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 non-metastatic 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 non-metastatic 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 during the interim from April to September 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) non-metastatic disease; (4) neoadjuvant immunotherapy; (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 7,691 studies identified, 6,370 were screened, and 8 included. Various agents, dosing regimens, and treatment durations were employed, with durations of immunotherapy ranging from 1-16 cycles. Complete R0 resections were consistently achieved in 98%-100% of resections. Of patients who received neoadjuvant immunotherapy and underwent resection, 50%-91% had ypT0N0 pathology. The safety profiles were generally favorable, with Grade 1-2 treatment-related adverse events (mostly immune-related) during immunotherapy reported in 22.2%-70% of patients. Postoperative complications following 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.

Patient and surgeon preferences for early ileostomy closure following restorative proctectomy for rectal cancer: why aren't we doing it?

BACKGROUND: Early ileostomy closure (EIC), ≤ 2 weeks from creation, is a relatively new practice. Multiple studies have demonstrated that this approach is safe, feasible, and cost-effective. Despite the demonstrated benefits, this is neither routine practice, nor has it been studied, in North America. This study aimed to assess patient and surgeon perspectives about EIC. METHODS: A mixed-methods, cross-sectional study of patients and surgeons was performed. Rectal cancer survivors from a single institution who underwent restorative proctectomy with diverting loop ileostomy and subsequent closure within the last 5 years were contacted. North American surgeons with high rectal cancer volumes (> 20 cases/year) were included. Surveys (patients) and semi-structured interviews (surgeons) were conducted. Analysis employed descriptive statistics and thematic analysis, respectively. RESULTS: Forty-eight patients were surveyed (mean age 65.1 ± 11.8 years; 54.2% male). Stoma closure occurred after a median of 7.7 months (IQR 4.8-10.9) and 50.0% (24) found it "difficult" or "very difficult" to live with their stoma. Patients considered improvement in quality of life and quicker return to normal function the most important advantages of EIC, whereas the idea of two operations in two weeks being too taxing on the body was deemed the biggest disadvantage. Most patients (35, 72.9%) would have opted for EIC. Surgeon interviews (15) revealed 4 overarching themes: (1) there are many benefits to EIC; (2) specific patient characteristics would make EIC an appropriate option; (3) many barriers to implementing EIC exist; and (4) many logistical hurdles need to be addressed for successful implementation. Most surgeons (12, 80.0%) would "definitely want to participate" in a North American randomized-controlled trial (RCT) on EIC for rectal cancer patients. CONCLUSIONS: Implementing EIC poses many logistical challenges. Both patients and surgeons are interested in further exploring EIC and believe it warrants a North American RCT to motivate a change in practice.

Clinical practice guidelines for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons and the Society of American Gastrointestinal and Endoscopic Surgeons.

The American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) are dedicated to ensuring high-quality innovative patient care for surgical patients by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus as well as minimally invasive surgery. The ASCRS and SAGES society members involved in the creation of these guidelines were chosen because they have demonstrated expertise in the specialty of colon and rectal surgery and enhanced recovery. This consensus document was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and develop clinical practice guidelines based on the best available evidence. While not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, healthcare workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient. This clinical practice guideline represents a collaborative effort between the American Society of Colon and Rectal Surgeons (ASCRS) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and was approved by both societies.

The SAGES MASTERS program presents: the 10 seminal articles for the Laparoscopic Right Colectomy Pathway.

BACKGROUND: As one of the 12 clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program, the Colorectal Pathway intends to deliver didactic content organized along 3 levels of performance (competency, proficiency and mastery) each represented by an anchoring procedure (laparoscopic right colectomy, laparoscopic left/sigmoid colectomy, and intracorporeal anastomosis during minimally invasive (MIS) ileocecal or right colon resection). In this article, the SAGES Colorectal Task Force presents focused summaries of the top 10 seminal articles selected for laparoscopic right colectomy which surgeons should be familiar with. METHODS: Using a systematic literature search of Web of Science, the most cited articles on laparoscopic right colectomy were identified, reviewed, and ranked by the SAGES Colorectal Task Force and invited subject experts. Additional articles not identified in the literature search were included if deemed impactful by expert consensus. The top 10 ranked articles were then summarized, with emphasis on relevance and impact in the field, findings, strengths and limitations, and conclusions. RESULTS: The top 10 seminal articles selected for the laparoscopic right colectomy anchoring procedure include articles on surgical techniques for benign and malignant disease, with anatomical and video illustrations, comparative outcomes of laparoscopic vs open colectomy, variations in technique with impact on clinical outcomes, and assessment of the learning curve. CONCLUSIONS: The top 10 seminal articles selected for laparoscopic right colectomy illustrate the diversity both in content and format of the educational curriculum of the SAGES Masters Program to support practicing surgeon progression to mastery within the Colorectal Pathway.

Perfusion Assessment in Left-Sided/Low Anterior Resection (PILLAR III): A Randomized, Controlled, Parallel, Multicenter Study Assessing Perfusion Outcomes With PINPOINT Near-Infrared Fluorescence Imaging in Low Anterior Resection.

