Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo.

Three-dimensional organoid culture technologies have revolutionized cancer research by allowing for more realistic and scalable reproductions of both tumour and microenvironmental structures1-3. This has enabled better modelling of low-complexity cancer cell behaviours that occur over relatively short periods of time4. However, available organoid systems do not capture the intricate evolutionary process of cancer development in terms of tissue architecture, cell diversity, homeostasis and lifespan. As a consequence, oncogenesis and tumour formation studies are not possible in vitro and instead require the extensive use of animal models, which provide limited spatiotemporal resolution of cellular dynamics and come at a considerable cost in terms of resources and animal lives. Here we developed topobiologically complex mini-colons that are able to undergo tumorigenesis ex vivo by integrating microfabrication, optogenetic and tissue engineering approaches. With this system, tumorigenic transformation can be spatiotemporally controlled by directing oncogenic activation through blue-light exposure, and emergent colon tumours can be tracked in real-time at the single-cell resolution for several weeks without breaking the culture. These induced mini-colons display rich intratumoural and intertumoural diversity and recapitulate key pathophysiological hallmarks displayed by colorectal tumours in vivo. By fine-tuning cell-intrinsic and cell-extrinsic parameters, mini-colons can be used to identify tumorigenic determinants and pharmacological opportunities. As a whole, our study paves the way for cancer initiation research outside living organisms.

Allura Red AC is a xenobiotic. Is it also a carcinogen?

Merriam-Webster and Oxford define a xenobiotic as any substance foreign to living systems. Allura Red AC (a.k.a., E129; FD&C Red No. 40), a synthetic food dye extensively used in manufacturing ultra-processed foods and therefore highly prevalent in our food supply, falls under this category. The surge in synthetic food dye consumption during the 70s and 80s was followed by an epidemic of metabolic diseases and the emergence of early-onset colorectal cancer in the 1990s. This temporal association raises significant concerns, particularly given the widespread inclusion of synthetic food dyes in ultra-processed products, notably those marketed toward children. Given its interactions with key contributors to colorectal carcinogenesis such as inflammatory mediators, the microbiome, and DNA damage, there is growing interest in understanding Allura Red AC's potential impact on colon health as a putative carcinogen. This review discusses the history of Allura Red AC, current research on its effects on the colon and rectum, potential mechanisms underlying its impact on colon health, and provides future considerations. Indeed, although no governing agencies classify Allura Red AC as a carcinogen, its interaction with key guardians of carcinogenesis makes it suspect and worthy of further molecular investigation. The goal of this review is to inspire research into the impact of synthetic food dyes on colon health.

Dietary phytoestrogen intake and ovarian cancer risk: a prospective study in the prostate, lung, colorectal and ovarian (PLCO) cohort.

Estrogen plays a crucial role in ovarian tumorigenesis. Phytoestrogens (PEs) are a type of daily dietary nutrient for humans and possess a mild estrogenic characteristic. This study aimed to assess the correlation of the consumption of dietary PEs with ovarian cancer risk using data in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Participants were enrolled in PLCO from 1993 to 2001. Hazard ratios (HR) and 95% confidence intervals (CI) were utilized to determine the association between the intake of PEs and ovarian cancer occurrence, which were calculated by the Cox proportional hazards regression analysis. In total, 24 875 participants were identified upon completion of the initial dietary questionnaire (DQX). Furthermore, the analysis also included a total of 45 472 women who filled out the diet history questionnaire (DHQ). Overall, after adjustment for confounders, the dietary intake of total PEs was significantly associated with the risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.69, 95% CI: 0.50-0.95; P for trend = 0.066). Especially, individuals who consumed the highest quartile of isoflavones were found to have a decreased risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.68, 95% CI: 0.50-0.94; P for trend = 0.032). However, no such significant associations were observed for the DQX group. In summary, this study suggests that increased dietary intake of total PEs especially isoflavones was linked with a lower risk for developing ovarian cancer. More research is necessary to validate the findings and explore the potential mechanisms.

Environmental drivers of the rising incidence of early-onset colorectal cancer in the United States.

