb weight loss. Laboratory data were notable for transaminitis and AFP was 2524 ng/mL. Computed tomography of the abdomen revealed abnormal thickening of the esophagus and multiple metastatic masses throughout the liver. Biopsy of one of the masses revealed adenocarcinoma of gastrointestinal origin. Subsequent upper endoscopy revealed an esophageal mass with biopsy notable for ulcerated dysplastic glandular mucosa with likely underlying malignancy. The patient underwent palliative esophageal stent placement but died two months later. Elevated AFP levels are an unusual occurrence in EAC. Prognosis is poor given its advanced presenting stage and high metastatic potential. Most cases are unsuccessfully treated with surgery and chemotherapy. Serial measurement of serum AFP may be useful for monitoring clinical status and treatment response. Clinicians should consider AFP-producing EAC in their differential diagnosis in the work-up of a liver mass in the setting of elevated AFP or liver function impairment, especially in the absence of chronic liver disease.

  20. RNA sequencing of esophageal adenocarcinomas identifies novel fusion transcripts, including NPC1-MELK, arising from a complex chromosomal rearrangement.

    PubMed

    Wang, Zhixiong; Cheng, Yulan; Abraham, John M; Yan, Rong; Liu, Xi; Chen, Wei; Ibrahim, Sariat; Schroth, Gary P; Ke, Xiquan; He, Yulong; Meltzer, Stephen J

    2017-06-22

    Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes. Five novel in-frame fusion transcripts were identified and verified in 40 EACs and in a validation cohort of 15 additional EACs (55 patients in all): fibroblast growth factor receptor 2 (FGFR2)-GRB2-associated binding protein 2 (GAB2) in 2 of 55 or 3.6%, Niemann-Pick C1 (NPC1)-maternal embryonic leucine zipper kinase (MELK) in 2 of 55 or 3.6%, ubiquitin-specific peptidase 54 (USP54)-calcium/calmodulin dependent protein kinase II γ (CAMK2G) in 2 of 55 or 3.6%, megakaryoblastic leukemia (translocation) 1 (MKL1)-fibulin 1 (FBLN1) in 1 of 55 or 1.8%, and CCR4-NOT transcription complex subunit 2 (CNOT2)-chromosome 12 open reading frame 49 (C12orf49) in 1 of 55 or 1.8%. A genomic analysis indicated that NPC1-MELK arose from a complex interchromosomal translocation event involving chromosomes 18, 3, and 9 with 3 rearrangement points, and this was consistent with chromoplexy. These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC. Cancer 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. A high-fat diet is associated with altered adipokine production and a more aggressive esophageal adenocarcinoma phenotype in vivo.

    PubMed

    Fowler, Aaron J; Richer, Amanda L; Bremner, Ross M; Inge, Landon J

    2015-04-01

    Obesity has been linked to esophageal adenocarcinoma (EAC). We hypothesize that adipokines, which are altered by obesity, could affect EAC growth rates and potentially serve as biomarkers of disease and targets for treatment. We have developed a potential murine model to investigate the effects of obesity-altered adipokines on EAC in vivo. Severe combined immune-deficient mice were fed either a high-fat diet (HFD) containing 60% animal fat, or a control diet with 10% animal fat, and monitored for weight gain for 5 weeks. All mice were subcutaneously implanted with EAC cells (OE33), and tumor volume was monitored for an additional 4 weeks by direct measurement and uptake of fluorescently labeled 2-D-deoxyglucose. At sacrifice, serum triglyceride levels and abdominal fat-pad weight were measured to assess obesity state. Adipokine levels were measured within abdominal fat of tumor-bearing mice. Mice fed the HFD displayed increased body weight, visceral fat, and serum leptin and triglycerides. All mice developed tumors; OE33 EAC cells in HFD mice displayed increased growth rates, proliferation, and metabolic activity relative to tumors of EAC in control diet mice. Adipokine expression in the abdominal fat revealed distinct changes associated with the HFD and increased body weight. Ad libitum feeding of the HFD was correlated with more-proliferative EAC tumors in vivo. This phenotype was associated with alterations to secreted adipokines, representing a potential mechanism for our observations. Further studies are necessary to explore findings, as they have potential to improve treatment of EAC. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  2. 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

  3. CpG island methylator phenotype in adenocarcinomas from the digestive tract: Methods, conclusions, and controversies

    PubMed Central

    Sánchez-Vega, Francisco; Gotea, Valer; Chen, Yun-Ching; Elnitski, Laura

    2017-01-01

    Over the last two decades, cancer-related alterations in DNA methylation that regulate transcription have been reported for a variety of tumors of the gastrointestinal tract. Due to its relevance for translational research, great emphasis has been placed on the analysis and molecular characterization of the CpG island methylator phenotype (CIMP), defined as widespread hypermethylation of CpG islands in clinically distinct subsets of cancer patients. Here, we present an overview of previous work in this field and also explore some open questions using cross-platform data for esophageal, gastric, and colorectal adenocarcinomas from The Cancer Genome Atlas. We provide a data-driven, pan-gastrointestinal stratification of individual samples based on CIMP status and we investigate correlations with oncogenic alterations, including somatic mutations and epigenetic silencing of tumor suppressor genes. Besides known events in CIMP such as BRAF V600E mutation, CDKN2A silencing or MLH1 inactivation, we discuss the potential role of emerging actors such as Wnt pathway deregulation through truncating mutations in RNF43 and epigenetic silencing of WIF1. Our results highlight the existence of molecular similarities that are superimposed over a larger backbone of tissue-specific features and can be exploited to reduce heterogeneity of response in clinical trials. PMID:28344746

  4. 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

  5. 76 FR 2439 - Request for Comments and Suggestions for the Agenda of the Environmental Affairs Council (Eac) of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-13

    ....gov with the subject line ``CAFTA-DR EAC Meeting'' or by fax to (202) 647-5947; and (2) Kelly Milton... Milton, 202-395-9590. SUPPLEMENTARY INFORMATION: Article 17.5 of the CAFTA-DR establishes...

  6. Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    Ross-Innes, Caryn S; Becq, Jennifer; Warren, Andrew; Cheetham, R Keira; Northen, Helen; O'Donovan, Maria; Malhotra, Shalini; di Pietro, Massimiliano; Ivakhno, Sergii; He, Miao; Weaver, Jamie M J; Lynch, Andy G; Kingsbury, Zoya; Ross, Mark; Humphray, Sean; Bentley, David; Fitzgerald, Rebecca C

    2015-09-01

    The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett's esophagus and EAC samples, together with one in-depth Barrett's esophagus case study sampled over time and space, we have provided the following new insights: (i) Barrett's esophagus is polyclonal and highly mutated even in the absence of dysplasia; (ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett's esophagus; and (iii) despite differences in specific coding mutations, the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett's epithelium, and a molecular Cytosponge technique overcomes sampling bias and has the capacity to reflect the entire clonal architecture.

  7. Surveillance endoscopy is associated with improved outcomes of oesophageal adenocarcinoma detected in patients with Barrett's oesophagus.

    PubMed

    El-Serag, Hashem B; Naik, Aanand D; Duan, Zhigang; Shakhatreh, Mohammad; Helm, Ashley; Pathak, Amita; Hinojosa-Lindsey, Marilyn; Hou, Jason; Nguyen, Theresa; Chen, John; Kramer, Jennifer R

    2016-08-01

    The effectiveness of surveillance endoscopy in patients with Barrett's oesophagus (BE) for reducing oesophageal adenocarcinoma (EAC)-related mortality in patients with BE is unclear. This is a cohort study of patients with BE diagnosed in the National Veterans Affairs hospitals during 2004-2009 excluding those with conditions that affect overall survival. We identified those diagnosed with EAC after BE diagnosis through 2011 and conducted chart reviews to identify BE surveillance programme, and indication for EAC diagnosis, verify diagnosis, stage, therapy and cause of death. We examined the association between surveillance indication for EAC diagnosis with or without surveillance programme and EAC stage and treatment receipt in logistic regression models, and with time to death or cancer-related death using a Cox proportional hazards regression model. Among 29 536 patients with BE, 424 patients developed EAC during a mean follow-up of 5.0 years. A total of 209 (49.3%) patients with EAC were in BE surveillance programme and were diagnosed as a result of surveillance endoscopy. These patients were more likely to be diagnosed at an early stage (stage 0 or 1: 74.7% vs 56.2, p<0.001), survived longer (median 3.2 vs 2.3 years; p<0.001) and have lower cancer-related mortality (34.0% vs 54.0%, p<0.0001) and had a trend to receive oesophagectomy (51.2% vs 42.3%; p=0.07) than 215 patients diagnosed by non-BE surveillance endoscopy (17.2% of whom were BE surveillance failure). BE surveillance endoscopy was associated with a decreased risk of cancer-related death (HR 0.47, 0.35 to 0.64), which was largely explained by the early stage of EAC at the time of diagnosis. Similarly, the adjusted mortality for patients with cancer in a prior surveillance programme for overall death was 0.63 (0.47 to 0.84) compared with patients with cancer not in a surveillance programme. Surveillance endoscopy among patients with BE is associated with significantly better EAC outcomes

  8. Immunostaining with EGFR mutation-specific antibodies: a reliable screening method for lung adenocarcinomas harboring EGFR mutation in biopsy and resection samples.

    PubMed

    Fan, Xiangshan; Liu, Biao; Xu, Haodong; Yu, Bo; Shi, Shanshan; Zhang, Jin; Wang, Xuan; Wang, Jiandong; Lu, Zhenfeng; Ma, Henghui; Zhou, Xiaojun

    2013-08-01

    Mutation analysis of epidermal growth factor receptor (EGFR) is essential in determining the therapeutic strategy for lung adenocarcinoma. Immunohistochemical (IHC) staining with EGFR mutation-specific antibodies of del E746-A750 in exon 19 and L858R in exon 21 has been evaluated in resection specimens in a few studies but rarely in biopsy samples. A total of 169 cases (78 biopsies and 91 resected specimens) of lung adenocarcinoma with EGFR mutation status predefined by direct DNA sequencing were histologically examined, and IHC was performed using EGFR mutation-specific antibodies of del E746-A750 and L858R. The cases with positive results by IHC but negative results by direct DNA sequencing were examined by amplified refractory mutation system. Our results showed that the frequency of EGFR mutations for both E746-A750 deletion and L858R mutation was 38.5% (65/169) by DNA sequencing or amplified refractory mutation system and 34.3% (58/169) by IHC in lung adenocarcinomas. Based on molecular test results, the overall sensitivity, specificity, positive predictive value, and negative predictive value of IHC using these 2 antibodies in all (biopsy/resection) cases were 87.7% (80%/94.3%), 99.0% (97.9%/100%), 98.3% (96%/100%), and 92.8% (88.7%/96.6%), respectively. Lung adenocarcinomas with a predominant acinar, papillary, lepidic, or solid growth pattern more often harbor EGFR mutation of del E746-A750 or L858R. In conclusion, the immunostaining with EGFR del E746-A750 and L858R mutation antibodies is a reliable screening method with high specificity and sensitivity for identifying the EGFR mutation in both resected and biopsied lung adenocarcinomas.

  9. Therapeutic targeting of the TNF superfamily: a promising treatment for advanced endometrial adenocarcinoma.

    PubMed

    Thangaraju, Shyam; Subramani, Elavarasan; Chakravarty, Baidyanath; Chaudhury, Koel

    2012-11-01

    Surgical treatment including total abdominal hysterectomy+bilateral salpingo oopherectomy (TAH+BSO) with pelvic and para-aortic lymphadenectomy may not be sufficient to treat cases with advanced endometrial adenocarcinoma (EAC), and in these cases, adjuvant treatments including radiotherapy and/or chemotherapy, are employed based upon the tumor location, type and stage of the disease. These treatment modalities have high incidence of systemic toxicity, thereby compelling clinicians to look for targeted therapy aiming specifically at the malignant cells. Bevacizumab (anti-VEGF), temsirolimus (mTOR inhibitor) and aflibercept (VEGF trap) are already under clinical trials in women with EAC. Targeting the ligands and receptors of the tumor necrosis factor (TNF) superfamily holds promise in this regard. The objective of this review is to provide an overview of the various mechanisms and pathways related to the TNF superfamily involved in advanced EAC and to identify the new therapeutic strategies for specifically targeting these impaired pathways. In addition, the development of treatments for EAC is also discussed. The possible therapeutic treatments include targeting TNFα and its receptors using monoclonal antibodies (MAbs) such as infliximab, adalimumab, etanercept, and certolizumab. Proteosome inhibitors including bortezomib and the anti CD-20 agent rituximab are used to inhibit the NF-κB pathway. Other options include targeting the FAS (CD95) pathway and the TNF-related apoptosis-inducing ligand (TRAIL) pathway using agents such as mapatumab, lexatumumab, and conatumumab. These pathways are known to be involved in the pathogenesis of EAC. Moreover, there is adequate evidence to warrant the use of drugs that target the TNF superfamily for the treatment of advanced EAC. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients.

    PubMed

    Dunne, Margaret R; Michielsen, Adriana J; O'Sullivan, Katie E; Cathcart, Mary Clare; Feighery, Ronan; Doyle, Brendan; Watson, Jenny A; O'Farrell, Naoimh J; Ravi, Narayanasamy; Kay, Elaine; Reynolds, John V; Ryan, Elizabeth J; O'Sullivan, Jacintha

    2017-07-01

    Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (<50%) HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.

  11. Impact of peritumoral and intratumoral budding in esophageal adenocarcinomas.

    PubMed

    Thies, Svenja; Guldener, Lars; Slotta-Huspenina, Julia; Zlobec, Inti; Koelzer, Viktor H; Lugli, Alessandro; Kröll, Dino; Seiler, Christian A; Feith, Marcus; Langer, Rupert

    2016-06-01

    Tumor budding has prognostic significance in many carcinomas and is defined as the presence of detached isolated single cells or small cell clusters up to 5 cells at the invasion front (peritumoral budding [PTB]) or within the tumor (intratumoral budding [ITB]). For esophageal adenocarcinomas (EACs), there are currently only few data about the impact of this morphological feature. We investigated tumor budding in a large collective of 200 primarily resected EACs. Pancytokeratin staining was demonstrated to be superior to hematoxylin and eosin staining for the detection of buds with substantial to excellent interobserver agreement and used for subsequent analysis. PTB and ITB were scored across 10 high-power fields (HPFs). The median count of tumor buds was 130/10 HPFs for PTB (range, 2-593) and 80/10 HPFs for ITB (range, 1-656). PTB and ITB correlated significantly with each other (r = 0.9; P < .001). High PTB and ITB rates were seen in more advanced tumor categories (P < .001 each); tumors with lymph node metastases (P < .001/P = .002); and lymphatic, vascular, and perineural invasion and higher tumor grading (P < .001 each). Survival analysis showed an association with worse survival for high-grade ITB (P = .029) but not PTB (P = .385). However, in multivariate analysis, lymph node and resection status, but not ITB, were independent prognostic parameters. In conclusion, PTB and ITB can be observed in EAC to various degrees. High-grade budding is associated with aggressive tumor phenotype. Assessment of tumor budding, especially ITB, may provide additional prognostic information about tumor behavior and may be useful in specific cases for risk stratification of EAC patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Recurrence Risk Stratification After Preoperative Chemoradiation of Esophageal Adenocarcinoma.

    PubMed

    Xi, Mian; Hallemeier, Christopher L; Merrell, Kenneth W; Liao, Zhongxing; Murphy, Mariela A Blum; Ho, Linus; Hofstetter, Wayne L; Mehran, Reza; Lee, Jeffrey H; Bhutani, Manoop S; Weston, Brian; Maru, Dipen M; Komaki, Ritsuko; Ajani, Jaffer A; Lin, Steven H

    2017-06-16

    To discern recurrence risk stratification and investigate its influence on postoperative surveillance in patients with esophageal adenocarcinoma (EAC) after neoadjuvant chemoradiotherapy (CRT). Reports documenting recurrence risk stratification in EAC after neoadjuvant CRT are scarce. Between 1998 and 2014, 601 patients with EAC who underwent neoadjuvant CRT followed by esophagectomy were included for analysis. The pattern, site, timing, and frequency of the first recurrence and potential prognostic factors for developing recurrences were analyzed. This cohort was used as the training set to propose a recurrence risk stratification system, and the stratification was further validated in another cohort of 172 patients. A total of 150 patients (25.0%) achieved pathologic complete response (pCR) after neoadjuvant CRT and the rest were defined as the non-pCR group (n = 451) in the training cohort. After a median follow-up of 63.6 months, the pCR group demonstrated a significantly lower locoregional (4.7% vs 19.1%) and distant recurrence rate (22.0% vs.44.6%) than the non-pCR group (P < 0.001). Based on independent prognostic factors, patients were stratified into 4 recurrence risk categories: pCR with clinical stage I/II, pCR with clinical stage III, non-pCR with pN0, and non-pCR with pN+, with corresponding 5-year recurrence-free survival rates of 88.7%, 65.8%, 55.3%, and 33.0%, respectively (P < 0.001). The risk stratification was reproducible in the validation cohort. We proposed a recurrence risk stratification system for EAC patients based on pathologic response and pretreatment clinical stage. Risk-based postoperative surveillance strategies could be developed for different risk categories.

  13. Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma

    PubMed Central

    Becker, Jessica; May, Andrea; Gerges, Christian; Anders, Mario; Veits, Lothar; Weise, Katharina; Czamara, Darina; Lyros, Orestis; Manner, Hendrik; Terheggen, Grischa; Venerito, Marino; Noder, Tania; Mayershofer, Rupert; Hofer, Jan-Hinnerk; Karch, Hans-Werner; Ahlbrand, Constantin J; Arras, Michael; Hofer, Sebastian; Mangold, Elisabeth; Heilmann-Heimbach, Stefanie; Heinrichs, Sophie K M; Hess, Timo; Kiesslich, Ralf; Izbicki, Jakob R; Hölscher, Arnulf H; Bollschweiler, Elfriede; Malfertheiner, Peter; Lang, Hauke; Moehler, Markus; Lorenz, Dietmar; Müller-Myhsok, Bertram; Ott, Katja; Schmidt, Thomas; Whiteman, David C; Vaughan, Thomas L; Nöthen, Markus M; Hackelsberger, Andreas; Schumacher, Brigitte; Pech, Oliver; Vashist, Yogesh; Vieth, Michael; Weismüller, Josef; Neuhaus, Horst; Rösch, Thomas; Ell, Christian; Gockel, Ines; Schumacher, Johannes

    2015-01-01

    The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett’s esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett’s esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P <  10−4 in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P < 10−5) although not genome-wide significantly associated with the BEACON GWAS. Therefore, both variants and corresponding genes represent promising candidates for future EAC association studies on independent samples. PMID:26383589

  14. SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading.

    PubMed

    Pityński, Kazimierz; Banas, Tomasz; Pietrus, Milosz; Milian-Ciesielska, Katarzyna; Ludwin, Artur; Okon, Krzysztof

    2015-01-01

    Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated. SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients. The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R(2) = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index. There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages.

  15. Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma

    PubMed Central

    Krause, Lutz; Nones, Katia; Loffler, Kelly A.; Nancarrow, Derek; Oey, Harald; Tang, Yue Hang; Wayte, Nicola J.; Patch, Ann Marie; Patel, Kalpana; Brosda, Sandra; Manning, Suzanne; Lampe, Guy; Clouston, Andrew; Thomas, Janine; Stoye, Jens; Hussey, Damian J.; Watson, David I.; Lord, Reginald V.; Phillips, Wayne A.; Gotley, David; Smithers, B.Mark; Whiteman, David C.; Hayward, Nicholas K.; Grimmond, Sean M.; Waddell, Nicola; Barbour, Andrew P.

    2016-01-01

    The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett’s esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. PMID:26905591

  16. Epidemiology of Barrett’s Esophagus and Esophageal Adenocarcinoma

    PubMed Central

    Runge, Thomas M.; Abrams, Julian A.; Shaheen, Nicholas J.

    2015-01-01

    Barrett’s esophagus (BE) is a common condition, and is the precursor to esophageal adenocarcinoma, a disease with increasing burden in the western world, especially in Caucasian males. The incidence of BE increased dramatically during the late-20th century and incidence estimates continue to increase, with a prominent male:female ratio. The prevalence is between 0.5 – 2.0 percent. A number of anthropomorphic and behavioral risk factors exist for BE including obesity and tobacco smoking, but GERD is the strongest risk factor, and the risk is more pronounced with long-standing GERD. Esophageal adenocarcinoma (EAC) is the most common form of esophageal cancer in the U.S. Risk factors include GERD, tobacco smoking, and obesity, while NSAIDs and statins may be protective. A major factor predicting progression from non-dysplastic BE to EAC is the presence of dysplastic changes seen on esophageal histology, although a number of issues limit the utility of dysplasia as a marker for disease. Length of the involved BE segment is another risk for progression to high-grade dysplasia and cancer. Biomarkers have shown promise, but none are approved for clinical use. PMID:26021191

  17. CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells

    PubMed Central

    Jiménez, Pilar; Chueca, Eduardo; Arruebo, María; Strunk, Mark; Solanas, Estela; Serrano, Trinidad; García-González, María A.; Lanas, Ángel

    2017-01-01

    The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor. OE19 and OE33 EAC cells surviving 5-FU exposure exhibited an increase in CSC markers CD24 and ABCG2 and also an increased resistance to apoptosis. EAC cell lines had the capacity to form multiple spheres displaying typical CSC functionalities such as self-renewal and increased CD24 levels. In addition, after the induction of differentiation, cancer cells reached levels of CD24 similar to those observed in the parental cells. Treatment with celecoxib alone or in combination with 5-FU also resulted in a reduction of CD24 expression. Moreover, celecoxib inhibited the growth of tumor spheres. These findings showing a reduction in CSC markers induced by celecoxib suggest that the COX-2 inhibitor might be a candidate for combined chemotherapy in the treatment of EAC. However, additional clinical and experimental studies are needed. PMID:28611669

  18. CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells.

    PubMed

    Jiménez, Pilar; Chueca, Eduardo; Arruebo, María; Strunk, Mark; Solanas, Estela; Serrano, Trinidad; García-González, María A; Lanas, Ángel

    2017-01-01

    The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor. OE19 and OE33 EAC cells surviving 5-FU exposure exhibited an increase in CSC markers CD24 and ABCG2 and also an increased resistance to apoptosis. EAC cell lines had the capacity to form multiple spheres displaying typical CSC functionalities such as self-renewal and increased CD24 levels. In addition, after the induction of differentiation, cancer cells reached levels of CD24 similar to those observed in the parental cells. Treatment with celecoxib alone or in combination with 5-FU also resulted in a reduction of CD24 expression. Moreover, celecoxib inhibited the growth of tumor spheres. These findings showing a reduction in CSC markers induced by celecoxib suggest that the COX-2 inhibitor might be a candidate for combined chemotherapy in the treatment of EAC. However, additional clinical and experimental studies are needed.

  19. Local Synthesis of Pepsin in Barrett's Esophagus and the Role of Pepsin in Esophageal Adenocarcinoma.

    PubMed

    Samuels, Tina; Hoekzema, Craig; Gould, Jon; Goldblatt, Matthew; Frelich, Matthew; Bosler, Matthew; Lee, Sang-Hyuk; Johnston, Nikki

    2015-11-01

    Despite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated. Normal and Barrett's biopsies from 8 Barrett's esophagus patients were collected for pepsin analysis via Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1 mg/mL; 1-20 hours), acid (pH 4)±pepsin (5 minutes); real-time RT-PCR, ELISA, and cell migration were assayed. Pepsin was detected in all 8 Barrett's and 4 of 8 adjacent normal specimens. Pepsinogen mRNA was observed in 22 Barrett's, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL-1β expression and cell migration in vitro. Pepsin is synthesized by metaplastic, Barrett's esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in the prevention of EAC. © The Author(s) 2015.

  20. Gastric adenocarcinoma.

    PubMed

    Ajani, Jaffer A; Lee, Jeeyun; Sano, Takeshi; Janjigian, Yelena Y; Fan, Daiming; Song, Shumei

    2017-06-01

    Gastric cancers, with gastric adenocarcinoma (GAC) as the most common histological type, impose a considerable global health burden. Although the screening strategies for early detection have been shown to be successful in Japan and South Korea, they are either not implemented or not feasible in most of the world, leading to late diagnosis in most patients. Helicobacter pylori infection contributes to the development of many endemic GACs, and pre-emptive eradication or early treatment of this bacterial infection might provide effective primary prevention. GACs are phenotypically and genotypically heterogeneous. Localized (clinical stage I) GAC is best treated either endoscopically or with limited surgical resection, but clinical stage II or stage III tumours require multidisciplinary adjunctive approaches in addition to surgery. Although GAC is highly treatable in its early stages, advanced (clinical stage IV) GAC has a median survival of just ∼9-10 months. However, detailed molecular and immune profiling of GAC is yielding promise; early studies with immune checkpoint inhibitors suggest that GAC is amenable to immune modulation. Molecular studies have yielded a vast quantity of new information for potential exploitation. Nevertheless, advances against GACs have lagged compared with other tumours of similar incidence, and more research is necessary to overcome the obstacles to prolong survival.

  1. Investigation of the sensitivity to EAC of steel T91 in contact with liquid LBE

    NASA Astrophysics Data System (ADS)

    Di Gabriele, F.; Doubková, A.; Hojná, A.

    2008-06-01

    The ferritic-martensitic steel T91 is one of the most promising material for application in the generation IV type reactors. However, there are critical issues, such as the susceptibility to damage of the steel in contact with the heavy liquid metals and their effect on the mechanical properties of structural materials. In this context, it was initiated a study of the boundary conditions, necessary to ascertain the sensitivity of the T91 to environmentally assisted cracking when loaded in contact with the liquid lead-bismuth eutectic. A series of tensile tests were carried out in a cell where the specimens were immersed in static LBE. Results showed that at high temperature the steel in contact with the liquid metal had a slight decrease of yield and UTS value and a marked increase in the elongation to rupture. However, at low temperature the elongation to rupture and the reduction of area decreased, indicating the sensitivity to EAC.

  2. Paullinia cupana Mart. var. sorbilis, guarana, increases survival of Ehrlich ascites carcinoma (EAC) bearing mice by decreasing cyclin-D1 expression and inducing a G0/G1 cell cycle arrest in EAC cells.

    PubMed

    Fukumasu, Heidge; Latorre, Andreia Oliveira; Zaidan-Dagli, Maria Lucia

    2011-01-01

    The objective of this work is to report the antiproliferative effect of P. cupana treatment in Ehrlich Ascites Carcinoma (EAC)-bearing animals. Female mice were treated with three doses of powdered P. cupana (100, 1000 and 2000 mg/kg) for 7 days, injected with 10(5) EAC cells and treated up to day 21. In addition, a survival experiment was carried out with the same protocol. P. cupana decreased the ascites volume (p = 0.0120), cell number (p = 0.0004) and hemorrhage (p = 0.0054). This occurred through a G1-phase arrest (p < 0.01) induced by a decreased gene expression of Cyclin D1 in EAC cells. Furthermore, P. cupana significantly increased the survival of EAC-bearing animals (p = 0.0012). In conclusion, the P. cupana growth control effect in this model was correlated with a decreased expression of cyclin D1 and a G1 phase arrest. These results reinforce the cancer therapeutic potential of this Brazilian plant. Copyright © 2010 John Wiley & Sons, Ltd.

  3. 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…

  4. 77 FR 54905 - Request for Substantive Comments on the EAC's Proposed Requirements for Version 1.1 of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    ... systems for a 90 day public comment period. SUPPLEMENTARY INFORMATION: Background The EAC made the... Voluntary Voting System Guidelines (VVSG) AGENCY: United States Election Assistance Commission. ACTION: Request for public comment on proposed requirements for Version 1.1 of the Voluntary Voting...

  5. 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…

  6. 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

  7. Epigenetic patterns in the progression of esophageal adenocarcinoma.

    PubMed

    Eads, C A; Lord, R V; Wickramasinghe, K; Long, T I; Kurumboor, S K; Bernstein, L; Peters, J H; DeMeester, S R; DeMeester, T R; Skinner, K A; Laird, P W

    2001-04-15

    Esophageal adenocarcinoma (EAC) arises after normal squamous mucosa undergoes metaplasia to specialized columnar epithelium (intestinal metaplasia or Barrett's esophagus), which can then ultimately progress to dysplasia and subsequent malignancy. Epigenetic studies of this model have thus far been limited to the DNA methylation analysis of a few genes. In this study, we analyzed a panel of 20 genes using a quantitative, high-throughput methylation assay, METHYLIGHT: We used this broader approach to gain insight into concordant methylation behavior between genes and to generate epigenomic fingerprints for the different histological stages of EAC. Our study included a total of 104 tissue specimens from 51 patients with different stages of Barrett's esophagus and/or associated adenocarcinoma. We screened 84 of these samples with the full panel of 20 genes and found distinct classes of methylation patterns in the different types of tissue. The most informative genes were those with an intermediate frequency of significant hypermethylation [ranging from 15% (CDKN2A) to 60% (MGMT) of the samples]. This group could be further subdivided into three classes, according to the absence (CDKN2A, ESR1, and MYOD1) or presence (CALCA, MGMT, and TIMP3) of methylation in normal esophageal mucosa and stomach, or the infrequent methylation of normal esophageal mucosa accompanied by methylation in all normal stomach samples (APC). The other genes were less informative, because the frequency of hypermethylation was below 5% (ARF, CDH1, CDKN2B, GSTP1, MLH1, PTGS2, and THBS1), completely absent (CTNNB1, RB1, TGFBR2, and TYMS1), or ubiquitous (HIC1 and MTHFR), regardless of tissue type. Each class undergoes unique epigenetic changes at different steps of disease progression of EAC, suggesting a step-wise loss of multiple protective barriers against CpG island hypermethylation. The aberrant hypermethylation occurs at many different loci in the same tissues, suggestive of an overall

  8. 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.

  9. Abnormal mismatch repair and other clinicopathologic predictors of poor response to progestin treatment in young women with endometrial complex atypical hyperplasia and well-differentiated endometrial adenocarcinoma: a consecutive case series.

    PubMed

    Zakhour, M; Cohen, J G; Gibson, A; Walts, A E; Karimian, B; Baltayan, A; Aoyama, C; Garcia, L; Dhaliwal, S K; Elashoff, D; Amneus, M; Walsh, C

    2017-09-01

    To report the response to progestin therapy in young women with endometrial complex atypical hyperplasia (CAH) or FIGO grade 1 endometrial adenocarcinoma (FIGO 1 EAC) based on clinicopathologic features, including abnormal DNA mismatch repair (MMR) by immunohistochemistry (IHC). Consecutive case series. Olive View-UCLA Medical Center in Sylmar, CA, USA, and Cedars-Sinai Medical Center in Los Angeles, CA, USA. Women ≤55 years old with CAH or FIGO 1 EAC. Response to progestin therapy in 84 consecutive patients was assessed based on clinicopathologic factors, including age, body mass index (BMI), initial histology, and IHC staining for MMR proteins. Rates of abnormal MMR protein expression and response to progestin therapy were determined. Six (7%) patients had abnormal IHC staining, of whom five (83%) had FIGO 1 EAC at initial diagnosis. Following progestin treatment, none of the endometrial lesions in patients with abnormal IHC for MMR proteins had resolution of hyperplasia or malignancy, in contrast to 41 (53%) with normal staining (P = 0.028). Age ≤40 years and initial lesion (CAH versus FIGO 1 EAC) were predictors of response to progestin; BMI was not. In this cohort, 7% of women ≤55 years of age with CAH or FIGO 1 EAC had loss of MMR proteins by IHC. These patients had a higher incidence of invasive cancer and a lower incidence of resolution with progestin therapy. Abnormal MMR protein expression predicts poor response to progestins in young women with CAH or FIGO 1 EAC. © 2017 Royal College of Obstetricians and Gynaecologists.

  10. Early adulthood body mass index, cumulative smoking, and esophageal adenocarcinoma survival.

    PubMed

    Spreafico, Anna; Coate, Linda; Zhai, Rihong; Xu, Wei; Chen, Zheng-Fei; Chen, Zhuo; Patel, Devalben; Tse, Brandon; Brown, M Catherine; Heist, Rebecca S; Dodbiba, Lorin; Teichman, Jennifer; Kulke, Matthew; Su, Li; Eng, Lawson; Knox, Jennifer; Wong, Rebecca; Darling, Gail E; Christiani, David C; Liu, Geoffrey

    2017-04-01

    Smoking and obesity are esophageal adenocarcinoma (EAC) risk factors. However, the same risk factors may also affect biological aggressiveness and cancer outcomes. Our study evaluated the combined effects of early-adulthood obesity and cumulative smoking on the EAC survival. In two EAC cohorts, Toronto (TO; N=235) and Boston (BO; N=329), associations between early adulthood body mass index (EA-BMI), BMI at 1year prior to diagnosis (BMI-1), and smoking with overall survival (OS) were assessed using Cox proportional hazard models, adjusted for relevant covariates. Both cohorts were predominantly Caucasian (89%), male (88%), ever-smokers (73%) with locally advanced/metastatic EAC (78%), and good ECOG performance status (90%); median packyears was 34; median EA-BMI, 24; median BMI-1, 25. No relationships with survival were found with BMI-1. For smoking and EA-BMI, TO, BO, and combined TO-BO analyses showed similar associations: smoking conferred worse OS in the combined TO-BO cohort, with adjusted hazard ratios (aHR) of 1.22 (95%CI: 1.15-1.43;p<0.0001) for each 20 pack-year increase. Likewise, EA-BMI ≥25 was associated with worse OS (EA-BMI of 25-<30, aHR=1.84,95%CI: 1.37-2.48; and EA-BMI>30, aHR=2.78, 95%CI: 1.94-3.99). Risk of death was also increased in remotely underweight patients with EA-BMI<18.5 (aHR=2.03,95%CI: 1.27-3.24), when compared to normal-EA-BMI (18≤EA-BMI<25). Two key modifiable behaviors, elevated BMI in early adulthood and heavy cumulative smoking history are independently associated with increased mortality risk in two North American cohorts of EAC patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Preference of endoscopic ablation over medical prevention of esophageal adenocarcinoma by patients with Barrett's esophagus.

    PubMed

    Yachimski, Patrick; Wani, Sachin; Givens, Tonya; Howard, Eric; Higginbotham, Tina; Price, Angie; Berman, Kenneth; Hosford, Lindsay; Katcher, Paul Menard; Ozanne, Elissa; Perzan, Katherine; Hur, Chin

    2015-01-01

    Endoscopic intervention or pharmacologic inhibition of cyclooxygenase might be used to prevent progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC). We investigated whether patients with BE prefer endoscopic therapy or chemoprevention of EAC. Eighty-one subjects with nondysplastic BE were given a survey that described 2 scenarios. The survey explained that treatment A (ablation), endoscopy, reduced lifetime risk of EAC by 50%, with 5% risk for esophageal stricture, whereas treatment B (aspirin) reduced lifetime risk of EAC by 50% and the risk of heart attack by 30%, yet increased the risk for ulcer by 75%. Subjects indicated their willingness to undergo either treatment A and/or treatment B if endoscopic surveillance were required every 3-5 years, every 10 years, or were not required. Visual aids were included to represent risk and benefit percentages. When surveillance was required every 3-5 years, more subjects were willing to undergo treatment A than treatment B (78%, 63 of 81 vs 53%, 43 of 81; P < .01). There were no differences in age, sex, education level, or history of cancer, heart disease, or ulcer between patients willing to undergo treatment A and those willing to undergo treatment B. Altering the frequency of surveillance did not affect patients' willingness to undergo either treatment. In a simulated scenario, patients with BE preferred endoscopic intervention over chemoprevention for EAC. Further investigation of the shared decision-making process regarding preventive strategies for patients with BE may be warranted. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. Cost-Effectiveness Analysis on Endoscopic Surveillance Among Western Patients With Barrett's Esophagus for Esophageal Adenocarcinoma Screening

    PubMed Central

    Yang, Yu; Chen, Hai-Ning; Wang, Rui; Tang, Yun-Jing; Chen, Xin-Zu

    2015-01-01

    Abstract Incidence of esophageal adenocarcinoma (EAC) has risen rapidly over the past decades in Western countries. As a premalignant lesion, Barrett's esophagus (BE) is an established risk factor of EAC. This study estimated the impact of surveillance endoscopy for BE on population's survival upon EAC by a whole-population cost-effectiveness analysis among modeled Western population. Possibilities and survival payoffs were retrieved through literature searching based on PubMed database. Patients with BE were classified as adequate surveillance (AS), inadequate surveillance (IAS), and no surveillance groups. Direct cost of endoscopy per person-year was estimated from diagnosis of BE to before diagnosis of EAC in the whole-population model, whereas the payoff was 2-year disease-specific survival rate of EAC. AS for patients with BE had lower cost-effectiveness ratio (CER) than that of IAS group, as well as lower incremental cost-effectiveness ratio (6116 €/% vs 118,347 €/%). Prolonging the surveillance years could decrease the yearly cost in whole population and also relevant CERs, despite increased total cost. Increasing the proportion of participants in AS group could improve the survival benefit. The maximal payoff was up to 2-year mortality reduction of 2.7 per 100,000 persons by spending extra €1,658,913 per 100,000 person-years. A longer endoscopic surveillance among BE subpopulation plan can reduce yearly budget. Attempt to increase the proportion of AS participants can induce decline in population mortality of EAC, despite extra but acceptable expenditure. However, regarding optimal cost-effectiveness, further studies are still required to identify a high-risk subpopulation out of BE patients for endoscopic surveillance. PMID:26426603

  13. Cost-Effectiveness Analysis on Endoscopic Surveillance Among Western Patients With Barrett's Esophagus for Esophageal Adenocarcinoma Screening

    PubMed Central

    Yang, Yu; Chen, Hai-Ning; Wang, Rui; Tang, Yun-Jing; Chen, Xin-Zu

    2015-01-01

    Abstract Incidence of esophageal adenocarcinoma (EAC) has risen rapidly over the past decades in Western countries. As a premalignant lesion, Barrett's esophagus (BE) is an established risk factor of EAC. This study estimated the impact of surveillance endoscopy for BE on population's survival upon EAC by a whole-population cost-effectiveness analysis among modeled Western population. Possibilities and survival payoffs were retrieved through literature searching based on PubMed database. Patients with BE were classified as adequate surveillance (AS), inadequate surveillance (IAS), and no surveillance groups. Direct cost of endoscopy per person-year was estimated from diagnosis of BE to before diagnosis of EAC in the whole-population model, whereas the payoff was 2-year disease-specific survival rate of EAC. AS for patients with BE had lower cost-effectiveness ratio (CER) than that of IAS group, as well as lower incremental cost-effectiveness ratio (6116 €/% vs 118,347 €/%). Prolonging the surveillance years could decrease the yearly cost in whole population and also relevant CERs, despite increased total cost. Increasing the proportion of participants in AS group could improve the survival benefit. The maximal payoff was up to 2-year mortality reduction of 2.7 per 100,000 persons by spending extra €1,658,913 per 100,000 person-years. A longer endoscopic surveillance among BE subpopulation plan can reduce yearly budget. Attempt to increase the proportion of AS participants can induce decline in population mortality of EAC, despite extra but acceptable expenditure. However, regarding optimal cost-effectiveness, further studies are still required to identify a high-risk subpopulation out of BE patients for endoscopic surveillance.

  14. Glucocorticoid-induced TNFR family-related receptor (GITR)-expression in tumor infiltrating leucocytes (TILs) is associated with the pathogenesis of esophageal adenocarcinomas with and without Barrett's mucosa.

    PubMed

    von Rahden, Burkhard H A; Kircher, S; Kafka, M; Stuermer, L; Reiber, C; Gattenlöhner, S; Germer, C T; Grimm, M

    2010-01-01

    Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett's esophagus (BE) regarded as precancerous lesion. Glucocorticoid-induced TNFR family-related Receptor (GITR)-mediated inflammation of tumor infiltrating leucocytes (TILs) in the tumor microenvironment might play a role during the multistep carcinogenetic process as either tumor promoting factor according to an inflammatory microenvironment or as a feature of anti-tumor activity. Immunohistochemical analysis of GITR expression was analyzed in esophageal cancer (n=70: 41 EAC with BE, 19 EAC without BE, and n=10 esophageal squamous-cell carcinomas, ESCC), the adenocarcinoma cell line OE-33, and peripheral blood leucocytes (PBLs) of EAC patients, furthermore in biopsies of BE without intraepithelial neoplasia (IN) (n=18). Results were correlated with clinicopathological parameters and five-year survival rates. Immunohistochemical GITR expression results were confirmed on mRNA level (RT-PCR). Quantification showed a significant increase of 25% GITR positive TILs in EAC with BE (p< 0.05) compared to 13% in adjacent BE, 24% in EAC without BE, 14% in ESCC, and 1% in BE without IN. High GITR levels were not significantly associated with clinicopathologic features which may predict worse clinical outcome and had no impact on survival (p= 0.7878). Increased GITR expression of peripheral blood leucocytes (PBLs) in EAC patients was shown on protein level (32%) and confirmed by RT-PCR (3.7-fold difference compared to normal tissue). This study provides for the first time evidence that GITR expression of TILs is associated in the pathogenesis of Barrett's esophagus. Our findings suggest that GITR-expression of TILs is associated with cancer progression. Its role as either tumor promoting factor %according to an in the inflammatory microenvironment or as a feature of anti-tumor activity and promising target for molecular therapies needs to be substantiated in further investigations.

  15. MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

    PubMed

    Zaidi, Ali H; Saldin, Lindsey T; Kelly, Lori A; Bergal, Linda; Londono, Ricardo; Kosovec, Juliann E; Komatsu, Yoshihiro; Kasi, Pashtoon M; Shetty, Amit A; Keane, Timothy J; Thakkar, Shyam J; Huleihel, Luai; Landreneau, Rodney J; Badylak, Stephen F; Jobe, Blair A

    2015-01-01

    To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC). The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies. The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors. The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2. In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.

  16. 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.

  17. Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences

    PubMed Central

    Pang, Chunhong; LaLonde, Amy; Godfrey, Tony E; Que, Jianwen; Sun, Jun; Wu, Tong Tong; Zhou, Zhongren

    2017-01-01

    Bile acid reflux in the esophagus plays an important role in the carcinogenesis of esophageal adenocarcinoma (EAC). The G-protein coupled bile acid receptor (TGR5) has been associated with the development of gastrointestinal cancer. However, little is known regarding the role of TGR5 in esophageal carcinoma and precancerous lesions. We analyzed genomic DNA from 116 EACs for copy number aberrations via Affymetrix SNP6.0 microarrays. The TGR5 gene locus was amplified in 12.7% (14/116) of the EACs. The TGR5 protein expression was also assessed using immunohistochemistry from tissue microarrays, including Barrett’s esophagus (BE), low-(LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CM), squamous epithelium (SE), EAC and squamous cell carcinoma. The TGR5 protein was highly expressed in 71% of EAC (75/106), 100% of HGD (11/11), 72% of LGD (13/18), 66% of BE (23/35), 84% of CM (52/62), and 36% of SE (30/83). The patients with high expression of TGR5 exhibited significantly worse overall survival compared to the patients with nonhigh expression. TGR5 high expression was significantly increased in the males compared to the females in all cases with an odds ratio of 1.9 times. The vitamin D receptor (VDR) was significantly correlated with TGR5 expression. Our findings indicated that TGR5 may play an important role in the development and prognosis of EAC through a bile acid ligand. Gender differences in TGR5 and VDR expression may explain why males have a higher incidence of EAC compared to females. PMID:28223834

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

    PubMed Central

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

    2016-01-01

    Background: 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. Materials and Methods: 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. Results: 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. Conclusion: A significant proportion of AIS/EAC is

  19. Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice.

    PubMed

    Smina, T P; Mathew, J; Janardhanan, K K

    2016-04-30

    G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities.

  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. Oncogene amplification in the proximal part of chromosome 6 in rat endometrial adenocarcinoma as revealed by combined BAC/PAC FISH, chromosome painting, zoo-FISH, and allelotyping.

    PubMed

    Adamovic, Tatjana; Trossö, Fredrik; Roshani, Leyla; Andersson, Lars; Petersen, Greta; Rajaei, Saide; Helou, Khalil; Levan, Göran

    2005-10-01

    The inbred BDII rat is a valuable experimental model for the genetic analysis of endometrial adenocarcinoma (EAC). One common aberration detected by comparative genomic hybridization in rat EAC was gain/amplification affecting the proximal part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting probes onto tumor cell metaphase preparations in order to detect and characterize gross RNO6 aberrations. In addition, the RNO6q11-q16 segment was analyzed by fluorescence in situ hybridization with probes representing 12 cancer-related genes in the region. The analysis revealed that seven tumors contained large RNO6-derived homogeneously staining regions (HSRs) in addition to several normal or near-normal RNO6 chromosomes. Five tumors (two of which also had HSRs) exhibited a selective increase of the RNO6q11-q16 segment, sometimes in conjunction with moderate amplification of one or a few genes. Most commonly, the amplification affected the region centered around band 6q16 and included the Mycn, Ddx1, and Rrm2 genes. A second region, centering around Slc8a1 and Xdh, also was affected by gene amplification but to a lesser extent. The aberrations in the proximal part of RNO6 were further analyzed using allelotyping of microsatellite markers in all tumors from animals that were heterozygous in the proximal RNO6 region. We could detect allelic imbalance (AI) in 12 of 20 informative tumors, 6 of which were in addition to those already analyzed by molecular cytogenetic methods as described. Our findings suggest that increase/amplification of genes in this chromosome region contribute to the development of this hormone-dependent tumor.

