會田 直弘

OBJECTIVES: About 90% of Japanese kidney transplantations are conducted from living donors, and their safety and the maintenance of their renal function are critical. This study aims to identify factors that affect the compensation of renal function in living kidney donors after donor nephrectomy. METHOD: In a retrospective cohort study, we reviewed data from 120 patients who underwent nephrectomy as living kidney transplant donors in our department from 2012 to 2021. Univariable and multivariable linear regression analyses were performed for donor factors affecting renal function after donor nephrectomy. RESULT: The multivariable linear regression model revealed that the donor's age (p = 0.025), preoperative estimated Glomerular Filtration Rate (eGFR) (p < 0.001), and hemoglobin A1c (HbA1c) (p = 0.043) were independent risk factors for eGFR at six months after nephrectomy. The eGFR deterioration was more strongly associated with age in females than in males, whereas higher HbA1c values were more strongly associated with eGFR deterioration in males. Higher donor age and higher HbA1c each enhance the deterioration of eGFR six months after living donor nephrectomy. The data suggest that old age in especially female donors and preoperative higher HbA1c in male donors have a harmful impact on their renal function compensation.

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.

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.

2010年の改正臓器移植法施行後より、脳死下臓器提供が増加したが心停止下臓器提供は減少し、結果、献腎移植件数は横ばいである。深刻な日本の臓器提供不足の現状を鑑み、心停止下臓器提供を増やすことは重要な課題の一つである。心停止ドナーを増やすことは以前より各地域における啓蒙活動が行われており、その活動は脳死下臓器提供の増加へもつながっていると考えらる。しかし、これらの活動が奏功し心停止ドナーが増えた時、我々移植医が対応可能であるかは疑問が残る。外科医の減少や脳死下臓器提供の増加により、数日間の待機を要する心停止下臓器提供への対応はさらに困難となっている。また、時間的には脳死下臓器提供よりさらにシビアな対応を迫られる心停止下臓器採取手技の次世代への継承も今後の大きな課題である。一方、一部の海外では肝や肺などの腎以外の心停止臓器提供が盛んに検討されている。しかし、これは日本の状況とは大きく異なり、レスピレーターオフが大前提である。以上から、心停止下臓器提供増加に向けて本邦でもレスピレーターオフの導入が検討される必要があると考える。日本救急医学会、日本集中治療医学会、日本循環器学会からは3学会合同の終末期医療に関するガイドラインが出されており、その中にレスピレーターオフについても言及されている。本邦におけるレスピレーターオフに関する現状、課題、今後について論じたい。

我々は本邦登録データから以下のファクトについて報告してきた.・膵腎同時移植（SPK）は患者生存を向上し,膵グラフト生着も良好である.・糖尿病歴が30年を超えると移植後の患者生存は悪化していく.・60歳以上からの膵提供では膵グラフト生着は劣る可能性が示唆された.・腎移植後膵移植（PAK）は,先行した腎移植による影響が大きく,待機患者の生命予後の改善効果は認められない.・PAKでは膵グラフト生着は不良であるが,ATGにより,グラフト生着はSPKと同等であった.・膵単独移植（PTA）は待機患者の生命予後の改善効果は認められない.・PTAでは膵グラフト生着も不良で,ATGによる導入でもグラフト生着の改善は期待できない.・先進医療で実施した膵島移植では,グラフト膵の需要と供給のバランスは供給が上回っている.・脳死ドナー膵からの膵島分離成績は心停止ドナー膵より良好で,移植機会の増加が期待できる.上記から膵臓移植と膵島移植のallocationについて考察すると,①SPKは患者生命予後の観点から,できるだけ早期の移植を推進すべきである.②腎移植後の1型糖尿病患者にはPAKと腎移植後膵島移植（IAK）の治療成績を説明し,どちらかの治療選択,もしくは両者を待機できるシステムを構築する.③腎不全を伴わない1型糖尿病患者には保険収載後,膵島移植が積極的に勧められるのではないか.と考えられる

