Field Of Pancreas Transplantation Research Articles

Breaking the limits of experimental pancreas transplantation: Working toward the clinical ideal graft

Pancreas transplantation is, at present, the only curative treatment for type-1 diabetes that maintains normoglycemia thus avoiding complications arising from poor glycemic control. Despite its great benefits, the number of pancreas transplants has decreased significantly since its inception in the late 1960s, largely due to demographic changes and the consequent suboptimal quality of donors. The selection criteria for pancreas donors mainly depend on morphological variables such as fatty infiltration, fibrosis, or edema, as well as both functional (amylase and lipase) and clinical variables of the donor. However, the final criterion in the decision-making process is the somewhat subjective assessment of a trained surgeon. That being said, the recent incorporation of graft perfusion machines into clinical practice seems to be changing the work dynamics of the donor organ retrieval team, facilitating decision-making based on objective morphological and functional criteria. Normothermic perfusion using perfusate with supplemental oxygen replicates near physiological parameters thus being a promising strategy for organ preservation. Nevertheless, optimum perfusion parameters are difficult to establish in pancreas transplantation given its complex vascular anatomy combined with an intrinsically low blood flow. The objective of this work is to analyze the results published in the recent literature relating to the considerations of ex-vivo normothermic graft perfusion machines and their usefulness in the field of pancreas transplantation.

Pancreatic transplant surgery and stem cell therapy: Finding the balance between therapeutic advances and ethical principles.

The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments, often characterized by high complexity from a surgical point of view, due to transplantation of multiple organs at the same time or at different times, and from an immunological point of view for stem cell therapy. The fundamental value in the field of organ transplants is, of course, a solidarity principle, namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery, or even of survival. The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems. The general principle of respect for human life, both of the donor and of the recipient, evokes the need not to put oneself and one’s neighbor in dangerous conditions. The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person, the respect due to the dead, the voluntary nature of the donation and the consent to the same, the gratuitousness of the donation, the scientific progress and the development of surgical techniques, and the policies of health promotion.

Editorial introductions

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Srinath ChinnakotlaSrinath ChinnakotlaDr Srinath Chinnakotla is a Professor of Surgery and Transplant Surgeon, University of Minnesota Medical School. He also serves as the Surgical Director of the Liver Transplant Program at University of Minnesota M Health affiliated Hospitals. Dr Chinnakotla received his medical degree from Jawaharlal Institute of Post-Graduate Medical Education and Research in 1990 and did his initial surgical training in India before relocating to the United States for a multi-organ Transplant Surgery Fellowship at the University Of Nebraska Medical Center. Prior to moving to Minneapolis. Dr Chinnakotla spent 10 years as staff transplant surgeon at Baylor University Medical Center, Dallas. He also served as Surgical Director of Pediatric Liver and Intestinal Transplantation at Children's Medical Center from 2007–2010. Dr Chinnakotla has over 20 years of experience as a staff transplant surgeon and has performed over 900 liver transplants, in both adults and children. His special interests include pediatric transplantation, living donor transplantation, complex and high-risk liver transplants and multi-organ transplants. He is also nationally and internationally known for developing the technique of total pancreatectomy and islet auto transplantation for use in small pediatric patients. Dr Chinnakotla has published more than 130 peer reviewed articles as well as a number of book chapters and review articles. He is a reviewer for several scientific journals. He has given presentations on a wide range of transplant surgery topics nationally. He has served on the Board of Directors, UNOS/OPTN and as Councilor Region 7 UNOS. Dr Chinnakotla is a member of ASTS, Fellow of American College of Surgeons and Member of the Southern Surgical Association. On a personal note, he enjoys most being with his children and family. His hobbies include boating, fishing and complaining about Minnesota winters. Jonathan A. FridellJonathan A. FridellDr Jonathan A. Fridell, MD is the Chief of Abdominal Transplant Surgery at Indiana University (IU). Having completed medical school, surgical training and a Master's degree in Surgical Research (Xenotransplantation) at McGill University in Montreal, Canada and Abdominal Transplant Surgery Fellowship at the Thomas E. Starzl Transplant Institute / University of Pittsburgh Medical Center in Pittsburgh, PA, he joined the faculty at IU in 2002. He has actively participated in all aspects of the abdominal transplant program including adult and pediatric liver, kidney, intestine, multivisceral and pancreas transplantation. He is best known for his contributions in the field of pancreas transplantation. His research is mostly focused on outcomes following pancreas transplantation and he has authored over 150 manuscripts and book chapters and is currently the Deputy Editor for Pancreas and Islet Transplantation for the journal Clinical Transplantation and an Associate Editor for the American Journal of Transplantation. Dr. Fridell also has a long history of participation with the Organ Procurement and Transplantation Network and the United Network for Organ Sharing (OPTN/UNOS) including a double term as the Chair of the Pancreas Transplant Committee. Augusto LauroAugusto LauroDr Augusto Lauro, MD PhD FACS FRCS Eng is an Attending Surgeon (Consultant) working at St. Orsola University Hospital in Bologna and an Assistant Professor (Lecturer) working at La Sapienza University in Rome. He was deeply involved in adult small bowel-multivisceral transplantation from 2002 up to 2017, while since the last 3 years he has been devoted to the surgical intestinal rehabilitation (rescue) field. He has attended by podium and poster presentations the IRTA (Intestinal Rehabilitation and Transplant Association) meetings since 2005 and he has written so far 75 PubMed papers about intestinal rescue and transplantation.

