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Background Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare. Case presentation We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy. Conclusions GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.

In general, gastrojejunal bypass is performed for unresectable gastric cancers with stenosis. It enables patients to take food and be discharged from the hospital earlier. Previously, we used to primarily perform open gastrojejunal bypass; however, recently, we perform laparoscopic gastrojejunal bypass because it is minimally invasive. We evaluated 31 patients who underwent gastrojejunal bypass for unresectable gastric cancer in our department between December 2009 and December 2019. We retrospectively compared the laparoscopic surgery group(n=7)with the open surgery group(n=24). No significant difference in patient background was found between the study groups. Compared to patients in the open surgery group, those in the laparoscopic group had significantly shorter postoperative hospital stay and time until initiation of oral intake, relatively lesser blood loss, and no postoperative complications. Moreover, more patients in the laparoscopic group than in the open surgery group were administered postoperative chemotherapy. Further, postoperative chemotherapy was administered sooner in the laparoscopic group than in the open surgery group. Laparoscopic gastrojejunal bypass is a safe and less invasive treatment for unresectable gastric cancer with stenosis. It may be superior to the conventional open surgery with regard to early postoperative chemotherapy for cancer.

An 84-year-old man on hemodialysis was referred to our department for an advanced gastric cancer with pyloric stenosis. Pre-operative CT showed thickening of the stomach wall at the primary lesion and regional lymph node metastasis, while no clear peritoneal metastasis was found. However, we found peritoneal disseminations during the operation, so gastrojejunal bypass was performed. After the operation, he hoped chemotherapy despite risk factors such as renal failure and old age. We introduced a reduced dose of weekly nab-paclitaxel to him. After 3 courses, CT showed the primary lesion had decreased in size, and after 6 courses, serum CA19-9 level decreased to 61.8 U/mL from 2,343 U/mL at the before treatment. No serious adverse events were observed during the chemotherapy. However, after 8 courses, the tumor markers was gradually re-increased, and CT showed the primary tumor re-increased after 9 courses. Therefore, he received irinotecan alone as the second-line. He is still alive 1 year and 8 months after diagnosis of gastric cancer. It is generally said that the risk of cancer chemotherapy for dialysis patients and the elderly is high. However, we suggest that it could be safely performed by examining the appropriate drug and dose. Weekly nab-paclitaxel regimen could be one of the promising options for these patients.

Digital ischemia is a serious problem in peripheral artery diseases (PAD) patients. Case 1: A 60-year-old woman with large arteriovenous fistula (AVF) complained of digital ischemia symptoms. The patient underwent dissection of AVF and distal bypass to the palmar arch with successful repair. Case 2: A 47-year-old female, diagnosed with renal failure, and scleroderma, complained of a digital gangrene. A bypass was performed from the left brachial artery to the superficial palmar arch. The digital gangrene showed a complete recovery within 2 months after surgery. Distal bypass to the palmar arch thus appears to be a useful procedure to re-establish digital circulation in PAD patients.

Background Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. Patients and Methods From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. Results One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. Conclusion Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.

Background Arteriovenous fistula (AVF) trouble in a dialysis patient sometimes results in severe forearm ischemia. Case presentation We present the case of 27-year-old man with severe steal syndrome complained of AVF malfunction. There was a condition where an upstream artery of AVF is occluded and AVF is maintained by regurgitation from the palmar arch with ischemic digits. The patient underwent distal dual bypass: proximal to peripheral artery arterioarterial and arteriovenous bypasses and brachial arterioplasty. His skin perfusion pressure improved from 17 to 90 mmHg with enough quantity of blood: 250 ml/min for hemodialysis. Conclusions In severe steal syndrome cases, it is often observed that proximal artery is occluded and AVF inflow was supplied from palmar circulation and collateral vessels. Distal dual bypass is effective to re-establish digital circulation and repair AVF malfunction simultaneously in PAD patients.

Background The management of acute or, in particular, chronic antibody-mediated rejection (AMR) resulting from donor-specific HLA antibodies (DSA) is a critical barrier to obtaining better long-term graft survival. To ascertain the efficacy of anti-AMR therapies, the transition of intra-graft DSA (g-DSA) was assessed. Methods Allograft biopsy specimens were analyzed by graft immunocomplex capture fluorescence analysis, as previously described. One hundred recipients who underwent graft biopsies between April 2016 and December 2017 were enrolled for this study. Fifteen recipients diagnosed with g-DSA positive (+) received anti-humoral treatments and underwent follow-up biopsies. g-DSA levels were assessed again by a follow-up biopsy at 6–12 months following the treatments. Results With anti-humoral treatments, 9 out of 15 recipients comprised a g-DSA negative (-) (3.59 ± 2.82-.58 ± .25): g-DSA6-12- group, while the remaining 6 recipients comprised a g-DSA +(20.6 ± 17.0-14.9 ± 14.1): g-DSA6-12+ group. The initial g-DSA scores were significantly higher in the g-DSA6-12+ group (P = .01). All samples were diagnosed as chronic AMR in the g-DSA+ groups, whereas there were 3 chronic AMR, 4 acute AMR, and 2 incomplete AMR samples in the g-DSA- group. Interestingly, the frequency of responsible DSA belonging to class II tended to be higher in the g-DSA6-12+ group (4/6) compared to the g-DSA6-12- group (2/9) (P = .14). Conclusion These results imply that chronic exposure to DSA causes significant and irreversible damage to the allograft. Timely and adequate anti-humoral intervention might reverse the early phase of AMR with complete clearance of g-DSA.

