Radical prostatectomy trends between 2010 and 2020 in Ehime, Japan, identified using data from the Medical Investigation Cancer Network (MICAN) study.

OBJECTIVES: The use of radical prostatectomy is increasing with the rising incidence of prostate cancer. We assessed the surgical trends related to radical prostatectomy using data from a multi-center, retrospective cohort study, the MICAN (Medical Investigation Cancer Network) study, which was conducted in all the urology-related medical facilities in Ehime Prefecture, Japan. METHODS: We compared data from the MICAN study with prostate biopsy registry data collected in Ehime between 2010 and 2020 and recorded the surgical trends. RESULTS: There was a significant increase in the mean age of patients with positive biopsies, and the positivity rate increased from 46.3% in 2010 to 60.5% in 2020, while the number of biopsies obtained decreased. The number of radical prostatectomies performed increased over the years, with robot-assisted radical prostatectomy becoming the predominant procedure. In 2020, robot-assisted radical prostatectomies accounted for 96.0% of the surgeries performed. The age at surgery also gradually increased. Of the registered patients aged ≤75 years, 40.5% underwent surgery in 2010, compared with 83.1% in 2020. The prevalence of surgery also increased from 4.6% to 29.8% in patients aged >75 years. There was a gradual increase in the proportion of high-risk cases, from 29.3% to 44.0%, but a decrease in that of low-risk cases, from 23.8% in 2010 to 11.4% in 2020. CONCLUSIONS: We have shown that the number of radical prostatectomies performed in Ehime is increasing in patients aged both ≤75 and >75 years. The proportion of low-risk cases has decreased, while that of high-risk cases has increased.

Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer.

AIM: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. METHODS: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. RESULTS: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. CONCLUSION: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

Fluorodeoxyglucose positron emission tomography/computed tomography for diagnosis of upper urinary tract urothelial carcinoma.

BACKGROUND: The purpose of this study was to assess the ability of fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to detect upper urinary tract urothelial carcinomas (UTUC) compared with pathological examination of tissues obtained by ureteroscopic biopsy and split cytologic analysis of urine obtained after retrograde pyelography. METHODS: Clinicopathological records of patients at our institution were retrospectively reviewed. Fifty patients with clinically suspected UTUC, who were histologically diagnosed by nephroureterectomy, partial ureterectomy, or endoscopic biopsy, were included. The patient cohort included 42 men and 8 women, with a median age of 73 (range 54-92) years. RESULTS: Only 27 % of 49 patients with UTUC had positive voided urine cytology, and 33 % of 40 patients had positive split urine cytology. In addition, 40 % of 10 patients had a positive endoscopic biopsy. However, 83 % of 48 patients with UTUC had positive results from FDG-PET/CT examination. The positive predictive value of FDG-PET/CT was 95 %. There were no correlations between sensitivity and tumor stage or tumor grade. Sensitivity of FDG-PET/CT for patients with and without diabetes mellitus was 60 and 89 %, respectively. CONCLUSIONS: These preliminary results from a small number of patients revealed that FDG-PET/CT enabled effective detection of UTUC.

[Clinicopathologic characteristics and prognosis of patients with adrenocortical carcinoma].

