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BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer and is associated with an increased lifetime risk of gastric and duodenal cancers of 8–16% and 7% respectively, therefore, we aim to describe an esophagogastroduodenoscopy (EGD) surveillance program for upper gastrointestinal (GI) precursor lesions and cancer in LS patients. METHODS: Patients who either had positive genetic testing or met clinical criteria for LS who had a surveillance EGD at our institution from 1996 to 2017 were identified. Patients were included if they had at least two EGDs or an upper GI cancer detected on the first surveillance EGD. EGD and pathology reports were extracted manually. RESULTS: Our cohort included 247 patients with a mean age of 47.1 years (SD 12.6) at first EGD. Patients had a mean of 3.5 EGDs (range 1–16). Mean duration of follow-up was 5.7 years. Average interval between EGDs was 2.3 years. Surveillance EGD detected precursor lesions in 8 (3.2%) patients, two (0.8%) gastric cancers and two (0.8%) duodenal cancers. Two interval cancers were diagnosed: a duodenal adenocarcinoma was detected 2 years, 8 months after prior EGD and a jejunal adenocarcinoma was detected 1 year, 9 months after prior EGD. CONCLUSIONS: Our data suggest that surveillance EGD is a useful tool to help detect precancerous and cancerous upper GI lesions in LS patients. To our knowledge, this is the first study to examine a program of surveillance EGDs in LS patients. More data are needed to determine the appropriate surveillance interval.

Bevacizumab is a humanized anti-vascular endothelial growth factor monoclonal antibody used in the treatment of cervical cancer, ovarian cancer, colorectal cancer, lung cancer, renal cell cancer, and recurrent glioblastomas. Its approval by US FDA was issued with a black box warning that its use has been associated with a risk of gastrointestinal (GI) tract perforation and that it should be discontinued in patients who have experienced such. The reported incidence of GI perforation in those receiving bevacizumab is as high as 3%. However, the incidence of GI perforation in those receiving bevacizumab undergoing GI endoscopic procedures has not been well studied. A retrospective, single-center observational study was conducted at Memorial Sloan Kettering Cancer Center (MSKCC) between 2011 and 2018. All patients who underwent upper GI endoscopy with percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic jejunostomy (PEJ) tube placement and received bevacizumab within 6 months of their endoscopic procedure were included. We identified 176 patients who underwent PEG or PEJ tube placement and received bevacizumab within 6 months. Eighty-one percent of patients were female (n = 144) and the median age was 61 years. Prior to endoscopic procedures, patients received a median of seven doses of bevacizumab. Patients received bevacizumab from 170 days before to 170 days after their endoscopic procedures (median 44 days). No GI perforations were observed during or after the time of the endoscopic procedures. Our study demonstrated that receiving bevacizumab within 6 months prior to their endoscopic procedure was not associated with an increased risk of GI tract perforation and thus not an absolute contraindication to proceeding with PEG and PEJ tube placement in these patients.

Purpose Malignant glioma (MG) is the most deadly primary brain cancer. Signaling though the PI3K/AKT/mTOR axis is activated in most MGs and therefore a potential therapeutic target. The mTOR inhibitor temsirolimus and the AKT inhibitor perifosine are each well‐tolerated as single agents but with limited activity reclinical data demonstrate synergistic anti‐tumor effects from combined treatment. Therefore, we initiated a phase I trial of combined therapy in recurrent MGs to determine safety and a recommended phase II dose. Methods Adults with recurrent MG, Karnofsky Performance Status ≥ 60 were enrolled, with no limit on the number of prior therapies. Temsirolimus dose was escalated using standard 3 + 3 design from 15 mg to 170 mg administered once weekly. Perifosine was fixed as a 600 mg load on day 1 followed by 100 mg nightly (single agent MTD) until dose level 7 when the load increased to 900 mg. Results We treated 35 patients with with glioblastoma (17) or other MGs (18; including nine anaplastic astrocytoma, nine anaplastic oligodendroglioma, one anaplastic oligoastrocytoma, and two low grade astrocytomas with radiographic transformation to MG). We observed five dose‐limiting toxicities (DLTs): one at dose level 3 (50mg temsirolimus), then two at dose level 7 expansion (170 mg temsirolimus), and then two more at dose level 6 expansion (170 mg temsirolimus). DLTs included thrombocytopenia (n = 3), intracerebral hemorrhage (n = 1) and lung infection (n = 1). Conclusion Combining the mTOR inhibitor temsirolimus dosed at 115 mg weekly and the AKT inhibitor perifosine dosed at 100 mg daily (following 600 mg load) is tolerable in heavily pretreated adults with recurrent MGs.

