Robin B. Mendelsohn

Carcinomatosis is not a contraindication to enteral stenting in selected patients with malignant gastric outlet obstruction

BACKGROUND Endoscopically inserted self-expandable metal stents (SEMSs) are used to palliate malignant gastric outlet obstruction (GOO). Peritoneal disease is considered a relative contraindication to SEMS placement given the risk of multifocal obstruction. OBJECTIVE To evaluate the success of SEMSs placed in patients with GOO with carcinomatosis. DESIGN Retrospective review of patients who underwent SEMS placement for malignant GOO. SETTING Large, urban cancer center. PATIENTS A total of 215 patients who were scheduled for SEMS placement for GOO. INTERVENTIONS SEMS placement. MAIN OUTCOME MEASUREMENTS Technical success, clinical success, early and late SEMS failure, and complications. RESULTS Technical success was achieved in 192 of 201 patients (95.5%). Of the 9 patients who did not achieve technical success, 6 had carcinomatosis. Among the 116 patients (60%) with carcinomatosis, clinical success was achieved 94 of them (81%). Of these 94 patients, 17 (18%) required reinterventions: 4 for early SEMS failure and 13 for late SEMS failure. Among the 76 patients (40%) without carcinomatosis, clinical success was achieved in 64 of them (84%). Of these 64 patients, 17 (27%) required reinterventions: 4 for early SEMS failure and 13 for late SEMS failure. Complication rates were similar for both groups. LIMITATIONS This was a retrospective review with experienced clinicians selecting patients whom they thought would benefit from SEMS placement. CONCLUSIONS This is the first study to evaluate the effect of carcinomatosis on the technical and clinical success of SEMSs in the palliation of malignant GOO. We found clinical outcomes comparable to those without peritoneal disease. Carcinomatosis should not be considered a contraindication to SEMS placement in selected patients with malignant GOO.

Biliary Self-Expandable Metal Stents Do Not Adversely Affect Pancreaticoduodenectomy

OBJECTIVES:Controversy exists regarding whether to place a plastic or a metal endobiliary stent in patients with resectable pancreatic cancer who require biliary drainage. Although self-expandable metal stents (SEMS) provide better drainage compared with plastic stents, concerns remain that SEMS may compromise resection and increase postoperative complications. Our objective was to compare surgical outcomes of patients undergoing pancreaticoduodenectomy (PD) with SEMS in place vs. plastic endoscopic stents (PES) and no stents (NS).METHODS:We performed a retrospective analysis from a prospective database of all patients undergoing either attempted or successful PD with SEMS, PES, or NS in place at the time of operation. Patients were compared with regard to perioperative complications, margin status, and the rate of intraoperative determination of unresectability.RESULTS:A total of 593 patients underwent attempted PD. Of these, 84 patients were locally unresectable intraoperatively and 509 underwent successful PD, of which 71 had SEMS, 149 had PES, and 289 had NS. Among patients who had a preoperative stent, SEMS did not increase overall or serious postoperative complications, 30-day mortality, length of stay, biliary anastomotic leak, or positive margin, but was associated with more wound infections and longer operative times. In those with adenocarcinoma, intraoperative determination of local unresectability was similar in the SEMS group compared with other groups, with 16 (19.3%) in SEMS compared with 29 (17.7%) in PES (P=0.862), and 31 (17.5%) in NS (P=0.732).CONCLUSIONS:Placement of SEMS is not contraindicated in patients with resectable pancreatic cancer who require preoperative biliary drainage.

Endoscopic Management of Esophageal Anastomotic Leaks After Surgery for Malignant Disease

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.

Mismatch repair deficient-crypts in non-neoplastic colonic mucosa in Lynch syndrome: insights from an illustrative case

Mono-allelic germline mutations in DNA mismatch repair (MMR) genes lead to Lynch syndrome (LS). Questions remain as to the timing of the inactivation of the wild-type allele in LS-associated tumorigenesis. Speculation exists that it happens after the neoplasia has been initiated. However, a recent study reported the presence of MMR-deficiency in non-neoplastic colonic crypts in LS; thus the possibility can be raised that these crypts may be tumor precursors, and as such, biallelic loss of MMR may occur prior to neoplasia. Here we report a unique case that showed findings supporting both of the two seemingly conflicting notions. The patient was a 40-year-old female with LS, MSH2 type, who underwent a segmental colectomy for an adenocarcinoma. By immunohistochemistry, the carcinoma lost MSH2/MSH6. Interestingly, there was also complete loss of MSH2/MSH6 in a distinct focus of 20 colonic crypts that were morphologically non-neoplastic, thus supporting the possibility of biallelic loss of MMR before initiation of neoplasia. However, in a separate adenoma, MMR was preserved in neoplastic glands with low grade dysplasia and lost only in glands with high grade dysplasia, i.e., MMR loss after tumor initiation. These are relevant findings with regard to the timing of MMR deficiency in LS tumorigenesis, and bring forth the possibility that varied tumorigenic pathways may exist. Additionally, we observed that the MMR-deficient non-neoplastic crypts harbored increased intraepithelial CD8-positive T-lymphocytes similar to the patient’s carcinoma, providing a potential new venue for the study of the natural antitumor immune responses in LS individuals.

