Successful Restoration of Fecal Continence Using Sacral Nerve Stimulation Following Chemoradiation and Transanal Excision of an Anal Melanoma With Partial Internal Anal Sphincter Resection: A Case Report.

OBJECTIVE: This case report provides evidence for our hypothesis that use of a sacral nerve stimulator may be considered in patients with fecal incontinence (FI) following chemoradiation and transanal operations in the setting of cancer including partial internal sphincter resections. MATERIALS AND METHODS: A 57-year-old female with a history of anal melanoma was treated with neoadjuvant chemoradiation followed by wide local, transanal tumor excision with partial internal anal sphincter resection that resulted in ≥2 full fecal incontinent episodes/week with gas, liquid, and solid stool leakage ≥10/day requiring pad changes. After seven years of progressive FI, a sacral nerve stimulator was implanted following pre-placement anorectal manometry. Pre and post implant validated Cleveland Cleveland Clinic/Wexner Fecal Incontinence questionnaires and daily stool diaries (Medtronic) were completed. Data was stored in and collected from the patient's electronic health record. RESULTS: The patient had a single episode of FI during the two week trial phase, but reports complete resolution of FI, urgency, and leakage since implantation through her 1-year post-implant follow-up visit. Additional improvements were noted in FI questionnaires: Cleveland Clinic/Wexner Fecal Incontinence Score of 17 at baseline to 3 post-implant and Fecal Incontinence Quality of Life Score of 3.585 at baseline to 3.93 post-implant. CONCLUSIONS: The application of sacral nerve stimulation may not be as limited as previously thought and should be considered for cancer survivors following chemoradiation and sphincter-sparing rectal and transanal resections. Though this single case report is suggestive, further research is necessary and would include a research protocol designed specifically for patients who have undergone chemoradiation and/or sphincter-sparing operations. We are currently working on such protocol at our institution.

DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.

PURPOSE: DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. METHODS: Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. RESULTS: The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. CONCLUSION: dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions.