[Assessment of Incidental Prostate Carcinoma Cases and Predictors by Holmium Laser Enucleation of the Prostate].

Surgery for benign prostatic hyperplasia (BPH) has greatly advanced with the development of laser technology ; and holmium laser enucleation of the prostate (HoLEP), which can be performed safely and with minimal invasiveness regardless of prostate size. Incidental prostate carcinoma (iPCa) following HoLEP occurs at a certain rate. Predictors, include age, biopsy, history, preoperative prostate specific antigen, and prostate volume. We compared cases with and without incidental carcinoma detection among 257 patients with BPH who underwent HoLEP at our hospital from July 2015 to December 2022. Among the 257 patients, 29 (11.3%) were found to have incidental carcinoma. Although 1 patient switched to endocrine therapy the remaining patients showed good prognosis under surveillance therapy. The proportion of cases with magnetic resonance imaging (MRI) findings suggestive of carcinoma was significantly higher in the incidental carcinoma detection group (p＝0.009). Furthermore, univariate analysis of incidental carcinoma predictive factors revealed a significant difference in MRI findings (odds ratio [OR] 2.92 ; confidence interval [CI] 1.33-6.42), and multivariate analysis showed similar results (OR 2.92 ; CI 1.33-6.42). At our hospital, we currently perform MRI scans for preoperative morphological assessments but not for cancer diagnosis. However, based on the results obtained, we aim to proactively utilize MRI for preoperative malignant screening, in addition to PSA.

Real-world outcomes and risk stratification in patients with metastatic castration-sensitive prostate cancer treated with upfront abiraterone acetate and docetaxel.

PURPOSE: We assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies. METHODS: The medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted. RESULTS: A total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34-0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33-1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42-2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups. CONCLUSIONS: Upfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.

Effect of Levofloxacin on the Efficacy and Adverse Events in Intravesical Bacillus Calmette-Guerin Treatment for Bladder Cancer: Results of a Randomized, Prospective, Multicenter Study.

BACKGROUND: Although bacillus Calmette-Guerin (BCG) is a standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), a high rate of adverse events with a variety of grades remains a difficulty. OBJECTIVE: In this randomized, prospective, multicenter study, we examined whether levofloxacin, given after each intravesical instillation of BCG, could improve its tolerance in patients with intermediate- to high-risk urothelial carcinoma of the bladder without compromising its efficacy. DESIGN, SETTING, AND PARTICIPANTS: Overall, 106 Japanese patients (85 men and 21 women; age: median, 69.5 yr) with primary or recurrent NMIBC were randomized after transurethral resection to induce treatment with intravesical BCG plus levofloxacin (group 1) or BCG alone (group 2). INTERVENTION: Patients who underwent intravesical instillation of BCG were randomized with or without levofloxacin administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events were assessed using the National Cancer Institute-Common Toxicity Criteria version 3.0. Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. RESULTS AND LIMITATIONS: There was no significant difference in baseline characteristics between the groups. The completion rate of group 1 (85.5%) was not significantly lower than that of group 2 (76.5%; p = 0.321). There was no significant difference in the completion rate of patients with pollakisuria, painful micturition, gross hematuria, fever elevation, and others between the groups. The incidence of adverse events in patients with high-grade pollakisuria (7.3% vs 25.4%, p = 0.041) and fever (0% vs 9.1%, p = 0.034) was significantly lower in group 1. The 5-yr progression-free and cancer-specific survival rates were significantly better in group 1. CONCLUSIONS: Prophylactic levofloxacin administration may reduce the severity of adverse events and contribute to better outcomes from BCG intravesical therapy in patients with NMIBC. PATIENT SUMMARY: Levofloxacin administration seems to be a safe and effective therapy for non-muscle-invasive bladder cancer patients treated with bacillus Calmette-Guerin intravesical therapy.

Real-world survival outcomes of adding docetaxel or abiraterone in patients with high-volume metastatic castration-sensitive prostate cancer: historically controlled, propensity score matched comparison with androgen deprivation therapy.

PURPOSE: This study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM). METHODS: Outcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS). RESULTS: After PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27-0.56 vs. HR 0.50; 95% CI 0.30-0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50-1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30-0.98 vs. HR 0.49; 95% CI 0.29-0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34-2.06). CONCLUSION: The comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI.

Short-term outcomes of risk-adapted upfront docetaxel administration in patients with metastatic hormone-sensitive prostate cancer: a multicenter prospective study in Japan.

