Interventional Radiology Approaches for Managing Postpancreatic Transplant Complications and Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-secreting beta cells in the pancreas, resulting in metabolic disturbances and long-term complications. While subcutaneous insulin remains the primary approach for achieving normoglycemia, pancreatic transplantation has emerged as an effective intervention for long-standing T1DM, providing insulin independence and normalized glycosylated hemoglobin levels. However, complications associated with pancreatic transplantation are frequent, necessitating thorough evaluation using diverse imaging modalities. This manuscript presents an overview of complications encountered with pancreatic transplantation, including vascular complications such as arterial and venous graft thrombosis, vessel stenosis, pseudoaneurysm, arterio-enteric fistula, and arteriovenous malformations. Additionally, the manuscript discusses other associated complications such as pancreatitis, pseudocyst formation, fistulas, pseudo-thrombosis of the iliac vein, post-transplantation lymphoproliferative disorder, and fluid collections. The integration of various imaging modalities plays a crucial role in diagnosing and managing these complications, with interventional radiologists assuming a vital role in employing image-guided procedures. Moreover, the manuscript explores pancreatic islet cell transplantation as a promising cellular-based therapy for T1DM, offering stable long-term glycemic control and decreased reliance on exogenous insulin in a significant proportion of recipients. This minimally invasive procedure involves the image-guided transcatheter infusion of islet cells obtained from deceased donors into the recipient's liver. The importance of interventional radiologists in managing complications related to pancreatic transplantation is underscored, with endovascular or image-guided approaches being utilized to address the diverse spectrum of encountered complications. Furthermore, the potential of islet cell transplantation as a minimally invasive alternative to traditional pancreatic transplantation is emphasized, as it offers the prospect of preventing many associated complications.

Subcutaneous device-free islet transplantation.

Diabetes mellitus is a chronic metabolic disease, characterized by high blood sugar levels; it affects more than 500 million individuals worldwide. Type 1 diabetes mellitus (T1DM) is results from insufficient insulin secretion by islets; its treatment requires lifelong use of insulin injections, which leads to a large economic burden on patients. Islet transplantation may be a promising effective treatment for T1DM. Clinically, this process currently involves directly infusing islet cells into the hepatic portal vein; however, transplantation at this site often elicits immediate blood-mediated inflammatory and acute immune responses. Subcutaneous islet transplantation is an attractive alternative to islet transplantation because it is simpler, demonstrates lower surgical complication risks, and enables graft monitoring and removal. In this article, we review the current methods of subcutaneous device-free islet transplantation. Recent subcutaneous islet transplantation techniques with high success rate have involved the use of bioengineering technology and biomaterial cotransplantation-including cell and cell growth factor co-transplantation and hydrogel- or simulated extracellular matrix-wrapped subcutaneous co-transplantation. In general, current subcutaneous device-free islet transplantation modalities can simplify the surgical process and improve the posttransplantation graft survival rate, thus aiding effective T1DM management.

Current practices in islet cell autotransplantation.

INTRODUCTION: Chronic pancreatitis and recurrent acute pancreatitis comprise a spectrum of disease that results in complications related to exocrine and endocrine insufficiency and chronic pain with narcotic dependence and poor quality of life. The mainstay of therapy has been medical and endoscopic therapy; surgery, especially total pancreatectomy, was historically reserved for few select patients as the obligate exocrine insufficiency and pancreatogenic diabetes (type 3C) are challenging to manage. The addition of islet cell autotransplantation after total pancreatectomy helps to mitigate brittle type 3c diabetes and prevents mortality related to severe hypoglycemic episodes and hypoglycemic unawareness. There have been more recent data demonstrating the safety of surgery and the beneficial long-term outcomes. AREAS COVERED: The purpose of this review is to describe the current practices in the field of islet cell autotransplantation including the selection and evaluation of patients for surgery, their preoperative work up and management, surgical approach, post-operative management and outcomes. EXPERT OPINION: Total pancreatectomy and islet cell autotransplantation has the ability to drastically improve quality of life and prevent brittle diabetes for patients suffering with chronic pancreatitis.

Total pancreatectomy with islet autotransplantation reduces opioid use and improves nutritional support in children with debilitating pancreatitis.

BACKGROUND: Chronic pancreatitis (CP) can result in opioid dependence and nutritional challenges in children. Total pancreatectomy with islet autotransplantation (TPIAT) is a viable surgical option in appropriately selected patients. We examined differences between children who met criteria for TPIAT versus those who did not and continued with non-operative management. METHODS: Retrospective observational cohort study of patients evaluated for TPIAT between August 2014 and July 2020 was performed. Cohort-based analyses between TPIAT and non-TPIAT groups were performed. RESULTS: Analyses included 121 patients, 69 of whom underwent TPIAT. Demographics, genetic risk factors, and anatomic variants did not differ between groups. TPIAT patients were more likely to have CP (88% vs 71%; p = 0.02), had higher median number of endoscopic retrograde cholangiopancreatography procedures (2.0 vs 1.0; p = 0.0001), and had higher likelihood of opioid use (61% vs 42%; p = 0.04) and nutritional supplementation (23% vs 4%; p = 0.004), compared to non-TPIAT. At 6 months post-TPIAT, patients had lower use of any analgesic pain medications (39% vs 73%; p = 0.0002) and lower use of opioids (9% vs 39%; p = 0.0006), compared to non-TPIAT patients at 6 months after evaluation. At 6 months post-TPIAT, rate of exclusively oral nutrition increased from 77% to 86%, and total parenteral nutrition use decreased from 13% to 0% (p = 0.02). CONCLUSIONS: In children referred for TPIAT evaluation, there is greater burden of disease in those selected for operation, compared to patients who do not undergo operation. TPIAT achieves lower analgesic pain medication use compared to continuation with non-TPIAT management and achieves freedom from nutritional supplementation. Level of evidence: Retrospective comparative study, Level III.

Nutritional Risks in Patients Undergoing Total Pancreatectomy Islet AutoTransplantation in the POST Consortium.

BACKGROUND AND AIMS: Total pancreatectomy with islet autotransplantation (TPIAT) can relieve pain for individuals with acute recurrent or chronic pancreatitis. However, TPIAT may increase the risk of poor nutritional status with complete exocrine pancreatic insufficiency, partial duodenectomy, and intestinal reconstruction. Our study's objective was to evaluate nutritional status, anthropometrics, and vitamin levels before and after TPIAT. METHODS: The multicenter Prospective Observational Study of TPIAT (POST) collects measures including vitamins A, D, and E levels, pancreatic enzyme dose, and multivitamin (MVI) administration before and 1-year after TPIAT. Using these data, we studied nutritional and vitamin status before and after TPIAT. RESULTS: 348 TPIAT recipients were included (68% adult, 37% male, 93% Caucasian). In paired analyses at 1-year follow-up, vitamin A was low in 23% (vs 9% pre-TPIAT, p < 0.001); vitamin E was low in 11% (vs 5% pre-TPIAT, p = 0.066), and 19% had vitamin D deficiency (vs 12% pre-TPIAT, p = 0.035). Taking a fat-soluble multivitamin (pancreatic MVI) was associated with lower risk for vitamin D deficiency (p = 0.002). Adults were less likely to be on a pancreatic MVI at follow-up (34% vs 66% respectively, p < 0.001). Enzyme dosing was adequate. More adults versus children were overweight or underweight pre- and post-TPIAT. Underweight status was associated with vitamin A (p = 0.014) and E (p = 0.02) deficiency at follow-up. CONCLUSIONS: Prevalence of fat-soluble vitamin deficiencies increased after TPIAT, especially if underweight. We strongly advocate that all TPIAT recipients have close post-operative nutritional monitoring, including vitamin levels. Pancreatic MVIs should be given to minimize risk of developing deficiencies.

Diffuse calcification of pancreas impairs endocrine function and predicts poor outcome in total pancreatectomy with islet autotransplantation.

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, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P < .01), and stimulated C-peptide levels were lower (P < .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P < .0001), with no insulin independence 12 months posttransplant (P < .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P < .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.

Quality of life after total pancreatectomy with islet autotransplantation for chronic pancreatitis in Japan.

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). RESULTS: Between August 2016 and June 2019, we performed this procedure in 5 patients. All patients were followed up for 12 months and all transplanted islets were still functioning at the 1-year follow-up. The major adverse events were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization; no case had sequelae. No major complications were due to islet transplantation. Pain scores improved postoperatively in all patients. Three QOL item dimensions role-physical (p = 0.03125), general health perception (p = 0.03125) and vitality (p = 0.03125) in the SF-36 were significantly improved 12 months after TPIAT. Mean values of many other QOL items improved, though not significantly. CONCLUSION: The QOL improvement after TPIAT for CP suggests its effectiveness in the Japanese population.

Encapsulated Cells for the Treatment of Diabetes: Danger of Acute Hypoglycemia Following Injury?

Transplants comprised of encapsulated islets have shown promise in treating insulin-dependent diabetes. A question raised in the scientific and clinical communities is whether the insulin released from an implanted encapsulation device damaged in an accident could cause a serious hypoglycemic event. In this commentary, we consider the different types of damage that a device can sustain, including the encapsulation membrane and the islets within, and the amount of insulin released in each case. We conclude that the probability that device damage would cause an adverse hypoglycemic event is indeed very low.

Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates.

The transplanting islets to the liver approach suffers from an immediate posttransplant loss of islets of more than 50%, progressive graft dysfunction over time, and precludes recovery of grafts should there be serious complications such as the development of teratomas with grafts that are stem cell-derived islets (SC-islets). The omentum features an attractive extrahepatic alternative site for clinical islet transplantation. We explore an approach in which allogeneic islets are transplanted onto the omentum, which is bioengineered with a plasma-thrombin biodegradable matrix in three diabetic non-human primates (NHPs). Within 1 week posttransplant, each transplanted NHP achieves normoglycemia and insulin independence and remains stable until termination of the experiment. Success was achieved in each case with islets recovered from a single NHP donor. Histology demonstrates robust revascularization and reinnervation of the graft. This preclinical study can inform the development of strategies for ß cell replacement including the use of SC-islets or other types of novel cells in clinical settings.

Factors associated with favourable 5 year outcomes in islet transplant alone recipients with type 1 diabetes complicated by severe hypoglycaemia in the Collaborative Islet Transplant Registry.

AIMS/HYPOTHESIS: Islet transplantation has been studied in small cohorts of recipients with type 1 diabetes complicated by severe hypoglycaemic events (SHEs). We determined factors associated with favourable outcomes in a large cohort of recipients reported to the Collaborative Islet Transplant Registry (CITR). METHODS: In 398 non-uraemic islet transplant alone (ITA) recipients with type 1 diabetes and SHEs, transplanted between 1999 and 2015 and with at least 1 year follow-up, we analysed specified favourable outcomes against each of all available characteristics of pancreas donors, islet grafts, recipients and immunosuppressive regimens, as well as immunosuppression and procedure-related serious adverse events (SAEs). RESULTS: Four factors were associated with the highest rates of favourable outcomes: recipient age ≥35 years; total infused islets ≥325,000 islet equivalents; induction immunosuppression with T cell depletion and/or TNF-α inhibition; and maintenance with both mechanistic target of rapamycin (mTOR) and calcineurin inhibitors. At 5 years after the last islet infusion, of the recipients meeting these four common favourable factors (4CFF; N=126), 95% were free of SHEs, 76% had HbA1c <53 mmol/mol (7.0%), 73% had HbA1c <53 mmol/mol (7.0%) and absence of SHEs, and 53% were insulin independent, significantly higher rates than in the remaining recipients (<4CFF; N=272). The incidence of procedural and immunosuppression-related SAEs per recipient that resulted in sequelae, disability or death was low in both the 4CFF (0.056 per person) and <4CFF (0.074 per person) groups. CONCLUSIONS/INTERPRETATION: In recipients with type 1 diabetes complicated by SHEs, islet transplantation meeting 4CFF protected 95% from SHEs at 5 years after the last islet infusion and exerted a large and significant benefit on glycaemic control, with an acceptable safety profile for this subgroup of type 1 diabetes.

Total Pancreatectomy With Islet Autotransplantation as an Alternative to High-risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial.

OBJECTIVE: To compare pancreaticoduodenectomy (PD) and total pancreatectomy (TP) with islet autotransplantation (IAT) in patients at high risk of postoperative pancreatic fistula (POPF). BACKGROUND: Criteria to predict the risk of POPF occurrence after PD are available. However, even when a high risk of POPF is predicted, TP is not currently accepted as an alternative to PD, because of its severe consequences on glycaemic control. Combining IAT with TP may mitigate such consequences. METHODS: Randomized, open-label, controlled, bicentric trial (NCT01346098). Candidates for PD at high-risk pancreatic anastomosis (ie, soft pancreas and duct diameter ≤3 mm) were randomly assigned (1:1) to undergo either PD or TP-IAT. The primary endpoint was the incidence of complications within 90 days after surgery. RESULTS: Between 2010 and 2019, 61 patients were assigned to PD (n=31) or TP-IAT (n=30). In the intention-to-treat analysis, morbidity rate was 90·3% after PD and 60% after TP-IAT ( P =0.008). According to complications' severity, PD was associated with an increased risk of grade ≥2 [odds ratio (OR)=7.64 (95% CI: 1.35-43.3), P =0.022], while the OR for grade ≥3 complications was 2.82 (95% CI: 0.86-9.24, P =0.086). After TP-IAT, the postoperative stay was shorter [median: 10.5 vs 16.0 days; P <0.001). No differences were observed in disease-free survival, site of recurrence, disease-specific survival, and overall survival. TP-IAT was associated with a higher risk of diabetes [hazard ratio=9.1 (95% CI: 3.76-21.9), P <0.0001], but most patients maintained good metabolic control and showed sustained C-peptide production over time. CONCLUSIONS: TP-IAT may become the standard treatment in candidates for PD, when a high risk of POPF is predicted.

