Satoru Kawakami

Long-term Oncological Outcome and Risk Stratification in Men with High-risk Prostate Cancer Treated with Radical Prostatectomy

OBJECTIVEnTo evaluate the long-term oncological outcome of radical prostatectomy for patients with high-risk prostate cancer.nnnMETHODSnAmong 378 patients with prostate cancer who underwent radical prostatectomy at our hospital, 189 had high-risk prostate cancer defined as presenting with at least one of the following high-risk factors: prostate-specific antigen >20 ng/ml, clinical T3 and biopsy Gleason score ≥8.nnnRESULTSnThe median follow-up was 8.1 years. Of all patients, 106 and 61 had one and two high-risk factors, respectively, and the remaining 22 had all three high-risk factors. Pathological examination of the prostatectomy specimens revealed organ-confined disease, specimen-confined disease and lymph node metastasis in 80 (42%), 102 (54%) and 22 (12%), respectively. The 10-year prostate-specific antigen failure-free and local progression-free survival rates were 48.5 and 87.6%, respectively. The 10-year cancer-specific and overall survival rates were 94.1 and 88.7%, respectively. The 10-year prostate-specific antigen failure-free survivals of patients with one, two and all three high-risk factors were 58.5, 39.9 and 22.7%, respectively (P = 0.0001). Of the 106 patients with one high-risk factor only, the high Gleason score group had the best 10-year prostate-specific antigen failure-free survival (69.1%); in particular, that of patients without Gleason grade 5 was 100% (P= 0.032).nnnCONCLUSIONSnApproximately half of patients with high-risk prostate cancer can be cured by radical prostatectomy without any adjuvant treatment. Radical prostatectomy for high-risk prostate cancer provides good long-term local cancer control and cancer-specific survival. In particular, radical prostatectomy for patients with only one high-risk factor can be considered a valuable therapeutic option as the first treatment.

Prognostic Significance of Cancer Volume Involving Seminal Vesicles in Patients With pT3bpN0 Prostate Cancer

OBJECTIVESnTo investigate the prognostic effect of the prostate cancer (PCa) volume involving the seminal vesicles (CVSVs) in the radical prostatectomy specimen from patients with Stage pT3bpN0 PCa.nnnMETHODSnWe retrospectively reviewed the clinical records of 27 patients with Stage pT3bpN0 PCa who had undergone radical prostatectomy alone. We measured the CVSVs using a grid method on the glass slide under microscopic inspection and investigated the association of the CVSVs with clinicopathologic variables.nnnRESULTSnProstate-specific antigen (PSA) failure was confirmed in 11 of the 27 patients (41%) during a median follow-up of 34 months. The 3-year PSA failure-free survival rate was 48%. The median CVSVs was 1.14 cm(3). On univariate analysis, a CVSVs of >1.63 cm(3) was associated with positive surgical margins (P = .018), bilateral seminal vesicle involvement (P = .03), a long maximal tumor dimension (P = .031), and a greater preoperative PSA level (P = .0007). The 3-year PSA failure-free survival rate for those with a CVSVs of <or=1.63 cm(3) vs >1.63 cm(3) was 80% and 0%, respectively (P = .0009). On multivariate analysis, only the PSA level and CVSVs were identified as significant and independent predictors of PSA failure. Stratifying patients into 3 risk groups by these predictors, the PSA failure-free survival rate for patients with a PSA level >or=10 ng/mL and a CVSVs of >1.63 cm(3) was significantly worse than for any other group.nnnCONCLUSIONSnThe CVSVs is useful and invaluable as an independent predictor of PSA failure in patients with Stage pT3bpN0 PCa. The measurement of the CVSVs is simple and helped to determine the indication for adjuvant treatment after radical prostatectomy.

Multiple primary malignant neoplasms associated with prostate cancer in 312 consecutive cases.

The relative risk for a second primary cancer after the diagnosis of prostate cancer and the prognostic impact of the association of multiple primary malignant neoplasms (MPMNs) in patients with prostate cancer were analyzed in a retrospective study. The development of MPMNs was examined in 312 consecutive patients who had been diagnosed with prostate cancer between 1966 and 1992. The population-based cancer incidence rates in Japan were utilized to calculate the expected number of MPMNs. Of the 312 patients, 60 fulfilled the diagnosis of MPMNs. In 13 men, prostate cancer and other malignancies were diagnosed simultaneously. In 35 of the 312 patients, prostate cancer was the second or third cancer diagnosis. In the remaining 287 patients, prostate cancer developed initially. Of the 287 patients, 12 developed a second primary malignancy compared with 17 expected (relative risk 0.71, 95% confidence interval 0.45-1.4). No single anatomic site showed a significantly increased risk above that expected either. The overall survival of patients with prostate cancer was not reduced by the association with MPMNs. This may be explained by the fact that the stage of the prostate cancer was lower in patients with MPMNs than in patients without MPMNs.

