L-Glutamine and Survival of Patients with Locally Advanced Head and Neck Cancer Receiving Chemoradiotherapy.

We previously reported that L-glutamine reduces the severity of mucositis caused by chemoradiotherapy in patients with head and neck cancer. However, the impact of glutamine on the anti-tumor effect of chemoradiotherapy remains controversial. This study, which included 40 patients, investigated whether L-glutamine influences survival. Radiation therapy (total: 66 or 70 Gy), cisplatin, and docetaxel were co-administered for a period of 6 weeks. Patients were randomly assigned to receive either glutamine (glutamine group, n = 20) or placebo (placebo group, n = 20) during the entire course of chemoradiotherapy. We compared the overall survival and progression-free survival rates between the two groups. At 5-year follow-up, 16 (80%) and 13 (72%) patients in the glutamine and placebo groups, respectively, survived (with no significant difference in overall survival [glutamine group: 55.2 ± 12.7 months vs. placebo group: 48.3 ± 21.3 months]). A total of 14 (70%) and 12 (67%) patients in the glutamine and placebo groups, respectively, did not experience disease progression (with no significant difference in progression-free survival [glutamine group: 46.7 ± 19.5 months vs. placebo group: 43.6 ± 25.2 months]). These findings indicate that L-glutamine does not influence the survival of patients with locally advanced head and neck cancer receiving chemoradiotherapy.

Size-mismatched transplantation from large donors to small recipients is associated with pancreas graft thrombosis: A retrospective national observational study.

INTRODUCTION: Donor-recipient (D/R) size mismatch has been evaluated for a number of organs but not for pancreas transplantation. METHODS: We retrospectively evaluated 438 patients who had undergone pancreas transplantation. The D/R body surface area (BSA) ratio was calculated, and the relationship between the ratio and graft prognosis was evaluated. We divided the patients into two groups and evaluated graft survival. The incidence of pancreas graft thrombosis resulting in graft failure within 14 days and 1-year graft survival were compared using Kaplan-Meier curves, and the prognostic factors associated with graft thrombosis were identified by univariate and multivariate analyses. RESULTS: The mean/median donor and recipient BSAs were 1.63 m2 /1.65 m2 , and 1.57 m2 /1.55 m2 , respectively; the mean and median D/R BSAs were both 1.05. The receiver operating characteristic curve cutoff for the D/R BSA ratio was 1.09, and significant differences were identified between patients with ratios of ≥1.09 (high group) versus <1.09 (low group). The incidence of graft thrombosis resulting in pancreas graft failure within 14 days was significantly higher in the high group than in the low group (p < .01). One-year overall and death-censored pancreas graft survival were significantly higher in the low group than in the high group (p < .01). Multivariate analysis identified recipient height, donor BSA, and donor hemoglobin A1c as significant independent factors for graft thrombosis. Cubic spline curve analysis indicated an increased risk of graft thrombosis with increasing D/R BSA ratio. CONCLUSION: D/R size mismatch is associated with graft thrombosis after pancreas transplantation.

Utilization of the Pancreas From Donors With an Extremely High Pancreas Donor Risk Index: Report of the National Registry of Pancreas Transplantation.

Pancreas transplants from expanded criteria donors are performed widely in Japan because there is a shortage of brain-dead donors. However, the effectiveness of this strategy is unknown. We retrospectively studied 371 pancreas transplants to evaluate the possibility of pancreas transplantation from expanded criteria donors by the Pancreas Donor Risk Index (PDRI). Patients were divided into five groups according to quintiles of PDRI values (Q1-Q5). The 1-year pancreas graft survival rates were 94.5% for Q1, 91.9% for Q2, 90.5% for Q3, 89.3% for Q4, and 79.6% for Q5, and were significantly lower with a lower PDRI (p = 0.04). A multivariate analysis showed that the PDRI, donor hemoglobin A1c values, and pancreas transplantation alone significantly predicted 1-year pancreas graft survival (all p < 0.05). Spline curve analysis showed that the PDRI was incrementally associated with an increased risk of 1-year graft failure. In the group with a PDRI ≥ 2.87, 8/56 patients had graft failures within 1 month, and all were due to graft thrombosis. The PDRI is a prognostic factor related to the 1-year graft survival rate. However, pancreas transplantation from high-PDRI donors shows acceptable results and could be an alternative when the donor pool is insufficient.

