Current treatment and future directions in the management of anal cancer.

Although rare, the rate of squamous cell carcinoma of the anus (SCCA) is rising globally. Most patients present with nonmetastatic disease and are curable with appropriate treatment, which has evolved significantly over the last several decades. Before the 1970s, SCCA was managed with radical surgery, resulting in a permanent colostomy. Researchers found that preoperative treatment with chemotherapy and concurrent radiation could achieve a pathologic complete response. After this observation, definitive therapy shifted from radical surgery to sphincter-preserving chemoradiation. Investigations into the necessity of chemotherapy and the optimal regimen found that chemotherapy with mitomycin-C and 5-fluorouracil is required for cure. Further studies evaluating the addition of induction or maintenance chemotherapy, monoclonal antibody therapy, or higher radiation doses have demonstrated no significant benefit to disease control. Advanced radiation delivery with intensity-modulated radiotherapy techniques is now considered the standard of care because of its prospectively determined, favorable acute toxicity profile compared with 3-dimensional conformal radiation. It is important to note that chemoradiation treatment response may be slow (up to 26 weeks) and should be assessed through serial clinical examinations. Today, surgical management of SCCA is reserved only for the lowest risk, early stage tumors or for recurrent/persistent disease. Current studies are evaluating radiation dose de-escalation in early stage disease and radiation dose escalation and the addition of immune checkpoint inhibitors in locally advanced cancers. In reviewing how and why modern-day treatment of SCCA was established, the objective of this report is to reenforce adherence to current treatment paradigms to assure the best possible outcomes for patients.

SWOG S1820: A pilot randomized trial of the Altering Intake, Managing Bowel Symptoms Intervention in Survivors of Rectal Cancer.

BACKGROUND: Survivors of rectal cancer experience persistent bowel dysfunction after treatments. Dietary interventions may be an effective approach for symptom management and posttreatment diet quality. SWOG S1820 was a pilot randomized trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention for bowel dysfunction in survivors of rectal cancer. METHODS: Ninety-three posttreatment survivors were randomized to the AIMS-RC group (N = 47) or the Healthy Living Education attention control group (N = 46) after informed consent and completion of a prerandomization run-in. Outcome measures were completed at baseline and at 18 and 26 weeks postrandomization. The primary end point was total bowel function score, and exploratory end points included low anterior resection syndrome (LARS) score, quality of life, dietary quality, motivation, self-efficacy, and positive/negative affect. RESULTS: Most participants were White and college educated, with a mean age of 55.2 years and median time since surgery of 13.1 months. There were no statistically significant differences in total bowel function score by group, with the AIMS-RC group demonstrating statistically significant improvements in the exploratory end points of LARS (p = .01) and the frequency subscale of the bowel function index (p = .03). The AIMS-RC group reported significantly higher acceptability of the study. CONCLUSIONS: SWOG S1820 did not provide evidence of benefit from the AIMS-RC intervention relative to the attention control. Select secondary end points did demonstrate improvements. The study was highly feasible and acceptable for participants in the National Cancer Institute Community Oncology Research Program. Findings provide strong support for further refinement and effectiveness testing of the AIMS-RC intervention.

Para-aortic Lymph Node Dissection for Colorectal Cancer: Predicting Pathologic Lymph Node Positivity and Optimizing Outcomes.

INTRODUCTION: In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. METHODS: An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). RESULTS: Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. CONCLUSIONS: Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.

Early Postoperative Prediction of Complications and Readmission After Colorectal Cancer Surgery Using an Artificial Neural Network.