＜背景＞I型糖尿病患者に対する移植医療の適応を考える上で,患者生命予後に与える影響を知ることは重要である.本邦膵臓移植レジストリデータとJOTの膵臓移植待機患者の生命予後を比較検討した. ＜方法＞膵臓移植(n=361)と,待機患者(n=699)の生命予後と比較検討した. ＜結果＞待機患者の1,5,10年の生存率はそれぞれ98.4％,90.3％,78.1％であったが,移植後の生存率はそれぞれ100％,97.5％,88.9％と有意に改善していた(P=0.029).さらに腎臓同時移植(SPK)待機患者の1,5,10年の生存率はそれぞれ98.2％,89.4％,75.4％であったのに対し,SPK後はそれぞれ100％,94.6％,88.8％と生存率は有意に改善していた(P = 0.026).Cox比例ハザード回帰による多変量解析では,手術前の糖尿病期間がSPK術後の患者生存に影響を与える独立した危険因子(ハザード比= 1.095,P = 0.012)であることが明らかにとなった.術前の糖尿病歴が35年以上では,移植後の生予後は有意に悪化することが示唆された. ＜結語＞膵臓移植は,1型糖尿病の患者,特に腎不全合併例にSPKを施行することによって,生命予後を改善することが明らかとなった.術前の糖尿病歴が短い方が移植後の生命予後の改善が図られるため,できるだけ早期の移植が肝要であると考えられた.

【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。

症例は30歳代,女性.糖尿病歴21年,透析歴5年で2018年7月に脳死下膵腎同時移植を施行された.ドナーは6歳以下の男児で,死因は低酸素脳症であった.移植直後よりインスリン,透析離脱し,以降もHbA1c 5.1%前後,Cre 0.8mg/dl前後を維持していた.移植後142日目に下血を認め,再入院した.造影CTでは小腸の一部が拡張し,粘膜の浮腫,造影異常を認め,出血源と判断したが,保存的に軽快した.移植後176日目に発熱のため,再々入院となった.PTLDも懸念し. PETを施行した.PETでは一部の拡張腸管のみに集積を認めた.後日,腸追及検査を施行したところ,この拡張腸管には腸追求によるガストログラフィンが流入しなかったため,Blind loop syndrome（BSL）と診断した.患者の同意がなかなか得られず,移植後234日目にようやく拡張腸管（blind loop）の切除術を行い,以降,発熱,下痢は軽快した.しかし,この手術前からAMY,Lipase,Creの上昇を認め,手術前後にステロイドパルス療法1回ずつ施行した. この間2回の移植腎生検を施行したが,診断はいずれも拒絶反応であった. AMY,Lipase,Creは一時低下するものの再上昇を認めるため,2回目の腎生検後,rATGを投与し,以降はHbA1c 5.1%,Cre 1.4前後を維持している.

2015年3月14日～15日に熱海で開催された日本移植学会第2回次世代リーダー養成コースに参加した。普段からほとんど休みがない中、当初は貴重な土日を使い、自己負担もありながら、参加することに正直抵抗があった。養成コースは、1日半程度缶詰状態であったが、他の参加された先生たちの経歴、研究成果、臨床に携わっていることが拝聴でき、それが非常に勉強になった。また、夜は本養成コースのもう一つのメインである親睦会があり、夜中まで飲み明かし、移植医療の未来について語り合った。その後、5年が経過している。当時、一緒に養成コースに参加した他施設、他臓器移植の先生と今でも摘出現場や、学会、会議などで席を共にする機会が多くある。一夜でも寝食を共にした先生たちとは開襟して話しやすく、仕事もしやすい。それぞれの臓器移植の問題点や目標を共有出来たことは、自分が従事している腎移植、膵移植にも生かされ、励みにもなっている。この経験は貴重な経験であり、今後、参加候補となった若い先生には是非、積極的に参加してほしい。そして、世代間で移植医療に関する諸問題を共有し、次世代の移植医療を担う人材として、是非この日本移植学会次世代リーダー養成コースを利用していただきたい。

T細胞性拒絶の制御により,移植成績は目覚ましく発展してきたが, 抗体産生を含むB細胞系を制御には現在も課題が残る.現在までの知見、今後の課題を明らかとするために,厚生労働科学研究費補助金免疫アレルギー疾患実用化研究事業（移植医療技術開発研究分野）「臓器移植における抗体関連型拒絶反応の新規治療法の開発に関する研究（江川班）」の事業として『臓器移植抗体陽性診療ガイドライン2018年版』が作成、出版された.膵移植に関しては、16のクリニカルクエスチョン（CQ）に対して、14名の膵移植実務者委員に協力を依頼し,各CQに対しシステマティックレビューを行った.2020年を迎え、同ガイドラインの改定が求められている.前回のシステマティックレビュー以降、膵移植における抗体陽性に関する新たな文献は3件のみであった.一方、江川班においては既存抗体陽性症例と抗体関連型拒絶（AMR）症例に対するリツキシマブの保険承認を目指した他施設共同臨床研究が行われている.膵移植においてはAMRに対するリツキシマブ投与例は無かったが,既存抗体陽性の4例にリツキシマブ投与が臨床試験として行われた.今後、これらから得られた知見を盛り込んだ新たなガイドラインの改定を目指していく予定である.

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.