Impact of Cytomegalovirus Infection and Disease on Graft Loss After Pancreas Transplantation: A Single-Institution Study in Japan.

BACKGROUND: Cytomegalovirus (CMV) is one of the most frequent infections after pancreas transplantation (PTx), and it is unclear whether CMV infection is associated with pancreas graft loss. A limited number of studies about the relationship between CMV infection and pancreas graft loss have been reported from Western countries, but there have been no reports from Japan. This study investigated the relationship between CMV infection and pancreas graft loss after PTx in a single Japanese institution. METHODS: This study included 58 patients who underwent PTx from deceased donors from April 2000 to March 2021 in our institution. We assessed pancreas graft loss based on CMV infection and disease and investigated the causes of graft loss, the time of onset of CMV disease, and the time of graft loss for each case. RESULTS: The numbers of patients in the 4 categories of donor (D) and recipient (R) pretransplant anti-CMV antibody status were as follows: 4 (6.9%) in the D-/R- group, 6 (10.3%) in the D-/R+ group, 34 (58.6%) in the D+/R+ group, and 14 (24.1%) in the D+/R- group. Of the 58 patients, 74.1% and 44.1% received diagnoses of CMV infection and disease after PTx, respectively. There were no significant differences in the survival rates of pancreas graft loss stratified by CMV infection (P = .1809) or disease (P = .6241). CONCLUSIONS: This study suggests that CMV infection and disease had no significant influence on pancreas graft loss in this Japanese institution.

Clinical Significance of the Interposition Graft for Reconstruction Between the Common Hepatic Artery and Gastroduodenal Artery for Arterial Patency of the Pancreas Graft in Pancreas Transplantation.

BACKGROUND: Due to the limited number of organ donations from deceased donors in Japan, pancreas grafts for pancreas transplantation (PTx) are frequently harvested from the donor in the same donation surgery as the liver graft. In such a situation, the common hepatic artery (CHA) and gastroduodenal artery (GDA) are dissected, resulting in decreased blood flow to the head of the pancreas graft. Therefore, GDA reconstruction using an interposition graft (I-graft) between the CHA and GDA has been traditionally performed to maintain blood flow. This study investigated the clinical significance of GDA reconstruction with the I-graft regarding the arterial patency of the pancreas graft in patients after PTx. METHODS: Fifty-seven patients underwent PTx for type 1 diabetes mellitus at our hospital between 2000 and 2021. Twenty-four cases in which GDA reconstruction was performed using the I-graft and artery blood flow of the pancreas graft was evaluated by contrast-enhanced computed tomography or angiography were included in this study. RESULTS: The patency of the I-graft was 95.8%, and only one patient had a thrombus in the I-graft. Nineteen patients (79.2%) had no thrombus in the artery of the pancreas graft; the other five cases had thrombus in the superior mesenteric artery (SMA). The patient with the thrombus in the I-graft required graftectomy for the pancreas graft. CONCLUSIONS: The patency of the I-graft was favorable. Furthermore, the clinical significance of the GDA reconstruction with the I-graft is suggested to maintain blood flow in the pancreas head if the SMA is occluded.

Clinical Impact of Ischemic Time of the Pancreas or Kidney Graft on Simultaneous Pancreas-Kidney Transplantation: A Single-Institution Study in Japan.

BACKGROUND: Total ischemic time (TIT) potentially affects graft survival in organ transplantation. However, in simultaneous pancreas-kidney (SPK) transplantation, the impact of TIT of the pancreas (P-TIT) and kidney graft (K-TIT) on posttransplant outcomes remains unclear. This study investigated the impact of P-TIT and K-TIT on postoperative outcomes in patients after SPK at our institution in Japan. PATIENTS AND METHODS: This study included 52 patients who underwent SPK at our hospital from April 2000 to March 2022. Of this patient group, the 52 patients were divided into a short P-TIT group (n = 25), long P-TIT group (n = 27), short K-TIT group (n = 42), and long K-TIT group (n = 10). Short- and long-term postoperative outcomes were compared between the groups. RESULTS: The long K-TIT group had a significantly higher rate of patients who did not urinate intraoperatively (50% vs 7%; P = .0007) and those requiring postoperative hemodialysis (80% vs 38%; P = .0169), as well as a significant longer duration of postoperative hemodialysis (97 ± 147 days vs 6 ± 9 days; P = .0016). These were not significantly different between the short and long P-TIT groups. Kidney or pancreas graft survival was not significantly different between the short and long P-TIT or K-TIT groups. CONCLUSIONS: Patients with prolonged K-TIT during SPK exhibited poor short-term outcomes, but no significant influence of K-TIT was identified on long-term outcomes. The P-TIT did not affect any significant outcomes. These results indicate that shortening K-TIT may improve short-term outcomes after SPK.