Incidence of early-onset (diagnosed before age 50) colorectal cancer (EOCRC) has increased alarmingly since the 1990s in the United States. This study investigated what environmental exposures may have driven this increase. We obtained EOCRC incidence data from the Surveillance, Epidemiology, and End Results Program, and data for 11 exposures, for example, body mass index (BMI), from long-term national surveys. We aggregated these data for 30 to 49-year-olds during 1992 to 2016 by population subgroups defined by calendar period, age, race and sex, and used negative binomial regression models to identify and estimate associations of EOCRC with multiple exposures. Furthermore, we used counterfactual modeling to quantify contributions of identified risk factors to EOCRC incidence. The top models (with lowest Bayesian Information Criteria) consistently identified excess body weight, represented by overweight and obesity (BMI ≥25) or obesity alone (BMI ≥30), as the strongest risk factor. The best-performing model estimated increased EOCRC incidence due to overweight and obesity, with an incidence rate ratio (95% confidence interval) of 1.20 (1.17-1.22) for white men, 1.04 (1.00-1.08) for black men, 1.17 (1.15-1.21) for white women and 1.03 (0.97-1.08) for black women. Increases in overweight and obesity prevalence contributed to an estimated 30% (standard error: 1%) for men and 28% (standard error: 2%) for women of ECORC incidence during 1992 to 2016. These findings suggest excess body weight substantially contributed to and is likely a primary driver of the rising incidence of EOCRC in the United States. Prevention of excess weight gain may help lower colorectal cancer risk early in life.

A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Association between weight cycling and risk of colorectal cancer: a prospective cohort study.

BACKGROUND: Weight cycling is the repeated episodes manifesting intentional weight loss and subsequent unintentional weight gain. Whether the frequency and magnitude of weight cycling is associated with colorectal cancer risk independent of body mass index (BMI) remains unknown. METHODS: Two prospective cohort studies, Nurses' Health Study I and Health Professionals Follow-up Study, followed 85,562 participants from 1992 to 2014. Participants completed a questionnaire regarding the frequency and magnitude of intentional weight loss in the past 4 years at the baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard model. RESULTS: We identified 1626 colorectal cancer cases during up to 22 years of follow-up. In the pooled analysis of HPFS and NHS, compared to non-weight cycling, moderate weight cycling (≥3 times of intentional weight loss of ≥2.3-4.4 kg) was associated with a reduced risk of colorectal cancer after adjustment for confounders, including attained BMI after weight cycling (HR = 0.82, 95% CI 0.69, 0.97). However, no significant association was observed in mild weight cyclers and in severe weight cyclers. CONCLUSIONS: Moderate weight cycling was associated with a lower risk of colorectal cancer independent of BMI. This finding needs further studies for replication and putative biological mechanisms.

Snare Tip Soft Coagulation vs Argon Plasma Coagulation vs No Margin Treatment After Large Nonpedunculated Colorectal Polyp Resection: a Randomized Trial.

BACKGROUND & AIMS: Thermal treatment of the defect margin after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions reduces the recurrence rate. Both snare tip soft coagulation (STSC) and argon plasma coagulation (APC) have been used for thermal margin treatment, but there are few data directly comparing STSC with APC for this indication. METHODS: We performed a randomized 3-arm trial in 9 US centers comparing STSC with APC with no margin treatment (control) of defects after EMR of colorectal nonpedunculated lesions ≥15 mm. The primary end point was the presence of residual lesion at first follow-up. RESULTS: There were 384 patients and 414 lesions randomized, and 308 patients (80.2%) with 328 lesions completed ≥1 follow-up. The proportion of lesions with residual polyp at first follow-up was 4.6% with STSC, 9.3% with APC, and 21.4% with control subjects (no margin treatment). The odds of residual polyp at first follow-up were lower for STSC and APC when compared with control subjects (P = .001 and P = .01, respectively). The difference in odds was not significant between STSC and APC. STSC took less time to apply than APC (median, 3.35 vs 4.08 minutes; P = .019). Adverse event rates were low, with no difference between arms. CONCLUSIONS: In a randomized trial STSC and APC were each superior to no thermal margin treatment after EMR. STSC was faster to apply than APC. Because STSC also results in lower cost and plastic waste than APC (APC requires an additional device), our study supports STSC as the preferred thermal margin treatment after colorectal EMR. (Clinicaltrials.gov, Number NCT03654209.).

