Bellmunt risk score as a survival predictor in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: The prognosis of metastatic castration-resistant prostate cancer (mCRPC) is influenced by numerous individual factors. Despite various proposed prognostic models, the clinical application of these remains limited, probably due to complexity. Our study aimed to evaluate the predictive value of the Bellmunt risk score, which is well-known for urothelial carcinoma and easily assessed, in mCRPC patients. METHODS: The Bellmunt risk score was calculated from three risk factors (Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥1, serum hemoglobin <10 g/dL, presence of liver metastases) in 125 patients who received first-line mCRPC treatment between 2005 and 2023. In addition, a modified score was established (one point each for hemoglobin <10 g/dL and the presence of liver metastases added to the ECOG PS). Associations with overall survival (OS) under first- and second-line therapy were tested using Cox regression analyzes, log-rank tests, concordance index (C-index) and time-dependent receiver operating characteristic. RESULTS: There is a significant correlation between the level of the Bellmunt risk score and shorter OS (hazard ratio: 3.23, 95% confidence interval: 2.06-5.05; log-rank p < 0.001; C-index: 0.724). The semi-quantitative modified risk score showed even better prognostic discrimination (log-rank p < 0.001, C-index: 0.764). The score and its dynamics were also predictive in the second-line setting (log-rank p < 0.001 and = 0.01; C-index: 0.742 and 0.595). CONCLUSIONS: The Bellmunt risk score is easy to assess and provides useful prognostic information in mCRPC, and can support physicians in their treatment decisions.

Metabolic profile and impact of diet in patients with primary hyperoxaluria.

PURPOSE: The primary goal of this pilot study was to evaluate metabolic characteristics and to examine the impact of diet in patients with primary hyperoxaluria (PH) under controlled, standardized conditions. METHODS: Four patients with genetically confirmed PH collected 24 h urines on their habitual, self-selected diets and on day 1, 6, 7, 8, and 11 under controlled, standardized conditions. The [13C2]oxalate absorption, calcium, and ammonium chloride loading tests were performed. RESULTS: While none of the patients had abnormal findings from the calcium loading test, incomplete distal renal tubular acidosis (RTA) was diagnosed in each of the four patients. Dietary intervention resulted in a significant decrease in urinary oxalate expressed as molar creatinine ratio (mmol/mol) between 30 and 40% in two of four patients. The evaluation of dietary records revealed a high daily intake of oxalate-rich foods as well as gelatin-containing sweets and meat products, rich sources of hydroxyproline, under the habitual, self-selected diets of the two responders. Intestinal oxalate hyperabsorption of 12.4% in one of the two patients may have additionally contributed to the increased urinary oxalate excretion under the individual diet. CONCLUSIONS: Our pilot data indicate that patients with PH may benefit from a restriction of dietary oxalate and hydroxyproline intake. Further research is needed to define the role of distal RTA in PH and to evaluate the hypothesis of an acquired acidification defect.

Fungaemia caused by obstructive renal candida bezoars leads to bilateral chorioretinitis: a case report.

BACKGROUND: Renal fungal bezoars are remarkably rare and mostly occur in immunodeficient patients. Only a small number of cases with immunocompetent patients have been published so far. The published treatment approaches comprised systemic antimycotic therapy and surgical or minimal invasive removal of the fungal balls. In some cases irrigation of the renal duct system with amphotericin B was performed. By obstruction of the urinary tract bezoars can lead to infected hydronephrosis and severe urosepsis with high lethality. Fungaemia can cause fungal colonization in different distant organs. Fulminant chorioretinitis and irreversible visual impairment can be the consequence of ocular fundus colonization. The following report highlights that a co-operation between urologists and ophthalmologists is absolutely indispensible in case of fungaemia. CASE PRESENTATION: Hereinafter we describe a case of an immunocompetent 56 years old woman, presenting with flank pain and shivering. The diagnosis turned out to be difficult due to initially negative urine culture. The fungaemia caused by obstructive nephropathy led to bilateral candida chorioretinitis. The patient was treated with intravenous amphotericin b and the bezoar was removed by percutaneous "nephrolitholapaxy". After two months, a follow up revealed the patient felt well, chorioretinal lesions regressed and urine culture did not show any fungal growth. CONCLUSION: To the best of our knowledge, this is the first case reporting on obstructive renal bezoars, which lead to haematogenous fungus spread and bilateral chorioretinitis. It points out that extensive ophthalmologic examination should be performed in case of fungaemia even if the patient is not suffering from any visual impairment.

