A core outcome set for acute necrotizing pancreatitis: An Eastern Association for the Surgery of Trauma modified Delphi method consensus study.

BACKGROUND: The management of acute necrotizing pancreatitis (ANP) has changed dramatically over the past 20 years including the use of less invasive techniques, the timing of interventions, nutritional management, and antimicrobial management. This study sought to create a core outcome set (COS) to help shape future research by establishing a minimal set of essential outcomes that will facilitate future comparisons and pooling of data while minimizing reporting bias. METHODS: A modified Delphi process was performed through involvement of ANP content experts. Each expert proposed a list of outcomes for consideration, and the panel anonymously scored the outcomes on a 9-point Likert scale. Core outcome consensus defined a priori as >70% of scores receiving 7 to 9 points and <15% of scores receiving 1 to 3 points. Feedback and aggregate data were shared between rounds with interclass correlation trends used to determine the end of the study. RESULTS: A total of 19 experts agreed to participate in the study with 16 (84%) participating through study completion. Forty-three outcomes were initially considered with 16 reaching consensuses after four rounds of the modified Delphi process. The final COS included outcomes related to mortality, organ failure, complications, interventions/management, and social factors. CONCLUSION: Through an iterative consensus process, content experts agreed on a COS for the management of ANP. This will help shape future research to generate data suitable for pooling and other statistical analyses that may guide clinical practice. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.

Addressing long-term mortality risk in patients undergoing total pancreatectomy with islet autotransplant (TPIAT): causes of death and risk factors.

BACKGROUND: Total pancreatectomy with islet autotransplant (TPIAT) can improve quality of life for individuals with pancreatitis but creates health risks including diabetes, exocrine insufficiency, altered intestinal anatomy and function, and asplenia. METHODS: We studied survival and causes of death for 693 patients who underwent TPIAT between 2001 and 2020, using the National Death Index with medical records to ascertain survival after TPIAT, causes of mortality, and risk factors for death. We used Kaplan Meier curves to examine overall survival, and Cox regression and competing-risks methods to determine pre-TPIAT factors associated with all-cause and cause-specific post-TPIAT mortality. RESULTS: Mean age at TPIAT was 33.6 years (SD = 15.1). Overall survival was 93.1% (95% CI 91.2, 95.1%) 5 years after surgery, 85.2% (95% CI 82.0, 88.6%) at 10 years, and 76.2% (95% CI 70.8, 82.3%) at 15 years. Fifty-three of 89 deaths were possibly related to TPIAT; causes included chronic gastrointestinal complications, malnutrition, diabetes, liver failure, and infection/sepsis. In multivariable models, younger age, longer disease duration, and more recent TPIAT were associated with lower mortality. CONCLUSIONS: For patients undergoing TPIAT to treat painful pancreatitis, careful long-term management of comorbidities introduced by TPIAT may reduce risk for common causes of mortality.

Primary Pancreatic Liposarcoma: An Unexpected Cause of a Pancreatic Mass.

Liposarcoma is the most common type of soft-tissue sarcoma and typically occurs in the extremities or retroperitoneum. Primary liposarcoma of the pancreas is exceedingly rare, with only 10 cases reported since 1979. We present a patient who was incidentally discovered to have a pancreatic mass on imaging, which was ultimately diagnosed as dedifferentiated pancreatic liposarcoma. We review the clinical and histologic features of pancreatic liposarcoma in this case and in the 10 previously reported cases to increase awareness and knowledge of this rare disease.

Nutritional Risks in Patients Undergoing Total Pancreatectomy Islet AutoTransplantation in the POST Consortium.

