Use of a large-diameter 30-French venting gastrostomy tube is effective and safe for symptom palliation in patients with malignant bowel obstruction.

Background: Treatment options for malignant bowel obstruction are limited, particularly in poor surgical candidates. Standard percutaneous endoscopic gastrostomy (PEG) tubes used for venting are of small caliber, limiting success. This study examines outcomes in patients who received larger-caliber 30-Fr PEGs for treatment of malignant bowel obstruction. Method: Retrospective chart review for all patients who received a large-caliber venting PEGs for malignant bowel obstruction in a series of patients at a single institution. Results: Thirty-six patients were included. The most common primary cancer diagnoses were ovarian (22%), mucinous appendiceal (19%), and colorectal (17%). Symptom relief was achieved in all patients (100%). Four patients (11%) sought medical care for recurrent symptoms due to an incorrect venting technique. Large-caliber venting PEGs were placed on the first admission for obstruction in 17 patients (47%), and were used to replace standard caliber PEGs in 8 patients because of persistent symptoms (22%). Significant ascites was observed in 12 patients (33%), but paracenteses were performed in only 3 of these patients prior to PEG placement. Most large-caliber venting PEGs were placed during hospital admission (34/36, 94%), and facilitated hospital discharge (33/34, 97%). Two significant (6%) and 2 minor adverse events (6%) occurred. Conclusions: This study demonstrates the efficacy and safety of large-caliber venting PEGs for malignant bowel obstruction. This facilitated hospital discharge in almost all patients and prevented readmissions when a correct venting technique was utilized; these PEGs were also effective in patients who had failed standard PEG tube venting.

A Patient-Derived Orthotopic Xenograft Model of Gastroesophageal-Junction Adenocarcinoma Translated to the Clinic by Tumor-Targeting Fluorescent Antibodies to Carcinoembryonic-Antigen-Related Cell-Adhesion Molecules.

BACKGROUND/AIM: During surgical resection of gastroesophageal-junction (GEJ) adenocarcinoma, the margin status is often difficult to visualize resulting in high recurrence rates. The aim of the present study was to develop a labelling technique that would allow improved visualization of GEJ tumor margins for surgeons to reduce recurrence rates in a patient-like model. MATERIALS AND METHODS: A patient GEJ tumor was obtained from an endoscopic biopsy and implanted subcutaneously in a nude mouse. A patient-derived orthotopic xenograft (PDOX) model was established by implanting tumor fragments grown from a subcutaneous model to the cardia of the stomach of nude mice. CC1/3/5-SAB, an antibody to carcinoembryonic-antigen-related cell-adhesion molecules, was conjugated with infrared dye IRDye800 to create SAB-IR800. Forty-eight hours after i.v. injection of SAB-IR800, GEJ-PDOX mice were imaged. RESULTS: Fluorescence imaging with SAB-IR800 brightly visualized the GEJ adenocarcinoma demonstrating specific targeting. In the PDOX model, injection of SAB-IR800 (50 µg) resulted in a tumor to background ratio of 1.78 at 48 hours and 1.86 at 72 hours. CONCLUSION: PDOX models of GEJ tumors can be established from patients by endoscopic biopsy without undergoing surgical resection. GEJ PDOX models should be useful for developing novel diagnostics and therapeutics for this recalcitrant disease.

Protocol of early lumen apposing metal stent removal for pseudocysts and walled off necrosis avoids bleeding complications.