We conducted a risk-adapted upfront docetaxel (DOC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Here, we reported an interim analysis of the study. The study enrolled 68 patients with newly diagnosed mHSPC between 2016 and 2018. According to the presence of visceral metastasis, an EOD score ≥ 3, or prostate-specific antigen (PSA) level at 3 months of ≥ 1 ng/mL, patients were divided into low- and high-risk groups. Patients were treated with androgen deprivation therapy (ADT) with or without bicalutamide; those in the high-risk group received upfront treatment involving six cycles of DOC (70 mg/m2). Short-term treatment effect, adverse events, and quality of life (QOL) were evaluated. Fifty (73.5%) were classified in the high-risk group, and 46 (67%) received upfront ADT + DOC. In the ADT + DOC group, 43.5% (20/46) patients achieved a PSA level ≤ 0.2 ng/mL. PSA nadir and time to PSA nadir were 0.291 ng/mL and 288 days, respectively. In the ADT + DOC group, 76.1% (35/42) patients had adverse events (AEs) of grade ≥ 3. During a median follow-up of 18.5 months, 36.4% (8/22) patients in the ADT group and 43.5% (20/46) in the ADT + DOC group had CRPC. Two QOL scores including the physical status and appetite loss at 6 months significantly worsened in the ADT + DOC group but was resolved by 12 months. Upfront DOC achieved high PSA responses without long-term QOL deterioration. However, the short-term outcomes were limited. Longer follow-up is needed to determine the survival advantage.

Host-related Risk Factors for Adherent Perinephric Fat in Healthy Individuals Undergoing Laparoscopic Living-donor Nephrectomy.

PURPOSE: The purpose of this study is to assess the risk factors and characteristics of adherent perinephric fat (APF) in healthy individuals. PATIENTS AND METHODS: Men who underwent laparoscopic donor nephrectomy were included. Video review was used to divide patients on the basis of APF severity. Relationship between APF scores and clinical and radiographic features was evaluated. RESULTS: Of the 92 patients, 43 (46.7%) and 8 (8.7%) were categorized as APF and severe APF, respectively. The median total operative time was significantly associated with APF severity. Sex, body mass index, and perinephric fat area, stranding, and thickness were significantly associated with severe APF. In the multivariate analysis, perinephric fat areas and stranding were independent risk factors for severe APF (HR, 1.189 and 14.450, respectively). In the 44 analyzed cytokines, levels of sIL-6R in the perinephric adipose tissue-conditioned medium were significantly higher for APF group than that for non-APF group (P=0.049). CONCLUSIONS: Host-related risk factors for APF could predict surgical difficulty in patients undergoing partial nephrectomy.

[Tuberous Sclerosis Complex Detected by Spontaneous Rupture of a Giant Renal Angiomyolipoma : A Case Report].

A woman in her 30s was admitted with abdominal pain and nausea. CT scan revealed a spontaneous rupture of the right giant renal angiomyolipoma, and trans-arterial embolization was performed successfully. With further examination, she was found to be affected with tuberous sclerosis complex (TSC) and she finally wastreated with everolimusfor prevention of recurrent spontaneous-rupture of renal angiomyolipoma.

Comparison of surgical stress in patients undergoing open versus laparoscopic radical prostatectomy by measuring perioperative serum cytokine levels.

PURPOSE: We evaluated the perioperative serum levels of inflammatory cytokines in patients with prostate cancer (PCa) treated with open or laparoscopic radical prostatectomy (RP) and assessed the surgical stress based on the cytokine levels in addition to conventional clinical stress markers after surgery. PATIENTS AND METHODS: One hundred sixty-five patients who received RP for clinically localized PCa were enrolled. Serum levels of interleukin (IL)-10, IL-6, tumor necrosis factor-α, IL-1ß, IL-8, and IL-12p70 were quantitatively measured using a multiplex bead array at three time points (i.e., before the operation [pre-OP], immediately after the operation [post-OP], and on postoperative Day 1 [POD1]). The perioperative changes in serum stress markers, including cytokines, were compared between patients who underwent open and laparoscopic RP, and the predictors for high levels of postoperative cytokines were assessed. RESULTS: The median age and estimated blood loss were significantly lower in the laparoscopic RP group than in the open RP group (P=.003 and P<.01, respectively). In all patients, body temperature, white blood cell count, and serum IL-10 and IL-6 levels were significantly higher at post-OP and POD1 than at pre-OP. Patients who underwent laparoscopic RP had significantly lower levels of serum IL-10, IL-6, and IL-1ß at post-OP and POD1 than those who underwent open RP. Multivariate regression analyses showed that the surgical group (open versus laparoscopic) was an independent influencing factor on the levels of serum IL-6 and IL-10 at POD1 (P=.031 and P<.004, respectively) among various clinical perioperative parameters. CONCLUSIONS: Several inflammatory cytokines, particularly IL-6 and IL-10, are potential surgical stress markers in patients with PCa treated with RP. Based on cytokine production, our data support the view that laparoscopic RP is less invasive than open RP.

