Total pancreatectomy islet transplantation

BACKGROUND: Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis. METHODS: This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases...

Islet transplantation is a therapeutic option to replace β-cell mass lost during type 1 or type 3c diabetes. Innate immune responses, particularly the instant blood-mediated inflammatory reaction and activation of monocytes, play a major role in the loss of transplanted islet tissue. In this study, we aimed to investigate the inhibition of toll-like receptor 4 (TLR4) on innate inflammatory responses. We first demonstrate a significant loss of graft function shortly after transplant through the assessment of miR-375 and miR-200c in plasma as biomarkers...

Islets experience enormous stress during the isolation process, leading to suboptimal endocrine function after total pancreatectomy with islet autotransplantation (TPIAT). Our investigation focused on inducing isolation stress in islets ex vivo, where proinflammatory cytokines and hypoxia prompted the release of stress exosomes (exoS ) sized between 50 and 200 nm. Mass spectrometry analysis revealed 3 distinct subgroups of immunogenic proteins within these exoS : damage-associated molecular patterns (DAMPs), chaperones, and autoantigens...

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care ( n = 16)...

Total pancreatectomy and autologous islet transplantation (TPAIT) is a procedure to ameliorate dysglycemia associated with post-pancreatectomy. Patients who undergo TPAIT are at risk of developing hypoglycemia postoperatively. The current literature suggests that hypoglycemia may be due to a glucagon-deficiency state. To date, there is minimal literature available that explores treatment options to minimize hypoglycemia in these patients. In this case, a 29-year-old female patient was administered a microdosing glucagon protocol post TPAIT and experienced improvements in hypoglycemia...

BACKGROUND: Insular allograft for unstable type 1 diabetes and autograft in pancreatectomy patients are nowadays considered established procedures with precise indications and predictable outcomes. The clinical outcome of islet transplantation is similar to that of pancreas transplantation, avoiding the complications associated with organ transplantation. OBJECTIVE: We hypothesised that transplantation of islets of Langerhans within an endocrine organ could better promote their engraftment and function...

BACKGROUND AND AIMS: Chronic pancreatitis may cause intractable abdominal pain, with total pancreatectomy sometimes being the last resort. To mitigate the subsequent diabetes, total pancreatectomy can be followed by islet autotransplantation (TP-IAT). The primary aim of this study was to assess the outcomes in patients undergoing TP-IAT at Karolinska University Hospital with respect to safety, postoperative complications, and islet graft function. A secondary aim was to compare liver to skeletal muscle as autotransplantation sites...

BACKGROUND: Although diabetes after total pancreatectomy and islet autotransplantation (TP-IAT) is one of the biggest concerns for TP-IAT recipients and physicians, reliable prediction of post-TP-IAT glycemic control remains unestablished. This study was conducted to identify early predictors of insulin independence and goal glycemic control by hemoglobin A1c (HbA1c) ≤ 6.5% after TP-IAT. METHODS: In this single-center, retrospective study, patients who underwent TP-IAT (n = 227) were reviewed for simple metabolic markers or surrogate indices of β-cell function obtained 3 mo after TP-IAT as part of standard clinical testing...

For children with diminished quality of life and chronic pain caused by acute recurrent or chronic pancreatitis who are undergoing total pancreatectomy with islet autotransplantation, postoperative nutrition support has several unique characteristics. Surgical complications may lead to delays in nutrition support initiation or require modifications to the regimen. Early postoperative dysmotility requires the use of temporary enteral nutrition until this improves. The resultant complete exocrine pancreatic insufficiency necessitates lifelong pancreatic enzyme replacement therapy and fat-soluble vitamin supplementation...

BACKGROUND: Total pancreatectomy and islet autotransplantation (TPIAT) is a recognised treatment for chronic pancreatitis (CP) with the potential to mitigate or prevent pancreatogenic diabetes. We present our 10-year follow-up of TPIAT patients. METHODS: The University Hospitals of Leicester performed 60 TPIAT procedures from September 1994 to May 2011. Seventeen patients completed their 10-year assessment and were grouped using the modified Auto-Igls criteria; good response, n=5 (insulin-independent for first 5 years post-TPIAT); partial response, n=6 (insulin requirements <20 iU/day post-TPIAT) and poor response, n=6 (insulin requirements ≥20 iU/day post-TPIAT)...

BACKGROUND: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes. METHODS: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP...

Total pancreatectomy with islet autotransplantation (TPIAT) is the treatment of choice to preserve pancreatic endocrine function, alleviate pain, and improve quality of life (QoL) when other strategies are ineffective for chronic pancreatitis (CP) patients. This study utilized pancreatic disease-specific surveys developed by the European Organisation for Research and Treatment of Cancer (EORTC) to conduct a comprehensive, single-center examination of a large cohort of patients to gain understanding of QoL post-TPIAT...

Children with intractable chronic pancreatitis may require total pancreatectomy with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the severity of post- pancreatectomy diabetes. We analyzed 635 mixed meal tolerance tests (MMTT) in 134 children undergoing TPIAT to determine whether superior survival of islet grafts explains higher rates of insulin independence previously reported in young children (n = 52, age 3-11 years) versus adolescents (n = 82, age 12-18 years)...

Chronic pancreatitis is a progressive and irreversible process of pancreatic inflammation and fibrosis that can lead to intractable abdominal pain and severely impaired quality of life (QoL). Often patients are refractory to standard medical or endoscopic treatments. Total pancreatectomy (TP) and islet auto-transplantation (TP-IAT) can offer pain relief to patients by removing the entire pancreas and the auto-transplant component ameliorates the resulting diabetes. QoL is significantly improved after TP-IAT when insulin independence is present...

In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification (FC), limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections...

BACKGROUND/OBJECTIVE: Total pancreatectomy is performed for pain relief in chronic pancreatitis. Concomitant autologous islet cell transplantation can be performed to improve glycemic control. We report the case of a patient with chronic pancreatitis who underwent a total pancreatectomy with autologous islet cell transplantation with increasing insulin requirements and its association with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder. CASE REPORT: A 40-year-old woman presented with abdominal pain and had elevated levels of serum lipase...

We previously published that insulin pump initiation immediately after IV insulin therapy was associated with improved post-surgical glycemic outcomes compared to multiple daily injections (MDI) in pediatric patients following a total pancreatectomy with islet autotransplantation (TPIAT). We investigated metabolic outcomes of this population at one-year post-TPIAT to assess if the improved outcomes in the early pump group were sustained over time. We retrospectively reviewed 40 patients post-TPIAT previously studied at 10-days post-surgery (15 used MDI and 25 used pump therapy immediately post-ICU, and all were discharged on pump therapy)...

BACKGROUND: Patients with chronic pancreatitis (CP) often have severe and intractable abdominal pain, leading to decreased quality of life (QOL), inability to work or attend school, and increased health care costs due to repeated emergency room visits and hospitalizations. METHODS: We evaluated the efficacy of total pancreatectomy and islet autotransplantation (TPIAT) in terms of pain control and QOL in CP patients treated at our center in Japan. To evaluate QOL, we used the Short-Form 36 Health Survey version 2 (SF-36v2® Standard, Japanese), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and Quality of Life Questionnaire-Pancreatic Modification (QLQ-PAN28)...

BACKGROUND: Chronic pancreatitis is a debilitating, life altering disease; however, the long-term outcomes following operative intervention have not been established. STUDY DESIGN: Patients who underwent operative intervention at a single institution between 2000 to 2020 for chronic pancreatitis were included and survival assessed utilizing the National Death Index. RESULTS: 493 patients who underwent 555 operative interventions for chronic pancreatitis over two decades were included...

BACKGROUND: Despite the increased use of total pancreatectomy with islet autotransplantation (TPIAT), systematic evidence of its outcomes remains limited. AIM: To evaluate the outcomes of TPIAT. METHODS: We searched PubMed, EMBASE, and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes. Data were extracted and analyzed using comprehensive meta-analysis software. The random-effects model was used for all variables...