Biomedical subjects

Toru Harabayashi

Publications and source records attributed to Toru Harabayashi.

At least 19 recordsLinked to original sources

PubMed2006

Reactivation of hepatitis in a bladder cancer patient receiving chemotherapy.

Reactivation of hepatitis is a serious complication of chemotherapy in hepatitis B virus (HBV) carriers. There are many reports of this in lymphoma patients but few in urological cancer patients. A 59-year-old woman with bladder cancer who was an HBV carrier developed severe liver dysfunction after 2 cycles of chemotherapy. The diagnosis was reactivation of hepatitis. She improved with administration of lamivudine with a steroid and is currently well without disease. Care should be taken about the risk of reactivation when performing chemotherapy in HBV carriers and prophylaxis by lamivudine should be considered.

Antineoplastic Agents↗

PubMed2006

Survival and prognostic classification of patients with metastatic renal cell carcinoma of bone.

OBJECTIVES: We retrospectively analyzed the survival of renal cell carcinoma patients with bone metastases, and identified prognostic factors and a model predictive for survival in these patients. METHODS: Fifty patients with renal cell carcinoma with osseous metastases were treated at Hokkaido University Hospital between 1980 and 2004. The relationship between several clinical features and survival was examined univariately. The Cox proportional hazards model was then used to form a multivariate model. RESULTS: The median survival time from the diagnosis of bone metastasis was 12 mo, and overall survival at 2 yr was 37%. Clinical features correlated with longer survival in the multivariate analysis were a long interval (24 mo or more) between the diagnosis of kidney cancer and that of osseous metastasis (hazard ratio [HR]: 2.608; 95% confidence interval [CI], 1.031-6.599) and the absence of extraosseous metastases (HR: 2.523; 95%CI, 1.023-6.220). By combining these two favorable factors, renal cell carcinoma patients with osseous metastases could be categorized into two different groups. The median time to death in 20 patients with zero favorable factors (poor prognosis) was 5 mo. On the other hand, 30 patients had one or two favorable factors (good prognosis); the median survival time in this group was 30 mo. There was a significant difference in survival duration between the two groups (p<0.001). CONCLUSIONS: Two prognostic factors predicting survival were identified and used to categorize renal cell carcinoma patients with bone metastasis into two prognostic groups.

Adult↗

PubMed2006

Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received prior cisplatin-based therapy.

BACKGROUND AND AIMS: The aim of the present phase II study was to evaluate the efficacy of combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin (PIN regimen) in patients with recurrent urothelial cancer who had been treated with cisplatin-based chemotherapy. PATIENTS/METHODS: Eligible patients were those with histologically confirmed urothelial cancer who had progressed or relapsed after cisplatin-based chemotherapy. The PIN regimen consisted of paclitaxel 175 mg/m(2) on day 1; ifosfamide 4.5 g/m2 divided over days 1, 2, and 3; and nedaplatin 70 mg/m(2) on day 1; PIN was given every 28 days. RESULTS: Among the 32 patients enrolled in the study (median age, 66 years), complete and partial responses were obtained in 5 patients and 19 patients, respectively, with an overall response rate of 75% (95% confidence interval [CI], 59-91%). The median time to progression was 8 months (range, 0-50+ months) and the median survival was 22 months (range, 4-52+ months). The 1- and 2-year overall survival rates were 53.7 and 42.9%, respectively. All patients experienced Grade 3 or 4 neutropenia, while Grade 3 or 4 thrombocytopenia was seen in 8 patients; Grade 3 or 4 anemia was seen in 6 patients; Grade 3 neuropathy was observed in 1 patient, for whom the PIN therapy was discontinued. There were no treatment-related deaths. CONCLUSION: The PIN combination was highly active and tolerable in previously treated patients with urothelial cancer as a second-line treatment.

Adult↗

PubMed2006

Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice.

AIM: To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation. METHODS: Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki-67 labeling index (LI) were examined to evaluate the preservation of original features. A growth delay assay after single-dose irradiation was performed in four representative xenografts. RESULTS: Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas similar to the original tumors, whereas the other 3 were Epstein-Barr virus-associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki-67 LI of the patients' tumors. Of these 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, and the Ki-67 LI of eight xenografts was within a range of 50% of the LI of the original tumors, although the other three xenografts increased by over 50%. Specific growth delay after irradiation, independent of the original tumor growth speed and Ki-67 LI, was observed in four xenografts. CONCLUSIONS: SCID mice are useful recipients for investigations of human urothelial cancer with a wide biological range. This easy-to-handle xenograft system can help to develop a better in vivo preclinical evaluation system for therapeutic agents as well as the investigation of tumor pathophysiology.

