Influence of social support and stressful life events on adherence to colorectal cancer screening using faecal occult blood test in Spanish medium risk population / Influencia del apoyo social y los acontecimentos vitales estresantes en el cribado de cáncer colorrectal con sangre oculta en heces en población española de riesgo medio

Introduction Colorectal cancer (CRC) is the second cause of cancer-related deaths worldwide. Five-year survival rate in Spain is 57%. The most important prognostic factor is the stage of the tumor at the diagnosis. CRC can be early diagnosed, but the adherence to screening programs is low (<50%). This study aims to ascertain the influence of social support and stressful life events on the adherence to the population screening of CRC with fecal occult blood test in Spanish average risk population. Methods Multicenter case–control study. We conducted a simple random sampling among individuals invited to participate in the colorectal cancer screening program. We analyzed epidemiological and social variables associated with lifestyle and behavioral factors. We performed a descriptive and a bivariant analyses and a logistic regression analysis. Results Four hundred and eight patients (237 cases and 171 controls) were included. Multivariant analyses showed independent association between higher adherence to the screening program and older age (OR: 1.06; 95% CI: 1.01–1.10), stable partner (OR: 1.77, 95% CI: 1.08–2.89) and wide social network (OR: 1.68; 95% CI: 1.07–2.66). Otherwise, lower adherence was associated to perceiving barriers to participate in the program (OR: 0.92; 95% CI: 0.88–0.96). We find a statistically significant association between lower adherence and high impact stressful life events in the bivariant analyses, and the tendency was maintained (OR: 0.63, 95% CI: 0.37–1.08) in the multivariant. Conclusion Social variables decisively influence the adherence to colorectal cancer screening. The implementation of social interventions that improve social support, reduce impact of stressful life events and the design of screening programs that decrease the perceived barriers, will contribute to increase the participation on these programs. Secondary, the colorectal cancer diagnosis will be made in early-stages with the consequent mortality reduction (AU)

Introducción El cáncer colorrectal (CCR) es la segunda causa de muerte por cáncer en el mundo. La tasa de supervivencia a cinco años en España es de 57%. El factor pronóstico más importante es el estadio del tumor en el momento del diagnóstico. El CCR se puede diagnosticar precozmente, pero la adherencia a los programas de cribado es baja (< 50%). Este estudio pretende conocer la influencia del apoyo social y los acontecimientos vitales estresantes en la adherencia al cribado poblacional de CCR con sangre oculta en heces en población española de riesgo medio. Métodos Estudio multicéntrico de casos y controles. Realizamos un muestreo aleatorio simple entre los individuos invitados a participar en un programa de cribado de CCR. Analizamos variables epidemiológicas y sociales asociadas al estilo de vida y factores conductuales. Realizamos un análisis descriptivo, un análisis bivariante y una regresión logística. Resultados Se incluyeron 408 pacientes (237 casos y 171 controles). El análisis multivariante demostró una asociación independiente entre una mayor adherencia al programa de cribado y mayor edad (OR: 1,06; IC 95%: 1,01-1,10), tener pareja estable (OR: 1,77, IC 95%: 1,08-2,89) y disponer de una amplia red social (OR: 1,68; IC 95%: 1,07-2,66). Por el contrario, la menor adherencia se asoció a la percepción de barreras para participar en el cribado (OR: 0,92; IC 95%: 0,88-0,96). Encontramos una asociación estadísticamente significativa entre menor adherencia y acontecimientos vitales estresantes de alto impacto en el análisis bivariante. La tendencia se mantuvo (OR: 0,63, IC 95%: 0,37-1,08) en el análisis multivariante (AU)

The Influence of the Preoperative Albumin to Alkaline Phosphatase Ratio on Overall Survival in Post-Radical Surgery for Colorectal Cancer and the Construction of a Nomogram Prediction Model.

PURPOSE: The albumin to alkaline phosphatase ratio (AAPR) is a newly developed blood biomarker that has been reported to have prognostic value in several types of cancers. The aim of this study was to investigate the predictive value of AAPR in overall survival after radical colon cancer surgery in patients with stage I-III colorectal cancer (CRC). METHODS: The clinical data of 221 eligible patients with stage I ∼ III CRC were retrospectively analyzed. A series of survival analyses were performed to assess the prognostic value of AAPR. Univariate and multifactorial Cox analyses were performed to identify independent risk factors. Columnar graph prediction models were further constructed based on independent risk factors such as AAPR, and their predictive properties were validated. RESULTS: The optimal cutoff value of preoperative AAPR for postoperative overall survival (OS) in patients undergoing laparoscopic radical CRC was .495 as shown by univariate and multifactorial Cox regression analysis. The factors of age ≤65 years, Tumor-Node-Metastasis (TNM) stage I-II, tumor grading (high/medium differentiation), CEA ≤5, and AAPR ≥.495 were associated with better OS (P < .05). CONCLUSIONS: Preoperative AAPR level was a good predictor of postoperative survival in patients undergoing laparoscopic radical CRC surgery, and AAPR <.495 was an independent risk factor for decreased postoperative OS.

Specialty-Certified Colorectal Surgeons Demonstrate Favorable Short-term Surgical Outcomes for Laparoscopic Low Anterior Resection: Assessment of a Japanese Nationwide Database.

BACKGROUND: There are few studies on the impact of a colorectal-specific technically certified surgeon on good surgical outcomes for laparoscopic low anterior resection in the real world. OBJECTIVE: To evaluate the short-term outcomes of laparoscopic low anterior resection with the participation of a certified colorectal surgeon. DESIGN: This was a retrospective cohort study using a Japanese nationwide database. SETTING: This study was conducted as a project for the Japan Society of Endoscopic Surgery and the Japanese Society of Gastroenterological Surgery. PATIENTS: This study included 41,741 patients listed in the National Clinical Database who underwent laparoscopic low anterior resection performed by certified, noncertified, and colorectal-specific certified surgeons, according to the Endoscopic Surgical Skill Qualification System, from 2016 to 2018. MAIN OUTCOME MEASURES: Operative mortality rate and anastomotic leak rate were the primary outcome measures. RESULTS: Overall 30-day mortality and operative mortality were 0.2% and 0.3%, respectively, without significant differences between all kinds of certified and noncertified surgeon groups. Overall anastomotic leak rate was 9.3%, with a significant difference between the 2 groups. Colorectal- and stomach-certified groups had lower 30-day mortality and operative mortality than the biliary-certified and noncertified groups. The anastomotic leak rate was the lowest in the colorectal-certified group. Based on a logistic regression analysis using the risk-adjusted model, operative mortality was significantly higher in the biliary-certified group than in the colorectal-certified group. Moreover, anastomotic leak rate was significantly lower in the colorectal-certified group than in the stomach-certified and noncertified groups. LIMITATIONS: This study was a retrospective study, and there was a possibility of different definitions of anastomotic leak due to the use of a nationwide database. CONCLUSIONS: The participation of a colorectal-specific certified surgeon may decrease the risk of operative mortality and anastomotic leak for laparoscopic low anterior resection. CIRUJANO COLORRECTAL ALTAMENTE CALIFICADO PROVOCA RESULTADOS QUIRRGICOS FAVORABLES A CORTO PLAZO PARA LA RESECCIN ANTERIOR BAJA LAPAROSCPICA EVALUACIN DE LA BASE DE DATOS NACIONAL JAPONESA: ANTECEDENTES:Hay pocos estudios sobre el impacto de un cirujano certificado técnicamente especializado en cáncer colorrectal con un buen resultado quirúrgico para la resección anterior baja laparoscópica en el mundo real.OBJETIVO:Evaluar los resultados a corto plazo de la resección anterior baja laparoscópica con la participación de un cirujano colorrectal certificado.DISEÑO:Este fue un estudio de cohorte retrospectivo que utilizó una base de datos nacional japonesa.AJUSTE:Este estudio se realizó como un proyecto para la Sociedad Japonesa de Cirugía Endoscópica y la Sociedad Japonesa de Cirugía Gastroenterológica.PACIENTES:este estudio incluyó a 41 741 pacientes incluidos en la base de datos clínica nacional que se sometieron a una resección anterior baja laparoscópica realizada por cirujanos certificados, no certificados y certificados específicamente colorrectales, según el Sistema de calificación de habilidades quirúrgicas endoscópicas de 2016 a 2018.PRINCIPALES MEDIDAS DE RESULTADO:La tasa de mortalidad operatoria y la tasa de fuga anastomótica fueron los resultados primarios.RESULTADOS:La mortalidad general a los 30 días y la mortalidad operatoria fueron del 0,2 % y el 0,3 %, respectivamente, sin diferencias significativas entre los grupos de todos los tipos de cirujanos certificados y no certificados. La tasa global de fuga anastomótica fue del 9,3 %, con una diferencia significativa entre los dos grupos. Los grupos con certificación colorrectal y estomacal tuvieron una mortalidad a los 30 días y una mortalidad operatoria más bajas que los grupos con certificación biliar y sin certificación. La tasa de fuga anastomótica fue la más baja en el grupo certificado colorrectal. Con base en un análisis de regresión logística utilizando el modelo ajustado por riesgo, la mortalidad operatoria fue significativamente más alta en el grupo con certificación biliar que en el grupo con certificación colorrectal. Además, la tasa de fuga anastomótica fue significativamente más baja en el grupo con certificación colorrectal que en los grupos con certificación estomacal y sin certificación.LIMITACIONES:Este estudio fue retrospectivo y existía la posibilidad de diferentes definiciones de fuga anastomótica debido al uso de una base de datos nacional.CONCLUSIONES:La participación de un cirujano certificado en video específico colorrectal puede disminuir el riesgo de mortalidad operatoria y fuga anastomótica para la resección anterior baja laparoscópica. (Traducción-Dr. Mauricio Santamaria ).