Background: EUS-guided drainage of pancreatic fluid collections (PFCs; pancreatic pseudocyst (PPC) or walled-off necrosis (WON)) using lumen apposing metal stents (LAMSs) is now standard of care. We adopted a protocol of early LAMS removal and prospectively followed patients to determine if this protocol avoids bleeding complications.Methods: Prospective, consecutive case series of all patients with PPC and WON who underwent drainage with LAMS at a tertiary care referral center from July 2016 to November 2018. LAMS was removed within 4 weeks for PPC and within 6 weeks for WON. Patients with residual necrosis after 6 weeks underwent removal of initial LAMS and replacement with new LAMS every 6 weeks until resolution. Patients were followed within protocol while monitoring for bleeding complications and clinical success. We also performed a literature review to determine rates of LAMS related bleeding at various timepoints.Results: Forty patients (PPC n = 19, WON n = 21) underwent drainage with LAMS. Median time for LAMS removal was 21.0 days for PPC and 33.5 days for WON. Technical success and clinical success were achieved in 40/40 patients with zero cases of delayed bleeding. A literature review of 21 studies and 1378 patients showed 52/1378 (3.8%) bleeding events with 24/52 (46.2%) events occurring within 1 week of LAMS placement.Conclusions: An early removal LAMS protocol for PFC is highly efficacious and prevents delayed bleeding. Based on analysis of published cases, half of LAMS related bleeding occurs within the first week suggesting procedural factors rather than stent dwell time impact risk of bleeding.

Endoscopic Management of Nonvariceal, Nonulcer Upper Gastrointestinal Bleeding.

Nonvariceal, nonulcer upper gastrointestinal hemorrhage (UGIH) is a less common cause for acute upper gastrointestinal bleeding. However, nonvariceal, nonulcer UGIH is an important entity to identify and treat appropriately to prevent bleeding-related morbidity and mortality. Over the past 40 years, there has been a revolution in gastrointestinal endoscopy and a similar revolution in the management of UGIH. The aim of this article is to focus on the endoscopic management of nonvariceal, nonulcer UGIH, with a focus on the newer diagnostic and treatment modalities currently available.

Preventing Rescue Surgeries by Endoscopic Clipping: A Valuable Resource in the Surgeon's Toolbox.

AIM: Over-the-scope-clip (OTSC) System is a relatively new endoluminal intervention for gastrointestinal (GI) leaks, fistulas, and bleeding. Here, we present a single center experience with the device over the course of 4 years. METHODS: Retrospective chart review was conducted for patients who received endoscopic OTSC treatment. Primary outcome is the resolution of the original indication for clip placement. Secondary outcomes are complications and time to resolution. RESULTS: Forty-one patients underwent treatment with the OTSC system from 2011 to 2015 with average follow-up of 152 days. The average age is 53.7. The most common site of clip placement was in the stomach (44%). Clips were placed after surgical complication for 28 patients (68%), endoscopic complications for 8 patients (19%), and spontaneous presentation in 5 patients (12%). Technical success was achieved in all patients. Overall, 34 patients (83%) were successfully treated. Nine patients required multiple clips and three patients required additional treatment modalities after OTSC. Four patients used the OTSC as a bridging therapy to surgery. Using OTSC for palliation versus nonpalliative indications was associated with lower rates of treatment success (50% versus 86%, P = .028). Using OTSC for symptoms <6 months had higher rates of treatment success than those experiencing longer symptoms (88% versus 65%, P = .045). There were no major morbidities or mortalities directly associated with the OTSC system. Complications from clip use were pain in two patients (5%) and hematemesis in one patient (3%). CONCLUSIONS: The OTSC System can be a very successful treatment for iatrogenic or spontaneous GI leaks and bleeds. Treatment success is more likely in patients treated within 6 months of diagnosis and less likely to when used for palliation. It was also successfully used as bridging therapy in several patients.

Gastric Medullary Carcinoma with Sporadic Mismatch Repair Deficiency and a TP53 R273C Mutation: An Unusual Case with Wild-Type BRAF.

Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1) and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C) mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

Low Rates of Malignancy and Mortality in Asymptomatic Patients With Suspected Neoplastic Pancreatic Cysts Beyond 5 Years of Surveillance.