Polyphenol Phase-II Metabolites are Detectable in Human Plasma after Ingestion of 13 C Labeled Spinach-a Pilot Intervention Trial in Young Healthy Adults.

SCOPE: After intrinsic labeling of spinach (Spinacia oleracea L., Chenopodiaceae) with 13 CO2 , we investigated if labeled polyphenol metabolites were detectable in human plasma. METHODS AND RESULT: In a pilot intervention trial, five healthy men consumed 5 g freeze-dried 13 C labeled spinach, including a total amount of 160 µmol methoxyflavonols, including 70 µmol 5,3',4'-trihydroxy-3-methoxy-6,7-methylendioxyflavone-4'-glucuronide. Plasma samples of all subjects were analyzed with regard to their 13 C/12 C ratio. Additionally, 13 C labeled metabolites of patuletin, spinacetin, and 5,3',4'-trihydroxy-3-methoxy-6,7-methylendioxyflavone (TMM) were analyzed in plasma samples in a subgroup of three subjects. TMM-glucuronide, TMM-sulfate, and spinacetin-glucuronide-sulfate, the latter as 12 C113 C16 and 13 C17 isotopologs, were tentatively identified. Plasma concentration of TMM-glucuronide and TMM-sulfate reached cmax from 19.1-54.3  and 22.5-125.5 nmol L-1 , respectively, 7-9 h post-ingestion. CONCLUSION: It seems likely that 13 C labeled TMM-glucuronide and TMM-sulfate are phase-II metabolites which were converted after colonic transformation. Variations in plasma kinetics were observed for these two metabolites and may be attributed to the individual composition of the microbiota. We conclude that 13 C labeled polyphenol metabolites are detectable and quantifiable in human plasma.

Minimally invasive treatment of female stress urinary incontinence with the adjustable single-incision sling system (AJUST ™) in an elderly and overweight population

ABSTRACT Introduction The prevalence of urinary incontinence is increasing. Two major risk factors are overweight and age. We present objective and subjective cure rates of elderly and overweight patients treated with an adjustable single-incision sling system (AJUST™, C.R. BARD, Inc.). Materials and Methods Between 04/2009 and 02/2012 we treated 100 female patients with the single incision sling. Patients were retrospectively evaluated by Stamey degree of incontinence, cough test, pad use, and overall satisfaction. The primary outcomes of the study were objective and subjective cure rates, secondary outcomes were the safety profile of the sling and complications. Results The overall success rate in this population was 84.6% with a mean follow-up of 9.3 months. The average usage of pads per day decreased from 4.9 to 1.6 and was significantly lower in patients with a BMI <30 (p=0.004). Postoperative residual SUI was also lower in patients with a BMI <30 (p=0.006). Postoperative satisfaction was better in patients with a lower BMI, but this difference did not reach a level of significance (p=0.055). There were no complications such as bleeding, bladder injury, or tape infection. Conclusions In elderly and obese patients a considerable success rate is achievable with this quick and minimal invasive procedure. However, the success rate shows a clear trend in favor of a lower body-mass-index. The cut-off point has been identified at a BMI of 30. The AJUST™ system can be regarded as safe and beneficial for elderly and obese patients.

Minimally invasive treatment of female stress urinary incontinence with the adjustable single-incision sling system (AJUST ™) in an elderly and overweight population.

INTRODUCTION: The prevalence of urinary incontinence is increasing. Two major risk factors are overweight and age. We present objective and subjective cure rates of elderly and overweight patients treated with an adjustable single-incision sling system (AJUST™, C.R. BARD, Inc.). MATERIALS AND METHODS: Between 04/2009 and 02/2012 we treated 100 female patients with the single incision sling. Patients were retrospectively evaluated by Stamey degree of incontinence, cough test, pad use, and overall satisfaction. The primary outcomes of the study were objective and subjective cure rates, secondary outcomes were the safety profile of the sling and complications. RESULTS: The overall success rate in this population was 84.6% with a mean follow-up of 9.3 months. The average usage of pads per day decreased from 4.9 to 1.6 and was significantly lower in patients with a BMI <30 (p=0.004). Postoperative residual SUI was also lower in patients with a BMI <30 (p=0.006). Postoperative satisfaction was better in patients with a lower BMI, but this difference did not reach a level of significance (p=0.055). There were no complications such as bleeding, bladder injury, or tape infection. CONCLUSIONS: In elderly and obese patients a considerable success rate is achievable with this quick and minimal invasive procedure. However, the success rate shows a clear trend in favor of a lower body-mass-index. The cut-off point has been identified at a BMI of 30. The AJUST™ system can be regarded as safe and beneficial for elderly and obese patients.