Colorectal cancer disparities in Latin America: Mortality trends 1990-2019 and a paradox association with human development.

BACKGROUND: Colorectal cancer mortality is growing in Latin America. It is known for a marked income disparity between its countries, and there is a consistent association with development. Our purpose was to describe trends in colorectal cancer mortality in Latin America between 1990 and 2019, identifying differences by human development categories. METHODS: We extracted age-adjusted mortality rate from the Global Burden of Disease (GBD) Study from 22 Latin American countries, subregions, and country groups previously ranked by the GBD study due to Sociodemographic Index (SDI) between 1990 and 2019. We applied the segmented regression model to analyze the time trend. Also, we estimated the correlation between mortality rates and Human Development Index (HDI) categories for countries. RESULTS: Between 1990 and 2019, colorectal cancer adjusted mortality rate increased by 20.56% in Latin America (95% CI 19.75% - 21.25%). Between 1990 and 2004, the average annual percentage change (APC) was 0.11% per year (95% CI 0.10-0.12), and between 2004 and 2019 there was a deceleration (APC = 0.04% per year, 95% CI 0.03%- 0.05%). There is great heterogeneity among the countries of the region. Correlation between these two variables was 0.52 for 1990 and 2019. When separated into HDI groups, the correlation varied in the direction of the association and its magnitude, typifying an effect modification known as Simpson's Paradox. CONCLUSIONS: Human development factors may be important for assessing variation in cancer mortality on a global scale. Studies that assess the social and -economic contexts of countries are necessary for robust evaluation and provision of preventive, diagnostic and curative services to reduce cancer mortality in Latin America.

Long-Term Survival, Prognostic Factors, and Selection of Patients With Colorectal Cancer for Liver Transplant: A Nonrandomized Controlled Trial.