Ultra-Processed Food Consumption and Gastrointestinal Cancer Risk: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ultra-processed food (UPF) intake has been associated with a higher risk of obesity, hypertension, type 2 diabetes, and cardiovascular diseases. The initial data on the relationship between UPF consumption and cancer risk were derived from retrospective observational studies with conflicting results. This systematic review and meta-analysis of prospective cohort studies aimed to investigate the association between UPF consumption and gastrointestinal cancer risk. METHODS: PubMed, Embase, and Cochrane databases were searched for prospective cohort studies that compared the highest vs the lowest level of UPF consumption according to NOVA food classification and reported the risk of gastrointestinal cancers by subsite. The association with cancer was quantified as hazard ratios (HR) using a random-effects model. RESULTS: Five prospective cohort studies were included in this review comprising 1,128,243 participants (241,201 participants in the highest and 223,366 in the lowest levels of UPF consumption). The mean follow-up ranged from 5.4 to 28 years. The highest UPF consumption was significantly associated with an increased risk of colorectal cancer (HR 1.11; 95% confidence interval [CI] 1.03-1.21; P = 0.01; I2 = 31%), colon cancer (HR 1.12; 95% CI 1.02-1.23; P = 0.02; I2 = 0%), and non-cardia gastric cancer (HR 1.43; 95% CI 1.02-2.00; P = 0.04; I2 = 0%) compared with the lowest UPF intake. However, no association was found between high UPF consumption and hepatocellular, esophageal, pancreatic, gastric cardia, and rectal cancer. DISCUSSION: The highest level of UPF consumption was significantly associated with colorectal and non-cardia gastric cancer.

Heavy-metal associated breast cancer and colorectal cancer hot spots and their demographic and socioeconomic characteristics.

PURPOSE: Cancer registries offer an avenue to identify cancer clusters across large populations and efficiently examine potential environmental harms affecting cancer. The role of known metal carcinogens (i.e., cadmium, arsenic, nickel, chromium(VI)) in breast and colorectal carcinogenesis is largely unknown. Historically marginalized communities are disproportionately exposed to metals, which could explain cancer disparities. We examined area-based metal exposures and odds of residing in breast and colorectal cancer hotspots utilizing state tumor registry data and described the characteristics of those living in heavy metal-associated cancer hotspots. METHODS: Breast and colorectal cancer hotspots were mapped across Kentucky, and area-based ambient metal exposure to cadmium, arsenic, nickel, and chromium(VI) were extracted from the 2014 National Air Toxics Assessment for Kentucky census tracts. Among colorectal cancer (n = 56,598) and female breast cancer (n = 77,637) diagnoses in Kentucky, we used logistic regression models to estimate Odds Ratios (ORs) and 95% Confidence Intervals to examine the association between ambient metal concentrations and odds of residing in cancer hotspots, independent of individual-level and neighborhood risk factors. RESULTS: Higher ambient metal exposures were associated with higher odds of residing in breast and colorectal cancer hotspots. Populations in breast and colorectal cancer hotspots were disproportionately Black and had markers of lower socioeconomic status. Furthermore, adjusting for age, race, tobacco and neighborhood factors did not significantly change cancer hotspot ORs for ambient metal exposures analyzed. CONCLUSION: Ambient metal exposures contribute to higher cancer rates in certain geographic areas that are largely composed of marginalized populations. Individual-level assessments of metal exposures and cancer disparities are needed.

A Perspective Review on Diet Quality, Excess Adiposity, and Chronic Psychosocial Stress and Implications for Early-Onset Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. Although the overall incidence of CRC has been decreasing over the past 40 y, early-onset colorectal cancer (EOCRC), which is defined as a CRC diagnosis in patients aged >50 y has increased. In this Perspective, we highlight and summarize the association between diet quality and excess adiposity, and EOCRC. We also explore chronic psychosocial stress (CPS), a less investigated modifiable risk factor, and EOCRC. We were able to show that a poor-quality diet, characterized by a high intake of sugary beverages and a Western diet pattern (high intake of red and processed meats, refined grains, and foods with added sugars) can promote risk factors associated with EOCRC development, such as an imbalance in the composition and function of the gut microbiome, presence of chronic inflammation, and insulin resistance. Excess adiposity, particularly obesity onset in early adulthood, is a likely contributor of EOCRC. Although the research is sparse examining CPS and CRC/EOCRC, we describe likely pathways linking CPS to tumorigenesis. Although additional research is needed to understand what factors are driving the uptick in EOCRC, managing body weight, improving diet quality, and mitigating psychosocial stress, may play an important role in reducing an individual's risk of EOCRC.

Intake of Sugar and Food Sources of Sugar and Colorectal Cancer Risk in the Multiethnic Cohort Study.