BACKGROUND AND AIMS: Total pancreatectomy with islet autotransplantation (TPIAT) can relieve pain for individuals with acute recurrent or chronic pancreatitis. However, TPIAT may increase the risk of poor nutritional status with complete exocrine pancreatic insufficiency, partial duodenectomy, and intestinal reconstruction. Our study's objective was to evaluate nutritional status, anthropometrics, and vitamin levels before and after TPIAT. METHODS: The multicenter Prospective Observational Study of TPIAT (POST) collects measures including vitamins A, D, and E levels, pancreatic enzyme dose, and multivitamin (MVI) administration before and 1-year after TPIAT. Using these data, we studied nutritional and vitamin status before and after TPIAT. RESULTS: 348 TPIAT recipients were included (68% adult, 37% male, 93% Caucasian). In paired analyses at 1-year follow-up, vitamin A was low in 23% (vs 9% pre-TPIAT, p < 0.001); vitamin E was low in 11% (vs 5% pre-TPIAT, p = 0.066), and 19% had vitamin D deficiency (vs 12% pre-TPIAT, p = 0.035). Taking a fat-soluble multivitamin (pancreatic MVI) was associated with lower risk for vitamin D deficiency (p = 0.002). Adults were less likely to be on a pancreatic MVI at follow-up (34% vs 66% respectively, p < 0.001). Enzyme dosing was adequate. More adults versus children were overweight or underweight pre- and post-TPIAT. Underweight status was associated with vitamin A (p = 0.014) and E (p = 0.02) deficiency at follow-up. CONCLUSIONS: Prevalence of fat-soluble vitamin deficiencies increased after TPIAT, especially if underweight. We strongly advocate that all TPIAT recipients have close post-operative nutritional monitoring, including vitamin levels. Pancreatic MVIs should be given to minimize risk of developing deficiencies.

Frequent guidewire passage into the pancreatic duct is an independent risk factor for postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among high-risk individuals: A post-hoc analysis of a randomized controlled trial data.

OBJECTIVES: To systematically evaluate the patient and procedural risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among patients receiving rectal indomethacin. METHODS: Data from a randomized controlled trial (RCT) of high-risk patients undergoing ERCP who received rectal indomethacin with or without topical epinephrine was evaluated. PEP was defined based on the consensus criteria. Pancreatic stenting was excluded to avoid confounding results with the role of epinephrine spray. Multivariable logistic regression analysis was used to identify patient and procedural risk factors for PEP. RESULTS: Among 960 patients enrolled in the RCT, the PEP incidence was 6.4%. An increased risk of PEP was seen with age <50 years and female gender (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.35-4.26), malignant biliary stricture(s) (OR 3.51, 95% CI 1.52-8.10), >2 guidewire passes into the pancreatic duct (PD) (OR 2.84, 95% CI 1.43-5.64), and pancreatic brush cytology (OR 6.37, 95% CI 1.10-36.90), whereas a decreased risk of PEP was seen with contrast- over guidewire-assisted cannulation (OR 0.14, 95% CI 0.02-0.99) and the use of lactated Ringer's (LR) over other fluid types (OR 0.52, 95% CI 0.27-0.98). There was a significant trend between the number of guidewire passes into the PD and PEP risk (P = 0.002). CONCLUSIONS: More than two guidewire passes into the PD and pancreatic brush cytology increased while the use of LR decreased the risk of PEP among high-risk patients receiving rectal indomethacin. Pancreatic stent placement and/or LR should be considered in patients with >2 guidewire passes into the PD.

Disconnected pancreatic duct syndrome in patients with necrotizing pancreatitis.

In a subset of patients with acute necrotizing pancreatitis, segmental necrosis affecting the main pancreatic duct may result in a discontinuity between the left-sided pancreas and the duodenum. Such an interruption in the setting of a viable upstream portion of the gland can give rise to the disconnected pancreatic duct syndrome (DPDS). By maintaining its secretory function, the disconnected segment may lead to persistent external pancreatic fistulae, recurrent pancreatic fluid collections, and/or obstructive recurrent acute or chronic pancreatitis of the isolated parenchyma. There are currently no universally accepted guidelines for the diagnosis or treatment of DPDS, and because the condition is underrecognized, the diagnosis is often delayed. DPDS is associated with a prolonged disease course and poses a burden on patients' quality of life as well as high health care resource utilization. The aim of our review is to summarize current knowledge, discuss diagnostic approaches, outline management options, and raise awareness of this challenging complication of necrotizing pancreatitis.

Mucosa-Associated Lymphoid Tissue Lymphoma Masked as Gastric Varices With Acute Upper Gastrointestinal Bleeding: A Case Report.

Extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is uncommon and difficult to diagnose due to varied clinical presentations and endoscopic appearances masquerading as other pathology. Rarely, it has been associated with acute upper gastrointestinal (GI) bleeding. We report on a 60-year-old male who presented with an acute upper GI bleed and endoscopic findings suggestive of isolated gastric varices (GV), ultimately determined to be MALT lymphoma. Complete remission was achieved with radiation therapy, with no recurrence at a 12-month follow-up. This case highlights a unique clinical and endoscopic presentation of MALT lymphoma which providers should be aware of. We emphasize the use of endoscopic ultrasound (EUS) evaluation for accurate diagnosis.

Intraportal Islet Autotransplantation Independently Improves Quality of Life After Total Pancreatectomy in Patients With Chronic Refractory Pancreatitis.

OBJECTIVE: To determine if islet autotransplantation (IAT) independently improves the quality of life (QoL) in patients after total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: TP-IAT is increasingly being used for intractable chronic pancreatitis. However, the impact of IAT on long-term islet function and QoL is unclear. METHODS: TP-IAT patients at our center >1 year after TP-IAT with ≥1 Short Form-36 QoL measure were included. Patients were classified as insulin-independent or insulin-dependent, and as having islet graft function or failure by C-peptide. The associations of insulin use and islet graft function with QoL measures were analyzed by using a linear mixed model, accounting for time since transplant and within-person correlation. RESULTS: Among 817 islet autograft recipients, 564 patients [median (interquartile range) age: 34 (20, 45) years, 71% female] and 2161 total QoL surveys were included. QoL data were available for >5 years after TP-IAT for 42.7% and for >10 years for 17.3%. Insulin-independent patients exhibited higher QoL in 7 of 8 subscale domains and for Physical Component Summary and Mental Component Summary scores ( P <0.05 for all). Physical Component Summary was 2.91 (SE=0.57) higher in insulin-independent patients ( P <0.001). No differences in QoL were observed between those with and without graft function, but islet graft failure was rare (15% of patients). However, glycosylated hemoglobin was much higher with islet graft failure. CONCLUSIONS: QoL is significantly improved when insulin independence is present, and glycosylated hemoglobin is lower with a functioning islet graft. These data support offering IAT, rather than just performing total pancreatectomy and treating with exogenous insulin.

Surgical approach and short-term outcomes in adults and children undergoing total pancreatectomy with islet autotransplantation: A report from the Prospective Observational Study of TPIAT.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation. METHODS: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n = 84) with adults (n = 195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP. RESULTS: Children more commonly underwent splenectomy (100% versus 91%, p = 0.002), pylorus preservation (93% versus 67%; p < 0.0001), Roux-en-Y duodenojejunostomy reconstruction (92% versus 35%; p < 0.0001), and enteral feeding tube placement (93% versus 63%; p < 0.0001). Median islet equivalents/kg transplanted was higher in children (4577; IQR 2816-6517) than adults (2909; IQR 1555-4479; p < 0.0001), with COBE purification less common in children (4% versus 15%; p = 0.0068). Median length of hospital stay was higher in children (15 days; IQR 14-22 versus 11 days; IQR 8-14; p < 0.0001), but 30-day readmissions were lower in children (13% versus 26%, p = 0.018). Rate of portal vein thrombosis was significantly lower in children than in adults (2% versus 10%, p = 0.028). There were no mortalities in the first 90 days post-TPIAT. CONCLUSIONS: Pancreatectomy techniques differ between children and adults, with islet yields higher in children. The rates of portal vein thrombosis and early readmission are lower in children.

Endoscopic Ultrasound Guided Fine-Needle Aspiration for Solid Lesions in Chronic Pancreatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with chronic pancreatitis (CP) are at a higher risk of developing pancreatic adenocarcinoma compared the general population with an estimated 5% risk of developing pancreatic cancer in 20 years. Endoscopic ultrasound fine needle aspiration (EUS-FNA) of solid pancreatic lesions (SPL) has an excellent sensitivity (85-90%) and specificity (98-100%) for diagnosing pancreatic malignancy. However, data on the performance characteristics of EUS-FNA in CP are mixed. AIMS: In this systematic review and meta-analysis, we aim to examine data from published studies on the diagnostic performance of EUS-FNA in detecting pancreatic malignancy in CP. METHODS: We conducted a comprehensive search of MEDLINE, Cochrane, EMBASE, Scopus databases for studies published in English language that reported performance characteristics of EUS-FNA for SPL up to November 2020. Two reviewers independently conducted screening, full text review and data extraction according to the PRISMA guidelines. Quality of included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. The parameters of interest were sensitivity, specificity, negative, and positive likelihood ratios. Cochran Q test and I statistics were used to determine the between-study heterogeneity. Funnel plots were used to describe publication bias. RESULTS: A total of 6753 studies were identified on initial search. Studies that reported EUS-FNA of cystic pancreas lesions were excluded. Eight studies met the inclusion criteria. Seven studies were retrospective, and one was prospective. A total of 593 patients with CP underwent EUS-FNA for SPL. The pooled sensitivity of EUS-FNA was 65% (95% CI 52.6-75.6%, I2 = 44%), specificity was 96.8% (75-99.7%, I2 = 89%), negative likelihood ratio (NLR) 41.4 (11.1-149.6, I2 = 70%), positive likelihood ratio (PLR) 24.1 (2.8-208, I2 = 90%). The pooled data from seven studies that compared 901 non-CP vs. 127 CP showed that the sensitivity of EUS-FNA in diagnosing pancreatic malignancy was 91.5 vs. 65.3% [OR (95% CI) 5.5 (2.9-10.2), I2: 31.8%]. The specificity pooled from six studies [333 non-CP vs. 357 CP] was 95.9% vs. 82.4%, [OR (95% CI) 1.3 (0.2-9.8), I2 = 73%]. The risk of bias was serious in one study, low in four studies and moderate in three studies. CONCLUSION: This pooled meta-analysis shows a low sensitivity of EUS-FNA in diagnosing malignancy in CP patients with SPL in comparison to patients without CP. Modalities such as EUS-fine needle biopsy have high sensitivity and specificity for diagnosing pancreatic cancer and should be considered in patients with CP and suspected pancreatic malignancy.

Visceral artery pseudoaneurysms in necrotizing pancreatitis: risk of early bleeding with lumen-apposing metal stents.

BACKGROUND AND AIMS: Visceral artery pseudoaneurysm (PSA) in necrotizing pancreatitis (NP) is associated with significant morbidity and mortality. This study aimed to evaluate the incidence, clinical presentation, management, and outcomes of PSA in NP. METHODS: All NP patients managed at our institution between 2010 and 2020 were retrospectively reviewed from a prospectively maintained database for PSA. Demographics, clinical presentation, method of diagnosis, management, and outcomes were collected. RESULTS: Thirty-nine of 607 patients (6.4%) with NP had a confirmed diagnosis of PSA. Demographics, presence of infected necrosis, development of organ failure(s), and severity of disease were similar between PSA and no PSA. Endoscopic and percutaneous drainages for walled-off necrosis (WON) were more common in the PSA group. Seven patients developed PSA without requiring any intervention for WON, and 17 patients (43.6%) had lumen-apposing metal stents (LAMSs) placed before PSA diagnosis. The time from NP diagnosis to PSA diagnosis was shorter in these patients (n = 17) compared with the remaining patients (n=22; 47 days [interquartile range {IQR}: 17-85] vs 109 days [IQR: 61-180.5, P=0.009]). In addition, 7 of 11 patients (63.6%) with early PSA (defined by <3 weeks from index cystgastrostomy/cystduodenostomy) had an indwelling LAMS at the time of the PSA diagnosis. Seventy-seven percent of patients presented with anemia, 74.3% with GI bleeding, and 30% with hemorrhagic shock. CT was diagnostic for PSA in 83.9% with a false-negative rate of 16.1%. Splenic (50%) and gastroduodenal (28%) arteries were the most common arteries involved by PSA. Angiography and embolization for PSA were successful in 33 of 35 patients. In-hospital mortality was observed in 9 patients (23.1%). CONCLUSIONS: Although visceral artery PSA affects a small percentage of NP patients, it is associated with significant morbidity and mortality. In addition, bleeding from PSA induced by erosion of LAMSs may occur in the first 2 weeks, prompting individualization of removal intervals.

Reduced bone mineral density in the first year after total pancreatectomy with islet autotransplantation (TPIAT).

BACKGROUND/OBJECTIVES: The effect of total pancreatectomy with islet autotransplantation (TPIAT) on bone mineral density (BMD) in patients with CP is unknown. We aimed to assess bone health in patients with CP after TPIAT. METHODS: We measured BMD, BMD Z-score, and bone mineral content (BMC) for total body, lumbar spine, right and left hip in 78 patients before and after TPIAT using dual-energy X-ray absorptiometry (DXA, n = 78 pre-TPIAT, n = 65 paired pre- and 12 months post-TPIAT, n = 33 paired 12 and 18 months post-TPIAT), and tested for association with clinical history including age, smoking status, and medications using paired and two-sample t-tests, linear regression, and Fisher's exact test. Laboratory measures related to bone health were also assessed. RESULTS: In the patients with pre-TPIAT DXA, 12% had low BMD (Z-score ≤ -2). BMD, BMD Z-score, and BMC all decreased from pre-to 12 months post-TPIAT. BMD declined by 1.7%-4.1% with the greatest change at the hips. Adjusted for change in lean and fat body mass, DXA changes remained significant for total body and hip. Serum carboxy-terminal collagen crosslinks telopeptide and alkaline phosphatase increased at 12 months post-TPIAT, suggesting possible increased bone remodeling. BMD, BMD Z-score, and BMC did not change between 12 months and 18 months in any of the four regions (p > 0.6). CONCLUSIONS: TPIAT is associated with decreases in BMD in the body, lumbar, and hip regions of patients with CP in the first year after TPIAT but these appear to stabilize between 12 and 18 months after TPIAT.

Early detection of pancreatic cancer: current state and future opportunities.

PURPOSE OF REVIEW: Pancreatic ductal adenocarcinoma (PDAC) is third leading cause of cancer death in the United States, a lethal disease with no screening strategy. Although diagnosis at an early stage is associated with improved survival, clinical detection of PDAC is typically at an advanced symptomatic stage when best in class therapies have limited impact on survival. RECENT FINDINGS: In recent years this status quo has been challenged by the identification of novel risk factors, molecular markers of early-stage disease and innovations in pancreatic imaging. There is now expert consensus that screening may be pursued in a cohort of individuals with increased likelihood of developing PDAC based on genetic and familial risk. SUMMARY: The current review summarizes the known risk factors of PDAC, current knowledge and recent observations pertinent to early detection of PDAC in these risk groups and outlines future approaches that will potentially advance the field.

Endoscopic polypectomy devices.

Video 1Use of submucosal injection prior to en-bloc endoscopic mucosal resection.Video 2Use of a detachable loop ligating device prior to hot snare resection of a pedunculated polyp.

Lumen-apposing metal stents (with videos).

BACKGROUND AND AIMS: Lumen-apposing metal stents (LAMSs) are a novel class of devices that have expanded the spectrum of endoscopic GI interventions. LAMSs with their dumbbell configuration, short saddle length, and large inner luminal diameter provide favorable stent characteristics to facilitate anastomosis formation between the gut lumen and adjacent structures. METHODS: The MEDLINE database was searched through April 2021 for articles related to LAMSs by using additional relevant keywords such as "walled-off pancreatic necrosis," "pseudocysts," "pancreatic fluid collection," "cholecystitis," "gastroenterostomy," in addition to "endoscopic treatment" and "endoscopic management," among others. RESULTS: This technology review describes the full spectrum of LAMS designs and delivery systems, techniques for deployment, procedural outcomes, safety, training issues, and financial considerations. CONCLUSIONS: Although LAMSs were initially introduced for drainage of pancreatic pseudocysts and walled-off necrosis, the versatility of these devices has led to a variety of off-label uses including gallbladder drainage, enteric bypass with the creation of gastroenterostomies, and treatment of luminal GI strictures.

Devices and techniques for flexible endoscopic management of Zenker's diverticulum (with videos).

BACKGROUND AND AIMS: Zenker's diverticulum (ZD) has traditionally been treated with open surgery or rigid endoscopy. With the advances in endoscopy, alternative flexible endoscopic treatments have been developed. METHODS: This document reviews current endoscopic techniques and devices used to treat ZD. RESULTS: The endoscopic techniques may be categorized as the traditional flexible endoscopic septal division and the more recent submucosal tunneling endoscopic septum division, also known as peroral endoscopic myotomy for ZD. This document also addresses clinical outcomes, safety, and financial considerations. CONCLUSIONS: Flexible endoscopic approaches treat symptomatic ZD with results that are favorable compared with traditional open surgical or rigid endoscopic alternatives.