Background A continued rise of hepatocellular carcinoma (HCC) incidence is noted. HCC main risk factors are hepatitis B, C, alcohol, and nonalcoholic steatohepatitis. The majority of biliary tumors are adenocarcinomas. Biliary tumors have been classically understood as three different diseases: gallbladder cancer, extrahepatic, and intrahepatic biliary tumors, with different clinical and biological characteristics. Methods Presenting the basic scientific components and clinical premises is supplemented by a thorough review of the new oncoming data especially for advanced disease is reported. This particularly true for the incredible advents in the treatment of advanced HCC. Results Surgery, liver transplantation, and radiofrequency ablation (RFA), are the sole proven curative therapies for HCC. Locally advanced disease is generally treated with different forms of local therapies, including but not limited to, transarterial embolization, chemoembolization, radioembolization, and radiation therapy. Novel five tyrosine kinase inhibitors are now added to sorafenib, and two of them are already FDA approved, being lenvatinib and regorafenib. Checkpoint inhibitors and combination of checkpoint inhibitors is another key advent. For biliary cancers, a novel approach to differentiate the three diseases based on biology and pathways is evolving. Surgery remain the sole curative approach. Capecitabine is now validated as an adjuvant treatment after resection. Several mutational taregts are being further investigated for the treatment of biliary cancers, particularly cholangiocarcinoma and gallbladder cancer. Principal conclusions Screening programs for HCC continue to evolve. Pathology evaluation may help distinguish variants or combined HCC and cholangiocarcinoma. Novel therapies are helping move the field forward at a fast pace.

Colonic stent placement in patients with large-bowel obstruction (LBO) secondary to extracolonic malignancy (ECM) has been evaluated in small series with heterogeneous results. Our aim is to better characterize the technical and clinical success of colonic stent placement and to identify factors that affect this success in ECM patients.All patients at a single high-volume center who presented for colonic stent placement for LBO because of ECM between 2001 and 2012 were retrospectively identified. The outcomes of interest were technical success, clinical success, stent occlusion rate, and overall survival.A total of 187 patients were identified. Mean age was 61.9 years (range, 23-89), and 150 (80.2%) were women. The most common malignancy type was urogynecologic (n = 104) and most common location sigmoid colon (n = 128). Overall, 142 patients (75.9%) achieved technical success and 102 patients (54.5%) clinical success. Radiographic presence of peritoneal carcinomatosis (P .001) and multifocal disease (P .001) were associated with both decreased technical and clinical success. Procedure-related adverse events were seen in 12 patients (6.4%). In patients with clinical success, the incidence of stent occlusion at 3 months was 14.7% (95% confidence interval, 7.8%-21.6%) and was higher in patients with prior radiation therapy (P = .011). The median overall survival for all patients from time of attempted stent placement was 3.3 months (95% confidence interval, 3.0-4.1).This study represents the largest retrospective series of colonic stent placement for LBO in ECM patients in the literature. Our technical success rate of 75.9%, clinical success rate of 54.5%, and 3-month stent occlusion rate of 14.7% suggest that stent placement is a viable palliative option for patients with advanced disease because of ECM. Patients with peritoneal carcinomatosis and multifocal disease have reduced technical and clinical success. However, these factors should not dissuade an attempt at stent placement, if risk-to-benefit analysis is favorable.

