Optical Coherence Tomography as a Tool for In Vivo Staging and Grading of Upper Urinary Tract Urothelial Carcinoma: A Study of Diagnostic Accuracy.

PURPOSE: Biopsies and cytology are cornerstones in the diagnosis of upper urinary tract urothelial carcinoma. However, a high rate of nondiagnostic biopsies, tumor upgrading and tumor up staging after nephroureterectomy has been observed. In this prospective in vivo study we evaluated the diagnostic accuracy of optical coherence tomography for the grading and staging of upper tract urothelial carcinoma. MATERIALS AND METHODS: A total of 26 patients underwent diagnostic ureterorenoscopy including biopsies and optical coherence tomography, followed by nephroureterectomy or segmental ureter resection. The sensitivity, specificity, negative predictive value and positive predictive value of upper tract urothelial carcinoma grading and staging by optical coherence tomography were evaluated according to the STARD (Standards for Reporting of Diagnostic Accuracy) initiative and the second stage (2a and 2b) of the IDEAL model. For tumor staging a 2×2 table for sensitivity and specificity was calculated. For tumor grading the Wilcoxon rank sum test was used to test µoct in low and high grade lesions followed by ROC analysis for sensitivity and specificity. RESULTS: In 83% the staging of lesions was in accordance with final histopathology. Sensitivity and specificity analysis for tumor invasion was 100% and 92%, respectively. Tumor size greater than 2 mm and inflammation were risks for false-positives. For low and high grade lesions median µoct was 2.1 and 3.0 mm-1, respectively (p <0.01). ROC analysis showed a sensitivity of 87% and a specificity of 90% using a µoct cutoff of 2.4 mm-1. CONCLUSIONS: This report describes optical coherence tomography as a real-time, intraoperatively diagnostic modality in the diagnostic evaluation of upper tract urothelial carcinoma. We confirmed the ability of optical coherence tomography to visualize, grade and stage urothelial carcinoma in the upper urinary tract.

New developments in castrate-resistant prostate cancer.

Castrate-resistant prostate cancer (CRPC) occurs when disease progresses in the presence of castrate levels of androgens and remains sensitive to further hormonal manipulation. For many years the treatment of CRPC was limited to the use of docetaxel for metastatic disease. However, this has recently changed with the approval of several new agents. Sipuleucel-T, an immunotherapeutic vaccine, is now available in the US for patients with non-metastatic CRPC and abiraterone, an oral enzyme inhibitor of androgen biosynthesis, as well as cabazitaxel, a cytotoxic chemotherapeutic, have been approved for the treatment of metastatic CRPC. Also, denosumab, a subcutaneous antibody, is now an option for the treatment of patients with CRPC with bone metastases, in addition to zoledronic acid, an intravenous bisphosphonate. Further treatment advances for metastatic CRPC therapeutics are in late stage phase III development. These include therapies affecting the androgen receptor (MDV3100) as well as additional immune-based therapeutics, PROSTVAC and ipilimumab. A broad range of agents is also emerging under the term targeted therapies. The endothelin-A receptor antagonist zibotentan, the tyrosine kinase inhibitors dasatinib, sorafenib and cabozantinib, the anti-angiogenic agent aflibercept, and the clusterin inhibitor custirsen, are all currently being tested for efficacy in metastatic CRPC. The mechanism of action of these and other promising agents are discussed alongside current therapeutic options and their potential place in the treatment landscape for CRPC is considered.

Controversies in the management of T1 urothelial bladder cancer.

T1 urothelial bladder cancers are in majority high-grade and seem to grow rapidly with the potential not only to recur, but also to progress to muscle invasion. Therefore, management discussions for patients with a high-grade T1 urothelial bladder cancer are critical. In this review, we aim to give an overview of the controversies encountered in the management of these tumors. Relevant information on T1 urothelial cell bladder cancer was identified through a literature search of published studies and review articles. Establishing an accurate diagnosis is of utmost importance in T1 bladder cancer; particularly understaging can adversely impact the survival of the patient. Therefore, a standard re-TUR is highly recommended in all T1 bladder cancer patients. On the other hand overtreatment affects the quality of life and can lead to unnecessary morbidity. The available treatment options range widely: they include transurethral resection alone with or without re-resection, adding intravesical therapy, radical cystectomy, and bladder sparing techniques using radiotherapy or combined chemoradiation. The choice and timing of the decision whether to pursue with conservative management (TUR and BCG) or to proceed with cystectomy (selected cases with adverse prognostic factors) should be continuously reconsidered on an individual patient basis. This is why the decision making is so difficult, and although we have come along a way in understanding the biological behavior of these tumors, both the choice and timing of treatment remain controversial. After ensuring that accurate staging has been done, the therapeutic options for T1 bladder tumors vary widely (from bladder sparing approaches to cystectomy) and a choice should be made based on individual patient basis.

Embryonic stem cell-like cells derived from adult human testis.

BACKGROUND: Given the significant drawbacks of using human embryonic stem (hES) cells for regenerative medicine, the search for alternative sources of multipotent cells is ongoing. Studies in mice have shown that multipotent ES-like cells can be derived from neonatal and adult testis. Here we report the derivation of ES-like cells from adult human testis. METHODS: Testis material was donated for research by four men undergoing bilateral castration as part of prostate cancer treatment. Testicular cells were cultured using StemPro medium. Colonies that appeared sharp edged and compact were collected and subcultured under hES-specific conditions. Molecular characterization of these colonies was performed using RT-PCR and immunohistochemistry. (Epi)genetic stability was tested using bisulphite sequencing and karyotype analysis. Directed differentiation protocols in vitro were performed to investigate the potency of these cells and the cells were injected into immunocompromised mice to investigate their tumorigenicity. RESULTS: In testicular cell cultures from all four men, sharp-edged and compact colonies appeared between 3 and 8 weeks. Subcultured cells from these colonies showed alkaline phosphatase activity and expressed hES cell-specific genes (Pou5f1, Sox2, Cripto1, Dnmt3b), proteins and carbohydrate antigens (POU5F1, NANOG, SOX2 and TRA-1-60, TRA-1-81, SSEA4). These ES-like cells were able to differentiate in vitro into derivatives of all three germ layers including neural, epithelial, osteogenic, myogenic, adipocyte and pancreatic lineages. The pancreatic beta cells were able to produce insulin in response to glucose and osteogenic-differentiated cells showed deposition of phosphate and calcium, demonstrating their functional capacity. Although we observed small areas with differentiated cell types of human origin, we never observed extensive teratomas upon injection of testis-derived ES-like cells into immunocompromised mice. CONCLUSIONS: Multipotent cells can be established from adult human testis. Their easy accessibility and ethical acceptability as well as their non-tumorigenic and autogenic nature make these cells an attractive alternative to human ES cells for future stem cell therapies.

Prognostic factors and percutaneous nephrolithotomy morbidity: a multivariate analysis of a contemporary series using the Clavien classification.

PURPOSE: We stratified factors affecting treatment morbidity, compared the outcomes of percutaneous nephrolithotomy procedures from a single department and provided evidence of treatment benefits when percutaneous nephrolithotomy is performed in an expert setting. MATERIALS AND METHODS: Since the department became a dedicated endourological center in 2002 we grouped all percutaneous nephrolithotomy procedures into those performed before 2002 (group 1) and after 2002 (group 2). The modified Clavien classification was used to score morbidity. Independent variables with an influence on complications were studied including stone size, operating time, operative complications, dilation device, urine culture, group allocation and lithotripsy device. Contingency and logistic regression were used for univariate and multivariate analysis. RESULTS: Of the 244 percutaneous nephrolithotomy procedures 68 comprised group 1 and 176 formed group 2. Statistical preoperative differences were patient age, the use of anticoagulants and positive urinary cultures. Group 1 had a complication rate of 56.8% and group 2 had a complication rate of 37.2%. There were significant differences between the groups (p = 0.007). Almost all complications were grade 1 to 2. On univariate analysis the influence variables were urine culture (OR 1.69), group allocation (OR 2.20), stone size (OR 2.28), dilation device (OR 4.8), lithotripsy device (OR 1.22), perioperative complications (OR 2.83) and surgical time (OR 1.87). On multivariate analysis the independent factors in the complicated outcome were stone size (OR 1.25), type of lithotripsy device (OR 1.35) and incidence of perioperative complications (OR 3.71). CONCLUSIONS: The dedicated setting for percutaneous nephrolithotomy at our center resulted in decreased operative time, more uneventful procedures and decreased hospitalization time. The modified Clavien morbidity score is a reliable tool for more objective outcome comparisons after renal stone treatment.

[Practice guideline 'Prostate cancer: diagnosis and treatment']. / Richtlijn 'Prostaatcarcinoom: diagnostiek en behandeling'.

--A national, multidisciplinary practice guideline was developed concerning diagnosis and treatment of patients with prostate cancer. Because of the lack of sufficient scientific evidence at this moment no practice guideline on screening is included. --The diagnosis of prostate cancer is made by transrectal ultrasound-guided prostate biopsies. The Gleason score is used for histological grading. --In localized prostate cancer and comorbidity 'active surveillance' is advised if the life expectancy is < 10 years. In healthy patients radical prostatectomy, external and internal radiotherapy are equivalent treatment options. The final decision is made after the patient has received adequate counselling. --In locally advanced prostate cancer in a patient with a life expectancy > or = 10 years external beam radiotherapy is the preferred treatment whether or not in combination with hormonal therapy. --In locally recurring prostate cancer following radical prostatectomy and prostate-specific antigen (PSA) < 1.0 ng/ml salvage radiotherapy can be advised. Recurrence following external beam radiotherapy may be treated by salvage radical prostatectomy or brachytherapy in selected cases. --In metastatic prostate cancer androgen deprivation therapy is advised, i.e. surgical castration, luteinizing hormone-releasing hormone (LH-RH) analogues, or parenteral estrogens. --In hormone resistant prostate cancer palliative treatment of painful metastases is advised, e.g. painkillers, local radiotherapy, or radionuclides. The role of docetaxel-based chemotherapy should be discussed. --During follow-up PSA is determined; digital rectal examination and imaging are performed whenever indicated.

[Pyelonephritis during pregnancy: a threat to mother and child]. / Pyelonefritis in de zwangerschap: een bedreiging voor moeder en kind.

Two pregnant women, aged 19 and 40 respectively, were diagnosed with pyelonephritis. The first patient was initially treated with amoxicillin; appropriate antibiotic treatment--consisting of amoxicillin and clavulanic acid--was delayed for 24 hours. The second patient immediately received appropriate treatment (ceftriaxone). The first patient eventually had a nephrostomy and died due to urosepsis with multiple organ failure. The second patient delivered a healthy son and recovered. Approximately 20% of the cases of pyelonephritis during pregnancy progress to urosepsis. Therefore, pregnant women with pyelonephritis should be treated immediately with an intravenous second- or third-generation cephalosporin or the combination ofamoxicillin and clavulanic acid. Treatment of pregnant patients with urosepsis should take place in an intensive care unit and include treatment of the underlying infection as well as support of vital functions. Nephrostomy in a pregnant patient with symptomatic hydronephrosis should only be performed when the symptoms persist despite adequate antibiotic treatment.

Highly selective embolization of bilateral cavernous arteries for post-traumatic penile arterial priapism.

High-flow priapism is characteristically diagnosed on clinical findings: a prolonged, non-painful erection with a delayed onset that develops after a penile or perineal trauma. If conservative measures fail arteriography is indicated, which shows a blush of extravasating contrast from an arterio-cavernous fistula (rarely, as in our case bilateral) that can be treated by embolization. The embolic agent is gelfoam or a microcoil. Bilateral embolization is indicated when unilateral treatment does not result in detumescence of the penis. When the embolization is done highly selective the risk of complications is low and the results on erectile function are good.

Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group.

OBJECTIVES: To compare toxicity, subjective response rate, time to subjective progression and overall survival in patients with painful bone metastases of hormone-resistant prostate cancer (HRPC) treated with a single intravenous injection of 150MBq (4mCi) Strontium(89) Chloride (S) or palliative local field radiotherapy (R) with the usual radiotherapy regimen used at each centre. The costs of both treatments were also assessed. PATIENTS AND METHODS: 101 patients were randomized to S and 102 to R. Time to event endpoints were compared with the Logrank test and Kaplan-Meier curves, in the intent-to-treat population (2-sided alpha=0.05). RESULTS: Baseline characteristics of both groups were comparable. There was a borderline statistically significant difference in overall survival in favour of the local field radiotherapy (R: 11 months; S: 7.2 months; p=0.0457). There was no difference in progression-free survival or time to progression. Subjective response was seen in 34.7% in the S-arm and in 33.3% in the R-arm. A biochemical response was observed in 10% and 13% of the R- and S-groups, respectively. There was no difference in treatment toxicity between the two groups. CONCLUSION: In symptomatic HRPC, pain treatment with local field radiotherapy is associated with a better overall survival compared to Strontium(89). The lower costs of local field radiotherapy also favour the use of this treatment in patients with HRPC. The reason for the apparent survival benefit of localised radiation treatment is not clear.

Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma.

OBJECTIVE: To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to clinical progression. Finally to compare TPS with prostate-specific antigen (PSA) measurements in terms of prognostic impact in patients with metastatic prostatic carcinoma. METHODS AND PATIENTS: TPS and PSA measurements were performed before start of and monthly during intermittent MAB in 68 patients participating in EORTC protocol 30954. Both TPS and PSA were measured in serum. Fifty-six patients from eight centers were included in the final analysis because at least three TPS values were available. TPS and PSA values were correlated with clinical course of the disease. Median follow-up was 21.3 months. Three patient groups were defined on clinical grounds: (a) clinically progressive disease (n=18); (b) clinically stable disease (n=33); and (c) patients who did not reach a predefined nadir PSA value following 9 months of treatment (n=5). RESULTS: Pretreatment TPS was significantly higher in the clinically progressive patients than in the other patient groups (p=0.0041). When grouping patients according to their pretreatment TPS values (cut-off value of 100 U/l) the pretreatment TPS value (>100 U/l) proved to be a statistically significant prognostic factor with respect to time to progression: elevated TPS was associated with a 3.8 increased risk for progressive disease (p=0.0055). Pretreatment PSA (>100 ng/ml) was of no prognostic value for time to progression. In five patients increase of TPS coincided with or preceded clinical progression during treatment, whereas PSA remained normal. CONCLUSION: Additional value of pretreatment TPS measurements in metastatic prostate cancer patients is found in defining the patients with rapid clinical progression. Following MAB an increase in TPS signifies clinical progression even if PSA is found to remain normal.