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The aim of this study is to describe the demographics and clinical features of patients with young onset (YO) CRC.A retrospective review of patients with CRC diagnosed between ages 20 and 49 years was evaluated at the Memorial Sloan Kettering Cancer Center from 1/2004 to 6/2019. We excluded those with a hereditary CRC syndrome, inflammatory bowel disease, or prior CRC diagnosis. Patient demographics; presenting symptoms; medical, surgical, and smoking history; family history of cancer; tumor characteristics; and pathology were obtained from the electronic medical record.We identified 3856 YO CRC patients (median age CRC diagnosis 43; 52.5% male). A total of 59.1% were overweight or obese (32.2% and 26.9%, respectively). Most (90.1%) had no family history of CRC in a first-degree relative; 56.3% of patients reported being never smokers; 5.2% had diabetes. The most common presenting symptoms were rectal bleeding (47.7%), abdominal pain/bloating (33.1%), and change in bowel habits (24.7%). The majority presented with left-sided cancers (77.3%), at late-stage disease (68.4% at stages 3 or 4).Most YO CRC patients presented with rectal bleeding or abdominal pain, left-sided cancers, and later-stage disease and had no family history of CRC in a first-degree relative. Over half were overweight and obese and were more likely to have never smoked. More data are needed to better understand YO CRC risk factors and to help identify high-risk populations who may benefit from earlier screening.

Objective Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. Summary of background data Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). Methods This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. Results Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12 months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. Conclusions This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

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.

Few Western studies have evaluated the long-term oncologic outcomes of minimally invasive surgery (MIS) approaches to gastrectomy for gastric cancer. This study aimed to compare the outcomes between minimally invasive and open gastrectomies and between laparoscopic and robotic gastrectomies at a high-volume cancer center in the United States. The study analyzed data for all patients undergoing curative gastrectomy for gastric adenocarcinoma from January 2007 to June 2017. Postoperative complications and disease-specific survival (DSS) were compared between surgical approaches. The median follow-up period for the 845 patients in this study was 38.5 months. The stage-stratified 5-year DSS did not differ significantly between open surgery (n = 534) and MIS (n = 311). The MIS approach resulted in significantly fewer complications, as confirmed by adjusted comparison (odds ratio [OR], 0.70; range, 0.49–1.00; p = 0.049). After adjustment, the two groups did not differ in terms of DSS (hazard ratio [HR], 0.83; range, 0.55–1.25; p = 0.362). The robotic operations (n = 190) had fewer conversions to open procedure (p = 0.010), a shorter operative time (212 vs 240 min; p < 0.001), more dissected nodes (27 vs 22; p < 0.001), fewer Clavien-Dindo grade ≥3 complications (5.8% vs 13.2%; p = 0.023), and a shorter postoperative stay (5 vs 6 days; p = 0.045) than the laparoscopic operations (n = 121). The DSS rate did not differ between the laparoscopic and robotic groups. The study findings demonstrated the long-term survival and oncologic equivalency of MIS gastrectomy and the open approach in a Western cohort, supporting the use of MIS at centers that have adequate experience with appropriately selected patients.

The purpose of this study was to identify factors associated with quality-of-life recovery after gastrectomy. Patients anticipated to undergo gastric cancer resection were invited to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and STO22 surveys in the preoperative setting and at 0–1.5 months (early), > 1.5–6 months (intermediate), and > 6–18 months (late) following resection. Quality-of-life recovery was measured as paired differences between pre- and postoperative results. Multivariable linear regression identified factors associated with preoperative quality of life and degree of change following resection. Across 393 participants, response rates at the intermediate and late postoperative time points were 58% (n = 228) and 71% (n = 277), respectively. Relative to baseline, median global health scale decreased in the early (− 15.1 pts, p

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.

The standard treatment of locally advanced rectal cancer is chemoradiation (CRT) followed by proctectomy and adjuvant chemotherapy. However, there is an emerging role for nonsurgical management after CRT or total neoadjuvant therapy (TNT) consisting of CRT and neoadjuvant chemotherapy. Endoscopic submucosal dissection (ESD) after CRT or TNT for rectal cancer, termed "salvage ESD," may be a viable nonsurgical option for carefully selected patients. We aimed to evaluate the feasibility and safety of salvage ESD.A retrospective chart review of cases of salvage ESD for locally advanced rectal cancer and standard ESD for rectal tumors without prior CRT from July 2018 to August 2020 at our institution was performed. Clinical factors and imaging, procedural, and pathology results were collected and compared.Twelve salvage ESD cases were compared with 27 standard ESD cases. Before CRT, 83.3% of lesions in the salvage ESD group were initially clinically staged as T3. The en-bloc resection rates were 92.7% and 91.7% (P = 1.00) and R0 resection rates 66.7% and 75.0% (P = .55) for the standard and salvage groups, respectively. In the salvage ESD group, no adverse events were observed, and 75.0% of the adenocarcinomas in the salvage ESD group had morphologically changed to hyperplasia or adenoma after CRT, with no identifiable lesions greater than T1 tumor depth.Salvage ESD for locally advanced rectal cancer is technically feasible with low adverse event rates. There may be a diagnostic role in salvage ESD in assessing pathologic response to CRT and a possible therapeutic role in resection of residual lesions with the potential to avoid surgery.