BACKGROUND: The influence of sugar intake on the risk of colorectal cancer (CRC) remains controversial, and there is a need to investigate the heterogeneity of effects among racial and ethnic groups. OBJECTIVES: To examine the association of intake of simple sugars and their food sources with CRC risk according to race/ethnicity in a multiethnic cohort study. METHODS: We analyzed data from 192,651 participants who participated in the Multiethnic Cohort Study comprising African American, Japanese American, Latino, Native Hawaiian, and White older adults living in Hawaii and California with an average follow-up of 19 y. Intakes of total and specific types of sugars and sugary foods were estimated from a quantitative food frequency questionnaire completed by the participants in 1993-1996. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC risk according to quintiles (Q) of sugar and food intakes using Cox models adjusted for potential confounders. RESULTS: As of December 2017, 4403 incident CRC cases were identified. Among all participants, multivariable-adjusted CRC HRs for Q2, Q3, Q4, and Q5 compared with Q1 for total sugars were 1.03 (95% CI: 0.94, 1.13), 1.05 (95% CI: 0.96, 1.16), 1.12 (95% CI: 1.01, 1.24), and 1.13 (95% CI: 1.01, 1.27), respectively. A similar positive association was observed for total fructose, glucose, fructose, and maltose but not for added sugars and sugary foods. The increased risk appeared to be limited to colon cancer and to be strongest among younger participants (i.e., 45-54 y at baseline); an association with CRC was observed for sugar-sweetened beverages in the latter group. Among racial and ethnic groups, increased risk of CRC was most apparent in Latinos. CONCLUSIONS: In this diverse cohort, intakes of total sugar, total fructose, glucose, fructose, and maltose were associated with an increased risk of CRC, and the association was strongest for colon cancer, younger participants, and Latinos.

Randomized trial of gastric and colorectal endoscopic submucosal dissection defect closure comparing a novel through-the-scope suturing system with an over-the-scope suturing system (with video).

BACKGROUND AND AIMS: Mucosal closure adds time but reduces adverse events associated with endoscopic submucosal dissection (ESD). We aimed to assess the closure time (CT), technical success, and cost-effectiveness between a novel through-the-scope helix tack suture system (TTSS) and the over-the-scope suturing system (OTSS). METHODS: In this single-center, prospective, randomized trial, all patients undergoing ESD with anticipated closure were randomized 1:1 to TTSS (study group) or OTSS (control group). Primary outcomes were CT and overall CT (OCT; CT + setup time). Secondary outcomes were rates of technical success, adverse events, and cost-effectiveness. RESULTS: Forty patients were randomized to OTSS (n = 20) or TTSS (n = 20). OTSS and TTSS groups were similar with respect to age, gender, proportion of colorectal polyps, proximal colon polyps, and mean size of the resected specimen (40.9 mm vs 40.4 mm). The mean CT was 18.4 minutes for OTSS and 23.3 minutes for TTSS (P = .36). The mean OCT was 32 minutes for OTSS and 39.5 minutes for TTSS (P = .36). Closure with a primary device was successful in 17 cases (85%) with OTSS and 18 cases (90%) with TTSS (P = .63). No closure-related intraprocedural adverse events or delayed perforations were noted. Mean cost of closure was significantly lower in the TTSS group for lesions <35 mm (P = .008). CONCLUSIONS: TTSS was not found to be superior to OTSS with respect to CT and technical and clinical success for closure of gastric and colorectal ESD defects. TTSS is more cost-effective for closure of lesions <35 mm. (Clinical trial registration number: NCT04925271.).

Dietary Factors Differ Between Young-Onset and Older-Onset Colorectal Cancer Patients.

We aimed to evaluate differences in dietary factors between young-onset (diagnosed at ages <50) and older-onset colorectal cancer (CRC). CRC patients diagnosed from 1998 to 2018 reported to the Puget Sound Surveillance, Epidemiology, and End Results registry were recruited using mail and telephone. Consented patients completed questionnaires assessing demographics, medical history, and CRC risk factors, including dietary factors. We used multi-variable logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing dietary intake in young-onset vs. older-onset CRC. Analyses included 1,087 young- and 2,554 older-onset CRC patients. Compared to older-onset CRC, young-onset CRC patients had lower intake of vegetables (OR for highest intake vs. lowest = 0.59 CI: 0.55, 0.64) and fruit (OR for highest intake vs. lowest = 0.94 CI: 0.88, 0.99) and higher intake of processed meat (OR for highest intake vs. lowest = 1.82 CI: 1.11, 2.99) and spicy food (OR for highest intake vs. lowest = 1.69 CI: 1.09, 2.61). There was no statistically significant difference between young- and older-onset CRC patients for red meat consumption. Dietary patterns differed between young- and older-onset CRC; young-onset CRC patients had lower intake of vegetables and fruit and higher intakes of processed meat and spicy food.

