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Wang H, Gou W, Nietert PJ, Hirsch J, Wang J, Allawi A, Mortadha AS, Cook K, Overstreet M, Wei H, Adams D, Lancaster WP, Morgan KA, Strange C. Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study. Cell Transplant 2024; 33:9636897241243014. [PMID: 38659255 PMCID: PMC11044796 DOI: 10.1177/09636897241243014] [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] [Received: 11/22/2023] [Revised: 02/28/2024] [Accepted: 03/04/2024] [Indexed: 04/26/2024] Open
Abstract
Stress-induced islet graft loss during the peri-transplantation period reduces the efficacy of islet transplantation. In this prospective, randomized, double-blind clinical trial, we evaluated the safety and efficacy of 60 mg/kg human alpha-1 antitrypsin (AAT) or placebo infusion weekly for four doses beginning before surgery in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT). Subjects were followed for 12 months post-TP-IAT. The dose of AAT was safe, as there was no difference in the types and severity of adverse events in participants from both groups. There were some biochemical signals of treatment effect with a higher oxygen consumption rate in AAT islets before transplantation and a lower serum C-peptide (an indicator of islet death) in the AAT group at 15 min after islet infusion. Findings per the statistical analysis plan using a modified intention to treat analysis showed no difference in the C-peptide area under the curve (AUC) following a mixed meal tolerance test at 12 months post-TP-IAT. There was no difference in the secondary and exploratory outcomes. Although AAT therapy did not show improvement in C-peptide AUC in this study, AAT therapy is safe in CP patients and there are experiences gained on optimal clinical trial design in this challenging disease.
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Affiliation(s)
- Hongjun Wang
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
- Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA
| | - Wenyu Gou
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Paul J. Nietert
- Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA
| | - Jason Hirsch
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Jingjing Wang
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Ahmed Allawi
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Abd S. Mortadha
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Kelsey Cook
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Morgan Overstreet
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Hua Wei
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - David Adams
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - William P. Lancaster
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Katherine A. Morgan
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Charlie Strange
- Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
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Hong S, Ren J, Zhang S, Yan Y, Liu S, Qi F. Comparison of clinical outcomes and prognosis between total pancreatectomy and pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. ANZ J Surg 2023; 93:2820-2827. [PMID: 37614050 DOI: 10.1111/ans.18653] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/16/2023] [Accepted: 07/26/2023] [Indexed: 08/25/2023]
Abstract
BACKGROUND To compare the clinical outcomes and prognosis of total pancreatectomy (TP) and pancreaticoduodenectomy (PD) for the treatment of pancreatic ductal adenocarcinoma (PDAC), and to explore the safety and indications of TP. METHODS A systematic search was conducted on PubMed, Web of Science, and Embase databases from January 1943 to March 2023 for literatures comparing TP and PD in the treatment of PDAC. The primary outcome was postoperative overall survival (OS), and secondary outcomes included surgery time, blood loss, readmission, hospital stay, perioperative mortality, and overall morbidity. Fixed-effect or random-effect models were selected based on heterogeneity, and odds ratio (OR), mean difference (MD), or hazard ratio (HR) with 95% confidence intervals (CI) were calculated. RESULTS A total of six studies involving 8396 patients were included in the meta-analysis. There was no statistically significant difference in OS after surgery between the two groups (HR = 1.08, 95% CI: 0.91-1.27; P = 0.38). The TP group had a longer surgery time (MD = 13.66, 95% CI: 4.57-22.75; P = 0.003) and more blood loss (MD = 133.17, 95% CI: 8.00-258.33; P = 0.04) than the PD group. There were no significant differences between the two groups in terms of hospital stay (MD = 0.09, 95% CI: -2.04 to 2.22; P = 0.93), readmission rate (OR = 1.39; 95% CI: 1.00-1.92; P = 0.05), perioperative mortality (OR = 1.29, 95% CI: 0.98-1.69; P = 0.07), and overall morbidity (OR = 0.80, 95% CI: 0.50-1.26; P = 0.33). CONCLUSION The surgical process of TP is relatively complex, but there is no difference in short-term clinical outcomes and OS compared to PD, making it a safe and reliable procedure. Indications and treatment outcomes for planned TP and salvage TP may differ, and more research is needed in the future for further classification and verification.
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Affiliation(s)
- Shengqian Hong
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China
| | - Jiao Ren
- Department of Radiology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China
| | - Sufang Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China
| | - Yulou Yan
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China
| | - Shiqi Liu
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China
| | - Fuzhen Qi
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, China
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Coluzzi M, Naziruddin B, Kumano K, Saracino G, Testa G, Beecherl E, Onaca N. Spleen-preserving total pancreatectomy and islet autotransplantation with complete preservation of the splenic arterial and venous supply does not impact islet yield and function. Am J Surg 2022; 224:1295-1300. [PMID: 35781373 DOI: 10.1016/j.amjsurg.2022.06.013] [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: 03/24/2022] [Revised: 06/10/2022] [Accepted: 06/20/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND Standard total pancreatectomy and islet autotransplantation (TPIAT) for chronic pancreatitis includes splenectomy, but TPIAT can be performed without splenectomy by full preservation of the blood supply to the spleen. METHODS We compared the metabolic and clinical outcomes of patients who underwent TPIAT at our center between 2015 and 2021 with or without splenectomy. A total of 89 patients were included in the study, and 17 of them underwent spleen-preserving total pancreatectomy (SPTP). RESULTS The two study groups had similar demographic and metabolic parameters. Short-term morbidity and long-term outcomes were similar. The operative time was significantly shorter with splenectomy: a median of 9.91 h (interquartile range [IQR] 8.89-10.83) compared to 10.78 h (IQR 10.2-11.6) for SPTP (P = 0.021). There was no difference between the groups in postoperative morbidity. Metabolic outcomes at 1 year were better in the SPTP group compared to the splenectomy group, with a median daily insulin requirement of 7 units (IQR 4-12) vs 15 units (IQR 7-26; P = 0.049) and a median C-peptide at 1 year of 0.65 (IQR 0.40-1.26) vs 1.00 (IQR 0.80-1.90; P = 0.63). The reduction in morphine milligram equivalents per day over time was significantly better in the SPTP group (P < 0.001), as was the decrease in pain score (P < 0.001). CONCLUSION TPIAT with full arterial and venous preservation of the spleen had no adverse impact on islet yield or function. TPIAT can be safely and effectively performed with preservation of the spleen and the entire splenic artery and vein. The spleen should be preserved when feasible in every TPIAT surgery.
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Affiliation(s)
- Mariagrazia Coluzzi
- Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA; Unit of General and Emergency Surgery, Azienda Ospedaliera Regionale San Carlo, Potenza, Italy
| | - Bashoo Naziruddin
- Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA.
| | - Kenjiro Kumano
- Baylor Scott and White Research Institute, Dallas, TX, USA
| | - Giovanna Saracino
- Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA
| | - Giuliano Testa
- Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA
| | - Ernest Beecherl
- Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA
| | - Nicholas Onaca
- Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA; LifeGift, Fort Worth, TX, USA
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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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Van Simaeys D, De La Fuente A, Zilio S, Zoso A, Kuznetsova V, Alcazar O, Buchwald P, Grilli A, Caroli J, Bicciato S, Serafini P. RNA aptamers specific for transmembrane p24 trafficking protein 6 and Clusterin for the targeted delivery of imaging reagents and RNA therapeutics to human β cells. Nat Commun 2022; 13:1815. [PMID: 35383192 PMCID: PMC8983715 DOI: 10.1038/s41467-022-29377-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 03/08/2022] [Indexed: 12/20/2022] Open
Abstract
The ability to detect and target β cells in vivo can substantially refine how diabetes is studied and treated. However, the lack of specific probes still hampers a precise characterization of human β cell mass and the delivery of therapeutics in clinical settings. Here, we report the identification of two RNA aptamers that specifically and selectively recognize mouse and human β cells. The putative targets of the two aptamers are transmembrane p24 trafficking protein 6 (TMED6) and clusterin (CLUS). When given systemically in immune deficient mice, these aptamers recognize the human islet graft producing a fluorescent signal proportional to the number of human islets transplanted. These aptamers cross-react with endogenous mouse β cells and allow monitoring the rejection of mouse islet allografts. Finally, once conjugated to saRNA specific for X-linked inhibitor of apoptosis (XIAP), they can efficiently transfect non-dissociated human islets, prevent early graft loss, and improve the efficacy of human islet transplantation in immunodeficient in mice.
