Masaki Togashi

Phase II study ofcis-diammine(glycolato)platinum, 254-S, in patients with advanced germ-cell testicular cancer, prostatic cancer, and transitional-cell carcinoma of the urinary tract

SummaryA multicenter cooperative study was conducted to evaluate the clinical efficacy and safety ofcis-diammine(glycolato)platinum (254-S), a second-generation anticancer platinum complex, in the treatment of genitourinary cancers. 254-S was given i. v. at 100 mg/m2 at 4-week intervals. As a result, 2 complete responses (CRs) and 8 partial responses (PRs) were obtained in 35 patients with transitional-cell carcinoma (TCC) of the urinary bladder or pyeloureter, 3 PRs were obtained in 16 subjects with prostatic cancer, and 6 CRs and 6 PRs were obtained in 15 patients with testicular cancer, generating objective response rates of 28.6% [95% confidence interval (CI), 14.6%–46.3%], 18.8% (95% CI, 4.0%–45.6%), and 80.0% (95% CI, 51.9%–95.7%), respectively. Bone marrow suppression was the dose-limiting toxicity, although it was reversible. Although no hydration was performed in approx. 40% of the patients, the incidence of nephrotoxic effects was low and most of those encountered were mild, the exception being one patient who showed severe renal insufficiency after the first treatment. Nausea and vomiting occurred in approx. 70% of the patients, but most gastrointestinal toxicities were controlled without antiemetic treatment. In addition, liver-function impairment was rarely observed. We conclude that 254-S is a promising cisplatin analogue for the treatment of genitourinary cancers and is worthy of further investigation in large-scale, randomized comparative studies with other platinum derivatives in both single-agent and combination regimens.

Peri-operative morbidity and mortality related to radical cystectomy: a multi-institutional retrospective study in Japan.

Study Type – Therapy (outcomes) Level of Evidence 2b Whats known on the subject? and What does the study add? Radical cystectomy remains associated with comparatively high perioperative morbidity and mortality, despite improvements in surgical techniques and perioperative care. At present, most studies on the complications associated with open radical cystectomy were derived from Western academic high‐volume centres, and data from Japan and other Asian countries were very limited. Using the modified Clavien grading system and 11 category grouping reported from MSKCC, we observed that 68% of patients experienced at least one complication within 90 days of surgery, and 17% of patients experienced major complications (90‐day mortality rate = 2%), which were compatible with reports from Western high‐volume centres. As far as we know, our report is the largest one regarding perioperative morbidity and mortality in Asian patients who underwent radical cystectomy.

Impact of Diagnostic Ureteroscopy on Intravesical Recurrence and Survival in Patients With Urothelial Carcinoma of the Upper Urinary Tract

PURPOSE We determined whether diagnostic ureteroscopy for upper urinary tract cancer affects intravesical recurrence and cancer specific mortality. MATERIALS AND METHODS In a retrospective, multi-institutional study we evaluated 208 patients undergoing nephroureterectomy for upper urinary tract cancer who had no perioperative systemic chemotherapy, history of invasive bladder cancer, distant metastasis or incomplete followup data. Of these 208 patients 55 who composed the study group underwent diagnostic ureteroscopy before nephroureterectomy while 153 serving as controls did not. We analyzed intravesical recurrence and cancer specific survival using the Kaplan-Meier method with the log rank test used to assess significance. RESULTS There was no significant difference between the 2 groups in patient characteristics or upper urinary tract cancer stage and grade while followup, and the proportion of multiple tumors and lymphovascular invasion positive tumors were significantly greater in controls. The 2-year bladder recurrence-free survival rate was 60.0% in the study group and 58.7% in controls. There was no significant difference in the intravesical recurrence rate between the 2 groups (log rank test p = 0.972). Estimated Kaplan-Meier cancer specific survival was 88.3% and 78.1% at 5 years in the study and control groups, respectively (log rank test p = 0.0687). CONCLUSIONS Diagnostic ureteroscopy did not affect intravesical recurrence or cancer specific survival in patients with upper urinary tract cancer undergoing nephroureterectomy.

Role of lymph node dissection in the treatment of urothelial carcinoma of the upper urinary tract: Multi-institutional relapse analysis and immunohistochemical re-evaluation of negative lymph nodes

