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The COVID-19 vaccine will be safe and effective in solid organ transplant recipients (SOTs). However, the blunted antibody responses were also of concern. Few studies have reported prolonged serologic follow-up after 2 doses of BNT162b2 vaccine in SOTs. We performed a single-center, prospective observational study of 78 SOTs who received 2 doses of BNT162b2 vaccine. We identified the trajectory of antibody titers after vaccination among SOTs with or without mycophenolate mofetil (MMF) or withdrawn from MMF. We found low seroconversion rates (29/42: 69%) and low antibody titers in SOTs treated with MMF. An inverse linear relationship between neutralizing antibody titers and MMF concentration was confirmed in restricted cubic spline plots (P for effect.01, P for nonlinearity = .08). For the trajectory of antibody responses, seroconversion and improved antibody titers were observed after withdrawal from MMF in SOTs who showed seronegative or low antibody titers at the first visit after 2 doses of vaccine (P for effect.01, P for nonlinearity.05, and P for interaction.01). We identified increased B-cell counts after withdrawal from MMF (P.01). The recovery of antibody responses was seen in SOTs withdrawn from MMF. The trajectories of antibody responses were modified by MMF administration.

Objectives High concentrations of low-density lipoprotein cholesterol (LDL-C) are a risk factor for cardiovascular disease. We validated the efficacy of the Martin method is useful in the estimation of LDL-C concentrations was validated in Japanese populations and derived a modified Martin method for easy laboratory information system applications. Methods We created 3 subject groups, including 2664 health check-up participants registered with the Resource Center for Health Science, 29,806 clinical patients (A) in the Gifu University Hospital, and 113,716 clinical patients (B) in the Fujita Health University Hospital. Each method to estimate serum LDL-C concentrations (Friedewald formula, Martin method and modified Martin method) was validated by correlation analysis with serum LDL-C concentrations measured using a direct method Results The correlation coefficients with the direct method in terms of the Friedewald formula, Martin method, and modified Martin method were 0.963, 0.972 and 0.970 in the health check-up participants; 0.946, 0.962 and 0.961 in clinical patients A; and 0.961, 0.979 and 0.978 in clinical patients B, respectively. Concordance ratios with using the direct method in the Friedewald formula, Martin method and modified Martin method were 82.8%, 85.5% and 85.3% in the health check-up participants; 76.4%, 80.5% and 80.2% in clinical patients A; and 76.1%, 82.6% and 82.6% in clinical patients B, respectively. Conclusion Our results show that the Martin and modified Martin methods display good performance in terms of the estimation of LDL-C concentrations among triglyceride concentrations of a wide range, and they may thus be useful for estimating LDL-C concentrations.

Objectives: We evaluated the applicability of a machine learning based Low-density lipoprotein-cholesterol (LDL-C) estimation method and the influence of the characteristics of the training datasets. Methods: Three training datasets were chosen from training datasets: health check-up participants at the Resource Center for Health Science (N = 2664), clinical patients at Gifu University Hospital (N = 7409), and clinical patients at Fujita Health University Hospital (N = 14842). Nine different machine learning models were constructed through hyperparameter tuning and 10-fold cross-validation. Another test dataset of another 3711 clinical patients at Fujita Health University Hospital was selected as the test set used for comparing and validating the model against the Friedewald formula and the Martin method. Results: The coefficients of determination of the models trained on the health check-up dataset produced coefficients of determination that were equal to or inferior to those of the Martin method. In contrast, the coefficients of determination of several models trained on clinical patients exceeded those of the Martin method. The means of the differences and the convergences to the direct method were higher for the models trained on the clinical patients' dataset than for those trained on the health check-up participants' dataset. The models trained on the latter dataset tended to overestimate the 2019 ESC/EAS Guideline for LDL-cholesterol classification. Conclusion: Although machine learning models provide valuable method for LDL-C estimates, they should be trained on datasets with matched characteristics. The versatility of machine learning methods is another important consideration.

Background Progranulin (GP88) is an 88-kDa glycoprotein growth factor with important biological effects in tumorigenesis and tumour survival. We investigated the usefulness of measuring serum GP88 concentrations as a predictive biomarker for hepatocellular carcinoma in patients with viral hepatitis C after treatment with direct-acting antiviral agents. Methods We measured the serum GP88 concentrations by using a sandwich enzyme-linked immunoassay from 67 healthy control subjects and 29 patients (20 patients who did not develop hepatocellular carcinoma and 9 patients who developed hepatocellular carcinoma after treatment) with viral hepatitis C after treatment with asunaprevir and daclatasvir. Results The serum GP88 concentrations of patients with chronic hepatitis C prior to antiviral treatment were significantly higher than those of healthy control subjects. After antiviral treatment, the serum GP88 concentrations of patients who eventually developed hepatocellular carcinoma were significantly higher than those who did not develop hepatocellular carcinoma. The changes in the serum GP88 concentrations before and after treatment in patients who developed hepatocellular carcinoma were significantly lower than those in patients who did not develop hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma was significantly higher in either patients with high serum GP88 concentrations after treatment or those with small changes of serum GP88 concentrations pre- and post-treatment. Conclusions Sustained high concentrations of serum GP88 in patients treated with direct-acting antiviral agents are correlated with the risk of developing hepatocellular carcinoma.