The patient was a 30-year-old man who underwent a medical examination for shortness of breath.An abdominal computed tomography(CT)scan revealed advanced ascending colon cancer with multiple metastases to the liver.We performed a laparoscopic right hemicolectomy first, due to the obstruction.Postoperatively, the patient received capecitabine plus oxaliplatin( CapeOX)chemotherapy.After 10 courses of CapeOX, the multiple liver metastases had reduced remarkably in size. Colectomy of the anastomosis and partial hepatectomy were then performed.Histological examination of the resected tissue revealed no residual cancer cells, suggestive of a pathological complete response.

Background Mizoribine (MZ) has been developed as an immunosuppressive agent in Japan, but it has a less-potent immunosuppressive effect up to 3 mg/kg/d. In the previous study, a Japanese multicenter study, we reported that high-dose MZ, at 6 mg/kg/d, with a calcineurin inhibitor was effective and safe in reducing the frequency of cytomegalovirus (CMV)-related events in ABO-incompatible (ABO-i) living-related kidney transplantation (LKT). In the present study, therefore, we investigated the effects of high-dose MZ with a CNI in ABO-i LKT recipients in a Japanese multicenter study. Methods A total of 37 patients were treated with high-dose MZ (6 mg/kg), a CNI (cyclosporine [CsA] or tacrolimus [Tac]), basiliximab (Bas), rituximab (Rit), and corticosteroids. CsA was started at a dose of 7 mg/kg to maintain blood levels [200 ng/mL (C0), 6000 ng-h/mL (AUC 0–9)]. Tac was started at a dose of 0.2 mg/kg to maintain blood levels [8–10 ng/mL (C0), 100 ng-h/mL (AUC 0–9)]. Bas (20 mg/body) was administrated on day 0 and day 4 after transplantation. Rit (100–200 mg/body) was administrated on day −14 and day −7 before transplantation. MZ was adjusted to maintain target C0 levels of 1.5 to 2.0 μg/mL. Results Patient and graft survival rates for 2 years were 100% in the CsA group (n = 22) and 93.3% in the Tac group (n = 15) (not significant, NS). Overall incidence of acute rejection for 2 years was 22.7% in the CsA group and 26.7% in the Tac group. Mean serum creatinine levels at 2 years were 1.29 ± 0.2 mg/dL in the CsA group and 1.21 ± 0.34 mg/dL in the Tac group (NS). The incidence of CMV disease was 0% in both groups, and positive rates of CMV antigenemia were 50.0% and 26.7% in the CsA and Tac groups, respectively (NS). Mean serum uric acid levels were 5.5 ± 1.3 mg/dL and 6.4 ± 1.2 mg/dL at 2 years (NS) in the CsA and Tac groups, respectively. Conclusions A high-dose MZ regimen including calcineurin inhibitor (CsA or Tac), Bas, Rit, and steroids was effective and safe in reducing the frequency of CMV-related events in ABO-i LKT.

OBJECTIVE To evaluate the utility and safety of high-dose mizoribine combination therapy using cyclosporine and tacrolimus as calcineurin inhibitors in patients undergoing kidney transplant. METHODS The present study enrolled 156 patients who received kidney transplants in 18 institutions between 2009 and 2013. ABO-incompatible and/or pre-sensitized recipients were excluded. Immunosuppression used cyclosporine (88) or tacrolimus (68) as a calcineurin inhibitor, and the dosage was adjusted based on blood concentrations. Mizoribine was started at 6 mg/kg/day, and the target trough level was 1-2 ng/mL. Primary efficacy end-points of this study were 2-year patient survival, 2-year graft survival and the acute rejection rate within 2 years after transplantation. RESULTS The 2-year patient and graft survival rates in the cyclosporine group were 98.9% and 94.3%, respectively, whereas those in the tacrolimus group were 100% and 98.5%, respectively, with no significant difference between groups. Rates of onset of rejection during the observation period were also equivalent, at 22.7% in the cyclosporine group and 17.6% in the tacrolimus group. Furthermore, groups showed no significant differences in transplanted renal function. No notable differences in adverse events were observed between groups. CONCLUSIONS A regimen of high-dose mizoribine in combination with calcineurin inhibitors basiliximab, and corticosteroids can provide effective immunosuppression while lowering the rate of cytomegalovirus infection in kidney transplant patients.

Mizoribine (MZR) has been developed as an immunosuppressive agent, but has a less potent immunosuppressive effect up to 3 mg/kg/day MZR. Therefore, we investigated whether high-dose MZR, at 6 mg/kg/day, would be effective and safe for kidney transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids.A total of 40 living related patients were administered MZR (6 mg/kg/day), CsA (7 mg/kg/day), prednisolone (maintenance dose 10 mg/day), and basiliximab (20 mg/body). A control group (n = 38) treated with CsA, mycophenolate mofetil (MMF, 25 mg/kg/day), basiliximab, and corticosteroids was also employed in this study.The 2-year graft survival rates for the MZR and MMF groups were 100 and 94.7 %, respectively. The rejection rate in the MZR group (25 %) was not significantly higher than that in the MMF group (16 %). Serum creatinine level was not significant between the two groups. The number of patients who developed cytomegalovirus (CMV) disease was 0 (0 %) in the MZR group and 7 (18.4 %) in the MMF group (P0.05). The number of patients treated with ganciclovir was 3 (7.5 %) and 11 (28.9 %) (P0.05), respectively.The combination of high-dose MZR with CsA, basiliximab, and corticosteroids can establish not only satisfactory immunosuppression but also a low rate of CMV infection in vivo.

