[THE RISK AND MANAGEMENT OF RADIATION INDUCED CYSTITIS AFTER RADIOTHERAPY FOR PROSTATE CANCER].

(Objectives) Radiation induced cystitis (RC) is one of the toxicities we must often treat after radiation therapy for prostate cancer.Some patients require urinary diversion with or without cystectomy.We evaluated the clinical risks and management of RC. (Patients and methods) The clinical records of 303 patients who underwent radiation therapy for prostate cancer (199 only radiation therapy; 104 adjuvant or salvage radiation therapy after radical prostatectomy) between 2005 and 2015 in our institute, were reviewed.We defined RC based on the presence of macrohematuria, not caused by reccurence of prostate cancer or occurrence of bladder cancer. (Results) The median follow up time was 37 months (range 1-132).Thirty patients (9.9%) developed RC.Compared to radiation therapy alone, adjuvant/salvage radiation therapy was found to be a risk for RC (4.5% vs. 20.1%, p< 0.01).Ten out of 30 RC patients needed hospitalization and 6 patients underwent urinary diversion with or without cystectomy.Two patients who underwent urinary diversion without cystectomy were hospitalized for a longer period compared with 4 patients with cystectomy. (Conclusion) Adjuvant/salvage therapy is a risk factor of RC after radiation therapy for prostate cancer.About 2% of the patients needed urinary diversion and cystectomy improved their prognosis.

LAPAROSCOPIC RADICAL NEPHRECTOMY FOR LARGE RENAL CELL CARCINOMA: RETROSPECTIVE ANALYSIS OF SAFETY AND ONCOLOGICAL OUTCOME.

(Objectives) To evaluate the safety and oncologic efficacy of laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) >7 cm, we retrospectively reviewed the clinical outcome and long-term cancer control of patients who underwent LRN in comparison to open radical nephrectomy (ORN). (Patients and methods) The clinical records of 79 patients with RCC >7 cm, who underwent radical nephrectomy (37 LRN; 42 ORN) between 1993 and 2014, were reviewed. (Results) The 2 groups (LRN and ORN) were comparable regarding age, body mass index and mean tumor size (86.5 mm vs. 94.6 mm).The operative time was significantly longer in the LRN group than ORN group (204 min vs. 168 min; p<0.05) and blood loss was significantly lower in the LRN group than in the ORN group (144 ml vs. 930 ml; p<0.05).No statistically significant difference was found in complication rate (10.8% vs. 23.8%) and the 2-year recurrence-free survival rate (85.6% vs. 83.8%). (Conclusion) Despite the longer operative time, LRN for large RCC was associated with lower blood loss. This study provides evidence of the safety and efficacy of LRN for large RCC.

Active surveillance criteria for prostate cancer: can they be applied to Japanese patients?

Prostate-specific antigen screening has significantly increased the percentage of men who are diagnosed with low-risk prostate cancer. All men undergoing retropubic radical prostatectomy for primary treatment of prostate cancer from April 2004 to September 2010 in our hospital were examined in order to determine whether active surveillance criteria could be applied to Japanese men. From pathological data of prostate biopsies, whether these men met five published criteria for active surveillance (Johns Hopkins Medical Institution, Prostate Cancer Research International: Active Surveillance Study, University of California, San Francisco, Toronto and Kakehi criteria) was evaluated. Men who met any of the criteria had a statistically significant lower extracapsular extension rate and organ-confinement rate. From the view of the possibility of Gleason upgrading and organ-confinement rate, the Johns Hopkins Medical Institution and Prostate Cancer Research International: Active Surveillance Study criteria showed to be appropriate for Japanese patients. However, the present study had limitations of selection bias and a limited number of cases.

Evaluation of docetaxel plus estramustine in the treatment of patients with hormone-refractory prostate cancer.

OBJECTIVES: To investigate the feasibility and efficacy of docetaxel-based chemotherapy in patients with hormone-refractory prostate cancer (HRPC). METHODS: Forty-six consecutive HRPC patients treated between January 2003 and March 2008 were included in this analysis. Docetaxel was given at a dose of 35 mg/m(2) twice every 3 weeks and oral estramustine concurrently for three consecutive days during weeks 1 and 2 of each cycle. During each treatment week, the dose of estramustine was 1260 mg on the first day, 980 mg on the second day and 840 mg on the third day. Patients were premedicated with 4 mg twice a day of oral dexamethasone for three consecutive days. Treatment was continued until evidence of disease progression or unacceptable toxicity. Prostate-specific antigen (PSA) levels were evaluated at least once every 4 weeks. RESULTS: Patients received a median of three cycles of chemotherapy. Of the evaluable 46 patients, 25 (54%) had a >or=50% PSA decline and 12 (26%) had a >or=75% PSA decline. Median time to PSA progression and overall survival time were 10.1 and 27.0 months, respectively. Median follow-up was 15.0 months. Major severe toxicities were grade 3 or 4 leukopenia in five (11%) patients. Mild toxicities included grade 1 or 2 nausea in eight (17%) patients. Two patients could not continue the treatment because of interstitial pneumonitis and a gastric hemorrhage, respectively. CONCLUSIONS: Docetaxel plus estramustine chemotherapy represents an active and well tolerated treatment for Japanese HRPC patients.

Low dose tamsulosin for stone expulsion after extracorporeal shock wave lithotripsy: efficacy in Japanese male patients with ureteral stone.

OBJECTIVE: We evaluated the efficacy of low dose tamsulosin after extracorporeal shock wave lithotripsy (ESWL) in Japanese male patients with ureteral stone. METHODS: One hundred and two Japanese male patients with ureteral stones who underwent ESWL were randomly divided into three groups. Group A (38 patients) was given tamsulosin (0.2 mg/day); group B (30 patients) was given c horeito, a herbal medicine (7.5 g/day); and group C (34 patients) received no medication. Stone clearance was assessed at 1, 7, 14, and 28 days after ESWL using plain abdominal radiography and abdominal ultrasonography. After 28 days, stone delivery was checked every 2 weeks. RESULTS: The stone-free rate was 84.21%, 90%, and 88.24% for groups A, B, and C, respectively (P = 0.3425). The mean expulsion time was 15.66 +/- 6.14 days in group A, 27.74 +/- 25.36 days in group B, and 35.47 +/- 53.70 days in group C. The expulsion time of group A was significantly shorter than that of groups B (P = 0.0116) and C (P = 0.0424). CONCLUSIONS: The addition of tamsulosin to conservative treatment appeared to be effective in shortening the stone expulsion time.

Neuroendocrine differentiation in stage D2 prostate cancers.

OBJECTIVES: Chromogranin A (CgA) and neuro-specific enolase (NSE) are gaining acceptance as markers of several types of neuroendocrine tumors and the concentration of CgA and NSE have been reported to be elevated in relation to neuroendocrine differentiation of prostate cancer. The aim of the present study was to examine the correlation between the immunohistochemical (IHC) findings and serum value for CgA and NSE in untreated stage D(2) prostate cancer patients. METHODS: Immunohistochemistry was carried out using antibodies against CgA and NSE in 58 patients and, pretreatment serum CgA and NSE levels were measured by monoclonal immunoradiometric assay in 18 patients with stage D(2) prostate cancer treated by androgen ablation. We examined the relationship of the pretreatment serum level to IHC findings for CgA and NSE in prostate cancer patients to clinicopathological parameters, and prognosis. Also, we evaluated the correlation of IHC findings to serum levels for CgA and NSE. RESULTS: There was a statistically significant correlation between CgA positivity and serum CgA level (P = 0.0421). However, there was no statistically significant correlation between NSE positivity and serum NSE level (P > 0.05). We divided stage D(2) patients into three groups according to IHC positivity of CgA and NSE. The cause-specific survival was significantly poorer in patients with strongly positive (++) patients for independent CgA and combined CgA with NSE (P = 0.0379). Multivariate analysis of cause-specific survivals in patients with stage D(2) prostate cancer demonstrated that strong IHC stain was considered as independent variable associated with greater risk of death (P = 0.0142). CONCLUSION: Neuroendocrine differentiation in stage D(2) prostate cancer has attracted considerable attention as a potentially findings prognosis. Thus, CgA had a stronger relationship between serum levels and IHC positivity in contrast to NSE, suggesting clinical usefulness as a tumor marker in predicting the extent of neuroendocrine differentiation in prostate cancer.

Clinical characteristics of aldosterone-producing microadenoma, macroadenoma, and idiopathic hyperaldosteronism in 93 patients with primary aldosteronism.

Primary aldosteronism (PA) due to aldosterone-producing adenoma (APA) is a form of surgically curable secondary hypertension, and distinguishing APA from idiopathic hyperaldosteronism (IHA) is important for treatment. We made a differential diagnosis between APA and IHA using imaging tests such as adrenal CT and MRI as well as adrenal venous sampling (AVS) in all 93 cases of PA presenting at our institutions over the last decade. We identified 27 patients with aldosterone-producing microadenoma (APmicroA), all of whom could be diagnosed by AVS but not by the imaging tests. Then, we compared the clinical and roent-genological findings of these 27 patients with those of 42 patients with aldosterone-producing macroadenoma (APmacroA) and of 24 patients with IHA. Using surgically removed adrenal tissues, histopathological examinations and immunohistochemical analyses of steroidogenic enzymes were conducted. The findings for APmicroA were similar to those for APmacroA, except with respect to the diameter of the adrenal adenomas. Endocrinological and roentgenological findings for APmicroA were similar to those for IHA, but not to those for APmacroA. The rate of cure of hypertension was much greater in patients with APmicroA than in patients with APmacroA after the unilateral adrenalectomy (odds ratio, 4.0; p=0.028). In conclusion, it is important to accurately diagnose APmicroA, in which the laterality of the hyperproduction of aldosterone is only detectable by AVS, and to treat these patients by unilateral adrenalectomy in order to avoid long-term medical treatment and prevent hypertensive vascular complications.

Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling.