Lymphoepithelioma-like carcinoma in the digestive tract is rare, particularly in the rectum. A 60-yearold woman diagnosed with rectal cancer was referred to our clinic for laparoscopic abdominoperineal resection of the rectum. The resected specimen was a type 2 lesion, 35 × 30 mm in size, located along the pectinate line of the left rectal wall. Histopathological staining showed a sheet of foci and a cord-like arrangement with loosely coupled and isolated tumor cells associated with a stroma composed of dense lymphocyte/plasma cell infiltrates, representative of lymphoepithelioma-like carcinoma. The patient was diagnosed with lymphoepithelioma-like carcinoma of the rectum, underwent resection without adjuvant chemotherapy, and remains disease free. This report describes a valuable case of rare lymphoepitheliomalike carcinoma of the rectum.

A 91-year-old man was referred to our hospital with intermittent dysphagia. He had undergone esophagectomy for esophageal cancer (T3N2M0 Stage III) 11 years earlier. Endoscopic examination revealed an anastomotic stricture; signs of inflammation, including redness, erosion, edema, bleeding, friability, and exudate with white plaques; and multiple depressions in the residual esophagus. Radiographical examination revealed numerous fine, gastrografinfilled projections and an anastomotic stricture. Biopsy specimens from the area of the anastomotic stricture revealed inflammatory changes without signs of malignancy. Candida glabrata was detected with a culture test of the biopsy specimens. The stricture was diagnosed as a benign stricture that was caused by esophageal intramural pseudodiverticulosis. Accordingly, endoscopic balloon dilatation was performed and antifungal therapy was started in the hospital. Seven weeks later, endoscopic examination revealed improvement in the mucosal inflammation; only the pseudodiverticulosis remained. Consequently, the patient was discharged. At the latest follow-up, the patient was symptomfree and the pseudodiverticulosis remained in the residual esophagus without any signs of stricture or inflammation.

The number of patients undergoing lower anterior resection for rectal cancer has been increasing recently, and therefore, the number of patients undergoing covering loop ileostomy and ileostomy closure is increasing. We performed laparoscopic ileostomy closure safely on 5 patients between 2012 and 2014. The essential points of this technique are that laparoscopy helps to detect adhesion point of the ileostomy and the abdominal wall, and that laparoscopic adhesiolysis is possible if the adhesive small bowel is tight. No patients experienced any complication after the procedure. Laparoscopic adhesiolysis was performed for 2 patients who had a tight adhesive small bowel, and it was not necessary to widen the incision. This is the first report from Japan in which loop ileostomy closure was performed with laparoscopic assistance. This technique is effective for preventing the complications related to loop ileostomy closure.

症例は64歳男(O型)で、13年前に血液透析導入となり、妻(A型)をドナーとする血液型不適合生体腎移植を希望した。入院時の抗A抗体価はIgMが64倍、IgGが4096倍以上と著明高値で、移植予定日14日前にリツキシマブ200mg/dayを投与し、同日よりミコフェノール酸モフェチル1000mgを開始した。さらに10日前よりcyclosporinを開始し、6、4、2日前に二重濾過血漿分離交換を、1日前に血漿交換を行って減感作療法としたが、抗体価のリバウンド現象を認めたためいったん延期した。同減感作プロトコールを1クール追加し、移植当日にリツキシマブ200mgをさらに投与し、移植を施行した。移植当日のIgG抗A抗体価は256倍であった。術後経過は良好で血清クレアチニン値は速やかに低下し、IgG抗A抗体価も徐々に低下して32〜64倍で維持され、その後も上昇はない。

A patient was 44-year-old-woman. She noticed a right breast mass 10 months ago. The mass got growth, so she visited our surgery. On the physical examination, two masses were palpable on the right upper outer quadrant. On the ultrasonography, two masses were detected as irregular hypoechoic area, so we suspected multiple breast cancer. We performed biopsy for larger mass and diagnosed invasive ductal carcinoma. We performed mastectomy and sentinel lymph node biopsy (SN). We performed SN with Radio colloid （99m-Tc) and Blue Dye. We dissected two axially sentinel lymph nodes （SLNs）, which was negative, and some lymph nodes around SLN （non-SLNs）. Pathologically, larger mass was diagnosed as papillotubular carcinoma. Because smaller one included lymph node component in the same film, it was diagnosed as an intramammary lymph node metastasis. One of non-SLN was also diagnosed as a metastasis. It is too difficult to have a preoperative diagnosis of intramammary lymph node metastasis. Generally, intramammary lymph node metastasis is a poor prognostic factor. Breast cancer with intramammary lymph node metastasis could spread to axial non-SLN metastasis, without axial SLN metastasis. We suggest that intramammary lymph node metastasis is an important factor of staging breast cancer.