A. Ami Sidi

Combined Thermo-Chemotherapy for Recurrent Bladder Cancer After Bacillus Calmette-Guerin

PURPOSE Despite an initial adequate response many patients with nonmuscle invasive urothelial cell carcinoma of the bladder eventually have recurrence after intravesical bacillus Calmette-Guerin treatments. We evaluated the efficacy of combined bladder wall hyperthermia and intravesical mitomycin C instillation (thermo-chemotherapy) in cases of recurrence after bacillus Calmette-Guerin. MATERIALS AND METHODS A total of 111 patients with recurrent papillary nonmuscle invasive urothelial cell carcinoma of the bladder after previous bacillus Calmette-Guerin treatment underwent complete bladder tumor resection and were referred for prophylactic adjuvant treatment with thermo-chemotherapy. Treatment was received on an outpatient basis weekly for 6 weeks, followed by 6 maintenance sessions at 4 to 6-week intervals. Each treatment included 2, 30-minute cycles of 20 mg mitomycin C and bladder wall hyperthermia to 42C +/- 2C. Cystoscopy and urine cytology were performed after the completion of induction treatment and every 3 months thereafter. RESULTS The Kaplan-Meier estimated disease-free survival rate was 85% and 56% after 1 and 2 years, respectively. No maintenance treatment was associated with decreased efficacy, that is the recurrence rate was 61% at 2 years vs 39% in those with maintenance treatments (p = 0.01). The progression rate was 3%. CONCLUSIONS Thermo-chemotherapy may be effective for papillary nonmuscle invasive urothelial cell carcinoma of the bladder that recurs after BCG treatment without increasing the risk of tumor progression. Maintenance therapy is important and improves the outcome.

Detecting DNA methylation of the BCL2, CDKN2A and NID2 genes in urine using a nested methylation specific polymerase chain reaction assay to predict bladder cancer.

PURPOSE Detection of methylated DNA has been shown to be a good biomarker for bladder cancer. Bladder cancer has the highest recurrence rate of any cancer and, as such, patients are regularly monitored using invasive diagnostic techniques. As urine is easily attainable, bladder cancer is an optimal cancer to detect using DNA methylation. DNA methylation is highly specific in cancer detection. However, it is difficult to detect because of the limited amount of DNA present in the urine of patients with bladder cancer. Therefore, an improved, sensitive and noninvasive diagnostic test is needed. MATERIALS AND METHODS We developed a highly specific and sensitive nested methylation specific polymerase chain reaction assay to detect the presence of bladder cancer in small volumes of patient urine. The genes assayed for DNA methylation are BCL2, CDKN2A and NID2. The regions surrounding the DNA methylation sites were amplified in a methylation independent first round polymerase chain reaction and the amplification product from the first polymerase chain reaction was used in a real-time methylation specific polymerase chain reaction. Urine samples were collected from patients receiving treatment at Wolfson Medical Center in Holon, Israel. RESULTS In a pilot clinical study using patient urine samples we were able to differentiate bladder cancer from other urogenital malignancies and nonmalignant conditions with a sensitivity of 80.9% and a specificity of 86.4%. CONCLUSIONS We developed a novel methylation specific polymerase chain reaction assay for the detection and monitoring of bladder cancer using DNA extracted from patient urine. The assay may also be combined with other diagnostic tests to improve accuracy.

Gene expression in the bladder carcinoma rat model

We investigated gene expression in N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN)‐induced rat bladder carcinoma in order to test its applicability as a model for the study of novel therapeutic modalities, particularly gene therapy. We administered BBN in the drinking water to Wistar rats for up to 30 wk and induced papillary transitional cell carcinoma (TCC), which is similar to the most prevalent type of human bladder cancer. Tumor evolution was similar to that found in previous studies. However, we described the morphological stages according to modern human bladder carcinoma terminology. Our main goal was to examine the expression levels of the H19 gene, of the insulin‐like growth factor 2 (Igf2) transcripts expressed from promoters P2 and P3 and of the telomerase subunits that we had previously investigated as tools for targeted gene therapy of bladder cancer. We detected at 30 wk of BBN exposure significant upregulation of these sequences in the rat bladder tumors, similar to our previous findings in human bladder cancer. To reinforce the similarity of this model to the corresponding human disease, we searched for additional tumor‐specific genes documented as having altered expression in human bladder carcinoma, using cDNA expression arrays (Clontech™). We suggest that BBN‐induced rat bladder cancer has morphological, biological, and molecular parallels to human bladder cancer and is an attractive model for studying novel alternatives of therapeutic intervention.

