Severe Phlebitis Accompanying Vascular Rejection Type Acute T Cell-Mediated Rejection in Renal Transplantation.

PURPOSE: Renal transplant patients with vascular rejection type acute T cell-mediated rejection (ATCMR) grade II have a poor prognosis. Vascular lesions in those cases are thought to randomly occur, thus we searched for a novel pathological marker related to vascular rejection in kidney transplantation. METHODS: We determined pathological characteristics in 14 ATCMR grade II patients treated during an acute phase from 2004 to 2013. We then examined whether those findings appeared in transplant kidney biopsy specimens, except for cases of vascular rejection, in patients examined from 2010 to 2014. RESULTS: In 9 of the 14 ATCMR grade II patients, phlebitis was accompanied by inflammatory cells that formed polypoid projections in the venous lumen and partial disappearance of vascular endothelium. Further investigation showed those inflammatory cells to be T cells and macrophages. Histological findings revealed coexisting phlebitis in 2 of 13 patients with ATCMR grade I, 3 of 24 with borderline changes, and none with normal findings. Phlebitis occurred at a significantly greater rate than the other findings in cases of vascular rejection (P < .05). However, there was no significant difference in regard to graft survival between patients with and without phlebitis (P = .1829). CONCLUSION: Our results suggest severe phlebitis as a novel finding associated with the pathology of vascular rejection in patients with a renal allograft.

Induction Immunosuppressive Therapy With Everolimus and Low-Dose Tacrolimus Extended-Release Preserves Good Renal Function at 1 Year After Kidney Transplantation.

BACKGROUND: Utilization of everolimus (EVR) has been increasing in recent years for patients undergoing renal transplantation to reduce calcineurin inhibitor (CNI) levels. However, an optimum regimen has yet to be established. METHODS: We retrospectively examined 12 renal transplant recipients who underwent an induction immunosuppressive protocol; the protocol comprises 5 agents, including EVR plus low-dose tacrolimus extended-release (TAC-ER) treatment. We compared those findings from those of 14 patients who underwent a conventional protocol without EVR. Clinical outcome and pathologic changes were assessed by using protocol graft biopsy findings obtained at 3 months and 1 year after transplantation. RESULTS: The estimated glomerular filtration rate was significantly higher for the EVR group at both 3 months and 1 year compared with the conventional group (P < .01 and P = .03, respectively). TAC-ER trough levels were also significantly lower at 3 months and 1 year (both, P < .01). Histologic findings of the 3-month protocol biopsy samples in the EVR group revealed 4 cases of borderline change and 2 of acute cellular-mediated rejection. The findings from the 1-year biopsy samples revealed 10 cases with normal findings with no evidence of CNI toxicity. Patients in the EVR group developed subclinical borderline change and acute cellular-mediated rejection after 3 months at a significantly higher rate than the conventional group (P = .02). CONCLUSIONS: Use of the present therapeutic strategy successfully maintained the trough of each drug at a lower level, and it also kept renal function stable up to 1 year after transplantation.

Analysis of lawsuits on malpractice related to spinal anesthesia in Japan--change in the causes of anesthetic malpractice related to judicial precedents.

We investigated the adjustments related to spinal anesthesia in Japan. There were 23 cases. Seventeen cases resulted in death, 3 cases did in central nerve injury and 3 cases did in peripheral nerve injuries. In 17 cases whose origin was inadequate patient control, 15 patients were younger than 15 years old. In 14 cases in which the patient was younger than 15 years old, acute appendicitis was connected. Continuous monitoring is necessary to prevent malpractice during and after operation.

Analytic validation of the enzyme multiplied immunoassay technique for the determination of mycophenolic acid in plasma from renal transplant recipients compared with a high-performance liquid chromatographic assay.

