Atsushi Higuchi

Management and outcome of living kidney grafts with multiple arteries.

PurposeKidney 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.MethodsWe 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.ResultsIn 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.ConclusionMultiple renal artery grafts procured by open nephrectomy can be transplanted as successfully as those with single arteries, by using meticulous suturing techniques.

Expression of Cyclooxygenase-1 and -2 in Human Breast Cancer

AbstractPurpose. 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.

Acute Peritonitis Caused by Intraperitoneal Rupture of an Infected Urachal Cyst: Report of a Case

Abstract.Embryologically, the urachus is the tubular structure that connects the dome of the bladder to the umbilicus. Incomplete obliteration of the urachal lumen results in several anomalies. The most common urachal abnormality is the urachal cyst and, while intraperitoneal rupture of an infected urachal cyst is very rare, acute peritonitis resulting from intraperitoneal rupture is the most dangerous of all complications associated with urachal anomalies. We report the case of an 80-year-old woman who underwent an emergency laparotomy for lower abdominal pain and signs of acute peritonitis, which revealed intraperitoneal rupture of an infected urachal cyst. Infected urachal cysts with intraperitoneal rupture are often misdiagnosed as a common acute abdomen and result in emergency exploratory laparotomy. These patients should be managed by complete excision of the urachal remnant to prevent any malignant change occurring, as malignant changes have been reported.

Clinicopathological evaluation of renal allograft treated with anti-CD25 monoclonal antibody.

Abstract:  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 nephrotoxity 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.

Ten-year protocol biopsy findings of renal allografts in the calcineurin inhibitor era

Abstract:  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.

An autopsy case of bacterial septic shock 12 years following ABO‐incompatible renal transplantation

Abstract:  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 Ι (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.

An Extrarenal Malignant Rhabdoid Tumor Suspected to Originate from the Mesentery in an Adult : Report of a Case

A malignant rhabdoid tumor is very rare and its prognosis is extremely poor. It was first described as a distinctive and highly malignant neoplasm of the infant kidney. Tumors with a similar appearance have been reported in various extrarenal sites. We herein report a case of a 41-year-old man who was admitted to our hospital complaining of a lower abdominal mass. After one series of examinations, the patient underwent a laparotomy. Most such tumors are situated in the mesentery and involve the small intestine, and thus we diagnosed it to originate from mesentery. This tumor could not be resected and only an excisional biopsy was done. It was histologically composed of a solid sheet arrangement with ovoid, round, and lateralized nuclei and mild acidophilic cytoplasm. Inclusion body-like structures were found in the cytoplasm. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and CAM5.2. The patient died 2 weeks after operation due to multiple organ failure.

Clinicopathological evaluation of renal allografts of four patients by 20‐year protocol biopsies

Abstract:  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 fate of renal allografts.

Therapeutic Drug Monitoring Of Mycophenolic Acid In Renal Transplant Recipients

Immunosuppressive regimens including mycophenolate mofetil (MMF, Cellcept) were used in a renal transplant transplant program since May 2000 including 67 patients in whom it was the primary drug. Acute rejection (AR) occurred in 9 cases (13%) with 1-year graft survival rate of 96.8%. Pharmacokinetic (PK) studies of mycophenolic acid (MPA) were performed in 46 recent patients (total, 127 times). There was no correlation between dose (mg/kg) and blood concentration (AUC0-9: r2= 0.27). AUC0-9 was well correlated with AUC0-4 (r2= 0.91), but not with a single timepoint concentration. MPA AUC0-9 level was significantly higher among the AR-negative group (n = 33; 34.2 +/- 16.8 ng.hr/mL) compared with AR-positive group (n = 3; 28.2 +/- 1.9 ng.hr/mL; P = .04085) over the 2 weeks after transplantation. MPA AUC0-9 level was higher among the adverse event (AE-positive) group (n = 15; 39.2 +/- 22.8 ng.hr/mL) compared with the negative group (n = 21; 30.1 +/- 8.0 ng.hr/mL; P = .08772) within 2 weeks after transplantation. These results suggest the necessity of measuring AUC for therapeutic drug monitoring (TDM) of MMF-containing immunosuppressive therapy. The possible target level of MPA AUC0-9 would be approximately 30 ng.hr/mL using the present immunosuppressive regimen.