  2. Esophageal adenocarcinoma and obesity: peritumoral adipose tissue plays a role in lymph node invasion.

    PubMed

    Trevellin, Elisabetta; Scarpa, Marco; Carraro, Amedeo; Lunardi, Francesca; Kotsafti, Andromachi; Porzionato, Andrea; Saadeh, Luca; Cagol, Matteo; Alfieri, Rita; Tedeschi, Umberto; Calabrese, Fiorella; Castoro, Carlo; Vettor, Roberto

    2015-05-10

    Obesity is associated with cancer risk in esophageal adenocarcinoma (EAC). Adipose tissue directly stimulates tumor progression independently from body mass index (BMI), but the mechanisms are not fully understood. We studied the morphological, histological and molecular characteristics of peritumoral and distal adipose tissue of 60 patients with EAC, to investigate whether depot-specific differences affect tumor behavior. We observed that increased adipocyte size (a hallmark of obesity) was directly associated with leptin expression, angiogenesis (CD31) and lymphangiogenesis (podoplanin); however, these parameters were associated with nodal metastasis only in peritumoral but not distal adipose tissue of patients. We treated OE33 cells with conditioned media (CM) collected from cultured biopsies of adipose tissue and we observed increased mRNA levels of leptin and adiponectin receptors, as well as two key regulator genes of epithelial-to-mesenchymal transition (EMT): alpha-smooth muscle actin (α-SMA) and E-cadherin. This effect was greater in cells treated with CM from peritumoral adipose tissue of patients with nodal metastasis and was partially blunted by a leptin antagonist. Therefore, peritumoral adipose tissue may exert a direct effect on the progression of EAC by secreting depot-specific paracrine factors, and leptin is a key player in this crosstalk.

  3. Recurrent gene amplifications in human type I endometrial adenocarcinoma detected by fluorescence in situ hybridization.

    PubMed

    Samuelson, Emma; Levan, Kristina; Adamovic, Tatjana; Levan, Göran; Horvath, György

    2008-02-01

    Determining what genes are actively involved in tumor development is important, because they may provide targets for directed therapy. Human tumors are greatly heterogeneous with respect to etiology and genetic background, which complicates the identification of common genetic aberrations. In contrast, genetic and environmental variation can be in part controlled in experimental animals, which facilitates identification of the important changes. In inbred BDII rats, which are genetically predisposed to endometrial adenocarcinomas (EAC), certain chromosome regions exhibit recurrent amplification in the tumors. Previous CGH analysis had shown that a subset of human EAC tumors exhibited increased copy numbers in the homologous chromosomal regions, located in human 2p21 approximately p25 and 7q21 approximately q31. Using fluorescence in situ hybridization analysis on imprints from 13 human EAC tumors, we determined the average copy numbers of each of 15 probes derived from cancer-related genes situated in these chromosome regions. Among the genes analyzed, those most often targeted by amplification were SDC1 and CYP1B1 in 2p21 approximately p25 and CDK6 and MET in 7q21 approximately q31, but all of the 15 genes tested were found to be amplified in at least two tumors.

  4. Pulmonary enteric adenocarcinoma.

    PubMed

    Handa, Yoshinori; Kai, Yuichiro; Ikeda, Takuhiro; Mukaida, Hidenori; Egawa, Hiromi; Kaneko, Mayumi

    2016-12-01

    A 70-year-old man was referred to our department due to abnormal shadows on a chest radiograph. Computed tomography of the chest revealed a 3-cm nodule in the right middle lung lobe, and bronchoscopy revealed adenocarcinoma cells with EGFR mutations. A lung resection was performed. Histological analysis revealed tumors comprising tall columnar cells that were similar to an adenocarcinoma of the sigmoid colon that had been resected 13 years previously. Metastatic colorectal carcinoma was initially considered, but immunohistochemical staining indicated pulmonary enteric adenocarcinoma. Pulmonary enteric adenocarcinoma was first described in 1991, and about 30 cases have since been described in the English literature. However, its concept and etiology are not clear. It is important to distinguish pulmonary enteric adenocarcinoma from metastatic colorectal carcinoma because of obvious differences in therapeutic strategies and prognosis, especially with a past history of colorectal carcinoma. Immunohistochemical and gene mutation analyses seemed to be helpful.

  5. Primary tumor microRNA signature predicts recurrence and survival in patients with locally advanced esophageal adenocarcinoma.

    PubMed

    Matsui, Daisuke; Zaidi, Ali H; Martin, Samantha A; Omstead, Ashten N; Kosovec, Juliann E; Huleihel, Luai; Saldin, Lindsey T; DiCarlo, Christina; Silverman, Jan F; Hoppo, Toshitaka; Finley, Gene G; Badylak, Stephen F; Kelly, Ronan J; Jobe, Blair A

    2016-12-06

    Esophageal adenocarcinoma (EAC) is an aggressive cancer necessitating the development of improved risk stratification tools for personalized care. Previously, microRNAs have been shown to correlate with the progression and prognosis of various cancer types; however, the value in EAC remains largely unexplored. We performed global microRNA profiling on 32 formalin-fixed, paraffin-embedded EAC specimens to identify microRNAs associated with progression. Literature search and pathway analysis further refined output to five significantly deregulated candidate biomarkers. Four of the five microRNAs (miR-652-5p, miR-7-2-3p, miR-3925-3p, and miR-219-3p) were validated by qRT-PCR. Survival outcomes were evaluated in testing set of 26 stage II/III EAC patients to determine the prognostic relevance of the selected microRNAs. In the testing set, miR-652-5p and miR-7-2-3p expressions were significantly associated with progression-free survival (p-value = .00771 and p-value = .00293). The highest area under receiver operating characteristic (ROC) curve was 0.8212 for the combination of miR-652-5p and miR-7-2-3p. Collectively, our findings demonstrated that the miR-652-5p/miR-7-2-3p signature may serve as a promising prognostic marker in patients with locally advanced EAC.

  6. Primary tumor microRNA signature predicts recurrence and survival in patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Matsui, Daisuke; Zaidi, Ali H.; Martin, Samantha A.; Omstead, Ashten N.; Kosovec, Juliann E.; Huleihel, Luai; Saldin, Lindsey T.; DiCarlo, Christina; Silverman, Jan F.; Hoppo, Toshitaka; Finley, Gene G.; Badylak, Stephen F.; Kelly, Ronan J.; Jobe, Blair A.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is an aggressive cancer necessitating the development of improved risk stratification tools for personalized care. Previously, microRNAs have been shown to correlate with the progression and prognosis of various cancer types; however, the value in EAC remains largely unexplored. We performed global microRNA profiling on 32 formalin-fixed, paraffin-embedded EAC specimens to identify microRNAs associated with progression. Literature search and pathway analysis further refined output to five significantly deregulated candidate biomarkers. Four of the five microRNAs (miR-652-5p, miR-7-2-3p, miR-3925-3p, and miR-219-3p) were validated by qRT-PCR. Survival outcomes were evaluated in testing set of 26 stage II/III EAC patients to determine the prognostic relevance of the selected microRNAs. In the testing set, miR-652-5p and miR-7-2-3p expressions were significantly associated with progression-free survival (p-value = .00771 and p-value = .00293). The highest area under receiver operating characteristic (ROC) curve was 0.8212 for the combination of miR-652-5p and miR-7-2-3p. Collectively, our findings demonstrated that the miR-652-5p/miR-7-2-3p signature may serve as a promising prognostic marker in patients with locally advanced EAC. PMID:27793030

  7. 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.

  8. Association of MDM2 T309G and p53 Arg72Pro polymorphisms and gastroesophageal reflux disease with survival in esophageal adenocarcinoma.

    PubMed

    Renouf, Daniel J; Zhai, Rihong; Sun, Bin; Xu, Wei; Cheung, Winson Y; Heist, Rebecca S; Kulke, Matthew H; Cescon, David; Asomaning, Kofi; Marshall, Ariella L; Li, Su; Christiani, David C; Liu, Geoffrey

    2013-09-01

    Although gastroesophageal reflux disease (GERD) is a risk factor for esophageal adenocarcinoma (EAC), some patients develop EAC in the absence of GERD. A putative mechanism of reflux-induced tumorigenesis involves disruptions in the p53 pathway. We assessed the interaction of GERD and p53 pathway polymorphisms on EAC prognosis. In a prospective cohort of 358 EAC patients, clinical data (including GERD history and survival) were collected. Germline DNA was genotyped for MDM2 T309G and p53 Arg72Pro. Cox proportional hazards models were used to determine adjusted hazard ratios (AHR) for associations between genotype, GERD, and genotype-GERD interactions with survival. Compared with other genotypes, MDM2 G/G (median overall survival 21 vs 30 months; P < 0.001) and p53 Pro/Pro (12 vs 30 months; P = 0.004) were associated with shorter survival. When analyzed by GERD, MDM2 G/G was associated with shorter survival in patients without GERD (AHR 3.4, 95% CI 2.0-6.0), but not in patients with GERD (AHR 1.1 [0.7-1.8]); the MDM2-GERD interaction was significant (P = 0.003). A similar trend was seen for p53 Pro/Pro (AHRs 2.5 without GERD vs 1.4 with GERD). Combined analysis of at-risk variants (MDM2 G or p53 Pro), revealed each additional at-risk variant was associated with shorter survival in patients without GERD (AHR 1.6) but not with GERD (AHR 1.0). MDM2 G/G and the combination of MDM2 G and p53 Pro were negative prognostic factors for EAC patients without GERD but not for those with GERD. There may be biological differences between GERD positive and GERD negative EAC. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  9. MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.

    PubMed

    Derouet, Mathieu Francois; Liu, Geoffrey; Darling, Gail Elizabeth

    2014-01-01

    Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC) pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival. This unexpected result was explored in this current study. In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4) and one ESCC cell line (KYSE-410). After validation of the expression of miR-145, hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, and cell invasion were analyzed. There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines and the control cell lines. miR-145 expression also had no effect on cisplatin resistance in two of three cell lines (OE33 and FLO-1), but miR-145 appeared to protect SK-GT-4 cells against cisplatin treatment. However, there was a significant difference in cell invasion, cell adhesion and resistance to anoikis. All three EAC miR-145 cell lines invaded more than their respective controls. Similarly, OE33 and SK-GT-4 miR-145 cell lines were able to survive longer in a suspension state. While expression of miR-145 in ESCC stopped proliferation and invasion, expression of miR-145 in EAC cells enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, expression of miR-145 appears to promote EAC progression by enhancing invasion and protection against anoikis, which could in turn facilitate distant metastasis.

  10. SOX15 governs transcription in human stratified epithelia and a subset of esophageal adenocarcinomas.

    PubMed

    Sulahian, Rita; Chen, Justina; Arany, Zoltan; Jadhav, Unmesh; Peng, Shouyong; Rustgi, Anil K; Bass, Adam J; Srivastava, Amitabh; Hornick, Jason L; Shivdasani, Ramesh A

    2015-11-01

    Intestinal metaplasia (Barrett's esophagus, BE) is the principal risk factor for esophageal adenocarcinoma (EAC). Study of the basis for BE has centered on intestinal factors, but loss of esophageal identity likely also reflects absence of key squamous-cell factors. As few determinants of stratified epithelial cell-specific gene expression are characterized, it is important to identify the necessary transcription factors. We tested regional expression of mRNAs for all putative DNA-binding proteins in the mouse digestive tract and verified esophagus-specific factors in human tissues and cell lines. Integration of diverse data defined a human squamous esophagus-specific transcriptome. We used chromatin immunoprecipitation (ChIP-seq) to locate transcription factor binding sites, computational approaches to profile transcripts in cancer datasets, and immunohistochemistry to reveal protein expression. The transcription factor SOX15 is restricted to esophageal and other murine and human stratified epithelia. SOX15 mRNA levels are attenuated in BE and its depletion in human esophageal cells reduced esophageal transcripts significantly and specifically. SOX15 binding is highly enriched near esophagus-expressed genes, indicating direct transcriptional control. SOX15 and hundreds of genes co-expressed in squamous cells are reactivated in up to 30% of EAC specimens. Genes normally confined to the esophagus or intestine appear in different cells within the same malignant glands. These data identify a novel transcriptional regulator of stratified epithelial cells and a subtype of EAC with bi-lineage gene expression. Broad activation of squamous-cell genes may shed light on whether EACs arise in the native stratified epithelium or in ectopic columnar cells.

  11. Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid.

    PubMed

    Ojima, Eisuke; Fujimura, Takashi; Oyama, Katsunobu; Tsukada, Tomoya; Kinoshita, Jun; Miyashita, Tomoharu; Tajima, Hidehiro; Fushida, Sachio; Harada, Shin-ichi; Mukaisho, Ken-ichi; Hattori, Takanori; Ohta, Tetsuo

    2015-08-01

    Reflux of bile acid into the esophagus induces esophagitis, inflammation-stimulated hyperplasia, metaplasia such as Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Caudal-type homeobox 2 (Cdx2) via nuclear factor (NF)-κB induced by bile acid is an important factor in the development of BE and EAC. In colorectal cancer, experimental data suggest a chemopreventive effect of ursodeoxycholic acid (UDCA). We hypothesized that UDCA may protect against the esophageal inflammation-metaplasia-carcinoma sequence by decreasing the overall proportion of the toxic bile acids. Wistar male rats that underwent a duodenoesophageal reflux procedure were divided into two groups. One group was given commercial chow (control group), and the other was given experimental chow containing UDCA (UDCA group). The animals were killed at 40 weeks after surgery, and their bile and esophagus were examined. In the UDCA group, the esophagitis was milder and the incidence of BE was significantly lower (p < 0.05) than in the control group, and EAC was not observed (p < 0.05). In analysis of the compartment of bile acid, UDCA was markedly increased in the UDCA group compared with the control group (32.7 ± 11.4 vs. 0.82 ± 0.33 mmol/L, p < 0.05) and cholic acid was decreased (32.7 ± 4.05 vs. 60.9 ± 8.26 mmol/L, p < 0.05). Expression intensity of Cdx2 and NF-κB was greater in the control group than in the UDCA group (p < 0.05). UDCA may be a chemopreventive agent against EAC by varying the bile acid composition.

  12. Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

    PubMed

    Ryom, L; Boesecke, C; Gisler, V; Manzardo, C; Rockstroh, J K; Puoti, M; Furrer, H; Miro, J M; Gatell, J M; Pozniak, A; Behrens, G; Battegay, M; Lundgren, J D

    2016-02-01

    The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview. © 2015 British HIV Association.

  13. Small Bowel Adenocarcinoma.

    PubMed

    Aparicio, Thomas; Zaanan, Aziz; Mary, Florence; Afchain, Pauline; Manfredi, Sylvain; Evans, Thomas Ronald Jeffry

    2016-09-01

    Small bowel adenocarcinomas (SBAs) are rare tumors, but their incidence is increasing. The most common primary location is the duodenum. Even though SBAs are more often sporadic, some diseases are risk factors. Early diagnosis of small bowel adenocarcinoma remains difficult, despite significant radiologic and endoscopic progress. After R0 surgical resection, the main prognostic factor is lymph node invasion. An international randomized trial (BALLAD [Benefit of Adjuvant Chemotherapy For Small Bowel Adenocarcinoma] study) will evaluate the benefit of adjuvant chemotherapy. For metastatic disease, retrospectives studies suggest that platinum-based chemotherapy is the most effective treatment. Phase II studies are ongoing to evaluate targeted therapy in metastatic SBA.

  14. Primary appendiceal mucinous adenocarcinoma.

    PubMed

    Behera, Prativa Kumari; Rath, Pramod Kumar; Panda, Rabiratna; Satpathi, Sanghamitra; Behera, Rajan

    2011-04-01

    Primary Adenocarcinomas of the appendix are extremely rare tumor. We report a case of primary mucinous adenocarcinoma in a 40 year old lady misdiagnosed as having acute appendicitis. All the routine investigations were within normal limit. USG of abdomen showed dilated appendix with little fluid collection adjacent to it and no other abnormality was seen which suggested acute appendicitis. Appendicectomy was done and excised appendix was sent for histopathological examination. Mucinous Adenocarcinoma of the appendix was confirmed after histopathological examination. Right hemicolectomy was done as a second stage procedure. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory.

  15. Adenocarcinoma of the urinary bladder.

    PubMed

    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.

  16. 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

  17. Prostate Ductal Adenocarcinoma.

    PubMed

    Amin, Ali

    2017-03-30

    Prostate ductal adenocarcinoma (PDA) is a rare subtype of prostate adenocarcinoma that shows more aggressive behavior than conventional prostatic acinar adenocarcinoma. PDA demonstrates similar clinical and paraclinical features such as prostatic acinar adenocarcinoma; therefore, clinical distinction of the 2 entities is very difficult (if not impossible) and histopathology plays an important role in the diagnosis of the disease. This review discusses all the necessary information needed for the diagnosis and prognosis of PDA including the morphologic features of PDA, an introduction about the known variants of PDA with helpful hints in grading of each variant, tips on differential diagnosis of PDA from the common morphologic mimickers, a detailed discussion on the value of immunohistochemistry in the diagnosis of PDA, and pathologic features that are helpful in determining the outcome.

  18. Follistatin Is a Novel Biomarker for Lung Adenocarcinoma in Humans

    PubMed Central

    Feng, Ye; Liu, Haiyan; Sun, Yang; Liu, Zhonghui; Ge, Jingyan; Cui, Xueling

    2014-01-01

    Background Follistatin (FST), a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear. Methods and Results The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis. Conclusions These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma. PMID:25347573

  19. Single nucleotide polymorphisms in the matrix metalloproteinase gene family and the frequency and duration of gastroesophageal reflux disease influence the risk of esophageal adenocarcinoma.

    PubMed

    Cheung, Winson Y; Zhai, Rihong; Bradbury, Penny; Hopkins, Jessica; Kulke, Matthew H; Heist, Rebecca S; Asomaning, Kofi; Ma, Clement; Xu, Wei; Wang, Zhaoxi; Hooshmand, Suzanne; Su, Li; Christiani, David C; Liu, Geoffrey

    2012-12-01

    The matrix metalloproteinase (MMP) family of proteins mediates various cellular pathways, including apoptosis and angiogenesis. Polymorphisms of MMP genes are associated with increased esophageal adenocarcinoma (EAC) risk. Gastroesophageal reflux disease (GERD) is an established EAC risk factor. We examined whether MMP polymorphism-EAC risk is modified by GERD. In total, 309 EAC patients and 279 frequency-matched healthy controls underwent MMP1 1G/2G, MMP3 6A/5A, MMP12 -82A/G and MMP12 1082A/G genotyping. Questionnaires collected GERD history. EAC risk was analyzed using logistic regression, adjusted for key covariates and stratified by GERD. Joint effects models explored GERD severity and duration, whereas additional models explored genotype-GERD interactions in EAC risk. We determined that each MMP1 and MMP3 minor (variant) allele was independently associated with increased EAC risk (adjusted odds ratio (AOR) 3.2, 95% confidence interval (CI) 2.0-5.1, p < 0.001 and AOR 1.8, 95% CI 1.1-2.7, p = 0.01, respectively) only among those with GERD but not in GERD-free individuals (all p = nonsignificant). There were significant interactions between the MMP1 variants and the presence of GERD (p = 0.002) and between MMP3 variants and GERD (p = 0.04). There was an equally strong interaction between cumulative GERD severity and MMP1 (p = 0.002). The AOR of each variant allele was 14.9 (95% CI 1.6-136) for individuals with severe GERD, 1.7 (95% CI 1.0-2.7) for mild-moderate GERD and 0.98 (95% CI 0.7-1.4) for those without GERD. This was further reflected in separate analyses of frequency and duration of GERD. In conclusion, MMP1 1G/2G (and possibly MMP3 6A/5A) polymorphisms alter EAC risk differentially for GERD and GERD-free individuals.

  20. 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

  1. Single nucleotide polymorphisms in the matrix metalloproteinase gene family and the frequency and duration of gastroesophageal reflux disease influence the risk of esophageal adenocarcinoma

    PubMed Central

    Cheung, Winson Y.; Zhai, Rihong; Bradbury, Penny; Hopkins, Jessica; Kulke, Matthew H.; Heist, Rebecca S.; Asomaning, Kofi; Ma, Clement; Xu, Wei; Wang, Zhaoxi; Hooshmand, Suzanne; Su, Li; Christiani, David C.; Liu, Geoffrey

    2013-01-01

    The matrix metalloproteinase (MMP) family of proteins mediates various cellular pathways, including apoptosis and angiogenesis. Polymorphisms of MMP genes are associated with increased esophageal adenocarcinoma (EAC) risk. Gastroesophageal reflux disease (GERD) is an established EAC risk factor. We examined whether MMP polymorphism-EAC risk is modified by GERD. In total, 309 EAC patients and 279 frequency-matched healthy controls underwent MMP1 1G/2G, MMP3 6A/5A, MMP12 −82A/G and MMP12 1082A/G genotyping. Questionnaires collected GERD history. EAC risk was analyzed using logistic regression, adjusted for key covariates and stratified by GERD. Joint effects models explored GERD severity and duration, whereas additional models explored genotype–GERD interactions in EAC risk. We determined that each MMP1 and MMP3 minor (variant) allele was independently associated with increased EAC risk (adjusted odds ratio (AOR) 3.2, 95% confidence interval (CI) 2.0–5.1, p < 0.001 and AOR 1.8, 95% CI 1.1–2.7, p = 0.01, respectively) only among those with GERD but not in GERD-free individuals (all p = nonsignificant). There were significant interactions between the MMP1 variants and the presence of GERD (p = 0.002) and between MMP3 variants and GERD (p = 0.04). There was an equally strong interaction between cumulative GERD severity and MMP1 (p = 0.002). The AOR of each variant allele was 14.9 (95% CI 1.6–136) for individuals with severe GERD, 1.7 (95% CI 1.0–2.7) for mild-moderate GERD and 0.98 (95% CI 0.7–1.4) for those without GERD. This was further reflected in separate analyses of frequency and duration of GERD. In conclusion, MMP1 1G/2G (and possibly MMP3 6A/5A) polymorphisms alter EAC risk differentially for GERD and GERD-free individuals. PMID:22422400

  2. A comparison of drug-treated and untreated HCT-116 human colon adenocarcinoma cells using a 2-D liquid separation mapping method based upon chromatofocusing PI fractionation.

    PubMed

    Yan, Fang; Subramanian, Balanehru; Nakeff, Alexander; Barder, Timothy J; Parus, Steven J; Lubman, David M

    2003-05-15

    A multidimensional chromatographic 2-D liquid-phase separation method has been developed for differential display of proteins from cell lysates and applied to a comparison of protein expression between Peninsularinone-treated and untreated HCT-116 human colon adenocarcinoma cells. The method involves fractionation according to pI using chromatofocusing with analytical columns in the first dimension followed by separation of the proteins in each pI fraction using nonporous reversed-phase HPLC. A 2-D map of the protein content of each cell line based upon pI versus hydrophobicity as detected by UV absorption was generated and a differential display map indicating the presence of up- or downregulated proteins displayed using ProteoVue and DeltaVue software. Using this method, > 1000 protein bands could be detected in 0.2 pH fractions over a pH range of 4-7. In addition, the liquid eluent from the separation was directed on-line into an electrospray TOF-MS to obtain an accurate molecular weight of the intact proteins. An accurate molecular weight together with the peptide map was used to obtain protein identification using database searching. The method has been shown to have high reproducibility for quantitative differential display analysis of interlysate comparisons, generation of accurate protein identifications, and ease of data interpretation. It has been used herein to identify proteins that change as a function of drug treatment. The relative simplicity of the current procedure and the potential for full automation will make this technique an essential tool in future proteomic studies.

  3. Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma

    PubMed Central

    Warren, Andrew; Cheetham, R. Keira; Northen, Helen; O’Donovan, Maria; Malhotra, Shalini; di Pietro, Massimiliano; Ivakhno, Sergii; He, Miao; Weaver, Jamie M.J.; Lynch, Andy G.; Kingsbury, Zoya; Ross, Mark; Humphray, Sean; Bentley, David; Fitzgerald, Rebecca C.

    2015-01-01

    The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett’s esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett’s esophagus and EAC samples, together with one in-depth Barrett’s esophagus case-study sampled over time and space, we have provided new insights on the following aspects: i) Barrett’s esophagus is polyclonal and highly mutated even in the absence of dysplasia; ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett’s esophagus; and iii) despite differences in specific coding mutations the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett’s epithelium and a molecular Cytosponge™ technique overcomes sampling bias and has capacity to reflect the entire clonal architecture. PMID:26192915

  4. Reduced genomic tumor heterogeneity after neoadjuvant chemotherapy is related to favorable outcome in patients with esophageal adenocarcinoma

    PubMed Central

    Obulkasim, Askar; Ylstra, Bauke; van Essen, Hendrik F.; Benner, Christian; Stenning, Sally; Langley, Ruth; Allum, William; Cunningham, David; Inam, Imran; Hewitt, Lindsay C.; West, Nicolas P.; Meijer, Gerrit A.; van de Wiel, Mark A.; Grabsch, Heike I.

    2016-01-01

    Neoadjuvant chemo(radio)therapy followed by surgery is the standard of care for patients with locally advanced resectable esophageal adenocarcinoma (EAC). There is increasing evidence that drug resistance might be related to genomic heterogeneity. We investigated whether genomic tumor heterogeneity is different after cytotoxic chemotherapy and is associated with EAC patient survival. We used arrayCGH and a quantitative assessment of the whole genome DNA copy number aberration patterns (‘DNA copy number entropy’) to establish the level of genomic tumor heterogeneity in 80 EAC treated with neoadjuvant chemotherapy followed by surgery (CS group) or surgery alone (S group). The association between DNA copy number entropy, clinicopathological variables and survival was investigated. DNA copy number entropy was reduced after chemotherapy, even if there was no morphological evidence of response to therapy (p<0.001). Low DNA copy number entropy was associated with improved survival in the CS group (p=0.011) but not in the S group (p=0.396). Our results suggest that cytotoxic chemotherapy reduces DNA copy number entropy, which might be a more sensitive tumor response marker than changes in the morphological tumor phenotype. The use of DNA copy number entropy in clinical practice will require validation of our results in a prospective study. PMID:27286451

  5. A novel intraperitoneal metastatic xenograft mouse model for survival outcome assessment of esophageal adenocarcinoma

    PubMed Central

    Awasthi, Niranjan; Li, Jun; Schwarz, Margaret A.; Schwarz, Roderich E.; von Holzen, Urs

    2017-01-01

    Esophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States. The 5-year survival rate of EAC is below 20% and most patients present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Improvement of EAC patient outcome requires well-characterized animal models in which to evaluate novel therapeutics. In this study we aimed to establish a peritoneal dissemination xenograft mouse model of EAC that would support survival outcome analyses. To find the best candidate cell line from 7 human EAC cell lines of different origin named ESO26, OE33, ESO51, SK-GT-2, OE19, OACM5.1C and Flo-1 were injected intraperitoneally/subcutaneously into SCID mice. The peritoneal/xenograft tumor formation and mouse survival were compared among different groups. All cell lines injected subcutaneously formed tumors within 3 months at variable rates. All cell lines except OACM5.1C formed intraperitoneal tumors within 3 months at variable rates. Median animal survival with peritoneal dissemination was 108 days for ESO26 cells (5X106), 65 days for OE33 cells (5X106), 88 days for ESO51 cells (5X106), 76 days for SK-GT-2 cells (5X106), 55 days for OE19 cells (5X106), 45 days for OE19 cells (10X106) and 82 days for Flo-1 cells (5X106). Interestingly, only in the OE19 model all mice (7/7 for 5X106 and 5/5 for10X106) developed bloody ascites with liver metastasis after intraperitoneal injection. The median survival time of these animals was the shortest (45 days for 10X106 cells). In addition, median survival was significantly increased after paclitaxel treatment compared with the control group (57 days versus 45 days, p = 0.0034) along with a significant decrease of the relative subcutaneous tumor volume (p = 0.00011). Thus peritoneal dissemination mouse xenograft model for survival outcome assessment after intraperitoneal injection of OE19 cells will

  6. Mucinous (colloid) adenocarcinomas secrete distinct O-acylated forms of sialomucins: a histochemical study of gastric, colorectal and breast adenocarcinomas.

    PubMed

    Sáez, C; Japón, M A; Poveda, M A; Segura, D I

    2001-12-01

    Mucinous (colloid) adenocarcinomas represent a distinct group of tumours defined by the presence of large amounts of extracellular mucins. By using histochemical methods, we analysed mucins secreted by mucinous versus non-mucinous adenocarcinomas and looked for differential secretion profiles. Sixty-four adenocarcinomas were studied (23 colorectal, 17 gastric, and 24 breast tumours). Thirty-two tumours were of the colloid type. The following methods were applied to paraffin tissue sections: (i) Alcian blue (pH 2.5) and periodic acid-Schiff (PAS); (ii) high iron diamine and Alcian blue (pH 2.5); (iii) periodic acid borohydride, potassium hydroxide, and PAS; (iv) periodic acid-thionine Schiff, potassium hydroxide, and PAS; and (v) periodic acid-borohydride and PAS. Most adenocarcinomas secreted acidic mucins, with sialomucins predominating over sulfomucins, except for non-mucinous adenocarcinomas of the breast which showed predominant neutral mucins. All mucinous adenocarcinomas contained C9-O-acyl sialic acid as mono, di(C8,C9)-, or tri(C7,C8,C9)-O-acyl forms. Acidic mucins secreted by the majority of non-colloid adenocarcinomas consisted of non-O-acylated sialomucins. C9-O-acylation of sialic acid is a characteristic feature of mucinous adenocarcinomas and can be readily detected by histochemical methods.

  7. Solid adenocarcinoma

    Cancer.gov

    Uniformly solid character of the lesions is usually indicative of a well differentiated tumor. No solid adenocarcinomas have observed in our series. However, rare cases have been described by others. In human pathology this diagnosis is usually based on detection of mucin after periodic acid-Schiff reaction with diastase (α-amylase) digestion.

  8. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    PubMed

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe

    2017-03-01

    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  9. The Ueno method for substaging pT1 colorectal adenocarcinoma by depth and width measurement: an interobserver study.

    PubMed

    Wang, L M; Guy, R; Fryer, E; Kartsonaki, C; Gill, P; Hughes, C; Szuts, A; Perera, R; Chetty, R; Mortensen, N

    2015-08-01

    Early pT1 polyp colorectal cancers (CRCs) present challenges for accurate pathology substaging. Haggitt and Kikuchi stages depend on polyp morphology and are often difficult to apply due to suboptimal orientation or fragmentation, or absence of the muscularis propria in polypectomy or submucosal resection specimens. European guidelines for quality assurance suggest using Ueno's more objective approach, using depth and width measurements beyond muscularis mucosae. We have investigated interobserver variation using Ueno's approach. Ten consecutive pT1 polyp CRCs were identified and the slides assessed by six gastrointestinal pathologists for depth and width of invasion. A further 60 polyps were studied by a group of specialist and general pathologists. Agreement was assessed by analysis of variance. A polyp CRC is classified as high risk if it has a depth ≥ 2000 μm or a width ≥ 4000 μm and low risk with a depth < 2000 μm or a width < 4000 μm. Concordance for the dichotomized values was assessed using the kappa statistic. The intraclass correlation coefficient (ICC) for depth was 0.83 and for width 0.56 in the 10-polyp group. The ICC for the 60-polyp CRCs was 0.67 for depth and 0.37 for width. In both groups, when polyp CRCs are divided into high- and low-risk categories based on depth, there was substantial and moderate agreement (κ = 0.80 and 0.47) but only fair agreement when based on width (κ = 0.34 and 0.35). Ueno's method has the advantage of being independent of polyp morphology. Our study shows better concordance for depth measurement and reproducibility in nonfragmented specimens, with poorer agreement when based on width. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

  10. Antineoplastic activity of N-(2-hydroxybenzylidene)2'-hydroxyphenylimine aqua nickel(II) complex [NI(H₂O)HHP] on ehrlich ascites carcinoma (EAC) in Swiss albino mice.

    PubMed

    Hossain, Israt Ara; Khanam, Jahan Ara; Jesmin, Mele; Ali, Mohammud Mohshin

    2016-01-01

    The present study is aimed at evaluating the antineoplastic activity of N[(2-hydroxybenzylidene)2'-hydroxyphenylimine] aqua nickel(II) complex abbreviated as [Ni(H2O)HHP] complex against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. The effectiveness of the drug at doses of 0.5, 1.0 and 2.0 mg/kg body weight was assessed for five consecutive days in previously inoculated tumor (137×10(4) EAC) cells containing mice. After administration of the last dose followed by 16 h fasting, the effect of the [Ni(H2O)HHP] complex on tumor was assessed by EAC cell growth inhibition, solid tumor mass, survival time, peritoneal cell count, hematological profiles like red blood cells (RBC), white blood cells (WBC), haemoglobin (Hb)% and differential counts (i.e., lymphocytes, neutrophils, monocytes) and biochemical parameters like serum glucose, total cholesterol, total protein, serum urea and liver enzymes, respectively. The results have been compared with the data obtained by using a standard and highly effective clinically used anticancer drug bleomycin. [Ni(H2O)HHP] complex at dose 2.0 mg/kg i.p. (intra peritoneal) showed a significant (P=0.001) decrease in tumor volume of each mice and increased the life span as well as mean survival time of EAC bearing mice. Hematological and biochemical parameters of EAC bearing mice get back normal values after 15 days of the initial treatment. From the above outcomes indicate the possible potential use of the compound as antitumor agent in advanced researches. Copyright © 2015 Elsevier GmbH. All rights reserved.

  11. Invasive Adenocarcinoma of the Lung is Associated with the Upper Lung Regions

    PubMed Central

    Kinsey, C. Matthew; Estepar, Raul San Jose; Zhao, Yang; Yu, Xiaojin; Diao, Nancy; Heist, Rebecca Suk; Wain, John C.; Mark, Eugene J.; Washko, George; Christiani, David C.

    2014-01-01

    Objectives We postulated that ventilation-perfusion (V/Q) relationships within the lung might influence where lung cancer occurs. To address this hypothesis we evaluated the location of lung adenocarcinoma, by both tumor lobe and superior-inferior regional distribution, and associated variables such as emphysema. Materials and Methods One hundred fifty-nine cases of invasive adenocarcinoma and adenocarcinoma with lepidic features were visually evaluated to identify lobar or regional tumor location. Regions were determined by automated division of the lungs into three equal volumes: (upper region, middle region, or lower region). Automated densitometry was used to measure radiographic emphysema. Results The majority of invasive adenocarcinomas occurred in the upper lobes (69%), with 94% of upper lobe adenocarcinomas occurring in the upper region of the lung. The distribution of adenocarcinoma, when classified as upper or lower lobe, was not different between invasive adenocarcinoma and adenocarcinoma with lepidic features (formerly bronchioloalveolar cell carcinoma, P=0.08). Regional distribution of tumor was significantly different between invasive adenocarcinoma and adenocarcinoma with lepidic features (P = 0.001). Logistic regression analysis with the outcome of invasive adenocarcinoma histology was used to adjust for confounders. Tumor region continued to be a significant predictor (OR 8.5, P=0.008, compared to lower region), whereas lobar location of tumor was not (P=0.09). In stratified analysis, smoking was not associated with region of invasive adenocarcinoma occurrence (p=0.089). There was no difference in total emphysema scores between invasive adenocarcinoma cases occurring in each of the three regions (P=0.155). There was also no difference in the distribution of region of adenocarcinoma occurrence between quartiles of emphysema (P=0.217). Conclusion Invasive adenocarcinoma of the lung is highly associated with the upper lung regions. This association is

  12. DNA methylation profiling of esophageal adenocarcinoma using Methylation Ligation-dependent Macroarray (MLM).

    PubMed

    Guilleret, Isabelle; Losi, Lorena; Chelbi, Sonia T; Fonda, Sergio; Bougel, Stéphanie; Saponaro, Sara; Gozzi, Gaia; Alberti, Loredana; Braunschweig, Richard; Benhattar, Jean

    2016-10-14

    Most types of cancer cells are characterized by aberrant methylation of promoter genes. In this study, we described a rapid, reproducible, and relatively inexpensive approach allowing the detection of multiple human methylated promoter genes from many tissue samples, without the need of bisulfite conversion. The Methylation Ligation-dependent Macroarray (MLM), an array-based analysis, was designed in order to measure methylation levels of 58 genes previously described as putative biomarkers of cancer. The performance of the design was proven by screening the methylation profile of DNA from esophageal cell lines, as well as microdissected formalin-fixed and paraffin-embedded (FFPE) tissues from esophageal adenocarcinoma (EAC). Using the MLM approach, we identified 32 (55%) hypermethylated promoters in EAC, and not or rarely methylated in normal tissues. Among them, 21promoters were found aberrantly methylated in more than half of tumors. Moreover, seven of them (ADAMTS18, APC, DKK2, FOXL2, GPX3, TIMP3 and WIF1) were found aberrantly methylated in all or almost all the tumor samples, suggesting an important role for these genes in EAC. In addition, dysregulation of the Wnt pathway with hypermethylation of several Wnt antagonist genes was frequently observed. MLM revealed a homogeneous pattern of methylation for a majority of tumors which were associated with an advanced stage at presentation and a poor prognosis. Interestingly, the few tumors presenting less methylation changes had a lower pathological stage. In conclusion, this study demonstrated the feasibility and accuracy of MLM for DNA methylation profiling of FFPE tissue samples. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. [Sinonasal adenocarcinomas: our experience].

    PubMed

    Llorente, José Luis; Núñez, Faustino; Rodrigo, Juan Pablo; Fernández León, Ramón; Alvarez, César; Hermsen, Mario; Suárez, Carlos

    2008-05-01

    Sinonasal adenocarcinoma is a rare epithelial cancer of the nasal cavities and paranasal sinuses and exposure to sawdust particles is a strong aetiological factor. Seventy-nine patients (78 men and 1 woman) operated on between 1986 and 2002 were studied. In 62 patients (78.5 %) there was a history of exposure to wood dust. The clinical factors presenting statistical significance in the multivariate analysis with prognosis were: the exclusive invasion of the middle concha (as good prognosis), recurrence and invasion of the dura mater (as bad prognosis). The actuarial survival rate was 36 % at 5 years falling to 28 % at 10 years. Exposure to wood dust, even over a short period of time, must be considered as a high risk factor for the development of a sinonasal adenocarcinoma. This tumour must be ruled out in all patients suffering any type of sinonasal pathology.

  14. Villoglandular papillary adenocarcinoma: case report

    PubMed Central

    Salek, Ghizlane; Lalya, Issam; Rahali, Driss Moussaoui; Dehayni, Mohamed

    2016-01-01

    Villoglandular papillary adenocarcinoma (VPA) is a very rare subtype of adenocarcinoma of the uterine cervix, but a well-recognized variant of cervical adenocarcinoma with a favorable prognosis and generally occurring in women of child-bearing age. Herein, we report a case of VPA diagnosed and managed successfully with conservative measure. This management is particularly desirable in young women to preserve reproductive capability. PMID:28293348

  15. Do mesothelin/MUC16 interactions facilitate adenocarcinoma metastases to intracranial meningiomas?

    PubMed Central

    Johnson, Mahlon D.

    2016-01-01

    Background: Meningiomas have been shown to express mesothelin, a high affinity binding site for MUC16, a transmembrane protein on adenocarcinoma cells. The mechanisms underlying adenocarcinoma metastases to meningiomas may provide insight into tumor-to-tumor metastases and adenocarcinoma metastases to leptomeningeal cells. Methods: Two meningiomas containing metastases from adenocarcinomas were identified and evaluated immunohistochemically for the expression and localization of mesothelin and MUC16. Results: Both meningiomas show extensive mesothelin immunoreactivity, and the adenocarcinomas metastatic to the meningiomas show mesothelin and MUC16 immunoreactivity at the interface with meningioma. Conclusions: Interactions between MUC16 and/or mesothelin on the cell membrane of adenocarcinoma cells with mesothelin on meningioma cells may facilitate adenocarcinoma metastases to meningiomas and possibly the leptomeninges. PMID:28144481

  16. DNA Methylation Changes in Atypical Adenomatous Hyperplasia, Adenocarcinoma In Situ, and Lung Adenocarcinoma

    PubMed Central

    Selamat, Suhaida A.; Galler, Janice S.; Joshi, Amit D.; Fyfe, M. Nicky; Campan, Mihaela; Siegmund, Kimberly D.; Kerr, Keith M.; Laird-Offringa, Ite A.

    2011-01-01

    Background Aberrant DNA methylation is common in lung adenocarcinoma, but its timing in the phases of tumor development is largely unknown. Delineating when abnormal DNA methylation arises may provide insight into the natural history of lung adenocarcinoma and the role that DNA methylation alterations play in tumor formation. Methodology/Principal Findings We used MethyLight, a sensitive real-time PCR-based quantitative method, to analyze DNA methylation levels at 15 CpG islands that are frequently methylated in lung adenocarcinoma and that we had flagged as potential markers for non-invasive detection. We also used two repeat probes as indicators of global DNA hypomethylation. We examined DNA methylation in 249 tissue samples from 93 subjects, spanning the putative spectrum of peripheral lung adenocarcinoma development: histologically normal adjacent non-tumor lung, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS, formerly known as bronchioloalveolar carcinoma), and invasive lung adenocarcinoma. Comparison of DNA methylation levels between the lesion types suggests that DNA hypermethylation of distinct loci occurs at different time points during the development of lung adenocarcinoma. DNA methylation at CDKN2A ex2 and PTPRN2 is already significantly elevated in AAH, while CpG islands at 2C35, EYA4, HOXA1, HOXA11, NEUROD1, NEUROD2 and TMEFF2 are significantly hypermethylated in AIS. In contrast, hypermethylation at CDH13, CDX2, OPCML, RASSF1, SFRP1 and TWIST1 and global DNA hypomethylation appear to be present predominantly in invasive cancer. Conclusions/Significance The gradual increase in DNA methylation seen for numerous loci in progressively more transformed lesions supports the model in which AAH and AIS are sequential stages in the development of lung adenocarcinoma. The demarcation of DNA methylation changes characteristic for AAH, AIS and adenocarcinoma begins to lay out a possible roadmap for aberrant DNA methylation events in tumor

  17. Antitumor effects of cyclin dependent kinase 9 inhibition in esophageal adenocarcinoma

    PubMed Central

    Tong, Zhimin; Chatterjee, Devkumar; Deng, Defeng; Veeranki, Omkara; Mejia, Alicia; Ajani, Jaffer A; Hofstetter, Wayne; Lin, Steven; Guha, Sushovan; Kopetz, Scott; Krishnan, Sunil; Maru, Dipen

    2017-01-01

    Role of cyclin dependent kinase 9(CDK9) as a potential target in esophageal adenocarcinoma (EAC) is unknown. We investigated CDK9 protein expression in EAC and Barrett's esophagus and role of CDK9 in oncogenic processes of EAC in vitro and in murine xenografts. The CDK9 expression was significantly higher in EAC as compared to Barrett's esophagus in patient samples. Stable shCDK9 in SKGT4 reduced proliferation by 37% at day 4, increased apoptosis at 48 hours and induced G1 cell cycle arrest at 48 hours (58.4% vs. 45.8%) compared to controls SKGT4 cells. SKGT4-shCDK9 cell-derived tumors were significantly smaller than control SKGT4-derived tumors in xenografts (72.89mm3 vs. 270mm3). Pharmaceutical inhibition of CDK9 by Flavopiridol (0.1μm for 48 hours) and CAN508 (20 and 40μm for 72 hours) induced significant reduction in proliferation and 2-fold increase in apoptosis in SKGT4, FLO1 and OE33 cells. In xenograft models, CAN508 (60 mg/kg/dayx10 days) and Flavopiridol (4mg/kg/dayx10 days) caused 50.8% and 63.1% reduction in xenograft tumors as compared to control on post-treatment day 21. Reduction of MCL-1 and phosphorylated RNA polymerase II was observed with transient shCDK9 in SKGT4 cells but not with stable shCDK9. CAN508 (20 and 40 μm) and Flavopiridol (0.1, 0.2 and 0.3 μm) for 4 hours showed reduction in MCL-1 mRNA (84% and 96%) and protein. Mcl-1 overexpression conferred resistance to Flavopiridol (0.2 μm or 0.4 μm for 48 hours) and CAN 508 (20 or 40μm for 72 hours). Chromatin immunoprecipitation demonstrated significant reduction of binding of transcriptional factor HIF-1α to MCL-1 promoter in FLO-1 cells by CDK9 inhibitors. PMID:28404924

  18. Antitumor effects of cyclin dependent kinase 9 inhibition in esophageal adenocarcinoma.

    PubMed

    Tong, Zhimin; Chatterjee, Devkumar; Deng, Defeng; Veeranki, Omkara; Mejia, Alicia; Ajani, Jaffer A; Hofstetter, Wayne; Lin, Steven; Guha, Sushovan; Kopetz, Scott; Krishnan, Sunil; Maru, Dipen

    2017-04-25

    Role of cyclin dependent kinase 9(CDK9) as a potential target in esophageal adenocarcinoma (EAC) is unknown. We investigated CDK9 protein expression in EAC and Barrett's esophagus and role of CDK9 in oncogenic processes of EAC in vitro and in murine xenografts. The CDK9 expression was significantly higher in EAC as compared to Barrett's esophagus in patient samples. Stable shCDK9 in SKGT4 reduced proliferation by 37% at day 4, increased apoptosis at 48 hours and induced G1 cell cycle arrest at 48 hours (58.4% vs. 45.8%) compared to controls SKGT4 cells. SKGT4-shCDK9 cell-derived tumors were significantly smaller than control SKGT4-derived tumors in xenografts (72.89mm3 vs. 270mm3). Pharmaceutical inhibition of CDK9 by Flavopiridol (0.1µm for 48 hours) and CAN508 (20 and 40µm for 72 hours) induced significant reduction in proliferation and 2-fold increase in apoptosis in SKGT4, FLO1 and OE33 cells. In xenograft models, CAN508 (60 mg/kg/dayx10 days) and Flavopiridol (4mg/kg/dayx10 days) caused 50.8% and 63.1% reduction in xenograft tumors as compared to control on post-treatment day 21. Reduction of MCL-1 and phosphorylated RNA polymerase II was observed with transient shCDK9 in SKGT4 cells but not with stable shCDK9. CAN508 (20 and 40 µm) and Flavopiridol (0.1, 0.2 and 0.3 µm) for 4 hours showed reduction in MCL-1 mRNA (84% and 96%) and protein. Mcl-1 overexpression conferred resistance to Flavopiridol (0.2 µm or 0.4 µm for 48 hours) and CAN 508 (20 or 40µm for 72 hours). Chromatin immunoprecipitation demonstrated significant reduction of binding of transcriptional factor HIF-1α to MCL-1 promoter in FLO-1 cells by CDK9 inhibitors.