The analysis of mycophenolic acid (MPA) has proved a valuable adjunct to the clinical care of organ transplant recipients. The analytic validation of the enzyme multiplied immunoassay technique (EMIT) for the determination of MPA in plasma is described. The EMIT MPA standard curve was 0 to 15.0 microg/mL, and curve storage was maintained for 4 weeks. The MPA EMIT assay proved reliable and reproducible, as shown by the intra-assay and interassay coefficients of variation (1.58-3.68% and 1.23-7.57%, respectively). Excellent linear correlation ( r = 0.999) was observed for dilution linearity. The sensitivity of the assay was 0.01 microg/mL. Recoveries of 99.4% to 104.2% were obtained by spiking aliquots of three controls of known MPA concentrations with MPA. No interference was observed for endogenous substances and coadministered immunosuppressant drugs, and no cross-reactivity from the major metabolite MPA glucuronide was found. The high-performance liquid chromatography (HPLC) assay used protein precipitation and C18 ion-pair chromatography with ultraviolet detection at 304 nm. Plasma concentrations of MPA were measured using EMIT and HPLC. A linear relationship was observed between EMIT and HPLC (EMIT = 1.091 x HPLC - 0.089; r 2 = 0.990, n = 129). These results indicate that EMIT is a simple, rapid, and sensitive assay method for the measurement of MPA in plasma.

Clinicopathological evaluation in non-episode biopsies of renal transplant allograft.

Histopathological findings in renal allograft with stable function remain unclear. We therefore performed non-episode biopsy in the long-surviving renal allograft to investigate the histopathological changes. Our data show that, although arteriolopathy is characteristic of drug-induced nephropathy, it is unrelated to dosage and concentration of cyclosporine or tacrolimus in non-episode biopsy. We evaluated therefore the clinicopathological findings of arteriolopathy in this study. Non-episode biopsy was defined as follows: as serum creatinine level lower than, 2.0 mg/dl and a urinary protein level lower than 500 mg/day. A total of 65 biopsy specimens were enrolled in this study as non-episode biopsy. Twenty-nine specimens revealed arteriolopathy. There were no statistically significant differences between arteriolopathy and dosage or concentration of cyclosporine or tacrolimus. Arteriolopathy in non-episode biopsy was related to time of biopsy, kidney age, hypertension, and hyperlipidemia, suggesting that it is important for graft survival to strictly control blood pressure and blood lipid level.

Arteriolopathy in non-episode biopsies of renal transplant allograft.

PURPOSE: We have been performing protocol biopsies since 1995 to predict the outcome of renal allograft. However, histopathological findings in renal allograft with stable function remain unclear. For this reason, we performed non-episode biopsy on long-surviving renal allograft and investigated the histopathological changes. Among the several diseases seen in non-episode biopsies, arteriolopathy, such as drug-induced nephropathy, is one of the most frequent diseases. However, it is unrelated to the dosage and the concentration of cyclosporine or tacrolimus. Consequently, we evaluated the clinicopathological findings of arteriolopathy in this study in order to clarify whether cyclosporine (CsA) or tacrolimus (FK506) is responsible for these findings. MATERIALS AND METHODS: We defined non-episode biopsy as a case with a serum creatinine level less than 2.0 mg/dL and containing less than 500 mg/dL of urinary protein. Final results showed that 71 cases were identified as non-episode biopsy. We then evaluated the histopathological findings and the clinical characteristics of these cases. RESULTS: Thirty-two of the 71 non-episode biopsy specimens showed findings of arteriolopathy. The frequency and the severity of arteriolopathy are not concerned with dosage and concentration of CsA or FK506. The arteriolopathy seen in non-episode biopsy was related to the time of the biopsy and the kidney age. Arteriolopathy in nonepisode biopsy also had a relationship with hypertension, suggesting that it is important to strictly control blood pressure for graft survival.

[A case of subclinical IgA nephropathy and cyclosporin associated arteriolopathy diagnosed by non-episode biopsy of graft kidney after renal transplantation].

We report a case of subclinical immunoglobulin A (IgA) nephropathy and cyclosporin associated arteriolopathy following renal transplantation. A 39-year-old male with chronic glomerulonephritis received kidney transplantation from a two- human leukocyte antigen (HLA) mismatched cadaveric donor. The initial immunosuppressive therapy was triple-drug therapy with cyclosporin, prednisolone and mizoribine. Four months after transplantation, he had an acute rejection episode, and the renal function was recovered by steroid pulse and 15-deoxyspergualin therapy. Eight years after transplantation, we conducted a non-episode biopsy of the renal allograft to examine subclinical lesions. The histopathological findings showed cyclosporin associate arteriolopathy (CAA) and IgA nephropathy. There was no sign of acute or chronic rejection. At the present time, the renal function of the allograft is good. In conclusion, the non-episode biopsy of renal allograft is useful for examination of subclinical lesions.