Mizoribine (MZR) is an immunosuppressive agent that exhibits a less potent immunosuppressive effect at doses up to 3 mg/kg/d. We investigated whether high-dose MZR is effective and safe for renal transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. Ninety Japanese renal transplant patients were administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose, 10 mg/d), and basiliximab (20 mg/body). They were compared with a control group of 81 renal transplant patients who received mycophenolate mofetil (MMF; 1500 mg/d), CsA, prednisolone, and basiliximab. The 2-year patient and graft survival rates were 98.9% and 97.8% in the MZR group and 98.8% and 97.5% in the MMF group, respectively. The rejection rate within 2 years after transplantation was 21.1% in the MZR group and 16.0% in the MMF group; the difference was nonsignificant. None of the MZR group developed cytomegalovirus (CMV) disease, whereas 12.3% of the MMF group contracted CMV (P < .0001). CMV viremia developed in 28.9% of the MZR group vs 46.9% of the MMF group (P < .0001); their peak antigen levels were 20.4 ± 44.1 and 252.8 ± 527.0 (P < .01). Furthermore, the incidence of gastrointestinal disorder, hyperlipidemia, and blood disorder was significantly lower in the MZR group than in the MMF group. The combination of high-dose MZR with CsA, basiliximab, and corticosteroids not only provides satisfactory immunosuppression but is also associated with a low incidence of CMV infection and gastrointestinal and blood disorders.

ポリカルボフィルカルシウム製剤服用後にイレウスにて開腹術を行った67歳の女性の症例について報告する．右卵巣嚢腫で手術既往があった．下痢のため近医よりポリカルボフィルカルシウム製剤を7日分処方された．服用12日目に腹部膨満と嘔吐が出現し，当院救急受診，入院となった．CTにて小腸の拡張と，小腸内に結腸内便様の内容物を認めた．イレウス管を挿入し保存的に経過を見たが，症状の増悪を見たため入院4日後に開腹した．癒着解除だけでは，腸内容を送り出せなかったため，小腸壁を切開し内容物を排出した．腹腔内の癒着のために腸管内容排出遅延が生じ，そのために服用していたポリカルボフィルカルシウム製剤が過度に膨潤，硬化した．このことによって，開腹術が必要となったと考えられた．この症例について，文献的考察を加えて報告する．

Introduction: When a patient who had renal replacement therapy becomes older, an elder donor candidate may be considered as a potential donor for living-related transplantation. Elder donor candidate might have pre-existing disease including mild renal dysfunction, such as proteinuria. Marginally appropriate donors might be considered for renal graft because of the shortage of donors. A successful outcome after kidney transplantation from a living-related donor diagnosed as membranous nephropathy is reported. Case report: A 38-yr-old male had been on continuous ambulatory peritoneal dialysis (CAPD) since the age of 37. His 63-yr-old father had mild proteinuria, and had been diagnosed with membranous nephropathy by needle biopsy at the age of 60. However, renal function of the father was found to be stable for three yr in a preoperative examination for donor; the father had normal renal function except for mild proteinuria. After adequate informed consent, we transplanted a kidney from the father, diagnosed with membranous nephropathy, to his son with a cyclosporine Abased immunosuppression regimen. In both the recipient and the donor, postoperative course was stable without complication such as rejection or infection. At 57 months after transplantation, the serum creatine level was 1.7 mg/dL in the recipient and 1.2 mg/dL in the donor. At 39 months after transplantation, allograft needle biopsy showed mild spike formation with partial thickening of the glomerular basement membrane (GBM). Decreases in electron-dense deposits and electron-lucent washout lesions with thickening of the GBM were observed using electron microscopy. This was diagnosed as Stage IV membranous nephropathy, showing clearance of the immune complexes and histological repair of the GBM. Conclusion: Donation of the kidney did not affect the residual renal function of the father with membranous nephropathy. Pre-existing membranous nephropathy itself might show remission after transplantation in the recipient. However, long-term careful observation for both the donor and recipient is required.

In the post-cyclosporine A era, it has been reported that acute rejection after kidney transplantation is commonly revealed as an asymptomatic increase in the serum creatinine level. Nephrotic range proteinuria is observed in patients with recurrent or de nova glomerulonephritis, or with chronic transplant nephropathy and glomerulopathy in the late phase. Acute rejection occurring with nephrotic range proteinuria without a rise of serum creatinine has been rarely reported. Here, we report a rare case of vascular rejection in a renal transplant recipient with nephrotic range proteinuria. A 34-yr-old male renal transplant recipient presented with acute vascular rejection and early-onset nephrotic syndrome. Severe nephrotic range proteinuria was detected with a minimally elevated level of serum creatinine. Biopsy showed severe glomerulitis and vasculitis, which was relieved by conversion of the immunosupressant regimen. Severe proteinuria was a sign of acute vascular rejection with severe glomerulitis and vasculitis. Careful observation to ensure maintenance of immunosuppression is necessary in such cases.

Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved. In this study, we examined the differences of gene polymorphism frequencies of apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important proteins for lipid transport, as well as of lipid parameters, between ONFH cases and referent patients among those who were subjected to renal transplantation.Subjects were 158 cases who had undergone renal transplant, including 34 cases that were diagnosed as ONFH after renal transplantation and 124 cases that were not. Four single nucleotide polymorphisms including C7623T and G12619A for the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship to ONFH was statistically evaluated.A higher frequency of 7623TT or CT of the ApoB gene was observed in ONFH cases than in referent patients (P = 0.033), resulting in an elevated odds ratio that was statistically significant (adjusted odds ratio = 6.37, 95% CI = 1.53-26.5, P = 0.011). No significant relationship was observed between other genes and ONFH. Regarding lipid parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045).For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.

Kidney allografts with multiple renal arteries (MRAs) have been used with increasing frequency since the advent of laparoscopic live donor nephrectomy. To determine if MRA grafts affect the short- and long-term outcomes of grafts and patients, we analyzed 340 grafts procured by open nephrectomy. We divided the graft recipients into five groups according to the methods used for vascular reconstruction. We compared patient and graft survival, serum creatinine levels, total (rewarm) ischemic times (TIT), incidence of acute tubular necrosis (ATN), need for antihypertensive drugs, incidence of acute rejection episodes, and vascular and urologic complications, between the MRA group and a control group of patients with single-artery renal grafts. In patients who underwent multiple anastomoses in situ, prolonged TIT resulted in an increased incidence of ATN, but there was no significant difference between the MRA groups and the control group (P = 0.45). The incidence of vascular complications was higher in the MRA groups (P < 0.01), but there were no significant differences in the other variables among the groups. Multiple renal artery grafts procured by open nephrectomy can be transplanted as successfully as those with single arteries, by using meticulous suturing techniques.

Kaposi's sarcoma is an uncommon neoplasm that occasionally involves the gastrointestinal tract in immunosuppressed individuals. Infection with human herpes virus 8 is known to be necessary for developing all forms of Kaposi's sarcoma. We report a renal transplant recipient who developed visceral Kaposi's sarcoma 18 months after the transplantation. In Oriental countries, the incidence of Kaposi's sarcoma is extremely low, and this is the first case of Kaposi's sarcoma arising from a transplant recipient in Japan. Standard forceps biopsies of the gastric lesions failed to make the correct diagnosis. However, endoscopic resection successfully led to the correct diagnosis of Kaposi's sarcoma and herpes simplex virus 8 infection as well. This is the first report of a patient with visceral Kaposi's sarcoma who underwent endoscopic resection that reliably confirmed histological diagnosis and the viral genome at the same time.

We report the case of an ABO-incompatible kidney transplant recipient who died suddenly following a good transplant course of 12 years. For 10 years after transplantation, the graft function had been stable (s-Cr: 1.0-1.5 mg/dL), although chronic hepatitis C had developed, with elevation of transaminase. In the 11th year, he was admitted into the hospital with low-grade fever and general fatigue. Jaundice and anaemia progressed, and he died 2 months after admission. The autopsy diagnosis was: (1) post-renal transplantation state, (2) phlegmonous enterocolitis with septic infarction, (3) cellulitis and necrotic myositis, and (4) sepsis. The transplanted kidney graft showed well-preserved glomeruli and tubules, corresponding to chronic allograft nephropathy (CAN) grade Iota (ci1, ct1, cv1), according to the Banff classification. The pathological changes observed in this long-surviving ABO-incompatible kidney graft were similar to those of an ABO-compatible graft, although its degree was milder.

The immunological barrier remains the major obstacle to the widespread use of transplantation as a replacement therapy for terminal organ failure. Since the first successful renal transplant performed by Hume et al in 1952, there has been an elusive search for agents rendering the immune mechanism unresponsive to the specific alloantigen stimulus of the engrafted organ while sparing nonspecific host resistance. Immunosuppressive therapies in organ transplantation can be divided into the following four main classes; chemical (pharmaceutical), biological (immunological), physical (radiological), and surgical. Of these, chemical agents (drugs) have continued to play a principal role. The discovery of new immunosuppressive drugs such as corticosteroids, azathioprine, cyclosporine (CsA), tacrolimus, mycophenolate mofetils and so on made an epoch at each stage in history of clinical organ transplantation. The recent immunosuppressants were designed to focus their action selectively on T and /or B cells by inhibiting cytokine synthesis (CsA, FK506), cytokine action (Rapamycin), or cell differentiation (15-deoxyspergualin) pathways rather than to act on immune systems in a nonselective fashion. CsA has improved the success of kidney transplantation, reducing the incidence and severity of acute rejection and improving the patient and graft survival. Sandimmun Neoral offers promise due to its better bioavailability and limited dependence on bile flow for absorption. Long-term studies are under way to determine its effectiveness and safety. Therapeutic drug monitoring and combination therapy with CsA are investigated also.