  19. [Mesocolic excision for colonic adenocarcinoma].

    PubMed

    Debove, Clotilde; Lefèvre, Jérémie H; Parc, Yann

    2017-02-01

    On the same principle than total mesorectal excision in rectal cancer, the effect of complete mesocolic excision on short and long-term outcomes is actually evaluated for colonic adenocarcinoma. This method, usually performed for left colectomy, offers a surgical specimen of higher quality, with a larger number of lymph nodes harvested. For right colectomy, surgical specifications make it less common complete mesocolic excision and conventional surgery offer comparable outcomes, as regards to postoperative morbidity and mortality rates. No differences are identified between laparoscopic and open surgery. On oncologic outcomes, only two studies report a higher free-disease survival after complete mesocolic excision. Then, there is evidence that complete mesocolic excision offers a higher rate of specimen with extensive lymph node resection, without increased morbidity rate. However, there is limited evidence that it leads to improve long-term oncological outcomes.

  20. Immunohistochemical identification method of tumour cells in the S phase of mitotic cycle and its usefulness in diagnostics of mammary gland adenocarcinomas in bitches.

    PubMed

    Nowak, M; Madej, J A; Dziegiel, P; Kanzawa, H

    2006-01-01

    The studies aimed at identification of neoplastic cells at the S phase of mitotic cycle in mammary gland adenocarcinomas of bitches. The material was sampled from bitches of various races, aging 6 to 12 years, in which the mammary gland tumours developed spontaneously. The tumours were verified histopathologically and, then, immunohistochemical reactions were performed in order to detect cells which had incorporated BrdU (bromodeoxyuridine), contained Ki-67 or PCNA antigen. The histological preparations were photographed and obtained pictures were subjected to computer-assisted image analysis using Axiophot microscope (Carl Zeiss) coupled to a computer and the Multi-ScaneBase V 8.08 software, working under Windows. Fifty percent of sections from mammary gland adenocarcinomas demonstrated BrdU labelling index of 4-5%, 40% of 1-3%, while in the remaining 10% of examined tumours no BrdU incorporation could be demonstrated. No evident relationship could be detected between the presence of BrdU incorporation and Ki-67 or PCNA antigen presence but a significant correlation was demonstrated between the expression of Ki-67 and PCNA.

  1. 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

  2. Quantitative CT Analysis of Pulmonary Ground-Glass Opacity Nodules for the Distinction of Invasive Adenocarcinoma from Pre-Invasive or Minimally Invasive Adenocarcinoma

    PubMed Central

    Son, Ji Ye; Lee, Ho Yun; Lee, Kyung Soo; Kim, Jae-Hun; Han, Joungho; Jeong, Ji Yun; Kwon, O Jung; Shim, Young Mog

    2014-01-01

    Objectives We aimed to analyze the CT findings of ground-glass opacity nodules diagnosed pathologically as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma in order to investigate whether quantitative CT parameters enable distinction of invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. Methods We reviewed CT images and pathologic specimens from 191 resected ground-glass opacity nodules with little or no solid component at CT. Nodule size, volume, density, mass, skewness/kurtosis, and CT attenuation values at the 2.5th–97.5th percentiles on histogram, and texture parameters (uniformity and entropy) were assessed from CT datasets. Results Of 191 tumors, 38 were AISs (20%), 61 were MIAs (32%), and 92 (48%) were invasive adenocarcinomas. Multivariate logistic regression analysis helped identify the 75th percentile CT attenuation value (P = 0.04) and entropy (P<0.01) as independent predictors for invasive adenocarcinoma, with an area under the receiver operating characteristic curve of 0.780. Conclusion Quantitative analysis of preoperative CT imaging metrics can help distinguish invasive adenocarcinoma from pre-invasive or minimally invasive adenocarcinoma. PMID:25102064

  3. 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

  4. [Uterine metastasis revealing gastric adenocarcinoma].

    PubMed

    Mambrini, P; Giovanini, M; Seitz, J F; Perrier, H; Allemand, I; Rabia, I; Monges, G; Lebreuil, G

    1995-01-01

    We report a case of metastasis to the uterine corpus revealing a primary gastric adenocarcinoma. A 26-year-old woman suffered from weight loss, vaginal bleeding, abdominal pain. An endometrial curettage showed apparently metastatic adenocarcinoma. The primary site of the tumour was gastric. The upper gastrointestinal endoscopy revealed an ulcus and aspect of linitis plastica in the fundus. Biopsies showed diffuse type adenocarcinoma. Because of extensive disease, laparotomy was not performed and exclusive palliative chemotherapy was started. The patient died 10 months after the diagnosis. Metastasis from primary gastric cancer to the female genital tract are rare and are usually observed in young premenopausal women with diffuse type gastric adenocarcinoma. This case report underlines the interest, for those patients of careful gynaecologic examination at the initial staging and after treatment.

  5. Primary bladder adenocarcinoma versus metastatic colorectal adenocarcinoma: a persisting diagnostic challenge

    PubMed Central

    2012-01-01

    Aim This study attempted to distinguish primary bladder adenocarcinoma (PBA) from metastatic colonic adenocarcinomas (MCA), which is a difficult diagnostic and clinical problem. Methods Twenty-four cases of bladder adenocarcinomas (12 primary & 12 metastatic colorectal) were included in the study with urothelial carcinoma (UC) and colonic adenocarcinoma (CA) as controls. A panel of immunohistochemical (IHC) stains along with fluorescence in-situ hybridization (FISH), using the UroVysion probe set, was performed. Results The majority of the PBAs presented with advanced disease. Enteric histologic subtype was the most common morphological variant. Strong nuclear with cytoplasmic-membranous staining of β-catenin was seen in 75% of MCA and only 16.7% PBA (<10% staining cells). Although abnormal nuclear staining with E-cadherin was seen in both PBA and MCA, it was more frequent in former. CK-7, CK-20, villin and CDX-2 stains were not helpful in distinguishing the two entities. FISH did not reveal any unique differences in chromosomal abnormality between the two groups. Conclusion Although there was a statistically significant difference in β-catenin and E-cadherin staining between two groups, we did not find any IHC or FISH marker that was specific for PBA. Distinction between PBA and MCA remains a diagnostic problem and clinical correlation is vital before rendering a diagnosis. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1393156268152357 PMID:23121893

  6. Apoptosis-inducing Effect of a Palladium(II) Complex-[PdCl(terpy)](sac).2H2O] on Ehrlich Ascites Carcinoma (EAC) in Mice.

    PubMed

    Ikitimur-Armutak, Elif I; Ulukaya, Engin; Gurel-Gurevin, Ebru; Yaylim, Ilhan; Isbilen-Basok, Banu; Sennazli, Gulbin; Yuzbasioglu-Ozturk, Gulay; Sonmez, Kivilcim; Celik, Faruk; Kucukhuseyin, Ozlem; Korkmaz, Gurbet; Yilmaz, Veysel T; Zeybek, Sakir Umit

    2016-01-01

    New compounds for cancer treatment are needed due to persistenly unsatisfactory management of cancer. [PdCl(terpy)](sac)·2H2O] (sac=saccharinate, and terpy=2,2':6',2"-terpyridine) is a compound synthesized for this purpose. We investigated its anti-proliferative and pro-apoptotic effects on Ehrlich Ascites Carcinoma (EAC) in vivo. 42 Balb-c female mice were subcutaneously (s.c.) injected with EAC cells (1st day) and then randomly divided into 5 groups: control (0.9% NaCl), complex (2 mg/kg), complex (3 mg/kg) cisplatin (4 mg/kg) and paclitaxel (12.5 mg/kg). On the 5th and 12th day animals were drug administrated. At 14th day, animals were sacrificed. Expression of cell death and/or cell cycle-related markers (Bcl-2, Bax, active caspase-3, p53, PCNA) and apoptosis were investigated immunohisto-chemically. Survival-related markers (Akt, GSK-3β, IGF-1R, IR, IRS-1, p70S6K, PRAS40) were evaluated by luminex analysis. Expression of p53, PCNA, Bcl-2 was found decreased (p<0.001) and that of active caspase-3, Bax, and apoptotic cells was found increased (p<0.001) in all groups. The survival-related markers did not show any statistical difference in complex groups. The Pd(II)-complex seems to have a strong anticancer activity on EAC by inducing apoptosis via both suppression of proliferation and activation of apoptosis in vivo, similar to the effects of cisplatin and paclitaxel. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Laparoscopy in the management of gastric adenocarcinoma.

    PubMed Central

    Burke, E C; Karpeh, M S; Conlon, K C; Brennan, M F

    1997-01-01

    OBJECTIVE: The authors determined the accuracy of laparoscopy in detecting metastatic disease in patients with gastric adenocarcinoma. SUMMARY BACKGROUND DATA: The majority of patients with gastric adenocarcinoma in the United States present with advanced disease. They are at high risk for intraabdominal metastatic spread. METHODS: One hundred eleven patients with gastric adenocarcinoma underwent laparoscopy at Memorial-Sloan Kettering Cancer Center from December 1991 to December 1995. All were judged to be free of intra-abdominal metastatic disease on preoperative computed tomographic scan imaging. RESULTS: Laparoscopic exploration was successful in 110 of 111 patients and accurately staged 94% of the patients with respect to metastatic disease with a sensitivity of 84% and a specificity of 100%. The prevalence rate of metastatic disease was 37%. Twenty-four patients underwent laparoscopy only and were discharged in an average 1.4 days versus 6.5 days in patients undergoing exploratory laparotomy without resection (p < 0.05). No patients undergoing laparoscopy only have returned for palliative surgery. CONCLUSIONS: Laparoscopy should be performed in nonobstructed, nonbleeding patients with advanced gastric cancer in the United States. More than one third of these patients have unsuspected metastatic disease at time of operation. Laparoscopy is highly accurate in detecting occult metastases and identifies a unique population of stage IV patients who may benefit from newer induction chemotherapeutic approaches while avoiding unnecessary laparotomy. Images Figure 4. PMID:9060581

  8. Construction and analysis of three networks of genes and microRNAs in adenocarcinoma

    PubMed Central

    NING, JIAHUI; GUO, XIAOXIN; WANG, NING; XUE, LUCHEN

    2015-01-01

    Adenocarcinoma is one of the most serious diseases that threaten human health. Numerous studies have investigated adenocarcinoma and have obtained a considerable amount of data regarding genes and microRNA (miRNA) in adenocarcinoma. However, studies have only focused on one or a small number of genes and miRNAs, and the data is stored in a scattered form, making it challenging to summarize and assess the associations between the genes and miRNAs. In the present study, three networks of genes and miRNAs in adenocarcinoma were focused on. This enabled the construction of networks of elements involved in adenocarcinoma and the analysis of these networks, rather than only discussing one gene. Transcription factors (TFs), miRNAs, and target and host genes of miRNAs in adenocarcinoma, and the regulatory associations between these elements were identified in the present study. These elements and associations were then used to construct three networks, which consisted of the differentially-expressed, associated and global networks. The similarities and differences between the three networks were compared and analyzed. In total, 3 notable TFs, consisting of TP53, phosphatase and tensin homolog and SMAD4, were identified in adenocarcinoma. These TFs were able to regulate the differentially-expressed genes and the majority of the differentially-expressed miRNAs. Certain important regulatory associations were also found in adenocarcinoma, in addition to self-regulating associations between TFs and miRNAs. The upstream and downstream elements of the differentially-expressed genes and miRNAs were recorded, which revealed the regulatory associations between genes and miRNAs. The present study clearly revealed components of the pathogenesis of adenocarcinoma and the regulatory associations between the elements in adenocarcinoma. The present study may aid the investigation of gene therapy in adenocarcinoma and provides a theoretical basis for studies of gene therapy methods as a

  9. 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.

  10. How Is Small Intestine Adenocarcinoma Staged?

    MedlinePlus

    ... Early Detection, Diagnosis, and Staging How Is Small Intestine Adenocarcinoma Staged? Staging is a process that tells ... distant m etastasis (M). T categories for small intestine adenocarcinoma T categories of small intestine cancer describe ...

  11. 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.

  12. Lifetime risk of esophageal adenocarcinoma in patients with Barrett's esophagus

    PubMed Central

    Gatenby, Piers; Caygill, Christine; Wall, Christine; Bhatacharjee, Santanu; Ramus, James; Watson, Anthony; Winslet, Marc

    2014-01-01

    AIM: To investigate the lifetime risk of development of esophageal adenocarcinoma and/or high-grade dysplasia in patients diagnosed with Barrett’s esophagus. METHODS: Data were extracted from the United Kingdom National Barrett’s Oesophagus Registry on date of diagnosis, patient age and gender of 7877 patients from who had been registered from 35 United Kingdom centers. Life expectancy was evaluated from United Kingdom National Statistics data based upon gender and age at year at diagnosis. These data were then used with published estimates of annual adenocarcinoma and high-grade dysplasia incidences from meta-analyses and large population-based studies to estimate overall lifetime risk of development of these study endpoints. RESULTS: The mean age at diagnosis of Barrett’s esophagus was 61.6 years in males and 67.3 years in females. The mean life expectancy at diagnosis was 23.1 years in males, 20.7 years in females and 22.2 years overall. Using data from published meta-analyses, the lifetime risk of development of adenocarcinoma was between 1 in 8 and 1 in 14 and the lifetime risk of high-grade dysplasia or adenocarcinoma was 1 in 5 to 1 in 6. Using data from 3 large recent population-based cohort studies the lifetime risk of adenocarcinoma was between 1 in 10 and 1 in 37 and of the combined end-point of high-grade dysplasia and adenocarcinoma was between 1 in 8 and 1 in 20. Age at Barrett’s esophagus diagnosis is reducing and life expectancy is increasing, which will partially counter-balance lower annual cancer incidence. CONCLUSION: There is a significant lifetime risk of development of high-grade dysplasia and adenocarcinoma in Barrett’s esophagus. PMID:25071359

  13. Low Risk of High-Grade Dysplasia or Esophageal Adenocarcinoma Among Patients With Barrett's Esophagus Less Than 1 cm (Irregular Z Line) Within 5 Years of Index Endoscopy.

    PubMed

    Thota, Prashanthi N; Vennalaganti, Prashanth; Vennelaganti, Sreekar; Young, Patrick; Gaddam, Srinivas; Gupta, Neil; Lieberman, David; Sampliner, Richard; Falk, Gary W; Mathur, Sharad; Kennedy, Kevin; Cash, Brooks D; Moawad, Fouad; Bansal, Ajay; Spaander, Manon C; Bruno, Marco J; Vargo, John; Sharma, Prateek

    2017-04-01

    Many patients with a < 1 cm segment of columnar metaplasia in the distal esophagus, also called an irregular Z line, are encountered. These patients, often referred to as patients with Barrett's esophagus (BE), are enrolled in surveillance programs. However, little is known about their risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). We aimed to determine the incidence of HGD and EAC in patients with irregular Z line with intestinal metaplasia. We performed a prospective, multicenter cohort study of patients who underwent endoscopic examination for BE at tertiary care referral centers in the United States and Europe. We analyzed data from 1791 patients (mean age, 56 ± 17 years) found to have non-dysplastic BE at the index endoscopy and after 1 year or more of follow-up. Patients were followed for a median of 5.9 years (interquartile range, 3.1-8.3 years). We calculated rates of progression to HGD or EAC between groups of patients with irregular Z line (n = 167) and those with BE of ≥ 1 cm (n = 1624). A higher proportion of patients in the irregular Z-line group were female (26.3%) than in the BE group (14.8% female BE) (P <.001). A lower proportion of patients in the irregular Z-line group were smokers (33.5%) than in the BE group (52.6% smokers). None of the patients with irregular Z line developed HGD or EAC during a median follow-up period of 4.8 years (interquartile range, 3.2-8.3 years). All 71 incident cases of HGD or EAC developed in patients with BE of ≥1 cm in length. On multivariate analysis, patients with irregular Z line and patients with BE of ≥ 1 cm did not differ significantly in age, race, or duration of follow-up. In a prospective, multicenter cohort study, we found that patients with irregular Z line do not develop HGD or esophageal cancer within 5 years after index endoscopy. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology

    PubMed Central

    Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

    2016-01-01

    Background There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19–9 (CA 19–9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. Methods CA 19–9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. Results The combination of CA 19–9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19–9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Conclusions Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis. PMID:26808421

  15. Synchronous Multiple Lung Adenocarcinomas: Estrogen Concentration in Peripheral Lung

    PubMed Central

    Shinchi, Yusuke; Sanada, Mune; Motooka, Yamato; Fujino, Kosuke; Mori, Takeshi; Suzuki, Makoto

    2016-01-01

    Background The detection rate of synchronous multiple lung adenocarcinomas (SMLA), which display multiple ground glass opacity nodules in the peripheral lung, is increasing due to advances in high resolution computed tomography. The backgrounds of multicentric development of adenocarcinoma are unknown. In this study, we quantitated estrogen concentration in the peripheral lungs of postmenopausal female patients with SMLA. Methods The tissue concentration of estrogens (estrone [E1] and estdadiol [E2]) in the noncancerous peripheral lung were measured with liquid chromatography/electrospray tandem mass spectrometry in postmenopausal female patients with lung adenocarcinoma. The expression levels of CYP19A1 in the normal lung were also quantitated with real-time PCR. Thirty patients with SMLA and 79 cases of control patients with single lung adenocarcinoma were analyzed. Results The concentrations of E1 and E2 in the noncancerous tissue were significantly higher in SMLA cases than control cases (P = 0.004 and P = 0.02, respectively). The minor allele (A) of single nucleotide polymorphism rs3764221 were significantly associated with higher concentration of E1 and E2 (P = 0.002 and P = 0.01, respectively) and higher CYP19A1 mRNA expression (P = 0.03). Conclusion The tissue estrogen concentration of peripheral lung was significantly higher in SMLA than control cases. The high concentration of estrogen may be one of the causes of multicentric development of peripheral lung adenocarcinomas. PMID:27526096

  16. [Endoscopic diagnosis of Barrett's adenocarcinoma].

    PubMed

    Yoshio, H; Takashi, Y; Mitsuyo, H; Nobuhiko, Y; Tatsurou, T; Kazuhiko, S; Yoko, H; Shigemasa, I; Hisanaga, M; Osamu, H; Katsuyoshi, S; Seishi, U; Matsushita, H; Masahiko, T

    1999-03-01

    Biopsy specimens can reveal that esophageal cancer is an adenocarcinoma but they cannot show that its origin is Barrett's mucosa. Therefore we must show during endoscopy that the tumor exists in Barrett's mucosa. We reported that Barrett's esophagus could be clearly diagnosed at endoscopy as the columnar mucosa lying on the longitudinal vessels in the lower esophagus. We define Barrett's esophagus as "the columnar mucosa in the esophagus which exists continuously more than 2 cm in circumference from the stomach." Short-segment Barrett's esophagus (SSBE) is "the columnar mucosa which exists in the esophagus continuously from the stomach but its length has a part under 2 cm in length." Endoscopically Barrett's adenocarcinoma is visualized as a lesion with a reddish and uneven mucosal surface. Barrett's adenocarcinomas occur in the SSBE as well. Endoscopic observation at periodic intervals is necessary not only for cases with Barrett's esophagus but also with SSBE. A further examination is necessary to determine the application of EMR for superficial Barrett's adenocarcinoma.

  17. Adherence to WCRF/AICR lifestyle recommendations for cancer prevention and the risk of Barrett's esophagus onset and evolution to esophageal adenocarcinoma: results from a pilot study in a high-risk population.

    PubMed

    Realdon, Stefano; Antonello, Alessandro; Arcidiacono, Diletta; Dassie, Elisa; Cavallin, Francesco; Fassan, Matteo; Nardi, Maria Teresa; Alberti, Alfredo; Rugge, Massimo; Battaglia, Giorgio

    2016-06-01

    While adherence to the World Cancer Research Fund (WCRF) guidelines on lifestyle and cancer was recently proven to be associated with an increased risk of esophageal cancer, no investigation has yet been carried out on its role on Barrett's esophagus (BE) development and its progression to esophageal adenocarcinoma (EAC). The primary aim of this study was to evaluate the role of adherence to WCRF lifestyle recommendations in BE onset and progression. The secondary aim was to investigate the association between disease progression and specific aspects of diet and lifestyle. Established risk factors for BE and EAC development and adherence to WCRF guidelines were assessed in 107 consecutive patients undergoing an upper gastrointestinal endoscopy for symptoms suggesting gastroesophageal reflux (GERD) and a suspected diagnosis of BE/dysplasia on BE. Patients were divided according to histology: those with GERD without metaplasia, with non-dysplastic BE, with low-grade dysplasia, with high-grade dysplasia or with early EAC. The four groups were expressed as an ordered categorical variable of disease progression. An ordered logit model was estimated to identify the independent predictors of disease progression. Adherence to WCRF guidelines was identified as independent protective factor (OR 0.51, 95 % CI 0.37-0.67) of disease progression. Disease progression was associated with reduced adherence to guidelines on physical activity (from 48.2 to 5.3 %, p = 0.001), sedentary habits (from 33.3 to 0 %, p = 0.03), fruit consumption (from 37.0 to 5.6 %, p = 0.02) and processed meat consumption (from 51.9 to 10.5 %, p = 0.002). Adherence to WCRF guidelines has a protective factor in BE onset and its evolution to EAC.

  18. Review of the investigation and surgical management of resectable ampullary adenocarcinoma

    PubMed Central

    Askew, James; Connor, Saxon

    2013-01-01

    Background Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with significant mortality and morbidity. Some recent publications have advocated the use of endoscopic papillectomy for the treatment of early ampullary adenocarcinoma. This article reviews investigations and surgical treatment options of ampullary tumours. Methods A systematic review of English-language articles was carried out using an electronic search of the Ovid MEDLINE (from 1996 onwards), PubMed and Cochrane Database of Systematic Reviews databases to identify studies related to the investigation and management of ampullary tumours. Results Distinguishing between ampullary adenoma and adenocarcinoma is challenging given the inaccuracy of endoscopic biopsy, for which high false negative rates of 25–50% have been reported. Endoscopic ultrasound is the most accurate method for local staging of ampullary lesions, but distinguishing between T1 and T2 adenocarcinomas is difficult. Lymph node metastasis occurs early in the disease process; it is lowest for T1 tumours, but the risk is still high at 8–45%. Case reports of successful endoscopic resection and transduodenal ampullectomy of T1 adenocarcinomas have been published, but their duration of follow-up is limited. Conclusions Optimal staging should be used to distinguish between ampullary adenoma and adenocarcinoma. Pancreaticoduodenectomy remains the treatment of choice for all ampullary adenocarcinomas. PMID:23458317

  19. Dome-type: a distinctive variant of colonic adenocarcinoma.

    PubMed

    Puppa, Giacomo; Molaro, Mariella

    2012-01-01

    Introduction. Ten cases of dome-type adenocarcinoma of the colon have been reported so far. Most of them were presented as early lesions, with endoscopic and microscopic distinguishing features. Methods and Results. A raised plaque was removed from the right colon during colonoscopy in a 56-year-old man. Histopathological examination showed a cancerized adenoma invading the submucosa with several typical features of dome-type adenocarcinoma, in particular the associated prominent lymphoid tissue. Immunohistochemistry showed retention of the mismatch repair proteins MLH-1, MSH-2, MLH-6, and PMS-2. Conclusion. We report an additional case of dome-type adenocarcinoma of the colon as an early, low-risk, and microsatellite stable tumor, indicating that this particular histotype may deserve specific consideration for both classification and management.

  20. 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.

  1. 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.

  2. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma

    SciTech Connect

    Abelson, Jonathan A.; Murphy, James D.; Minn, Ann Yuriko; Chung, Melody; Fisher, George A.; Ford, James M.; Kunz, Pamela; Norton, Jeffrey A.; Visser, Brendan C.; Poultsides, George A.; Koong, Albert C.; Chang, Daniel T.

    2012-03-15

    Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  3. Elevated nuclear CCND1 expression confers an unfavorable prognosis for early stage lung adenocarcinoma patients

    PubMed Central

    Xu, Ping; Zhao, Mengyang; Liu, Zhen; Liu, Yiyi; Chen, Yiyu; Luo, Rongcheng; Fang, Weiyi

    2015-01-01

    Purposes: To examine the expression pattern of CCND1 and analyze the correlation of its nuclear expression with clinicopathologic features and prognosis in lung adenocarcinoma. Methods: CCND1 mRNA and protein levels in lung adenocarcinoma tissues were examined. The relationship between nuclear CCND1 protein expression and clinical features including survival prognosis was analyzed. Results: CCND1 mRNA levels were markedly increased in lung adenocarcinoma (P=0.0019). Western blot analysis confirmed increased nuclear CCND1 protein expression in lung adenocarcinoma specimens. Immunohistochemistry analysis confirmed that CCND1 protein was predominantly nuclear localized in lung adenocarcinoma cells and significantly elevated relative to normal lung tissues (P<0.001). Furthermore, high levels of nuclear CCND1 were positively correlated with clinical stage (P=0.026). Patients with nuclear CCND1 expression had a significantly shorter overall survival time than did patients with low expression. Interestingly, nuclear CCND1 expression in clinical stage I+II, but not clinical stage III, was shown associated with poor prognosis and shorter overall survival time for lung adenocarcinoma patients by strata analysis. Finally, nuclear CCND1 expression tended to be an independent prognostic indicator (P=0.087) for lung adenocarcinoma patient survival. Conclusion: Increased nuclear CCND1 is a potential unfavorable prognostic factor for lung adenocarcinoma patients, especially those with clinical early stage (stage I+II). PMID:26884860

  4. Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients

    PubMed Central

    Zhan, J; Niu, M; Wang, P; Zhu, X; Li, S; Song, J; He, H; Wang, Y; Xue, L; Fang, W; Zhang, H

    2014-01-01

    Background: Little is known about the tumour suppressive proteins and the underlying mechanisms that suppress colon cancer progression. Homeodomain-containing transcription factor HOXB9 plays an important role in embryogenesis and cancer development. We here aim to uncover the potential role of HOXB9 in the regulation of colon adenocarcinoma progression including epithelial-to-mesenchymal transition. Methods: HOXB9 expression in colon adenocarcinoma cells and patients was analysed by western blot and immunohistochemistry separately. Correlation between HOXB9 expressions with patients' survival was assessed by Kaplan–Meier analysis. HOXB9-regulated target gene expression was determined by RNA sequencing in HOXB9-overexpressing colon adenocarcinoma cells. Results: Elevated HOXB9 expression was identified in well-differentiated colon adenocarcinoma patients and was associated with a better overall patients' survival. Overexpression of HOXB9 inhibited colon adenocarcinoma cell growth, migration, invasion in vitro and tumour growth, liver as well as lung metastases in nude mice; whereas silencing HOXB9 promoted these functions. HOXB9 promoted colon adenocarcinoma differentiation via a mechanism that stimulates mesenchymal-to-epithelial transition, involving downregulation of EMT-promoting transcriptional factors including Snail, Twist, FOXC2 and ZEB1 and upregulation of epithelial proteins including E-cadherin, claudins-1, -4, -7, occludin and ZO-1. Conclusions: HOXB9 is a novel tumour suppressor that inhibits colon adenocarcinoma progression by inducing differentiation. Elevated expression of HOXB9 predicts a longer survival in colon adenocarcinoma patients. PMID:25025961

  5. Penile metastases of rectal adenocarcinoma.

    PubMed

    Persec, Z; Persec, J; Sovic, T; Rako, D; Savic, I; Marinic, D K

    2014-02-01

    Penile metastases are very rare and arise most frequently from genitourinary cancers. Penile metastases from rectal adenocarcinoma are less common and only 50 or so cases have been reported. We present a 43-year-old man with penile metastases from a rectal adenocarcinoma. Two years before admittance to our department, abdomino-perineal resection of the rectum (Miles operation) was performed for a Dukes B (T3N0M0) rectal adenocarcinoma; the surgical resection margins wee negative. Adjuvant chemotherapy and radiotherapy treatment were administered. One year after initial management, excision of a local recurrence was performed followed by further chemotherapy. The patient subsequently noticed lesions of the penis measuring up to 1.2 cm in diameter. Biopsy revealed metastatic adenocarcinoma. Computed tomography showed normal structure of penis with subcutaneous nodular thickening. Soon thereafter, the entire shaft of the penis becomes indurated and the patient developed urinary obstruction. A suprapubic cystostomy was performed. The patient died within 6 months. Penile metastases arise most frequently from genitourinary cancers, primarily from the bladder and the prostate gland. Metastasis to the penis from a rectal adenocarcinoma occurs much less commonly. Other reported primary origins of penile metastases include malignancies of the lung, nasopharynx and melanoma. The major symptoms are penile nodular mass, malignant priapism, penile pain and tenderness, difficulty in micturition, and urinary retention. Possible routes of metastasis are arterial, retrograde venous spread, retrograde lymphatic spread, but direct tumor infiltration/extension is also possible. Penile metastases from rectal adenocarcinoma usually occur within 2 years after diagnosis of the primary tumor. The prognosis is very poor regardless of treatment modality. Treatment is more often palliative than curative. Survival usually varies from 7 months to 2 years. Long-term survival (9 years) has been

  6. Hepatoid Adenocarcinoma of the Urachus

    PubMed Central

    Jimenez, Carlos Andrés; Carrascal, Edwin

    2016-01-01

    Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI) reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP) and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis. PMID:27803830

  7. Oncocytic Adenocarcinoma of the Orbit.

    PubMed

    Harris, Gerald J; Paul, Sean; Hunt, Bryan C

    Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.

  8. Optimal lymphadenectomy for esophageal adenocarcinoma.

    PubMed

    Oezcelik, A

    2013-08-01

    Recently published data have shown that an extended lymphadenectomy during the en bloc esophagectomy leads to a significant increased long-term survival for esophageal adenocarcinoma. On the other hand some studies indicate that the increased survival is based on stage migration and that the surgical complication rate is increased after extended lymphadenectomy. The aim of this review was to give an overview about all aspects of an extended lymphadenectomy in patients with esophageal adenocarcinoma. The review of the literature shows clearly that the number of involved lymph nodes is an independent prognostic factor in patients with esophageal adenocarcinoma. Furthermore, an extended lymphadenectomy leads to an increased long-term survival. Some studies describe that 23 lymph nodes should be removed to predict survival; other studies 18 lymph nodes or 15 lymph nodes. Opponents indicate that the survival benefit is based on stage migration. The studies with a large study population have performed a Cox regression analyzes and identified the number of lymph nodes removed as an independent factor for improved survival, which means it is significant independently from other parameters. Under these circumstances is stage migration not an option to explain the survival benefit. An important difficulty is, that there is no standardized definition of an extended lymphadenectomy, which means the localization and number of removed lymph nodes differ depending from the performing centre. The controversies regarding the survival benefit of the lymphadenectomy is based on the lack of standardisation of the lymphadenectomy. The main goal of further studies should be to generate a clear definition of an extended lymphadenectomy in patients with esophageal adenocarcinoma.

  9. Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma

    PubMed Central

    Stefanius, Karoliina; Ylitalo, Laura; Tuomisto, Anne; Kuivila, Rami; Kantola, Tiina; Sirniö, Päivi; Karttunen, Tuomo J; Mäkinen, Markus J

    2011-01-01

    Aims To define the occurrence of KRAS and BRAF mutations, microsatellite instability (MSI), and MGMT and hMLH1 methylation and expression in colorectal serrated adenocarcinoma. Methods and results KRAS codon 12/13 and 59/61 and BRAF V600E mutations, MSI, and MGMT and hMLH1 methylation and expression in 42 serrated adenocarcinomas and 17 serrated adenomas were compared with those in 59 non-serrated colorectal carcinomas (CRCs) and nine adenomas. KRAS and BRAF mutations were observed in 45% and 33% of serrated adenocarcinomas and in 27% and 0% of non-serrated CRCs (P < 0.001). The KRAS c12G→A transition was the predominant type of mutation in serrated adenocarcinomas. Forty-two per cent of BRAF-mutated serrated adenocarcinomas showed high-level MSI (MSI-H) (P = 0.075), 100% showed hMLH1 methylation (P = 0.001) and 90.9% showed MGMT methylation (P = 0.019). Fifty-six per cent of serrated adenocarcinomas with microsatellite stability/low-level microsatellite instability harboured KRAS mutations. In non-serrated cancers, KRAS mutations were not associated with MSI status. Conclusions A high combined mutation rate (79–82%) of KRAS and BRAF in serrated adenomas and adenocarcinomas indicates that mitogen-activated protein kinase activation is a crucial part of the serrated pathway. BRAF mutations are specific for serrated adenocarcinoma and identify a subset of serrated adenocarcinomas with gene methylation and a tendency for MSI-H. A high frequency of KRAS mutations in serrated adenocarcinomas suggests that a significant proportion of KRAS-mutated CRCs originate from serrated precursors, thus challenging the traditional model of Vogelstein. PMID:21457162

  10. Radiologic Evaluation of Small Lepidic Adenocarcinomas to Guide Decision Making in Surgical Resection.

    PubMed

    Wilshire, Candice L; Louie, Brian E; Manning, Kristin A; Horton, Matthew P; Castiglioni, Massimo; Gorden, Jed A; Aye, Ralph W; Farivar, Alexander S; Vallières, Eric

    2015-09-01

    The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of pulmonary adenocarcinomas identifies indolent lesions associated with low recurrence, superior survival, and the potential for sublobar resection. The distinction, however, is determined on the pathologic evaluation, limiting preoperative surgical planning. We sought to determine whether preoperative computed tomography (CT) characteristics could guide decisions about the extent of the pulmonary resection. We reviewed the preoperative CT scans for 136 patients identified to have adenocarcinomas with lepidic features on the final pathologic evaluation. The solid component on CT was substituted for the invasive component, and patients were radiologically classified as adenocarcinoma in situ, 3 cm or less with no solid component; minimally invasive adenocarcinoma, 3 cm or less with a solid component of 5 mm or less; or invasive adenocarcinoma, exceeding 3 cm or solid component exceeding 5 mm, or both. Analysis of variance, t test, χ(2) test, and Kaplan-Meier methods were used for analysis. The radiologic classification identified 35 adenocarcinomas in situ (26%) and 12 minimally invasive (9%) and 89 invasive adenocarcinoma (65%) lesions. At a 32-month median follow-up, patient outcomes associated with the radiologic classification were similar to the pathologic-based classification: the radiologic classification identified 14 of 16 patients with recurrent disease and all 6 who died of lung cancer. In addition, patients with radiologic adenocarcinoma in situ and minimally invasive adenocarcinoma who underwent sublobar resections had no recurrence and 100% disease-free and overall survival at 5 years. The radiologic classification of patients with lepidic adenocarcinomas is associated with similar oncologic and survival outcomes compared with the pathologic classification and may guide decision making in the approach to surgical resection

  11. Metastatic adenocarcinoma of unknown primary origin.

    PubMed

    Hammar, S P

    1998-12-01

    Adenocarcinomas account for up to 60% of all metastatic neoplasms of unknown primary origin. In general, adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site. Some metastatic adenocarcinomas have distinctive histological features that allow for their site determination (eg, colonic adenocarcinoma, bronchioloalveolar cell carcinoma), although the majority of metastatic adenocarcinomas have histological features that are not distinctive enough to allow for a specific diagnosis of their origin. For this reason, electron microscopy and immunohistochemistry have been used to help identify the exact type (origin) of metastatic adenocarcinomas. Relatively specific ultrastructural features used to diagnose metastatic adenocarcinomas of unknown primary origin include tubular myelin, intranuclear surfactant apoprotein tubular inclusions, Clara cell granules, uniform short microvilli with filamentous cores and core rootlets, Langerhans cells associated with neoplastic cells, cytoplasmic hyaline globules, lipid droplets, glycogen, and cytoplasmic crystals. Only a few of these ultrastructural features are absolutely specific. Relatively specific immunohistochemical tests used to diagnose metastatic adenocarcinomas of unknown primary origin include prostate-specific antigen, thyroglobulin, estrogen and progesterone receptor proteins, thyroid transcription factor-I, and surfactant apoproteins. Of these, prostate-specific antigen and thyroglobulin are the most specific. The purpose of this article is to discuss the use of electron microscopy and immunohistochemistry in the site-specific diagnosis of metastatic adenocarcinomas of unknown primary origin.

  12. 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

  13. Absence or low IGF-1R-expression in esophageal adenocarcinoma is associated with tumor invasiveness and radicality of surgical resection.

    PubMed

    De Bruijn, Kirstin; Biermann, Katharina; Shapiro, Joel; Dogan, Fadime; Spaander, Manon; Janssen, Joseph; Wijnhoven, Bas; Borsboom, Gerard; Hofland, Leo; van Eijck, Casper

    2015-06-01

    Esophageal adenocarcinoma (EAC) incidence increases, maybe due to increasing prevalences of obesity and diabetes. Concurrent hyperinsulinemia might promote carcinogenesis via the insulin-like growth factor-I receptor (IGF-1R). Expression of the IGF-1R was studied in correlation with diabetes and prognostic parameters. Patients with EAC undergoing esophagectomy were prospectively selected. From resected tumors a tissue microarray was constructed. Immunohistochemistry evaluated IGF-1R-expression. Logistic-, cox regression models and survival analyses assessed if diabetes and IGF-1R-expression were associated with prognostic parameters. IGF-1R-expression in normal and Barrett tissues was studied. Absence or low IGF-1R-expression was associated with T3-, grade 3 tumors and R1 resections (P = 0.001, P = 0.025, P < 0.001, respectively). Logistic regression showed that this was associated with R1 resections (HR 0.24, 95%CI 0.11-0.52). Diabetes was not associated with IGF-1R-expression (P = 0.612). Absence or low IGF-1R-expression decreased 5-year overall survival (P = 0.023) univariably, but not multivariably. IGF-1R-expression was present in Barrett tissues, but diminished in high-grade dysplasia. Absence or low expression of IGF-1R was associated with high grade- and advanced tumors and less radical resections. IGF-1R might be a tumor marker in Barrett's esophagus since a change in expression patterns was found in the course from normal esophageal tissue to adenocarcinoma. © 2015 Wiley Periodicals, Inc.

  14. Secretory adenocarcinoma of the endometrium.

    PubMed

    Tobon, H; Watkins, G J

    1985-01-01

    Secretory adenocarcinomas of the endometrium are uncommon tumors distinct from clear cell carcinomas. We reviewed nine cases that included the original endometrial curettings and the specimens of uteri with both adnexa [total abdominal hysterectomy-bilateral salpingo-oophorectomy (TAH-BSO)]. The patients' ages ranged from 36 to 79 years (with an average of 55 years). Six women were postmenopausal, and most complained of vaginal bleeding. Two patients were nulliparous and the others had one to four children. Four patients were obese, of whom one was diabetic and hypertensive. Eight tumors were of grade I and one was grade II. The histologic pattern was comparable to that of secretory endometrium, days 17 to 22, and the glands were positive with periodic acid-Schiff (whether predigested or not); they were partly positive with alcian blue and negative with Best Carmine. The carcinoma in one case was positive for carcinoembryonic antigen; all cases were negative with alpha-fetoprotein. Six patients were staged as IA and three as IB. One 47-year-old patient had a concurrent endometrioid adenocarcinoma (grade II) of the right ovary with squamous, clear cell, and mucinous components. Three cases had no tumour penetration of the myometrium while in the others penetration varied from 5 to 70%. One patient received intracavitary radium prior to TAH-BSO and two had postoperative radiation. All patients are alive 11 to 113 months following surgery. Secretory adenocarcinoma of the endometrium should be separated from clear cell carcinoma, as it has the pattern of secretory endometrium day 17 to 22, is very well differentiated, and has a relatively good prognosis.

  15. A retrospective study of ampullary adenocarcinomas: overall survival and responsiveness to fluoropyrimidine-based chemotherapy†

    PubMed Central

    Jiang, Z.-Q.; Varadhachary, G.; Wang, X.; Kopetz, S.; Lee, J. E.; Wang, H.; Shroff, R.; Katz, M.; Wolff, R. A.; Fleming, J.; Overman, M. J.

    2013-01-01

    Background Whether carcinomas of the ampulla of Vater should be classified with biliary tract tumors and treated in a similar manner remains unknown. We sought to compare the outcomes of similarly staged periampullary adenocarcinomas (AAs) and analyze the chemotherapy responsiveness of AAs. Patients and methods A total of 905 patients with resected periampullary adenocarcinomas were identified from a prospective surgical registry from 1988 to 2010. A second cohort of 64 metastatic AA patients from 1992 to 2009 who received either front-line fluoropyrimidine-based or gemcitabine-based chemotherapy was also identified. Results Overall survival (OS) for AAs was similar to survival with duodenal adenocarcinomas, but was significantly different from both extrahepatic biliary and pancreatic adenocarcinomas (P < 0.001 for each comparison). In multivariate analysis, AAs had a significantly improved OS in comparison with extrahepatic biliary adenocarcinomas (HR = 1.97, P = 0.006). Fluoropyrimidine-based as opposed to gemcitabine-based chemotherapy for metastatic AAs resulted in a significant improvement in time to progression (P = 0.001) but only a trend toward benefit for OS (P = 0.07) in multivariate analysis. Conclusions Differences in the natural history of ampullary and extrahepatic biliary adenocarcinomas exist. Analyses of metastatic ampullary adenocarcinomas suggest that fluoropyrimidine-based chemotherapy may represent a more appropriate front-line chemotherapy approach. PMID:23704197

  16. Whole genome sequencing analysis of lung adenocarcinoma in Xuanwei, China

    PubMed Central

    Wang, Xiao; Li, Jing; Duan, Yong; Wu, Huifei; Xu, Qiuyue

    2017-01-01

    Background The lung cancer mortality rate in Xuanwei city is among the highest in China and adenocarcinoma is the major histological type. Lung cancer has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons; however, the pathogenesis of lung cancer has not yet been fully elucidated. Methods We performed whole genome sequencing with lung adenocarcinoma and corresponding non‐tumor tissue to explore the genomic features of Xuanwei lung cancer. We used the Molecule Annotation System to determine and plot alterations in genes and signaling pathways. Results A total of 3 428 060 and 3 416 989 single nucleotide variants were detected in tumor and normal genomes, respectively. After comparison of these two genomes, 977 high‐confidence somatic single nucleotide variants were identified. We observed a remarkably high proportion of C·G‐A·T transversions. HECTD4, RCBTB2, KLF15, and CACNA1C may be cancer‐related genes. Nine copy number variations increased in chromosome 5 and one in chromosome 7. The novel junctions were detected via clustered discordant paired ends and 1955 structural variants were discovered. Among these, we found 44 novel chromosome structural variations. In addition, EGFR and CACNA1C in the mitogen‐activated protein kinase signaling pathway were mutated or amplified in lung adenocarcinoma tumor tissue. Conclusion We obtained a comprehensive view of somatic alterations of Xuanwei lung adenocarcinoma. These findings provide insight into the genomic landscape in order to further learn about the progress and development of Xuanwei lung adenocarcinoma. PMID:28083984

  17. Drug-sensitive FGFR3 mutations in lung adenocarcinoma

    PubMed Central

    Chandrani, P.; Prabhash, K.; Prasad, R.; Sethunath, V.; Ranjan, M.; Iyer, P.; Aich, J.; Dhamne, H.; Iyer, D. N.; Upadhyay, P.; Mohanty, B.; Chandna, P.; Kumar, R.; Joshi, A.; Noronha, V.; Patil, V.; Ramaswamy, A.; Karpe, A.; Thorat, R.; Chaudhari, P.; Ingle, A.; Choughule, A.

    2017-01-01

    Background Lung cancer is the leading cause of cancer-related deaths across the world. In this study, we present therapeutically relevant genetic alterations in lung adenocarcinoma of Indian origin. Materials and methods Forty-five primary lung adenocarcinoma tumors were sequenced for 676 amplicons using RainDance cancer panel at an average coverage of 1500 × (reads per million mapped reads). To validate the findings, 49 mutations across 23 genes were genotyped in an additional set of 363 primary lung adenocarcinoma tumors using mass spectrometry. NIH/3T3 cells over expressing mutant and wild-type FGFR3 constructs were characterized for anchorage independent growth, constitutive activation, tumor formation and sensitivity to FGFR inhibitors using in vitro and xenograft mouse models. Results We present the first spectrum of actionable alterations in lung adenocarcinoma tumors of Indian origin, and shows that mutations of FGFR3 are present in 20 of 363 (5.5%) patients. These FGFR3 mutations are constitutively active and oncogenic when ectopically expressed in NIH/3T3 cells and using a xenograft model in NOD/SCID mice. Inhibition of FGFR3 kinase activity inhibits transformation of NIH/3T3 overexpressing FGFR3 constructs and growth of tumors driven by FGFR3 in the xenograft models. The reduction in tumor size in the mouse is paralleled by a reduction in the amounts of phospho-ERK, validating the in vitro findings. Interestingly, the FGFR3 mutations are significantly higher in a proportion of younger patients and show a trend toward better overall survival, compared with patients lacking actionable alterations or those harboring KRAS mutations. Conclusion We present the first actionable mutation spectrum in Indian lung cancer genome. These findings implicate FGFR3 as a novel therapeutic in lung adenocarcinoma. PMID:27998968

  18. Uterine adenocarcinoma with feline leukemia virus infection.

    PubMed

    Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin

    2011-12-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.

  19. Microbiome in reflux disorders and esophageal adenocarcinoma.

    PubMed

    Yang, Liying; Chaudhary, Noami; Baghdadi, Jonathan; Pei, Zhiheng

    2014-01-01

    The incidence of esophageal adenocarcinoma has increased dramatically in the United States and Europe since the 1970s without apparent cause. Although specific host factors can affect risk of disease, such a rapid increase in incidence must be predominantly environmental. In the stomach, infection with Helicobacter pylori has been linked to chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. However, the role of H. pylori in the development of esophageal adenocarcinoma is not well established. Meanwhile, several studies have established that a complex microbiome in the distal esophagus might play a more direct role. Transformation of the microbiome in precursor states to esophageal adenocarcinoma-reflux esophagitis and Barrett metaplasia-from a predominance of gram-positive bacteria to mostly gram-negative bacteria raises the possibility that dysbiosis is contributing to pathogenesis. However, knowledge of the microbiome in esophageal adenocarcinoma itself is lacking. Microbiome studies open a new avenue to the understanding of the etiology and pathogenesis of reflux disorders.