[Histopathological findings and clinical effects for acute rejections].

We reviewed 115 cases of acute rejection following renal transplantation. All cases were diagnosed after graft biopsy, and showed histopathological evidence of acute rejection. They were treated with administration of OKT3, 15-deoxyspergualin (DSG), anti-lymphocyte globulin (ALG) or methylprednisolone (MP). All rejections were histopathologically classified according to the Banff working classification. The clinical effects of each drug were evaluated both at 1 month and 1 year following the therapy for rejection, by measurement of serum creatinine level. The effective rate both at 1 month and 1 year was related with the Banff working classification ( p < 0.0001). At 1 month after treatment, there were no significant differences between the OKT3, DSG or ALG group and MP group in cases of borderline change and AR grade I. In cases of grade II and grade III, a significant difference was observed between the OKT3 or ALG group and MP group (p < 0.05). The DSG group showed a slightly better outcome than the MP group, although the difference was not significant. In conclusion, the Banff schema is shown to be valid for classification of acute renal allograft rejection, and it is necessary to determine the treatment for acute rejection according to histopathological classification.

Morphological findings in non-episode biopsies of kidney transplant allografts treated with FK506 or cyclosporine.

We conducted an analysis of biopsy specimens of non-episode renal allografts from patients treated with tacrolimus (FK506) or cyclosporine (CsA) to evaluate chronic drug-induced nephropathy in stable allografts. A total of 38 biopsy specimens from stable functioning renal allografts were examined. The patients had been treated with FK506 (n = 16) or CsA (n = 18) as main immunosuppressant for 0.3 to 7.4 years. Of the 38 biopsy specimens, 15 showed mild drug-induced arteriolopathy (hyalinosis or insudative change of arterioles and small arteries) with striped-form interstitial fibrosis, 10 showed minimum interstitial cellular infiltration (borderline rejection), 2 showed IgA nephropathy, 4 showed evidence of chronic rejection (transplant nephropathy) and 12 showed no abnormal findings. Of 34 renal allograft biopsy specimens with stable function, 22 (65%) showed pathological evidence of drug-induced nephropathy. There were no significant qualitative or quantitative differences between FK506- and CsA-associated nephropathy.

[A case of renal schwannoma].

A case of renal schwannoma is presented. A 51-year-old female was admitted to our hospital because of a left renal mass on April, 16, 1987. A drip infusion pyelogram showed encasement of the lower and medial calyx. An abdominal CT-scan showed a 2.5 cm mass with irregular density. Selective left renal arteriography showed the hypovascular tumor of the left kidney. Transperitoneal radical nephrectomy was performed on May, 1, 1987. Histological diagnosis was renal schwannoma arising from renal pelvis. The patient was well without recurrence 20 months after operation. Our present case is the 12th case of renal schwannoma reported in the English and Japanese literature.

[Intermittent intravenous high-dose cyclophosphamide therapy for advanced prostatic cancer with distant metastasis].

Twelve patients with advanced carcinoma of the prostate were treated with intravenous high-dose cyclophosphamide. All were hormone-resistant cases. At an interval of 3-4 weeks, cyclophosphamide was administered intravenously. The standard dosage of cyclophosphamide was 1,000 mg/m2 and a 10% lower dose was administered to patients with liver dysfunction, anemia and elderly patients. The results of 10 patients were evaluable. One case showed objective partial response, 1 case was stable and 8 patients showed objective progression according to the NPCP efficacy evaluation standard. The overall response rate was 20%, which we did not consider satisfactory. As to toxicity of cyclophosphamide, one patient died of severe acute hepatic failure, but in others, complications were mild to tolerable.

[Foreign body in the kidney: a case report and a review of the Japanese literature].

A 50-year-old female was admitted to our hospital with the chief complaint of right lumbago. She had undergone acupuncture for right lumbago several years earlier. Radiography revealed a linear metallic shadow in the right kidney. Computed tomographic scan revealed it to be located in the right renal parenchyma. The foreign body was extracted operatively. Including our case, 43 cases of foreign bodies in the upper urinary tract found in the Japanese literature so far are reviewed.

[Four cases of sperm invasion].

Four cases of spermatic invasion of epididymis are presented. All four cases were fertile. The etiology, histological findings, and role of sperm invasion in male infertility are discussed.

