Histopathology of castration-resistant prostate cancer confirms changes in bone metastasis during radium-223 treatment: A case report.

Radium-223 is used for treating castration-resistant prostate cancer with bone metastases. Here, we report the case of a 76-year-old man diagnosed with castration-resistant prostate cancer with bone metastases who was started on radium-223. Although the patient ultimately died from causes unrelated to the treatment before starting the third treatment course, we observed that radium-223 was more effective in areas closer to the bone cortex than in deeper tumor regions. Through histopathological analysis, we provide important mechanistic insights on the therapeutic effect of radium-223 in human prostate cancer bone metastases.

Cefaclor as a first-line treatment for acute uncomplicated cystitis: a retrospective single-center study.

BACKGROUND: Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. METHODS: We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. RESULTS: Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum ß-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P < 0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% (n = 24) or 93.3% (n = 14). The rate in patients with resistance to both antibiotics was 60.0% (n = 9), and the pathogens in the other 40.0% (n = 6) of patients with treatment failure were E. coli-ESBL. CONCLUSION: Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

Gleason Pattern 5 is a Possible Pathologic Predictor for Biochemical Recurrence after Laparoscopic Radical Prostatectomy

Objective: Several prognostic factors for biochemical recurrence after radical prostatectomy have been reported, including initial prostate-specific antigen level, Gleason score, positive surgical margin, and seminal vesicle invasion. Here we investigate whether Gleason pattern 5 is a predictor for biochemical recurrence. Methods: This retrospective study included 168 patients who underwent laparoscopic radical prostatectomy from 2006 to 2015. The relationship between biochemical recurrence after laparoscopic radical prostatectomy and the presence of Gleason pattern 5, even as a tertiary pattern, was investigated. Biochemical recurrence was defined when the prostate-specific antigen level rose to >0.2 ng/ml after having decreased to <0.1 ng/ml following laparoscopic radical prostatectomy. Biochemical recurrence-free survival was estimated by the Kaplan-Meier method. Multivariate analysis was performed using a Cox proportional hazards regression model. Results: The median age was 66 years, median initial prostate-specific antigen level was 6.9 ng/ml, and median follow-up period was 47.3 months. Biochemical recurrence was recognized in 27 patients (16.1%) after laparoscopic radical prostatectomy, and 5-year biochemical recurrence-free survival was 78.6%. Gleason pattern 5 was noted in 5 patients as the primary pattern, in 10 as the secondary pattern, and in 5 as the tertiary pattern. According to multivariate analysis, presence of Gleason pattern 5 (HR = 4.75, p=0.001) and positive surgical margin (HR = 4.66, p=0.001) were independent predictive factors for biochemical recurrence-free survival. Conclusion: Gleason pattern 5 appears to be an important predictive factor for biochemical recurrence after laparoscopic radical prostatectomy.

Feeding Solanum glaucophyllum to preparturient multiparous cows prevents postparturient hypocalcemia.

Solanum glaucophyllum (SG) contains 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) glycosides. We investigated the effect of SG on hypocalcemia in cows. Serum levels of 1,25-(OH)2D3, total calcium and phosphorus dose-relatedly increased after feeding with SG, while serum magnesium and chloride levels fell (P < 0.05). We also performed an ethylenediaminetetraacetic acid (EDTA) infusion to induce artificial hypocalcemia. Cows that had been fed 4.0 mg/kg body weight of SG daily for 2 weeks had a higher serum concentration of total calcium at the end of EDTA infusion than those not fed SG (P < 0.05). In a field trial, multiparous cows were assigned to one of four groups: (1) no SG, (2) 1.3 g or (3) 2.6 g of SG daily from 14 days before the estimated calving day until 3 days after calving, or (4) a single feed of 35.75 g SG at 3 days before the estimated calving day. The concentrations of serum total calcium after the calving in each treatment group were (1) 7.4, (2) 7.9, (3) 8.0 and (4) 8.9 mg/dL and higher for (4) than for (1) (P < 0.05). The data suggests that feeding a high dose of SG before the calving may maintain higher concentrations of serum calcium after the calving.

Effects of a combination of hinokitiol (ß-thujaplicin) and an organic acid mixture on ruminal fermentation in heifers fed a high-grain diet.