Background The International Reporting Items for Practice Guidelines in Health Care (RIGHT) statement is a set of recommendations for the reporting in clinical practice guidelines (CPGs). We aimed to assess the reporting quality of CPGs for pancreatic cancer following the RIGHT checklist. Methods Guidelines for pancreatic cancer were identified by searching electronic databases, guideline databases, and medical society websites. The reporting quality was evaluated by calculating the adherence to the items of the RIGHT checklist and summarizing them over the seven domains and the entire checklist. We also present results stratified by selected characteristics. Results A total of 22 guidelines were found eligible. Mean overall adherence to the RIGHT items was 60.0%. All guidelines adhered to the RIGHT items 3, 7a, 13a, while no guidelines reported the items 14c or 18b, which are some of the topics dealing with rationale for recommendations and funding source, respectively. Of the seven domains of the RIGHT checklist, "Review and quality assurance" and "Funding and declaration and management of interests" had the lowest reporting rates (25.0% and 43.2%, respectively); the remaining five domains had reporting rates >50%. CPGs that reported funding support, were published in higher-impact journals, and that applied a grading system for the quality of evidence, tended to have higher reporting rates. Conclusions Our results show that reporting quality of pancreatic cancer CPGs still needs to be improved. The use of the RIGHT statement should be encouraged when developing new guidelines.

Purpose: VEGFR2-directed therapy is commonly used to treat metastatic esophagogastric cancer, but disease progresses in most patients within months. Therapeutic resistance is likely mediated in part by co-occurring amplifications of the genes for multiple oncogenic receptor tyrosine kinases (RTK). We therefore tested the efficacy of combined inhibition of VEGFR1-3, PDGFα/β, and FGFR1-3 using nintedanib. Patients and Methods: Patients with metastatic esophagogastric adenocarcinoma and disease progression on first-line chemotherapy were treated with nintedanib 200 mg twice daily. The primary endpoint was progression-free survival (PFS) at 6 months; secondary endpoints included tumor response and safety. Tumor biopsies were profiled by targeted capture next-generation sequencing (NGS) to identify molecular predictors of drug response. Results: The study achieved its primary endpoint; 6 of 32 patients (19%) were progression-free at 6 months. With a median follow-up of 14.5 months among survivors, median overall survival (OS) was 14.2 months [95% confidence interval (CI), 10.8 months–NR]. Nintedanib was well tolerated; grade ≥ 3 toxicities were uncommon and included grade 3 hypertension (15%) and liver enzyme elevation (4%). FGFR2 alterations were identified in 18% of patients but were not predictive of clinical outcome on nintedanib therapy. Alterations in cell-cycle pathway genes were associated with worse median PFS (1.61 months for patients with cell-cycle pathway alterations vs. 2.66 months for patients without, P = 0.019). Conclusions: Nintedanib treatment resulted in modest disease stabilization in patients with metastatic esophagogastric cancer. Alterations in cell-cycle pathway genes and increased global copy-number alteration (CNA) burden warrant further study as prognostic or predictive biomarkers.

OBJECTIVE: Post-operative peripancreatic fluid collection (PFC) is a common complication following pancreatic resection. The aim of this retrospective match-controlled study was to compare the success rates and outcomes between endoscopic and percutaneous drainage procedures. METHODS: Patients who underwent either endoscopic or percutaneous drainage of post-operative PFC between 2008 and 2015 were extracted from a prospectively-maintained database. The two groups were matched on the type of surgery, presence of a surgical drain and the post-operative timing of the drainage procedure. Differences between the two groups were tested using McNemar’s and Wilcoxon signed rank tests. RESULTS: Thirty-nine matched patients were identified in each group with a median age of 62 years. For the primary drainage, technical success was achieved in almost all patients in both endoscopic and percutaneous groups (100% and 97%, p=NS), while clinical success was achieved in 67% and 59%, respectively (p=0.63). At least one “salvage” drainage procedure was required in 13 endoscopic patients versus 16 in the percutaneous group. Clinical success was achieved following the first salvage procedure in 85% of the endoscopic patients and 88% of the percutaneous patients (p=0.62). Stent/drain duration (59 vs 33 days, p

BACKGROUND AND PURPOSE: While multiple Asian and a few Western retrospective series have demonstrated the feasibility and safety of robotic-assisted gastrectomy for gastric cancer, its reliability for thorough resection, especially for locoregional disease, has not yet been firmly established, and reported learning curves vary widely. To support wider implementation of robotic gastrectomy, we evaluated the learning curve for this approach, assessed its oncologic feasibility, and created a selection model predicting the likelihood of conversion to open surgery in a United States patient population. METHODS: We retrospectively reviewed data on all consecutive patients who underwent robotic gastrectomy at a high-volume institution between May 2012 and March 2019. RESULTS: Of the 220 patients with gastric cancer selected to undergo curative-intent robotic gastrectomy, surgery was completed using robotics in 159 (72.3%). The median number of removed lymph nodes was 28, and ≥ 15 lymph nodes were removed in 94% of procedures. Surgical time decreased steadily over the first 60–80 cases. Complications were generally minor; 7% of patients experienced complications of grade 3 or higher, with an anastomotic leak rate of 2% and mortality rate 0.9%. Factors predicting conversion to open surgery included neoadjuvant chemotherapy, BMI ≥ 31, and tumor size ≥ 6 cm. CONCLUSIONS: These findings support the safety and oncologic feasibility of robotic gastrectomy for selected patients with gastric cancer. Proficiency can be achieved by 20 cases and mastery by 60–80 cases. Ideal candidates for this approach are patients with few comorbidities, BMI < 31, and tumors < 6 cm.

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: Elevation in the serum immunoglobulin-G4 (IgG4) level has been used as a diagnostic marker to distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC), but its true utility is ill-defined. This study evaluates the clinical utility of IgG4 in differentiating AIP from PDAC. METHODS: All patients evaluated in the hepatopancreaticobiliary surgery clinics with measured serum IgG4 were included. Patients were divided into normal IgG4 (

The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability–high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein–Barr virus–positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance. Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49–58. ©2017 AACR. See related commentary by Sundar and Tan, p. 14. See related article by Pectasides et al., p. 37. This article is highlighted in the In This Issue feature, p. 1

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.

In 2015, the American Gastroenterological Association recommended the discontinuation of radiographic surveillance after 5 years for patients with stable pancreatic cysts. The current study evaluated the yield of continued surveillance of pancreatic cysts up to and after 5 years of follow up.A prospectively maintained registry of patients evaluated for pancreatic cysts was queried (1995-2016). Patients who initially underwent radiographic surveillance were divided into those with5 years and ≥5 years of follow up. Analyses for the presence of cyst growth (5 mm increase in diameter), cross-over to resection, and development of carcinoma were performed.A total of 3024 patients were identified, with 2472 (82%) undergoing initial surveillance. The ≥5 year group (n = 596) experienced a greater frequency of cyst growth (44% vs. 20%; P0.0001), a lower rate of cross-over to resection (8% vs 11%; P = 0.02), and a similar frequency of progression to carcinoma (2% vs 3%; P = 0.07) compared with the5 year group (n = 1876). Within the ≥5 year group, 412 patients (69%) had demonstrated radiographic stability at the 5-year time point. This subgroup, when compared with the5 year group, experienced similar rates of cyst growth (19% vs. 20%; P= 0.95) and lower rates of cross-over to resection (5% vs 11%; P0.0001) and development of carcinoma (1% vs 3%; P= 0.008). The observed rate of developing cancer in the group that was stable at the 5-year time point was 31.3 per 100,000 per year, whereas the expected national age-adjusted incidence rate for this same group was 7.04 per 100,000 per year.Cyst size stability at the 5-year time point did not preclude future growth, cross-over to resection, or carcinoma development. Patients who were stable at 5 years had a nearly 3-fold higher risk of developing cancer compared with the general population and should continue long-term surveillance.

Background Angiogenesis is critical to gastroesophageal adenocarcinoma growth and metastasis. Regorafenib is a multikinase inhibitor targeting angiogenic and stromal receptor tyrosine kinases. We evaluated whether regorafenib augments the antitumor effect of first-line chemotherapy in metastatic esophagogastric cancer. Materials and methods Patients with previously untreated metastatic gastroesophageal adenocarcinoma received 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) every 14 days and regorafenib 160 mg daily on days 4 to 10 of each 14-day cycle. The primary endpoint was 6-month progression-free survival (PFS). To identify predictive biomarkers of outcome, we examined correlations between genomic characteristics of sequenced pretreatment tumors and PFS. Results Between August 2013 and November 2014, 36 patients with metastatic esophagogastric cancer were accrued to this single-center phase II study (NCT01913639). The most common grade 3-4 treatment-related adverse events were neutropenia (36%), leucopenia (11%) and hypertension (8%). The 6-month PFS was 53% (95% confidence interval [CI], 38%-71%), the objective response rate was 54% (95% CI, 37%-70%), and the disease control rate was 77% (95% CI, 67%-94%). Next-generation sequencing did not identify any genomic alterations significantly correlated with response, and there was no association between homologous recombination deficiency and PFS with platinum-based chemotherapy. Conclusion Regorafenib (one week on-one week off schedule) is well tolerated in combination with first-line FOLFOX but does not improve 6-month PFS relative to historical control. Implications for practice Prognosis for metastatic esophagogastric cancer remains poor despite modern systemic therapy regimens. This phase II trial indicates that the combination of regorafenib and FOLFOX is well tolerated but does not add to the efficacy of first-line chemotherapy in metastatic esophagogastric cancer. Notably, recently reported data suggest potential synergy between regorafenib and the PD-1 inhibitor nivolumab. As this study demonstrates that regorafenib plus FOLFOX is safe, and combined chemotherapy and immunotherapy show favorable toxicity profiles, future studies combining immunotherapy with regorafenib and chemotherapy may be feasible.

Pancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.

Opioid-induced constipation (OIC) has become increasingly prevalent with the rise of prescription opioid use and can significantly impact quality of life, especially in patients with advanced illness. Methylnaltrexone has proven effective in treating cancer patients with OIC who have not responded adequately to conventional laxative therapy, though use is relatively contraindicated in those with peritoneal carcinomatosis due to theoretical risk and reported cases of perforation. The aim of this study was to evaluate the safety of methylnaltrexone in patients with carcinomatosis. We performed a retrospective review of 3058 pediatric and adult patients who received methylnaltrexone at Memorial Sloan Kettering Cancer Center from 2009–2016. Data collected included age, cancer diagnosis, history of abdominal surgery, prior radiation therapy, evidence of peritoneal carcinomatosis, and complications. Charts were reviewed for any complications at 24 hours, 72 hours, and one week following drug administration, as well as at present. We identified 3058 patients (median age 56, range 1–95) who received a total of 3995 doses of methylnaltrexone. Three hundred thirty three (median age 55, range 4–88) had peritoneal carcinomatosis. The most common primary malignancies included pancreatic (17.7%), ovarian (13.5%), colon (7.2%), and lung (6.6%). 228/333 (68.4%) had a history of abdominal surgery and 85/333 (25.5%) underwent prior radiation therapy. Three patients had adverse outcomes or complications, with only one (0.3%) thought to be related to methylnaltrexone use. To our knowledge, this is the largest study to evaluate the outcomes of patients with carcinomatosis receiving methylnaltrexone and the first to include pediatric patients. We found one perforation attributed to methylnaltrexone. Methylnaltrexone should be considered for treatment of refractory OIC in cancer patients with peritoneal carcinomatosis due to low risk of complications.

IMPORTANCE: CDH1 variants are increasingly identified on commercially available multigene panel tests, calling for data to inform counseling of individuals without a family history of gastric cancer. OBJECTIVES: To assess association between CDH1 variant pathogenicity or family history of gastric or lobular breast cancer and identification of signet ring cell cancer and to describe outcomes of risk-reducing minimally invasive and open total gastrectomy. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was performed from January 1, 2006, to January 1, 2020, in 181 patients with CDH1 germline variants from a single institution. INTERVENTIONS: Genetic counseling, esophagogastroduodenoscopy, and possible total gastrectomy. MAIN OUTCOMES AND MEASURES: CDH1 variant classification, family cancer history, findings of signet ring cell carcinoma at esophagogastroduodenoscopy and surgery, postoperative events and weight changes, and follow-up. RESULTS: Of 181 individuals with CDH1 germline variants (mean [SD] age at time of testing, 44 [15] years; 126 [70%] female), 165 harbored a pathogenic or likely pathogenic variant. Of these patients, 101 underwent open (n = 58) or minimally invasive (n = 43) total gastrectomy. Anastomotic leaks that required drainage were infrequent (n = 3), and median long-term weight loss was 20% (interquartile range [IQR], 10%-23%). In those undergoing minimally invasive operations, more lymph nodes were retrieved (median, 28 [IQR, 20-34] vs 15 [IQR, 9-19]; P

TPS4672 Background: KRAS alterations are the most frequent driver alterations identified in pancreas cancer; however, KRAS has remained an elusive therapeutic target. siG12D-LODER is a novel, miniature bio-degradable polymeric matrix encompassing a novel small interfering RNA targeting KRAS G12D and all additional G12X mutations (G12C, G12V...). The siG12D-LODER is inserted directly into the pancreas tumor via endoscopic intervention. A Phase 1/2a dose escalation and expansion study of patients receiving a one-time dose of siG12D-LODER with ongoing chemotherapy demonstrated that the combination was well-tolerated and safe and exhibited promising potential efficacy with 10/12 patients achieving disease control and median overall survival 15.1 months (Golan, Oncotarget 2015). Methods: This phase 2 study was initially designed as a randomized, two arm, open label study of gemcitabine and nab-paclitaxel with or without siG12D-LODER for patients with locally advanced pancreas cancer with planned 40 patients in each arm and primary endpoint of progression-free survival. Eighteen patients were enrolled in the chemotherapy alone arm and 18 in the chemotherapy and siG12D-LODER arm. After an interim analysis, the study design has been amended and is now a single arm study in which patients (N=39) with both borderline resectable and locally advanced pancreas cancer will receive investigator’s choice of chemotherapy (the combination of gemcitabine/nab-paclitaxel or modified FOLFIRINOX) and all patients will receive up to three doses of the siG12D-LODER administered once every 12 weeks. Primary endpoint is overall response rate after final siG12D-LODER insertion. Secondary endpoints include duration of response, progression-free survival, overall survival, time to response, percentage of patients proceeding to surgical resection, and percentage of patients receiving radiation therapy. Exploratory analyses include evaluation of KRAS mutation status and monitoring of circulating free DNA and circulating tumor cells. The amended protocol is now open for accrual and four patients having been enrolled to date. Trial accrual is anticipated to be completed by December 2020. Clinical trial information: NCT01676259 .