PURPOSE: Adrenocortical carcinoma (ACC) is a rare condition associated with poor prognosis. This study aimed to evaluate the clinicopathologic characteristics and prognosis of 7 patients with ACC. PATIENTS AND METHODS: The clinicopathologic characteristics, treatment, and survival of 7 patients with pathologically confirmed ACC treated at our institution between January 2002 and December 2012 were retrospectively examined. RESULTS: The study cohort comprised 4 male and 3 female patients (median age at diagnosis, 63 years [range, 36-71 years]). The median tumor size was 7.0 cm (range, 4.0-13.0 cm), and the median follow-up duration was 22 months (range, 9-107 months). One patient had stage I ACC, 4 had stage III, and 2 showed metastasis. The patient with stage I disease underwent laparoscopic adrenorectomy and those with stage III disease underwent adrenorectomy with the excision of adjacent organs. Four of these 5 patients are alive without recurrence at a median of 55 months (range, 22-107 months) after surgery. Of the 2 patients with metastases, 1 received combined chemotherapy with etoposide, adriamycin, and cisplatin plus mitotane without surgical resection but died 19 months later, and the other, with a solitary lung metastasis, underwent adrenorectomy and metastatectomy followed by adjuvant treatment with mitotane and is alive without recurrence at 9 months after treatment. The 3-year cause-specific survival rate was 56%. CONCLUSIONS: Patients with advanced-stage tumors showed long-term survival with complete tumor resection at diagnosis; hence, this seems to be most beneficial treatment option for patients with ACC.

Cisplatin resistance by induction of aldo-keto reductase family 1 member C2 in human bladder cancer cells.

Cisplatin is currently the most effective anti-tumor agent available against bladder cancer. To clarify the mechanism underlying cisplatin resistance in bladder cancer, the present study examined the role of the aldo-keto reductase family 1 member C2 (AKR1C2) protein on chemoresistance using a human bladder cancer cell line. The function of AKR1C2 in chemoresistance was studied using the human HT1376 bladder cancer cell line and the cisplatin-resistant HT1376-CisR subline. AKR1C2 was expressed in HT1376-CisR cells, but not in the parental cells. The effect of small interfering (si) RNAs and an inhibitor targeting AKR1C2 was examined to determine whether cisplatin sensitivity can be rescued by blocking AKR1C2 expression or function. Silencing of AKR1C2 mRNA or inhibition of AKR1C2 by 5ß-cholanic acid resulted in a decrease in the survival of cells following cisplatin exposure. Intracellular accumulation of reactive oxygen species (ROS) was determined using a 2,7-dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescent probe. Cisplatin exposure increased the level of intracellular ROS in HT1376 cells in a dose-dependent manner. The ROS levels in HT1376-CisR cells were significantly lower than those in HT1376 cells and knockdown of AKR1C2 mRNA significantly restored ROS levels. Cisplatin exposure did not increase intracellular ROS in HT1376-CisR cells, although the level of intracellular ROS increased in HT1376 cells following cisplatin exposure. Silencing of AKR1C2 mRNA restored the ROS increase response to cisplatin and menadione as an oxidative stressor in HT1376-CisR cells. Menadione has the function of an oxidative stressor. The silencing of AKR1C2 mRNA restored the increased ROS response to cisplatin and menadione in HT1376-CisR cells. These results indicate that induction of AKR1C2 in human bladder cancer cells aids in the development of cisplatin resistance through antioxidative effects. The results of this study indicate that AKR1C2 may be an effective molecular target for restoring cisplatin resistance.

Quality of life improvements among cancer patients in remission following the consumption of Agaricus blazei Murill mushroom extract.

OBJECTIVES: The aim of this preliminary clinical study was to assess if the daily intake of Agaricus blazei Murill (ABM) granulated powder (SSI Co., Ltd., Tokyo, Japan) for 6 months improved the quality of life (QOL) in cancer patients in remission. DESIGN: Open study. SETTING: Subjects diurnally took 1 (1.8 g; N=23), 2 (3.6 g; N=22), or 3 (5.4 g; N=22) packs/day orally for 6 months. MAIN OUTCOME MEASURES: The SF-8 Health Survey questionnaire was used to evaluate the QOL. The differences between the SF-8 baseline scores at the time of entry and 6-months after ABM treatment were evaluated. RESULTS: The results showed a significant improvement in QOL in both physical and mental components. More specifically, QOL effects of ABM in different genders showed males improved physical components, while females improved only mental components. QOL effects in the different age groups showed that ages 65 and under improved mental components, while ages 66 and older improved physical components. Furthermore, with respect to optimal dose effects of ABM with respect to QOL improvement, two packs per day for 6 months showed improvements in both physical and mental components. CONCLUSION: This preliminary longitudinal clinical study demonstrated that daily intake of ABM appears to improve both physical and mental components based on SF-8 qualimetric analysis.