Transobturator Tape Procedure With and Without Concomitant Vaginal Surgery

PURPOSE We evaluated results and complications of the transobturator tape procedure for female stress urinary incontinence and assessed the effect of concomitant vaginal surgery on the outcome. MATERIALS AND METHODS We prospectively studied consecutive women who underwent the transobturator tape procedure without (group 1) or with (group 2) concomitant vaginal surgery at our institution from 2003 to 2006. Followup was at least 12 months. Preoperative evaluations included medical history, Urogenital Distress Inventory-6, physical examination, urinalysis and culture, and urodynamics. The procedure was performed as an out-in technique. Therapeutic success was defined as complete continence not requiring pad protection. All other outcomes were classified as failures. RESULTS A total of 96 patients with a mean age of 63 years (range 37 to 89) who fulfilled study entry criteria comprised the study cohort. Group 1 included 35 patients and group 2 included 61 with 1 or more concomitant vaginal surgeries, including hysterectomy in 28, anterior colporrhaphy in 61, posterior colporrhaphy in 11, and excision of a vaginal granuloma with suture thread and excision of the eroded part of the tape in 1 each. There were no intraoperative complications. One patient per group had transient leg pain. Seven group 2 patients had voiding dysfunction, of whom 3 underwent tape release for a presumed obstructed urethra. Postoperatively 29 women (82.86%) in group 1 and 52 (85.2%) in group 2 were continent throughout the 36.1-month followup (range 12 to 54). CONCLUSIONS Transobturator tape is safe and effective for stress urinary incontinence. Voiding dysfunction is more prevalent after concomitant vaginal surgery but that surgery does not affect the transobturator tape continence outcome.

Concomitant Laparoscopic Renal Surgery and Cholecystectomy: Outcomes and Technical Considerations

INTRODUCTION We report our experience with simultaneous laparoscopic treatment of coexisting kidney and gallbladder pathologies, assess the feasibility of this technique, and highlight some technical considerations. METHODS Our institutional database was searched for the records of simultaneous laparoscopic kidney surgery and laparoscopic cholecystectomy between 2002 and 2008. We retrieved data on patient demographics, preoperative work-up, surgical information, and postoperative outcome in terms of final pathology, complications, and hospital stay. RESULTS A total of 19 patients had undergone laparoscopic renal surgery combined with cholecystectomy. Renal surgery consisted of a laparoscopic partial nephrectomy in 5 patients (26.3%), a laparoscopic radical nephrectomy in 12 (63.2%), and a simple nephrectomy in 2 (10.5%). Laparoscopic cholecystectomy was performed as a second surgery in all 19 patients. Two patients simultaneously underwent a third procedure: one was a bilateral salpingo-oophorectomy, and the other was a postoperative ventral hernia repair with mesh. The average renal surgery time was 144 minutes, and the average cholecystectomy time was 28.0 minutes. All procedures were successfully completed laparoscopically with no conversions. The mean hospital stay was 4.2 days (median 4, range 2-8). CONCLUSIONS Combining laparoscopic renal surgery and laparoscopic cholecystectomy is a feasible, efficacious, and safe strategy that requires close collaboration between urologists and general surgeons. This approach offers the patient the benefits of minimally invasive surgery together with the obvious advantages of simultaneous treatment of coexisting pathologies.

Laparoscopic partial nephrectomy for multiple tumours: feasibility and analysis of peri-operative outcomes.

