Jason R. Gee

Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson Cancer Center experience with 100 consecutive patients.

Micropapillary bladder carcinoma is a rare variant of urothelial carcinoma. To improve understanding of this disease, the authors performed a retrospective review of their experience.

The Case for Early Cystectomy in the Treatment of Nonmuscle Invasive Micropapillary Bladder Carcinoma

PURPOSE Micropapillary bladder carcinoma is a rare variant of UC. Due to paucity of data regarding treatment outcomes, patients with nonmuscle invasive micropapillary UC often receive intravesical therapy in an attempt at bladder preservation. MATERIALS AND METHODS We reviewed the records of all patients evaluated at our institution who had micropapillary UC of the bladder. Of these, 44 had nonmuscle invasive disease at presentation and form the basis of this report. RESULTS Mean patient age was 64.3 years (range 45 to 81) with a male-to-female ratio of 13:1. Stage distribution at presentation was 5 Ta (11%), 4 CIS (9%) and 35 T1 (80%). Median CSS was 81 months. Kaplan-Meier estimates of 5 and 10-year CSS rates were 64% and 26%, respectively. Intravesical BCG therapy was attempted in 27 patients (61%). Of these 27 patients, 67% (18 of 27) had progression (cT2 or greater), including 22% in whom metastatic disease developed. Only 19% of patients (5 of 27, all T1) remain disease-free with an intact bladder at a median followup of 30 months. A total of 30 patients (68%) underwent cystectomy. Among patients who underwent cystectomy after progression (18), median CSS was 61.7 months with no patient surviving 10 years, whereas among those undergoing cystectomy as initial therapy (12), median survival was not reached and the 10-year CSS rate was 72%. CONCLUSIONS Intravesical BCG therapy appears to be ineffective against micropapillary UC. Our results suggest that the optimal treatment strategy for nonmuscle invasive micropapillary UC is radical cystectomy performed before progression.

Long-term outcome of hematuria home screening for bladder cancer in men

The objectives of this study were to determine whether bladder cancer (BC) screening in healthy men could lead to earlier detection and reduced BC mortality compared with unscreened men and to determine long‐term outcomes of a geographically defined, unscreened population with newly diagnosed BC.

ICUD-EAU international consultation on bladder cancer 2012: Screening, diagnosis, and molecular markers

CONTEXT AND OBJECTIVE To present a summary of the 2nd International Consultation on Bladder Cancer recommendations on the screening, diagnosis, and markers of bladder cancer using an evidence-based strategy. EVIDENCE ACQUISITION A detailed Medline analysis was performed for original articles addressing bladder cancer with regard to screening, diagnosis, markers, and pathology. Proceedings from the last 5 yr of major conferences were also searched. EVIDENCE SYNTHESIS The major findings are presented in an evidence-based fashion. Large retrospective and prospective data were analyzed. CONCLUSIONS Cystoscopy alone is the most cost-effective method to detect recurrence of bladder cancer. White-light cystoscopy is the gold standard for evaluation of the lower urinary tract; however, technology like fluorescence-aided cystoscopy and narrow-band imaging can aid in improving evaluations. Urine cytology is useful for the diagnosis of high-grade tumor recurrence. Molecular medicine holds the promise that clinical outcomes will be improved by directing therapy toward the mechanisms and targets associated with the growth of an individual patients tumor. The challenge remains to optimize measurement of these targets, evaluate the impact of such targets for therapeutic drug development, and translate molecular markers into the improved clinical management of bladder cancer patients. Physicians and researchers eventually will have a robust set of molecular markers to guide prevention, diagnosis, and treatment decisions for bladder cancer.

Meta-analysis of the complications of laparoscopic renal surgery : Comparison of procedures and techniques

PURPOSE We performed a meta-analysis of the literature to define the current expectations of complications during laparoscopic renal surgery. MATERIALS AND METHODS References were searched in the MEDLINE database from 1995 to 2004 using the terms complications and laparoscopic nephrectomy. Inclusion criteria were any series with greater than 20 cases, patient age older than 16 years and any complications listed for certain procedures, including laparoscopic radical nephrectomy, HA laparoscopic radical nephrectomy, LPN, HALPN, laparoscopic donor nephrectomy, HA laparoscopic donor nephrectomy, laparoscopic simple nephrectomy, laparoscopic nephroureterectomy and retroperitoneal laparoscopic nephrectomy. A data extraction form was created to categorize major or minor complications. A 5 member panel adhered to the strict criteria and extracted data from articles that met inclusion criteria. Data were entered into a spreadsheet and a meta-analysis was performed. RESULTS Initial review identified 73 of 405 references that were acceptable for retrieval and data extraction, of which 56 met inclusion criteria. The overall major and minor complication rates of laparoscopic renal surgery were 9.5% and 1.9%, respectively. There was a significant difference between the major complication rates of LPN and HALPN (21.0% vs 3.3%, p <0.05). CONCLUSIONS Our results show that patients who undergo laparoscopic renal surgery may have an overall major complication rate of 9.5%. The highest major complication rate is associated with technically challenging LPN (21%). There appears to be a significantly higher wound complication rate associated with HA surgery in comparison to that of standard laparoscopy (1.9% vs 0.2%, p <0.05).