Case 1: A 59-year-old man was diagnosed with type 3 gastric cancer cStage Ⅲ(MU, Gre, tub2por, cT4aN2M0)induced by gastric perforation. The first surgery involving resection of the lesser curvature of stomach lymph node was judged to be difficult, and eventually exploratory laparotomy was performed. He received 3 courses of chemotherapy using S-1 plus oxaliplatin(SOX)(S-1 120mg/m2/day, day 1-14, oxaliplatin 100 mg/m2, day 1, followed by 7 days of rest). He subsequently underwent curative laparotomy gastrectomy plus D2(-No. 10)lymph node dissection, and Roux-en-Y reconstruction. Histological type was judged to be Grade 3. Case 2: A 69-year-old man was diagnosed with type 2 esophageal gastric junctional cancer,(GE, Less, tub2, cT4aN3M1[LYM])of cStage Ⅳ. He received 6 courses of chemotherapy using trastuzu- mab plus S-1 plus oxaliplatin(HER plus SOX)(trastuzumab 8mg/kg[2nd course 6mg/kg], day 1, S-1 120mg/m2/day, day 1-14, oxaliplatin 100mg/m2[5th course 80 mg/m2], on day 1, followed by 7 days of rest). He subsequently underwent laparotomy of the lower esophageal total gastrectomy plus D2(-No. 10, +No. 16, No. 110)lymph node dissection, and Roux-en-Y reconstruction as conversion surgery. Histological type was Grade 3. Both were impressive cases suggesting the usefulness of SOX therapy as a multidisciplinary treatment strategy for advanced gastric cancer.

Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA2nd/AA1st ratio in subjects who progressed from a healthy state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD.

GP88 (Progranulin; PGRN) is a secreted glycosylated protein with important functions in several processes, including immune response and cancer growth. Recent reports have shown that PGRN is a therapeutic target for rheumatoid arthritis (RA) because of its capability to bind with tumor necrosis factor receptor (TNFR). However, the serum PGRN level in RA patients has not been investigated. We used enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of PGRN in 417 healthy subjects, 56 patients with RA and 31 patients with osteoarthritis (OA). In RA patients, we also measured the serum TNF-α and sTNFR concentration. Immunohistochemical staining of PGRN was performed using synovectomy tissue of RA patients. The serum PGRN normal range was established as 40.1 ± 8.7 ng/ml. PGRN levels were not influenced by sex or age. A significant increase in serum PGRN levels was observed in RA (50.2 ± 11.1 ng/ml) and OA (45.4 ± 6.6 ng/ml) groups compared to those in age-matched healthy controls (40.4 ± 9.9 ng/ml) (p

A 78-year-old woman underwent right S6 segmentectomy and upper lobe partial resection for adenocarcinoma. About 11 months after the operation, she was diagnosed as having empyema with bronchopleural fistula and open thoracotomy was performed. From the following day, active hemorrhage from the pulmonary artery into the thoracic cavity(500~800 ml) repeated. Tamponade, surgical treatment such as putting hemostasis sheet, or covering with a pedicled latissimus dorsi muscle flap could not prevent rebleeding. Therefore selective pulmonary artery coil embolization was performed, after that the rebleeding did not occur.

The regulation of local l -tryptophan concentrations by tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase (IDO) induced by various stimuli such as interferon-γ (IFN-γ) is one of the key mechanisms in antimicrobial effect. Recently, IDO is also focused on an immunosuppressive mechanism shared by several different immune cell types. Here, we show that inhibition of increased IDO activity maybe involved in the antiparasitic mechanism during Toxoplasma gondii (T. gondii) infection in vivo. In this study, we investigated the role of IDO by using IDO-gene-deficient (IDO KO) mice and by administering a competitive enzyme inhibitor, 1-methyl- d , l -tryptophan (1MT), to wild-type mice following T. gondii infection. Although depletion of lung l -tryptophan did not occur in IDO KO mice after T. gondii infection, the increased mRNA expression of T. gondii surface antigen gene 2 (SAG2) and the inflammatory cytokines in the lung were drastically reduced in the IDO KO mice following infection. We also found that complete depletion of lung l -tryptophan was observed in wild-type mice after infection, but not in mice treated with 1MT. At the same time, 1MT suppressed the increased mRNA expression of SAG2. Taken together, we observed that the inflammatory damage was significantly decreased by the administration of 1MT in the lung after infection. Inhibition of the IDO activity or the elimination of IDO’s substrate may be an effective therapy against microbial diseases.