Impact of Decompression Tube Placement in Duodenal Graft on Graft Perforation After Pancreas Transplantation.

BACKGROUND: Duodenal graft perforation (DGP) is a serious complication after pancreas transplantation (PTx) and can lead to pancreas graft loss. Here, we investigated whether the placement of a decompression tube (DT) for the duodenal graft during PTx is clinically useful for preventing DGP. METHODS: This study included 54 patients who received PTx for type 1 diabetes at our institution between 2000 and 2020. Among these cases, 28 included DT placement (51.9%; DT group), and the remaining 26 without DT placement (non-DT group) were used as historical controls for comparison to the cases with DT placement. RESULTS: Among all 54 cases, DGP occurred in 7 (13.0%). The DGP incidence did not significantly differ between the DT group (10.7%, 3/28 cases) and the non-DT group (15.4%, 4/26 cases) (P = .6994). Logistic regression analysis showed that DT placement did not affect DGP risk. Notably, 5 cases in the DT group (17.9%) exhibited adverse effects that were likely the result of DT placement, including bleeding from tube contact (2 cases), enterocutaneous fistula at the DT placement site (2 cases), and intraabdominal abscess around the DT site (1 case). Pancreas graft survival after PTx did not significantly differ between the DT and non-DT groups (P = .6260). CONCLUSIONS: The DT group did not exhibit superior outcomes compared with the non-DT group. This result suggests that DT placement did not have a clinical impact on DGP prevention after PTx.

Different timing and risk factors of cause-specific pancreas graft loss after simultaneous pancreas kidney transplantation.

In cases after pancreas transplantation (PTx), the pancreas graft might be lost for various reasons, including a pancreatoduodenal graft-related complication or patient death with a functioning graft. Although the causes seem to have distinct characteristics, the causes of pancreas graft loss have not been characterized. This study aimed to characterize the causes of pancreas graft loss by analyzing data from a Japanese nationwide registry. This study included 391 patients who received simultaneous pancreas-kidney transplantation among 461 patients with PTx during the study period in approved institutions in Japan. We characterized each cause in terms of the timing of the cause-specific graft loss and preoperative factors associated with graft loss based on nationwide data from a Japanese nationwide registry. Among the 391 cases, 113 lost the pancreas graft due to patient death with a functioning graft (DWFG; n = 34, 44.2%), graft thrombus (n = 22, 28.6%), or chronic rejection (CR; n = 7, 9.1%). Average (± standard deviation) time from PTx to graft loss due to DWFG, graft thrombus, and CR was 3.70 ± 4.36, 0.02 ± 0.01, and 2.37 ± 2.08 years, respectively. Duration of type 1 diabetes mellitus and donor body mass index were significantly associated with pancreas graft loss due to DWFG and graft thrombus, respectively. This characterization showed that the timing and preoperative factors associated with pancreas graft loss were significantly different for different causes of graft loss. These results may inform PTx follow-up protocols to ensure that appropriate care is based on the cause of graft loss.

A case of intraductal papillary mucinous neoplasm developing in the native pancreas after pancreas transplantation treated by total pancreatectomy.

Post-transplant patients reportedly have a higher risk of de novo neoplasms. However, intraductal papillary mucinous neoplasm (IPMN) of the native pancreas after pancreas transplantation (PTx) has not been well investigated. The choice of treatment, especially invasive treatment, for de novo neoplasms in transplant patients should consider their impaired immunity. In this context, we present a case of IPMN developing in the native pancreas of a PTx patient. A 53-year-old man underwent a follow-up abdominal computed tomography scan 6 years after a simultaneous pancreas-kidney transplant for type 1 diabetes mellitus with end-stage diabetic nephropathy requiring hemodialysis. The scan revealed IPMN in the pancreas head; an enhancing internal solid component suggested a high risk of malignancy, indicating surgical resection. Partial pancreatectomy or pancreaticoduodenectomy was anatomically indicated, but considering the insulin-secreting ability of the transplanted pancreas and the potential high risk of postoperative pancreatic fistula due to immune impairment after partial pancreatectomy, total pancreatectomy (TP) was performed. The patient is alive with good pancreas graft function, no signs of indigestion for 18 months after TP, and no evidence of IPMN recurrence. This report should help clinicians characterize de novo IPMN in the native pancreas and determine IPMN therapeutic options for transplant patients.