Primary Urethral Plasmacytoma Treated with High-Dose-Rate Brachytherapy: A Case Report.

Primary urethral solitary plasmacytoma is a very rare variant of extramedullary plasmacytoma. In total, only 9 cases have been reported so far. Patients were treated either by surgery or by external radiation therapy. Here, we report on a 22-year-old man, initially presenting with a palpable induration at the penis, intermittent dysuria and haematospermia, which was due to histologically confirmed solitary urethral kappa-restricted plasmacytoma. The patient subsequently underwent percutaneous and endo-urethral high-dose-rate brachytherapy with a total dose of 42 Gy applied in 14 fractions. Besides an uncomplicated urinary tract infection and hyperpigmentation of the penis, the patient tolerated the radiotherapy well and is still free of disease after 15 months follow-up.

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer.

INTRODUCTION: Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). MATERIALS AND METHODS: We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. RESULTS: Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both--NMIBC and MIBC--had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. CONCLUSIONS: Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis.

Long Term Progression-Free Survival in a Patient with Locally Advanced Prostate Cancer under Low Dose Intermittent Androgen Deprivation Therapy with Bicalutamide Only.

Androgen deprivation is a common treatment option in patients with locally advanced or metastatic prostate cancer. No case of long term treatment with an intermittent approach with only low dose bicalutamide (50 mg daily) has been described yet. We report a 60-year-old patient, initially presenting with a PSA elevation of 19.2 ng/mL in 1996. After diagnosis of well to moderately differentiated prostate cancer by transrectal biopsy, the patient underwent an open radical prostatectomy. Final diagnosis was adenocarcinoma of the prostate, classified as pT3a, pR1, pV0, and pL1. Adjuvant intermittent androgen deprivation therapy with flutamide 250 mg was applied, which was changed to bicalutamide 50 mg once daily when it became available in 2001. Six on-phases were performed and PSA values never exceeded 20 ng/mL. The patient did not experience any serious side effects. To date, there are no clinical or radiological signs of progression. Current PSA value is 3.5 ng/mL.

Urolithiasis--an interdisciplinary diagnostic, therapeutic and secondary preventive challenge.

BACKGROUND: The prevalence of urolithiasis in Germany is 4.7%; its incidence has trebled in the last three decades. The risk of recurrence is 50-80%, depending on the type of stone, unless secondary prevention is instituted. Risk-adapted secondary prevention lowers this risk to 10-15%. METHODS: This review is based on publications retrieved by a selective search in PubMed using the key words "urolithiasis," "urinary stones," "epidemiology," "lithogenesis," "biominerals," "risk factors," and "diagnosis, therapy, metaphylaxis." These publications were evaluated with the aid of the urolithiasis guideline of the European Association of Urology. RESULTS: Acute renal colic can usually be diagnosed without sophisticated equipment. Stones can be dealt with by a variety of techniques depending on their size and location, including extracorporeal shock-wave lithotripsy, ureterorenoscopy, percutaneous nephrolitholapaxy, and open surgery. Most ureteric stones of diameter up to 5 mm pass spontaneously. 75% of patients have no complications. The basic evaluation needed for secondary prevention can be carried out by any physician on an ambulatory basis. In the 25% of patients who have complications, a more extensive interdisciplinary evaluation of metabolic parameters should be performed in a clinical center for urinary stones. CONCLUSION: Urolithiasis has many causes and can be treated in many different ways. An extensive metabolic work-up is often necessary for secondary prevention. The various treatment options must be considered for their suitability in each individual patient. Robust data are now available on surgical and interventional methods, but there are as yet no high-quality trials of secondary prevention. Further research should concentrate on the etiology and pathogenesis of urolithiasis.

Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer.

Prostaglandins, especially prostaglandin E2 (PGE2), and COX-2 play an important role in carcinogenesis of many tumors including bladder cancer (BCA). The PGE2 receptors EP1-4 regulate tumor cell growth, invasion and migration in different tumor entities but EP expression in BCA remains to be determined. In the present study we examined the expression of EP1-4 in non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and normal urothelial tissue (NU) using immunohistochemistry. Nuclear and cytoplasmic EP1-4 expression was correlated with clinicopathological parameters and survival of BCA patients. EP1, EP2 and EP3 were significantly less expressed in the cytoplasm und nucleus of NMIBC and MIBC than in NU; EP4 cytoplasmic staining in MIBC was significantly higher compared to NU. The cytoplasmic staining was significantly more abundant in MIBC than in NMIBC in all investigated receptors except EP2. The level of EP staining in NMIBC was correlated with staging and grading, especially cytoplasmic EP1. Nuclear staining of EP1 was an independent predictor of BCA recurrence-free survival in NMIBC patients. EP receptors are dysregulated in BCA. The increase of EP1 may be used as prognostic parameter in NMIBC patients and its dysregulation could be targeted by specific EP1 inhibitors.

Induced urinary crystal formation as an analytical strategy for the prediction and monitoring of urolithiasis and other metabolism-related disorders.

Crystal formation reflects the entire composition of the surrounding solution. In case of urolithiasis, induced crystal formation in native urine has led to the development of the Bonn-Risk-Index (BRI), a valuable tool to quantify an individual's risk of calcium oxalate urolithiasis. If the progression of a disease is associated with characteristic changes in the activities of urinary components, this leads to an altered urinary crystallisation capacity. Therefore, the results of induced urinary crystal formation can be used to detect and monitor any disease linked to the altered urinary composition. Since crystal formation inherently takes into account the entire urinary composition, the influence of the disease on individual urinary parameters does not have to be known in order to monitor the consequent pathologic alterations. In this paper, we review the background of urinary crystal formation analysis and describe its established application in urolithiasis monitoring as well as potential further fields of clinical application.

Kidney sparing surgery for urothelial carcinoma of the pyelocalyceal system: is there a role for open techniques? Results from a small series.

PURPOSE: To evaluate individually tailored open nephron-sparing surgical techniques for urothelial carcinoma of the pyelocalyceal system (UCPCS). MATERIALS AND METHODS: Four patients underwent nephron-sparing surgery for UCPCS including, open partial resection of the pyelon with peritoneal reconstruction, partial nephrectomy, open partial resection of the pyelon with kidney autotransplantation, combined open resection and calicoscopic laser coagulation. RESULTS: Recurrence-free survival was 24 months without any impairment of kidney function in all patients. CONCLUSION: Open nephron-sparing surgery for UCPCS should be taken into consideration for selected cases.

Diagnostic meaning of urodynamic studies in pouch incontinence: results of a small series.

INTRODUCTION: To evaluate the meaning of urodynamic parameters in patients with pouch incontinence. MATERIALS AND METHODS: Thirteen urodynamic studies in patients with an ileal nipple as the efferent segment of an ileocecal pouch or ileum/ileocecal-augmented bladder were performed. The recorded parameters included pouch capacity, leak point pressure/volume, maximum pouch pressure, compliance, static and dynamic closure pressure, and functional length. Three patients suffered from urinary incontinence. RESULTS: In all cases of incontinent patients, no functional length or static or dynamic closure pressure could be revealed. In 8 of 10 cases of continent patients, a positive functional length as well as static and/or dynamic closure pressure were measured (mean value in continent patients: 15.9 mm, 14.5 cm H2O and 26.5 cm H2O, respectively). In 2 of 3 cases of incontinent patients, the pouch compliance was restricted (21 and 37 ml/cm H2O). The pouch capacity of continent patients was greater than the capacity of incontinent patients (377.4 vs. 185.7 ml). CONCLUSIONS: Positive functional length, static and dynamic closure pressures, and a high pouch capacity with an unrestricted compliance are predictive for pouch continence. They may individually not determine continence, but combining them can. However, the meaning of urodynamic studies in pouch incontinence is not the same as with the urinary bladder.

Spindle cell rhabdomyosarcoma of the prostate.

The spindle cell rhabdomyosarcoma is a rare variant of the embryonal rhabdomyosarcoma, mostly occurring in childhood. Only a few cases are described in adults. To date, no case of the spindle cell subtype of the prostatic embryonal rhabdomyosarcoma has been published. We report on a 23-year-old man, initially presenting with obstructive micturition problems, perineal pain and night sweat. After diagnosis by transrectal biopsy of the prostate, radiochemotherapy within the CWS 2002 P study was applied: nine cycles of vincristine, doxorubicin, actinomycin D, ifosfamide, and fractionated radiotherapy of the tumor and suspect lymph nodes (final dose 50.4 Gy). The tumor initially shrank, but an early local recurrence arose. Second-line chemotherapy was applied, followed by a salvage radical cytoprostatectomy. The patient died of disseminated disease 14 months after diagnosis.