患者は70歳台男性．便秘を主訴に近医を受診後，当院に紹介となった．CT，注腸造影，骨シンチグラフィーで多発骨転移を有する4型直腸癌と診断した．根治手術不能と判断し人工肛門造設術を施行し，粘膜下生検で低分化型腺癌と診断された．その後modified FOLFOX6を4回施行したが効果がなかったため，modified FOLFIRIに変更した．縮小効果を認め腹会陰式直腸切断術を施行した．切除標本の病理検査で組織学的CR(complete response）であった．しかし，休薬中に急激に骨髄転移の増悪をきたしDICの病態を示すようになった．抗DIC療法を行い再度mFOLFIRIが有効で病状コントロールができた．大腸癌原発巣の病理組織学的CRはめずらしい事，休薬中に急激に骨髄転移の増悪を来たした事，再度のmFOLFIRIが有効であった事など進行大腸癌治療に際し種々の示唆を与える貴重な症例と考え報告した．

The EndoBarrier has a weak point caused by a Teflon membrane, which completely inhibits the movement of water and food. We developed a new type of gastro jejunal inner lumen bypass device (GJB) using an artificial net that has a hole instead of a membrane. We inserted a net in the gastric antrum-duodenum–jejunum via open laparotomy. The growth of pigs with long nets was suppressed compared with the sham operation. However, there were no differences in blood biochemistry or anatomical findings at autopsy between the groups. As a result, GJB can control the growth of pigs without requiring dietary restriction.

症例は61歳の女性で, 腹部緊満と黄疸を主訴に多発性肝嚢胞と診断され, 肝移植目的で紹介された. 血液検査からはDICの状態であったが, 各種画像診断は肝の著明な肥大と出血による不均一な嚢胞内容がみられたものの, 肝嚢胞に矛盾する所見ではなかった. その後急激な病状の進行により14日後に死亡し, 剖検から肝血管肉腫と診断され, 移植の適応外と判明した. 多発性肝嚢胞は良性疾患であるのに対し, 肝血管肉腫は予後不良で現在確立された治療法はない. 通常両疾患は画像診断で比較的容易に鑑別され, 本例のごとく鑑別上問題となった症例の報告はない. しかし, 臨床経過の速い多発性肝嚢胞では選択する治療方針が根本的に異なるため, 確定診断をつけるために可能な限り生検による組織診断の必要がある. そして全身状態が逼迫していれば, 画像診断と臨床経過より血管肉腫を慎重に鑑別しなければならない.

症例は54歳,女性.左腋窩の3 cmの腫瘤で紹介され,超音波ガイド下穿刺吸引細胞診の結果腺癌のリンパ節転移と判明した.しかしその後の全身精査では原発巣が不明で,腋窩リンパ節郭清を施行した.リンパ節のホルモンレセプター陽性で潜在性乳癌が強く疑われたため,本人の希望も考慮し2群郭清を伴う胸筋温存乳房切除術を施行した.術後病理検索で3 mm径のinvasive ductal carcinoma scirrhous typeが判明し,また2群リンパ節陽性(病期IIIA)であったため放射線・内分泌化学療法を行った.腋窩リンパ節転移を伴う潜在癌の多くは乳癌であり,原発部位の同定に努め病期II以上の乳癌治療に準じるべきである.しかし病巣が不明の場合,上腕浮腫や疼痛の回避,リンパ節のホルモンレセプター検索のためレベルI, IIのリンパ節郭清は必要と考える.また現時点で乳房切除の可否については確立した方針はなく,今後治療の標準化が望まれる.

症例は73歳,女性, S状結腸癌によるイレウスのため,腫瘍を切除後,人工肛門の造設を行った.術後19日目に大腸内視鏡検査にて,口側の結腸に広範囲の縦走潰瘍を認め閉塞性大腸炎と診断した.さらに術後48日目の大腸内視鏡検査では,この部分が高度の狭窄となっていたため,人工肛門と共に切除した.このように,閉塞性大腸炎の潰瘍病変は原因の除去にもかかわらず,狭窄型虚血性大腸炎の像を呈することがあり,注意を要する.

症例は88歳,女性.痴呆症にて他院の老人健康施設に入所していたが,腹痛のため当院を受診した.胸部単純X線および腹部CTにて, free airと上行結腸に腫瘤を認め,腸管穿孔の診断にて,緊急手術を施行した.開腹したところ,上行結腸の腫瘤とその口側の回腸に5mmの穿孔を認め,その内腔には棒状の異物,ストローが存在しており,痴呆のため誤嚥したものと思われた.切除標本では,上行結腸癌と回腸の穿孔を認め,腫瘤により停滞した回腸内異物により腸管穿孔をおこしたものと診断した.以上のように痴呆を有する患者では,腸管異物や潜在する悪性腫瘍にも注意するべきと思われた.

気腫性胆嚢炎および胆嚢捻転症はいずれも比較的稀な疾患である.今回われわれは胆嚢捻転症に気腫性胆嚢炎を合併したきわめて稀な症例に対し腹腔鏡下胆嚢摘出術を施行し良好な結果を得た.症例は91歳の女性,痩せ型で,急激な腹痛で発症した. CT上胆嚢の肝床付着部は狭く浮遊胆嚢状で胆嚢壁内および内腔にガス像を認めた.気腫性胆嚢炎と胆嚢捻転症の合併を疑い緊急腹腔鏡下胆嚢摘出術を施行した.胆嚢は著明に腫大し胆嚢間膜と胆嚢管を中心に時計方向に約180°捻転していた.胆嚢捻転発症例の解剖学的な特徴および術中胆嚢穿刺により手術は容易であった.順調に経過し術後12日目に退院した.気腫性胆嚢炎の発症機序として胆嚢捻転症も念頭に置く必要があるものと思われた.また今回検索しえた範囲内では両疾患の合併例は報告がなく,本症例はきわめて稀な例と思われた.

症例は60歳,男性.主訴は全身倦怠感. AFP産生横行結腸癌の切除術後40日目に血中AFPの再上昇と腹部CT検査で肝に腫瘤を認めたため転移性肝癌の診断で外側区域切除術を施行した.組織学的には結腸とほぼ同一の低分化腺癌で, AFP免疫染色では低分化な組織の一部に陽性像を認めた.血中AFP値は急速に低下し第2回手術後2カ月目より正常範囲内となり, 24カ月を経過した現在肝のほか腹腔内臓器に転移,再発を認めていない. AFP産生大腸癌の報告は極めて稀であるが,高度な肝転移症例が多く予後不良であり,肝切除術が施行された症例は本症例を含めてわずか7例で,うち1例は肝切除術後3カ月の短期で癌死している. AFP産生消化管癌の治療にあたっては肝転移に対する検索を常に行い,術後早期より血中AFP測定や画像診断などによる厳重な経過観察が必要と思われた.また消化管癌の治療に際しては血中AFPの術前からの測定は必須であると考えられた.

OBJECTIVE: To evaluate the outcome of living related liver transplantation (LRLT) in adult patients and to assess graft size disparity and graft regeneration. SUMMARY BACKGROUND DATA: Although LRLT has been accepted as an optional life-saving procedure for pediatric patients with end-stage liver disease, the feasibility of LRLT for adult patients has not been reported with reference to a clinical series. METHODS: Adult-to-adult LRLT was performed using whole left lobar grafts in 13 patients (5 with primary biliary cirrhosis, 6 with familial amyloid polyneuropathy, 1 with biliary atresia, and 1 with citrullinemia). The 13 donors comprised 5 husbands, 3 sons, 2 sisters, 2 fathers, and 1 mother. The ratio of the graft volume to standard liver volume (GV/SV ratio) was calculated for use as a parameter of graft size disparity. RESULTS: Although the liver graft was markedly small for size (GV/SV ratio 32%-59% at the time of LRLT), none of the 13 patients developed postoperative liver failure. Eleven of the patients are still alive and well with satisfactory graft function 2 to 35 months after LRLT. Graft liver volume increased rapidly after LRLT and approximated the standard liver volume with time. CONCLUSIONS: Our LRLT program for adult patients has produced good results. LRLT in adults can be indicated for selected donor-recipient combinations.

Aim This study aimed to clarify whether different anti-tumor necrosis factor (TNF) drugs can improve endothelial function better than conventional disease-modifying anti-rheumatic drugs (DMARDs) in a series of Japanese patients with rheumatoid arthritis (RA). Method Twenty-five patients who met the American College of Rheumatology 1987 revised diagnostic criteria for RA were randomly selected for this study. The percentage of brachial flow-mediated dilation (%FMD) and maximum carotid intima-media thickness were examined by ultrasonography. Results The %FMD in the group treated with anti-TNF therapy was significantly higher than that in the group treated with DMARDs (P

Background We describe a 1-year-old female who underwent living-related liver transplantation for biliary atresia and developed Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder. This disorder was resolved after withdrawal of immunosuppression therapy and administration of a high dose of acyclovir. Methods To quantify the extent of EBV activation and EBV load in peripheral blood, we measured the levels of EBV-infected peripheral lymphocytes by in situ hybridization (ISH) of EBV-encoded small mRNA 1 (EBER1). Results The decline in the number of EBER1-positive lymphocytes (from 362/50,000 mononuclear cells to 0/50,000) after treatment was in accord with the patient's clinical improvement. Conclusions This finding showed that quantitative analysis of EBV-infected peripheral lymphocytes by ISH of EBER1 is very useful for monitoring the EBV load and response to treatment of patients with EBV-related disorders. Furthermore, ISH may become an important tool for the early diagnosis and prevention of life-threatening posttransplant lymphoproliferative disorder in posttransplant patients.