BACKGROUND & AIMS: The 2015 American Gastroenterological Association guidelines recommend discontinuation of surveillance of pancreatic cysts after 5 years, although there are limited data to support this recommendation. We aimed to determine the rate of pancreatic cancer development from neoplastic pancreatic cysts after 5 years of surveillance. METHODS: We performed a retrospective multicenter study, collecting data from 310 patients with asymptomatic suspected neoplastic pancreatic cysts, identified by endoscopic ultrasound from January 2002 to June 2010 at 4 medical centers in California. All patients were followed up for 5 years or more (median, 87 mo; range, 60-189 mo). Data were used to calculate the risk for pancreatic cancer and all-cause mortality. RESULTS: Three patients (1%) developed invasive pancreatic adenocarcinoma. Based on American Gastroenterological Association high-risk features (cyst size > 3 cm, dilated pancreatic duct, mural nodule), risks for cancer were 0%, 1%, and 15% for patients with 0, 1, or 2 high-risk features, respectively. Mortality from nonpancreatic causes was 8-fold higher than mortality from pancreatic cancer after more than 5 years of surveillance. CONCLUSIONS: There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years. Patients with pancreatic lesions and 0 or 1 high-risk feature have a less than 1% risk of developing pancreatic cancer, therefore discontinuation of surveillance can be considered for select patients. Patients with neoplastic pancreatic cysts with 2 high-risk features have a 15% risk of subsequent pancreatic cancer, therefore surgery or continued surveillance should be considered.

Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer.

BACKGROUND: The risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed in the 2012 international consensus guidelines ("Fukuoka criteria"). METHODS: Retrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest-Risk Group", LRG). RESULTS: After exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001). CONCLUSIONS: This study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with "high-risk stigmata" or "worrisome features" criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk.

Low yield of routine duodenal biopsies for evaluation of abdominal pain.

AIM: To determine the yield of biopsying normal duodenal mucosa for investigation of abdominal pain. METHODS: This is a retrospective chart review of consecutive patients who underwent esophagogastroduodenoscopy (EGD) with duodenal biopsies of normal appearing duodenal mucosa for an indication that included abdominal pain. All the patients in this study were identified from an electronic endoscopy database at a single academic medical center and had an EGD with duodenal biopsies performed over a 4-year period. New diagnoses that were made as a direct result of duodenal biopsies were identified. All duodenal pathology reports and endoscopy records were reviewed for indications to perform the examination as well as the findings; all the medical records were reviewed. Exclusion criteria included age less than 18 years, duodenal mass, nodule, or polyp, endoscopic duodenitis, duodenal scalloping, known celiac disease, positive celiac serology, Crohns disease, or history of bone marrow transplant. Information was collected in a de-identified database with pertinent demographic information including human immunodeficiency virus (HIV) status, and descriptive statistics were performed. RESULTS: About 300 patients underwent EGD with biopsies of benign appearing or normal appearing duodenal mucosa. The mean age of patients was 44.1 ± 16.8 years; 189 of 300 (63%) were female. A mean of 4.3 duodenal biopsies were performed in each patient. In the subgroup of patients with abdominal pain without anemia, diarrhea, or weight loss the mean age was 43.4 ± 16.3 years. Duodenal biopsies performed for an indication that included abdominal pain resulting in 4 new diagnoses (3 celiac disease and 1 giardiasis) for an overall yield of 1.3%. 183 patients with abdominal pain without anemia, diarrhea, or weight loss (out of the total 300 patients) underwent duodenal biopsy of duodenal mucosa resulting in three new diagnoses (two cases of celiac disease and one giardiasis) for a yield of 1.6%. Duodenal biopsies of 19 HIV patients presenting for evaluation of abdominal pain did not reveal any new diagnoses. Information pertaining to new diagnoses is provided. CONCLUSION: Routine biopsy of normal appearing duodena in patients with abdominal pain should be reserved for those with a high pre-test probability given its low diagnostic yield.

Strongyloides stercoralis Hyperinfection Syndrome Presenting as Severe, Recurrent Gastrointestinal Bleeding, Leading to a Diagnosis of Cushing Disease.

