Ken-ichi Tobisu

Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan

Objectives To assess the time trends, morbidity and mortality of contemporary anatomical radical retropubic prostatectomy (RRP) in a multi‐institutional study in Japan, where RRP has become more popular in the last decade.

Long-term results of a randomized trial for the treatment of stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities

OBJECTIVES To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Use of pretreatment prostate specific antigen doubling time to predict outcome after radical prostatectomy.

The objective of this study was to better understand the implications of the rate of prostate-specific antigen (PSA) changes in prostate carcinoma. We retrospectively calculated PSA doubling times prior to surgery in 62 patients with prostate carcinoma. The calculated values were compared with final pathologic findings and with rates of PSA failure after surgery. PSA values increased during the period of observation in 82.3% of the patients, whereas 17.7% had levels that remained stable. The median calculated PSA doubling time in those with increasing levels was 25.8 months, with doubling times ≤24 months observed in 37.1% of the patients. Stage pT3 disease was more common in patients with PSA doubling times of ≤36 months than in those with doubling times >36 months (P=0.02). Biochemical failure was more common in patients with rapid PSA doubling times (P<0.01). The calculated PSA doubling time prior to radical surgery is significantly associated with the final pathologic findings. Early PSA failure is more common in patients with rapid PSA doubling times prior to radical surgery.

Percentage of positive biopsy cores, preoperative prostate-specific antigen (PSA) level, pT and Gleason score as predictors of PSA recurrence after radical prostatectomy: a multi-institutional outcome study in Japan.

To evaluate the clinical outcome of radical prostatectomy (RP) in Japan, by retrospectively analysing the clinicopathological data in patients with clinical T1‐T2 prostate cancer treated by RP, as there can be prostate‐specific antigen (PSA) recurrence after RP in substantially many patients, and its character can differ according to ethnic group and/or country.

Clinical Significance of Nonpalpable Prostate Cancer with Favorable Biopsy Features in Japanese Men

Objective: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men.Patients and Methods: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly.Results: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan–confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm3. Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan–confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0.5 cm3 was 0.61 using a cut–off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13.Conclusions: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.

Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan.

OBJECTIVES To assess the time trends, morbidity and mortality of contemporary anatomical radical retropubic prostatectomy (RRP) in a multi-institutional study in Japan, where RRP has become more popular in the last decade. PATIENTS AND METHODS Between January 1991 and August 1998, 638 patients underwent RRP at seven urological centres in Japan. Major complications (within 30 days of surgery) and the 30-day mortality were reviewed retrospectively. Of the patients, 12.9% were < 60 years old, 56.3% were 60-69 years old and 30.9% were >/= 70 years old (median age 67). Results The number of RRPs increased markedly, by more than sevenfold, from 1991-92 to 1996-97, mainly because there were more patients undergoing RRP in their sixth decade. The contribution of T1c disease increased in absolute and relative terms, from 13.9% in 1991-92 to 37.9% in 1997-98. Over time, the mean blood loss and the allogeneic transfusion rate decreased steadily. There was a trend toward more favourable outcomes for pathological variables (an increased percentage of organ-confined disease, decreased margin positivity and a decreased incidence of positive lymph node metastasis). The most common complications were wound-related (7.5%), or anastomotic leakage (4.1%). Major cardiopulmonary complications occurred in only two patients (0.31%, both pulmonary embolisms). One patient died from cerebral haemorrhage within 30 days of surgery, giving a mortality rate of 0.16%. CONCLUSION s This study indicates a trend towards selecting patients most likely to benefit from RRP. Although the procedure is technically demanding, it can have an acceptably low rate of early complications, little mortality and need for allogeneic transfusion. The assessment of morbidity suggests a lower incidence of catastrophic thrombo-embolic and cardiac complications in Japanese patients than in Western men. The present data may be useful in decision-analysis models evaluating the role of therapy for Asian men with early-stage prostate cancer.

Sequential changes in the prostate of rats treated with chlormadinone acetate, testosterone and N-nitroso-N-methylurea.

An attempt was made to induce prostatic adenocarcinoma in rats. Temporary chemical castration of F344 rats was achieved by administration of diet containing 0.05% chlormadinone acetate (CMA) for three weeks. The prostate was then stimulated by three consecutive daily intramuscular injections of testosterone propionate (100 mg./kg.). On the day after the last testosterone injection, N-nitroso-N-methylurea (NMU) (50 mg./kg.) was injected intravenously. Animals were sacrificed 10 days and 4, 20, 40 and 60 weeks after NMU treatment. Well-differentiated adenocarcinomas were obtained in three of fifty-four animals (5.6%) by this treatment and a high incidence of simple hyperplasia (88%) and atypical hyperplasia (19%) was also observed at 60 weeks. More studies are necessary to develop a protocol resulting in more rapid induction of prostatic adenocarcinomas at higher incidence.

Signet-Ring Cell Carcinoma of the Urinary Bladder Associated with Transitional Cell Carcinoma of the Right Ureter

We report on a case of a 72-year-old male with vesical signet-ring cell carcinoma containing a transitional cell carcinoma (TCC) component. It was associated with pure TCC of the right ureter. No other microscopic changes were found in the bladder. The pathogenesis of this signet-ring cell carcinoma is described.

Relationship Between Papillary and Nodular Transitional Cell Carcinoma in the Human Urinary Bladder

A total of 186 cystectomized specimens were examined by step-sectioning to determine the relation between papillary and nodular transitional cell carcinomas of the urinary bladder. Tumors were classified as papillary (PC), nodular (NC), and carcinoma in situ (CIS) according to their gross and microscopic configurations. These cases, grouped as simple combinations of PC, NC, and CIS, namely, PC, PC + CIS, PC + NC, PC + NC + CIS, NC, NC + CIS, and CIS, were analyzed with respect to (a) the time from the initial symptom to cystectomy, (b) the treatment before cystectomy, (c) the grade, (d) the stage of tumors, (e) the multiplicity of tumors, (f) the presence of papillary structures inside or on the surface of nodular carcinoma, and (g) data on survival after cystectomy. Of the tumors, 17 were classified as CIS and 80 as PC and PC + CIS. Studies on 57 cases suggested an early change from PC to a mixture of PC and NC through papillonodular carcinoma during development, whereas 6 showed late development of NC during repeated recurrence of PC. These courses indicate that some cases of NC developed from PC. On the other hand, 26 cases exhibited direct progression from CIS to NC. Thus nodular invasive carcinomas may develop in two ways: by emergence of a more anaplastic cell population within a preexisting low grade papillary carcinoma; and by de novo development of an invasive nodular carcinoma directly from CIS.

Two Cases of Bladder Carcinoma with Similar Initial Features That Exhibited Completely Different Clinical Courses

Two cases of bladder carcinoma are described. The patients were of similar age, were both smokers and were treated for the same period, but exhibited completely different later clinical courses. Initially, both had a single, papillary, pedunculate tumor, identified as a transitional cell carcinoma, grade 2, pTa. One patient, six years later, had multiple papillary tumors covering almost all the mucosal surface and underwent simple cystectomy. Histologically the tumors were identified as transitional cell carcinomas, grade 2, pT1. The other patient, nine years later, had a single nodular invasive tumor with a concomitant, very tiny papillary tumor and underwent radical cystectomy. Histologically the tumor was transitional cell carcinoma, grade 2 greater than 3, pT4. Many of the questions raised by these cases are unanswered, but comparison of such cases should provide some clues to the natural history of bladder carcinoma.