Evaluation and Management of Malignant Colorectal Polyps.

The detection rate of dysplastic colorectal polyps has significantly increased with improved screening programs. Treatment of dysplastic polyps attempt to limit morbidity of a procedure while also considering the risk of occult lymph node metastasis. Therefore, a variety of methods have been developed to predict the rate of lymph node metastasis to help identify the optimal treatment of patients. These include both the endoscopic and pathologic assessment of the lesion. In order to reduce the morbidity of surgery for patients with low-risk lesions, multiple endoscopic therapies have been developed, including endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic intermuscular dissection, and transanal endoscopic surgery.

Colorectal Neoplasia in the Setting of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (colorectal adenocarcinoma [CRC]) compared with the general population. IBD-related CRC is related to poorer outcomes than non-IBD-related CRC, and it accounts for 10% to 15% of death in patients with IBD. As such, screening guidelines have been made specific to this population recommending shorter intervals of endoscopic screening to detect dysplasia and CRC relative to the general population. Advances in endoscopic technology allow for improved visualization of dysplasia, which has led to widespread adoption of dye-spray chromoendoscopy with targeted biopsy.

Colorectal Disease and the Gut Microbiome: What a Surgeon Needs to Know.

The gut microbiome is defined as the microorganisms that reside within the gastrointestinal tract and produce a variety of metabolites that impact human health. These microbes play an intricate role in human health, and an imbalance in the gut microbiome, termed gut dysbiosis, has been implicated in the development of varying diseases. The purpose of this review is to highlight what is known about the microbiome and its impact on colorectal cancer, inflammatory bowel disease, constipation, Clostridioides difficile infection, the impact of bowel prep, and anastomotic leaks.

Medical Management of Inflammatory Bowel Disease.

The past few decades have seen significant advancements in the medical management of both ulcerative colitis (UC) and Crohn's disease (CD). The previous dependence on steroids is no longer an acceptable strategy following the Food and Drug Administration approval for several new classes of medication. These medications include aminosalicylates, immunomodulators, biologics, and oral targeted small-molecule inhibitors. This article highlights several key trials and discusses modern treatment paradigms for both UC and CD based on disease severity.

Combinatorial Inhibition of Complement Factor D and BCL2 for Early-Onset Colorectal Cancer.