AIM To determine the role of lymph node dissection (LND) in the treatment of urothelial carcinoma (UC) of the upper urinary tract (UUT). PATIENTS AND METHODS [Study-1] A retrospective multi-institutional study evaluated 293 patients undergoing predominantly nephroureterectomy for UC of the UUT. Of 293 patients, 267 patients had pure UC and 26 demonstrated other histological components. Regarding the pathological node status, 130 patients had pN0 disease, 141 patients had pNx disease and 22 patients had pN+ disease. The sites of initial recurrence and time to first recurrence were reviewed. The sites of recurrence were classified as locoregional or distant recurrence. The relationship between node status and future recurrence was analyzed. [Study-2] Fifty-one patients treated by nephroureterectomy at Hokkaido University Hospital were included. All had LND and all LNs were negative on hematoxylin and eosin staining. We re-evaluated the presence of micrometastasis in LND specimens by anti-cytokeratin immunohistochemistory. RESULTS [Study-1] Of 293 patients, 76 developed disease relapse. Regional lymph node recurrence was the most common site (34 patients). On multivariate analyses that adjusted for the effect of tumor stage and tumor grade, pNx (skipping LND) was an adverse factor not only for locoregional recurrence, but also for distant relapse. [Study-2] Immunohistochemistry identified micrometastases in 7 (14%) of 51 patients. Regarding survival, 5 of these 7 patients with micrometastases were alive at last follow-up. CONCLUSIONS On relapse analysis, skipping LND was an adverse factor not only for locoregional recurrence, but also for distant relapse. Immunohistochemistry detected micrometastases in about 14% of patients previously diagnosed as pN0. These findings further support a potential therapeutic benefit of LND by eliminating micrometastases.

Clinical Experience of Incidentally Discovered Adrenal Tumor with Particular Reference to Cortical Function

We reviewed 14 male and 9 female patients with adrenal tumor discovered incidentally by imaging studies in an attempt to assess adrenal function, mainly cortical function. Pathological diagnosis consisted of cortical adenoma in 12 patients, cortical nodular hyperplasia in 2, medullary hyperplasia in 1, cavernous hemangioma in 1, metastatic tumor in 4 and cyst in 2. Another adrenal cyst was diagnosed by percutaneous puncture. In all patients peripheral levels of plasma cortisol and aldosterone were normal. Plasma catecholamine levels were also normal except for 1 patient with medullary hyperplasia who had equivocal elevation. Among the patients with cortical adenoma and hyperplasia, however, 5 of 10 (50%) had excessive excretion of 24-hour urinary 17-hydroxycorticosteroids, 4 of 13 (31%) had a loss of plasma cortisol circadian rhythm and 7 of 14 (50%) had insufficient suppression on the dexamethasone test. Furthermore all patients had an increased ipsilateral uptake that was not suppressed after dexamethasone on 131iodine-adosterol scintigraphy, while a diminished contralateral uptake was noted in 5 of 15 (33%). Postoperatively, hypertension decreased to normal in 2 of 3 patients and impaired glucose tolerance was improved in 1 of 2. Two patients with cortical adenoma who exhibited a loss of plasma cortisol circadian rhythm experienced postoperative adrenal insufficiency. These data indicate that a considerable number of incidentally discovered adrenal tumors are not nonfunctioning particularly in reference to glucocorticoid secretion, and adrenalectomy seems to be beneficial in some of those patients with hypertension or impaired glucose tolerance.

Identification Of Icam-1-positive Cells In The Nongrafted And Transplanted Rat Kidney—an Immunohistochemical And Ultrastructural Study

Cellular localization of intercellular adhesion molecule-1 (ICAM-1) in rat nongrafted intact kidneys and in transplanted kidneys was investigated using monoclonal anti-rat ICAM-1, 1A29. The major ICAM-1-positive cells in the nongrafted and isografted kidneys were endothelial cells in the large vessels and intertubular capillaries, as observed using light microscopy. A weak, but specific expression of ICAM-1 antigen was noted in the glomeruli, but the exact localization and cell type were not clearly discernible. In the allograft, the ICAM-1-positive cells found in the nongrafted and isografted kidneys also expressed ICAM-1 antigen. In addition, tubular epithelial cells at the luminal border and some infiltrating cells in the allograft expressed IC AM-1. In the allograft, some graft-infiltrating cells were shown to be lymphocyte function-associated antigen-1 (LFA-1) -positive. As the nature of ICAM-1-positive cells in the infiltrates was unclear, we examined ICAM-1-positive cells using immunoelectron microscopy and the directimmunoperoxidase method. Glomerular endothelial cells, podocytes, and Bowmans capsular epithelial cells expressed ICAM-1 antigen in the nongrafted and transplanted kidneys. Among the infiltrating cells in the allograft, the major ICAM-1 positive cells were macrophagelike tissues, and some blastic lymphocytes also expressed ICAM-1. Only rarely did the proximal tubular cells express ICAM-1 antigen at the luminal surfaces in the intact kidney. In the allograft, the proximal, distal, and collecting ductular epithelial cells expressed ICAM-1 at the luminal surface, and in addition, the ICAM-1 antigen was also localized at the basal surfaces of some of the renal proximal tubular epithelial cells. The upregulated ICAM-1 expression in the allograft may accelerate graft rejection by augmenting adhesiveness of LFA-1-positive graft-infiltrating cells.

