Efficacy of Mycobacterium Phlei Cell Wall-Nucleic Acid Complex (MCNA) in BCG-Unresponsive Patients.

Background: We have previously reported the results of a prospective multi-institutional study on the efficacy of MCNA in patients who recurred after intravesical BCG treatment [1]. Since that publication, a new standardized definition for BCG-unresponsiveness has been established [2]. Objective: We re-analyzed the oncologic outcomes following intravesical MCNA in patients classified as BCG-unresponsive according to the new definition. Methods: For this analysis, we focused on the enrolled patients who satisfied the requirements for BCG Unresponsiveness: i.e. adequate BCG treatment (at least 5/6 induction and 2/3 maintenance instillations) and high grade tumor within 6 months of prior BCG. Treatment course included 6 weekly intravesical instillations of 8 mg MCNA followed by 3 weekly instillations at months 3, 6, 12, 18, and 24. Followup assessments included cystoscopy, urine cytology and biopsy. Patients absent of high grade disease confirmed by central review of biopsy were deemed disease-free. Results: Of the 129 patients enrolled, 94 (68 CIS with/without papillary tumors, 26 papillary only tumors) fit the criteria for the new BCG Unresponsive definition. Overall, disease free survival (DFS) for all BCG unresponsive patients was 48.9% (95% CI 38.0-59.0%) at 6 months, 34.8% (95% CI 24.7-45%) at 1 year and 28.3% (15.7-34.3%) at 2 years post induction. In the group with papillary tumors, DFS measured at months 6, 12, and 24 were: 61.2% (38.2-77.8%), 61.2(38.2-77.8%), and 50.1% (27.5-69%). In the CIS-containing group, the corresponding DFS were: 44.8% (32.3-56.4%), 26.5% (16.3-37.9%), and 16.6% (8.6-26.9%), respectively. Conclusions: For patients who are BCG Unresponsive, MCNA has the potential to render 26.5% of patients with CIS and 61.2% of patients with papillary tumors disease-free for at least 1 year with an intact bladder. The higher efficacy noted in the true BCG-unresponsive cohort than was previously reported with all-comers emphasizes the importance of having clearly defined criteria for clinical trials investigating new intravesical therapies after BCG failure.

Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guérin.

PURPOSE: Patients with high risk recurrences after bacillus Calmette-Guérin failure have limited options. We performed an open label study to evaluate the efficacy and safety of intravesical MCNA in this setting. MATERIALS AND METHODS: Patients were treated intravesically with 8 mg MCNA weekly for 6 weeks followed by 3 weekly instillations at months 3, 6, 12, 18 and 24. Cystoscopy and cytology were performed every 3 months for 2 years with mandatory biopsy at 6 months and as clinically indicated thereafter. The primary efficacy end point was the disease-free survival rate at 1 year. RESULTS: A total of 129 patients were enrolled in study, including 91 with carcinoma in situ with or without papillary disease and 38 with papillary only tumors. Most patients had high risk disease. A total of 107 cases were bacillus Calmette-Guérin refractory and 2 or more prior bacillus Calmette-Guérin induction courses had been given in 68. Median followup in all patients was 34.7 months. The overall disease-free survival rate was 25.0% at 1 year and 19.0% at 2 years. In patients with papillary only tumors the disease-free survival rate was 35.1% and 32.2% at 1 and 2 years, respectively. The median disease-free duration in the 30 responders was 32.7 months. The progression-free survival rate was 87.3%, 79.8% and 77.7% at 1, 2 and 3 years, respectively, with a progression event in 28 patients. MCNA was well tolerated and few adverse events led to treatment discontinuation. CONCLUSIONS: Intravesical MCNA achieved significant activity in patients at high risk with nonmuscle invasive bladder cancer in whom bacillus Calmette-Guérin treatment failed, especially those with papillary only tumors and those with bacillus Calmette-Guérin relapse. A durable response was seen, particularly in patients with a response at 1 year. MCNA offers an option for patients who are not candidates for or who refuse cystectomy.

Five-year weight loss experience of outpatients receiving laparoscopic adjustable gastric band surgery.

BACKGROUND: This study evaluated the efficacy and safety of laparoscopic adjustable gastric banding (LAGB) in a large cohort of morbidly obese patients followed for up to 5 years. METHODS: Morbidly obese patients, ≥ 16 years of age, who underwent LAGB surgery at the Surgical Weight Loss Clinic in Ontario, Canada, between May 2005 and January 2011 were eligible for this retrospective chart review. Electronic files were searched to identify all patients who met the inclusion/exclusion criteria. Demographics, weights at baseline and follow-up visits (up to 60 months following surgery), and post-operative complications were documented. As follow-up visits occurred at unevenly spaced intervals within and across patients, modeling methods were used to more accurately assess mean % weight loss (WL) and % excess weight loss (EWL) over time. RESULTS: This study included 2,815 patients (82 % female, mean age 43 years, mean baseline BMI 44.6 kg/m(2)) followed for a mean of 21.8 ± 15.4 months. Complications developed in 238 patients (8.5 %), the most frequent being prolapse/slippage (4.2 %), tubing/access port problems (1.2 %), and explantation (1.2 %). Mean %WL and %EWL progressed continuously over the first 2.5 years post-LAGB, plateauing at 20 and 49 %, respectively, for up to 5 years of follow up. Factors associated with increased weight loss were time since surgery, greater baseline weight (excess weight), older age at time of surgery, and male gender. CONCLUSIONS: Weight loss was maintained for up to 5 years in our population of patients who underwent LAGB for the treatment of morbid obesity.