Association between various indices of obesity and intraoperative factors in laparoscopic donor nephrectomy.

PURPOSE: Obesity has been considered a potential risk factor for complications during laparoscopic surgery. The purpose of this study is to retrospectively investigate the association of various obesity indices and intraoperative factors in laparoscopic donor nephrectomy. PATIENTS AND METHODS: This study included 70 and 44 patients who underwent laparoscopic donor nephrectomy by a transperitoneal approach and retroperitoneal approach, respectively. We measured fat thickness and fat areas on preoperative computerized tomography (CT) images. The median value of fat thickness or of the subcutaneous fat area, visceral fat area, perirenal fat area, or total fat area among subjects was used as a cutoff to define fatty and non-fatty groups. The operative time and estimated blood loss were then compared between the two groups. RESULTS: In the transperitoneal approach group, there was no statistically significant difference in any of the indices or intraoperative factors between the fatty and non-fatty groups defined using any of the fat parameters. In the retroperitoneal approach group, patients in the fatty group categorized by perirenal fat thickness and visceral fat area had significantly greater estimated blood loss than those in the non-fatty group. Also, in the retroperitoneal approach group, patients in the fatty group categorized by perirenal fat area had significantly greater estimated blood loss and longer operating time than those in the non-fatty group (P=.02 and P=.014, respectively). CONCLUSIONS: The results indicate that the visceral fat, and in particular the perirenal fat area measured using CT scan imaging, influences operating time and estimated blood loss after retroperitoneal approach surgery but not in transperitoneal approach surgery. In donors with a high volume of perirenal fat, the transperitoneal approach may be recommended for laparoscopic nephrectomy.

Comparison of the clinical outcome and systemic inflammatory marker levels between retroperitoneal and transperitoneal laparoscopic donor nephrectomy.

BACKGROUND AND PURPOSE: Whether the retroperitoneal approach (RA) or the transperitoneal approach (TA) for performing laparoscopic donor nephrectomy (LDN) in kidney transplant donors is less invasive is unclear. In this study, we compared the clinical outcome and systemic inflammatory marker levels between RA and TA to assess surgical invasiveness. PATIENTS AND METHODS: We enrolled 105 donors (RA: 41, TA: 64) who underwent LDN in our hospital. Evaluation of both approaches included comparison of conventional clinical parameters and preoperative, immediate postoperative, and 1-day postoperative levels of the following circulating inflammatory cytokines: Tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10, and IL-12p70. RESULTS: The frequency of right nephrectomy being performed was significantly lower in the TA than in the RA group (3/64 vs 12/41, P<0.001). Other clinical parameters in the TA group, including the frequency of surgical complications and incidence of delayed graft function, were comparable to those in the RA group. Immediate and 1-day postoperative mean serum IL-6 levels were significantly higher in the RA than in the TA group (P=0.023 and 0.044, respectively). The 1-day postoperative mean serum IL-10 level was also significantly higher in the RA than in the TA group (P=0.041). Meanwhile, the mean serum IL-6 and IL-10 levels were not associated with surgical duration or estimated intraoperative blood loss. CONCLUSIONS: Conventional clinical parameters related to surgical invasiveness were comparable in both approaches, thus indicating that both LDN approaches were similar and equally effective as minimally invasive procedures. The clinical significance of the higher postoperative mean serum IL-6 and IL-10 levels in the RA group remains to be clarified in a future study.

Short-term clinicopathological outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade, followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with high-risk localized prostate cancer.

BACKGROUND: To assess the outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with a high risk of localized prostate cancer (PCa). METHODS: Complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m2) with estramustine phosphate (560 mg) were given to 18 PCa patients before radical prostatectomy. Subsequently, the clinical and pathological outcomes were analyzed. RESULTS: No patients had severe adverse events during chemohormonal therapy, and hence they were treated with radical prostatectomy. Two patients (11.1%) achieved pathological complete response. Surgical margins were negative in all patients. At a median follow-up of 18 months, 14 patients (77.8%) were disease-free without PSA recurrence. All 4 patients with PSA recurrence had pathologic T3b or T4 disease and 3 of these 4 patients had pathologic N1 disease. CONCLUSION: We found that neoadjuvant chemohormonal therapy with complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy was safe, feasible, and associated with favorable pathological outcomes in patients with a high risk of localized PCa.

[Granulocyte colony stimulating factor-producing spindle cell renal cell carcinoma successfully treated by chemotherapy consisting of gemcitabine and doxorubicin].

A 62-year-old female patient with a chief complaint of back pain and continuous fever was referred to our hospital. A computed tomography scan revealed a left renal tumor (76×54×67 mm) without a metastatic lesion. Laboratory examination showed an elevated white blood cell count of 23,200/µl. The patient underwent left radical nephrectomy and the histopathological diagnosis was spindle cell renal cell carcinoma (G3-4, pT4, pN2) with positive staining for granulocyte colony-stimulating factor. One month later, a computed tomography scan showed an enlarged locally recurrent tumor mass. Three cycles of combination chemotherapy consisting of gemcitabine (1,500 mg/m2, day 1) and doxorubicine (50 mg/m2, day 1) resulted in an 83% reduction of the tumor mass. A follow-up computed tomography scan after 2 weeks revealed rapid regrowth of the recurrent tumor. The patient died 199 days after the surgery. Combination chemotherapy consisting of gemcitabine and doxorubicin is a treatment option for patients with spindle cell renal cell carcinoma.

What is the most preferred wound site for laparoscopic donor nephrectomy?: a questionnaire assessment.

INTRODUCTION: Although specimen extraction site selection for laparoscopic donor nephrectomy (LDN) is relatively flexible and is mostly selected by surgeons from the patient's standpoint, the patient's request may differ from the medical worker's recommendation. The cosmetic aspect may also differ with age, gender, and the extent of medical knowledge. We performed an unsigned questionnaire assessment of individual preferences for LDN wound sites. MATERIALS AND METHODS: Between August 2007 and October 2008, we surveyed LDN wound site preferences among 148 physicians, 263 nurses, and 266 outpatients of urology at Akita University Hospital. They were questioned for their age, gender, occupation (medical worker or not), and for the most preferred surgical wound site among the following: A, lower vertical midline: B, upper vertical midline: C, anterior subcostal: D, Pfannenstiel: E, Gibson: and F, subcostal flank. The valid response rate was 93.5% (677/724). RESULTS: Wound sites preferred (ranked in descending order) were F (48.3%), D (25.6%), E (10.5%), A (9.0%), C (5.2%), and B (1.4%). The subcostal flank incision was the most preferred in almost all the categories. Second preferences were Pfannenstiel incisions in women and incisions on the lower abdomen in men. Overall, flank and lower abdominal incisions tended to be preferred, and mid and upper abdominal incisions tended to be avoided. Medical workers selected the subcostal flank and Pfannenstiel incisions more frequently than outpatients. With increasing age, the selection rates of the Gibson and the lower vertical midline incisions increased, whereas the subcostal flank and the Pfannenstiel incisions decreased. CONCLUSIONS: The subcostal flank was the most preferred LDN sites. Age, gender, and the extent of medical knowledge may influence the individual preferences for LDN wound sites.

[Primary retroperitoneal carcinoid tumor associated with multiple endcrine neoplasia (men) type 1: a case report].

We report an extremely rare case of a 69-year-old man having a retroperitoneal carcinoid tumor associated with multiple endocrine neoplasia (MEN) type 1. The patient whose son and daughter were previously diagnosed with MEN type 1 was admitted to the Department of Endocrinology at our hospital for evaluation of this disorder. Computed tomography (CT) and ultrasonography revealed a parathyroid and retroperitoneal tumor (43 mm x 34 mm). The patient did not consent to surgical management of the tumor; however three years later, a follow-up CT revealed tumor enlargement (55 mm x 50 mm). We were unable to rule out a malignancy, and subsequently resected the tumor. A pathological diagnosis of retroperitoneal carcinoid was made. No local recurrence or metastasis have been observed for 21 months.

Laparoscopic nephrectomy in patients with renal vein and/or inferior vena cava anomalies: Video presentation.