Combined chemotherapy with gemcitabine and carboplatin for metastatic urothelial carcinomas in patients with high renal insufficiency.

BACKGROUND: This was a retrospective study to evaluate the activity and toxicity of a combined chemotherapeutic regimen of gemcitabine and carboplatin (GCa) in patients with metastatic urothelial carcinomas (UCs) with special regard to patients with highly impaired renal function. METHODS: Eleven patients whose creatinine clearance was 30 ml/min or under and who had been diagnosed with metastatic UC were treated with GCa. The patient cohort comprised 4 males and 7 females, with a median age of 74 (range 67-84) years. The median follow-up was 19 (range 1-58) months. RESULTS: Five of the 11 patients (45%) showed an objective response, with 2 achieving a clinically complete response and 3 a partial response with GCa. The grade 3/4 toxicity of the regimen was primarily hematological, including anemia (55%), neutropenia (45%), and thrombocytopenia (45%). Four patients (36%) could not complete the treatment in total. Grade 3 pneumonitis was found in one patient, and the treatment was terminated. Grade 4 febrile neutropenia occurred in the patient on hemodialysis, and the patient was forced to discontinue the chemotherapy. Another 2 patients also called off the treatment due to a pulmonary adverse event and an elevation of serum creatinine, respectively. CONCLUSIONS: GCa appears to be effective for the treatment of metastatic UCs in patients with impaired renal function, but it is necessary to pay attention to the occurrence of severe adverse events.

Modified FOLFOX6 chemotherapy in patients with metastatic urachal cancer.

BACKGROUND: To improve the prognosis of patients with urachal cancer and establish an effective chemotherapeutic regimen for distant metastases. METHODS: We conducted a retrospective study to evaluate the efficacy and safety of a modified combination of 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) therapy in patients with metastatic urachal cancer. RESULTS: Five patients were treated with mFOLFOX6. Their median age was 65 years (range 41-80). The median follow-up time was 42 months (range 18-46). Two of the 5 patients (40%) showed an objective response: 1 achieved a clinically complete response and 1 a partial response. The grade 3/4 toxicity associated with this regimen was primarily neutropenia, but febrile neutropenia was not observed. Oxaliplatin treatment was discontinued because of a grade 2 allergic reaction in 1 patient. Grade 2 peripheral sensory neuropathy caused by oxaliplatin was observed in 2 patients, and the OPTIMOX (stop and go) approach had to be adopted. CONCLUSIONS: mFOLFOX6 appears to be effective for the treatment of metastatic urachal cancer.

Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission.

Although many cancer patients use complementary and alternative medicine, including Agaricus blazei Murill (ABM), safety is not yet well understood. Cancer survivors took 1.8, 3.6, or 5.4 g ABM granulated powder (Kyowa Wellness Co., Ltd., Tokyo, Japan) per day orally for 6 months. Adverse events were defined by subjective/objective symptoms and laboratory data according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day, resp.). Adverse events were observed in 9 patients (12%). Most were digestive in nature such as nausea and diarrhea, and one patient developed a liver dysfunction-related food allergy, drug lymphocyte product. However, none of these adverse events occurred in a dose-dependent manner. This study shows that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. This trial supports previous evidence that the ABM product is generally safe, excluding possible allergic reaction.

Tertiary Gleason pattern 5 and oncological outcomes after radical prostatectomy.