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Affiliation(s)
- Dimitri Van Simaeys
- Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Adriana De La Fuente
- Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Serena Zilio
- Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Alessia Zoso
- Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Victoria Kuznetsova
- Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Oscar Alcazar
- Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Peter Buchwald
- Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Andrea Grilli
- Center for Genome Research, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Jimmy Caroli
- Center for Genome Research, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Silvio Bicciato
- Center for Genome Research, Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Paolo Serafini
- Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA. .,Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, USA. .,Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
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Parajuli KR, Zhang Y, Cao AM, Wang H, Fonseca VA, Wu H. Pax4 Gene Delivery Improves Islet Transplantation Efficacy by Promoting β Cell Survival and α-to-β Cell Transdifferentiation. Cell Transplant 2021; 29:963689720958655. [PMID: 33086892 PMCID: PMC7784573 DOI: 10.1177/0963689720958655] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The transcription factor Pax4 plays an essential role in the development of insulin-producing β cells in pancreatic islets. Ectopic Pax4 expression not only promotes β cell survival but also induces α-to-β cell transdifferentiation. This dual functionality of Pax4 makes it an appealing therapeutic target for the treatment of insulin-deficient type 1 diabetes (T1D). In this study, we demonstrated that Pax4 gene delivery by an adenoviral vector, Ad5.Pax4, improved β cell function of mouse and human islets by promoting islet cell survival and α-to-β cell transdifferentiation, as assessed by multiple viability assays and lineage-tracing analysis. We then explored the therapeutic benefits of Pax4 gene delivery in the context of islet transplantation using T1D mouse models. Both mouse-to-mouse and human-to-mouse islet transplantation, via either kidney capsule or portal vein, were examined. In all settings, Ad5.Pax4-treated donor islets (mouse or human) showed substantially better therapeutic outcomes. These results suggest that Pax4 gene delivery into donor islets may be considered as an adjunct therapy for islet transplantation, which can either improve the therapeutic outcome of islet transplantation using the same amount of donor islets or allow the use of fewer donor islets to achieve normoglycemia.
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Affiliation(s)
- Keshab R Parajuli
- Section of Endocrinology, Department of Medicine, Tulane University Health Science Center, New Orleans, LA, USA
| | - Yanqing Zhang
- Section of Endocrinology, Department of Medicine, Tulane University Health Science Center, New Orleans, LA, USA
| | - Alexander M Cao
- Section of Endocrinology, Department of Medicine, Tulane University Health Science Center, New Orleans, LA, USA
| | - Hongjun Wang
- Department of Surgery, Medical University of South Carolina, Charleston, SC, USA
| | - Vivian A Fonseca
- Section of Endocrinology, Department of Medicine, Tulane University Health Science Center, New Orleans, LA, USA
| | - Hongju Wu
- Section of Endocrinology, Department of Medicine, Tulane University Health Science Center, New Orleans, LA, USA
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Shah I, Sheth SG, Kothari DJ. Pain management in chronic pancreatitis incorporating safe opioid practices: Challenge accepted. World J Gastroenterol 2021; 27:3142-3147. [PMID: 34163102 PMCID: PMC8218357 DOI: 10.3748/wjg.v27.i23.3142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/15/2021] [Accepted: 05/21/2021] [Indexed: 02/06/2023] Open
Abstract
Patients with chronic pancreatitis often experience severe, unrelenting abdominal pain, which can significantly impact their quality of life. Pain control, therefore, remains central to the overall management of chronic pancreatitis. Most of the strategies aimed at treating the pain of chronic pancreatitis are based on expert opinion and vary from one institution to another, as there are no uniform guidelines to direct a stepwise approach towards achieving this goal. In this editorial, we comment on best practice strategies targeted towards pain control in chronic pancreatitis, specifically highlighting the use of opioid medications in this patient population. We discuss various safe and efficacious prescription monitoring practices in this article.
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Affiliation(s)
- Ishani Shah
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Sunil G Sheth
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Darshan J Kothari
- Department of Gastroenterology, Duke University Medical Center, Durham, NC 27710, United States
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Atypical Hepatic Steatosis Patterns on MRI After Total Pancreatectomy With Islet Autotransplant. AJR Am J Roentgenol 2021; 217:100-106. [PMID: 33909467 DOI: 10.2214/ajr.20.23303] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE. The purpose of this retrospective study was to investigate the prevalence and patterns of hepatic steatosis after total pancreatectomy with islet autotransplant (TPIAT) and to determine if the unique patterns of steatosis seen in this study correlated with islet graft function. MATERIALS AND METHODS. Fifty-two subjects who had undergone MRI after TPIAT were reviewed for the presence of hepatic steatosis. Patterns of steatosis were categorized into three groups: normal (no steatosis), homogeneous, and atypical. Demographics and outcomes were compared between the groups. Islet graft function 1 year after surgery was classified as full graft function, partial graft function, and graft failure. Statistical analysis was performed using ANOVA, Kruskal-Wallis, and Fisher exact tests. RESULTS. Sixty-three percent of patients had steatosis present on MRI after TPIAT (33 subjects of 52 total), and 48% (25/52) exhibited an atypical pattern. Twenty-four percent of the 37 patients who had MRI examinations before TPIAT showed steatosis preoperatively, yet none of these showed an atypical steatosis pattern. Islet graft function was not statistically different between the groups. The only statistically significant variable difference between the groups was body mass index (p = .02). CONCLUSION. Steatosis is a common finding after TPIAT, and atypical steatosis patterns frequently develop after the procedure, implying that the procedure itself is the causal factor. There was no correlation between islet graft function and the presence or pattern of steatosis. An atypical pattern of hepatic steatosis can therefore be considered an incidental finding after TPIAT and does not require additional workup or treatment.
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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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10
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Factors Associated With Morbidity Following Total Pancreatectomy and Islet Autotransplantation: A NSQIP Analysis. Transplant Proc 2021; 53:705-711. [PMID: 33563474 DOI: 10.1016/j.transproceed.2020.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/28/2020] [Accepted: 11/23/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND Total pancreatectomy with islet autotransplantation is a therapeutic surgical option for patients with chronic pancreatitis leading to significant reduction in pain, improvement in quality of life, and potential for preservation of partial to full endocrine function. Data on the factors associated with short-term morbidities are limited. METHODS We queried the American College of Surgeons National Surgery Quality Improvement Project for patients undergoing total pancreatectomy with islet autotransplantation from 2005 to 2015. We determined 30-day morbidity and mortality and performed univariate and multivariate analysis to determine the preoperative and intraoperative factors associated with development of postoperative infectious complications. RESULTS The rate of 30-day postoperative morbidity in 384 patients undergoing total pancreatectomy with islet autotransplantation was 36% with an overall mortality of 1%. Postoperative infectious complications developed in 29% of patients and were associated with increased operative time (P = .016),and higher postoperative wound class (P = .045). After risk adjustment, only increased operative time was independently associated with increased rates of infectious complications (OR=1.1, 95% CI = 1.01-1.13, P = .02). CONCLUSIONS Total operative time is independently associated with increased postoperative infectious complications in total pancreatectomy with islet autotransplantation. Future interventions aimed at optimizing islet isolation, surgical approach, and refinement of patient selection criteria present opportunities for reducing operative time and potentially reducing the morbidity of this surgical procedure.
