Essential Fatty Acid Deficiency is Common after Total Pancreatectomy and Islet AutoTransplantation.

OBJECTIVES: Total pancreatectomy and islet autotransplantation (TPIAT) for pancreatitis may induce risk for essential fatty acid deficiency (EFAD) due to exocrine pancreatic insufficiency and intestinal alterations. The prevalence of EFAD post-TPIAT is currently unknown. METHODS: We abstracted essential fatty acid (EFA) profiles (n = 332 samples) for 197 TPIAT recipients (72% adult, 33% male). Statistical analyses determined the prevalence of, and associations with, EFAD post-operatively. EFAD was defined as a Triene-to-Tetraene ratio ≥ 0.05 if <18 years old, or ≥ 0.038 if ≥18 years old. RESULTS: Prevalence of EFAD was 33%, 49%, and 53.5% at 1, 2, and ≥ 3 years. At 1 year post-TPIAT, older age at transplant (p = 0.03), being an adult versus a child (p = 0.0024), and obstructive etiology (p = 0.0004) were significant predictors of EFAD. Only 6% of children had EFAD 1 year post-TPIAT vs. 46% of adults. ALA levels were lower with lower BMI at transplant (p = 0.011). EFAD was associated with the presence of other intestinal diseases (p < 0.0001). CONCLUSIONS: One-third of individuals had EFAD 1 year post-TPIAT, highlighting the need for systematic monitoring. Older age at transplant increased risk and adults were more affected than children. Other diagnoses affecting intestinal health may further increase risk for EFAD.

Rise in First-Time ERCP For Benign Indications >1 Year After Cholecystectomy Is Associated With Worse Outcomes.

BACKGROUND & AIMS: Greater availability of less invasive biliary imaging to rule out choledocholithiasis should reduce the need for diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in patients who have a remote history of cholecystectomy. The primary aims were to determine the incidence, characteristics, and outcomes of individuals who undergo first-time ERCP >1 year after cholecystectomy (late-ERCP). METHODS: Data from a commercial insurance claim database (Optum Clinformatics) identified 583,712 adults who underwent cholecystectomy, 4274 of whom underwent late-ERCP, defined as first-time ERCP for nonmalignant indications >1 year after cholecystectomy. Outcomes were exposure and temporal trends in late-ERCP, biliary imaging utilization, and post-ERCP outcomes. Multivariable logistic regression was used to examine patient characteristics associated with undergoing late-ERCP. RESULTS: Despite a temporal increase in the use of noninvasive biliary imaging (35.9% in 2004 to 65.6% in 2021; P < .001), the rate of late-ERCP increased 8-fold (0.5-4.2/1000 person-years from 2005 to 2021; P < .001). Although only 44% of patients who underwent late-ERCP had gallstone removal, there were high rates of post-ERCP pancreatitis (7.1%), hospitalization (13.1%), and new chronic opioid use (9.7%). Factors associated with late-ERCP included concomitant disorder of gut-brain interaction (odds ratio [OR], 6.48; 95% confidence interval [CI], 5.88-6.91) and metabolic dysfunction steatotic liver disease (OR, 3.27; 95% CI, 2.79-3.55) along with use of anxiolytic (OR, 3.45; 95% CI, 3.19-3.58), antispasmodic (OR, 1.60; 95% CI, 1.53-1.72), and chronic opioids (OR, 6.24; 95% CI, 5.79-6.52). CONCLUSIONS: The rate of late-ERCP postcholecystectomy is increasing significantly, particularly in patients with comorbidities associated with disorder of gut-brain interaction and mimickers of choledocholithiasis. Late-ERCPs are associated with disproportionately higher rates of adverse events, including initiation of chronic opioid use.

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.

Visceral Fat Predicts New-Onset Diabetes After Necrotizing Pancreatitis.

OBJECTIVES: We aimed to estimate the incidence of new-onset diabetes (NOD) and identify risk factors for NOD in patients with necrotizing pancreatitis (NP). METHODS: Necrotizing pancreatitis patients were reviewed for NOD, diagnosed >90 days after acute pancreatitis. Baseline demographics, comorbidities, clinical outcomes, computed tomography (CT) characteristics of necrotic collections, and CT-derived abdominal fat measurements were analyzed to identify predictors for NOD. RESULTS: Among 390 eligible NP patients (66% men; median age, 51 years; interquartile range [IQR], 36-64) with a median follow-up of 400 days (IQR, 105-1074 days), NOD developed in 101 patients (26%) after a median of 216 days (IQR, 92-749 days) from NP. Of the NOD patients, 84% required insulin and 69% developed exocrine pancreatic insufficiency (EPI). Age (odds ratio [OR], 0.98), male sex (OR, 2.7), obesity (OR, 2.1), presence of EPI (OR, 2.7), and diffuse pancreatic necrosis (OR, 2.4) were independent predictors. In a separate multivariable model assessing abdominal fat on CT, visceral fat area (highest quartile) was an independent predictor for NOD (OR, 3.01). CONCLUSIONS: New-onset diabetes was observed in 1 of 4 patients with NP, most within the first year and requiring insulin. Male sex, obesity, diffuse pancreatic necrosis, development of EPI, and high visceral adiposity identified those at highest risk.

Early Metabolic Measures Predict Long-term Insulin Independence in Recipients of Total Pancreatectomy and Islet Autotransplantation.

Background: Although diabetes after total pancreatectomy and islet autotransplantation (TP-IAT) is one of the biggest concerns for TP-IAT recipients and physicians, reliable prediction of post-TP-IAT glycemic control remains unestablished. This study was conducted to identify early predictors of insulin independence and goal glycemic control by hemoglobin A1c (HbA1c) ≤ 6.5% after TP-IAT. Methods: In this single-center, retrospective study, patients who underwent TP-IAT (n = 227) were reviewed for simple metabolic markers or surrogate indices of ß-cell function obtained 3 mo after TP-IAT as part of standard clinical testing. Long-term metabolic success was defined as (1) insulin independence and (2) HbA1c ≤ 6.5% 1, 3, and 5 y after TP-IAT. Single- and multivariate modeling used 3-mo markers to predict successful outcomes. Results: Of the 227 recipients, median age 31 y, 30% male, 1 y after TP-IAT insulin independence, and HbA1c ≤ 6.5% were present in 39.6% and 72.5%, respectively. In single-predictor analyses, most of the metabolic markers successfully discriminated between those attaining and not attaining metabolic goals. Using the best model selected by random forests analysis, we accurately predicted 1-y insulin independence and goal HbA1c control in 77.3% and 86.4% of the patients, respectively. A simpler "clinically feasible" model using only transplanted islet dose and BETA-2 score allowed easier prediction at a small accuracy loss (74.1% and 82.9%, respectively). Conclusions: Metabolic testing measures performed 3 mo after TP-IAT were highly associated with later diabetes outcomes and provided a reliable prediction model, giving valuable prognostic insight early after TP-IAT and help to identify recipients who require early intervention.

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.

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.

Predicting need for intervention in acute necrotizing pancreatitis following discharge- A single center experience in 525 patients.

BACKGROUND AND AIMS: The clinical course of necrotizing pancreatitis (NP) is variable and unpredictable, with some patients managed conservatively, but a significant proportion become symptomatic and needing intervention for drainage and/or necrosectomy. The aim of this study was to identify patients based on baseline clinical and imaging metrics who will likely need intervention and therefore closer follow-up. METHODS: All NP patients managed in our institution between 2010 and 2019 were identified from a prospective database and those who did not undergo intervention during initial hospitalization were followed longitudinally post discharge until clinical and imaging resolution of necrosis. Patients were categorized into a conservative arm or intervention arm (endoscopic/percutaneous/surgical drainage and/or necrosectomy) for criteria defined according to IAP/APA guidelines. Clinical and imaging characteristics during initial presentation were analyzed between the two groups to identify independent predictors for eventual intervention using multivariable logistic regression. A nomogram was designed based on factors that were significant as defined by P value < 0.05. RESULTS: Among 525 patients, 340 who did not meet criteria for intervention during initial admission were included for study and followed for an average 7.4 ± 11.3 months. 140 were managed conservatively and 200 needed intervention (168 within 6 months and 32 after 6 months). Independent predictors of need for eventual intervention were white race [OR 3.43 (1.11-10.62)], transferred status [OR 3.37 (1.81-6.27)], and need for TPN [OR 6.86 (1.63-28.9)], necrotic collection greater than 6 cm [OR 8.66 (4.10-18.32)] and necrotic collection with greater than 75% encapsulation [OR 41.3 (8.29-205.5)]. A prediction model incorporating these factors demonstrated an area under the curve of 0.88. CONCLUSIONS: Majority of NP patients do not need intervention during initial admission but may require drainage/necrosectomy mostly in the first 6 months following discharge. Need for subsequent intervention can be accurately predicted by a combination of clinical and imaging features on index admission.

Per-oral pancreatoscopy-guided lithotripsy vs. extracorporeal shock wave lithotripsy for treating refractory main pancreatic duct stones in chronic pancreatitis: Protocol for an open-label multi-center randomized clinical trial.

