Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of Mcm5 and nuclear matrix protein 22.

BACKGROUND: Urinary biomarkers for bladder cancer detection are constrained by inadequate sensitivity or specificity. Here we evaluate the diagnostic accuracy of Mcm5, a novel cell cycle biomarker of aberrant growth, alone and in combination with NMP22. METHODS: 1677 consecutive patients under investigation for urinary tract malignancy were recruited to a prospective blinded observational study. All patients underwent ultrasound, intravenous urography, cystoscopy, urine culture and cytologic analysis. An immunofluorometric assay was used to measure Mcm5 levels in urine cell sediments. NMP22 urinary levels were determined with the FDA-approved NMP22® Test Kit. RESULTS: Genito-urinary tract cancers were identified in 210/1564 (13%) patients with an Mcm5 result and in 195/1396 (14%) patients with an NMP22 result. At the assay cut-point where sensitivity and specificity were equal, the Mcm5 test detected primary and recurrent bladder cancers with 69% sensitivity (95% confidence interval = 62-75%) and 93% negative predictive value (95% CI = 92-95%). The area under the receiver operating characteristic curve for Mcm5 was 0.75 (95% CI = 0.71-0.79) and 0.72 (95% CI = 0.67-0.77) for NMP22. Importantly, Mcm5 combined with NMP22 identified 95% (79/83; 95% CI = 88-99%) of potentially life threatening diagnoses (i.e. grade 3 or carcinoma in situ or stage ≥pT1) with high specificity (72%, 95% CI = 69-74%). CONCLUSIONS: The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways.

Evolution of care pathway for laparoscopic radical prostatectomy.

PURPOSE: We report results of the introduction of a laparoscopic radical prostatectomy (LRP) care pathway. This included the introduction of a transversus abdominis plane (TAP) local anesthetic block and other measures to reduce the impact of factors known to delay postoperative recovery. Outcomes including pain, analgesic requirements, complications, and length of stay are reported. PATIENTS AND METHODS: Two hundred consecutive patients undergoing LRP from 2008 to 2010 were prospectively studied. A detailed perioperative care pathway was developed and implemented. The pathway was modified after a pain audit to include bilateral transversus abdominis plane regional anesthetic blockade. Same day discharge criteria were applied to suitable patients. Demographics and perioperative and follow-up data were prospectively collected and recorded on a database. RESULTS: Overall, 78% of cases were discharged after 1 night stay; 14 patients were managed as true day cases without overnight stay. Operative time (P<0.0001), intraoperative blood loss (P=0.018), %≤ 1 day stay (P=0.0091), transfusion, and conversion rate (nil in latter 100 cases) all improved significantly in the second 100 group of patients compared with the first 100 cases. The introduction of TAP blocks led to significant reductions of mean intraoperative and postoperative opiate use (17.3 mg to 1.3 mg and 1.9 mg to 0.2 mg morphine, respectively) without any significant effect on perceived pain. True day cases did not experience a significantly different rate of complications than the whole cohort. CONCLUSIONS: Through a structured care pathway incorporating the TAP block, 1 night stay laparoscopic prostatectomy can be safely delivered with reduced inpatient stay costs. In selected patients, day-case prostatectomy is feasible.

Mcm2, Geminin, and KI67 define proliferative state and are prognostic markers in renal cell carcinoma.

PURPOSE: The origin licensing factors minichromosome maintenance 2 (Mcm2) and Geminin have recently been identified as critical regulators of growth and differentiation. Here we have investigated the regulation of these licensing factors together with Ki67 to further elucidate the cell cycle kinetics of renal cell carcinoma (RCC). Furthermore, we have examined the role of Ki67, Mcm2, and Geminin in disease-free survival after nephrectomy in patients with localized RCC. EXPERIMENTAL DESIGN: Tissue sections from 176 radical nephrectomy specimens were immunohistochemically stained with Mcm2, Geminin, and Ki67 antibodies. Labeling indices (LI) for these markers were compared with clinicopathologic parameters (median follow-up 44 months). RESULTS: In RCC, Mcm2 is expressed at much higher levels than Ki-67 and Geminin, respectively [medians 41.6%, 7.3%, and 3.5% (P < 0.001)] and was most closely linked to tumor grade (P < 0.001). For each marker, Kaplan-Meier survival curves provided strong evidence that increased expression is associated with reduced disease-free survival time (P < 0.001). Additionally, an Mcm2-Ki67 LI identified a unique licensed but nonproliferating population of tumor cells that increased significantly with tumor grade (P = 0.004) and was also of prognostic value (P = 0.01). On multivariate analysis, grade, vascular invasion, capsular invasion, Ki67 LI >12%, and age were found to be independent prognostic markers. CONCLUSIONS: Although Ki67 is identified as an independent prognostic marker, semiquantitative assessment is difficult due to the very low proliferative fraction identified by this marker. In contrast, Mcm2 identifies an increased growth fraction that is closely linked to grade, provides prognostic information, and is amenable to semiquantitative analysis in routine pathologic assessment.

Vesicocervical fistula: rare complication of cesarean section demonstrated by magnetic resonance imaging.

We report a rare complication of cesarean section in a 46-year-old woman presenting with incontinence. The patient was noted at cystoscopy to have a lesion on the posterior wall of the bladder. Histologic examination of the biopsied lesion demonstrated endocervical tissue, and subsequent magnetic resonance imaging revealed a vesicocervical fistula. She was treated by open excision of the fistula and repair of the bladder and cervix with omental interposition. Only 16 cases of vesicocervical fistulas have been previously reported, and this is the first to demonstrate the finding on magnetic resonance imaging.