This study evaluated the effects of hinokitiol (a natural antibacterial compound extracted from Thujopsis dolabrata var. hondai) and an organic acid mixture (citrate content 50%) on ruminal fermentation. Antibacterial properties were examined by measuring minimal inhibitory concentration. Hinokitiol at 1.56µg/mL or an organic acid mixture at 1600µg/mL inhibited Streptococcus bovis growth. The combination of 0.78µg/mL hinokitiol and 200µg/mL of an organic acid mixture also inhibited S. bovis growth. Both hinokitiol and the hinokitiol and an organic acid mixture combination showed strong antibacterial properties on Gram-positive bacteria such as S. bovis, but relatively weak antibacterial activities on Gram-negative bacteria such as Megasphaera elsdenii. Three ruminally cannulated heifers were fed a bloat-producing diet containing barley, pelleted alfalfa meal, soybean meal and salt without long-cut roughage to investigate the ruminal characteristics in vivo. Feeding to heifers a bloat-producing diet containing 7.8mg/kg hinokitiol and 0.2% of an organic acid mixture significantly decreased the increase in stable ingesta volume. Hinokitiol or an organic acid mixture did not affect ruminal volatile fatty acids, protozoa and bacteria. These results suggest that a combination of hinokitiol and an organic acid mixture might reduce frothy bloat in cattle fed high-grain diets.

Proteomic study of sera from patients with bladder cancer: usefulness of S100A8 and S100A9 proteins.

To effectively obtain tumour-specific markers, fractionated proteins obtained using reversed-phase high-performance liquid chromatography for patient-matched pre- and postoperative sera from bladder cancer patients were compared by two-dimensional gel electrophoresis. The usefulness of the identified proteins was confirmed immunohistochemically. S100A8 and S100A9 were identified as tumour-associated proteins. The increased immunoreactive expression of S100A8 protein was associated with bladder wall muscle invasion of the tumour and cancer-specific survival (p<0.05), and the increased immunoreactive expression of S100A9 protein was associated with the tumour grade (p<0.05). In addition, increased expressions of both proteins was associated with recurrence-free survival at a median follow-up of 32.9 months (both p<0.05). On multivariate analysis, the expression of S100A8 was a significant predictor of recurrence (p<0.05). These findings may help to identify biologically aggressive tumors and, thus, patients who might benefit from more intensive adjuvant therapy.

Nomogram to predict seminal vesicle invasion using the status of cancer at the base of the prostate on systematic biopsy.

OBJECTIVE: The aim of this study was to predict seminal vesicle invasion (SVI) by developing a new nomogram based on clinical features including the status of cancer at the base of the prostate on systematic biopsy. METHODS: We studied the 466 patients with T1-3N0M0 prostate cancer who were treated with radical prostatectomy at three institutions. Preoperative clinical variables were correlated with the presence or absence of SVI with an area under the curve (AUC) of receiver-operator characteristics analysis. A nomogram was developed to predict SVI based on logistic regression analysis. RESULTS: A total of 81 patients (17%) had SVI. Cancer was present in a biopsy core from the base of the prostate in 209 patients, of whom 32.5% had SVI, compared with only 5% of the 257 patients without cancer at the base of the prostate (P < 0.005). On multivariate analysis, serum prostate-specific antigen, biopsy Gleason score, clinical T stage, and presence or absence of cancer in a biopsy core at the base of the prostate were significant predictors of SVI (P < 0.005 for all). The AUC of a standard model including clinical stage, Gleason score, and prostate-specific antigen was 0.83, which was significantly enhanced by including the presence of cancer at the base of the prostate (none, unilateral or bilateral lobes) (AUC 0.87, P= 0.023). Based on the logistic analysis, we developed the nomogram to predict SVI. The calibration plots appeared to be excellent. CONCLUSION: The information of presence or absence of cancer at the base from prostate biopsy and the resulting nomogram allow an accurate prediction of SVI in patients undergoing radical prostatectomy for prostate cancer.

Loss expression of uroplakin III is associated with clinicopathologic features of aggressive bladder cancer.

OBJECTIVES: Tissue-specific expression is of key importance in gene therapy and can be achieved by using tissue-specific promoters to drive therapeutic gene expression. The uroplakin (UP) promoter is a powerful tool for bladder cancer gene therapy, but the role of UP protein in the bladder remains unknown. This study aimed to detect UP III expression in transitional cell carcinoma (TCC) of the bladder and to determine whether the role of UP III heterogeneity is associated with predicting disease recurrence and patient survival. METHODS: Immunohistochemical staining for UP III was carried out in 92 archival radical cystectomy and 38 normal specimens and correlated with pathologic features and clinical outcomes. RESULTS: UP III expression was significantly decreased in bladder cancer tissues compared with normal controls (P <0.0001). Loss of UP III expression was associated with high-grade, muscle-invasive cancer, lymphovascular invasion (P <0.01), and decreased cancer-specific survival at a median follow-up of 25.3 months (P = 0.04). When adjusted for the effects of standard pathologic features, only lymph node metastases were associated with bladder cancer progression (P = 0.01) and mortality (P = 0.04). CONCLUSIONS: Loss of UP III expression is associated with established markers of biologically aggressive bladder cancer such as lymphovascular invasion, pathologic stage, and grade. UP III expression has limited prognostic value in patients with bladder TCC, but gene therapy viral vectors driven by the UP promoter would drive therapeutic gene expression in high-UP-expressing TCC cells, but not in aggressive low-UP-expressing TCC cells.