4568 Background: Pembrolizumab is approved for chemotherapy-refractory PD-L1 CPS >1 mEG cancer. In clinical trials, pts with MSI-H, EBV+ and PD-L1 CPS >10 EG cancers derive the greatest benefit with immune checkpoint blockade (ICB). Pre-clinical data suggest that the gut microbiome modulates response to ICB; however, the EG cancer microbiome has not been characterized in EG cancer with respect to PD-L1 and MSI-H status. Therefore, we evaluated the EG tumor microbiome in the context of PD-L1 expression in order to define biologically unique EG tumor phenotypes for future therapeutic development. Methods: Clinical and pathologic characteristics, including age, stage at diagnosis, tumor PD-L1 CPS, HER2 IHC, EBV ISH, genomic analysis, treatment history and survival status were reviewed. CPS was stratified a priori using cutoffs of >1/>10/>20 due to biologic differences. MSK-IMPACT, a capture-based next-generation sequencing platform that detects mutations, copy-number alterations, and select fusions was used to detect non-human bacterial reads identified in the NCBI NT database. Bacterial species found in >2 pts were analyzed and stratified by highest PD-L1 CPS score for each individual patient (Vanderbilt, AMP 2018) and Bonferroni correction was used for odds ratio (OR) confidence intervals where each unique species was considered an independent hypothesis. Results: Molecular data from 311 pts was clinically annotated. PD-L1 results (Table) correlated with bacterial species identified on tumor sequencing. PD-L1 CPS >1 was associated with Selenomonas sputigena (OR: 8.2, 95% CI:1.2-53.6), and PD-L1 CPS >20 was associated with presence of Bifidobacterium dentium (OR: 7.4, 95% CI:1.1-48.5) and Prevotella denticola (OR: 4.2, 95% CI: 1.1-16.6) after multiple comparison correction for the 166 bacterial species identified in the cohort. No differences were seen between PD-L1 < 10 vs >10. Four patients were also found to have EBV+ tumors using this approach, including the 1/54 patients identified by EBER ISH. Conclusions: PD-L1 > 20 EG cancer represents a biologically unique subset, enriched for Bifidobacterium dentium and Prevotella denticola. Correlation between PD-L1 expression, microbial and immune environment, and survival on ICB is underway. [Table: see text]

The anti-HER2 antibody trastuzumab is standard care for advanced esophagogastric (EG) cancer with ERBB2 (HER2) amplification or overexpression, but intrinsic and acquired resistance are common. We conducted a phase II study of afatinib, an irreversible pan-HER kinase inhibitor, in trastuzumab-resistant EG cancer. We analyzed pretreatment tumor biopsies and, in select cases, performed comprehensive characterization of postmortem metastatic specimens following acquisition of drug resistance. Afatinib response was associated with coamplification of EGFR and ERBB2. Heterogeneous 89Zr-trastuzumab PET uptake was associated with genomic heterogeneity and mixed clinical response to afatinib. Resistance to afatinib was associated with selection for tumor cells lacking EGFR amplification or with acquisition of MET amplification, which could be detected in plasma cell-free DNA. The combination of afatinib and a MET inhibitor induced complete tumor regression in ERBB2 and MET coamplified patient-derived xenograft models established from a metastatic lesion progressing on afatinib. Collectively, differential intrapatient and interpatient expression of HER2, EGFR, and MET may determine clinical response to HER kinase inhibitors in ERBB2-amplified EG cancer. Significance: Analysis of patients with ERBB2-amplified, trastuzumab-resistant EG cancer who were treated with the HER kinase inhibitor afatinib revealed that sensitivity and resistance to therapy were associated with EGFR/ERBB2 coamplification and MET amplification, respectively. HER2-directed PET imaging and cell-free DNA sequencing could help guide strategies to overcome the emergence of resistant clones. See related commentary by Klempner and Catenacci, p. 166. This article is highlighted in the In This Issue feature, p. 151

Lynch syndrome is an autosomal dominant condition caused by pathogenic mutations in the DNA mismatch repair (MMR) genes. Although commonly associated with clinical features such as intellectual disability and congenital anomalies, contiguous gene deletions may also result in cancer predisposition syndromes. We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anastomosis for a pT3N1 sigmoid adenocarcinoma. Germline genetic testing of the MSH2, MSH6, and EPCAM genes revealed full gene deletions. SNP-array based DNA copy number analysis identified a deletion of 4.8 Mb at 2p16.3-p21. In addition to the three Lynch syndrome associated genes, the deleted chromosomal section encompassed genes including NRXN1, CRIPT, CALM2, FBXO11, LHCGR, MCFD2, TTC7A, EPAS1, PRKCE, and 15 others. Contiguous gene deletions have been described in other inherited cancer predisposition syndromes, such as Familial Adenomatous Polyposis. Our report and review of the literature suggests that contiguous gene deletion within the 2p16-p21 chromosomal region is a rare cause of Lynch syndrome, but presents with distinct phenotypic features, highlighting the need for recognition and awareness of this syndromic entity.

