Toshitsugu Oka

Involvement of Epstein-Barr virus expression in testicular tumors

PURPOSE Because orchitis has been described as a symptom of infectious mononucleosis which is caused by Epstein-Barr virus (EBV), a human tumor virus, we tried to ascertain the relationship between EBV and testicular tumors. MATERIALS AND METHODS Sixteen seminomas, 11 embryonal carcinomas and 25 nonmalignant control testes were examined for persistence and expression of the EBV genome. To detect expression of EBV, mRNA in situ hybridization and immunofluorescence staining by monoclonal antibodies were performed. To confirm the EBV genome in testes, we used nested polymerase chain reaction (PCR). RESULTS Messenger RNA in situ hybridization showed that all 27 seminomas and embryonal carcinomas expressed EB viral RNA, but the 25 nonmalignant testes did not. Monoclonal antibody staining showed EBV-related nuclear antigen (EBNA) 2 and latent membrane protein (LMP) 1 expression in testicular tumors. Nested polymerase chain reaction detected the EBV genome in normal testes as well as in testicular tumors. CONCLUSIONS These results suggest that EBV is related to testicular tumors.

Clinical Outcome and Prognostic Factors of Sorafenib in Japanese Patients with Advanced Renal Cell Carcinoma in General Clinical Practice

OBJECTIVE Effects of sorafenib in general clinical practice, especially those with patients of Asian ethnicity, have been rarely investigated. We assessed efficacy, safety and prognostic factors for progression-free survival in Japanese patients receiving sorafenib for advanced renal cell carcinoma. METHODS We performed a retrospective analysis of 159 Japanese patients with renal cell carcinoma. Progression-free survival was estimated by the Kaplan-Meier method. Objective response (per Response Evaluation Criteria in Solid Tumors) and safety were assessed. Cox proportional hazards model was used to identify independent prognostic factors for progression-free survival. RESULTS The median progression-free survival was 9.0 months (95% confidence interval, 7.5-10.6 months). In 142 patients with measurable lesions, the objective response rate was 21.8%, and disease control was achieved in 85 (59.9%) patients. Adverse events of any grade occurred in 152 patients (95.6%). Most common adverse events causing discontinuation or interruption of sorafenib were hand-foot skin reaction (22%), rash (10.7%) and liver dysfunction (10.7%). Dose reduction or therapy interruption due to adverse events was required in 128 patients (80.5%). Univariate and multivariate analysis revealed that favorable prognosis according to Memorial Sloan-Kettering Cancer Center prognostic factors and relative dose intensity during the first month of treatment of ≥50% were significant factors for predicting superior progression-free survival with sorafenib treatment. CONCLUSIONS Sorafenib was effective in Japanese patients with advanced renal cell carcinoma in general clinical practice and was tolerated although most patients required dose reduction or interruption of therapy. Future studies should establish new strategies for treatment without sacrificing both efficacy and patient quality of life.

Immunohistochemical study of nodular hyperplastic parathyroid glands in patients with secondary hyperparathyroidism

Thirty-seven nodular hyperplastic parathyroid glands obtained by subtotal parathyroidectomy from 11 haemodialysed patients with secondary hyperparathyroidism were examined both pathologically and immunohistochemically. Four consecutive sections of the largest section-surface of each gland were subject to 4 different stains (haematoxyline-eosin, Grimelius, and the immunohistochemical stains for parathyroid hormone and chromogranin A) for comparison of each nodule. It was found that the major part of each nodule consisted of a single cell type with a single pattern of cells. These reacted uniformly to each stain. The mechanism involved in the storage and secretion of the secretory granule appeared to be regulated at the nodule and not at the cell level. The results suggest that the nodules may come from a monoclonal proliferation of a single parathyroid cell. Our present light microscopic immunohistochemical study, failed to demonstrate completely identical immunoreactive positivity of each nodule or each parathyroid cell to PTH. Chromogranin A or secretory protein-I did not indicate the coexistence of PTH and SP-I in the same secretory granule, which was in good agreement with the electron microscopic immunocytochemical study of Arps using bovine parathyroid glands. Our present study, however, provides good evidence that chromogranin A positivity is demonstrable in the human parathyroid gland outside the adrenal medulla and sympathetic nerves.

Solitary late recurrence of renal cell carcinoma.

Solitary late recurrence is an unpredictable behavior pattern of renal cell carcinoma. We describe a patient with recurrence at the cranial bone 10 years after surgical management and another with recurrence at the sacral bone 13 years after treatment with radiotherapy and alpha-interferon. Both patients have been followed satisfactorily for 9 months. Unpredictable behavior of renal cell carcinoma makes lifelong followup of patients necessary. If a solitary recurrence is detected operative management definitely should be considered depending on the site of recurrence.

Estimation by infrared spectrophotometer of the calcium oxalate dihydrate to calcium oxalate monohydrate ratio.