Importance: Liver transplant for colorectal cancer with liver metastases was abandoned in the 1990s due to poor overall survival. From 2006, liver transplant for in nonresectable colorectal liver metastases has been reexamined through different prospective trials. Objective: To determine predictive factors for transplant long-term survival and cure after liver transplant. Design, Setting, and Participants: This was a prospective, nonrandomized controlled cohort study derived from different clinical trials on liver transplant for colorectal liver metastases from 2006 to 2020 at Oslo University Hospital. The trials differed in prognostic inclusion criteria, but the design was otherwise identical regarding follow-up scheme to determine disease recurrence, overall survival, and survival after relapse. Final data analysis was performed on December 31, 2021. All patients with colorectal liver metastases from comparable prospective liver transplant studies were included. Exposure: Liver transplant. Main outcomes and measures: Disease-free survival, overall survival, and survival time after recurrence were determined in all participants. Results: A total of 61 patients (median [range] age, 57.8 [28.7-71.1] years; 35 male [57.4%]) underwent liver transplant at Oslo University Hospital. Posttransplant observation time ranged from 16 to 165 months, and no patient was lost to follow-up. Median disease-free period, overall survival, and survival after relapse were 11.8 (95% CI, 9.3-14.2) months, 60.3 (95% CI, 44.3-76.4) months, and 37.1 (95% CI, 4.6-69.5) months, respectively. Negative predictive factors for overall survival included the following: largest tumor size greater than 5.5 cm (median OS, 25.3 months; 95% CI, 15.8-34.8 months; P <.001), progressive disease while receiving chemotherapy (median OS, 39.8 months; 95% CI, 28.8-50.7 months; P = .02), plasma carcinoembryonic antigen values greater than 80 µg/L (median OS, 26.6 months; 95% CI, 22.7-30.6 months; P <.001), liver metabolic tumor volume on positron emission tomography of greater than 70 cm3 (26.6 months; 95% CI, 11.8-41.5 months; P <.001), primary tumor in the ascending colon (17.9 months; 95% CI, 0-37.5 months; P <.001), tumor burden score of 9 or higher (23.3 months; 95% CI, 19.2-27.4 months; P = .02), and 9 or more liver lesions (42.5 months; 95% CI, 17.2-67.8 months; P = .02). An Oslo score of 0 or Fong Clinical Risk Score of 1 yielded 10-year survival of 88.9% and 80.0%, respectively. Conclusions and relevance: Results of this nonrandomized controlled trial suggest that selected patients with liver-only metastases and favorable pretransplant prognostic scoring had long-term survival comparable with conventional indications for liver transplant, thus providing a potential curative treatment option in patients otherwise offered only palliative care.

Patients younger than 40 years with colorectal cancer have a similar prognosis to older patients.

PURPOSE: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. In recent years, the proportion of patients diagnosed with CRC at younger ages has increased. The clinicopathological features and oncological outcomes in younger patients with CRC remain controversial. We aimed to analyze the clinicopathological features and oncological outcomes in younger patients with CRC. METHODS: We examined 980 patients who underwent surgery for primary colorectal adenocarcinoma between 2006 and 2020. Patients were divided into two cohorts: younger (< 40 years old) and older (≥ 40 years old). RESULTS: Of the 980 patients, 26 (2.7%) were under the age of 40 years. The younger group had more advanced disease (57.7% vs. 36.6%, p = 0.031) and more cases beyond the transverse colon (84.6% vs. 65.3%, p = 0.029) than the older group. Adjuvant chemotherapy was administered more frequently in the younger group (50% vs. 25.8%, p < 0.01). Relapse-free survival and overall survival were similar between the groups at all stages. Moreover, in stages II and III they were also comparable, regardless of the administration of adjuvant chemotherapy. CONCLUSIONS: Younger patients with CRC have a prognosis equivalent to that of older patients. Further studies are needed to establish the optimal treatment strategies for these patients.

Mental disorders, participation, and trajectories in the Danish colorectal cancer programme: a population-based cohort study.

BACKGROUND: People with mental disorders exhibit increased mortality due to colorectal cancer, despite having a similar incidence to the general population. We aimed to evaluate the extent to which people with mental disorders participate in organised colorectal cancer screening. METHODS: We conducted a population-based cohort study of all Danish residents aged 50-74 years who were invited to undergo biennial faecal immunochemical testing between March 1, 2014, and Sept 30, 2018. We used national registry data from all first-time invitees. The primary endpoint was participation within 90 days of invitation. We calculated the proportion who participated and assessed their screening results and adherence to and completeness of follow-up colonoscopy according to their history of mental disorders, classified as none, mild or moderate, or severe. We computed crude and adjusted participation differences in percentage points and participation ratios using the pseudo-observations method. FINDINGS: Of 2 036 704 people who were invited, we included 2 036 352 in the final cohort, of whom 1 008 045 (49·5%) were men and 1 028 307 (50·5%) were women, with a mean age of 60·7 years (SD 8·3, range 49-78). Data on ethnicity were not collected. Compared with people with no mental disorders, the adjusted analysis showed lower participation among people with mild or moderate mental disorders (men: participation difference -4·4 percentage points [95% CI -4·7 to -4·1]; women: -3·8 percentage points [-4·1 to -3·6]) and severe mental disorders (men: participation difference -13·8 percentage points [-14·3 to -13·3]; women: -15·4 percentage points [-15·8 to -14·9]). People with mental disorders had a higher proportion of positive faecal immunochemical test results, lower adherence to colonoscopy, and more incomplete colonoscopies than people without mental disorders. INTERPRETATION: People with mental disorders were less likely to participate in colorectal cancer screening than those without these disorders. Patients with mental disorders could benefit from support or encouragement from their general practitioner or mental health-care facility to participate in cancer screening. Potential interventions should consider type of mental disorder, as needs might differ. FUNDING: Danish Cancer Society, Danish Health Foundation.

