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.

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.

Evolution and evidence-based adaptations in techniques for peroral endoscopic myotomy for achalasia.

Achalasia is an esophageal motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation and failed peristalsis. Common clinical manifestations include dysphagia to solid and liquid foods, chest pain, regurgitation, and weight loss, resulting in significant morbidity and healthcare burden. Historically, surgical Heller myotomy and pneumatic dilation were the first-line therapeutic options for achalasia. This convention was shaken in 2009 when Inoue and colleagues introduced an endoscopic approach to dissect the muscle fibers of the LES, known as peroral endoscopic myotomy (POEM). Since incorporation of POEM into standard practice, the overall myotomy technique has remained unchanged; however, adaptations in the thickness and length of myotomy have evolved. Full-thickness myotomy is recognized to have similar clinical success and faster procedure times compared with selective circular muscle myotomy. Although myotomy length for type 1 and type 2 achalasia has classically been >6 cm, recent studies demonstrated similar outcomes with reduction of myotomy length to <3 cm. Length of myotomy for type 3 achalasia has been tailored to treat the entire length of spastic muscle segment, and the modality to gauge the optimal thickness and length of myotomy in this group has yet to be established. In addition to changes in POEM technique, the postoperative management of POEM has also changed, favoring reduced postprocedure imaging, antibiotic use, and hospitalizations.

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.

Comparative efficacy of first-line therapeutic interventions for achalasia: a systematic review and network meta-analysis.

BACKGROUND: Several interventions with variable efficacy are available as first-line therapy for patients with achalasia. We assessed the comparative efficacy of different strategies for management of achalasia, through a network meta-analysis combining direct and indirect treatment comparisons. METHODS: We identified six randomized controlled trials in adults with achalasia that compared the efficacy of pneumatic dilation (PD; n = 260), laparoscopic Heller myotomy (LHM; n = 309), and peroral endoscopic myotomy (POEM; n = 176). Primary efficacy outcome was 1-year treatment success (patient-reported improvement in symptoms based on validated scores); secondary efficacy outcomes were 2-year treatment success and physiologic improvement; safety outcomes were risk of gastroesophageal reflux disease (GERD), severe erosive esophagitis, and procedure-related serious adverse events. We performed pairwise and network meta-analysis for all treatments, and used GRADE criteria to appraise quality of evidence. RESULTS: Low-quality evidence, based primarily on direct evidence, supports the use of POEM (RR [risk ratio], 1.29; 95% confidence intervals [CI], 0.99-1.69), and LHM (RR, 1.18 [0.96-1.44]) over PD for treatment success at 1 year; no significant difference was observed between LHM and POEM (RR 1.09 [0.86-1.39]). The incidence of severe esophagitis after POEM, LHM, and PD was 5.3%, 3.7%, and 1.5%, respectively. Procedure-related serious adverse event rate after POEM, LHM, and PD was 1.4%, 6.7%, and 4.2%, respectively. CONCLUSIONS: POEM and LHM have comparable efficacy, and may increase treatment success as compared to PD with low confidence in estimates. POEM may have lower rate of serious adverse events compared to LHM and PD, but higher rate of GERD.

American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in familial adenomatous polyposis syndromes.

Familial adenomatous polyposis (FAP) syndrome is a complex entity, which includes FAP, attenuated FAP, and MUTYH-associated polyposis. These patients are at significant risk for colorectal cancer and carry additional risks for extracolonic malignancies. In this guideline, we reviewed the most recent literature to formulate recommendations on the role of endoscopy in this patient population. Relevant clinical questions were how to identify high-risk individuals warranting genetic testing, when to start screening examinations, what are appropriate surveillance intervals, how to identify endoscopically high-risk features, and what is the role of chemoprevention. A systematic literature search from 2005 to 2018 was performed, in addition to the inclusion of seminal historical studies. Most studies were from worldwide registries, which have compiled years of data regarding the natural history and cancer risks in this cohort. Given that most studies were retrospective, recommendations were based on epidemiologic data and expert opinion. Management of colorectal polyps in FAP has not changed much in recent years, as colectomy in FAP is the standard of care. What is new, however, is the developing body of literature on the role of endoscopy in managing upper GI and small-bowel polyposis, as patients are living longer and improved endoscopic technologies have emerged.

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.

ASGE guideline on the management of achalasia.

Achalasia is a primary esophageal motor disorder of unknown etiology characterized by degeneration of the myenteric plexus, which results in impaired relaxation of the esophagogastric junction (EGJ), along with the loss of organized peristalsis in the esophageal body. The criterion standard for diagnosing achalasia is high-resolution esophageal manometry showing incomplete relaxation of the EGJ coupled with the absence of organized peristalsis. Three achalasia subtypes have been defined based on high-resolution manometry findings in the esophageal body. Treatment of patients with achalasia has evolved in recent years with the introduction of peroral endoscopic myotomy. Other treatment options include botulinum toxin injection, pneumatic dilation, and Heller myotomy. This American Society for Gastrointestinal Endoscopy Standards of Practice Guideline provides evidence-based recommendations for the treatment of achalasia, based on an updated assessment of the individual and comparative effectiveness, adverse effects, and cost of the 4 aforementioned achalasia therapies.

ASGE review of adverse events in colonoscopy.

Colonoscopy is the most commonly performed endoscopic procedure and overall is considered a low-risk procedure. However, adverse events (AEs) related to this routinely performed procedure for screening, diagnostic, or therapeutic purposes are an important clinical consideration. The purpose of this document from the American Society for Gastrointestinal Endoscopy's Standards of Practice Committee is to provide an update on estimates of AEs related to colonoscopy in an evidence-based fashion. A systematic review and meta-analysis of population-based studies was conducted for the 3 most common and important serious AEs (bleeding, perforation, and mortality). In addition, this document includes an updated systematic review and meta-analysis of serious AEs (bleeding and perforation) related to EMR and endoscopic submucosal dissection for large colon polyps. Finally, a narrative review of other colonoscopy-related serious AEs and those related to specific colonic interventions is included.

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.

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.

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.

Endoscopic ultrasound in the diagnosis of pancreatic cancer.

INTRODUCTION: Cross sectional imaging is important for initial evaluation of pancreatic cancer, whereas endoscopic ultrasound (EUS) will often help better visualize, differentiate and make final tissue diagnosis. It plays an important role in the multi-disciplinary evaluation and staging of pancreatic cancer as accurate staging has significant impact on treatment decisions. AREAS COVERED: This review will cover the yield and utility of EUS and EUS FNA for diagnosis of pancreas cancer. In addition, this article reviews the utility and diagnostic yield of the non-invasive imaging modalities, including surface ultrasound, CT scan, PET CT scan and MRI. Tumor size, histology and disease processes that mimic pancreatic cancers will also be reviewed. EXPERT OPINION: The accurate diagnosis and staging of pancreatic neoplasms is essential for optimal patient management. Abdominal imaging with multidetector CT or MRI is the most important initial step in the evaluation of pancreatic cancer because they are widely available and can detect most masses and/or demonstrate dilated bile or pancreatic ducts indicative of obstruction. Endoscopic ultrasound will remain important for detecting small tumors, ruling out diseases that mimic adenocarcinoma and for obtaining tissue diagnosis with fine needle aspiration.

Long-term risk of cholangitis in patients with metal stents for malignant biliary obstruction.

BACKGROUND: Patients with malignant biliary obstruction are commonly living longer than previously due to improved oncologic therapies, often exceeding expected times of self-expanding metal stent patency. AIMS: The purpose of this study was to assess the long-term risk and impact of cholangitis in these patients. METHODS: Retrospective review of electronic medical records at an academic medical center. RESULTS: One hundred and one patients had a self-expanding metal stent placed for malignant biliary obstruction. The median survival after SEMS was 214 days. Of these patients, 22 % developed at least one episode of cholangitis requiring inpatient admission, 20 % (9/45) of patients were hospitalized for cholangitis at 6 months, 40 % (8/20) at 1 year, and 75 % (3/4) at 2 years. All of the (8/8) patients receiving chemotherapy prior to hospitalization for cholangitis experienced delays in subsequent chemotherapy. Follow-up of 36 episodes of cholangitis revealed a 14 % 30-day mortality. CONCLUSIONS: Cholangitis develops commonly in long-term survivors with self-expanding metal stents for malignant biliary obstruction, and is associated with delays in chemotherapy and a 14 % 30-day mortality.