Purpose. We investigated the expression of cyclooxygenase (Cox-1 and Cox-2) in mammary tissues from patients with breast cancer. Methods. We used reverse transcriptase–polymerase chain reaction (RT-PCR) and immunohistochemistry. Results. The cancer cells showed very weak expression of Cox-1, but strong expression of immunoreactive Cox-2. In contrast, immunoreactive Cox-2 was very weak in all of the benign mammary tumors examined, including fibroadenoma (FA) and mastopathy (MP). Immunoreactive Cox-1 was also very weak in these benign tumors. The extent and intensity of immunoreactive Cox-2 polypeptides was significantly greater in the cancer cells than in the FA cells or MP cells. RT-PCR analysis showed enhanced expression of Cox-2, but not Cox-1 in breast cancer tissue, and faint expression of Cox-2 in benign tissue. Conclusions. These results demonstrated that human breast cancer cells generated Cox-2, indicating that Cox-2 might play an important role in the proliferation of breast cancer cells.

Background. Tissue factor (TF) expression is induced on macrophages and endothelial cells during the immune response. We designed an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) to specifically inhibit the expression of rat TF to study the effects of the AS ODN on renal ischemia-reperfusion injury in the rat. Method. AS-1 ODN for TF was delivered intravenously to inhibit the expression of TF in endothelial cells. After 8 hr, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 min of ischemia, and rats were killed at 0, 1.5, 5, 12, and 24 hr after reperfusion. TF expression was analyzed by immunohistochemical staining using monoclonal antibody. Results. In the untreated ischemic group, 0 of 20 rats survived beyond day 3. However, treatment with AS-1/TF led to 12 of 20 rats surviving beyond day 4. TF was detected on distal tubular epithelial cells, endothelial cells, and blood vessels but not on necrotic and proximal tubular epithelial cells. The necrotic area extended and encompassed nearly all of the ischemic kidney within 12 hr after reperfusion. The necrotic area and the grade of TF staining were more significantly reduced in the AS-1/TF-treated group than in the control group. Furthermore, fluorescein isothiocyanate-labeled AS-1/TF was significantly intense in tubular epithelial cells 8 hr after intravenous administration. Conclusions. The results indicate that AS-1/TF inhibited the ischemia-reperfusion injury of the kidney. Microcirculatory incompetence resulting from microthrombus may cause the formation and development of necrosis.

Twenty-year protocol biopsies were performed in four cases of renal transplant recipients with grafts that had survived 20 years or more. All four recipients received transplants from their parents and never had episodes of acute rejection. They were maintained with the conventional immunosuppressive protocol including azathioprine, mizoribine. and prednisolone. Three of them had past history of malignant diseases such as breast cancer and tongue cancer. In spite of fair graft function, the microscopic findings of 20-year protocol biopsy showed various degrees of histological damage: e.g. obsolescence of the glomeruli, glomerulosclerosis. arteriole wall thickening, interstitial fibrosis and tubular atrophy. Although two of the four grafts were functioning with low serum creatinine levels (1.3-1.4 mg dL - 1 ) at 24 years and 26 years following transplantation, respectively, the function of the other two grafts had decreased more than 20 years after transplantation. In the two grafts with decreased function, glomerulosclerosis and arteriole wall thickening tended to be more severe (Banff classification of chronic allograft nephropathy [CAN] grade II and III) at the 20-year protocol biopsy compared with the two well-functioning grafts (CAN grade I and II). We conclude that the protocol biopsies even at 20 years can contribute to predict the late of rental allografts.

Living-related renal transplantation is the optimal therapy for patients with end-stage renal disease (ESRD). Normally, complications are rare in living-related donor nephrectomy. However, we experienced a case of pulmonary embolism (PE). The incidence of PE in living donor nephrectomy is rare, but the total incidence of PE in surgical operations has recently increased. The patient in the case reported here was diagnosed relatively early and recovered with appropriate treatment. It is very important for surgeons to realize that serious complications such as PE can develop in any case of living donor nephrectomy.

We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 μg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng · h/mL (area under the curve 0–9 ). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 ± 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 ± 1.79 mg/dL at 1 month and 7.06 ± 1.78 mg/dL at 3 months. We observed that a high-dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients.

Tissue factor (TF) is an initiation factor for blood coagulation and its expression is induced on endothelial cells during inflammatory or immune responses. We designed an antisense oligodeoxynucleotide (AS-1/TF) for rat TF and studied its effect on hepatic ischemic reperfusion injury. AS-1/TF was delivered intravenously to Lewis rats. After 10 h, hepatic artery and portal vein were partially clamped. Livers were reperfused after 180 min and harvested. TF expression was studied using immunohistochemical staining. One of 10 rats survived in a 5-day survival rate and TF was strongly stained on endothelial cells in non-treatment group. However, by treatment with AS-1/TF, six of seven survived and TF staining was significantly reduced. Furthermore, we observed that fluorescein-labeled AS-1/TF was absorbed into endothelial cells. These results suggest that AS-1/TF can strongly suppress the expression of TF and thereby inhibit ischemic reperfusion injury to the rat liver.