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11
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Williams GM. Robot-Assisted Total Pancreatectomy With Autologous Islet Cell Transplantation: Perioperative Nursing Considerations. AORN J 2020; 112:353-365. [PMID: 32990974 DOI: 10.1002/aorn.13180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Chronic pancreatitis (CP) is an inflammatory disease of the pancreas that causes pain and gastrointestinal problems in patients. Robot-assisted total pancreatectomy with autologous islet cell transplantation (TPAIT) is a surgical procedure for treating patients with CP that has been unresponsive to other treatments. After performing a total pancreatectomy, the surgical team isolates islet cells and then infuses them into the patient's liver. To provide the best possible care for patients undergoing TPAIT, perioperative nurses should understand the physiological functions of the pancreas, the etiology of and treatment options for CP, and their role in coordinating care for this patient population. This article discusses the disease process for CP, reasons for choosing the robotic approach to TPAIT, preparation of the OR for the procedure, the role of the RN circulator during a robot-assisted TPAIT, and nursing management of the patient during the postoperative phase of care.
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12
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Ali KF, Hatipoglu B. Pancreatic Islet Cell Transplantation: Graft Stability and Metabolic Outcomes. OBM TRANSPLANTATION 2020; 4:1-9. [PMID: 32775966 PMCID: PMC7409867 DOI: 10.21926/obm.transplant.2003115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Pancreatic islet transplantation is a rapidly evolving field. It has been increasingly regarded as a promising approach for the correction of dysglycemia associated with type 1 diabetes mellitus (allogenic islet transplantation), or the prevention of surgical diabetes in chronic pancreatitis subjects undergoing total pancreatectomy (autologous islet transplantation). In this review, we discuss the latest literature pertaining to metabolic outcomes of autologous and allogenic islet transplantation, shedding close light on our own latest experience in the autologous islet transplantation setting.
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Affiliation(s)
- Khawla F Ali
- Department of Medicine, Royal College of Surgeons in Ireland-Medical University of Bahrain, Bahrain
| | - Betul Hatipoglu
- Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA
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13
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Siegel M, Barlowe T, Smith KD, Chaidarun SS, LaBarre N, Joseph Elmunzer B, Morgan KA, Gardner TB. Islet autotransplantation improves glycemic control in patients undergoing elective distal pancreatectomy for benign inflammatory disease. Clin Transplant 2020; 34:e13891. [PMID: 32356311 DOI: 10.1111/ctr.13891] [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: 01/30/2020] [Revised: 04/07/2020] [Accepted: 04/28/2020] [Indexed: 11/27/2022]
Abstract
Islet autotransplantation (IAT) is increasingly being performed to mitigate against the diabetic complications of pancreatic resection in patients with benign inflammatory pancreatic disorders; however, the glycemic benefit of IAT in patients undergoing partial pancreatic resection is not known. We aimed to determine whether IAT improved glycemic outcomes in patients undergoing distal pancreatectomy for benign inflammatory disease. We performed a multicenter, retrospective case-control study of patients who underwent distal pancreatic resection with IAT at two U S tertiary care centers. The primary outcome was the mean change in pre- vs post-operative HgA1c following transplant as well as the development of new post-operative diabetes. Nine patients requiring distal pancreatectomy for benign disease underwent IAT and were compared to 13 historical controls without IAT. Baseline characteristics were similar between groups. With a median follow-up of 22 months, those who received an IAT had a smaller increase in their pre- vs post-operative HgA1c (0.42 vs 2.83, P = .004), and one case patient (14.3%) vs three control patients (23.1%) developed new post-operative diabetes (P = .581). We conclude that patients undergoing distal pancreatic resection for benign inflammatory disease should be considered for IAT, as long-term glycemic outcomes appear to be improved in those undergoing transplant.
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Affiliation(s)
- Matthew Siegel
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Trevor Barlowe
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Kerrington D Smith
- Section of General Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Sushela S Chaidarun
- Section of Endocrinology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Nicolas LaBarre
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Badih Joseph Elmunzer
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Katherine A Morgan
- Division of Gastrointestinal and Laparoscopic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Timothy B Gardner
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
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14
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Yang BC, Wu SY, Leung PS. Alcohol ingestion induces pancreatic islet dysfunction and apoptosis via mediation of FGF21 resistance. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:310. [PMID: 32355754 PMCID: PMC7186649 DOI: 10.21037/atm.2020.02.129] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Background Disruption of β-cell insulin secretion and viability caused by excessive ethanol consumption increases type 2 diabetes mellitus (T2DM) pathogenesis risk. Fibroblast growth factor 21 (FGF21) plays a significant role in regulating lipid and glucose homeostasis. Recently, FGF21, best known for its role in lipid and glucose homeostasis regulation, and its obligate co-receptor β-klotho have been shown to inhibit ethanol ingestion and metabolism. It remains unclear whether heavy ethanol intake modulates islet FGF21 expression and function. This study investigated the relationship between ethanol exposure, FGF21, and islet function in vivo/ex vivo islet and in vitro cell models. Methods Mice were gavaged with 3.5 g/kg ethanol or saline for 1–3 weeks (long-term exposure). Human MIN6 cells and isolated islets were cultured and treated with 80 mM ethanol for 24 h (short-term exposure) to mimic excessive ethanol consumption. We applied the oral glucose tolerance test (OGTT), blood glucometry, enzyme-linked immunosorbent assay (ELISAs) for insulin and FGF21, glucose stimulated insulin secretion (GSIS) testing, reverse-transcription (RT)-polymerase chain reaction (PCR), and western blot experiments. Results Long-term ethanol treatment induced FGF21 resistance in mouse pancreatic islets. Moreover, ethanol exposure damaged insulin secretory ability and glucose homeostasis. In vitro and ex vivo experiments showed that short-term ethanol treatment upregulated the expression of FGF21 signaling pathway-related genes and proteins, without affecting β-cell survival or function. Conclusions Long-term ethanol consumption induces FGF21 resistance-mediated pancreatic β-cell dysfunction, and thus diabetes pathogenesis risk.
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Affiliation(s)
- Bao Chen Yang
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Shang Ying Wu
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Po Sing Leung
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
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15
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Shahbazov R, Naziruddin B, Salam O, Saracino G, Levy MF, Beecherl E, Onaca N. The impact of surgical complications on the outcome of total pancreatectomy with islet autotransplantation. Am J Surg 2020; 219:99-105. [DOI: 10.1016/j.amjsurg.2019.04.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 04/04/2019] [Accepted: 04/08/2019] [Indexed: 02/07/2023]
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Verma N, Rajab A, Buss J, Lara L, Porter K, Hart P, Conwell D, Washburn WK, Black S, Kuntz K, Meng S. Immediate Postoperative Insulin Requirements May Predict Metabolic Outcome after Total Pancreatectomy and Islet Autotransplantation. J Diabetes Res 2020; 2020:9282310. [PMID: 33426086 PMCID: PMC7772034 DOI: 10.1155/2020/9282310] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 12/10/2020] [Indexed: 11/17/2022] Open
Abstract
Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.
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Affiliation(s)
- Neha Verma
- The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210
- Essen Medical Associates, Bronx, New York, NY, USA 10452
| | - Amer Rajab
- The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210
| | - Jill Buss
- The Ohio State University, Columbus, OH, USA 43210
| | - Luis Lara
- The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210
| | - Kyle Porter
- The Ohio State University, Columbus, OH, USA 43210
| | - Philip Hart
- The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210
| | - Darwin Conwell
- The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210
| | | | - Sylvester Black
- The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210
| | - Kristin Kuntz
- The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210
| | - Shumei Meng
- The Ohio State University Wexner Medical Center, Columbus, OH, USA 43210
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17
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Abstract
OBJECTIVES Autologous islet transplantation (AIT) is performed to preserve insulin secretory function in chronic pancreatitis patients undergoing total pancreatectomy (TP). No data exist on the effect of time lapse on beta cell function post TP-AIT. We aimed to investigate the factor of time lapse on beta cell function following TP-AIT. METHODS Retrospectively, we identified 31 adult patients with chronic pancreatitis who underwent TP-AIT between 2008 and 2016. Changes in beta cell function were assessed using (1) BETA-2 scores and (2) analysis of posttransplant mixed-meal tolerance testing. RESULTS Significant decrease in functional beta cell capacity expressed by BETA-2 scores was seen in the first 2 years following TP-AIT, with an annual decrease of 6.3 points in median BETA-2 score (interquartile range, 4.6-11.6; P = 0.002). In the mixed-meal tolerance testing analysis, nonsignificant trends toward higher glucose, lower insulin, and lower C-peptide were seen with time lapse. Additionally, higher hemoglobin A1c values (P = 0.033) and higher insulin requirements (P = 0.04) were seen with longer follow-up after AIT. CONCLUSIONS A steady drop in functional beta cell capacity was observed in the 2 years following TP and AIT. To our knowledge, to date this is the first report of the BETA-2 score applicability in the AIT setting.