A 50-year-old male immigrant from Ethiopia presented for consultation after 3 years of hematochezia/melena requiring > 25 units of blood transfusions. Physical examination revealed severe proximal muscle wasting and weakness, central obesity, proptosis, and abdominal striae, accompanied by eosinophilia, elevated hemoglobin A1c, elevated 24-hour urinary cortisol, lack of suppression of 8 am cortisol levels by 1 mg dexamethasone, and inappropriately elevated random adrenocorticotropic hormone (ACTH) level. Histopathological examination of gastrointestinal biopsies showed large numbers of Strongyloides stercoralis, indicating Strongyloides hyperinfection. Treatment with 2 days of ivermectin led to resolution of gastrointestinal bleeding. This syndrome was due to chronic immunosuppression from a pituitary ACTH (corticotroph) microadenoma, of which resection led to gradual normalization of urine cortisol, improved glycemic control, resolution of eosinophilia, and no recurrence of infection.

Rapid Growth Rates of Suspected Pancreatic Cyst Branch Duct Intraductal Papillary Mucinous Neoplasms Predict Malignancy.

BACKGROUND: The majority of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) are recommended for surveillance imaging based on consensus guidelines. However, growth rates that should prompt concern for malignant transformation of BD-IPMN are unknown. AIMS: To determine whether BD-IPMN growth can predict an increased risk of malignancy and define growth rates concerning for malignant BD-IPMN. METHODS: The study is a retrospective, multicenter study of suspected BD-IPMN patients undergoing imaging surveillance. All patients underwent EUS evaluation followed by surveillance imaging. RESULTS: Two hundred and eighty-four patients with suspected BD-IPMN without worrisome features or high-risk stigmata were followed for a median 56 months and underwent a median of four imaging studies. Nine patients (3.2 %) developed malignant BD-IPMN. Malignant BD-IPMN grew at a faster rate (18.6 vs. 0.8 mm/year; P = 0.05) compared to benign BD-IPMN. BD-IPMN growth rate between 2 and 5 mm/year was associated with an increased risk of malignancy with hazard ratio (HR) of 11.4 (95 % CI 2.2-58.6) when compared to subjects with BD-IPMN growth rate <2 mm/year (P = 0.004). BD-IPMN growth rate ≥5 mm/year had a hazard ratio of 19.5 (95 % CI 2.4-157.8) (P = 0.005). BD-IPMN growth rate of 2 mm/year had a sensitivity of 78 %, specificity of 90 %, and accuracy of 88 % to identify malignancy. Total BD-IPMN growth was also associated with increased risk of malignancy (P = 0.003) with all malignant IPMNs growing at least 10 mm prior to cancer diagnosis. CONCLUSIONS: BD-IPMN growth rates ≥2 mm/year and total growth of ≥10 mm should be considered worrisome features for BD-IPMN at increased risk of malignancy.

Laparo-endoscopic transgastric resection of gastric submucosal tumors.

BACKGROUND: Laparoscopic and endoluminal surgical techniques have evolved and allowed improvements in the methods for treating benign and malignant gastrointestinal diseases. To date, only case reports have been reported on the application of a laparo-endoscopic approach for resecting gastric submucosal tumors (SMT). In this study, we aimed to evaluate the efficacy, safety, and oncologic outcomes of a laparo-endoscopic transgastric approach to resect tumors that would traditionally require either a laparoscopic or open surgical approach. Herein, we present the largest single institution series utilizing this technique for the resection of gastric SMT in North America. METHODS: We performed a retrospective review of a prospectively collected patient database. Patients who presented for evaluation of gastric SMT were offered this surgical procedure and informed consents were obtained for participation in the study. RESULTS: Fourteen patients were included in this study between August/2010 and January/2013. Eight (8) patients (57.1 %) were female and the median age was 56 years (range 29-78). Of the 14 cases, 8 patients (57.1 %) underwent laparo-endoscopic resection of SMTs with transgastric extraction, 5 patients (35.7 %) had conversions to traditional laparoscopic surgery, and 1 patient (7.2 %) was abandoned intraoperatively. The median operative time for this cohort was 80 min (range 35-167). Ten patients (71.4 %) had GISTs, 3 (21.4 %) had leiomyomas, and 1 (7.1 %) had schwannoma. There were no intraoperative complications. Two patients had postoperative staple line bleeding that required repeat endoscopy. The median hospital stay was 1 day (range 1-6) and there were no postoperative mortalities. At 12-month follow-up visit, only one GIST patient (10 %) had tumor recurrence. CONCLUSION: Our experience suggests that this surgical approach is safe and efficient in the resection of gastric SMT with transgastric extraction. This study found no intraoperative complications and optimal oncologic outcomes during the follow-up period. Minimally invasive surgical approaches are emerging as a valid and potentially better approach for resecting malignancies; however, continued investigation is underway to further validate this data.