Background. Tissue factor (TF) is a membrane-bound glycoprotein that is the primary cellular initiator of the blood clotting cascade and its expression is induced on macrophages and endothelial cells during the inflammatory or immune response. Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation through its ability to inhibit tissue factor activity. We studied the role of TF in the kidney following warm ischemic reperfusion and studied the effect of TFPI in vivo . Materials and Methods. After laparotomy of Lewis rats, the right kidney was harvested and left renal artery and vein were clamped. The kidney was reperfused after 60, 120, and 180 min of ischemia. Rats were sacrificed at 0, 1.5, 5, 12, and 24 h after reperfusion with or without TFPI treatment, and the kidney was harvested. Blood samples were collected at 0, 5, 12, and 24 h after reperfusion from the abdominal aorta. Blood urea nitrogen and kalium were monitored. TF expression was also studied by immunohistochemical staining with a monoclonal antibody (HTF-K108). Results. Histologically, the necroses of the tubular epithelial cells were observed 1.5 h after reperfusion. Immunohistochemically, TF staining was positive on the glomerular endothelial cells and stimulated monocytes but negative on the tubular epithelial cells. The necrotic area extended and encompassed almost all of the ischemic kidney by 12 h after reperfusion. TF was stained on the glomerular base membrane, the glomerular endothelial cells, and the stimulated monocytes but was not evident on the necrotic tubular epithelial cells. Fibrinogen was also observed in the glomerular endothelial cells at 5–12 h after reperfusion, while it was slight in normal tissue. With TFPI treatment, the necrotic area was narrow and TF was slightly stained on the endothelial cells. Conclusions. These results suggest that TF plays an important role in the development of renal injury after ischemia and reperfusion. The microcirculatory incompetence due to microthrombus might cause the formation and development of the necrosis. These results also suggest that TFPI plays a key role in modulating tissue factor-dependent blood coagulation, therefore TFPI is a strong medication for prevention of ischemic reperfusion injury.

A 51-year-old female received a kidney transplant, donated by her husband. The patient was induced with tacrolimus, mycophenolate mofetil and prednisolone. After methyl predonisolone pulse therapy without biopsy, allograft biopsy on POD 160 showed severe tubulo-interstitial nephritis with intranuclear inclusions. Urine cytology also showed decoy cells. Blood PCR detected an increase of BK virus DNA. She was diagnosed as having BK virus-associated nephropathy . Reduction of tacrolimus and switching of mycophenolate mofetil to mizoribine were done. Serum Creatinin (sCr) still rose to 3.0 mg/dl with persistent viremia and viruria. From on POD 268, 0.25 mg/kg of cidofovir was administered intravenously every two weeks over about four months. Biopsy on POD 387 revealed the disappearance of tubulitis with intranuclear inclusions, and decoy cells also disappeared from urine cytology. BK virus DNA in the blood decreased under the threshold level. sCr was stable and remained about 2.2 mg/dl for three months after the final treatment of cidofovir.

Introduction. The shortage of grafts in living kidney transplantation has forced the use of marginal grafts with arterial disease or grafts with multiple renal arteries (MRA). We reviewed the outcomes of transplants using allografts with MRA procured by open donor nephrectomy and report two cases requiring vascular reconstruction. Patients and methods. We reviewed 31 cases where renovascular reconstruction of an MRA graft was performed. A ex vivo pantaloon (side-to-side) anastomosis to create a common channel was performed in 24 cases including two cases of renal artery aneurysms in the grafts, where vascular reconstruction was performed in the same fashion after resection of the aneurysm. In four cases, an accessory artery was anastomosed sequentially after revasculization of the main artery. In three cases of grafts with multiple renal arteries, multiple anastomoses were done in situ after various ex vivo renovascular reconstructions. Results. Twenty one MRA grafts including grafts with a renal aneurysm are functioning well for a mean follow-up 135 months. The graft survival rate was 71.0% at 5 years after transplantation and 67.7% at 10 years. The donors whose grafts had a renal aneurysm were also well and normotensive with normal renal function at present. Ten grafts failed mainly due to chronic allograft nephropathy. Conclusion. MRA grafts procured by open nephrectomy, including those with renal artery aneurysms, were engrafted successfully by applying appropriate renovascular surgery. The use of those grafts was safe for both the recipient and the donor.

Aim Although better graft survival in patients treated with CsA has been obtained, chronic rejection continues to be a common complication in renal transplantation. In this study, we examined the graft survivals and complications among renal transplant patients followed for more than 25 years. Methods Between April 1970 and April 1979, 110 consecutive renal transplantations from living donors were performed in 110 patients. There were 83 men and 27 women of mean age of 27 ± 7.0 years. A combination of azathioprine (AZ) and prednisolone (PSL) was used for the initial immunosuppressive therapy in all patients. Results Over 25 years postoperatively, 41 patients died with or without a functioning graft due to complications including infections and malignancies. Therefore, the 25-year patient survival was 62.5% and 34 patients returned to hemodialysis, yielding an actual 25-year graft survival of 36/110 (32.1%). The longest surviving graft is 30 years and 2 months. The main causes of death were infectious disease and malignancy; 73% of graft loss was due to chronic rejection. Mean serum creatinine of the patient with functioning grafts over 25 years is 1.2 mg/dL; 75% of patients displayed a value under 1.5 mg/dL. The mean dosage of Az was 52.3 mg/d and PSL was 5.6 mg/d.

