Alterations in blood microbiota after colonic cancer surgery.

BACKGROUND: Mechanisms contributing to the perioperative stress response remain poorly understood. This study investigated changes in the amount of bacterial DNA in blood and the diversity of blood microbiota in the perioperative period in patients undergoing minimally invasive surgery for colonic cancer in an enhanced recovery after surgery setting. METHODS: DNA encoding the bacterial 16S ribosomal RNA gene (16S rDNA) in whole blood obtained the day before surgery, and on postoperative day (POD) 1 and POD 10-14 was amplified and quantified by PCR before sequencing for taxonomic assignment. Richness, evenness and similarity measures were calculated to compare microbiota between days. Differences in relative abundance were analysed using the linear discriminant analysis effect size (LEfSe) algorithm. RESULTS: Thirty patients were included between January and July 2016. The concentration of bacterial 16S rDNA in blood increased between the day before surgery and POD 1 (P = 0.025). Bacterial richness was lower on POD 10-14 than on the day before surgery and POD 1 (both P < 0·001). LEfSe analysis comparing the day before surgery and POD 10-14 identified changes in the abundance of several bacteria, including Fusobacterium nucleatum, which was relatively enriched on POD 10-14. CONCLUSION: These findings suggest that the blood of patients with colonic cancer harbours bacterial 16S rDNA, which increases in concentration after surgery.

ANTECEDENTES: Los mecanismos que contribuyen a la respuesta al estrés perioperatorio siguen siendo poco conocidos. Este estudio investigó los cambios en la cantidad de ADN bacteriano en la sangre y la diversidad de la microbiota sanguínea en el período perioperatorio en pacientes sometidos a cirugía mínimamente invasiva por cáncer de colon en el contexto de un programe de recuperación mejorada después de la cirugía. MÉTODOS: El ADN que codifica el gen de ARN ribosómico (rNDA) 16S bacteriano en sangre completa obtenido el día antes de la cirugía, el día 1 del postoperatorio y el día 10-14 del postoperatorio se amplificó y cuantificó mediante qPCR antes de la secuenciación para la asignación taxonómica. Se calcularon medidas de riqueza, uniformidad y similitud para comparar la microbiota entre los diferentes días. Las diferencias en la abundancia relativa se analizaron mediante un algoritmo de análisis discriminante lineal de tamaño de efecto (linear discriminant analysis effect size, LEfSe). RESULTADOS: De enero a julio de 2016 se incluyeron 30 pacientes. La concentración de 16S rNDA bacteriano en sangre aumentó desde el día antes de la operación al día 1 del postoperatorio. La riqueza bacteriana disminuyó en el día 10-14 del postoperatorio en comparación con el preoperatorio y el día 1 del postoperatorio. La comparación del preoperatorio y del día 10-14 postoperatorio por LEfSe identificó cambios en la abundancia de varias bacterias, incluida Fusobacterium nucleatum que mostró un enriquecimiento relativo el día 10-14 del postoperatorio. CONCLUSIÓN: Estos hallazgos sugieren que la sangre de los pacientes con cáncer de colon alberga 16S rNDA bacteriano cuya concentración aumenta tras la cirugía.

Associations between blood cultures after surgery for colorectal cancer and long-term oncological outcomes.

BACKGROUND: Systemic inflammation following curative surgery for colorectal cancer may be associated with increased risk of recurrence. [Correction added on 29 November 2019, after first online publication: text amended for accuracy.] This study investigated whether a clinically suspected infection, for which blood cultures were sent within 30 days after surgery for colorectal cancer, was associated with long-term oncological outcomes. METHODS: This register-based national cohort study included all Danish residents undergoing surgery with curative intent for colorectal cancer between January 2003 and December 2013. Patients who developed recurrence or died within 180 days after surgery were not included. Associations between blood cultures taken within 30 days after primary surgery and overall survival, disease-free survival and recurrence-free survival were analysed using Cox regression models adjusted for relevant clinical confounders, including demographic data, cancer stage, co-morbidity, blood transfusion, postoperative complications and adjuvant chemotherapy. RESULTS: The study included 21 349 patients, of whom 3390 (15·9 per cent) had blood cultures taken within 30 days after surgery. Median follow-up was 5·6 years. Patients who had blood cultures taken had an increased risk of all-cause mortality (hazard ratio (HR) 1·27, 95 per cent c.i. 1·20 to 1·35; P < 0·001), poorer disease-free survival (HR 1·22, 1·16 to 1·29; P < 0·001) and higher risk of recurrence (HR 1·15, 1·07 to 1·23; P < 0·001) than patients who did not have blood cultures taken. CONCLUSION: A clinically suspected infection requiring blood cultures within 30 days of surgery for colorectal cancer was associated with poorer oncological outcomes.

