Impact of Ethno-racial Factors on Clinical Outcomes and Health Care Utilization in Chronic Pancreatitis.

BACKGROUND: Healthcare disparities adversely affect clinical outcomes in racial and ethnic minorities. Chronic pancreatitis (CP) is a complex disorder, and pressures for time and cost-containment may amplify the disparity for minorities in this condition. This study aimed to assess ethno-racial differences in the clinical outcomes of CP patients cared for at our institution. METHODS: This is a study of CP patients with available ethno-racial information followed at our pancreas center. We reviewed their demographics, comorbidities, clinical outcomes, and resource utilization: pain, frequent flares (≥ 2/year), local complications, psychosocial variables, exocrine, and endocrine insufficiency, imaging, endoscopic procedures, and surgeries. The outcomes underwent logistic regression to ascertain association(s) with covariates and were expressed as odds ratio (95% confidence intervals). RESULTS: Of the 445 CP patients, there were 23 Hispanics, 330 Non-Hispanic Whites, 47 Non-Hispanic Blacks, 16 Asian Americans, and 29 patients from Other/mixed races. Over a median follow-up of 7 years, no significant differences in the pain profile (p = 0.36), neuromodulator use (p = 0.94), and opioid use for intermittent (p = 0.34) and daily pain (p = 0.80) were observed. Frequent flares were associated with Hispanic ethnicity [2.98(1.20-7.36); p = 0.02], despite adjustment for smoking [2.21(1.11-4.41); p = 0.02)] and alcohol [1.88(1.06-3.35); p = 0.03]. Local complications (pseudocysts, mesenteric thrombosis, and biliary obstruction), exocrine and endocrine dysfunction, and healthcare resource utilization (cross-sectional imaging, endoscopic procedures, celiac blocks, or surgeries) were comparable across all ethno-racial groups. CONCLUSIONS: Although no significant differences in clinical outcomes, and health resource utilization were noted across ethno-racial groups, Hispanic ethnicity had significant association with CP flares. This study calls for further investigation of an understudied minority population with CP.

Impact of Geospatial Food Access on Acute Pancreatitis Outcomes.

BACKGROUND AND AIM: Food access is an important social determinant of health and refers to geographical and infrastructural aspects of food availability. Using publicly available data on food access from the United States Department of Agriculture (USDA), geospatial analyses can identify regions with variable food access, which may impact acute pancreatitis (AP), an acute inflammatory condition characterized by unpredictable outcomes and substantial mortality. This study aimed to investigate the association of clinical outcomes in patients with AP with geospatial food access. METHODS: We examined AP-related hospitalizations at a tertiary center from January 2008 to December 2018. The physical addresses were geocoded through ArcGIS Pro2.7.0 (ESRI, Redlands, CA). USDA Food Access Research Atlas defined low food access as urban areas with 33% or more of the population residing over one mile from the nearest food source. Regression analyses enabled assessment of the association between AP outcomes and food access. RESULTS: The study included 772 unique patients with AP residing in Massachusetts with 931 AP-related hospitalizations. One hundred and ninety-eight (25.6%) patients resided in census tracts with normal urban food access and 574 (74.4%) patients resided in tracts with low food access. AP severity per revised Atlanta classification [OR 1.88 (95%CI 1.21-2.92); p = 0.005], and 30-day AP-related readmission [OR 1.78(95%CI 1.11-2.86); p = 0.02] had significant association with food access, despite adjustment for demographics, healthcare behaviors, and comorbidities (Charlson Comorbidity Index). However, food access lacked significant association with AP-related mortality (p = 0.40) and length of stay (LOS: p = 0.99). CONCLUSION: Low food access had a significant association with 30-day AP-related readmissions and AP severity. However, mortality and LOS lacked significant association with food access. The association between nutrition, lifestyle, and AP outcomes warrants further prospective investigation.

Disparities in race, ethnicity, sex, and age inclusion in pancreatic cancer screening studies: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Substantial differences exist in pancreatic cancer outcomes across ethnoracial stratifications. We sought to assess racial, ethnic, sex, and age reporting and inclusion of participants in pancreatic cancer screening studies. METHODS: A systematic search of Cochrane Library, Ovid Embase, Google Scholar, Ovid MEDLINE, PubMed, Scopus, and Web of Science Core Collection from inception to 2022 was conducted. Original studies on pancreatic cancer screening were identified and assessed for reporting and inclusion on race, ethnicity, sex, and age. The pooled proportions of study participants for these characteristics were calculated and compared with population-based benchmarks. RESULTS: Among 27 eligible pancreatic cancer screening studies, 26 reported data on either sex, race, or ethnicity, with a total of 5273 participants. Information on participant sex was reported by 26, race by 12, and ethnicity by 8 studies. Participants in these studies were almost all white (pooled proportion, 93.1%; 95% confidence interval [CI], 89.7-96.4) and non-Latino (pooled proportion, 97.4%; 95% CI, 94.0-100), and these groups were over-represented when compared with the general population. Female participants were well represented, with a pooled proportion of 63.2% (95% CI, 59.9-66.6). When reported, mean or median participant age was <60 years. Meta-regression revealed higher proportions of female participants in studies from the United States (P = .002). No association between increasing participation of racial or ethnic under-represented populations and study quality, ascending year of publication, or source of study funding was noted. CONCLUSIONS: Substantial disparities in race, ethnicity, sex, and age reporting and inclusion in pancreatic cancer studies were noted, even among high-quality and publicly funded studies.

Surveillance of Pancreatic Cystic Neoplasms.

Pancreatic cystic neoplasms (PCNs) are increasingly detected because of the widespread use of cross-sectional imaging and overall aging population. While the majority of these cysts are benign, some can progress to advanced neoplasia (defined as high-grade dysplasia and invasive cancer). As the only widely accepted treatment for PCNs with advanced neoplasia is surgical resection, accurate preoperative diagnosis, and stratification of malignant potential for deciding about surgery, surveillance or doing nothing remains a clinical challenge. Surveillance strategies for pancreatic cysts (PCNs) combine clinical evaluation and imaging to assess changes in cyst morphology and symptoms that may indicate advanced neoplasia. PCN surveillance heavily relies on various consensus clinical guidelines that focus on high-risk morphology, surgical indications, and surveillance intervals and modalities. This review will focus on current concepts in the surveillance of newly diagnosed PCNs, especially on low-risk presumed intraductal papillary mucinous neoplasms (those without worrisome features and high-risk stigmata), and appraise current clinical surveillance guidelines.

Burden of bone disease in chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND: Bone disease is an under-recognized cause of morbidity in chronic pancreatitis (CP). Over the past decade, publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem. AIM: To quantify the prevalence of osteopenia, osteoporosis, and fragility fractures in CP patients and investigate the associated clinical features and outcomes. METHODS: A systematic search identified studies investigating bone disease in CP patients from Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until October 2022. The outcomes included prevalence of osteopenia, osteoporosis, and fragility fractures, which were meta-analyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features. RESULTS: Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis. The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2% (95%CI: 35.2%-47.3%) and 20.9% (95%CI: 14.9%-27.6%), respectively. The pooled prevalence of fragility fractures described among CP was 5.9% (95%CI: 3.9%-8.4%). Meta-regression revealed significant association of pancreatic enzyme replacement therapy (PERT) use with prevalence of osteoporosis [coefficient: 1.7 (95%CI: 0.6-2.8); P < 0.0001]. We observed no associations with mean age, sex distribution, body mass index, alcohol or smoking exposure, diabetes with prevalence of osteopenia, osteoporosis or fragility fractures. Paucity of data on systemic inflammation, CP severity, and bone mineralization parameters precluded a formal meta-analysis. CONCLUSION: This meta-analysis confirms significant bone disease in patients with CP. Other than PERT use, we observed no patient or study-specific factor to be significantly associated with CP-related bone disease. Further studies are needed to identify confounders, at-risk population, and to understand the mechanisms of CP-related bone disease and the implications of treatment response.

Utility of promoter hypermethylation in malignant risk stratification of intraductal papillary mucinous neoplasms.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs), a type of cystic pancreatic cancer (PC) precursors, are increasingly identified on cross-sectional imaging and present a significant diagnostic challenge. While surgical resection of IPMN-related advanced neoplasia, i.e., IPMN-related high-grade dysplasia or PC, is an essential early PC detection strategy, resection is not recommended for IPMN-low-grade dysplasia (LGD) due to minimal risk of carcinogenesis, and significant procedural risks. Based on their promising results in prior validation studies targeting early detection of classical PC, DNA hypermethylation-based markers may serve as a biomarker for malignant risk stratification of IPMNs. This study investigates our DNA methylation-based PC biomarker panel (ADAMTS1, BNC1, and CACNA1G genes) in differentiating IPMN-advanced neoplasia from IPMN-LGDs. METHODS: Our previously described genome-wide pharmaco-epigenetic method identified multiple genes as potential targets for PC detection. The combination was further optimized and validated for early detection of classical PC in previous case-control studies. These promising genes were evaluated among micro-dissected IPMN tissue (IPMN-LGD: 35, IPMN-advanced neoplasia: 35) through Methylation-Specific PCR. The discriminant capacity of individual and combination of genes were delineated through Receiver Operating Characteristics curve analysis. RESULTS: As compared to IPMN-LGDs, IPMN-advanced neoplasia had higher hypermethylation frequency of candidate genes: ADAMTS1 (60% vs. 14%), BNC1 (66% vs. 3%), and CACGNA1G (25% vs. 0%). We observed Area Under Curve (AUC) values of 0.73 for ADAMTS1, 0.81 for BNC1, and 0.63 for CACNA1G genes. The combination of the BNC1/ CACNA1G genes resulted in an AUC of 0.84, sensitivity of 71%, and specificity of 97%. Combining the methylation status of the BNC1/CACNA1G genes, blood-based CA19-9, and IPMN lesion size enhanced the AUC to 0.92. CONCLUSION: DNA-methylation based biomarkers have shown a high diagnostic specificity and moderate sensitivity for differentiating IPMN-advanced neoplasia from LGDs. Addition of specific methylation targets can improve the accuracy of the methylation biomarker panel and enable the development of noninvasive IPMN stratification biomarkers.

Benefit of Extended Surveillance of Low-Risk Pancreatic Cysts After 5-Year Stability: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Low-risk branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) lacking worrisome features (WF) and high-risk stigmata (HRS) warrant surveillance. However, their optimal duration, especially among cysts with initial 5 years of size stability, warrants further investigation. We systematically reviewed the surveillance of low-risk BD-IPMNs and investigated the incidence of WF/HRS and advanced neoplasia, high-grade dysplasia, and pancreatic cancer during the initial (<5 years) and extended surveillance period (>5-years). METHODS: A systematic search (CRD42020117120) identified studies investigating long-term IPMN surveillance outcomes of low-risk IPMN among the Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until July 9, 2021. The outcomes included the incidence of WF/HRS and advanced neoplasia, disease-specific mortality, and surveillance-related harm (expressed as percentage per patient-years). The meta-analysis relied on time-to-event plots and used a random-effects model. RESULTS: Forty-one eligible studies underwent systematic review, and 18 studies were meta-analyzed. The pooled incidence of WF/HRS among low-risk BD-IPMNs during initial and extended surveillance was 2.2% (95% CI, 1.0%-3.7%) and 2.9% (95% CI, 1.0%-5.7%) patient-years, respectively, whereas the incidence of advanced neoplasia was 0.6% (95% CI, 0.2%-1.00%) and 1.0% (95% CI, 0.6%-1.5%) patient-years, respectively. The pooled incidence of disease-specific mortality during initial and extended surveillance was 0.3% (95% CI, 0.1%-0.6%) and 0.6% (95% CI, 0.0%-1.6%) patient-years, respectively. Among BD-IPMNs with initial size stability, extended surveillance had a WF/HRS and advanced neoplasia incidence of 1.9% (95% CI, 1.2%-2.8%) and 0.2% (95% CI, 0.1%-0.5%) patient-years, respectively. CONCLUSIONS: A lower incidence of advanced neoplasia during extended surveillance among low-risk, stable-sized BD-IPMNs was a key finding of this study. However, the survival benefit of surveillance among this population warrants further exploration through high-quality studies before recommending surveillance cessation with certainty.

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival.

PURPOSE: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies. METHODS: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I v higher-stage). Overall survival was determined using the Kaplan-Meier method. RESULTS: Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003). CONCLUSION: Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.

International external validation of a stratification tool to identify branch-duct intraductal papillary mucinous neoplasms at lowest risk of progression.

BACKGROUND: Identifying branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) at lowest risk of progression may allow for a reduced intensity of surveillance. OBJECTIVE: We aimed to externally validate the previously developed Dutch-American Risk stratification Tool (DART-1; https://rtools.mayo.edu/DART/), which identifies cysts at low risk of developing worrisome features (WFs) or high-risk stigmata (HRS). METHODS: Three prospective cohorts of individuals under surveillance for BD-IPMNs were combined, independent from the original development cohort. We assessed the performance (discrimination and calibration) of DART-1, a multivariable Cox-proportional logistic regression model with five predictors for the development of WFs or HRS. RESULTS: Of 832 individuals (mean age 77 years, SD 11.5) under surveillance for a median of 40 months (IQR 44), 163 (20%) developed WFs or HRS. DART-1's discriminative ability (C-statistic 0.68) was similar to that in the development cohort (0.64-0.72) and showed moderate calibration. DART-1 adequately estimated the risk for patients in the middle risk quintile, and slightly underestimated it in the lowest quintiles. Their range of predicted versus observed 3-year risk was 0%-0% versus 0%-3.7% for Q1; 0.3%-0.4% versus 3%-11% for Q2; and 2.6%-3% versus 2.4%-9.8% for Q3. The development of WFs or HRS was associated with pancreatic cancer (p < 0.001). Vice versa, in absence of WFs or HRS, the risk of malignancy was low (0.3%). CONCLUSIONS: The performance of DART-1 to predict the development of WFs or HRS in BD-IPMN was validated in an external international cohort, with a discriminative ability equal as in the development cohort. Risk estimations were most accurate for patients with BD-IPMNs in the middle risk quintile and slightly underestimated in the lowest quintiles.

Comorbidities Drive the Majority of Overall Mortality in Low-Risk Mucinous Pancreatic Cysts Under Surveillance.

BACKGROUND & AIMS: The Charlson Comorbidity Index (CACI) has been suggested as a tool to determine comorbidity burden and guide management for patients with mucinous pancreatic cysts (Intrapapillary Mucinous Neoplasms and Mucinous Cystic Neoplasms), but has not been studied well among "low-risk" mucinous pancreatic cysts i.e. without worrisome features (WF) and high-risk stigmata (HRS). This study sought to determine the comorbidity burden among surveillance population of low-risk pancreatic cysts and provide their follow-up mortality outcomes. METHODS: A single center study retrospectively reviewed a prospective pancreatic cyst database and included individuals with low-risk cysts undergoing serial imaging during 2016. Electronic medical records were reviewed to determine their baseline age-adjusted CACI (age-CACI). After 4 years, their progression to WF, disease specific (pancreatic malignancy-related, DSM), extra-pancreatic (EPM), and overall mortalities (OM) were determined using Kaplan-Meir Survival Analysis. RESULTS: 502 individuals underwent prospective surveillance. The study included 440 individuals with low-risk suspected or presumed mucinous cysts and excluded 50 and 12 individuals with WF and HRS respectively. Over a median follow-up of 56 months, 12 WF progressions, 2 DSMs, 42 EPMs, and 44 OMs were observed. Baseline age-CACI had good predictive capacity for 4-year EPM (Area-Under Curve: 0.87; p< .0001). The median age-CACI of 4 enabled cohort stratification into Low (age-CACI <4) and High CACI (age-CACI ≥4) groups. A significantly higher OM (p< .001) was observed among the High CACI group as compared to the Low CACI group. CONCLUSION: Through real-time application of CACI to patient outcomes, our analysis supports incorporation of this comorbidity assessment tool in making shared surveillance decisions among low-risk pancreatic cyst population.