Background Renal cancers commonly occur in the native kidneys of renal transplant recipients, whereas renal cancer in the grafted kidney has been reported occasionally. Renal cancer in the grafted kidney occurred 16 years after graft loss in this case, which would be a more rare case. Case Report A 60-year-old man who had a kidney transplant from his mother at the age of 31 years and had hemodialysis again because of chronic rejection from the age of 44 years had right lower abdominal pain. Computerized tomography (CT) showed tumor involvement in the grafted kidney. Positron-emission tomography–CT also showed hot spots in the liver, cervical vertebra, and costal bone. Needle biopsy for grafted kidney and liver tumors were done, and pathologic findings revealed renal cancer of grafted kidney and metastatic liver tumor. Graftectomy was done, and renal cancer was diagnosed as spindle cell carcinoma. Irradiation for cervical bone metastasis was done after the surgery. He complained of abdominal pain and eating disturbance 2 months after the surgery. CT showed a huge recurrence tumor and multiple tumor dissemination. Small intestine was involved and obstructed by the main tumor. He died of recurrence of renal cancer 3 months after the surgery. Conclusions It is reported that the rate of renal cell carcinoma in the grafted kidney was 0.19%–0.5% and it occurred at a mean of 12.6 years after renal transplantation. Herein, we report a rare case of renal cancer that occurred 29 years after renal transplantation. Long-term observation should be required for recipients who had rehemodialysis.

Introduction The shortage of cadaver organs has led to expansion of living donor kidney transplantations with, 30% increase among ABO-incompatible cases in Japan and the use of marginal extended donors. Herein we have reported the outcome after an ABO-incompatible kidney transplantation from an aged living-related donor who suffered from mild diabetes mellitus and hypertension. Case Report A 48-year-old man underwent ABO-incompatible kidney transplantation from his 76-year-old father, using anti-CD20 antibody induction, followed by cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone. After the operation, MMF was switched to high-dose mizoribine (MZ). He was discharged from the hospital on postoperative day (POD) 28 with a serum creatinine (sCr) of 1.47 mg/dL. On POD 34 when the sCr was 8.14 mg/dL, his urine examination showed uric acid crystals with serum uric acid of 24.6 mg/dL. Biopsy findings showed no evidence of acute rejection but mild tubulointerstitial injury. Hemodialysis performed twice to reduce uric acid was accompanied by hydration. CsA/MZ was switched to tacrolims/MMF; benzbromarone, to febuxostat to treat hyperuric acidemia. On POD 58, sCr reduced to 1.75 mg/dL he was discharged. On POD 416, graft function was stable with sCr of 1.70 mg/dL. Conclusion Common side effect of MZ is hyperuricemia which presumably caused acute renal failure of this aged marginal donor kidney.

A lack of deceased kidney donors in Japan has led to dependence on living donors in as many as 80% of cases. At the same time, indications for living-donor kidney donation have been expanding in terms of donor medical status as well as HLA matching and ABO compatibility, thus emphasizing the donor shortage. To facilitate final medical decision-making for living kidney donation, we attempted kidney biopsy in six donor candidates who had problems such as mild diabetes and slight proteinuria. The biopsy specimens showed various degrees of tissue injury ranging from partial glomerular sclerosis to arteriole hyalinization. On the basis of the biopsy findings, kidney donation was subsequently performed in three of the six cases with full informed consent, and not done in the remaining three cases. Longer-term studies will be needed to clarify the outcome in both the donors and recipients in these cases.

BACKGROUND: The lack of deceased donors in Japan means that living-donor kidney transplantation is necessary in as many as 80% of cases. However, there are few data on perioperative complications and long-term outcome for live kidney donors. METHODS: To determine associated perioperative morbidity and long-term mortality among live kidney donors, we reviewed 601 donor nephrectomies performed at our institution between 1970 and 2006 and attempted to contact all of the donors (or their families) to ascertain their present physical status. The survival rate and causes of death were compared with an age- and gender-matched cohort from the general population. RESULTS: Although three donors (0.5%) experienced major perioperative complications, that is, femoral nerve compression, pulmonary thrombosis, and acute renal failure, all of the donors recovered and left hospital without complications. Among 481 donors (80%) for whom details were available at the time of inspection, 426 (88.5%) were still surviving. Donor survival rates at 5, 10, 20, and 30 years were 98.3%, 94.7%, 86.4%, and 66.2%, respectively. The mean interval between kidney donation and death was 183+/-102 (7-375) months, and the mean age at death was 70+/-11 years. The survival rate of kidney donors was better than the age- and gender-matched cohort from the general population, and the patterns and causes of death were similar. CONCLUSIONS: Our data suggest that continuation of living-donor kidney transplantation programs is justified in short- and long-term donor safety.

In coping with the shortage of deceased kidney donors, living donor kidney transplantation is mainly performed in Japan. We started our living unrelated spousal kidney transplantation program in 1989. In this analysis, we compared the results of 64 spousal transplantations performed between September 1989 and May 2007 with those of living related and deceased donor grafts. Despite the older age of the recipients and the lower HLA matching, the graft survival rates of spousal transplants were as good as those from living related donors and better than those from deceased donors, (P < .01). The graft survival rate of spousal kidney transplantation is improving with advances in immunosuppression, so spouses are considered important donors in Japan, which lacks deceased donors.