Background & Aims The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. Methods We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts ( BRAF , CDKN2A , CTNNB1 , GNAS , KRAS , NRAS , PIK3CA , RNF43 , SMAD4 , TP53 , and VHL ); to identify loss of heterozygozity at CDKN2A , RNF43 , SMAD4 , TP53 , and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. Results We identified molecular markers and clinical features that classified cyst type with 90%−100% sensitivity and 92%−98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. Conclusions We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.

Background. Endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) are both used to resolve jaundice before surgery for perihilar cholangiocarcinoma (PHC). PTBD has been associated with seeding metastases. The aim of this study was to compare overall survival (OS) and the incidence of initial seeding metastases that potentially influence survival in patients with preoperative PTBD versus EBD. Methods. Between 1991 and 2012, a total of 278 patients underwent preoperative biliary drainage and resection of PHC at 2 institutions in the Netherlands and the United States. Of these, 33 patients were excluded for postoperative mortality. Among the 245 included patients, 88 patients who underwent preoperative PTBD (with or without previous EBD) were compared to 157 patients who underwent EBD only. Survival analysis was done with Kaplan-Meier and Cox regression with propensity score adjustment. Results. Unadjusted median OS was comparable between the PTBD group (35 months) and EBD-only group (41 months; P = 0.26). After adjustment for propensity score, OS between the PTBD group and EBD-only group was similar (hazard ratio, 1.05; 95 % confidence interval, 0.74-1.49; P = 0.80). Seeding metastases in the laparotomy scar occurred as initial recurrence in 7 patients, including 3 patients (3.4 %) in the PTBD group and 4 patients (2.7 %) in the EBD-only group (P = 0.71). No patient had an initial recurrence in percutaneous catheter tracts. Conclusions. The present study found no effect of PTBD on survival compared to patients with EBD and no increase in seeding metastases that developed as initial recurrence. These data suggest that PTBD can safely be used in preoperative management of PHC.

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.

Endoscopic ultrasound (EUS) is a guideline-recommended diagnostic test to estimate pretreatment clinical stage in gastric cancer. The impact of EUS to discriminate long-term outcomes has not been established.The objectives of our study were to (1) evaluate the association between EUS and pathologic stage; (2) evaluate the ability of EUS to predict disease-specific survival (DSS); and (3) determine how neoadjuvant chemotherapy (NCT) affects these relationships.A prospective gastric cancer database at a tertiary care cancer center identified 734 patients who underwent curative intent resection. Patients were separated into EUS low-risk (T1-2, N0) and EUS high-risk (T3-4 Nany, or Tany N+) groups. Agreement statistics and 5-year DSS were estimated stratified by NCT.Between 1987 and 2015, 68% (502/734) of patients were not treated with NCT. Among these patients, percentage agreement between EUS and pathology was moderate (individual T stage: 52%; N stage: 70%; risk group: 73%). EUS accurately estimated pathologic risk group in 73% (365/502) of patients, whereas it overestimated pathologic risk group in 19% (93/502) of patients and underestimated risk in 8% (41/502) of patients. EUS in non-NCT staging was able to discriminate DSS for T stage (hazard ratio [HR] 5.07, p 0.05), N stage (HR 3.58, p 0.05), and risk group (HR 6.35, p 0.05). Among patients treated with NCT, EUS was unable to discriminate DSS for T stage (HR 0.94, p 0.05), N stage (HR 1.46, p 0.05) and risk group (HR 0.50, p 0.05).Pretreatment clinical staging based on EUS alone could lead to over- or under treatment in 27% of patients and can discriminate DSS in NCT-naive patients. EUS should be used in the context of other validated clinical risk tools.

