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Background: The role of neoadjuvant short-course radiation therapy (SCRT) in treating rectal adenocarcinoma is a topic of ongoing debate. Growing interest in total neoadjuvant therapy has spurred discussion on the optimal sequence of preoperative SCRT and chemotherapy., Patients and Methods: All patients receiving SCRT (5 Gy × 5 fractions) were identified. Details about preoperative treatments, radiation toxicities, and postoperative complications were collected. Patients were divided into 2 groups: those who underwent surgery within 14 days of completing SCRT and those with a longer delay. Outcomes compared included extent of pathologic response, margin-negative resection rate, acute radiation toxicities, and postoperative complications., Results: Fifty-seven patients with locally advanced or metastatic rectal cancer received SCRT between 2008 and 2018. Thirty-nine of 57 patients underwent definitive pelvic surgery with total mesorectal excision. There were no significant differences in tumor downstaging, radial margin status, or percent tumor viability between patients with immediate surgery versus delayed surgery. The delay group had higher rates of nodal downstaging (64.7% vs. 18.2%; P = .003). There were no differences in total or grade 3+ gastrointestinal radiation toxicity, postoperative complications, reoperation, readmission, and mortality between the 2 groups., Conclusions: Though not yet common in the United States, SCRT has compared favorably with long course chemoradiation in multiple trials. Moreover, it is associated with greater efficiency and less disruption to chemotherapy. Our data show similar response and toxicity outcomes between the immediate and delay groups, suggesting SCRT is well-tolerated regardless of treatment sequence. Recently completed prospective trials may reveal the optimal preoperative treatment sequence., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tenofovir administration via rectal douching results in higher rectal-mucosa drug concentration than oral administration. Many who engage in receptive anal intercourse (RAI) use cleansing rectal douches. To inform development of a behaviorally-congruent tenofovir douche, 4751 individuals ≥ 18 years-old, born male, from all US states/territories, who engaged in anal intercourse responded to an online survey. Of those who reported RAI in the prior 3 months, 80% douched beforehand, 82% within 1 h, mean 2.9 consecutive applications; 27% douched afterwards, 83% within 1 h, mean 1.7 consecutive applications. Among multidose users, 78% applied doses within 2 min, and 76% retained liquid < 1 min. Most used tap water (89%) in an enema bottle (50%) or rubber bulb (43%), and douched for cleanliness (97%), to avoid smelling bad (65%), and to enhance pleasure (24%). 98% reported high likelihood of using an HIV-prevention douche. An ideal product will protect within a user's typical number of applications, within 1 h, and be dissolvable in tap water.

Background: Adjuvant chemotherapy is currently offered routinely, as standard, after radical resection for patients with rectal cancer receiving neo-adjuvant chemoradiation. However, the efficacy of adjuvant chemotherapy in patients with ypTis-2N0M0 has not been documented to the same extent, and the survival benefit remained controversial. The purpose of this work was to determine the role of chemotherapy in patients with ypTis-2N0M0 classification., Materials and Methods: Data were obtained from the Surveillance, Epidemiology, and End Results database ( n  = 4,217). A propensity score model was utilized to balance baseline covariates., Results: Of the 4,217 included patients, 335 with ypTis-2N0M0 did not receive adjuvant chemotherapy. There were comparable cancer-specific survivals (CSS) between those undergoing adjuvant chemotherapy or not (log-rank test = 0.136, p  = .712) in the overall sample. After propensity score matching, the cancer-specific survival did not differ between the chemotherapy and observation groups (log-rank test = 0.089, p  = .765). Additionally, the Cox model did not demonstrate adjuvant chemotherapy as the prognostic factor, with hazard ratio = 0.95 (95% confidence interval 0.69-1.32) for CSS. Furthermore, the 10-year cumulative CSS was 78.7% and 79.4% between the chemotherapy and observation groups, indicating no significance, and no impact of adjuvant chemotherapy on survival was observed in different subgroups stratified by T stage, histological grade, histology, lymph nodes, and tumor size., Conclusion: Patients with ypTis-2N0 rectal cancer did not benefit from adjuvant chemotherapy after preoperative radiology and radical surgery in this cohort study. These results provided new insight into the routine use of adjuvant chemotherapy for patients with rectal cancer with completed neo-adjuvant radiotherapy and curative surgery., Implications for Practice: Inconsistent recommendations for patients with rectal cancer receiving neo-adjuvant chemoradiation are offered by clinical guidelines. Adjuvant chemotherapy had no cancer-specific survival benefit, not only in the whole cohort, but also in the propensity score-matched cohort. A Cox model also confirmed adjuvant chemotherapy was not a significant prognostic factor in ypTis-2N0 rectal cancer. No survival benefit conferred by adjuvant chemotherapy was observed, regardless of whether T stage, histological type, grade, lymph nodes and tumor size varied., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Study Objective: To evaluate the diagnostic accuracy and learning curve of a sonographic mapping protocol for deep endometriosis (DE)., Design: Retrospective cohort study (Canadian Task Force classification II-3)., Setting: Tertiary referral center in the United States., Patients: 117 consecutive patients who presented to our gynecology clinic with complaints of significant noncyclic pelvic pain of at least 6 months' duration, and/or clinical findings concerning for deep endometriosis and who were referred for transvaginal ultrasound with bowel preparation., Interventions: Patients underwent transvaginal ultrasound with bowel-preparation (TVUS-BP) performed by a single radiologist. Findings suspicious for DE were reported and correlated with surgical and histopathological findings. The duration of the examination and number of cases required to achieve proficiency were calculated for positive, equivocal, and negative findings., Measurements and Main Results: Among 117 patients (median age, 35 years; range, 19-54 years) referred for TVUS-BP, 113 had complete examinations. Fifty-seven of these 113 patients underwent surgical exploration within 1 year, and DE was identified surgically in 23 of them. DE of the rectosigmoid colon and/or rectovaginal septum was detected with a sensitivity of 94% (95% confidence interval [CI], 70%-100%) and specificity of 100% (95% CI, 91%-100%). DE of the retrocervical region and/or uterosacral ligaments was detected with a sensitivity of 86% (95% CI, 65%-97%) and specificity of 94% (95% CI, 81%-99%). Proficiency, defined by a flattening of the learning curve, was achieved after 70 to 75 scans. The mean duration of the examination was 42 ± 4 minutes initially, but declined to 15 ± 4 minutes once proficiency was achieved. Cases of equivocal or minimal disease demonstrated the greatest decline in examination duration., Conclusion: A newly applied TVUS-BP protocol for detection of pelvic DE is highly accurate and required only a modest learning curve to achieve procedural proficiency in a US tertiary referral center where physicians interpret but typically do not perform TVUS exams. Overcoming diagnostic uncertainty regarding minimal or equivocal disease appeared to be an important factor in the initial learning curve. With adequate training, TVUS-BP may be adapted as a primary diagnostic tool for detecting pelvic DE., (Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.)

This study was designed to assess the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic (PD) responses to rectal administration of tenofovir (TFV) 1% vaginally formulated gel and oral tenofovir disoproxil fumarate (TDF). This study was designed as a phase 1, randomized, two-site (United States), double-blind, placebo-controlled study of sexually abstinent men and women. Eighteen participants received a single 300-mg exposure of oral TDF and were then randomized 2:1 to receive a single and then seven daily exposures of rectal TFV or hydroxyethyl cellulose (HEC) placebo gel. Safety endpoints included clinical adverse events (AEs) and mucosal safety parameters. Blood and colonic biopsies were collected for PK analyses and ex vivo HIV-1 challenge. No serious AEs were reported. However, AEs were significantly increased with 7-day TFV gel use, most prominently with gastrointestinal AEs (p=0.002). Only 25% of participants liked the TFV gel. Likelihood of use "if somewhat protective" was ∼75% in both groups. Indices of mucosal damage showed minimal changes. Tissue TFV diphosphate (TFV-DP) C(max) 30 min after single rectal exposure was 6-10 times greater than single oral exposure; tissue TFV-DP was 5.7 times greater following 7-day versus single rectal exposure. In vivo exposure correlated with significant ex vivo tissue infectibility suppression [single-rectal: p=0.12, analysis of covariance (ANCOVA) p=0.006; 7-day rectal: p=0.02, ANCOVA p=0.005]. Tissue PK-PD was significantly correlated (p=0.002). We conclude that rectal dosing with TFV 1% gel resulted in greater TFV-DP tissue detection than oral dosing with reduced ex vivo biopsy infectibility, enabling PK-PD correlations. On the basis of increased gastrointestinal AEs, rectally applied, vaginally formulated TFV was not entirely safe or acceptable, suggesting the need for alternative rectal-specific formulations.