Animals↗

PubMed2006

Laparoscopic removal of a retroperitoneal extralobar pulmonary sequestration in an adult.

A 41-year-old male patient presented with dull left flank pain. A computed tomography (CT) showed a subdiaphragmatic retroperitoneal extra-adrenal mass. A magnetic resonance image demonstrated it was hypointense on T1 weighted and hyperintense on T2. Serum analyses for adrenal hormones revealed no abnormality. [I131]metaiodo-benzylguanidene scintigraphy showed no abnormal uptake. The patient underwent laparoscopic removal to manage the symptoms and to make a pathological diagnosis, which was an extralobar pulmonary sequestration. Another congenital lung malformation was not detected on chest CT scan. The symptom was relieved postoperatively.

Adult↗

PubMed2006

[Transrectal biopsy of the prostate for the detection of non-palpable prostate cancer: a comparison of 6 versus 12 core biopsy].

PURPOSE: Several studies suggest that extended transrectal prostate biopsy more than 6 core may improve the cancer detection rate. We compared 6 and 12 core biopsies to determine the impact on cancer detection and complication rate. PATIENTS AND METHODS: We retrospectively evaluated 150 patients who underwent transrectal ultrasound guided prostate biopsy between January 1999 and December 2003. Patients who were suspected to have prostate cancer on digital rectal examination and/or who had a history of previous prostate biopsy were excluded. Sextant biopsy was performed in 52 patients (6 core group) and 12 core biopsy was performed in 98 patients (12 core group). The cancer detection rate and post-biopsy complication rate were estimated. RESULTS: There was no significant difference in the overall cancer detection rate between 6 and 12 core groups (17 of 52 men or 32.7% versus 35 of 98 men or 35.7%). In addition, even if calculated the cancer detection rate stratified according to a PSA of 0 to 4.0, 4.1 to 10.0 and greater than 10.0 ng/ml, there was no significant difference between both groups. There was also insignificant difference of complication rate between both groups. CONCLUSIONS: The results of our study showed that there was no significant difference in cancer detection and complication rate between both groups.

Aged↗

PubMed2005

Negative feedback regulation of T helper type 1 (Th1)/Th2 cytokine balance via dendritic cell and natural killer T cell interactions.

The ability of extracellular stimuli to modulate dendritic cell (DC) activation of natural killer T (NKT) cells was not well understood. We investigated the effects of the T helper type 1 (Th1)/Th2-cytokine environment on DC induction of NKT cell-mediated cytokine production in mice. Pretreatment of myeloid DCs with Th1 or Th2 cytokines, interleukin (IL)-4 or interferon (IFN)-gamma, led to the enhanced production of reciprocal cytokines by NKT cells (eg, IL-4 pretreatment led to the enhanced production of Th1 cytokines) in vitro and in vivo. Thus, the recognition of Th1 or Th2 cytokines by DCs acts as a negative feedback loop to maintain Th1/Th2-cytokine balance via NKT cell functions. Using these data, we manipulated cytokine levels and innate cytolytic activity in vivo to increase an antitumor response. This is the first description of a novel regulation system governing Th1/Th2 cytokine balance involving DCs and NKT cells.

Animals↗

PubMed2005

Advanced renal pelvic carcinoma associated with dermatomyositis.

Dermatomyositis is an uncommon in flammatory myopathy with characteristic cutaneous manifestations which is frequently linked to several cancers. A 42-year-old man presented with left flank pain with typical symptoms of dermatomyositis. Computed tomography showed a solid mass in the pelvis of the left kidney and lymphadenopathy in the retroperitoneum. Since the general condition of the patient rapidly deteriorated because of marked muscle weakness of the respiratory muscles, the patient initially underwent medical treatment with prednisolone. After the improvement of respiratory function, the patient underwent radical nephroureterectomy and retroperitoneal lymphadenectomy. The pathological specimen showed moderately differentiated adenocarcinoma, stage pT3N2. After surgery, the patient showed a marked improvement of clinical symptoms related to dermatomyositis. Twenty-two months later, multiple organ metastases occurred and the patient died of cancer. We should point out the significance of surgical and medical treatment for these patients.