Late-Stage Pancreatic Cancer Detected During High-Risk Individual Surveillance: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Identification and resection of successful targets, that is, T1 N0M0 pancreatic ductal adenocarcinoma (PDAC) and high-grade precursors during surveillance of high-risk individuals (HRIs) confers improved survival. Late-stage PDACs refer to T2-4 N0M0 and nodal or distant metastatic PDAC stages diagnosed during the follow-up phase of HRI surveillance. This study aimed to quantify late-stage PDACs during HRI surveillance and identify associated clinicoradiologic factors. METHODS: A systematic search (PROSPERO:CRD42018117189) from Cochrane Library, Embase, Google Scholar, Medline, PubMed, Scopus, and Web of Science was last performed on April 18, 2021. Only original HRI surveillance manuscripts that specified follow-up strategies were included, and studies with only baseline information were excluded. Cumulative incidences of advanced neoplasia: high-grade precursors and all PDACs, and surveillance-detected/interval late-stage PDACs were calculated through random-effects model. Incidence of late-stage PDACs underwent metaregression to identify association with HRI clinicoradiologic features. Publication bias was assessed through the funnel plot and Egger's regression line. RESULTS: Thirteen original surveillance studies included 2169 HRIs followed over 7302.72 patient-years. Cumulative incidence of advanced neoplasia and late-stage PDACs was 3.3 (95% confidence interval [CI]: 0.6-7.4) and 1.7 (95% CI: 0.2-4.0) per 1000 patient-years, respectively. Late-stage PDACs lacked significant association with surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Limited information on diagnostic error, symptoms, timing of presentation, lesion site, and surveillance adherence precluded formal meta-analysis. CONCLUSION: A sizeable proportion of late-stage PDACs were detected during follow-up. Their incidence lacked association with baseline clinicoradiologic features. Further causal investigation of stage-based outcomes is warranted for overall improvement in HRI surveillance.

Methylation-based Cell-free DNA Signature for Early Detection of Pancreatic Cancer.

OBJECTIVES: The potential of DNA methylation alterations in early pancreatic cancer (PC) detection among pancreatic tissue cell-free DNA seems promising. This study investigates the diagnostic capacity of the 4-gene methylation biomarker panel, which included ADAMTS1, BNC1, LRFN5, and PXDN genes, in a case-control study. METHODS: A genome-wide pharmacoepigenetic approach identified ADAMTS1, BNC1, LRFN5, and PXDN genes as putative targets. Tissue samples including stage I-IV PC (n = 44), pancreatic intraepithelial neoplasia (n = 15), intraductal papillary mucinous neoplasms (n = 24), and normal pancreas (n = 8), and cell-free DNA, which was acquired through methylation on beads technology from PC (n = 22) and control patients (n = 10), were included. The 2-∆ct was the outcome of interest and underwent receiver operating characteristic analysis to determine the diagnostic accuracy of the panel. RESULTS: Receiver operating characteristic analysis revealed an area under the curve of 0.93 among ADAMTS1, 0.76 among BNC1, 0.75 among PXDN, and 0.69 among LRFN5 gene. The combination gene methylation panel (ADAMTS1, BNC1, LRFN5, and PXDN) had an area under the curve of 0.94, with a sensitivity of 100% and specificity of 90%. CONCLUSIONS: This methylation-based biomarker panel had promising accuracy for PC detection and warranted further validation in prospective PC surveillance trials.

Evaluation of diagnostic yield of EUS among patients with asymptomatic common bile duct dilation: systematic review and meta-analysis.

BACKGROUND AND AIMS: Common bile duct (CBD) dilation is a frequent indication for EUS. Among asymptomatic individuals, biliary dilation may not be clinically significant; however, EUS is often relied on for the exclusion of benign and malignant pathology that might require further intervention. The yield of EUS evaluation for this indication is not well characterized and has significant implications for health resource utilization because asymptomatic biliary dilation is prevalent. Through this systematic review, we sought to appraise the yield of EUS evaluation of asymptomatic patients with radiologic evidence of isolated CBD dilation. METHODS: A protocolled search (PROSPERO: CRD42020193428) extracted original studies from the Cochrane Library, Ovid Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science Core Collection that described diagnostic yield of EUS among asymptomatic patients with biliary dilation. Cumulative EUS diagnostic yield was calculated through meta-analysis of proportions using inverse variance methods and a random-effects model. RESULTS: Of 2616 studies, 8 delineated the EUS yield among 224 asymptomatic patients. The cumulative yield of EUS for any pathology was 11.2% (95% confidence interval [CI], 3.6%- 21.6%). The EUS yield for benign etiologies was 9.2% (95% CI, 1.1%-21.9%), of which choledocholithiasis comprised 3.4% (95% CI, 0%-11.2%) and malignant etiologies .5% (95% CI, 0%-3.4%) of cases. CONCLUSIONS: EUS in patients with asymptomatic CBD dilation does yield findings of choledocholithiasis and malignancy, albeit at low rates. A cost-effectiveness analysis is warranted to further guide clinical decision-making in this area.