Current state of pancreas transplantation in Japan based on the nationwide registry.

In Japan, 437 pancreas transplantations (PTx) were carried out between 2000 and 2019. Clinical data for all PTx cases are registered in the Japan Pancreas Transplant Registry of the Japan Society for Pancreas and Islet Transplantation. Here we analyzed the registry data to describe the current status of PTx in Japan. The 437 PTx included 410 from deceased donors (407 from brain-dead and 3 from non-heart-beating donors) and 27 from living donors. We investigated the clinical characteristics of the 410 PTx from deceased donors. The rate of marginal donors using expanded donor criteria was higher in Japan than in other countries. At 1/5/10 years post-PTx, the overall survival rates were 95.8%/94.2%/88.7%, and the graft survival rates were 85.9%/76.2%/67.4% for pancreas and 93.2%/90.8%/78.2% for kidney (non-censored for death). These rates were comparable to those in other countries. When stratified by PTx category, survival was significantly better following simultaneous pancreas-kidney transplantation (SPK) compared to pancreas-after-kidney transplantation (PAK) or PTx alone (PTA). Immunological rejection was more frequently the cause of graft loss in PAK/PTA cases than in SPK cases, potentially contributing to the poorer survival in PAK/PTA. These outcomes highlight two main concerns: substantial incidence of pancreas graft loss, and inferior outcomes after PAK/PTA. Overall, PTx outcome is favorable in Japan, despite the high rate of marginal donors. To improve outcomes, it is important to prevent and manage each cause of pancreas graft loss. Overcoming the poorer survival in PAK/PTA may require new immunosuppressive protocols or allogenic islet transplantation.

Remote Reminiscence Using Immersive Virtual Reality May Be Efficacious for Reducing Anxiety in Patients with Mild Cognitive Impairment Even in COVID-19 Pandemic: A Case Report.

To prevent cognitive decline, non-pharmacological therapies such as reminiscence for mild cognitive impairment (MCI) are required, however, the use of nursing homes was limited due to coronavirus disease 2019 (COVID-19). Therefore, the demand for remote-care is increasing. We hypothesized that immersive virtual reality (iVR) could be used more effectively than conventional reminiscence for anxiety. We first examined the effectiveness and safety of reminiscence using iVR (iVR reminiscence session) in patients with MCI. After COVID-19 imposed restriction on visiting nursing homes, we conducted online iVR reminiscence session (remote iVR reminiscence session) and compared its effectiveness with that of interpersonal iVR reminiscence session (face-to-face iVR reminiscence session). The results of two elderly with MCI suggested that iVR reminiscence could reduce anxiety and the burden of care without serious side effects. The effects of remote iVR reminiscence might be almost as effective as those of face-to-face one.

Outcomes of pancreas transplantation in older versus younger recipients: a comparative analysis.

PURPOSE: The feasibility of pancreas transplantation (PT) in older recipients remains a matter of debate. We examined the influence of recipient age on PT outcomes and identified the prognostic factors for older recipients. METHODS: We compared the outcomes of PT in recipients aged < 50 years (younger group; n = 285) with those in recipients aged ≥ 50 years (older group; n = 94). Prognostic factors in the older group were analyzed by a logistic regression model and the influence of recipient age on survival outcomes were analyzed using propensity score matching. RESULTS: The patient survival rate was significantly worse in the older group (P < 0.001). Patient death from infection or/and multiple organ failure or cardiac/cerebrovascular events was also more frequent in the older group than in the younger group (P = 0.012 and P = 0.045, respectively). A longer duration of diabetes was an independent risk factor of 1-year mortality in the older group. In a propensity score-matched comparison, the older recipients (n = 77) had significantly poorer survival than the younger recipients (n = 77) (P = 0.026). CONCLUSIONS: PT should be considered with appropriate caution, especially for older recipients with a long duration of diabetes.

Impact of the revision of the law on pancreatic transplants in Japan-An analysis of the Japanese Pancreas Transplants Registry.