Adenocarcinoma↗

PubMed2004

Gelsolin gene silencing involving unusual hypersensitivities to dimethylsulfate and KMnO4 in vivo footprinting on its promoter region.

We previously reported that gelsolin gene expression is reduced in various tumors. In an effort to gain further insights into the mechanism of gelsolin downregulation in tumors, we examined the in vivo properties of the gelsolin promoter in urinary bladder cancer cell lines. Neither mutation nor hypermethylation was responsible for gene silencing at the promoter. After exposure to trichostatin A (TSA), a histone deacetylase inhibitor, gelsolin promoter activity was markedly enhanced in the cancer cells, not in cells derived from normal tissue. Chromatin immunoprecipitation assays revealed that both histones H3 and H4 were hypoacetylated in the promoter region of the cancer cells, and the accumulation of acetylated histones was detected by TSA treatment. In vivo footprinting analysis revealed the presence of dimethylsulfate (DMS) hypersensitive site in the untranslated region around nucleotide--35 only in the cancer cells but not in cells derived from normal tissue, and analysis of KMnO4 reactive nucleotides showed that the stem loop structure could be formed in vivo of the cancer cells. This novel stem loop structure may play a part in regulating the transcription of the gelsolin gene in the cancer cells. These results suggest that nucleosome accessibility through histone deacetylation and structural changes (DMS hypersensitivity and stem loop structure) in the promoter region form the basis of the mechanism leading to the silencing of gelsolin gene in human bladder cancer.

Base Sequence↗

PubMed2004

Management of renal angiomyolipomas associated with tuberous sclerosis complex.

PURPOSE: Intensive management is generally recommended for angiomyolipomas associated with tuberous sclerosis complex (TSC), which are known to have a more aggressive nature than sporadic tumors. In this study we evaluated the management of these tumors. MATERIALS AND METHODS: The records of 6 men and 6 women with TSC and a mean age of 28.8 years) with angiomyolipomas treated from 1984 to 2000 were retrospectively analyzed. All patients had bilateral multiple tumors (mean size 6.6 cm). There were 10 lesions classified as small (less than 4 cm), 6 medium (4 to 10 cm) and 8 large lesions (10 cm or greater). Computerized tomography was repeated annually for followup observation and semiannually after embolization. RESULTS: Excluding from study 3 tumors treated prophylactically intervention was required in 20%, 50% and 100% of small, medium and large tumors, respectively. Among 14 tumors followed by observation, 8 grew and 4 required intervention. Uncontrollable hemorrhage did not develop in any patient. While some tumors showed remarkable growth in decade 3, growth did not exceed 1.5 cm per year. Embolization was performed in 11 tumors and tumors shrank in 10. Although 1 patient experienced renal atrophy, all patients but 1 are alive without renal failure with a mean followup of 60 months. CONCLUSIONS: Although asymptomatic angiomyolipomas associated with TSC grow gradually, severe hemorrhage is rare and most tumors can be managed conservatively with annual computerized tomography. Embolization is the first choice of intervention but should be reserved until symptoms develop.

Adolescent↗

PubMed2004

Impact of cyclooxygenase-2 gene expression on tumor invasiveness in a human renal cell carcinoma cell line.

PURPOSE: We have previously confirmed that cyclooxygenase-2 (COX-2) is expressed in a human renal cell carcinoma (RCC) cell line and it has an important role in cell tumorigenesis and angiogenesis. In the current study we evaluated the impact on cell adhesion and tumor invasiveness in human RCC cell lines by transfection of COX-2 sense and antisense cDNAs. MATERIALS AND METHODS: A human RCC cell line that expresses COX-2 was transfected with COX-2 sense or antisense cDNA. E-cadherin expression in parental cells of OS-RC-2 and transfectants was detected by real-time polymerase chain reaction and Western blotting. The expression of beta-catenin was detected by Western blotting. Zymography was used to detect gelatinase activity. CD44 expression in parental cells and transfectants was detected by fluorescence activated cell sorting. Cell adhesion was detected by adhesion assay and cell invasive ability was detected by invasion assay. RESULTS: E-cadherin expression was increased in antisense transfectants and decreased in sense transfectants compared with parental cells at the mRNA and protein levels. However, obvious consistent changes in beta-catenin expression could not be confirmed in parental cells and transfectants, nor were there any significant differences in gelatinase activity in parental cells and transfectants. CD44 expression was increased in sense transfectants and decreased in antisense transfectants compared with parental cells. Adhesion to hyaluronan coated wells was significantly enhanced in sense transfectants and inhibited in antisense transfectants compared with parental cells. Compared with parental cells invasive ability was significantly increased in sense transfectants and decreased in antisense transfectants. CONCLUSIONS: The results demonstrate that COX-2 expression has a crucial role in cell invasion ability and the suppression of COX-2 expression might regulate adhesion molecule expression and inhibit invasive ability in the RCC cell line OS-RC-2.

