Improved Survival in a Cohort of Patients Aged 75 Years and Older With Fecal Immunochemical Testing-Detected Colorectal Cancer.

BACKGROUND: Fecal immunochemical testing is an accepted form of colorectal cancer screening and is recommended for adults up to the age of 75 years in Canadian guidelines. However, many individuals 75 years and older continue to receive fecal immunochemical testing despite being outside accepted guidelines. OBJECTIVE: This study aimed to determine whether patients aged 75 years and older with screen-detected cancer demonstrated improved outcomes and survival compared with patients with non-screen-detected cancer. DESIGN: This is a retrospective population-based cohort study. SETTINGS: Provincial data were collected from the Alberta Cancer Registry and the Alberta Colorectal Cancer Screening Program between November 2013 and 2019. PATIENTS: We identified an aggregated patient cohort aged 75 years and older with a diagnosis of colorectal cancer from November 2013 to November 2019, as well as patients 75 years and older who underwent fecal immunochemical testing within these dates. MAIN OUTCOME MEASURES: The proportion of screen-detected colorectal cancers was calculated. Surgical intervention, hospital length of stay, postoperative mortality, and overall survival were analyzed. RESULTS: Between November 2013 and 2019, 3586 patients 75 years and older were diagnosed with colorectal cancer; 690 (19%) were "screen-detected." Screen-detected patients were almost 3 times more likely to undergo surgery (OR, 2.83) and had a 36% overall survival benefit (HR, 0.64) compared with non-screen-detected patients, adjusted for other variables such as age, Charlson Comorbidity Index, and stage. LIMITATIONS: The retrospective study design prevents conclusions regarding causation. CONCLUSIONS: Screen detection of colorectal cancer in patients aged 75 years and older is associated with improved overall survival when controlling for other potential confounders. When compared with their non-screen-detected counterparts, these patients have an earlier stage of disease and are more likely to undergo surgical intervention with improved outcomes, irrespective of age. These data may support screening for appropriately selected patients who would otherwise fall outside of current guidelines. See Video Abstract at http://links.lww.com/DCR/B986 . SOBREVIDA MEJORADA EN UNA COHORTE DE PACIENTES DE AOS O MS CON CNCER COLORRECTAL DETECTADOS POR RIF: ANTECEDENTES:La prueba basada en una Reacción Inmunoquímica Fecal - RIF, es una forma aceptada de detección de cáncer colorrectal y esta recomendada en adultos a partir de los 75 años en las guías canadienses. Sin embargo, muchas personas de 75 años o más continúan realizándose pruebas inmunoquímicas fecales a pesar de estar fuera de las guías aceptadas.OBJETIVO:Poder determinar si los pacientes de 75 años o más con detección RIF positiva a un cáncer demuestran mejores resultados y sobrevida comparados con los pacientes sin detección.DISEÑO:Estudio de cohortes retrospectivo basado en una población definida.CONFIGURACIÓN:Se recopilaron los datos provinciales del Registro de cánceres y del Programa de detección de cáncer colorrectal de Alberta, Canada, entre 2013 y 2019.PACIENTES:Identificamos una cohorte agregada de pacientes de 75 años o más con diagnóstico de cáncer colorrectal desde noviembre de 2013 hasta noviembre de 2019, así como pacientes de 75 años o más que se sometieron a pruebas inmunoquímicas fecales dentro de las fechas mencionadas.PRINCIPALES MEDIDAS DE RESULTADO:Se calculó la proporción de cánceres colorrectales detectados mediante un cribado. Se analizaron la intervención quirúrgica, la duración de la estadía hospitalaria, la mortalidad post-operatoria y la sobrevida global.RESULTADOS:Entre noviembre de 2013 y noviembre 2019, 3586 pacientes de 75 años o más, fueron diagnosticados con cáncer colorrectal; 690 (19%) fueron detectados por cribado. Los pacientes detectados mediante el cribado, tenían casi tres veces más probabilidades de someterse a una cirugía (Razón de Probabilidad de 2,83) y beneficiaron de una sobrevida general del 36 % (HR 0,64) comparados con los pacientes sin detectación por cribado, corregidos por otras variables como la edad, el índice de comorbilidad de Charlson y el estadío del tumor.LIMITACIONES:El diseño retrospective del presente estudio impide obtener conclusiones con respecto a la causalidad.CONCLUSIONES:La detección por cribado de cáncer colorrectal en pacientes de 75 años o más se asocia con una mejor sobrevida general cuando se controlan los otros posibles factores de confusión. Comparando con las contrapartes no detectadas por cribado, estos pacientes se encuentran en una etapa más temprana de la enfermedad y es más probable que se sometan a una intervención quirúrgica con mejores resultados, independientemente a la edad. Estos datos pueden respaldar la detección de pacientes adecuadamente seleccionados que, de otro modo, quedarían fuera de las pautas actuales. Consulte Video Resumen en http://links.lww.com/DCR/B986 . (Traducción-Dr. Xavier Delgadillo ).

Self-Expanding Metal Stents Do Not Adversely Affect Long-term Outcomes in Acute Malignant Large-Bowel Obstruction: A Retrospective Analysis.

BACKGROUND: Self-expanding metal stents as a bridge to surgery in acute malignant large-bowel obstruction has gained popularity. However, long-term oncologic outcomes have not been well established. OBJECTIVE: To investigate long-term oncologic outcomes of patients undergoing curative resection after the placement of a colonic stent compared with emergency surgery for acute malignant large-bowel obstruction. DESIGN: This is a retrospective study. SETTING: All patients presenting at 3 tertiary care centers between April 2002 and December 2012 with a diagnosis of complete malignant large-bowel obstruction were reviewed. Patients with disease distal to the hepatic flexure were selected for analysis. PATIENTS: One hundred twenty-two patients who underwent either emergency surgery or placement of a colonic stent with curative intent were included. INTERVENTIONS: Patients receiving emergency surgery within 24 hours of presenting with obstructive symptoms, including those with failed stents, were included in the emergency surgery group. All patients with clinically successful stent deployment before surgery were included in the stent group. MAIN OUTCOME MEASURES: Overall survival and disease-free survival were calculated using the Kaplan-Meier method. RESULTS: Sixty-four patients underwent emergency surgery, and 58 patients underwent placement of a self-expanding metal stent. Groups were similar in terms of sex, tumor stage and grade, and Charlson and Charlson-Age Comorbidity Index scores. Patients in the surgery group were older than patients in the stent group. There were no differences in the number of lymph nodes harvested, positive nodes, rates of vascular and perineural invasion, or utilization of chemotherapy. Thirty-day mortality after resection was similar between groups (7.41% vs 4.41%; p > 0.05). Patients who underwent colonic stenting as a bridge to surgery had similar 10-year overall survival (40.5% vs 32.7%; p = 0.13) and 10-year disease-free survival (40.2% vs 33.8%; p = 0.26) compared with those who underwent emergency surgery. Similar results were seen on intention-to-treat analysis. LIMITATIONS: This was a small retrospective study. CONCLUSIONS: Stent insertion followed by oncologic resection is associated with similar overall survival and disease-free survival compared with emergency resection. Stent insertion as a bridge to surgery should be considered in patients presenting with malignant colorectal obstruction. See Video Abstract at http://links.lww.com/DCR/B714Los Stents Metálicos Autoexpandibles No Afectan Negativamente Los Resultados A Largo Plazo En La Obstrucción Maligna Aguda Del Colon: Un Análisis Retrospectivo. ANTECEDENTES: Los stents metálicos autoexpandibles como puente a una cirugía en la obstrucción maligna aguda del colon han ganado popularidad. Sin embargo, no se han establecido bien los resultados oncológicos a largo plazo. OBJETIVO: Investigar los resultados oncológicos a largo plazo de los pacientes sometidos a resección curativa después de la colocación de un stent colónico en comparación con la cirugía de urgencia para la obstrucción maligna aguda del colon. DISEO: Estudio retrospectivo. MBITO: Entre abril de 2002 y diciembre de 2012, se revisaron todos los pacientes que acudieron a tres centros de tercer nivel con un diagnóstico de obstrucción maligna completa del colon. Se seleccionaron para el análisis los pacientes con enfermedad distal al ángulo hepático. PACIENTES: Se incluyeron 122 pacientes que fueron operados de urgencia o a una colocación de un stent colónico con intención curativa. PROCEDIMIENTOS: Los pacientes que se sometieron a cirugía de urgencia dentro de las 24 horas posteriores a la presentación de síntomas obstructivos; se incluyeron aquellos con stents fallidos en el grupo de cirugía de urgencia. Todos los pacientes con colocación clínicamente exitosa del stent antes de la cirugía se incluyeron en el grupo de stent. PRINCIPALES VARIABLES ANALIZADAS: La sobrevida global y la sobrevida libre de enfermedad se calcularon mediante el método de Kaplan-Meier. RESULTADOS: Sesenta y cuatro pacientes fueron llevados a cirugía urgente y en 58 pacientes se colocó de un stent metálico autoexpandible. Los grupos fueron similares en relación a sexo, estadio y grado del tumor, puntuación de comorbilidad de Charlson y Charlson-Age. Los pacientes del grupo de cirugía eran mayores que los del grupo de stents. No hubo diferencias en el número de ganglios linfáticos recolectados, ganglios positivos, tasas de invasión vascular y perineural o utilización de quimioterapia. La mortalidad a los 30 días después de la resección fue similar entre los grupos (7,41% frente a 4,41%; p> 0,05). Los pacientes que se sometieron a la colocación de un stent colónico como puente a la cirugía tuvieron una sobrevida general a diez años similar (40,5% vs 32,7%; p = 0,13) y una sobrevida libre de enfermedad a diez años (40,2% vs 33,8%, respectivamente; p = 0,26) en comparación a los operados de urgencia. Se observaron resultados similares en el análisis por intención de tratamiento. LIMITACIONES: Estudio retrospectivo reducido. CONCLUSIONES: La utilización de un stent y posteriormente la resección oncológica se asocia a una sobrevida general y una sobrevida libre de enfermedad similar en comparación con la resección de urgencia. La utilización de un stent como puente a la cirugía debe considerarse en pacientes que presentan obstrucción colorrectal maligna. Consulte Video Resumen en http://links.lww.com/DCR/B714. (Traducción-Dr. Lisbeth Alarcon-Bernes).

Evaluation of the Implementation of Multiple Enhanced Recovery After Surgery Pathways Across a Provincial Health Care System in Alberta, Canada.

Importance: Engaging multidisciplinary care teams in surgical practice is important for the improvement of surgical outcomes. Objective: To evaluate the association of multiple Enhanced Recovery After Surgery (ERAS) pathways with ERAS guideline adherence and outcomes. Design, Setting, and Participants: This quality improvement study compared a pre-ERAS cohort (2013-2017) with a post-ERAS cohort (2014-2018). All patients were from Alberta Health Services in Alberta, Canada, and had available ERAS and up to 1-year postsurgery administrative data. Data collected included age, sex, body mass index, tobacco and alcohol use, diabetes, comorbidity index, and surgical characteristics. Data analysis was performed from May 7, 2020, to February 1, 2021. Interventions: Implementation of 5 ERAS pathways (colorectal, liver, pancreas, gynecologic oncology, and radical cystectomy) across 9 sites. Main Outcomes and Measures: Adherence to ERAS guidelines was measured by the percentage of patients whose care met the common ERAS pathway care element criteria. Surgical procedures were grouped by complexity; complications were classified by severity. Outcome measures for the pre-post-ERAS cohorts included length of stay (LOS), readmission, complications, and mortality. Results: A total of 7757 patients participated in the study, including 984 in the pre-ERAS cohort (median [interquartile range] age, 62 [53-71] years; 526 [53.5%] female) and 6773 in the post-ERAS cohort (median [interquartile range] age, 62 [53-71] years; 3470 [51.2%] male). In the total cohort, care-element adherence improved from 52% to 76% (P < .001), no significant differences were found in serious complications (from 6.2% to 4.9%; P = .08) or 30-day mortality (from 0.71% to 0.93%; P = .50), 1-year mortality decreased from 7.1% to 4.6% (P < .001), mean (SD) LOS decreased from 9.4 (7.0) to 7.8 (5.0) days (P < .001), and 30-day readmission rates were unchanged (from 13.4% to 11.7%; P = .12). After adjustment for patient characteristics, the LOS mean difference decreased 0.71 days (95% CI, -1.13 to -0.29 days; P < .001), with no significant differences in adjusted 30-day readmission (-3.5%; 95% CI, -22.7% to 20.4%; P = .75), serious complications (1.3%; 95% CI, -26.2% to 39.0%; P = .94), or mortality (30-day mortality: 42% [95% CI, -35.4% to 212.3%]; P = .38; 1-year mortality: 8% [95% CI, -20.5% to 46.8%]; P = .62). The adjusted 1-year readmission rate was -15.6% (95% CI, -27.7% to -1.5%; P = .03) in favor of ERAS, and readmission LOS was shorter by 1.7 days (95% CI, -3.3 to -0.1 days; P = .04). Conclusions and Relevance: The results of this quality improvement study suggest that implementation of ERAS across multiple pathways may improve health care practitioner adherence to ERAS guidelines, LOS, and readmission rates at a system level.

Classic and Novel Histopathologic Risk Factors for Lymph Node Metastasis in T1 Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Treatment of endoscopically resected T1 colorectal cancers is based on the risk of lymph node metastasis. Risk is based on histopathologic features, although there is lack of consensus as to what constitutes high-risk features. OBJECTIVE: The purpose of this study was to conduct a systematic review and meta-analysis of histopathologic risk factors for lymph node metastasis. DATA SOURCES: A search of MEDLINE, Embase, Scopus, and Cochrane controlled register of trials for risk factors for lymph node metastasis was performed from inception until August 2018. STUDY SELECTION: Included patients must have had an oncologic resection to confirm lymph node status and reported at least 1 histopathologic risk factor. INTERVENTION: Rates of lymph node positivity were compared between patients with and without risk factors. MAIN OUTCOME MEASURES: We report the results of the meta-analysis as ORs. RESULTS: Of 8592 citations, 60 met inclusion criteria. Pooled analyses found that lymphovascular invasion, vascular invasion, neural invasion, and poorly differentiated histology were significantly associated with lymph node metastasis, as were depths of 1000 µm (OR = 2.76), 1500 µm (OR = 4.37), 2000 µm (OR = 2.37), submucosal level 3 depth (OR = 3.08), and submucosal level 2/3 (OR = 3.08) depth. Depth of 3000 µm, Haggitt level 4, and widths of 3000 µm and 4000 µm were not significantly associated with lymph node metastasis. Tumor budding (OR = 4.99) and poorly differentiated clusters (OR = 14.61) were also significantly associated with lymph node metastasis. LIMITATIONS: Included studies reported risk factors independently, making it impossible to examine the additive metastasis risk in patients with numerous risk factors. CONCLUSIONS: We identified 1500 µm as the depth most significantly associated with lymph node metastasis. Novel factors tumor budding and poorly differentiated clusters were also significantly associated with lymph node metastasis. These findings should help inform guidelines regarding risk stratification of T1 tumors and prompt additional investigation into the exact contribution of poorly differentiated clusters to lymph node metastasis.

New Ileostomy Formation and Subsequent Community-onset Acute and Chronic Kidney Disease: A Population-based Cohort Study.

OBJECTIVE: The aim of this study was to examine relationships between ileostomy formation and subsequent kidney disease. SUMMARY AND BACKGROUND DATA: Colonic absorptive capacity loss from ileostomy formation can cause volume depletion and could result in kidney disease. METHODS: We conducted a population-based cohort study comparing patients who underwent ileostomy formation with or without bowel resection (ileostomy group) to patients who underwent bowel resection without ileostomy formation (reference group). Adjusted odds ratios (aORs) for community-onset acute kidney injury (AKI) within 3 months and new-onset chronic kidney disease (CKD) within 1 year following hospital discharge were determined. RESULTS: Among 19,889 patients, 4136 comprised the ileostomy group and 15,753 comprised the reference group; 1350 patients experienced community-onset AKI and 464 developed new-onset CKD. The aOR for community-onset AKI with ileostomy formation was 4.08 [95% confidence interval (CI) = 3.62-4.61] for any stage AKI, 7.08 (95% CI = 5.66-8.85) for stage ≥2 injury, and 7.67 (95% CI = 5.06-11.63) for stage 3 injuries. Community-onset AKI modified associations between ileostomy formation and new-onset CKD (P = 0.002). Odds of new-onset CKD were increased in the ileostomy group relative to the reference group for patients both with (aOR = 4.99; 95% CI = 3.42-7.28) and without (aOR = 2.45; 95% CI = 1.85-2.23) previous community-onset AKI episodes. In analyses comparing patients that underwent ileostomy formation and subsequent reversal within 1 year to the reference group without ileostomy, the relationship with new-onset CKD was attenuated for patients both with (aOR = 2.49; 95% CI = 1.50-4.12) and without (aOR = 0.97; 95% CI = 0.67-1.40) previous community-onset AKI episodes. CONCLUSIONS: Ileostomy formation is strongly associated with subsequent kidney disease. Vigilance for this complication and new strategies for prevention and treatment are necessary.

Malignant Colorectal Polyp Pathology: Are We Getting Sufficient Information to Make Decisions?

BACKGROUND: The College of American Pathologists has published guidelines for malignant colorectal polyp pathology reports that list histopathological features that are "core elements" and "optional." Lack of element reporting may result in inaccurate tumor risk stratification.This study aimed to perform a population-based assessment of pathology reporting for T1 colorectal cancers and determine the completeness of reporting for core and optional histopathological elements.This is a retrospective cohort study.This study reviews the pathology reports of endoscopically resected malignant colorectal polyps in Alberta, Canada between 2014 and 2016.Individuals aged 18 years or older with T1 colorectal polyps were selected.Histopathological elements were dichotomized into core and optional. Malignant polyps were classified as high risk or low risk for lymph node metastases and local intraluminal recurrence. Addendum reports were compared with first reports.After applying exclusion criteria, 431 polyps were analyzed. The mean age of patients was 65.5 years; 59.4% were male. Histological grade, deep margin, and lymphovascular invasion were reported in 82.4%, 86.8% and 75.6%; all 3 were reported in only 66.4%. Tumor budding (not in the 2016 guidelines) was reported in 14.4%. One hundred ninety polyps (44.1%) were high risk. Thirty-seven polyps (8.3%) had an addendum report. Following the addendum, 1 polyp was downgraded to low risk, and 9 polyps were upgraded to high risk.The main limitation of the study is its retrospective nature. The decision making surrounding treatment for T1 cancers is complex, and factors other than histopathological tumor features may have been part of treatment decisions.There is a high rate of incomplete reporting of core and optional elements for malignant colorectal polyp pathology reports in Alberta. Several variables used by colorectal surgeons for decision making, such as tumor budding and depth of submucosal invasion, are not considered core elements and are infrequently reported. A pathology review by a second pathologist often results in a change in risk stratification. See Video Abstract at http://links.lww.com/DCR/B98. PATOLOGÍA DEL PÓLIPO COLORRECTAL MALIGNO: ¿ESTAMOS OBTENIENDO INFORMACIÓN SUFICIENTE PARA TOMAR DECISIONES?: El Colegio de Patólogos Americanos publico pautas para informes de patología de pólipos colorrectales malignos que enumeran características histopatológicas como "elementos centrales" y "opcionales". La falta de información elemental puede resultar en una estratificación de riesgo tumoral imprecisa.Valoración basada en una población de los informes de patología para los cánceres colorrectales T1 y determinar la precisión de los informes en cuanto los elementos histopatológicos centrales y opcionales.Estudio de cohorte retrospectivo.Este estudio revisa los informes de patología de pólipos colorrectales malignos resecados endoscópicamente en Alberta, Canadá, entre 2014 y 2016.personas mayores de 18 años con pólipos colorrectales T1.Los elementos histopatológicos se dicotomizaron entre elementales y opcionales. Pólipos malignos se clasificaron como de alto riesgo o bajo riesgo de metástasis en los ganglios linfáticos y recurrencia intraluminal local. Los informes enmendados se compararon con los informes originales.Después de aplicar los criterios de exclusión, se analizaron 431 pólipos. La edad media fue 65.5 años, con 59.4% masculinos. El grado histológico, el margen profundo y la invasión linfovascular se informaron confirmaron en 82.4%, 86.8% y 75.6% respectivamente; las tres características se demostraron en solo 66.4%. Un patrón tumoral en ciernes se reporto en 14.4-una característica que no se usaba en las guías de 2016. Ciento noventa pólipos (44.1%) eran de alto riesgo. Treinta y siete pólipos (8.3%) requirieron de un informe enmendado. Aplicación de los nuevos criterios resulto en que 1 pólipo se redujo a bajo riesgo y 9 pólipos se actualizaron como a alto riesgo.La principal limitación del estudio es el diseño retrospectivo. La toma de decisiones en torno al tratamiento de los cánceres T1 es compleja y otros factores además de las características histopatológicas del tumor pueden haber sido parte de las decisiones terapéuticas.Hay una alta tasa de informes incompletos de elementos centrales y opcionales para informes de patología de pólipos colorrectales malignos en Alberta. Algunas variables utilizadas por los cirujanos colorrectales para la toma de decisiones, como el patrón tumoral en ciernes y la profundidad de la invasión submucosa, no se consideran elementos centrales y se informan con poca frecuencia. Una revisión de patología realizada por un segundo patólogo a menudo resulta en un cambio en la estratificación del riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B98. (Traducción-Dr. Adrian E. Ortega).

Expedited discharge in uncomplicated acute appendicitis: Decreasing the length of stay while maintaining quality.

BACKGROUND: An expedited discharge protocol for uncomplicated appendicitis was developed at a Canadian academic hospital to determine if patients could be safely discharged home early without negatively impacting care and patient satisfaction. METHODS: A non-randomized prospective quality improvement project was completed between February 01, 2017 and January 31, 2018. The project included patients between 16 and 65 years with uncomplicated appendicitis managed with laparoscopic appendectomy. The primary outcome was average length of stay post PACU. 30 day ED visit, cross-sectional imaging and readmission rate were balancing measures. The CTM-3 tool was used to measure patient satisfaction. RESULTS: 450 patients had emergent laparoscopic appendectomy. 287 (63.8%) patients met the project inclusion criteria. The average length of stay decreased 41.0% to 13.1 h. The 30 day ED visit, cross-sectional imaging and readmission rate were 9.8%, 4.5% and 1.0% respectively compared with 8.1%, 4.5% and 2.5% at baseline. Patient satisfaction was 3.72/4 compared to 3.74/4. CONCLUSION: An expedited discharge after an uncomplicated laparoscopic appendectomy is safe and feasible without a negative impact on 30-day ED visit, diagnostic imaging or readmission.

Synchronous colorectal liver metastases: a national survey of surgeon opinions on simultaneous resection and multidisciplinary cooperation.

BACKGROUND: The management of patients with synchronous colorectal liver metastases (sCRLM) has evolved significantly (improved chemotherapy, hepatic surgery advancements, colonic stenting, consultation synergies). We sought to better understand surgeon viewpoints on optimal referral patterns and the delivery of simultaneous resections. METHODS: A 40 question on-line survey was offered to members of the Canadian surgical community. Statistical analysis was descriptive. RESULTS: A total of 52 surgeons responded. Most colorectal surgeons (CRS) had access to and a good working relationship with regional hepatobiliary (HPB) surgeons (86%) and medical oncologists (100%). The majority (92%) believed there was a role for simultaneous resection of sCRLM, with 69% having first hand experience. Many CRS (62%) discussed all cases of known hepatic metastases with HPB prior to any resection. When a lesion was asymptomatic/minimally symptomatic, most CRS (92%) discussed them with medical oncology/HPB prior to resection (8%). Bilobar metastases (58%), patient comorbidities (35%), portal lymphadenopathy (35%), and patient age (15%) restricted CRS from obtaining HPB consultations. Many CRS (46%) did not believe that resecting hepatic metastases prior to the primary lesion might be beneficial. Most CRS (60%) reported they could not accurately predict hepatic resectability, with only 27% familiarity with evidence-based guidelines. Despite working in smaller hospitals with less access to HPB and less experience with simultaneous resections, non-CR general surgeons more commonly supported a 'liver-first' approach. CONCLUSIONS: There was general agreement between CRS and general surgeons on numerous topics, but additional education is required with regard to HPB surgical capabilities and to provide truly individualized patient-centered care.

A quantitative multimodal metabolomic assay for colorectal cancer.

BACKGROUND: Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation. METHODS: The well-characterized Biocrates P150 kit was used to quantify 163 metabolites in patients with CRC (N = 62), adenoma (N = 31), and age- and gender-matched disease-free controls (N = 81). Metabolites included in the analysis included phosphatidylcholines, sphingomyelins, acylcarnitines, and amino acids. Using a training set of 32 CRC and 21 disease-free controls, a multivariate metabolomic orthogonal partial least squares (OPLS) classifier was developed. An independent set of 28 CRC and 20 matched healthy controls was used for validation. Features characterizing 31 colorectal adenomas from their healthy matched controls were also explored, and a multivariate OPLS classifier for colorectal adenoma could be proposed. RESULTS: The metabolomic profile that distinguished CRC from controls consisted of 48 metabolites (R2Y = 0.83, Q2Y = 0.75, CV-ANOVA p-value < 0.00001). In this quantitative assay, the coefficient of variance for each metabolite was <10%, and this dramatically enhanced the separation of these groups. Independent validation resulted in AUROC of 0.98 (95% CI, 0.93-1.00) and sensitivity and specificity of 93% and 95%. Similarly, we were able to distinguish adenoma from controls (R2Y = 0.30, Q2Y = 0.20, CV-ANOVA p-value = 0.01; internal AUROC = 0.82 (95% CI, 0.72-0.93)). When combined with the previously generated GC-MS signatures for CRC and adenoma, the candidate biomarker performance improved slightly. CONCLUSION: The diagnostic power for metabolomic tests for colorectal neoplasia can be improved by utilizing a multimodal approach and combining metabolites from diverse chemical classes. In addition, quantification of metabolites enhances separation of disease-specific metabolomic profiles. Our future efforts will be focused on developing a quantitative assay for the metabolites comprising the optimal diagnostic biomarker.

Weekend Surgical Care and Postoperative Mortality: A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: An association between weekend health care delivery and poor outcomes has become known as the "weekend effect." Evidence for such an association among surgery patients has not previously been synthesized. OBJECTIVE: To systematically review associations between weekend surgical care and postoperative mortality. METHODS: We searched PubMed, EMBASE, and references of relevant articles for studies that compared postoperative mortality either; (1) according to the day of the week of surgery for elective operations, or (2) according to weekend versus weekday admission for urgent/emergent operations. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for postoperative mortality (≤90 d or inpatient mortality) were pooled using random-effects models. RESULTS: Among 4027 citations identified, 10 elective surgery studies and 19 urgent/emergent surgery studies with a total of >6,685,970 and >1,424,316 patients, respectively, met the inclusion criteria. Pooled odds of mortality following elective surgery rose in a graded manner as the day of the week of surgery approached the weekend [Monday OR=1 (reference); Tuesday OR=1.04 (95% CI=0.97-1.11); Wednesday OR=1.08 (95% CI=0.98-1.19); Thursday OR=1.12 (95% CI=1.03-1.22); Friday OR=1.24 (95% CI=1.10-1.38)]. Mortality was also higher among patients who underwent urgent/emergent surgery after admission on the weekend relative to admission on weekdays (OR=1.27; 95% CI=1.08-1.49). CONCLUSIONS: Postoperative mortality rises as the day of the week of elective surgery approaches the weekend, and is higher after admission for urgent/emergent surgery on the weekend compared with weekdays. Future research should focus on clarifying underlying causes of this association and potentially mitigating its impact.

Postoperative Nonsteroidal Anti-inflammatory Drug Use and Intestinal Anastomotic Dehiscence: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonsteroidal anti-inflammatory drugs are commonly used analgesics in colorectal surgery. Controversy exists regarding the potential association between these drugs and anastomotic dehiscence. OBJECTIVE: This study aimed to determine whether postoperative nonsteroidal anti-inflammatory drug use is associated with intestinal anastomotic dehiscence. DATA SOURCES: PubMed, EMBASE, CENTRAL, and references of included articles were searched without date or language restriction. STUDY SELECTION: Randomized controlled trials and observational studies that compared postoperative nonsteroidal anti-inflammatory drug use with nonuse and reported on intestinal anastomotic dehiscence were selected. INTERVENTION: The use of postoperative nonsteroidal anti-inflammatory drugs relative to placebo or nonuse was investigated. MAIN OUTCOME MEASURES: Risk ratios and adjusted or unadjusted odds ratios for anastomotic dehiscence were pooled across randomized controlled trials and observational studies using DerSimonian and Laird random-effects models. RESULTS: Among 4395 citations identified, 6 randomized controlled trials (n = 473 patients) and 11 observational studies (n > 20,184 patients) were included. Pooled analyses revealed that nonsteroidal anti-inflammatory drug use was nonsignificantly associated with anastomotic dehiscence in randomized controlled trials (risk ratio, 1.96; 95% CI, 0.74-5.16; I = 0%) and significantly associated with anastomotic dehiscence in observational studies (OR, 1.46; 95% CI, 1.14-1.86; I = 54%). In stratified analyses of observational study data, the pooled OR for anastomotic dehiscence was statistically significant for studies of nonselective nonsteroidal anti-inflammatory drug use (6 studies; > 4900 patients; OR, 2.09; 95% CI, 1.65-2.64; I = 0%), but was not statistically significant for studies of cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug use (3 studies; >697 patients; OR, 1.34; 95% CI, 0.78-2.31; I = 0%). LIMITATIONS: Studies varied by patient selection criteria, drug exposures, and definitions of anastomotic dehiscence. Analyses of randomized controlled trials and cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs were potentially underpowered. CONCLUSIONS: Pooled observational data suggest an association between postoperative nonsteroidal anti-inflammatory drug use and intestinal anastomotic dehiscence. Caution may be warranted in using these medications in patients at risk for this complication.

A validated metabolomic signature for colorectal cancer: exploration of the clinical value of metabolomics.

BACKGROUND: Timely diagnosis and classification of colorectal cancer (CRC) are hindered by unsatisfactory clinical assays. Our aim was to construct a blood-based biomarker series using a single assay, suitable for CRC detection, prognostication and staging. METHODS: Serum metabolomic profiles of adenoma (N=31), various stages of CRC (N=320) and healthy matched controls (N=254) were analysed by gas chromatography-mass spectrometry (GC-MS). A diagnostic model for CRC was derived by orthogonal partial least squares-discriminant analysis (OPLS-DA) on a training set, and then validated on an independent data set. Metabolomic models suitable for identifying adenoma, poor prognosis stage II CRC and discriminating various stages were generated. RESULTS: A diagnostic signature for CRC with remarkable multivariate performance (R(2)Y=0.46, Q(2)Y=0.39) was constructed, and then validated (sensitivity 85%; specificity 86%). Area under the receiver-operating characteristic curve was 0.91 (95% CI, 0.87-0.96). Adenomas were also detectable (R(2)Y=0.35, Q(2)Y=0.26, internal AUROC=0.81, 95% CI, 0.70-0.92). Also of particular interest, we identified models that stratified stage II by prognosis, and classified cases by stage. CONCLUSIONS: Using a single assay system, a suite of CRC biomarkers based on circulating metabolites enables early detection, prognostication and preliminary staging information. External population-based studies are required to evaluate the repeatability of our findings and to assess the clinical benefits of these biomarkers.

Practice Guideline for the Surveillance of Patients After Curative Treatment of Colon and Rectal Cancer.

Current evidence suggests improved rates of curative secondary treatment following identification of recurrence among patients who participate in a surveillance program after initial curative resection of colon or rectal cancer. The newer data show that surveillance CEA, chest and liver imaging,and colonoscopy can also improve survival through early diagnosis of recurrence; thus, these modalities are now included in the current guideline. Although the optimum strategy of surveillance for office visits, CEA, chest and liver imaging, and colonoscopy is not yet defined, routine surveillance does improve the detection of recurrence that can be resected with curative intent. Recommended surveillance schedules are shown in Table 4. However, the factors to be considered when recommending surveillance include underlying risk for recurrence, patient comorbidity, and the ability to tolerate major surgery to resect recurrent disease or palliative chemotherapy, performance status, physiologic age, preference, and compliance. The success of surveillance for early detection of curable recurrence will depend on patient and provider involvement to adhere to the surveillance schedule and avoid unnecessary examination. It should be noted that, after curative resection of colorectal cancer, patients are still at risk for other common malignancies(lung, breast, cervix, prostate) for which standard screening recommendations should be observed and measures to maintain general health (risk reduction for cardiovascular disease, eg, cessation of smoking, control of blood pressure and diabetes mellitus, balanced diet, regular exercise and sleep, and flu vaccines) should be recommended.

Hospital volume and other risk factors for in-hospital mortality among diverticulitis patients: A nationwide analysis.

BACKGROUND: Previous studies have found that a higher volume of colorectal surgery was associated with lower mortality rates. While diverticulitis is an increasingly common condition, the effect of hospital volume on outcomes among diverticulitis patients is unknown. OBJECTIVE: To evaluate the relationship between hospital volume and other factors on in-hospital mortality among patients admitted for diverticulitis. METHODS: Data from the Nationwide Inpatient Sample (years 1993 to 2008) were analyzed to identify 822,865 patients representing 4,108,726 admissions for diverticulitis. Hospitals were divided into quartiles based on the volume of diverticulitis cases admitted over the study period, adjusted for years contributed to the dataset. Mortality according to hospital volume was modelled using logistic regression adjusting for age, sex, race, comorbidities, health care insurance, admission type, calendar year, colectomy, disease severity and clustering. Risk estimates were expressed as adjusted ORs with 95% CIs. RESULTS: Patients at high-volume hospitals were more likely to be admitted emergently, undergo surgical treatment and have more severe disease. In-hospital mortality was higher among the lowest quartile of hospital volume compared with the highest volume (OR 1.13 [95% CI 1.05 to 1.21]). In-hospital mortality was increased among patients admitted emergently (OR 2.58 [95% CI 2.40 to 2.78]) as well as those receiving surgical treatment (OR 3.60 [95% CI 3.42 to 3.78]). CONCLUSIONS: Diverticulitis patients admitted to hospitals with a low volume of diverticulitis cases had an increased risk for death compared with those admitted to high-volume centres.