Study Type – Therapy (case series)

Laparoendoscopic Single-site Repair of Incisional Hernias After Urological Surgery

OBJECTIVE To report the first series of postoperative ventral hernias (POVH) repair with laparoendoscopic single-site (LESS) approach after urological procedures. POVH are well-known complications of urological surgery and often require surgical correction. Minimally invasive repair techniques have been developed to diminish parietal trauma and enhance functional results. METHODS This study was based on a retrospective review of patients undergoing POVH repair after urological surgery at an academic institution from 2004 to 2010. Patient characteristics, perioperative details, as well as follow-up were reviewed and summarized. Using a transperitoneal approach, abdominal wall defect was identified, prepared, and closed with a mesh tailored to cover 3-5 cm beyond the edge of the defect and secured in a double-crown fashion. RESULTS In 3 patients POVH was represented by a port-site hernia after laparoscopic partial nephrectomy; in the remaining 2 patients POVH occurred at midline following radical cystectomy. Hernia occurrence was identified within 2 months from the initial surgery in all but 1 patient. Blood loss was minimal, operative times were 30-150 minutes, and no intraoperative complications occurred. Three patients developed a transient seroma and 1 patient had ileus. Over a 1- to 20-month follow-up, there have been no wound or mesh complications, and no hernia recurrences were identified. CONCLUSION In this initial series, POVH after urological surgery were successfully treated with LESS approach. In experienced hands, LESS may provide a viable alternative to conventional laparoscopy for POVH repair. More studies are needed to confirm these initial results and to determine whether reduced parietal trauma favors LESS in POVH repair.

Transient Neurological Symptoms After Isobaric Subarachnoid Anesthesia with 2% Lidocaine: The Impact of Needle Type

BACKGROUND:The reported incidence of transient neurological symptoms (TNS) after subarachnoid lidocaine administration is as high as 40%. We designed this clinical trial to determine the incidence of TNS with two different pencil-point spinal needles: one-orifice (Atraucan) and two-orifice (Eldor) spinal needles. METHODS:Ninety-nine ASA physical status I or II patients undergoing surgical procedures of the urinary bladder or prostate were prospectively allocated to receive spinal anesthesia with 40 mg, 2% isobaric lidocaine plus fentanyl injected through either a 26-gauge Atraucan (n = 52) or a 26-gauge Eldor (n = 47) spinal needle. During the first three postoperative days, patients were observed for postoperative complications, including TNS. The primary end-point for this trial was the percentage of TNS in both double- and single-orifice spinal needle procedures. RESULTS:The incidence of TNS was higher when spinal anesthesia was done through the Atraucan needle (28.8% vs 8.5%, P = 0.006). Fifty percent of the patients in the double-orifice group versus 100% of the single-orifice group developed TNS after surgery in the lithotomy position (P = 0.014). The relative risk for developing TNS with the Eldor needle was 0.29 (95% CI: 0.07–0.75) compared with the Atraucan needle. CONCLUSIONS:The use of a double-orifice spinal needle was associated with a lower incidence of TNS, which may have been due to the needle design.

Routine Diagnostic Ureteroscopy for Suspected Upper Tract Transitional-Cell Carcinoma

BACKGROUND AND PURPOSE Upper tract transitional-cell carcinoma (utTCC) is uncommon. Standard evaluation includes imaging, cytology, and cystoscopy and gold standard treatment is nephroureterectomy (NU) with solid oncologic outcomes and elevated morbidity. In this study, we report on the value of including routine ureteroscopy (URS) for evaluating suspected utTCC in shifting the treatment toward less morbid options and increasing preoperative diagnostic accuracy. PATIENTS AND METHODS Records of patients presenting between 2002 and 2013 with suspected utTCC were reviewed. Since 2010, URS has been included routinely in the evaluation protocol. Demographic, clinical, and pathologic characteristics were recorded and compared between earlier experience (group 1) and with routine URS (group 2). In addition, the number needed to treat (NNT) was calculated with respect to shifting the procedure choice from NU to other options as well as in reducing the rates of misdiagnoses. RESULTS A total of 118 patients were included: 63 in group 1 and 55 in group 2. The pathology-confirmed TCC rates were comparable between the two groups (78 vs 85%). The rates of NU decreased with routine URS use from 89% to 69% (P=0.011, NNT=5.05) whereby patients were treated endoscopically or with distal ureterectomy. Misdiagnoses decreased from 15.5% to 2.1% with routine URS (P=0.021, NNT=7.44). Sepsis occurred in two patients after URS. CONCLUSIONS In this initial study, routine URS evaluation for suspected utTCC appears to enable an increased use of other treatment choices rather then NU, with an estimated five URS avoiding one NU. Moreover, routine URS reduced the rates of misdiagnosis of TCC. Complications associated with URS may add an additional morbidity burden, however.

Laparoscopic partial nephrectomy: beyond the straightforward T1a

Study Type – Therapy (case series)