Carcinoma, Renal Cell↗

PubMed2004

Multiple primary malignancies in Japanese patients with renal cell carcinoma.

AIM: To evaluate the incidence, nature and prognosis of multiple primary malignancies involving renal cell carcinoma (RCC) in Japan. METHODS: Between 1975 and 1998, 319 patients underwent an operation for RCC at Hokkaido University, Sapporo, Japan. The incidence of other primary malignancies was determined and classified as antecedent, synchronous or subsequent. Follow-up was obtained by thorough chart review or telephone interview, and ranged from 0 to 276 months (median 49.0 months). To analyze the influence of other primary malignancies on prognosis, overall and cause-specific survival rates of the patients with an antecedent or synchronous malignancy were compared to the remaining patients. RESULTS: Of the 319 patients there was at least one other malignancy in 38 patients (12%). Four patients had two other malignancies. The other malignancies were antecedent in 13, synchronous in 19 and subsequent in 10 patients. Twenty-two patients had gastrointestinal cancer. In cases of antecedent or synchronous diagnosis of other primary malignancies, RCC was commonly incidental, small or low-stage. Multivariate analysis using Cox's proportional hazards model showed that, for overall survival, the presence of other antecedent or synchronous malignancies was the second most significant prognostic factor, following the pathological stage of RCC. CONCLUSIONS: In Japanese patients with RCC, the incidence of other primary malignancies was not uncommon and these malignancies contributed to the prognosis of these patients. Therefore, the malignant potential of individual tumors should be paid careful attention in the management of these patients.

Age Factors↗

PubMed2004

Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancer.

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of adjuvant combination chemotherapy for locally advanced urothelial cancer. METHODS: Between 1987 and 1998, 56 patients with locally advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical nephroureterectomy and regional lymphadenectomy. Thirty-one patients had lymph node-positive disease and 25 patients did not. Twenty patients underwent adjuvant chemotherapy and 36 patients were observed after surgery. Cox proportional hazards models were used to determine the impact of numerous clinicopathological findings on survival. A subgroup analysis of patients with lymph node-positive disease was conducted to evaluate disease-free survival and overall survival rates. RESULTS: In this series, the median follow-up period was 39 months (range, 4-163) after surgery. Disease-free and overall survival rates of all 56 patients were 45% and 58%, respectively, at 3 years. Only lymph node status was significantly associated with disease-free and overall survival in the multivariate analyses. In a subgroup analysis of patients with lymph node-positive disease, 16 patients who underwent adjuvant chemotherapy had superior disease-free survival compared to 15 patients with no adjuvant chemotherapy (P = 0.0376). CONCLUSION: These findings show that the prognosis of advanced urothelial cancer is significantly associated with nodal status. Furthermore, adjuvant combination chemotherapy has a positive impact on survival in patients with lymph node-positive disease.

Adult↗

PubMed2004

Laparoscopic radical nephrectomy in the elderly.

OBJECTIVE: To evaluate the efficacy and outcome of laparoscopic radical nephrectomy (LRN) in patients aged >75 years, and to compare the results with those obtained from patients younger than this undergoing laparoscopic surgery for the same indication. PATIENTS AND METHODS: From a retrospective review of 33 patients aged >75 years undergoing LRN, 28 were for tumour. A group of 28 consecutive patients aged <75 years undergoing laparoscopy for the same indication were used for comparison. The two groups were compared for American Society of Anesthesiology (ASA) physical status score, comorbidity, previous surgical history, operative duration, estimated blood loss, tumour size, complications during and after surgery, conversion rates, time to oral intake and drain removal, perioperative mortality and hospital stay. RESULTS: Only the initial ASA score was significantly higher for the older patients. All other variables before, during and after surgery were similar for both groups. CONCLUSIONS: The final outcome of laparoscopic surgery in elderly patients was as promising as in their younger counterparts. Therefore, elderly patients should not be excluded from LRN, even though they usually present with more comorbidities.