ANTECEDENTES: La inflamación sistémica en el cáncer colorrectal puede asociarse con un aumento del riesgo de recidiva. En este estudio se investigó si la sospecha clínica de infección, en la que se obtuvieron cultivos de sangre periférica durante los primeros 30 días de la cirugía por cáncer colorrectal, se asociaba con los resultados oncológicos a largo plazo. MÉTODOS: Se trata de un estudio de cohortes de un registro de una base de datos nacional, que incluyía todos los sujetos residentes en Dinamarca sometidos a cirugía por cáncer colorrectal con intención curativa desde enero de 2003 a diciembre de 2013. Los pacientes con recidiva o que fallecieron durante los primeros 180 días después de la cirugía fueron excluidos. Se estimaron las asociaciones entre los cultivos de sangre periférica efectuados en los primeros 30 días tras la cirugía primaria y la supervivencia global, supervivencia libre de enfermedad y supervivencia libre de recidiva mediante modelos de regresión de Cox, ajustados por variables clínicas confusoras relevantes (incluyendo datos demográficos, estadio del cáncer, comorbilidad, transfusión de sangre, complicaciones postoperatorias y quimioterapia adyuvante). RESULTADOS: El estudio incluyó 21.349 pacientes, de los cuales en 3.390 (16%) se habían obtenido cultivos de sangre periférica durante los primeros 30 días tras la cirugía. La mediana de seguimiento fue de 5,6 años. Los pacientes en los que se había obtenido cultivos de sangre periférica presentaron un riesgo aumentado de mortalidad por cualquier causa (cociente de riesgos instantáneos, hazard ratio, HR 1,27, i.c. del 95% 1,20-1,35; P < 0.0001), peor supervivencia libre de enfermedad (HR 1,22, i.c. del 95% 1,16-1,29; P < 0,0001) y mayor riesgo de recidiva (HR 1,15, i.c. del 95% 1,07-1,23; P < 0,0001) que los pacientes en los que no se habían obtenido cultivos. CONCLUSIÓN: La presencia de una infección sospechada clínicamente para la cual se requiere obtener cultivos de sangre periférica en los primeros 30 días tras cirugía por cancer colorrectal se asoció con peores resultados oncológicos.

30-Day, 90-day and 1-year mortality after emergency colonic surgery.

PURPOSE: Emergency surgery is an independent risk factor in colonic surgery resulting in high 30-day mortality. The primary aim of this study was to report 30-day, 90-day and 1-year mortality rates after emergency colonic surgery, and to report factors associated with 30-day, 90-day and 1-year mortality. Second, the aim was to report 30-day postoperative complications and their relation to in-hospital mortality. METHODS: All patients undergoing acute colonic surgery in the period from May 2009 to April 2013 at Copenhagen University Hospital Herlev, Denmark, were identified. Perioperative data was collected from medical journals. RESULTS: 30-day, 90-day and 1-year mortality was 21, 30 and 41%, respectively. Age >70 years, Performance status ≥3 and resection with stoma were independent factors associated with 30-day mortality. Age >70 years, Performance status ≥3, resection with stoma and malignant disease were independent risk factors associated with 90-day mortality. Age >70 years, Performance status ≥3, resection with stoma and malignant disease were independent factors associated with 1-year mortality. Overall, 30-day complication rate was 63%, with cardiopulmonary complications leading to most postoperative deaths. CONCLUSION: Mortality and complication rates after emergency colonic surgery are high and associated with patient related risk factors that cannot be modified, but also treatment related outcomes that are modifiable. An increased focus on medical and other preventive measures should be explored in the future.