Enteral stenting for gastric outlet obstruction and afferent limb syndrome following pancreaticoduodenectomy.

BACKGROUND: Obstruction of the afferent or efferent limbs of a gastrojejunal anastomosis is a potential complication after pancreaticoduodenectomy (PD) resulting in either gastric outlet obstruction or afferent limb syndrome. The use of self-expanding metal stents for the management of anastomotic strictures after resection of pancreatic cancer has not been well studied. We present four such cases and review published data regarding this population. METHODS: Retrospective chart review and literature search. Outcomes were summarized with descriptive statistics. RESULTS: At our institution, 4 patients underwent metal stent placement for gastrojejunal obstruction after PD for pancreatic cancer. Enteral stents were placed in two patients across the afferent limb, in one patient across the efferent limb, and in another patient across both limbs. Similar cases in the literature revealed that the anastomotic stricture was malignant in 26 of 27 cases. Clinical improvement occurred in 88%. Afferent limb syndrome was successfully treated in 5 of 6 cases. Median survival was 3.5 months after stent placement. CONCLUSIONS: Effective palliation of both gastric outlet obstruction and afferent limb syndrome after PD can be provided with enteral stenting. Gastrojejunal strictures after PD for pancreatic cancer are usually malignant with median survival of 3.5 months after stent placement.

Increased rates of duodenal obstruction in pancreatic cancer patients receiving modern medical management.

BACKGROUND: Duodenal obstruction from pancreatic cancer historically occurs in 2-25 % of patients without surgery, but with new advances in chemotherapy and radiation therapy, the life expectancy of pancreatic cancer has increased. AIM: The aim of the study was to determine the rate of development of duodenal obstruction requiring intervention in patients with pancreatic head adenocarcinoma who do not undergo surgical resection, but receive modern chemoradiation. METHODS: It is a retrospective single center study. Inclusion criteria were patients with pancreatic cancer who underwent ERCP with metal biliary stent and then chemoradiation who subsequently developed symptomatic duodenal obstruction and underwent either metal duodenal stent placement or surgical duodenal bypass. RESULTS: Twenty-four of 63 patients (38 %, 95 % CI 26-50 %) with unresectable pancreatic cancer and biliary stents who received chemotherapy and/or radiation therapy developed duodenal obstruction. The average length of time from diagnosis of pancreatic adenocarcinoma to development of outlet obstruction was 11.4 ± 4.9 months (range 1.5-40 months). Average length of time from development of duodenal obstruction to death was 4.8 ± 2.1 months (range 0.5-60 months). Average survival time from diagnosis to death was 16.6 ± 5.6 months (range 4.5-58 months). CONCLUSION: Thirty-eight percent of patients with unresectable pancreatic head adenocarcinoma and metal biliary stents who receive chemotherapy and/or radiation therapy eventually develop symptomatic duodenal obstruction requiring duodenal stent or surgical bypass. This rate of duodenal obstruction is nearly twice that of previous reports using older oncologic therapy and will likely increase as patients survive longer with advances in medical therapy for pancreatic cancer.