  20. Current status of endoscopic diagnosis and treatment of superficial Barrett's adenocarcinoma in Asia-Pacific region.

    PubMed

    Goda, Kenichi; Singh, Rajvinder; Oda, Ichiro; Omae, Masami; Takahashi, Akiko; Koike, Tomoyuki; Uedo, Noriya; Hirasawa, Dai; Fujishiro, Mitsuhiro; Hirasawa, Kingo; Morita, Yoshinori; Ho, Lawrence K Y; Ajioka, Yoichi

    2013-05-01

    The incidence of Barrett's adenocarcinoma has increased dramatically over the past few decades in most Western countries. While Barrett's esophagus is uncommon and adenocarcinoma is still rare in Asian populations, several Asian studies have indicated that the prevalence of esophageal adenocarcinoma is gradually increasing. Therefore, in order to determine the best way to treat superficial Barrett's adenocarcinoma, 12 expert endoscopists and a pathologist from the Asia-Pacific region conducted a session entitled 'The current status of endoscopic diagnosis and treatment of superficial Barrett's adenocarcinoma'. After three keynote lectures, three Japanese panels presented cases of superficial Barrett's adenocarcinomas diagnosed by image-enhanced endoscopy (IEE). We then confirmed the results of a questionnaire on the diagnosis and treatment of superficial Barrett's adenocarcinomas. Finally, a panel introduced an Asia-Pacific international study on simplified narrow-band imaging (NBI) classification of Barrett's esophagus and neoplasias. After a discussion, we proposed consensus statements on endoscopic diagnosis and treatment of superficial Barrett's adenocarcinoma as follows. Representative characteristics by conventional white light endoscopy are a reddish area or a lesion located on the anterior to right side wall. IEE may be useful for characterizing the tumor and diagnosing lateral tumor extension. Superficial Barrett's adenocarcinoma adjacent to the squamocolumnar junction is sometimes associated with subsquamous tumor extension. IEE may be useful to detect the subsquamous tumor extension especially when using NBI or an acetic acid-spraying method. Endoscopic mucosal resection or endoscopic submucosal dissection for mucosal carcinomas could provide excellent prognosis. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

  1. Expression of Tiam1 predicts lymph node metastasis and poor survival of lung adenocarcinoma patients

    PubMed Central

    2014-01-01

    Background To assess the value of Tiam1 in predicting lymph node metastasis and survival after curative resection in patients with lung adenocarcinoma. Methods Immunohistochemical staining for Tiam1 was performed on 98 adenocarcinoma and 30 normal lung tissues. The association of Tiam1 protein expression with the clinicopathological characteristics and the prognosis of lung adenocarcinoma were subsequently assessed. Results Immunohistochemical analysis showed that 60 of 98 (61.22%) adenocarcinoma tissues showed high expression of Tiam1, and high Tiam1 expression was significantly associated with advanced TNM stage (P < 0.0005) and lymph node status (P < 0.0005) of lung adenocarcinoma. Moreover, the lung adenocarcinoma patients with low Tiam1 expression had higher overall survival than patients with high Tiam1 expression (log rank value = 10.805, P = 0.001). High expression of Tiam1 predicted poor overall survival of patients in stages I + II (P = 0.006). Furthermore, multivariate analysis indicated that high expression of Tiam1 protein was an independent prognostic factor for overall survival (P = 0.011) in patients with lung adenocarcinoma. Conclusion These findings suggest for the first time that Tiam1 expression may be beneficial in predicting lymph node metastasis and survival of patients with lung adenocarcinoma. A future study will investigate whether Tiam1 can serve as a novel therapeutic target in lung adenocarcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1377798917111123. PMID:24661909

  2. Evaluation of a Tier I screening battery for detecting endocrine-active compounds (EACs) using the positive controls testosterone, coumestrol, progesterone, and RU486.

    PubMed

    O'Connor, J C; Davis, L G; Frame, S R; Cook, J C

    2000-04-01

    After previously examining 12 compounds with known endocrine activities, we have now evaluated 4 additional compounds in a Tier I screening battery for detecting endocrine-active compounds (EACs): a weak estrogen receptor (ER) agonist (coumestrol; COUM), an androgen receptor (AR) agonist (testosterone; TEST), a progesterone receptor (PR) agonist (progesterone; PROG), and a PR antagonist (mifepristone; RU486). The Tier I battery incorporates 2 short-term in vivo tests (5-day ovariectomized female battery; 15-day intact male battery) and an in vitro yeast transactivation system (YTS). The Tier I battery is designed to identify compounds that have the potential to act as agonists or antagonists to the estrogen, androgen, progesterone, or dopamine receptors; steroid biosynthesis inhibitors (aromatase, 5alpha-reductase, and testosterone biosynthesis); or compounds that alter thyroid function. In addition to the Tier I battery, a 15-day dietary restriction experiment was performed using male rats to assess confounding due to treatment-related decreases in body weight. In the Tier I female battery, TEST administration increased uterine weight, uterine stromal cell proliferation, and altered hormonal concentrations (increased serum testosterone [T] and prolactin [PRL]; and decreased serum FSH and LH). In the male battery, TEST increased accessory sex gland weights, altered hormonal concentrations (increased serum T, dihydrotestosterone [DHT], estradiol [E2], and PRL; decreased serum FSH and LH), and produced microscopic changes of the testis (Leydig cell atrophy and spermatid retention). In the YTS, TEST activated gene transcription in the yeast containing the AR or PR. In the female battery, COUM administration increased uterine weight, uterine stromal cell proliferation, and uterine epithelial cell height, and increased serum PRL concentrations. In the male battery, COUM altered hormonal concentrations (decreased serum T, DHT, E2; increased serum PRL) and, in the YTS

  3. 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

  4. [An unusual secondary localization of bronchial adenocarcinoma].

    PubMed

    Mirallie, E; Courant, O; Sagan, C; Letessier, E; Paineau, J; Visset, J

    1993-01-01

    The authors report a rare case of metastatic carcinoma of the large bowel, secondary to a primary bronchogenic adenocarcinoma. Abdominal pain developed in a 44-year old man 5 months after lobectomy for lung adenocarcinoma. The diagnosis of a large caecal extraluminal mass was established by means of sonography, scanner and laparoscopy. Palliative resection (brain metastases) was performed. Postoperative histological examination revealed the resected tumor to be identical to the lung adenocarcinoma. The patient eventually died 4 months after resection (complication of intracranial hypertension). Diagnosis and therapeutic features of metastatic extra-thoracic lung carcinoma are discussed.

  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. Pulmonary adenocarcinoma with mucin production modulates phenotype according to common genetic traits: a reappraisal of mucinous adenocarcinoma and colloid adenocarcinoma

    PubMed Central

    Sonzogni, Angelica; Bianchi, Fabrizio; Fabbri, Alessandra; Cossa, Mara; Rossi, Giulio; Cavazza, Alberto; Tamborini, Elena; Perrone, Federica; Busico, Adele; Capone, Iolanda; Picciani, Benedetta; Valeri, Barbara; Pastorino, Ugo

    2017-01-01

    Abstract Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK‐rearranged adenocarcinomas (ALKA), 8 non‐mucinous KRAS‐mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX‐2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone‐related (oestrogen and progesterone receptors), pan‐mucinous (HNF4A) and pan‐epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes. Unsupervised clustering analysis using molecular features identified cluster 1 (IMA and ICA), cluster 2 (ALKA and KRASA) and cluster 3 (MBA) (p < 0.0001). Cluster 1 showed four histology‐independent sub‐clusters (S1 to S4) pooled by HFN4A and MUC5AC but diversely reacting for TTF1, MUC1, MUC2, MUC6 and CDX2. Sub‐cluster S1 predominantly featured intestinal‐alveolar, S2 gastrointestinal, S3 gastric and S4 alveolar differentiation. In turn, KRASA and ALKA shared alveolar lineage alongside residual MUC5AC expression, with additional focal CDX2 and diffuse vimentin, respectively. A proximal‐to‐distal scheme extending from terminal (TB) and respiratory (RB) bronchioles to alveolar cells was devised, where S3 originated from distal TB (cellular mucinous adenocarcinoma), S2 from proximal RB (secreting mucinous adenocarcinoma), S1 from intermediate RB (mucin lake‐forming colloid adenocarcinoma), S4 from distal RB (colloid alveolar adenocarcinoma), KRASA from juxta‐alveolar RB (KRAS‐mutated non‐mucinous adenocarcinoma) and ALKA from juxta‐bronchial alveolar cells (ALK‐translocated adenocarcinoma). TNGS analysis

  7. Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis

    PubMed Central

    Chunhua, Ma; Yuan, Lv; Ning, Mu; Jinduo, Li; Bin, Wang; Liwei, Sun

    2016-01-01

    Abstract Objective To discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis. Methods 5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid. Results 5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method. Conclusion ARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

  8. [The morphological features of the uterine body adenocarcinoma].

    PubMed

    Dzhaparidze, N A; Chakvetatdze, L B; Dzhikia, I D

    2014-06-01

    The anthors studied the morphological features of uterine adenocarcinoma using immunohistochemical methods. The endometrial tissue was studed resulting from surgery - hysterectomy with oophorectomy in 103 patients aged 45-76 years with a clinical diagnosis of endometrial cancer. To exclude false-positive and false-negative results, we carry out same investigation on 12 patients with morphological diagnosis easy-glandular hyperplasia of the endometrium. The results showed that the endometrioid adenocarcinomas exhibit the high and moderate expression of estrogen and progesterone receptors and low rate of the proliferation marker Ki-67. For serous-paapillary andenocarcionoma of the uterine body the negative ER-PR-receptor over expression phenotype and proliferation marker Ki-67 superexpression are characteristic. The results showed that in a simple-glandular endometrial hyperplasia is determined a moderate expression of estrogen and progesterone receptors, as for the Ki-67 proliferation marker an expression was found only in the single arears with an average of 5-8% of findings. Based at shis study it may be concluded thate the use of immunohistochemical studies particularly a detection of negative estrogen and progesterone resceptor phenotype and high expression of the proliferation marker Ki-67 is an additional defferential diagnostic eriterion for the diagnosis of serous papillary adenocarcinoma of the uterine body thet will ensure adepuate therapeutis approach to patients suffering from this disorder. Given he fact that serous papillary carcinoma of the endometrium is the most common neoplesm of the rarer forms of endometrial cancer with an extremely peculiar aggressive coures a ssurgical treatment as in overian cancer is recommended for this parthology, including a hysterectomy with bilateral oophorectomy, lymphadenectomy, omentektomy, cytological examination of the abdomend and biopsy of suspicious areas of the abdominal cavity, with adjuvant treatment including

  9. 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

  10. Colonic adenocarcinoma with metastasis to the gingiva.

    PubMed

    Alvarez-Alvarez, Carlos; Iglesias-Rodríguez, Begoña; Pazo-Irazu, Susana; Delgado-Sánchez-Gracián, Carlos

    2006-01-01

    Metastatic tumors involve the oral cavity, and the most common primary sites are the breast and lung. Most cases affect the mandible and maxilla in that order, although some of them can be located in the soft perioral tissues. We report the case of a 62-year-old male who had been diagnosed with sigmoid adenocarcinoma with nodal and liver metastasis, who presented 6 months later with a gingival polypoid tumor, at first considered as a primary neoplasm of gingiva, that was diagnosed in a biopsy as metastatic intestinal adenocarcinoma. The histological evaluation is essential to separate adenocarcinoma from the commoner in this site squamous cell carcinoma, and the immunohistochemical techniques are useful to distinguish metastatic tumor versus primary adenocarcinoma from the minor salivary glands of the area. The intraoral spread of a disseminated neoplasm is generally a sign of bad prognosis, although a longer survival can be expected if a radical surgical treatment of a solitary metastasis is carried out.

  11. Catumaxomab for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas

    ClinicalTrials.gov

    2017-05-31

    Gastric Adenocarcinoma With Peritoneal Carcinomatosis; Siewert Type II Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis; Siewert Type III Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis

  12. Risk factors for Barrett’s oesophagus and oesophageal adenocarcinoma: Results from the FINBAR study

    PubMed Central

    Anderson, Lesley A; Watson, RG Peter; Murphy, Seamus J; Johnston, Brian T; Comber, Harry; Mc Guigan, Jim; Reynolds, John V; Murray, Liam J

    2007-01-01

    AIM: To investigate risk factors associated with Barrett’s oesophagus and oesophageal adenocarcinoma. METHODS: This all-Ireland population-based case-control study recruited 224 Barrett’s oesophagus patients, 227 oesophageal adenocarcinoma patients and 260 controls. All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors. RESULTS: Gastro-oesophageal reflux was associated with Barrett’s [OR 12.0 (95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48 (95% CI 2.25-5.41)]. Oesophageal adenocarcinoma patients were more likely than controls to be ex- or current smokers [OR 1.72 (95% CI 1.06-2.81) and OR 4.84 (95% CI 2.72-8.61) respectively] and to have a high body mass index [OR 2.69 (95% CI 1.62-4.46)]. No significant associations were observed between these risk factors and Barrett's oesophagus. Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50 (95% CI 0.30-0.86)]. CONCLUSION: A high body mass index, a diet low in fruit and cigarette smoking may be involved in the progression from Barrett’s oesophagus to oesophageal adenocarcinoma. PMID:17461453

  13. Possible involvement of leptin and leptin receptor in developing gastric adenocarcinoma

    PubMed Central

    Zhao, Liang; Shen, Zhi-Xiang; Luo, He-Sheng; Shen, Lei

    2005-01-01

    AIM: To investigate the expression of leptin and leptin receptor (ob-R) in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing intestinal-type gastric adenocarcinoma. METHODS: Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and mild to severe gastric epithelial dysplasia. Positive staining was identified and percentage of positive staining was graded. RESULTS: Dual expression of leptin and leptin receptor were detected in 80% (16/20) intestinal metaplasia, 86.3% (25/30) mild gastric epithelial dysplasia, 86.7% (26/30) moderate gastric epithelial dysplasia, 93.3% (28/30) severe gastric epithelial dysplasia, 91.3% (55/60) intestinal-type gastric adenocarcinoma and 30.0% (9/30) diffuse-type gastric carcinoma. The percentage of dual expression of leptin and leptin receptor in intestinal-type gastric adenocarcinoma was significantly higher than that in diffuse-type gastric adenocarcinoma (χ2 = 37.022, P<0.01). CONCLUSION: Our results indicate the presence of an autocrine loop of leptin system in the development of intestinal-type gastric adenocarcinoma. PMID:16437696

  14. Pathologic classification of adenocarcinoma of lung.

    PubMed

    Van Schil, Paul E; Sihoe, Alan D L; Travis, William D

    2013-10-01

    Recently, the 1999/2004 World Health Organization (WHO) classification of adenocarcinoma became less useful from a clinical standpoint as most adenocarcinomas belonged to the mixed subtype and the term bronchioloalveolar carcinoma (BAC) gave rise to much confusion among clinicians. For these reasons a new adenocarcinoma classification was introduced in 2011 by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS). This represents an international, multidisciplinary effort joining pathologists, molecular biologists, pulmonary physicians, thoracic oncologists, radiologists, and thoracic surgeons. Currently, a distinction is made between pre-invasive lesions, minimally invasive and invasive lesions. The confusing term BAC is not used anymore and new subcategories include adenocarcinoma in situ and minimally invasive adenocarcinoma. Several aspects of this classification are discussed with main emphasis on its correlation with imaging techniques and its impact on diagnosis, treatment and prognosis. On chest computed tomography (CT) a distinction is made between solid and subsolid nodules, the latter comprising ground glass opacities (GGO), and partly solid lesions. Several studies incorporating CT and positron emission tomographic (PET) data show a good imaging-pathologic correlation. With the implementation of screening programs early lung cancer has become a hotly debated topic and sublobar resection is currently reconsidered for early lesions without lymph node involvement. This new classification will also have an impact on the TNM classification. Thoracic surgeons will continue to play a major role in the application, evaluation and further refinement of this new adenocarcinoma classification.

  15. Pulmonary adenocarcinoma: A renewed entity in 2011

    PubMed Central

    Kadara, Humam; Kabbout, Mohamed; Wistuba, Ignacio I.

    2014-01-01

    Lung cancer, of which non-small-cell lung cancer comprises the majority, is the leading cause of cancer-related deaths in the United States and worldwide. Lung adenocarcinomas are a major subtype of non-small-cell lung cancers, are increasing in incidence globally in both males and females and in smokers and non-smokers, and are the cause for almost 50% of deaths attributable to lung cancer. Lung adenocarcinoma is a tumour with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy is still largely unknown. This review will describe advances in the molecular pathology of lung adenocarcinoma with emphasis on genomics and DNA alterations of this disease. Moreover, the review will discuss recognized lung adenocarcinoma preneoplastic lesions and current concepts of the early pathogenesis and progression of the disease. We will also portray the field cancerization phenomenon and lineage-specific oncogene expression pattern in lung cancer and how both remerging concepts can be exploited to increase our understanding of lung adenocarcinoma pathogenesis for subsequent development of biomarkers for early detection of adenocarcinomas and possibly personalized prevention. PMID:22040022

  16. Rare pancreas tumor mimicking adenocarcinoma: Extramedullary plasmacytoma

    PubMed Central

    Akyuz, Filiz; Şahin, Davut; Akyuz, Umit; Vatansever, Sezai

    2014-01-01

    Neoplastic proliferation of plasma cells is called plasma cell dyscrasias, and these neoplasms can present as a solitary neoplasm or multiple myeloma. Extramedullary plasmacytoma, in particular pancreatic plasmacytoma, is a rare manifestation of multiple myeloma. Although computerized tomography is useful for the diagnosis of extramedullary plasmacytoma, there are no specific radiologic markers that distinguish it from adenocarcinoma. Histological confirmation by biopsy is necessary for accurate diagnosis and management of the tumor. Endosonography is the most sensitive method for the diagnosis of pancreatic tumors, and the use of fine needle aspiration by endosonography is associated with a lower risk for malignant seeding and complications. Here, we report a case of pancreatic plasmacytoma in newly identified multiple myeloma as diagnosed by endosonography. Endosonography is a reliable and rapid method for the diagnosis of extramedullary plasmacytoma. Therefore, endosonographic fine needle aspiration should be the first choice for histological evaluation when pancreatic plasmacytoma is suspected. Ideally, the pathology would be performed at the same site as endosonographic biopsy. PMID:24634714

  17. Expression of SNCG, MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma and their clinical significance

    PubMed Central

    Zheng, Shufang; Shi, Lifang; Zhang, Yi; He, Tao

    2014-01-01

    Objectives: The purpose of the study was to detect the expression of SNCG, MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma, and to evaluate their roles in the carcinogenesis of gastric adenocarcinoma, development, invasion and metastasis as well as their clinical significance. Methods: The expression of SNCG, MAP2, SDF-1 and CXCR4 was detected by SP immunohistochemical method in 225 cases of gastric adenocarcinoma and 105 cases of nonneoplastic adjacent gastric tissue. The expression of SNCG, MAP2, SDF-1 and CXCR4 mRNA was also detected by RT-PCR method in 50 cases of gastric adenocarcinoma and 30 cases of nonneoplastic adjacent gastric tissue. Results: The expression of SNCG, MAP2, SDF-1 and CXCR4 in the gastric adenocarcinoma was remarkably higher than those in the nonneoplastic adjacent gastric tissue (P < 0.01); The positive expression of SNCG and MAP2 was correlated with the depth of tumor invasion and the metastasis of lymph nodes (P < 0.05), and that of SDF-1 and CXCR4 was correlated with the metastasis of lymph nodes (P < 0.05). Conclusions: SNCG, MAP2, SDF-1 and CXCR4 may play an important role in the carcinogenesis, progression, invasion and metastasis of gastric adenocarcinoma. However, it still needs more exploration whether they can serve as promising therapeutic targets of gastric adenocarcinoma. PMID:25400739

  18. Increased risk of oesophageal adenocarcinoma among upstream petroleum workers

    PubMed Central

    Kirkeleit, Jorunn; Riise, Trond; Bjørge, Tone; Moen, Bente E; Bråtveit, Magne; Christiani, David C

    2013-01-01

    Objectives To investigate cancer risk, particularly oesophageal cancer, among male upstream petroleum workers offshore potentially exposed to various carcinogenic agents. Methods Using the Norwegian Registry of Employers and Employees, 24 765 male offshore workers registered from 1981 to 2003 was compared with 283 002 male referents from the general working population matched by age and community of residence. The historical cohort was linked to the Cancer Registry of Norway and the Norwegian Cause of Death Registry. Results Male offshore workers had excess risk of oesophageal cancer (RR 2.6, 95% CI 1.4 to 4.8) compared with the reference population. Only the adenocarcinoma type had a significantly increased risk (RR 2.7, 95% CI 1.0 to 7.0), mainly because of an increased risk among upstream operators (RR 4.3, 95% CI 1.3 to 14.5). Upstream operators did not have significant excess of respiratory system or colon cancer or mortality from any other lifestyle-related diseases investigated. Conclusion We found a fourfold excess risk of oesophageal adenocarcinoma among male workers assumed to have had the most extensive contact with crude oil. Due to the small number of cases, and a lack of detailed data on occupational exposure and lifestyle factors associated with oesophageal adenocarcinoma, the results must be interpreted with caution. Nevertheless, given the low risk of lifestyle-related cancers and causes of death in this working group, the results add to the observations in other low-powered studies on oesophageal cancer, further suggesting that factors related to the petroleum stream or carcinogenic agents used in the production process might be associated with risk of oesophageal adenocarcinoma. PMID:19858535

  19. Well-differentiated adenocarcinoma associated with ulcerative colitis

    PubMed Central

    Yamamoto, Tomoko; Hiroi, Atsuko; Itagaki, Hiroko; Kato, Yoichiro; Iizuka, Bunei; Itabashi, Michio; Shibata, Noriyuki; Nagashima, Yoji

    2017-01-01

    Objectives: Adenocarcinoma is known to be associated with ulcerative colitis, but the diagnosis is sometimes challenging, both clinically and pathologically. Methods and Results: We present a case of extremely well-differentiated adenocarcinoma associated with ulcerative colitis, in which preoperative diagnosis was not possible. Glands in biopsy specimens showed a serrated appearance that looked like low-grade dysplasia or regenerative mucosa. After an operation due to severe symptoms of stenosis, carcinoma was diagnosed. Tumor cells, especially in invasive glands, tended to show stronger immunoreactivity against anti-CK7, TNF-α and Aurora B antibodies compared to cells of mucosal lesion. Interestingly, CD44v6, one of the adhesion molecules, was less expressed in invasive glands, while those glands exhibited stronger expression of a disintegrin and metalloproteinase 17 (ADAM 17), one of the sheddases that cleaves an extracellular domain of CD44. Conclusions: These observations appear interesting to consider the pathogenesis and to diagnose extremely well-differentiated adenocarcinoma in ulcerative colitis, although further investigation is needed. PMID:28255443

  20. In compressed lung tissue microscopic sections of adenocarcinoma in situ may mimic papillary adenocarcinoma.

    PubMed

    Thunnissen, Erik; Beliën, Jeroen A M; Kerr, Keith M; Chung, Jin-Haeng; Flieder, Douglas B; Noguchi, Masayuki; Yatabe, Yasushi; Hwang, David M; Lely, Rutger J; Hartemink, Koen J; Meijer-Jorna, Lorine B; Tsao, Ming-Sound

    2013-12-01

    Surgical removal and pathologic handling of lung tissue has a compressive effect upon its architecture. The effect of surgical atelectasis on morphology has not been examined in depth, especially with respect to lung adenocarcinomas. To examine the influence of surgical atelectasis on morphologic lepidic growth pattern, mimicking papillary adenocarcinoma pattern. In 2 cases serial sections of resected pulmonary adenocarcinoma were used, as was a 3-dimensional reconstruction. Elastin stains were performed on primary and metastatic adenocarcinomas. Perfusion fixation of another case showed marked morphologic differences of less compressed peripheral lung tissue, emphasizing the preexisting alveolar structure. An elastic stain may help identify true lesional architecture. We demonstrate that microscopic sections of adenocarcinoma in situ in compressed/collapsed tissue may give rise to a pseudopapillary pattern mimicking invasive adenocarcinoma. Accurate appreciation of different tumor architecture in lung adenocarcinoma has important biologic and clinical implications. Pathologists should be aware of the possibility of misclassification of adenocarcinoma pattern due to tissue artifacts caused by lung tissue handling.

  1. Desmoplasia of Pancreatic Ductal Adenocarcinoma

    PubMed Central

    PANDOL, STEPHEN; EDDERKAOUI, MOUAD; GUKOVSKY, ILYA; LUGEA, AURELIA; GUKOVSKAYA, ANNA

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is characterized by remarkable desmoplasia. The desmoplasia is composed of extracellular matrix (ECM) proteins, myofibroblastic pancreatic stellate cells, and immune cells associated with a multitude of cytokines, growth factors, and ECM metabolizing enzymes. The mechanisms of participation of this complex matrix process in carcinogenesis are only starting to be appreciated. Recent studies showed key roles for stellate cells in the production of ECM proteins as well as cytokines and growth factors that promote the growth of the cancer cells all present in the desmoplastic parts of PDAC. In addition, interactions of ECM proteins and desmoplastic secreted growth factors with the cancer cells of PDAC activate intracellular signals including reactive oxygen species that act to make the cancer cells resistant to dying. These findings suggest that the desmoplasia of PDAC is a key factor in regulating carcinogenesis of PDAC as well as responses to therapies. A better understanding of the biology of desmoplasia in the mechanism of PDAC will likely provide significant opportunities for better treatments for this devastating cancer. PMID:19896098

  2. 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.

  3. The significance of programmed cell death ligand 1 expression in resected lung adenocarcinoma.

    PubMed

    Wu, Shafei; Shi, Xiaohua; Sun, Jian; Liu, Yuanyuan; Luo, Yufeng; Liang, Zhiyong; Wang, Jinghui; Zeng, Xuan

    2017-03-07

    Lung adenocarcinoma (AD) is a common variant of non-small cell lung cancer (NSCLC). Programmed cell death protein 1/programmed cell death ligand 1 (PD1/PD-L1) are promising immunotherapy targets and its expression may be an important biomarker of predicting clinical response. In this study, we evaluated PD-L1 expression in conjunction with clinicopathological characteristics and outcomes in resected lung adenocarcinoma. This study included 133 cases of lung adenocarcinoma. PD-L1 expression rate in lung adenocarcinoma was 16.5% at the mRNA level and 13.5% at the protein level, and the kappa coefficient of the two examination methods was 0.824 (P = 0.219, highly correlated). PD-L1 was highly expressed in male patients and smokers with lung adenocarcinoma (P = 0.019 and 0.002, respectively), while no associations were identified between PD-L1 expression and age, tumor size, clinical stage, positive pleural invasion, lymph node metastasis, or therapy methods. Overexpression of PD-L1 was a significant indicator of shorter recurrence free survival time and overall survival (P = 0.000 and 0.000, respectively). Multivariate analysis revealed that PD-L1 expression was an independent risk factor for poor recurrence free survival and overall survival (P = 0.009 and 0.016, respectively). Expression of PD-L1 was examined with immunohistochemistry, using the VENTANA PD-L1 (SP263) rabbit monoclonal antibody. mRNA levels of PD-L1 were evaluated using in situ hybridization. PD-L1 overexpression is more frequently observed in male patients and smokers in lung adenocarcinoma. PD-L1 expression is an indicator of worse prognosis in surgically resected lung adenocarcinoma patients.

  4. Survival after attempted surgical resection and intraoperative radiation therapy for pancreatic and periampullary adenocarcinoma

    SciTech Connect

    O'Connor, John K.; Sause, William T. . E-mail: ldwsause@ihc.com; Hazard, Lisa J.; Noyes, R. Dirk

    2005-11-15

    Purpose: To evaluate a single institution's experience with intraoperative radiation therapy (IORT) in combination with attempted surgical resection for pancreatic and periampullary adenocarcinoma. Methods and Materials: From May 1986 until June 2001, 77 patients at LDS Hospital underwent attempted surgical resection and IORT for pancreatic or periampullary adenocarcinoma. A potentially curative resection was defined as surgery with negative or microscopic positive margins. No patients had metastatic disease at the time of surgery and IORT. Forty-four patients with tumors located in the pancreas and 9 patients with periampullary tumors underwent potentially curative surgical resection and IORT. Twenty-four patients had pancreatic tumors deemed unresectable and underwent surgical bypass and IORT. Actuarial survival was calculated from the date of IORT until last follow-up or death by use of the Kaplan-Meier method. Results: Patients undergoing a potentially curative resection and IORT for periampullary adenocarcinoma had a median survival of 167 months and a 56% 5-year actuarial survival, compared with a median survival of 16 months and a 19% 5-year actuarial survival for patients undergoing the same treatment for pancreatic adenocarcinoma (p = 0.03). Patients with unresectable disease who underwent bypass and IORT had a median survival of 11 months and a 0% 3-year survival, significantly worse than patients able to undergo surgical resection and IORT (p = 0.0002). The operative mortality for all patients undergoing potentially curative resection and IORT was 3.7%. Conclusions: Intraoperative radiation therapy is well tolerated and does not increase the morbidity or mortality of potentially curative surgical resection for pancreatic or periampullary adenocarcinoma. Patients with periampullary adenocarcinoma have a better prognosis than those with pancreatic adenocarcinoma, and patients with unresectable pancreatic disease fared worse.

  5. Comparative Survival of Patients With Anal Adenocarcinoma, Squamous Cell Carcinoma of the Anus, and Rectal Adenocarcinoma.

    PubMed

    Franklin, Robert A; Giri, Smith; Valasareddy, Poojitha; Lands, Lindsey T; Martin, Mike G

    2016-03-01

    Anal adenocarcinoma (AA) represents 5% to 10% of anal cancer. Little is known about its natural history and prognosis. Using population-based data, we defined the outcomes of AA relative to other anorectal malignancies. We analyzed the Surveillance, Epidemiology, and End Results 18 database to identify patients ≥ 18 years old with AA, squamous cell carcinoma of the anus (SCCA), and rectal adenocarcinoma (RA) diagnosed between 1990 and 2011. Median overall survival (OS), 1-year, 3-year, 5-year, and 10-year OS were computed using actuarial methods. The log rank test was used to estimate the difference between Kaplan-Meier survival curves. A Cox proportional hazard regression model was used to adjust the effects of other covariates on survival, including age, year diagnosed, sex, stage, surgery, and radiation. Of 57,369 cases, 0.8% (n = 462) were patients with AA, 87.8% (n = 50,382) were patients with RA, and 11.4% (n = 6525) were patients with SCCA. The median age for AA was 69 years (range, 20-96 years), 66 years (range, 18-103 years) for RA, and 66 years (range, 14-104 years) for SCCA. The median OS was significantly lower for AA (33 months), compared with SCCA (118 months) and RA (68 months) (P < .01). In multivariate analysis, AA had a worse prognosis compared with SCCA (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.59-0.75; P < .01) and RA (HR, 0.68; 95% CI, 0.61-0.77; P < .01), after adjusting for age, sex, race, stage, grade, radiation, and surgery. There was a strong trend for improved survival among patients who received radical surgery (HR, 0.71; 95% CI, 0.51-1.00; P = .05). AA confers a significantly worse prognosis than SCCA and RA. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Lysosomal exoglycosidases in serum and urine of patients with colon adenocarcinoma.

    PubMed

    Szajda, Slawomir Dariusz; Snarska, Jadwiga; Puchalski, Zbigniew; Zwierz, Krzysztof

    2008-01-01

    The aim of this study is to evaluate the usefulness of determination the activity of lysosomal exoglycosidases: N-acetyl-beta-D-hexosaminidase (HEX - E.C. 3.2.1.30), beta-D-galactosidase (GAL - E.C. 3.2.1.23), alpha-L-fucosidase (FUC - E.C. 3.2.1.51) and alpha-D-mannosidase (MAN - E.C. 3.2.1.24) in blood serum and urine in diagnostics of colon adenocarcinoma. The activity of lysosomal exoglycosidases was determined by the method of Marciniak et al. adapted to serum and urine of patients with adenocarcinoma of the colon. A significant increase in concentration of the activity of HEX, GAL and FUC was found in blood serum, as well as HEX and GAL in urine, of patients with colon adenocarcinoma, in comparison with healthy people. With the method of Marciniak et al. for determination the activity of HEX, GAL and FUC in blood serum as well as HEX and GAL in urine, the cases of colon adenocarcinoma were significantly differentiated from healthy people. The high diagnostic value, sensitivity and specificity of the method of Marciniak et al., suggests the possibility of its use for determination of the activity of HEX, FUC and GAL in blood serum as well as HEX and GAL in urine, in the diagnostics of colon adenocarcinoma.

  7. Typing of colon and lung adenocarcinoma by high throughput imaging mass spectrometry.

    PubMed

    Kriegsmann, Mark; Longuespée, Rémi; Wandernoth, Petra; Mohanu, Cristina; Lisenko, Katharina; Weichert, Wilko; Warth, Arne; Dienemann, Hendrik; De Pauw, Edwin; Katzenberger, Tiemo; Aust, Daniela; Baretton, Gustavo; Kriegsmann, Joerg; Casadonte, Rita

    2017-07-01

    In advanced tumor stages, diagnosis is frequently made from metastatic tumor tissue. In some cases, the identification of the tumor of origin may be difficult by histology alone. In this setting, immunohistochemical and molecular biological methods are often required. In a subset of tumors definite diagnosis cannot be achieved. Thus, additional new diagnostic methods are required for precise tumor subtyping. Mass spectrometric methods are of special interest for the discrimination of different tumor types. We investigated whether it is possible to discern adenocarcinomas of colon and lung using high-throughput imaging mass spectrometry on formalin-fixed paraffin-embedded tissue microarrays. 101 primary adenocarcinoma of the colon and 91 primary adenocarcinoma of the lung were used to train a Linear Discriminant Analysis model. Results were validated on an independent set of 116 colonic and 75 lung adenocarcinomas. In the validation cohort 109 of 116 patients with colonic and 67 of 75 patients with lung adenocarcinomas were correctly classified. The ability to define proteomic profiles capable to discern different tumor types promises a valuable tool in cancer diagnostics and might complement current approaches. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Ductal variant of prostate adenocarcinoma harbor Xenotropic murine leukemia virus related virus (XMRV) infection: a novel finding in subtype of prostate cancer

    PubMed Central

    Baig, Faraz Ahmed; Mirza, Talat; Hamid, Amna; Syed, Serajuddaula; Jamal, Qamar

    2017-01-01

    Objective Xenotropic murine leukemia virus related virus (XMRV), is the first gammaretrovirus identified a decade ago, in human tissue bearing adenocarcinoma of prostate, followed by several researches documenting little or no prevalence of XMRV in prostate cancer samples. However, the status of XMRV within subtype of prostate adenocarcinoma has not been investigated yet. In this study, we investigated the relationship between XMRV and broad spectrum morphological entities of prostate adenocarcinoma, including acinar, ductal and other rare subtypes. Material and methods The prevalence of XMRV DNA in different histological subtypes of prostate adenocarcinoma was examined after characterizing the tumors into groups, using formalin-fixed, paraffin-embedded tissue samples from newly diagnosed prostate adenocarcinomas and archival prostate cancer tissue from our XMRV case control analysis. Broad-spectrum XMRV DNA amplification was performed by end-point polymerase chain reaction, using commercially available primer set. Results The study included 100 patients with prostate cancer. XMRV DNA was detected in 4 of 8 (50%) ductal adenocarcinomas, exhibiting papillary and cribriform histological features. XMRV DNA was not detected in any other variant of adenocarcinoma including acinar (0/91) and mucinous carcinomas (0/1). Majority of XMRV positive cases were biologically aggressive and present cancer at an early age upon diagnosis. Conclusion Ductal adenocarcinomas demonstrate a significant association of XMRV DNA while other histological variants of prostate adenocarcinoma seem unrelated to XMRV infection. PMID:28861296

  9. What Happens After Treatment for Small Intestine Adenocarcinoma?

    MedlinePlus

    ... After Treatment What Happens After Treatment for Small Intestine Adenocarcinoma? For some people with small intestine cancer, ... Small Intestine Adenocarcinoma Stops Working More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  10. What Are the Risk Factors for Small Intestine Adenocarcinoma?

    MedlinePlus

    ... Prevention What Are the Risk Factors for Small Intestine Adenocarcinoma? A risk factor is anything that changes ... Small Intestine Adenocarcinoma Be Prevented? More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  11. What Should You Ask Your Doctor About Small Intestine Adenocarcinoma?

    MedlinePlus

    ... What Should You Ask Your Doctor About Small Intestine Adenocarcinoma? It’s important to have honest, open discussions ... Doctor About Small Intestine Adenocarcinoma? More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  12. Generalized Lymphadenopathy: Unusual Presentation of Prostate Adenocarcinoma

    PubMed Central

    Cetin, Bulent; Cetin, Zeynep; Buyukberber, Suleyman; Gonul, Ipek Isık; Sahiner, Ilgin; Coskun, Ugur; Benekli, Mustafa

    2011-01-01

    Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. Here, we report the case of a 59-year-old male patient with supraclavicular, mediastinal, hilar, and retroperitoneal and inguinal lymphadenopathy, which suggested the diagnosis of lymphoma. There were no urinary symptoms. A biopsy of the inguinal lymph node was compatible with adenocarcinoma, whose prostatic origin was shown by immunohistochemical staining with PSA. The origin of the primary tumor was confirmed by directed prostate biopsy. We emphasize that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate diagnostic and therapeutic approach. PMID:22606612

  13. Adenocarcinoma of Meckel's cave: case report.

    PubMed

    Tacconi, L; Arulampalam, T; Johnston, F; Symon, L

    1995-12-01

    A rare localization of adenocarcinoma in Meckel's cave is reported in a 58-year-old woman, who had a 5-month history of pain and altered sensation in the second division of the left trigeminal nerve. Removal of the lesion was achieved by a subtemporal route. Histology showed this to be an adenocarcinoma. The patient underwent investigations for a primary tumor; the investigations were all negative, and the patient was subsequently treated with a course of radiotherapy. At 4-month follow-up, there was no evidence of recurrence, and she remains symptomatically well. The various mechanisms of secondary localization are discussed.

  14. Mutation analysis of the p53, APC, and p16 genes in the Barrett's oesophagus, dysplasia, and adenocarcinoma.

    PubMed Central

    González, M V; Artímez, M L; Rodrigo, L; López-Larrea, C; Menéndez, M J; Alvarez, V; Pérez, R; Fresno, M F; Pérez, M J; Sampedro, A; Coto, E

    1997-01-01

    AIMS: To study the loss of heterozygosity and the presence of mutations at the p53, p16/CDKN2, and APC genes in Barrett's oesophagus, low grade dysplastic oesophageal epithelium, and adenocarcinoma of the oesophagus; to relate the presence of alterations at these genes with the progression from Barrett's oesophagus to adenocarcinoma. METHODS: DNA was extracted from paraffin blocks containing tissue from Barrett's oesophagus (12 samples), low grade dysplasia (15 cases), and adenocarcinoma (14 cases). Loss of heterozygosity (LOH) at the p53, p16, and APC genes was determined by comparing the autoradiographic patterns of several microsatellite markers between the normal tissue and the malignant tissue counterpart. SSCP was used to determine the presence of mutations at p53 (exons 5 to 8), p16 (exon 2), and APC. Homozygous deletion of the p16 gene was defined through polymerase chain reaction followed by Southern blot. RESULTS: LOH at the p53, p16, and APC genes was not observed in Barrett's oesophagus without dysplasia, and increased to 90% (p53), 89% (p16), and 60% (APC) in the adenocarcinomas. The p53 gene was mutated in only two adenocarcinomas (codons 175 and 245). In one case a mutation at the APC gene (codon 1297) was found. No patient had mutation at the second exon of p16. However, this gene was homozygously deleted in three of the 12 adenocarcinomas. CONCLUSIONS: The tumour suppressor genes p53, p16, and APC are often deleted in adenocarcinomas derived from Barrett's oesophagus. Mutations at these genes are also found in the adenocarcinomas, including the homozygous deletion of the p16 gene. However, the absence of genetic alterations in the Barrett's oesophagus and the low grade dysplastic epithelia suggest that mutations at these genes develop later in the progression from Barrett's oesophagus to adenocarcinoma. Images PMID:9155671

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

    NASA Astrophysics Data System (ADS)

    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 DT and D 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.

  16. Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification.

    PubMed

    Noro, R; Honda, K; Tsuta, K; Ishii, G; Maeshima, A M; Miura, N; Furuta, K; Shibata, T; Tsuda, H; Ochiai, A; Sakuma, T; Nishijima, N; Gemma, A; Asamura, H; Nagai, K; Yamada, T

    2013-10-01

    Even if detected at an early stage, a substantial number of lung cancers relapse after curative surgery. However, no method for distinguishing such tumors has yet been established. The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridization on tissue microarrays comprising 543 surgically resected adenocarcinomas of the lung. Amplification (an increase in the copy number by ≥ 2.0 fold) of the ACTN4 gene was detected in two of seven lung adenocarcinoma cell lines and 79 (15%) of 543 cases of pathological stage I-IV lung adenocarcinoma. Multivariate analysis revealed that ACTN4 gene amplification was the most significant independent factor associated with an extremely high risk of death (hazard ratio, 6.78; P = 9.48 × 10(-5), Cox regression analysis) among 290 patients with stage I lung adenocarcinoma. The prognostic significance of ACTN gene amplification was further validated in three independent cohorts totaling 1033 patients. Amplification of the ACTN4 gene defines a small but substantial subset of patients with stage I lung adenocarcinoma showing a distinct outcome. Such patients require intensive medical attention and might benefit from postoperative adjuvant chemotherapy.

  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. Human Papillomavirus in Endometrial Adenocarcinomas: Infectious Agent or a Mere “Passenger”?

    PubMed Central

    Giatromanolaki, A.; Sivridis, E.; Papazoglou, D.; Koukourakis, M. I.; Maltezos, E.

    2007-01-01

    Aims. To investigate the possible association of human papillomavirus (HPV) with endometrial hyperplasias and neoplasia. Does HPV play any role in the initiation or prognosis of endometrial adenocarcinomas? Methods. Twenty-five endometrial adenocarcinomas of the endometrioid cell type, with and without squamous differentiation, and twenty-four endometrial hyperplasias of various forms (simple, complex, and atypical) were analyzed for the presence of type 16 and 18 HPV by the polymerase chain reaction (PCR). The results were related to histopathological features of the tumour, and the patients' age, and prognosis. Results. Six of 25 endometrial adenocarcinomas were HPV 16-positive (24%), and 5 of 25 (20%) were HPV 18-positive. Simple endometrial hyperplasias was associated somewhat more commonly with HPV 16 and 18 (2/8 and 1/8 cases, resp.) than hyperplasias progressing to endometrial adenocarcinomas, namely, atypical endometrial hyperplasia (1/8 and 0/8 cases, resp.). None of the positive cases in the series, whether hyperplastic or neoplastic, demonstrated cytological evidence of HPV infection. There was no relation between HPV-positive cases and squamous differentiation, depth of myometrial invasion, lymphatic involvement, lymphocytic response, patients' age, or prognosis. Conclusion. It appears that the presence of HPV in the endometrium, as detected by PCR, does not play any role in the initiation or prognosis of endometrial adenocarcinoma. PMID:18274613

  19. Semiquantitative Computed Tomographic Characteristics for Lung Adenocarcinoma and Their Association with Lung Cancer Survival

    PubMed Central

    Wang, Hua; Schabath, Matthew B.; Liu, Ying; Berglund, Anders E.; Bloom, Gregory C.; Kim, Jongphil; Stringfield, Olya; Eikman, Edward A.; Klippenstein, Donald L.; Heine, John J.; Eschrich, Steven A.; Ye, Zhaoxiang; Gillies, Robert J.

    2015-01-01

    Background Computed tomographic (CT) characteristics derived from noninvasive images that represent the entire tumor may have diagnostic and prognostic value. The purpose of this study was to assess the association of a standardized set of semiquantitative CT characteristics of lung adenocarcinoma with overall survival. Patients and Methods An initial set of CT descriptors was developed to semiquantitatively assess lung adenocarcinoma in patients (n=117) who underwent resection. Survival analyses were used to determine the association between each characteristic and overall survival. Principle component analysis (PCA) was used to determine characteristics that may differentiate histological subtypes. Results Characteristics significantly associated with overall survival included pleural attachment (p < 0.001), air bronchogram (p = 0.03), and lymphadenopathy (p = 0.02). Multivariate analyses revealed pleural attachment was significantly associated with an increased risk of death overall (hazard ratio [HR] = 3.21; 95% confidence interval [CI] 1.53 – 6.70) and among patients with lepidic predominant adenocarcinomas (HR = 5.85; 95% CI 1.75 – 19.59), while lymphadenopathy was significantly associated with an increased risk of death among patients with adenocarcinomas without a predominant lepidic component (HR = 3.07; 95% CI 1.09 – 8.70). A PCA model showed that texture (ground-glass opacity component) was most important for separating the two subtypes. Conclusion A subset of the semiquantitative characteristics described herein has prognostic importance and ability to distinguish between different histological subtypes of lung adenocarcinoma. PMID:26077095

  20. Multivariate prognostic analysis of adenocarcinoma of the uterine cervix treated with radical hysterectomy and systematic lymphadenectomy

    PubMed Central

    Kato, Tatsuya; Takeda, Mahito; Hosaka, Masayoshi; Mitamura, Takashi; Kobayashi, Noriko; Sudo, Satoko; Kaneuchi, Masanori; Kudo, Masataka; Sakuragi, Noriaki

    2013-01-01

    Objective The aim of this study was to investigate the prognostic factors and treatment outcome of patients with adenocarcinoma of the uterine cervix who underwent radical hysterectomy with systematic lymphadenectomy. Methods A total of 130 patients with stage IB to IIB cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy from 1982 to 2005 were retrospectively analyzed. Clinicopathological data including age, stage, tumor size, the number of positive node sites, lymphovascular space invasion, parametrial invasion, deep stromal invasion (>2/3 thickness), corpus invasion, vaginal infiltration, and ovarian metastasis, adjuvant therapy, and survival were collected and Cox regression analysis was used to determine independent prognostic factors. Results An estimated five-year survival rate of stage IB1 was 96.6%, 75.0% in stage IB2, 100% in stage IIA, and 52.8% in stage IIB. Prognosis of patients with one positive-node site is similar to that of those with negative-node. Prognosis of patients with multiple positive-node sites was significantly poorer than that of negative and one positive-node site. Multivariate analysis revealed that lymph node metastasis, lymphovascular space invasion, and parametrial invasion were independent prognostic factors for cervical adenocarcinoma. Survival of patients with cervical adenocarcinoma was stratified into three groups by the combination of three independent prognostic factors. Conclusion Lymph node metastasis, lymphovascular space invasion, and parametrial invasion were shown to be independent prognostic factors for cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy. PMID:23875071

  1. 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

  2. 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 ...

