Autologous Islet Cell Transplantation Research Articles

Robotic total pancreatectomy with autologous islet cell transplant: safety evaluation and outcomes

Robotic total pancreatectomy with autologous islet cell transplant: safety evaluation and outcomes

Robotic total pancreatectomy with autologous islet cell transplant: safety evaluation and outcomes

Robotic total pancreatectomy with autologous islet cell transplant: safety evaluation and outcomes

Incidence and Significance of Microbiological Results and Antimicrobial Prophylaxis in Patients Undergoing Total Pancreatectomy with Autologous Islet Cell Transplant

Introduction: The impact of microbiological findings in the preservation, cannulation solutions, and final islet cell product is debatable amongst providers taking care of patient undergoing total pancreatectomy with autologous islet cell-transplantation (TPAIT). It is further challenged by the lack of guidelines on the type and duration of antimicrobial prophylaxis needed. We aimed to correlate post-op infections to theses cultures and the efficacy of antimicrobial prophylaxis. Methods: Twenty-two patient’s (February 1, 2018 to August 31, 2021) microbiological data from the preservation, cannulation, and final islet cell cultures and their 60 days post-transplant infections were retrospectively analyzed. Results: Microbial cultures were positive in 5 (22.7%) patient’s preservation solution, 4 (18.2%) cannulation solution, and 6 (27.3%) final products (Table 1). Most common antimicrobial prophylaxis regimens were piperacillin/tazobactam (pip/tazo), vancomycin, and micafungin (n=9). The average duration was seven days (range: 2-10). Six patients were discharged on amoxicillin/clavulanic acid. Three patients (14%) had infections: 2 (9%) had Clostridium difficile (22 and 37 days after surgery), 1 (5%) had Candida albicans growing from the abdominal collection (59 days) with no growth in any of the isolation cultures, and 1 (5%) had Burkholderia cepacia in urine (44 days). Conclusion: Isolation procedure and final product cultures were not associated with any infections. Broad spectrum antimicrobial use intra- and post-operatively and extended oral antimicrobial therapy may have minimized the number of infectious outcomes. Consideration is warranted regarding the use of antimicrobial prophylaxis and duration as some of these agents pose a risk for C. difficile.Tabled 1EP02F-020Final Islet Cell CulturePreservation SolutionCannulation Solution1Yeast like organisms in anaerobic cultureNegativeYeast like organisms in anaerobic culture2Initially resulted as gram positive cocci with final identification as Granulicatella adiacensNegativeInitially resulted with gram negative rods in both aerobic and anaerobic cultures. Final report of Klebsiella pneumonia in the aerobic culture and Enterobacter species in anaerobic culture.3Streptococcus massiliensis from aerobic cultureNegativeNegative4Yeast like organisms in anaerobic cultureGram negative rods in aerobic and anaerobic culturesGram negative rods in aerobic and anaerobic cultures5NegativeGram positive rods in anaerobic cultureNegative6Gram positive cocci in anaerobic cultureGram negative rods in aerobic cultureNegative7Gram positive cocci in aerobic and anaerobic culturesGram negative rods in aerobic and anaerobic culturesGram negative rods in aerobic and anaerobic cultures8NegativeGram positive cocci in anaerobic cultureNegative Open table in a new tab

306.3: Safety and Efficacy of Total Pancreatectomy and Autologous Islet Cell Transplantation Compared to Parenchymal Preserving Pancreatic Surgery for Pancreatitis

306.3: Safety and Efficacy of Total Pancreatectomy and Autologous Islet Cell Transplantation Compared to Parenchymal Preserving Pancreatic Surgery for Pancreatitis

Use of Continuous Glucose Monitoring for evaluation of hypoglycemia pre- and post-operatively for patients undergoing Total Pancreatectomy with Autologous Islet Cell Transplant.

