Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer.

BACKGROUND: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup. METHODS: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722). RESULTS: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6). CONCLUSIONS: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.

Introducing Neoadjuvant Immunotherapy for Colorectal Cancer: Advancing the Frontier.

OBJECTIVE: To give surgeons a review of the current and future use of neoadjuvant immunotherapy in patients with localized colorectal cancer. BACKGROUND: Immunotherapy has revolutionized the standard of care in oncology and improved survival outcomes in several cancers. However, the applicability of immunotherapy is still an ongoing challenge. Some cancer types are less responsive to immunotherapy, and the heterogeneity in responses within cancer types is poorly understood. Clinical characteristics of the patient, the timing of immunotherapy in relation to surgery, diversities in the immune responses, clonal heterogeneity, different features of the tumor microenvironment, and genetic alterations are some factors among many that may influence the efficacy of immunotherapy. RESULTS: In this narrative review, we describe the major types of immunotherapy used to treat localized colorectal cancer. Furthermore, we discuss the prediction of response to immunotherapy in relation to biomarkers and radiological assessment. Finally, we consider the future perspectives of clinical implications and response patterns, as well as the potential and challenges of neoadjuvant immunotherapy in localized colorectal cancer. CONCLUSIONS: Establishing mismatch repair status at the time of diagnosis is central to the potential use of neoadjuvant immunotherapy, in particular immune checkpoint inhibitors, in localized colorectal cancer. To date, efficacy is primarily seen in patients with deficient mismatch repair status and POLE mutations, although a small group of patients with proficient mismatch repair does respond. In conclusion, neoadjuvant immunotherapy shows promising complete response rates, which may open a future avenue of an organ-sparing watch-and-wait approach for a group of patients.

Use of proton pump inhibitors after laparoscopic gastric bypass and sleeve gastrectomy: a nationwide register-based cohort study.

BACKGROUND/OBJECTIVES: L-RYGB and L-SG are the dominant bariatric procedures worldwide. While L-RYGB is an effective treatment of coexisting gastroesophageal reflux disease (GERD), L-SG is associated with an increased risk of de-novo or worsening of GERD. The study aimed to evaluate the long-term use of proton pump inhibitors (PPI) following laparoscopic Roux-en-Y gastric bypass (L-RYGB) and sleeve gastrectomy (L-SG). SUBJECTS/METHODS: This nationwide register-based study included all patients undergoing L-RYGB or L-SG in Denmark between 2008 and 2018. In total, 17,740 patients were included in the study, with 16,096 and 1671 undergoing L-RYGB and L-SG, respectively. The median follow up was 11 years after L-RYGB and 4 years after L-SG. Data were collected through Danish nationwide health registries. The development in PPI use was assessed through postoperative redeemed prescriptions. GERD development was defined by a relevant diagnosis code associated with gastroscopy, 24 h pH measurement, revisional surgery or anti-reflux surgery. The risk of initiation of PPI treatment or GERD diagnosis was evaluated using Kaplan-Meier plots and COX regression models. The risk of continuous PPI treatment was examined using logistic regression modeling. RESULTS: The risk of initiating PPI treatment was significantly higher after L-SG compared with L-RYGB (HR 7.06, 95% CI 6.42-7.77, p < 0.0001). The risk of continuous PPI treatment was likewise significantly higher after L-SG (OR 1.45, 95% CI 1.36-1.54, p < 0.0001). The utilization of PPI consistently increased after both procedures. The risk of GERD diagnosis was also significantly higher after L-SG compared with L-RYGB (HR 1.93, 95% CI 1.27-2.93, p < 0.0001). CONCLUSIONS: The risk of initiating and continuing PPI treatment was significantly higher after L-SG compared with L-RYGB, and a continuous increase in the utilization of PPI was observed after both procedures.

Surgical stress response in robot-assisted versus laparoscopic surgery for colon cancer (SIRIRALS): randomized clinical trial.

BACKGROUND: Evidence for the routine use of robotic technology and its impact on short-term outcomes in colon cancer surgery is lacking. The aim of this study was to compare the surgically induced systemic stress response and clinical and patient-reported outcomes for patients undergoing robot-assisted or laparoscopic colon cancer surgery. METHODS: In this double-blinded superiority RCT completed between August 2021 and March 2023, patients with stage 1-3 colon cancer were randomized in a 1 : 1 ratio to undergo either robot-assisted or laparoscopic colon cancer surgery. The primary outcome was changes in the systemic stress response, characterized by C-reactive protein expression in the first three postoperative days. Secondary outcomes were intraoperative and postoperative complications and patient-reported outcomes. The latter included quality of recovery-15 and pain intensity using a visual analogue scale. RESULTS: In total, 128 patients were screened for potential inclusion in this study; 50 patients (25 in the robot-assisted group and 25 in the laparoscopic group) were included in the final follow-up and analysis. The postoperative C-reactive protein response was higher on the first postoperative day in the laparoscopic group (mean difference = 19.88 mg/l, 95% c.i. 3.89-35.86; P = 0.045). No statistically significant differences were noted for C-reactive protein expression on the second and third postoperative days. CONCLUSION: Adopting robot-assisted surgery for stage 1-3 colon cancer is associated with a reduction in the surgical stress response. REGISTRATION NUMBER: NCT04687384 (http://www.clinicaltrials.gov).

Risk Factors for Persistent Postoperative Opioid Use After Surgery for IBD: An Observational Cohort Study.

BACKGROUND: Patients with IBD are at increased risk of persistent opioid use, wherein surgery plays an important role. OBJECTIVE: Identify risk factors for persistent postoperative opioid use in patients with IBD undergoing GI surgery and describe in-hospital postoperative opioid treatment. DESIGN: This was a retrospective observational cohort study. ORs for persistent postoperative opioid use were calculated using preoperative and in-hospital characteristics, and in-hospital opioid use was described using oral morphine equivalents. SETTING: This study was conducted at a university hospital with a dedicated IBD surgery unit. PATIENTS: Patients who underwent surgery for IBD from 2017 to 2022 were included. MAIN OUTCOME MEASURES: Our main outcome measure was persistent postoperative opioid use (1 or more opioid prescriptions filled 3-9 months postoperatively). RESULTS: We included 384 patients, of whom 36 (9.4%) had persistent postoperative opioid use, but only 11 (2.9%) of these patients were opioid naive preoperatively. We identified World Health Organization performance status >1 (OR 8.21; 95% CI, 1.19-48.68), preoperative daily opioid use (OR 12.84; 95% CI, 4.78-35.36), psychiatric comorbidity (OR 3.89; 95% CI, 1.29-11.43) and in-hospital mean daily opioid use (per 10 oral morphine equivalent increase; OR 1.22; 95% CI, 1.12-1.34) as risk factors for persistent postoperative opioid use using multivariable regression analysis. LIMITATIONS: Our observational study design and limited sample size because of it being a single-center study resulted in wide CIs. CONCLUSIONS: We identified risk factors for persistent postoperative opioid use in patients undergoing surgery for IBD. Results indicate a need for optimization of pain treatment in patients with IBD both before and after surgery. These patients might benefit from additional opioid-sparing measures. See Video Abstract. FACTORES DE RIESGO EN LA ADMINISTRACION DURADERA DE OPIOIDES EN EL POSTOPERATORIO EN CASOS DE CIRUGA POR ENFERMEDAD INFLAMATORIA INTESTINAL ESTUDIO OBSERVACIONAL DE COHORTES: ANTECEDENTES:Los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de recibir opioides de manera duradera, casos donde la cirugía juega un papel importante.OBJETIVO:Identificar los factores de riesgo en la administración duradera de opioides en el post-operatorio de cirugía gastrointestinal en casos de EII y describir el tratamiento intra-hospitalario con los mismos.DISEÑO:Estudio observacional retrospectivo de cohortes. La relación de probabilidades (odds ratio - OR) en la adminstracion duradera de opioides post-operatorios fué calculada utilizando las características pré-operatorias y hospitalarias, donde la administración de opioides intra-hospitalarios fué descrita con la utilización de equivalentes de morfina oral.AMBIENTE:Estudio realizado en un hospital universitario con una unidad de cirugía dedicada a la EII.PACIENTES:Se incluyeron todos los pacientes sometidos a cirugía por EII entre 2017 y 2022.PRINCIPALES MEDIDAS DE RESULTADO:Nuestra principal medida de resultado fué la administración post-operatoria duradera de opioides (≥1 receta completa de opioides entre 3 y 9 meses después de la operación).RESULTADOS:Incluimos 384 pacientes, de los cuales 36 (9,4%) recibieron opioides de manera duradera en el post-operatorio, de los cuales solamente 11 pacientes (2,9%) no habían recibido opioides antes de la operación. Identificamos el estado funcional de la OMS > 1 (OR 8,21, IC 95% 1,19-48,68), el uso diario de opioides pré-operatorios (OR 12,84, IC 95% 4,78-35,36), los casos de comorbilidad psiquiátrica (OR 3,89, IC 95% 1,29-11,43) y el uso medio diario de opioides en el hospital (por cada aumento de 10 equivalentes de morfina oral) (OR 1,22, IC del 95%: 1,12-1,34 como factores de riesgo para la administración de opioides de manera duradera en el post-operatorio mediante el análisis de regresión multivariable.LIMITACIONES:Nuestro diseño de estudio observacional y el tamaño de la muestra limitada debido a que fue un estudio en un solo centro, dando como resultado intervalos de confianza muy amplios.CONCLUSIONES:Se identificaron los factores de riesgo en la administración duradera de opioides en el post-operatorio de cirugía gastrointestinal en casos de EII. Los resultados demuestran la necesidad de optimizar el tratamiento del dolor en pacientes con EII, tanto antes como después de la cirugía. Estos pacientes podrían beneficiarse de medidas adicionales de ahorro de opioides. (Traducción-Dr. Xavier Delgadillo).

Perioperative Metformin Treatment to Reduce Postoperative Hyperglycemia After Colon Cancer Surgery: A Randomized Clinical Trial.

BACKGROUND: Surgery induces a stress response causing insulin resistance that may result in postoperative hyperglycemia. Postoperative hyperglycemia is associated with increased incidence of complications, longer hospitalization and greater mortality. OBJECTIVE: This study examined the effect of metformin treatment on the percentage of patients experiencing postoperative hyperglycemia after elective colon cancer surgery. DESIGN: This was a randomized double-blind placebo-controlled trial. SETTINGS: The study was conducted at Slagelse Hospital, