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Vanek P, Freeman ML. Updates in the Management of Chronic Pancreatitis: Navigating Through Recent Advances. Gastroenterol Clin North Am 2025; 54:157-174. [PMID: 39880525 DOI: 10.1016/j.gtc.2024.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
This article provides an up-to-date review of the management of chronic pancreatitis, highlighting advancements in medical therapy, nutritional support, endoscopic and surgical approaches, and emerging treatments. Nutritional management accentuates addressing malabsorption and nutrient deficiencies. Advances in endoscopy and parenchyma-sparing surgical techniques have opened new avenues for improved patient outcomes, with total pancreatectomy and islet autotransplantation offering the only definitive solution for selected patients. Additionally, emerging therapies, including anti-inflammatory and immune-modulating agents, show promise for future treatment options. Emphasizing a multidisciplinary approach, this review aims to equip health care professionals with a comprehensive overview of current management strategies and future directions.
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Affiliation(s)
- Petr Vanek
- Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 77900 Olomouc, Czech Republic; Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Zluty Kopec 7, 65653 Brno, Czech Republic
| | - Martin L Freeman
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
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Yadav D, Zyromski NJ, Whitcomb DC, Bellin MD, Cote GA, Dasyam A. Recurrent Acute Pancreatitis: Many Faces(/Facets) of a Challenging Disease. Gastroenterology 2025:S0016-5085(25)00416-0. [PMID: 40015521 DOI: 10.1053/j.gastro.2025.01.249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 01/22/2025] [Accepted: 01/30/2025] [Indexed: 03/01/2025]
Affiliation(s)
- Dhiraj Yadav
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Nicholas J Zyromski
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana
| | - David C Whitcomb
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Melena D Bellin
- Division of Pediatric Endocrinology, University of Minnesota/Masonic Children's Hospital, Minneapolis, Minnesota
| | - Gregory A Cote
- Division of Gastroenterology & Hepatology, Oregon Health & Science University, Portland, Oregon
| | - Anil Dasyam
- Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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3
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Mattke J, Eaton A, Wijkstrom M, Witkowski P, Trikudanathan G, Singh VK, Schwarzenberg SJ, Ramanathan K, Pruett TL, Posselt A, Nathan JD, Morgan K, Mokshagundam SP, Lara L, Gardner TB, Freeman M, Downs E, Chinnakotla S, Beilman GJ, Ahmad S, Adams D, Abu-El-Haija M, Naziruddin B, Bellin MD. Islet Isolation Outcomes in Patients Undergoing Total Pancreatectomy With Islet Autotransplantation in the POST Consortium. Transplantation 2025; 109:207-216. [PMID: 38984544 PMCID: PMC11631693 DOI: 10.1097/tp.0000000000005127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/11/2024]
Abstract
BACKGROUND In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes. METHODS We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses. RESULTS In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures ( P < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity ( P = 0.002) or overweight status pre-TPIAT ( P < 0.001) and lower with non-White race ( P = 0.03), genetic pancreatitis ( P = 0.02), history of lateral pancreaticojejunostomy ( P = 0.03), and presence of atrophy ( P = 0.006) or ductal changes ( P = 0.014) on imaging. IEQ/kg was higher in females ( P = 0.01) and Hispanic participants ( P = 0.046) and generally lower with older age (nonlinear association, P < 0.001) and pancreatic atrophy ( P < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively. CONCLUSIONS Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results.
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Affiliation(s)
- Jordan Mattke
- Islet Cell Processing Laboratory, Baylor Health, Dallas, TX
| | - Anne Eaton
- Division of Biostatistics and Health Data Science, University of Minnesota School of Public Health, Minneapolis, MN
| | - Martin Wijkstrom
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Piotr Witkowski
- The Transplantation Institute, University of Chicago, Chicago, IL
| | - Guru Trikudanathan
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - Vikesh K Singh
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD
| | | | - Karthik Ramanathan
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Timothy L Pruett
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Andrew Posselt
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Jaimie D Nathan
- Department of Pediatric Abdominal Transplant and Hepatopancreatobiliary Surgery, Nationwide Children's Hospital, Columbus, OH
| | - Katherine Morgan
- Department of Surgery, The Medical University of South Carolina, Charleston, SC
| | | | - Luis Lara
- Department of Medicine, The Ohio State Wexner University Medical Center, Columbus, OH
| | - Timothy B Gardner
- Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - Martin Freeman
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - Elissa Downs
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
| | - Srinath Chinnakotla
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Gregory J Beilman
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Syed Ahmad
- Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - David Adams
- Department of Surgery, The Medical University of South Carolina, Charleston, SC
| | - Maisam Abu-El-Haija
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | | | - Melena D Bellin
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
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Oikawa R, Takemura N, Shimoda M, Nakamura M, Mihara F, Inagaki F, Kokudo N. Simplified technique in total pancreatectomy with islet cell autotransplantation after Frey's procedure: a case report. Surg Case Rep 2024; 10:272. [PMID: 39601997 PMCID: PMC11602881 DOI: 10.1186/s40792-024-02066-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND The selection of the surgical approach for chronic pancreatitis (CP) is determined by various factors including inflammatory location, presence of pancreatic duct dilatation, or possibility of cancer. Total pancreatectomy (TP), with or without islet cell autotransplantation, is considered for patients with refractory CP after the failure of other surgical treatments. Considering the increasing incidence of CP requiring surgical treatment, the number of cases in which TP is performed after previous surgical treatment is expected to increase. CASE PRESENTATION We reported a case of TPIAT in a patient with alcoholic CP who had previously undergone Frey's procedure. During the operation, the sufficient length of the elevated jejunal loop for pancreaticojejunostomy in Frey's procedure allowed it to be used directly for biliary jejunostomy during TP. In addition, jejunojejunostomy from the previous operation could be used, and these methods contributed to simplifying the operative procedure. We need open hemostasis on post-operative day (POD) 1and a percutaneous drainage tube replacement for an intraperitoneal abscess on POD 24. The patient was discharged from the hospital on POD 37 with normal serum C-peptide level, which suggests favorable insulin secretion from transplanted islets, and the epigastric pain that suffered her preoperatively resulted in a dramatic improvement. CONCLUSIONS When performing the Frey's procedure, the elevated jejunal loop and Y-anastomosis jejunal loop with sufficient length allow them to be used directly for the reconstructions in the possible subsequent TP.
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Affiliation(s)
- Ryo Oikawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Nobuyuki Takemura
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan.
| | - Masayuki Shimoda
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Mai Nakamura
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Fuminori Mihara
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Fuyuki Inagaki
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-Ku, Tokyo, 162-8655, Japan
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Scott A, Khoruts A, Freeman ML, Beilman G, Ramanathan K, Bellin MD, Trikudanathan G. Successful Use of Fecal Microbiota Transplantation in Management of Nonobstructive Recurrent Cholangitis Following Total Pancreatectomy and Islet Autotransplant. ACG Case Rep J 2024; 11:e01527. [PMID: 39399248 PMCID: PMC11469898 DOI: 10.14309/crj.0000000000001527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 08/29/2024] [Indexed: 10/15/2024] Open
Abstract
Alterations in the gut microbiome have been implicated in various pathologies. Fecal microbiota transplantation (FMT) has been offered as a novel treatment for conditions implicated in the disruption of the gut-microbiota axis. This case report details the successful treatment of recurrent nonobstructive cholangitis following a single FMT application in a patient who had previously undergone a hepatobiliary tract surgical diversion. Cholangitis was suspected secondary to reflux of an altered microbiome into the surgically reanastomosed biliary tract, and FMT was justified based on the history of recurrent Clostridioides difficile infections. This case supports the further evaluation of the utility of FMT as one potential treatment of post hepatobiliary surgical diversion cholangitis.
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Affiliation(s)
- Adam Scott
- University of Minnesota Medical School, Minneapolis, MN
| | | | | | - Greg Beilman
- University of Minnesota Medical Center, Minneapolis, MN
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Barthold L, Smith KD, Chaidarun SS, Fischer DA, Gardner TB. Quality of Life Following Total Pancreatectomy With Islet Autotransplantation: A Patient Experience Survey. Pancreas 2024; 53:e652-e656. [PMID: 38696457 DOI: 10.1097/mpa.0000000000002353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/04/2024]
Abstract
OBJECTIVES Total pancreatectomy with islet autotransplantation (TPIAT) is performed to improve the quality of life (QOL) of patients with chronic pancreatitis. Few reports have documented QOL following TPIAT, with none using the pancreatitis-specific Pancreatitis Quality of Life Instrument (PANQOLI). We surveyed patients at our center who underwent TPIAT to document postoperative QOL. MATERIALS AND METHODS We collected survey data from 18 adult patients who underwent TPIAT at our medical center from 2012 to 2020. Patients were asked questions assessing QOL following TPIAT and completed the Short-Form Health Survey and PANQOLI instruments. RESULTS Forty-three patients who underwent TPIAT were mailed surveys, and 18 were returned. The mean age was 45 years, and 67% of respondents were female. Almost half (44%) had hereditary pancreatitis. Sixty-seven percent believed that their overall QOL had improved after surgery. The mean postoperative Short-Form Health Survey physical score was 38.9 and mean mental score was 44. The mean PANQOLI score was 66 (physical function 20, role function 16, emotional function 14, self-worth 15). Following surgery, 33% were using opiate medications and 67% were using antihyperglycemic medications. CONCLUSIONS TPIAT resulted in improved self-reported QOL in most patients, although postoperative physical and mental QOL are less compared to the average healthy United States adult.
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Affiliation(s)
- Laura Barthold
- From the Geisel School of Medicine, Dartmouth College, Hanover
| | | | | | | | - Timothy B Gardner
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
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Darden CM, Mohammed ARH, Kirkland J, Kuncha J, Lawrence MC, Danobeitia JS, Beecherl E, Lee SHS, Gupta A, Naziruddin B. Total pancreatectomy with islet autotransplantation outcomes in patients with pancreatitis of genetic etiology: A single-center experience with a large cohort of patients. J Gastrointest Surg 2024; 28:1309-1318. [PMID: 38834105 DOI: 10.1016/j.gassur.2024.05.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 04/15/2024] [Accepted: 05/27/2024] [Indexed: 06/06/2024]
Abstract
PURPOSE Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for patients with chronic pancreatitis (CP) when other interventions are unsuccessful. CP has many etiologies including heredity. Metabolic and pain relief outcomes after TPIAT are presented among patients with a genetic CP etiology compared with those with a nongenetic etiology in a large cohort of patients who underwent this procedure at our center. METHODS A retrospective analysis was performed of 237 patients undergoing TPIAT between 2006 and 2023. We analyzed the differences in patients with genetic (n = 56) vs nongenetic CP etiologies (n = 181) in terms of pre-TPIAT factors including patient characteristics and disease state, results from the isolation process, and outcomes such as long-term glycemic and pain control. RESULTS Patients with genetic CP underwent TPIAT at a significantly younger age (32.3 vs 41.3 years nongenetic; P < .0001) and endured symptoms for a significantly longer period (10 vs 6 years; P < .01). A significantly lower mass of islets was isolated from patients with genetic CP (P < .01), which increased with body mass index in both groups. Despite lower yields, patients with genetic CP maintained metabolic function similar to patients with nongenetic CP, as indicated by insulin independence and C-peptide, blood glucose, and hemoglobin A1C levels after TPIAT. Post-transplant narcotic usage and pain scores significantly decreased compared with those before TPIAT, and more patients with genetic CP were pain free and narcotic free after TPIAT. CONCLUSION Our data validate TPIAT as a beneficial procedure for patients enduring CP of genetic etiology. Pain that is inevitably recurrent after minor interventions owing to the nature of the disease and favorable TPIAT outcomes should be considered in the decision to perform early TPIAT in cases of genetic CP.
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Affiliation(s)
- Carly M Darden
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
| | | | - Jeffrey Kirkland
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
| | - Jayachandra Kuncha
- Islet Cell Laboratory, Baylor Scott & White Research Institute, Dallas, TX, United States
| | - Michael C Lawrence
- Islet Cell Laboratory, Baylor Scott & White Research Institute, Dallas, TX, United States
| | - J Sebastian Danobeitia
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
| | - Ernest Beecherl
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
| | - Seung Hee S Lee
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
| | - Amar Gupta
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States
| | - Bashoo Naziruddin
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, United States.
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8
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Kawka M, Lucas A, Riad AM, Hawkins D, de Madaria E, West H, Jakaityte I, Lee MJ, Kouli O, Ruanne R, Gujjuri RR, Brown S, Cambridge WA, Pandanaboyana S, Kamarajah SK, McLean KA. Quality of life instruments in acute and chronic pancreatitis: a consensus-based standards for the selection of health measurement instruments (COSMIN) approach. HPB (Oxford) 2024; 26:859-872. [PMID: 38735815 DOI: 10.1016/j.hpb.2024.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 04/07/2024] [Accepted: 04/18/2024] [Indexed: 05/14/2024]
Abstract
BACKGROUND Pancreatitis is a common surgical emergency, associated with pain and poor quality of life for patients. However, assessment of patient-reported outcome measures in these patients is unclear. This study aimed to identify and evaluate the methodological quality of the health-related quality of life instruments used for patients with acute or chronic pancreatitis. METHODS Prospective studies that evaluated health-related quality of life in acute or chronic pancreatitis were identified from systematic review of MEDLINE, EMBASE, and Web of Science until 28th June 2023 (PROSPERO: CRD42021274743). Instrument characteristics were extracted, and methodological quality assessed using COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) guidelines and GRADE approach. Narrative synthesis was conducted, with recommendations for use based on COSMIN criteria, evaluated according to World Health Organisation (WHO) quality of life domains. RESULTS From 3850 records screened, 41 quality of life instruments were identified across 138 studies included. The majority (69.8%, n = 26) were designed to assess general health-related quality of life, whereas the remainder were abdominal-specific (n = 5) or pancreas-specific (n = 10). Only ten instruments (24.3%) demonstrated sufficient content validity, incorporating items in ≥5 WHO quality of life domains. However, only nine instruments (21.9%) incorporated public and patient involvement. Only the Gastrointestinal Quality of Life Index and PAN-PROMISE met the criteria to be recommended for use based on COSMIN methodological assessment. CONCLUSION There is significant heterogeneity in instruments used to assess quality of life after pancreatitis, with almost all instruments considered insufficient. Robust, validated, and relevant instruments are needed to better understand and determine appropriate interventions to improve quality of life for these patients.
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Yamane K, Anazawa T, Nagai K, Ito T, Hatano E. Current status of total pancreatectomy with islet autotransplantation for chronic and recurrent acute pancreatitis. Ann Gastroenterol Surg 2024; 8:401-412. [PMID: 38707227 PMCID: PMC11066494 DOI: 10.1002/ags3.12767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 11/17/2023] [Accepted: 12/12/2023] [Indexed: 05/07/2024] Open
Abstract
Total pancreatectomy with islet autotransplantation (TPIAT) is an established and effective treatment modality for patients diagnosed with intractable chronic pancreatitis (CP) and recurrent acute pancreatitis (RAP). TPIAT primarily aims to manage debilitating pain leading to impaired quality of life among patients with CP or RAP, which can be successfully managed with medical, endoscopic, or surgical interventions. TPIAT is significantly successful in relieving pain associated with CP and improving health-related quality of life outcomes. Furthermore, the complete loss of pancreatic endocrine function attributed to total pancreatectomy (TP) can be compensated by autologous islet transplantation (IAT). Patients receiving IAT can achieve insulin independence or can be less dependent on exogenous insulin compared with those receiving TP alone. Historically, TPIAT has been mainly used in the United States, and its outcomes have been improving due to technological advancements. Despite some challenges, TPIAT can be a promising treatment for patients with CP-related intractable pain. Thus far, TPIAT is not commonly performed in Japan. Nevertheless, it may improve health-related quality of life in Japanese patients with CP, similar to Western patients. This review article aimed to provide an overview of the indications, related procedures, and outcomes of TPIAT and to discuss future prospects in Japan.
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Affiliation(s)
- Kei Yamane
- Department of SurgeryGraduate School of Medicine, Kyoto UniversityKyotoJapan
| | - Takayuki Anazawa
- Department of SurgeryGraduate School of Medicine, Kyoto UniversityKyotoJapan
| | - Kazuyuki Nagai
- Department of SurgeryGraduate School of Medicine, Kyoto UniversityKyotoJapan
| | - Takashi Ito
- Department of SurgeryGraduate School of Medicine, Kyoto UniversityKyotoJapan
| | - Etsuro Hatano
- Department of SurgeryGraduate School of Medicine, Kyoto UniversityKyotoJapan
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Nanno Y, Hodges JS, Freeman ML, Trikudanathan G, Schwarzenberg SJ, Downs EM, Ramanathan K, Pruett TL, Beilman GJ, Chinnakotla S, Hering BJ, Bellin MD. Early Metabolic Measures Predict Long-term Insulin Independence in Recipients of Total Pancreatectomy and Islet Autotransplantation. Transplant Direct 2024; 10:e1561. [PMID: 38094130 PMCID: PMC10715795 DOI: 10.1097/txd.0000000000001561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 10/07/2023] [Indexed: 01/05/2024] Open
Abstract
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 β-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.
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Affiliation(s)
- Yoshihide Nanno
- Department of Surgery, University of Minnesota, Minneapolis, MN
- Schulze Diabetes Institute, Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - James S. Hodges
- Division of Biostatistics, University of Minnesota, Minneapolis, MN
| | | | | | | | - Elissa M. Downs
- Department of Pediatrics, University of Minnesota, Minneapolis, MN
| | | | | | | | - Srinath Chinnakotla
- Schulze Diabetes Institute, Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN
- Department of Pediatrics, University of Minnesota, Minneapolis, MN
| | - Bernhard J. Hering
- Department of Surgery, University of Minnesota, Minneapolis, MN
- Schulze Diabetes Institute, Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN
| | - Melena D. Bellin
- Schulze Diabetes Institute, Department of Surgery, University of Minnesota School of Medicine, Minneapolis, MN
- Department of Pediatrics, University of Minnesota, Minneapolis, MN
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11
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Vasu S, Saracino G, Darden CM, Kumano K, Liu Y, Lawrence MC, Naziruddin B. Clinical and biological significance of circulating miRNAs in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation. Clin Transl Med 2023; 13:e1434. [PMID: 37846205 PMCID: PMC10579997 DOI: 10.1002/ctm2.1434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 09/12/2023] [Accepted: 09/30/2023] [Indexed: 10/18/2023] Open
Abstract
BACKGROUND Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes. METHODS Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool. RESULTS Alterations were found in circulating miRNAs in CP patients compared to healthy controls. Further studies were conducted on 12 circulating miRNAs enriched in the pancreas, other tissues and other diseases including cancer and fibrosis. Approximately 2888 mRNAs in the pancreas were their targets, demonstrating interactions with 76 small molecules. Three miRNAs exhibited interactions with morphine and five exhibited interactions with glucose. The miRNA panel targeted 22 genes associated with pancreatitis. The islet-specific, acinar cell-specific and liver-specific miRNAs were elevated at 6 h after islet infusion and returned to baseline levels 3 months after TPIAT. Circulating levels of miRNAs returned to pre-transplant levels 1-year post-transplant. Circulating miRNAs measured before and 6 h after islet infusion were directly or inversely associated with metabolic outcomes at 3 and 6 months post-transplant. CONCLUSIONS miRNAs may contribute to CP pathogenesis, and elevated circulating levels may be specific to pancreatic inflammation and fibrosis, warranting further investigation.
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Affiliation(s)
- Srividya Vasu
- Islet Cell LaboratoryBaylor Scott and White Research InstituteDallasTexasUSA
| | - Giovanna Saracino
- Baylor Simmons Transplant InstituteBaylor University Medical CenterDallasTexasUSA
| | - Carly M. Darden
- Islet Cell LaboratoryBaylor Scott and White Research InstituteDallasTexasUSA
| | - Kenjiro Kumano
- Department of Gastroenterological SurgeryOkayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayamaJapan
| | - Yang Liu
- The University of Texas Southwestern Medical CenterDallasTexasUSA
| | - Michael C. Lawrence
- Islet Cell LaboratoryBaylor Scott and White Research InstituteDallasTexasUSA
| | - Bashoo Naziruddin
- Baylor Simmons Transplant InstituteBaylor University Medical CenterDallasTexasUSA
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Chen ME, Desai CS. Current practices in islet cell autotransplantation. Expert Rev Endocrinol Metab 2023; 18:419-425. [PMID: 37680038 DOI: 10.1080/17446651.2023.2256407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 08/28/2023] [Accepted: 09/04/2023] [Indexed: 09/09/2023]
Abstract
INTRODUCTION Chronic pancreatitis and recurrent acute pancreatitis comprise a spectrum of disease that results in complications related to exocrine and endocrine insufficiency and chronic pain with narcotic dependence and poor quality of life. The mainstay of therapy has been medical and endoscopic therapy; surgery, especially total pancreatectomy, was historically reserved for few select patients as the obligate exocrine insufficiency and pancreatogenic diabetes (type 3C) are challenging to manage. The addition of islet cell autotransplantation after total pancreatectomy helps to mitigate brittle type 3c diabetes and prevents mortality related to severe hypoglycemic episodes and hypoglycemic unawareness. There have been more recent data demonstrating the safety of surgery and the beneficial long-term outcomes. AREAS COVERED The purpose of this review is to describe the current practices in the field of islet cell autotransplantation including the selection and evaluation of patients for surgery, their preoperative work up and management, surgical approach, post-operative management and outcomes. EXPERT OPINION Total pancreatectomy and islet cell autotransplantation has the ability to drastically improve quality of life and prevent brittle diabetes for patients suffering with chronic pancreatitis.
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Affiliation(s)
- Melissa E Chen
- Department of Surgery, University of North Carolina, Chapel Hill, NC, USA
| | - Chirag S Desai
- Department of Surgery, University of North Carolina, Chapel Hill, NC, USA
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Khazaaleh S, Babar S, Alomari M, Imam Z, Chadalavada P, Gonzalez AJ, Kurdi BE. Outcomes of total pancreatectomy with islet autotransplantation: A systematic review and meta-analysis. World J Transplant 2023; 13:10-24. [PMID: 36687559 PMCID: PMC9850868 DOI: 10.5500/wjt.v13.i1.10] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/24/2022] [Accepted: 12/23/2022] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation (TPIAT), systematic evidence of its outcomes remains limited.
AIM To evaluate the outcomes of TPIAT.
METHODS We searched PubMed, EMBASE, and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes. Data were extracted and analyzed using comprehensive meta-analysis software. The random-effects model was used for all variables. Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic. Publication bias was assessed using Egger’s test.
RESULTS Twenty-one studies published between 1980 and 2017 examining 1011 patients were included. Eighteen studies were of adults, while three studied pediatric populations. Narcotic independence was achieved in 53.5% [95% Confidence Interval (CI): 45-62, P < 0.05, I2 = 81%] of adults compared to 51.9% (95%CI: 17-85, P < 0.05, I2 = 84%) of children. Insulin-independence post-procedure was achieved in 31.8% (95%CI: 26-38, P < 0.05, I2 = 64%) of adults with considerable heterogeneity compared to 47.7% (95%CI: 20-77, P < 0.05, I2 = 82%) in children. Glycated hemoglobin (HbA1C) 12 mo post-surgery was reported in four studies with a pooled value of 6.76% (P = 0.27). Neither stratification by age of the studied population nor meta-regression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies.
CONCLUSION These results indicate acceptable success for TPIAT. Future studies should evaluate the discussed measures before and after surgery for comparison.
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Affiliation(s)
- Shrouq Khazaaleh
- Department of Internal Medicine, Cleveland Clinic Fairview Hospital, Cleveland, OH 44126, United States
| | - Sumbal Babar
- Department of Internal Medicine-Infectious Diseases Division, University of Texas Health Science Center at San Antonio, San Antonio, TX 78249, United States
| | - Mohammad Alomari
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FI 33324, United States
| | - Zaid Imam
- Department of Gastroenterology and Hepatology, William Beaumont Hospital, Royal Oak, MI 48073, United States
| | - Pravallika Chadalavada
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FI 33331, United States
| | - Adalberto Jose Gonzalez
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FI 33331, United States
| | - Bara El Kurdi
- Department of Gastroenterology and Hepatology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78249, United States
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Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation. Pancreatology 2022; 22:1175-1180. [PMID: 36198489 DOI: 10.1016/j.pan.2022.09.242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/01/2022] [Accepted: 09/21/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND Hepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents. OBJECTIVES To define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT. METHODS In this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis. RESULTS A total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2-25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2-40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96). CONCLUSION Our study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.
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Finn SMB, Bellin MD. Total Pancreatectomy with Islet Autotransplantation: New Insights on the Pathology and Pathogenesis of Chronic Pancreatitis from Tissue Research. Surg Pathol Clin 2022; 15:503-509. [PMID: 36049832 PMCID: PMC9623848 DOI: 10.1016/j.path.2022.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure undertaken in some patients with severe pain or disability from recurrent acute and chronic pancreatitis (CP). TPIAT provides a rare opportunity to study human pancreas tissue from patients affected with pancreatitis, and particularly from patients with genetic forms of pancreatitis. Research to date suggests distinct histopathology and potentially differential pathophysiology of distinct etiologies of CP. Histopathology specimens have helped better define the success and limitations of clinical diagnostic imaging tools, such as magnetic retrograde cholangiopancreatography and endoscopic ultrasound.
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Affiliation(s)
- Sadé M B Finn
- Department of Surgery, University of Minnesota Medical School, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA
| | - Melena D Bellin
- Department of Pediatrics and Department of Surgery, University of Minnesota Medical School, MMC 391, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
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16
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Psaltis E, Varghese C, Pandanaboyana S, Nayar M. Quality of life after surgical and endoscopic management of severe acute pancreatitis: A systematic review. World J Gastrointest Endosc 2022; 14:443-454. [PMID: 36051991 PMCID: PMC9329852 DOI: 10.4253/wjge.v14.i7.443] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 05/03/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Treatment for severe acute severe pancreatitis (SAP) can significantly affect Health-related quality of life (HR-QoL). The effects of different treatment strategies such as endoscopic and surgical necrosectomy on HR-QoL in patients with SAP remain poorly investigated.
AIM To critically appraise the available evidence on HR-QoL following surgical or endoscopic necrosectomy in patient with SAP.
METHODS A literature search was performed on PubMed, Google™ Scholar, the Cochrane Library, MEDLINE and Reference Citation Analysis databases for studies that investigated HR-QoL following surgical or endoscopic necrosectomy in patients with SAP. Data collected included patient characteristics, outcomes of interventions and HR-QoL-related details.
RESULTS Eleven studies were found to have evaluated HR-QoL following treatment for severe acute pancreatitis including 756 patients. Three studies were randomized trials, four were prospective cohort studies and four were retrospective cohort studies with prospective follow-up. Four studies compared HR-QoL following surgical and endoscopic necrosectomy. Several metrics of HR-QoL were used including Short Form (SF)-36 and EuroQol. One randomized trial and one cohort study demonstrated significantly improved physical scores at three months in patients who underwent endoscopic necrosectomy compared to surgical necrosectomy. One prospective study that examined HR-QoL following surgical necrosectomy reported some deterioration in the functional status of the patients. On the other hand, a cohort study that assessed the long-term HR-QoL following sequential surgical necrosectomy stated that all patients had SF-36 > 60%. In the only study that examined patients following endoscopic necrosectomy, the HR-QoL was also very good. Three studies investigated the quality adjusted life years suggesting that endoscopic and surgical approaches to management of pancreatic necrosis were comparable in cost effectiveness. Finally, regarding HR-QoL between open necrosectomy and minimally invasive approaches, patients who underwent the later had a significantly better overall quality of life, vitality and mental health.
CONCLUSION This review would suggest that the endoscopic approach might offer better HR-QoL compared to surgical necrosectomy. However, the available comparative literature was very limited. More randomized trials powered to detect differences in HR-QoL are required.
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Affiliation(s)
- Emmanouil Psaltis
- Department of HPB and Transplant Surgery, Newcastle upon Tyne NE7 7DN, United Kingdom
- Department of Surgery, Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom
| | - Chris Varghese
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1010, New Zealand
| | - Sanjay Pandanaboyana
- Department of HPB and Transplant Surgery, Newcastle upon Tyne NE7 7DN, United Kingdom
- Department of Surgery, Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom
| | - Manu Nayar
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom
- Department of Gastroenterology, Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom
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Effectiveness of Intraoperative Versus Dedicated Islet Cell Laboratory Isolation for Total Pancreatectomy With Islet Autotransplant. Transplant Direct 2022; 8:e1314. [PMID: 35415216 PMCID: PMC8989781 DOI: 10.1097/txd.0000000000001314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/11/2022] [Accepted: 02/12/2022] [Indexed: 11/25/2022] Open
Abstract
Background. Total pancreatectomy with islet autotransplantation (TPIAT) requires a complex islet isolation process of the explanted pancreas. Islet isolation has historically required a specialized laboratory to perform islet isolation. We report our experience with a novel technique of intraoperative islet isolation that does not require a specialized islet laboratory, thereby making the isolation process simpler, more accessible, and less costly. Methods. We performed a retrospective, comparative effectiveness analysis of 50 adult patients who underwent TPIAT from 2012 to 2020 (TPIAT with remote isolation [n = 20] versus intraoperative isolation of islet cells [n = 30]). The primary outcome was islet equivalents per body weight (IEQ/kg) for patients in each group. Results. Mean IEQ/kg‘s (4294 remote group versus 3015 intraoperative group, P = 0.06) and 1-y postoperative C-peptide levels (1.51 ng/mL remote group versus 0.91 ng/mL intraoperative group, P = 0.10) were not different between groups. Mean 1-y HbA1c levels (7.7% in the remote group versus 7.1% intraoperative group, P = 0.67) and 1-y insulin requirements (P = 0.31) were not statistically different. Lower average cost of hospitalization was seen in the intraoperative group, although this was not statistically significant ($104 398 remote versus $78 986 intraoperative, P = 0.81). Conclusions. Intraoperative islet isolation has similar effectiveness in regard to glycemic outcomes compared with the use of a dedicated islet cell isolation laboratory at a lower cost.
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18
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Ludwig S, Distler M, Schubert U, Schmid J, Thies H, Welsch T, Hempel S, Tonn T, Weitz J, Bornstein SR, Ludwig B. Quality of life and metabolic outcomes after total pancreatectomy and simultaneous islet autotransplantation. COMMUNICATIONS MEDICINE 2022; 2:24. [PMID: 35603294 PMCID: PMC9053265 DOI: 10.1038/s43856-022-00087-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 02/07/2022] [Indexed: 12/16/2022] Open
Abstract
Background Pancreas surgery remains technically challenging and is associated with considerable morbidity and mortality. Identification of predictive risk factors for complications have led to a stratified surgical approach and postoperative management. The option of simultaneous islet autotransplantation (sIAT) allows for significant attenuation of long-term metabolic and overall complications and improvement of quality of life (QoL). The potential of sIAT to stratify a priori the indication for total pancreatectomy is yet not adequately evaluated. Methods The aim of this analysis was to evaluate the potential of sIAT in patients undergoing total pancreatectomy to improve QoL, functional and overall outcome and therefore modify the surgical strategy towards earlier and extended indications. A center cohort of 24 patients undergoing pancreatectomy were simultaneously treated with IAT. Patients were retrospectively analyzed regarding in-hospital and overall mortality, postoperative complications, ICU stay, hospital stay, metabolic outcome, and QoL. Results Here we present that all patients undergoing primary total pancreatectomy or surviving complicated two-stage pancreas resection and receiving sIAT show excellent metabolic outcome (33% insulin independence, 66% partial graft function; HbA1c 6,1 ± 1,0%) and significant benefit regarding QoL. Primary total pancreatectomy leads to significantly improved overall outcome and a significant reduction in ICU- and hospital stay compared to a two-stage completion pancreatectomy approach. Conclusions The findings emphasize the importance of risk-stratified pancreas surgery. Feasibility of sIAT should govern the indication for primary total pancreatectomy particularly in high-risk patients. In rescue completion pancreatectomy sIAT should be performed whenever possible due to tremendous metabolic benefit and associated QoL.
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Affiliation(s)
- Stefan Ludwig
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Technische Universität Dresden, D-01307 Dresden, Germany
| | - Marius Distler
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Technische Universität Dresden, D-01307 Dresden, Germany
- Paul Langerhans Institute Dresden of the Helmholtz Center Munich at The University Hospital Carl Gustav Carus and Faculty of Medicine of the Technische Universität Dresden, D-01307 Dresden, Germany
- Center for Diabetes Research (DZD e.V.), D-85764 Neuherberg, Germany
| | - Undine Schubert
- Paul Langerhans Institute Dresden of the Helmholtz Center Munich at The University Hospital Carl Gustav Carus and Faculty of Medicine of the Technische Universität Dresden, D-01307 Dresden, Germany
- Center for Diabetes Research (DZD e.V.), D-85764 Neuherberg, Germany
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany
| | - Janine Schmid
- Paul Langerhans Institute Dresden of the Helmholtz Center Munich at The University Hospital Carl Gustav Carus and Faculty of Medicine of the Technische Universität Dresden, D-01307 Dresden, Germany
- Center for Diabetes Research (DZD e.V.), D-85764 Neuherberg, Germany
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany
| | - Henriette Thies
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany
| | - Thilo Welsch
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Technische Universität Dresden, D-01307 Dresden, Germany
| | - Sebastian Hempel
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Technische Universität Dresden, D-01307 Dresden, Germany
| | - Torsten Tonn
- Experimental Transfusion Medicine, Faculty of Medicine of the Technische Universität Dresden, D-01307 Dresden, Germany
- DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, D-01307 Dresden, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Technische Universität Dresden, D-01307 Dresden, Germany
- Paul Langerhans Institute Dresden of the Helmholtz Center Munich at The University Hospital Carl Gustav Carus and Faculty of Medicine of the Technische Universität Dresden, D-01307 Dresden, Germany
- Center for Diabetes Research (DZD e.V.), D-85764 Neuherberg, Germany
| | - Stefan R. Bornstein
- Paul Langerhans Institute Dresden of the Helmholtz Center Munich at The University Hospital Carl Gustav Carus and Faculty of Medicine of the Technische Universität Dresden, D-01307 Dresden, Germany
- Center for Diabetes Research (DZD e.V.), D-85764 Neuherberg, Germany
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany
- DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, D-01307 Dresden, Germany
- Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, SE1 1UL UK
| | - Barbara Ludwig
- Paul Langerhans Institute Dresden of the Helmholtz Center Munich at The University Hospital Carl Gustav Carus and Faculty of Medicine of the Technische Universität Dresden, D-01307 Dresden, Germany
- Center for Diabetes Research (DZD e.V.), D-85764 Neuherberg, Germany
- Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany
- DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, D-01307 Dresden, Germany
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Phillips AE, Steel JL, Amin A, Wijkstrom M, Zureikat A, Tillman E, Jones R, Patel S, Fehrman N, Starinsky S, Nalitt H, Yadav D, Slivka A, Bellin MD, Carroll A, Humar A. Psychosocial outcomes 1-year post total pancreatectomy and autologous islet cell transplant. Pediatr Transplant 2022; 26:e14167. [PMID: 34668626 DOI: 10.1111/petr.14167] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/01/2021] [Accepted: 10/02/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND A paucity of research regarding the psychosocial outcomes after TPIAT exists. METHODS Adults (>18 years), adolescents (13-18 years), and children (5-12 years) with their parents were administered questionnaires at the time of evaluation for TPIAT and 1-year postsurgery to assess psychosocial outcomes. RESULTS A total of 13 adults (6 male, 46%; mean age 35.2 years) and 9 children/adolescents (4 female, 44.4%; mean age 11.78 years) with CP were included in the study. A total of 69.2% of the adults and 66.7% of the children and adolescents were insulin dependent at 1-year postsurgery. In adults, improvements on the SF-36 pain (p = .001) and general health (p = .045) subscales were generally observed 1-year postsurgery. Adult patients who underwent robotic-assisted surgery compared to open surgery specifically reported better general health on the SF-36 (p < .05) at 1 year. For children and adolescents, reductions in average pain in the last week (p < .05), pain interference (p < .001), and fatigue were observed (p < .05) at 1-year postsurgery. For the entire sample, using repeated measures ANOVA and covarying for age, significant differences were found 1-year postsurgery in average pain in the last week (p = .034) and pain interference with the following categories: general activity (p < .001), walking (p = .04), normal work (p = .003), sleep (p = .002), and enjoyment in life (p = .007). CONCLUSIONS While few transplant centers offer this treatment, the improvement in quality of life suggests this may be a viable treatment option for those with CP complicated by intractable pain. (IRB Approval PRO 19080302).
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Affiliation(s)
- Anna E Phillips
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Jennifer L Steel
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.,Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.,Department of Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Aarshati Amin
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Martin Wijkstrom
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Amer Zureikat
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Emily Tillman
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Rachel Jones
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Seema Patel
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.,Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Nicole Fehrman
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.,Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Stefanie Starinsky
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.,Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Hailey Nalitt
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.,Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Dhiraj Yadav
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Adam Slivka
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Melena D Bellin
- Division of Pediatric Endocrinology and Schulze Diabetes Institute, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - Antoinette Carroll
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Abhinav Humar
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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20
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Boucher AA, Wastvedt S, Hodges JS, Beilman GJ, Kirchner VA, Pruett TL, Hering BJ, Schwarzenberg SJ, Downs E, Freeman M, Trikudanathan G, Chinnakotla S, Bellin MD. Portal Vein Thrombosis May Be More Strongly Associated With Islet Infusion Than Extreme Thrombocytosis After Total Pancreatectomy With Islet Autotransplantation. Transplantation 2021; 105:2499-2506. [PMID: 33988346 DOI: 10.1097/tp.0000000000003624] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Total pancreatectomy with islet autotransplantation (TPIAT) involves pancreatectomy, splenectomy, and reinjection of the patient's pancreatic islets into the portal vein. This process triggers a local inflammatory reaction and increase in portal pressure, threatening islet survival and potentially causing portal vein thrombosis. Recent research has highlighted a high frequency of extreme thrombocytosis (platelets ≥1000 × 109/L) after TPIAT, but its cause and association with thrombotic risk remain unclear. METHODS This retrospective single-site study of a contemporary cohort of 409 pediatric and adult patients analyzed the frequency of thrombocytosis, risk factors for thrombosis, and antiplatelet and anticoagulation strategies. RESULTS Of 409 patients, 67% developed extreme thrombocytosis, peaking around postoperative day 16. Extreme thrombocytosis was significantly associated with infused islet volumes. Thromboembolic events occurred in 12.2% of patients, with portal vein thromboses occurring significantly earlier than peripheral thromboses. Portal vein thromboses were associated with infused islet volumes and portal pressures but not platelet counts or other measures. Most thromboembolic events (82.7%) occurred before the postoperative day of maximum platelet count. Only 4 of 27 (14.8%) of portal vein thromboses occurred at platelet counts ≥500 × 109/L. Perioperative heparin was given to all patients. Treatment of reactive thrombocytosis using aspirin in adults and hydroxyurea in children was not associated with significantly decreased thromboembolic risk. CONCLUSIONS These results suggest that post-TPIAT thrombocytosis and portal vein thromboses may be linked to the islet infusion inflammation, not directly to each other, and further reducing this inflammation may reduce thrombosis and thrombocytosis frequencies simultaneously.
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Affiliation(s)
- Alexander A Boucher
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - Solvejg Wastvedt
- Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN
| | - James S Hodges
- Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN
| | - Gregory J Beilman
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Varvara A Kirchner
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Timothy L Pruett
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Bernhard J Hering
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | | | - Elissa Downs
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
| | - Martin Freeman
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - Guru Trikudanathan
- Department of Medicine, University of Minnesota Medical School, Minneapolis, MN
| | - Srinath Chinnakotla
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Melena D Bellin
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
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21
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Lara LF, Wastvedt S, Hodges JS, Witkowski P, Wijkstrom M, Walsh RM, Singh VK, Schwarzenberg SJ, Pruett TL, Posselt A, Naziruddin B, Nathan JD, Morgan KA, Mitchell R, Kirchner VA, Mokshagundam SL, Hatipoglu B, Gardner TB, Freeman ML, Chinnakotla S, Beilman GJ, Abu-El-Haija M, Conwell DL, Bellin MD. The Association of Smoking and Alcohol Abuse on Anxiety and Depression in Patients With Recurrent Acute or Chronic Pancreatitis Undergoing Total Pancreatectomy and Islet Autotransplantation: A Report From the Prospective Observational Study of TPIAT Cohort. Pancreas 2021; 50:852-858. [PMID: 34347725 PMCID: PMC8373657 DOI: 10.1097/mpa.0000000000001850] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown. METHODS We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes. RESULTS Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005). CONCLUSIONS Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed.
