Trends and Determinants of Location of Death Due to Colorectal Cancer in the United States : A Nationwide Study.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States (US); however, there are limited data on location of death in patients who die from CRC. We examined the trends in location of death and determinants in patients dying from CRC in the US. METHODS: We utilized the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to extract nationwide data on underlying cause of death as CRC. A multinomial logistic regression was performed to assess associations between clinico-sociodemographic characteristics and location of death. RESULTS: There were 850,750 deaths due to CRC from 2003 to 2019. There was a gradual decrease in deaths in hospital, nursing home, or outpatient facility/emergency department over time and an increase in deaths at home and in hospice. Relative to White decedents, Black, Asian, and American Indian/Alaska Native decedents were less likely to die at home and in hospice compared with hospitals. Individuals with lower educational status also had a lower risk of dying at home or in hospice compared with in hospitals. CONCLUSIONS: The gradual shift in location of death of patients who die of CRC from institutionalized settings to home and hospice is a promising trend and reflects the prioritization of patient goals for end-of-life care by healthcare providers. However, there are existing sociodemographic disparities in access to deaths at home and in hospice, which emphasizes the need for policy interventions to reduce health inequity in end-of-life care for CRC.

Incidence of Secondary Cancers After Neoadjuvant Therapy for Locally Advanced Rectal Cancer.

INTRODUCTION: Whether neoadjuvant chemoradiation for locally advanced rectal cancer (LARC) induces secondary cancers is controversial. This retrospective cohort study describes the incidence of secondary cancers in LARC patients. METHODS: We compared 364 LARC patients who received conventional (50.4 Gy) or short course neoadjuvant radiation (25 Gy x 5 fractions) followed by resection to 142 patients with surgically resected rectal cancer who did not receive radiation at a single institution from 2004 to 2018. Secondary cancer was defined as any nonmetastatic noncolorectal malignancy diagnosed via biopsy or definitive imaging criteria at least 6 mo after completion of neoadjuvant therapy or after resection in the comparison group. RESULTS: Among the neoadjuvant radiation group (364 patients, 40% female, age 61 ± 13 y), 32 patients developed 34 (9.3%) secondary cancers. Three cases involved a pelvic organ. Among the comparison group (142 patients, 39% female, age 64 ± 15 y), 15 patients (10.6%) developed a secondary cancer. Five cases involved pelvic organs. Secondary cancer incidence did not differ between groups. Latency period to secondary cancer diagnosis was 6.7 ± 4.3 y. Patients who received radiation underwent longer median follow-up (6.8 versus 4.5 y, P < 0.01) and were significantly less likely to develop a pelvic organ cancer (odds ratio 0.18; 95% confidence interval, 0.04-0.83; P = 0.02). No genetic mutations or cancer syndromes were identified among patients with secondary cancers. CONCLUSIONS: Neoadjuvant chemoradiation is not associated with increased secondary cancer risk in LARC patients and may have a local protective effect on pelvic organs, especially prostate. Ongoing follow-up is critical to continue risk assessment.

Association depressive symptoms with memory function and social capital before and during COVID-19 in community-dwelling older adults in rural Japan: A retrospective study with a longitudinal data.

OBJECTIVES: This study aimed to investigate the impact of memory function and social capital on depressive symptoms during the COVID-19 pandemic among older adults in rural Japan. METHODS: A retrospective study with longitudinal data was conducted during COVID-19 from May 2021 to November 2021 (T2) in Kurogawa, Japan. The candidate population for this study was 145 with the following requirements: (1) older individuals aged 65 years or above who were registered in the Kurogawa study, and (2) those with previous data (from November 2016 to February 2020; T1 as pre-pandemic). Memory function was assessed using the Wechsler Memory Scale-Revised Logical Memory II delayed recall part A (LM II-DR). Depressive symptoms were assessed using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15). Social capital was evaluated through civic participation, social cohesion, and reciprocity. Fear of the COVID-19 infection (FCV-19S) was evaluated. RESULTS: The final analysis included 96 participants (mean age = 81.0 years, SD = 4.8) Multivariate analysis for GDS-15 score by Mixed Model Repeated Measures (MMRM) revealed significant associations between LM II-DR (ß = -0.13, 95% CI: -0.21-0.05, p = 0.002) and FCV-19S during COVID-19 (ß = 0.08, 95% CI: 0.01-0.15, p = 0.02) with GDS-15 score. However, civic participation, social cohesion and reciprocity were not associated with GDS-15 score. CONCLUSIONS: Among older adults in rural Japan, memory function and fear of the COVID-19 infection were significantly associated with depressive symptoms in MMRM analysis. However, social capital was not associated with depressive symptoms. This highlights the need to address memory function and fear of the COVID-19 infection in interventions for older adults during crises like the COVID-19 pandemic.

Development and multicentre validation of the FLEX score: personalised preoperative surgical risk prediction using attention-based ICD-10 and Current Procedural Terminology set embeddings.

BACKGROUND: Preoperative knowledge of surgical risks can improve perioperative care and patient outcomes. However, assessments requiring clinician examination of patients or manual chart review can be too burdensome for routine use. METHODS: We conducted a multicentre retrospective study of 243 479 adult noncardiac surgical patients at four hospitals within the Mass General Brigham (MGB) system in the USA. We developed a machine learning method using routinely collected coding and patient characteristics data from the electronic health record which predicts 30-day mortality, 30-day readmission, discharge to long-term care, and hospital length of stay. RESULTS: Our method, the Flexible Surgical Set Embedding (FLEX) score, achieved state-of-the-art performance to identify comorbidities that significantly contribute to the risk of each adverse outcome. The contributions of comorbidities are weighted based on patient-specific context, yielding personalised risk predictions. Understanding the significant drivers of risk of adverse outcomes for each patient can inform clinicians of potential targets for intervention. CONCLUSIONS: FLEX utilises information from a wider range of medical diagnostic and procedural codes than previously possible and can adapt to different coding practices to accurately predict adverse postoperative outcomes.

Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Salivary 3-methoxy-4-hydroxyphenylglycol and MRI-based volume change of the precuneus in community-dwelling elderly people.

BACKGROUND: The noradrenergic systems in the brain maintain cognitive functions including attention/concentration and establishment of long-term memory. In addition, hypofunction of noradrenergic systems is supposed to be involved in the pathophysiology of Alzheimer's disease. In this study, we tried to examine the possible associations of concentrations of basal salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), a major metabolite of noradrenaline, and brain volume changes during 4 years in elderly people living in a rural community. METHODS: The survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 226 residents. Measurements of sMHPG and brain MRIs were collected at Time 1 (2005-2007). Follow-up brain MRIs were taken at Time 2 (2009-2011). A total of 70 participants (18 men, mean age 71.9 ± 4.8 years; 52 women, mean age 72.0 ± 4.3 years) completed this survey. Concentrations of sMHPG at baseline were divided into two groups using the mean value (12.83 ng/ml). We compared the brain volumes between groups with higher and lower sMHPG concentrations over time using voxel-based morphometry implemented with statistical parametric mapping. RESULTS: In participants with higher sMHPG concentrations at baseline, brain volumes including right precuneus were significantly larger 4 years after baseline than those with lower sMHPG concentrations at baseline. No interaction between sMHPG concentration and MRI acquisition interval was found. CONCLUSION: Our results suggest that higher sMHPG concentrations in elderly people might be associated with maintenance of brain volume, especially in brain regions closely related to cognitive function.

Molecular Basis of Extramural Vascular Invasion (EMVI) in Colorectal Carcinoma.

BACKGROUND: Extramural vascular invasion (EMVI) is a known poor prognostic factor in colorectal carcinoma; however, its molecular basis has not been defined. This study aimed to assess the expression of molecular markers in EMVI positive colorectal carcinoma to understand their tumor microenvironment. METHODS: Immunohistochemistry was performed on tissue microarrays of surgically resected colorectal cancer specimens for immunological markers, and BRAFV600E mutation (and on the tissue blocks for mismatch repair proteins). Automated quantification was used for CD8, LAG3, FOXP3, PU1, and CD163, and manual quantification was used for PDL1, HLA I markers (beta-2 microglobulin, HC10), and HLA II. The Wilcoxon rank-sum test was used to compare EMVI positive and negative tumors. A logistic regression model was fitted to assess the predictive effect of biomarkers on EMVI. RESULTS: There were 340 EMVI positive and 678 EMVI negative chemo naïve tumors. PDL1 was barely expressed on tumor cells (median 0) in the entire cohort. We found a significantly lower expression of CD8, LAG3, FOXP3, PU1 cells, PDL1 positive macrophages, and beta-2 microglobulin on tumor cells in the EMVI positive subset (p ≤ 0.001). There was no association of BRAFV600E or deficient mismatch repair proteins (dMMR) with EMVI. PU1 (OR 0.8, 0.7-0.9) and low PDL1 (OR 1.6, 1.1-2.3) independently predicted EMVI on multivariate logistic regression among all biomarkers examined. CONCLUSION: There is a generalized blunting of immune response in EMVI positive colorectal carcinoma, which may contribute to a worse prognosis. Tumor-associated macrophages seem to play the most significant role in determining EMVI.

Impact of Bundled Payment Care Improvement Initiative on Health Care Expenditure in Major Bowel Procedures.

BACKGROUND: The Bundled Payments for Care Improvement initiative links payments for Medicare beneficiaries during an episode of care (90 days from index surgery). OBJECTIVE: This study aimed to determine whether major bowel participating Bundled Payments for Care Improvement organizations experience greater cost savings for colectomy while maintaining satisfactory quality outcomes compared to nonparticipating organizations. DESIGN: This is an Analysis of all Bundled Payments for Care Improvement participating hospitals for major bowel procedures (major bowel group) and propensity score-matched against Bundled Payments for Care Improvement organizations that do not include major bowel procedures (nonmajor bowel group) and those that do not participate in any Bundled Payments for Care Improvement program (non-Bundled Payments for Care Improvement group). SETTING: Programs accepting Medicare and Medicaid in the United States. PATIENTS: Patients included were major bowel cases in the Medicare Standard Analytic file within Medicare Severity Diagnosis-Related Groups 329-331 at participating facilities between January 1, 2011, and June 30, 2016. MAIN OUTCOME MEASURES: Main outcome measures included average total care expenditure and quality of care (length of stay, morbidity, and mortality) from 3 days preoperatively to 90 days postoperatively. RESULTS: We abstracted 7609 major bowel episodes from 23 major bowel group facilities, 21,872 episodes from nonmajor bowel-matched hospitals, and 19,383 episodes from non-Bundled Payments for Care Improvement-matched hospitals. From the baseline (January 2011 to June 2012) to final period (July 2015 to June 2016), we noted a $2955 average reduction in care expenditures. The largest decrease in average total episode expenditure occurred within the major bowel group (14% reduction) compared to the other groups (6% reduction for nonmajor bowel and 5% reduction for non-Bundled Payments for Care Improvement). Utilizing a generalized estimating equation to adjust for patient demographics, comorbidities, and hospital characteristics, the average total episode expenditure for the major bowel group decreased by $4885 (95% CI $4838-$4932; p < 0.001) compared to $2050 (95% CI $2038-$2061) for the non-Bundled Payments for Care Improvement group. All groups had similar reductions in length of stay, 30-day and 90-day complication rates, and readmission rates. LIMITATIONS: Analyses were limited by the retrospective nature of the study. CONCLUSIONS: Bundled Payments for Care Improvement participation for major bowel procedures resulted in a greater decrease in average total cost per episode of care than in nonparticipating hospitals without compromise in quality of care. See Video Abstract at http://links.lww.com/DCR/B837.IMPACTO DE LA INICIATIVA BUNDLED PAYMENT AGRUPADOS PARA LA MEJORA DE LA ATENCIÓN DEL GASTO SANITARIO EN LOS PROCEDIMIENTOS INTESTINALES MAYORESANTECEDENTES:La iniciativa de Bundled Payment para la mejora de la atención vincula los pagos para los beneficiarios de Medicare durante un episodio de atención (90 días desde la cirugía índice).OBJETIVO:Determinar si las principales organizaciones de Bundled Payment para el mejoramiento de la atención relacionados a los procedimientos intestinales experimentan mayores ahorros en los costos para una colectomía manteniendo resultados satisfactorios de calidad en comparación con las organizaciones no participantes.DISEÑO:Análisis de todos los hospitales participantes del programa Bundled Payment para la mejora de la atención para procedimientos intestinales mayores (grupo que incluyen procedimientos intestinales mayores) y puntaje de propensión comparado con las organizaciones que no incluyen dichos procedimientos (grupo que no incluye procedimientos intestinales mayores) y aquellos que no participan en ningún programa de Bundled Payment para la mejora de la atención (grupo no BPCI).MARCO:Programas que aceptan Medicare y Medicaid en los Estados Unidos.PACIENTES:Casos intestinales mayores en el archivo analítico estándar de Medicare dentro de los grupos relacionados con el diagnóstico 329-331 en los centros participantes entre el 1/1/2011-30/6/2016.PRINCIPALES MEDIDAS DE RESULTADO:Gasto total promedio y calidad de la atención (duración de la estadía, morbilidad, mortalidad) desde los 3 días preoperatorio hasta los 90 días postoperatorio.RESULTADOS:Hemos extraído 7609 episodios intestinales mayores de 23 instalaciones del grupo que incluyen procedimientos intestinales mayores, 21.872 episodios de hospitales del grupo que no incluyen procedimientos intestinales mayores y 19.383 episodios de hospitales del grupo no BPCI. Desde la línea de base (1/2011 - 6/2012) hasta el período final (7/2015 - 6/2016), notamos una reducción promedio de $2955 en los gastos de atención. La mayor disminución en el gasto promedio total por episodios ocurrió dentro del grupo que incluyen intestinales mayores (14% de reducción) en comparación con los otros grupos (6% de reducción para el grupo que no incluyen procedimientos intestinales mayores, 5% de reducción para el no BPCI). Utilizando una ecuación de estimación generalizada para ajustar los datos demográficos del paciente, las comorbilidades y las características del hospital, el gasto total promedio por episodio para el grupo que incluyen procedimientos intestinales mayores disminuyó en $ 4885 (IC del 95%: $4838-4932; p <0,001) en comparación con $2050 (IC del 95%: $2038-2061) para el grupo que no pertenece al programa BPCI. Todos los grupos tuvieron reducciones similares en la duración de la estancia, tasas de complicaciones de 30/90 días y de readmisión.LIMITACIONES:Análisis limitados por la naturaleza retrospectiva del estudio.CONCLUSIONES:La participación de Bundled Payment para la mejora de la atención en aquellos procedimientos intestinales mayores resultó en una disminución mayor en el costo total promedio por episodio de atención que en los hospitales no participantes, sin comprometer la calidad de la atención. Consulte Video Resumen en http://links.lww.com/DCR/B837. (Traducción-Dr Osvaldo Gauto).

Tumour genotypes account for survival differences in right- and left-sided colon cancers.

AIM: We sought to identify genetic differences between right- and left-sided colon cancers and using these differences explain lower survival in right-sided cancers. METHOD: A retrospective review of patients diagnosed with colon cancer was performed using The Cancer Genome Atlas, a cancer genetics registry with patient and tumour data from 20 North American institutions. The primary outcome was 5-year overall survival. Predictors for survival were identified using directed acyclic graphs and Cox proportional hazards models. RESULTS: A total of 206 right- and 214 left-sided colon cancer patients with 84 recorded deaths were identified. The frequency of mutated alleles differed significantly in 12 of 25 genes between right- and left-sided tumours. Right-sided tumours had worse survival with a hazard ratio of 1.71 (95% confidence interval 1.10-2.64, P = 0.017). The total effect of the genetic loci on survival showed five genes had a sizeable effect on survival: DNAH5, MUC16, NEB, SMAD4, and USH2A. Lasso-penalized Cox regression selected 13 variables for the highest-performing model, which included cancer stage, positive resection margin, and mutated alleles at nine genes: MUC16, USH2A, SMAD4, SYNE1, FLG, NEB, TTN, OBSCN, and DNAH5. Post-selection inference demonstrated that mutations in MUC16 (P = 0.01) and DNAH5 (P = 0.02) were particularly predictive of 5-year overall survival. CONCLUSIONS: Our study showed that genetic mutations may explain survival differences between tumour sites. Further studies on larger patient populations may identify other genes, which could form the foundation for more precise prognostication and treatment decisions beyond current rudimentary TNM staging.

Infiltrating Tumor Border Configuration is a Poor Prognostic Factor in Stage II and III Colon Adenocarcinoma.

INTRODUCTION: Tumor border configuration (TBC) is a prognostic factor in colorectal adenocarcinoma; however, the significance of TBC is not well-documented in colon adenocarcinoma alone. OBJECTIVE: Our aim was to study the effect of TBC on overall and disease-free survival in stage II and III colon adenocarcinoma. METHODS: We included patients with stage II and III colon adenocarcinoma who were surgically treated at a tertiary medical center between 2004 and 2015, to ensure long-term follow-up. Patients were stratified into four groups based on stage and TBC. A Cox regression was used to model the relationship of groups while accounting for relevant confounders. RESULTS: The cohort consisted of 700 patients (371 stage II and 329 stage III). Infiltrating TBC was statistically significantly associated with stage (p < 0.001) and extramural vascular invasion (p < 0.001), but not histologic grade (p = 0.7). Compared with pushing TBC, infiltrating TBC increased the hazard of death by a factor of 1.8 [95% confidence interval (CI) 1.4-2.4; p < 0.001] and 1.7 (95% CI 1.3-2.2; p < 0.001). The hazard of death in patients with stage II disease (infiltrating TBC) or stage III disease (pushing TBC) was not significantly different (adjusted hazard ratio 1.1, 95% CI 0.7-1.7; p = 0.8). CONCLUSION: Infiltrating TBC is a high-risk feature in patients with stage II and III colon adenocarcinoma. Stage II disease patients with infiltrating TBC and who are node-negative should be considered for adjuvant chemotherapy.