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18
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Retrospective Evaluation of the Perioperative Management of Patients Undergoing Total Pancreatectomy With Islet Autotransplantation: Single Institution Review. Pancreas 2019; 48:228-232. [PMID: 30629028 PMCID: PMC7179733 DOI: 10.1097/mpa.0000000000001236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVE The aim of this retrospective descriptive study was to examine associations with the perioperative management of patients undergoing total pancreatectomy with islet autotransplantation, which may impact complication rate and hospital length of stay. METHODS We retrospectively collected data on 165 patients, and 161 patients were included in the final analysis. Data collected included preoperative, intraoperative, and postoperative patient and procedural characteristics. RESULTS Approximately 46.6% of patients experienced 1 or more complications. The occurrence of complications was associated with postoperative day 1 hemoglobin levels, use of intraoperative goal-directed therapy, estimated intraoperative blood loss, and total amount of intraoperative insulin given. Hospital length of stay was significantly associated with number of complications, use of goal-directed therapy, procedure duration, and postoperative day 1 hemoglobin levels. CONCLUSIONS Overall, our retrospective descriptive study adds to the emerging body of literature determining optimal perioperative management of patients undergoing total pancreatectomy with islet autotransplantation.
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19
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Farina M, Alexander JF, Thekkedath U, Ferrari M, Grattoni A. Cell encapsulation: Overcoming barriers in cell transplantation in diabetes and beyond. Adv Drug Deliv Rev 2019; 139:92-115. [PMID: 29719210 DOI: 10.1016/j.addr.2018.04.018] [Citation(s) in RCA: 129] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/19/2018] [Accepted: 04/25/2018] [Indexed: 02/07/2023]
Abstract
Cell-based therapy is emerging as a promising strategy for treating a wide range of human diseases, such as diabetes, blood disorders, acute liver failure, spinal cord injury, and several types of cancer. Pancreatic islets, blood cells, hepatocytes, and stem cells are among the many cell types currently used for this strategy. The encapsulation of these "therapeutic" cells is under intense investigation to not only prevent immune rejection but also provide a controlled and supportive environment so they can function effectively. Some of the advanced encapsulation systems provide active agents to the cells and enable a complete retrieval of the graft in the case of an adverse body reaction. Here, we review various encapsulation strategies developed in academic and industrial settings, including the state-of-the-art technologies in advanced preclinical phases as well as those undergoing clinical trials, and assess their advantages and challenges. We also emphasize the importance of stimulus-responsive encapsulated cell systems that provide a "smart and live" therapeutic delivery to overcome barriers in cell transplantation as well as their use in patients.
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Abstract
First described in the early 1980s, total pancreatectomy with autologous islet cell transplantation for the treatment of chronic pancreatitis is still only offered in select centers worldwide. Indications, process details including surgery as well as islet isolation, and results are reviewed. In addition, areas for further research to optimize results are identified.
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Affiliation(s)
- Beth Schrope
- Department of Surgery, Columbia University College of Physicians and Surgeons, 161 Fort Washington Avenue, 8th Floor, New York, NY 10032, USA.
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21
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Ahn CH, Jang JY, Lee SO, Yoon JW, Kim SW, Park KS, Jung HS. Liver transaminase levels after intraportal autologous islet transplantation after partial pancreatectomy were associated with long-term metabolic outcomes. Diabetes Res Clin Pract 2018; 143:232-238. [PMID: 30036613 DOI: 10.1016/j.diabres.2018.07.019] [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: 03/09/2018] [Revised: 06/21/2018] [Accepted: 07/17/2018] [Indexed: 11/28/2022]
Abstract
AIMS To investigate the changes of post-procedural liver transaminase levels after autologous islet transplantation (ITx), and their associations with glycemic outcomes. METHODS Non-diabetic patients who underwent distal pancreatectomy for benign tumors were enrolled. Islets isolated from the healthy part of the resected pancreas were transplanted via the portal vein. Metabolic parameters were evaluated in the subjects for 5 years. RESULTS Eight patients completed the study and four developed postoperative diabetes mellitus (PODM). Disposition index (DI) at postoperative 1 year showed prominent difference between the patients who develop PODM or not: DI was preserved in the PODM-free patients (49.7 ± 4.5 to 70.8 ± 14.4, P = 0.182), while it significantly decreased in the PODM patients (69.3 ± 9.9 to 28.5 ± 3.9, P = 0.019). The preoperative liver transaminase levels were not different between the two groups. However, transient increase in liver transaminase levels during the first week after ITx was observed only in the PODM patients, and their peak values demonstrated significant negative correlation with the changes in DI (r = -0.774 for alanine transaminase, r = -0.759 for aspartate transaminase; P < 0.05). CONCLUSIONS Elevation of serum transaminases after ITx could be one of the factors determining insulin secretion and PODM.
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Affiliation(s)
- Chang Ho Ahn
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seong Ok Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ji Won Yoon
- Department of Internal Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sun-Whe Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyong Soo Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hye Seung Jung
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea.
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22
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Patient and Procedural Factors Associated With Increased Islet Cell Yield in Total Pancreatectomy With Islet Autotransplantation. Pancreas 2018; 47:985-989. [PMID: 30044306 DOI: 10.1097/mpa.0000000000001116] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVES Total pancreatectomy with islet autotransplantation (TPIAT) offers symptom relief to highly selected patients with recurrent acute and/or chronic pancreatitis. However, with variable clinical response, it is important to refine islet manipulation technique and patient selection criteria. This study explores the variables associated with high islet cell yield, a driver of success in TPIAT. METHODS This study evaluated patients who underwent TPIAT at Dartmouth-Hitchcock Medical Center from 2012 to 2016. Odds ratios were calculated for various patient and procedural characteristics. The primary clinical outcome was the number of isolated islet equivalents per kilogram body weight. RESULTS Thirty-eight patients met inclusion criteria. Patients with no computed tomography or magnetic resonance imaging evidence of chronic pancreatitis, without pancreatic duct stones, and without parenchymal stones were associated with higher odds of success (P = 0.02, P = 0.02, and P = 0.002, respectively). Patients with preoperative glycated hemoglobin greater than 5.6, with islet cell suspensions positive for cultures, and with positive gram stains were associated with lower odds of success (P = 0.02, P = 0.01, and P = 0.02, respectively). CONCLUSIONS Factors that diminish a successful islet cell harvest during TPIAT include the presence of infected islets, an elevated preoperative glycated hemoglobin, and the presence of pancreatic duct stones.
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23
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Ali KF, San Martin VT, Stevens T, Walsh RM, Bottino R, Trucco M, Hatipoglu B. Autoimmunity in Autologous Islet Transplantation. ACTA ACUST UNITED AC 2018; 2. [PMID: 32095782 PMCID: PMC7039533 DOI: 10.21926/obm.transplant.1803014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Total pancreatectomy (TP) is increasingly being utilized for definitive treatment in patients with debilitating chronic pancreatitis (CP). In an effort to prevent surgical diabetes, the procedure can be performed in conjunction with transplantation of islets of Langerhans recovered from the patients’ own resected pancreas (autologous islet transplantation, AIT). Given that patients undergoing TP and AIT are traditionally assumed not to be at risk for the development of beta-cell autoimmunity, it is possible that the presence of autoimmune islet graft failure has been overlooked and underreported in this patient population. Herein, we describe two cases who underwent TP and AIT and later developed new-onset beta-cell autoimmunity (as evidenced by de novo glutamic acid decarboxylase antibody positivity), accompanied by complete insulin-dependent states. These cases emphasize the need for considering a possible autoimmune phenomenon in the workup of TP and AIT patients who manifest with unexpected and rapid deterioration in their glycemic control.