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Affiliation(s)
- Luis F. Lara
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Medical Center, Columbus, OH
| | - Solvejg Wastvedt
- School of Public Health, University of Minnesota Minneapolis, MN
| | - James S. Hodges
- School of Public Health, University of Minnesota Minneapolis, MN
| | | | - Martin Wijkstrom
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Vikesh K. Singh
- Department of Medicine, Division of Gastroenterology, John Hopkins Medical Institutions, Baltimore, MD
| | | | - Timothy L. Pruett
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Andrew Posselt
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Bashoo Naziruddin
- Department of Surgery, Islet Cell Processing Laboratory, Baylor Health, Dallas, TX
| | - Jaimie D. Nathan
- Division of Surgery, Cincinnati Children’s Hospital Medical Center
- Department of Surgery, University of Cincinnati, Cincinnati, OH
- Department of Pediatrics, University of Cincinnati, Cincinnati, OH
| | - Katherine A. Morgan
- Department of Surgery, Division of GI and Laparoscopic Surgery, Medical University of South Carolina, Charleston, SC
| | - Rebecca Mitchell
- School of Public Health, University of Minnesota Minneapolis, MN
| | - Varvara A. Kirchner
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | | | - Betul Hatipoglu
- Department of Medicine, Division of Clinical and Molecular Endocrinology, University Hospitals, Cleveland, OH
| | - Timothy B. Gardner
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - Martin L. Freeman
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical School, Minneapolis, MN
| | - Srinath Chinnakotla
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Gregory J. Beilman
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Maisam Abu-El-Haija
- Department of Pediatrics, University of Cincinnati, Cincinnati, OH
- Division of Pediatric Gastroenterology, Cincinnati Children’s Hospital
| | - Darwin L. Conwell
- Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Medical Center, Columbus, OH
| | - Melena D. Bellin
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN
- Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Medical School, Minneapolis, MN
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22
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Jabłońska B, Mrowiec S. Total Pancreatectomy with Autologous Islet Cell Transplantation-The Current Indications. J Clin Med 2021; 10:2723. [PMID: 34202998 PMCID: PMC8235694 DOI: 10.3390/jcm10122723] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/13/2021] [Accepted: 06/16/2021] [Indexed: 11/18/2022] Open
Abstract
Total pancreatectomy is a major complex surgical procedure involving removal of the whole pancreatic parenchyma and duodenum. It leads to lifelong pancreatic exocrine and endocrine insufficiency. The control of surgery-induced diabetes (type 3) requires insulin therapy. Total pancreatectomy with autologous islet transplantation (TPAIT) is performed in order to prevent postoperative diabetes and its serious complications. It is very important whether it is safe and beneficial for patients in terms of postoperative morbidity and mortality, and long-term results including quality of life. Small duct painful chronic pancreatitis (CP) is a primary indication for TPAIT, but currently the indications for this procedure have been extended. They also include hereditary/genetic pancreatitis (HGP), as well as less frequent indications such as benign/borderline pancreatic tumors (intraductal papillary neoplasms, neuroendocrine neoplasms) and "high-risk pancreatic stump". The use of TPAIT in malignant pancreatic and peripancreatic neoplasms has been reported in the worldwide literature but currently is not a standard but rather a controversial management in these patients. In this review, history, technique, indications, and contraindications, as well as short-term and long-term results of TPAIT, including pediatric patients, are described.
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Affiliation(s)
- Beata Jabłońska
- Department of Digestive Tract Surgery, Medical University of Silesia, 40-752 Katowice, Poland;
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23
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Swentek L, Chung D, Ichii H. Antioxidant Therapy in Pancreatitis. Antioxidants (Basel) 2021; 10:657. [PMID: 33922756 PMCID: PMC8144986 DOI: 10.3390/antiox10050657] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/15/2021] [Accepted: 04/19/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatitis is pathologic inflammation of the pancreas characterized by acinar cell destruction and oxidative stress. Repeated pancreatic insults can result in the development of chronic pancreatitis, characterized by irreversible fibrosis of the pancreas and many secondary sequelae, ultimately leading to the loss of this important organ. We review acute pancreatitis, chronic pancreatitis, and pancreatitis-related complications. We take a close look at the pathophysiology with a focus on oxidative stress and how it contributes to the complications of the disease. We also take a deep dive into the evolution and current status of advanced therapies for management including dietary modification, antioxidant supplementation, and nuclear factor erythroid-2-related factor 2-Kelch-like ECH-associated protein 1(Nrf2-keap1) pathway activation. In addition, we discuss the surgeries aimed at managing pain and preventing further endocrine dysfunction, such as total pancreatectomy with islet auto-transplantation.
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Affiliation(s)
| | | | - Hirohito Ichii
- Department of Surgery, University of California, Irvine, CA 92868, USA; (L.S.); (D.C.)
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24
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Saleh M, Sharma K, Kalsi R, Fusco J, Sehrawat A, Saloman JL, Guo P, Zhang T, Mohamed N, Wang Y, Prasadan K, Gittes GK. Chemical pancreatectomy treats chronic pancreatitis while preserving endocrine function in preclinical models. J Clin Invest 2021; 131:143301. [PMID: 33351784 PMCID: PMC7843231 DOI: 10.1172/jci143301] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 12/01/2020] [Indexed: 12/20/2022] Open
Abstract
Chronic pancreatitis affects over 250,000 people in the US and millions worldwide. It is associated with chronic debilitating pain, pancreatic exocrine failure, and high risk of pancreatic cancer and usually progresses to diabetes. Treatment options are limited and ineffective. We developed a new potential therapy, wherein a pancreatic ductal infusion of 1%-2% acetic acid in mice and nonhuman primates resulted in a nonregenerative, near-complete ablation of the exocrine pancreas, with complete preservation of the islets. Pancreatic ductal infusion of acetic acid in a mouse model of chronic pancreatitis led to resolution of chronic inflammation and pancreatitis-associated pain. Furthermore, acetic acid-treated animals showed improved glucose tolerance and insulin secretion. The loss of exocrine tissue in this procedure would not typically require further management in patients with chronic pancreatitis because they usually have pancreatic exocrine failure requiring dietary enzyme supplements. Thus, this procedure, which should be readily translatable to humans through an endoscopic retrograde cholangiopancreatography (ERCP), may offer a potential innovative nonsurgical therapy for chronic pancreatitis that relieves pain and prevents the progression of pancreatic diabetes.
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Affiliation(s)
- Mohamed Saleh
- Division of Pediatric Surgery
- Division of Pediatric Endocrinology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | | | | | | | | | - Jami L. Saloman
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Ping Guo
- Department of Clinical Science, Colorado State University, Fort Collins, Colorado, USA
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25
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Abstract
Acute pancreatitis is one of the most common reasons for gastroenterology-related hospitalization in the United States. With significant morbidity and subsequent mortality related to both the acute presentation and subsequent sequelae, prompt diagnosis and appropriate management are critical, especially in the first 24 hours of illness. It is also important to accurately recognize complications, such as pancreatic fluid collections and vascular events, and identify a definitive cause so that a strategy to prevent future attacks can be implemented.
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26
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Imaging prediction of islet yield and post-operative insulin requirement in children undergoing total pancreatectomy with islet autotransplantation. Pancreatology 2021; 21:269-274. [PMID: 33339723 DOI: 10.1016/j.pan.2020.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 11/10/2020] [Accepted: 12/02/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Predicting post-operative glycemic control in children undergoing total pancreatectomy with islet autotransplantation (TPIAT) remains difficult. The purpose of our study was to explore preoperative imaging as a marker for islet yield and insulin need in pediatric patients undergoing TPIAT. METHODS This was a retrospective study of children (≤18 years) who had undergone TPIAT between April 2015 and December 2018 and had 6 or more months of post-TPIAT follow-up. Patient specific factors (height, weight, body mass index [BMI], body surface area [BSA]) and pancreas volume segmented from the most recent pre-operative cross-sectional imaging were explored as predictors of islet yield (total islet counts [TIC], total islet equivalents [TIE], islet equivalents per kilogram body weight [IEQ/kg]) and glycemic control (total daily dose of insulin per kilogram body weight [TDD/kg], insulin independence) using Pearson correlation and univariate and multiple regression. RESULTS Thirty-three patients, median age 13 years (IQR: 10-15 years), 64% female (21/33) met inclusion criteria. Nine patients (27%) achieved insulin independence at six months. Median TIE isolated was 310,000 (IQR: 200,000-460,000). Segmented pancreas volume was moderately associated with TIE (coefficient estimate = 0.34, p = 0.034). On multiple regression analysis, there was no significant predictor of insulin independence but number of attacks of pancreatitis (estimate = 0.024; p = 0.018) and segmented pancreas volume by body weight (estimate = -0.71; p < 0.001) were significant predictors of insulin TDD/kg. CONCLUSION Pancreas volume segmented from pre-TPIAT imaging has predictive performance for post-TPIAT insulin need in children.
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27
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De Paep DL, Gillard P, Ling Z, Verbeke H, Maleux G, Vandecaveye V, Debaveye Y, Keymeulen B, van der Merwe S, Pipeleers D, Pirenne J, van Malenstein H, Jacobs-Tulleneers-Thevissen D. Use of hyperglycemic clamp to assess pancreatectomy and islet cell autotransplant in patient with heterotaxy syndrome and dorsal pancreas agenesis leading to chronic pancreatitis. Am J Transplant 2020; 20:3662-3666. [PMID: 32476268 DOI: 10.1111/ajt.16084] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 04/28/2020] [Accepted: 05/15/2020] [Indexed: 01/25/2023]
Abstract
Patients with heterotaxy syndrome (HS) can present with an associated complete dorsal pancreas agenesis (DPA). They are considered to be at increased risk for developing diabetes due to a reduced functional beta cell mass (FBM) as well as for chronic pancreatitis leading to unmanageable pain. We report the case of a young woman with chronic pancreatitis due to HS and associated DPA. She presented with a severe persisting upper abdominal pain refractory to nonsurgical treatment. Unlike in previously reported cases, she had a high FBM (ie, 150% of normoglycemic controls) as determined by hyperglycemic clamp. She underwent a total pancreatectomy followed within 24 hours by an intraportal autologous islet cell transplant containing 4 × 106 beta cells (4700 islet equivalent)/kg body weight. After surgery, the pain resolved, eliminating the need for analgesics. The intraportal implant established an adequate FBM (72% of controls at posttransplant month 2), achieving glycemic control without need for insulin administration. A hyperglycemic clamp can assess the utility and efficacy of an intraportal islet cell autotransplant following total pancreatectomy in patients with HS and complete DPA.
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Affiliation(s)
- Diedert L De Paep
- Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.,Department of Surgery, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Pieter Gillard
- Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.,Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Zhidong Ling
- Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
| | - Hilde Verbeke
- Center for Algology & Pain Management, University Hospitals Leuven, Leuven, Belgium
| | - Geert Maleux
- Department of Radiology, University Hospitals Leuven, Leuven, Belgium
| | | | - Yves Debaveye
- Clinical Division of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Bart Keymeulen
- Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
| | - Schalk van der Merwe
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Daniel Pipeleers
- Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
| | - Jacques Pirenne
- Department of Abdominal Transplant Surgery and Transplantation Coordination, University Hospitals Leuven, Leuven, Belgium
| | - Hannah van Malenstein
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Daniel Jacobs-Tulleneers-Thevissen
- Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.,Department of Surgery, Universitair Ziekenhuis Brussel, Brussels, Belgium.,Department of Abdominal Transplant Surgery and Transplantation Coordination, University Hospitals Leuven, Leuven, Belgium
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28
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Narayanan S, Bhutiani N, Adamson DT, Jones CM. Pancreatectomy, Islet Cell Transplantation, and Nutrition Considerations. Nutr Clin Pract 2020; 36:385-397. [PMID: 33002260 DOI: 10.1002/ncp.10578] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Pancreatic islet transplantation is a reliable approach for treating insulin-deficient diabetes. This established β-cell replacement approach has shown considerable improvements in the last 2 decades. It has helped achieve metabolic homeostasis and safe outcomes for a subset of patients with type 1 diabetes and severe pancreatitis. Nutrition support, until recently, was considered as a secondary factor, merely identified as a means of providing all the necessary nutrients for such patients. However, new literature suggests that several factors, such as the route, timing, quantity, and composition of all the nutrients administered, have key disease-altering properties and are vital during the perioperative management of such patients. This review will highlight the benefits of performing the clinical islet transplantation on a subgroup of patients with type 1 diabetes and pancreatitis and summarize new data that identify the pivotal role of nutrition support as a critical intervention in their management.