BACKGROUND: Early predictors of postoperative complications can risk-stratify patients undergoing colorectal cancer surgery. However, conventional regression models have limited power to identify complex nonlinear relationships among a large set of variables. We developed artificial neural network models to optimize the prediction of major postoperative complications and risk of readmission in patients undergoing colorectal cancer surgery. OBJECTIVE: The aim of this study was to develop an artificial neural network model to predict postoperative complications using postoperative laboratory values, and compare these models' accuracy to standard regression methods. DESIGN: This retrospective study included patients who underwent elective colorectal cancer resection between January 1, 2016, and July 31, 2021. Clinical data, cancer stage, and laboratory data from postoperative day 1 to 3 were collected. Models of complications and readmission risk were created using multivariable logistic regression and single-layer neural networks. SETTING: National Cancer Institute-Designated Comprehensive Cancer Center. PATIENTS: Adult colorectal cancer patients. MAIN OUTCOME MEASURES: Accuracy of predicting postoperative major complication, readmission and anastomotic leak using the area under the receiver-operating characteristic curve. RESULTS: Neural networks had larger areas under the curve for predicting major complications compared to regression models (neural network 0.811; regression model 0.724, p < 0.001). Neural networks also showed an advantage in predicting anastomotic leak (p = 0.036) and readmission using postoperative day 1-2 values (p = 0.014). LIMITATIONS: Single-center, retrospective design limited to cancer operations. CONCLUSIONS: In this study, we generated a set of models for early prediction of complications after colorectal surgery. The neural network models provided greater discrimination than the models based on traditional logistic regression. These models may allow for early detection of postoperative complications as soon as postoperative day 2. See Video Abstract.

Baseline characteristics and recruitment for SWOG S1820: altering intake, managing bowel symptoms in survivors of rectal cancer (AIMS-RC).

PURPOSE: Many survivors of rectal cancer experience persistent bowel dysfunction. There are few evidence-based symptom management interventions to improve bowel control. The purpose of this study is to describe recruitment and pre-randomization baseline sociodemographic, health status, and clinical characteristics for SWOG S1820, a trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention. METHODS: SWOG S1820 aimed to determine the preliminary efficacy, feasibility, and acceptability of AIMS-RC, a symptom management intervention for bowel health, comparing intervention to attention control. Survivors with a history of cancers of the rectosigmoid colon or rectum, within 6-24 months of primary treatment completion, with a post-surgical permanent ostomy or anastomosis, and over 18 years of age were enrolled. Outcomes included total bowel function, low anterior resection syndrome, quality of life, motivation for managing bowel health, self-efficacy for managing symptoms, positive and negative affect, and study feasibility and acceptability. RESULTS: The trial completed accrual over a 29-month period and enrolled 117 participants from 34 institutions across 17 states and one US Pacific territory. At baseline, most enrolled participants reported self-imposed diet adjustments after surgery, persistent dietary intolerances, and bowel discomfort post-treatment, with high levels of constipation and diarrhea (grades 1-4). CONCLUSIONS: SWOG S1820 was able to recruit, in a timely manner, a study cohort that is demographically representative of US survivors of rectal cancer. Baseline characteristics illustrate the connection between diet/eating and bowel symptoms post-treatment, with many participants reporting diet adjustments and persistent inability to be comfortable with dietary intake. GOV REGISTRATION DATE: 12/19/2019. GOV IDENTIFIER: NCT#04205955.

Germline Cancer Risk Profiles of Patients With Young-Onset Colorectal Cancer: Findings From a Prospective Universal Germline Testing and Telegenetics Program.

