Systematic Review of Neoadjuvant Immunotherapy for Mismatch Repair Deficient Locally Advanced Colon Cancer: An Emerging Strategy.

BACKGROUND: In April 2023, the National Comprehensive Cancer Network endorsed neoadjuvant immunotherapy for select patients with nonmetastatic mismatch repair deficient colon cancer. Approximately 15% of incident colon cancers are mismatch repair deficient, resulting in a distinct molecular subtype with high microsatellite instability that is responsive to immune checkpoint inhibition. OBJECTIVE: To describe the existing evidence supporting neoadjuvant immunotherapy for mismatch repair deficient, microsatellite unstable nonmetastatic colon cancer. DATA SOURCES: A medical librarian performed PubMed, Embase, and Web of Science searches most recently on April 24, 2023. The PubMed search was re-run on September 26, 2023, to identify any additional studies published between April 24 and September 26, 2023. STUDY SELECTION: Two authors screened titles and abstracts in the published studies. The inclusion criteria were 1) English language, 2) adults with primary cancer of the colon, 3) nonmetastatic disease, 4) neoadjuvant immunotherapy, and 5) reporting on 10 or more cases. INTERVENTION: Neoadjuvant immunotherapy. MAIN OUTCOME MEASURES: Safety (grade 3+ treatment-related adverse events) and efficacy (complete pathologic responses). RESULTS: From 7691 studies identified, 6370 were screened and 8 were included. Various agents, dosing regimens, and treatment durations were used, with durations of immunotherapy ranging from 1 to 16 cycles. Complete R0 resections were consistently achieved in 98% to 100% of resections. Of patients who received neoadjuvant immunotherapy and underwent resection, 50% to 91% had ypT0N0 pathology. The safety profiles were generally favorable, with grade 1 to 2 treatment-related adverse events (mostly immune-related) during immunotherapy reported in 22.2% to 70% of patients. Postoperative complications after neoadjuvant immunotherapy were reassuring, with no severe complications reported. LIMITATIONS: Small number of heterogeneous and uncontrolled studies precluding a meta-analysis. CONCLUSIONS: Neoadjuvant immune checkpoint inhibition is associated with high rates of pathologic complete responses in locally advanced colon cancer. The literature is limited, particularly for postoperative outcomes, and more studies are needed to understand the safety and positioning of these regimens in the neoadjuvant context.

International Continence Society best practice statement for use of sacral neuromodulation.

AIMS: Sacral neuromodulation (SNM) is an accepted therapy for a variety of conditions. However, despite over 20 years of experience, it remains a specialized procedure with a number of subtleties. Here we present the recommendations issued from the International Continence Society (ICS) SNM Consensus Panel. METHODS: Under the auspices of the ICS, eight urologists, three colorectal surgeons and two urogynecologists, covering a wide breadth of geographic and specialty interest representation, met in January 2017 to discuss best practices for neuromodulation. Suggestions for statements were submitted in advance and specific topics were assigned to committee members, who prepared and presented supporting data to the group, at which time each topic was discussed in depth. Best practice statements were formulated based on available data. This document was then circulated to multiple external reviewers after which final edits were made and approved by the group. RESULTS: The present recommendations, based on the most relevant data available in the literature, as well as expert opinion, address a variety of specific and at times problematic issues associated with SNM. These include the use of SNM for a variety of underlying conditions, need for pre-procedural testing, use of staged versus single-stage procedures, screening for success during the trial phase, ideal anesthesia, device implantation, post-procedural management, trouble-shooting loss of device function, and future directions for research. CONCLUSIONS: These guidelines undoubtedly constitute a reference document, which will help urologists, gynecologists, and colorectal surgeons optimize their use of SNM for refractory urinary urgency and frequency, UUI, NOR, and FI.

Surviving rectal cancer: examination of racial disparities surrounding access to care.

BACKGROUND: The aim of this study was to evaluate whether survival differences are attributable to disproportionate access to stage-specific rectal cancer treatment recommended by the National Comprehensive Care Network. METHODS: A retrospective analysis of the National Cancer Data Base between 1998 and 2006 was performed. A series of Kaplan-Meier survival analyses were used to compare 5-y survival among race cohorts. Propensity score matching was used to compare Caucasian and African American patients who received the same treatment by accounting for covariates. RESULTS: 5-y overall survival in African Americans was 50.7% versus 56.2% in Caucasians (P < 0.001). In patients with stage I-III disease, 5-y survival was 58.7% in African Americans versus 63.1% in Caucasians (P < 0.001). Analysis of patients receiving surgery for stage I-III disease, revealed a 61.1% 5-y survival in African Americans versus 65.8% in Caucasians (P < 0.001). Propensity score matching did not eliminate the racial disparity. The median survival for Caucasian patients was 109.6 mo as compared to 85.8 mo for African Americans (P < 0.001). CONCLUSIONS: These data show that access to standard care appears to decrease but not eliminate the survival differences between African Americans and Caucasians with rectal cancer.

Dynamic Article: Percutaneous Nerve Evaluation Versus Staged Sacral Nerve Stimulation for Fecal Incontinence.

BACKGROUND: Sacral neuromodulation using a 2-staged approach is an established therapy for fecal incontinence. Office-based percutaneous nerve evaluation is a less-invasive alternative to the stage 1 procedure but is seldom used in the evaluation of patients with fecal incontinence. OBJECTIVE: The aim of this study was to determine the clinical success of percutaneous nerve evaluation versus a staged approach. DESIGN: This was a retrospective review of a prospectively maintained, single-institution database of patients treated with sacral neuromodulation for fecal incontinence. SETTINGS: This study was conducted at a single academic medical center. PATIENTS: Eighty-six consecutive patients were treated with sacral neuromodulation for fecal incontinence. INTERVENTIONS: Percutaneous nerve evaluation was compared with a staged approach. MAIN OUTCOME MEASURES: The primary outcome measured was the proportion of patients progressing to complete implantation based on >50% improvement in Wexner score during the testing phase. RESULTS: Percutaneous nerve evaluation was performed in 45 patients, whereas 41 underwent a staged approach. The mean baseline Wexner score did not differ between testing groups. Success was similar between the staged approach and percutaneous nerve evaluation (90.2% versus 82.2%; p = 0.36). The mean 3-month Wexner score was not significantly different between testing methods (4.4 versus 4.1; p = 0.74). However, infection was more likely to occur after the staged approach (10.5% versus 0.0%; p < 0.05). LIMITATIONS: This study was limited by its retrospective nature and potential for selection bias. CONCLUSIONS: Percutaneous nerve evaluation offers a viable alternative to a staged approach in the evaluation of patients for sacral neuromodulation in the setting of fecal incontinence. Not only are success rates similar, but percutaneous nerve evaluation also has the benefit of limiting patients to 1 operating room visit and has lower rates of infection as compared with the traditional staged approach for sacral neuromodulation.

Is sacral neuromodulation here to stay? Clinical outcomes of a new treatment for fecal incontinence.

INTRODUCTION: Sacral neuromodulation (SNM) was approved by the FDA for the treatment of fecal incontinence (FI) in 2011, and previous industry-sponsored trials have shown excellent clinical outcomes. The purpose of this study is to examine clinical outcomes of patients treated during our initial experience with SNM. METHODS: A prospective database of patients treated with SNM for FI by one of three colorectal surgeons at two separate institutions was maintained starting in 2011. Patients showing ≥50% improvement of weekly incontinent episodes during test stimulation were offered permanent implantation of the SNM device. Disease severity was tracked using the Wexner score. RESULTS: A total of 145 patients received a full system implantation (of 152 who received test stimulation). The median preoperative Wexner score of 14 decreased to 3, 3 months after implantation and persisted to 12 months. At 12 months, 95.2% of patients achieved >50% improvement in Wexner Score and 67.6% achieved >75% improvement. The most common adverse event was infection (3.4%). Three patients (2.1%) required lead revision. CONCLUSIONS: SNM is a safe and effective therapy for the treatment of FI. Postoperative patient surveillance is important, as many patients require programming changes, and some will require a lead revision over time.

Quantifying patient improvement following sacral neuromodulation: is it time for a new scoring system for fecal incontinence?

BACKGROUND: The Cleveland Clinic Florida Fecal Incontinence score is widely used to assess the severity of fecal incontinence. OBJECTIVE: We hypothesized that the Cleveland Clinic Fecal Florida Incontinence score is useful at establishing baseline disease severity, but it may underestimate the response to treatment following sacral neuromodulation because of the large number of patients who still wear a pad despite improved continence, as well as the inability to track improvements in urgency. DATA SOURCES: Data were obtained from prospectively maintained database of patients treated with sacral neuromodulation for fecal incontinence at 2 institutions beginning in 2011. DESIGN: A retrospective review of the individual components of Cleveland Clinic Fecal Florida Incontinence scores in response to treatment with sacral neuromodulation was performed. SETTINGS: The study was conducted at 1 academic medical center and 1 community medical center. PATIENTS: One hundred twenty-one consecutive patients were treated with sacral neuromodulation for fecal incontinence. INTERVENTIONS: No interventions occurred. MAIN OUTCOME MEASURES: Individual components of posttreatment Cleveland Clinic Florida Fecal Incontinence scores and subjective improvement in fecal urgency were the primary outcomes measured. RESULTS: The median preoperative Cleveland Clinic Fecal Florida Incontinence score of 14 decreased to 3 (interquartile range, 2-4) at 12 months. Of the patients, 66.1% reported still wearing a pad after the procedure. The reason for wearing a pad was residual fecal incontinence (41%), habit despite normal continence (35.3%), and urinary incontinence with complete fecal continence (23.5%). Of patients who report wearing a pad, 59% have falsely elevated Cleveland Clinic Fecal Florida Incontinence scores owing to wearing a pad despite complete fecal continence. Additionally, 96.3% of patients reported improvement in fecal urgency. LIMITATIONS: This retrospective study did not include a comparison with an alternative scoring system. CONCLUSIONS: Although the Cleveland Clinic Fecal Florida Incontinence score is a validated scale, which is simple to use for baseline disease severity, it may underestimate patient response to treatment. Additionally, it does not capture improvement in urgency. The ideal scoring system would be easy to use in clinical practice, and would account for improvement in fecal urgency.