Background Marginally appropriate donors may be considered to extend the donor criteria for renal transplantation because of the donor shortage. We have reported a successful outcome after kidney transplantation from a living-related donor diagnosed with membranous nephropathy. Case Report A 38-year-old man began continuous ambulatory peritoneal dialysis (CAPD) at the age of 37. His 63-year-old father showed mild proteinuria, diagnosed as membranous nephropathy by needle biopsy. However, the father had normal renal function on preoperative examination, except for mild proteinuria. After adequate informed consent, we transplanted a kidney from the father who was diagnosed with membranous nephropathy into his son using a cyclosporine (CsA)-based immunosuppressive regimen. The postoperative course was good in both the recipient and the donor without rejection or infection. At 57 months after transplantation, the serum creatinine level was 1.7 mg/dL in the recipient and 1.2 mg/dL in the donor. An allograft needle biopsy at 39 months after transplantation showed mild spike formation with partial thickening of the glomerular basement membrane (GBM). Electron microscopy showed decreased electron-dense deposits and electron-lucent washout lesions with thickening of the GBM. This was diagnosed as stage IV membranous nephropathy, resulting from clearance of immune complexes and histological repair of the GBM. Conclusions For the present donor, graft donation did not affect his residual renal function. Preexisting membranous nephropathy itself may show remission after transplantation into the recipient to achieve successful results, however, long-term careful observation of both the donor and recipient is required.

A 51-year-old female received a kidney transplant, donated by her husband. The patient was induced with tacrolimus, mycophenolate mofetil and prednisolone. After methyl prednisolone pulse therapy without biopsy, allograft biopsy on POD 160 showed severe tubulo-interstitial nephritis with intranuclear inclusions. Urine cytology also showed decoy cells. Blood PCR detected an increase of BK virus DNA. She was diagnosed as having BK virus-associated nephropathy . Reduction of tacrolimus and switching of mycophenolate mofetil to mizoribine were done. Serum Creatinin (sCr) still rose to 3.0 mg/dl with persistent viremia and viruria. From on POD 268, 0.25 mg/kg of cidofovir was administered intravenously every two weeks over about four months. Biopsy on POD 387 revealed the disappearance of tubulitis with intranuclear inclusions, and decoy cells also disappeared from urine cytology. BK virus DNA in the blood decreased under the threshold level. sCr was stable and remained about 2.2 mg/dl for three months after the final treatment of cidofovir.

Osteonecrosis of the femoral head (ONF) is a necrosis due to disruption of the blood flow. The disease often occurs in association with corticosteroid treatment. The pathology of corticosteroid-induced ONF is unclear, although abnormalities in the coagulation and fibrinolytic systems or in the lipid metabolism have been reported to be involved. We examined the relationships between development of ONF and genetic variations and plasma level of lipoprotein(a) (Lp(a)), which is closely involved in the coagulation and fibrinolytic systems and lipid metabolism.The study population consisted of 112 renal transplant patients undergoing corticosteroid treatment. Their apolipoprotein (a) [apo(a)] isoform was determined by Western blotting, and patients were classified into low molecular weight (LMW) or high molecular weight (HMW) groups. The plasma Lp(a) level was measured. Patients were also examined for 3 single-nucleotide polymorphisms (SNP), -773 (G/A), +93 (C/T), and +121 (G/A). Relationships between these 3 genetic factors of Lp(a) and ONF development were examined using statistical methods including multivariate analysis.A strong relationship was observed between the apo(a) molecular weight phenotype and ONF development, with an increased risk of ONF development for the LMW group (adjusted odds ratio 5.75, 95% CI 1.76-18.74, p = 0.0038). No significant relationships were observed between ONF and plasma Lp(a) level and SNP.Apo(a) molecular weight phenotype would be a useful predictor of ONF that develops after corticosteroid treatment.

Ten-year protocol biopsies were performed in 16 patients treated with calcineurin inhibitor (CNI) continuously. All kidney grafts were functioning well at the time of biopsy with the mean serum creatinine level of 1.6 +/- 0.8 mg/dL. The specimen of biopsy showed various degrees of tissue injury. According to the Banff grading, allograft glomerulopathy (cg) was observed in one case. Interstitial fibrosis (ci) and tubular atrophy (ct) were observed more frequently in 13 (81%) and 15 (93%) cases, respectively. Fibrous intimal thickening (cv) was seen in one (7%) case. Arteriolar hyaline thickening (ah) was seen in 14 (87%) cases. These findings were associated with chronic rejection in one case, recurrence of original disease in four (25%) cases, toxicity of CNI in 14 (87%) cases. Longer follow-up studies are needed to confirm whether CNI should be continued or not in the long-term period following kidney transplantation for better graft survival.

Twenty-seven living-donor kidney recipients were treated with the antibody against CD25 as the induction immunosuppressive agent. They did not develop acute rejection within 1 month after transplantation, and mean serum creatinine level at 1 month was 1.0 +/- 0.4 mg/dL. There were no findings of acute rejection or drug-induced nephrotoxicity in protocol biopsies at 1 month following transplantation. After 1 month had passed, acute rejection occurred in three cases. The pathological grade of acute rejection varied from borderline to grade III by Banff classification. The careful inspection is necessary to find out the occurrences of acute rejection more than 2 months after transplantation because immunological situation has been changing around this period.