BACKGROUND Direct percutaneous endoscopic jejunostomy (DPEJ) is used for enteral nutrition (EN) in patients with postoperative anastomotic leaks after esophagectomy/gastrectomy and at high risk for aspiration. We characterized the indications, technical success, procedural/nutrition outcomes, and adverse events in a large cohort of patients undergoing DPEJ insertion. METHODS Patients undergoing DPEJ insertion between January 2009 and March 2015 were identified from an institutional endoscopy database. Demographic, procedural, and nutrition outcome data were collected from electronic medical records. Regression analyses were used to identify predictors of adverse events and procedural success. RESULTS A total of 452 patients underwent 480 attempts at DPEJ insertion. Indications included preoperative or postoperative weight loss (64%), postoperative upper gastrointestinal (UGI) anastomotic leak (13%), aspiration prevention (10%), and other (13%). Of attempted procedures, 398 (83%) were successful. Feeding was initiated in 389 (98%) of patients; a median of 1775 calories was delivered daily. Median body mass index (BMI) at baseline was 22.9 (11.4-44.7) and did not change over follow-up. Median change in BMI after DPEJ was similar in groups that received EN with palliative and curative intent. Adverse events following 480 attempted DPEJ insertions included 13 (3%) immediate and 74 (15%) delayed, 13 (3%) of which were serious. Patients with head and neck cancer had more adverse events than those with esophageal cancer (P = .020). CONCLUSION DPEJ is a successful and safe procedure that effectively provides access for EN support in malnourished patients and patients with postoperative UGI cancer.

Chronic infection with hepatitis B virus (HBV) has never been described as a risk factor for small bowel adenocarcinoma, although infection is a known risk factor for hepatocellular carcinoma. From May 2009 to December 2014, we implemented an institution-wide screening program for hepatitis B viral serologies prior to starting chemotherapy. Evidence of exposure [hepatitis B core antibody (anti- HBc) positivity in the absence of hepatitis B surface antigen (HBsAg) positivity] was highest in patients with hepatocellular carcinoma (21.1%), followed by small bowel cancer (12.5%). The small bowel adenocarcinoma cases with anti-HBc positivity were reviewed. Special attention was paid to known risk factors for small bowel cancers. One patient had a diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC). However, the other patients had no genetic syndromes, history of inflammatory bowel disease or other chronic inflammation to explain their risk. We postulate exposure to bile acids, tumorigenesis of hepatocytes and cholangiocytes, and/or damage to the intestinal mucosa secondary to HBV exposure/ infection as potential mechanisms for development of small bowel adenocarcinoma. More research is warranted to further elucidate this association.

Patients with prior pancreaticobiliary or distal gastric cancer treated surgically may have local anastomotic recurrence with obstruction of the afferent and efferent jejunal limbs. This report describes the efficacy and safety of simultaneous endoscopic insertion of self-expanding metal stents into the afferent and efferent jejunal limbs in patients with gastric outlet obstruction (GOO) of post-surgical anatomy for palliation of recurrent malignancy. Patients were identified from an endoscopic database at a specialized cancer center between September 2007 and March 2014. Technical success was defined as single-session insertion of afferent and efferent jejunal limb enteral stents. Clinical success was defined as immediate symptom relief and ability to advance diet. A durable response was defined as symptom relief of at least 60 days or until hospice placement or death. Twenty-three patients were identified who underwent insertion of two 22-mm-diameter uncovered duodenal stents. Stent length varied from 60 to 120 mm. Stents were placed under endoscopic and fluoroscopic guidance. Three patients required balloon dilation to facilitate stent insertion. Average procedure time was 58.8 min (range 28–120). Technical success was achieved in 23/24 (96 %) patients. Clinical success was achieved in 19/23 (83 %) patients. Following initial stent insertion and prior to subsequent re-intervention, 11/19 (58 %) patients had a durable response with a median duration of 70 days (range 4–315). Eight (42 %) patients underwent subsequent re-intervention at a median of 22 days (range 11–315). Five patients had stent revision and were able to tolerate oral intake. Two patients had percutaneous endoscopic gastrostomy/jejunostomy insertion. One patient required surgical diversion for persistent obstruction. Complications included stent migration and post-stent insertion bacteremia due to food bolus obstruction. Recurrent malignant GOO in patients with post-surgical anatomy treated with simultaneous endoscopic enteral stenting of afferent and efferent jejunal limbs has a high rate of technical and clinical success and low rate of complications and provides effective palliation.