Laparoscopic nephrectomy is a standard surgery for the treatment of many types of renal tumor, renal pelvic tumor, and benign disease. Renal vein and inferior vena cava anomalies are not uncommon, having been detected at an incidence of 2-17%. With the increasing number of patients undergoing laparoscopic nephrectomy, surgeons have more opportunities to encounter major anomalies of the renal vein and inferior vena cava. This video presents images of the management of the renal pedicle in laparoscopic nephrectomy in cases where there were anomalies of the renal vein and inferior vena cava. Patient 1 had left renal tumor with the left inferior vena cava, patient 2 had left ureteral tumor with double inferior vena cava, patient 3 had left renal tumor with double inferior vena cava and a circumaortic renal vein, patient 4 had left renal tumor with a retro-aortic renal vein, and patient 5 had left renal tumor with a circumaortic renal vein. Multiple renal arteries were present in patients 3, 4, and 5. In laparoscopic nephrectomy complicated by anomalies of the renal vein and inferior vena cava, (i) surgical staff should be alert for the potential presence of aberrant veins and multiple renal arteries that may not be visualized in preoperative imaging. (ii) An anterior transperitoneal approach is well-suited in the understanding of positional relationships of vessels and anatomical landmarks in cases of vascular anomalies. (iii) With recent advances in diagnostic imaging modalities, such as multislice computed tomography (CT) and 3-D CT, it has become easier to identify the major arterial and venous anomalies. However, intraoperative observation and assessment remain important and mandatory in the management of smaller anomalous vessels accompanied by major anomalies.

Cystoprostatectomy as a treatment of prostate cancer involving the bladder neck.

OBJECTIVE: We evaluated the clinicopathological findings and short- and long-term outcomes of prostate cancer (PCa) patients with bladder neck invasion who underwent cystoprostatectomy. PATIENTS AND METHODS: Between 1989 and 2005, we performed 17 cystoprostatectomies for PCa patients having bladder neck invasion without distant visceral or distant lymph node metastasis. Of the 17 patients, 11 were treated with neoadjuvant hormone therapy and all patients were treated with adjuvant hormone therapy immediately after surgery. RESULTS: All 7 patients in whom pelvic lymph node swelling was identified by preoperative imaging studies had pathological lymph node metastasis. Of the 10 patients judged as cN0 preoperatively, 7 (70.0%) had lymph node metastasis. Although local recurrence was found in 2 (11.8%) patients, no additional urinary diversion or inconvenient urinary symptoms due to PCa progression were observed in any patients. The 5-year prostate-specific antigen recurrence-free survival rate was 62.2%. Cause-specific survival at 5 years after surgery was 87.1%. The 5-year cause-specific survival rate of node-positive patients was 92.3%. CONCLUSION: Cystoprostatectomy followed by immediate hormone therapy may be a feasible treatment option to achieve excellent local control for patients with previously untreated PCa, even in the presence of pelvic lymph node metastasis.

Clinical significance of a single nucleotide polymorphism and allelic imbalance of matrix metalloproteinase-1 promoter region in prostate cancer.

Matrix metalloproteinase-1 (MMP-1) is associated with cancer invasion and metastasis. The 2G allele of the polymorphic site in the MMP-1 promoter was demonstrated to have a higher transcription activity than the 1G allele. Allelic imbalance (AI) at 11q22 harboring the MMP-1 is frequently observed in various cancers and may be associated with an advanced disease. We conducted a case-control study to determine the association of the MMP-1 genotype with susceptibility to prostate cancer involving 283 prostate cancer patients and 251 controls. Furthermore, AI, retention allele of the MMP-1 promoter, and MMP-1 protein expression were analyzed in 77 prostate cancer specimens. The MMP-1 promoter polymorphism was associated with neither susceptibility nor progression of prostate cancer. Tumors with 1G/2G and 2G/2G genotypes had a significantly higher MMP-1 expression level compared to those with 1G/1G genotype (P=0.006 and 0.013, respectively). AI at 11q22 was observed in 13 (40.6%) of 32 informative cases. Retention of the 1G and 2G alleles were observed in 4 and 9 cases, respectively. AI was significantly associated with the Gleason score (P=0.003) and pathological stage (P=0.022). In addition, retention of the 2G allele showed a significant association with the pathological stage (P=0.026). AI at 11q22 region, retention of the 2G allele, specifically appeared to be involved in the progression of prostate cancer. However, the presence of the 2G allele of the MMP-1 promoter polymorphism itself seems to influence neither the susceptibility nor the progression of prostate cancer.

The novel tumor-suppressor Mel-18 in prostate cancer: its functional polymorphism, expression and clinical significance.

Mel-18 is a member of the polycomb group (PcG) proteins, which are chromatin regulatory factors and play important roles in development and oncogenesis. This study was designed to investigate the clinical and prognostic significance of Mel-18 in patients with prostate cancer. A total of 539 native Japanese subjects consisting of 393 prostate cancer patients and 146 controls were enrolled in this study. Mel-18 genotyping was analyzed using a PCR-RFLP method and an automated sequencer using the GENESCAN software. Immunohistochemistry revealed that Mel-18 expression was diminished in high grade and high stage prostate cancers. Moreover, patients with positive Mel-18 expression had significantly longer PSA recurrence-free survival than patients negative for Mel-18 expression (p=0.038). A Mel-18 1805A/G SNP was located in the 3' untranslated region and was predicted to alter the secondary structure of the mRNA. Mel-18 mRNA expression of the 1805A allele was clearly higher than expression of the 1805G allele by allele specific quantitative RT-PCR. In multivariate analysis, a homozygous G allele genotype and negative Mel-18 expression were independent risk factors predicting high PSA recurrence after radical prostatectomy, with HRs of 2.757 (p=0.022) and 2.271 (p=0.045), respectively. Moreover, the G allele was also an independent predictor of poor cancer-specific survival with an HR of 4.658 (p=0.019) for patients with stage D2 prostate cancer. This is the first study to provide important evidence demonstrating that Mel-18 is a tumor suppressor and possible therapeutic target, as well as a diagnostic marker for poor prognosis in prostate cancer patients.

Characterization of prostate cancer detected at repeat biopsy.

BACKGROUND: The aim of this study was to investigate the characteristics of prostate cancer patients who were diagnosed at repeat biopsy and compare them to non-cancerous patients or patients who were diagnosed at initial biopsy. METHODS: We carried out a retrospective analysis of clinical and pathological data from 576 patients, which included data on the period of time from radical prostatectomy to biochemical failure. RESULTS: Cancer was diagnosed in 191 (33%) of 576 patients at initial biopsy and in 23 (18%) of 127 patients who underwent a repeat biopsy. Cut-off values of 0.80 and 0.30 for prostate specific antigen velocity (PSAV) and prostate specific antigen density (PSAD), respectively, were determined using ROC curve analysis. Based on these values, PSAV and PSAD were able to predict 94% (46 of 49) of negative repeat biopsies, indicating that these patients had undergone unnecessary repeat biopsies. Although the patients who were diagnosed at repeat biopsy had a higher rate of organ-confined tumor than those who were diagnosed at initial biopsy (73% and 44%, respectively; P = 0.041), there were no differences in the recurrence rate or the duration of biochemical failure-free survival between the two groups. CONCLUSION: PSAV and PSAD may be useful indicators of the results of repeat biopsies. Although prostate cancer that was diagnosed at repeat biopsy was associated with a more favorable pathological profile, it was not associated with a better outcome after radical prostatectomy.

[Combination therapy consisting of gemcitabine, docetaxel and carboplatin as a second-line chemotherapy for patients with MVAC-treated metastatic urothelial carcinoma].

From 2001 to 2006, 11 patients with MVAC-treated metastatic urothelial carcinoma received as a second-line therapy GDC therapy consisting of gemcitabine (1,000 mg/m2) on day land 8, docetaxel (80 mg/m2) on day 1 and carboplatin (AUC 5) on day 1 in each 21-day cycle. The 11 patients received a total of 42 cycles. The median progression-free survival and the median overall survival were 3 months (range 0-51) and 10 months (range 2-51), respectively. The median overall survival from diagnosis of the metastasis was 13.0 months (range 7-55). Complete response and partial response rates were 1/11 (9%) and 5/11 (45%), respectively. One- and two-year survival rates were 36 and 9%, respectively. Grade 3 or 4 hematologic toxicity included neutropenia (69.0%), thrombocytopenia (47.6%) and anemia (45.2%). Non-hematologic toxicity of grade 3 or 4 consisted mainly of diarrhea (23.8%) and anorexia (21.4%). GDC regimen as a second-line chemotherapy was effective in 54% of patients with MVAC-treated metastatic urothelial carcinoma, although the high incidence of hematologic toxicities and short period of progression-free survival remain to be major problems.