Superior vena cava syndrome caused by supraclavicular lymph node metastasis of renal cell carcinoma

A 65-year-old woman presented with gross hematuria in February 1997. Left renal tumor was revealed and radical nephrectomy was performed. Pathological examination revealed papillary renal cell carcinoma, pT3aN1M1 (ipsilateral adrenal gland). Interferon-α was administered for 1 year. Two years after the nephrectomy, metastasis to the left supraclavicular lymph node appeared. Seven years after the nephrectomy, the metastatic tumor invaded the brachiocephalic vein and extended to the superior vena cava (SVC), compatible with SVC syndrome. Although interferon-α and external-beam radiotherapy was performed, she died in February 2005. Autopsy revealed a left supraclavicular lymph node metastasis invading the thyroid gland, mediastinum, and brachiocephalic vein. The tumor thrombus descended via the SVC into the right atrium. The right lung artery was obstructed by tumor thrombus. There were no visceral metastases and no local recurrence.

Gasless Single Port Surgery for Renal Cell Carcinoma: Minimum Incision Endoscopic Surgery

Advances in minimally invasive urologic surgery have accumulated rapidly in recent years with the advent of laparoscopic and robot-assisted surgeries (Clayman, 1991; Guillonneau, 1999; Dasgupta, 2009; Lee, 2009). The procedures for renal cell carcinoma (RCC), radical nephrectomy and partial nephrectomy are among those that have benefited from such innovation. Both laparoscopic surgery and robot-assisted surgery have markedly reduced the invasiveness of surgeries compared to conventional open procedures; laparoscopic surgery is characterized by the use of endoscopy, insufflation with carbon dioxide (CO2) gas, and insertion of instruments from several trocar ports, while robot-assisted surgery also incorporates stereovision and state-of-the-art movable instruments.

Risk Stratification of High-grade Prostate Cancer Treated with Antegrade Radical Prostatectomy with Intended Wide Resection

OBJECTIVEnThe aim of this study was to assess the surgical outcome of high-grade prostate cancer (PCA) treated with antegrade radical prostatectomy with intended wide resection (aRP) and to establish the risk stratification.nnnMETHODSnA consecutive 77 Japanese patients with Gleason score 8-10 PCA were treated with aRP alone and excluding patients with persistently elevated prostate-specific antigen (PSA), prospectively observed without any treatment until PSA failure was confirmed. PSA failure-free, cancer-specific and overall survival curves were generated with Kaplan-Meier method and the difference between groups was assessed with log-rank test. Coxs proportional hazards model was used to elucidate predictors of PSA failure.nnnRESULTSnDuring a median follow-up of 6 years, PSA failure was observed in 41 (53%) of the 77 patients. Five- and 10-year PSA failure-free survival rates of the entire cohort were 44.6% and 40.1%, respectively. Both overall and cancer-specific survival rates of the entire cohort at 5 and 10 years were 96.8% and 87.9%, respectively. In a multivariate analysis, PSA (P = 0.008), specimen confinement (SC) (P = 0.006) and persistently elevated PSA after aRP were identified as significant and independent predictors of PSA failure. When stratifying patients into three risk groups according to PSA level and SC status, PSA failure-free survival rate in patients with PSA < 10 ng/ml and specimen-confined disease (SCD) was significantly better than that in those of any other groups.nnnCONCLUSIONSnGood prognosis can be expected in patients with high-grade PCA treated with aRP alone when PSA < 10 ng/ml and the tumor was removed as an SCD.

Profound bicalutamide withdrawal syndrome in a hormone-refractory T4N1 prostate cancer permitting both salvage radiotherapy and cessation of hormonal therapy.

Antiandrogen withdrawal syndrome (AWS) is a well-known phenomenon in combined androgen blockade (CAB) refractory prostate cancer. It is often defined as more than 50% decline in prostate-specific antigen (PSA) value after cessation of antiandrogen regardless of radiological improvement. Its response rate and duration is generally limited. We herein report a case of CAB refractory T4N1 prostate cancer with a profound bicalutamide withdrawal syndrome, which permitted salvage radiotherapy. A 74-year-old Japanese man with clinical T3bN0M0 prostate cancer with biopsy Gleason score 4 + 5 = 9 and initial PSA 40.4 ng/mL underwent lutenizing hormone-releasing hormone analog (LHRHa) monotherapy. After a nadir at 1.0 ng/mL 5 months later, PSA level re-elevated to 5.5 ng/mL 14 months after the diagnosis and bicalutamide 80 mg/day was added up to CAB. In spite of temporal stabilization of PSA for 3 months, it rose to 101.6 ng/mL 22 months later and he was referred to our hospital for further treatment. Computed tomography (CT) revealed a recurrent primary tumor invading to the bladder neck and a right obturator lymph node metastasis (clinical T4N1M0, Fig. 1a). Two months after the cessation of bicalutamide, PSA level began to decrease. Nine months after the cessation, 99% decrease in PSA was observed and the recurrent primary tumor as well as the metastatic lymph node disappeared (Fig. 1b). Consequently a total of 70 Gy external beam radiation therapy was delivered to the prostate and the right obturator region. After confirming the PSA level below the detection limit (<0.2 ng/mL), LHRHa was discontinued 12 months after the bicalutamide cessation. Thereafter, PSA continued to fall below 0.07 ng/mL even in the full recovery of serum testosterone level (Fig. 1c). He is doing well without any evidence of disease progression either clinically or biochemically more than 7.5 years after the diagnosis and 5.5 years after the onset of AWS. The following aspects are to be noted in the current case: although presented as a locally advanced and metastatic hormone refractory prostate cancer, (i) AWS manifested an extraordinarily profound response demonstrated by both biochemical and radiological normalization, (ii) the profound AWS permitted salvage local treatment, (iii) the successful local treatment made hormonal therapy unnecessary, and