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation.

BACKGROUND: Hepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents. OBJECTIVES: To define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT. METHODS: In this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis. RESULTS: A total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2-25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2-40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96). CONCLUSION: Our study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.

Perioperative Coagulation Changes in Total Pancreatectomy and Islet Autotransplantation.

OBJECTIVES: Thrombotic complications after total pancreatectomy with islet autotransplantation (TPIAT) are common. However, the systemic changes to coagulation in the perioperative period have not been well studied. Our objective was to evaluate the derangements in coagulation in the perioperative period for this procedure. METHODS: This was a prospective observational study of patients undergoing elective TPIAT for chronic pancreatitis. Multiple methods of evaluating coagulation, including 2 viscoelastic assays and standard laboratory assays were obtained at defined intraoperative and postoperative intervals. RESULTS: Fifteen patients were enrolled. Laboratory values demonstrated initial intraoperative hypercoagulability before significant systemic anticoagulation after islet infusion with heparin. Hypercoagulability is again seen at postoperative days 3 and 7. Subgroup analysis did not identify any major coagulation parameters associated with portal vein thrombosis formation. CONCLUSIONS: Apart from the immediate period after islet cell and heparin infusion, patients undergoing TPIAT are generally hypercoagulable leading to a high rate of thrombotic complications. Portal vein thrombosis development had minimal association with systemic derangements in coagulation as it is likely driven by localized inflammation at the time of islet cell infusion. This study may provide the groundwork for future studies to identify improvements in thrombotic complications.

Total pancreatectomy and islet cell autotransplantation: a 10-year update on outcomes and assessment of long-term durability.

BACKGROUND: Total pancreatectomy and islet cell autotransplantation (TPIAT) offers an effective, lasting solution for the management of chronic pancreatitis up to 5-years post-operatively. Our aim was to assess durability of TPIAT at 10-years. METHODS: Patients undergoing TPIAT for chronic pancreatitis eligible for 10-year follow-up were included. Primary outcomes, including endocrine function and narcotic requirements, were reported at 5-, 7.5-, and 10-years post-operatively. RESULTS: Of the 231 patients who underwent TPIAT, 142 met inclusion criteria. All patients underwent successful TPIAT with an average of 5680.3 islet equivalents per body weight. While insulin independence tended to decrease over time (25.7% vs. 16.0% vs. 10.9%, p = 0.11) with an increase in HbA1C (7.6% vs. 8.2% vs. 8.4%, p = 0.09), partial islet function persisted (64.9% vs. 68.0% vs. 67.4%, p = 0.93). Opioid independence was achieved and remained durable in the majority (73.3% vs. 72.2% vs. 75.5%, p = 0.93). Quality of life improvements persisted, with 85% reporting improvement from baseline at 10-years. Estimated median overall survival was 202.7 months. CONCLUSION: This study represents one of the largest series reporting on long-term outcomes after TPIAT, demonstrating excellent long-term pain control and durable improvements in quality of life. Islet cell function declines over time however stable glycemic control is maintained.

Immune-Protective Formulations and Process Strategies for Improved Survival and Function of Transplanted Islets.

Type 1 diabetes (T1D) is an autoimmune disease caused by the immune system attacking and destroying insulin-producing ß cells in the pancreas. Islet transplantation is becoming one of the most promising therapies for T1D patients. However, its clinical use is limited by substantial cell loss after islet infusion, closely related to immune reactions, including instant blood-mediated inflammatory responses, oxidative stress, and direct autoimmune attack. Especially the grafted islets are not only exposed to allogeneic immune rejection after transplantation but are also subjected to an autoimmune process that caused the original disease. Due to the development and convergence of expertise in biomaterials, nanotechnology, and immunology, protective strategies are being investigated to address this issue, including exploring novel immune protective agents, encapsulating islets with biomaterials, and searching for alternative implantation sites, or co-transplantation with functional cells. These methods have significantly increased the survival rate and function of the transplanted islets. However, most studies are still limited to animal experiments and need further studies. In this review, we introduced the immunological challenges for islet graft and summarized the recent developments in immune-protective strategies to improve the outcomes of islet transplantation.