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Affiliation(s)
- Khawla F Ali
- Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, USA
| | | | - Tyler Stevens
- Digestive Disease Institute, Cleveland Clinic, Cleveland, USA
| | - R Matthew Walsh
- Digestive Disease Institute, Cleveland Clinic, Cleveland, USA
| | - Rita Bottino
- Institute for Cellular Therapeutics, Allegheny-Singer Research Institute, Pittsburgh, PA, USA
| | - Massimo Trucco
- Institute for Cellular Therapeutics, Allegheny-Singer Research Institute, Pittsburgh, PA, USA
| | - Betul Hatipoglu
- Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, USA
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24
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Incidental Neuroendocrine Tumor Discovered After Total Pancreatectomy Intended for Islet Autotransplantation: Important Considerations for Surgical Decision-Making. Pancreas 2018; 47:778-782. [PMID: 29894419 DOI: 10.1097/mpa.0000000000001069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Total pancreatectomy (TP) is a treatment option for patients experiencing chronic pancreatitis (CP) refractory to medical management. Patients who are candidates for TP benefit from islet autotransplantation (IAT), which preserves available β-cell mass and thereby reduces the risk of brittle diabetes. Malignancy is an absolute contraindication for IAT to prevent the transplantation of occult malignant cells. We present the case of a patient with CP who was approved to undergo TP with IAT (TPIAT) but was intraoperatively discovered to have a pancreatic neuroendocrine tumor. The case illustrates a number of important surgical decision-making considerations for patients undergoing TPIAT and should help guide surgeons should they be presented with this clinical scenario. We stress the importance of vigilance for possible malignancy and to consider an intraoperative biopsy to further investigate unexpected findings that might represent an occult pancreatic malignancy in patients with CP undergoing TPIAT.
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25
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Bennike TB, Bellin MD, Xuan Y, Stensballe A, Møller FT, Beilman GJ, Levy O, Cruz-Monserrate Z, Andersen V, Steen J, Conwell DL, Steen H. A Cost-Effective High-Throughput Plasma and Serum Proteomics Workflow Enables Mapping of the Molecular Impact of Total Pancreatectomy with Islet Autotransplantation. J Proteome Res 2018; 17:1983-1992. [PMID: 29641209 DOI: 10.1021/acs.jproteome.8b00111] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Blood is an ideal body fluid for the discovery or monitoring of diagnostic and prognostic protein biomarkers. However, discovering robust biomarkers requires the analysis of large numbers of samples to appropriately represent interindividual variability. To address this analytical challenge, we established a high-throughput and cost-effective proteomics workflow for accurate and comprehensive proteomics at an analytical depth applicable for clinical studies. For validation, we processed 1 μL each from 62 plasma samples in 96-well plates and analyzed the product by quantitative data-independent acquisition liquid chromatography/mass spectrometry; the data were queried using feature quantification with Spectronaut. To show the applicability of our workflow to serum, we analyzed a unique set of samples from 48 chronic pancreatitis patients, pre and post total pancreatectomy with islet autotransplantation (TPIAT) surgery. We identified 16 serum proteins with statistically significant abundance alterations, which represent a molecular signature distinct from that of chronic pancreatitis. In summary, we established a cost-efficient high-throughput workflow for comprehensive proteomics using PVDF-membrane-based digestion that is robust, automatable, and applicable to small plasma and serum volumes, e.g., finger stick. Application of this plasma/serum proteomics workflow resulted in the first mapping of the molecular implications of TPIAT on the serum proteome.
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Affiliation(s)
- Tue Bjerg Bennike
- Department of Pathology , Harvard Medical School , Boston , Massachusetts , United States.,Department of Pathology , Boston Children's Hospital , Boston , Massachusetts , United States.,Precision Vaccines Program , Boston Children's Hospital , Boston , Massachusetts , United States.,Department of Health Science and Technology , Aalborg University , Aalborg , Denmark
| | - Melena D Bellin
- Department of Surgery , University of Minnesota Medical Center , Minneapolis , Minnesota , United States.,Department of Pediatrics , University of Minnesota Medical Center , Minneapolis , Minnesota , United States
| | - Yue Xuan
- Thermo Fisher Scientific , Bremen , Germany
| | - Allan Stensballe
- Department of Health Science and Technology , Aalborg University , Aalborg , Denmark
| | | | - Gregory J Beilman
- Department of Surgery , University of Minnesota Medical Center , Minneapolis , Minnesota , United States
| | - Ofer Levy
- Precision Vaccines Program , Boston Children's Hospital , Boston , Massachusetts , United States.,Division of Infectious Diseases, Department of Medicine , Boston Children's Hospital , Boston , Massachusetts , United States
| | - Zobeida Cruz-Monserrate
- Division of Gastroenterology, Hepatology and Nutrition , The Ohio State University Wexner Medical Center , Columbus , Ohio United States
| | - Vibeke Andersen
- Focused Research Unit for Molecular Diagnostic and Clinical Research (MOK), IRS-Center Sonderjylland , Hospital of Southern Jutland , Aabenraa , Denmark.,Institute of Molecular Medicine , University of Southern Denmark , Odense , Denmark
| | - Judith Steen
- F.M. Kirby Neurobiology Center, Boston Children's Hospital, and Department of Neurology , Harvard Medical School , Boston , Massachusetts , United States
| | - Darwin L Conwell
- Division of Gastroenterology, Hepatology and Nutrition , The Ohio State University Wexner Medical Center , Columbus , Ohio United States
| | - Hanno Steen
- Department of Pathology , Harvard Medical School , Boston , Massachusetts , United States.,Department of Pathology , Boston Children's Hospital , Boston , Massachusetts , United States.,Precision Vaccines Program , Boston Children's Hospital , Boston , Massachusetts , United States
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26
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Bellin MD, Abu-El-Haija M, Morgan K, Adams D, Beilman GJ, Chinnakotla S, Conwell DL, Dunn TB, Freeman ML, Gardner T, Kirchner VA, Lara LF, Long-Simpson L, Nathan JD, Naziruddin B, Nyman JA, Pruett TL, Schwarzenberg SJ, Singh VK, Smith K, Steel JL, Wijkstrom M, Witkowski P, Hodges JS. A multicenter study of total pancreatectomy with islet autotransplantation (TPIAT): POST (Prospective Observational Study of TPIAT). Pancreatology 2018; 18:286-290. [PMID: 29456124 PMCID: PMC5879010 DOI: 10.1016/j.pan.2018.02.001] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Accepted: 02/02/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND/OBJECTIVES Total pancreatectomy with islet autotransplantation (TPIAT) is considered for managing chronic pancreatitis in selected patients when medical and endoscopic interventions have not provided adequate relief from debilitating pain. Although more centers are performing TPIAT, we lack large, multi-center studies to guide decisions about selecting candidates for and timing of TPIAT. METHODS Multiple centers across the United States (9 to date) performing TPIAT are prospectively enrolling patients undergoing TPIAT for chronic pancreatitis into the Prospective Observational Study of TPIAT (POST), a NIDDK funded study with a goal of accruing 450 TPIAT recipients. Baseline data include participant phenotype, pancreatitis history, and medical/psychological comorbidities from medical records, participant interview, and participant self-report (Medical Outcomes Survey Short Form-12, EQ-5D, andPROMIS inventories for pain interference, depression, and anxiety). Outcome measures are collected to at least 1 year after TPIAT, including the same participant questionnaires, visual analog pain scale, pain interference scores, opioid requirements, insulin requirements, islet graft function, and hemoglobin A1c. Health resource utilization data are collected for a cost-effectiveness analysis. Biorepository specimens including urine, serum/plasma, genetic material (saliva and blood), and pancreas tissue are collected for future study. CONCLUSIONS This ongoing multicenter research study will enroll and follow TPIAT recipients, aiming to evaluate patient selection and timing for TPIAT to optimize pain relief, quality of life, and diabetes outcomes, and to measure the procedure's cost-effectiveness. A biorepository is also established for future ancillary studies.
