Prospective randomized study correlating intra-operative urethral mucosal injury with early period after transurethral resection of the prostate stricture urethra: A novel concept.

Objective: To investigate the incidence of urethral stricture during the early period after transurethral resection of the prostate (TURP) and correlate its incidence with intra-operative urethral mucosal injury during TURP. Also to compare the other established risk factors affecting the development of urethral stricture among patients undergoing monopolar or bipolar TURP over a period of 6 months follow-up as the prospective randomized study. Methods: One hundred and fifty men older than 50 years with lower-urinary tract symptoms associated with benign prostatic hyperplasia were randomized to undergo either standard monopolar TURP with glycine as the irrigation fluid or bipolar TURP with normal saline as irrigant. The prostate size, operative time, intra-operative mucosal rupture, catheter time, catheter traction duration, uroflowmetry, and post-operative stricture rate were compared. Results: A total of 150 patients underwent TURP, including 74 patients undergoing monopolar TURP (one patient was excluded as his post-operative histopathological examination report was of adenocarcinoma prostate) and 75 patients undergoing bipolar-TURP, all of which were performed using a 26 Fr sheath resectoscope. The mean International Prostate Symptom Score and maximum urinary flow rate score at post-operative 3 months and 6 months were comparable between the groups. Out of 149 patients, nine patients (6.0%) developed urethral stricture. The severity of the injury (urethral mucosal injury) correlated with the likelihood of developing a subsequent complication (stricture urethra). Patients with stricture had significantly larger prostate volume than patients without stricture (65.0 mL vs. 50.0 mL; p=0.030). Patients with stricture had longer operative time than patients without stricture (55.0 min vs. 40.0 min; p=0.002). In both procedures, formation of post-operative stricture urethra was independently associated with intra-operative mucosal injury. Conclusion: Intra-operative recognition of urethral mucosal injury helps in prediction of stricture urethra formation in early post-operative period.

Tumor-informed ctDNA assessment as a valuable prognostic and predictive biomarker in diffuse large B-cell lymphoma.

Background: A novel approach for molecular residual disease (MRD) detection and treatment monitoring is needed in diffuse large B-cell lymphoma (DLBCL) to identify patients with a poor prognosis. We performed a retrospective evaluation of commercial ctDNA testing in patients with stage I-IV DLBCL to evaluate the prognostic and predictive role of tumor-informed ctDNA assessment. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for ctDNA detection and quantification. Results: In total, 50 patients (median age: 59 years; median follow-up: 12.68 months) were analyzed, of which 41 had pretreatment time points with ctDNA detected in 95% (39/41). Baseline ctDNA levels correlated with R-IPI scores and stage. ctDNA clearance during first-line therapy was predictive of improved therapy responses and outcomes (EFS, HR: 6.5, 95% CI: 1.9-22, p=0.003 and OS, HR: 22, 95% CI: 2.5-191, p=0.005). Furthermore, 48% (13/27) of patients cleared their ctDNA following the first cycle of treatment. Patients who cleared their ctDNA, irrespective of their R-IPI score, had superior outcomes compared to ctDNA-positive patients. ctDNA clearance outperformed other factors associated with EFS in multivariate analysis (HR: 49.76, 95% CI:1.1-2225.6, p=0.044). Finally, ctDNA clearance predicted complete response (CR)/no evidence of disease (NED) on average 97 days (range: 0-14.7 months) ahead of imaging/biopsy. Conclusion: ctDNA testing in patients with DLBCL is predictive of patient outcomes and may enable personalized surveillance, intervention, and/or trial options.