Exploring the Relationship Between Diet, Lifestyle and Gut Microbiome in Colorectal Cancer Development: A Recent Update.

Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. Despite advances in treatment modalities, its prevalence continues to rise, notably among younger populations. Unhealthy dietary habits, sedentary routines, and obesity have been identified as one of the key contributors to the development of colorectal cancer, apart from genetic and epigenetic modifications. Recognizing the profound impact of diet and lifestyle on the intricate gut microbiota ecosystem offers a promising avenue for understanding CRC development and its treatment. Gut dysbiosis, characterized by imbalances favoring harmful microbes over beneficial ones, has emerged as a defining feature of CRC. Changes in diet and lifestyle can profoundly alter the composition of gut microbes and the metabolites they produce, potentially contributing to CRC onset. Focusing on recent evidence, this review discussed various dietary factors, such as high consumption of red and processed meats and low fiber intake, and lifestyle factors, including obesity, lack of physical activity, smoking, and excessive alcohol consumption, that influence the gut microbiome composition and elevate CRC risk.

Microbiome Dysbiosis, Dietary Intake and Lifestyle-Associated Factors Involve in Epigenetic Modulations in Colorectal Cancer: A Narrative Review.

Background: Colorectal cancer is the second cause of cancer mortality and the third most commonly diagnosed cancer worldwide. Current data available implicate epigenetic modulations in colorectal cancer development. The health of the large bowel is impacted by gut microbiome dysbiosis, which may lead to colon and rectum cancers. The release of microbial metabolites and toxins by these microbiotas has been shown to activate epigenetic processes leading to colorectal cancer development. Increased consumption of a 'Westernized diet' and certain lifestyle factors such as excessive consumption of alcohol have been associated with colorectal cancer.Purpose: In this review, we seek to examine current knowledge on the involvement of gut microbiota, dietary factors, and alcohol consumption in colorectal cancer development through epigenetic modulations.Methods: A review of several published articles focusing on the mechanism of how changes in the gut microbiome, diet, and excessive alcohol consumption contribute to colorectal cancer development and the potential of using these factors as biomarkers for colorectal cancer diagnosis.Conclusions: This review presents scientific findings that provide a hopeful future for manipulating gut microbiome, diet, and alcohol consumption in colorectal cancer patients' management and care.

Challenges and Opportunities in the Elective Management of Diverticulitis: Perspectives From a National Sample of Colorectal Surgeons.