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Affiliation(s)
- Siddharth Narayanan
- Division of Transplantation, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Neal Bhutiani
- Division of Transplantation, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Dylan T Adamson
- Division of Transplantation, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | - Christopher M Jones
- Division of Transplantation, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville, Louisville, Kentucky, USA
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29
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Extreme Thrombocytosis after Pediatric Pancreatectomy with Islet Autotransplantation Is Unique Compared to Other Postsplenectomy States. J Pediatr Surg 2020; 55:1645-1650. [PMID: 31677823 DOI: 10.1016/j.jpedsurg.2019.09.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/25/2019] [Accepted: 09/01/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hematologic trends after pancreatectomy with islet autotransplantation (IAT), which involves splenectomy, have been rarely studied. Reactive thrombocytosis (RT, platelets ≥500 K/μL) often occurs postoperatively, similar to other postsplenectomy states, but the degree of similarities and true incidence are unknown. STUDY DESIGN A single-site, retrospective, observational cohort study of patients who underwent total splenectomy between 2010 and 2018 was performed. Thrombocytosis incidence and pharmacologic management strategies were evaluated, including cohort-based analyses for IAT versus other splenectomy indications. RESULTS Analyses included 112 patients overall, 42 of whom underwent IAT. RT occurred frequently (93.8%) despite most patients having normal preoperative platelet counts. IAT patients had significantly higher peak platelet counts compared to non-IAT patients and the rate of platelet rise for IAT patients was significantly faster. IAT was uniquely predictive of developing extreme thrombocytosis (ExT, platelets ≥1000 K/μL, 90% vs. 15.7%, risk ratio 4.11, P < 0.0001) despite standardized hydroxyurea use. Thrombotic events were infrequent and did not differ between groups. CONCLUSIONS RT was common regardless of splenectomy indication but ExT was uniquely associated with IAT despite cytoreductive pharmacotherapy. These results strongly suggest that splenectomy is unlikely to be the sole contributor to post-IAT RT but further investigations into this phenomenon are needed. LEVEL-OF-EVIDENCE RATING Treatment study, Level III (retrospective comparative study).
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30
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Abstract
OBJECTIVE When total pancreatectomy with islet autotransplantation (TPIAT) is performed for chronic pancreatitis, the pancreas and most of the duodenum are removed, with Roux-en-Y reconstruction of the gastrointestinal tract. Enteroendocrine cells in the intestines and pancreas secrete hormones coordinating digestion and motility, but anatomic reconstruction alters transit of nutrients to these cells. We hypothesized that TPIAT leads to changes in enteroendocrine hormones. METHODS Glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and pancreatic polypeptide (PP) were measured from mixed-meal tolerance tests of 34 clinical trial participants before and 18 months after TPIAT. Area under the curve of GLP-1 and PYY-stimulated responses were calculated by trapezoidal method, and the PP response was measured as the stimulated max minus baseline (ΔPP). RESULTS Area under the curve of GLP-1 and PYY increased significantly after TPIAT (GLP-1 average +553.1 pg/mL per minute, P = 0.004; PYY average +4647.9 pg/mL per minute, P = 0.02). ΔPP trended toward lower after TPIAT (average, -52.2 pg/mL, P = 0.06). CONCLUSIONS In this novel study of enteroendocrine hormones in TPIAT patients, stimulated levels of GLP-1 and PYY were significantly higher after versus before TPIAT. ΔPP was lower after TPIAT, but not significantly. These hormone changes have potential clinical implications that warrant further research.
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31
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Abu-El-Haija M, Anazawa T, Beilman GJ, Besselink MG, Del Chiaro M, Demir IE, Dennison AR, Dudeja V, Freeman ML, Friess H, Hackert T, Kleeff J, Laukkarinen J, Levy MF, Nathan JD, Werner J, Windsor JA, Neoptolemos JP, Sheel ARG, Shimosegawa T, Whitcomb DC, Bellin MD. The role of total pancreatectomy with islet autotransplantation in the treatment of chronic pancreatitis: A report from the International Consensus Guidelines in chronic pancreatitis. Pancreatology 2020; 20:762-771. [PMID: 32327370 DOI: 10.1016/j.pan.2020.04.005] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 03/18/2020] [Accepted: 04/06/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Advances in our understanding of total pancreatectomy with islet autotransplantation (TPIAT) have been made. We aimed to define indications and outcomes of TPIAT. METHODS Expert physician-scientists from North America, Asia, and Europe reviewed the literature to address six questions selected by the writing group as high priority topics. A consensus was reached by voting on statements generated from the review. RESULTS Consensus statements were voted upon with strong agreement reached that (Q1) TPIAT may improve quality of life, reduce pain and opioid use, and potentially reduce medical utilization; that (Q3) TPIAT offers glycemic benefit over TP alone; that (Q4) the main indication for TPIAT is disabling pain, in the absence of certain medical and psychological contraindications; and that (Q6) islet mass transplanted and other disease features may impact diabetes mellitus outcomes. Conditional agreement was reached that (Q2) the role of TPIAT for all forms of CP is not yet identified and that head-to-head comparative studies are lacking, and that (Q5) early surgery is likely to improve outcomes as compared to late surgery. CONCLUSIONS Agreement on TPIAT indications and outcomes has been reached through this working group. Further studies are needed to answer the long-term outcomes and maximize efforts to optimize patient selection.
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Affiliation(s)
- Maisam Abu-El-Haija
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Takayuki Anazawa
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Japan
| | - Gregory J Beilman
- Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Marc G Besselink
- Department of Surgery, Amsterdam Gastroenterology and Metabolism, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO, USA
| | - Ihsan Ekin Demir
- Department of Surgery, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Ashley R Dennison
- Department of Hepatobiliary and Pancreatic Surgery, University of Leicester, UK
| | - Vikas Dudeja
- Department of Surgery, University of Miami, Miami, FL, USA
| | - Martin L Freeman
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Helmut Friess
- Department of Surgery, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Germany
| | - Jorg Kleeff
- Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - Johanna Laukkarinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Finland
| | - Marlon F Levy
- Division of Transplant Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA
| | - Jaimie D Nathan
- Division of Pediatric General and Thoracic Surgery Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Jens Werner
- Department of General, Visceral, and Transplant Surgery, University of Munich, LMU, Germany
| | - John A Windsor
- Surgical and Translational Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - John P Neoptolemos
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Andrea R G Sheel
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - David C Whitcomb
- Department of Medicine, Cell Biology & Physiology, and Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Melena D Bellin
- Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN, USA; Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA.
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32
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Nguyen TT, Emami F, Yook S, Nguyen HT, Pham TT, Pathak S, Regmi S, Kim JO, Yong CS, Kim JR, Jeong JH. Local release of NECA (5'-(N-ethylcarboxamido)adenosine) from implantable polymeric sheets for enhanced islet revascularization in extrahepatic transplantation site. J Control Release 2020; 321:509-518. [PMID: 32087300 DOI: 10.1016/j.jconrel.2020.02.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 02/06/2020] [Accepted: 02/16/2020] [Indexed: 12/20/2022]
Abstract
Clinical intraportal pancreatic islet infusion is popular for treating type I diabetes. However, multiple doses of islets and anti-rejection protocols are needed to compensate for early large cell losses post-infusion due to the harsh hepatic environment. Thus, extrahepatic sites are utilized to enable efficient islet engraftment and reduce islet mass. Here, we reported an effective islet revascularization protocol that was based on the co-implantation of islet/fibrin gel construct with poly(lactic-co-glycolic) acid sheet releasing NECA (5'-(N-ethylcarboxamido) adenosine; a potent agonist of adenosine) into mouse epididymal fat pad. Thin, flexible sheets (d = 4 mm) prepared by simple casting exhibited sustained NECA release for up to 21 days, which effectively improved early islet engraftment with a median diabetic reversal time of 18.5 days. Western blotting revealed the facilitative effect of NECA on VEGF expression from islets in vitro and from grafts in vivo. In addition, NECA directly promoted the angiogenic activities of islet-derived endothelial cells by enhancing their proliferation and vessel-like tube formation. As a result, neovasculatures were effectively formed in the engrafted islet vicinity, as evidenced by vasculature imaging and immunofluorescence. Taken together, we suggest NECA-releasing PLGA sheets offer a safe and effective drug delivery system that enhances islet engraftment while reducing islet mass at extrahepatic sites for clinical relevance.
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Affiliation(s)
- Tiep Tien Nguyen
- College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Fakhrossadat Emami
- College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea
| | - Simmyung Yook
- College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea.
| | - Hanh Thuy Nguyen
- College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Tung Thanh Pham
- College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Shiva Pathak
- College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Shobha Regmi
- College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Jong Oh Kim
- College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Chul Soon Yong
- College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea
| | - Jae-Ryong Kim
- Department of Biochemistry and Molecular Biology and Smart-Aging Convergence Research Center, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea
| | - Jee-Heon Jeong
- College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea.
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Abstract
Introduction: Pancreas divisum is the most common congenital malformation of the pancreas with the majority asymptomatic. The etiological role, pathogenesis, clinical significance and management of pancreas divisum in pancreatic disease has not been clearly defined and our understanding is yet to be fully elucidated.Areas covered: This review describes the role of pancreas divisum in the development of pancreatic disease and the ambiguity related to it. In our attempt to offer clarity, a comprehensive search on PubMed, Ovid, Embase and Cochrane Library from inception to May 2019 was undertaken using key words "pancreas divisum", "idiopathic recurrent acute pancreatitis" and "chronic pancreatitis".Expert opinion: Current research fails to define a clear association between pancreas divisum and pancreatic disease. Though debatable, several studies do suggest a pathological role of pancreas divisum in pancreatic disease and a benefit of minor papilla therapy in the setting of acute recurrent pancreatitis. Surgical and endoscopic therapeutic modalities have not been directly compared. With the current data available, it would be imprudent to advise a definitive line of management for pancreatic disease associated with pancreas divisum and should involve a comprehensive discussion with the individual patient to define expectations before embarking on any medical and/or interventional therapy.