症例は52歳の成人女性で, 1984年に皮膚掻痒感で発症し, Scheuer I期の原発性胆汁性肝硬変 (PBC) と診断され, 外来で経過観察されていた. 1992年頃より黄疸が出現し, 1993年3月に当科入院したが, 黄疸の高度進行, 腹水の増加, 肝性脳症の悪化, 肝腎症候群を認め, 血漿交換を含めた内科的治療も奏功しなかった. そこで本人と家族が肝移植を強く希望したため, 正式にインフォームド・コンセントを得て, 1993年10月20日信州大学第1外科へ移送し, 同年11月2日, 長男 (25歳) をドナー (グラフト肝重量402g) とする成人間生体部分肝移植を施行した. その後, 原病の再発とも思われる組織像と, 抗糸粒体抗体, 抗PDH抗体, IgM, ALPの上昇を認めた. 術後約3年半を経た現在, 上述のように血清学的には原疾患の再発が示唆されるが, QOLはよく, 日常生活に支障は生じていない. 一方, ドナーである長男も結婚し, 普通と全く変わらない生活を送っている. 以上PBCに対する治療として, 生体肝移植は我が国で選択されうるべき治療法の一つであり, 今後その推進に力を注ぐ必要があると思われた.

Partial liver transplantation using a graft from a living donor (PLT) has been carried out for children with incurable hepatic disorders. We have extended this technique to 5 adult patients (4 female and 1 male) with familial amyloid polyneuropathy (FAP). All were proven to have a TTR Met30 mutation. Four of these 5 patients are alive 5 to 28 months after operation, and 3 patients with a shorter duration of illness (less than jive years) showed remarkable clinical improvement. Periodic nausea and vomiting ceased and other autonomic symptoms including orthostatic hypotension, abnormal bowel movements and dysuria were also improving soon after PLT. Somatic motor and sensory neuropathic symptoms tended to improve very gradually. on the other hand. further progression of FAP symptoms was observed in one severely disabled patient with a 7 year-history of this disease. One other patient with a similar condition died 3 months after PLT. The donors who consisted of 2 sisters and 3 husbands recovered without compl...

bacteremia, presumably from the colon. Mycotic suprarenal aortic aneurysms caused by B fragilis are very rare. We have found two case reports of patients treated surgically for B fragilis mycotic suprarenal aneurysms (4,5). Complicating this patient’s presentation is a history of lepromatous leprosy. Leprosy has well-documented effects on small arteries, veins, and nerves. We have not found literature describing the effects of leprosy on the aorta or its vasa vasorum. Although it is conceivable that lepromatous involvement of the aorta may have played a role in the development of this patient’s aneurysm, that role must remain speculative given endovascular treatment with no pathologic specimen obtainable. Aortic mycotic aneurysm is a fulminant infectious disease and may potentially progress to rupture and death unless appropriate treatment is instituted. The conventional strategy for the treatment of mycotic aneurysm is surgical intervention followed by long-term antibiotic therapy, which is essential to control systemic sepsis and to achieve cardiovascular stability (3). The surgical procedures are associated with substantial mortality rates associated with the risk of recurrent infection. Stanley et al (6) have reported endovascular stent treatment of four patients with mycotic aneurysms of the thoracic aorta. Semba et al (7) reported efficacy with endovascular treatment of a ruptured thoracic aortic aneurysm, which is known to be associated with high operative mortality and morbidity. The same group also successfully treated three patients with mycotic aortic aneurysm, including one patient with ruptured aneurysm, with stent-graft placement (8). There were no perioperative deaths or life-threatening complications during follow-up in their series. Successful outcomes in these small series, as well as the excellent outcome of our patient, suggest that endovascular stent-graft repair can play a role in definitive therapy for patients with mycotic thoracic aneurysms. The role of acute bacteremic infection in the development of mycotic aneurysms is well-known. The combined effect of underlying chronic lepromatous infection, an entity with documented vascular sequelae, is unknown and may warrant further study.

In view of the relative scarcity of pediatric cadaveric donors, living-related liver transplantation has recently been accepted as an alternative approach. It is also the only method of liver transplantation available in countries where cadaveric organ procurement is prohibited. Here we describe our experience of living-related liver transplantation in 17 patients at Shinshu University Hospital. The safety of the donor operation is of paramount importance in this type of liver transplantation. In Japan, retransplantation is very difficult in the event of the liver graft becoming nonfunctional. We have therefore placed emphasis on the donor hepatectomy technique as well as on surgical procedures and postoperative care to prevent graft loss in the recipient. Fifteen of the 17 patients who received liver transplants are currently alive; and 1 died of cytomegalovirus infection, and 1 of pulmonary complications. The actuarial 1-year survival rate for our series, determined by Kaplan-Meier analysis, was 89.5%. Although living-related liver transplantation requires a complicated surgical procedure, it has achieved reasonable results for both donors and recipients. We consider that living-related liver transplantation is a useful and reasonable option for patients requiring liver transplantation.