BACKGROUND: Diverticulitis is a complex, heterogeneous disease process that affects a diverse population of patients. In the elective management of this disease, treatment guidelines have shifted toward patient-centered, individualized decision-making. It is not known what challenges surgeons face as they approach these nuanced treatment decisions in practice. OBJECTIVE: This study aimed to identify opportunities to support colorectal surgeons in elective diverticulitis treatment. DESIGN: This was a qualitative study using standardized, semistructured interviews to explore the perspectives of 29 colorectal surgeons recruited using a purposive sampling technique. Data were analyzed using an "open-coding" approach. SETTINGS: Interviews with a national sample of colorectal surgeons were conducted from a single center using an online video platform. PATIENTS: This study did not involve patients. MAIN OUTCOME MEASURES: Interviews explored surgeons' experiences treating diverticulitis in the elective setting, focusing on perceived challenges in providing patient-centered care as well as opportunities to improve treatment decisions. RESULTS: Our qualitative analysis identified an overarching challenge in elective diverticulitis management for surgeons: difficulty ensuring adequate patient understanding of the risks and benefits of various treatments. This was thought to be due to 1) preexisting patient expectations about treatment and 2) lack of data regarding long-term treatment outcomes. Surgeons identified 2 potential opportunities to combat these challenges: 1) patient education and 2) additional research regarding treatment outcomes, with potential for the development of diverticulitis-specific decision support tools. LIMITATIONS: These results are based on a national sample of colorectal surgeons, but they capture qualitative data that is not intended to provide generalizable findings. CONCLUSIONS: As surgeons work toward providing individualized care for diverticulitis patients, they find it difficult to adequately counsel patients regarding the patient-specific risks of various treatments. The results of this study identify specific contributors to this problem as well as potential targets for intervention, which can guide future efforts to support surgeons in providing patient-centered care. See Video Abstract . DESAFOS Y OPORTUNIDADES EN EL MANEJO ELECTIVO DE LA DIVERTICULITIS PERSPECTIVAS DE UNA MUESTRA NACIONAL DE CIRUJANOS COLORRECTALES: ANTECEDENTES:La diverticulitis es un proceso patológico complejo y heterogéneo que afecta a una población diversa de pacientes. En el manejo electivo de esta enfermedad, las pautas de tratamiento se han desplazado hacia una toma de decisiones individualizada y centrada en el paciente. No se sabe qué desafíos enfrentan los cirujanos al abordar estas decisiones de tratamiento matizadas en la práctica.OBJETIVO:Identificar oportunidades para apoyar a los cirujanos colorrectales en el tratamiento electivo de la diverticulitis.DISEÑO:Este fue un estudio cualitativo que utilizó entrevistas semiestructuradas estandarizadas para explorar las perspectivas de 29 cirujanos colorrectales reclutados mediante una técnica de muestreo intencional. Los datos se analizaron utilizando un enfoque de "codificación abierta".ESCENARIO:Las entrevistas con una muestra nacional de cirujanos colorrectales se realizaron desde un solo centro utilizando una plataforma de video en línea.PRINCIPALES MEDIDAS DE RESULTADO:Las entrevistas exploraron las experiencias de los cirujanos en el tratamiento de la diverticulitis en el entorno electivo, centrándose en los desafíos percibidos en la prestación de atención centrada en el paciente, así como en las oportunidades para mejorar las decisiones de tratamiento.RESULTADOS:Nuestro análisis cualitativo identificó un desafío general en el manejo de la diverticulitis electiva para los cirujanos: la dificultad para asegurar que el paciente comprenda adecuadamente los riesgos y beneficios de los diversos tratamientos. Se pensó que esto se debía a 1) las expectativas preexistentes del paciente sobre el tratamiento y 2) la falta de datos sobre los resultados del tratamiento a largo plazo. Los cirujanos identificaron dos oportunidades potenciales para combatir estos desafíos: 1) educación del paciente y 2) investigación adicional sobre los resultados del tratamiento, con potencial para el desarrollo de herramientas de apoyo a la toma de decisiones específicas para la diverticulitis.LIMITACIONES:Estos resultados se basan en una muestra nacional de cirujanos colorrectales, pero capturan datos cualitativos que no pretenden proporcionar hallazgos generalizables.CONCLUSIONES:A medida que los cirujanos trabajan para brindar atención individualizada a los pacientes con diverticulitis, les resulta difícil aconsejar adecuadamente a los pacientes sobre los riesgos específicos de los pacientes para los diversos tratamientos. Los resultados de este estudio identifican contribuyentes específicos a este problema, así como objetivos potenciales para la intervención, que pueden guiar los esfuerzos futuros para ayudar a los cirujanos a brindar atención centrada en el paciente. (Traducción-Dr. Felipe Bellolio ).

Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy: A European multicenter cohort study.

BACKGROUND AND OBJECTIVES: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status. METHODS: A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAFV600E mutation, and BRAF mutated tumors were further analyzed for hypermethylation status in the promoter region of MLH1 to distinguish between sporadic and hereditary cases. Swedish and Finish patients were matched with their respective National Cancer Registries. For the Czech cohort, thorough scrutiny of medical files was performed to identify any non-colorectal malignancy within 20 years before or after the diagnosis of CRC. Poisson regression analysis was performed to identify the incidence rates of non-colorectal malignancies. For validation purposes, standardized incidence ratios were calculated for the Swedish cases adjusted for age, year, and sex. RESULTS: Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60-75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89-3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67-3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28-2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72-3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05-2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63-3.42, p = 0.005), respectively. CONCLUSION: In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.

Risk Factors Associated with Advanced Colorectal Neoplasia in Adults Younger than Age 45.