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.

Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan.

Secondary hypertension (SH) including endocrine hypertension has been reported to be uncommon. We estimated the prevalence of SH among hypertensive patients. We prospectively studied 1,020 hypertensive patients. As an initial screening, we measured plasma aldosterone concentration, plasma renin activity, serum cortisol concentration and plasma catecholamine concentration and conducted abdominal ultrasonography (US). As a secondary screening, we performed furosemide plus upright test, captopril renography, dexamethasone suppression test, 24-h urine catecholamine measurement and abdominal CT. Finally, primary aldosteronism with the exception of idiopathic hyperaldosteronism, pheochromocytoma, and Cushing's syndrome were diagnosed by histopathological examination of surgical specimens. Idiopathic hyperaldosteronism was clinically diagnosed by adrenocorticotrophic hormone (ACTH)-stimulated adrenal venous sampling and renovascular hypertension by renal arteriography. There were 61 patients with primary aldosteronism, 5 with renovascular hypertension, 11 with Cushing's syndrome, 10 with preclinical Cushing's syndrome and 6 with pheochromocytoma, and the prevalence of SH was 9.1% among 1,020 hypertensive patients. In 76 (82%) of 93 patients with SH, hypertension was cured or improved after unilateral adrenalectomy, transsphenoidal pituitary adenectomy or percutaneous transluminal angioplasty. With the exception of US and CT, all initial and secondary screening tests were found to be sensitive and specific for differentiating SH from essential hypertension (EH). In conclusion, the measurement of various hormone concentrations was very sensitive for ruling out SH--a condition for which, in the present study, there were few specific signs or symptoms--while CT and US examinations were not always useful for differentiating SH from EH. The prevalence of curable SH among hypertensive subjects was higher in this study, which was conducted by our simple method of screening tests, than in previous reports. Hypertensive patients should be screened for SH and the underlying disease treated appropriately to avoid long-term use of antihypertensive drugs and risks of atherosclerotic complications.

[Silicate calculi: report of four cases].

Among four patients with silicate calculi, stones were spontaneously discharged in two and after extracorporeal shock-wave lithotripsy in two. Two of them had a history of taking magnesium silicate. Thirty two cases of silicate calculi previously reported in the Japanese literature were reviewed.

Efficacy and safety of laparoscopic surgery for pheochromocytoma.

OBJECTIVE: Laparoscopic surgery for primary aldosteronoma and Cushing's syndrome is well established. We report on our experiences with laparoscopic adrenalectomy for pheochromocytoma, and assess the efficacy and safety of the laparoscopic approach. METHODS: Between April 1998 and April 2003, a total of 23 patients underwent laparoscopic adrenalectomy for pheochromocytoma at Chiba University Hospital and Yokohama Rosai Hospital, Japan. We compared the surgical outcomes of these patients with those of 106 patients with adrenal tumors due to other pathologies who underwent laparoscopic adrenalectomy during the same period. RESULTS: The mean tumor size of pheochromocytoma was 4.96 cm. Mean operative time was 192.7 min, and mean estimated blood loss was 130 mL. Neither mean operative time nor mean estimated blood loss was greater for patients with pheochromocytoma. Intraoperative hypertension (systolic blood pressure > 180 mmHg) occurred in 39.1% (9/23) of patients with pheochromocytoma. During the follow-up period, there were no mortalities or recurrences of endocrinopathy. CONCLUSIONS: Laparoscopic adrenalectomy for pheochromocytoma is a safe and minimally invasive procedure.

Laparoscopic adrenalectomy in patients with large adrenal tumors.

OBJECTIVES: The maximum size of adrenal tumors that should be removed by laparoscopic adrenalectomy is controversial. We conducted a retrospective comparison of the results of laparoscopic adrenalectomy between patients with adrenal tumors > or =6 cm ('large tumors') and patients with adrenal tumors <6 cm ('small tumors'). METHODS: The participants in the study were 16 patients with large tumors and 111 patients with small tumors. The patients comprised 59 men and 68 women (mean age, 49.0 years; age range, 23-79) with varying diagnoses. Of the 16 patients with large tumors, five had Cushing's syndrome, four had pheochromocytomas, six had a non-functional tumor and one had malignant lymphoma. Adrenal tumors were confirmed by hormonal assays, biochemical tests and computed tomography. Of the 16 large tumors, five tumors were on the right and 11 were on the left. RESULTS: We found no significant differences in general demographic parameters between patients with large and small tumors. The mean duration of surgery was not significantly different between two groups. (large tumors, 210 min; small tumors,175 min). The mean volume of blood loss was 212 mL for large tumors and 30 mL for small tumors (P < 0.001, significant difference). There was no significant difference in time until walking, duration of hospitalization or number of using analgesics used. The time to first oral intake of group 1 (<6 cm) was significantly shorter than group 2 (> or =6 cm). Tumor size (> or =7.5 cm) was an independent predictor of a longer operation and greater blood loss in large tumors. CONCLUSIONS: Laparoscopic adrenalectomy for large tumors was safe and minimally invasive.