Importance Postoperative complications are associated with increased hospital costs following major surgery, but the mechanism by which they increase cost and the categories of care that drive this increase are poorly described. Objective To describe the association of postoperative complications with hospital costs following total gastrectomy for gastric adenocarcinoma. Design, Setting, and Participants This retrospective analysis of a prospectively collected gastric cancer surgery database at a single National Cancer Institute–designated comprehensive cancer center included all patients undergoing curative-intent total gastrectomy for gastric adenocarcinoma between January 2009 and December 2012 and was conducted in 2015 and 2016. Main Outcomes and Measures Ninety-day normalized postoperative costs. Hospital accounting system costs were normalized to reflect Medicare reimbursement levels using the ratio of hospital costs to Medicare reimbursement and categorized into major cost categories. Differences between costs in Medicare proportional dollars (MP $) can be interpreted as the amount that would be reimbursed to an average hospital by Medicare if it paid differentially based on types and extent of postoperative complications. Results In total, 120 patients underwent curative-intent total gastrectomy for stage I through III gastric adenocarcinoma between 2009 and 2012. Of these, 79 patients (65.8%) were men, and the median (interquartile range) age was 64 (52-70) years. The 51 patients (42.5%) who underwent an uncomplicated total gastrectomy had a mean (SD) normalized cost of MP $12 330 (MP $2500), predominantly owing to the cost of surgical care (mean [SD] cost, MP $6830 [MP $1600]). The 34 patients (28.3%) who had a major complication had a mean (SD) normalized cost of MP $37 700 (MP $28 090). Surgical care was more expensive in these patients (mean [SD] cost, MP $8970 [MP $2750]) but was a smaller contributor to total cost (24%) owing to increased costs from room and board (mean [SD] cost, MP $11 940 [MP $8820]), consultations (mean [SD] cost, MP $3530 [MP $2410]), and intensive care unit care (mean [SD] cost, MP $7770 [MP $14 310]). Conclusions and Relevance Major complications were associated with tripled normalized costs following curative-intent total gastrectomy. Most of the excess costs were related to the treatment of complications. Interventions that decrease the number or severity of postoperative complications could result in substantial cost savings.

Purpose: Molecular profiling in cancer has identified potential actionable drug targets that have prompted attempts to discover clinically validated biomarkers to guide therapeutic decision-making and enrollment to clinical trials. We evaluated whether comprehensive genetic analysis of patients with pancreatic adenocarcinoma is feasible within a clinically relevant timeframe and whether such analyses provide predictive and/or prognostic information along with identification of potential targets for therapy. Experimental Design: Archival or prospectively acquired FFPE samples and matched normal DNA from N = 336 patients with pancreatic cancer were analyzed using a hybridization capture–based, next-generation sequencing assay designed to perform targeted deep sequencing of all exons and selected introns of 410 key cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles. Results: The median time from protocol consent to reporting of the genomic results was 45 days with a median time from tissue delivery of 20 days. All genetic alterations identified were stratified based upon prior evidence that the mutation is a predictive biomarker of drug response using the MSKCC OncoKB classification. Three of 225 patients (1%) received a matched therapy based upon the sequencing results. Conclusions: The practical application of molecular results to guide individual patient treatment is currently limited in patients with pancreatic adenocarcinoma. Future prospective molecular profiling efforts should seek to incorporate routine germline genetic analysis and the identification of DNA profiles that predict for clinical benefit from agents that target DNA damage repair and or immunotherapy. Clin Cancer Res; 23(20); 6094–100. ©2017 AACR.

Esophageal and gastric cancers are common malignancies, both in the United States and worldwide, that carry significant morbidity and mortality. Malnutrition is a common complication in patients with esophageal and gastric cancers and it portends a poor prognosis. For patients who undergo surgical therapy for these types of cancers, preoperative and postoperative nutritional optimization have been shown to improve outcomes. The support can be accomplished in different manners, including orally, enterally, or parentally. In patients who do not undergo surgery but receive chemotherapy and/or radiation, nutritional support is also an important aspect of the multidisciplinary care approach.

The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for KRAS gene mutations with carefully thresholded protein biomarkers to determine whether the combination of these markers was superior to any single marker. The cohort tested included 221 patients with resectable pancreatic ductal adenocarcinomas and 182 control patients without known cancer. KRAS mutations were detected in the plasma of 66 patients (30%), and every mutation found in the plasma was identical to that subsequently found in the patient's primary tumor (100% concordance). The use of KRAS in conjunction with four thresholded protein biomarkers increased the sensitivity to 64%. Only one of the 182 plasma samples from the control cohort was positive for any of the DNA or protein biomarkers (99.5% specificity). This combinatorial approach may prove useful for the earlier detection of many cancer types.

The role for neoadjuvant systemic therapy in resectable pancreas adenocarcinoma remains undefined.We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable pancreas adenocarcinoma.Eligible patients were screened using computed tomography-pancreas angiography, laparoscopy, endoscopic ultrasonography, and fine-needle aspiration cytology to identify 38 patients who received 4 cycles of neoadjuvant gemcitabine 1000 mg/m intravenously over 100 minutes and oxaliplatin 80 mg/m intravenously over 2 hours, every 2 weeks. Patients whose tumors remained resectable at restaging proceeded to operation and subsequently received 5 cycles of adjuvant gemcitabine (1000 mg/m intravenously over 30 minutes days 1, 8, and 15 every 4 weeks). The primary endpoint was 18-month overall survival and secondary endpoints included radiological, tumor marker and pathological response to neoadjuvant therapy, time to recurrence, patterns of failure, and feasibility of obtaining preoperative core biopsies.Thirty-five of 38 patients (92%) completed neoadjuvant therapy. Twenty-seven patients underwent tumor resection (resectability rate 71%), of which 26 initiated adjuvant therapy for a total of 23 patients (60.5%) who completed all planned therapy. The 18-month survival was 63% (24 patients alive). The median overall survival for all 38 patients was 27.2 months (95% confidence interval: 17-NA) and the median disease-specific survival was 30.6 months (95% confidence interval: 19-NA).This study met its endpoint and provided a signal suggesting that exploration of neoadjuvant systemic therapy is worthy of further investigation in resectable pancreas adenocarcinoma. Improved patient selection and more active systemic regimens are key. Clinical trials identification: NCT00536874.