BACKGROUND: Indocyanine green fluoroscopy has been shown to improve anastomotic leak rates in early phase trials. OBJECTIVE: We hypothesized that the use of fluoroscopy to ensure anastomotic perfusion may decrease anastomotic leak after low anterior resection. DESIGN: We performed a 1:1 randomized controlled parallel study. Recruitment of 450 to 1000 patients was planned over 2 years. SETTINGS: This was a multicenter trial. PATIENTS: Included patients were those undergoing resection defined as anastomosis within 10 cm of the anal verge. INTERVENTION: Patients underwent standard evaluation of tissue perfusion versus standard in conjunction with perfusion evaluation using indocyanine green fluoroscopy. MAIN OUTCOME MEASURES: Primary outcome was anastomotic leak, with secondary outcomes of perfusion assessment and the rate of postoperative abscess requiring intervention. RESULTS: This study was concluded early because of decreasing accrual rates. A total of 25 centers recruited 347 patients, of whom 178 were randomly assigned to perfusion and 169 to standard. The groups had comparable tumor-specific and patient-specific demographics. Neoadjuvant chemoradiation was performed in 63.5% of perfusion and 65.7% of standard (p > 0.05). Mean level of anastomosis was 5.2 ± 3.1 cm in perfusion compared with 5.2 ± 3.3 cm in standard (p > 0.05). Sufficient visualization of perfusion was reported in 95.4% of patients in the perfusion group. Postoperative abscess requiring surgical management was reported in 5.7% of perfusion and 4.2% of standard (p = 0.75). Anastomotic leak was reported in 9.0% of perfusion compared with 9.6% of standard (p = 0.37). On multivariate regression analysis, there was no difference in anastomotic leak rates between perfusion and standard (OR = 0.845 (95% CI, 0.375-1.905); p = 0.34). LIMITATIONS: The predetermined sample size to adequately reduce the risk of type II error was not achieved. CONCLUSIONS: Successful visualization of perfusion can be achieved with indocyanine green fluoroscopy. However, no difference in anastomotic leak rates was observed between patients who underwent perfusion assessment versus standard surgical technique. In experienced hands, the addition of routine indocyanine green fluoroscopy to standard practice adds no evident clinical benefit. See Video Abstract at http://links.lww.com/DCR/B560. VALORACIN DE LA IRRIGACIN DE LADO IZQUIERDO/RESECCIN ANTERIOR BAJA PILAR III UN ESTUDIO ALEATORIZADO, CONTROLADO, PARALELO Y MULTICNTRICO QUE EVALA LOS RESULTADOS DE LA IRRIGACIN CON PINPOINT IMGENES DE FLUORESCENCIA CERCANA AL INFRARROJO EN LA RESECCIN ANTERIOR BAJA: ANTECEDENTES:Se ha demostrado que la fluoroscopia con verde de indocianina mejora las tasas de fuga anastomótica en ensayos en fases iniciales.OBJETIVO:Nuestra hipótesis es que la utilización de fluoroscopia para asegurar la irrigación anastomótica puede disminuir la fuga anastomótica luego de una resección anterior baja.DISEÑO:Realizamos un estudio paralelo, controlado, aleatorizado 1:1. Se planificó el reclutamiento de 450-1000 pacientes durante 2 años.AMBITO:Multicéntrico.PACIENTES:Pacientes sometidos a resección definida como una anastomosis dentro de los 10cm del margen anal.INTERVENCIÓN:Pacientes que se sometieron a la evaluación estándar de la irrigación tisular contra la estándar en conjunto con la valoración de la irrigación mediante fluoroscopia con verde indocianina.PRINCIPALES VARIABLES EVALUADAS:El principal resultado fue la fuga anastomótica, y los resultados secundarios fueron la evaluación de la perfusión y la tasa de absceso posoperatorio que requirió intervención.RESULTADOS:Este estudio se cerró anticipadamente debido a la disminución de las tasas de acumulación. Un total de 25 centros reclutaron a 347 pacientes, de los cuales 178 fueron, de manera aleatoria, asignados a perfusión y 169 a estándar. Los grupos tenían datos demográficos específicos del tumor y del paciente similares. Recibieron quimio-radioterapia neoadyuvante el 63,5% de la perfusión y el 65,7% del estándar (p> 0,05). La anastomosis estuvo en un nivel promedio de 5,2 + 3,1 cm en perfusión en comparación con 5,2 + 3,3 cm en estándar (p> 0,05). Se reportó una visualización suficiente de la perfusión en el 95,4% de los pacientes del grupo de perfusión. El absceso posoperatorio que requirió tratamiento quirúrgico fue de 5,7% de los perfusion y en el 4,2% del estándar (p = 0,75). Se informó fuga anastomótica en el 9,0% de la perfusión en comparación con el 9,6% del estándar (p = 0,37). En el análisis de regresión multivariante, no hubo diferencias en las tasas de fuga anastomótica entre la perfusión y el estándar (OR 0,845; IC del 95% (0,375; 1,905); p = 0,34).LIMITACIONES:No se logró el tamaño de muestra predeterminado para reducir satisfactoriamente el riesgo de error tipo II.CONCLUSIÓN:Se puede obtener una visualización adecuada de la perfusión con ICG-F. Sin embargo, no se observaron diferencias en las tasas de fuga anastomótica entre los pacientes que se sometieron a evaluación de la perfusión versus la técnica quirúrgica estándar. En manos expertas, agregar ICG-F a la rutina de la práctica estándar no agrega ningún beneficio clínico evidente. Consulte Video Resumen en http://links.lww.com/DCR/B560. (Traducción-Dr Juan Antonio Villanueva-Herrero).