Survival of patients with transitional cell carcinoma of the urinary bladder in indonesia: a single institution review.

OBJECTIVE: To describe for the first time the survival of bladder transitional cell carcinoma (TCC) in Indonesia, according to clinicopathological characteristics. MATERIALS AND METHODS: Retrospective study of bladder TCC survival in a single institution, Cipto Mangunkusumo Hospital, Indonesia's national tertiary referral centre, between the years 1995 and 2005. The Kaplan-Meier method was used to determine the overall survival (OS). RESULTS: The evaluable data covered 254 cases of primary bladder TCC, in which 95 (37.4%) were non muscle-invasive bladder cancer (NMIBC), and 159 cases (62.6%) were muscle-invasive (MIBC). Of these, 105 cases (41.4%) with a follow-up period up to five years were eligible for survival analysis. The mean age was 56.5 +/- 12.1 years old, with a male to female ratio of 6:1. The 5-year OS for all bladder TCC was 27.6%, with a mean survival time of 32.6 months. For NMIBC, the 5-year OS was 53.8% with a mean survival of 54.5 months. For MIBC, the 5-year OS was 19% with a mean survival of 25.4 months. Regarding pathological stage, the 5-year OS for stage 0, I, II, III, and IV was 83.3%, 45%, 30%, 18.8%, and 9.1%, respectively. CONCLUSION: The overall survival of bladder TCC in Indonesia is low compared to other countries. Possible explanations include the high number of advanced-stage tumours at initial presentation, under-staging, significant number of treatment refusal by our patients, and the non-standardized use of adjuvant therapy in our centre.

Testosterone replacement therapy in prostate cancer patients: is it safe?

The increasing population of elderly men means there is also an increase in those suffering from late-onset hypogonadism and testosterone deficiency, with all its attending consequences such as reduced libido, erectile dysfunction, metabolic disturbances, cardiovascular disease, decreased bone density and reduced quality of life. The use of testosterone replacement therapy may benefit such patients but remains controversial, especially with regard to the risk it may have on prostate cancer. However, there is no conclusive evidence that testosterone therapy increases the risk of developing prostate cancer nor is there any evidence to suggest that it can convert subclinical or indolent prostate cancer into a clinically significant one. In fact, a number of recent reports have shown that it is safe to give testosterone therapy in patients who have been successfully treated for early prostate cancer. Therefore, the purpose of this review is to discuss the role of testosterone replacement therapy, focusing on those with prostate cancer, as well as the risks and benefits that every physician must consider before commencing treatment.

Prognostic factors for upper tract transitional cell carcinoma: a retrospective review of 66 patients.

OBJECTIVE: We assessed the prognostic factors on recurrence and disease-specific survival of patients treated for upper tract transitional cell carcinoma (TCC). METHODS: Data on 66 patients who were treated for upper tract TCC in a single centre over a 13-year period were analysed. Mean follow-up time was 49.2 months. Fifty-five out of 66 (83.3%) underwent nephroureterectomy with excision of a bladder cuff. Four (6.1%) patients had nephrectomy alone while three (4.5%) had renal-sparing surgery. Four patients did not receive surgery due to advanced age and other comorbidities. Age, sex, tumour location, stage and grade were analysed as prognostic factors for disease recurrence and disease-specific survival using log rank univariate analysis. RESULTS: Disease recurrence occurred in 45 (68.2%) patients at a median time of 11.0 months. Recurrences were found in the bladder in 27.3%, the contralateral renal pelvis in 4.5%, local retroperitoneum in 19.7%, distant sites in 13.6%, with simultaneous local and distant metastases occurring in 3.0%. Tumour stage was the only significant prognostic factor for recurrence. Presence of extraurothelial recurrence, stage and grade were significant prognostic factors for disease-specific survival. CONCLUSION: Tumour stage was the most consistent predictor of both disease recurrence and survival. These findings would guide the need for any adjuvant chemoradiotherapy.

Differential expression of vascular endothelial growth factor165b in transitional cell carcinoma of the bladder.

Angiogenesis or the development of new blood vessels from the surrounding vasculature is essential for the growth and progression of solid tumors. Vascular endothelial growth factor (VEGF), a positive regulator of angiogenesis, plays a pivotal role in tumor angiogenesis and shows a high expression in almost all known tumors, including transitional cell carcinoma (TCC) of the bladder. A novel isoform, VEGF(165)b containing a novel exon 9, was recently identified in renal cell carcinoma and was shown to be down-regulated and inhibitory in nature. We aimed to analyze quantitatively expression of this isoform, VEGF(165)b, in TCC of the bladder and compare it to the benign part of the same organ. A real-time reverse transcriptase polymerase chain reaction protocol was set up to quantitate simultaneously the messenger ribonucleic acid levels of VEGF and VEGF(165)b from 34 clinical samples representing bladder cancer and matched benign tissue. Expression of VEGF(165)b showed a >or=3.0-fold change in 27 of 34 (79%) bladder tumors than the benign samples. Increased expression of VEGF(165)b was seen in superficial tumors as compared to invasive tumors, which was statistically significant (P < 0.001). Therefore, VEGF(165)b was up-regulated in TCC of the bladder.