Total pancreatectomy with autologous islet transplant (TPAIT) is indicated for patients with chronic pancreatitis to improve quality of life while reducing complications from hypoglycemia. Continuous glucose monitoring (CGM) was used to assess overall islet function and the incidence of hypoglycemia pre- and post-operatively. Nineteen patients who underwent TPAIT at a single center from 2018 to 2020 were included. Pre-operatively, patients were defined by diabetic status. HbA1c, stimulated C-peptide, and CGM were used to characterize glycemic function. Pre-operatively, three patients had diabetes, and 16 patients did not have diabetes. Eight out of 16 non-diabetic patients were insulin independent (50%). Of six non-diabetic patients with>10% hypoglycemia on pre-operative CGM, 33% were insulin-independent post-operatively (P=.3). Of non-diabetic patients with ≥ 80% time in the euglycemic range, 62% were insulin-independent post-operatively (P=.2). For patients without diabetes, the median percent time in hypoglycemic range was reduced from 8% to 1% (P=.001). Delta C-peptide had a positive correlation with islet yield (P=.03). Conventional evaluation of TPAIT patients assesses primarily beta cell function. As pancreatogenic diabetes is concerning principally for the risk of hypoglycemia, assessment of alpha cell function can improve the quality of care. CGM better captures islet function and increases the identification of hypoglycemia.

Total Pancreatectomy with Autologous Islet Cell Transplantation-The Current Indications.

Total pancreatectomy is a major complex surgical procedure involving removal of the whole pancreatic parenchyma and duodenum. It leads to lifelong pancreatic exocrine and endocrine insufficiency. The control of surgery-induced diabetes (type 3) requires insulin therapy. Total pancreatectomy with autologous islet transplantation (TPAIT) is performed in order to prevent postoperative diabetes and its serious complications. It is very important whether it is safe and beneficial for patients in terms of postoperative morbidity and mortality, and long-term results including quality of life. Small duct painful chronic pancreatitis (CP) is a primary indication for TPAIT, but currently the indications for this procedure have been extended. They also include hereditary/genetic pancreatitis (HGP), as well as less frequent indications such as benign/borderline pancreatic tumors (intraductal papillary neoplasms, neuroendocrine neoplasms) and “high-risk pancreatic stump”. The use of TPAIT in malignant pancreatic and peripancreatic neoplasms has been reported in the worldwide literature but currently is not a standard but rather a controversial management in these patients. In this review, history, technique, indications, and contraindications, as well as short-term and long-term results of TPAIT, including pediatric patients, are described.

What Is New with Total Pancreatectomy and Autologous Islet Cell Transplantation? Review of Current Progress in the Field.

Patients with chronic pancreatitis have benefited from total pancreatectomy and autologous islet cell transplantation (TPAIT) since the 1970s. Over the past few decades, improvements have been made in surgical technique and perioperative management that have led to improved success of islet cell function, insulin independence and patient survival. This article focuses on recent updates and advances for the TPAIT procedure that continue to expand and innovate the impact on patients with debilitating disease.

Glycemic outcomes of parenchymal preserving surgery compared to total pancreatectomy with autologous islet cell transplant when stratified by pre-operative type 3 diabetic status

