Pancreas transplantation following total pancreatectomy for chronic pancreatitis

Cerise, Adam; Nagaraju, Santosh; Powelson, John A.; Lutz, Andrew J.; Fridell, Jonathan A.

doi:10.1111/ctr.13731

Cited by 11 publications

(6 citation statements)

References 34 publications

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“…Although it is possible that PTx and the resulting optimized glycemic control may result in stabilization, or possibly improvement, in diabetic nephropathy, the introduction of nephrotoxic medications, particularly calcineurin inhibitors, may worsen renal function [14][15][16] or rarely result in the eventual requirement for renal replacement therapy or kidney transplant [17]. Apancreatic patients following total pancreatectomy for benign disease have brittle diabetes because they lack all glucose homeostatic mechanisms (not just insulin secretion) and lack pancreatic exocrine function so they would also benefit from PTA [18]. Rarely, insulin allergy, extreme insulin sensitivity, or erratic insulin absorption may result in true failures of exogenous insulin therapy irrespective of compliance [19].…”

Section: Key Pointsmentioning

confidence: 99%

Modern indications for referral for kidney and pancreas transplantation

Fridell

Stratta

2022

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Pancreas transplantation (PTx) is currently the only therapy that can predictably achieve sustained euglycemia independent of exogenous insulin administration in patients with insulin-dependent diabetes mellitus. This procedure involves a complex abdominal operation and lifetime dependence on immunosuppressive medications. Therefore, PTx is most frequently performed in combination with other organs, usually a kidney transplant for end stage diabetic nephropathy. Less frequently, solitary PTx may be indicated in patients with potentially life-threatening complications of diabetes mellitus. There remains confusion and misperceptions regarding indications and timing of patient referral for PTx. Recent findings In this review, the referral, evaluation, and listing process for PTx is described, including a detailed discussion of candidate assessment, indications, contraindications, and outcomes. Summary Because the progression of diabetic kidney disease may be less predictable than other forms of kidney failure, early referral for planning of renal and/or pancreas transplantation is paramount to optimize patient care and allow for possible preemptive transplantation.

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Section: Key Pointsmentioning

confidence: 99%

Modern indications for referral for kidney and pancreas transplantation

Fridell

Stratta

2022

Current Opinion in Nephrology &Amp; Hypertension

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“…These percentages are much lower than what was reported for patients undergoing total pancreas transplantation. Based on a report summarizing data from 2005 to 2016 (from one single transplantation center), 75% of the patients who obtained pancreas transplantation following total pancreatectomy remained insulin-independent [until their time of death, or until the present day (5)].…”

Section: Why the Need For Stem-cell Based Therapy In Diabetes?mentioning

confidence: 99%

Stem Cell-Based Clinical Trials for Diabetes Mellitus

Klerk

Hebrok

2021

Front. Endocrinol.

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Since its introduction more than twenty years ago, intraportal allogeneic cadaveric islet transplantation has been shown to be a promising therapy for patients with Type I Diabetes (T1D). Despite its positive outcome, the impact of islet transplantation has been limited due to a number of confounding issues, including the limited availability of cadaveric islets, the typically lifelong dependence of immunosuppressive drugs, and the lack of coverage of transplant costs by health insurance companies in some countries. Despite improvements in the immunosuppressive regimen, the number of required islets remains high, with two or more donors per patient often needed. Insulin independence is typically achieved upon islet transplantation, but on average just 25% of patients do not require exogenous insulin injections five years after. For these reasons, implementation of islet transplantation has been restricted almost exclusively to patients with brittle T1D who cannot avoid hypoglycemic events despite optimized insulin therapy. To improve C-peptide levels in patients with both T1 and T2 Diabetes, numerous clinical trials have explored the efficacy of mesenchymal stem cells (MSCs), both as supporting cells to protect existing β cells, and as source for newly generated β cells. Transplantation of MSCs is found to be effective for T2D patients, but its efficacy in T1D is controversial, as the ability of MSCs to differentiate into functional β cells in vitro is poor, and transdifferentiation in vivo does not seem to occur. Instead, to address limitations related to supply, human embryonic stem cell (hESC)-derived β cells are being explored as surrogates for cadaveric islets. Transplantation of allogeneic hESC-derived insulin-producing organoids has recently entered Phase I and Phase II clinical trials. Stem cell replacement therapies overcome the barrier of finite availability, but they still face immune rejection. Immune protective strategies, including coupling hESC-derived insulin-producing organoids with macroencapsulation devices and microencapsulation technologies, are being tested to balance the necessity of immune protection with the need for vascularization. Here, we compare the diverse human stem cell approaches and outcomes of recently completed and ongoing clinical trials, and discuss innovative strategies developed to overcome the most significant challenges remaining for transplanting stem cell-derived β cells.

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“…While most patients undergoing pancreas transplantation have type 1 diabetes, SPK transplants are increasingly being performed for those with type 2 diabetes, with 14% of all pancreas transplant recipients now carrying a primary diagnosis of type 2 diabetes in the USA [5]. Rarely, pancreas transplants are performed for less common forms of diabetes mellitus, including post-pancreatectomy diabetes mellitus, in which pancreas transplantation can reverse both endocrine and exocrine insufficiency [11,12], and in CFRD, in which pancreas transplantation has been combined with liver or lung transplantation [4].…”

Section: Pancreas Transplantationmentioning

confidence: 99%

Transplant strategies for type 1 diabetes: whole pancreas, islet and porcine beta cell therapies

Bellin

Dunn

2020

Diabetologia

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Whole-organ pancreas and islet transplantations are performed in a highly selected group of patients with diabetes mellitus, primarily those with type 1 diabetes mellitus, complicated by recurrent severe hypoglycaemia or renal failure requiring kidney transplantation. Clinical accessibility to pancreases or islets, and patient characteristics and therapeutic goals, may dictate choice of procedure. Pancreas transplantation is most often performed simultaneous with a kidney transplant, but patients with particularly labile type 1 diabetes may be considered for a pancreas transplant alone. While highly successful at restoring insulin independence, pancreas transplants carry the significant risks of major surgery and immunosuppression. Islet transplantation is a relatively minor procedure, usually performed for labile type 1 diabetes with severe hypoglycaemia. It is highly successful at resolving hypoglycaemia, but more than one pancreas donor may be required for insulin independence. Both pancreas and islet transplantation are limited in applicability by a paucity of deceased donors. Pigs provide one promising replenishable source of islets. Porcine islets can successfully reverse diabetes mellitus in non-human primates under the appropriate immunosuppressive conditions, with promise for eventually translating this success to a larger population of patients with diabetes mellitus in the future.

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Pancreas transplantation following total pancreatectomy for chronic pancreatitis

Cited by 11 publications

References 34 publications

Modern indications for referral for kidney and pancreas transplantation

Modern indications for referral for kidney and pancreas transplantation

Stem Cell-Based Clinical Trials for Diabetes Mellitus

Transplant strategies for type 1 diabetes: whole pancreas, islet and porcine beta cell therapies

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