BACKGROUND: Colorectal cancer (CRC) is rising in young adults between ages 20 to 49 years. CRC screening is endorsed for average-risk individuals beginning at ages 45 to 49 years. Targeting screening for individuals <45 years may be warranted if risk factors for advanced neoplasia can be identified. AIM: To identify factors associated with advanced colorectal neoplasia in adults aged <45 years. METHOD: Individuals ages 18 to 44 years who underwent colonoscopy at Cleveland Clinic between 2011 and 2021 with ≥1 advanced neoplasm (AN) were included. Patients with inflammatory bowel disease or inherited CRC syndromes were excluded. Demographics, comorbidities, family history of CRC, and colonoscopy indication were obtained. Patients with a normal colonoscopy constituted the control group. A multivariable logistic regression model was used to investigate the relationship between clinical variables and the presence of advanced colorectal neoplasia. RESULTS: In all, 13,006 patients were included, of which 651 (5%) patients had AN: 404 (62%) with tubular adenoma ≥10 mm, 29 (4.5%) tubular adenoma with high-grade dysplasia, 210 (32%) tubulovillous adenomas, 27 (4%) traditional serrated adenomas, 82 (13%) sessile serrated lesions ≥10 mm, 7(2%) sessile serrated lesions with dysplasia, and 29 (4.4%) patients had a CRC. Factors associated with AN were older age (means 38.5 vs. 36.6 y), history of smoking, diabetes, non-White race, higher body mass index (29.9 vs. 28.5 kg/m 2 ), and lower vitamin D (27.6 vs. 32.2 ng/dl), all P <0.001. In the reduced multivariable model, factors associated with AN included tobacco use (OR 2.026 (current vs. never, P <0.0001), age (OR increase by 1.06 per year, P <0.0001), male gender (OR 1.476, P <0.0001), family history of CRC (OR 3.91, P <0.0001), aspirin use (1.31, P =0.035), and diabetes (OR 2.106, P 0.001). CONCLUSION: Increasing age, male gender, exposure to tobacco, family history of CRC, diabetes, and aspirin use were independently associated with advanced neoplasia in adults younger than 45. Targeted early screening to young adults with these risk factors may be justified. Large collaborative prospective studies are needed to validate our findings.

Interval Colorectal Cancer in Inflammatory Bowel Disease: A Review.

Inflammatory bowel disease (IBD) increases the risk of dysplasia and colorectal cancer (CRC). Moreover, colitis-associated CRC is responsible for a disproportionate number of CRC-related mortality. For this reason, societies recommend screening and surveillance colonoscopy as the standard of care for patients with ulcerative colitis and Crohn's colitis. Nonetheless, interval cancer defined as CRC detected within the appropriate surveillance interval might still occur despite following guideline recommendations. Even though there is limited data on risk factors associated with interval CRC in IBD, patient and disease-associated factors and technical aspects of the surveillance might play a role. This review aims to provide information on the epidemiology of interval CRC in IBD, the factors that might be associated with its occurrence, and the challenges of CRC screening and dysplasia management in patients with IBD.

The association of diet-dependent acid load with colorectal cancer risk: a case-control study in Korea.

Acid-base disequilibrium is a contributor to cancer development because it affects molecular activities such as insulin-like growth factor 1 levels and adiponectin production. However, evidence of an association of diet-induced acid-base imbalance with colorectal cancer (CRC) is limited. We examined whether colorectal carcinogenesis is attributable to a diet with a high acid load. We recruited a total of 923 CRC cases and 1846 controls at the National Cancer Center in Korea for inclusion in a case-control study. We collected information on nutrient intake and specific clinical parameters of CRC by using a semiquantitative FFQ and medical records, respectively. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to estimate diet-dependent acid load. We used an unconditional logistic regression model to analyse the association. Dietary acid load scores had a positive association with the odds of CRC (OR = 2·31 (95 % CI 1·79, 2·99) and OR = 2·14 (95 % CI 1·66, 2·76) for PRAL and NEAP, respectively, Pfor trend < 0·001). A stronger positive association was observed for females (OR = 3·09, 95 % CI 1·93, 4·94) than for males (OR = 1·71, 95 % CI 1·27, 2·31). Furthermore, acidogenic diets appeared to affect rectal cancer more strongly than colon cancer in females. Our study contributes to reinforcing epidemiological evidence regarding a detrimental effect of acidogenic diets on colorectal carcinogenesis. Thus, it is important to pay attention to the balance of acidogenic (e.g. poultry and red meat) and alkalinogenic foods (e.g. fruits and vegetables) in CRC prevention, especially for females.