Khurshid A. Guru

To create a risk stratification model for biochemical recurrence by examining the relationship between the positive surgical margin status and biochemical recurrence in patients with prostate cancer after radical prostatectomy. This retrospective study included 3,010 patients who received radical prostatectomy. We analyzed the effect of postoperative pathological results using the Kaplan–Meier method and Cox model regression analysis in patients with no positive lymph node. A risk stratification model incorporating the total positive surgical margin length was constructed based on factors predicting biochemical recurrence. Among the total 1,865 patients, 346 (19%) experienced biochemical recurrence after radical prostatectomy and 377 (20%) had a positive surgical margin. The median positive surgical margin count was 1, and the median total positive surgical margin length measured 1.0 mm. The multivariable regression analysis revealed significant associations between biochemical recurrence and the following factors: preoperative prostate-specific antigen level > 20 ng/mL (p < 0.001), pathological Gleason grade (p < 0.001), extraprostatic extension (p < 0.001), seminal vesicle invasion (p < 0.001), lymphovascular invasion (p = 0.010), and total positive surgical margin length of ≥ 1 mm (p < 0.001). Patients were classified into good-, intermediate-, and poor-risk groups corresponding to the presence of 0, 1, or ≥ 2 factors, respectively. The 5-year survival rates without biochemical recurrence were 93%, 81%, and 47%, respectively. Our risk stratification model for biochemical recurrence after radical prostatectomy incorporates preoperative prostate-specific antigen level and pathological results, thereby aiding in patient counseling and the selection of appropriate adjunctive therapy after radical prostatectomy.

Among the photosensitizers (PSs) developed in our laboratory, 3-(1′-hexyloxy) ethyl-3-devinyl pyropheophorbide-a (HPPH) is undergoing Phase-II multicenter clinical trials for the treatment of head and neck and esophageal cancers. The PS exhibits absorption at 665 nm (in vivo) and shows desired pharmacokinetics with limited skin phototoxicity in patients, compared to FDA-approved Photofrin. This study determined the effect of HPPH-PDT in vitro and in vivo on human bladder cancer (BCa) tissue grown in immune-deficient mice. We observed high tumor uptake/retention of HPPH at 24 h post injection. The anticancer activity of HPPH-PDT was associated with undesirable induction of COX-2, the key enzyme enhancing the production of prostaglandin E2 (PGE2), a pathway we previously found accompanying tumors associated with immune suppression and tumor progression. Combination of COX-2 inhibition with PDT or with BCG-immunotherapy showed an improved rate of tumor cures. Hence, HPPH-PDT in combination with COX-2 inhibitors not only reduces the expression of COX-2, IL-6, VEGF, and PGE2 but also enhances long-term tumor cure.

In QUILT-3.032, the efficacy of IL-15 receptor agonist, nogapendekin alfa inbakicept (NAI) in combination with BCG for BCG-unresponsive high-grade papillary-only non-muscle invasive bladder cancer (NMIBC) was assessed. Herein we report the 36-month follow-up among participants with BCG-unresponsive papillary disease (Cohort B). NCT03022825 is an open-label, multi-center study with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received 400μg NAI plus 50mg BCG intravesically weekly for six consecutive weeks. The primary endpoint is disease-free survival (DFS) at 12-months. Progression-free survival (PFS), disease-specific survival (DSS), and cystectomy avoidance were assessed. Treatment-related adverse events (TRAEs) were assessed. At July 15, 2024 data cutoff, the DFS rates at 12-, 24-, and 36-months were 58.2% (95% CI 46.6, 68.2), 52.1% (95% CI 40.3, 62.7), and 38.2% (95% CI 25.6, 50.6), respectively. The PFS rates at 12- and 36-months were 94.9% (95% CI 86.9, 98.0) and 83.1% (95% CI 69.5, 91.0). The DSS rates at 12- and 36-months were 98.7% (95% CI 91.4, 99.8) and 96.0% (95% CI 88.2, 98.7). The median DSS has not been reached. Cystectomy avoidance rates at 12- and 36-months were 92.2% (95% CI 83.4, 96.4) and 81.8% (95% CI 68.1, 90.1), with median time to cystectomy not reached. Most TRAEs were grade 1-2 (61%) with 3% grade 3, and no grade 4-5. The 12- and 36-month DFS, PFS, DSS, and cystectomy avoidance rates demonstrate the effectiveness and safety of NAI plus BCG in the management of BCG-unresponsive papillary disease.

