Laparoscopic ventral onlay ureteroplasty with buccal mucosa graft for complex proximal ureteral stricture

ABSTRACT Introduction: There is lack of papers dedicated to the laparoscopic buccal mucosa graft (BMG) ureteroplasty of the complex upper ureteral stricture. The aim of this study is to evaluate the results of laparoscopic BMG ureteroplasty in patients with complex proximal ureteral stricture. Material and methods: Twenty-four patients underwent laparoscopic ventral onlay BMG ureteroplasty for long or recurrent proximal ureteral stricture not amenable to uretero-ureteral anastomosis over 2019-2022. Patient demographics, operative time, estimated blood loss, length of stay, follow-up, intra- and postoperative complication rate and percentage of stricture-free at last visit were analyzed. Results: The mean stricture length was 3.6 cm. The mean operative time was 208.3 min, while mean blood loss was 75.8 mL. The length of hospital stay was 7.3 days. No intraoperative complications were observed. Postoperatively, seven patients developed complications (29.2%). Five patients experienced a Grade II (according to Clavien nomenclature). Two patients developed a Grade IIIa complication, which included leakage of the anastomosis site. The mean follow-up was on the 22 months with stricture free rate 87.5%. Conclusion: Patients with proximal ureteral strictures could be effectively treated by laparoscopic ventral onlay ureteroplasty with a buccal mucosa graft

Prevalence of cutaneous beta and gamma human papillomaviruses in the anal canal of men who have sex with women

Background: Data regarding anal cutaneous HPV detection among HIV-positive and HIV-negative persons largely relies on studies among men who have sex with men in limited geographical settings. Understanding the distribution, determinants, and potential human health effects of anal cutaneous HPV types among men who have sex with women (MSW) is important. Methods: Anal canal swab samples from 415 Russian MSW (384 HIV-negative and 31 HIV-positive) were tested for 43 β-HPVs and 29 γ-HPVs, using a multiplex PCR combined with Luminex technology. Results: β-HPV was detected in 24.4% and γ-HPV in 15.9% of anal samples of all Russian MSW. In total, 34 β-HPV and 19 γ-HPV types were detected, with the most commonly detected β-HPV types being 110, 22 and 124 and the most common γ-HPV types being 95, 132 and 50. For both genera, being HIV-positive at the time of testing was a significant determinant of detection (74.2% for β-HPVs and 48.4% for γ-HPVs compared to 20.1% and 12.5% in HIV-negative MSW, respectively). Conclusions: A wide spectrum and moderate prevalence of anal β-HPV and γ-HPV types was found in our MSW study sample, suggesting that routes other than penile-anal intercourse may be important in cutaneous HPV transmission. Keywords: Anal cutaneous HPV, Beta-HPV, Gamma-HPV, HIV-negative MSW, Penile-anal, HPV transmissio

Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (<1%) patient in the chemotherapy group (acute kidney injury). Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted. Funding: AstraZeneca