Claude C. Abbou

Laparoscopic partial nephrectomy. The European experience.

Laparoscopic partial nephrectomy is technically difficult but oncologically effective. The operation should be performed in centers with expertise. Hemostasis can be achieved using bipolar coagulation and fibrin glue-coated cellulose. Further studies will determine whether less invasive alternatives (focused ultrasound, cryotherapy) will meet the high standard of open (or laparoscopic) nephron-sparing surgery for small renal cell carcinoma.

Regional copy number–independent deregulation of transcription in cancer

Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.

Comparison of predictive accuracy of four prognostic models for nonmetastatic renal cell carcinoma after nephrectomy: a multicenter European study.

The objective of the current study was to compare, in a large multicenter study, the discriminating accuracy of four prognostic models developed to predict the survival of patients undergoing nephrectomy for nonmetastatic renal cell carcinoma (RCC).

The prognostic value of p53 nuclear overexpression and MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder.

There is controversy regarding the value of biologic markers as prognostic indicators independent of clinicopathologic parameters in transitional cell carcinoma (TCC) of the bladder. The authors examined the prognostic value of p53 tumor suppressor gene expression and the proliferative marker MIB‐1 in TCC of the bladder.

Increased Immunodetection of Acidic Fibroblast Growth Factor in Bladder Cancer, Detectable in Urine

Acidic fibroblast growth factor is a regulatory peptide involved in cell proliferation, differentiation and motility. We used a polyclonal antiserum raised against purified native bovine acidic fibroblast growth factor, with no cross-reactivity for basic fibroblast growth factor to detect acidic fibroblast growth factor in tissue extracts and urine samples by means of a competitive enzyme immunoassay. Histochemical analysis was also performed on 10 specimens of normal urothelium and 50 of bladder cancer. Acidic fibroblast growth factor immunoreactive material was found in normal urothelium (1.77 +/- 2 ng./gm. tissue) and was increased more than 10-fold in patients with transitional cell carcinoma of the bladder (20.36 +/- 12 ng./gm. tissue). Immunohistochemical analysis localized immunoreactivity in the epithelial compartment of bladder tumors. Acidic fibroblast growth factor was assayed in urine from 579 individuals comprising a control group (114) and patients with benign prostatic hypertrophy (133), carcinoma of the prostate (96) or transitional cell carcinoma of the bladder (236). There was a significant difference in the frequency of urinary acidic fibroblast growth factor detection among the patients with invasive transitional cell carcinoma, the control group (p < 0.001) and the patients with prostatic disease (p < 0.01). The sensitivity was 72% and the specificity was 91%. Furthermore, the frequency of acidic fibroblast growth factor detection by enzyme immunoassay in the urine and the intensity of immunostaining was correlated with the stage of the disease. These data strongly suggest that acidic fibroblast growth factor is a potential marker for bladder tumors that may be of use in the noninvasive followup of patients with bladder cancer. We present a simple and reliable enzyme immunoassay for the detection of acidic fibroblast growth factor in voided urine that might be useful to quantitate this marker.

Laparoscopic Radical Nephroureterectomy: Results of an International Multicenter Study

OBJECTIVE To report a multicenter analysis after laparoscopic radical nephroureterectomy for pathologically confirmed upper tract transitional cell carcinoma. MATERIALS AND METHODS A total of 116 patients (72 males; mean age 68 years) underwent laparoscopic radical nephroureterectomy at five international institutions: 51 transperitoneally, 65 retroperitoneally. Location of the primary tumor was pelvicalyceal in 70 patients (60%), ureteral in 27 (23%), and multifocal in 19 (17%). In 18 patients (15%), transurethral resection was performed for concomitant bladder tumor. The median follow-up time was 25 months (range 3-93). A minimum follow-up of 1 and 2 years was available in 77 and 41 patients, respectively. RESULTS Five patients (4%) were converted to open surgery. The specimen was extracted intact in all 116 patients: using an Endocatch bag in 78 patients, a Lapsac in 5, and manually in 33. Pathologic staging was pTis in 5 (4%), pTa in 41 patients (35%), pT1 in 31 (26%), pT2 in 18 (15%), pT3 in 16 (13%), and pT4 in 5 (4%). Pathological grade was grade I in 26 patients (23%), grade II in 41 (35%), grade III in 34 (29%) and grade IV in 15 (12%). Histopathology revealed a positive surgical margin in five patients (4.5%): renal hilum (one), periureteral soft tissue (two), distal edge of the ureter/ bladder cuff (two). Local recurrence was noted in two patients (1.7%). Bladder recurrence was noted in 28 patients (24%) with a mean time to recurrence of 13.9+/-11.5 months. Distant metastases occurred in 11 patients (9%): lung (5), liver (3), bones (2), adrenal (1); mean time to metastasis was 13 months. Overall, 23 patients (20%) died. One-year and 2-year cancer-specific survival was 92% and 87%, respectively. Two-year cancer-specific survival according to pathologic stage was 89% for patients with pT1 disease, 86% for pT2, 77% for pT3, and 0% for pT4 (p=0.0001). Two-year survival according to pathologic grade was 88% for grade I, 90% for grade II, 80% for grade III, and 90% for grade IV (p>0.05). CONCLUSION Laparoscopic radical nephroureterectomy appears to be an effective minimally invasive treatment for select patients with upper tract transitional cell carcinoma. Although the 2-year survival data reported herein are encouraging, longer follow-up is needed before laparoscopy can be considered as a standard treatment.

The Learning Curve for Laparoscopic Radical Prostatectomy: An International Multicenter Study

PURPOSE It is not yet possible to estimate the number of cases required for a beginner to become expert in laparoscopic radical prostatectomy. We estimated the learning curve of laparoscopic radical prostatectomy for positive surgical margins compared to a published learning curve for open radical prostatectomy. MATERIALS AND METHODS We reviewed records from 8,544 consecutive patients with prostate cancer treated laparoscopically by 51 surgeons at 14 academic institutions in Europe and the United States. The probability of a positive surgical margin was calculated as a function of surgeon experience with adjustment for pathological stage, Gleason score and prostate specific antigen. A second model incorporated prior experience with open radical prostatectomy and surgeon generation. RESULTS Positive surgical margins occurred in 1,862 patients (22%). There was an apparent improvement in surgical margin rates up to a plateau at 200 to 250 surgeries. Changes in margin rates once this plateau was reached were relatively minimal relative to the CIs. The absolute risk difference for 10 vs 250 prior surgeries was 4.8% (95% CI 1.5, 8.5). Neither surgeon generation nor prior open radical prostatectomy experience was statistically significant when added to the model. The rate of decrease in positive surgical margins was more rapid in the open vs laparoscopic learning curve. CONCLUSIONS The learning curve for surgical margins after laparoscopic radical prostatectomy plateaus at approximately 200 to 250 cases. Prior open experience and surgeon generation do not improve the margin rate, suggesting that the rate is primarily a function of specifically laparoscopic training and experience.

Open versus laparoscopic radical prostatectomy: Part II.

notably the nodes were withdrawn in a protective bag [7]. In the largest series of node dissection in node-positive patients there were no cases of peritoneal, parietal or trocar port seeding, even in hormone-resistant patients [8]. Although the follow-up is short, prostate cancer does not appear to implant readily on the peritoneum or trocar track. The laparoscopic extraperitoneal approach avoids this potential risk of intraperitoneal dissemination [9–12].

Do Prognostic Parameters of Remission versus Relapse after Bacillus Calmette–Guérin (BCG) Immunotherapy Exist?: Analysis of a Quarter Century of Literature

OBJECTIVE To review prognostic factors identified in clinical trials for remission versus relapse after intravesical adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy for superficial bladder cancer (Ta, T1, and carcinoma in situ). MATERIALS AND METHODS Information was retrieved by a MEDLINE search of the English literature. Indexing terms comprised bladder cancer, bladder neoplasm, BCG vaccine, superficial bladder cancer, immunotherapy, intravesical therapy, prognostic marker, and Bacillus Calmette-Guérin. Fifty clinical studies were assessed for the strength of their results on the therapeutic response to BCG instillation. Emphasis was placed on clinical trials that assessed tumor and/or host characteristics, immunological reactions, recurrence rates, progression rates and disease-specific survival after BCG. RESULTS The predictive value of host factors is extremely controversial, but marked adverse reactions to BCG instillation appear to be associated with a better tumor response. Traditional pathological tumor characteristics, molecular markers (p53) and immunological status (PPD skin test) do not appear to have prognostic value in this setting. There is increasing evidence that immunologic markers are predictive of the BCG response, but most of them have not yet been assessed in large prospective studies. Histologic/cytologic response criteria are the critical determinant of post-BCG outcome. CONCLUSIONS After a quarter century of clinical research, no independent prognostic factor for the bladder tumor response to BCG has yet been identified. Sophisticated individual therapeutic approaches (SITA) appear to be the most promising. Nomograms based on host, tumor and immunological characteristics may help with clinical decision-making and with rationalized BCG schedule design.

Decreased expression of keratinocyte growth factor receptor in a subset of human transitional cell bladder carcinomas

Growth factors and growth factor receptors are involved in tumor progression. The fibroblast growth factor receptor 2 gene encodes distinct isoforms. The isoforms which bind KGF (keratinocyte growth factor or FGF-7) are called KGF-R or FGFR2b. KGF-R is expressed in different epithelia and is involved in the control of epithelial-mesenchymal interactions. Expression of KGF-R mRNA was examined in normal human bladder and transitional cell carcinoma of the bladder (TCC) by semi-quantitative RT – PCR using TFIID and GAPDH as internal standards. In normal bladder, the KGF-R mRNA was detected in the urothelium but not in the underlying stroma. In TCCs, the level of KGF-R mRNA was generally either normal or low. Eighteen out of 54 TCCs had a KGF-R mRNA level below 30% of that found in normal urothelium. This decrease in KGF-R mRNA was not accompanied by an increase in BEK (FGFR2c) mRNA, the other major splice variant of the fibroblast growth factor receptor 2 gene. Expression of the KGF-R was also monitored by immunohistochemistry using a functional KGF-immunoglobulin chimera. The receptor was uniformly expressed throughout the normal urothelium except for the umbrella cells. Immunoreactivity for KGF-R was found to be negative in tumors with low levels of KGF-R mRNA, while the peritumoral normal urothelium was positive. Among patients with muscle invasive tumors, those exhibiting a low level of KGF-R mRNA had a significantly higher proportion of cancer deaths. Our results suggest that decreased expression of KGF-R can be considered as a marker of tumor progression in muscle invasive TCCs.