Purpose The management of superficial primary and recurrent esophageal cancer (EC) in medically inoperable patients is complex. Endoluminal high-dose-rate (HDR) brachytherapy has shown mixed results in terms of toxicity and local control. In this study, we examined the outcomes and toxicities in a set of patients with superficial primary and recurrent EC treated with a consistent HDR technique. Methods and Materials Between 8/2008 and 7/2011, 14 patients were treated with HDR intraluminal brachytherapy, 10 (71.4%) with recurrent disease, and 4 (28.6%) with previously unirradiated lesions. Patients received three weekly fractions to a median dose of 12 Gy (range, 10–15 Gy); dose was prescribed to 7-mm median depth with mucosal dose limited to 8–10 Gy using a 12–14-mm applicator. Results Median followup was 15.4 months. Overall freedom from failure (OFFF) and overall survival (OS) at 18 months were 30.8% (95% confidence interval [CI]: 5.2, 56.4) and 72.7% (95% CI: 45.3, 100), respectively. For patients with recurrent disease, OFFF and OS at 18 months were 11.1% (95% CI: 0, 32.1) and 55.6% (95% CI: 15.4, 95.8), respectively. For patients with previously unirradiated disease, OFFF and OS at 18 months were 75.0% (95% CI: 31.6, 100) and 100.0%, respectively. Eight (57.1%) patients had Grade 1 acute adverse effects; 6 (42.9%) patients had chronic Grade 1 adverse effects; 1 (7.1%) patient developed Grade 2 stricture. Grade 3 tracheoesophageal fistula occurred in 1 (7.1%) patient. One patient died before completion of treatment of unrelated causes. Conclusions HDR endoluminal brachytherapy is a well-tolerated treatment for superficial primary and recurrent EC in medically inoperable patients.

In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P < 0.001). Heterogeneity was attributable to one study; with that study excluded, the pooled odds ratio was 0.73 (95% CI: 0.64, 0.84) (Pheterogeneity = 0.23). Hay fever (odds ratio = 0.74, 95% CI: 0.56, 0.96) and allergy to animals (odds ratio = 0.62, 95% CI: 0.41, 0.94) were related to lower risk, while there was no statistically significant association with other allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age.

BACKGROUND: Inclusion of minorities is an important but challenging aspect of epidemiologic studies in the United States. One aspect of this challenge that has received little attention is the actual number of minorities with specific cancers. The authors aimed to understand how population characteristics affect the numbers of minority cancer cases in Surveillance, Epidemiology, and End Results (SEER) regions. METHODS: By using SEER data, the authors identified 6 cancers with higher incidence rates in racial and ethnic minorities and reviewed the annual number of cases of those cancers in SEER areas where there are large numbers of blacks, Hispanics, and Asians. The authors examined the age characteristics of the populations in SEER areas using data from the US Census. RESULTS: Although there are substantial numbers of cases for the most common cancers with higher incidence in blacks, their numbers are quite small for other cancers

Background: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. Patients and methods: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10 947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). Results: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of =2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (=65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). Conclusions: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Learning Objectives After completing this course, the reader will be able to: Describe the genetic syndromes associated with pancreas adenocarcinoma.Explain the potential role of platinum-based therapy and PARP inhibitors in BRCA-mutated pancreas adenocarcinoma. CME This article is available for continuing medical education credit at CME.TheOncologist.com Background. BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported. Methods. Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center. Results. Fifteen patients, five male, with a BRCA1 (n = 4) or BRCA2 (n = 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response. Conclusion. BRCA mutation–associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC.

Though genome-wide association studies (GWAS) have identified numerous susceptibility loci for common diseases, their use is limited due to the expense of genotyping large cohorts of individuals. One potential solution is to use ‘additional controls’, or genotype data from control individuals deposited in public repositories. While this approach has been used by several groups, the genetically heterogeneous nature of the population of the United States makes this approach potentially problematic. We empirically investigated the utility of this approach in a US-based GWAS. In a small GWAS of pancreatic cancer in New York, we observed clear population structure differences relative to controls from the database of Genotypes and Phenotypes (dbGaP). When we conduct the GWAS using these additional controls, we find large inflation of the test statistic that is properly corrected by using eigenvectors from principal components analysis as covariates. To deal with errors introduced due to different sources, we propose simultaneously genotyping a small number of controls along with cases and then comparing this group to the additional controls. We show that removing SNPs that show differences between these control groups reduces false-positive findings. Thus, through an empirical approach, this report provides practical guidance for using additional controls from publicly available datasets.

Survival from pancreatic adenocarcinoma remains extremely poor, approximately 5% at 5 years. Risk factors include smoking, high body mass index (BMI), family history of pancreatic cancer, and long-standing diabetes; in contrast, allergies are associated with reduced risk. Little is known about associations between these factors and survival. We analyzed overall survival in relation to risk factors for 475 incident cases who took part in a hospital based case-control study. Analyses were conducted separately for those who did (160) and did not (315) undergo tumor resection. Kaplan-Meier methods were used to describe survival according to smoking, BMI, family history, diabetes, and presence of allergies. Cox proportional hazards models were used to adjust for covariates. There was no association with survival based on smoking, family history, or history of diabetes in either group. Among patients with resection, those with allergies showed nonstatistically significant longer survival, a median of 33.1 months (95% CI: 19.0-52.5) vs. 21.8 months (95% CI: 18.0-33.1), p = 0.25. The adjusted hazard ratio (HR) was 0.72 (95% CI: 0.43-1.23), p = 0.23. Among patients without resection, those with self-reported allergies survived significantly longer than those without allergies: 13.3 months (95% CI: 10.6-16.9) compared to 10.4 months (95% CI: 8.8-11.0), p = 0.04, with an adjusted HR of 0.68 (95% CI: 0.49-0.95), p = 0.02. Obesity was nonsignificantly associated with poorer survival, particularly in the resected group (HR = 1.62, 95% CI: 0.76-3.44). The mechanisms underlying the association between history of allergies and improved survival are unknown. These novel results need to be confirmed in other studies.

Hepatocellular carcinoma has been commonly associated with multiple etiologic factors including hepatitis B and C, alcoholic liver disease, and more rarely congenital metabolic liver diseases. 'Cardiac cirrhosis' is the cirrhosis resulting from prolonged passive liver venous congestion secondary to right-sided congestive heart failure; hepatocellular carcinoma is a rarely reported outcome. In this study we present two female patients with congenital heart defects treated with the Fontan procedure who survived into their third decade, and developed hepatocellular carcinoma in the setting of cardiac cirrhosis. The Fontan procedure diverts blood from the inferior vena cava and superior vena cava to the pulmonary arteries, thereby increasing survival in infants born with a single effective ventricle. As such patients live longer, however elevated pulmonary and right-sided heart pressures cause chronic passive liver congestion and eventual cardiac cirrhosis. The two patients in this study had no risk factors for hepatocellular carcinoma other than cardiac cirrhosis secondary to their prolonged survival after their Fontan procedure. In conclusion, we suggest that cardiac cirrhosis may be a risk factor for developing hepatocellular carcinoma and recommend close follow-up and hepatocellular carcinoma screening for patients with known right heart failure and passive hepatic congestion.

Background There is a dearth of data in a younger population of patients with pancreatic ductal adenocarcinoma (PAC) regarding epidemiology, genetics, prognosis, and outcome. This report examines a large cohort of patients with PAC ≤45 years of age evaluated at MSKCC over a 12-year period. Methods A retrospective analysis of patients referred to MSKCC with PAC identified from the institutional tumor registry, who were ≤45 years on the date of the diagnostic biopsy, between January 1995 and February 2008, was performed. Information reviewed included demographics, clinical and pathological staging, surgical management, therapy, date of relapse, death or last follow-up. Survival curves were estimated using the Kaplan–Meier method and compared using the log-rank test. Results One hundred thirty-six cases of PAC, age ≤45 years at diagnosis, were identified. Seventy-four (54%) females, 62 (46%) males. Age range: 24–45; 4, 38, and 94 patients in age groups 20–29, 30–39, 40–45 years, respectively. Fifty (37%) had a smoking history. Fourteen (10.3%) had a positive family history of PAC. Thirty-five (25.7%) underwent a curative resection for localized disease. Twenty-eight (20.1%) presented with locally advanced, inoperable disease. Sixty-eight (50%) presented as AJCC Stage IV. Twenty-three (37%) of those resected underwent adjuvant chemoradiation. Thirteen received adjuvant gemcitabine. The median overall survival for the entire cohort was 12.3 months (95% CI 10.2–14.0 months). The median overall survival for the patients with locally resectable disease was 41.8 months (95% CI 20.3–47 months). The median overall survival for the patients who presented with locally advanced, unresectable disease was 15.3 months (95% CI 12–19.3 months). The median overall survival for those who presented with metastatic disease was 7.2 months (95% CI 5.2–9.5 months). Conclusions This is the largest reported cohort of young patients with PAC ≤45 years of age. The data suggest that patients with stages I–II disease may have an improved prognosis, however the prognosis for stages III–IV patients appears to be similar to the typical (older) patient population with PAC. J. Surg. Oncol. 2009;100:8–12. © 2009 Wiley-Liss, Inc.

Background : Several studies in epidemiology indicate that risk of pancreatic cancer is reduced in individuals with allergies. Although genes have been identified that are critical in allergic response, polymorphisms in these genes have not been studied in relation to risk of pancreatic cancer. We hypothesized that variants in these genes are related to risk. Methods : We investigated the association of allergies and pancreatic cancer in a hospital-based case–control study with 405 cases and 212 controls. In a subgroup of 149 cases and 135 controls, we studied the association of variants in IL-4 (C-589T, G3017T) and IL-4Rα (Gln576Arg) with allergies and with risk of pancreatic cancer. Results : We found reduced risk of pancreatic cancer associated with allergies, with adjusted odds ratios of 0.58 (95% CI 0.40–0.84) for any allergies, 0.45 (95% CI 0.29–0.70) for hay fever, and 0.43 (95% CI 0.23–0.80) for animals. The minor allele at each locus studied was associated with reduced risk of allergies in controls, leading us to hypothesize that they would be associated with increased risk of pancreatic cancer. Overall, there was no association between the genotypes studied and risk of pancreatic cancer. In analyses within strata defined by presence or absence of allergies, there were differences in risk associated with genotype for IL-4 G3017T: there was slightly increased risk among those with allergies and reduced risk among those without allergies. Conclusions : The consistent association of allergies with risk of pancreatic cancer and these results suggest that associations between variants in genes related to allergic response and pancreatic cancer warrant further study.

Background Esophageal anastomotic leaks after cancer surgery remain a major cause of morbidity and mortality. Endoscopic interventions, including covered metal stents (cSEMS), clips, and direct percutaneous endoscopic jejunostomy (dPEJ) tubes are increasingly used despite limited published data regarding their utility in this setting. This study aimed to determine the efficacy and safety of a multimodality endoscopic approach to anastomotic leak management after operation for esophageal or gastric cancer. Methods We performed a retrospective review of prospectively maintained databases of gastric and esophageal operations at our hospital between January 2003 and December 2012. Included patients had an operation for esophageal or gastric cancer, demonstrated evidence of an anastomotic leak at the esophageal anastomosis, and underwent attempted endoscopic therapy. Healing was defined as clinical and radiographic leak resolution. Results Forty-nine patients with leaks underwent endoscopic management. Of the 49 patients, 31 (63%) received cSEMS, 40 (82%) had dPEJ tubes inserted, and 3 (6%) received clips. Twenty-three (47%) patients underwent a combined approach. Overall, 88% of patients achieved healing in a median of 83 days. Twenty-two of 23 patients (96%) who underwent a multimodality endoscopic approach healed. Only 1 patient had a major complication associated with stent erosion into the pulmonary artery, which was successfully treated with operative repair. Conclusions Esophageal anastomotic leaks after esophageal and gastric cancer operations can be managed successfully and safely with endoscopic therapy. Combining cSEMS for leak control and dPEJ tube placement for nutritional support was highly effective in achieving healing, without the need for surgical repair.

Background: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication after immunosuppression from chemotherapeutic agents and can lead to significant morbidity and mortality. We previously reported 23 HBV reactivations in patients of diverse nationalities without association with a particular malignancy or medication. Our institution subsequently initiated a protocol in which all new patients receiving immunosuppressive therapy are screened for HBV and offered anti-viral prophylaxis. The aim of this study is to report the prevalence of HBV surface antigen (HBsAg) and HBV core antibody (HBcAb) positivity since the inception of this screening program.Methods:We conducted a prospective study of all patients at Memorial Sloan-Kettering Cancer Center who were started on immunosuppressive therapy and screened for HBV from May 2009 to November 1, 2012. Patients were screened using tests for HBsAg and HBcAb. If either of these were positive, PCR for HBV DNA was reflexively measured. Patient demographics --including type of malignancy-were recorded. Results: Between May 1 2009 and November 1 2012, 17183 patients met criteria for screening and 12,328 patients (median age 64 years [24-95], 54.4% male) were screened for HBV prior to initiation of immunosuppression (71.75% compliance). Testing revealed 78(0.6%) patients positive for both HbsAg and HbcAb (median age 58, 69.2% male).Of this group, 47/78 (60.26%) had detectable HBV DNA PCR (955766.7 mean, 521 median) .Primary diagnoses of these patients included lymphoma 6.4%, leukemia 2.6%, and myriad solid tumors 91.0%. In addition, 994 patients (8.1%) were negative for HBsAg and positive for HBcAb (median age 58, 53.2% male), Diagnoses among this group included 6.0% lymphoma, 2.0% leukemia and 92.0 % solid tumor. Of this group, 7 (0.7%) had detectable HBV DNA PCR ([41-1,740,000 IU/mL]). Conclusion: In our population screened for HBV prior to initiation of immunosuppression, we report a prevalence of 0.6% for HBsAg positive patients and 8.1% for HBsAg negative, HBcAb positive patients. Screening of these

covered 20-mm SEMS which combines bilateral flared ends and three rows of anchoring flaps on the stent body for the prevention of migration. Aim: To evaluate the clinical efficacy and safety of the HANARO-Utrecht stent for the palliation of malignant dysphagia. Methods: Consecutive patients who underwent HANARO-Utrecht stent placement for palliation of malignant dysphagia in four centers from June 2011 until October 2012 were included. Patients were contacted after 2 weeks and monthly thereafter until death. Technical success, recurrent dysphagia, migration, survival and complications were evaluated. Results: Forty patients (29 men (72.5%), mean age 68 11 years) were included. Malignant dysphagia was caused by esophageal cancer (n 32), malignant extrinsic compression (n 5), tumor recurrence after esophagectomy (n 2) and gastric cancer (n 1). Four patients (10%) had an esophageal-respiratory fistula and 26 patients (65%) had undergone previous radiation and/or chemotherapy. Stent placement was technically successful in 38 patients (95%), in 1 patient the stent collapsed during repositioning and a second stent was placed through the stent and in 1 patient the stent was placed more distally than intended despite repositioning. Thirty-four patients (85%) remained dysphagia free during followup (median 59 days, range 2-397), while 6 patients (17%) had recurrent dysphagia after a median of 39 days (range 9-48), due to stent migration (n 5) and tissue overgrowth (n 1). In 4 of these patients, the stent had partially migrated and could be repositioned endoscopically, while in 2 patients a new stent was placed. One patient presented with recurrent partial migration after 59 days, for which repeat repositioning was performed. Fourteen patients are still alive after a median of 59 days (range 15-397) and 26 patients died after a median of 58 days (range 2-210), due to disease progression (n 20), complicated pneumonia (n 3), cardiac disease (n 1), euthanasia (n 1) and acute hypoxemia due to tumor ingrowth in the trachea (n 1). In total, 24 major complications occurred in 18 patients (47%), including severe pain (n 7), severe nausea and/or vomiting (n 6), bleeding (n 4), aspiration pneumonia (n 4), fistula formation (n 2) and tracheal compression (n 1). Conclusion: Despite the specific anti-migration features of the HANARO-Utrecht stent, migration was the main cause of recurrent dysphagia. We also observed a relatively high complication rate, especially severe pain, nausea and vomiting after placement, further improvements in stent design are needed.

173 Background: The epidemiology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is poorly defined. Methods: An epidemiologic questionnaire was administered to patients (pts) with IPMN (n=79), pancreatic adenocarcinoma (PC) (n=689) and healthy controls (n=307). Results were adjusted for age, gender and BMI. IPMN was defined either by surgical pathology (n=62) or characteristic endoscopic ultrasound appearance and cyst fluid CEA>200 ng/ml (n=17). Results: In unadjusted analysis IPMN pts were more likely to be ≥ 70 years of age (OR 5.40 [2.88, 10.46]) when compared with PC pts (OR 2.82) and controls. After adjustment for age, gender and BMI, current tobacco smoking was associated with PC (OR 3.06 [1.78, 5.23]) but not IPMN. Pts with IPMN more often had diabetes mellitus for >3 years compared with controls (OR 3.25 [1.45, 7.00], while pts with PC (OR 1.52 (0.86, 2.67]) did not. IPMN pts were more likely to have a history of hypercholesterolemia compared with controls (OR 1.77 [1.05-2.98]); this was not seen for PC pts (OR 1.16 [0.87-1.55]). A first degree relative with PC was not associated with increased risk for IPMN (OR 0.84 [0.27, 2.62]) or PC (OR 1.48 [0.82, 2.67]). Compared to PC, pts with IPMN were more likely to have a history of an unrelated cancer (OR 1.84 [1.08, 3.14]). Conclusions: Risk factors for IPMN and PC may differ. Compared to PC and control pts, IPMN patients were older; more often had diabetes mellitus and hypercholesterolemia; and did not currently smoke. IPMN was more often associated with a prior history of cancer than PC. No significant financial relationships to disclose.

268 Background: BRCA1 and -2 germ-line mutations are associated with increased risk of PAC; approximately 5% of all cases of PAC are estimated to be due to an inherited genetic mutation (Lynch, HT, et al. Pancreatology, 2001;1(5):466-471). Other BRCA-associated cancers have demonstrated increased sensitivity to platinum chemotherapy and PARP inhibitors (PARPi) with improved clinical outcomes compared to sporadic cases (J Clin Oncol, 2008 Dec 1;26(34):5530-6). Outcomes in BRCA-associated pancreatic cancer are unknown. Methods: Patients with a known BRCA1 or -2 mutation and a diagnosis of PAC were retrospectively identified from the MSKCC Familial Pancreas Cancer Registry and via institutional database review. Outcomes and clinical characteristics were reviewed. 7 patients (1 male) with BRCA2 mutation and PAC, 4 patients (1 male) with BRCA1 mutation and PAC, were identified. Two further cases of BRCA mutation and cholangiocarcinoma were identified. Results: See Table for patient demographics. Treatment for advanced disease included a PARP inhibitor (PARPi) in 2 cases; both pts had a radiologic partial response (PR) to therapy. Five patients received platinum-based chemotherapy for advanced disease, 4 of whom had a PR. Median survival for all patients was 27.6 months. Conclusions: The use of platinum- containing chemotherapy, radiation therapy, and PARPi to target the BRCA-associated defective DNA repair mechanism is deserving of further investigation in these patients. PARPi have demonstrated promising efficacy in patients with BRCA-mutated breast and ovarian cancer and are undergoing prospective evaluation in PAC. Genetic testing in patients presenting with a personal history or strong family history of BRCA associated cancers may help to guide choice of therapy. [Table: see text] No significant financial relationships to disclose.

9088 Background: Reactivation of hepatitis B virus (HBV) infection following immunosuppressive therapy can cause significant morbidity and mortality. This study aims to estimate the frequency and c...

9009 Background: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication after immunosuppressive therapy and can lead to significant morbidity and mortality. We previous...