Pancreatic leak is a major cause of morbidity after pancreatectomy. Traditionally, peripancreatic fluid collections have been managed by percutaneous or operative drainage. Data for endoscopic ultrasound (EUS)-guided drainage of postoperative fluid collections are limited. Here we report on the safety, efficacy, and timing of EUS-guided drainage of postoperative peripancreatic collections.This is a retrospective review of 31 patients who underwent EUS-guided drainage of fluid collections after pancreatic resection. Technical success was defined as successful transgastric deployment of at least one double pigtail plastic stent. Clinical success was defined as resolution of the fluid collection on follow-up CT scan and resolution of symptoms. Early drainage was defined as initial transmural stent placement within 30 days after surgery.Endoscopic ultrasound-guided drainage was performed effectively with a technical success rate of 100%. Clinical success was achieved in 29 of 31 patients (93%). Nineteen of the 29 patients (65%) had complete resolution of their symptoms and collection with the first endoscopic procedure. Repeat drainage procedures, including some with necrosectomy, were required in the remaining 10 patients, with eventual resolution of collection and symptoms. Two patients who did not achieve durable clinical success required percutaneous drainage by interventional radiology. Seventeen (55%) of 31 patients had successful early drainage completed within 30 days of their operation.Endoscopic ultrasound-guided drainage of fluid collections after pancreatic resection is safe and effective. Early drainage (30 days) of postoperative pancreatic fluid collections was not associated with increased complications in this series.

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.

Total gastrectomy (TG) is commonly performed for the treatment of patients with gastric cancer. However, reconstruction of the esophagojejunal (EJ) anastomosis can be technically demanding, with reported anastomotic leak rates in the Western world still approaching 10–15 %. We report our experience using the transoral anvil delivery system (OrVil™) for creation of the EJ anastomosis after TG. From 2007 to 2011, 48 consecutive patients with gastric cancer underwent open (n = 31) or laparoscopic (n = 17) TG. EJ reconstruction was performed with the transoral anvil deliver system (OrVil™) in an end-to-side fashion. Demographic, clinic, and perioperative data were obtained from a prospectively maintained database. Of the 48 patients, 83 % were male. Median age at resection was 64 years. Median body mass index was 27.1 kg/m2. Seventy-nine percent (n = 38) of patients had at least one comorbidity. Fifteen patients (31 %) had at least one perioperative complication. There was one perioperative death (2 %) following a duodenal stump leak. There were four EJ leaks (8 %) and two EJ stenoses (independent of leak; 4 %). There was one EJ leak (6 %) and one EJ stenosis (6 %) following a case that was first attempted laparoscopically. There were no deaths as a consequence of an EJ leak. The use of the transoral anvil delivery system during EJ reconstruction is a safe and effective option for reconstruction after open or laparoscopic TG with acceptable mortality and morbidity. The anastomotic leak rate appears to be comparable to that of other techniques.

Objective: The aim of this study was to describe postoperative outcomes of total gastrectomy at our institution for patients with hereditary diffuse gastric cancer (HDGC). Background: HDGC, which is mainly caused by germline mutations in the E-cadherin gene (CDH1), renders a lifetime risk of gastric cancer of up to 70%, prompting a recommendation for prophylactic total gastrectomy. Methods: A prospective gastric cancer database identified 41 patients with CDH1 mutation who underwent total gastrectomy during 2005 to 2015. Perioperative, histopathologic, and long-term data were collected. Results: Of the 41 patients undergoing total gastrectomy, median age was 47 years (range 20 to 71). There were 14 men and 27 women, with 25 open operations and 16 minimally invasive operations. Median length of stay was 7 days (range 4 to 50). In total, 11 patients (27%) experienced a complication requiring intervention, and there was 1 peri-operative mortality (2.5%). Thirty-five patients (85%) demonstrated 1 or more foci of intramucosal signet ring cell gastric cancer in the examined specimen. At 16 months median follow-up, the median weight loss was 4.7 kg (15% of preoperative weight). By 6 to 12 months postoperatively, weight patterns stabilized. Overall outcome was reported to be “as expected” by 40% of patients and “better than expected” by 45%. Patient-reported outcomes were similar to those of other patients undergoing total gastrectomy. Conclusion: Total gastrectomy should be considered for all CDH1 mutation carriers because of the high risk of invasive diffuse-type gastric cancer and lack of reliable surveillance options. Although most patients have durable weight loss after total gastrectomy, weights stabilize at about 6 to 12 months postoperatively, and patients report outcomes as being good to better than their preoperative expectations. No patients have developed gastric cancer recurrence after resections.