Improving staging of rectal cancer in the pelvis: the role of PET/MRI.

PURPOSE: The role of positron emission tomography/magnetic resonance (PET/MR) in evaluating the local extent of rectal cancer remains uncertain. This study aimed to investigate the possible role of PET/MR versus magnetic resonance (MR) in clinically staging rectal cancer. METHODS: This retrospective two-center cohort study of 62 patients with untreated rectal cancer investigated the possible role of baseline staging PET/MR versus stand-alone MR in determination of clinical stage. Two readers reviewed T and N stage, mesorectal fascia involvement, tumor length, distance from the anal verge, sphincter involvement, and extramural vascular invasion (EMVI). Sigmoidoscopy, digital rectal examination, and follow-up imaging, along with surgery when available, served as the reference standard. RESULTS: PET/MR outperformed MR in evaluating tumor size (42.5 ± 21.03 mm per the reference standard, 54 ± 20.45 mm by stand-alone MR, and 44 ± 20 mm by PET/MR, P = 0.004), and in identifying N status (correct by MR in 36/62 patients [58%] and by PET/MR in 49/62 cases [79%]; P = 0.02) and external sphincter infiltration (correct by MR in 6/10 and by PET/MR in 9/10; P = 0.003). No statistically significant differences were observed in relation to any other features. CONCLUSION: PET/MR provides a more precise assessment of the local extent of rectal cancers in evaluating cancer length, N status, and external sphincter involvement. PET/MR offers the opportunity to improve clinical decision-making, especially when evaluating low rectal tumors with possible external sphincter involvement.

Is Microsatellite Status Associated With Prognosis in Stage II Colon Cancer With High-Risk Features?

BACKGROUND: The influence of microsatellite instability on prognosis in high-risk stage II colon cancer is unknown. OBJECTIVE: This study aimed to investigate the relationship between microsatellite instability and overall survival in high-risk stage II colon cancer. DESIGN: This is a retrospective review of the National Cancer Database from 2010 to 2016. SETTINGS: This study included national cancer epidemiology data from the American College of Surgeons Commission on Cancer. PATIENTS: Included were 16,788 patients with stage II colon adenocarcinoma and known microsatellite status (1709 microsatellite unstable). MAIN OUTCOME MEASURES: The primary outcome measured was overall survival. RESULTS: Microsatellite unstable cancers with high-risk features had significantly better overall survival than microsatellite stable cancers with high-risk features (5-year survival 80% vs 72%, p = 0.01), and had survival equivalent to microsatellite stable cancers with low-risk features (5-year survival, 80%). When stratified by specific high-risk features, patients with lymphovascular invasion, perineural invasion, or high-grade histology had overall survival similar to patients without these features, only in microsatellite unstable cancers. However, patients with high-risk features of T4 stage, positive margins, and <12 lymph nodes saw no survival benefit based on microsatellite status. This was confirmed on multivariable Cox regression modeling. A subgroup analysis of patients who did not receive chemotherapy similarly demonstrated that microsatellite unstable cancers with lymphovascular invasion, perineural invasion, or high-grade histology had overall survival similar to microsatellite unstable cancers without those features. LIMITATIONS: The study is limited by the lack of specific clinical data and potential treatment bias. CONCLUSIONS: In microsatellite unstable cancers, lymphovascular invasion, perineural invasion, and high-grade histology are not associated with worse overall survival, even when deferring adjuvant chemotherapy. These data support National Comprehensive Cancer Network recommendations to forego chemotherapy in stage II cancers with microsatellite instability and these features. In contrast, some high-risk features were associated with worse survival despite microsatellite unstable biology, and therapies to improve survival need to be explored. See Video Abstract at http://links.lww.com/DCR/B500. ¿EL ESTADO MICROSATÉLITE ESTÁ ASOCIADO CON EL PRONÓSTICO EN EL CÁNCER DE COLON EN ESTADIO II CON CARACTERÍSTICAS DE ALTO RIESGO: Se desconoce la influencia de la inestabilidad microsatélite en el pronóstico del cáncer de colon en estadio II de alto riesgo.Investigar la relación entre la inestabilidad microsatélite y la supervivencia general en el cáncer de colon en estadio II de alto riesgo.Revisión retrospectiva de la base de datos nacional del cáncer de 2010 a 2016.Este estudio incluyó datos nacionales de epidemiología del cáncer de la Comisión de Cáncer del Colegio Americano de Cirujanos.16,788 pacientes con adenocarcinoma de colon en estadio II y estado microsatélite conocido (1,709 microsatélite inestables).Supervivencia global.Los cánceres microsatélite inestables con características de alto riesgo tuvieron una supervivencia general significativamente mejor que los cánceres microsatélite estables con características de alto riesgo (supervivencia a 5 años 80% vs 72%, p = 0.01), y tuvieron una supervivencia equivalente a los cánceres microsatélite estables con características de bajo riesgo (supervivencia a 5 años 80%). Al estratificar por características específicas de alto riesgo, los pacientes con invasión linfovascular, invasión perineural o histología de alto grado tuvieron una supervivencia general similar a la de los pacientes sin estas características, solo en cánceres microsatélite inestables. Sin embargo, los pacientes con características de alto riesgo en estadio T4, márgenes positivos y <12 ganglios linfáticos no tuvieron ningún beneficio de supervivencia basado en el estado de microsatélites. Esto se confirmó en un modelo de regresión de Cox multivariable. Un análisis de subgrupos de pacientes que no recibieron quimioterapia demostró de manera similar que los cánceres microsatélite inestables con invasión linfovascular, invasión perineural o histología de alto grado tenían una supervivencia general similar a los cánceres microsatélite inestables sin esas características.El estudio está limitado por la falta de datos clínicos específicos y el posible sesgo de tratamiento.En los cánceres microsatélite inestables, la invasión linfovascular, la invasión perineural y la histología de alto grado no se asocian con una peor sobrevida general, incluso cuando se aplaza la quimioterapia adyuvante. Estos datos respaldan las recomendaciones de la National Comprehensive Cancer Network de omitir la quimioterapia en los cánceres en estadio II con inestabilidad microsatélite y estas características. Por el contrario, algunas características de alto riesgo se asociaron con una peor supervivencia a pesar de la biología microsatélite inestable, y es necesario considerar las terapias para mejorar la supervivencia.Consulte Video Resumen en http://links.lww.com/DCR/B500. (Traducción-Dr. Jorge Silva Velazco).