Introduction Open ureteroenteric reimplantation (OUER) of ureteroenteric strictures (UESs) is related to important morbidity. Robot-assisted ureteroenteric reimplantation (RUER) has been proposed to provide similar outcomes with lower morbidity. We aimed to compare perioperative and functional outcomes between RUER and OUER. Methods A retrospective multicenter study of 80 patients, who underwent 82 ureteroenteric reimplantations (17 OUER vs 65 RUER) at 8 institutions between 2009–2021 for benign UESs after radical cystectomy. All the open procedures were performed by the same center in order to compare the robotic approach with a standardized technique. Data were reviewed for demographics, stricture characteristics, and perioperative outcomes. Complication and stricture recurrence rates were compared between both groups. Results Among 82 reimplantations, 44 were left sided (54%) and 12 bilateral (14%). Median time from cystectomy to diagnosis of stricture was 6 months (range 3–18). Baseline characteristics (gender, age, BMI, side, type of urinary diversion and previous abdominal radiotherapy) were comparable between RUER and OUER groups, except for ASA score and rates of prior robotic cystectomy. The 30-day overall postoperative complication rate was 37% in RUER compared to 70.6% in OUER (p = 0.026). Patients who underwent a RUER had statistically significant lower rate of intraoperative blood transfusion (0% vs 12%, p = 0.041), urinary tract infection (12% vs 53%, p < 0.001), bowel injury (0% vs 12%, p = 0.041) and high-grade complications (Clavien III-IV) (4.6% vs 23.5%, p = 0.031). RUER patients had shorter median length of hospital stay (3 days IQR[1–6] vs 6 IQR[3–9], p = 0.018) and lower readmission rate (4.6% vs 29.4%, p = 0.008). After a median follow-up of 23.5 months (8.7–43), 80% of RUER cases were stricture free compared to 90% of OUER (p = 0.42). Conclusions RUER achieved a success rate comparable to that of open revisions and may provide some advantages in terms of perioperative outcomes. Prospective and larger studies are warranted to prove its superiority compared to the standard open technique.

Introduction and Hypothesis: Robot-assisted radical nephroureterectomy (RANU) has emerged as a valid alternative to open or laparoscopic nephroureterectomy in recent years. However, different types of robotic platforms can limit surgical maneuvers in various ways. This study aimed to describe the surgical procedure and demonstrate RANU’s technical feasibility and safety using the Hugo robot-assisted surgery (RAS) system. Materials and Methods: Using the Hugo RAS system, we reported data from the first five consecutive patients who underwent RANU at Tottori University Hospital. We adjusted the docking angles of the four independent arm carts in each case and performed a complete RANU via a transperitoneal approach. We collected patients’ sociodemographic and perioperative data, including complications, and compared them retrospectively with data obtained using the da Vinci surgical system. Results: Arms positions were modified after the first patient to be placed all at the back of the patient. Median overall operative time was 283 minutes (203–377) and the median time using the robotic system was 187 minutes (121–277). The median estimated blood loss was 20 mL (5–155). None of the patients required a blood transfusion and none suffered postoperative complications of Clavien–Dindo grade ≥3. These outcomes were similar to those obtained with the da Vinci Xi system. Conclusion: This series represents the first report of RANU executed using the novel Hugo RAS system. Our proposed arm-setup will assist other surgeons and help ensure safe implementation of RANU on the Hugo platform.

We aimed to investigate the differences in perioperative outcomes, especially ureteroenteric strictures, between patients who underwent a stented ureteroenteric anastomosis at the time of robot-assisted radical cystectomy (RARC) and ileal conduit vs those who did not. A retrospective review of our RARC database was performed (2009-2023). Patients were divided into those who received stented ureteroenteric anastomosis vs those who did not. Propensity score matching was performed in the ratio of 3 (stented ureteroenteric anastomosis) to 1 (stent-free) in terms of age, gender, BMI, race, American Society of Anesthesiologists score, neoadjuvant chemotherapy, Charlson Comorbidity Index, prior radiation therapy, previous abdominal surgery history, clinical T3/clinical T4 stage, preoperative metastasis, and preoperative hydronephrosis. A cumulative incidence curve was used to depict ureteroenteric strictures and a Cox regression model was used to identify variables associated with ureteroenteric strictures. Four hundred eighty-eight patients underwent RARC, 366 individuals underwent a stented ureteroenteric anastomosis, and 122 patients underwent a stent-free approach. There was no significant difference in 90-day overall complications, high-grade complications, readmissions, UTIs, leakage, and ileus (P > .05). Ureteroenteric strictures occurred at a rate of 13% and 18% at 1 and 2 years, respectively in the stented group, vs 7% and 10% in the stent-free group (P = .05). Stent placement was significantly associated with ureteroenteric strictures. Stent-free ureteroenteric anastomosis was associated with fewer strictures following RARC and ileal conduit.