Varicocele complicating spontaneous arteriovenous fistula.

We describe herein a rare case of a varicocele complicating spontaneous arteriovenous fistula. A 40-year-old man was referred to our hospital in November 2006, complaining of a non-tender mass in the left scrotum at the age of 15 and thereafter. On examination, his left scrotum revealed a large varicocele, but no manifest superficial thrill was noted. Scrotal ultrasonograpy revealed approximately 7 cm large varicocele. Computed tomography angiography revealed the existence of an arteriovenous fistula between the left testicular artery and the veins of the left pampiniform plexus. We laparoscopically carried out internal spermatic vessels ligation under the diagnosis of a varicocele complicating a spontaneous arteriovenous fistula. The postoperative course was uneventful. At 18 months postoperatively, the varicocele and fistula had not recurred.

Case of seminoma with possible spontaneous regression without extragonadal metastatic lesion.

We present an extraordinarily rare finding of a testicular seminoma apparently in the process of spontaneous regression without accompanying metastatic lesion. A 35-year-old man visited our institute for persistent scrotal induration after the administration of antibiotics for several weeks. Ultrasonography and magnetic resonance imaging showed a capsulized tumor in his left atrophic testicle, without other visceral tumor or lymphadenopathy. We performed left radical orchiectomy. Histological examination revealed a fibrotic tumor with a small area of pure seminoma apparently undergoing spontaneous regression, and an intratubular germ cell neoplasia, unclassified, occurring diffusely. The patient is free of disease at 1 year after surgery.

[Case of local recurrence of the periurethral proximal-type epithelioid sarcoma successfully treated by repeated regional excision].

Proximal-type epithelioid sarcomas are rare soft tissue neoplasms occuring in the soma or thigh and often repeat recurrence and metastasis. We present a case of locally recurrenced proximal-type epithelioid sarcoma that could be treated by regional excision alone. A 62-year-old man visited our institute for a growing mass in the perineal region. Computed tomography (CT) showed a periurethral tumor 22 x 13 mm in diameter in the perineal region. The tumor was excised regionally, and the pathological examination with immunohistochemical staining revealed that the tumor was proximal-type epithelioid sarcoma. Local recurrence of the tumor occurred 2 years 7 months later without any metastatic lesion, and regional excision was performed again. Pathological diagnosis was proximal type epithelioid sarcoma and it was identical to the primary tumor. The patient is free of the disease 1 year after the second surgery of the tumor.

[A case of adrenocortical adenoma coexisting with gastrointestinal stromal tumor].

A 48-year-old man was referred to our institute for the evaluation of a concomitant gastric submucosal tumor and right adrenal tumor, incidentally found by ultrasound examination. Computed tomography showed a mass with a diameter of 6 cm adjacent to the stomach and the right adrenal tumor with a diameter of 3 cm. These tumors had similar characteristics in both plain and enhanced imagings. By magnetic resonance imaging, the intensity of the right adrenal tumor was equivalent to the liver in both T1 and T2 weighted images. On the other hand, the gastric submucosal tumor showed low intensity in T1 weighted images and high intensity in T2 weighted images. An adosterol scintigram showed slight accumulation at the region of adrenal tumor. The results of all conducted serum and urinary hormonal examinations were found to be within the normal range. Adrenalectomy and partial gastrectomy were performed laparoscopically. Pathological diagnosis of the adrenal tumor was a cortical adenoma, and that of the gastric submucosal tumor was gastrointestinal stromal tumor (GIST). The gastric tumor was immunohistochemically stained positive with the C-kit and CD34 and negative for s-100 protein and desmin. Histopathological diagnosis was coincident with gastric GIST and right adrenocortical adenoma, and the GIST was diagnosed as a high risk tumor because its diameter was over 5 cm.

Significance of the craniocaudal distribution of cancer in radical prostatectomy specimens.

