Pancreatic cyst features predict future development of pancreatic cancer: results of a nested case-control study.

BACKGROUND AND AIMS: Risk factors for pancreatic cancer among patients with pancreatic cysts are incompletely characterized. The primary aim of this study was to evaluate risk factors for development of pancreatic cancer among patients with pancreatic cysts. METHODS: We conducted a retrospective case-control study of U.S. veterans with a suspected diagnosis of branch-duct intraductal papillary mucinous neoplasm from 1999 to 2013. RESULTS: Age (hazard ratio [HR], 1.03 per year; 95% confidence interval [CI], 1.00-1.06), larger cyst size at cyst diagnosis (HR, 1.03 per mm; 95% CI, 1.01-1.04), cyst growth rate (HR, 1.22 per mm/y; 95% CI, 1.14-1.31), and pancreatic duct dilation (5-9.9 mm: HR, 3.78; 95% CI, 1.90-7.51; ≥10 mm: HR, 13.57; 95% CI, 5.49-33.53) were found to be significant predictors for pancreatic cancer on multivariable analysis. CONCLUSIONS: Age, cyst size, cyst growth rate, and high-risk or worrisome features were associated with a higher risk of developing pancreatic cancer. Applying current and developing novel strategies is required to optimize early detection of pancreatic cancer after cyst diagnosis.

AGA Clinical Practice Update on Management of Subepithelial Lesions Encountered During Routine Endoscopy: Expert Review.

BEST PRACTICE ADVICE STATEMENTS: BEST PRACTICE ADVICE 1: Forceps bite-on-bite or deep-well biopsies or tunnel biopsies can sometimes establish a pathologic diagnosis of SEL. BEST PRACTICE ADVICE 2: EUS is the modality of choice to evaluate indeterminate SEL of the GI track and/or if non-diagnostic tissue by forceps biopsies. BEST PRACTICE ADVICE 3: SEL arising from the submucosa can be sampled using tunnel biopsies (or deep-well biopsies), EUS guided fine-needle aspiration (FNA), EUS guided fine-needle biopsy (FNB), or advanced endoscopic techniques (unroofing or endoscopic submucosal resection). BEST PRACTICE ADVICE 4: SEL arising from muscularis propria should be sampled (preferably using FNB or FNA) to determine whether the lesion is a GIST or leiomyoma. Structural assessment and staining will allow differentiation of mesenchymal tumors and assessing their malignant potential. BEST PRACTICE ADVICE 5: Endoscopic resection techniques have been described for removal of SEL and should be limited to endoscopists skilled in advanced tissue resection techniques. BEST PRACTICE ADVICE 6: Management of each SEL depends on the size of the lesion, histopathology, their malignant potential, and presence of symptoms. BEST PRACTICE ADVICE 7: SEL that have an endoscopic appearance consistent with a lipoma or pancreatic rest and normal mucosal biopsies do not need further evaluation or surveillance. BEST PRACTICE ADVICE 8: For SEL arising from muscularis propria that are less than 2 cm in size, surveillance using EUS should be considered. BEST PRACTICE ADVICE 9: Gastric GIST larger than 2 cm should be considered for resection. BEST PRACTICE ADVICE 10: Subepithelial lesions that are ulcerated, bleeding, or causing symptoms should be considered for resection.

Comparison of cold snare and hot snare polypectomy for the resection of sporadic nonampullary duodenal adenomas.

BACKGROUND AND AIMS: Nonampullary duodenal adenomas can undergo malignant transformation, making endoscopic resection, often by hot snare (HSP) or cold snare polypectomy (CSP), necessary. Although CSP has been shown to be safer for removal of colon polyps, data comparing these techniques for the resection of duodenal adenomas are limited. Our aim was to compare the safety and efficacy of CSP and HSP for the removal of nonampullary duodenal adenomas. METHODS: We performed a retrospective cohort study of patients referred to 2 academic medical centers with a histologically confirmed sporadic, nonampullary duodenal adenoma who underwent endoscopic snare polypectomy between January 1, 2007 and March 1, 2021. Patients with underlying polyposis syndromes were excluded. Outcomes included postprocedural adverse events and polyp recurrence. RESULTS: Of 110 total patients, 69 underwent HSP and 41 underwent CSP. Intraprocedural bleeding was similar between both groups, but 7 patients in the HSP group experienced delayed adverse events versus none in the CSP group (P = .04). Fifty-four patients had complete polyp resection and subsequent surveillance endoscopies. Multivariate analysis showed polyp size to be associated with recurrence (per mm; odds ratio, 1.11; 95% confidence interval, 1.04-1.20; P < .01). Endoscopic resection technique (HSP vs CSP) was not a predictor of recurrence (P = .18). CONCLUSIONS: HSP led to more delayed adverse events compared with CSP, whereas no significant differences on outcomes were noted, suggesting that CSP is equally effective and potentially safer for the removal of duodenal adenomas.

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.

Pancreas Cancer Incidence and Pancreas Cancer-Associated Mortality Are Low in National Cohort of 7211 Pancreas Cyst Patients.

BACKGROUND AND AIMS: Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period. METHODS: We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999-2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality. RESULTS: Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4 years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths). CONCLUSIONS: Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance.

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.

Biallelic Mismatch Repair Deficiency in an Adolescent Female.

Constitutional (Biallelic) Mismatch Repair Deficiency is a rare autosomal recessive disorder characterized by numerous cancers presenting as early as the first decade of life. Biallelic germline variants in one of four mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) cause this devastating disease. Given the rarity of the syndrome, often-asymptomatic tumors, and overlap with neurofibromatosis-1, diagnosis is frequently unrecognized or delayed. We present a unique case of a 14-year-old female with minimal gastrointestinal symptoms diagnosed with invasive adenocarcinoma secondary to biallelic PMS2 variants.

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.

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.