BACKGROUND: Colorectal cancer is being increasingly diagnosed in people younger than 50 years. An inheritable cancer predisposition has been reported in 22% of the young-onset cases. Assessment of germline risk is critical for personalized cancer care. OBJECTIVE: The study aimed to implement universal germline cancer risk assessment and testing and to define the germline cancer risk profiles of patients presenting with young-onset disease. DESIGN: This is a prospective cohort study. SETTINGS: This study was conducted at a tertiary-referral academic medical center. PATIENTS: This study included newly diagnosed patients presenting to surgical clinics between September 2019 and February 2021 who were treated on a standardized care pathway including the universal germline risk assessment. INTERVENTIONS: Patients received educational material on young-onset disease, genetic testing, and insurance coverage followed by genetic counseling (either remotely by telegenetics or in person). Consenting patients were assessed on a 47-gene common hereditary cancer panel. MAIN OUTCOME MEASURES: The primary outcome was a proportion of patients with identifiable germline cancer predisposition. RESULTS: Among 500 patients with colorectal cancer, 185 (37%) were 50 years of age or younger (median: 44). A family history was absent for the majority of patients (123; 67%), and in 15 patients, tumors (8.1%) were deficient in DNA mismatch repair. Germline testing was completed in 130 patients (70%); the remainder were pending (7%), deceased (1%), or declined (22%). Pathogenic germline mutations were identified in 25 of 130 (19%) patients: 12 in mismatch repair genes and 13 in other genes. A variant of uncertain significance was found in 23 (18%) patients. Importantly, a pathogenic germline mutation was identified in 12% of the patients without a family history (versus 32% with; p = 0.015) and in 13% of those with proficient mismatch repair colorectal cancers (versus 71% if deficient; p < 0.001). LIMITATIONS: The study is limited by its implementation at a single tertiary academic institution. CONCLUSIONS: One in 5 patients with young-onset disease harbored germline cancer predisposition. This detection rate, coupled with a high level of interest and acceptance from patients and feasibility of implementation, supports universal germline cancer risk assessment in this patient population. See Video Abstract at http://links.lww.com/DCR/B925 . PERFILES DE RIESGO DE CNCER DE LNEA GERMINAL DE PACIENTES CON CNCER COLORRECTAL DE INICIO JOVEN HALLAZGOS DE UN PROGRAMA UNIVERSAL PROSPECTIVO DE PRUEBAS DE LNEA GERMINAL Y TELEGENTICA: ANTECEDENTES:El cáncer colorrectal se diagnostica cada vez más en personas menores de 50 años. Se ha informado una predisposición hereditaria al cáncer en el 22 % de los casos de aparición temprana. La evaluación del riesgo de la línea germinal es fundamental para la atención personalizada del cáncer.OBJETIVO:Implementar la evaluación y las pruebas universales de riesgo de cáncer de línea germinal, y definir los perfiles de riesgo de cáncer de línea germinal de los pacientes que presentan una enfermedad de aparición temprana.DISEÑO:Un estudio de cohorte prospectivo.AJUSTE:Un centro médico académico de referencia terciaria.PACIENTES:Los pacientes recién diagnosticados que se presentaron en clínicas quirúrgicas entre Septiembre de 2019 y Febrero de 2021 fueron tratados en una vía de atención estandarizada que incluye una evaluación de riesgo de línea germinal universal.INTERVENCIÓN:Los pacientes recibieron material educativo sobre enfermedades de aparición temprana, pruebas genéticas y cobertura de seguro, seguido de asesoramiento genético (ya sea a distancia por telegenética o en persona). Los pacientes que dieron su consentimiento fueron evaluados en un panel de cánceres hereditarios comunes de 47 genes.MEDIDA DE RESULTADO PRINCIPAL:Proporción de pacientes con predisposición identificable al cáncer de línea germinal.RESULTADOS:Entre 500 pacientes con cáncer colorrectal, 185 (37%) tenían 50 años o menos (mediana: 44). No había antecedentes familiares en la mayoría (123, 67%) y 15 tumores (8,1%) eran deficientes en la reparación del desajuste de ácido desoxirribonucleico. La prueba de línea germinal se completó en 130 pacientes (70%); el resto estaban pendientes (7%), fallecidos (1%) o declinados (22%). Se identificaron mutaciones patogénicas de la línea germinal en 25 (de 130, 19%) pacientes: 12 en genes de reparación de errores de emparejamiento y 13 en otros genes. Se encontró una variante de significado incierto en 23 (18%) pacientes. Es importante señalar que se identificó una mutación germinal patogénica en el 12% de los pacientes sin antecedentes familiares (frente al 32% con; p = 0,015) y en el 13% de aquellos con cánceres colorrectales competentes en la reparación de errores de emparejamiento (frente al 71% si eran deficientes; p < 0,001).LIMITACIÓN:Implementado en una sola institución académica terciaria.CONCLUSIÓN:Uno de cada cinco pacientes con enfermedad de inicio joven albergaba predisposición al cáncer de línea germinal. Esta tasa de detección, junto con un alto nivel de interés y aceptación por parte de los pacientes y la viabilidad de la implementación, respaldan la evaluación universal del riesgo de cáncer de línea germinal en esta población de pacientes. Consulte el Video Resumen en http://links.lww.com/DCR/B925 . (Traducción-Dr. Yesenia Rojas-Khalil ).

High Rate of Positive Circumferential Resection Margin in Colon Cancer: A National Appraisal and Call for Action.

OBJECTIVE: To identify rates of positive circumferential resection margin (CRM) for colon cancer surgery in the US. SUMMARY BACKGROUND DATA: CRM is one of the most important determinants of local control in colorectal cancers. The extent to which CRM involvement exists after colon cancer surgery is unknown. METHODS: Colon cancer cases with resection 2010 to 2015 were identified from the National Cancer Data Base. Adjusting for patient and tumor characteristics, comparisons were made between cases with CRM > 1 mm (negative margin) and those with margin involved with tumor or ≤ 1 mm (positive margin, CRM+). Hospital-level analysis was performed, examining observed-to-expected CRM+ rates. RESULTS: In total, 170,022 cases were identified: 150,291 CRM- and 19,731 CRM+ (11.6%). Pathologic T-category was the greatest predictor of CRM+, with higher rates in pT4(25.8%), pT4A(24.7%), and pT4B(31.5%) versus pT1(4.5%), pT2(6.3%) and pT3 (10.9%, P < 0.001). Within pT4 patients, predictors of CRM+ included signet-ring histology (38.1% vs 26.7% nonmucinous, and 26.9% mucinous adenocarcinoma, P < 0.001), removing < 12 lymph nodes (36.5% vs 26.1% >12, P < 0.001), community facilities (32.7%) versus academic/research (23.6%, P < 0.001), year (30.1% 2010 vs 22.6% 2015, P < 0.001), and hospital volume (24.5% highest quartile vs 32.7% lowest, P < 0.001). Across 1288 hospitals, observed-to-expected ratios for CRM+ ranged from 0 to 7.899; 429 facilities had higher than expected rates. CONCLUSIONS: Overall rate of CRM+ in US colon cancer cases is high. Variation exists across hospitals, with higher than expected rates in many facilities. Although biology is a major influencing factor, CRM+ rates represent an area for multidisciplinary improvement in quality of colon cancer care.

Definitive Intensity-Modulated Chemoradiation for Anal Squamous Cell Carcinoma: Outcomes and Toxicity of 428 Patients Treated at a Single Institution.

BACKGROUND: Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers. METHODS: Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan-Meier method. RESULTS: A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity. CONCLUSIONS: Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.

Quality and Location of the Surgical Episode Mediate a Large Proportion of Socioeconomic-Based Survival Disparities in Patients with Resected Stage I-III Colon Cancer.

INTRODUCTION: Lower socioeconomic status (SES) is associated with shorter overall survival (OS) in patients with locoregional colon cancer. We aimed to estimate: (1) the proportion of SES-based OS disparities mediated by disparities in the quality and location of surgical treatment in patients with resected stage I-III colon cancer and (2) the relative importance of components of surgical quality. PATIENTS AND METHODS: We examined patients ages 18-80 years with resected stage I-III colon adenocarcinoma using the 2010-2016 National Cancer Database. SES was defined at the zip code level. Inverse odds weighting mediation analysis was used to estimate the proportion mediated (PM) for nine treatment quality-related and facility-related factors and composite PMs in models including all nine mediators. Models compared high SES patients with each lower SES stratum. RESULTS: Among 171,009 patients, 5-year OS increased from 70.4% in low SES patients to 78.1% in high SES. When high SES patients were compared with low, lower-middle, and upper-middle SES patients, PM ranges among lower SES strata were: minimally invasive surgery 16.0-16.6%, lymph nodes examined 7.7-9.6%, positive margins 3.8-6.5%, length of stay 16.7-28.1%, readmissions insignificant to 3.7%, treatment at > 1 CoC facility 2.7-3.1%, facility type insignificant to 7.3%, facility volume 2.9-8.2%, and adjusted facility 90-day mortality rates 33.2-42.8%. Composite PMs were 76.9% (95% CI 61.3%, 92.4%) for low SES, 68.7% (95% CI 56.4%, 81.1%) for lower-middle SES, and 60.9% (95% CI 43.1%, 78.6%) for upper-middle SES. CONCLUSIONS: These data suggest that improving the quality of the surgical episode for disadvantaged patients undergoing resection for locoregional colon cancer could decrease SES-based survival disparities by over half.

International Consensus Definition of Low Anterior Resection Syndrome.

BACKGROUND: Low anterior resection syndrome is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The low anterior resection syndrome score was designed as a simple tool for clinical evaluation of low anterior resection syndrome. Although the low anterior resection syndrome score has good clinical utility, it may not capture all important aspects that patients may experience. OBJECTIVE: The aim of this collaboration was to develop an international consensus definition of low anterior resection syndrome that encompasses all aspects of the condition and is informed by all stakeholders. DESIGN: This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. PARTICIPANTS: Three expert groups participated: patients, surgeons, and other health professionals from 5 regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in 3 languages (English, Spanish, and Danish). MAIN OUTCOME MEASURE: The primary outcome measured was the priorities for the definition of low anterior resection syndrome. RESULTS: Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96%, and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to 8 symptoms and 8 consequences that capture essential aspects of the syndrome. LIMITATIONS: Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. CONCLUSIONS: This is the first definition of low anterior resection syndrome developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of low anterior resection syndrome. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in low anterior resection syndrome over time and with intervention.

Prevalence of high-grade anal dysplasia among women with high-grade lower genital tract dysplasia or cancer: Results of a pilot study.

OBJECTIVE: To estimate the prevalence of high-grade anal dysplasia in women with high-grade dysplasia or carcinoma of the cervix, vagina or vulva. METHODS: In this cross-sectional study, participants underwent anal cytology, anal HPV testing with Cervista HPV16/18 and high-resolution anoscopy (HRA). Patients with HSIL (high-grade squamous cell intraepithelial lesion) or greater on anal cytology or anal biopsy were referred to a colorectal surgery specialist for further evaluation. RESULTS: Seventy-five women were enrolled in the study, including 47 with cervical (cervix group), 10 with vaginal (vagina group), 15 with vulvar (vulva group), 1 with cervical and vaginal, and 2 with vulvar and vaginal disease. The median age in the cervix group (40 years (range 26-69)) was substantially younger than in the vagina (60 years (38-69)) and the vulva (59 years (36-75)) groups. Anal HSIL based on composite endpoints of the most severe cytology or histology result was diagnosed in 6 patients (8.0%). Anal cytology revealed HSIL in 2 (2.7%), atypical squamous cells of undetermined significance (ASCUS) in 12 (16.0%), low-grade squamous cell intraepithelial lesion (LSIL) in 2 (2.7%), and was normal in 59 (78.7%) patients. Anal HPV16/18 test was positive in 15 (20.0%), negative in 48 (64.0%) and insufficient in 12 (16.0%) patients. Of the 6 women with high-grade anal dysplasia, three (50%) had a positive anal HPV16/18 test. No case of anal cancer was observed. CONCLUSION: Our results suggest that the prevalence of anal HSIL is elevated among women with HPV-related lower genital tract dysplasia or cancer. To further support the inclusion of this high-risk group into screening guidelines for anal dysplasia, further studies are necessary to determine what screening strategy is suited to this population.

Oncological Outcomes After Robotic Proctectomy for Rectal Cancer: Analysis of a Prospective Database.

OBJECTIVE: The aim of this study is to evaluate the oncological outcomes of robotic total mesorectal excision (TME) at an NCI designated cancer center. SUMMARY BACKGROUND DATA: The effectiveness of laparoscopic TME could not be established, but the robotic-assisted approach may hold some promise, with improved visualization and ergonomics for pelvic dissection. Oncological outcome data is presently lacking. METHODS: Patients who underwent total mesorectal excision or tumor-specific mesorectal excision for rectal cancer between April 2009 and April 2016 via a robotic approach were identified from a prospective single-institution database. The circumferential resection margin (CRM), distal resection margin, and TME completeness rates were determined. Kaplan-Meier analysis of disease-free survival and overall survival was performed for all patients treated with curative intent. RESULTS: A total of 276 patients underwent robotic proctectomy during the study period. Robotic surgery was performed initially by 1 surgeon with 3 additional surgeons progressively transitioning from open to robotic during the study period with annual increase in the total number of cases performed robotically. Seven patients had involved circumferential resection margins (2.5%), and there were no positive distal or proximal resection margins. One hundred eighty-six patients had TME quality assessed, and only 1 patient (0.5%) had an incomplete TME. Eighty-three patients were followed up for a minimum of 3 years, with a local recurrence rate of 2.4%, and a distant recurrence rate of 16.9%. Five-year disease-free survival on Kaplan-Meier analysis was 82%, and 5-year overall survival was 87%. CONCLUSIONS: Robotic proctectomy for rectal cancer can be performed with good short and medium term oncological outcomes in selected patients.

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.

Oncologic Outcomes of Extended Robotic Resection for Rectal Cancer.

BACKGROUND: Surgery for locally advanced rectal cancers beyond the plane of total mesorectal excision (TME) or extramesorectal nodal involvement should include complete resection. This study evaluated the oncologic feasibility and safety of robot-assisted surgery for rectal cancer beyond the TME plane. METHODS: The study analyzed the operative, perioperative, and oncologic outcomes for all patients who underwent robot-assisted extended rectal cancer surgery from April 2009 to February 2015. RESULTS: Of 36 patients, 22 underwent multivisceral en bloc resection, and 18 underwent extramesorectal lymph node (EMRLN) dissection. The median tumor location was 5 cm [interquartile range (IQR), 2.2-9.0 cm] from the anal verge. A total of 32 patients underwent neoadjuvant chemoradiation therapy. The median body mass index of the patients was 26.8 kg/m(2) (IQR, 24.0-31.9 kg/m(2)). Conversion was required for one patient because of inability to tolerate the Trendelenburg position. All the resections were R0, and there were no incomplete TMEs. The vagina and prostate or periprostatic structures were the most commonly resected (n = 13/22), and the lateral pelvic nodes were the most common EMRLNs (n = 16/18). The median numbers of examined mesorectal lymph nodes and EMRLNs were respectively 20 (IQR, 18.0-28.0) and 2.5 (IQR, 1.0-6.0). The median hospital stay was 4 days (IQR, 3.0-5.5 days). Six patients experienced Clavien-Dindo grade 3 complications, the most common of which was deep abscess (n = 5, 13.8 %). The 5-year actuarial local recurrence rate was 3.6 %. CONCLUSIONS: Minimally invasive resection for rectal cancer can be performed with extended lymph node dissection or en bloc multivisceral resection using the surgical robot in selected patients. This technique is feasible and has acceptable morbidity.

Metachronous serrated neoplasia is uncommon after right colectomy in patients with methylator colon cancers with a high degree of microsatellite instability.

