Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

NCCN Guidelines Insights: Rectal Cancer, Version 6.2020.

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E- or HER2 amplification-positive disease.

Pelvic/Perineal Reconstruction: Time to Consider the Anterolateral Thigh Flap as a First-line Option?

BACKGROUND: Abdominoperineal resection (APR) and pelvic exenteration continue to be common procedures for the treatment of colorectal malignancy. The workhorse flap for reconstruction in these instances has been the vertical rectus abdominis myocutaneous flap. The associated donor site morbidity, however, cannot be ignored. Here, we provide a review of the literature and present the senior author's (A.M.) experience using the pedicled anterolateral thigh (ALT) flap for reconstruction of soft tissue defects following APR and pelvic exenteration. METHODS: Patients who underwent pelvic/perineal reconstruction with pedicled ALT flaps between 2017 and 2019 were included in the study. Parameters of interest included age, gender, body mass index, comorbidities, history of radiation, extent of ablative surgery, and postoperative complication rate. RESULTS: A total of 23 patients (16 men and 7 women) with a median age and body mass index of 66 years (inter-quartile range [IQR]: 49-71 years) and 24.9 kg/m2 (IQR: 24.2-26.7 kg/m2) were included in the study, respectively. Thirteen (56.5%) patients presented with rectal cancer, 5 (21.7%) with anal squamous cell carcinoma (SCC), 4 (17.4%) with Crohn's disease, and 1 (4.3%) with Paget's disease. Nineteen patients (82.6%) received neoadjuvant radiation. Nine (39.1%) patients experienced 11 complications (2 major and 9 minor). The most common complication was partial perineal wound dehiscence (N = 6 [26.1%]). Stable soft tissue coverage was achieved in all but one patient. CONCLUSIONS: The ALT flap allows for stable soft tissue coverage following APR and pelvic exenteration without being associated with abdominal donor site morbidity. Consideration to its use as a first-line reconstructive option should be given in pelvic/perineal reconstruction.

Oncologic and Perioperative Outcomes of Laparoscopic, Open, and Robotic Approaches for Rectal Cancer Resection: A Multicenter, Propensity Score-Weighted Cohort Study.

BACKGROUND: Minimally invasive approaches have been shown to reduce surgical site complications without compromising oncologic outcomes. OBJECTIVE: The primary aim of this study is to evaluate the rates of successful oncologic resection and postoperative outcomes among laparoscopic, open, and robotic approaches to rectal cancer resection. DESIGN: This is a multicenter, quasiexperimental cohort study using propensity score weighting. SETTINGS: Interventions were performed in hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program. PATIENTS: Adult patients who underwent rectal cancer resection in 2016 were included. MAIN OUTCOME MEASURES: The primary outcome was a composite variable indicating successful oncologic resection, defined as negative distal and radial margins with at least 12 lymph nodes evaluated. RESULTS: Among 1028 rectal cancer resections, 206 (20%) were approached laparoscopically, 192 (18.7%) were approached robotically, and 630 (61.3%) were open. After propensity score weighting, there were no significant sociodemographic or preoperative clinical differences among subcohorts. Compared to the laparoscopic approach, open and robotic approaches were associated with a decreased likelihood of successful oncologic resection (ORadj = 0.64; 95% CI, 0.43-0.94 and ORadj = 0.60; 95% CI, 0.37-0.97), and the open approach was associated with an increased likelihood of surgical site complications (ORadj = 2.53; 95% CI, 1.61-3.959). Compared to the laparoscopic approach, the open approach was associated with longer length of stay (6.8 vs 8.6 days, p = 0.002). LIMITATIONS: This was an observational cohort study using a preexisting clinical data set. Despite adjusted propensity score methodology, unmeasured confounding may contribute to our findings. CONCLUSIONS: Resections that were approached laparoscopically were more likely to achieve oncologic success. Minimally invasive approaches did not lengthen operative times and provided benefits of reduced surgical site complications and decreased postoperative length of stay. Further studies are needed to clarify clinical outcomes and factors that influence the choice of approach. See Video Abstract at http://links.lww.com/DCR/B70. RESULTADOS ONCOLÓGICOS Y PERIOPERATORIOS DE LOS ABORDAJES LAPAROSCÓPICOS, ABIERTOS Y ROBÓTICOS PARA LA RESECCIÓN DEL CÁNCER RECTAL: UN ESTUDIO DE COHORTE MULTICÉNTRICO Y PONDERADO DEL PUNTAJE DE PROPENSIÓN: Se ha demostrado que los enfoques mínimamente invasivos reducen las complicaciones del sitio quirúrgico sin comprometer los resultados oncológicos.El objetivo principal de este estudio es evaluar las tasas de resección oncológica exitosa y los resultados postoperatorios entre los abordajes laparoscópico, abierto y robótico para la resección del cáncer rectal.Este es un estudio de cohorte cuasi-experimental multicéntrico que utiliza la ponderación de puntaje de propensión.Las intervenciones se realizaron en hospitales que participan en el Programa Nacional de Mejora de la Calidad Quirúrgica del Colegio Americano de Cirujanos.Se incluyeron pacientes adultos que se sometieron a resección de cáncer rectal en 2016.El resultado primario fue una variable compuesta que indicaba una resección oncológica exitosa, definida como márgenes negativos distales y radiales con al menos 12 ganglios linfáticos evaluados.Entre 1,028 resecciones de cáncer rectal, 206 (20%) fueron abordadas por vía laparoscópica, 192 (18.7%) robóticamente y 630 (61.3%) abiertas. Después de ponderar el puntaje de propensión, no hubo diferencias sociodemográficas o clínicas preoperatorias significativas entre las subcohortes. En comparación con el abordaje laparoscópico, los abordajes abiertos y robóticos se asociaron con una menor probabilidad de resección oncológica exitosa (ORadj = 0.64; IC 95%, 0.43-0.94 y ORadj = 0.60; IC 95%, 0.37-0.97), y el abordaje abierto se asoció con una mayor probabilidad de complicaciones del sitio quirúrgico (ORadj = 2.53; IC 95%, 1.61-3.959). En comparación con el abordaje laparoscópico, el abordaje abierto se asoció con una estadía más prolongada (6.8 frente a 8.6 días, p = 0.002).Este fue un estudio de cohorte observacional que utilizó un conjunto de datos clínicos preexistentes. A pesar de la metodología de puntuación de propensión ajustada, la confusión no medida puede contribuir a nuestros hallazgos.Las resecciones que se abordaron por vía laparoscópica tuvieron más probabilidades de lograr el éxito oncológico. Los enfoques mínimamente invasivos no alargaron los tiempos quirúrgicos y proporcionaron beneficios de la reducción de las complicaciones del sitio quirúrgico y la disminución de la duración de la estadía postoperatoria. Se necesitan más estudios para aclarar los resultados clínicos y los factores que influyen en la elección del enfoque. Vea video resumen en http://links.lww.com/DCR/B70.