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Affiliation(s)
- Melena D Bellin
- University of Minnesota Medical School, Minneapolis, MN, United States.
| | | | - Katherine Morgan
- The Medical University of South Carolina, Charleston, SC, United States
| | - David Adams
- The Medical University of South Carolina, Charleston, SC, United States
| | - Gregory J Beilman
- University of Minnesota Medical School, Minneapolis, MN, United States
| | | | - Darwin L Conwell
- The Ohio State Wexner University Medical Center, Columbus, OH, United States
| | - Ty B Dunn
- University of Minnesota Medical School, Minneapolis, MN, United States
| | - Martin L Freeman
- University of Minnesota Medical School, Minneapolis, MN, United States
| | - Timothy Gardner
- Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
| | | | - Luis F Lara
- The Ohio State Wexner University Medical Center, Columbus, OH, United States
| | | | - Jaimie D Nathan
- Cincinnati Children's Hospital, Cincinnati, OH, United States
| | | | - John A Nyman
- University of Minnesota Medical School, Minneapolis, MN, United States
| | - Timothy L Pruett
- University of Minnesota Medical School, Minneapolis, MN, United States
| | | | - Vikesh K Singh
- John Hopkins Medical Institutions, Baltimore, MD, United States
| | | | - Jennifer L Steel
- University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | - Martin Wijkstrom
- University of Pittsburgh Medical Center, Pittsburgh, PA, United States
| | | | - James S Hodges
- University of Minnesota School of Public Health, Minneapolis, MN, United States
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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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28
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Kang ZS, Wang C, Han XL, Du JJ, Li YY, Zhang C. Design, synthesis and biological evaluation of non-secosteriodal vitamin D receptor ligand bearing double side chain for the treatment of chronic pancreatitis. Eur J Med Chem 2018; 146:541-553. [DOI: 10.1016/j.ejmech.2018.01.073] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 01/21/2018] [Accepted: 01/22/2018] [Indexed: 12/23/2022]
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29
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Durie P, Baillargeon JD, Bouchard S, Donnellan F, Zepeda-Gomez S, Teshima C. Diagnosis and management of pancreatic exocrine insufficiency (PEI) in primary care: consensus guidance of a Canadian expert panel. Curr Med Res Opin 2018; 34:25-33. [PMID: 28985688 DOI: 10.1080/03007995.2017.1389704] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Pancreatic exocrine insufficiency (PEI) results in maldigestion due to inadequate activity of pancreatic enzymes in the small bowel. PEI can arise from a variety of medical conditions that reduce enzyme synthesis within the pancreatic parenchyma or from secondary factors that may occur despite optimal parenchymal function, such as pancreatic duct obstruction or impaired or poorly synchronized enzyme release. PURPOSE To provide practical guidance for primary care physicians managing patients who are at risk of PEI or who present with symptoms of PEI. METHODS For each of six key clinical questions identified by the authors, PubMed searches were conducted to identify key English-language papers up to April 2017. Forward and backward searches on key articles were conducted using Web of Science. Clinical recommendations proposed by the co-chairs (P.D. and C.T.) were vetted and approved based on the authors? FINDINGS The most characteristic symptom of PEI is steatorrhea ? voluminous, lipid-rich stools; other common signs and symptoms include unexplained weight loss and deficiencies of fat-soluble vitamins and other micronutrients. Pancreatic enzyme replacement therapy (PERT) can relieve symptoms and long-term sequelae of PEI. Diagnosis of PEI and initiation of PERT are usually the responsibility of gastroenterology specialists. However, primary care physicians (PCPs) are well positioned to identify potential cases of PEI and to participate in the collaborative, long-term management of patients already seen by a specialist. CONCLUSIONS In this document, a panel of Canadian gastroenterologists has conducted a critical review of the literature on PEI and PERT and has developed practical diagnostic and treatment recommendations for PCPs. These recommendations provide guidance on identifying patients at risk of PEI, the triggers for PEI testing and referral, and best practices for co-managing patients with confirmed PEI.
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Affiliation(s)
- P Durie
- a Hospital for Sick Children and University of Toronto , Toronto , ON , Canada
| | - J-D Baillargeon
- b Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke , Sherbrooke , QC , Canada
| | - S Bouchard
- c Centre Hospitalier de l'Université de Montréal , Montréal , QC , Canada
| | - F Donnellan
- d Vancouver General Hospital , Vancouver , BC , Canada
| | | | - C Teshima
- f St. Michael's Hospital and University of Toronto , Toronto , ON , Canada
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Tillou JD, Tatum JA, Jolissaint JS, Strand DS, Wang AY, Zaydfudim V, Adams RB, Brayman KL. Operative management of chronic pancreatitis: A review. Am J Surg 2017; 214:347-357. [PMID: 28325588 DOI: 10.1016/j.amjsurg.2017.03.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 11/26/2016] [Accepted: 03/08/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Pain secondary to chronic pancreatitis is a difficult clinical problem to manage. Many patients are treated medically or undergo endoscopic therapy and surgical intervention is often reserved for those who have failed to gain adequate pain relief from a more conservative approach. RESULTS There have been a number of advances in the operative management of chronic pancreatitis over the last few decades and current therapies include drainage procedures (pancreaticojejunostomy, etc.), resection (pancreticoduodenectomy, etc.) and combined drainage/resection procedures (Frey procedure, etc.). Additionally, many centers currently perform total pancreatectomy with islet autotransplantation, in addition to minimally invasive options that are intended to tailor therapy to individual patients. DISCUSSION Operative management of chronic pancreatitis often improves quality of life, and is associated with low rates of morbidity and mortality. The decision as to which procedure is optimal for each patient should be based on a combination of pathologic changes, prior interventions, and individual surgeon and center experience.
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Affiliation(s)
- John D Tillou
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Jacob A Tatum
- Department of Surgery, The University of Virginia Health System, Charlottesville, VA, USA
| | - Joshua S Jolissaint
- Department of Surgery, The University of Virginia Health System, Charlottesville, VA, USA
| | - Daniel S Strand
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA
| | - Andrew Y Wang
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA
| | - Victor Zaydfudim
- Department of Surgery, The University of Virginia Health System, Charlottesville, VA, USA
| | - Reid B Adams
- Department of Surgery, The University of Virginia Health System, Charlottesville, VA, USA
| | - Kenneth L Brayman
- Department of Surgery, The University of Virginia Health System, Charlottesville, VA, USA.
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Abstract
Clinical pancreatic islet transplantation can be considered one of the safest and least invasive transplant procedures. Remarkable progress has occurred in both the technical aspects of islet cell processing and the outcomes of clinical islet transplantation. With >1,500 patients treated since 2000, this therapeutic strategy has moved from a curiosity to a realistic treatment option for selected patients with type 1 diabetes mellitus (that is, those with hypoglycaemia unawareness, severe hypoglycaemic episodes and glycaemic lability). This Review outlines the techniques required for human islet isolation, in vitro culture before the transplant and clinical islet transplantation, and discusses indications, optimization of recipient immunosuppression and management of adjunctive immunomodulatory and anti-inflammatory strategies. The potential risks, long-term outcomes and advances in treatment after the transplant are also discussed to further move this treatment towards becoming a more widely available option for patients with type 1 diabetes mellitus and eventually a potential cure.