Opportunities for Achieving the Cancer Moonshot Goal of a 50% Reduction in Cancer Mortality by 2047.

On February 2, 2022, President Biden and First Lady Dr. Biden reignited the Cancer Moonshot, setting a new goal to reduce age-standardized cancer mortality rates by at least 50% over the next 25 years in the United States. We estimated trends in U.S. cancer mortality during 2000 to 2019 for all cancers and the six leading types (lung, colorectum, pancreas, breast, prostate, liver). Cancer death rates overall declined by 1.4% per year from 2000 to 2015, accelerating to 2.3% per year during 2016 to 2019, driven by strong declines in lung cancer mortality (-4.7%/year, 2014 to 2019). Recent declines in colorectal (-2.0%/year, 2010-2019) and breast cancer death rates (-1.2%/year, 2013-2019) also contributed. However, trends for other cancer types were less promising. To achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed. We reviewed opportunities to prevent, detect, and treat these common cancers that could further reduce population-level cancer death rates and also reduce disparities. SIGNIFICANCE: We reviewed opportunities to prevent, detect, and treat common cancers, and show that to achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed. See related commentary by Bertagnolli et al., p. 1049. This article is highlighted in the In This Issue feature, p. 1027.

The Intersection of Race and Rurality and its Effect on Colorectal Cancer Survival.

INTRODUCTION: Outcomes in colorectal cancer treatment are historically worse in Black people and residents of rural areas. Purported reasons include factors such as systemic racism, poverty, lack of access to care, and social determinants of health. We sought to determine whether outcomes worsened when race and rural residence intersected. METHODS: The National Cancer Database was queried for individuals with stage II-III colorectal cancer (2004-2018). To examine the intersectionality of race/rurality on outcomes, race (Black/White) and rurality (based on county) were combined into a single variable. Main outcome of interest was 5-year survival. Cox hazard regression analysis was performed to determine variables independently associating with survival. Control variables included age at diagnosis, sex, race, Charlson-Deyo score, insurance status, stage, and facility type. RESULTS: Of 463 948 patients, 5717 were Black-Rural, 50 742 were Black-Urban, 72 241 were White-Rural, and 33 5271 were White-Urban. Five-year mortality rate was 31.6%. Univariate Kaplan-Meier survival analysis demonstrated race-rurality was associated with overall survival (P < .001), with White-Urban having the greatest mean survival length (47.9 months) and Black-Rural with the lowest (46.7 months). Multivariable analysis found that Black-Rural (1.26, 95% confidence interval [1.20-1.32]), Black-Urban (1.16, [1.16-1.18]), and White-Rural (HR: 1.05; (1.04-1.07) had increased mortality when compared to White-Urban individuals (P < .001). CONCLUSION: Although White-Rural individuals fared worse than White-Urban, Black individuals fared worst of all, with the poorest outcomes observed in Black individuals in rural areas. This suggests that both Black race and rurality negatively affect survival, and act synergistically to further worsen outcomes.

Regorafenib, Ipilimumab, and Nivolumab for Patients With Microsatellite Stable Colorectal Cancer and Disease Progression With Prior Chemotherapy: A Phase 1 Nonrandomized Clinical Trial.