Combination chemotherapy of ifosfamide, 5-fluorouracil, etoposide and cisplatin as perioperative treatment in lymph node positive bladder carcinoma patients treated by radical cystectomy

Objectives:u2003 To evaluate the efficacy and toxicity of perioperative combination chemotherapy with ifosfamide, 5‐fluorouracil, etoposide and cisplatin (IFEP) in bladder cancer patients with regional lymph node metastases treated by radical cystectomy.

Renal Cell Carcinoma in Dialysis Patients with End Stage Renal Disease: Focus on Surgery and Pathology

In 1977, Dunnill et al. from Oxford at first reported that 14 of 30 dialysis patients with end stage renal disease (ESRD) examined at autopsy had acquired cystic disease of the kidney (ACDK) and that six of these 14 patients had renal cell carcinoma (RCC), including one with distant RCC metastatsis.1 It is now well established that patients with ESRD are more prone to RCCs with an incidence of approximately 3 to 5 %.2-5 These studies may misrepresent the true incidence RCC because they primarily relay upon screening radiology, particularly ultrasonography (US), for detection. Better estimate was provided by a single-center study in which most renal transplant patients undergo ipsilateral native nephrectomy at surgery. Based upon strict pathologic criteria reported by Denton et al., prevalence of ACDK, renal adenoma and RCC and oncocytoma were found in 33%, 14%, 4.2% and 0.6% of 260 patients6, which may be lower than the true incidence given that only one kidney was removed. Chen et al. found higher incidence of RCCs vs. the general population, with a standardized incidence ratio of RCC in dialysis patients of 24.1 (p <.01)7. Ishikawa et al. were able to demonstrate that time spent on haemodialysis was the most important risk factor for ACDK and also for the development of RCC. This important observation did highlight the key features of ACDK developing on haemodialysis and apparently increasing the likelihood of RCC2,8,9. Hughson’s work suggested that during this time there was a progression of cystic lesions from simple to complex or hyperplastic cysts and on to renal tumor formation10. A recent nation-wide survey in Japan revealed a 15-fold increase in the number of dialysis patients with RCC in the last 2 decades8. Reasons for this rapid increase can be postulated as follows: the increasing number of dialysis patients: the increasing duration of dialysis in these patients: and the prevalence of tumor screening in dialysis patients by imaging studies. The prevalence of ACDK in the haemodialysis population in Japan appears to be higher than that in the USA or Europe and patient survival on dialysis in Japan is significantly longer. These are probably because of different patterns of primary renal disease and reduced cardiovascular comorbidity compared with Western populations11. The presence of RCCs also appears to vary within different populations. Kojima’s study of 2624

Successful 2-year-long remission following repeated salvage surgery in a patient with chemotherapy-resistant metastatic nonseminomatous germ cell tumor

A 34 year-old man with a diagnosis of nonseminomatous testicular cancer with retroperitoneal lymph node metastasis (T1N3M0S2, stage IIIb; intermediate prognosis, made after right inguinal orchiectomy was performed) was referred to our hospital after having had a total of eight courses of systemic chemotherapy and external-beam radiotherapy to the retroperitoneal region in the previous 1 year. His serum α-fetoprotein (AFP) level remained elevated. Two courses of paclitaxel, etoposide, and cisplatin combined chemotherapy (TEP; paclitaxel 120u2009mg/m2 day 1, etoposide 80u2009mg/m2 days 2–5, cisplatin 20u2009mg/m2 days 2–5) failed to normalize the AFP level. During the following 2 years he underwent salvage surgery four times; infrarenal retroperitoneal lymph node dissection (RPLND), left neck lymph node dissection, thoracic duct excision, and suprarenal RPLND. Viable cancer cells were found in all surgically resected specimens, except for the neck lymph node specimen. The serum AFP level was normalized and he has been well without relapse for 2 years after the last surgery. The present case suggests that repeated salvage surgery may be beneficial in selected patients with a chemotherapy-resistant metastatic germ cell tumor.