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Affiliation(s)
- A M James Shapiro
- Clinical Islet Transplant Program, University of Alberta, 2000 College Plaza, 8215 112th Street, Edmonton, Alberta T6G 2C8, Canada
- The Diabetes Research Institute Federation, 1450 NW 10 Avenue, Miami, Florida 33136, USA
- The Cure Alliance, 550 Bay Point Road, Miami, Florida 33137, USA
| | - Marta Pokrywczynska
- The Diabetes Research Institute Federation, 1450 NW 10 Avenue, Miami, Florida 33136, USA
- The Cure Alliance, 550 Bay Point Road, Miami, Florida 33137, USA
- Department of Regenerative Medicine, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Karlowicza 24 Street, 85-092 Bydgoszcz, Poland
| | - Camillo Ricordi
- The Diabetes Research Institute Federation, 1450 NW 10 Avenue, Miami, Florida 33136, USA
- The Cure Alliance, 550 Bay Point Road, Miami, Florida 33137, USA
- Diabetes Research Institute and Cell Transplant Program, University of Miami Miller School of Medicine, 1450 NW 10th Avenue, Miami, Florida 33136, USA
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Kesseli SJ, Wagar M, Jung MK, Smith KD, Lin YK, Walsh RM, Hatipoglu B, Freeman ML, Pruett TL, Beilman GJ, Sutherland DER, Dunn TB, Axelrod DA, Chaidarun SS, Stevens TK, Bellin M, Gardner TB. Long-Term Glycemic Control in Adult Patients Undergoing Remote vs. Local Total Pancreatectomy With Islet Autotransplantation. Am J Gastroenterol 2017; 112:643-649. [PMID: 28169284 DOI: 10.1038/ajg.2017.14] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 01/04/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation. METHODS We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant. RESULTS Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group. CONCLUSIONS At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.
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Affiliation(s)
- Samuel J Kesseli
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Matthew Wagar
- Section of Endocrinology, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - Min K Jung
- Section of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Kerrington D Smith
- Section of General Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Yu Kuei Lin
- Department of Endocrinology, Endocrinology and Metabolism Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - R Matthew Walsh
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Betul Hatipoglu
- Section of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Martin L Freeman
- Section of Gastroenterology, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - Timothy L Pruett
- Deparment of Surgery, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - Gregory J Beilman
- Deparment of Surgery, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - David E R Sutherland
- Deparment of Surgery, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - Ty B Dunn
- Deparment of Surgery, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - David A Axelrod
- Section of Transplant Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Sushela S Chaidarun
- Section of Endocrinology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
| | - Tyler K Stevens
- Section of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Melena Bellin
- Section of Endocrinology, University of Minnesota Medical Center, Minneapolis, Minnesota, USA
| | - Timothy B Gardner
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
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John GK, Singh VK, Moran RA, Warren D, Sun Z, Desai N, Walsh C, Kalyani RR, Hall E, Hirose K, Makary MA, Stein EM. Chronic Gastrointestinal Dysmotility and Pain Following Total Pancreatectomy with Islet Autotransplantation for Chronic Pancreatitis. J Gastrointest Surg 2017; 21:622-627. [PMID: 28083839 DOI: 10.1007/s11605-016-3348-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 12/30/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND The prevalence and impact of chronic gastrointestinal dysmotility following total pancreactectomy with islet autotransplantation (TP-IAT) for chronic pancreatitis is not known. METHODS A cross-sectional study of all patients who underwent TP-IAT at our institution from August 2011 to November 2015 was undertaken. The GCSI (Gastroparesis Cardinal Symptom Index), PAGI-SYM (Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index), PAC-SYM (Patient Assessment of Constipation Symptoms), Bristol stool chart, 12-item Short Form Health Survey (SF-12), and visual analog scale for pain were administered ≥4 weeks following TP-IAT. KEY RESULTS The prevalence of any dysmotility symptoms in patients who completed the survey (33/45, 73%) post-TP-IAT was 45%. Post-TP-IAT, the mean reduction in opioid dosing was 77.6 oral morphine equivalents (OMEs) (95% CI 32.1-123.0, p = 0.002) with 42% of patients requiring no opioids. There was significant negative correlation between dysmotility scores and SF-12 physical scores (r = -0.46, p = 0.008, 95% CI -0.70 to -0.13). Self-reported abdominal pain had significant negative correlation with both physical and mental SF-12 scores (r = -0.67, p < 0.001, 95% CI -0.83 to -0.41 and r = -0.39, p = 0.03, 95% CI -0.65 to -0.04). There was no correlation between gastrointestinal dysmotility and self-reported pain. CONCLUSIONS AND INFERENCES Symptoms of chronic gastrointestinal dysmotility and chronic abdominal pain are common post-TP-IAT and will need to be better recognized and differentiated to improve the management of these patients.
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Affiliation(s)
- George K John
- Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Vikesh K Singh
- Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA.,Pancreatitis Center, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Robert A Moran
- Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA.,Pancreatitis Center, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Daniel Warren
- Division of Surgical Oncology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Zhaoli Sun
- Division of Surgical Oncology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Niraj Desai
- Division of Surgical Oncology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Christi Walsh
- Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Rita R Kalyani
- Division of Transplant Surgery, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Erica Hall
- Division of Transplant Surgery, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Kenzo Hirose
- Pancreatitis Center, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA.,Division of Surgical Oncology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Martin A Makary
- Pancreatitis Center, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA.,Division of Surgical Oncology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA
| | - Ellen M Stein
- Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA. .,Pancreatitis Center, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA. .,Division of Endocrinology, Diabetes, & Metabolism, Johns Hopkins Hospital, 1830 East Monument St, Suite 429, Baltimore, MD, 21287, USA.
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Islet Cell Yield Following Remote Total Pancreatectomy With Islet Autotransplant is Independent of Cold Ischemia Time. Pancreas 2017; 46:380-384. [PMID: 28129232 PMCID: PMC5308539 DOI: 10.1097/mpa.0000000000000792] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Total pancreatectomy with islet autotransplantation is increasingly being performed remotely, that is, removing the pancreas in 1 location, isolating the islet cells in another location, then returning the islets to the original location for reimplantation into the patient. We determined the influence of extended cold ischemia time on key clinical outcomes in remote islet autotransplantation. METHODS We evaluated patients who underwent remote islet autotransplantation at 2 centers from 2011 to 2014. Patients were divided into 2 groups: those with and those without a decrease in C-peptide greater than 50% from baseline. The primary clinical outcome was the quantity of isolated islet equivalents per kilogram body weight (IEQs/kg). RESULTS Twenty-five patients met inclusion criteria; 15 had a decrease in C-peptide greater than 50% from baseline and had lower corresponding IEQs/kg compared with those without a decrease greater than 50% (4045 vs 6654 IEQs/kg, P = 0.01). There was no difference in cold ischemia time between the 2 groups (664 vs 600 minutes, P = 0.25). Daily insulin use at 1 year nearly met statistical significance (25.3 vs 8 U, P = 0.06), as did glycated hemoglobin (8.07 vs 6.69 mmol/L, P = 0.06). CONCLUSIONS Cold ischemia time does not influence islet yield in patients undergoing pancreatectomy with remote isolation.
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Dytz MG, Marcelino PAH, de Castro Santos O, Zajdenverg L, Conceição FL, Ortiga-Carvalho TM, Rodacki M. Clinical aspects of pancreatogenic diabetes secondary to hereditary pancreatitis. Diabetol Metab Syndr 2017; 9:4. [PMID: 28101143 PMCID: PMC5237278 DOI: 10.1186/s13098-017-0203-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Accepted: 01/07/2017] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Hereditary pancreatitis is a rare inherited form of pancreatitis, characterized by recurrent episodes of acute pancreatitis with early onset and/or chronic pancreatitis, and presenting brittle diabetes, composed of episodes of nonketotic hyperglycemia and severe hypoglycemia. The existing literature regarding this form of diabetes is scarce. In this report, clinical features of pancreatogenic diabetes secondary to hereditary pancreatitis are presented along with recommendations for appropriate medical treatment. RESULTS Clinical data from five patients of a family with pancreatogenic diabetes secondary to hereditary pancreatitis were analyzed. The average time between hereditary pancreatitis and diabetes diagnosis was 80 ± 24 months (range: 60-180 months) with a mean age of 25.6 ± 14.7 years (range: 8-42 years), four patients used antidiabetic agents for 46 ± 45 months and all progressed to insulin therapy with a mean dose of 0.71 ± 0.63 IU/kg (range: 0.3-1.76 IU/kg). The glycemic control had a high variability with average capillary blood glucose of 217.00 ± 69.44 mg/dl (range: 145-306 mg/dl) and the average HbA1c was 9.9 ± 1.9% (range: 7.6-11.6%). No ketoacidosis episodes occurred and there were several episodes of hospitalization for severe hypoglycemia. CONCLUSIONS Diabetes mellitus secondary to hereditary pancreatitis presents with early onset, diverse clinical presentation and with extremely labile glycemic control. Diabetes treatment varies according to the presentation and insulin is frequently necessary for glycemic control.