Introduction: Surgery for chronic pancreatitis (CP) can result in type 3c diabetes with severe hypoglycemic events (SHE) and hypoglycemic unawareness (HU). The aim of this study is to compare glycemic outcomes between total pancreatectomy and autologous islet cell transplant (TPAIT) and parenchymal preserving surgery (PPS). Methods: All patients undergoing CP surgery at a single center from 2017-2019 were included. Glycemic outcomes were compared between 2 groups: (1) TPAIT and (2) PPS and stratified between pre-operatively diabetic/pre-diabetic (DM) and non-diabetic (NDM). Results: 32 patients underwent surgery, 14 (43.8%) TPAIT and 18 (56.2%) PPS. In Group 1, 6 (42.9%) patients had DM pre-operatively. Following TPAIT, 9 (64.3%) patients were insulin dependent at discharge (6 [100%] DM vs. 3 [37.5%] NDM, p = 0.02). In Group 2, 12 (66.7%) had DM pre-operatively, 2 (16.7%) insulin dependent. While 4 (33.3%) in Group 2 required insulin at discharge, 2 had weaned off by 3-month follow up. Between TPAIT and PPS, there was a significant difference in number of patients requiring insulin in the immediate post-operative period (64.3% vs. 22.2%, p =0.02). However, by 3 months there was no significant difference when stratified by pre-operative DM status. No patient in either group experienced SHE or HU. Conclusion: While more patients required insulin following TPAIT than PPS, when stratified by pre-operative diabetic status, there was no statistical difference in glycemic outcomes over time. Therefore, apprehension regarding type 3c diabetes should not be a hinderance to choosing TPAIT in patients with diffuse pancreatic disease.PP04-052Number of patients requiring insulin when stratified by pre-operative type 3 diabetic statusTotal (n= 32)Non-diabetic TPAIT (n= 8)Non-diabetic PPS (n=6)p ValueDM/Pre-DM TPAIT (n= 6)DM/Pre-DM PPS (n=12p ValuePre- operatively, n (%)3 (9.4%)0 (0)0 (0)NA1 (16.7%)2 (16.7%)1.00At Discharge, n (%)13 (40.6%)3 (37.5%)0 (0)0.096 (100%)4 (33.3%)0.007At 1 month, n (%)13 (56.5%)4 (80.0%)0 (0)0.026 (100%)3 (37.5%)0.02At 3 months, n (%)11 (61.1%)3 (50.0%)0 (0)0.16 (100)2 (66.7)0.1 Open table in a new tab

Surgical therapy for patients with chronic and recurrent acute pancreatitis: parenchymal preserving or total pancreatectomy with autologous islet cell transplant

Introduction: Surgeons are often biased for choosing either the parenchymal preserving surgery (PPS) or the total pancreatectomy with autologous islet cell transplant (TPAIT) for chronic or recurrent pancreatitis (CP), depending on their personal beliefs and the availability of the islet isolation facilities. Aim is to evaluate the outcomes of both PPS and TPAIT at a single center having capacity to offer both surgeries. Methods: 152 patients with CP were evaluated between September 2017 to 2019; 32 were offered surgery based on the algorithm in Figure 1. Each surgery was performed by a single surgeon, alleviating potential bias due to surgeon preference or technical expertise. Quality of life (QOL), glycemic control, and reduction in narcotic use was evaluated in each patient. Outcomes were compared using Pearson's c2 test, student's t-test, and Kruskal-Wallis rank test. Results: Post-operatively 100% of TPAIT patients and 93.3% of PPS patients reported great improvement in QOL by 3 months (p=0.3). At 2 months only 7 (63.6%) of TPAIT and 6 (60.0%) of PPS patients required narcotics. All PPS patients weaned off narcotics by 3 months; however, 1 TPAIT patient continued to require narcotics at 1 year. Endocrine variables are shown in Table 1. 4 (28.6%) of TPAIT patients completely insulin independent. No hypoglycemic morbidity-mortality occurred. Conclusion: While TPAIT patients may have insulin requirement post-operatively, overall outcomes are comparable. In patients with non-localized disease, advantages of TPAIT in terms of preventing pain, pancreatic cancer and avoiding hypoglycemic complication cannot be overlooked when compared with PPS surgery.Table 1.Endocrine outcomes following TPAIT vs. PPSTPAITPPSp-valueAll patients Insulin dependent, n (%)At 3 months9 (75.0)2 (33.3)0.09At 1 year4 (100)2 (66.7)0.2Pre-operatively diabetic/pre-diabetic insulin dependent, n (%)At 3 months6 (100)2 (66.7)0.1At 1 year2 (100)2 (66.7)0.8Pre-operatively non-diabetic insulin dependent, n (%)At 3 months3 (50.0)0 (0)0.1At 1 year2 (100)NRNA Open table in a new tab

Alterations in portal flow dynamics following total pancreatectomy and autologous islet cell transplant

