[RETROSPECTIVE ANALYSIS OF POSITIVE SURGICAL MARGIN AT RADICAL PROSTATECTOMY].

We retrospectively reviewed 182 patients who underwent radical prostatectomy in our hospital between April, 2009 to December, 2012, and who had not received any prior hormonal therapy. We also excluded the patients who couldn't followed up more than 6 months after surgery and pN1 patients. Positive surgical margins were observed in 65 cases. We determined what were the significant factors associated with the margin status. The another aim of present study is to evaluate the risk factor which might have significance for biochemical recurrence. BMI ≥ 25.0, prostate volume < 40 cm3, and biopsy positive core ≥ 25% were significant predictors of positive surgical margin. PSA nadir ≥ 0.02 ng/ml and pT3 were the significant factors which associated with biochemical recurrence of those patients with positive margin status.

Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer.

BACKGROUND: A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). METHODS: Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. RESULTS: The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. CONCLUSIONS: The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.

Importance of continuing therapy and maintaining one-month relative dose intensity in sunitinib therapy for metastatic renal cell carcinoma.

Sunitinib is a multikinase inhibitor used as first- and second-line treatment of metastatic renal cell carcinoma. However, there are few reports on the necessary doses of sunitinib to get better clinical outcome in general practice with Japanese patients. We examined the relationship between the efficacy and the necessary doses of sunitinib therapy in a multi-institutional retrospective study. A study population of 94 metastatic renal cell carcinoma patients was eligible for this investigation. The most frequent grade 3/4 laboratory adverse events were decreased platelet (31.9 %) and white blood cell (21.3 %) counts. Treatment was discontinued in 18 patients (31.0 %) initially receiving a 50-mg/day dose within only one course, and median 1-month relative dose intensity was 74.3 %. Median progression-free survival time was 2.3 months in patients treated for only one course and 10.8 months in patients treated for more than one course (P < 0.001). Multivariate analysis showed that only one course of treatment and 60 % and less of 1-month relative dose intensity were significantly associated with inferior progression-free survival (P < 0.001 and P = 0.027, respectively). Moreover, modified Memorial Sloan-Kettering Cancer Center poor risk was significantly associated with progression-free survival time. It is difficult for Japanese patients to continue an initial dose of sunitinib therapy without drug withdrawal. Continuing therapy for more than one course and maintaining more than 60 % of 1-month relative dose intensity were very important in the prolongation of progression-free survival time regardless of the initial treatment doses.

[A case report of retrocaval ureter associated with right ureteral tumors].

A case of retrocaval ureter associated with right ureteral tumor in a 70-year-old male is reported. The diagnosis was confirmed by CT and RP. Retroperitoneoscopic nephroureterectomy was performed. The histology of the tumor was urethelial carcinoma. After 20 months, there was neither evidence of recurrence nor metastasis. To our knowledge, this is the 11th case of retrocaval ureter associated with upper urinary tract tumors.

Pulmonary metastasectomy in patients with renal cell carcinoma: a single-institution experience.

BACKGROUND: Pulmonary metastasectomy in patients with renal cell carcinoma (RCC) remains controversial. The purpose of our analysis was to explore the outcome of patients with RCC who underwent pulmonary metastasectomy at our institution. METHODS: We reviewed data on 25 patients who underwent resection of lung metastasis from 1998 to 2008 at our institution. RESULTS: All patients were treated by radical nephrectomy for primary RCC. Progression-free survival (PFS) ranged from 0.3 to 198.8 months (median 7.4 months), and overall survival (OS) ranged from 2.4 to 198.8 months (median 33.9 months). The 5-year PFS rate was 24.9%, and the OS rate was 35.5%. Although differences in the resectability of the metastasectomy and OS were not significant in univariate or multivariate analyses, the relationship between PFS and the radicality of pulmonary metastasectomy was significant in both the univariate and multivariate analyses (P = 0.004, 0.012, respectively). CONCLUSIONS: The results of pulmonary metastasectomy for patients with RCC at our institution indicate that pulmonary metastasectomy should be performed only when the pulmonary metastasis can be completely resected. Additional studies are therefore necessary to evaluate the prognostic factors and to determine the selection criteria for pulmonary metastasectomy in the new era of molecular-targeted agents.

Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

OBJECTIVE: • To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. PATIENTS AND METHODS: • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. RESULTS: • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). CONCLUSION: • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy.

Excision repair cross-complementing group 1 may predict the efficacy of chemoradiation therapy for muscle-invasive bladder cancer.

PURPOSE: Chemoradiation therapy (CRT) is now widely recognized as bladder-preserving therapy for muscle-invasive bladder cancer (MIBC). However, some patients who fail CRT may miss the chance to be cured by cystectomy. Therefore, it is important to select patients with MIBC who are expected to have a good response to CRT. Several reports indicate that the excision repair cross-complementing group 1 (ERCC1) gene is associated with resistance to cisplatin and radiation therapy. In this study, we examined the correlation between ERCC1 and CRT in vitro and in vivo in bladder cancer. EXPERIMENTAL DESIGN: Bladder cancer cell lines T24, 5637, Cl8-2 (multidrug-resistant subline of T24), and CDDP10-3 (cisplatin-resistant subline of T24) were used for in vitro assays to measure ERCC1 expression level and growth inhibition with cisplatin or ionizing radiation (IR). We then examined by immunohistochemistry that whether ERCC1 nuclear staining correlates with the efficacy of CRT using cisplatin in 22 patients with MIBC. RESULTS: Cl8-2 cells expressed ERCC1 mRNA 5.96-fold higher than did T24. Cl8-2 and CDDP10-3 were more resistant to cisplatin or IR than was T24. Resistance to IR, but not to cisplatin, was removed by suppressing ERCC1 using siRNA in both Cl8-2 and CDDP10-3 cells. In immunohistochemistry with ERCC1, 6 of 8 positive cases did not have complete response to CRT, whereas 12 of 14 negative cases had complete response. Sensitivity and specificity were 75% and 85.7%, respectively (P = 0.008). CONCLUSION: Although further study is needed, ERCC1 expression level may predict the efficacy of CRT for MIBC.

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

OBJECTIVE: To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. METHODS: Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. RESULTS: Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. CONCLUSIONS: The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

[A case report of retroperitoneal fibrosis associated with IgG4-related sclerosing disease].

A 67-year-old man had undergone a right ureteronephrectomy because of a right ureter tumor, but the pathological diagnosis was inflammatory tissue with plasma cells, lymphocytes, and fibrosis. About 3 years later, abdominal computed tomography (CT) revealed a solid tumor at the left renal hilus. We resected the tumor and the pathological diagnosis was the same as before. More than 2 years later, because of elevated pancreatic enzymes, immunoglobulin G (IgG) and IgG4, more detailed examinations ware done, and he was diagnosed with IgG4-related autoimmune pancreatitis. We believe that the retroperitoneal tumor was retroperitoneal fibrosis associated with IgG4-related sclerosing disease. Now, he is being treated with steroid therapy. IgG4-related sclerosing disease is a systemic disease whose concept is now being established. Much more work is needed to understand this disease.

Decreased infiltration of macrophage scavenger receptor-positive cells in initial negative biopsy specimens is correlated with positive repeat biopsies of the prostate.

Macrophage scavenger receptor (MSR)-positive inflammatory cells and tumor-associated macrophages (TAMs) have been reported to regulate the growth of various cancers. In this study, the infiltration of MSR-positive cells and TAMs was analyzed to predict the outcome of repeat biopsy in men diagnosed as having no malignancy at the first prostate biopsy. Repeat biopsy of the prostate was carried out in 92 patients who were diagnosed as having no malignancy at the first biopsy. Of these, 30 patients (32.6%) were positive for prostate cancer at the repeat biopsy. Tumor-associated macrophages and MSR-positive cells were immunohistochemically stained with mAbs CD68 and CD204, respectively. Six ocular measuring fields were chosen randomly under a microscope at x400 power in the initial negative biopsy specimens, and the mean TAM and MSR counts for each case were determined. No difference in TAM count was found between the cases with or without prostate cancer. By contrast, the MSR count in patients with cancer was significantly lower than that in patients without cancer at the repeat biopsy (P < 0.001). Logistic regression analysis indicated that the MSR count at first biopsy is a significantly better predictive factor for positive repeat biopsy than PSA velocity, interval between first and repeat biopsies, or TAM count. Decreased infiltration of MSR-positive cells in negative first biopsy specimens was correlated with positive findings in the repeat biopsy. The MSR count might be a good indicator for avoiding unnecessary repeat biopsies.

SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer.

Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.

Tumor multiplicity is an independent prognostic factor of non-muscle-invasive high-grade (T1G3) bladder cancer.

OBJECTIVE: Non-muscle-invasive high-grade (T1G3) bladder cancers have high potential for progression. The objective of this study is to clarify the clinicopathological factors affecting the outcome of T1G3 bladder cancer. METHODS: We retrospectively reviewed 60 cases of T1G3 bladder cancer between 1994 and 2006. The correlations of both intravesical recurrence and progression with prognostic factors, such as T stage, history of bladder cancer, multiplicity, concomitant carcinoma in situ, tumor size, intravesical instillation of bacillus Calmette-Guérin and intravesical chemotherapy, were evaluated by multivariate analysis with the Cox proportional hazards model. RESULTS: Median follow-up period was 52 months (4-105 months). Thirty-seven cases of intravesical recurrence (61.7%) were observed during follow-up. Two- and 5-year recurrence-free survival rates were 44.1% and 36.1%, respectively. Tumor multiplicity and instillation of bacillus Calmette-Guérin were significantly correlated with intravesical recurrence on multivariate analysis. Ten cases of progression (16.7%) were observed during the follow-up period. Two- and 5-year progression-free survival rates were 87.7% and 83.4%, respectively. Only tumor multiplicity was significantly correlated with progression on multivariate analysis. CONCLUSIONS: T1G3 cancers with multiple lesions showed high risks of intravesical recurrence and progression. Although bacillus Calmette-Guérin instillation reduced the risk of intravesical recurrence, no effect was observed on disease progression.

[Synchronous bilateral chromophobe cell renal carcinoma: a case report].

An 81-year-old female presented with abdominal discomfort. Computed tomography scan showed a 26 x 22 mm tumor in the left kidney and 43 x 37 mm tumor in the right kidney. Clinical diagnosis was bilateral renal cell carcinoma, left; cT1a, right; cT1bN0M0. We planned primary unilateral partial nephrectomy, followed by secondary contralateral radical nephrectomy. Left partial nephrectomy was performed and 4 months later, laparoscopic right renal nephrectomy was performed without serious postoperative renal dysfunction. Pathological diagnosis of both tumors was chromophobe renal carcinoma. The patient has been doing well without any evidence of recurrence or metastasis.

Brain metastases from testicular germ cell tumors: a retrospective analysis.

OBJECTIVES: To review our series of testicular germ cell tumors with brain metastases and to establish an optimal treatment strategy for them. METHODS: Twenty-seven cases of testicular germ cell tumors from three institutions were retrospectively reviewed. RESULTS: Twenty-six were non-seminomatous tumors and only one was a seminoma. Based on the International Germ Cell Consensus Classification, two cases were classified as good prognosis, seven as intermediate prognosis and 18 as poor prognosis. Chemotherapy was carried out in all patients. Additionally, whole-brain radiotherapy was performed in 10 cases, stereotactic radiosurgery in six, whole-brain radiotherapy combined with stereotactic radiosurgery in three and complete surgical resection in five. Three patients received chemotherapy only. Cancer-specific 5- and 10-year survival rates were both 35.9%. The prognosis of those with brain metastases at the time of diagnosis tended to be better than those developing brain metastases during treatment. Those with a single brain metastasis showed significantly better survival than those with multiple brain metastases. No other significant prognostic factor was found at multivariate analysis. CONCLUSION: Testicular germ cell tumors with brain metastases can be managed with the combination of whole-brain radiotherapy, stereotactic radiotherapy, and/or surgical resection in combination with chemotherapy.

[Adrenal ganglioneuroma in a 14-year-old girl: a case report].

A 14-year-old girl was referred to our hospital for examination of a right adrenal tumor, incidentally found by abdominal ultrasound sonography. Computed tomographic scan and magnetic resonance imaging showed a 44 x 20 mm solid tumor in the right adrenal region. Endocrinological examination were within normal limits except for slightly increased serum aldosterone. Laparoscopic adrenalectomy was performed and the tumor was histologically diagnosed as ganglioneuroma originated from the right adrenal medulla.

[A case of recurrent ileal conduit hemorrhage].

A 68-year-old man visited our department with a complaint of persistent hemorrhage from ileal conduit. He had undergone total cystourethrectomy and ileal conduit construction for invasive bladder cancer in April 2000. He had been suffering from persistent stomal bleeding, although he received ligation of varices as well as occasional transfusions. Revision of the ileal conduit was performed in September 2002. Stomal bleeding has not recurred for 19 months.

[A case of extra-adrenal pheochromocytoma presenting with lung metastasis].

A 34-year-old man was referred to our hospital for small lung nodules. An imaging study including a computed tomographic scan and magnetic resonance imaging showed bilateral lung tumors and huge mass arising from the lower pole of the right kidney as well. The patient underwent right radical nephrectomy in May 2002. Pathological examination revealed that the tumor was pheochromocytoma, which developed from extra-adrenal tissue. In 6 cycles of CVD systemic chemotherapy (Cyclophosphamide 750 mg/m2, Vincristine 1.4 mg/m2, Dacarbazine 600 mg/m2), the lung tumors were decreasing in size, and were removed by a surgical procedure in January 2003. Pathological examination revealed that the lung tumors were pheochromocytomas metastasized from the primary tumor. He is alive without evidence of disease 5 months after the lung operation.

[Malignant pheochromocytoma responsive to multimodal therapy: a case report].

A 62-year-old man underwent right adrenalectomy for pheochromocytoma in May 1987. He was referred to our department for a right renal tumor suggested by ultrasound sonography in December 2000. Computated tomography and MRI showed a 10 cm mass arising from the upper pole of the right kidney. 131I-MIBG scintigram showed strong radio isotope accumulation consistent with the tumor. Right nephrectomy and subsegmental hepatectomy were performed. Histological findings led to the diagnosis of malignant pheochromocytoma. In February 2001, he complained of paraplasia due to Th2 bone metastasis. Radiation and CVD (cyclophosphamide, vincristine, dacarbazine) chemotherapy resulted in tumor regression and marked improvement of clinical symptoms.

[A case of Lambert-Eaton myasthnic syndrome associated with small cell lung carcinoma representing as urinary retention].

A 65-year-old male was admitted with the chief complaint of voiding difficulty on 28 October, 2001. He was in the state of urinary retention. Urological investigation including cystosocopy, urethrocystography, and urodynamic study revealed an areflex-type bladder, according to the new International Continence Society (ICS) classification with no prostatic urethral obstruction. He was diagnosed with neurogenic bladder although the cause of detrusor areflex was unknown. Because all medication was ineffective, transurethral resection of prostate was performed on 11 January, 2002, but urinary retention could not be relieved. After operation, he complained of muscle weakness of upper extremities and poor control of bowels. He was diagnosed with Lambert-Eaton myasthenic syndrome associated with small cell lung carcinoma. His myasthenic symptoms, including autonomic symptoms were relieved after chemotherapy and radiation for small cell lung carcinoma.

[A case of inguinal lymph node metastasis and urethral remnant tumor arising eight years after cystourethrectomy for bladder cancer].

A 59-year-old man had undergone total cystourethrectomy for bladder cancer (TCC G2 > G3 pT1) in July, 1991. Eight years later, he visited our department complaining of bleeding from external urethral meatus. Imaging study including computed tomographic (CT) scan and magnetic resonance imaging (MRI) showed a tumor arising from the urethral remnant and left inguinal lymph node involvement. Partial penectomy and left inguinal lymphadenectomy were performed. Histopathological examination revealed that both tumors were transitional cell carcinomas suggesting recurrence of bladder cancer. Two courses of M-VAC chemotherapy were given as adjuvant therapy.