[Primary hyperparathyroidism in a child with parathyroid crisis--review of 24 cases reported in Japan].

A 9-year-old boy, who had been admitted to the Pediatric Department for the examination of IgA nephropathy, was transferred to our urological clinic on Aug. 6, 1985, because of parathyroid crisis. Before urological consultation, he had been complaining of bilateral knee and calcaneal pain, anorexia and abdominal pain, which had persisted for several days. Laboratory data indicated serum Ca of 17.6 mg/dl, iP of 2.3 mg/dl and iPTH of 0.77 ng/ml. Roentgenographic examination such as chest, extremities and neck computed tomography showed no abnormal findings. The final diagnosis was parathyroid crisis caused by primary hyperparathyroidism and neck exploration was carried out on August. 10. Left upper parathyroid gland, which was 1 cm in diameter, was surgically removed. The other three glands were normal in size. Histological examination of the resected parathyroid gland revealed chief cell adenoma. In the post-operative course, serum Ca level was soon reduced to the normal range and bone pain disappeared rapidly. During the follow up period of 2.5 years, the patient was clinically free of recurrence. Only 23 cases of primary hyperparathyroidism in children have been reported in the Japanese literature. The clinical characteristics of these specific cases are that primary hyperparathyroidism in children shows a low incidence of renal lesion, but the complicated bone disease is of higher incidence compared with the adult cases. Histopathologically, parathyroid adenoma was frequently observed (14/19), and the other 5 cases were parathyroid hyperplasia.

Small cell carcinoma of the urinary bladder: a case of remarkable remission with combined chemotherapy.

A 67-year-old man presented with asymptomatic gross hematuria. Cystoscopy and radiographic studies revealed a large tumor on the left lateral wall of the urinary bladder. Also, computer tomographic (CT) scan of the pelvic cavity showed metastasis to the left external iliac node. The light microscopic appearance of cold punch biopsy specimens for the tumor was closely akin to small cell carcinoma of the lung. Ultrastructurally, the tumor cells exhibited small numbers of neurosecretory granules in the cytoplasm. After surgical treatment, the patient was treated with combined chemotherapy using cis-diamminedichloroplatinum (CDDP) and etoposide. On CT scan, a remarkable remission was shown to have been induced at the metastatic site after three cycles of the therapy. Though the morphology of bladder tumors has not received very much attention, this report emphasizes that detailed pathological examination is of therapeutic importance.

[A clinical study on 34 cases of urothelial cancer of upper urinary tract].

Thirty-four cases of tumor of the renal pelvis or ureter or both have been treated in our department during the past decade. The primary tumor was in the renal pelvis in 11 cases, in the ureter in 21 cases and in the ureter and renal pelvis in 2 cases, a co-existent tumor in the bladder was found in 4 cases. Seventeen patients had a tumor on the right side and 17 on the left side. The most frequent symptom was gross hematuria (70.6%) and flank pain was the presenting symptom in 7 cases (20.6%). On the intravenous pyelography, a filling defect in the renal pelvis or ureter (41.2%) and nonvisualization (53.0%) were frequent findings. Twenty-nine cases had undergone total nephroureterectomy with resection of a bladder cuff, 3 had simple nephrectomy and 2 had open biopsy alone. Postoperative radiation therapy was done in 1 case, chemotherapy in 10 cases, and 6 cases of them were treated by CAP therapy (cis-dichlorodiamine platinum, doxorubicin and cyclophosphamide). Actual and relative 5-year survival rates were 53.8% and 63.5%, and no significant difference was found in survival rate between the patients with renal pelvic tumors and those with ureteral tumors.

[Neurofibrosarcoma of the perineum associated with von Recklinghausen's disease: a case report and review of the literature].

A case of perineal neurofibrosarcoma associated with von Recklinghausen's disease is reported. The patient was a 30-year-old man, who complained of a mass between the scrotum and anus. The mass was asymptomatic. On Jan. 13, 1981, simple excision was performed. Histological examination revealed neurofibrosarcoma. After 3 months he had recurrence of the perineal tumor. Combined chemotherapy and radiation therapy were performed. But, his condition became worse due to general metastasis and he died 12 months after operation. A total of 22 cases of perineal neoplasms are reviewed.