Diverticular Disease Epidemiology: Rising Rates of Diverticular Disease Mortality Across Developing Nations.

BACKGROUND: The incidence of diverticular disease is growing in the Western world. However, the global burden of disease is unknown in the developing world. OBJECTIVE: This study aimed to determine the global burden of diverticular disease as measured by disease-specific mortality while identifying indicators of rising disease rates. DESIGN: We undertook an ecological analysis based on data from the World Health Organization Mortality Database. Then, we analyzed global age-adjusted mortality rates from diverticular disease and compared them to national rates of overweight adults, health expenditures, and dietary composition. SETTINGS: National vital statistics data were collected. PATIENTS: Diverticular disease deaths from January 1, 1994 through December 31, 2016 were evaluated. MAIN OUTCOME MEASURES: The primary outcome measured was the national age-adjusted mortality rate. RESULTS: The average age-adjusted mortality rate for diverticular disease was 0.51 ± 0.31/100,000 with a range of 0.11 to 1.75/100,000. During the study period, we noted that 57% of nations had increasing diverticular disease mortality rates, whereas only 7% had decreasing rates. More developed nations (40%) than developing nations (24%) were categorized as having high diverticular disease mortality burden over the time period of the study, and developed nations had higher percentages of overweight adults (58.9 ± 3.1%) than developing nations (50.6 ± 6.7%; p < 0.0001). However, developing nations revealed more rapid increases in diverticular disease mortality (0.027 ± 0.024/100,000 per year) than developed nations (0.005 ± 0.025/100,000 per year; p = 0.001), as well as faster expanding proportions of overweight adults (0.76 ± 0.12% per year) than in already developed nations (0.53 ± 0.10% per year; p<0.0001). LIMITATIONS: Ecological studies cannot define cause and effect. CONCLUSIONS: There is considerable variability in diverticular disease mortality across the globe. Developing nations were characterized by rapid increases in diverticular disease mortality and expanding percentages of overweight adults. Public health interventions in developing nations are needed to alter mortality rates from diverticular disease. See Video Abstract at http://links.lww.com/DCR/B397. EPIDEMIOLOGÍA DE LA ENFERMEDAD DIVERTICULAR: TASAS CRECIENTES DE MORTALIDAD POR ENFERMEDAD DIVERTICULAR EN LOS PAÍSES EN DESARROLLO: La incidencia de la enfermedad diverticular está creciendo en el mundo occidental. Sin embargo, la carga mundial de la enfermedad es desconocida en el mundo en desarrollo.Determinar la carga global de la enfermedad diverticular medida por la mortalidad específica de la enfermedad mientras se identifican los indicadores de aumento de las tasas de enfermedad.Realizamos un análisis ecológico basado en datos de la Base de datos de mortalidad de la Organización Mundial de la Salud. Luego, analizamos las tasas globales de mortalidad ajustadas por edad por enfermedad diverticular y las comparamos con las tasas nacionales de adultos con sobrepeso, gastos de salud y composición dietética.Datos nacionales de estadísticas vitales.Muertes por enfermedades diverticulares desde el 1 de enero de 1994 hasta el 31 de diciembre de 2016.Tasa nacional de mortalidad ajustada por edad.La tasa promedio de mortalidad ajustada por edad para la enfermedad diverticular fue de 0,51 ± 0,31 / 100,000 con un rango de 0,11 a 1,75 / 100,000. Durante el período de estudio, notamos que el 57% de las naciones tenían tasas crecientes de mortalidad por enfermedades diverticulares, mientras que solo el 7% tenían tasas decrecientes. Las naciones más desarrolladas (40%) que las naciones en desarrollo (24%) se clasificaron como que tienen una alta carga de mortalidad por enfermedad diverticular durante el período de tiempo del estudio, y las naciones desarrolladas tuvieron porcentajes más altos de adultos con sobrepeso (58.9 ± 3.1%) que las naciones en desarrollo (50,6 ± 6,7%) (p <0,0001). Sin embargo, las naciones en desarrollo revelaron aumentos más rápidos en la mortalidad por enfermedades diverticulares (0.027 ± 0.024 / 100,000 por año) que las naciones desarrolladas (0.005 ± 0.025 / 100,000 por año) (p = 0.001), así como proporciones de adultos con sobrepeso en expansión más rápida (0.76 ± 0.12% por año) que en las naciones ya desarrolladas (0.53 ± 0.10% por año) (p <0.0001).Los estudios ecológicos no pueden definir causa y efecto.Existe una considerable variabilidad en la mortalidad por enfermedad diverticular en todo el mundo. Los países en desarrollo se caracterizaron por un rápido aumento en la mortalidad por enfermedades diverticulares y porcentajes crecientes de adultos con sobrepeso. Se necesitan intervenciones de salud pública en los países en desarrollo para alterar las tasas de mortalidad por enfermedad diverticular. Consulte Video Resumen en http://links.lww.com/DCR/B397.

Ten-year survival after pathologic complete response in rectal adenocarcinoma.

BACKGROUND: Multimodal treatment is the standard of care for rectal adenocarcinoma, with a subset of patients achieving a pathologic complete response (pCR). While pCR is associated with improved overall survival (OS), long-term data on patients with pCR is limited. METHODS: This is a single institution retrospective cohort study of all patients with clinical stages II/III rectal adenocarcinoma who underwent neoadjuvant chemoradiation therapy and operative resection (January 1, 2004-December 31, 2017). PCR was defined as no tumor identified in the rectum or associated lymph nodes by final pathology. RESULTS: Of 370 patients in this cohort, 50 had a pCR (13.5%). For pCR patients, 5-year disease-free survival (DFS) was 92%, 5-year OS was 95%. Twenty-six patients had surgery > 10 years before the study end date, of which 20 had an OS > 10 years (77%) with median OS 12.1 years and 95% alive to date (19/20). Of the 50 pCR patients, there was a single recurrence in the lung at 44.3 months after proctectomy which was surgically resected. CONCLUSION: For patients with rectal adenocarcinoma that undergo neoadjuvant chemoradiation and surgical resection, pCR is associated with excellent long-term DFS and OS. Many patients live greater than 10 years with no evidence of disease recurrence.

The growing trend for no primary surgery in colorectal cancer.

AIM: In colorectal cancer (CRC), surgery of the primary site is commonly curative. Our aim was to determine estimates of 'no surgery' for primary CRC while identifying common reasons for no surgery. METHOD: We identified all patients with a diagnosis of colorectal adenocarcinoma from the National Cancer Database between January 2004 and December 2016. Then, we identified patients who did not undergo surgery on the primary tumour and their demographic, tumour and institutional characteristics. Kaplan-Meier and logistic regression analyses were used to evaluate specific factors associated with overall survival as related to no surgery and recommendations against operative management. RESULTS: A total of 1,208,878 patients with CRC were identified, 14.5% of whom had no surgery of the primary cancer. No surgery was more common in rectal cancer than in colon cancer. Despite a steady incidence of CRC diagnoses, the likelihood of no surgery grew by 170% over the study period. Metastatic disease was noted in 53.7% of the no surgery cohort. Nine per cent of the no surgery patient cohort received a recommendation against surgery despite the absence of metastatic disease, 7.5% refused surgery and only 2% underwent palliative surgery. On multivariable analysis, patients who were not recommended to have surgery were more likely to be older, uninsured, comorbid and receive care at a single hospital. The no surgery patients had significantly lower overall survival. CONCLUSION: A substantial proportion of patients with CRC do not have surgery. Interventions aimed at expanding access and promoting second opinions at other cancer hospitals might reduce the growing rate of no surgery in CRC.

Recurrence of Clostridium Difficile and Cytomegalovirus Infections in Patients with Ulcerative Colitis Who Undergo Ileal Pouch-Anal Anastomosis.

BACKGROUND: Patients with ulcerative colitis (UC) are at increased risk for infections such as Clostridium difficile and cytomegalovirus (CMV) colitis due to chronic immunosuppression. These patients often undergo multiple surgeries putting them at risk for recurrence of the infection. However, rates of recurrence in this setting and outcomes are not well understood. AIM: The aim of this study is to determine rates of recurrence of C difficile and CMV infection in patients undergoing multistage UC surgeries and effects of antibiotic prophylaxis on outcomes. METHODS: All patients with UC who underwent IPAA between 2001 and 2017 (at two tertiary referral centers were identified. History of C. difficile or CMV colitis prior to any surgery and recurrence after IPAA was noted RESULTS: A total of 633 patients with UC who underwent IPAA were identified, of whom 8.1% patients had C. difficile and 2.7% had CMV infections. 9.8% of C. difficile and 5.9% of CMV patients recurred after IPAA. Rates of abdominal sepsis (14.7% vs. 12.7%), 90-day mortality (0% vs. 0.4%), pouchitis (36.8% vs. 45.0%), or return to stoma (7.4% vs. 5.4%) were similar between patients who did or did not have infections. In patients with C. difficile infection prior to first surgery, none of the patients who received prophylaxis had recurrent infection. CONCLUSIONS: Rates of C. difficile and CMV infections remain high in patients undergoing surgery for UC, with substantial minority developing recurrent infection during subsequent surgical procedures. Antibiotic prophylaxis in patients with a history of C difficile may reduce the rate of recurrent infection.

Concordance Between Registry and Administrative Data in the Determination of Comorbidity: A Multi-institutional Study.

OBJECTIVE: To characterize agreement between administrative and registry data in the determination of patient-level comorbidities. BACKGROUND: Previous research finds poor agreement between these 2 types of data in the determination of outcomes. We hypothesized that concordance between administrative and registry data would also be poor. METHODS: A cohort of inpatient operations (length of stay 1 day or greater) was obtained from a consortium of 8 hospitals. Within each hospital, National Surgical Quality Improvement Program (NSQIP) data were merged with intra-institutional inpatient administrative data. Twelve different comorbidities (diabetes, hypertension, congestive heart failure, hemodialysis-dependence, cancer diagnosis, chronic obstructive pulmonary disease, ascites, sepsis, smoking, steroid, congestive heart failure, acute renal failure, and dyspnea) were analyzed in terms of agreement between administrative and NSQIP data. RESULTS: Forty-one thousand four hundred thirty-two inpatient surgical hospitalizations were analyzed in this study. Concordance (Cohen Kappa value) between the 2 data sources varied from 0.79 (diabetes) to 0.02 (dyspnea). Hospital variation in concordance (intersite variation) was quantified using a test of homogeneity. This test found significant intersite variation at a level of P < 0.001 for each of the comorbidities except for dialysis (P = 0.07) and acute renal failure (P = 0.19). These findings imply significant differences between hospitals in their generation of comorbidity data. CONCLUSION: This study finds significant differences in how administrative versus registry data assess patient-level comorbidity. These differences are of concern to patients, payers, and providers, each of which had a stake in the integrity of these data. Standardized definitions of comorbidity and periodic audits are necessary to ensure data accuracy and minimize bias.

Are There Variations in Mortality From Diverticular Disease By Sex?

BACKGROUND: Previous data reveal that females account for a disproportionate majority of all patients diagnosed with diverticulitis. OBJECTIVE: This study analyzed the variation in mortality from diverticular disease by sex. DESIGN: This was a nationwide retrospective cohort study. SETTINGS: Data were obtained from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research national registry. PATIENTS: All citizens of the United States who died from an underlying cause of death of diverticulitis between January 1999 and December 2016 were included. MAIN OUTCOME MEASURES: The primary outcome addressed was overall mortality rate of diverticulitis by sex. Secondary outcomes included pattern variances in demographics and secondary causes of death. RESULTS: During the study period, 55,096 patients (0.12%) died with an underlying cause of death of diverticulitis from a total of 44,915,066 deaths. Compared with other causes, females were disproportionally more likely to die from diverticulitis than males (0.17% females vs 0.08% males; p < 0.001). Age-adjusted incidence of death was higher for females compared with males. Female patients were less likely to die within the hospital compared with males (OR = 0.72 (95% CI, 0.69-0.75); p < 0.001). Conversely, female patients were more likely to die either at nursing homes or hospice facilities (OR = 1.64 (95% CI, 1.55-1.73); p < 0.001). In addition, females with an underlying cause of death of diverticulitis were less likely to have a surgical complication as their secondary cause of death (OR = 0.72 (95% CI, 0.66-0.78); p < 0.001) but more likely to have nonsurgical complications related to diverticulitis such as sepsis (OR = 1.04 (95% CI, 1.01-1.05); p < 0.03), nonsurgical GI disorders such as obstruction (OR = 1.16 (95% CI, 1.09-1.24); p < 0.001), or chronic pelvic fistulizing disease (OR = 1.43 (95% CI, 1.23-1.66); p < 0.001). LIMITATIONS: The study was limited by a lack of more specific clinical data. CONCLUSIONS: Females have a higher incidence of diverticular disease mortality. Their deaths are more commonly secondary to nonsurgical infections, obstruction, or pelvic fistulae. Female patients represent a particularly vulnerable population that may benefit from more intensive diverticulitis evaluation. See Video Abstract at http://links.lww.com/DCR/B257. ¿EXISTEN VARIACIONES EN LA MORTALIDAD POR ENFERMEDAD DIVERTICULAR POR GÉNERO?: Los datos anteriores revelan que las mujeres representan una mayoría desproporcionada de todos los pacientes diagnosticados con diverticulitis.Este estudio analizó la variación en la mortalidad por enfermedad diverticular por género.Estudio de cohorte retrospectivo a nivel nacional.Los datos se obtuvieron del registro nacional WONDER del Centro de Control de Enfermedades.Se incluyeron todos los ciudadanos de los Estados Unidos que murieron por una causa subyacente de muerte (UCOD por sus siglas en inglés) de diverticulitis del 1 / 1999-12 / 2016.El resultado primario abordado fue la tasa de mortalidad general de la diverticulitis por género. Los resultados secundarios incluyeron variaciones de patrones en la demografía y causas secundarias de muerte.Falta de datos clínicos más específicos.Durante el período de estudio, 55.096 pacientes (0,12%) murieron con un UCOD de diverticulitis de un total de 44.915.066 muertes. En comparación con otras causas, las mujeres tenían una probabilidad desproporcionadamente mayor de morir de diverticulitis que los hombres (0.17% F vs. 0.08% M, p <0.001). La incidencia de muerte ajustada por edad fue mayor para las mujeres que para los hombres. Las pacientes femeninas tenían menos probabilidades de morir en el hospital en comparación con los hombres (OR 0.72, IC 0.69-0.75, p <0.001). Por el contrario, las pacientes femeninas tenían más probabilidades de morir en asilos de ancianos o en centros de cuidados paliativos (OR 1.64, IC 1.55-1.73, p <0.001). Además, las mujeres con una UCOD de diverticulitis tenían menos probabilidades de tener una complicación quirúrgica como causa secundaria de muerte (OR 0.72, CI 0.66-0.78, p <0.001) pero más probabilidades de tener complicaciones no quirúrgicas relacionadas con la diverticulitis, como sepsis (OR 1.04, CI 1.01-1.05, p <0.03), trastornos gastrointestinales no quirúrgicos como obstrucción (OR 1.16, CI 1.09-1.24, p <0.001), o enfermedad fistulizante pélvica crónica (OR 1.43, CI 1.23-1.66, p <0,001).Las mujeres tienen una mayor incidencia de mortalidad por enfermedad diverticular. Sus muertes son más comúnmente secundarias a infecciones no quirúrgicas, obstrucción o fístulas pélvicas. Las pacientes femeninas representan una población particularmente vulnerable que puede beneficiarse de una evaluación más intensiva de diverticulitis. Consulte Video Resumen en http://links.lww.com/DCR/B257.

Bowel Function After J-Pouch May Be More Complex Than Previously Appreciated: A Comprehensive Analysis to Highlight Existing Knowledge Gaps.

BACKGROUND: Functional outcomes following J-pouch for ulcerative colitis have been studied, but lack standardization in which symptoms are reported. Furthermore, the selection of symptoms studied has not been patient centered. OBJECTIVE: This study aimed to utilize a validated bowel function survey to determine which symptoms are present after J-pouch creation, and whether patients display a functional profile similar to low anterior resection syndrome. DESIGN: This study is a retrospective analysis of a prospectively maintained single-center database. SETTINGS: This study was conducted at the colorectal surgery center of a tertiary care academic hospital PATIENTS:: Included were 159 patients with J-pouch, ≥6 months after ileostomy reversal. MAIN OUTCOME MEASURES: The primary outcomes were individual answers to the Memorial Sloan Kettering Cancer Center Bowel Function Instrument. The original Bowel Function Instrument validation cohort was used as an historical comparison (n = 127). RESULTS: The mean total Bowel Function Instrument score for the J-pouch cohort was 59.9 ± 9.7 compared with a reported average score of 63.7 ± 11.6 for patients with low anterior resection in the validation cohort (p < 0.001), indicating worse bowel function in patients with J-pouch. When evaluating the Bowel Function Instrument subscales, patients with J-pouch reported frequency subscale scores of 18.2 ± 3.8, diet scores of 12.2 ± 3.8, and urgency scores of 15.9 ± 3.7, compared with 21.7 ± 4.5 (p < 0.001), 14.1 ± 3.7 (p < 0.001), and 15.0 ± 3.9 (p = 0.04) for patients undergoing rectal resection. Furthermore, 90.4% of patients with J-pouch state that they are sometimes, rarely, or never able to wait 15 minutes to get to the toilet. In addition, 56.4% of patients report having another bowel movement within 15 minutes of the last bowel movement, sometimes, always, or most of the time, and 50.6% of patients say that they sometimes, rarely, or never feel like their bowels have been totally emptied after a bowel movement. LIMITATIONS: This study is limited because it took place at a single center and the Bowel Function Instrument was only validated for patients undergoing rectal resection. CONCLUSIONS: Patients that undergo J-pouch surgery exhibit a constellation of bowel function symptoms that is more complex than fecal incontinence and frequency alone, despite the focus on these functional outcomes in the literature. See Video Abstract at http://links.lww.com/DCR/B73. LA FUNCIÓN INTESTINAL DESPUÉS DE LA BOLSA EN J PUEDE SER MÁS COMPLEJA DE LO QUE SE APRECIABA ANTERIORMENTE: UN ANÁLISIS EXHAUSTIVO PARA RESALTAR LAS BRECHAS DE CONOCIMIENTO EXISTENTES: Se han estudiado los resultados funcionales después de la bolsa en J para la colitis ulcerosa, pero carecen de estandarización en la que se informen los síntomas. Además, la selección de los síntomas estudiados no se ha centrado en el paciente.Utilizar una encuesta validada de la función intestinal para determinar qué síntomas están presentes después de la bolsa en J y si los pacientes muestran un perfil funcional similar al síndrome de resección anterior baja.Análisis retrospectivo de una base de datos de un solo centro mantenida prospectivamente.Centro de cirugía colorrectal de un hospital académico de atención terciaria.159 pacientes con bolsa en J, ≥6 meses después de la reversión de ileostomía.Instrumento para la función intestinal del "Memorial Sloan Kettering Cancer Center"; cohorte de validación original de instrumentos de función intestinal utilizada como comparación histórica (n = 127).La puntuación media total del instrumento de función intestinal para la cohorte de bolsa J fue 59.9 ± 9.7 en comparación con un puntaje promedio reportado de 63.7 ± 11.6 para pacientes con resección anterior baja en la cohorte de validación (p < 0.001), lo que indica peor función intestinal en pacientes con bolsa en J. Al evaluar las subescalas del instrumento de función intestinal, los pacientes con bolsa en J informaron puntuaciones de subescala de frecuencia de 18.2 ± 3.8, puntuaciones de dieta de 12.2 ± 3.8 y puntuaciones de urgencia de 15.9 ± 3.7, en comparación con 21.7 ± 4.5 (p < 0.001), 14.1 ± 3.7 (p < 0.001) y 15.0 ± 3.9 (p = 0.04) respectivamente para pacientes con resección rectal. Además, el 90.4% de los pacientes con bolsa en J afirman que a veces, rara vez o nunca pueden esperar 15 minutos para llegar al baño. Además, el 56.4% de los pacientes reportan haber tenido otra evacuación intestinal dentro de los 15 minutos posteriores a la última evacuación intestinal, a veces, siempre o la mayor parte del tiempo, y el 50.6% de los pacientes dicen que a veces, rara vez o nunca sienten que sus intestinos han sido vaciados totalmente después de una evacuación intestinal.Estudio en un solo centro, instrumento de función intestinal validado solo para pacientes con resección rectalLos pacientes que se someten a una bolsa en J exhiben una constelación de síntomas de la función intestinal que es más compleja que la incontinencia fecal y la frecuencia sola, a pesar del enfoque en estos resultados funcionales en la literatura.Consulte Video Resumen en http://links.lww.com/DCR/B73. (Traducción-Dr. Gonzalo Federico Hagerman).

Detrimental impact of symptom-detected colorectal cancer.

BACKGROUND: The incidence and mortality rates of colorectal cancer (CRC) have been steadily decreasing, largely attributable to screening colonoscopies that either remove precancerous lesions or identify CRC earlier. We aimed to assess the prognostic difference between colorectal cancers diagnosed by screening (SC), diagnostic (DC), or surveillance (SU) colonoscopies. METHODS: All 1809 surgically treated patients with primary CRC diagnosed through colonoscopy at our tertiary center (2004-2015) were extracted from a prospectively maintained database. Oncologic outcomes were compared, including multivariate Cox regression. RESULTS: Diagnostic patients presented with more advanced disease (15.0% vs. 53.2% (SC) and 55.3% (SU) AJCC I, P < 0.001), subsequently leading to impaired survival and higher recurrence rates (P < 0.001). After adjustment for age, ASA-score and gender, oncologic outcomes remained significantly worse after DC. Hazard ratios (HR) of overall mortality (OS) compared to DC were 0.36 for SC and 0.58 for SU (P < 0.001). Adjusted HRs of disease-free survival (DFS) were 0.43 and 0.32, respectively (P < 0.001). Worse outcomes in OS withstood adjustment for stage, tumor site and (neo)adjuvant treatment (SC: HR 0.46, P < 0.001; SU: HR 0.73, P = 0.036). The benefits of SC were particularly seen in colon cancer, stages I-II and female patients. With regard to DFS, outcomes were less profound and mainly true in early stage disease and surveillance patients. CONCLUSIONS: This study demonstrates the enormous impact of asymptomatic screening in CRC. Patients with CRC diagnosed through screening or surveillance had a significantly better prognosis compared to patients who presented symptomatically. This emphasizes the importance of screening.