Cancer Care Ontario Guidelines for radical prostatectomy: striving for continuous quality improvement in community practice.

OBJECTIVE: : Cancer Care Ontario has published an evidence-based guideline on their website "Guideline for Optimization of Surgical and Pathological Quality Performance for Radical Prostatectomy in Prostate Cancer Management: Surgical and Pathological Guidelines." The evidentiary base for this guideline was recently published in CUAJ. The CCO guideline proposes the following: a positive surgical margin (PSM) rate of <25% for organ-confined disease (pT2), a perioperative mortality of <1%, a rate of rectal injury <1%, and a blood transfusion rate <10% in non-anemic patients. The objective of this study was to review the radical prostatectomy practice at the Grey Bruce Health Services, an Ontario community hospital, and to compare our performance in relation to the Cancer Care Ontario guideline and the literature. METHODS: : We conducted a retrospective review of all radical prostatectomies performed at the Grey Bruce Health Services from January 1, 2006 to December 31, 2007. The following data were obtained from clinical records and pathology reports: patient age, pre-biopsy prostate-specific antigen, biopsy Gleason score, resected prostate gland weight, radical prostatectomy Gleason score, surgical margin status, pathological tumour stage (pT), lymph node dissection status, perioperative incidence of transfusion of blood products and if the patient was anemic (hemoglobin <140 g/L) preoperatively, incidence of rectal injury, and perioperative mortality within 30 days following surgery. RESULTS: : Using the method proposed by D'Amico, most patients undergoing radical prostatectomy were intermediate risk (62%), with a minority of low-risk (24%) and high-risk (14%) patients. The overall PSM rate was 37%. The rate of PSMs in organ-confined disease (pT2) was 26%. There was a statistically significant trend between increasing D'Amico risk category and increasing rate of PSM (Cochran-Armitage trend test, p = 0.023). There was a strong correlation between the pathological tumour stage and the rate of PSM (Cochran-Armitage trend test, p = 0.0003). The rate of blood transfusion in non-anemic patients was 6%. There was 1 patient (0.8%) who experienced a rectal injury. There were no perioperative deaths in our study group. CONCLUSION: : Our results show that a community hospital group can appropriately select patients to undergo radical prostatectomy, as well as achieve an acceptable rate of PSMs. We believe that ongoing critical appraisal and reflective practice are essential to improving surgical outcomes and providing quality care.

Prostate gland biopsies and prostatectomies: an Ontario community hospital experience.

OBJECTIVE: Transrectal ultrasound-guided core biopsies of the prostate gland and prostatectomies have become common procedures at many community hospitals in Canada, especially in the era of serum prostate-specific antigen (PSA) screening for prostate cancer. The Gleason grading of prostate cancer in biopsies and prostatectomies is a major determinant used for treatment planning. There is evidence in the literature that suggests important discordance between community hospital pathologists and urological pathologists with respect to the Gleason grading of prostate cancer. Our objective was to determine the diagnostic rates and Gleason scoring patterns for prostate gland biopsies and prostatectomies at our institution compared with the literature. METHODS: We conducted a retrospective review of all prostate gland biopsies and prostatectomies performed at the Grey Bruce Health Services from January 2005 to September 2005. We collected data from 194 biopsies and 44 prostatectomies. We obtained prebiopsy serum PSA levels and digital rectal exam results for all patients from urologists' office records. RESULTS: The average age for men having biopsies was 65.8 (standard deviation [SD] 8.6) years, and the average prebiopsy serum PSA level was 8.7 (median 7.1, SD 6.2) mug/L. The rates of diagnosis from prostate gland biopsies of benign (17.6%), high-grade prostatic intraepithelial neoplasia (11.0%), atypical small acinar proliferation suspicious for invasive malignancy (13.2%) and invasive prostatic adenocarcinoma (58.2%) at our institution were significantly different than those reported in the literature (p < 0.001). We observed a significant variation in the rates of these diagnoses among the community hospital pathologists in our study (p = 0.004). There was a strong correlation between the increasing number of positive core biopsy sites and increasing Gleason scores in biopsies (p < 0.001). There was also a strong correlation between increasing pre-biopsy serum PSA levels and increasing Gleason scores in biopsies (p < 0.001). A substantial proportion (21.9%) of the biopsies given the Gleason score of 6 had a Gleason score of 7 in the prostatectomy specimen. CONCLUSION: Our results showed a significant difference in prostate gland biopsy categorical diagnoses compared with the literature. There were also significant differences in categorical diagnoses of prostate gland biopsies among the community hospital pathologists in our study. The data identify a strong positive correlation between the increasing number of positive core biopsy sites and increasing Gleason scores in biopsies, as well as a strong positive correlation between increasing prebiopsy serum PSA levels and increasing Gleason scores in biopsies that revealed cancer. We would encourage other community hospital pathologists, in collaboration with their urologists, to review periodically their prostate gland pathology practices in an attempt to improve the uniformity of diagnoses.