Molecular Screening for Lynch Syndrome in Young Patients With Colorectal Adenomas

Background: The frequency of mismatch repair (MMR) deficiency (dMMR) in patients < 50 years with adenomas without a known germline mutation is unknown. Our aim was to define the frequency of dMMRs in adenomas from patients aged < 50 years. Patients and Methods: We identified all patients aged 18 to 49 years who had undergone colonoscopy at Memorial Sloan Kettering Cancer Center from 2008 to 2013 and were identified as having tubular, villous, or tubulovillous adenomas on pathology. Patients with a personal history of colorectal cancer, polyposis syndrome, or inflammatory bowel disease before colonoscopy were excluded. Age, demographic data, family history of cancer, personal history of cancer, use of radiation, reason for colonoscopy, and colonoscopy findings were recorded. Polyps were stained using immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 proteins. Results: A total of 208 patients with 266 polyps were identified. Of the 266 polyps, 259 could be stained. Of the 208 patients, 82 (40%) were men; their mean age was 44 years. The indication for colonoscopy was screening for 120, diagnostic for 75, and therapeutic for 15. Of the 259 examined polyps, 246 (95%) were tubular adenomas and 13 were tubulovillous adenomas (5%). One patient (0.4%) was found to have dMMRs in 1 polyp. This patient was a 42‐year‐old woman with a history of endometrial cancer who had undergone colonoscopy for hematochezia. A 15‐mm transverse tubular adenoma was found that was deficient in MLH1 and PMS2. Conclusion: Our results indicate that routine screening of polyps in patients aged < 50 years old is not an effective tool for identifying Lynch syndrome carriers. &NA; Lynch syndrome, the most common cause of hereditary colorectal cancer, is caused by mutations in mismatch repair (MMR) proteins. Identification of Lynch syndrome before the cancer diagnosis is critical. We stained 266 polyps of patients aged < 50 years looking for MMR deficiencies and found 1 polyp that was MMR deficient. Routine polyp staining for MMR did not effectively identify LS carriers.

Direct Percutaneous Endoscopic Jejunostomy: Procedural and Nutrition Outcomes in a Large Patient Cohort

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.

Adenoma Prevalence in Blacks and Whites Having Equal Adherence To Screening Colonoscopy: The National Colonoscopy Study

Is the higher reported colorectal cancer (CRC) mortality in blacks versus whites in the United States due to pathology or disparities in screening? Our study used patient navigation (PN) to assist blacks and whites adhere to screening colonoscopy and compared adenomas detected in each group.

954 Prevalence of Colorectal Adenomas in Blacks, Whites and Hispanics Having Screening Colonoscopy in a Patient Navigation Program: A Prospective Multicenter Study

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third most common cause of cancer deaths in both men and women in the United States. Blacks have been reported to have a higher incidence and mortality and a more proximal anatomic distribution of CRC compared to whites and Hispanics. However, it is unclear whether this is due to biological differences in the pathology of adenomatous polyps or lower screening rates. Existing data consisting of retrospective studies and one single center prospective study indicate that factors such as access to health care and modifiable risk factors may be responsible for these racial disparities as opposed to biological differences. Methods: In 2003, the New York City Department of Health and Mental Hygiene (NYC DOHMH) implemented the Colonoscopy Patient Navigator Program (CPNP). Ten New York City Hospital Sites, five public and five private, participated in the study. Through a one to one relationship, PN helped to bridge disparities by scheduling appointments, educating regarding bowel preparation and addressing obstacles. Data were prospectively collected from 2005 through the first quarter of 2012 from centers with at least three consecutive years of reporting while using PN. Patient information including name, contact information, gender, date of birth, ethnicity and insurance information was collected by each PN during the initial contact after the patient was referred for screening colonoscopy (sCo). Adenoma and cancer detection rates, pathology and location were recorded and stratified by patient demographic characteristics including age, gender, and race. Results: With the assistance of PN, 29,711 individuals ages 50 and older underwent complete sCo. A total of 6226 adenomas and 35 cancers were found. The prevalence of adenomas was higher among white patients than black patients (27.45% versus 19.35%, p value < 0.05) (See tables 1 and 2). With the exception of the hepatic flexure, whites had a statistically significant higher prevalence of adenomas, segment by segment, than blacks and Hispanics. Conclusion: This is a prospective multicenter center study of a large urban cohort investigating the prevalence of adenomas in blacks versus whites and Hispanics using a PN program. Preliminary data do not show that blacks have an increased risk of adenomas compared to whites and Hispanics. This suggests that the higher incidence and mortality from CRC in blacks that was reported in other studies aremore likely a function of access to colonoscopy as opposed to biologic factors. Table 1: Results of completed screening colonoscopy exams cross-tabulated by patient race (age ≥ 50)

Sa1019 Incidence of Hepatitis B Surface Antigen and Hepatitis B Core Antibody in a Screening Population Undergoing Chemotherapy

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