BACKGROUND: Right-sided serrated polyps are precursors to sporadic microsatellite unstable colon cancers via the methylator pathway and have a high rate of synchronous and metachronous lesions. Serrated polyps also occur in Lynch syndrome, where right-sided microsatellite unstable cancers arise from germline mutations in mismatch repair genes. OBJECTIVE: The aim of this study was to compare serrated neoplasia in patients with sporadic and hereditary microsatellite unstable colon cancer and to examine the effect of right colectomy on the risk of metachronous polyps and cancers. DESIGN: This is a retrospective, descriptive, cohort study from database and chart review. SETTING: This study was conducted at a tertiary care hospital with a center for hereditary colorectal cancer. PATIENTS: Patients who had colon cancers with a high degree of microsatellite instability, methylator cancers, and Lynch syndrome cancers, were included. INTERVENTIONS: Interventions included colectomy, surveillance colonoscopy, and polypectomy. MAIN OUTCOME MEASURES: The primary outcomes measured were the incidence and location of metachronous polyps and cancers. RESULTS: Eighty-five patients were included: 47 with methylator cancers and 38 with Lynch syndrome. Median ages at surgery were 75 years (range, 41-90) and 48 years (range, 27-77), p < 0.0001. Forty-six (98%) patients with methylator cancers and 17 (45%) patients with Lynch syndrome underwent a right colectomy, p < 0.0001. Metachronous cancers occurred in 19/60 (32%) of patients with Lynch syndrome and no patients with methylator cancers, p < 0.0001. Thirty-four patients with methylator cancers had colonoscopic follow-up, with a median of 2 colonoscopies per patient over a 32-month follow-up (range, 1-136). Sixty-three percent of patients with Lynch syndrome had colonoscopic follow-up, median of 4 colonoscopies per patient over 102 months (range, 1-462), p < 0.0001. Four (9%) patients with methylator cancers each had 1 metachronous serrated polyp, compared with 10/37 (27%) patients with Lynch syndrome (p = 0.049), whose median number of polyps was 2 (range, 1-8). Characteristics of other associated polyps were similar between cohorts. LIMITATIONS: This study is somewhat limited by potential inherent bias from its retrospective design. Also, a high number of deaths in the CIMP+ cohort could have contributed to the low number of serrated polyps detected on colonoscopy surveillance, but given current understanding of serrated polyp growth, this may truly represent the left colon's tendency not to develop serrated polyps. CONCLUSIONS: Cancers with a high degree of microsatellite instability arise through 2 different molecular mechanisms. Metachronous serrated neoplasia, benign and malignant, following right colectomy in patients with the CpG-island methylator phenotype of colorectal cancer is uncommon. However, the colons of patients with Lynch syndrome are at high risk after segmental colectomy.

The current multidisciplinary management of rectal cancer.

Multidisciplinary management of rectal cancer has rapidly evolved over the last several years. This review describes recent data surrounding total neoadjuvant therapy, organ preservation, and management of lateral pelvic lymph nodes. It then presents our treatment algorithm for management of rectal cancer at The University of Texas MD Anderson Cancer Center in the context of this and other existing literature. As part of this discussion, the review describes how we tailor management based upon both patient and tumor-related factors in an effort to optimize patient outcomes.

Daily Vaginal Dilator Use During Radiation for Women With Squamous Cell Carcinoma of the Anus: Vaginal Wall Dosimetry and Patient-Reported Sexual Function.

PURPOSE: At our institution, we treat patients with a daily vaginal dilator (VD) during chemoradiation (CRT) for squamous cell carcinoma of the anus (SCCA). We evaluated compliance with daily VD use, radiation dose to the vaginal wall (VW), and anterior vaginal wall (AVW), and patient-reported long-term sexual function. METHODS AND MATERIALS: We included women with SCCA who received definitive, intensity-modulated radiation therapy-based CRT. Women who were alive without evidence of disease received a patient-reported outcome survey, which included the Female Sexual Function Index (FSFI). We identified factors associated with FSFI, such as radiation dose to the VW and AVW using linear regression models and used Youden index analysis to estimate a dose cutoff to predict sexual dysfunction. RESULTS: Three hundred thirty-nine consecutively treated women were included in the analysis; 285 (84.1%) were treated with a daily VD. Of 184 women alive without disease, 90 patients (49%) completed the FSFI, and 51 (56.7%) were sexually active with valid FSFI scores. All received therapy with a daily VD. Forty-one women (80%) had sexual dysfunction. Univariate analysis showed higher dose to 50% (D50%) of the AVW correlated with worse FSFI (ß -.262; P = .043), worse desire FSFI subscore (ß -.056; P = .003), and worse pain FSFI subscore (ß -.084; P = .009). Younger age correlated with worse pain FSFI subscale (ß .067; P = .026). Age (ß .070; P = .013) and AVW D50% (ß -.087; P = .009) were significant on multivariable analysis. AVW D50% >48 Gy predicted increased risk of sexual dysfunction. CONCLUSIONS: Daily VD use is safe and well tolerated during CRT for SCCA. Using a VD during treatment to displace the AVW may reduce the risk for sexual dysfunction. Limiting the AVW D50% <48 Gy may further reduce the risk but additional data are needed to validate this constraint.