11C-acetate positron-emission tomography/computed tomography imaging for detection of recurrent disease after radical prostatectomy or radiotherapy in patients with prostate cancer.

OBJECTIVES: To evaluate, in a prospective study, the effectiveness of computed tomography (CT)-matched 11C-acetate (AC) positron-emission tomography (PET) in patients with prostate cancer (PCa) who had prostate-specific antigen (PSA) relapse after radical prostatectomy (RP) or radiotherapy (RT). PATIENTS AND METHODS: In 103 relapsing patients after RP (n = 97) or RT (n = 6) AC-PET images and CT scans were obtained. In patients with AC-PET-positive results with localized PCa recurrence, detected lesions were resected and histologically verified or, after local RT, followed-up by PSA testing. Patients with distant disease on AC-PET were treated with androgen deprivation/chemotherapy. RESULTS: Of 103 patients, 42 were AC-PET-positive. PSA levels were <1.0, <2.0 and <4.0 ng/mL in six, 16 and 20 patients, respectively. In 25/42 patients AC-PET suggested lymph node metastases: 16/25 patients underwent surgery (10/16 metastasis, 6/16 inflammation); 9/25 patients underwent RT of lymph node metastases, which was followed by decreasing PSA level. In 17/42 patients who had distant disease, systemic treatment was commenced. Combining patients who underwent surgery and those who underwent RT, 19/25 patients were true-positive in terms of AC-PET (positive predictive value 76%). In 5/19 patients, PSA level was <2.0 ng/mL, in 2/19 patients it was <1.0 ng/mL and in 14/19 patients it was 5.4-23.1 ng/mL. In AC-PET-positive patients after surgery or RT (without androgen deprivation), median (range) time to renewed PSA increase was 6 (5-9) months. CONCLUSIONS: Only a minority of patients with relapsing PCa appear to benefit from AC-PET for guiding potential local treatment. False-positive results show that factors other than tumour metabolism induce increased AC uptake. The time free of recurrence after local treatment was shorter than expected.

E-Learning in Urology: Implementation of the Learning and Teaching Platform CASUS® - Do Virtual Patients Lead to Improved Learning Outcomes? A Randomized Study among Students.

BACKGROUND: E-learning is playing an increasing role in medical education, supporting a problem-based and practical oriented education without putting patients at risk and compensating for the decrease in instructor-centered teaching. Not much research has been done concerning learning effects and reaction on behalf of the students. METHODS: We created computer-based cases for four important diagnoses in urology using the authoring system CASUS®. Fourth-year medical school students were randomized into two groups: (1) the CASUS® group, using the online cases for preparation, and (2) the book group, using a textbook. A multiple-choice test referring to the prepared topic had to be completed at the beginning of each lecture and the results were analyzed. Evaluation of the students concerning the acceptance of the program was done at the end of the semester. RESULTS: Members of the CASUS® group scored significantly higher with an average of 20% better test results than students using textbooks for preparation. Evaluation regarding the program showed a highly positive rating. Limitations include the small study population and the possibly biased test performance of the students. CONCLUSION: Computerized patient cases facilitate practice-oriented teaching and result in an interesting and engaging learning model with improved learning outcomes.

Hedgehog-signaling is upregulated in non-producing human adrenal adenomas and antagonism of hedgehog-signaling inhibits proliferation of NCI-H295R cells and an immortalized primary human adrenal cell line.

Hedgehog (Hh)-signaling pathway is important in embryonic development. Activation of Hh-signaling is associated with tumorigenesis. Recent studies demonstrate that Hh-signaling is involved in the development of the adrenal gland in mice and is important in regulating adrenal proliferation. We studied the expression of Sonic hedgehog (SHH), Smoothened (SMO), Patched1 (PTCH1) and GLI family zinc finger 1 (GLI1) in human adrenal and in adrenocortical tumors using immunohistochemistry and semi-quantitative reverse transcriptase-polymerase chain reaction. Modulation of GLI1 and SMO messenger ribonucleic acid (mRNA) expression was investigated with forskolin. The role of Hh-signaling was studied in NCI-H295R cells and in an immortalized primary cell line using the Hh-agonist smoothened agonist (SAG) and the Hh-antagonist cyclopamine. The Hh-pathway components SHH, GLI1, PTCH1 and SMO were detectable in all adrenal glands. While in cortisol-producing adenomas (CPA), Hh-signaling expression levels were comparable to that in normal adrenal cortex, a much higher mRNA expression of GLI1, SMO and SHH was observed in non-producing adenomas (NPA). Interestingly, stimulation of cultured adrenal cells with forskolin led to a decrease in expression of GLI1 and SMO mRNAs. Antagonism of Hh-signaling resulted in a lower proliferation rate of adrenocortical cells, while Hh-agonism had no significant effect on adrenal cell proliferation. Our data show Hh-signaling activity in adult adrenal glands. Activation of the PKA pathway results in lower expression of Hh-signaling proteins. This might explain the lower expression of the Hh components GLI1 and SMO in CPA in comparison to the higher expression in NPA. Hh-signaling might be involved in the tumorigenesis of NPA.

Phase II study to assess the efficacy, safety and tolerability of the mitotic spindle kinesin inhibitor AZD4877 in patients with recurrent advanced urothelial cancer.

BACKGROUND: AZD4877 is a potent inhibitor of the mitotic spindle kinesin, Eg5. Early-phase clinical studies in a broad range of cancers showed that AZD4877 is well tolerated. This Phase II study evaluated the efficacy, safety and pharmacokinetics (Cmax) of AZD4877 in patients with previously treated advanced urothelial cancer (ClinicalTrials.gov identifier NCT00661609). PATIENTS AND METHODS: AZD4877 25 mg was administered once-weekly for 3 weeks of each 4-week cycle until disease progression, death, unacceptable toxicity or withdrawal. The primary objective was to determine the objective response rate (RECIST). Recruitment was to be halted if ≤ 2 of the first 20 evaluable patients achieved an objective tumor response. Cmax was assessed on days 1 and 8 of cycle 1. RESULTS: None of the first 20 patients evaluable for efficacy achieved an objective response; enrollment was therefore halted. During this initial analysis, a further 21 patients were recruited. Overall, 39 patients were evaluable for efficacy, including one with confirmed partial response (PR) and seven patients with stable disease for ≥ 8 weeks (including one unconfirmed PR). The most commonly reported treatment-related adverse events (TRAEs) were neutropenia (22 patients), fatigue (12), leukopenia (7) and constipation (6); the most commonly reported grade ≥ 3 TRAE was neutropenia (21). Four patients had serious TRAEs. On days 1 and 8, the geometric mean Cmax of AZD4877 was 138 ng/ml (CV = 75 %) and 144 ng/ml (CV = 109 %), respectively. CONCLUSIONS: AZD4877 was generally tolerable in patients with advanced urothelial cancer. Given the limited clinical efficacy, further development of AZD4877 in urothelial cancer is not planned.

The risk of urinary incontinence after partial urethral resection in patients with anterior vulvar cancer.

OBJECTIVE: The number of women with vulvar carcinoma located in the anterior fourchette in immediate proximity to the urethral opening has increased. A retrospective analysis was performed in order to evaluate the risk of urinary incontinence after tumor-resection, standard inguinal lymphadenectomy and additional partial urethral resection. STUDY DESIGN: Between 2002 and 2007, 19 women with vulvar carcinomas located close to the urethral opening and consequently treated by additional partial urethral resection of up to 1.5 cm, were evaluated for urinary loss postoperatively by standard incontinence questionnaire. All patients complaining about some kind of urinary loss underwent urodynamic measurement. Results were compared with 21 controls (women with anterior vulvar cancer treated without urethral resection). RESULTS: Five of 19 women (26%) of the study group complained about urinary disturbances and received urodynamic evaluation. Ninety-five percent of the patients (18/19 women) were continent by urodynamic criteria; in one woman the measurement was unreliable. One patient in the control group (1/21 women) complained of an increase of urge symptoms that had been present preoperatively. CONCLUSIONS: Twenty-six percent of our patients after partial urethral resection reported incontinence symptoms, though this was not always confirmed by urodynamics. We conclude that the risk of urinary stress incontinence after partial urethral resection in anterior vulvar carcinoma is acceptable.

Abdominal perforation after rupture of a diamond-studded wire: a case report.

INTRODUCTION: There are numerous cases of abdominal injuries due to bullets. Abdominal injuries due to bullets are a diagnostic and therapeutic challenge. Here, an unusual case of an abdominal perforation caused by a metal projectile, lead to confusion in the interpretation of the preoperative computer tomography. CASE PRESENTATION: We present an unusual case of a 32-year-old male worker who sustained a "shot" to the left upper abdominal quadrant, as a result of a work-related accident. The projectile derived from a special wire that tore during operation. One chain element happened to accelerate towards the patients belly and perforated the abdominal wall. Computer tomography located the radiopaque projectile to the cortex of the left kidney and showed a lesion of the tail of the pancreas. The presence of intraperitoneal free air suggested a gastrointestinal perforation. Immediate open exploration of the peritoneal cavity and the retroperitoneal space revealed perforating lesions of the anterior and posterior gastric wall, as well as the pancreatic tail. The projectile was finally retrieved in the upper pole of the left kidney. The patient had a good clinical course subsequent to surgery and was discharged in good general condition. CONCLUSION: This case represents a rare form of a retained bullet injury and corroborates the need of sufficient measures of worker-protection in area of diamond-studded wire cutting devices.

Clinical and functional results after continent cutaneous urinary diversion with the ileal double-T-pouch.

INTRODUCTION: The aim of the study was to assess the clinical and functional results after continent cutaneous diversion with the ileal double-T-pouch. PATIENTS AND METHODS: Between July 1998 and July 2006, 19 patients underwent continent urinary diversion with a cutaneous ileal double-T-pouch. Follow-up investigations included blood chemistry, renal ultrasound and evaluation of the outlet function. The median follow-up was 24 months (range 3-76). RESULTS: There were no intraoperative complications and no perioperative mortality. Early postoperative complications not related to urinary diversion occurred in 6 patients (31.6%). Five patients developed complications related to the urinary diversion (26.3%). The mean operating time was 580 min (420-840). Including the patients who had good results after reoperation, 16 out of the 19 patients (84.2%) were continent day and night without any catheterization difficulties. The average pouch capacity was 490 ml (range 250-1,100). A mild acidosis was the only metabolic disorder observed. During follow-up renal function remained stable in all patients, urinary reflux, recurrent pyelonephritis or stone formation were not found. Three patients with a body mass index >30 developed a necrosis of the efferent loop resulting in pouch cutaneous fistulas. CONCLUSIONS: Continent cutaneous urinary diversion with the ileal double-T-pouch led to good intermediate functional and clinical results. However, construction of the pouch is sophisticated, resulting in a long operation time. The double-T-pouch is not recommended in obese patients.