OBJECTIVES: To examine the differences in the distribution of prostate cancer (PCa) in the craniocaudal dimension and their potential significance. METHODS: We studied 1253 patients with clinically localized PCa treated with radical prostatectomy (RP) from 1983 to 2000. We analyzed the clinicopathological features according to the craniocaudal distribution (apex, mid, base) of the largest cancer focus. RESULTS: Of these patients, 456 (36%) had the largest cancer focus in the apex, 728 (58%) in the mid, and 69 (6%) in the base. The cancers in the apex were less invasive than those in the mid or base, as evidenced by the lower frequency of extracapsular extension (27% vs 43%, 52%, respectively) and/or seminal vesicle involvement (5% vs 13%, 20%, respectively). The frequency of the largest cancer focus in the apex has increased significantly over time, from 26% before 1995 to 46% after 1995 (P < 0.001). Serum prostate specific antigen non-progression rate at 10 years for patients with a cancer at the apex was 83%, which was better than 76% and 77% of patients with a cancer at the mid or base (P = 0.029, P = 0.14, respectively). CONCLUSION: The cancers dominant at the apex are increasing over time and represent half of the patients treated by RP in recent years. These cancers tend to be less aggressive compared to those in the mid or base of the prostate. This knowledge may be useful in understanding the biology of and maximizing the detection of PCa.

Expression of S100A2 and S100A4 predicts for disease progression and patient survival in bladder cancer.

OBJECTIVES: To determine the expression patterns and prognostic value of S100A2 and S100A4 in surgical specimens from radical cystectomy for transitional cell carcinoma of the urinary bladder. METHODS: Immunohistochemical staining for S100A2 and S100A4 was performed in 92 archived radical cystectomy and 38 normal specimens. The immunoreactivity of these proteins was stratified on a 0 to 6 scale and then correlated with the pathologic features and clinical outcome. RESULTS: S100A2 expression was significantly decreased in the bladder cancer specimens compared with the controls (P <0.0001), and S100A4 expression was significantly greater in the bladder cancer specimens (P = 0.03). The loss of expression of S100A2 and increased expression of S100A4 were associated with muscle invasion (P <0.05). These alterations in expression were also associated with a greater risk of disease progression and a decreased chance of cancer-specific survival at a median follow-up of 25.3 months (P <0.0001 for both). After adjusting for the effects of the pathologic findings, S100A4 expression remained a significant predictor of disease progression (P <0.0001) and cancer-specific survival (P <0.0001). CONCLUSIONS: S100A4 appeared to be an independent predictor for the treatment outcome in bladder cancer. The expression patterns of S100A2 and S100A4 correlated well with the pathologic stage, disease progression, and cancer-specific mortality. This finding could aid in identifying more biologically aggressive cancers and thus patients who might benefit from more intensive adjuvant therapy.

Primary symptomatic perivesical paraganglioma: a case report.

Paraganglioma, extra-adrenal pheochromocytomas, are relatively rare in adults, with most arising from para-aortic sympathetic and visceral organs, such as the bladder. Paraganglioma localized at the extravesical retroperitoneal pelvic cavity is extremely rare. We report a case of symptomatic perivesical pheochromocytoma in a 34-year-old man treated by surgical excision. Symptoms related to cathecolamine secretion ceased after surgery, and the patient has remained disease-free for 24 months.

[The clinicopathological characteristics in renal cell carcinoma with end-stage renal disease].

OBJECTIVES: The influence and the interdependence of pathological and clinical factors on prognostic differences between renal cell carcinoma (RCC) with end-stage renal disease (ESRD) and RCC without ESRD after nephrectomy has remained unclear. We compare the clinicopathological features between RCC with and without ESRD. MATERIALS AND METHODS: From June 1993 to May 2000, 150 RCC patients who underwent nephrectomy were pathologically defined to have pT1 to pT3NXM0. The patients were followed for 1 to 84 months (median 30 months) after the surgery. Total of 16 patients with ESRD and 134 patients without ESRD were studied, and the differences of clinicopathological features between two groups were statistically compared. RESULTS: We compare the clinicopathological features between RCC with and without ESRD. Patients' age, tumor size, rate of incidental cancer, pathological T stage, and grade were not significantly different between two groups. The 5-year recurrence-free probability rate was significantly higher in patients without ESRD than in patients with ESRD (log-rank test: p = 0.04). The status of ESRD, patients age and pathological T stage were significant predictors of recurrence when analyzed by Cox proportional hazards analysis (p = 0.01, p = 0.03 and p = 0.02, respectively). CONCLUSIONS: This study demonstrated that the ESRD is an independent prognostic factor in RCC patients after surgery. These results reflect that the patients with ESRD have higher risk of tumor progression. Therefore, early detection of tumors is particularly important in these patients by regular abdominal ultrasound or CT screening.