Preferences for Risks and Benefits of Islet Cell Transplantation for Persons With Type 1 Diabetes With History of Episodes of Severe Hypoglycemia: A Discrete-Choice Experiment to Inform Regulatory Decisions.

BACKGROUND: The advisory panel for US Food and Drug Administration (FDA) recently endorsed pancreatic islet cell transplantation (ICT) therapy for suboptimally controlled type 1 diabetes (T1D), and FDA approval is under consideration. An important part of regulatory approval includes the patient perspective, through discrete choice. We developed a discrete-choice instrument and used it to determine how 90 people with T1D weigh the risks and benefits of ICT to inform regulatory decisions. METHODS: Sawtooth software created a random, full-profile, balanced-overlap experimental design for a measure with 8 attributes of ICT risks/benefits, each with 3 to 5 levels. We asked 18 random task pairs, sociodemographics, diabetes management, and hypoglycemia questions. Analysis was performed using random parameters logistic regression technique. RESULTS: The strongest preference was for avoiding the highest chance (15%) of serious procedure-related complications (ß = -2.03, P < 0.001). The strongest positive preference was for gaining 5-y insulin independence (ß = 1.75, P < 0.001). The desire for 5-y HbA1C-defined clinical treatment success was also strong (ß = 1.39, P < 0.001). Subgroup analysis suggested strong gender differences with women showing much higher preferences for all benefits (68% higher for 5-y insulin independence), and men were generally more risk averse than women. Those with high versus low diabetes distress showed 3 times stronger preference for 5-y insulin independence but also twice preference to avoid risks of serious complications. CONCLUSIONS: Despite showing the most preference for avoiding serious ICT complications, people with T1D had a strong preference for achieving ICT benefits, especially insulin independence. We identified important attributes of ICT and demonstrated that patients are willing to make these trade-offs, showing support for the introduction of ICT.

Outcomes Following Extrahepatic and Intraportal Pancreatic Islet Transplantation: A Comparative Cohort Study.

BACKGROUND: Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited. METHODS: This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018. Primary outcome was stimulated C-peptide level. Secondary outcomes were fasting plasma glucose, BETA-2 scores, and fasting C-peptide level. Multivariable logistic modeling evaluated factors independently associated with a composite variable of early graft failure and primary nonfunction within 60 d of ITx. RESULTS: Of 264 patients, 9 (3.5%) received extrahepatic ITx (gastric submucosal = 2, subcutaneous = 3, omental = 4). Group demographics were similar at baseline (age, body mass index, diabetes duration, and glycemic control). At 1-3 mo post-first infusion, patients receiving extrahepatic ITx had significantly lower stimulated C-peptide (0.05 nmol/L versus 1.2 nmol/L, P < 0.001), higher fasting plasma glucose (9.3 mmol/L versus 7.3 mmol/L, P < 0.001), and lower BETA-2 scores (0 versus 11.6, P < 0.001) and SUITO indices (1.5 versus 39.6, P < 0.001) compared with those receiving intraportal ITx. Subjects receiving extrahepatic grafts failed to produce median C-peptide ≥0.2 nmol/L within the first 60 d after transplant. Subsequent intraportal infusion following extrahepatic transplants achieved equivalent outcomes compared with patients receiving intraportal transplant alone. Extrahepatic ITx was independently associated with early graft failure/primary non-function (odds ratio 1.709, confidence interval 73.8-39 616.0, P < 0.001), whereas no other factors were independently predictive. CONCLUSIONS: Using current techniques, intraportal islet infusion remains the gold standard for clinical ITx, with superior engraftment, graft function, and glycemic outcomes compared with extrahepatic transplantation of human islets.

The Influence of Microenvironment on Survival of Intraportal Transplanted Islets.

Clinical islet transplantation has the potential to cure type 1 diabetes. Despite recent therapeutic success, it is still uncommon because transplanted islets are damaged by multiple challenges, including instant blood mediated inflammatory reaction (IBMIR), inflammatory cytokines, hypoxia/reperfusion injury, and immune rejection. The transplantation microenvironment plays a vital role especially in intraportal islet transplantation. The identification and targeting of pathways that function as "master regulators" during deleterious inflammatory events after transplantation, and the induction of immune tolerance, are necessary to improve the survival of transplanted islets. In this article, we attempt to provide an overview of the influence of microenvironment on the survival of transplanted islets, as well as possible therapeutic targets.