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Affiliation(s)
- Aditya Gutta
- Advanced Endoscopy Gastroenterology Fellow, Indiana University School of Medicine, Division of Gastroenterology, 550 N. University Blvd, Indianapolis, IN 46202
| | - Evan Fogel
- Professor of Medicine, Indiana University School of Medicine, Division of Gastroenterology, 550 N. University Blvd, Suite 1602, Indianapolis, IN 46202
| | - Stuart Sherman
- Professor of Medicine, Glen Lehman Professor in Gastroenterology, Indiana University School of Medicine, Division of Gastroenterology, 550 N. University Blvd, Suite 1634, Indianapolis, IN 46202
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Lara LF, Bellin MD, Ugbarugba E, Nathan JD, Witkowski P, Wijkstrom M, Steel JL, Smith KD, Singh VK, Schwarzenberg SJ, Pruett TL, Naziruddin B, Long-Simpson L, Kirchner VA, Gardner TB, Freeman ML, Dunn TB, Chinnakotla S, Beilman GJ, Adams DB, Morgan KA, Abu-El-Haija MA, Ahmad S, Posselt AM, Hughes MG, Conwell DL. A Study on the Effect of Patient Characteristics, Geographical Utilization, and Patient Outcomes for Total Pancreatectomy Alone and Total Pancreatectomy With Islet Autotransplantation in Patients With Pancreatitis in the United States. Pancreas 2019; 48:1204-1211. [PMID: 31593020 PMCID: PMC7952005 DOI: 10.1097/mpa.0000000000001405] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES A selective therapy for pancreatitis is total pancreatectomy and islet autotransplantation. Outcomes and geographical variability of patients who had total pancreatectomy (TP) alone or total pancreatectomy with islet autotransplantation (TPIAT) were assessed. METHODS Data were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample database. Weighed univariate and multivariate analyses were performed to determine the effect of measured variables on outcomes. RESULTS Between 2002 and 2013, there were 1006 TP and 825 TPIAT in patients with a diagnosis of chronic pancreatitis, and 1705 TP and 830 TPIAT for any diagnosis of pancreatitis. The majority of the TP and TPIAT were performed in larger urban hospitals. Costs were similar for TP and TPIAT for chronic pancreatitis but were lower for TPIAT compared with TP for any type of pancreatitis. The trend for TP and TPIAT was significant in all geographical areas during the study period. CONCLUSIONS There is an increasing trend of both TP and TPIAT. Certain groups are more likely to be offered TPIAT compared with TP alone. More data are needed to understand disparities and barriers to TPIAT, and long-term outcomes of TPIAT such as pain control and glucose intolerance need further study.
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Affiliation(s)
- Luis F. Lara
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Melena D. Bellin
- Division of Pediatric Endocrinology, University of Minnesota Medical School, Minneapolis, MN
| | - Emmanuel Ugbarugba
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Jaimie D. Nathan
- Department of Surgery, Cincinnati Children’s Hospital, Cincinnati, OH
| | | | - Martin Wijkstrom
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Jennifer L. Steel
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Kerrington D. Smith
- Division of Surgical Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - Vikesh K. Singh
- Division of Gastroenterology and Hepatology, Johns Hopkins Medical Center, Baltimore, MD
| | | | - Timothy L. Pruett
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Bashoo Naziruddin
- Islet Cell Laboratory, Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | | | - Varvara A. Kirchner
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Timothy B. Gardner
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - Martin L. Freeman
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical School, Minneapolis, MN
| | - Ty B. Dunn
- Division of Transplant Surgery, The University of Pennsylvania, Philadelphia, PA
| | - Srinath Chinnakotla
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - Gregory J. Beilman
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN
| | - David B. Adams
- Department of Surgery, Medical University of South Carolina, Charleston, SC
| | | | | | - Syed Ahmad
- Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - Andrew M. Posselt
- Department of Surgery, University of California-San Francisco, San Francisco, CA
| | | | - Darwin L. Conwell
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH
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McEachron KR, Skube ME, Yang Y, Hodges JS, Wilhelm J, Beilman G, Chinnakotla S, Schwarzenberg SJ, Bellin MD. Utility of arginine stimulation testing in preoperative assessment of children undergoing total pancreatectomy with islet autotransplantation. Clin Transplant 2019; 33:e13647. [PMID: 31230395 DOI: 10.1111/ctr.13647] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 06/14/2019] [Accepted: 06/19/2019] [Indexed: 12/18/2022]
Abstract
Metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT) are influenced by the islet mass transplanted. Preclinical and clinical studies indicate that insulin and C-peptide levels measured after intravenous administration of the beta cell secretagogue arginine can be used to estimate the available islet mass. We sought to determine if preoperative arginine stimulation test (AST) results predicted transplanted islet mass and metabolic outcomes in pediatric patients undergoing TPIAT. We evaluated the association of preoperative C-peptide and insulin responses to AST with islet isolation metrics using linear regression, and with postoperative insulin independence using logistic regression. Twenty-six TPIAT patients underwent preoperative AST from 2015 to 2018. The acute C-peptide response to arginine (ACRarg) was correlated with isolated islet equivalents (IEQ; r = 0.59, P = 0.002) and islet number (IPN; r = 0.48, P = 0.013). The acute insulin response to arginine (AIRarg) was not significantly correlated with IEQ (r = 0.38, P = 0.095) or IPN (r = 0.41, P = 0.071). Neither ACRarg nor AIRarg was associated with insulin use at 6 months postoperatively. Preoperative C-peptide response to arginine correlates with islet mass available for transplant in pediatric TPIAT patients. AST represents an additional tool before autotransplant to provide counseling on likely islet mass and to inform quality improvements of islet isolation techniques.
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Affiliation(s)
- Kendall R McEachron
- Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota
| | - Mariya E Skube
- Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota
| | - Yi Yang
- Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, Minnesota
| | - James S Hodges
- Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, Minnesota
| | - Joshua Wilhelm
- University of Minnesota Schulze Diabetes Institute, Minneapolis, Minnesota
| | - Gregory Beilman
- Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota
| | - Srinath Chinnakotla
- Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota.,Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota
| | - Sarah J Schwarzenberg
- Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota
| | - Melena D Bellin
- Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota.,Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota
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36
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Gurria JP, Boucher AA, Hornung L, Palumbo JS, Badia P, Luchtman-Jones L, Abu-El-Haija M, Lin TK, Nathan JD. Thrombopoietin Contributes to Extreme Thrombocytosis After Pediatric Pancreatectomy With Islet Autotransplantation. Pancreas 2019; 48:652-655. [PMID: 31091211 DOI: 10.1097/mpa.0000000000001313] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE This study aims to explore the role of thrombopoietin (TPO) production in extreme thrombocytosis that is often observed after pancreatectomy with islet autotransplantation (IAT) and the effectiveness of hydroxyurea in thrombocytosis management. METHODS Retrospective chart review was performed for all patients who underwent pancreatectomy with IAT at our institution between April 1, 2015, and December 31, 2016. Data evaluated included demographics, platelet counts, TPO levels, and thrombocytosis management strategies. RESULTS Twelve total and 1 subtotal pancreatectomy with IAT cases were reviewed. All operations included splenectomy. No major surgical or thrombotic complications occurred. Thrombopoietin levels, normal preoperatively, rose significantly (median, 219 pg/mL) soon after surgery, peaking on median postoperative day 3. Platelet counts, also normal preoperatively, increased within a week of surgery, with 92% over 1000 K/μL (median peak platelet count, 1403 K/μL). Platelet counts and TPO levels dropped after hydroxyurea initiation in most patients. CONCLUSIONS After pancreatectomy with IAT, patients experienced marked TPO rise and subsequent thrombocytosis, and both decreased significantly after hydroxyurea initiation. These data suggest that TPO elevation and associated increased platelet production may be one driver of early extreme post-total pancreatectomy with islet autotransplantation thrombocytosis, and this process may be modulated by hydroxyurea.
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Affiliation(s)
- Juan P Gurria
- From the Division of Pediatric General and Thoracic Surgery
| | | | - Lindsey Hornung
- Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital
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37
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Guda NM, Trikudanathan G, Freeman ML. Idiopathic recurrent acute pancreatitis. Lancet Gastroenterol Hepatol 2019; 3:720-728. [PMID: 30215363 DOI: 10.1016/s2468-1253(18)30211-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 06/15/2018] [Accepted: 06/15/2018] [Indexed: 12/19/2022]
Abstract
Idiopathic recurrent acute pancreatitis is clinically challenging and has substantial socioeconomic consequences. Investigations are expensive and often reveal little about the cause of the disease. Little is known about the interaction between genetic, environmental, anatomical, and other factors that contribute to the disease. Data on the efficacy, safety, and long-term outcomes of endoscopic therapies are scarce. The effect of idiopathic recurrent pancreatitis on quality of life is often underestimated. A more thorough examination of the causes of the disease and the roles of other associated risk factors is needed, as are well designed clinical studies with robust and objectively measurable outcomes. Ideally, evaluation of the causes of disease and therapy should be done only in specialised centres, should follow a protocol, and all outcomes should be formally assessed.
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Affiliation(s)
- Nalini M Guda
- School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA; Aurora Saint Luke's Medical Center, Milwaukee, WI, USA.
| | - Guru Trikudanathan
- Department of Gastroenterology, University of Minnesota, Minneapolis, MN, USA
| | - Martin L Freeman
- Division of Gastroenterology, Hepatology, and Nutrition, Advanced Endoscopy Fellowship, and Islet Autotransplantation, University of Minnesota, Minneapolis, MN, USA
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38
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Kwon CI, Cho JH, Choi SH, Ko KH, Tirkes T, Gromski MA, Lehman GA. Recent advances in the diagnosis and management of chronic pancreatitis. Korean J Intern Med 2019; 34:242-260. [PMID: 30840807 PMCID: PMC6406102 DOI: 10.3904/kjim.2019.051] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 02/13/2019] [Indexed: 02/06/2023] Open
Abstract
Chronic pancreatitis is a chronic condition characterized by pancreatic inflammation that causes fibrosis and the destruction of exocrine and endocrine tissues. Chronic pancreatitis is a progressive disease, and no physiological treatment is available to reverse its course. However, with advances in medical technology, the existing diagnostic and treatment methods for chronic pancreatitis are evolving. Managing patients with chronic pancreatitis is challenging and necessitates a multidisciplinary approach. In this review, we discuss the recent advances in the diagnosis and management of chronic pancreatitis and introduce future alternative modalities.