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Affiliation(s)
- Marcio Garrison Dytz
- Endocrinology Section, Department of Internal Medicine, Medical School, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Laboratory of Translational Endocrinology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Diabetes and Nutrology Section, Department of Internal Medicine, Medical School, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
- Endocrinology Section, Hospital Universitário Clementino Fraga Filho, Rua Rodolpho Paulo Rocco 255, Ilha do Fundão, Rio de Janeiro, RJ 21941-913 Brazil
| | - Pedro Arthur Hamamoto Marcelino
- Diabetes and Nutrology Section, Department of Internal Medicine, Medical School, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Olga de Castro Santos
- Endocrinology Section, Department of Internal Medicine, Medical School, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Lenita Zajdenverg
- Diabetes and Nutrology Section, Department of Internal Medicine, Medical School, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Flavia Lucia Conceição
- Endocrinology Section, Department of Internal Medicine, Medical School, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Tânia Maria Ortiga-Carvalho
- Laboratory of Translational Endocrinology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
| | - Melanie Rodacki
- Diabetes and Nutrology Section, Department of Internal Medicine, Medical School, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
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Hafezi-Nejad N, Singh VK, Johnson SI, Makary MA, Hirose K, Fishman EK, Zaheer A. Surgical approaches to chronic pancreatitis: indications and imaging findings. Abdom Radiol (NY) 2016; 41:1980-96. [PMID: 27207476 DOI: 10.1007/s00261-016-0775-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Chronic pancreatitis (CP) is an irreversible, inflammatory process characterized by progressive fibrosis of the pancreas that can result in abdominal pain, exocrine insufficiency, and diabetes. Inadequate pain relief using medical and/or endoscopic therapies is an indication for surgery. The surgical management of CP is centered around three main operations including pancreaticoduodenectomy (PD), duodenum-preserving pancreatic head resection (DPPHR) and drainage procedures, and total pancreatectomy with islet autotransplantation (TPIAT). PD is the method of choice when there is a high suspicion for malignancy. Combined drainage and resection procedures are associated with pain relief, higher quality of life, and superior short-term and long-term survival in comparison with the PD. TPIAT is a reemerging treatment that may be promising in subjects with intractable pain and impaired quality of life. Imaging examinations have an extensive role in pre-operative and post-operative evaluation of CP patients. Pre-operative advanced imaging examinations including CT and MRI can detect hallmarks of CP such as calcifications, pancreatic duct dilatation, chronic pseudocysts, focal pancreatic enlargement, and biliary ductal dilatation. Post-operative findings may include periportal hepatic edema, pneumobilia, perivascular cuffing and mild pancreatic duct dilation. Imaging can also be useful in the detection of post-operative complications including obstructions, anastomotic leaks, and vascular lesions. Imaging helps identify unique post-operative findings associated with TPIAT and may aid in predicting viability and function of the transplanted islet cells. In this review, we explore surgical indications as well as pre-operative and post-operative imaging findings associated with surgical options that are typically performed for CP patients.
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Desai CS, Khan KM, Cui W. Islet autotransplantation in a patient with hypercoagulable disorder. World J Transplant 2016; 6:437-441. [PMID: 27358790 PMCID: PMC4919749 DOI: 10.5500/wjt.v6.i2.437] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 03/22/2016] [Accepted: 04/22/2016] [Indexed: 02/05/2023] Open
Abstract
Total pancreatectomy and islet auto transplantation is a good option for chronic pancreatitis patients who suffer from significant pain, poor quality of life, and the potential of type 3C diabetes and pancreatic cancer. Portal vein thrombosis is the most feared complication of the surgery and chances are increased if the patient has a hypercoagulable disorder. We present a challenging case of islet auto transplantation from our institution. A 29-year-old woman with plasminogen activator inhibitor-4G/4G variant and a clinical history of venous thrombosis was successfully managed with a precise peri- and post-operative anticoagulation protocol. In this paper we discuss the anti-coagulation protocol for safely and successfully caring out islet transplantation and associated risks and benefits.
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Schuetz C, Markmann JF. Islet cell transplant: Update on current clinical trials. CURRENT TRANSPLANTATION REPORTS 2016; 3:254-263. [PMID: 28451515 DOI: 10.1007/s40472-016-0103-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
In the last 15 years clinical islet transplantation has made the leap from experimental procedure to standard of care for a highly selective group of patients. Due to a risk-benefit calculation involving the required systemic immunosuppression the procedure is only considered in patients with type 1 diabetes, complicated by severe hypoglycemia or end stage renal disease. In this review we summarize current outcomes of the procedure and take a look at ongoing and future improvements and refinements of beta cell therapy.
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Affiliation(s)
- Christian Schuetz
- Islet transplantation laboratory, Division of Transplantation, Department of Surgery
| | - James F Markmann
- Islet transplantation laboratory, Division of Transplantation, Department of Surgery
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40
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Rhett JM, Wang H, Bainbridge H, Song L, Yost MJ. Connexin-Based Therapeutics and Tissue Engineering Approaches to the Amelioration of Chronic Pancreatitis and Type I Diabetes: Construction and Characterization of a Novel Prevascularized Bioartificial Pancreas. J Diabetes Res 2015; 2016:7262680. [PMID: 26788521 PMCID: PMC4691620 DOI: 10.1155/2016/7262680] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 07/31/2015] [Accepted: 08/18/2015] [Indexed: 01/08/2023] Open
Abstract
Total pancreatectomy and islet autotransplantation is a cutting-edge technique to treat chronic pancreatitis and postoperative diabetes. A major obstacle has been low islet cell survival due largely to the innate inflammatory response. Connexin43 (Cx43) channels play a key role in early inflammation and have proven to be viable therapeutic targets. Even if cell death due to early inflammation is avoided, insufficient vascularization is a primary obstacle to maintaining the viability of implanted cells. We have invented technologies targeting the inflammatory response and poor vascularization: a Cx43 mimetic peptide that inhibits inflammation and a novel prevascularized tissue engineered construct. We combined these technologies with isolated islets to create a prevascularized bioartificial pancreas that is resistant to the innate inflammatory response. Immunoconfocal microscopy showed that constructs containing islets express insulin and possess a vascular network similar to constructs without islets. Glucose stimulated islet-containing constructs displayed reduced insulin secretion compared to islets alone. However, labeling for insulin post-glucose stimulation revealed that the constructs expressed abundant levels of insulin. This discrepancy was found to be due to the expression of insulin degrading enzyme. These results suggest that the prevascularized bioartificial pancreas is potentially a tool for improving long-term islet cell survival in vivo.
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Affiliation(s)
- J. Matthew Rhett
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Hongjun Wang
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Heather Bainbridge
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Lili Song
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Michael J. Yost
- Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
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41
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Parekh D, Natarajan S. Surgical Management of Chronic Pancreatitis. Indian J Surg 2015; 77:453-69. [PMID: 26722211 DOI: 10.1007/s12262-015-1362-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 09/30/2015] [Indexed: 12/13/2022] Open
Abstract
Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.
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Affiliation(s)
- Dilip Parekh
- Department of Surgery, Keck School of Medicine, University of Southern California, 1510 San Pablo Street, Los Angeles, CA 90033 USA
| | - Sathima Natarajan
- Department of Surgery, Keck School of Medicine, University of Southern California, 1510 San Pablo Street, Los Angeles, CA 90033 USA ; Department of Pathology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA USA
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