Minimally invasive treatment of ureteropelvic junction obstruction: long-term experience with an algorithm for laser endopyelotomy and laparoscopic retroperitoneal pyeloplasty.

PURPOSE: First line treatment of ureteropelvic junction obstruction is still open dismembered pyeloplasty. The development of videoendoscopic techniques like endopyelotomy and laparoscopy offers less invasive alternatives. The long-term outcome of an algorithm selectively using these techniques is presented. MATERIALS AND METHODS: From February 1995 to March 2006, 256 patients with ureteropelvic junction obstruction were treated with 113 laser endopyelotomies and 143 laparoscopic retroperitoneal pyeloplasties. According to changing selection criteria, an early group (92 in 1995 to 1999) treated with laser endopyelotomy for extrinsic as well as intrinsic stenoses, and a late group (164 in 2000 to 2006) treated with laser endopyelotomy for intrinsic stenosis, were evaluated. In the late group extrinsic ureteropelvic junction obstruction was treated with nondismembered pyeloplasty in cases of anteriorly and by dismembered pyeloplasty in cases of posteriorly crossing vessels or a redundant renal pelvis. RESULTS: Operating time of laser endopyelotomy averaged 34 (range 10 to 90) minutes with a complication rate of 5.3% and a success rate of 72.6% (intrinsic 85.7% vs extrinsic 51.4%). Operating time of laparoscopic retroperitoneal pyeloplasty averaged 124 (range 37 to 368) minutes with a 6.3% complication rate and an overall success rate of 94.4% (intrinsic 100% vs extrinsic 93.8%). In the late group the LAP success rate was 98.3% with no significant differences related to the cause of ureteropelvic junction obstruction (intrinsic 100% vs extrinsic 98.1%) or the type of pyeloplasty (YV plasty 97.0% vs Anderson-Hynes 97.7%). CONCLUSIONS: Laparoscopic retroperitoneal pyeloplasty yields an efficacy similar to that of open surgery. The inferior success of laser endopyelotomy even in optimally selected cases and the increasing expertise with endoscopic suturing may favor laparoscopic pyeloplasty with or without robotic assistance in the future.

A new postoperative predictor of time to urinary continence after laparoscopic radical prostatectomy: the urine loss ratio.

OBJECTIVES: To assess the correlation of a newly defined parameter, "urine loss ratio" (ULR), with the time to continence and probability for incontinence after laparoscopic radical prostatectomy (LRP). MATERIALS AND METHODS: A standardized "micturition protocol" that uses 24-h pad testing to objectively quantify urine loss after removal of the catheter was obtained from 939 patients who underwent LRP and were provided complete follow-up regarding continence. ULR was defined as the weight of urine loss in the pad divided by daily micturition volume, distinguishing between ULR on the first day after catheter removal and the last day of hospital stay. The time to continence was classified as early (0-3 mo), midterm (4-12 mo), and late continence (13-24 mo). RESULTS: Early continence was attained in 69.8% (n=655) of patients, midterm continence in 18.4% (n=173), and late continence in 3.5% (n=33). Of 939 patients in whom first-day ULR was quantified, 495 patients were not discharged immediately and their last-day ULR was quantified (2.3 d following catheter removal). There was a linear correlation between time to continence and ULR, which was more significant for last- than first-day ULR (p<0.001). A cutoff point of more than 15% of urine loss indicates a high risk of incontinence (ie, 8-fold for first-day ULR, 55-fold for last-day ULR). CONCLUSION: ULR predicts the time to continence and may be used to select patients for specific rehabilitation programs and early adjuvant medical therapy, particularly when urine loss exceeds 15%.

Ureteral reimplantation for management of ureteral strictures: a retrospective comparison of laparoscopic and open techniques.

OBJECTIVES: To compare the results of laparoscopic ureteral reimplantation with a previous series of open surgery. MATERIALS AND METHODS: We compared ten patients who underwent laparoscopic vesicopsoas-hitch with (n=4) or without Boari-flap (n=6) technique for ureteral obstructions with ten patients treated by open ureteroneocystostomy for similar pathologies. Patient demographics, preoperative symptoms, radiologic imaging, and postoperative outcomes were analyzed. Postoperative observation time averaged 17 mo (range: 9-23) in the laparoscopic and 65 mo (range: 18-108) in the open group. Success was defined as relief of obstruction in postoperative imaging studies and relief of pain. RESULTS: Mean length of stricture (28.5 vs. 25 mm) was comparable in both groups. In laparoscopy versus open surgery, mean operative time (228 vs. 187 min) was longer, blood loss (370 vs. 610 ml) and analgesic requirement (4.9 vs. 21.5mg) were significantly lower, and mean time to oral intake (1.5 vs. 2.9 d), hospital stay (9.2 vs. 19.1 d), and convalescence time (2.3 vs. 4.2 wk) were significantly shorter. Success rates yielded 10 of 10 after laparoscopy and 8 of 10 after open surgery. No intra- or postoperative major complications occurred in the laparoscopic series. After open surgery, two patients had major postoperative complications, including urinary extravasation with abdominal haematoma and anastomostic stricture, respectively. CONCLUSIONS: Laparoscopic ureteroneocystostomy is feasible, providing functional outcomes comparable to open surgery while offering the advantages of a minimal invasive technique (e.g., less postoperative analgesics, and shorter hospitalization and convalescence). Nevertheless, it requires a high level of laparoscopic expertise and should be carried out only in specialist centers.

Assessing the predictive validity and efficacy of a multimodal training programme for laparoscopic radical prostatectomy (LRP).

OBJECTIVES: To assess the predictive validity (ability to correlate to real-life environment) and efficacy of a training programme for laparoscopic radical prostatectomy (LRP), based on a structured and progressive pelvitrainer component with hands-on clinical training in the operating room (OR). METHODS: Prospective data on 500 LRP cases were analysed with 80 excluded due to incomplete records. The operation was divided into multiple steps. Times for these steps were compared among 11 surgeons with different laparoscopic expertise (first-, second-, and third-generation surgeons in order of decreasing experience) and correlated to times for specific exercises on the pelvitrainer that simulated particular steps. Perioperative parameters were also evaluated among the three groups. RESULTS: Pelvitrainer times achieved by trainees (third-generation surgeons) did not differ significantly with times for corresponding steps of LRP. There was also no significant difference for total OR time between the second- and third-generation surgeons (205 and 207 min, respectively; p>0.05) although the time for the first-generation surgeons was faster than both (176 min). Short-term quality indicators for first, second, and third generations included transfusion rates (2.3%, 2.4%, and 2.6%, respectively), positive margin rates (20.3%, 21.5%, and 23.0%) and complications, which did not differ significantly among the generations although the first-generation surgeons had the lowest rates. CONCLUSIONS: A carefully designed training programme that incorporates both pelvitrainer and mentor-based operative training is essential for the effective and safe transfer of skills and knowledge required to learn LRP.

VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression.

Growth of new blood vessels (angiogenesis), required for all tumor growth, is stimulated by the expression of vascular endothelial growth factor (VEGF). VEGF is up-regulated in all known solid tumors but also in atherosclerosis, diabetic retinopathy, arthritis, and many other conditions. Conventional VEGF isoforms have been universally described as proangiogenic cytokines. Here, we show that an endogenous splice variant, VEGF(165)b, is expressed as protein in normal cells and tissues and is circulating in human plasma. We also present evidence for a sister family of presumably inhibitory splice variants. Moreover, these isoforms are down-regulated in prostate cancer. We also show that VEGF(165)b binds VEGF receptor 2 with the same affinity as VEGF(165) but does not activate it or stimulate downstream signaling pathways. Moreover, it prevents VEGF(165)-mediated VEGF receptor 2 phosphorylation and signaling in cultured cells. Furthermore, we show, with two different in vivo angiogenesis models, that VEGF(165)b is not angiogenic and that it inhibits VEGF(165)-mediated angiogenesis in rabbit cornea and rat mesentery. Finally, we show that VEGF(165)b expressing tumors grow significantly more slowly than VEGF(165)-expressing tumors, indicating that a switch in splicing from VEGF(165) to VEGF(165)b can inhibit tumor growth. These results suggest that regulation of VEGF splicing may be a critical switch from an antiangiogenic to a proangiogenic phenotype.

VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma.

Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is the most potent growth factor of tumor neovasculature, has been shown to be up-regulated in every tumor studied thus far, and is correlated with tumor stage and progression. To determine whether specific VEGF splice variants were differentially expressed in renal cell carcinomas, 18 polar tumor samples were analyzed by reverse transcription-PCR using primers designed to differentiate between VEGF splice variants. Control tissue was derived from the opposite normal pole. An amplicon of length consistent with the previously described variant VEGF(148) was found in normal kidney tissue. Subsequent sequencing revealed a new VEGF isoform formed by differential splicing from the end of exon 7 into the 3' untranslated region of the mRNA. Cloning of this transcript showed that translation would result in a 165-amino acid peptide with an alternative terminal 6 amino acids, followed by a stop codon. We have termed this new isoform VEGF165b. This isoform was present in 17 of 18 normal kidney samples but only 4 of 18 cases from matched malignant tissue. VEGF165b was therefore expressed in a significantly higher proportion of normal tissue than malignant tissue from the same patients (P < 0.001). To determine the functional significance of this new isoform, we expressed the full-length protein in a heterologous expression system. Conditioned medium containing this isoform significantly and dose dependently inhibited VEGF165-mediated proliferation, migration of endothelial cells, and vasodilatation of mesenteric arteries. This novel isoform VEGF165b is therefore an endogenous inhibitory form of VEGF that is down-regulated in renal tumors and, therefore, may be anti-angiogenesis.