BACKGROUNDS/OBJECTIVES: Patients with chronic pancreatitis may develop pancreatic duct stones that can obstruct outflow leading to ductal hypertension and pain. Both endoscopic retrograde pancreatography (ERP) with per-oral pancreatoscopy (POP) and intraductal lithotripsy and extracorporeal shock wave lithotripsy (ESWL) are feasible options to attempt ductal stone clearance. This study aims to compare POP-guided lithotripsy with ESWL in the management of refractory symptomatic main pancreatic duct stones. METHODS: This is an open-label, multi-center, parallel, randomized clinical trial. Patients with chronic pancreatitis and main pancreatic duct stones ≥5 mm who fail standard ERP methods for stone removal will be eligible for this study. In total, 150 subjects will be randomized 1:1 to either ESWL or POP. A maximum of 4 sessions of either ESWL or POP will be allowed in each arm, with crossover permitted thereafter. The primary outcome is complete stone clearance and secondary outcomes include quality of life, pain scores, number of interventions, and daily opiate requirements. CONCLUSIONS: This study aims to answer the question of which lithotripsy method is superior in removing refractory pancreatic duct stones while addressing the effects of lithotripsy on quality of life and pain in patients with chronic calcific pancreatitis (ClinicalTrials.gov NCT04115826).

Decreased Intestinal Microbiota Diversity Is Associated With Increased Gastrointestinal Symptoms in Patients With Chronic Pancreatitis.

OBJECTIVES: Chronic pancreatitis (CP) is characterized by abdominal pain, recurrent hospitalizations, frequent exposure to antibiotics, nutritional deficiencies, and chronic opioid use. Data describing the gut microbial community structure of patients with CP is limited. We aimed to compare gut microbiota of a group of patients with severe CP being considered for total pancreatectomy with islet autotransplantation (TPIAT) with those of healthy controls and to associate these differences with severity of clinical symptoms. METHODS: We collected stool from healthy donors (n = 14) and patients with CP (n = 20) undergoing workup for TPIAT, in addition to clinical metadata and a validated abdominal symptoms severity survey. RESULTS: Patients with CP had significantly lower alpha diversity than healthy controls ( P < 0.001). There was a significantly increased mean relative abundance of Faecalibacterium in healthy controls compared with patients with CP ( P = 0.02). Among participants with CP, those with lower alpha diversity reported worse functional abdominal symptoms ( P = 0.006). CONCLUSIONS: These findings indicate that changes in gut microbial community structure may contribute to gastrointestinal symptoms and provide basis for future studies on whether enrichment of healthy commensal bacteria such as Faecalibacterium could provide clinically meaningful improvements in outcomes for CP patients undergoing TPIAT.

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.

Multidisciplinary Care for Adults With Chronic Pancreatitis: Incorporating Psychological Therapies to Optimize Outcomes.

ABSTRACT: Chronic pancreatitis (CP) is associated with a high disease burden, extensive negative impact on quality of life, increased rates of depression and anxiety, and significant health care utilization and expenditures. Pain is a hallmark feature of CP, present in up to 90% of patients with this condition, and can lead to high rates of disability, hospitalization, and opioid medication use. Current perspectives on the management of CP have evolved to advocate a multidisciplinary approach which offers new pathways for helping patients manage symptoms. Psychologists play an important role in a multidisciplinary team effort by applying scientifically based psychological principles and techniques to improve pain and adaptation to chronic illness. This review will detail the fundamentals of delivering psychological interventions for adults with CP managed in an outpatient setting. Recommendations for integrating psychological care in multidisciplinary management of CP will be offered. Future directions for psychological care in CP multidisciplinary teams are also discussed.

Endoscopic Management of Complications in Chronic Pancreatitis.

PURPOSE OF REVIEW: Management of complications in patients with chronic pancreatitis is often suboptimal. This review discusses detailed endoscopic approaches for managing complications in CP. LITERATURE FINDINGS: CP is characterized by progressive and irreversible destruction of pancreatic parenchyma and ductal system resulting in fibrosis, scarring, and loss of glandular function. Abdominal pain remains is the most common symptom of the disease and the main aim of medical, endoscopic, and surgical therapy is to help relieve symptoms, prevent disease progression, and manage complications related to CP. In fact, advances in our understanding of CP have improved medical care and quality of life in these patients. With significant sequela, morbidity and a progressive nature, a thorough understanding of the pathophysiology, natural course, diagnostic approaches, and optimal management strategies for this disease is warranted. The existing modalities and new innovations in this field are safe, effective, and likely to have a positive impact on management of complication in CP whenever used in the right context.

Quadruple, 4-segment, triple sector "Y-shaped stents" in complex hilar cholangiocarcinoma after cholangitis from plastic stents.

Video 1Video showing successful placement of 4 uncovered self-expanding metal stents in a stent-in-stent, Y-shaped configuration for cholangitis from plastic stents in a patient with unresectable cholangiocarcinoma.

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.

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.