  3. Aggressive digital papillary adenoma-adenocarcinoma.

    PubMed

    Keramidas, Evangelos G; Miller, Gavin; Revelos, Kyriakos; Kitsanta, Panagiota; Page, Robert E

    2006-01-01

    Aggressive digital papillary adenocarcinoma and aggressive digital papillary adenoma are rare tumours of the sweat glands. They are most common in the most distal part of the fingers and are locally aggressive with a 50% local recurrence rate; 14% of tumours metastasize. We present two cases.

  4. Perspectives in the treatment of pancreatic adenocarcinoma

    PubMed Central

    Cid-Arregui, Angel; Juarez, Victoria

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and, in most cases, PDAC is diagnosed at advanced disease stages, when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize, which involve essential adaptive changes in cellular metabolism, signaling, adhesion and immunoediting. In addition, PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades, gemcitabine has been the reference for the systemic treatment of PDAC. However, recently, a regimen combining fluorouracil, irinotecan, oxaliplatin, and leucovorin (FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC, with survival outcomes of 11.3 and 8.5 mo on phase III trials, respectively, over single-agent gemcitabine. With the pending issue of their higher toxicities, these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition, the efficacy of oral fluoropyrimidine (S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past, with only one drug (erlotinib) approved to date. Besides, a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise, immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the

  5. Multiphoton morpho-functional imaging of healthy colon mucosa, adenomatous polyp and adenocarcinoma

    PubMed Central

    Cicchi, Riccardo; Sturiale, Alessandro; Nesi, Gabriella; Kapsokalyvas, Dimitrios; Alemanno, Giovanni; Tonelli, Francesco; Pavone, Francesco S.

    2013-01-01

    Two-photon spectral resolved imaging was used to image fresh human biopsies of colon tissue and to characterize healthy colon mucosa, adenomatous polyp and adenocarcinoma by means of a morpho-functional analysis. Morphological examination, performed using endogenous tissue fluorescence, discriminated adenomatous and adenocarcinoma tissues from normal mucosa in terms of cellular asymmetry and nucleus-to-cytoplasm ratio. Good agreement was found between multiphoton images and histological examination performed on the same samples. Further characterization, performed by means of spectral-resolved analysis of NADH and FAD fluorescence, demonstrated an altered metabolic activity in both adenomatous and adenocarcinoma tissues compared to healthy mucosa. This morpho-functional approach may represent a powerful method to be used in combination with endoscopy for in vivo optical diagnosis of colon cancer and may be extended to other tissues. PMID:23847743

  6. 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.

  7. Invasive Squamous Carcinoma and Adenocarcinoma of an Unreconstructed Exstrophic Bladder with HPV Infection

    PubMed Central

    Altan, Mesut; Çıtamak, Burak; Haberal, Hakan Bahadır; Söğütdelen, Emrullah; Bozaci, Ali Cansu; Baydar, Dilek Ertoy; Doğan, Hasan Serkan; Tekgül, Serdar

    2016-01-01

    Bladder exstrophy is a complex abnormality and is traditionally treated within the early years of life. It is associated with an increased risk of bladder cancer, with 95% of the arising tumors being adenocarcinomas and 3 to 5% being squamous cell carcinomas. HPV infections are also associated with an increased risk of bladder cancer. This case represents a patient with bladder exstrophy that gave rise to coinciding squamous cell carcinoma and adenocarcinoma. Final pathology results showed an infection with HPV. We presented the management of the case and discussed the diagnosis and treatment methods for this patient. PMID:27390585

  8. 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...

  9. 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...

  10. Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma

    PubMed Central

    Koh, Hyun Min; Jang, Bo Geun; Hyun, Chang Lim; Kim, Young Sill; Hyun, Jin Won; Chang, Weon Young; Maeng, Young Hee

    2017-01-01

    Background Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea. Methods AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues. Results AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001). Conclusions AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients. PMID:28013532

  11. 184AA3: A Xenograft Model of ER+ Breast Adenocarcinoma

    PubMed Central

    Hines, William C.; Kuhn, Irene; Thi, Kate; Chu, Berbie; Stanford-Moore, Gaelen; Sampayo, Rocío; Garbe, James C.; Stampfer, Martha; Borowsky, Alexander D.; Bissell, Mina

    2015-01-01

    Purpose 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. Methods 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. Results Xenografts of one cell line, 184AA3, consistently formed ER+ adenocarcinomas that had a high proliferative rate and other features consistent with “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. Conclusions This model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing and drug development. PMID:26661596

  12. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma.

    PubMed

    Schultz, Nicolai A; Werner, Jens; Willenbrock, Hanni; Roslind, Anne; Giese, Nathalia; Horn, Thomas; Wøjdemann, Morten; Johansen, Julia S

    2012-12-01

    MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P=2.06 × 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from non-neoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic

  13. The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: Results from the Leiden-EAC and ESPOIR cohorts.

    PubMed

    Boeters, Debbie M; Gaujoux-Viala, Cécile; Constantin, Arnaud; van der Helm-van Mil, Annette H M

    2017-10-01

    The 2010 ACR/EULAR criteria were derived to classify rheumatoid arthritis (RA) earlier in time. Previous studies indeed observed that the 2010 criteria were fulfilled earlier than the 1987 criteria. This study determined whether the 2010 criteria perform equally in early classification of autoantibody-positive and autoantibody-negative RA. From the total Leiden-EAC (n = 3448) and ESPOIR (n = 813) RA patients who fulfilled the 1987 RA criteria at 1 year but not at presentation were selected (n = 463 and n = 53, respectively), as these patients were classified with delay with the 1987 criteria. These RA patients were studied on fulfilling the 2010 criteria at baseline (as 2010 positivity indicated that these RA patients were earlier identified) and these analyses were stratified for patients with and without anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF). Analyses were repeated for DMARD start within the first year as reference for RA (instead of fulfilling the 1987 criteria). In the EAC, 75% of the selected RA patients did already fulfill the 2010 criteria at baseline. In ESPOIR this was 57%, indeed demonstrating early classification with the 2010 criteria. Among the selected autoantibody-positive RA patients of the EAC, 93% was already identified at baseline with the 2010 criteria. Within autoantibody-negative RA this was 51% (p < 0.001), indicating that 49% of autoantibody-negative RA patients were not early classified with the 2010 criteria. Similarly, within autoantibody-positive RA patients in ESPOIR 92% were 2010 positive at baseline, whereas this was only 25% within autoantibody-negative RA (p < 0.001), indicating that 75% of autoantibody-negative RA patients were not early classified with the 2010 criteria. Similar results were obtained when DMARD start was the reference for RA. The 2010 criteria perform well in the early identification of autoantibody-positive RA, but autoantibody-negative RA patients are still frequently missed

  14. Introducing crucial protein panel of gastric adenocarcinoma disease

    PubMed Central

    Rezaei-Tavirani, Mostafa; Rezaei-Tavirani, Majid; Mansouri, Vahid; Mahdavi, Seyed Mohammad; Valizadeh, Reza; Rostami-Nejad, Mohammad; Zali, Mohammad Reza

    2017-01-01

    Aim: Since interactome analysis of diseases can provide candidate biomarker panel related to the diseases, in this research, protein-protein interaction (PPI) network analysis is used to introduce the involved crucial proteins in Gastric adenocarcinoma (GA). Background: Gastric adenocarcinoma (GA) is the most common type of stomach cancer. There is no efficient diagnostic molecular method for GA. Method: Applying Cytoscape software 3.4.0 and String Database, the PPI network was constructed for 200 genes. Based on centrality parameters, the critical nodes were screened. Gene ontology of the key proteins for pathway analysis and molecular function processing were done and the highlighted pathways and activities were discussed. Results: Among 200 initial genes, 141 genes were included in a main connected network. Seven crucial proteins, including tumor protein p53, epidermal growth factor receptor, albumin, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), v-akt murine thymoma viral oncogene homolog 1, v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) and catenin (cadherin-associated protein), beta 1, 88kDa, and Myogenic differentiation 1, were introduced as key nodes of the network. These identified proteins are mostly involved in pathways and activities related to cancer. Conclusion: In conclusion, the finding is corresponding to the significant roles of these introduced proteins in GA disease. This protein panel may be a useful probe in the management of GA. PMID:28331560

  15. Variation of tumoral marker after radiofrequency ablation of pancreatic adenocarcinoma

    PubMed Central

    Barbi, Emilio; Girelli, Roberto; Tinazzi Martini, Paolo; De Robertis, Riccardo; Ciaravino, Valentina; Salvia, Roberto; Butturini, Giovanni; Frigerio, Isabella; Milazzo, Teresa; Crosara, Stefano; Paiella, Salvatore; Pederzoli, Paolo; Bassi, Claudio

    2016-01-01

    Background To evaluate the correlation between variations of CA 19.9 blood levels and the entity of necrosis at CT after radiofrequency ablation (RFA) of unresectable pancreatic adenocarcinoma. Methods In this study, from June 2010 to February 2014, patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure were included. All these patients underwent RFA. CT study was performed 1 week after RFA. The dosage of CA 19.9 levels was performed 1 month after RFA. Features of necrosis at CT, as mean entity, density and necrosis percentages compared to the original lesion, were evaluated and compared by using t-test with CA 19.9 blood levels variations after RFA procedure. Results In this study were included 51 patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure and with CT study and CA 19.9 available for analysis. After the procedure, CA 19.9 blood levels reduced in 24/51 (47%), remained stable in 10/51 (20%) and increased in 17/51 (33%). In patients with CA 19.9 levels reduced, the tumor marker were reduced less than 20% in 4/24 (17%) and more than 20% in 20/24 (83%); instead the tumor marker were reduced less than 30% in 8/24 (33%) and more than 30% in 16/24 (67%). At CT scan necrotic area density difference was not statistically significant. Also there was no statistically significant difference among the mean area, the mean volume and the mean ablation volume in percentage related to the treated tumor among the three different groups of patients divided depending on the CA 19.9 blood levels. But a tendency to a statistically significant difference was found in comparing the mean percentage of ablation volume between two subgroups of patients with a decrease of CA 19.9 levels with less or more than 20% reduction of tumor markers and between two subgroups with less or more than

  16. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    PubMed Central

    Che, Keying; Zhao, Yang; Qu, Xiao; Pang, Zhaofei; Ni, Yang; Zhang, Tiehong; Du, Jiajun; Shen, Hongchang

    2017-01-01

    Purpose Gastric carcinoma (GC) is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma. Materials and methods Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS) was statistically analyzed. Results Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145) of them. Single cell invasion and large cell invasion were observed in 62.8% (186) and 16.9% (50) of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0.001). Similarly, the OS of patients with single cell invasion and large cell invasion was reduced (single cell invasion, HR: 3.553, P<0.001; large cell invasion, HR: 2.466, P<0.001). Following multivariate analysis, tumor budding and single cell invasion were observed to be independent risk factors for gastric adenocarcinoma (P<0.05). According to the Lauren classification, patients with intestinal-type adenocarcinoma had better outcomes than those with diffuse-type adenocarcinoma (HR: 2.563, P<0.001). Conclusion Tumor budding and single cell invasion in gastric adenocarcinoma are associated with an unfavorable prognosis. PMID:28255247

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

    PubMed

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

    2017-02-28

    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. 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. 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. 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.

  18. Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

    PubMed Central

    Tse, Darren; Zhai, Rihong; Zhou, Wei; Heist, Rebecca S.; Asomaning, Kofi; Su, Li; Lynch, Thomas J.; Wain, John C.; Christiani, David C.

    2011-01-01

    Purpose Functional variation in DNA repair capacity through single nucleotide polymorphisms (SNPs) of key repair genes is associated with a higher risk of developing various types of cancer. Studies have focused on the nucleotide excision repair (NER) and base excision repair (BER) pathways. We investigated whether variant alleles in seven SNPs within these pathways increased the risk of esophageal adenocarcinoma. Methods DNA was extracted from prospectively collected blood specimens. The samples were genotyped for SNPs in NER genes (XPD Lys751Gln, XPD Asp312Asn, ERCC1 8092C/A, and ERCC1 118C/T), and BER genes (XRCC1 Arg399Gln, APE1 Asp148Glu, and hOGG1 Ser326Cys). The presence of variant alleles was correlated with risk of esophageal adenocarcinoma both individually and jointly. Results Variant alleles in NER SNPs XPD Lys751Gln (AOR = 1.50, 95% CI 1.1–2.0), ERCC1 8092 C/A (AOR = 1.44, 95% CI 1.1–1.9), and ERCC1 118C/T (AOR = 1.42, 95% CI 1.0–1.9) were individually associated with esophageal adenocarcinoma risk. An increasing number of variant alleles in NER SNPs showed a significant trend with esophageal adenocarcinoma risk (p = 0.007). Conclusions The presence of variant alleles in NER genes increases risk of esophageal adenocarcinoma. There is evidence of an additive role for SNPs along a common DNA repair pathway. Future larger studies of esophageal adenocarcinoma etiology should evaluate entire biological pathways. PMID:18478337

  19. Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

    SciTech Connect

    Chang, Joe Y. . E-mail: jychang@mdanderson.org; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

    2006-04-01

    Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival.

  20. Immunohistochemical Typing of Adenocarcinomas of the Pancreatobiliary System Improves Diagnosis and Prognostic Stratification

    PubMed Central

    Fernandez-Woodbridge, Alejandro; Alistair D'souza, Melroy; Zhang, Qianni; Bozoky, Benedek; Kandaswamy, Senthil Vasan; Catalano, Piera; Heuchel, Rainer; Shtembari, Sonia; Del Chiaro, Marco; Danielsson, Olof; Björnstedt, Mikael; Löhr, J. Matthias; Isaksson, Bengt; Verbeke, Caroline; Bozóky, Béla

    2016-01-01

    Background & Aims Adenocarcinomas of the pancreatobiliary system are currently classified by their primary anatomical location. In particular, the pathological diagnosis of intrahepatic cholangiocarcinoma is still considered as a diagnosis of exclusion of metastatic adenocarcinoma. Periampullary cancers have been previously classified according to the histological type of differentiation (pancreatobiliary, intestinal), but overlapping morphological features hinder their differential diagnosis. We performed an integrative immunohistochemical analysis of pancreato-biliary tumors to improve their diagnosis and prediction of outcome. Methods This was a retrospective observational cohort study on patients with adenocarcinoma of the pancreatobiliary system who underwent diagnostic core needle biopsy or surgical resection at a tertiary referral center. 409 tumor samples were analyzed with up to 27 conventional antibodies used in diagnostic pathology. Immunohistochemical scoring system was the percentage of stained tumor cells. Bioinformatic analysis, internal validation, and survival analysis were performed. Results Hierarchical clustering and differential expression analysis identified three immunohistochemical tumor types (extrahepatic pancreatobiliary, intestinal, and intrahepatic cholangiocarcinoma) and the discriminant markers between them. Among patients who underwent surgical resection of their primary tumor with curative intent, the intestinal type showed an adjusted hazard ratio of 0.19 for overall survival (95% confidence interval 0.05–0.72; p value = 0.014) compared to the extrahepatic pancreatobiliary type. Conclusions Integrative immunohistochemical classification of adenocarcinomas of the pancreatobiliary system results in a characteristic immunohistochemical profile for intrahepatic cholangiocarcinoma and intestinal type adenocarcinoma, which helps in distinguishing them from metastatic and pancreatobiliary type adenocarcinoma, respectively. A diagnostic

  1. Clinicopathology and Outcomes for Mucinous and Signet Ring Colorectal Adenocarcinoma: Analysis from the National Cancer Data Base

    PubMed Central

    Hyngstrom, John R.; Hu, Chung-Yuan; Xing, Yan; You, Y. Nancy; Feig, Barry W.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Cormier, Janice N.; Chang, George J.

    2013-01-01

    Purpose We evaluated clinical features and survival outcomes among patients with signet ring and mucinous histologies of colorectal adenocarcinoma using data from the National Cancer Data Base (NCDB). Methods Patients aged 18–90 years with colorectal adenocarcinoma diagnosed between 1998 and 2002 were identified from the NCDB. Site-stratified (colon vs rectum) survival analysis was performed using multivariate relative survival adjusted for multiple clinicopathologic and treatment variables. Results The study included 244,794 patients: 25,546 (10%) with mucinous, 2,260 (1%) with signet ring, and 216,988 (89%) with nonmucinous, non–signet ring adenocarcinoma. Mucinous and signet ring cancers were more frequently right-sided (60% and 62%, respectively) than were nonmucinous, non–signet ring adenocarcinomas (42%, P < .001). Signet ring histology was associated with a higher stage (P < .001), and 77.2% of signet ring tumors were high-grade lesions, compared with 20% of mucinous and 17% of non–signet ring, nonmucinous adenocarcinomas (P < .001). After adjustment for covariates, signet ring histology was independently associated with higher risk of death (HR 1.42, 95% confidence interval [CI] 1.33-1.51, and HR 1.57, CI 1.38-1.77, for tumors located in the colon and rectum, respectively). Mucinous tumors of the rectum (HR 1.22, CI 1.16-1.29), but not the colon (HR 1.03, CI 1.00-1.06), were associated with increased risk of death. Conclusion Signet ring cell adenocarcinomas of the colon and rectum and mucinous adenocarcinomas of the rectum are associated with poorer survival. These aggressive histologic variants of colorectal adenocarcinoma should be targeted for research initiatives to improve outcomes. PMID:22476818

  2. Twist1 correlates with poor differentiation and progression in gastric adenocarcinoma via elevation of FGFR2 expression

    PubMed Central

    Zhu, Dong-Yuan; Guo, Qi-Sen; Li, Yan-Liang; Cui, Bin; Guo, Jun; Liu, Ji-Xiao; Li, Peng

    2014-01-01

    AIM: To explore the correlation between Twist-related protein (Twist)1, fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma differentiation and progression. METHODS: We evaluated Twist1 and FGFR2 in 52 gastric adenocarcinoma samples by immunohistochemistry and quantitative real time polymerase chain reaction, and analyzed the correlation between Twist1, FGFR2 and cancer differentiation. We also detected Twist1 and FGFR2 expression in gastric adenocarcinoma cell lines, and evaluated Twist1 influence on FGFR2 expression. In addition, we studied the role of FGFR2 in Twist1-promoted cancer progression, including proliferation, invasion and epithelial-mesenchymal transition (EMT). RESULTS: Twist1 and FGFR2 were detected in almost all the gastric adenocarcinoma samples. Twist1 (P = 0.0213) and FGFR2 (P = 0.0310) mRNA levels had a significant association with gastric adenocarcinoma differentiation. Moreover, Twist1 and FGFR2 expression in poorly differentiated cells (SNU-1 and SNU-16) was notably higher than in well-differentiated cells (MKN-7 and MKN-28). In poorly differentiated gastric adenocarcinomas, FGFR2 mRNA level was significantly positively correlated with Twist1 mRNA level (P = 0.004). Twist1 was proved to promote FGFR2 by regulating Twist1 expression by knockdown and overexpression. Additionally, Twist1 could induce proliferation, invasion and EMT in gastric cancer; of these, FGFR2 was required for invasion and EMT, rather than proliferation. CONCLUSION: Twist1 and FGFR2 are highly associated with differentiation of gastric adenocarcinoma; Twist1 can facilitate invasion and EMT in gastric adenocarcinoma via promotion of FGFR2 expression. PMID:25561797

  3. FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

    ClinicalTrials.gov

    2016-09-15

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

  4. Follistatin is a novel biomarker for lung adenocarcinoma in humans.

    PubMed

    Chen, Fangfang; Ren, Ping; Feng, Ye; Liu, Haiyan; Sun, Yang; Liu, Zhonghui; Ge, Jingyan; Cui, Xueling

    2014-01-01

    Follistatin (FST), a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear. The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80), which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40) using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis. These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

  5. Expression of Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptor in Pancreatic Ductal Adenocarcinomas, Neuroendocrine Tumours and Chronic Pancreatitis

    PubMed Central

    Angelescu, Radu; Burada, Florin; Angelescu, Cristina; Gheonea, Dan Ionut; Iordache, Sevastița; Mixich, Francisc; Ioana, Mihai; Săftoiu, Adrian

    2013-01-01

    Objective: Angiogenesis is a crucial event for pancreatic carcinogenesis, and it also plays an important role in chronic pancreatitis. The aim of our study was to evaluate the mRNA expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in chronic inflammatory or malignant pancreatic pathology in order to elucidate the differences in expression patterns and potential clinical implications. Methods: Thirty-five patients who had undergone endoscopic ultrasonography followed by endoscipic ultrasound-guided fine needle aspiration (EUS-FNA) of focal pancreatic masses were included in the study. VEGF and EGFR mRNA expression levels in the samples collected by EUS-FNA were analyzed using quantitative real-time polymerase chain reaction (PCR). Results: VEGF expression was detected in all chronic pancreatitis and adenocarcinoma samples and in only 62.5% of pancreatic neuroendocrine tumors. EGFR expression was detected in only 40% of the chronic pancreatitis cases, 76.9% of adenocarcinomas and in 50% of pancreatic neuroendocrine tumors. Both VEGF and EGFR mRNA levels were significantly higher in pancreatic ductal adenocarcinoma than those in normal tissue. VEGF expression inversely correlated with pancreatic ductal adenocarcinoma size, while EGFR expression was related to local invasiveness of adenocarcinoma. Conclusion: Both VEGF and EGFR mRNA expression in EUS-FNA samples may be used as a diagnostic marker associated with invasiveness in patients with pancreatic adenocarcinoma. PMID:24949370

  6. Identification of Factors for the Preoperative Prediction of Tumour Subtype and Prognosis in Patients with T1 Lung Adenocarcinoma

    PubMed Central

    Zhang, Yong-Kui; Chai, Zhen-da; Hu, Xiao-fei; Tan, Lin-lin; Wang, Zhao-yu; Chen, Zhi-jun

    2016-01-01

    Aims. Identification of factors that can predict the subtypes of lung adenocarcinoma preoperatively is important for selecting the appropriate surgical procedure and for predicting postoperative survival. Methods. We retrospectively evaluated 87 patients with lung adenocarcinomas ≤30 mm. Results. Preoperative radiological findings, serum CEA level, serum microRNA-183 (miR-183) level, and tumour size differed significantly between patients with adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) and those with invasive adenocarcinoma (IAC). Receiver operating characteristic curves and univariate analysis revealed that patients who were older than 57 years or had a pure solid nodule or a tumour with mixed ground-glass opacity (mGGO), a tumour >11 mm, a serum CEA level >2.12 ng/mL, or a serum miR-183 level >1.233 (2−ΔΔCt) were more likely to be diagnosed with IAC than with AIS or MIA. The combination of all five factors had an area under the curve of 0.946, with a sensitivity of 89.13% and a specificity of 95.12%. Moreover, patients with a cut-off value >0.499 for the five-factor combination had poor overall survival. Conclusions. The five-factor combination enables clinicians to distinguish AIS or MIA from IAC, thereby aiding in selecting the appropriate treatment, and to predict the prognosis of lung adenocarcinoma patients. PMID:28115792

  7. Pancreatic Adenocarcinoma, Version 2.2012

    PubMed Central

    Tempero, Margaret A.; Arnoletti, J. Pablo; Behrman, Stephen W.; Ben-Josef, Edgar; Benson, Al B.; Casper, Ephraim S.; Cohen, Steven J.; Czito, Brian; Ellenhorn, Joshua D. I.; Hawkins, William G.; Herman, Joseph; Hoffman, John P.; Ko, Andrew; Komanduri, Srinadh; Koong, Albert; Ma, Wen Wee; Malafa, Mokenge P.; Merchant, Nipun B.; Mulvihill, Sean J.; Muscarella, Peter; Nakakura, Eric K.; Obando, Jorge; Pitman, Martha B.; Sasson, Aaron R.; Tally, Anitra; Thayer, Sarah P.; Whiting, Samuel; Wolff, Robert A.; Wolpin, Brian M.; Freedman-Cass, Deborah A.; Shead, Dorothy A.

    2013-01-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting. PMID:22679115

  8. Gall bladder Adenocarcinoma in a Young Girl.

    PubMed

    Date, Shivprasad V; Rizvi, S J

    2015-04-01

    A 16-year-old girl presented with abdominal discomfort, weakness, and jaundice. General examination revealed deep icterus with hard lymph nodes in left supraclavicular region. On gastrointestinal examination, we appreciated a hard intra-abdominal lump in the right hypochondrium. Biochemical evaluation showed features of obstructive jaundice. Imaging confirmed the presence of gall bladder lump with multiple intra-abdominal lymph nodes. Fine needle aspiration cytology of neck nodes demonstrated metastatic adenocarcinoma. Fine needle aspiration cytology of the gall bladder lump (done under sonographic guidance) confirmed poorly differentiated adenocarcinoma. To the best of our knowledge, malignancy of the gall bladder has not been reported in individuals less than 18 years in India, and only three cases have been reported worldwide in English literature.

  9. Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma.

    PubMed

    Rodić, Nemanja; Steranka, Jared P; Makohon-Moore, Alvin; Moyer, Allison; Shen, Peilin; Sharma, Reema; Kohutek, Zachary A; Huang, Cheng Ran; Ahn, Daniel; Mita, Paolo; Taylor, Martin S; Barker, Norman J; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Boeke, Jef D; Burns, Kathleen H

    2015-09-01

    Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed after the disease has metastasized; it is among the most lethal forms of cancer. We recently described aberrant expression of an open reading frame 1 protein, ORF1p, encoded by long interspersed element-1 (LINE-1; L1) retrotransposon, in PDAC. To test whether LINE-1 expression leads to somatic insertions of this mobile DNA, we used a targeted method to sequence LINE-1 insertion sites in matched PDAC and normal samples. We found evidence of 465 somatic LINE-1 insertions in 20 PDAC genomes, which were absent from corresponding normal samples. In cases in which matched normal tissue, primary PDAC and metastatic disease sites were available, insertions were found in primary and metastatic tissues in differing proportions. Two adenocarcinomas secondarily involving the pancreas, but originating in the stomach and duodenum, acquired insertions with a similar discordance between primary and metastatic sites. Together, our findings show that LINE-1 contributes to the genetic evolution of PDAC and suggest that somatic insertions are acquired discontinuously in gastrointestinal neoplasms.

  10. Isolation, cultivation and identification of human lung adenocarcinoma stem cells

    PubMed Central

    ZHANG, DE-GENG; JIANG, AI-GUI; LU, HUI-YU; ZHANG, LI-XIN; GAO, XIAO-YAN

    2015-01-01

    Recently, an increasing number of studies have demonstrated that lung cancer is a stem cell disease. However, ideal cell surface markers for isolating stem cells in lung cancer are yet to be identified. In the present study, a cell population with a cluster of differentiation (CD)133+ phenotype was successfully isolated from a single cell suspension of lung adenocarcinoma tissue using magnetic-activated cell sorting (MACS) and enriched in a serum-free culture. In comparison to CD133− cells, the CD133+ cells exhibited an enhanced capacity for self-renewal and differentiation, and a greater potential for in vivo tumor formation, in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tumors could be induced in NOD/SCID mice by the transplantation of 102 stem-like cells per mouse. The results of the present study demonstrated that CD133 may serve as a specific cell surface marker for lung adenocarcinoma stem cells, and that MACS combined with serum-free culture is an effective method for isolating and enriching lung cancer stem cells. PMID:25435932

  11. Raman Spectroscopy Study of Prostatic Adenocarcinoma Bulk Tissues

    NASA Astrophysics Data System (ADS)

    Devpura, S.; Dai, H.; Thakur, J. S.; Naik, R.; Cao, A.; Pandya, A.; Auner, G. W.; Sarkar, F.; Sakr, W.; Naik, V.

    2009-03-01

    Prostate cancer is one of the most common types of cancer among men. The mortality rate for this disease can be dramatically reduced if it can be diagnosed in its early stages. Raman spectroscopy is one of the optical techniques which can provide fingerprints of a disease in terms of its molecular composition which changes due to the onset of disease. The aim of this project is to investigate the differences in the Raman spectra to identify benign epithelium (BE), prostatic intraepithelial neoplasia (PIN) and adenocarcinoma of various Gleason grades in archived bulk tissues embedded in paraffin wax. For each tissue, two adjacent tissue sections were cut and dewaxed, where one of the sections was stained using haematoxylin and eosin for histological examination and the other unstained adjacent section was used for Raman spectroscopic studies. We have collected Raman spectra from 10 prostatic adenocarcinoma dewaxed tissue sections using Raman microscope (785 nm excitation laser). The data were analyzed using statistical methods of principal component analysis and discriminant function analysis to classify the tissue regions. The results indicate that Raman Spectroscopy can differentiate between BE, PIN and Cancer regions.

  12. 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.

  13. Correlation in histological subtypes with high resolution computed tomography signatures of early stage lung adenocarcinoma

    PubMed Central

    Miao, Yingying; Zhang, Jianya; Zou, Jiawei; Zhu, Qingqing

    2017-01-01

    Background Uncertainty remains on the association between image characteristics of the nodules in computed tomography (CT) scans and lung adenocarcinoma histopathologic subtypes. We aimed to estimate the correlation between preoperative high resolution computed tomography (HRCT) scan and postoperative histopathology of stage IA lung adenocarcinoma in East Asian Chinese population. Methods We retrospectively reviewed the clinical records and HRCT images of 190 patients (106 female and 84 male) with resected, preoperatively untreated stage IA adenocarcinomas. The relationship between image characteristics of nodules at preoperative HRCT and their histological subtypes after resection were analyzed. The one-way ANOVA, chi-square test and logistic regression were used for analysis. Results In 190 patients with stage IA lung adenocarcinoma, median tumor diameter was significantly lower in lepidic predominant invasive adenocarcinoma (LPA) (15.96±6.95 mm). Univariate analysis revealed that ground-glass opacity (GGO) proportion (P<0.001), margin (P<0.001), border definition (P=0.015), pleural retraction (P<0.001) and enhancement (P<0.001) had statistically significant differences in four histological subtypes. The multivariate analysis referenced for lepidic group which indicated that GGO proportion and pleural retraction were independent associated with acinar group (RR=4.221, 95% CI: 1.770–10.066, P=0.001; RR=0.380, 95% CI: 0.158–0.916, P=0.031, respectively). Male and whose nodule margin with spiculation or lobulation were prone to papillary predominant invasive adenocarcinoma (PPA) (RR=0.288, 95% CI: 0.090–0.920, P=0.036; RR=0.250, 95% CI: 0.070–0.887, P=0.032, respectively). GGO proportion and nodule margin were independent related factors in solid predominant invasive adenocarcinoma (SPA) (RR=13.338, 95% CI: 2.974–59.811, P=0.001; RR=0.097, 95% CI: 0.016–0.606, P=0.013, respectively). Conclusions Nodules with spiculation or lobulation and less GGO

  14. 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

  15. Comprehensive study of mutational and clinicopathologic characteristics of adenocarcinoma with lepidic pattern in surgical resected lung adenocarcinoma.

    PubMed

    Xu, Ye; Zhu, Chen; Qian, Wenliang; Zheng, Min

    2017-01-01

    Although many studies have explored clinicopathologic characteristics and prognosis of lung adenocarcinoma, a few literatures reported the mutational status of lung adenocarcinomas with lepidic pattern and whether there is difference between adenocarcinomas with pure lepidic component and lepidic predominant adenocarcinomas remain unknown. One hundred and thirty-three patients including 92 adenocarcinomas with pure lepidic component and 41 lepidic predominant adenocarcinomas were subjected to the study. All the clinicopathologic data, the follow-up information and the status of gene mutations including EGFR, KRAS, HER2, BRAF, AKT1, ALK, RET and ROS1 were investigated. Of the 133 lung adenocarcinomas with lepidic pattern, 87.22 % (116/133) were detected harboring mutations in our tested genes, among which 90.52 % (105/116) harbored EGFR mutation. There are three KRAS mutations and two BRAF mutations in our cohort, and we revealed two ALK fusion and one RET fusion. No ROS1 fusion was discovered. There was no significant difference in gene mutations between adenocarcinomas with pure lepidic component and lepidic predominant adenocarcinomas except EGFR mutation (p = 0.039). Lepidic predominant adenocarcinomas seemed to have more EGFR mutation. The post-recurrence survival was significantly prolonged in patients who received TKIs. Adenocarcinoma with lepidic pattern is a low-grade lung tumor with favorable prognosis and displays frequent EGFR mutation. Compared with lepidic predominant adenocarcinomas, lung adenocarcinomas with pure lepidic component have a better prognosis. On the basis of these results, we also suggested the application of EGFR-TKIs therapy for EGFR mutation-positive patients after recurrence could achieve prolonged survival.

  16. Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions

    PubMed Central

    Gnoni, Antonio; Licchetta, Antonella; Scarpa, Aldo; Azzariti, Amalia; Brunetti, Anna Elisabetta; Simone, Gianni; Nardulli, Patrizia; Santini, Daniele; Aieta, Michele; Delcuratolo, Sabina; Silvestris, Nicola

    2013-01-01

    Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy. PMID:24084722

  17. Comprehensive molecular profiling of lung adenocarcinoma

    PubMed Central

    2014-01-01

    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. PMID:25079552

  18. [Atypical metastatic site of lung adenocarcinoma].

    PubMed

    Sakhri, L; Mennecier, B; Jacqmin, D; Di Marco, A; Schumacher, C; Chenard, M-P; Bergmann, E; Quoix, E

    2011-12-01

    The case concerns a 40 years old smoker male, treated for an adenocarcinoma of the left upper lobe, metastatic in muscle extended to the right femur cortex. The patient had first a surgical excision of the mass of the thigh, an intramedullary femoral nailing, and six courses of chemotherapy (cisplatin-vinorelbine) with concurrent thoracic radiotherapy. This treatment led to disease stability. One year later, hematuria revealed a bladder tumor. Cystoscopy with biopsy concluded to an adenocarcinoma pulmonary origin. The PET-scanner showed an uptake of the bladder mass, a hypermetabolic right adrenal gland and subcutaneous left shoulder nodule. The patient had a partial cystectomy associated with enterocystoplasty and left ureteral reimplantation, plus excision of the subcutaneous nodule located in the left shoulder and a right adrenalectomy during the same time. All of the sites were metastasis from adenocarcinoma of pulmonary origin. A salvage chemotherapy was initiated. In the vast majority of cases, bladder metastasis as primary bladder tumours is revealed by hematuria, cystitis or sometimes vague pelvic pain. Our case is a very unusual bladder metastatic site from lung cancer. We will discuss the different procedures and the therapeutic strategies on the basis of the published data.

  19. 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.

  20. Intraoperative molecular imaging to identify lung adenocarcinomas

    PubMed Central

    Newton, Andrew D.; Kennedy, Gregory T.; Predina, Jarrod D.; Low, Philip S.

    2016-01-01

    Intraoperative molecular imaging is a promising new technology with numerous applications in lung cancer surgery. Accurate identification of small nodules and assessment of tumor margins are two challenges in pulmonary resections for cancer, particularly with increasing use of video-assisted thoracoscopic surgery (VATS). One potential solution to these problems is intraoperative use of a fluorescent contrast agent to improve detection of cancer cells. This technology requires both a targeted fluorescent dye that will selectively accumulate in cancer cells and a specialized imaging system to detect the cells. In several studies, we have shown that intraoperative imaging with indocyanine green (ICG) can be used to accurately identify indeterminate pulmonary nodules. The use of a folate-tagged fluorescent molecule targeted to the folate receptor-α (FRα) further improves the sensitivity and specificity of detecting lung adenocarcinomas. We have demonstrated this technology can be used as an “optical biopsy” to differentiate adenocarcinoma versus other histological subtypes of pulmonary nodules. This strategy has potential applications in assessing bronchial stump margins, identifying synchronous or metachronous lesions, and rapidly assessing lymph nodes for lung adenocarcinoma. PMID:28066672

  1. Discontinuous unilateral involvement of 12 part core biopsies by adenocarcinoma predicts bilateral involvement of subsequent radical prostatectomy.

    PubMed

    Lowenthal, Brett Matthew; Liao, Xiaoyan; Wen, Fang; Bagherzadeh, Nader; Mahooti, Sepi

    2016-08-01

    At our institution, percent tumor burden in prostate core biopsies is quantified using variations of one of two methods. Measurement by the Aggregate method reports only adenocarcinoma and omits intervening stroma and benign prostatic glands while the Discontinuous method includes the intervening stroma and benign glands between distinct foci of adenocarcinoma. In this study, we selected cases with 12-part core biopsies that were followed by a radical prostatectomy within two years. Interestingly, we found that when adenocarcinoma involved prostate 12-part core biopsies and subsequent resection unilaterally, there is no significant difference in absolute percentage of tumor using either measuring method (P = 0.4). In contrast, when adenocarcinoma involved the biopsies unilaterally and subsequent prostatectomy bilaterally, the two measurement methods had a statistically significant difference in percentage scores (P = 0.002). In the study cohort, other factors including Gleason score (P = 0.88) and total number of adenocarcinoma-involved cores (P = 0.27) did not introduce any significant correlation with bilateral involvement. In this study, we found that biopsies that discontinuously and unilaterally involve half of a prostate are much more likely to involve both lobes than those that are unilateral and present in nodular aggregates.

  2. Solitary Psoas Muscle Metastasis of Gastroesphageal Junction Adenocarcinoma

    PubMed Central

    Azadeh, Payam; Yaghobi Joybari, Ali; Sarbaz, Samaneh; Ghiasi, Hosein Ali; Farasatinasab, Maryam

    2016-01-01

    Metastasis of gastroesphageal junction (GEJ) adenocarcinoma in skeletal muscle is rare and primary sites for skeletal muscle metastases are usually lung, renal and colorectal cancer. We have encountered with the first case report of solitary psoas muscle metastasis of GEJ adenocarcinoma. Here we describe a 65 years old man was diagnosed with GEJ adenocarcinoma in Gastroenterology Department, Imam Hussein Hospital, Tehran, Iran in February 2014. We were not able to use PET techniques due to lack of access. Staging CT scans demonstrated a small mass lateral to right psoas muscle. A CT-guided core needle biopsy of right psoas muscle was performed that supported a diagnosis of adenocarcinoma consistent with primary adenocarcinoma of the GEJ. Distant metastasis to skeletal muscle rarely occurs in patients with GEJ adenocarcinoma, but heightened awareness to these soft tissue lesions is warranted. CT or MR imaging could show findings suggestive of metastatic disease, although PET is preferable modality. PMID:26870148

  3. Higher prevalence of obesity in gastric cardia adenocarcinoma compared to gastric non-cardia adenocarcinoma.

    PubMed

    Cho, Yuri; Lee, Dong Ho; Oh, Hong Sang; Seo, Ji Yeon; Lee, Dong Hyeon; Kim, Nayoung; Jeong, Sook Hyang; Kim, Jin Wook; Hwang, Jin Hyuk; Park, Young Soo; Lee, Sang Hyub; Shin, Cheol Min; Jo, Hyun Jin; Jung, Hyun Chae; Yoon, Yong Bum; Song, In Sung

    2012-10-01

    Obesity is one of the main risk factors for gastric cardia adenocarcinoma (GCA) in the West. Also, recent studies have suggested that GCA is distinct from distal stomach tumor, with differing risk factors, tumor characteristics, and biological behavior. The objective of our research was to evaluate the relationship between obesity and GCA compared to non-cardia adenocarcinoma. A total of 298 patients who were diagnosed with gastric adenocarcinoma and underwent surgery at Seoul National University Bundang Hospital were evaluated. Ninety-one cases were GCA, and 207 cases were non-cardiac adenocarcinoma. Obesity was estimated by body mass index (BMI, kg/m(2)). The degree of obesity was determined by using BMI <18.5, 18.5-23.9, 24-27.9, and ≥ 28 (kg/m(2)) as the cut-off points for underweight, normal weight, overweight, and obese, respectively. Association with obesity was estimated by odds ratio (OR) and 95% confidence interval (CI). Obesity was more prevalent in patients with GCA at the time of diagnosis for gastric cancer. Among obese persons with a BMI of 28 kg/m(2) or higher, the OR was 3.937 (95% CI, 1.492-10.389; p = 0.006) for GCA compared to non-cardia adenocarcinoma. For overweight individuals, the OR was 2.194 (95% CI, 1.118-4.305; p = 0.022). Multivariate analysis of age, Helicobacter pylori infection, smoking, stage, and BMI with logistic regression was performed. BMI was an independent risk factor for GCA (OR, 1.123; 95% CI, 1.037-1.217; p = 0.004). Obesity was more prevalent in patients with GCA compared to that in patients with gastric non-cardia adenocarcinoma. Also, BMI was an independent risk factor for GCA.

  4. Ductal Adenocarcinoma of the Prostate: A Case Report

    PubMed Central

    Hayashi, Yutaro; Kawahara, Takashi; Iwashita, Hiromichi; Shimokihara, Kota; Tsutsumi, Sohgo; Takamoto, Daiji; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-ichi; Miyoshi, Yasuhide; Yumura, Yasushi; Yao, Masahiro; Inayama, Yoshiaki; Uemura, Hiroji

    2016-01-01

    Ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate. A 73-year-old male was referred to our hospital for the further examination of an elevated prostate-specific antigen level of 23.4 ng/mL. Radical prostatectomy (RP) was performed based on the diagnosis obtained by a prostate needle biopsy. The RP specimen revealed ductal adenocarcinoma of the prostate with positive capsular penetration. We herein report a rare case of ductal adenocarcinoma of the prostate. PMID:28101029

  5. [Relationship between EGFR Mutations and Pathological Classification and 
Specimen of Lung Adenocarcinoma].

    PubMed

    Kang, Lifei; Zheng, Jie; Zhu, Xiang

    2017-06-20

    With the development of genetic mutations and targeted drugs, accurate therapy of lung adenocarcinoma attracts much more attention, and more research is focued on epidermal growth factor receptor (EGFR). It is unclear whether the result of EGFR mutation and pathology type is consistent with different specimens. In our study, by comparing the relationship between EGFR mutations and pathological classification of lung adenocarcinoma in surgical resection of specimen and biopsy specimen, to discuss the relationship between EGFR mutations and pathological classification of and the influence of specimen type on EGFR gene detection. A total of 163 cases of surgical resection of sample of lung adenocarcinoma (pulmonary resection and pulmonary lobectomy) and 173 cases of biopsy specimen [mucosa biopsy, needle biopsy of lung, and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)] were performed by gene sequencing method and amplification refractory mutation system (ARMS) and the majority of the type was confirmed (lepidic, acinar, papillary, micropapillary, solid) according to the classification of lung adenocarcinoma in 2015 World Health Organization (WHO). The statistics was used in surgical and biopsy sample respectively. The gene mutation of EGFR in surgical and biopsy sample of lung adenocarcinoma was 62.58% (102/163) and 65.9% (114/173) respectively, and no significant difference was found (P>0.05). The mutation of EGFR in female was predominant both of the two groups (P<0.05). The mutation rate of EGFR over the age of 60 was significantly lower than that below 60 in surgical specimen, while it was not related to age in biopsy sample. The constituent ratio of pathology type was different in the two groups (χ2=8.04, P<0.05). Among 102 cases of lung adenocarcinoma in surgical specimen, the acinar took up the highest proportion (54.9%), followed by the lepidic (23.53%) and the papillary (17.65%). The solid adenocarcinoma accounted for the

  6. Cathepsin D and carcino-embryonic antigen in serum, urine and tissues of colon adenocarcinoma patients.

    PubMed

    Szajda, Slawomir Dariusz; Snarska, Jadwiga; Jankowska, Anna; Roszkowska-Jakimiec, Wieslawa; Puchalski, Zbigniew; Zwierz, Krzysztof

    2008-01-01

    Application of neoplastic markers in early diagnosis of colorectal carcinoma has brought fresh hope to millions of sufferers. However such a marker, distinctive for this particular carcinoma and allowing its detection at a sufficiently early stage of development has not yet been found. Cathepsin D (CD) is lysosomal aspartyl proteinase. It is a component of a proteolytic cascade participating actively in neoplastic invasion as well as in metastasis formation. Carcino-embryonic antigen (CEA) is a useful marker in oncological diagnostics of colorectal cancer. CEA undergoes expression in all kinds of adenocarcinoma and is found both intercellularly and extracellularly. High concentrations of CEA in the blood serum confirm neoplastic changes in the digestive tract with high probability. The objective of this study has been to evaluate CD activity in the blood serum, urine and tumor tissues as well as in the colon biopsies which were not changed macroscopically and CEA concentration in the serum of colon adenocarcinoma, considering the extent of spread of cancer (TNM), the grade of the differentiation of cancer cell (G) as well as the tumor size. The possibility of application of CD along with CEA as markers of colon adenocarcinoma has also been examined. The examination included the serum and urine of 21 patients as well as 12 tissues biopsies with histopathologically confirmed colon adenocarcinoma. The reference group for the blood and urine comprised of 17 healthy controls, and for the colon adenocarcinoma tissues- samples collected from 14 people from the sites most distant from the resected tumor on the boundaries which were free of cancer cells. Activity of CD in the blood serum, urine as well as tissues was determined with a modified Greczaniuk et al. method and expressed by the amount of released tyrosine as the concentration of the activity in nmolTyr/mL/6h, whereas the specific activity was expressed in nmol Tyr/mg of protein /6h. The specific activity of CD in

  7. Early-stage adenocarcinoma of the esophagus with mid to deep submucosal invasion (pT1b sm2-3): the frequency of lymph-node metastasis depends on macroscopic and histological risk patterns.

    PubMed

    Manner, H; Wetzka, J; May, A; Pauthner, M; Pech, O; Fisseler-Eckhoff, A; Stolte, M; Vieth, M; Lorenz, D; Ell, C

    2016-03-08

    The rate of lymph-node (LN) metastasis in early adenocarcinoma (EAC) of the esophagus with mid to deep submucosal invasion (pT1b sm2/3) has not yet been precisely defined. The aim of the this study was to evaluate the rate of LN metastasis in pT1b sm2/3 EAC depending on macroscopic and histological risk patterns to find out whether there may also be options for endoscopic therapy as in cancers limited to the mucosa and the upper third of the submucosa. A total of 1.718 pt with suspicion of EAC were referred for endoscopic treatment (ET) to the Dept. of Internal Medicine II at HSK Wiesbaden 1996-2010. In 230/1.718 pt, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of pT1b EAC (ER/surgery) was made. Of these, 38 pt had sm2 lesions, and 69 sm3. Rate of LN metastasis was analyzed depending on risk patterns: histologically low-risk (hisLR): G1-2, L0, V0; histologically high-risk (hisHR): ≥1 criterion not fulfilled; macroscopically low-risk (macLR): gross tumor type I-II, tumor size ≤2 cm; macroscopically high-risk (macHR): ≥1 criterion not fulfilled; combined low-risk (combLR): hisLR+macLR; combined high-risk (combHR): at least 1 risk factor. LN rate was only evaluated in pt who had proven maximum invasion depth of sm2/sm3, and who in case of ET had a follow-up (FU) by EUS of at least 24 months. 23/38 pt with pT1b sm2 lesions and 39/69 pt with sm3 lesions fulfilled our inclusion criteria. In the pT1b sm2 group, rate of LN metastasis in the hisLR, hisHR, combLR, and combHR groups were 8.3% (1/12), 36.3% (4/11), 0% (0/5), and 27.8% (5/18). In the pT1b sm3 group, rate of LN metastasis in the hisLR, hisHR, combLR and combHR groups were 28.6% (2/7), 37.5% (12/32), 25% (1/4), and 37.1% (13/35). 30-day mortality of surgery was 1.7% (1/58 pt). In EAC with pT1b sm2/3 invasion, the frequency of LN metastasis depends on macroscopic and histological risk patterns. Surgery remains the standard treatment, because the rate of LN metastasis appears to be

  8. 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

  9. Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus.

    PubMed Central

    Stewart, J R; Hoff, S J; Johnson, D H; Murray, M J; Butler, D R; Elkins, C C; Sharp, K W; Merrill, W H; Sawyers, J L

    1993-01-01

    OBJECTIVE: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus. SUMMARY BACKGROUND DATA: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently. METHODS: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection. RESULTS: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827). CONCLUSIONS: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus. PMID:8215648

  10. TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients

    PubMed Central

    Piro, G; Giacopuzzi, S; Bencivenga, M; Carbone, C; Verlato, G; Frizziero, M; Zanotto, M; Mina, M M; Merz, V; Santoro, R; Zanoni, A; De Manzoni, G; Tortora, G; Melisi, D

    2015-01-01

    Background: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. Methods: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT–PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. Results: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). Conclusions: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy. PMID:26291056

  11. Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma

    PubMed Central

    Toki, Fumiaki; Takahashi, Atsushi; Aihara, Ryusuke; Ogata, Kyoichi; Ando, Hiroyuki; Ohno, Tetsuro; Mochiki, Erito; Kuwano, Hiroyuki

    2010-01-01

    AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RESULTS: The G-related mucin phenotypes were highly expressed in all the histological subtypes of AGA. The expression of the GI phenotype in SIG patients was lower than that in DAC patients (P = 0.02), and this phenotype was observed in 56% of the non-SIG patients in the intramucosal layer. Among non-SIG cases, the expression of the GI phenotype was significantly higher in patients with extended adenocarcinomas and those with positive rates of lymph node metastasis. There was no difference between the expressions of the G and other GI phenotypes factors. Among DAC and non-SIG patients, there were no differences between the survival rates of the corresponding patient groups. CONCLUSION: The GI phenotype might possess more invasive characteristics than the G phenotype in non-SIG. Neither of the phenotypes indicated a poor prognosis of DAC and non-SIG. PMID:20533596

  12. Differential co-expression analysis of a microarray gene expression profiles of pulmonary adenocarcinoma.

    PubMed

    Fu, Shijie; Pan, Xufeng; Fang, Wentao

    2014-08-01

    Lung cancer severely reduces the quality of life worldwide and causes high socioeconomic burdens. However, key genes leading to the generation of pulmonary adenocarcinoma remain elusive despite intensive research efforts. The present study aimed to identify the potential associations between transcription factors (TFs) and differentially co‑expressed genes (DCGs) in the regulation of transcription in pulmonary adenocarcinoma. Gene expression profiles of pulmonary adenocarcinoma were downloaded from the Gene Expression Omnibus, and gene expression was analyzed using a computational method. A total of 37,094 differentially co‑expressed links (DCLs) and 251 DCGs were identified, which were significantly enriched in 10 pathways. The construction of the regulatory network and the analysis of the regulatory impact factors revealed eight crucial TFs in the regulatory network. These TFs regulated the expression of DCGs by promoting or inhibiting their expression. In addition, certain TFs and target genes associated with DCGs did not appear in the DCLs, which indicated that those TFs could be synergistic with other factors. This is likely to provide novel insights for research into pulmonary adenocarcinoma. In conclusion, the present study may enhance the understanding of disease mechanisms and lead to an improved diagnosis of lung cancer. However, further studies are required to confirm these observations.

  13. Prognostic impact of GATA binding protein-3 expression in primary lung adenocarcinoma.

    PubMed

    Hashiguchi, Toshihiro; Miyoshi, Hiroaki; Nakashima, Kazutaka; Yokoyama, Shintaro; Matsumoto, Ryoichi; Murakami, Daigo; Mitsuoka, Masahiro; Takamori, Shinzo; Akagi, Yoshito; Ohshima, Koichi

    2017-05-01

    GATA binding protein-3 (GATA3) is a transcription factor that regulates cell differentiation and maintenance in some types of normal cells. This study aimed to investigate the association between GATA3 expression and primary lung adenocarcinoma and to clarify the clinical significance of GATA3 expression in lung adenocarcinoma. Immunohistochemical GATA3 expression was evaluated using completely resected lung adenocarcinoma samples from 95 cases. GATA3 immunohistochemical staining was performed and scored. Associations between clinicopathological factors and GATA3 expression were analyzed by using the χ(2) test and Fisher exact test. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-free survival (DFS). Forty-nine cases expressed high levels of GATA3, which were associated with lymphatic invasion (P=.003). In univariate and multivariate analyses, vascular invasion (P<.001) and high GATA3 expression (P=.023) were identified as independent risk factors for OS. Higher pathological stages (P=.012), vascular invasion (P=.010), and high GATA3 expression (P=.009) were identified as independent risk factors for DFS. The high GATA3 expression group exhibited statistically worse OS (P=.031) and DFS (P=.011) than the low-expression group based on the Kaplan-Meier curves. In resected lung adenocarcinoma, high GATA3 expression is associated with poorer prognosis for both OS and DFS. Therefore, the immunohistochemical evaluation of GATA3 represents a potentially useful prognostic tool for postoperative patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Small nuclear ribonucleoprotein associated polypeptide N accelerates cell proliferation in pancreatic adenocarcinoma.

    PubMed

    Ma, Jin; Zhang, Zhuo; Wang, Jiancheng

    2015-10-01

    The spliceosome, the large RNA‑protein molecular complex, is crucial for pre‑mRNA splicing. Several antitumor drugs have been found to tightly bind to the components of the spliceosome and mutations in the spliceosome have been reported in several types of cancer. However, the involvement of the spliceosome in pancreatic adenocarcinoma remains unclear. In the present study, small nuclear ribonucleoprotein associated polypeptide N (SNRPN), a key constituent of spliceosomes, was disrupted in BxPC‑3 pancreatic adenocarcinoma cells using lentivirus‑mediated RNA interference (RNAi). It was found that knockdown of SNRPN reduced the proliferation ability of BxPC‑3 cells, as determined by an MTT assay. Furthermore, cell colony formation was impaired in SNRPN depleted adenocarcinoma cells and cell cycle analysis showed that depletion of SNRPN led to S phase cell cycle arrest and apoptosis. These results suggest that SNRPN is a key player in pancreatic adenocarcinoma cell growth, and targeted loss of SNRPN may be a potential therapeutic method for pancreatic cancer.

  15. Mesothelin Expression in Gastric Adenocarcinoma and Its Relation to Clinical Outcomes

    PubMed Central

    Han, Song-Hee; Joo, Mee; Kim, Hanseong; Chang, Sunhee

    2017-01-01

    Background Although surgical resection with chemotherapy is considered effective for patients with advanced gastric cancer, it remains the third leading cause of cancer-related death in South Korea. Several studies have reported that mesothelial markers including mesothelin, calretinin, and Wilms tumor protein 1 (WT1) were positive in variable carcinomas, associated with prognosis, and were evaluated as potential markers for targeted therapy. The aim of this study was to assess the immunohistochemical expression of mesothelial markers (mesothelin, calretinin, and WT1) in gastric adenocarcinoma and their relations to clinocopathological features and prognosis. Methods We evaluated calretinin, WT1, and mesothelin expression by immunohistochemical staining in 117 gastric adenocarcinomas. Results Mesothelin was positively stained in 30 cases (25.6%). Mesothelin expression was related to increased depth of invasion (p = .002), lymph node metastasis (p = .013), and presence of lymphovascular (p = .015) and perineural invasion (p = .004). Patients with mesothelin expression had significantly worse disease-free survival rate compared with that of nonmesothelin expression group (p = .024). Univariate analysis showed that mesothelin expression is related to short-term survival. None of the 117 gastric adenocarcinomas stained for calretinin or WT1. Conclusions Mesothelin expression was associated with poor prognosis. Our results suggest that mesothelin-targeted therapy should be considered as an important therapeutic alternative for gastric adenocarcinoma patients with mesothelin expression. PMID:28196410

  16. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

    PubMed Central

    Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

    2015-01-01

    Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

  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. Laparoscopic Diagnosis of Adenocarcinoma of the Appendix Mimicking Serous Papillary Adenocarcinoma of the Peritoneum

    PubMed Central

    Yoshimura, Mayumi; Terai, Yoshito; Konishi, Hiromi; Tanaka, Yoshimichi; Tanaka, Tomohito; Sasaki, Hiroshi; Ohmichi, Masahide

    2013-01-01

    Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of primary surgery. We performed diagnostic laparoscopic surgery in order to make a correct diagnosis based on the histological tissue. The vermiform appendix was found to contain a tumor measuring 1.5 cm wide and 4.5 cm long. Laparoscopic appendectomy, partial omentectomy, and partial resection of the lesion in the peritoneum were performed. The histological diagnosis was mucinous adenocarcinoma of the vermiform appendix, and the stage was T4NxM1. The patient received adjuvant chemotherapy with mFOLFOX 6 (5FU, leucovorin, and oxaliplatin). She achieved stable disease and was alive with disease eleven months after surgery. We therefore recommend that gynecologists should not rule out the possibility of appendiceal cancer, even in cases with preoperative findings similar to those of serous papillary adenocarcinoma of the peritoneum with peritoneal disseminated tumors. PMID:24383020

  19. [Primary adenocarcinoma of the terminal ileum, synchronous].

    PubMed

    Candia-de la Rosa, René Francisco; Sampayo-Candia, Raúl; Bretón-Toral, José Christian; Candia-Archundia, Francisco; Candia-García, Raúl

    2015-01-01

    Among the rarest types of cancer found are the small intestine malignancies, representing only 2% of all gastrointestinal cancer and 0.1-0.3% of all malignancies. The most common subtype of this tumour is the adenocarcinoma, which is located mainly in the duodenum, jejunum and, rarely, in ileum. A 75 year-old male, with no any surgical history, who in the previous three months, referred to two clinical episodes of partial bowel obstruction and unquantified weight loss. When admitted into the surgical service, the patient referred to a partial bowel obstruction of more than one week onset. A laparotomy was performed, finding 3 stenosis rings at the ileum end portion, carrying out an intestinal resection and enteral-enteral anastomosis. On the seventh day there was dehiscence of the anastomosis and abdominal sepsis. New surgery was performed with the resection of the intestinal anastomosis and an ileostomy. The pathologist report indicated a small bowel adenocarcinoma moderately differentiated, ulcerated, and multifocal. It was classified as stage III or T3N1M0. The patient progress was satisfactorily, managed as outpatient with postoperative chemotherapy with 5 fluorouracil and cisplatin. The patient died a year later due to liver metastases. Due to the extreme rarity of the case, is very likely that general surgeons may find one or two cases of adenocarcinoma of the ileum in their professional career. Thus, they must suspect this pathology when faced with an episode of intestinal obstruction in the adult. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  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. [Endoscopic ultrasonography in determining resectability of the pancreatic adenocarcinoma].

    PubMed

    Solodinina, E N; Starkov, Yu G; Kurushkina, N A; Egorov, V I

    2014-01-01

    The publication presents the results of the examination and treatment of 82 patients with pancreatic adenocarcinoma. The main objective of the work is the evaluation of endosonography diagnostic significance in identifying tumor vascular invasion and determining resectability of the tumor. The paper describes an EUS methodology, type of echoendoscopes and ultrasound criteria for tumor invasion to the blood vessels. Vessel invasion during endosonography was suspected in 48 (58.5%) cases, according to surgery data, tumor invasion into upper abdomen vessels was detected in 51 patients (62.2%). Sensitivity of endosonography in detecting vessel invasion was 90.2%, specificity--93.5%, accuracy--91.5%. Endosonography being in trend of present day ideas about the criteria of pancreatic cancer resectability is the leading method in the selection of patients to surgery.

  2. [Detection of T-antigen in colorectal adenocarcinoma and polyps].

    PubMed

    Xu, S; Lu, Y; Wang, Q

    1995-10-01

    Galactose oxidase method was employed to detect the beta-D-Gal (1-->3) -D-Gal NAc residue of T-antigen present in the large intestinal mucus of 156 subjects. The positive rates of the test were 84.4%, 29.1%, and 7.2% in the mucus samples obtained from 32 patients with colorectal adenocarcinomas, 55 with polyps and 69 controls respectively. Chi-square test demonstrated that there were significant differences between the group of carcinoma and control (P < 0.001) as well as between also polyp and control (P < 0.01). The test had a high sensitivity (84.4%) and specificity (92.8%) in the diagnosis of colorectal cancer and may be used as a practical mass screening test for colorectal neoplasms.

  3. Mouse Models of Pancreatic Ductal Adenocarcinoma.

    PubMed

    Ponz-Sarvise, Mariano; Tuveson, David A; Yu, Kenneth H

    2015-08-01

    Only 10% to 15% of patients with pancreatic ductal adenocarcinoma (PDAC) are candidates for potentially curative surgery due to the location or spread of disease at the time of diagnosis. Despite rapid progress in the understanding of the molecular mechanisms underlying PDAC, translation to effective therapies has been modest at best. One of the key tools available for studying biology and developing more effective therapeutics is the laboratory mouse, mus musculus. This article explores new and innovative approaches to mouse modeling and how these approaches can be utilized to move the field forward. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Phenotypic characterization of the infiltrating immune cells in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma.

    PubMed

    Hussein, Mahmoud-Rezk A; Al-Assiri, Mana; Musalam, Adel O

    2009-04-01

    Immune cell infiltrate is a constant feature in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. This study elaborates on the cells of the immune system present in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. Here, we hypothesized that "the development of benign nodular prostatic hyperplasia and prostatic adenocarcinoma is associated with numeric alterations of the immune cell infiltrate". A total of 50 transurethral prostatic resection specimens, each entailing normal prostate, benign nodular prostatic hyperplasia and high grade prostatic adenocarcinoma were evaluated for the density and phenotype of the immune cells using immunohistological methods and mouse monoclonal antibodies decorating T cells (CD3), histiocytes (CD68) and B lymphocytes (CD20). Immune cell infiltrate was composed of T cells, histiocytes and B-lymphocytes. CD(+)3 T lymphocytes and CD68(+) cells were the predominant cell populations. We observed variations in the density of the immune cells among the normal prostate, benign nodular prostatic hyperplasia and high grade prostatic adenocarcinoma. Compared with normal prostate, benign nodular prostatic hyperplasia had a statistically significant high density of immune cells (3.4+/-0.4versus 13.5+/-1.0, P<0.00). In contrast, a significant decrease in the counts of these cells was observed in high-grade prostatic adenocarcinoma compared to benign nodular prostatic hyperplasia (13.5+/-1.0 versus 5.2+/-0.3, P<0.01). The increased density of immune cells (predominantly CD(+)3 T cells) in benign nodular prostatic hyperplasia suggests that the initial response to cellular damage is mediated by cell-mediated immunity. The decreased density of immune cells in high-grade prostatic adenocarcinoma may reflect immunosuppression. The underlying mechanisms of these numeric variations are open for further investigations.

  5. 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:…

  6. 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:…

  7. Eccrine adenocarcinoma of the footpads in 2 cats.

    PubMed Central

    Fuentealba, I C; Illanes, O G; Haines, D M

    2000-01-01

    Adenocarcinoma of sweat glands of the footpads was diagnosed in 2 cats. Clinical signs included lameness and swelling of multiple digits. Pulmonary metastasis was detected in one case. Diagnosis was based on histopathological and immunohistochemical findings. Eccrine adenocarcinoma should be included in the differential diagnosis of footpads lesions in aged cats. Images Figure 1. Figure 2. PMID:10816835

  8. 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.

  9. GATA6 expression in Barrett's oesophagus and oesophageal adenocarcinoma.

    PubMed

    Pavlov, Kirill; Honing, Judith; Meijer, Coby; Boersma-van Ek, Wytske; Peters, Frans T M; van den Berg, Anke; Karrenbeld, Arend; Plukker, John T M; Kruyt, Frank A E; Kleibeuker, Jan H

    2015-01-01

    Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia-dysplasia-carcinoma sequence, but the underlying mechanisms are poorly understood. The transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gene amplification was recently linked with poor survival in oesophageal adenocarcinoma. To study the expression of GATA6 during Barrett's oesophagus development and malignant transformation. To determine the prognostic value of GATA6 in oesophageal adenocarcinoma. Two retrospective cohorts were derived from the pathological archive of the University Medical Center Groningen. The first cohort contained 130 tissue samples of normal squamous epithelium, metaplasia, dysplasia and oesophageal adenocarcinoma. The second cohort consisted of a tissue microarray containing tissue from 92 oesophageal adenocarcinoma patients. Immunohistochemistry was used to examine GATA6 protein expression and to correlate GATA6 expression in oesophageal adenocarcinoma with overall and disease-free survival. The percentage of GATA6-positive cells was low in squamous epithelium (10%) but increased progressively in Barrett's oesophagus (30%, P < 0.001) and high-grade dysplasia (82%, P = 0.005). GATA6 expression was not associated with overall or disease-free survival in oesophageal adenocarcinoma patients (P = 0.599 and P = 0.700 respectively). GATA6 expression is progressively increased during Barrett's oesophagus development and its malignant transformation. However, no prognostic value of GATA6 expression could be found in oesophageal adenocarcinoma. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  10. Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review

    PubMed Central

    Yako, Yandiswa Yolanda; Kruger, Deirdré; Smith, Martin; Brand, Martin

    2016-01-01

    Objectives A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. Materials and Methods A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Results Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19–9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response. Conclusion Our review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals. PMID:27170998

  11. The frequency and clinical impact of HER2 alterations in lung adenocarcinoma

    PubMed Central

    Kim, Eun Kyung; Kim, Kyung A.; Lee, Chang Young

    2017-01-01

    Human epidermal growth factor receptor 2 (HER2 or ErbB2) can be overexpressed, amplified and/or mutated in malignant tumors, and is a candidate for therapeutic targeting. However, molecular associations and clinical significances of these alterations were controversial in lung cancer. In this study, we investigated the frequency and clinicopathological significance of HER2 dysregulation in patients with lung adenocarcinoma. HER2 protein overexpression, gene amplification, and gene mutation were evaluated by immunohistochemistry (IHC), silver in situ hybridization, and direct sequencing, respectively. The H-scoring method and American Society of Clinical Oncology/College of American Pathologists breast cancer guidelines were used to interpret IHC results. Genetic analyses of EGFR and KRAS mutations, and of ALK and ROS1 rearrangements, were also performed. Of the 321 adenocarcinoma patients identified, HER2 overexpression (H-score ≥200) and gene amplification were found in 6 (1.9%) and 46 (14.3%), respectively. HER2 overexpression was correlated with papillary predominant histology; furthermore, it indicated poor overall survival and was an independent prognostic factor. HER2 amplification was associated with pleural invasion and showed a tendency towards shorter overall and disease-free survival. High-level gene amplification (HER2/CEP17 ratio ≥5 or copy number ≥10) was a poor prognostic factor for disease-free survival. HER2 mutations were detected in 6.7% (7 of 104) of driver oncogene-negative adenocarcinomas. Our study suggests that HER2 overexpression or amplification is a poor prognostic factor in lung adenocarcinoma, although the frequency of such events is low. Since molecular targeted agents are being tested in clinical trials, awareness of the specific HER2 status can influence the prognostic stratification and treatment of patients with molecularly defined subsets of lung adenocarcinoma. PMID:28146588

  12. 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

  13. The new IASLC-ATS-ERS lung adenocarcinoma classification: what the surgeon should know.

    PubMed

    Eguchi, Takashi; Kadota, Kyuichi; Park, Bernard J; Travis, William D; Jones, David R; Adusumilli, Prasad S

    2014-01-01

    In 2011, a new histologic classification of lung adenocarcinomas was proposed from a joint working group of the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, based on the recommendation of an international and multidisciplinary panel. This classification proposed a method of comprehensive histologic subtyping (lepidic, acinar, papillary, micropapillary, and solid pattern) based on semiquantitative assessment of histologic patterns (in 5% increments), with the ultimate goal of choosing a single, predominant pattern. Prognostic subsets could then be described for the classification. Patients with completely resected adenocarcinoma in situ and minimally invasive adenocarcinomas experienced low risk of recurrence. Patients with micropapillary or solid predominant tumors have a high risk of recurrence or cancer-related death. Patients with acinar and papillary predominant tumors comprise an intermediate-risk group. Herein, we review the outline of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society classification, a summary of published validation studies of this new classification, and then discuss the key surgical issues; we mainly focused on limited resection as an adequate treatment for early-stage lung adenocarcinomas, as well as preoperative and intraoperative diagnoses. We also review the published studies that identified the importance of histologic subtypes in predicting recurrence, both rates and patterns, in early-stage lung adenocarcinomas. This new classification for the most common type of lung cancer is useful for surgeons, as its implementation would require only hematoxylin-and-eosin histology slides, which is the common type of stain used in hospitals. It can be implemented with routine pathology evaluation and with no additional costs. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance

    PubMed Central

    Ghaffarzadehgan, Kamran; Jafarzadeh, Mostafa; Raziee, Hamid Reza; Sima, Hamid Reza; Esmaili-Shandiz, Ehsan; Hosseinnezhad, Hanieh; Taghizadeh-Kermani, Ali; Moaven, Omeed; Bahrani, Maryam

    2008-01-01

    AIM: To evaluate the relation of cluster of differentiation 44 (CD44) expression with clinicopathological features of gastric adenocarcinoma, and also its effect on prognosis with an emphasis on the differences between intestinal and diffuse types. METHODS: From 2000 to 2006, 100 patients with gastric adenocarcinoma, who had undergone total or subtotal gastrectomy without any prior treatment, were studied. Haematoxylin & eosin (HE) staining was used for histological evaluation, including the type (Lauren’s classification) and grading of the tumor. The expression of CD44 in the gastric adenocarcinoma mucosa and the adjacent mucosa were determined by immunohistochemistry. The survival analysis was obtained using the Kaplan-Meier test. RESULTS: Of 100 patients, 74 (74%) patients were male. The tumors were categorized as intestinal type (78%) or diffuse type (22%). Sixty-five percent of patients were CD44-positive. CD44 expression was not detected in normal gastric mucosa. Rather, CD44 was more commonly expressed in the intestinal subtype (P = 0.002). A significant relation was seen between the grade of tumor and the expression of CD44 (P = 0.014). The survival analysis showed a poor prognosis of patients with CD44-positive tumors (P = 0.008); and this was more prominent in the intestinal (P = 0.001) rather than diffuse type. CONCLUSION: Cell adhesion molecule CD44 is highly expressed in gastric adenocarcinoma. CD44 expression is correlated with a poor prognosis in patients with the intestinal type of gastric adenocarcinoma. CD44 can, therefore, be utilized as a prognostic marker for this group of patients. PMID:19009655

  15. The New IASLC/ATS/ERS Lung Adenocarcinoma Classification: what the surgeon should know

    PubMed Central

    Eguchi, Takashi; Kadota, Kyuichi; Park, Bernard J.; Travis, William D.; Jones, David R.; Adusumilli, Prasad S.

    2014-01-01

    In 2011, a new histologic classification of lung adenocarcinomas was proposed from a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), based on the recommendation of an international and multidisciplinary panel. This classification proposed a method of comprehensive histologic subtyping (lepidic, acinar, papillary, micropapillary, and solid pattern) based on semi-quantitative assessment of histologic patterns (in 5% increments) with the ultimate goal of choosing a single, predominant pattern. Prognostic subsets could then be described for the classification. Patients with completely resected adenocarcinomas in situ (AIS) and minimally invasive adenocarcinomas (MIA) experienced low risk of recurrence. Patients with micropapillary or solid predominant tumors have a high risk for recurrence or cancer-related death. Patients with acinar and papillary predominant tumors comprise an intermediate-risk group. Herein, we review the outline of the proposed IASLC/ATS/ERS classification, a summary of published validation studies of this new classification and then discuss surgical key issues; we mainly focused on limited resection as an adequate treatment for early-stage lung adenocarcinomas as well as pre- and intraoperative diagnoses. We also review the published studies that identified the importance of histological subtypes in predicting recurrence, both rates and patterns, in early-stage lung adenocarcinomas. This new classification for the most common type of lung cancer is useful for surgeons, as its implementation would require only hematoxylin and eosin (H&E) histology slides, which is the common type of stain used in hospitals. It can be implemented with routine pathology evaluation and with no additional costs. PMID:25527015

  16. Usefulness of chromoendoscopy and magnifying narrow band imaging endoscopy for diagnosis of demarcation of adenocarcinoma in Barrett's esophagus.

    PubMed

    Yamashina, Takeshi; Uedo, Noriya; Matsui, Fumi; Ishihara, Ryu; Tomita, Yasuhiko

    2013-05-01

    It is often difficult to accurately delineate the borders and extent of early-stage esophageal adenocarcinoma in patients with Barrett's esophagus using conventional white light endoscopy. Chromoendoscopy enhances the characteristics of the mucosa and improves detection and delineation of small or flat lesions difficult to identify by conventional endoscopy. Magnifying endoscopy with narrow-band imaging (NBI) is a novel endoscopic imaging technology that contrasts the vascular architecture and surface structure of the superficial mucosa. As magnifying NBI can view only a narrow area of the mucosa, this method cannot determine the circumference of the lesion and evaluate its complete extent. Indigocarmine chromoendoscopy is useful for delineating the extent of Barrett's adenocarcinoma. Chromoendoscopy and magnifying NBI are complementary methods, with both being required for the accurate diagnosis of tumor extent in patients with superficial Barrett's esophageal adenocarcinoma. © 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.

  17. Neoadjuvant treatment for resectable pancreatic adenocarcinoma

    PubMed Central

    Wong, John; Solomon, Naveenraj L; Hsueh, Chung-Tsen

    2016-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID:26862486

  18. Metastasis of Prostate Adenocarcinoma to the Testis

    PubMed Central

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  19. Aggressive papillary adenocarcinoma on atypical localization

    PubMed Central

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  20. Inverted gastric adenocarcinoma of fundic gland mucosa type colliding with well differentiated adenocarcinoma: A case report.

    PubMed

    Takahashi, Keitaro; Fujiya, Mikihiro; Ichihara, Shin; Moriichi, Kentaro; Okumura, Toshikatsu

    2017-06-01

    Gastric adenocarcinoma of fundic gland mucosa type (GA-FGM) is a rare tumor composed of atypical cells with differentiation toward the fundic gland as well as the foveolar epithelium. Including our case, only 9 cases of GA-FGMs were reported from 2010 to 2016. An 87-year-old man was referred to our institution for endoscopic resection of a gastric lesion. The tumor was classified as type 0-I + IIa according to the Paris classification. Magnifying endoscopy with narrow band imaging (ME-NBI) revealed different structures of crypts and vessels among the components, illustrating the collision of 2 types of gastric cancer. We performed endoscopic submucosal dissection and successfully removed the tumor en bloc. The histological findings differed markedly between the 0-I lesion and the 0-IIa lesion. The superficial part of the 0-I lesion consisted of a papillary structure, and the deeper part consisted of a tubular structure that showed inverted downward growth to the submucosal layer with the lamina muscularis mucosae. Immunohistochemically, the superficial part of the 0-I lesion was positive for MUC5AC, which had differentiated to foveolar epithelium. The deeper part was positive for pepsinogen-I and MUC6, which had differentiated to fundic gland. The 0-I lesion was diagnosed as gastric phenotype of adenocarcinoma differentiated to fundic gland mucosa with upward growth in the superficial part and downward growth in the deeper part. The 0-IIa lesion was composed of a tubular structure positive for MUC2, and it was diagnosed as an intestinal phenotype of well differentiated adenocarcinoma. The boundary was clear, and no transitional tissue was observed between the 0-I and 0-IIa lesions, suggesting that the 0-I + IIa lesion was a gastric collision tumor of GA-FGM and well differentiated adenocarcinoma. We herein report the first case of inverted GA-FGM colliding with well differentiated adenocarcinoma. ME-NBI can be used to diagnose GA-FGM even if the lesion

  1. Modelling of survival of patients with colon adenocarcinoma based on multivariable analysis of the state of cancer cell nuclear apparatus.

    PubMed

    Grabovoy, A N; Kolesnik, O O; Savchyn, T M; Antoniuk, S A

    2016-03-01

    The creation of a mathematical model of survival in patients with colon adenocarcinoma based on multivariable analysis of the state of cancer cell nuclear apparatus. The study was performed on 141 samples of biopsy materials or material obtained during surgical treatment of the patients with colon adenocarcinoma or benign colon neoplasms with the use of histological, morphometric, densitometric, immunohistochemical and mathematical methods. It has been shown that each discrete pattern of the state of adenocarcinoma cell nuclei (quantity of DNA, the number and volume of nuclear organizer regions, expression rates of Ki-67, Bcl-2 and p53) is prognostically invalid in the case of its separate use. Combination of these characteristics significantly enhances prognostic validity of the survival model. Based on equation of Cox proportional hazards, survival model of good quality for the patients with moderately and poorly differentiated adenocarcinoma and increased average DNA content in tumor cell nuclei has been created. The proposed survival model for colon adenocarcinoma demonstrates the quality twice superior to the model based on the use of tumor grade only (G) which in fact is presently used as a sole common independent histological criterion of prognosis.

  2. Warranting Investigation of Primary Lung Adenocarcinoma in Patients With an Extrapulmonary Malignancy and Lung Nodules Due to High Frequency

    PubMed Central

    Zhu, Bing; Dalal, Shavari; Kamp, David W.; Lin, Xiaoqi

    2016-01-01

    Objectives To distinguish primary lung adenocarcinoma (PLA) from metastatic adenocarcinoma/malignancy to optimize therapy. Methods We investigated the utility of thyroid transcription factor 1 (TTF-1) and napsin A in distinguishing PLA from metastatic adenocarcinoma/malignancy and assessed the frequency of PLA in patients with extrapulmonary malignancy/adenocarcinoma (PLA-EPM/EPA). Results TTF-1 and napsin A identified PLA in PLA-EPM/EPA with a sensitivity of 89.4% and 93.3% and a specificity of 93.9% and 94.7%, respectively. PLA was confirmed in 47.4% of PLA-EPM and 40.2% of PLA-EPA. Overall, 38.5% of patients with PLA had EPM. The common organs for PLA-EPA were breast (35.8%), colon (13.2%), and others, whereas the common organs resulting in pulmonary metastasis were the colon (32.8%), breast (28.1%), and others. A patient with a smoking history and without EPM had a higher chance of having PLA. Multiple nodules are not a reliable indication of metastatic adenocarcinoma. Conclusions Our results firmly support the role of TTF-1 and napsin A in identifying PLA-EPM/EPA. We reason that all new lung nodules in patients with a history of EPM should be screened using these techniques due to the high frequency of PLA-EPM, which will affect treatment and prognosis of patients with EPM/EPA. PMID:24515772

  3. Solid predominant histologic subtype and early recurrence predict poor postrecurrence survival in patients with stage I lung adenocarcinoma

    PubMed Central

    Han, Baohui; Zhang, Jie; Zhao, Heng; Fang, Wentao; Luo, Qingquan; Yang, Jun; Yang, Yunhai; Zhu, Lei; Chen, Tianxiang; Cheng, Xinghua; Huang, Qingyuan; Wang, Yiyang; Zheng, Jiajie; Chen, Haiquan

    2017-01-01

    Introduction This study investigated the correlation between histologic predominant pattern and postrecurrence survival (PRS), and identified the clinicopathologic factors influencing PRS in patients with completely resected stage I lung adenocarcinoma. Methods A total of 136 stage I lung adenocarcinoma patients who experienced tumor recurrence after completely resection were included in this study. To analysis the association between histologic predominant pattern and PRS, invasive adenocarcinomas with mixed histologic components were divided into 2 groups: solid and nonsolid group (including lepidic, acinar, papillary, micropapillary) based on the histologic predominant pattern. PRS was analyzed to identify the prognostic predictors using the Kaplan-Meier approach and multivariable Cox models. Results For all stage I invasive adenocarcinoma patients, the majority of postsurgical recurrences occurred within 2 years. Patients with solid predominant histological pattern were associated with unfavorable PRS (HR, 2.40; 95%CI 1.13-5.08, p=.022). There was a significant difference for poor PRS for patients who diagnosed tumor recurrence shorter than 12 months after surgery (HR, 2.34; 95%CI 1.12-4.90, p=.024). Extrathoracic metastasis was associated with poor media PRS in univariable analysis (p =.011), however, there was no significant PRS difference in multivariable analysis (HR, 1.56; 95%CI 0.65-3.73, p=.322) compared with intrathoracic metastasis. Conclusions Solid predominant histologic subtype and recurrence free interval less than 12 months predict worse PRS in patients with stage I lung adenocarcinoma. PMID:27732964

  4. Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

    PubMed

    Yako, Yandiswa Yolanda; Kruger, Deirdré; Smith, Martin; Brand, Martin

    2016-01-01

    A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19-9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response. Our review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals.

  5. 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

  6. Clinicopathologic and prognostic significance of c-MYC copy number gain in lung adenocarcinomas

    PubMed Central

    Seo, A N; Yang, J M; Kim, H; Jheon, S; Kim, K; Lee, C T; Jin, Y; Yun, S; Chung, J-H; Paik, J H

    2014-01-01

    Background: c-MYC copy number gain (c-MYC gain) has been associated with aggressive behaviour in several cancers. However, the role of c-MYC gain has not yet been determined in lung adenocarcinomas classified by genetic alterations in epidermal growth factor receptor (EGFR), KRAS, and anaplastic lymphoma kinase (ALK) genes. We investigated the clinicopathologic and prognostic significance of c-MYC gain for disease-free survival (DFS) and overall survival (OS) according to EGFR, KRAS, and ALK gene status and stages in lung adenocarcinomas. Methods: In 255 adenocarcinomas resected in Seoul National University Bundang Hospital from 2003 to 2009, fluorescence in situ hybridisation (FISH) with c-MYC probe and centromeric enumeration probe 8 (CEP8) was analysed using tissue microarray containing single representative core per each case. EGFR (codon 18 to 21) and KRAS (codon 12, 13, and 61) mutations were analysed by polymerase chain reaction and direct sequencing method from formalin-fixed, paraffin-embedded tissue sections. ALK rearrangement was determined by FISH method. c-MYC gain was defined as >2 copies per nucleus, chromosome 8 gain as ⩾3 copies per nucleus, and gain of c-MYC:CEP8 ratio (hereafter, c-MYC amplification) as ⩾2. Results: We observed c-MYC gain in 20% (51 out of 255), chromosome 8 gain in 5.5% (14 out of 255), c-MYC amplification in 2.4% (6 out of 255), EGFR mutation in 49.4% (118 out of 239), KRAS mutation in 5.7% (7 out of 123), and ALK rearrangement in 4.9% (10 out of 205) of lung adenocarcinomas. c-MYC gain was observed in 19% (22 out of 118) of patients with lung adenocarcinomas with an EGFR mutation, but not in any patients with a KRAS mutation, or an ALK rearrangement. c-MYC gain (but not chromosome 8 gain or c-MYC amplification) was an independent poor-prognostic factor in the full cohort of lung adenocarcinoma (P=0.022, hazard ratio (HR)=1.71, 95% confidence interval (CI), 1.08–2.69 for DFS; P=0.032, HR=2.04, 95% CI, 1.06–3.91 for OS

  7. A quantitative investigation of fucosylated serum glycoproteins with application to esophageal adenocarcinoma.

    PubMed

    Mann, Benjamin; Madera, Milan; Klouckova, Iveta; Mechref, Yehia; Dobrolecki, Lacey E; Hickey, Robert J; Hammoud, Zane T; Novotny, Milos V

    2010-06-01

    Although glycoproteomic studies provide unique opportunities for cancer research, it has been necessary to develop specific methods for analysis of oncologically interesting glycoproteins. We describe a general, multimethodological approach for quantitative glycoproteomic analysis of fucosylated glycoproteins in human blood serum. A total of 136 putative fucosylated glycoproteins were identified with very high confidence in three clinically relevant sample pools (N=5 for each), with a mean CV of 3.1% observed for replicate analyses. Two samples were collected from subjects diagnosed with esophagus disease states, high-grade dysplasia plus esophageal adenocarcinoma, while the third sample was representative of a disease-free condition. Some glycoproteins, observed to be significantly upregulated in esophageal adenocarcinoma, i.e. more than twofold higher than in the disease-free condition, are briefly discussed. Further investigation will be necessary to validate these findings; however, the method itself is demonstrated to be an effective tool for quantitative glycoproteomics of clinical samples.

  8. New subtype of gastric adenocarcinoma: mixed fundic and pyloric mucosa-type adenocarcinoma.

    PubMed

    Kanesaka, Takashi; Uedo, Noriya; Yao, Kenshi; Tanabe, Hiroshi; Yamasaki, Yasushi; Takeuchi, Yoji; Iwashita, Akinori; Tomita, Yasuhiko

    2017-06-01

    A 73-year-old woman underwent upper endoscopic screening that revealed a 30-mm superficial elevated lesion in the anterior wall of the upper gastric body. The lesion had a whitish color and coarse granular surface in conventional white light endoscopy. Magnifying narrow-band imaging indicated irregular microvascular and microsurface patterns within a demarcation line. The microvessels had a distorted polygonal shape within the area surrounded by the marginal crypt epithelium. The patient underwent endoscopic resection. Histological examination of the resected specimen showed a very well- to well-differentiated tubular adenocarcinoma with differentiation toward the mixed fundic and pyloric mucosa, without chief cells. The histological and serological findings indicated the absence of Helicobacter pylori infection. The present case demonstrates a new histological subtype of gastric adenocarcinoma, which has characteristic endoscopic findings.

  9. Clinicopathologic features and prognosis of duodenal adenocarcinoma and comparison with ampullary and pancreatic ductal adenocarcinoma.

    PubMed

    Zenali, Maryam; Overman, Michael J; Rashid, Asif; Broaddus, Russell B; Wang, Hua; Katz, Matthew H; Fleming, Jason B; Abbruzzese, James L; Wang, Huamin

    2013-12-01

    Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic features and prognostication data for DAC are limited. There are no published studies directly comparing the prognosis of DAC to that of ampullary adenocarcinoma (AA) and of pancreatic ductal adenocarcinoma (PDA) after resection. In this study, we examined the clinicopathologic features of 68 patients with DAC, 92 patients with AA, and 126 patients with PDA who underwent resection. Patient clinicopathologic and survival information were extracted from medical records. Statistical analysis was performed using Statistical Package for the Social Sciences with 2-sided significance level of .05. Patients with DAC had higher American Joint Committee on Cancer (AJCC) stage than AA patients (P = .001). Lymph node metastasis (P = .013) and AJCC stage (P = .02) correlated with overall survival in DAC patients. Patients with DAC or AA had lower frequencies of lymph node metastasis and positive margin and better survival than those with PDA (P < .05). However, no differences in nodal metastasis, margin status, or survival were observed between DAC patients and those with AA. Our study showed that lymph node metastasis and AJCC stage are important prognostic factors for overall survival in DAC patients. Patients with DAC had less frequent nodal metastasis and better prognosis than those with PDA. There was no significant difference in prognosis between DAC and AA.

  10. 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.

  11. Determination of poor prognostic immune features of tumour microenvironment in non-smoking patients with lung adenocarcinoma.

    PubMed

    Kinoshita, Tomonari; Kudo-Saito, Chie; Muramatsu, Reiko; Fujita, Tomonobu; Saito, Miyuki; Nagumo, Haruna; Sakurai, Toshiharu; Noji, Shinobu; Takahata, Emi; Yaguchi, Tomonori; Tsukamoto, Nobuo; Hayashi, Yuichiro; Kaseda, Kaoru; Kamiyama, Ikuo; Ohtsuka, Takashi; Tomizawa, Kenji; Shimoji, Masaki; Mitsudomi, Tetsuya; Asamura, Hisao; Kawakami, Yutaka

    2017-09-23

    We have previously demonstrated that the prognostic significance of tumour-infiltrating CD8(+) T cells significantly differs according to histological type and patient smoking habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating CD8(+) T cells may not be activated sufficiently in the immunosuppressive microenvironment in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical evaluation using an alternative counting method and multicolour staining method (n = 234), and assessed immune-related gene expression by using genetic analytical approaches (n = 58). We found that high infiltration of activated CD8(+) T cells expressing interferon gamma (IFN-γ) and granzyme was correlated with postoperative survival in patients with non-adenocarcinoma. On the contrary, CD8(+) T-cell accumulation was identified as a worse prognostic factor in patients with adenocarcinoma, particularly in non-smokers. Infiltrating CD8(+) T cells were significantly less activated in this microenvironment with high expression of various immunoregulation genes. Potentially immunoregulatory CD8(+) FOXP3(+) T cells and immunodysfunctional CD8(+) GATA3(+) T cells were increased in adenocarcinoma of non-smokers. CD4(+) FOXP3(+) regulatory T cells expressing chemokine receptor-4 (CCR4)- and chemokine ligand (CCL17)-expressing CD163(+) M2-like macrophages also accumulated correlatively and significantly in adenocarcinoma of non-smokers. These characteristic immune cells may promote tumour progression possibly by creating an immunosuppressive microenvironment in non-smoking patients with lung adenocarcinoma. Our findings may be helpful for refining the current strategy of personalised immunotherapy including immune-checkpoint blockade therapy for NSCLC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. 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.

  13. 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.

  14. Lung adenocarcinoma masquerading as refractory Klebsiella pneumoniae.

    PubMed

    McCartney, Clair; Moghadam, Afshin; Sriram, Krishna B

    2014-04-04

    We report the case of a middle-aged man where a diagnosis of Klebsiella pneumoniae obscured the underlying malignancy. The patient was hospitalised for management of a presumed refractory community-acquired pneumonia with radiological features of right lower lobe consolidation. Bronchoscopy did not identify an endobronchial lesion and washings grew K pneumoniae. CT-guided fine-needle aspirate samples did not detect any malignancy. However, despite appropriate antibiotic treatment there was no improvement in the patient's clinical condition. Consequently, a CT-guided lung core biopsy was performed to obtain more tissue for histopathology, which was diagnostic of primary lung adenocarcinoma. This case highlights the need to continue to investigate a patient who is not progressing as clinically appropriate to their original diagnosis.

  15. Current status of ramucirumab in gastroesophageal adenocarcinoma.

    PubMed

    Elimova, Elena; Lin, Quan; Song, Shumei; Ajani, Jaffer A

    2017-08-01

    Outcomes of patients with advanced gastric or gastroesophageal junction adenocarcinoma (GEAC) remain poor despite recent advances. The standard of care in the management of this disease had not changed much over the past decade. In the first line, a platinum containing doublet/triplet is used, while in <20% of patients with human epithelial growth factor receptor type 2 overexpressing GEACs, trasuzumab can provide a modest advantage. Until recently, no standard second-line regimens existed; however, the results of the REGARD and RAINBOW trials led to the approval of ramucirumab in the second-line setting. From these trials it is clear that paclitaxel and ramucirumab should be used if possible. The placement of ramucirumab may become less clear as the data from immune oncology trials in GEAC emerge.

  16. Preclinical models of pancreatic ductal adenocarcinoma.

    PubMed

    Hwang, Chang-Il; Boj, Sylvia F; Clevers, Hans; Tuveson, David A

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult human malignancies to treat. The 5-year survival rate of PDA patients is 7% and PDA is predicted to become the second leading cancer-related cause of death in the USA. Despite intensive efforts, the translation of findings in preclinical studies has been ineffective, due partially to the lack of preclinical models that faithfully recapitulate features of human PDA. Here, we review current preclinical models for human PDA (eg human PDA cell lines, cell line-based xenografts and patient-derived tumour xenografts). In addition, we discuss potential applications of the recently developed pancreatic ductal organoids, three-dimensional culture systems and organoid-based xenografts as new preclinical models for PDA.

  17. Optic nerve metastasis caused by lung adenocarcinoma.

    PubMed

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

    2017-06-21

    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.

  18. 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

  19. Quantitative expression analysis and prognostic significance of L-DOPA decarboxylase in colorectal adenocarcinoma

    PubMed Central

    Kontos, C K; Papadopoulos, I N; Fragoulis, E G; Scorilas, A

    2010-01-01

    Background: L-DOPA decarboxylase (DDC) is an enzyme that catalyses, mainly, the decarboxylation of L-DOPA to dopamine and was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of the DDC gene and to evaluate its clinical utility in tissues with colorectal adenocarcinoma. Methods: Total RNA was isolated from colorectal adenocarcinoma tissues of 95 patients. After having tested RNA quality, we prepared cDNA by reverse transcription. Highly sensitive quantitative real-time PCR method for DDC mRNA quantification was developed using the SYBR Green chemistry. GAPDH served as a housekeeping gene. Relative quantification analysis was performed using the comparative CT method (2−ΔΔCT). Results: DDC mRNA expression varied remarkably among colorectal tumours examined in this study. High DDC mRNA expression levels were found in well-differentiated and Dukes' stage A and B tumours. Kaplan–Meier survival curves showed that patients with DDC-positive tumours have significantly longer disease-free survival (P=0.009) and overall survival (P=0.027). In Cox regression analysis of the entire cohort of patients, negative DDC proved to be a significant predictor of reduced disease-free (P=0.021) and overall survival (P=0.047). Conclusions: The results of the study suggest that DDC mRNA expression may be regarded as a novel potential tissue biomarker in colorectal adenocarcinoma. PMID:20424616

  20. [Secondary neoplasms of the larynx from a colonic adenocarcinoma].

    PubMed

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-26

    Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, followed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extremely rare. Tumours spreading to the larynx may be asymptomatic or may result in hoarseness, stridor or airway obstruction. Patients with metastasis of colonic adenocarcinoma to the larynx usually present with disseminated disease. We present a case of an isolated laryngeal metastasis from a colonic adenocarcinoma. The patient was treated with endoscopic surgery and radiation.

  1. 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.

  2. Primary Adenocarcinoma of an Ileostomy in Crohn's Disease

    PubMed Central

    Prasad, Meena A.; Lo, Amy; Bellaguarda, Emanuelle; Strong, Scott; Hanauer, Stephen B.

    2016-01-01

    Although Crohn's disease has been associated with an increased risk of small bowel adenocarcinoma, primary adenocarcinoma arising from an ileostomy is a complication that has been rarely documented in Crohn's disease. Chronic small bowel inflammation may lead to development of malignancy through the dysplasia-carcinoma sequence. We report a case of a 61-year-old woman with Crohn's ileocolitis diagnosed with a primary adenocarcinoma at the ileostomy with metastases to the liver 47 years after proctocolectomy, and review the literature. PMID:27622191

  3. Abiraterone Acetate and Castration Resistant Ductal Adenocarcinoma of the Prostate

    PubMed Central

    Linden-Castro, Edgar; Pelayo-Nieto, Marcela; Alias-Melgar, Alejandro; Espinosa-Perezgrovas, Daniel; Ramirez-Galindo, Ivan; Catalan-Quinto, Gabriel

    2014-01-01

    Ductal adenocarcinoma of the prostate is a rare histological variant that only represents <1% of prostate tumors. This histological variant has several important clinical implications with respect to their evolution, clinical prognosis, and treatment. We report the case of a 64-year-old patient with ductal adenocarcinoma of the prostate, which progresses to castration-resistant prostate cancer, that was treated with abiraterone acetate with good clinical response, to our knowledge, the first case of ductal adenocarcinoma of the prostate in treatment with abiraterone acetate. PMID:24891969

  4. Mesonephric adenocarcinoma of the uterine cervix and literature review

    PubMed Central

    Anagnostopoulos, Antonios; Ruthven, Stuart; Kingston, Robert

    2012-01-01

    Mesonephric adenocarcinoma is a rare type of cervical cancer that derives from mesonephric remnants in the uterine cervix. To the best of our knowledge, this is the 34th case of mesonephric adenocarcinoma in adult women documented in the literature. We present an asymptomatic 64-year-old postmenopausal woman presenting with a suspicious-looking cervix as an incidental finding and diagnosed with a stage IB mesonephric adenocarcinoma of the cervix. This case was managed with radical hysterectomy, bilateral salpingoophorectomy and pelvic lymphadenectomy. The rarity of such cases imposes challenges on the management in terms of diagnosis, prognosis and therapeutic options. PMID:23230242

  5. Survival of women with microinvasive adenocarcinoma of the cervix is not improved by radical surgery.

    PubMed

    Bean, Lisa M; Ward, Kristy K; Plaxe, Steven C; McHale, Michael T

    2017-09-01

    (local excision compared with simple hysterectomy [P = .64]; local excision compared with radical hysterectomy [P = .82]; or simple hysterectomy compared with radical hysterectomy [P = .70]). Among patients with adenocarcinoma, 0.97% had positive pelvic lymph nodes, none had positive aortic lymph nodes, and 91.85% had confirmed negative lymph nodes. For squamous cell carcinoma, 0.72% of patients had positive pelvic lymph nodes and 0.10% had positive aortic lymph nodes. There was no significant difference in survival when patients were compared by cell type or procedure, suggesting that survival of patients with microinvasive adenocarcinoma is not improved by utilizing more invasive surgical methods. Regardless of histology, the frequency of nodal involvement was very low among both groups, supporting an overall excellent prognosis for all patients with microinvasive disease. We submit these data as evidence that preoperative planning of more conservative techniques is appropriate, not just for those with squamous histology or who desire future fertility, but for all patients with microinvasive cervical disease. Copyright © 2017. Published by Elsevier Inc.

  6. Expression heterogeneity research of ITGB3 and BCL-2 in lung adenocarcinoma tissue and adenocarcinoma cell line.

    PubMed

    Xia, Zong-Jiang; Hu, Wei; Wang, Yue-Bin; Zhou, Kun; Sun, Guo-Ju

    2014-06-01

    To analyze expression heterogeneity of Integrin beta 3 (ITGB3) and B-cell lymphoma 2 (BCL-2) in lung adenocarcinoma tissue and adenocarcinoma cell line and further provide theoretical direction for molecular biological research of lung adenocarcinoma. Tissue microarray was used to observe relation among expression, heterogeneitpy and clinical characteristics of ITGB3 and BCL-2 in lung cancer. ITGB3 and BCL-2 increased significantly in A549 cells in CAFs group withβ-actin as control; the expression level of BCL-2 also increased in ITGB3 transfected cells with GFP plasmid transfected A549 cells as control; immunohistochemistry staining showed that positive rates of ITGB3, ITGB1 and BCL-2 in normal lung tissues were 0, the positive rates in lung adenocarcinoma were 7.04%, 84.51% and 4.23%, respectively; in the results of immunohistochemistry staining, the expression of Girdin protein in lung adenocarcinoma was homogeneous, however protein expression of ITGB3, ITGB1 and BCL-2 showed different patterns in the same location with significant heterogeneity; majority of ITGB3, ITGB1 or BCL-2 positive tissue showed heterogeneity that expression in trailing edge was higher than that of trailing edge in lung adenocarcinoma tissue, the patients with BCL-2 heterogeneity showed higher lymph node metastasis ratio and lower clinical stage (P<0.05); and the expression of ITGB3 and the clinical characteristics of patients were not significant related (P>0.05). Expression of ITGB3 and BCL-2 in lung adenocarcinoma and adenocarcinoma cell line showed heterogeneity that expression in trailing edge was higher than that of trailing edge, which may play an important role in promoting tumor lymph node metastasis and vascular invasion, and provides a new research direction for exploration of lung adenocarcinoma metastasis mechanism. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  7. 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

  8. Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses.

    PubMed

    Lavin, Yonit; Kobayashi, Soma; Leader, Andrew; Amir, El-Ad David; Elefant, Naama; Bigenwald, Camille; Remark, Romain; Sweeney, Robert; Becker, Christian D; Levine, Jacob H; Meinhof, Klaus; Chow, Andrew; Kim-Shulze, Seunghee; Wolf, Andrea; Medaglia, Chiara; Li, Hanjie; Rytlewski, Julie A; Emerson, Ryan O; Solovyov, Alexander; Greenbaum, Benjamin D; Sanders, Catherine; Vignali, Marissa; Beasley, Mary Beth; Flores, Raja; Gnjatic, Sacha; Pe'er, Dana; Rahman, Adeeb; Amit, Ido; Merad, Miriam

    2017-05-04

    To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell analysis of the tumor, non-involved lung, and blood cells, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor-infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Diagnosis potential of near infrared Mueller Matrix imaging for colonic adenocarcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Jianfeng; Zheng, Wei; Lin, Kan; Huang, Zhiwei

    2016-03-01

    Mueller matrix imaging along with polar decomposition method was employed for the colonic adenocarcinoma detection by polarized light in the near-infrared spectral range (700-1100 nm). A high-speed (<5s) Muller matrix imaging system with dual-rotating waveplates was developed. 16 (4 by 4) full Mueller matrices of the colonic tissues (i.e., normal and caner) were acquired. Polar decomposition was further implemented on the 16 images to derive the diattentuation, depolarization, and the retardance images. The decomposed images showed clear margin between the normal and adenocarcinomaous colon tissue samples. The work shows the potential of near-infrared Mueller matrix imaging for the early diagnosis and detection of malignant lesions in the colon.

  10. Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins.

    PubMed

    Keating, Jane J; Okusanya, Olugbenga T; De Jesus, Elizabeth; Judy, Ryan; Jiang, Jack; Deshpande, Charuhas; Nie, Shuming; Low, Philip; Singhal, Sunil

    2016-04-01

    During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection. Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma. The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (p < 0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5. Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.

  11. 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

  12. 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.

  13. BITC Sensitizes Pancreatic Adenocarcinomas to TRAIL-induced Apoptosis

    PubMed Central

    Wicker, Christina A.; Sahu, Ravi P.; Kulkarni-Datar, Kashmira; Srivastava, Sanjay K.; Brown, Thomas L.

    2010-01-01

    Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is often associated with mutations in codon 12 of the K-Ras gene (K-Ras 12), which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC). BITC is a component of cruciferous vegetables and a cell cycle inhibitor. BxPC3, MiaPaCa2 and Panc-1 human pancreatic adenocarcinoma cell lines were examined for TRAIL resistance. Our studies show BITC induced TRAIL sensitization by dual activation of both the extrinsic and intrinsic apoptotic pathways. PMID:20559452

  14. Human chorionic gonadotropin and CA 15-3 producing adenocarcinoma.

    PubMed

    Uçkaya, G; Ozet, A; Arpaci, A; Kömürcü, S

    1998-01-01

    50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (beta HCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although beta HCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

  15. Metachronous Colon Metastases from Gastric Adenocarcinoma: A Case Report

    PubMed Central

    Pace, Ugo; Contino, Gianmarco; Chiappa, Antonio; Bertani, Emilio; Bianchi, Paolo P.; Fazio, Nicola; Renne, Giuseppe; Di Meglio, Giovanni; Andreoni, Bruno

    2009-01-01

    The colon is a very rare metastatic localization. Here we report a case of colonic metastases from gastric adenocarcinoma whose clinical presentation was suggestive of a de novo adenocarcinoma of the ascending colon. The authors discuss that in the presence of a previous history of gastric cancer, immunohistochemical analysis on endoscopic biopsies may help in the definition of a differential diagnosis. Furthermore, this rare metastatic localization might suggest a poor prognosis and a more accurate diagnostic work-up. PMID:20740169

  16. Discordance of Mutation Statuses of Epidermal Growth Factor Receptor and K-ras between Primary Adenocarcinoma of Lung and Brain Metastasis.

    PubMed

    Rau, Kun-Ming; Chen, Han-Ku; Shiu, Li-Yen; Chao, Tsai-Ling; Lo, Yi-Ping; Wang, Chin-Chou; Lin, Meng-Chih; Huang, Chao-Cheng

    2016-04-07

    Mutations on epidermal growth factor receptor (EGFR) of adenocarcinomas of lung have been found to be associated with increased sensitivity to EGFR tyrosine kinase inhibitors and K-ras mutations may correlate with primary resistance. We aimed to explore the discordant mutation statuses of EGFR and K-ras between primary tumors and matched brain metastases in adenocarcinomas of lung. We used a sensitive Scorpion ARMS method to analyze EGFR mutation, and Sanger sequencing followed by allele-specific real-time polymerase chain reaction to analyze K-ras mutation. Forty-nine paired tissues with both primary adenocarcinoma of lung and matched brain metastasis were collected. Thirteen patients (26.5%) were discordant for the status of EGFR between primary and metastatic sites. K-ras gene could be checked in paired specimens from 33 patients, thirteen patients (39.6%) were discordant for the status of K-ras. In primary lung adenocarcinoma, there were 14 patients of mutant EGFR had mutant K-ras synchronously. This study revealed that the status of EGFR mutation in lung adenocarcinomas is relatively consistent between primary and metastatic sites compared to K-ras mutation. However, there are still a few cases of adenocarcinoma of lung showing discordance for the status of EGFR mutation. Repeated analysis of EGFR mutation is highly recommended if tissue from metastatic or recurrent site is available for the evaluation of target therapy.

  17. 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

  18. The Management and Prognostic Prediction of Adenocarcinoma of Appendix

    PubMed Central

    Xie, Xin; Zhou, Zhangjian; Song, Yongchun; Li, Wenhan; Diao, Dongmei; Dang, Chengxue; Zhang, Hao

    2016-01-01

    Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell’s C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation. PMID:27982068

  19. Claudin-1 correlates with poor prognosis in lung adenocarcinoma.

    PubMed

    Sun, Bing-Sheng; Yao, Yi-Qun; Pei, Bao-Xiang; Zhang, Zhen-Fa; Wang, Chang-Li

    2016-09-01

    This study was conducted to investigate the clinical significance of claudin-1 (CLDN1) expression in patients with lung adenocarcinoma. We examined CLDN1 protein expression by immunohistochemistry in a tissue microarray from 258 patients with lung adenocarcinoma. We investigated messenger ribonucleic acid (mRNA) expression in H358 (formerly bronchioloalveolar carcinoma) and lung adenocarcinoma cell lines (A549) by real-time reverse transcriptase-polymerase chain reaction. Multivariate analysis showed that prognostic factors for lung adenocarcinoma were histologic type, CLDN1, T stage and N stage. Patients with positive CLDN1 expression had a poorer prognosis than patients with negative CLDN1 expression. CLDN1 expression was correlated with Ras and epidermal growth factor receptor (EGFR) expression. Patients with positive expressions of both CLDN1 and Ras/EGFR had a poorer prognosis than patients with CLDN1 (+) Ras/EGFR(-) or CLDN1 (-) Ras/EGFR(+) and patients with negative expressions of both CLDN1 and Ras/EGFR. CLDN1 mRNA expression was lower in the H358 compared with the lung adenocarcinoma cell line (A549). The combination of CLDN1 and Ras/EGFR is a valuable independent prognostic predictor for lung adenocarcinoma. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  20. 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.

  1. Histopathologic parameters and DNA analysis in colorectal adenocarcinomas.

    PubMed

    Crissman, J D; Zarbo, R J; Ma, C K; Visscher, D W

    1989-01-01

    Human colon adenocarcinomas have histological parameters that are clearly associated with prognosis. These include tumor grade, pattern of invasion, presence of lymphocytes, and vascular involvement by tumor. The latter remains controversial with respect to the relative importance of intramural and extramural vascular involvement. Some studies show a poor prognosis for intramural invasion of capillary size vascular channels by tumor. On the other hand, when veins are involved by tumor, the presence of tumor in large extramural veins appears to have a much more ominous effect than intramural tumor involvement of small veins. The results of DNA analysis of colorectal adenocarcinomas varied greatly depending on study methodology but several important points can be summarized: (1) higher stage tumors have a greater proportion of aneuploid tumors; (2) aneuploid tumors tend to have a higher growth rate (SPF) and poorer survival than diploid tumors; and (3) aneuploid tumors are associated with histological parameters indicative of a poor prognosis such as vascular invasion, but ploidy is not related to tumor grade. One of the major problems in drawing firm conclusions about the relationship of flow cytometric DNA measurements to prognosis is great variability among the reported studies. The types of variation appear to fall into two major categories: patient selection and technical problems. The former are especially relevant in retrospective studies in which there is poor patient definition (site, grade, stage, and other standard tumor definitions) and a bias for selecting early stage tumors which have improved survivals. The latter includes a spectrum of technical problems inherent in this widely but not necessarily uniformly applied laboratory procedure. This is particularly true for DNA analysis of nuclei removed from paraffin tissue blocks. For the most part, quality control measurements including cell yields, the efficiency of extraction or disaggregation of

  2. Pancreas Adenocarcinoma: Ascites, Clinical Manifestations, and Management Implications

    PubMed Central

    Hicks, Angel Mier; Chou, Joanne; Capanu, Marinela; Lowery, Maeve A.; Yu, Kenneth H.; O’Reilly, Eileen M.

    2016-01-01

    This was a cohort analysis evaluating patients with pancreatic adenocarcinoma who presented with or developed ascites. Among the 180 patients analyzed, the use of serial paracenteses and indwelling catheters is a common practice to effect symptom palliation. The complication rate was higher in patients with indwelling catheters. Analyzing ascitic fluid and calculating the serum ascites albumin gradient can help attribute the etiology of the ascites and potentially identify which patients may benefit from diuretics or other intervention. Background Ascites develops in a subset of patients with pancreatic adenocarcinoma (PAC) at presentation or as the disease advances. Limited data exist on the prognostic importance of malignant ascites in PAC. Our hypothesis is that this information will provide an understanding of the natural history and facilitate management decisions. Methods We conducted a retrospective analysis of 180 patients treated at Memorial Sloan Kettering Cancer Center diagnosed between January 1, 2009 and December 31, 2014, with PAC and with ascites either at presentation or that developed during the disease course. Results For the 180 patients, the overall survival was 15 months. The time from diagnosis to ascites presentation was 11 months, and the survival time after ascites development was 1.8 months (range, 1.6–2.3 months; 95% confidence interval). Of 62 patients (34%) who had ascitic fluid analyzed, 36 (58%) had positive cytology. Fifty-one (82%) patients had a serum ascites albumin gradient ≥ 1, and 11 (18%) had serum ascites albumin gradient < 1. Sixty-four (36%) patients had their ascites managed solely by serial paracenteses. A total of 116 patients required a catheter; of these, 108 (93%) had a Tenckhoff catheter, 4 (3%) a Pleurx catheter, 4 (3%) a pigtail catheter, and 1 (1%) a Denver catheter. Eight (7%) patients required 2 catheters to be placed, and in 6 (5%), Tenckhoff catheters had to be removed. The main observed complications were

  3. 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

  4. Clinical outcomes among women with mucinous adenocarcinoma of the ovary

    PubMed Central

    Massad, L. Stewart; Gao, Feng; Hagemann, Ian; Powell, Mathew

    2016-01-01

    Background/Aims Patterns of metastasis and clinical behavior of mucinous ovarian cancers are poorly understood because of their rarity. Methods A retrospective review of records of women identified with pure mucinous invasive ovarian/tubal/peritoneal cancer 1992–2012 at one institution. Survival differences were compared using Kaplan-Meier methods with log-rank tests. Results Among 42 women with mucinous adenocarcinomas the median age was 55 years (range 33–83 years). Most cancers were well differentiated (n = 26, 68%) and stage I/II (n = 31, 74%). One of 27 women with sampled nodes had nodal metastasis; one additional woman recurred in a pelvic node. Most had no visible residual tumor after initial surgery, but of 10 women with stage III/IV cancer and documented residual, 8 had >2cm residual. Except for one woman alive with disease at last follow-up, all who recurred died of disease. Five-year survival was 83% for stage I/II cases but 29% among stage III/IV cases. Stage was a strong predictor of survival (hazard ratio of death among women with stage III/IV cancer 7.73, 95% C.I. 2.33–25.66, P<0.001 vs women with stage I/II cancer). Conclusion Mucinous ovarian cancers have a distinct biology, such that lymphadenectomy for staging is unnecessary and metastatic cancers have poor prognosis. PMID:26583769

  5. mRNA profiling of the cancer degradome in oesophago–gastric adenocarcinoma

    PubMed Central

    Baren, J P; Stewart, G D; Stokes, A; Gray, K; Pennington, C J; O'Neill, R; Deans, D A C; Paterson-Brown, S; Riddick, A C P; Edwards, D R; Fearon, K C H; Ross, J A; Skipworth, R J E

    2012-01-01

    Background: Degradation of the extracellular matrix is fundamental to tumour development, invasion and metastasis. Several protease families have been implicated in the development of a broad range of tumour types, including oesophago–gastric (OG) adenocarcinoma. The aim of this study was to analyse the expression levels of all core members of the cancer degradome in OG adenocarcinoma and to investigate the relationship between expression levels and tumour/patient variables associated with poor prognosis. Methods: Comprehensive expression profiling of the protease families (matrix metalloproteinases (MMPs), members of the ADAM metalloproteinase-disintegrin family (ADAMs)), their inhibitors (tissue inhibitors of metalloproteinase), and molecules involved in the c-Met signalling pathway, was performed using quantitative real-time reverse transcription polymerase chain reaction in a cohort of matched malignant and benign peri-tumoural OG tissue (n=25 patients). Data were analysed with respect to clinico-pathological variables (tumour stage and grade, age, sex and pre-operative plasma C-reactive protein level). Results: Gene expression of MMP1, 3, 7, 9, 10, 11, 12, 16 and 24 was upregulated by factors >4-fold in OG adenocarcinoma samples compared with matched benign tissue (P<0.01). Expression of ADAM8 and ADAM15 correlated significantly with tumour stage (P=0.048 and P=0.044), and ADAM12 expression correlated with tumour grade (P=0.011). Conclusion: This study represents the first comprehensive quantitative analysis of the expression of proteases and their inhibitors in human OG adenocarcinoma. These findings implicate elevated ADAM8, 12 and 15 mRNA expression as potential prognostic molecular markers. PMID:22677901

  6. Contrast-enhanced ultrasound improves accurate identification of appendiceal mucinous adenocarcinoma in an old patient

    PubMed Central

    Shang, Jing; Ruan, Li-tao; Dang, Ying; Wang, Yun-yue; Song, Yan; Lian, Jie

    2016-01-01

    Abstract Background: Adenocarcinoma of appendiceal origin is far rarer than other colorectal carcinomas and its preoperative diagnosis is challenging. To our knowledge, utility of contrast-enhanced ultrasound (CEUS) to diagnose it is much less. Method: A 61-year-old man presented with abdominal pain in the right lower quadrant for 20 days. In order to fulfill an accurately preoperative diagnosis, he received laboratory and imaging tests such as carcinoembryonic antigen (CEA), computer tomography (CT), CEUS and endoscope. Diagnosis and Intervention: He was initially suspected of suffering appendicitis, while his white blood cell count was normal and carcinoembryonic antigen (CEA) in serum was remarkably increased. Both routine ultrasound and computer tomography (CT) examinations supported suppurative appendicitis. The overall data, however, failed to excluded neoplastic pathology thoroughly. Therefore, CEUS was carried out and showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The result of the follow-up biopsy guided by endoscope was consistent with appendiceal tumor. The patient received laparoscopic right hemicolectomy. Histopathology confirmed as well differentiated mucinous adenocarcinoma of appendix origin. His postoperative course was uneventful, and he had a regular diet again without any complaint. Result: Serum CEA was remarkably increased (12.00 ng/mL). Both routine ultrasound and CT examinations supported suppurative appendicitis. However, CEUS examination showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The follow-up biopsy guided by endoscope and surgical specimens confirmed as well differentiated mucinous adenocarcinoma of appendix origin. Conclusion: Most mucinous adenocarcinoma mimicking appendicitis results in difficult diagnosis preoperatively. Clinician and radiologist should be

  7. Evidence for Treatment and Survival Disparities by Age in Pancreatic Adenocarcinoma

    PubMed Central

    Amin, Sunil; Lucas, Aimee L.; Frucht, Harold

    2013-01-01

    Objectives Studies demonstrate safety and survival benefits of surgical resection in older individuals with pancreatic adenocarcinoma. We investigated treatment disparities by age. Methods The Surveillance, Epidemiology, and End Results database for survival and treatment of pancreatic adenocarcinoma between 1983 and 2007 stratified by age: younger than 50 years, between 50 and 70 years, or older than 70 years. Kaplan-Meier curves and Cox proportional hazards models were used for survival differences, and logistic regression models were used for treatment disparities and the decision to refuse surgery. Results A total of 45,509 patients had microscopically confirmed pancreatic adenocarcinoma. Of these, 7374 (16%) received surgery and 9842 (22%) received radiation. Younger patients were more likely to receive both surgery and radiation. The prevalence of surgery decreased from 21% for those younger than 50 years to 19% for those between 50 and 70 years to 13% for those older than 70 years (P < 0.001). Radiation decreased from 28% to 25% to 17% (P < 0.001). Overall survival decreased with increasing age at diagnosis, 10.4 months (age <50 years) to 9.1 months (age 50–70 years) to 6.4 months (age >70 years) controlling for stage, sex, race, radiation, and surgery (P < 0.001). Increasing age negatively predicted the odds of receiving both surgery and radiation and increased the likelihood of refusing surgery. Conclusions Treatment disparities exist by age despite advances in radiation and surgical treatment. Increased treatment in the elderly will increase overall survival from pancreatic adenocarcinoma. PMID:22836862

  8. Clinical Significance of DNA Damage Response Factors and Chromosomal Instability in Primary Lung Adenocarcinoma.

    PubMed

    Okamoto, Tatsuro; Kohno, Mikihiro; Ito, Kensaku; Takada, Kazuki; Katsura, Masakazu; Morodomi, Yosuke; Toyokawa, Gouji; Shoji, Fumihiro; Maehara, Yoshihiko

    2017-04-01

    The purpose of this study was to investigate the biological role of DNA damage-response genes and chromosomal instability in primary lung adenocarcinoma. We investigated 60 surgically-resected lung adenocarcinomas. Levels of checkpoint kinase 2 gene (CHEK2) and breast cancer type 1 susceptibility protein gene (BRCA1) mRNA expression were evaluated by polymerase chain reaction (PCR). Epidermal growth factor receptor (EGFR) mutations (exon 19 deletion and exon 21 mutation) were detected by the PCR clamp method. Mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS) and TP53 were examined by direct sequencing. Expression levels of p27 and p16 proteins were assessed by immunohistochemistry. Chromosomal aberrations (CA) were examined in 20 samples with single-nucleotide polymorphism-comparative genomic hybridization. CHEK2 mRNA levels were significantly increased in tumor tissues compared to normal tissues (p=0.0123, paired t-test), whereas BRCA mRNA levels were not increased. TP53 mutation positivity and BRCA1 mRNA expression were positively associated with CHEK2 mRNA expression status (p=0.022 and p=0.0008). High CHEK2 mRNA expression was associated with poor recurrence-free survival (p=0.028). CHEK2 mRNA levels were higher in samples with a high CA frequency than in those with a low CA frequency (averages: 0.326 vs. 0.185; p=0.0129). The CHEK2 mRNA expression level was found elevated in lung adenocarcinoma and was related to a poor prognostic outcome. The CHEK2 pathway may be important for the proliferation of lung adenocarcinoma, especially in tumors with chromosomal instability. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. A Rare Case of Mixed Neuroendocrine Tumor and Adenocarcinoma of the Pancreas

    PubMed Central

    Lasithiotakis, Konstantinos; Andreou, Alexandros; Aggelaki, Sofia; Tzardi, Maria; Chalkiadakis, George; Chrysos, Emmanuel

    2016-01-01

    Introduction. Neuroendocrine carcinoma (NEC) of pancreas is a rare tumor with aggressive progression and poor prognosis. Its coexistence with adenocarcinoma poses significant clinical problems and has not been addressed in the literature. Methods. We describe a case of a 51-year-old male who underwent pancreatoduodenectomy due to pancreatic head tumor 1.5 × 1 × 1.4 cm. Histological examination of the specimen revealed a mixed neoplasm: (1) a well differentiated adenocarcinoma, neoplastic blasts of which are extended focally to the submucosa without invading the muscular layer, and (2) a low differentiated NEC consisting of solid clusters and pagetoid formations. All 18 lymph nodes of the specimen were free of neoplastic disease and the surgical margins of the specimen were tumor-free. No adjuvant treatment was administered and two months after the operation the patient developed liver metastasis. FNA cytology of the hepatic lesions revealed low grade carcinoma with neuroendocrine characteristics. Five lines of chemotherapy were administered: VP + CDDP, paclitaxel + ifosfamide + Mesna + CDDP, Folfox + Avastin, Folfiri + Avastin, and CAV. During his treatment he revealed PD and succumbed to his disease 13 months after the operation. Conclusion. Coexistence of NEC with adenocarcinoma of the pancreas is a very rare entity presenting significant challenges regarding its adjuvant treatment and the treatment of distant relapse. PMID:27610261

  10. From reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma

    PubMed Central

    Wang, Rui-Hua

    2015-01-01

    The occurrence of gastroesophageal reflux disease is common in the human population. Almost all cases of esophageal adenocarcinoma are derived from Barrett’s esophagus, which is a complication of esophageal adenocarcinoma precancerous lesions. Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett’s esophagus. The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia, which is closely associated with the development of esophageal adenocarcinoma. However, the exact mechanism of injury is not completely understood. Various animal models of the developmental mechanisms of disease, and theoretical and clinical effects of drug treatment have been widely used in research. Recently, animal models employed in studies on gastroesophageal reflux injury have allowed significant progress. The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results. In this article, various modeling methods are reviewed, with discussion of the major findings on the developmental mechanism of Barrett’s esophagus, which should help to develop better prevention and treatment strategies for Barrett’s esophagus. PMID:25954094

  11. The role of contrast-enhanced endoscopic ultrasound in pancreatic adenocarcinoma

    PubMed Central

    Săftoiu, Adrian; Vilmann, Peter; Bhutani, Manoop S.

    2016-01-01

    Contrast-enhanced endoscopic ultrasound (CE-EUS) allows characterization, differentiation, and staging of focal pancreatic masses. The method has a high sensitivity and specificity for the diagnosis of pancreatic adenocarcinoma which is visualized as hypo-enhanced as compared to the rest of the parenchyma while chronic pancreatitis and neuroendocrine tumors are generally either iso-enhanced or hyper-enhanced. The development of contrast-enhanced low mechanical index harmonic imaging techniques used in real time during endoscopic ultrasound (EUS) allowed perfusion imaging and the quantification of intensity of the contrast signal through time-intensity curve analysis. Thus, contrast harmonic imaging-EUS has been used to differentiate pancreatic adenocarcinoma based on lower values of the peak enhancement. Future applications of CE-EUS in pancreatic adenocarcinoma include not only use of targeted contrast agents for early detection, tridimensional and fusion techniques for enhanced staging and resectability assessment but also novel applications of perfusion imaging for monitoring ablative therapy, improved local detection through EUS-guided sampling of portal vein flow or enhanced drug delivery through sonoporation and ultrasound-induced release of the drugs locally. PMID:28000627

  12. Pathologic stratification of operable lung adenocarcinoma using radiomics features extracted from dual energy CT images

    PubMed Central

    Lee, Ho Yun; Sohn, Insuk; Kim, Hye Seung; Son, Ji Ye; Kwon, O Jung; Choi, Joon Young; Lee, Kyung Soo; Shim, Young Mog

    2017-01-01

    Purpose To evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment. Results Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i-uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514–1), 0.8610 (95% CI: 0.7547–0.9672), and 0.8394 (95% CI: 0.7045–0.9743), respectively. Materials and Methods A total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades. Conclusions Quantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma. PMID:27880938

  13. Effect of Neoadjuvant Chemoradiotherapy on Locally Advanced Rectal Mucinous Adenocarcinoma: A Propensity Score-Matched Study

    PubMed Central

    Sun, Yan-wu; Lin, Hui-ming; Lu, Xing-rong; Huang, Ying; Xu, Zong-bin; Huang, Sheng-hui; Wang, Xiao-jie

    2017-01-01

    Aims. To compare the surgical and oncological outcomes of rectal mucinous adenocarcinomas treated with neoadjuvant chemoradiotherapy versus surgery alone. Methods. A total of 167 locally advanced rectal mucinous adenocarcinoma patients treated with neoadjuvant chemoradiotherapy and surgery alone between 2008 and 2014 were matched using propensity score; the surgical and oncological outcomes were compared. Results. Ninety-six patients were matched. Postoperative morbidity was similar between groups. Sphincter preservation rate was higher in patients receiving neoadjuvant chemoradiotherapy (79.2% versus 60.4%, P = 0.045), especially for tumors ≥ 3 cm but ≤5 cm from the anal verge (75.0% versus 44.0%, P = 0.036). With a median follow-up of 54.8 months, the 5-year overall survival rate (neoadjuvant chemoradiotherapy versus surgery alone: 79.6% versus 67.1%; P = 0.599) and disease-free survival rate (75.6% versus 64.2%; P = 0.888) were similar. The 5-year local recurrence rate was lower in patients receiving neoadjuvant chemoradiotherapy (7.7% versus 26.0%, P = 0.036), while no difference was observed in distant metastasis. A poor response to chemoradiation was associated with higher local recurrence (P = 0.037). Conclusions. Compared with surgery alone, neoadjuvant chemoradiotherapy was found to increase the sphincter preservation rate and reduce local recurrence, thus being beneficial for locally advanced rectal mucinous adenocarcinoma patients. PMID:28400820

  14. External assessment of the Early Mortality Risk Score in patients with adenocarcinoma undergoing pancreaticoduodenectomy

    PubMed Central

    Joliat, Gaëtan-Romain; Petermann, David; Demartines, Nicolas; Schäfer, Markus

    2015-01-01

    Background Pancreaticoduodenectomies (PD) still have a substantial mortality rate. Recently, different scores have been published to predict the mortality risk pre-operatively after PD. This retrospective study was designed to perform an external assessment of an Early Mortality Risk Score (EMRS). Methods From 2000 to 2012, all PD cases performed at our institution were documented. Only patients treated for pancreatic head adenocarcinomas were included. Survival time and EMRS (based on age, tumour size, tumour differentiation and comorbidities) were calculated for every patient. Relative risks (RR) of early death 9 and 12 months after PD were then calculated. Results Of 270 PD for various aetiologies, 120 PD for adenocarcinomas were included. The median follow-up was 37 months, and the overall median survival was 19 months. EMRS of 4 showed a mortality RR of 5.1 at 9 months (P = 0.048) and of 4.5 at 12 months (P = 0.020). Conclusions EMRS of 4 is a predictor of tumour-related mortality at 9 and 12 months after PD for adenocarcinoma. The EMRS was externally assessed in our patient cohort and can be implemented in clinical practice. Clinical implications of this score still need to be studied. PMID:25906918

  15. 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

  16. Clinicopathological Features of Low-Grade Thyroid-like Nasopharyngeal Papillary Adenocarcinoma

    PubMed Central

    Li, Minhua; Wei, Jiangguo; Yao, Xiaofei; Wang, Cheng

    2017-01-01

    Purpose Primary low-grade thyroid-like papillary adenocarcinomas are extremely rare neoplasms that generally originate in the nasopharynx. Here, we describe a novel case of a 15-year-old Chinese girl who was diagnosed with low-grade thyroid-like papillary adenocarcinoma, including a brief review of the literature to reveal the clinicopathological features of low-grade thyroid-like nasopharyngeal papillary adenocarcinoma. Materials and Methods Immunohistochemistry was used to evaluate the expression of pan-cytokeratin (CKpan), cytokeratin (CK) 7, thyroid transcription factor 1 (TTF-1), vimentin, epithelial membrane antigen (EMA), thyroglobulin, CD15, S100, P40, CK20, CDX-2, glial fibrillary acidic protein (GFAP), and Ki-67. Additionally, in situ hybridization investigation was utilized to identify the presence of small Epstein-Barr virus (EBV)–encoded RNA. Results Histopathological analysis revealed florid proliferation of papillary structures lined by columnar epithelial cells with fibrovascular cores. Immunohistochemically, the neoplastic cells were positive for CKpan, CK7, TTF-1, vimentin, and EMA, but negative for thyroglobulin, CD15, S100, P40, CK20, CDX-2, and GFAP. The Ki-67–labeling index reached 5% in the most concentrated spot. In situ hybridization for EBV was negative. Conclusion Due to the distinct rarity of low-grade thyroid-like papillary adenocarcinomaswith a favorable clinical outcome, a nationwide effort to raise public awareness of this neoplasm is required. PMID:27384157

  17. Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin.

    PubMed

    Park, Won Young; Kim, Mi Hyun; Shin, Dong Hoon; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Park, Do Youn; Lee, Chang Hun; Sol, Mee Young

    2012-09-01

    Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma.

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

    PubMed Central

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

    2009-01-01

    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. PMID:19674468

  19. 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 Central

    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

    Objective 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). Methods 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 χ2 test; a meta-analysis was performed on the 2 cohorts using the Mantel-Haenszel method. Results 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)). Conclusions 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. PMID:26629363

  20. Expression and Diagnostic Value of HE4 in Pancreatic Adenocarcinoma

    PubMed Central

    Huang, Tianhe; Jiang, Shi-Wen; Qin, Liangyi; Senkowski, Christopher; Lyle, Christian; Terry, Karen; Brower, Steven; Chen, Haibin; Glasgow, Wayne; Wei, Yongchang; Li, Jinping

    2015-01-01

    Human epididymis protein 4 (HE4) is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. The diagnostic value of HE4 in pancreatic adenocarcinoma remains unknown. Here we elucidate mRNA, protein and serum level of HE4 in pancreatic adenocarcinoma. HE4 mRNA level in tumor adjacent tissues and pancreatic adenocarcinoma tissues were tested by real time-PCR. Tissue microarray containing normal, adenocarcinoma, and adjacent pancreatic tissue was tested by immunohistochemistry (IHC). Serum level of HE4, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3) and carbohydrate antigen 125 (CA125) were detected by ELISA assay in control and tumor patients. Further we compared the sensitivity and specificity of determining HE4, CA19-9, CA15-3, and CA125 for diagnosis of pancreatic adenocarcinoma and assessed the complementary diagnostic value of HE4, CA19-9, CA15-3 and CA125. Real time PCR showed significantly increased HE4 mRNA level in pancreatic adenocarcinoma compared with control. Result of IHC showed that HE4 significantly higher expressed in the human pancreatic carcinoma tissues than in both normal and adjacent non-tumorous pancreatic tissues, and the staining intensity is inversely correlated with the clinical stage. HE4 was highly expressed in early stage of pancreatic adenocarcinoma. Serum HE4 level is higher in cases with pancreatic adenocarcinoma than in the controls. Serum HE4 levels could research to a sensitivity of 45.83% and specificity of 93.75% when the Cutoff was set at 4.59 ng/mL. The Combined HE4 and CA19-9 increased the sensitivity to 83.33%; and interestingly, the combination of HE4 with CA15-3 led to the most powerful sensitivity of 87.5%. Combined with CA19-9 and CA15-3, HE4 could be a potential biomarker to improve the diagnostic power for pancreatic adenocarcinoma. PMID:25642754

  1. Management of stage II endometrial adenocarcinoma

    SciTech Connect

    Trimble, E.L.; Jones, H.W. III

    1988-03-01

    Charts of 36 patients with clinical stage II endometrial adenocarcinoma over ten years were reviewed. All were staged before any treatment, in accordance with International Federation of Gynecology and Obstetrics (FIGO) guidelines. Although details of treatment varied, two main protocols were used. Fourteen patients were treated with the standard protocol involving external whole-pelvis radiation, followed by intracavitary cesium and then hysterectomy. In 1981, a modified protocol was introduced, which called for a hysterectomy immediately following intrauterine and vaginal cesium. External radiation therapy was given only to those patients found to have deep myometrial invasion or cervical involvement. Of 14 patients treated by this protocol, seven had no surgical indication for postoperative external radiation. There was no increase in recurrence in these patients, and the five-year survival rate was 76% for patients treated with the modified protocol compared with 65% for those who had standard therapy. Morbidity related to external radiation therapy occurred in two patients with the standard protocol and one patient who received pelvic radiation on the modified protocol.

  2. Gland cell carcinoma (adenocarcinoma) of the cervix.

    PubMed

    Hopkins, M P; Schmidt, R W; Roberts, J A; Morley, G W

    1988-11-01

    A review of 203 patients with adenocarcinoma of the cervix treated at the University of Michigan Medical Center from 1970-1985 is reported. The following subtypes were identified: endocervical, 94 (46%); adenosquamous, 67 (33%); papillary, 21 (11%); clear cell, 16 (8%); and mucoid, five (4%). The distribution by stage of disease included stage I, 125 (62%); stage II, 40 (20%); stage III, 25 (12%); and stage IV, 13 (6%). One patient was lost to follow-up. Overall, 107 patients (53%) died from disease. The cumulative 5-year survival rate varied significantly according to the following: stage of disease--stage I 60%, stage II 47%, stage III 8%, stage IV 0%; tumor grade--well-differentiated 75%, moderately differentiated 57%, poorly differentiated 29%; lymph node status--negative nodes 79%, positive nodes 12%; patient age--less than 40 years 65%, 40-60 years 46%, over 60 years 30%; and interval from previous pelvic examination--within 1 year 65%, 1-3 years 41%, beyond 3 years 36%. The histologic subtype did not significantly influence survival. Treatment strategies should be directed at high-risk groups as defined by the stage of disease, tumor differentiation, and lymph node status.

  3. 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

  4. Advanced gastric adenocarcinoma: optimizing therapy options.

    PubMed

    Mizrak Kaya, Dilsa; Harada, Kazuto; Shimodaira, Yusuke; Amlashi, Fatemeh G; Lin, Quan; Ajani, Jaffer A

    2017-03-01

    Gastric adenocarcinoma (GAC) is the fifth most common cancer and third leading cause of cancer related mortality worldwide. When localized, cure is achievable with surgery and adjunctive therapies in some patients, however, once advanced, GAC is not a curable condition. Only two targeted agents (trastuzumab and ramucirumab) have been approved and apatinib was approved only in China. Because of the heterogeneous nature of GAC, it is not possible to assess a standard therapeutic approach. Areas covered: In this review, we aimed to describe the optimal systemic therapy regimens for advanced GAC. A literature search was performed to identify all phase II-III studies about advanced GAC from PubMed, clinicaltrials.gov, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) websites. Expert commentary: A combination of a platinum compound and a fluoropyrimidine is ideal as first line therapy. Trastuzumab should be added if the tumor is HER2 positive. In the second line setting, paclitaxel/ramucirumab is preferred over ramucirumab alone. Recently, two similar molecular classifications for GAC have been proposed. A better understanding of molecular and immune biology of GAC could identify new therapeutic targets.

  5. Annexin A3 Knockdown Suppresses Lung Adenocarcinoma

    PubMed Central

    Liu, Qing-Qing; Zhang, Yue-Hua; Qiu, Jing-Hua

    2016-01-01

    Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin. PMID:27995049

  6. 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.

  7. 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

  8. Interventional Nanotheranostics of Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Li, Junjie; Liu, Fengyong; Gupta, Sanjay; Li, Chun

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of all pancreatic cancer. Nanoparticles (NPs) offer new opportunities for image-guided therapy owing to the unique physicochemical properties of the nanoscale effect and the multifunctional capabilities of NPs. However, major obstacles exist for NP-mediated cancer theranostics, especially in PDAC. The hypovascular nature of PDAC may impede the deposition of NPs into the tumor after systemic administration, and most NPs localize predominantly in the mononuclear phagocytic system, leading to a relatively poor tumor-to-surrounding-organ uptake ratio. Image guidance combined with minimally invasive interventional procedures may help circumvent these barriers to poor drug delivery of NPs in PDAC. Interventional treatments allow regional drug delivery, targeted vascular embolization, direct tumor ablation, and the possibility of disrupting the stromal barrier of PDAC. Interventional treatments also have potentially fewer complications, faster recovery, and lower cost compared with conventional therapies. This work is an overview of current image-guided interventional cancer nanotheranostics with specific attention given to their applications for the management of PDAC. PMID:27375787

  9. [Omics technologies in diagnostics of lung adenocarcinoma].

    PubMed

    Novikova, S E; Kurbatov, L K; Zavialova, M G; Zgoda, V G; Archakov, A I

    2017-05-01

    To date lung adenocarcinoma (LAC) is the most common type of lung cancer. Numerous studies on LAC biology resulted in identification of crucial mutations in protooncogenes and activating neoplastic transformation pathways. Therapeutic approaches that significantly increase the survival rate of patients with LAC of different etiology have been developed and introduced into clinical practice. However, the main problem in the treatment of LAC is early diagnosis, taking into account both factors and mechanisms responsible in tumor initiation and progression. Identification of a wide biomarker repertoire with high specificity and reliability of detection appears to be a solution to this problem. In this context, proteins with differential expression in normal and pathological condition, suitable for detection in biological fluids are the most promising biomarkers. In this review we have analyzed literature data on studies aimed at search of LAC biomarkers. The major attention has been paid to protein biomarkers as the most promising and convenient subject of clinical diagnosis. The review also summarizes existing knowledge on posttranslational modifications, splice variants, isoforms, as well as model systems and transcriptome changes in LAC.

  10. Pancreatic adenocarcinoma pathology: changing “landscape”

    PubMed Central

    Brosens, Lodewijk A. A.; Hackeng, Wenzel M.; Offerhaus, G. Johan; Hruban, Ralph H.