Introduction: The aim of this study is to evaluate doppler ultrasonography (DUS) flow dynamics following total pancreatectomy and autologous islet cell transplant (TPAIT). Methods: Retrospective analysis of prospectively collected data was done from February 2018 to September 2019. DUS measuring portal vein (PV) branch velocity (PVV) was performed on post-operative day (POD) 1, 2, and 5, and as applicable due to abnormal liver function tests (LFT). Results: Fifteen cases of TPAIT were performed. The mean change in PV pressure at infusion was 5.4 cm H2O [1.5 -26 (SD 6.3)]. The lowest mean flow was observed on POD 1 in the main and right posterior PV; on POD 2 in the right anterior and left PV. Correlation analysis showed weak correlation between LFTs and PVV, not significant until POD 5 (r = 0.55, p = 0.04). In the post-discharge period LFTs and PVV correlation was strongly statistically significant (r = 1.0, p-value < 0.001). There was a strong negative correlation between islet cell volume infused and right anterior PVV on POD 2 (r = -0.88, p = 0.02). Islet cell mass and PVV did not significantly correlate until POD 5 (r = 0.80, p = 0.03). No patients had PVT. Two patients had post-operative bleeding, both of which had extremely low velocities (main PVV 0.181). Conclusion: The correlation between PVV and LFTs is not significant until the post-discharge period when US is performed due to clinical concern rather than protocol. The value of scheduled post-operative velocity measurement may be overstated.

Comparative outcomes of total pancreatectomy and autologous islet cell transplant to parenchymal preserving surgery in patients with chronic pancreatitis when the surgical team has options to choose

Presenter: Brittney M Williams MD, MPH | University of North Carolina at Chapel Hill Background: Surgical management of refractory chronic and recurrent acute pancreatitis is challenging due to lack of standardized guidelines for patient selection. Patients are often selected based on individual surgeon preference, center’s availability and expertise for parenchymal preserving surgery (PPS) or total pancreatectomy with autologous islet cell transplant (TPAIT). We aim to evaluate perioperative outcomes of TPAIT vs. PPS following use of a patient-centered selection algorithm rather than therapeutic availability-centered decisions. Methods: From 2017 to 2020, patients with chronic or recurrent acute pancreatitis were evaluated and offered surgery based on an algorithm designed with consideration of dominant area of disease, ductal dilatation, and glycemic control. Surgeries were performed by same team under one lead surgeon eliminating technical bias. Retrospective analysis of all surgical patients was performed and perioperative outcomes were compared. Results: 50 patients underwent surgery (20 [40%] TPAIT and 30 [60%] PPS – 1 [2%] completion pancreatectomy, 13 [26%] distal pancreatectomies, 2 [4%] Frey procedures, 1 [2%] Roux-en-Y biliary bypass procedure, 4 [8%] total pancreatectomies, and 9 [18%] Whipple procedures). There was no significant difference in baseline characteristics. 4 (13%) PPS patients required non-operative intervention for leak and 2 (10%) TPAIT patients underwent re-laparotomy for bleeding. There was no significant difference in delayed feeding, wound infection, or readmission rate between groups; however, length of stay was longer following TPAIT. There was no incidence of portal vein thrombosis in TPAIT group. There was no mortality in either group. Conclusion: Operative intervention for chronic pancreatitis using a patient selection algorithm can result in similar perioperative outcomes between approaches. While TPAIT does require a longer length of surgery due to the islet isolation procedure, patients appropriately selected for this surgery have minimal perioperative complications and similar outcomes.

Portal flow dynamics after total pancreatectomy and autologous islet cell transplantation.