BACKGROUND: In Japan, it has been about 10 years since the revision of the law on donating brain-dead organs. The present study compared the outcomes of pancreatic transplant before and after the revision of the law. METHODS: The 437 patients who had received pancreas transplantation were divided into two groups according to the time when pancreas transplantation was performed between era 1 (before the revision) and 2 (after the revision), and compared in the patient and pancreas graft survival. RESULTS: While the annual number of brain-dead donors was <10 in era 1, and this number significantly increased in era 2 to >50. This resulted in an increased number of pancreas transplantations: >30 cases per year. The comparison data after a propensity score-matched analysis revealed that the death-censored pancreatic graft survival at 1, 3, and 5 years after pancreas transplantation in era 2 was 94.9%, 92.0%, and 92.0%, which, while lacking significance, tended to be better than the values of 90.5%, 83.1%, and 78.2%, respectively, in era 1. CONCLUSIONS: The revision of the law on donating brain-dead organs increased the number of pancreas transplantations. Technical improvements in surgery due to increased experience with performing pancreas transplants may help improve pancreatic graft survival.

Clinical impact of pancreas donor age on outcomes following pancreas transplantation: Analysis of a nationwide registry in Japan.

OBJECTIVES: Clinical impact of pancreas donor age on pancreas transplantation (PTx) outcome has not been well investigated. Here we analyzed the nationwide PTx registry in Japan to assess posttransplant outcomes in donor age-stratified groups. METHODS: This study included 410 cases of PTx performed in Japan between 2000 and 2019. Analyses were performed using clinical data from the Japan Pancreas Transplant Registry of Japan Society for Pancreas and Islet Transplantation. RESULTS: The 410 PTx cases were classified based on donor age: <10 years (n = 10, 2.4%), 10-19 years (n = 30, 7.3%), 20-29 years (n = 64, 15.6%), 30-39 years (n = 75, 18.3%), 40-49 years (n = 114, 27.8%), 50-59 years (n = 90, 22.0%), and ≥60 years (n = 27, 6.6%). The incidence of early pancreas graft loss (8.9%, 36/410 cases) did not exhibit a significant linear correlation with donor age. Posttransplant pancreas graft survival (1-/3-/5-/10-year rates of 85.9%/80.6%/76.2%/67.4% among all cases) was also not significantly associated with donor age. CONCLUSION: Pancreas donor age was not significantly associated with posttransplant outcome. This finding supports the use of expanded criteria donors, with regards to pancreas donor age, for PTx in cases of type 1 diabetes mellitus.

Impact of an older donor pancreas on the outcome of pancreas transplantation: single-center experience of the expansion of donor criteria.

PURPOSE: The impact of using an older donor pancreas on the clinical outcomes of pancreas transplantation (PTx) is unknown. We investigated this by comparing the outcomes of PTx using older and younger donors in a single Japanese center, to expand the donor criteria. METHODS: The subjects were 54 patients who received PTx from deceased donors in our institution. Posttransplant outcomes were analyzed based on donor age, with older donors defined as those aged ≥ 60 years. RESULTS: The donors included six older (11.1%; aged 64 ± 4 years) and 48 younger donors (88.9%; aged 43 ± 12 years). There was no significant difference in the donor age between the recipients with vs. those without postoperative complications or between those with vs. those without early pancreas graft loss. Long-term outcomes, including overall, pancreas graft, and kidney graft survival after PTx, did not differ significantly between the older and younger donor groups. Graft age, defined as the age of the donor at the time of procurement plus the graft survival period, was not associated with graft loss. CONCLUSION: Our results suggest that post-transplant outcomes of PTx using pancreas from older donors aged ≥ 60 years are comparable to those using pancreas from younger donors, and support expansion of the donor pool for transplantation therapy for type 1 diabetes mellitus.

Impact of Pancreas Transplantation on the Patient Survival-An Analysis of the Japanese Pancreas Transplants Registry.

BACKGROUND: The impact of pancreas transplantation, including kidney transplantation on patients' life prognoses, is unclear in Japan. An analysis of the data of the Japan Pancreas Transplant Registry was performed to compare the patient survival between on the waiting list and after pancreas transplantation, and investigate the factors that affect the patient survival after pancreatic transplantation. METHODS: The life prognoses of 361 patients who underwent pancreas transplantation from 2000 to December 2018 were examined. RESULTS: The survival rates at 1, 5, and 10 years on the waiting list were 98.4%, 90.3%, and 78.1%, respectively, while those after transplantation were significantly improved (p = 0.029) at 100%, 97.5%, and 88.9%, respectively. Furthermore, the survival rates of patients waiting for simultaneous pancreas and kidney transplantation (SPK) at 1, 5, and 10 years were 98.2%, 89.4%, and 75.4%, respectively, while those after SPK were also significantly improved (p = 0.026) at 100%, 94.6%, and 88.8%. The multivariable analysis revealed that the duration of diabetes before surgery was the only independent risk factor (hazard ratio = 1.095, p = 0.012) that affected the patient survival after SPK. CONCLUSION: Pancreas transplantation was found to improve the life prognosis of patients with type 1 diabetes, especially those with end-stage renal failure waiting for SPK.

Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages.

Disturbed activation of autophagy is implicated in the pathogenesis of inflammatory bowel disease. Accordingly, several autophagy-related genes have been identified as Crohn's disease susceptibility genes. We screened the autophagy activators from a library including 3,922 natural extracts using a high-throughput assay system. The extracts identified as autophagy activators were administered to mice with 2% dextran sodium sulfate (DSS). Among the autophagy inducers, Sanguisorba officinalis L. (SO) suppressed DSS-induced colitis. To identify the mechanism by which SO ameliorates colitis, epithelial cell and innate myeloid cells-specific Atg7-deficient mice (Villin-cre; Atg7f/f and LysM-cre; Atg7f/f mice, respectively) were analyzed. SO-mediated inhibition of colitis was observed in Villin-cre; Atg7f/f mice. However, SO and a mixture of its components including catechin acid, ellagic acid, gallic acid, and ziyuglycoside II (Mix4) did not suppressed colitis in LysM-cre; Atg7f/f mice. In large intestinal macrophages (Mφ) of Atg7f/f mice, SO and Mix4 upregulated the expression of marker genes of anti-inflammatory Mφ including Arg1, Cd206, and Relma. However, these alterations were not induced in LysM-cre; Atg7f/f mice. These findings indicate that SO and its active components ameliorate DSS-induced colitis by providing intestinal Mφ with anti-inflammatory profiles via promotion of Atg7-dependent autophagy.

Are the outcomes of Japanese pancreas transplantation utilizing extended-criteria donors acceptable? A propensity score matching analysis for donors <50 or ≥50 years old.

In Japan, about 30% of pancreatic transplant donors are ≥50 years old, making them "extended-criteria donors (ECDs)." We analyzed 361 cases of transplantation involving donors from the Japanese pancreas transplantation registry to evaluate the acceptability of ECDs. The patient survival rates at 1, 5, and 10 years after transplantation were 96.6%, 94.9%, and 88.3%, respectively. The survival rates of pancreas and kidney grafts at 1, 5, and 10 years were 85.3%, 74.8%, and 70.6%, and 94.2%, 90.9%, and 80.9%, respectively. Multivariate analysis revealed that no particular donor factors significantly influenced the pancreatic graft survival. Patients were divided into 2 groups: donors ≥50 years old (older group) and those <50 years old (younger group). After propensity score matching, the overall pancreatic graft survival at 1, 5, and 10 years after transplantation in the older group was 82.8%, 71.8%, and 69.5%, respectively, which was almost the same as in the younger group (84.9%, 70.2%, and 67.4%, respectively). No donor factors markedly influenced the pancreatic graft survival, and the outcomes of pancreas transplantation from ECDs ≥50 years old were comparable to those from younger donors.

Pancreas transplantation for type 1 diabetes in Japan: past, present and future prospects.

In Japan, the first pancreas transplantation was performed in 1984 from a brain-dead donor; subsequently, however, the concept of brain death became a social issue. Thereafter, the "Organ Transplant Act", which enables brain-dead transplantation, was enacted in 1997, and then revised in 2010 so that donation after brain death became possible only with the consent of the family. Under the recipient selection and registration system developed after the enactment of the "Organ Transplant Act", more than 400 pancreas transplants have been carried out at facilities certified for brain-dead pancreas transplantation in Japan. Of the 410 total cadaveric pancreas transplants performed by the end of 2019, the patient survival and pancreatic and kidney graft survival rates were considered to be comparable to those in the United States and Europe despite the high frequency of marginal donors. Minimally invasive allogenic islet transplantation came to be covered by national health insurance in 2020 following good outcomes of a recent trial. Furthermore, to overcome the serious donor shortage in Japan, development of xenogeneic islet transplantation and regenerative medicine using stem cells is in progress, with xenotransplantation using porcine islets appearing particularly promising.