Importance: Immunotherapy combinations with activity in patients with microsatellite stable (MSS) metastatic colorectal cancer need to be identified. Objective: To determine the recommended phase 2 dose (RP2D) of regorafenib, ipilimumab, and nivolumab (RIN) and evaluate its activity in an expansion cohort of patients with MSS metastatic colorectal cancer. Design, Setting, and Participants: This nonrandomized clinical trial was a single-center 3 + 3 dose de-escalation study with an effectiveness expansion cohort at the RP2D. After the identification of the RP2D, a study amendment was executed to explore a regorafenib dose optimization strategy to mitigate skin-related toxic effects. Study enrollment occurred between May 12, 2020, and January 21, 2022. The trial was conducted at a single academic center. A total of 39 patients with MSS metastatic colorectal cancer whose disease progressed after standard chemotherapy and who had not received prior regorafenib or anti-programmed cell death protein 1 therapy were included. Interventions: Patients received regorafenib daily for 21 days every 4 weeks; fixed-dose ipilimumab, 1 mg/kg, intravenously every 6 weeks; and fixed-dose nivolumab, 240 mg intravenously every 2 weeks. Patients were treated until progression, unacceptable toxic effects, or completion of 2 years of therapy. Main Outcomes and Measures: The primary end point was RP2D selection. Secondary end points were safety and overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumours at the RP2D level. Results: A total of 39 patients were enrolled, 23 (59.0%) were female, median age was 54 years (range, 25-75 years), 3 were Black (7.7%), and 26 were White (66.7%). No dose-limiting toxic effects were noted in the first 9 patients at the starting dose of RIN, with regorafenib dosed at 80 mg daily. No dose de-escalation was needed. This dose was declared the RP2D. Twenty more patients were enrolled at this level. The ORR, median progression-free survival (PFS), and overall survival (OS) in the RP2D cohort were 27.6%, 4 months (IQR, 2-9 months), and 20 months (IQR, 7 months to not estimable), respectively. For the 22 patients without liver metastases, the ORR, PFS, and OS were 36.4%, 5 months (IQR, 2-11), and greater than 22 months, respectively. A dose optimization cohort with regorafenib at 40 mg/d on cycle 1 and 80 mg/d on cycle 2 and beyond was associated with lower skin and immune toxic effects but had limited activity with stable disease for 5 of 10 patients as the best response. Conclusions and Relevance: Results of this nonrandomized clinical trial suggest that RIN at the RP2D demonstrated interesting clinical activity in patients with advanced MSS colorectal cancer without liver metastases. These findings should be confirmed in randomized clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04362839.

Relationship between DHX15 expression and survival in colorectal cancer

Objective: to explore the relationship between the expression of DEAH-box RNA helicase 15 (DHX15) in colorectal cancer (CRC), its clinical pathological features and survival. Method: DHX15 expression data with clinical pathological features from the Cancer Gene Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were statistically analyzed for the association between DHX15 expression and overall survival in CRC. The expression of DHX15 was performed by immunohistochemical staining (IHC) using tumor and the adjacent normal tissue, mounted in tissue microarrays. The significance of DHX15 expression to predict survival and prognosis of CRC were analyzed using the Kaplan-Meier method, univariate and multivariate Cox regression analysis. Results: low expression of DHX15 mRNA and DHX15 protein in CRC were both negative factors for survival. Overall survival of patients with low-expression of DHX15 was significantly lower (χ2 = 8.452, p = 0.004) by Kaplan-Meier evaluation. Low expression of DHX15 in CRC tissues correlated with distal lymph node metastasis (χ² = 7.120, p = 0.008), TNM stage (χ² = 3.935, p = 0.047) and disease recurrence (χ² = 9.524, p = 0.002) in CRC. Low expression of DHX15 (HR = 4.012, 95 % CI: 1.462-11.013, p = 0.007), late TNM stage (HR = 0.067, 95 % CI: 0.029-0.156, p < 0.001) and recurrence (HR = 0.008, 95 % CI: 0.002-0.034, p < 0.001) were risk factors related to the prognosis of CRC patients by univariate Cox regression analysis. Conclusion: our findings reveal a key role for DHX15 in the progress of CRC metastasis and recurrence. DHX15 may be a potential biomarker for CRC targeted therapy (AU)