The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance.

The Resource Center for Health Science (RECHS) has initiated a project based on the development and utilization of Bio-Resources/Database (BR/DB), comprising personal health records(PHR), such as health/medical records of the health of individuals, physically consolidated with bio-resources, e.g. serum, urine etc. taken from the same individuals. This is characterized as analytical alterations of BR/DB annually collected from healthy individuals, targeting 100,000, but not as data dependent on the number of unhealthy individuals so far investigated. The purpose is to establish a primary defense for the improvement of QOL by applying BR/DB to analysis by epidemiology and clinical chemistry. Furthermore, it also contributes to the construction of a PHR system planned as a national project. The RECHS coordinating activities are fully dependent on as many general hospitals as possible on the basis of regional medical services, and academia groups capable of analyzing BR/DB.

To characterize the potential utility of the University of Wisconsin (UW) solution, 37 grafts preserved in UW solution (UW group) were compared with 38 grafts preserved in Euro-Collins (EC) solution (EC group). Patients in both groups underwent similar perioperative management. Donor and recipient data in the two groups were similar. The mean cold ischemia time (CIT) of the UW group was 6.51±2.06 h (range: 3.17–14.65 h); this was significantly longer than that of the EC group, of 4.80±1.68 h (range: 1.67–8.83h) (P

良性肝内胆管狭窄はまれな疾患とされている.我々は肝内胆管癌による悪性肝内胆管狭窄を疑って手術を施行し, 術後に良性肝内胆管狭窄と診断された3例を経験したので報告した.症例1;61歳の男性, 右前上亜区域胆管の狭窄を認め同区域の動脈にencasementを認めたため, 悪性病変を疑い肝右葉切除を施行した.症例2;58歳の男性, 左外側区域胆管の不整な狭窄像を認め, 悪性を否定できず肝左葉切除を施行した.症例3;45歳の女性, 肝左葉外側区域胆管に完全閉塞を認め, 胆管癌を疑い左葉切除を施行した.術後経過はいずれも良好であり, 症例1, 2では腫瘍マーカーの正常化, 症例3では症状の改善が得られた.肝内胆管狭窄の治療方針の選択においては, 悪性を否定しえない症例や胆管炎を繰り返す症例に対しては肝切除も考慮すべきと考えられる.

A new lymphoma cell line, designated SUBL, was established from a Japanese patient with Epstein-Barr virus (EBV)-associated lymphoma, which developed during FK 506 therapy after liver transplantation. This cell line has undergone 80 passages over a period of 22 months. The cultured cells were positive for CD19, CD20, CD21, CD22, CD23, and HLA-DR, and negative for CD10 and surface immunoglobulins. Immunoglobulin gene analysis revealed rearrangements of JH and JK. T-cell antigens or T-cell receptor gene rearrangements were not observed on the cell line. The SUBL cells were positive for Epstein-Barr virus nuclear antigen (EBNA). The EBV genome was detected in the original tissue and the cell line by the in situ hybridization method. These data indicate that this cell line represents the B-cell lineage at a pre-B-cell stage. SUBL cells showed successful heterotransplantation to mice with severe combined immunodeficiency (SCID). Chromosomal analysis revealed the karyotype 46,XY,t(2;3)(p11;q27). Molecular studies showed that c-myc, N-myc, and bcl-2 were not rearranged. This cell line will provide a useful in vitro system to study the relationship between chromosomal abnormalities and the activation of cellular oncogenes.

Since June 1990, living related liver transplantions has been conducted in 8 patients at the department. In this study, these 8 patients are divided into 2 groups; group 1 comprizing of 5 patients who received continuously at a dose of 0.01 μg/kg/min during surgery, and group 2 comprizing of 2 patients who did not receive PGE1; and the following variables were studied. Hepatic tissue flow (HTF) (graft in recipient/left lateral segment of donor), hepatic arterial blood stream velocity (HAV) (POD1/just after reperfusion), portal venous blood stream velocity (PVV) (POD1/just after reperfusion) and arterial blood keton body ratio (AKBR) (POD1/at the time of closure of abdomen). No significant differences in these variables was noted between two groups, but the results of group 1 showed a higher tendency than those of group 2. When HTF, HAV and PVV values were compared between before and after administration of PGE1 after reperfusion, those after administration were 1.22, 2.50 and 1.16 times larger than those before it is concluded that PGE1 administration during the operation of living related liver transplantation was effective, but further accumulation of such cases and discussions are nacessary.