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improve the prognosis of patients with pancreatic cancer, it is essential to diagnose and treat pancreatic cancer in the earliest stage. Prevention of pancreatic cancer by treating noninvasive precursor lesions just before they invade tissues can potentially lead to even better outcomes. Pancreatic carcinogenesis results from a stepwise progression in which accumulating genetic alterations drive neoplastic progression in well-defined precursor lesions, ultimately giving rise to an invasive adenocarcinoma. A thorough understanding of the genetic changes that drive pancreatic carcinogenesis can lead to identification of biomarkers for early detection and targets for therapy. Recent next-generation sequencing (NGS) studies have shed new light on our understanding of the natural history of pancreatic cancer and the precursor lesions that give rise to these cancers. Importantly, there is a significant window of opportunity for early detection and treatment between the first genetic alteration in a cell in the pancreas and development of full-blown pancreatic cancer. The current views on the pathology and genetics of pancreatic carcinogenesis that evolved from studies of pancreatic cancer and its precursor lesions are discussed in this review. PMID:26261723

  11. Genetic alterations in lung adenocarcinoma with a micropapillary component

    PubMed Central

    FURUKAWA, MASASHI; TOYOOKA, SHINICHI; ICHIMURA, KOUICHI; YAMAMOTO, HIROMASA; SOH, JUNICHI; HASHIDA, SHINSUKE; OUCHIDA, MAMORU; SHIEN, KAZUHIKO; ASANO, HIROAKI; TSUKUDA, KAZUNORI; MIYOSHI, SHINICHIRO

    2016-01-01

    Pulmonary adenocarcinoma (PA) with a micropapillary component (PA-MPC) is known as an aggressive subtype of PA. The molecular profiles of PA-MPC have not been well characterized. the pathological reports of patients who underwent surgical resection for lung cancer between April, 2004 and May, 2012 were reviewed. Of the 674 patients diagnosed with PA, 28 were found to have MPC. A total of 138 resected PAs without MPC were selected in the same period to serve as age-, gender- and smoking status-matched controls to the PA-MPC group. Mutational status was determined by the following two methods: SNaPshot assay based on multiplex polymerase chain reaction (PCR), primer extension and capillary electrophoresis that was designed to assess 38 somatic mutations in 8 genes [AKT1, BRAF, endothelial growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), mitogen-activated protein kinase kinase 1, neuroblastoma RAS viral oncogene homolog, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA) and phosphatase and tensin homolog]; and a PCR-based sizing assay that assesses EGFR exon 19 (deletions), EGFR exon 20 (insertions) and human epidermal growth factor receptor 2 exon 20 (insertions). echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene (EML4-ALK) was screened by ALK immunohistochemistry and confirmed using the reverse transcription PCR assay and the break-apart fluorescence in situ hybridization assay. Regarding genetic alterations, 13 (46.4%) of the 28 PA-MPCs harbored mutually exclusive mutations: 9 (32.1%) EGFR mutations, 1 (3.6%) KRAS mutation and 3 (10.7%) EML4-ALK fusion genes. PAs without MPC harbored 42 (30.4%) EGFR mutations, 17 (12.3%) KRAS mutations, 3 (2.2%) EML4-ALK fusion genes and 1 (0.7%) PIK3CA mutation. EML4-ALK fusion genes appeared to occur significantly more frequently in PA-MPCs compared with PAs without MPC (P=0.027). Although the sample size was small, our study

  12. Coexistence of gastrointestinal stromal tumors and gastric adenocarcinomas.

    PubMed

    Yan, Yan; Li, Ziyu; Liu, Yiqiang; Zhang, Lianhai; Li, Jiyou; Ji, Jiafu

    2013-04-01

    The purpose of this study is to detect the clinicopathology of gastrointestinal stromal tumors (GISTs) occurring synchronously with gastric adenocarcinomas and to unveil the potential underlying relationship between the synchronous GIST and gastric adenocarcinoma. This study included 15 patients with incidental GISTs found during operations for gastric adenocarcinoma and 30 patients who underwent gastrectomy for gastric cancer without discovering GIST between January 2005 and December 2010 at the Beijing Cancer Institute. We collected the clinicopathological data and analyzed the KIT/PDGFRA mutational status of GISTs, corresponding gastric adenocarcinoma specimens, and the normal tissue around the cancer lesions. Additionally, as a control group, the mutational status of the patients with gastric adenocarcinoma and no other tumors was assayed. Overall, 18 GISTs were found in 15 gastric adenocarcinoma patients. Multiple GIST lesions were found in three cases (20 %). The patients' age ranged from 46 to 85 years, with an average of 67.6 years. The average size of the GISTs was 0.85 cm. All mesenchymal lesions showed low proliferative activity, were of low or very low risk, and were identified as CD117-positive by immunostaining. In GIST lesions, mutations in KIT were detected in 7 out of 13 cases, and of these mutations, 6 were found in exon 11 (46.2 %), and 1 was found in exon 9 (7.7 %). A total of five deletions and one point mutation were in exon 11, and one insertion was in exon 9. Mutations were not detected in exon 17 or 13 of KIT. There was no remarkable mutation analyzed in the gastric adenocarcinoma lesions or normal tissues from either the test or control groups. Clinicopathological profiles and molecular analysis of KIT/PDGFRA showed no obvious relationship between gastric cancer and GISTs in tumor genesis, such as similar oncogene mutations.

  13. 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.

  14. Genetic progression of Barrett's oesophagus to oesophageal adenocarcinoma.

    PubMed

    Gregson, Eleanor M; Bornschein, Jan; Fitzgerald, Rebecca C

    2016-08-09

    Barrett's oesophagus (BE) is the premalignant condition associated with the development of oesophageal adenocarcinoma (OAC). Diagnostically, p53 immunohistochemistry remains the only biomarker recommended clinically to aid histopathological diagnosis. The emerging mutational profile of BE is one of highly heterogeneous lesions at the genomic level with many mutations already occurring in non-dysplastic tissue. As well as point mutations, larger scale copy-number changes appear to have a key role in the progression to OAC and clinically applicable assays for the reliable detection of aneuploidy will be important to incorporate into future clinical management of patients. For some patients, the transition to malignancy may occur rapidly through a genome-doubling event or chromosomal catastrophe, termed chromothripsis, and detecting these patients may prove especially difficult. Given the heterogeneous nature of this disease, sampling methods to overcome inherent bias from endoscopic biopsies coupled with the development of more objective biomarkers than the current reliance on histopathology will be required for risk stratification. The aim of this approach will be to spare low-risk patients unnecessary procedures, as well as to provide endoscopic therapy to the patients at highest risk, thereby avoiding the burden of incurable metastatic disease.

  15. Pancreatic adenocarcinomas frequently show p53 gene mutations.

    PubMed Central

    Scarpa, A.; Capelli, P.; Mukai, K.; Zamboni, G.; Oda, T.; Iacono, C.; Hirohashi, S.

    1993-01-01

    Thirty-four pancreatic adenocarcinomas were studied for the presence of p53 gene mutations by the single-strand conformation polymorphism method and by direct sequencing of PCR-amplified fragments. p53 protein expression was immunohistochemically evaluated using monoclonal PAb1801 and polyclonal CM1 antibodies. Mutations were detected in 14 cases. The transitions were six G to A and two A to G; the transversions were one C to G and two A to C; the remaining three were frameshift mutations. Immunostaining results were identical with both antibodies. Nuclear immunohistochemical p53-positive cells were found in nine p53 mutated cases and in 12 cases in which no mutation was detected. In most of these latter cases only a minority of cancer cells showed immunohistochemical positivity. Twenty-nine cases, including all p53 mutated cancers, were known to contain codon 12 Ki-ras gene mutations. Also in the light of the demonstrated cooperation of ras and p53 gene alterations in the transformation of cultured cells, our data suggest that p53 mutation is one of the genetic defects that may have a role in the pathogenesis of a proportion of pancreatic cancers. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8494051

  16. Effect of gyromagnetic fields on human prostatic adenocarcinoma cells

    PubMed Central

    Lei, Hongen; Xu, Yongde; Guan, Ruili; Li, Meng; Hui, Yu; Gao, Zhezhu; Yang, Bicheng; Xin, Zhongcheng

    2015-01-01

    Purpose To investigate the biological effect of gyromagnetic fields (GMFs) on cell proliferation and apoptosis of human prostatic adenocarcinoma cells and explore the underlying mechanisms. Methods PC-3 cells were grouped into normal control (NC) and GMF treatment groups. Cell proliferation was analyzed with kit-8 and Ki67 immunofluorescence staining, while cell apoptosis was analyzed with flow cytometry double staining of Annexin V-PE/7-AAD. The Akt and p38 MAPK/Caspase signaling pathways were analyzed by western blotting and immunofluorescence staining, and cell polarization was analyzed with PARD3. Results Cell proliferation and activity of the Akt pathway were significantly decreased by the GMF, while cell apoptosis, activity of p38 MAPK, and PARD3-positive cell number were significantly increased in the GMF group compared to the NC group. Conclusion GMFs inhibit cell proliferation, induce apoptosis, and regulate tumor cell polarity conditions, potentially through down-regulating Akt, activating the p38 MAPK/Caspase pathway, and promoting PARD3 expression in PC-3 cells. PMID:26648740

  17. The global landscape of intron retentions in lung adenocarcinoma

    PubMed Central

    2014-01-01

    Background The transcriptome complexity in an organism can be achieved by alternative splicing of precursor messenger RNAs. It has been revealed that alternations in mRNA splicing play an important role in a number of diseases including human cancers. Methods In this study, we exploited whole transcriptome sequencing data from five lung adenocarcinoma tissues and their matched normal tissues to interrogate intron retention, a less studied alternative splicing form which has profound structural and functional consequence by modifying open reading frame or inserting premature stop codons. Results Abundant intron retention events were found in both tumor and normal tissues, and 2,340 and 1,422 genes only contain tumor-specific retentions and normal-specific retentions, respectively. Combined with gene expression analysis, we showed that genes with tumor-specific retentions tend to be over-expressed in tumors, and the abundance of intron retention within genes is negatively related with gene expression, indicating the action of nonsense mediated decay. Further functional analysis demonstrated that genes with tumor-specific retentions include known lung cancer driver genes and are found enriched in pathways important in carcinogenesis. Conclusions We hypothesize that intron retentions and consequent nonsense mediated decay may collectively counteract the over-expression of genes promoting cancer development. Identification of genes with tumor-specific retentions may also help develop targeted therapies. PMID:24646369

  18. Pathology of pancreatic ductal adenocarcinoma: facts, challenges and future developments.

    PubMed

    Esposito, Irene; Konukiewitz, Björn; Schlitter, Anna Melissa; Klöppel, Günter

    2014-10-14

    Despite major improvements concerning its diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology, as interface discipline between basic and clinical medicine, has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition, by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC, a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC. This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results. Finally, recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response. The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.

  19. Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma

    PubMed Central

    Reznik, Robert; Hendifar, Andrew E.; Tuli, Richard

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided. PMID:24624093

  20. Comparative Proteomic Profiling of Pancreatic Ductal Adenocarcinoma Cell Lines

    PubMed Central

    Kim, Yikwon; Han, Dohyun; Min, Hophil; Jin, Jonghwa; Yi, Eugene C.; Kim, Youngsoo

    2014-01-01

    Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and - sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines. PMID:25518923

  1. 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.

  2. Barrett esophagus: when to endoscope.

    PubMed

    Butt, Joshua; Kandel, Gabor

    2014-01-01

    Increasing interest in identifying an effective strategy for decreasing the burden of esophageal adenocarcinoma (EAC) has been fuelled by the rising EAC rates worldwide, the morbidity associated with esophagectomy, and the development of endoscopic methods for curing early-stage EAC. In the face of this enthusiasm, however, we should be cautious about continuing our current evidence-free approach to screening and one with unclear benefits and unclear costs to the community. The literature is increasingly recognizing that the value of traditional endoscopy for screening and surveillance of Barrett esophagus may be more limited than initially believed. A better understanding of the risk factors for Barrett esophagus and progression to dysplasia and a more individualized risk calculation will be useful in defining populations to consider for Barrett screening. The development of novel, nonendoscopic screening techniques and of less expensive endoscopic techniques holds promise for a cost-effective screening and surveillance method to curtail the increasing rates of EAC.

  3. MicroRNA profiling of primary pulmonary enteric adenocarcinoma in members from the same family reveals some similarities to pancreatic adenocarcinoma-a step towards personalized therapy.

    PubMed

    Garajová, Ingrid; Funel, Niccola; Fiorentino, Michelangelo; Agostini, Valentina; Ferracin, Manuela; Negrini, Massimo; Frassineti, Giovanni Luca; Gavelli, Giampaolo; Frampton, Adam Enver; Biasco, Guido; Giovannetti, Elisa

    2015-01-01

    Primary pulmonary enteric adenocarcinoma (PEAC) is defined as a pulmonary adenocarcinoma with a predominant component of intestinal differentiation and tumor cells positive for at least one intestinal marker. The aim of the present study was the molecular and histological characterization of a PEAC from a patient with two other family members affected by similar lung tumors, which has never been reported before. We evaluated the molecular characteristics of the proband's PEAC by using a previously validated 47-microRNA (miRNA) cancer-specific array and a predictive method to estimate tissue-of-origin probabilities. Immunohistochemical (IHC) staining for thyroid transcription factor (TTF-1), napsin A, caudal-related homeobox 2 (CDX2), cytokeratins, and mucins, as well as mutational analyses for epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and anaplastic lymphoma kinase (ALK) were performed on formalin-fixed, paraffin-embedded (FFPE) tissues. The occurrence of PEAC in two family members was associated with similar clinicopathological features (age at diagnosis, smoking habit, tumor localization, multiple colonic polyps), histologic findings (TTF-1 negativity and CDX2 positivity), and genetic findings (KRAS (Gly12Asp) mutation, but no EGFR/ALK aberrations). miRNA profiling revealed similarities with non-small cell lung cancer (NSCLC; 75.98 %) and some overlap with pancreatic ductal adenocarcinoma (PDAC; 23.34 %), but not with colorectal cancer (CRC; less than 0.5 %). Notably, these PEACs share key PDAC-associated miRNAs associated with tumor aggressiveness (miR-31*/-126*/-506/-508-3p/-514). We describe for the first time PEAC in members from the same family, associated with similar clinical and genetic features. miRNA profiling of the PEAC resembled a NSCLC signature, with partial overlap to a PDAC pattern. This could explain its aggressive behavior and therefore help to guide future tailored-therapeutic approaches.

  4. Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma

    SciTech Connect

    Safran, Howard . E-mail: hsafran@lifespan.org; Di Petrillo, Thomas; Akerman, Paul; Ng, Thomas; Evans, Devon; Steinhoff, Margaret; Benton, David; Purviance, John; Goldstein, Lisa; Tantravahi, Umadevi; Kennedy, Teresa R.N.

    2007-02-01

    Purpose: To determine the overall survival for patients with locally advanced, HER2 overexpressing, esophageal adenocarcinoma receiving trastuzumab, paclitaxel, cisplatin, and radiation on a Phase I-II study. Methods and Materials: Patients with adenocarcinoma of the esophagus without distant organ metastases and 2+/3+ HER2 overexpression by immunohistochemistry (IHC) were eligible. All patients received cisplatin 25 mg/m{sup 2} and paclitaxel 50 mg/m{sup 2} weekly for 6 weeks with radiation therapy (RT) 50.4 Gy. Patients received trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg. Results: Nineteen patients were entered: 7 (37%) had celiac adenopathy, and 7 (37%) had retroperitoneal, portal adenopathy, or scalene adenopathy. Fourteen of 19 patients (74%) had either 3+ HER2 expression by immunohistochemistry, or an increase in HER2 gene copy number by HER2 gene amplification or high polysomy by fluorescence in situ hybridization. The median survival of all patients was 24 months and the 2-year survival was 50%. Conclusions: Assessment of the effect of trastuzumab in the treatment of patients with esophageal adenocarcinoma overexpressing HER2 is limited by the small number of patients in this study. Overall survival, however, was similar to prior studies without an increase in toxicity. Evaluation of HER2 status should be performed in future trials for patients with adenocarcinoma of the esophagus that investigate therapies targeting the HER family.

  5. The incremental benefit of EUS for identifying unresectable disease among adults with pancreatic adenocarcinoma: A meta-analysis

    PubMed Central

    James, Paul D.; Zhang, Mei; Belletrutti, Paul J.; Mohamed, Rachid; Ghali, William; Roberts, Derek J.; Martel, Guillaume; Heitman, Steven J.

    2017-01-01

    Background and study aims It is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma. Patients and methods We searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression. Results Among 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10–33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8–24%) after a CT scan was performed. Limitations The majority of the included studies were retrospective. Conclusions EUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma. PMID:28319148

  6. Preoperative computed tomography measurements of pancreatic steatosis and visceral fat: prognostic markers for dissemination and lethality of pancreatic adenocarcinoma

    PubMed Central

    Mathur, Abhishek; Hernandez, Jonathan; Shaheen, Fawad; Shroff, Miloni; Dahal, Sujat; Morton, Connor; Farrior, Thomas; Kedar, Raj; Rosemurgy, Alexander

    2011-01-01

    Background Increased visceral fat and pancreatic steatosis promote lymphatic metastases and decreased survival in patients with pancreatic adenocarcinoma after pancreatoduodenectomy (PD). Objectives We aim to determine the utility of preoperative computed tomography (CT) measurements of pancreatic steatosis and visceral fat as prognostic indicators in patients with pancreatic adenocarcinoma. Methods High-resolution CT scans of 42 patients undergoing PD for pancreatic adenocarcinoma were reviewed. Attenuation in CT of the pancreas, liver and spleen were measured in Hounsfield units and scored by two blinded investigators. Perirenal adipose tissue was measured in mm. Results Lymphatic metastases were present in 57% of patients. Age, gender, tumour size and margin status were similar in patients with and without nodal metastases. Node-positive patients had increased visceral but not subcutaneous fat pads compared with node-negative patients and decreased CT attenuation of the pancreatic body and tail and liver. Node-positive patients stratified by visceral adiposity (≥10 mm vs. <10 mm) demonstrated poorer survival (7 ± 1 months vs. 16 ± 2 months; P < 0.01). Conclusions In resected pancreatic adenocarcinoma, increased pancreatic steatosis and increased visceral fat stores are associated with lymphatic metastases. Furthermore, increased visceral fat is associated with abbreviated survival in patients with lymphatic metastases. Hence, increased visceral fat may be a causative factor of abbreviated survival and serves a prognostic role in patients with pancreatic malignancies. PMID:21609373

  7. Epidermal growth factor receptor mutation in adenocarcinoma lung in a North Indian population: Prevalence and relation with different clinical variables

    PubMed Central

    Kasana, Basharat Ahmad; Dar, Waseem Raja; Aziz, Sheikh Aijaz; Lone, Abdul Rashid; Sofi, Najeeb Ullah; Dar, Imtiyaz Ahmad; Latief, Muzamil; Arshad, Faheem; Hussain, Moomin; Hussain, Mir

    2016-01-01

    Introduction: Lung cancer is one of the most common causes of cancer deaths worldwide. Adenocarcinoma is taking over squamous cell lung cancer as the predominant histological subtype. Several cytotoxic drugs are available for the treatment of lung cancer, but side effects limit their use. Recently, targeted therapies for cancers have come into clinical practice. Aims and Objectives: To determine the prevalence of epidermal growth factor receptor (EGFR) mutation in adenocarcinoma lung in a North Indian population and its relation with different clinical variables. Materials and Methods: A total of 57 patients who met inclusion criteria were recruited into the study. Relevant history, clinical examination and investigations were done. EGFR mutation was done in all patients. Results: A total of twenty patients tested positive for EGFR mutation. EGFR was more frequently detected in female patients (53.8%), while as only 19.4% of the male patients expressed EGFR mutation, which was statistically very significant (P = 0.007). EGFR mutation was more frequently detected in nonsmokers (52%) as compared to smokers (21.9%) which also was statistically significant (P value of 0.018). EGFR mutation was more common in Stage III and IV adenocarcinomas (48%) as compared to Stage I and II (21.4%) which was statistically significant (P value 0.034). Conclusion: EGFR mutation should be routinely done in all patients of adenocarcinoma lung particularly non-smoker females with Stage III and IV disease. PMID:27688613

  8. Caspase 8 polymorphisms contribute to the prognosis of advanced lung adenocarcinoma patients after platinum-based chemotherapy.

    PubMed

    Liu, Di; Xu, Wen; Ding, Xi; Yang, Yang; Lu, Yanlin; Fei, Ke; Su, Bo

    2017-02-16

    Lung cancer is the leading cause of cancer deaths in China, and about 60% of the cases are diagnosed with histological adenocarcinoma. The caspase 8 (CASP8) gene is a critical initiator of the extrinsic apoptosis pathway. To explore the relationship between tagSNPs or haplotypes of CASP8 and the efficacy of platinum-based chemotherapy in advanced lung adenocarcinoma patients of China, we recruited 555 advanced adenocarcinoma patients. We extracted the genomic DNA from patients' peripheral blood samples and sequenced tagSNPs of CASP8. We calculated the individual haplotype of CASP8 frequencies using the PHASE 2.0 program. The association between CASP8 tagSNPs and overall survival (OS) was calculated by univariate and multivariate Cox regression analysis. A univariate logistic regression analysis was done to analyze the CASP8 tagSNPs and the toxicity of platinum-based chemotherapy. The same statistical methods were used for exploring haplotypes of CASP8. Rs3769821 and rs1045494 of CASP8 were independent prognosis factors for overall survival (OS) using multivariate Cox's regression models. For the haplotype of the seven tagSNPs, haplotype AGGAAAGA was correlated with the efficacy of platinum-based chemotherapy. The polymorphisms of CASP8, rs7608692, and haplotype AGAACAG correlated with neutropenia toxicity. The haplotype GGGGAAA was associated with thrombocytopenia toxicity. We conclude that the polymorphisms of CASP8 contribute to the prognosis of advanced lung adenocarcinoma and influence the quality of life and survival.

  9. Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett's esophagus, dysplasia and adenocarcinoma

    PubMed Central

    Lehenkari, Petri P.; Saarnio, Juha; Karttunen, Tuomo J.; Kauppila, Joonas H.

    2016-01-01

    Background Toll-like receptors (TLRs) recognize microbial and endogenous ligands and have already shown to play a role in esophageal cancer. In this study, we evaluated especially TLRs that sense bacterial cell wall components in Barrett's esophagus, dysplasia and esophageal adenocarcinoma. Methods TLRs 1, 2, 4 and 6 were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal dysplasia (n = 30) or adenocarcinoma (n = 99). Structures and lesions were evaluated including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37), and esophageal adenocarcinoma (n = 99). Results We found TLR1, TLR2, TLR4 and TLR6 expression in all lesions. TLR expression increased in Barrett's mucosa and dysplasia. There was profound increase of TLR expression from gastric- to intestinal-type columnar epithelium. In cancers, high nuclear and cytoplasmic staining of TLR4 associated with metastatic disease and poor prognosis. Conclusions TLR1, TLR2, TLR4 and TLR6 are upregulated during malignant changes of esophageal columnar epithelium. Increased TLR4 expression associates with advanced stage and poor prognosis in esophageal adenocarcinoma. PMID:27008696

  10. 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.

  11. Lung Adenocarcinoma Staging Using the 2011 IASLC/ATS/ERS Classification: A Pooled Analysis of Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma.

    PubMed

    Behera, Madhusmita; Owonikoko, Taofeek K; Gal, Anthony A; Steuer, Conor E; Kim, Sungjin; Pillai, Rathi N; Khuri, Fadlo R; Ramalingam, Suresh S; Sica, Gabriel L

    2016-09-01

    Lung adenocarcinoma accounts for almost 60% of non-small-cell lung cancer. According to the 2011 International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) classification and 2015 World Health Organization classification of tumors of the lung, lepidic-predominant adenocarcinomas ≤ 3 cm in size can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma, lepidic predominant. AIS lesions, which are noninvasive, and MIA lesions, which show ≤ 0.5 cm of invasion, have been recommended to be considered stage pTis (adenocarcinoma) and pT1(mi), respectively. We conducted a systematic analysis of the published data to evaluate the prognostic differences between AIS and MIA. A comprehensive search of published studies was conducted from the electronic databases using relevant search criteria. Studies that reported outcomes for ≥ 8 cases classified as AIS or MIA using the 2011 IASLC/ATS/ERS criteria were selected for the present analysis. A systematic analysis of the extracted data were performed using Comprehensive Meta-Analysis software, version 2.2. Nineteen studies published from 2011 to 2015 were eligible. A total of 972 patients were included (429 with AIS and 294 with MIA; 2 studies reported AIS and MIA together, n = 249). The median age was 65.5 years, 63% were female, and 40% were smokers. The 5-year disease-free survival rate for the whole population was 97.9%. The 5-year disease-free survival rate was 100% for AIS and MIA pooled from the studies that reported the 2 groups separately. The 5-year overall survival rate for the entire group was 97.5%, and the 5-year overall survival rate was 100% for AIS and 98.5% for MIA. No significant differences were found in the survival rates between patients with lung adenocarcinoma categorized as MIA or AIS. This finding raises questions regarding the evidence for TNM staging of AIS

  12. Lymph Node Positivity in Appendiceal Adenocarcinoma: Should Size Matter?

    PubMed

    Gahagan, John V; Whealon, Matthew D; Phelan, Michael J; Mills, Steven; Pigazzi, Alessio; Stamos, Michael J; Nguyen, Ninh T; Carmichael, Joseph C

    2017-07-01

    The management algorithm for appendiceal adenocarcinoma is not well defined. This study sought to determine whether tumor size or depth of invasion better correlates with the presence of lymph node metastases in appendiceal adenocarcinoma, and to compare these rates with colon adenocarcinoma. A retrospective review of the National Cancer Database was performed to identify patients with appendiceal or colonic adenocarcinoma from 2004 to 2013 who underwent surgical resection. Cases were categorized by tumor size and by T stage. Rates of lymph node metastases were examined as a function of size and T stage. A total of 3,402 appendiceal and 314,864 colonic cases were identified. For appendiceal adenocarcinoma, larger tumor size was associated with higher T stage: Pearson correlation of 0.41 (95% CI 0.408 to 0.414; p < 0.001). Lymph node metastases were present in 19.1%, 27.8%, 39.6%, 39.4%, 42.4% and 39.1% for tumor sizes <1 cm, >1 to 2 cm, >2 to 3 cm, >3 to 4 cm, >4 to 5 cm, and >5 cm, respectively. Lymph node metastases were present in 0%, 11.2%, 12.3%, 35.5%, and 40.0% for in situ, T1, T2, T3, and T4 tumors, respectively. There was no difference in the rates of lymph node metastases between appendiceal and colonic adenocarcinoma for tumor sizes <3 cm, or for in situ and T1 tumors. Rates of lymph node metastases are higher in colonic adenocarcinoma for tumor sizes >3 cm and for T2, T3, and T4 tumors (p < 0.01). In appendiceal adenocarcinoma, the rate of lymph node metastases is substantial, even for small tumors. Tumor size should play no role in the decision of whether to perform a hemicolectomy. Appendectomy alone does not produce an adequate lymph node sample. Right hemicolectomy should be performed for all appendiceal adenocarcinomas. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Utility of Genomic Analysis in Differentiating Synchronous and Metachronous Lung Adenocarcinomas from Primary Adenocarcinomas with Intrapulmonary Metastasis.

    PubMed

    Saab, Jad; Zia, Hamid; Mathew, Susan; Kluk, Michael; Narula, Navneet; Fernandes, Helen

    2017-06-01

    Distinguishing synchronous and metachronous primary lung adenocarcinomas from adenocarcinomas with intrapulmonary metastasis is essential for optimal patient management. In this study, multiple lung adenocarcinomas occurring in the same patient were evaluated using comprehensive histopathologic evaluation supplemented with molecular analysis. The cohort included 18 patients with a total of 52 lung adenocarcinomas. Eleven patients had a new diagnosis of multiple adenocarcinomas in the same lobe (n=5) or different lobe (n=6). Seven patients had a history of lung cancer and developed multiple new tumors. The final diagnosis was made in resection specimens (n=49), fine needle aspiration (n=2), and biopsy (n=1). Adenocarcinomas were non-mucinous, and histopathologic comparison of tumors was performed. All tumors save for one were subjected to ALK gene rearrangement testing and targeted Next Generation Sequencing (NGS). Using clinical, radiologic, and morphologic features, a confident conclusion favoring synchronous/metachronous or metastatic disease was made in 65% of patients. Cases that proved challenging included ones with more than three tumors showing overlapping growth patterns and lacking a predominant lepidic component. Genomic signatures unique to each tumor were helpful in determining the relationship of multiple carcinomas in 72% of patients. Collectively, morphologic and genomic data proved to be of greater value and achieved a conclusive diagnosis in 94% of patients. Assessment of the genomic profiles of multiple lung adenocarcinomas complements the histological findings, enabling a more comprehensive assessment of synchronous, metachronous, and metastatic lesions in most patients, thereby improving staging accuracy. Targeted NGS can identify genetic alterations with therapeutic implications. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Gli promotes epithelial-mesenchymal transition in human lung adenocarcinomas

    PubMed Central

    Jin, Joy Q.; Woodard, Gavitt A.; Tolani, Bhairavi; Luh, Thomas M.; Giroux-Leprieur, Etienne; Mo, Minli; Chen, Zhao; Che, Juanjuan; Zhang, Zhenfa; Zhou, Yong; Wang, Lei; Hao, Xishan; Jablons, David; Wang, Changli; He, Biao

    2016-01-01

    Adenocarcinoma is the most common type of lung cancer. Epithelial-mesenchymal transition (EMT) is required for tumor invasion/metastasis and the components that control this process are potential therapeutic targets. This study we examined the role of Gli in lung adenocarcinoma and whether its activation regulates metastasis through EMT in lung adenocarcinoma. We found that tumors with high Gli expression had significantly lower E-Cadherin expression in two independent cohorts of patients with lung adenocarcinoma that we studied. In vitro up-regulation of SHh resulted in increased cell migration while small molecule inhibitors of Smo or Gli significantly reduced cell mobility both in a wound healing assay and in a 3D cell invasion assay. Inhibition of Gli in vivo decreased tumor growth and induced an increase in E-Cadherin expression. Our results indicate that Gli may be critical for lung adenocarcinoma metastasis and that a novel Gli inhibitor shows promise as a therapeutic agent by preventing cell migration and invasion in vitro and significantly reducing tumor growth and increasing E-Cadherin expression in vivo. PMID:27533453

  15. Effect of antifreeze proteins on frozen primary prostatic adenocarcinoma cells.

    PubMed

    Koushafar, H; Rubinsky, B

    1997-03-01

    Recent studies show that prostate adenocarcinoma cells can survive cryosurgery and that cell destruction depends on the specific thermal parameters used during freezing. The goal of this preliminary study is to determine whether certain chemical compounds, known as antifreeze proteins, can induce complete human primary prostatic adenocarcinoma cell destruction by freezing, regardless of the thermal parameters used. The study also examines the mechanism by which antifreeze proteins bring about cell destruction. Antifreeze proteins were added to solutions containing human primary prostatic adenocarcinoma cells. The cells were frozen with controlled thermal parameters using a directional solidification apparatus attached to a light microscope. Cell viability was determined after thawing as a function of antifreeze protein concentration and cooling rate during freezing. The dose response study shows that for all the cooling rates tested, 10-mg/mL solutions of antifreeze protein cause the complete destruction of human primary prostatic adenocarcinoma cells frozen to a temperature at which, without these proteins, the cells survive freezing. Light microscopy shows that the lethal effect of the antifreeze proteins is related to the formation of intracellular ice in the frozen cells. CONCLUSIONS; This preliminary study has demonstrated that antifreeze proteins have the ability to generate complete destruction of prostatic adenocarcinoma cells frozen to high subzero temperatures irrespective of the cooling rates used during freezing. This suggests that introducing antifreeze proteins into undesirable tissues prior to freezing may increase the efficacy and the control over tissue destruction by cryosurgery.

  16. ATM protein is deficient in over 40% of lung adenocarcinomas.

    PubMed

    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

    2016-09-06

    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  17. 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.

  18. Multigene deletions in lung adenocarcinomas from irradiated and control mice

    SciTech Connect

    Zhang, Y.; Woloschak, G.E.

    1996-06-01

    K-ras codon 12 point mutations mRb and p53 gene deletions were examined in tissues from 120 normal lungs and lung adenocarcinomas that were Formalin-treated and paraffin-embedded 25 years ago. The results showed that 12 of 60 (20%) lung adenocarcinomas had mRb deletions. All lung adenocarcinomas that were initially found bearing deleted mRb had p53 deletions (15 of 15; 100%). A significantly higher mutation frequency for K-ras codon 12 point mutations was also found in the lung adenocarcinomas from mice exposed to 24 once-weekly neutron irradiation (10 of 10; 100%) compared with those exposed to 24 or 60 once-weekly {gamma}-ray doses (5 of 10; 50%). The data suggested that p53 and K-ras gene alterations were two contributory factors responsible for the increased incidence of lung adenocarcinoma in B6CF{sub 1} male mice exposed to protracted neutron radiation.

  19. Sirt3 is a tumor suppressor in lung adenocarcinoma cells.

    PubMed

    Xiao, Kui; Jiang, Jiehan; Wang, Wei; Cao, Shan; Zhu, Liming; Zeng, Huihui; Ouyang, Ruoyun; Zhou, Rui; Chen, Ping

    2013-09-01

    Sirt3, a member of the mammalian sirtuin family protein that is localized to mitochondria, is a NAD+-dependent deacetylase and plays an important role in the control of metabolic activity. Recently, several studies have shown the potential role of Sirt3 in certain types of tumors such as breast cancer and hepatocellular carcinoma. However, the role of Sirt3 in lung adenocarcinoma has never been studied. In the present study, we found that Sirt3 protein expression was downregulated in human lung adenocarcinoma tissue when compared with that in adjacent normal tissue. Overexpression of Sirt3 using adenovirus significantly inhibited the growth of the A549 lung adenocarcinoma cell line. In this cell line, overexpression of Sirt3 induced apoptosis, which was evidenced by Annexin V + PI assay and cleaved caspase-3 immunoblotting. Furthermore, overexpression of Sirt3 increased the bax/bcl-2 and bad/bcl-x/L ratios, and promoted AIF translocation to the nucleus. Finally, Sirt3 overexpression upregulated p53 and p21 protein levels, and decreased intracellular ROS levels. Collectively, our data suggest that Sirt3 is a tumor suppressor in lung adenocarcinoma development and progression and may be a promising therapeutic target for lung adenocarcinoma.

  20. Intestinal Type Adenocarcinoma from Inverted Papilloma: A Rare Recurrence

    PubMed Central

    Singh, Garima; Singh, Meeta; Chandana, Mansi; Nargotra, Namrata

    2016-01-01

    Inverted Papilloma (IP) is an uncommon and locally aggressive benign tumour of sinonasal region, which tends to recur after surgical resection. Most tumours are confined to the lateral nasal wall and sinuses, with maxillary sinus being most commonly affected and a male preponderance. It has a known association with in situ and invasive carcinomas with a <10% rate of malignant transformation. Most common association has been seen with squamous cell carcinoma and extremely rare association with adenocarcinoma and small cell carcinoma. A 36-year-old male presented with a left sided polypoidal nasal mass and underwent a polypectomy. Pathology results showed IP with mild dysplasia. The polypoidal growth reappeared on the same side after a period of 10 months and on histopathological examination, the growth revealed features of intestinal type adenocarcinoma. IP recurring as adenocarcinoma is rare and even after exhaustive literature search only few cases could be found. Two studies have described recurrence of adenocarcinoma in existing IP previously. We report an unusual case of inverted papilloma showing malignant transformation into an intestinal type adenocarcinoma in a 36-year-old male patient within 10 months of previous surgery. PMID:28050382

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

    PubMed Central

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

    2015-01-01

    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. PMID:26356813

  2. Gemcitabine resistance in pancreatic ductal adenocarcinoma.

    PubMed

    Binenbaum, Yoav; Na'ara, Shorook; Gil, Ziv

    2015-11-01

    Pancreatic ductal adenocarcinoma (PDA) ranks fourth among cancer related deaths. The disappointing 5-year survival rate of below 5% stems from drug resistance to all known therapies, as well as from disease presentation at a late stage when PDA is already metastatic. Gemcitabine has been the cornerstone of PDA treatment in all stages of the disease for the last two decades, but gemcitabine resistance develops within weeks of chemotherapy initiation. From a mechanistic perspective, gemcitabine resistance may result from alterations in drug metabolism until the point that the cytidine analog is incorporated into the DNA, or from mitigation of gemcitabine-induced apoptosis. Both of these drug resistance modalities can be either intrinsic to the cancer cell, or influenced by the cancer microenvironment. Mechanisms of intrinsic gemcitabine resistance are difficult to tackle, as many of the genes that drive the carcinogenic process itself also interfere with gemcitabine-induced apoptosis. In this regard, recent understanding of the involvement of microRNAs in gemcitabine resistance may offer new opportunities to overcome intrinsic gemcitabine resistance. The characteristically fibrotic and immune infiltrated stroma of PDA that accompanies tumor inception and expansion is a lush ground for treatments aimed at targeting tumor microenvironment-mediated drug resistance. In the last couple of years, drugs interfering with tumor microenvironment have matured to clinical trials. Although drugs inducing 'stromal depletion' have yet failed to improve survival, they have greatly increased our understanding of tumor microenvironment-mediated drug resistance. In this review we summarize the current knowledge on intrinsic and environment-mediated gemcitabine resistance, and discuss the impact of these pathways on patient screening, and on future treatments aimed to potentiate gemcitabine activity.

  3. Genetically engineered mouse models of pancreatic adenocarcinoma.

    PubMed

    Guerra, Carmen; Barbacid, Mariano

    2013-04-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of human cancer for which there are no effective therapies. Deep sequencing of PDAC tumors has revealed the presence of a high number of mutations (>50) that affect at least a dozen key signaling pathways. This scenario highlights the urgent need to develop experimental models that faithfully reproduce the natural history of these human tumors in order to understand their biology and to design therapeutic approaches that might effectively interfere with their multiple mutated pathways. Over the last decade, several models, primarily based on the genetic activation of resident KRas oncogenes knocked-in within the endogenous KRas locus have been generated. These models faithfully reproduce the histological lesions that characterize human pancreatic tumors. Decoration of these models with additional mutations, primarily involving tumor suppressor loci known to be also mutated in human PDAC tumors, results in accelerated tumor progression and in the induction of invasive and metastatic malignancies. Mouse PDACs also display a desmoplastic stroma and inflammatory responses that closely resemble those observed in human patients. Interestingly, adult mice appear to be resistant to PDAC development unless the animals undergo pancreatic damage, mainly in the form of acute, chronic or even temporary pancreatitis. In this review, we describe the most representative models available to date and how their detailed characterization is allowing us to understand their cellular origin as well as the events involved in tumor progression. Moreover, their molecular dissection is starting to unveil novel therapeutic strategies that could be translated to the clinic in the very near future. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    PubMed

    Souza, Rhonda F

    Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-x03BA;B activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-x03BA;B activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention.

  5. Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma Cells

    PubMed Central

    Suzuki, Erika; Demo, Susan; Deu, Edgar; Keats, Jonathan; Arastu-Kapur, Shirin; Bergsagel, P. Leif; Bennett, Mark K.; Kirk, Christopher J.

    2011-01-01

    Bortezomib (Velcade™) is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM). Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ∼30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response. PMID:22216088

  6. Adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive pulmonary adenocarcinoma--analysis of interobserver agreement, survival, radiographic characteristics, and gross pathology in 296 nodules.

    PubMed

    Boland, Jennifer M; Froemming, Adam T; Wampfler, Jason A; Maldonado, Fabien; Peikert, Tobias; Hyland, Courtney; de Andrade, Mariza; Aubry, Marie Christine; Yang, Ping; Yi, Eunhee S

    2016-05-01

    The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society and 2015 World Health Organization classifications of lung adenocarcinoma recommend designating tumors showing entirely lepidic growth as adenocarcinoma in situ (AIS) and lepidic tumors with invasion less than or equal to 5 mm as minimally invasive adenocarcinoma (MIA), both of which have superior outcome to conventional invasive adenocarcinoma (IA). Data on interobserver variability within this classification are limited, and further validation of the superior survival of AIS and MIA is needed. A total of 296 surgically excised pulmonary adenocarcinomas were reviewed from 254 patients (1997-2009). Slides were independently reviewed by 2 pulmonary pathologists who categorized tumors as AIS, MIA, or IA. Of 296 nodules, 244 (82.4%) were agreed upon by both observers: 10 AIS, 61 MIA, and 173 IA (κ = 0.63, good agreement). In 6 cases (2%), there was disagreement between AIS and MIA; in 45 cases (15%), there was disagreement between MIA and IA; and in 1 case, there was disagreement between AIS and IA. Overall survival was significantly different among categories as determined by both observers. Cases with disagreement between MIA and IA had similar survival to agreed MIA. Disease-specific 10-year survival was 100% for AIS (both observers) and 97.3% and 97.6% for MIA, although this did not reach statistical significance compared to IA for either observer. Good agreement was present between observers when classifying tumors as AIS, MIA, and IA. Significant differences in overall survival were present between the 3 groups for both observers, and interobserver variability was evident. Patients with AIS and MIA experienced excellent DSS.

  7. Utility of Histoscanning™ prior to prostate biopsy for the diagnosis of prostate adenocarcinoma.

    PubMed

    Núñez-Mora, C; García-Mediero, J M; Patiño, P; Orellana, C; Garrido, A; Rojo, A; Rendón, D

    2013-06-01

    HistoScanning™ (HS) is a method of ecographic diagnosis of prostate cancer. We analyze the effectiveness of the HS realization prior to the biopsies for the prostate adenocarcinoma diagnosis. From August to October 2012 we have carried out a study with HS prior to the biopsies in 32 patients. In all cases sextants transrectal biopsies have been realized (two cores in each sextant) in the periphery zone. In those sextants in which there were suspicious areas with HS, the biopsies were addressed to those areas. Transperineal biopsies were added to those zones placed in the half-front or apical prostatic zone. The medium age was 63.7 years (range 40-82) with a medium PSA of 8.0 ng/ml (range 3.5-36.2) and a medium prostatic volume of 46.6cc (range 18.2-103.2). In eight cases it was the first biopsy, in 14 cases they were repetition biopsies and 10 patients had a previous diagnosis of prostate adenocarcinoma (8 in a program of active surveillance and 2 T1a in RTU of previous prostate). In the 32 patients a medium of 7,5 zones were biopsied (range 6-9) with a total of 239 zones studied. There were identified a medium of 3.2 zones with suspicious areas (ZS) with HS (range 2-5) with a total of 103 ZS. In 72 zones of 25 patients it was found adenocarcinoma or PIN (2 PIN, 11 score Gleason 6, 7 score Gleason 7, 3 score Gleason 8 and 2 score Gleason 9). There were 35 positive false zones in 20 patients (11 normal parenquima and 9 chronic inflammation). Negative falses were produced in 5 zones in 5 patients (2PIN, 2 score Gleason 6 and 1 score Gleason 7) although in all 5 cases adenocarcinoma was encountered (o discovered) in other zones. The HS presented a sensibility of a 93.5% with a specificity of 79.5%. The positive predictive value was of the 67.35% with a negative predictive value of 96.5%. In spite of being a selected serie, with a high rate of patients with adenocarcinoma, the exploration with HS has presented a great sensibility and a high negative predictive value

  8. A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma

    PubMed Central

    Kadota, Kyuichi; Suzuki, Kei; Kachala, Stefan S.; Zabor, Emily C.; Sima, Camelia S.; Moreira, Andre L.; Yoshizawa, Akihiko; Riely, Gregory J.; Rusch, Valerie W.; Adusumilli, Prasad S.; Travis, William D.

    2015-01-01

    , and necrosis, mitotic count was not an independent predictor of recurrence (p=0.178). However, patients with the high architectural/mitotic grade remained at significantly increased risk of recurrence (high vs. low: p=0.005) after adjusting for clinical factors. We proposed this combined architectural/mitotic grade for lung adenocarcinoma as a practical method that can be applied in routine practice. PMID:22499226

  9. A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma.

    PubMed

    Kadota, Kyuichi; Suzuki, Kei; Kachala, Stefan S; Zabor, Emily C; Sima, Camelia S; Moreira, Andre L; Yoshizawa, Akihiko; Riely, Gregory J; Rusch, Valerie W; Adusumilli, Prasad S; Travis, William D

    2012-08-01

    distinct categories (P=0.001). After adjusting for clinicopathologic factors including sex, stage, pleural/lymphovascular invasion, and necrosis, mitotic count was not an independent predictor of recurrence (P=0.178). However, patients with the high architectural/mitotic grade remained at significantly increased risk of recurrence (high vs low: P=0.005) after adjusting for clinical factors. We proposed this combined architectural/mitotic grade for lung adenocarcinoma as a practical method that can be applied in routine practice.

  10. Lymphocyte-to-monocyte ratio can predict mortality in pancreatic adenocarcinoma

    PubMed Central

    Singh, Gurshawn; Nassri, Ammar; Kim, David; Zhu, Hong; Ramzan, Zeeshan

    2017-01-01

    AIM To determine if the lymphocyte-to-monocyte ratio (LMR) could be helpful in predicting survival in patients with pancreatic adenocarcinoma. METHODS We retrospectively reviewed the medical records of all patients diagnosed with pancreatic adenocarcinoma in the VA North Texas Healthcare System from January 2005 to December 2010. The LMR was calculated from peripheral blood cell counts obtained at the time of diagnosis of pancreatic cancer by dividing the absolute lymphocyte count by the absolute monocyte count. A Univariable Cox regression analysis was performed using these data, and hazard ratios (HR) and 95%CI were calculated. The median LMR (2.05) was used to dichotomize patients into high-LMR and low-LMR groups and the log rank test was used to compare survival between the two groups. RESULTS We identified 97 patients with pancreatic adenocarcinoma (all men, 66% white, 30% African-American). The mean age and weight at diagnosis were 66.0 ± 0.9 (SEM) years and 80.4 ± 1.7 kg respectively. Mean absolute lymphocyte and monocyte values were 1.50 ± 0.07 K/μL and 0.74 ± 0.03 K/μL respectively. Mean, median and range of LMR was 2.36, 2.05 and 0.4-12 respectively. In the univariable Cox regression analysis, we found that an increased LMR was a significant indicator of improved overall survival in patients with pancreatic adenocarcinoma (HR = 0.83; 95%CI: 0.70-0.98; P = 0.027). Kaplan-Meier analysis revealed an overall median survival of 128 d (95%CI: 80-162 d). The median survival of patients in the high-LMR (> 2.05) group was significantly greater than the low-LMR group (≤ 2.05) (194 d vs 93 d; P = 0.03), validating a significant survival advantage in patients with a high LMR. CONCLUSION The LMR at diagnosis is a significant predictor for survival and can provide useful prognostic information in the management of patients with pancreatic adenocarcinoma. PMID:28217375