Aged↗

PubMed2004

Evaluation of urinary extravasation and results after continence-preserving radical retropubic prostatectomy.

OBJECTIVE: To evaluate the feasibility of urinary catheter removal 10 days after a radical retropubic prostatectomy (RRP) by assessing the incidence of urinary extravasation and its effect on postoperative stricture and continence rates. PATIENTS AND METHODS: During a 4.5-year period, 619 patients undergoing RRP were evaluated. If no extravasation was detected on gravity cystography, the urinary catheter was removed 10 days after RRP. In patients with significant extravasation the catheter was left in place for 3 weeks. Overall stricture and continence rates were recorded in patients at 3, 6 and 12 months after surgery. RESULTS: There was extravasation during cystography in 29 patients (4.6%). At 3, 6 and 12 months, continence rates after catheter removal at 10 days were 74.9%, 87.9%, and 93.6%, respectively, while in the late-removal group they were 72.4%, 84.6% and 90.9%, respectively, with no significant difference between the groups. At 3 months the overall continence rate was 74.8% and at 12 months up to 93.5%. There was no difference in stricture rates between the groups, with an overall stricture rate of 0.7%. CONCLUSIONS: Catheter removal 10 days after RRP is feasible, giving excellent early and late continence rates, with low anastomotic stricture rates obtained using good surgical technique. Extravasation at 10 days was rare and with proper management did not influence the final results.

Adult↗

PubMed2004

[Paclitaxel, ifosfamide, nedaplatin (TIN) for patients with metastatic urothelial cancer].

TIN (ifosfamide 1.5 g/m2 daily for 3 days, paclitaxel 175 mg/m2, and nedaplatin 70 mg/m2 on day 1) was administered to patients with metastatic urothelial cancer previously treated by platinum-based chemotherapy and repeated every 4 weeks. Four patients received maintenance therapy, which consisted of 5'-DFUR 800 mg/day orally for 12 weeks and 1 subsequent course of TIN. This therapy regimen was repeated for 2 years from initiation of TIN. Eleven of 12 patients (91.6%) demonstrated a major response (3 complete responses, 8 partial responses), with durations of response ranging from 3 to 20 months. Progression-free survival time was from 0 to 20 months (median 8 months). One-year progression-free survival rate was 45.8%. Overall survival time was from 2 to 20 months (median 10.5 months). One-year overall survival rate was 53.5%. Grade 3/4 hematologic toxicity involved neutropenia in 100% and thrombocytopenia in 33.3%. Febrile neutropenia was observed in 5 patients (41.6%). Grade 3 nonhematologic toxicity involved malaise in 15.3%. No patient discontinued this therapy because of complications. TIN is a potent, well-tolerated regimen for previously treated patients with urothelial cancer.

Aged↗

PubMed2003

Ureteral stricture developing after partial nephrectomy with a microwave tissue coagulator: case report.

A 32-year-old man with a 1.7-cm tumor in the left kidney underwent laparoscopy-assisted partial nephrectomy. Although his postoperative course was uneventful, a 6-month postoperative CT scan showed hydronephrosis secondary to a severe stricture at the ureteropelvic junction. Heat injury to the urinary tract was strongly suspected. The use of microwave tissue coagulator for the tumor close to the renal sinus and excessive coagulation should be avoided to prevent heat-related complications.

Adult↗

PubMed2003

[Ureteral and bladder metastases of renal cell carcinoma following synchronous renal cell carcinoma and bladder cancer; a case report].

A 73-year-old man presented with gross hematuria. Ultrasonography and computerized tomography showed small bladder tumors and a left renal mass protruding to renal pelvis. Transurethral resection of bladder tumor and ureteroscopic tumor biopsy were performed, and pathological examinations revealed transitional cell carcinoma in the bladder and renal cell carcinoma in the kidney. He underwent left radical nephrectomy. A 4-month postoperative cystoscopy revealed a solitaly non-papillary tumor in the bladder. Transurethral resection was performed and pathological diagnosis was metastasis from renal cell carcinoma. At that time, multiple metastases to ureteral stump and lung were found. He had undergone palliative treatment because of his poor general condition until he died 26 months postoperatively. Care should be taken for management of ureteral stump when diagnostic ureteroscopy was done for renal cell carcinoma invading the renal pelvis.

Aged↗