Indoleamine 2,3-dioxygenase, the l-tryptophan–degrading enzyme, plays a key role in the powerful immunomodulatory effects on several different types of cells. Because modulation of IDO activities after viral infection may have great impact on disease progression, we investigated the role of IDO following infection with LP-BM5 murine leukemia virus. We found suppressed BM5 provirus copies and increased type I IFNs in the spleen from IDO knockout (IDO−/−) and 1-methyl-d-l-tryptophan–treated mice compared with those from wild-type (WT) mice. Additionally, the number of plasmacytoid dendritic cells in IDO−/− mice was higher in the former than in the WT mice. In addition, neutralization of type I IFNs in IDO−/− mice resulted in an increase in LP-BM5 viral replication. Moreover, the survival rate of IDO−/− mice or 1-methyl-d-l-tryptophan–treated mice infected with LP-BM5 alone or with both Toxoplasma gondii and LP-BM5 was clearly greater than the survival rate of WT mice. To our knowledge, the present study is the first report to observe suppressed virus replication with upregulated type I IFN in IDO−/− mice, suggesting that modulation of the IDO pathway may be an effective strategy for treatment of virus infection.

Donor safety is the first consideration in living related liver transplantation. Left hemihepatectomy including the middle hepatic vein is a reasonable donor procedure for obtaining a large graft for living related liver transplantation. This procedure, however, needs to be modified in donors with hepatic venous variation. While carrying out donor hepatectomy, we encountered two cases showing a variant form of hepatic venous drainage comprising a thick middle hepatic vein draining segment 6 of the liver. This variation made it necessary to preserve the middle hepatic vein in the donor liver remnant. Failure to recognize such a variant would result in congestion in the remaining right liver of the donor. To guarantee donor safety, evaluation of the drainage area of the corresponding hepatic vein is a matter of great importance in donor hepatectomy.

Purpose: The purpose of this study was to determine whether liver volume increase can predict recipient outcome. Materials and Methods: Size-matched left lobe transplantation was performed for 16 patients. Computed tomography was performed in Week 1 after transplantation. Rate of liver volume increase was compared between survivors and deceased subjects. Results: Mean rate of liver volume increase was significantly higher for survivors than for fatalities. Conclusion: Rate of liver volume increase might be useful for predicting outcome of living donor liver transplantation.

Background. We describe the case of a man with intrahepatic arterioportal fistulae located in the left lobe, whose left lateral segment was transplanted into his son who was suffering from severe acute hepatitis B. Methods. A male infant with severe acute hepatitis B was considered to be a candidate for liver transplantation. The father was willing to be the donor. Preoperative evaluation of the donor revealed intrahepatic arterioportal fistulae, however, duplex ultrasonography showed normograde portal blood flow. A living-related liver transplantation was performed. Results. The postoperative course for both the donor and recipient was uneventful. The recipient is free of recurrent hepatitis B and has normograde portal blood flow. Conclusions. The present case suggests that there may be a symptomless population with intrahepatic arterioportal fistulae, which cause various degrees of disruption of the portal blood flow. Duplex ultrasonography might be helpful in the evaluation of candidates for liver donation.

Yamanouchi magnetic compression anastomosis (YMCA) is a novel interventional method that creates an anastomosis between the bile duct and small intestine. The method uses two magnets to compress the stricture transmurally, causing gradual ischemic necrosis of the stricture. This ischemic necrosis creates an anastomosis between the two magnets. The present report describes two cases in which YMCA was successfully applied to treat bilioenteric anastomotic stricture after living-donor liver transplantation. These two patients exhibited good long-term clinical courses.

Type II citrullinemia is an adult-onset hepatocerebral disease caused by a deficiency of argininosuccinate synthetase in liver. A 25-year-old Japanese man suddenly developed encephalopathy, showing disorientation and flapping tremor. Plasma concentrations of ammonia and citrulline were extremely high, and hepatic argininosuccinate synthetase activity was deficient. The patient's condition deteriorated rapidly in spite of intensive medications. Therefore, we performed a partial liver transplantation using a graft obtained from his healthy 61-year-old father. After surgery, his neurological symptoms soon disappeared and plasma levels of ammonia and citrulline were normalized within 3 months after operation. Type II citrullinemia is one fulminant form of various liver-based metabolic diseases, and immediate liver transplantation is necessary to rescue patients with this disease. As liver transplantation from cadaveric donor is still not possible in Japan, it seems justifiable to use living related partial liver transplantation for our patient.