THE ROLE OF LYMPH-NODE DISSECTION IN THE TREATMENT OF UPPER URINARY TRACT CANCER: A MULTI-INSTITUTIONAL STUDY

To determine the role of lymph‐node (LN) dissection in patients undergoing surgery for upper urinary tract (UUT) cancer.

Experience With Revascularizing Renal Artery Aneurysms: is it Feasible, Safe and Worth Attempting?

PURPOSE We retrospectively evaluated the feasibility and efficacy of surgical revascularization for renal artery aneurysms. MATERIALS AND METHODS Beginning in 1984, 12 patients with renal artery aneurysm underwent renal revascularization regardless of clinical features. Postoperative results were analyzed regarding split renal function, patency of the revascularized arteries, blood pressure control and surgical complications. RESULTS Postoperative renal function was stable or improved in all but 1 case and patency in branched arteries was preserved in 86%. Hypertension in 8 patients was cured in 7 (88%), including 2 with renovascular hypertension, and improved in 1 (12%). Complications were minimal with only 1 ureteral stricture that required reoperation. CONCLUSIONS The majority of renal artery aneurysm cases are amenable to surgical repair. Carefully performed renal revascularization is rewarding in that high blood pressure is better controlled, renal function is improved and the potential risk of rupture is obviated.

The Proportion of Free to Total Prostate Specific Antigen A Method of Detecting Prostate Carcinoma

Prostate specific antigen (PSA) is the most useful marker for prostate carcinoma (CaP). However, the sensitivity and specificity for PSA are not sufficient for the diagnosis of organ‐confined prostate carcinoma. Recent studies have revealed that anti‐PSA antibody identifies both PSA complexed to alpha‐1‐antichymotrypsin and free PSA, whereas anti‐gamma‐seminoprotein antibody recognizes free PSA exclusively. To enhance the ability of PSA to detect CaP in patients with total PSA levels of 10 ng/mL or lower, we developed the ratio of gamma‐seminoprotein and PSA (free/total PSA index).

Measurement of Prostate Specific Antigen and γ-Seminoprotein Ratio: A New Means of Distinguishing Benign Prostatic Hyperplasia and Prostate Cancer

We measured a ratio of serum prostate specific antigen (PSA) and gamma-seminoprotein concentrations (referred to as the PSA/gamma-seminoprotein ratio) and evaluated its usefulness for the diagnosis of prostate cancer. Between April 1988 and October 1992, 214 men underwent prostatic biopsy and/or transurethral resection of the prostate, and the disease was diagnosed pathologically. Of 214 patients 127 were diagnosed as having benign prostatic hyperplasia, prostatitis or a normal prostate (no cancer), while 87 had prostate cancer. Of 61 patients with a serum PSA level greater than 10 ng./ml. 50 (82.0%) had prostate cancer, compared to 31 of 84 (36.9%) with a serum PSA level of 3.0 to 10 ng./ml. Of 113 patients with a serum gamma-seminoprotein level greater than 4.0 ng./ml. 52 (46.0%) had prostate cancer. The mean plus or minus standard deviation of the PSA/gamma-seminoprotein ratio for 127 patients without cancer was 0.942 +/- 0.564, while that for 87 prostate cancer patients was 12.840 +/- 45.327 (Wilcoxon p < 0.0001). The mean plus or minus standard deviation of the PSA/gamma-seminoprotein ratios for 37 prostate cancer patients with a PSA level of 10 ng./ml. or less and for 50 prostate cancer patients with a PSA level of more than 10 ng./ml. were 2.044 +/- 0.767 and 20.829 +/- 58.757, respectively. Even the mean PSA/gamma-seminoprotein ratio for prostate cancer patients with a PSA level of 10 ng./ml. or less was significantly greater than that for patients without cancer (Wilcoxon p < 0.0001). The sensitivities for PSA (cutoff value 3.0 ng./ml.), gamma-seminoprotein (cutoff value 4.0 ng./ml.) and PSA/gamma-seminoprotein ratio (cutoff value 1.45) were 93.1%, 59.8% and 92.0%, respectively, and the specificities were 49.6%, 52.0% and 91.3%, respectively. Of 91 patients with a PSA/gamma-seminoprotein ratio of 1.45 or more 80 (87.9%) had prostate cancer, while 116 of 123 (94.3%) with a PSA/gamma-seminoprotein ratio of less than 1.45, had no cancer. These results suggest that PSA/gamma-seminoprotein ratio yields the same sensitivity as PSA and more specificity than PSA levels, offering significant advantage over PSA in detecting prostate cancer. The mean plus or minus standard deviations of PSA/gamma-seminoprotein ratios for stages A, B, C and D prostate cancer were 1.847 +/- 0.786 (11 patients), 2.740 +/- 1.536 (30), 7.626 +/- 9.140 (12) and 27.149 +/- 70.500 (34), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)