COVID-19 related pancreatic cancer surveillance disruptions amongst high-risk individuals.

BACKGROUND: COVID-19 pandemic-related disruptions to EUS-based pancreatic cancer surveillance in high-risk individuals remain uncertain. METHODS: Analysis of enrolled participants in the CAPS5 Study, a prospective multicenter study of pancreatic cancer surveillance in high-risk individuals. RESULTS: Amongst 693 enrolled high-risk individuals under active surveillance, 108 (16%) had an EUS scheduled during the COVID-19 pandemic-related shutdown (median length of 78 days) in the spring of 2020, with 97% of these procedures being canceled. Of these canceled surveillance EUSs, 83% were rescheduled in a median of 4.1 months, however 17% were not rescheduled after 6 months follow-up. Prior history of cancer was associated with increased likelihood of rescheduling. To date no pancreatic cancer has been diagnosed among those whose surveillance was delayed. CONCLUSIONS: COVID-19 delayed pancreatic cancer surveillance with no adverse outcomes in efficiently rescheduled individuals. However, 1 in 6 high-risk individuals had not rescheduled surveillance, indicating the need for vigilance to ensure timely surveillance rescheduling.

Managing Gallstone Disease in the Elderly.

Geriatric patients tend to have subtle presentations of biliary disorders and, if untreated, can decompensate acutely. Each biliary disorder warrants formulation of an individualized treatment plan with a multidisciplinary approach. Acute cholecystitis, a common complication of gallstones, is initially managed by conservative measures and subsequently, among patients with optimal surgical risk, through laparoscopic or open cholecystectomy. High-risk patients undergo temporization, percutaneous or endoscopic, followed by definitive intervention. Acute cholecystitis with complications (ie, perforation, gangrene, or small bowel obstruction) warrants emergent cholecystectomy. Gallstone migration into the biliary system can cause choledocholithiasis, often complicated by biliary pancreatitis or cholangitis if not intervened. Therapy for choledocholithiasis is based on biliary clearance through endoscopic and, infrequently, surgical approaches.

Alternative uses of lumen apposing metal stents.

The advent of lumen apposing metal stents (LAMS) has revolutionized the management of many complex gastroenterological conditions that previously required surgical or radiological interventions. These procedures have garnered popularity due to their minimally invasive nature, higher technical and clinical success rate and lower rate of adverse events. By virtue of their unique design, LAMS provide more efficient drainage, serve as conduit for endoscopic access, are associated with lower rates of leakage and are easy to be removed. Initially used for drainage of pancreatic fluid collections, the use of LAMS has been extended to gallbladder and biliary drainage, treatment of luminal strictures, creation of gastrointestinal fistulae, pancreaticobiliary drainage, improved access for surgically altered anatomy, and drainage of intra-abdominal and pelvic abscesses as well as post-surgical fluid collections. As new indications of endosonographic techniques and LAMS continue to evolve, this review summarizes the current role of LAMS in the management of these various complex conditions and also highlights clinical pearls to guide successful placement of LAMS.

EUS-guided needle biopsy for autoimmune pancreatitis.

Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA), though a well-established method for specimen acquisition from pancreatic neoplasm, has a limited role for non-focal benign pancreatic diseases such as autoimmune pancreatitis (AIP) due to sample inadequacy and architectural distortion. Core biopsies through EUS-trucut biopsy (EUS-TCB) or newer generation EUS-fine needle biopsy (EUS-FNB) enable better histopathologic review through greater tissue specimen size and visualization of the histologic milieu. We systematically reviewed EUS-guided sample acquisition (FNA or core biopsy) and the role of EUS-guided needle biopsy in evaluation of AIP. EUS-guided needle biopsy provided significantly higher adequacy of specimen (96.8% vs 79.8%; p = 0.016) and higher diagnostic sensitivity (60.20% vs 42.02%; p < 0.0001) compared to EUS-FNA for AIP. More evidence is imperative in evaluating the feasibility, safety, and diagnostic utility of EUS-guided needle biopsy for AIP.

Current Approaches to Pancreatic Cancer Screening.

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of only 8% and is estimated to be the second leading cause of cancer-related deaths by 2021. Prior convention held that screening for PDAC would not be beneficial; however, a deeper understanding of the carcinogenesis pathway supports a potential window of opportunity among the target population. Screening for PDAC is not a standard practice among the general population because of its low incidence. However, screening may be beneficial for individuals with familial history, chronic diseases with genetic predispositions, or inherited cancer syndromes, such as hereditary breast ovarian cancer syndrome, hereditary pancreatitis, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, Lynch syndrome (hereditary nonpolyposis colorectal cancer), ataxia telangiectasia, and Li-Fraumeni syndrome, all of which have been associated with an increased risk of developing PDAC. The screening strategies among these high-risk individuals are targeted to identify precursor lesions and PDAC at an early resectable stage. This review describes the risk factors for pancreatic cancer, especially the genetic risk factors in high-risk individuals and current screening strategies available for PDAC.

De-novo Gastrointestinal Anastomosis with Lumen Apposing Metal Stent.

Gastric outlet obstruction, afferent or efferent limb obstruction, and biliary obstruction among patients with altered anatomy often require surgical intervention which is associated with significant morbidity and mortality. Endoscopic dilation for benign etiologies requires multiple sessions, whereas self-expandable metal stents used for malignant etiologies often fail due to tumor in-growth. Lumen apposing metal stents, placed endoscopically with the intent of creating a de-novo gastrointestinal anastomosis bypassing the site of obstruction, can potentially achieve similar efficacy, with a much lower complication rate. In our study cohort (n=79), the composite technical success rate and clinical success rate was 91.1% (72/79) and 97.2% (70/72), respectively. Five different techniques were used: 43% (34/79) underwent the balloon-assisted method, 27.9% (22/79) underwent endoscopic ultrasound-guided balloon occluded gastro-jejunostomy bypass, 20.3% (16/79) underwent the direct technique, 6.3% (5/79) underwent the hybrid rendezvous technique, and 2.5% (2/79) underwent natural orifice transluminal endoscopic surgery (NOTES)-assisted procedure. All techniques required an echoendoscope except NOTES. In all, 53.2% (42/79) had non-cautery enhanced Axios stent, 44.3% (35/79) had hot Axios stent, and 2.5% (2/79) had Niti-S spaxus stent. Symptom-recurrence was seen in 2.8%, and 6.3% had a complication (bleeding, abdominal pain or peritonitis). All procedures were performed by experts at centers of excellence with adequate surgical back up.

Contrast Enhanced Harmonic Endoscopic Ultrasound: A Novel Approach for Diagnosis and Management of Gastrointestinal Stromal Tumors.

The histologic analysis of gastrointestinal stromal tumors (GISTs) is a common method to detect the mitotic activity and to subsequently determine the risk of GISTs for malignancy. The potential false negative error due to inadequate yield of specimens and actual determination of malignancy risk requires analysis of the whole tumor. We aimed to assess the role of contrast enhanced endoscopic ultrasound (CE-EUS) in the management of GISTs. Two authors individually did review of English literatures to identify nine peer-reviewed original articles using keywords- contrast endoscopic ultrasound, GIST and submucosal tumor. Studies were heterogeneous in their aims looking either at differentiating submucosal lesions from GISTs, estimating malignant potential of GISTs with histologic correlation or studying the role of angiogenesis in malignant risk stratification. CE-EUS had moderate to high efficacy in differentiating GISTs from alternative submucosal tumors. CE-EUS had a higher sensitivity than EUS-guided fine needle aspiration, contrast computed tomography and Doppler EUS for detection of neo-vascularity within the GISTs. However, the evidence of abnormal angiogenesis within GIST as a prognostic factor needs further validation. CE-EUS is a non-invasive modality, which can help differentiate GISTs and provide valuable assessment of their perfusion patterns to allow better prediction of their malignant potential but more experience is needed.