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Affiliation(s)
- Chang-Il Kwon
- Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Jae Hee Cho
- Division of Gastroenterology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Sung Hoon Choi
- Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Kwang Hyun Ko
- Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Temel Tirkes
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark A. Gromski
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Glen A. Lehman
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
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39
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Abstract
The selection of optimum surgical procedure from the range of reported operations for chronic pancreatitis (CP) can be difficult. The aim of this study is to explore geographical variation in reporting of elective surgery for CP. A systematic search of the literature was performed using the Scopus database for reports of five selected procedures for CP: duodenum-preserving pancreatic head resection, total pancreatectomy with islet autotransplantation (TPIAT), Frey pancreaticojejunostomy, thoracoscopic splanchnotomy and the Izbicki V-shaped resection. The keyword and MESH heading 'chronic pancreatitis' was used. Overall, 144 papers met inclusion criteria and were utilized for data extraction. There were 33 reports of duodenum-preserving pancreatic head resection. Twenty-one (64%) were from Germany. There were 60 reports of TPIAT, 53 (88%) from the USA. There are only two reports of TPIAT from outwith the USA and UK. The 34 reports of the Frey pancreaticojejunostomy originate from 12 countries. There were 20 reports of thoracoscopic splanchnotomy originating from nine countries. All three reports of the Izbicki 'V' procedure are from Germany. There is geographical variation in reporting of surgery for CP. There is a need for greater standardization in the selection and reporting of surgery for patients with painful CP.
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40
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Abstract
PURPOSE OF REVIEW Patients suffering from chronic pancreatitis often require surgical intervention to treat their disease. This review discusses surgical options as well as reviews current trends and research in the operative management of chronic pancreatitis. RECENT FINDINGS Relevant current topics in the field include the appropriate timing of surgery as well as the relative benefits of various procedures, particularly duodenum-preserving pancreatic head resection versus pancreaticoduodenectomy. Multiple studies have found that surgery earlier in the disease course results in improved outcomes. Furthermore, the recent literature reports similar outcomes of duodenum-preserving pancreatic head resection when compared with pancreaticoduodenectomy. SUMMARY It is important for treating clinicians to be well versed on the interplay of medical, endoscopic, and surgical strategies to carefully tailor a patient's treatment plan. Each patient warrants careful consideration and an individualized approach in collaboration with multidisciplinary colleagues.
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41
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Abstract
PURPOSE OF REVIEW We reviewed the current state of total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis and recurrent acute pancreatitis (RAP). RECENT FINDINGS An increasing number of centers in the United States and internationally are performing TPIAT. In selected cases, TPIAT may be performed partially or entirely laparoscopically. Islet isolation is usually performed at the same center as the total pancreatectomy surgery, but new data suggest that diabetes outcomes may be nearly as good when a remote center is used for islet isolation. Ongoing clinical research is focused on patient and disease factors that predict success or failure to respond to TPIAT. Causes of persistent abdominal pain after TPIAT may include gastrointestinal dysmotility and central sensitization to pain. Several clinical trials are underway with anti-inflammatory or other islet protective strategies to better protect islets at the time of infusion and thereby improve the diabetes results of the procedure. SUMMARY In summary, there is an increasing body of literature emerging from multiple centers highlighting the benefits and persistent challenges of TPIAT for chronic pancreatitis and RAP. Ongoing study will be critical to optimizing the success of this procedure.
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42
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Abstract
Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research.
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43
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Coté GA, Yadav D, Abberbock JA, Whitcomb DC, Sherman S, Sandhu BS, Anderson MA, Lewis MD, Alkaade S, Singh VK, Baillie J, Banks PA, Conwell D, Guda NM, Muniraj T, Tang G, Brand R, Gelrud A, Amann ST, Forsmark CE, Wilcox MC, Slivka A, Gardner TB. Recurrent Acute Pancreatitis Significantly Reduces Quality of Life Even in the Absence of Overt Chronic Pancreatitis. Am J Gastroenterol 2018; 113:906-912. [PMID: 29867178 PMCID: PMC6136830 DOI: 10.1038/s41395-018-0087-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Accepted: 03/13/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The impact of recurrent acute pancreatitis (RAP) on quality of life (QOL) is unknown. We hypothesized that RAP would reduce QOL even in the absence of chronic pancreatitis (CP). METHODS Data were pooled from three prospective, cross-sectional studies conducted across 27 U.S. centers (the North American Pancreatitis Studies); these included subjects with chronic pancreatitis (n = 1086), RAP alone (n = 508), and non-disease controls (n = 1025). QOL was measured using the Short Form 12 (SF-12), generating a Physical Component Summary (PCS) and the Mental Component Summary score (MCS). Multivariable regression models were developed to measure the effect of RAP on QOL, the predictors of lower QOL in those with RAP, and the differential effect QOL predictors between CP and RAP. RESULTS Compared to controls (51.0 ± 9.4), subjects with RAP (41.1 ± 11.4) and CP (37.2 ± 11.8) had lower PCS (p < 0.01). Subjects with CP had lower PCS compared to those with RAP (p < 0.01). Similarly, MCS was lower among RAP (44.6 ± 11.5) and CP (42.8 ± 12.2) subjects compared to controls (51.7 ± 9.1, p < 0.01). Subjects with CP had lower MCS compared to those with RAP (p < 0.01). After controlling for independent predictors of PCS, RAP was associated with lower PCS (estimate -8.46, p < 0.01) and MCS (estimate -6.45, p < 0.0001) compared to controls. The effect of endocrine insufficiency on PCS was differentially greater among RAP subjects (-1.28 for CP vs. -4.9 for RAP, p = 0.0184). CONCLUSIONS Even in the absence of CP, subjects with RAP have lower physical and mental QOL. This underscores the importance of identifying interventions to attenuate RAP before the development of overt CP.
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Affiliation(s)
- Gregory A Coté
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Dhiraj Yadav
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Judah A Abberbock
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - David C Whitcomb
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Stuart Sherman
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Bimaljit S Sandhu
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Michelle A Anderson
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Michele D Lewis
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Samer Alkaade
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Vikesh K Singh
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - John Baillie
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Peter A Banks
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Darwin Conwell
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Nalini M Guda
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Thiruvengadam Muniraj
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Gong Tang
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Randall Brand
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Andres Gelrud
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Stephen T Amann
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Christopher E Forsmark
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Mel C Wilcox
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Adam Slivka
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Timothy B Gardner
- Medical university of South Carolina, Charleston, SC, USA. University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Indiana university School of Medicine, Indianapolis, IN, USA. Richmond Gastroenterology Associates, Richmond, VA, USA. university of Michigan, Ann Arbor, MI, USA. Mayo Clinic, Jacksonville, FL, USA. Saint Louis university, St. Louis, MO, USA. Johns Hopkins Medical Institutions, Baltimore, MD, USA. Virginia Commonwealth university, Richmond, VA, USA. Brigham and Women's Hospital, Boston, MA, USA. Ohio State university, Columbus, OH, USA. Aurora St. Luke's Medical Center, Milwaukee, WI, USA. Yale School of Medicine, New Haven, CT, USA. University of Chicago, Chicago, IL, USA. Digestive Health Specialists, Tupelo, MS, USA. University of Florida, Gainesville, FL, USA. University of Alabama, Birmingham, AL, USA. Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
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Psychiatric Comorbidities in Patients Undergoing Total Pancreatectomy With Islet Cell Autotransplantation and Associated Mortality. Pancreas 2018; 47. [PMID: 29521946 PMCID: PMC9648619 DOI: 10.1097/mpa.0000000000001010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Total Pancreatectomy and Islet Autotransplant in the Treatment of Chronic Pancreatitis: Tread Very, Very Carefully. Am J Gastroenterol 2018; 113:322-323. [PMID: 29134966 DOI: 10.1038/ajg.2017.419] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Freeman AJ, Hofmekler T, Berauer JP, Palle S. Update in Pediatric Gastroenterology, Hepatology and Nutrition. UPDATE IN PEDIATRICS 2018:267-311. [DOI: 10.1007/978-3-319-58027-2_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Total Pancreatectomy With Islet Autotransplantation for Acute Recurrent and Chronic Pancreatitis. ACTA ACUST UNITED AC 2017; 15:548-561. [PMID: 28895017 DOI: 10.1007/s11938-017-0148-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW The first total pancreatectomy and islet autotransplantation (TP-IAT) was performed for chronic pancreatitis in 1977 with the goal to ameliorate the pain and simultaneously preserve islet function. We reviewed the recent medical literature regarding indications, patient suitability, current outcomes, and challenges in TP-IAT. RECENT FINDINGS Current indications for TP-IAT include intractable pain secondary to chronic pancreatitis (CP) or acute recurrent pancreatitis (ARP) with failed medical and endoscopic/surgical management. Independent studies have shown that TP-IAT is associated with elimination or significant improvement in pain control and partial or full islet graft function in the majority of patients. In single-center cost analyses, TP-IAT has been suggested to be more cost-effective than medical management of chronic pancreatitis. While initially introduced as a surgical option for adults with long-standing chronic pancreatitis, TP-IAT is now often utilized in children with chronic pancreatitis and in children and adults with intractable acute recurrent pancreatitis. The surgical procedure has evolved over time with some centers offering minimally invasive operative options, although the open approach remains the standard. Despite many advances in TP-IAT, there is a need for further research and development in disease diagnosis, patient selection, optimization of surgical technique, islet isolation and quality assessment, postoperative patient management, and establishment of uniform metrics for data collection and multicenter studies. TP-IAT is an option for patients with otherwise intractable acute recurrent or chronic pancreatitis which presents potential for pain relief and improved quality of life, often with partial or complete diabetes remission.
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Faghih M, Gonzalez FG, Makary MA, Singh VK. Total pancreatectomy for recurrent acute and chronic pancreatitis: a critical review of patient selection criteria. Curr Opin Gastroenterol 2017; 33:330-338. [PMID: 28700371 PMCID: PMC5881167 DOI: 10.1097/mog.0000000000000390] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW Critical review of the indications for total pancreatectomy and highlight limitations in current diagnostic criteria for chronic pancreatitis. RECENT FINDINGS The diagnosis of noncalcific chronic pancreatitis remains controversial because of an overreliance on nonspecific imaging and laboratories findings. Endoscopic ultrasound, s-magnetic resonance cholangiopancreatography, and/or endoscopic pancreatic function testing are often used to diagnose noncalcific chronic pancreatitis despite the fact that there is no gold standard for this condition. Abdominal pain is not specific for chronic pancreatitis and is more likely to be encountered in patients with functional gastrointestinal disorders based on the high incidence of these conditions. The duration of pain and opioid analgesic use results in central sensitization that adversely affects pain outcomes after total pancreatectomy. An alcoholic cause is associated with poorer pain outcomes after total pancreatectomy. SUMMARY The lack of a gold standard for noncalcific chronic pancreatitis limits the diagnostic accuracy of imaging and laboratory tests. The pain of chronic pancreatitis is nonspecific and is affected by duration, preoperative opioid use, and cause. These factors will need to be considered in the development of future selection criteria for this morbid surgery.
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Affiliation(s)
- Mahya Faghih
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | | | - Martin A. Makary
- Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Vikesh K. Singh
- Pancreatitis Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
- Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
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Abstract
PURPOSE OF REVIEW Summarize key clinical advances in chronic pancreatitis reported in 2016. RECENT FINDINGS Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. SUMMARY Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.
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