Quality of life after pancreas transplantation: time to look again

To summarize the existing body of literature regarding quality of life after pancreas transplantation, discuss the limitations of existing studies and make an argument for the need for future investigation on this important topic using standard verifiable instruments and utility measurements. Reinvigorating support for pancreas transplantation as a life-extending and quality-of-life-enhancing treatment for complicated diabetes mellitus remains a work in progress. Over the past two decades, improvements in surgical management, donor selection, recipient selection and immunosuppression have dramatically improved patient and graft outcomes, achieving durable restoration of normal glucose homeostasis in over 90% of patients. These significant advances in the field of pancreas transplantation have presumably had a positive effect on quality of life of pancreas recipients in the current era; however, this remains unconfirmed. Technical success in pancreas transplantation has improved dramatically since quality of life was last vigorously investigated in pancreas transplant recipients. Comprehensive review of the literature demonstrates the need and potential usefulness of further study substantiating quality of life benefit after pancreas transplantation, as it remains one of the primary considerations for this procedure.

Long-term benefits of pancreas transplantation

Pancreas transplantation has emerged as an effective treatment for patients with diabetes mellitus, especially those with established end-stage renal disease. Surgical and immunosuppressive advances have significantly improved allograft survival. With more recipients enjoying normoglycemia for longer periods of time, the opportunity to study more closely the effects of pancreas transplantation has arisen. This review will focus on these long-term benefits. The field of pancreas transplantation has been limited by a lack of randomized, controlled trials and relatively poor graft survival rates historically, however we can still glean many important points from the existing literature. The procedure reduces mortality compared with diabetic kidney transplant recipients and waitlisted patients. Improvements in diabetic nephropathy and retinopathy have also been demonstrated. Pancreas transplantation can improve cardiovascular risk profiles, improve cardiac function and decrease cardiovascular events. Lastly, improvements in diabetic neuropathy and quality of life can result from pancreas transplantation. Pancreas transplantation remains the most effective method to establish durable normoglycemia for patients with diabetes mellitus. Well designed clinical studies to assess outcomes and adverse events will be of paramount importance in providing optimal care to patients with diabetes mellitus.

The History of the EuroSPK - Study Group

The EuroSPK Study group was created during the 4th Spitzingsee 1997 workshop in Kühtai, Austria. Thanks to W. Land for the incentive to gather European Centres - with Switzerland and Israel - and propose them to joint efforts and share data in the field of pancreas transplantation. Today, two prospective randomized studies have been already performed; a lot of data and results have been generated and worldwide spread. The spirit of the group will continue with a new interest in innate immunity and prevention of the ischemic reperfusion injury in pancreas transplantation.

Infectious complications following 72 consecutive enteric-drained pancreas transplants

New immunosuppressive protocols and advanced surgical technique resulted in an improved outcome of pancreatic transplantation (PTx) with infection remaining the most common complication. Seventy-two enteric-drained whole PTxs performed at the Innsbruck University Hospital between September 2002 and October 2004 were retrospectively analyzed. Prophylactic immunosuppression consisted of either the standard protocol consisting of single bolus antithymocyteglobulin (ATG) (Thymoglobulin, Sangstat or ATG Fresenius) induction (9 mg/kg), tacrolimus (TAC), mycophenylate mofetil (MMF) and steroids (38 patients) or a 4-day course of ATG (4 mg/kg) tacrolimus and steroids with MMF (n = 19), or Sirolimus (n = 15). Perioperative antimicrobial prophylaxis consisted of Piperacillin/Tazobactam (4.5 g q 8 h) in combination with ciprofloxacin (200 mg q 12 h) and fluconazole (400 mg daily). Ganciclovir was used for cytomegalovirus (CMV) prophylaxis if donor was positive and recipient-negative. Patient, pancreas, and kidney graft survival at 1 year were 97.2%, 88.8%, and 93%, respectively, with no difference between the groups. All retransplants (n = 8) and single transplants (n = 8) as well as all type II diabetics and nine of 11 patients older 55 years received standard immunosuppression (IS). The rejection rate was 14% and infection rate 46% with no difference in terms of incidence or type according to the three groups. Severe infectious complications included intra-abdominal infection (n = 12), wound infection (n = 7), sepsis (n = 13), respiratory tract infection (n = 4), urinary tract infection (n = 12), herpes simplex/human herpes virus 6 infection (n = 5), CMV infection/disease (n = 7), post-transplant lymphoproliferative disorder (PTLD, n = 3), invasive filamentous fungal infection (n = 4), Clostridial/Rotavirus colitis (n = 1), and endocarditis (n = 1). All four patients in this series died of infectious complications (invasive aspergillosis n = 2) (one with Candida glabrata superinfection), invasive zygomycosis (n = 1), PTLD (n = 1). Five grafts were lost (vascular thrombosis n = 3, pancreatitis n = 1, noncompliance n = 1). Infection represented the most frequent complication in this series and all four deaths were of infectious origin. Better prophylaxis and management of infections now should be the primary target to be addressed in the field of pancreas transplantation.

Pancreas Transplantation

During the past decade, marked improvement has been made in the field of pancreas transplantation. The best results have been obtained in patients receiving a simultaneous pancreas-kidney transplant using the bladder drainage technique. An overall improvement in the secondary complications of diabetes has been documented in patients receiving successful pancreatic grafts. Pancreatic islet cell transplantation remains largely experimental at this time.