Robotic transperineal prostate biopsy: pilot clinical study.

OBJECTIVE: To develope a robot (BioXbot) that performs mapping transperineal prostate biopsy (PB) with two perineal skin punctures under ultrasound guidance. Our pilot study's clinical endpoints were complications and its technical endpoints were the duration for each phase. METHODS: This institution review board-approved prospective clinical trial included patients with indications for PB. Two urologists performed these PBs. In the lithotomy position and under general anesthesia, the transrectal biplane ultrasound probe acquired transverse images of the prostate gland. The urologist defined its boundaries and planned the biopsy. It guided the PB in 3 axes, passing through a single perineal skin puncture for each prostate side. After each biopsy, it automatically moved to the next position. The steps were repeated on the contralateral side. RESULTS: Our 20 patients had a mean prostate-specific antigen of 8.4 ± 4.9 ng/mL. Two patients had 2 previous biopsies, whereas the rest had one. The mean number of biopsies taken was 28.5 ± 6.2 in a mean total procedure time of 32.5 ± 3.2 minutes. We detected 3 patients with prostate cancer with Gleason score 3 + 3. Two patients required brief bladder catheterization after their biopsy. Their prostate volumes were >50 mL and the number of biopsies taken was >30 cores. There was no mechanical failure, sepsis, bleeding per-rectal, or perineal hematoma. CONCLUSION: This pilot study demonstrated BioXbot's safety and feasibility as a biopsy platform. It can potentially be used for image-guided PB and focal therapy.

Inhibition of angiogenic and non-angiogenic targets by sorafenib in renal cell carcinoma (RCC) in a RCC xenograft model.

BACKGROUND: It is widely recognised that sorafenib inhibits a range of molecular targets in renal cell carcinoma (RCC). In this study, we aim to use patient-derived RCC xenografts to delineate the angiogenic and non-angiogenic molecular targets of sorafenib therapy for advanced RCC (aRCC). METHODS: We successfully generated three patient RCC-derived xenografts in severe combined immunodeficient mice, consisting of three different RCC histological subtypes: conventional clear cell, poorly differentiated clear cell RCC with sarcomatoid changes, and papillary RCC. This study also used clear cell RCC cells (786-0/EV) harbouring mutant VHL to investigate the clonogenic survival of cells transfected with survivin sense and antisense oligonucleotides. RESULTS: All three xenografts retain their original histological characteristics. We reported that sorafenib inhibited all three RCC xenograft lines regardless of histological subtypes in a dose-dependant manner. Sorafenib-induced growth suppression was associated with not only inhibition of angiogenic targets p-PDGFR-ß, p-VEGFR-2, and their downstream signalling pathways p-Akt and p-ERK, cell cycle, and anti-apoptotic proteins that include cyclin D1, cyclin B1, and survivin but also upregulation of proapoptotic Bim. Survivin knockdown by survivin-specific antisense-oligonucleotides inhibited colony formation and induced cell death in clear cell RCC cells. CONCLUSION: This study has shed light on the molecular mechanisms of sorafenib in RCC. Inhibition of non-angiogenic molecules by sorafenib could contribute in part to its anti-tumour activities observed in vivo, in addition to its anti-angiogenic effects.

Robotic ultrasound-guided prostate intervention device: system description and results from phantom studies.

BACKGROUND: We introduce the first robotic ultrasound-guided prostate intervention device and evaluate its safety, accuracy and repeatability. METHODS: The robotic positioning system (RPS) determines a target's x, y and z axes. It is situated with a biplane ultrasound probe on a mobile horizontal platform. The integrated software acquires ultrasound images for three-dimensional (3D) modelling, coordinates target planning and directs the RPS. RESULTS: The egg phantom evaluates the software's safety and workflow protocol. Two random targets are planned in each quadrant and biopsy needles are inserted. All were within three separate eggs. Metal wire tips are targeted and their distances from the biopsy needle tips are measured. With 20 wires, < 1 mm accuracy is obtained. Repeatability is demonstrated when previous positions are returned to with similar accuracy. CONCLUSION: Our device demonstrates safety in a defined boundary with a repeatable accuracy of < 1 mm. It can be used for accurate prostate biopsy and treatment delivery.

Predictors of androgen independence in metastatic prostate cancer.

OBJECTIVE: To assess the factors that influence the onset of androgen independence (AI, which heralds a dismal outcome) in patients with metastatic prostate carcinoma. PATIENTS AND METHODS: The records of 361 consecutive patients with prostate carcinoma diagnosed and treated in the authors' institution from 1 January 1996 to 31 December 1999 were reviewed retrospectively; 92 with metastatic prostate carcinoma were assessed (median age 71.0 years, range 42-93). Patients were included if they developed metastatic disease from prostate cancer at the time of diagnosis. The nadir for prostate specific antigen (PSA) level was defined as the date of the lowest PSA level after hormonal therapy, and AI was defined as the date of the third consecutive PSA increase above the nadir value by any threshold. RESULTS: The median Gleason sum was 8 and the modal Gleason score 4 + 5. The median (range) pretreatment PSA level was 274.0 (1.3-2179) ng/mL. Of the 92 men, 57 (62%) attained a nadir PSA, including 23 with a nadir of < 2 ng/mL; 32 (35%) progressed to AI within 2 years and 27% reached a nadir PSA but did not develop AI. The mean (sd) time from diagnosis to the nadir PSA was 13.7 (11.8) months, while the mean time from diagnosis to progression to AI was 30.3 (15.6) months. Univariate analysis showed that a nadir PSA level after treatment of >/= 1 ng/mL (P = 0.0128) was an early predictor of progression to AI; a nadir PSA level of >/= 2 ng/mL (P = 0.0216) was a predictor of poor overall survival. CONCLUSION: Failure to attain a nadir PSA of < 1 ng/mL after treatment predicts progression to AI and a nadir PSA of > 2 ng/mL predicts poorer overall survival. The development of skeletal events predicts the onset of AI but occurs late in the disease and is unsuitable as an early prognostic marker.

Endorectal magnetic resonance imaging and spectroscopy for the detection of tumor foci in men with prior negative transrectal ultrasound prostate biopsy.

PURPOSE: We determined the ability of combined endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) to detect prostate cancer foci prospectively in men with prior negative transrectal ultrasound (TRUS) prostate biopsy. MATERIALS AND METHODS: Endorectal MRI with spectroscopy was performed in 24 consecutive patients with 1 or more prior negative TRUS prostatic biopsies for persistently increased prostate specific antigen and/or abnormal digital rectal examination. All studies were interpreted by a dedicated radiologist who reported areas of interest in the peripheral zone as normal, equivocal or suspicious on MRI and MRSI separately. Equivocal and suspicious areas were then correlated with a 3-dimensional prostate model. All patients underwent a standard TRUS 10-core peripheral zone biopsy with up to 4 additional biopsies targeted at the equivocal or suspected sites. RESULTS: Prostate cancer was detected in 7 of 24 subjects (29.2%). Considering the equivocal category as test negative the sensitivity, specificity, positive and negative predictive values, and the accuracy of MRI, MRSI and combined MRI/MRSI for the detection of prostate cancer were 57.1%, 57.1% and 100.0%, 88.2%, 82.4% and 70.6%, 66.7%, 57.1% and 58.3%, 83.3%, 82.1% and 100%, and 79.2%, 75.0% and 79.2%, respectively. The site of positive biopsy correlated correctly in 50% and 28.6% of MRI and MRSI labeled suspicious cores, respectively. CONCLUSIONS: MRI and MRSI have the potential to identify cancer foci and direct TRUS in patients with a previous negative TRUS biopsy. Further, larger studies are required to quantify the amount of benefit.

Use of the scrotal remnant as a tissue-expanding musculocutaneous flap for scrotal reconstruction in Paget's disease.

Wide excision of extramammary Paget's disease of the penoscrotal region may leave large defects that cannot be closed easily. The authors describe their experience with a series of 6 patients in whom reconstruction of the scrotal defect was undertaken using the scrotal remnant raised as a stretchable musculocutaneous flap. It was observed that as little as a third of the residual scrotum could be expanded to resurface the entire scrotum. All flaps survived completely. Severe scrotal edema and ecchymosis were observed in 1 patient but the symptoms resolved completely with Trendelenburg positioning. The penile defects were resurfaced individually with thick skin grafts. Good-quality take with no chordee was observed in all patients after initial reconstruction. One patient developed penile contracture after reexcision of recurrent disease. Mean follow-up was 22 months (range, 3-60 months). Large defects of as much as two thirds of the scrotum may be reconstructed successfully using the tissue-expanding scrotal musculocutaneous flap.

Ureteroscopy as an out-patient procedure: the Singapore General Hospital Urology Centre experience.

OBJECTIVE: To study the safety and efficacy of ureteroscopy as an out-patient procedure. DESIGN: Retrospective study. SETTING: Teaching hospital, Singapore. SUBJECTS AND METHODS: Operating facilities for out-patient ureteroscopy were introduced in late 1998. A retrospective review of all patients undergoing ureteroscopy from March 1999 to December 2000 was conducted. Clinical records were reviewed for operating time, surgical outcome and complications, and length of hospital stay and re-admissions. RESULTS: Two hundred and ten patients underwent ureteroscopy for a variety of indications--115 patients were admitted to hospital as in-patients and 95 patients were treated as out-patients. Ureteroscopy and laser lithotripsy were performed using general or regional anaesthesia. Patients assessed to be American Society of Anesthesiology class I or II were eligible for an out-patient procedure. American Society of Anesthesiology class was found to be lower for those treated as out-patients compared with those undergoing in-patient procedures--63% versus 28% for class I and 36% versus 69% for class II. Mean operating time was 37 minutes for out-patient procedures and 57 minutes for in-patient procedures (P<0.01). Complications were low for out-patients, with six unplanned re-admissions, mostly for minor complications. All patients were discharged the following day. CONCLUSION: Ureteroscopy can be offered selectively as an out-patient procedure to patients with low surgical risk, especially American Society of Anesthesiology class I patients, and others expected to have an uncomplicated surgical procedure.

Comparison of laparoscopic and open adrenalectomy--a Singapore experience.

OBJECTIVE: We present our experience with laparoscopic adrenalectomy for benign adrenal diseases and compare clinical outcomes with the conventional open approach. METHODS: Between 1990 and 2001, two consecutive series of patients who underwent adrenalectomy for small, benign adrenal diseases were reviewed retrospectively. Patients with large tumours(> 7 cm), cancer and phaeochromocytoma were excluded. Fifty-eight patients underwent laparoscopic adrenalectomy and 48 patients had open surgery for benign adrenal diseases. Perioperative and postoperative records of both approaches were reviewed. RESULTS: The two groups were comparable in terms of patient age, sex, weight and side of lesion.The common indications for surgery were Conn's syndrome and Cushing's syndrome. The sizes of tumour were comparable between the laparoscopic and open groups (mean, 2.1 cm vs 2.4 cm). Despite the longer operating time (mean, 128 minutes vs 87 minutes), the postoperative morbidity, parenteral analgesic requirement and length of postoperative hospital stay (3.2 days vs 7.2 days) were less inpatients undergoing laparoscopic adrenalectomy. Patients also enjoyed earlier return to oral intake and ambulation. There were fewer complications in the laparoscopic group. There was no conversion to open surgery. CONCLUSION: Laparoscopic adrenalectomy is safe and has become the treatment of choice for small, benign adrenal lesions at our institution.

A twelve-year review of radical cystectomies in Singapore General Hospital.

INTRODUCTION: Bladder carcinoma is the tenth most common cancer affecting men in Singapore. This study reviews the complication rates and long-term outcome after radical cystectomy for bladder carcinoma. PATIENTS AND METHODS: A retrospective case-record review of 90 consecutive radical cystectomies in the Department of Urology at the Singapore General Hospital from 1 January 1989 to 31 December 2000 was performed. Patients were included if they were operated for muscle-invasive tumour, high-grade tumour with carcinoma in-situ (CIS), recurring multifocal high-grade tumour, CIS unresponsive to intravesical therapy, or endoscopically uncontrollable tumour. Patients were excluded if they had metastatic disease or non-bladder primary carcinomas. RESULTS: The patients were predominantly male (M:F, 80:10) and Chinese (Chinese:Malay:Indian:Others, 70:10:3:7) with a mean age of 64.1 +/- 9.9 years (range, 39 to 83 years). Fifty-one patients underwent ileal conduit creation, 36 had ileal neobladder creation, 2 had ureterosigmoidostomies and 1 had Mainz II pouch creation following radical cystectomy. Perioperative mortality was 2.2% (n = 2). Early complications constituted 39% (n = 35), whilst late complications constituted 14% (n = 13) of cases. The mean follow-up was 27.1 +/- 29.7 months (range, 1 to 137 months). The mean time to recurrence was 26.0 +/- 29.5 months (range, 3 to 137 months). The overall survival was 70%, 43% and 37% at 1, 3 and 5 years, respectively. The disease-free survival was 64%, 35% and 32% at 1, 3 and 5 years, respectively. CONCLUSION: The results of our radical cystectomies for bladder carcinoma are comparable to other established urology units although the morbidity remained significant.

Clinical safety profile of sildenafil in Singaporean men with erectile dysfunction: pre-marketing experience (ASSESS-I evaluation).

Safety and tolerability of sildenafil citrate was assessed in a population subset of 60 Singaporean men with erectile dysfunction taken from the Asian Sildenafil Efficacy and Safety Study (ASSESS-I), a double-blind, placebo-controlled, flexible-dose study. The men, from two centres, with > or = 6 months' history of erectile dysfunction, were randomized to two treatment arms for 12 weeks. One group (30 patients) received sildenafil (initial dose 50 mg taken 1 h before sexual activity for the first 2 weeks, increased to 100 mg or decreased to 25 mg, according to efficacy and/or tolerability). The remaining 30 patients received a matching placebo. Incidence and type of adverse effects were evaluated at 2, 4, 8 and 12 weeks. Nine patients (30.0%) on sildenafil (33.1% in the full ASSESS-I study) and one patient (3.3%) on placebo (22.8% in the full ASSESS-I study) experienced treatment-related adverse events, the most frequent being headache in the sildenafil group (reported by five patients [16.7%]; 11.0% in the full ASSESS-I study). Flushing, visual disturbance, dizziness, insomnia, myalgia and back pain each occurred in one patient in the sildenafil group (3.3%); in the placebo group, one patient (3.3%) had headache. Importantly, the incidence of cardiovascular and respiratory system adverse events were relatively less than in the full ASSESS-I population (cardiovascular 3.3% in the present study versus 10.2% in the full ASSESS-I population; respiratory 3.3% versus 5.5%). All adverse events were transient and mild, and did not lead to treatment withdrawal. There was no effect on sitting blood pressure, heart rate or standard laboratory parameters; more importantly, there was no incidence of myocardial infarction, stroke or priapism. These results should reassure Singaporean patients and their physicians of the safety of sildenafil for erectile dysfunction.

Single centre review of radiologically-guided percutaneous nephrostomies: a report of 273 procedures.

INTRODUCTION: To evaluate the technical success and complications associated with radiologically-guided percutaneous nephrostomies (PCNs) in a single centre. MATERIALS AND METHODS: A total of 273 PCNs performed in 190 patients in our hospital over a 3-year period from January 1997 to December 1999 were retrospectively reviewed. The study population consisted of 97 males and 93 females, ranging in age from 13 to 91 years. The main indications were urinary obstruction (77.7%), pyonephrosis (18.3%) and urinary diversion (4%). Demographic variables, technical and risk factors related to the procedure, complications, effect on urine cultures and body temperature; and subsequent patient management were examined. RESULTS: The technical success rate was 99%. The 30-day mortality was 7.2%, none of which were procedure related. Haemorrhage requiring transfusion occurred in 4.3% while septicaemia affected 3.2% of patients. Drainage catheter complications included catheter dislodgement and blockage which were 11.9% and 4.1%, respectively. Thirty-one per cent of PCNs subsequently underwent ureteric stenting as the definitive treatment modality. CONCLUSION: Radiologically-guided PCN is a safe procedure with a high technical success rate.