Portal vein thrombosis (PVT) is a serious complication of total pancreatectomy and autologous islet cell transplant (TPAIT); therefore, portal flow dynamics are monitored by Doppler ultrasound postoperatively. The practical value of scheduled Doppler ultrasound examinations and the relationship between portal vein velocity, liver function, and complications have not been clearly studied. A retrospective review of 16 TPAIT was performed. Correlation analysis of portal vein velocity with indices of liver function, portal pressure, and volume of islet cells infused was conducted. There was no correlation between portal vein velocity and postoperative liver function tests (LFTs). Larger volume of islet cells infused and higher intraoperative portal pressure correlated with decreased postoperative portal flow. There was no significant difference in portal pressure, portal vein velocity, or LFTs between those with normal and abnormal pre-infusion liver histopathology. While no PVT occurred, there were two cases of postoperative bleeding related to anticoagulation. Segmental portal vein velocities are low in the setting of high tissue volume and portal pressure, but are not associated with variation in LFTs. Therefore, patient management in response to changes in velocities without clinical symptoms may be unnecessary.

Perioperative Outcomes of Parenchymal Preserving Pancreatic Operation Compared with Total Pancreatectomy with Autologous Islet Cell Transplantation Using a Patient Selection Algorithm

Williams, Brittney M. MD; Baldwin, Xavier MD; Vonderau, Jennifer S. PA-C; Desai, Chirag S. MD, FACS Author Information

Robot‐Assisted Total Pancreatectomy With Autologous Islet Cell Transplantation: Perioperative Nursing Considerations

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.

Do post-operative complications following total pancreatectomy and autologous islet cell transplantation (tpiat) affect long term insulin independence?

Do post-operative complications following total pancreatectomy and autologous islet cell transplantation (tpiat) affect long term insulin independence?

The role of surgery in chronic pancreatitis

Chronic pancreatitis (CP) remains a complex condition resulting in significant morbidity and suffering in patients, often over a long period of time. Treatment is mostly centred on a conservative approach, with a variety of more aggressive options being trialled over the years utilising numerous endoscopic and surgical techniques. This review provides an overview of current treatment options for CP, the literature search was performed via PubMed. Personal experiences from the authors on how to approach the disease from the surgeon’s perspective are added. The outline includes pathophysiologic aspects, classifications and patient-centred surgical approaches. There has not been a standardized treatment for CP so far as clinical and radiological appearance of the disease have a wide range due to great heterogeneity of this complex disease; therefore, level 1 evidence for treatment of CP remains low. More recently, different approaches to surgical management have been trialled. With personalized surgery, long-term pain relief is achievable in up to 90% with low morbidity. Autologous islet cell transplantation is a feasible option in selected patients to avoid endocrine insufficiency. A tailored approach to CP patients is mandatory in this heterogeneous disease. Surgery provides good outcomes especially as prophylaxis for and treatment of chronic pain. A multidisciplinary approach is mandatory, including physicians, pancreatic surgeons, endoscopists, dieticians and radiologists.

Effect of liver histopathology on islet cell engraftment in the model mimicking autologous islet cell transplantation

ABSTRACTBackground: The inflammatory milieu in the liver as determined by histopathology is different in individual patients undergoing autologous islet cell transplantation. We hypothesized that inflammation related to fatty-liver adversely impacts islet survival. To test this hypothesis, we used a mouse model of fatty-liver to determine the outcome of syngeneic islet transplantation after chemical pancreatectomy. Methods: Mice (C57BL/6) were fed a high-fat-diet from 6 weeks of age until attaining a weight of ≥28 grams (6–8 weeks) to produce a fatty liver (histologically > 30% fat);steatosis was confirmed with lipidomic profile of liver tissue. Islets were infused via the intra-portal route in fatty-liver and control mice after streptozotocin induction of diabetes. Outcomes were assessed by the rate of euglycemia, liver histopathology, evaluation of liver inflammation by measuring tissue cytokines IL-1β and TNF-α by RT-PCR and CD31 expression by immunohistochemistry. Results: The difference in the euglycemic fraction between the normal liver group (90%, 9/10) and the fatty-liver group (37.5%, 3/8) was statistically significant at the 18th day post- transplant and was maintained to the end of the study (day 28) (p = 0.019, X2 = 5.51). Levels of TNF–α and IL-1β were elevated in fatty-liver mice (p = 0.042, p = 0.037). Compared to controls cytokine levels were elevated after islet cell transplantation and in transplanted fatty-liver mice as compared to either fatty- or islet transplant group alone (p = NS). A difference in the histochemical pattern of CD31 could not be determined. Conclusion: Fatty-liver creates an inflammatory state which adversely affects the outcome of autologous islet cell transplantation.

Expanding the indications for pancreas resection and autologous islet cell transplantation (IAT) in both adults and children

Introduction: Pancreas resection combined with IAT is a controversial procedure with limited experience in the UK and is not funded by the NHS. We present our experience of IAT in patients with chronic pancreatitis and pancreatic trauma including the UK's first paediatric transplant. Methods: We have performed 6 pancreatic resections with IAT over 18 months. 3 patients with chronic pancreatitis (2 hereditary, 1 idiopathic) have undergone total pancreatectomy and IAT. Two patients had previous Frey procedures. 3 patients (2 adults, 1 child) sustained blunt pancreatic trauma and underwent extended left pancreatectomy combined with IAT. Complications were graded according to the Clavien-Dindo classification. Results: In the chronic pancreatitis group the islet yield was low due to fibrosis /previous drainage procedures (<50,000 IEQ). The first patient is now opiate independent and the remaining 2 patients continue on reducing doses. All have marked improvement in their quality of life. All require low dose insulin analogue therapy with in vivo C-peptide secretion. In contrast the trauma patients had a much greater islet yield (99,750–298,149 IEQ). All are insulin independent. There were no complications related to portal vein infusion and no deaths, one patient required re-laparotomy for an infected collection. Conclusions: Pancreatectomy and IAT can be used as a salvage procedure in patients who have failed all other therapy but in our opinion results would be superior if performed earlier in the course of their disease. It is also a feasible management option for complex pancreatic trauma in both adults and children.

Pancreatic islet autotransplantation for nonmalignant and malignant indications.

The standard therapy for patients with chronic pancreatitis (CP) and severe abdominal pain is total pancreatectomy (TP) followed by islet autotransplantation (IAT) to prevent the development of brittle diabetes. In adult patients, narcotic independence is achieved in up to 73% of patients 1 to 5 years after transplantation whereas insulin independence is achieved in up to 40% of patients 1 to 2 years after transplantation. Pediatric patients have shown similar outcomes for narcotic independence (up to 79%) but better outcomes for insulin independence (up to 56% 1 year after transplantation). The quality of life of both adult and pediatric patients improved significantly after TP-IAT using the Medical Outcomes Study SF-36 survey. IAT after pancreatectomy is also performed for patients with benign and malignant disease of the pancreas. The limited studies in this patient population suggest that IAT may be potentially beneficial for carefully selected patients when sufficient numbers of islet cells can be isolated. Further studies involving a larger number of patients are needed to determine the risks and benefits of IAT in patients with malignancy. The feasibility of IAT depends on the availability of a laboratory that can isolate the pancreatic islet cells. An on-site laboratory is the traditional model; however, remote processing of pancreatic islets has been reported to result in successful outcomes. This review discusses the outcomes of adult and pediatric autologous pancreatic islet cell transplantation for CP and pancreatic tumors as well as laboratory processing of pancreatic islet cells.

Total pancreatectomy with islet autologous transplantation: the cure for chronic pancreatitis?

Chronic pancreatitis (CP) is a debilitating disease that leads to varying degrees of pancreatic endocrine and exocrine dysfunction. One of the most difficult symptoms of CP is severe abdominal pain, which is often challenging to control with available analgesics and therapies. In the last decade, total pancreatectomy with autologous islet cell transplantation has emerged as a promising treatment for the refractory pain of CP and is currently performed at approximately a dozen centers in the United States. While total pancreatectomy is not a new procedure, the endocrine function-preserving autologous islet cell isolation and re-implantation have made the prospect of total pancreatectomy more acceptable to patients and clinicians. This review will focus on the current status of total pancreatectomy with autologous islet cell transplant including patient selection, technical considerations, and outcomes. As the procedure is performed at an increasing number of centers, this review will highlight opportunities for quality improvement and outcome optimization.