Small Bowel Adenocarcinoma, Version 1.2020, NCCN Clinical Practice Guidelines in Oncology.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract that has increased in incidence across recent years. Often diagnosed at an advanced stage, outcomes for SBA are worse on average than for other related malignancies, including colorectal cancer. Due to the rarity of this disease, few studies have been done to direct optimal treatment, although recent data have shown that SBA responds to treatment differently than colorectal cancer, necessitating a separate approach to treatment. The NCCN Guidelines for Small Bowel Adenocarcinoma were created to establish an evidence-based standard of care for patients with SBA. These guidelines provide recommendations on the workup of suspected SBA, primary treatment options, adjuvant treatment, surveillance, and systemic therapy for metastatic disease. Additionally, principles of imaging and endoscopy, pathologic review, surgery, radiation therapy, and survivorship are described.

Anal Carcinoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Anal Carcinoma provide recommendations for the management of patients with squamous cell carcinoma of the anal canal or perianal region. Primary treatment of anal cancer usually includes chemoradiation, although certain lesions can be treated with margin-negative local excision alone. Disease surveillance is recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is essential for optimal patient care.

Rectal Cancer, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer. This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection.

NCCN Guidelines Insights: Colon Cancer, Version 2.2018.

The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions.

Rectal Cancer, Version 2.2015.

The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease.

Insulin increases the release of proinflammatory mediators.

BACKGROUND: Strict glucose control with insulin is associated with decreased mortality in a mixed patient population in the intensive care unit. Controversy exists regarding the relative benefits of glucose control versus a direct advantageous effect of exogenous insulin. As a combined medical/surgical population differs significantly from the critically injured patient primed for secondary insult, our purpose was to determine the influence of insulin on activated macrophages. Our hypothesis was that insulin would directly abrogate the inflammatory cascade. METHODS: Differentiated human monocytic THP-1 cells were stimulated with endotoxin (lipopolysaccharide [LPS], 100 ng/mL) for 6 hours. Cells were treated +/-10(-7) M insulin for 1 hour and 24 hours. Total RNA was isolated and gene expression for TNF-alpha and IL-6 performed using Q-RT-PCR. Supernatants were assayed for TNF-alpha and IL-6 protein by ELISA. RESULTS: At 1 hour, compared with macrophages treated with LPS alone, macrophages treated with insulin produced significantly more TNF-alpha protein (11.4 +/- 5.9 pg/mL vs. 32.5 +/- 3.1 pg/mL; p < 0.03). At 24 hours compared with macrophages treated with LPS alone, macrophages treated with insulin produced significantly more TNF-alpha protein (83 +/- 2.02 pg/mL vs. 114 +/- 6.54 pg/mL; p < 0.01). However, gene expression of TNF-alpha and IL-6 was not different in LPS stimulated macrophages with and without insulin treatment at both 1 hour and 24 hours. CONCLUSION: Contrary to our hypothesis, insulin does not have direct anti-inflammatory properties in this experimental model. In fact, insulin increases proinflammatory cytokine protein levels from activated macrophages.