OBJECTIVES: This study examined the rate of Gleason pattern 5 and the influence of tertiary Gleason pattern 5 on oncological outcomes. METHODS: Four hundred sixty-six patients underwent a radical prostatectomy between 1993 and 2008. Each surgical specimen was reviewed and assessed for the tumor diameter, Gleason score (which was based on the 2005 International Society of Urological Pathology Consensus Conference criteria) and the percentage of Gleason pattern 5. RESULTS: The median patient age was 68.0 years old and the median prostate-specific antigen level was 9.28 ng/ml. A tertiary Gleason pattern 5 was present in 24.2% of patients with a Gleason score of <9; in 12.2% of patients with a Gleason score of 3 + 4 and in 45.9% of patients with a Gleason score of 4 + 3. A multivariate analysis showed that a tertiary Gleason pattern 5 was not independently associated with biochemical recurrence-free survival among patients in the Gleason score of 7 and 8 pN0 groups. One hundred eighty-seven patients had any rate of Gleason pattern 5 and significantly worse pathological factors, compared with patients who did not have this pattern. A multivariate analysis of all patients showed that the surgical margin, Gleason score, prostate-specific antigen level and pathological stage were all independent predictors of biochemical recurrence. However, the rate of Gleason pattern 5 was not an independent factor. CONCLUSIONS: Tertiary Gleason pattern 5 was not a significant predictive factor for biochemical recurrence. The rate of Gleason pattern 5 was associated with adverse pathological factors.

Docetaxel-prednisolone combination therapy for Japanese patients with hormone-refractory prostate cancer: a single institution experience.

OBJECTIVE: To evaluate the efficacy and toxicity of docetaxel plus prednisolone treatment in Japanese patients with hormone-refractory prostate cancer (HRPC). METHODS: From April 2004 through August 2008, we used docetaxel plus prednisolone to treat 55 HRPC patients (median age, 72 years). Eighteen patients (32.7%) had measurable soft tissue lesions, whereas 52 patients (94.5%) had bone metastases. During the 21-day treatment cycle, docetaxel (70 mg/m(2)) was administered once every 21 days and oral prednisolone (5 mg), twice daily. Prostate-specific antigen (PSA) response, defined as a reduction of at least 50% in the baseline levels for 4 weeks, was evaluated. RESULTS: The median follow-up period was 30.1 months; median overall survival, 15.3 months and median progression-free survival, 7.5 months. During follow-up, 37 patients (67.3%) achieved the PSA response, and 5 of 18 (27.8%) patients with measurable disease showed a partial response. Among the 27 patients who experienced cancer pain before treatment initiation, 15 (55.5%) reduced their analgesic drug intake. Multivariate analysis of the prognostic variables revealed a significant association between the overall survival and pain (P = 0.033). Hematological toxicity (grades 3-4) included neutropenia (87.3%), febrile neutropenia (25.5%) and thrombocytopenia (5.5%). Frequent non-hematological adverse events were general edema (52.7%), general fatigue (32.7%) and sensory neuropathy (30.9%). Three patients died of adult respiratory distress syndrome (ARDS). CONCLUSION: Docetaxel plus prednisolone treatment is effective in Japanese HRPC patients. The main toxicity is neutropenia, which can be safely controlled by outpatient treatment with granulocyte-colony stimulating factor. However, the Japanese patients in our study developed ARDS more frequently than other patients in previous studies did.

Health-related quality of life using SF-8 and EPIC questionnaires after treatment with radical retropubic prostatectomy and permanent prostate brachytherapy.

OBJECTIVE: The health-related quality of life (HRQOL) after treatment of prostate cancer is examined using a new HRQOL tool. HRQOL, based on the expanded prostate cancer index composite (EPIC) and SF-8 questionnaires, was prospectively compared after either a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) at a single institute. METHODS: Between October 2005 and June 2007, 96 patients were treated by an RRP and 88 patients were treated by a PPB. A HRQOL survey was completed at baseline, and at 1, 3, 6 and 12 months after treatment, prospectively. RESULTS: The general HRQOL in the RRP and PPB groups was not different after 3 months. However, at baseline and 1 month after treatment, the mental component summary was significantly better in the PPB group than in the RRP group. Moreover, the disease-specific HRQOL was worse regarding urinary and sexual functions in the RRP group. Urinary irritative/obstructive was worse in the PPB group, but urinary incontinence was worse in the RRP group and had not recovered to baseline after 12 months. The bowel function and bother were worse in the PPB group than in the RRP group after 3 months. In the RRP group, the patients with nerve sparing demonstrated the same scores in sexual function as the PPB group. CONCLUSIONS: This prospective study revealed the differences in the HRQOL after an RRP and PPB. Disease-specific HRQOL is clarified by using EPIC survey. These results will be helpful for making treatment decisions.

Bladder preservation therapy conducted by intra-arterial chemotherapy and radiotherapy for muscle invasive bladder cancer.

OBJECTIVE: A previous paper reported favorable results of intra-arterial chemotherapy in combination with radiotherapy for muscle-invasive bladder cancer. The current study will update those results. METHODS: Between January 1992 and December 2006, 94 patients with confirmed muscle invasion were treated with intra-arterial chemotherapy and concurrent radiotherapy after an initial complete transurethral resection. Intra-arterial chemotherapy consisted of cisplatin (Days 1-3) and pirarubicin (Days 8-10), and radiation was administered with the chemotherapy (2 Gy/session) with a total dosage of 44 Gy. The median age was 67.0 years. There were 60 patients in T2, 19 patients in T3 and 15 patients in T4. The median follow-up period was 72.9 months in the survivors. RESULTS: Among these patients, 84 patients (89.4%) obtained a complete response (CR) and 10 patients did not achieve a CR. Between the CR and non-CR patients, the clinical stage and the existence of hydronephrosis were significantly different. The cause-specific survival rates at 5 and 10 years were 76.2% and 67.5%, respectively. The overall survival rates at 5 and 10 years were 66.6% and 47.4%, respectively. A Cox proportional hazard model showed that only the cause-specific survival rate was associated with a CR after treatment. The bladder preservation rates were 89.7% at 5 years and 87.6% at 10 years. Myelosuppression was the major adverse event but it was manageable. Non-hematological sever adverse events were rare. CONCLUSIONS: Bladder preservation therapy shows good survival and good bladder preservation rates. Clinical stage T2 and the absence of hydronephrosis are favorable factors.

Radiation pneumonitis caused by a migrated brachytherapy seed lodged in the lung.

We report a case of radiation pneumonitis caused by a migrated seed lodged in the lung after prostate brachytherapy. A 71-year-old man underwent transperineal interstitial permanent prostate brachytherapy for localized prostate cancer. On the day after brachytherapy, a routine postimplant chest X-ray revealed migration of one seed to the lower lobe of the left lung. After 1 month, pulmonary opacities were observed in the left lower lobe but not near the seed. He was diagnosed with bacterial pneumonia, and antibiotic therapy was commenced. Two months after brachytherapy, the patient's symptoms, laboratory data and pulmonary opacities improved; however, an abnormal shadow (consolidation) developed around the migrated seed. Lung consolidation disappeared almost completely 12 months after brachytherapy without any medical treatment. The abnormal shadow probably represented radiation pneumonitis. To the best of our knowledge, this is the first report of radiation pneumonitis caused by a migrated brachytherapy seed in the lung.

A prospective longitudinal study comparing a radical retropubic prostatectomy and permanent prostate brachytherapy regarding the health-related quality of life for localized prostate cancer.