Cytokeratin 20, AN43, PGDH, and COX-2 expression in transitional and squamous cell carcinoma of the bladder

Bladder tumors from Egyptian patients with a high prevalence of bilharziasis were immunohistochemically analyzed for the expression of cytokeratin 20 (CK20), AN43, prostaglandin dehydrogenase (PGDH), and cyclooxygenase-2 (COX-2). The tumors included 26 transitional cell carcinomas (TCC), 10 squamous cell carcinomas (SCC) and 2 tumors of mixed TCC/SCC histology. Of the 28 TCC tumors, 21 (75%) expressed CK20 and 25 (89%) expressed AN43. CK20 was not expressed in any of the 10 SCC tumors and AN43 was expressed in 2 of them. PGDH was expressed in 18 (64%) of the 28 tumors with TCC histology and 1 of the 10 SCC. A subset of 21 tumors (16 TCC and 5 SCC) was tested for COX-2 expression. COX-2 was detected in 69% of the 16 TCC tumors examined but was not seen in the SCC tumors. As tumors increased in stage, the expression of these proteins changed. CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage.

Chemoprevention of superficial bladder cancer

Patients who have bladder cancer with superficial disease are at high risk for recurrence but low risk for progression to muscle invasive disease and are regularly monitored with cystoscopy to detect recurrent tumors. This clinical setting (high recurrence rate, excellent surveillance, and low risk of progression in stage) provides an ideal setting for secondary chemoprevention. Vitamins, difluoromethylornithine, and cyclooxygenase inhibitors have demonstrated activity in preclinical models of bladder cancer. Limited clinical data suggests that vitamins and their analogs may be useful for decreasing the rate of tumor recurrence in patients with superficial bladder cancer. Ongoing clinical trials are exploring the roles of fenretinide, difluoromethylornithine, and celecoxib in the treatment of patients with a history of superficial bladder cancer.

Reduced bladder cancer recurrence rate with cardioprotective aspirin after intravesical bacille Calmette‐Guérin

To evaluate the recurrence‐free survival (RFS) rate of patients taking cardioprotective aspirin after intravesical bacille Calmette‐Guérin (BCG) for high‐grade noninvasive urothelial carcinoma of the bladder, as preventing the recurrence of superficial bladder cancer might decrease patient morbidity and mortality from this disease, and nonsteroidal anti‐inflammatory agents (NSAIDs) have shown promise in preclinical prevention through inhibition of the prostaglandin pathway and other mechanisms.

A Bayesian adaptive design with biomarkers for targeted therapies.

Background Targeted therapies are becoming increasingly important for the treatment of various diseases. Biomarkers are a critical component of a targeted therapy as they can be used to identify patients who are more likely to benefit from a treatment. Targeted therapies, however, have created major challenges in the design, conduct, and analysis of clinical trials. In traditional clinical trials, treatment effects for various biomarkers are typically evaluated in an exploratory fashion and only limited information about the predictive values of biomarkers obtained. Purpose New study designs are required, which effectively evaluate both the diagnostic and the therapeutic implication of biomarkers. Methods The Bayesian approach provides a useful framework for optimizing the clinical trial design by directly integrating information about biomarkers and clinical outcomes as they become available. We propose a Bayesian covariate-adjusted response-adaptive randomization design, which utilizes individual biomarker profiles and patient’s clinical outcomes as they become available during the course of the trial, to assign the most efficacious treatment to individual patients. Predictive biomarker subgroups are determined adaptively using a partial least squares regression approach. Results A series of simulation studies were conducted to examine the operating characteristics of the proposed study design. The simulation studies show that the proposed design efficiently identifies patients who benefit most from a targeted therapy and that there are substantial savings in the sample size requirements when compared to alternative designs. Limitations The design does not control for the type I error in the traditional sense and a positive result should be confirmed by conducting an independent phase III study focusing on the selected biomarker profile groups. Conclusions We conclude that the proposed design may serve a useful role in the early efficacy phase of targeted therapy development. Clinical Trials 2010; 7: 546—556. http://ctj.sagepub.com

Phase II open label, multi-center clinical trial of modulation of intermediate endpoint biomarkers by 1α-hydroxyvitamin D2 in patients with clinically localized prostate cancer and high grade pin

Prostate cancer is the most common malignancy and second leading cause of cancer related deaths in American men supporting the study of prostate cancer chemoprevention. Major risk factors for this disease have been associated with low serum levels of vitamin D. Here, we evaluate the biologic activity of a less calcemic vitamin D analog 1α‐hydroxyvitamin D2 [1α‐OH‐D2] (Bone Care International, Inc.) in patients with prostate cancer and high grade prostatic intraepithelial neoplasia (HG PIN).