According to the theoretical expression for calibration curve as a function of the optical absorption ratio of two peaks and with the analysis of the infrared spectra of the mixture samples of commercial calcium oxalate monohydrate and synthesized calcium oxalate dihydrate, the following quadratic equation was obtained; Y = 1.79 X2 - 30.90 X + 107.04 in which Y is the percentage of the purity of calcium oxalate dihydrate and X is the ratio of the relative optical absorption at 660 cm.-1 (the wave number at a characteristic absorption peak of calcium oxalate monohydrate) to that at 610 cm.-1 (that of calcium oxalate dihydrate) by regarding the line as a base-line that links the absorption valley at around 700 cm.-1 with that at 550 cm.-1 The linear correlation coefficient of the actual purity to the estimated purity obtained from this formula of calcium oxalate dihydrate is 0.995. When this formula is applied to the results derived from the infrared spectra of the mixture samples of commercial calcium oxalate monohydrate and calcium oxalate dihydrate obtained from urinary stones in duplicate in each percentage, the linear correlation coefficient is 0.991. This estimation method by infrared spectrophotometer of the calcium oxalate dihydrate to calcium oxalate monohydrate ratio gave a very close correlation between actual and estimated purity of calcium oxalate dihydrate and seems useful in the study of calcium oxalate urolithiasis.

Role of Magnesium in the Growth of Calcium Oxalate Monohydrate and Calcium Oxalate Dihydrate Crystals

Since about 85% of synthesized calcium oxalate dihydrate (COD) crystals proved not to have changed into calcium oxalate monohydrate (COM) crystals at 30 min of incubation time at 37 degrees C when our evaluation method of the COD-to-COM ratio was being used, we made a comparative study of the inhibitory effects of magnesium, one of the well-known inhibitors of calcium oxalate stone formation, on the growth of seeded COM and COD crystals. The results demonstrated that magnesium in identical concentrations might have stronger inhibitory effects on the growth of COM crystals than on that of COD crystals and suggested that these different effects of magnesium on the growth of COM and COD crystals might arise not only from the difference between the specific surface areas of COM and COD crystals, but also from that between the direct inhibitory effects of magnesium on these two types of calcium oxalate crystal growth.

Xanthoma of the Bladder

We report a case of xanthoma of the bladder incidentally discovered during transurethral ureteral lithotripsy for a right ureteral stone and histopathologically diagnosed by cold cup biopsy. Xanthoma, a disorder of the lipid metabolism without tumorous or inflammatory changes, is rare in the bladder with only 7 cases reported previously. Interestingly, 5 of these 7 cases were reported in the Japanese literature, as were cases of xanthogranulomatous cystitis. We have no explanation for this occurrence. Xanthoma, caused by macrophages with the ability to phagocytose, is a benign lesion. It is necessary to continue careful followup by cystoscopy to determine if xanthoma increases or decreases in size.

BLADDER CANCER PRODUCING GRANULOCYTE COLONY-STIMULATING FACTOR : A CASE REPORT

A rare case of bladtier cancer prtducing granulocyte colony‐stimulating factor (G‐CSF) is reported. A 63‐year‐old man with a progressive, grade 3 transitional cell bladder cacinoma, showed niarked leukocytosis (maximum 181,800/mm1) and an elevated serum G‐CSF to 131.7 pg/mL. After rdical cystectomy and neoadjuvant chemotherapy, the tumor recurred locally. Immunohistochemical examination with monoclonal antibody specific for G‐CSF revealed positive staininfi in the lotal recurrtant tumor. To our knowledge, there have been only seven cases reported of bladder cancer producing C;‐CSF.

Xanthine Calculi in the Patient with the Lesch-Nyhan Syndrome Associated with Urinary Tract Infection

A Japanese boy with Lesch-Nyhan syndrome who passed xanthine calculi is reported. After pyelolithotomy for a left renal stone, made up of ammonium urate, associated with urinary tract infection, a high dose of allopurinol was given because of the persistence of pyuria. In the present case, the administration of a high dose of allopurinol, given for the prevention of ammonium urate stone formation in infected urine, induced xanthine calculi formation and we had difficulty in the management of this patient with Lesch-Nyhan syndrome associated with urinary tract infection. However, we believe it a basic necessity to cure our patient of his urinary tract infection and prevent recurrent ammonium urate stone formation because of the risk of renal deterioration.

Ureteropelvic Junction Obstruction with Renal Pelvic Calcification: A Case Report

Calcification in the wall of the renal pelvis is rare. We report on a 65-year-old man with hydronephrosis secondary to ureteropelvic junction obstruction with renal pelvic calcification. Calcium deposit was found in the wall of the severely dilated renal pelvis. Pathological examination revealed a damaged and hyalinized fibrous renal pelvic wall and serum calcium level was normal. Thus, we speculated that this calcification was dystrophic. Chronic extensive dilatation with intermittent hemorrhage of the renal pelvic wall may have caused this dystrophic renal pelvic calcification.