BACKGROUND: The tumor immune microenvironment is distinct between early-onset and late-onset colorectal cancer, which facilitates tumor progression. We previously identified several genes, including complement factor D, as having increased expression in patients with early-onset colorectal cancer. OBJECTIVE: This study aimed to assess and validate the differential expression of immune genes in early-onset and late-onset colorectal cancer. We also aimed to test known drugs targeting genes increased in early-onset colorectal cancer in preclinical mouse models. DESIGN: A retrospective cohort study with analysis was performed using tumor RNA from formalin-fixed paraffin-embedded cell culture and immunohistochemistry to validate gene expression and function and in vivo preclinical tumor study to assess drug efficacy. SETTINGS: The Oregon Colorectal Cancer Registry was queried to identify patients with colorectal cancer. PATIENTS: The study included 67 patients with early-onset colorectal cancer and 54 patients with late-onset colorectal cancer. INTERVENTIONS: Preclinical animal models using the HCT-116 colon cancer cell line were treated with the complement factor D inhibitor danicopan and the BCL2 inhibitor venetoclax, or with vehicle controls. MAIN OUTCOME MEASURES: Elevated RNA signatures using NanoString data were evaluated by the retrospective cohort. When inhibiting these markers in the mouse preclinical model, tumor volume and weight were the main outcome measures. RESULTS: After updating our sample size from our previously published data, we found that complement factor D and BCL2, genes with known function and small molecule inhibitors, are elevated in patients with early-onset colorectal cancer. When inhibiting these markers with the drugs danicopan and venetoclax in a mouse model, we found that the combination of these drugs decreased tumor burden but also resulted in toxicity. LIMITATIONS: This study is limited by a small sample size and a subcutaneous tumor model. CONCLUSIONS: Combinatorial inhibition of early-onset associated genes complement factor D and BCL2 slows the growth of early-onset colorectal cancer in a mouse preclinical model. See Video Abstract . INHIBICIN COMBINADA DEL FACTOR DCOMPLEMENTARIO Y DEL BCL EN CASOS DE CNCER COLORRECTAL DE APARICIN TEMPRANA: ANTECEDENTES:El microambiente inmunológico del tumor es distinto entre el cáncer colorrectal de aparición temprana y el de aparición tardía, lo que facilita la progresión de dicho tumor. Anteriormente identificamos varios genes, incluidos el factor D-Complementario, con una mayor expresión en pacientes con cáncer colorrectal de aparición temprana.OBJETIVO:El presente estudio tuvo como objetivo el evaluar y validar la expresión diferenciada de genes inmunes en casos de cáncer colorrectal de aparición temprana y tardía. También nos propusimos evaluar los fármacos conocidos dirigidos sobre los genes aumentados en el cáncer colorrectal de aparición temprana en modelos pre-clínicos en ratones.DISEÑO:Estudio de cohortes con análisis retrospectivo utilizando el ARN tumoral procedente de cultivos celulares fijados con formalina e incluidos en parafina, y el analisis por inmunohistoquímica para validar la expresión y la función genética. Se realizó el estudio pre-clínico de los tumores in vivo para evaluar la eficacia de los fármacos.AJUSTES:Se consultó el Registro de Oregon de casos de Cáncer Colorrectal para encontrar los pacientes afectados.SUJETOS:67 pacientes con cáncer colorrectal de aparición temprana y 54 pacientes con cáncer colorrectal de aparición tardía.INTERVENCIONES (SI LAS HUBIESE):Los modelos animales pre-clínicos que utilizaron la línea celular de cáncer de colon HCT-116 se trataron con el inhibidor del factor D-Complementario o Danicopan y con el inhibidor de BCL-2 o Venetoclax, ambos con control del transportador.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron las firmas de ARN elevadas utilizando los datos del NanoString a partir de la cohorte retrospectiva. Al inhibir estos marcadores del modelo pre-clínico en los ratones, el volumen y el peso del tumor fueron las principales medidas de resultado.RESULTADOS:Después de actualizar el tamaño de nuestra muestra a partir de datos publicados con anterioridad, encontramos que el factor D-Complementario y BCL-2, genes con función conocida e inhibidores de moléculas pequeñas, se encuentran elevados en aquellos pacientes con cáncer colorrectal de aparición temprana. Al inhibir estos marcadores con los medicamentos Danicopan y Venetoclax en el modelo de ratones vivos, encontramos que la combinación de estos dos farmacos disminuyó la carga tumoral pero también produjo toxicidad.LIMITACIONES:Estudio limitado por un tamaño de muestra pequeño y el modelo de tumor subcutáneo.CONCLUSIONES:La inhibición combinada de genes asociados de aparición temprana, el factor D-Complementario y el BCL-2, enlentecen el crecimiento del cáncer colorrectal de aparición temprana del modelo preclínico en ratones. (Traducción-Dr. Xavier Delgadillo ).

Updated Management of Colorectal Cancer Liver Metastases: Scientific Advances Driving Modern Therapeutic Innovations.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States and accounts for an estimated 1 million deaths annually worldwide. The liver is the most common site of metastatic spread from colorectal cancer, significantly driving both morbidity and mortality. Although remarkable advances have been made in recent years in the management for patients with colorectal cancer liver metastases, significant challenges remain in early detection, prevention of progression and recurrence, and in the development of more effective therapeutics. In 2017, our group held a multidisciplinary state-of-the-science symposium to discuss the rapidly evolving clinical and scientific advances in the field of colorectal liver metastases, including novel early detection and prognostic liquid biomarkers, identification of high-risk cohorts, advances in tumor-immune therapy, and different regional and systemic therapeutic strategies. Since that time, there have been scientific discoveries translating into therapeutic innovations addressing the current management challenges. These innovations are currently reshaping the treatment paradigms and spurring further scientific discovery. Herein, we present an updated discussion of both the scientific and clinical advances and future directions in the management of colorectal liver metastases, including adoptive T-cell therapies, novel blood-based biomarkers, and the role of the tumor microbiome. In addition, we provide a comprehensive overview detailing the role of modern multidisciplinary clinical approaches used in the management of patients with colorectal liver metastases, including considerations toward specific molecular tumor profiles identified on next generation sequencing, as well as quality of life implications for these innovative treatments.

Gut microbial metabolites and its impact on human health.

One of the primary methods by which the gut microbiome interacts with its host is through the interactions that occur through the production of the metabolites produced, either directly, or indirectly, through microbial metabolism. Decades of research has demonstrated that these metabolic products play a vital role in human health, either for its benefit or detriment. This review article highlights the main metabolites produced by the interactions between diet and the gut microbiome, bile acids and the gut microbiome, and products produced by the gut microbiome alone. Additionally, this article reviews the literature on the effects that these metabolites play on human health.

Synbiotics and Surgery: Can Prebiotics and Probiotics Affect Inflammatory Surgical Outcomes?

PURPOSE OF REVIEW: Prebiotics, probiotics, and synbiotics have received increasing attention over the years for their beneficial impact on the gut microbiome and for their systemic anti-inflammatory effects. They have also been shown to improve surgical outcomes. Here, we review the inflammatory effects of surgery as well as the data which suggests a benefit of prebiotics, probiotics, and synbiotics taken in the perioperative period. RECENT FINDINGS: Synbiotics and fermented foods may have an even greater anti-inflammatory effect than probiotics or prebiotics alone. Recent data suggest that the anti-inflammatory effects and microbiome changes brought on by prebiotics, probiotics, and synbiotics have the potential to improve surgical outcomes. We highlight the potential to alter systemic inflammation, surgical and hospital-acquired infections, colorectal cancer formation, recurrence, and anastomotic leak. Synbiotics could also impact metabolic syndrome. Prebiotics, probiotics, and especially synbiotics may be extremely beneficial when taken in the perioperative period. Even short-term gut microbiome pre-habilitation could alter surgical outcomes significantly.

All Fiber is Not Fiber.

PURPOSE OF REVIEW: Epidemiologic studies and clinical trials have demonstrated the benefits of dietary fiber. This occurs through a combination of the physiochemical properties of fiber and through microbial fermentation that occurs in the colon which result in the production of short-chain fatty acids (SCFA). The purpose of this review is to highlight the physiochemical properties of fiber that result in the range of physiologic effects and to review the literature on the health benefits of acetate, propionate, and butyrate. RECENT FINDINGS: Of the variety of properties and functions exerted by dietary fibers, the fermentability and production of SCFA's are emphasized in this review. Studies done in both animal and humans reveal the anti-obesity, anti-inflammatory, and possible anti-neoplastic roles SCFAs exert at the mucosal level. Many clinical questions remain regarding the optimal dose, type, and method of delivery of fiber to exert the desired beneficial effects. It has the potential to be used in the management of clinical symptoms, prevention of disease, and improvement in human health. Further studies to address this novel use of fiber has the potential to make a large impact in clinical practice.

Feasibility of an Image-Based Mobile Health Protocol for Postoperative Wound Monitoring.

BACKGROUND: Surgical site infection (SSI) is the most common nosocomial infection and the leading cause of readmission among surgical patients. Many SSIs develop in the postdischarge period and are inadequately recognized by patients. To address this, we developed a mobile health protocol of remote wound monitoring using smartphone technology. The current study aims to establish its feasibility among patients and providers. STUDY DESIGN: We enrolled vascular surgery patients during their inpatient stay. They were trained to use our mobile health application, which allowed them to transmit digital images of their surgical wound and answer a survey about their recovery. After hospital discharge, participants completed the application daily for 2 weeks. Providers on the inpatient team reviewed submissions daily and contacted patients for concerning findings. RESULTS: Forty participants were enrolled. Forty-five percent of participants submitted data every day for 2 weeks, with an overall submission rate of 90.2%. Submissions were reviewed within an average of 9.7 hours of submission, with 91.9% of submissions reviewed within 24 hours. We detected 7 wound complications with 1 false negative. Participant and provider satisfaction was universally high. CONCLUSIONS: Patients and their caregivers are willing to participate in a mobile health program aimed at remote monitoring of postoperative recovery, and they are able to complete it with a high level of fidelity and satisfaction. Preliminary results indicate the ability to detect and intervene on wound complications.

Feasibility of Implementing a Patient-Centered Postoperative Wound Monitoring Program Using Smartphone Images: A Pilot Protocol.

BACKGROUND: Surgical site infections (SSI) represent a significant public health problem as the most common nosocomial infection and a leading cause of unplanned hospital readmissions among surgical patients. Many develop following hospital discharge and often go unrecognized by patients. Telemedicine offers the opportunity to leverage the mobile technology to remotely monitor wound recovery in the transitional period between hospital discharge and routine clinic follow-up. However, many existing telemedicine platforms are episodic, replacing routine follow-up, rather than equipped for continued monitoring; they include only low-risk patient populations and those who already have access to and comfort with the necessary technology; and transmit no visual information. OBJECTIVE: Drawing upon the Coleman model for care transitions and the Proctor model for implementation, we propose a protocol of postoperative wound monitoring using smartphone digital images. In this study, we will establish the feasibility of such a program, both for patients and for the clinical care team. METHODS: We will recruit 40 patients or patient/caregiver pairs from our inpatient vascular surgery service. Eligible patients will be English-speaking, 18 years of age or older, and have an incision at least 3 cm in length. Participants will receive a training session, during which they will learn to use the device and the wound monitoring smartphone app. Following hospital discharge, they will submit digital images of their wound and responses to a survey about their recovery for 14 days. Experienced health care providers on the vascular surgery inpatient service will review transmitted data daily and contact patients for any concerning findings. RESULTS: Primary outcomes will include participant adherence to the protocol, time required for providers to review submissions, time from submission to provider review, and participant satisfaction. Secondary outcomes will include SSI detection and hospital readmission. CONCLUSIONS: Health systems are increasingly dedicating efforts to transitional care improvement programs. This feasibility trial will confirm whether patients and their caregivers can learn to use a postdischarge wound monitoring smartphone app and will assess patient and provider satisfaction. This protocol will provide preliminary evidence for a shift in the delivery of postdischarge care in a patient-centered and cost-effective manner. TRIAL REGISTRATION: Clinicaltrials.gov NCT02735525; https://clinicaltrials.gov/ct2/show/NCT02735525 (Archived by WebCite at http://www.webcitation.org/6oIvN4Mab).

Cardiac sympathetic denervation in 6-OHDA-treated nonhuman primates.

Cardiac sympathetic neurodegeneration and dysautonomia affect patients with sporadic and familial Parkinson's disease (PD) and are currently proposed as prodromal signs of PD. We have recently developed a nonhuman primate model of cardiac dysautonomia by iv 6-hydroxydopamine (6-OHDA). Our in vivo findings included decreased cardiac uptake of a sympathetic radioligand and circulating catecholamines; here we report the postmortem characterization of the model. Ten adult rhesus monkeys (5-17 yrs old) were used in this study. Five animals received 6-OHDA (50 mg/kg i.v.) and five were age-matched controls. Three months post-neurotoxin the animals were euthanized; hearts and adrenal glands were processed for immunohistochemistry. Quantification of immunoreactivity (ir) of stainings was performed by an investigator blind to the treatment group using NIH ImageJ software (for cardiac bundles and adrenals, area above threshold and optical density) and MBF StereoInvestigator (for cardiac fibers, area fraction fractionator probe). Sympathetic cardiac nerve bundle analysis and fiber area density showed a significant reduction in global cardiac tyrosine hydroxylase-ir (TH; catecholaminergic marker) in 6-OHDA animals compared to controls. Quantification of protein gene protein 9.5 (pan-neuronal marker) positive cardiac fibers showed a significant deficit in 6-OHDA monkeys compared to controls and correlated with TH-ir fiber area. Semi-quantitative evaluation of human leukocyte antigen-ir (inflammatory marker) and nitrotyrosine-ir (oxidative stress marker) did not show significant changes 3 months post-neurotoxin. Cardiac nerve bundle α-synuclein-ir (presynaptic protein) was reduced (trend) in 6-OHDA treated monkeys; insoluble proteinase-K resistant α-synuclein (typical of PD pathology) was not observed. In the adrenal medulla, 6-OHDA monkeys had significantly reduced TH-ir and aminoacid decarboxylase-ir. Our results confirm that systemic 6-OHDA dosing to nonhuman primates induces cardiac sympathetic neurodegeneration and loss of catecholaminergic enzymes in the adrenal medulla, and suggests that this model can be used as a platform to evaluate disease-modifying strategies aiming to induce peripheral neuroprotection.