OBJECTIVE: The health-related quality of life (HRQOL) after a radical retropubic prostatectomy (RRP) or a permanent prostate brachytherapy (PPB) was prospectively compared at a single institute. METHODS: Between 2003 and 2005, 122 patients were treated by RRP and 82 patients were treated by PPB. A QOL survey was completed at baseline, and 1, 3, 6 and 12 months after treatment, prospectively. RESULTS: The general HRQOL was not different between the RRP and PPB groups after 3 months. However, at 1 month after treatment, the general HRQOL scores, except for general health, were significantly better in the PPB group than that in the RRP group. Moreover, the disease-specific QOL was worse in urinary and sexual functions in the RRP group. Urinary function in the RRP group had not recovered to baseline after 12 months. Although the urinary function in the PPB group was better than that of the RRP group, urinary bother continued to worsen until 6 months and thereafter it recovered gradually. The bowel function was not worse in the PPB group but bowel bother was worse at 6 months in the PPB group. In the RRP group, the patients with nerve sparing demonstrated better in sexual function than those without nerve sparing, but the recovery did not reach the level of the PPB group. CONCLUSIONS: This prospective study revealed the differences in the QOL after RRP and PPB. These results will be helpful for making treatment decisions.

[Primary urothelial carcinoma of the prostate: a case of spread along ducts and into seminal vesicles].

A 75-year-old man was referred to our department with prostate cancer. When our pathologist reviewed the biopsy specimen, he was diagnosed as intraductal urothelial carcinoma. Transurethral random biopsy showed the urothelial carcinoma in the prostate ducts but no cancer in the bladder. He was diagnosed as primary urothelial carcinoma of the prostate ducts (cTis pd cN0 M0), and radical cystoprostatectomy were performed. Histopathological examination showed urothelial carcinoma in situ spread along ducts and ejaculatory ducts and into seminal vesicles but there was not invasion of prostatic stroma. (pTis pd pN0 M0 Urothelial carcinoma G3 pL0 pV0) He had no adjuvant therapy, he is alive without any evidence of tumor recurrence after surgery.

Health-related quality of life after bladder preservation therapy for muscle invasive bladder cancer.

OBJECTIVE: To assess health-related quality of life (QOL) of bladder cancer patients following bladder preservation therapy (BPT). METHODS: Eighty patients with muscle-invasive bladder cancer had been treated between January 1992 and July 2005 at our institutions with BPT consisting of transurethral resection, intra-arterial chemotherapy and radiotherapy. Among them, 48 were alive and free from recurrence at the time of survey and were asked to participate. A total of 168 patients who had been treated for superficial bladder cancer in the same period were used as a control group. Three questionnaires, namely the International Prostate Symptom Score (IPSS), the SF-36, and the Expanded Prostate Cancer Index Composite (EPIC) were used. RESULTS: Thirty-three patients in the BPT group (68.8%) and 128 patients in the control group (76.2%) answered the QOL survey. There was no significant difference in age, gender and other clinical factors among these two groups. No significant difference was found between the groups according to IPSS. The QOL score of BPT was lower than that of the control group in the SF-36, but there was no significant difference without body pain (P = 0.047). There was a tendency toward a diminished physical functioning (P = 0.053) and role-physical (P = 0.064) in BPT. The EPIC scores for urinary function, especially storage and voiding symptoms, and bowel function were significantly lower in the BPT group. At multivariable analysis, body pain and bowel function were associated with the type of treatment. CONCLUSION: Although some of the QOL outcome parameters after BPT were found to be lower than the control group, these differences were not significant. Overall, patients retaining their bladder had an acceptable health related QOL.

[A case of small cell carcinoma in the urinary bladder responding to gemcitabine/cisplatin combination therapy as neoadjuvant chemotherapy].

We report a case of primary small cell carcinoma of the urinary bladder. A 79-year-old man with the chief complaints of macrohematuria and pollakisuria was admitted to our hospital. Cystoscopy and computed tomography (CT) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was small cell carcinoma of the urinary bladder, and he underwent 3 courses of neoadjuvant chemotherapy including gemcitabine and cisplatin with a preoperative diagnosis of cT3bN0M0. After the chemotherapy, cystoscopy and CT showed complete remission. Total cystectomy with ileal conduit was performed following 3 courses of chemotherapy. Microscopic examination revealed that the small cell carcinoma had disappeared and the converted squamous cell carcinoma remained only in a small part of the specimens. The patient was carefully followed for 10 months after operation, with no tumor recurrence.