伊藤 泰平

OBJECTIVES: Type 1 diabetes mellitus (T1DM) patients with diabetic kidney disease-induced kidney failure have a significantly impaired quality of life (QOL), resulting in a high level of physical, mental, and social anxiety. In this study, we evaluated the QOL of T1DM patients on the list for pancreas transplantation (PTx) at their registration, and determined whether PTx improved their QOL. METHODS: There were 58 patients (men/women, 22/36; mean age, 42.8±8.0 years) with T1DM and who were registered on the waiting list for PTx. Quantitative QOL assessment was performed using the Medical Health Survey Short Form (SF-36) version 2. Changes in the QOL before and after PTx were also examined in 24 of these patients. RESULTS: The mean value of each endpoint and the summary score of the SF-36 physical (PCS), mental (MCS), and role (RCS) components were all below the national normal level at PTx registration. No significant difference in QOL scores was observed in the intergroup comparison of 35 patients on dialysis, 13 patients without dialysis, and ten patients after kidney transplantation. The 24 patients who underwent PTx showed improvement in PCS, MCS, and most SF-36 scores. CONCLUSION: T1DM patients waiting for PTx had a decreased QOL, regardless of dialysis, and PTx improved their QOL.

OBJECTIVES: Delta C-peptide derived by the glucagon stimulation test is a reliable value for the evaluation of the pancreatic endocrine function after pancreas transplantation. We examined the associations between delta C-peptide as pancreatic graft endocrine function and donor background factors. METHODS: Sixty-five cases of pancreatic transplantation from brain-dead donors, which were performed in our facility, were enrolled in this study. Enrolled recipients underwent a glucagon stimulation test within 1 to 3 months after transplantation to evaluate the pancreatic graft endocrine function with delta C-peptide to compare donor background factors. RESULTS: The following factors were associated with significant deterioration of the delta C-peptide: age of 50 years or greater, death from cerebrovascular accident, hemoglobin A1c level of 5.6% or greater, creatinine level of 1.0 mg/dL or greater, C-reactive protein level of 25 mg/dL or greater, and sodium level of 150 mmol/L or greater. In addition, increased numbers of these donor factors indicated significantly greater deterioration of the posttransplant pancreatic endocrine function (P < 0.001). CONCLUSIONS: To secure insulin independence after pancreas transplantation, which means maintaining a delta C-peptide level of 1.0 ng/mL or greater on a glucagon stimulation test, the utilization of donors, who possesses more than equal to 3 of the donor factors identified in this study, should be carefully considered.

脳死下・心停止後臓器摘出における勤務実態と就労管理・補償・待遇の現状に関する日本移植学会アンケート調査より、膵臓移植における移植時レシピエント年齢と移植後予後との関連性について報告した。解析対象は過去約19年間の膵臓移植症例379例(24〜69歳、中央値44歳)で、経過観察期間は6日〜18.8年(中央値4.95年)であった。レシピエントを50歳未満285例(若年群)と50歳以上94例(高齢群)に分け、傾向スコアマッチングによる検討を行った。結果、移植後1年以内の死亡率は年齢の上昇に伴って高くなる傾向を認め、高齢群は若年群と比較して死亡率が高かった。また、糖尿病歴は若年群では予後に影響していなかったが、高齢群では予後に影響を与えていた。

BACKGROUND: In Japan, donations after circulatory death kidney transplantation are widely performed due to legislation delays. The number of donations after brain death kidney transplantations is increasing, but the target remains unmet. We reviewed the outcomes of donation after circulatory death in Japan. METHODS: We analyzed 2923 deceased kidney transplantations (2239: donation after circulatory death (DCD), 684: donation after brain death (DBD)) performed in Japan from 2000 to 2019. The outcomes of the DCD and DBD groups were compared. We examined the risk factors for graft loss in the DCD group. RESULTS: The 5-year patient survival and death-censored graft survival rates of the DCD group, obtained by propensity score matching, were 93.6% and 95.2%, respectively, which were equivalent to 94.2% and 93.8%, respectively, obtained in the DBD group. Older donors (≥ 50 years) and prolonged cold ischemia time (≥ 12 h) were risk factors for graft loss; in the presence of these, graft survival was lower in the DCD group. CONCLUSIONS: Older donors and prolonged cold ischemia time reduced graft survival in the DCD group. Proper evaluation of donors and careful preparation for transplant surgery are, therefore, essential to ensure good transplant outcomes.

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.

膵移植後に抗体関連型拒絶反応(AMR)を発現し、rituximabを使用した4例を報告した。移植時年齢は30歳代から50歳代で、男女各2例であった。AMRは移植後40日目から143日目に診断され、rituximabは拒絶反応発現から最短で1日、最長で20日に1回投与されていた。投与量は81mg/bodyが1例、200mg/bodyが3例で、AMR治療後の膵グラフト生着は1例(25%)で得られていた。有害事象としてはサイトメガロウイルス抗原血症による感染症が1例、骨髄抑制が2例で認められたが、いずれも回復し、患者生命予後に影響を与える有害事象はみられなかった。

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.

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.

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.

【背景】膵臓移植においてレシピエント年齢が移植成績に与える影響は明らかではない。本邦登録データを用いて、レシピエント年齢と移植後予後との関連性について検討した。【対象・方法】2000年から2019年4月までに施行された379例（生体を除く）の膵臓移植患者を後方視的に検討した。主要評価項目を患者生存期間とし、比例ハザードモデルに基づき50歳をカットオフとし若年群（n=285）と高齢群（n=94）とに群別。両群間の患者背景を傾向スコアでマッチさせ、生存期間、術後合併症、死因を比較した。また高齢群における予後因子を検討した。【結果】傾向スコアマッチ後、高齢群(n=77)の５年生存率は86.9%と、若年群(n=77)の97.1%と比べ有意に低かった(P= 0.026)。一方、グラフト生着率、術後合併症発生率においては両群に有意な差は認めなかった。死因別では高齢群で感染または多臓器不全、心・脳血管系イベントが有意に多く、高齢群で観察期間中に死亡した16例のうち10例は術後1年以内であった。多変量解析の結果、高齢群における術後1年以内の死亡リスク因子は糖尿病罹患期間であった（P= 0.005）。【結語】50歳以上のレシピエントに対する膵臓移植は、50歳未満と比較して有意に移植後の生存率が不良であるが、糖尿病歴が短い症例ほど生存率が改善する可能性が示唆され、より早期の移植が望ましいと考えられた。

Background: The pool of brain-dead donors (BDDs) was increased with the revision to the relevant law in 2010, and islet transplantation from BDDs was started in 2013. The present study assessed the influence of using pancreases from BDDs on islet transplantation in Japan. Methods: The donor information registered with the secretariat of islet transplants from 2012 was reviewed, and the results of 86 clinical islet isolations performed in Japan between 2003 and 2018 with non-heart-beating donors (NHBDs) (n = 71) and BDDs (n = 15) were investigated. Results: The number of cases for which donor information was registered with the secretariat of islet transplants increased to 1.84 cases/month from 2013 to 2018 in comparison to 1.44/month in 2012, when only NHBDs were used. The median pancreatic islet yield was 275,550 IEQ (Islet equivalents) in the NHBD group but 3,627,000 in the BDD group, which amounted to a statistically significant difference (p = 0.02). As a result, 38/71 cases (53.5%) were achieved successful islet isolation (&gt 5000 IEQ per recipient weight (kg)) was achieved in 38/71 cases (53.5%) in the NHBD group, and 12/15 cases (80.0%) in the BDD group thus, the rate of successful islet transplantation was higher in the BDD group. Conclusion: The use of pancreases from BDDs has increased the overall number of cases for which donor information is registered with the secretariat of islet transplants and has improved the performance of islet isolation, thereby increasing the probability of successfully achieving islet transplantation.

OBJECTIVES: Contrast-enhanced ultrasonography can evaluate microcirculation. Thus, we used contrast-enhanced ultrasonography in evaluating pancreas graft perfusion and examined the relationship between graft circulation and function.METHODS: Contrast-enhanced ultrasonography was performed in 17 cases within 24 hours and at 1, 3, 5, 7, 14, 21, and 28 days after transplantation (Tx). The time between the time to peak intensity in the parenchyma and that in the vein was defined as delta-Tp(P-V). Graft function was evaluated with oral glucose tolerance test (OGTT) at 1 and 3 months after Tx, and glucagon stimulation test at 1 month after Tx.RESULTS: Differences in delta-Tp(P-V) between individual cases were more significant early after Tx, and delta-Tp(P-V) within 24 hours (delta-Tp[P-V]24h) was used in the subsequent analysis. Delta-Tp(P-V)24 hours showed a negative correlation with C-peptide increment in the glucagon stimulation test and the area under the curve of insulin level in oral glucose tolerance test. The cases were divided into the following 2 groups: the standard group (delta-Tp[P-V]24h ≤6.10 seconds) and the delayed group (&gt;6.10 seconds). The area under the curve of insulin level increased significantly from 1 to 3 months after Tx in the standard group only.CONCLUSIONS: These results suggest that delta-Tp(P-V)24 hours affects insulin secretion after Tx. Contrast-enhanced ultrasonography is useful in predicting endocrine function of the graft.

De novo renal cell carcinoma (RCC) rarely occurs in kidney allografts; however, the risk of RCC in these patients is 100-fold that of the general healthy population. Although total nephrectomy has been the standard treatment for kidney allograft RCC, several authors have reported that early-stage RCC in kidney allografts was successfully treated with nephron-sparing surgery. We herein describe a new procedure involving renal autotransplantation and extracorporeal nephron-sparing surgery, which was performed to treat de novo RCC near the hilum of a transplanted kidney. In the 22 months since transplantation, the patient's renal function has been favorable, and no recurrence has been observed. In conclusion, renal autotransplantation is a feasible technique for the treatment of RCC in kidney allografts, especially RCC located near the hilum.

2012年に藤田保健衛生大学に臓器移植科が開設され、完全後腹膜鏡下ドナー腎採取術を導入した。2012年10月から2015年9月までに39例のドナー腎採取を施行し、その間、以下の改良点を加えた。A.3ポート操作から単孔式コンパート 脈管切離を残すのみとなった段階で、1stポート創と2ndポート創を延長し、GelPortを装着、単孔式にコンパートして腎を採取する。同法は(1)筋繊維走行に沿って解放するため筋肉は切離しない(2)温阻血時間の短縮が見込まれる利点がある。温阻血時間は5.9±4.3分から2.7±0.7と有意に短縮され、疼痛緩和から術後入院期間も6.3±1.3日から5.5±0.7と有意に短縮された。B.3D video systemの導入 導入により平均出血量は2D視野で76.7±84.5gであったのに対し、3D視野で36.1±29.6と減少した。(著者抄録)

腎移植患者19名(男性14名、女性5名、献腎移植7名・生体腎移植12名)を対象に、消化器悪性腫瘍に対し末梢血液全血細胞を用いた網羅的遺伝子発現解析を行い、スクリーニング検査としての有用性について検討した。なお、移植時年齢は23〜64歳(中央値46歳)、検査時年齢は33〜70歳(中央値54歳)、悪性腫瘍の既往は腎癌3例、骨肉腫と甲状腺癌1例、子宮頸癌1例、悪性リンパ腫1例であった。遺伝子変動数が陽性と判断されたのは19回、境界が18回、陰性が16回であった。健常人と比べたところ、腎移植患者においては有意に増加していた。21遺伝子のパターン分析から境界と判断されたのは25回、陰性が28回であった。階層クラスタリング解析により陽性と判断されたのは2回、境界が11回、陰性が40回であった。アルゴリズムを用い、胃/大腸癌、膵臓癌、胆道癌の有無を判別し、最終的に陽性と判断された例はなかった。

BackgroundA total of 26 pancreas transplants from brain dead donors, including 21 simultaneous pancreas and kidney (SPK) transplantation procedures, have been performed at Fujita Health University Hospital since the new pancreas transplant program was initiated in August 2012. The objective of this study is to investigate the outcomes of pancreatic transplantation in our facility in first 3 years of the program. MethodsThe background characteristics of the donors and the outcomes of 26 pancreas transplant recipients were analyzed. ResultsThe mean age of the recipients was 44.0years, and all recipients had a long-term history of diabetes (mean: 30.2years). In the SPK cases, the patients also had a long history of hemodialysis (mean: 6.3years). Although the average donor age was 41.0years and more than half of the donors were marginal donors (defined according to Kapur's criteria and Troppmann's criteria), the patient survival and pancreatic graft survival rates were 100% and 91.7%, respectively. Unfortunately, two recipients experienced graft failure due to graft thrombosis, which resulted in graft loss. ConclusionsThe new pancreas transplant program at Fujita Health University has provided excellent outcomes for patients with type 1 diabetes.

63歳、男性。両下肢浮腫を主訴に受診。造影CTで直径5cm大の左腎腫瘍と肝静脈流入部直下まで達する下大静脈腫瘍塞栓を認め、腫瘍塞栓により下大静脈は完全閉塞していた。IVCフィルター留置後、左腎癌(eT3bN0M0)の診断で左腎摘除術および腫瘍塞栓摘出術を予定した。術中、右腎茎部周囲および下大静脈近傍の側副血行路からの出血が持続し血圧維持が困難となったため、やむを得ず右腎を摘出した。また、腫瘍塞栓が血管壁と強固に癒着していたため、下大静脈を離断し左腎とともに合併切除した。一旦閉創後、右腎を右腸骨窩に自家腎移植した。病理診断はClear cell carcinom、G2、pT3bN0であった。術後に腎不全を認めたが持続血液透析を行い、術後86日目に透析を離脱し社会復帰している。(著者抄録)

<p>【Objective】Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplant malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas and biliary tract cancer).<br/>【Methods】Nineteen patients were included in this study, and a total of fifty-three gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2,665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm.<br/>【Results】The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison to the general population (1,091±63 vs. 823±94, p=0.0024). The number of genes with altered expression decreased after the induction of mTOR inhibitor (1,484±227 vs. 883±154, p=0.0439). No cases of possible digestive cancer were detected in this study period.<br/>【Conclusion】The gene expression profiling of peripheral blood samples may be a useful and non-invasive diagnostic tool that allows for the early detection of cancer of the digestive system.</p>