The case of a 48-year-old woman with a left adrenocortical adenoma and showing hypokalemia, hypertension and normoreninemic normoaldosteronism is reported. Basal plasma adrenocorticotrophic hormone (ACTH) and cortisol levels were within the reference ranges. The patient's plasma cortisol level decreased insufficiently at night, and was insufficiently decreased by nighttime administration of dexamethasone. She showed no Cushingnoid stigmata. Iodocholesterol scintigraphy revealed tumor-sided uptake alone. The plasma dehydroepiandrosterone-sulfate level was low-to-normal for her age. Metabolic alkalosis and increased potassium clearance after sodium thiosulfate loading were revealed. The plasma aldosterone level was within the normal range, but it was statistically higher than the range for patients with pre-clinical Cushing's syndrome. However, peripheral plasma renin activity (PRA) increased normally after the patient resumed an upright posture following furosemide administration. After adenomectomy the hypokalemia and hypertension were resolved, and the plasma ACTH, cortisol, and PRA remained within the reference ranges. The plasma aldosterone level decreased slightly, but also remained within the reference range after adenomectomy. Paradoxical hyperplasia in the non-neoplastic adrenal glomerulosa zone, which indicates primary aldosteronism, and slight atrophy of the non-neoplastic adrenal cortex, which indicates pre-clinical Cushing's syndrome, were demonstrated. These findings satisfied the criteria of pre-clinical Cushing's syndrome, but did not completely satisfy those of primary aldosteronism. However, the level of CYP11 B2 mRNA in the tumor was in the lower-limit of the range for adenomas associated with primary aldosteronism and was higher than the ranges for adenomas associated with pre-clinical Cushing's syndrome and overt Cushing's syndrome. Based on these results, this case was suspected to constitute a variant of pre-clinical Cushing's syndrome with slight hypersecretion of aldosterone.

To establish criteria for venous reconstruction of middle hepatic vein (MHV) tributaries of the right liver graft in adult-to-adult living donor liver transplantation (LDLT).In adult LDLT using the right hemiliver, the MHV is usually separated from the graft, which results in potential venous congestion in the major part of the right paramedian sector (segments 5 and 8). It is controversial whether MHV tributaries should be reconstructed.Thirty-nine donors for LDLT were enrolled in the study. After liver transection, temporary arterial clamping was carried out to visualize congestion in the right paramedian sector by occlusion of MHV tributaries. Intra- and postoperative (on postoperative days 3 and 7) Doppler ultrasonography was performed to check the hepatic venous and portal flow in the veno-occlusive area.In 29 of 37 donors (78%), the liver surface of the veno-occlusive area was discolored with temporary arterial clamping. The discolored area was calculated to represent approximately two thirds of the right paramedian sector on computed tomography volumetry. All of the cases with discoloration exhibited absent venous flow and regurgitated portal flow in the discolored area by intraoperative Doppler ultrasonography. These ultrasonographic findings resolved by postoperative day 7 in 6 of 14 cases (43%).The state of venous congestion in the right liver graft can be correctly assessed by the temporary arterial clamping method and intraoperative Doppler ultrasonography. If the venocongestive area is demonstrated to be so large that the graft volume excluding this area is thought to be insufficient for postoperative metabolic demand, venous reconstruction is recommended.

Background. Decompensated hepatitis C virus (HCV)-related cirrhosis is the main indication for liver transplantation. We report the first successful living-related liver transplantation in a 49-year-old hemophilia A patient with end-stage HCV-related cirrhosis using a graft obtained from his 20-year-old daughter, an obligate carrier. Methods. The donor’s autologous fresh-frozen plasma rich in factor VIII (FVIII) by treatment with 1-deamino-8-D-arginine vasopressin was prepared before the operation. At induction, 1-deamino-8-D-arginine vasopressin was given to the donor to increase plasma FVIII level. In addition, autologous fresh-frozen plasma containing high FVIII concentrate was infused intraoperatively. The right lobe was harvested from the donor and transplanted orthotopically. The recipient was treated postoperatively with recombinant FVIII and immunosuppressive agents. Results. The donor did not receive recombinant FVIII or allogenic blood during perioperative periods. No bleeding was encountered in the donor perioperatively. The recipient showed a steady increase in FVIII activity postoperatively and was discharged 40 days after transplantation. Ribavirin and interferon-α were provided for 3 months postoperatively to prevent potential recurrence of HCV infection. Serum HCV-RNA by RT-PCR became negative after such treatment. Conclusions. End-stage liver disease in patients with hemophilia A can be an indication for living-related liver transplantation. Furthermore, a graft from a living-related donor with hemophilia A carrier seems to be suitable provided such individuals receive adequate support for coagulopathies.

Better outcomes of the patients receiving liver transplantation for viral hepatitis and hepatocellular carcinoma (HCC) are achieved by improved patient selection and perioperative treatment with antiviral agents including lamivudine, ribavirin and interferon. Patient selection is accomplished by high-quality imaging as well as exclusion of patients with large tumors, obvious extrahepatic disease or macroscopic vascular invasion. Using such criteria, a 5-year survival of 92% has been reached in the Queensland Liver Transplant Service on a small number of highly selected patients with HCC. The treatment algorithm of Makuuchi has guided us in recommending resection, estimating to what extent the liver resection can be performed safely, and timing liver transplantation when it is the only option. Adult-to-adult living-donor liver transplantation is being performed safely in many centers worldwide. The transplantation of liver from living donors to HCC patients, when standard criteria for the likelihood of good outcomes are fulfilled, will increase in Japan in the near future.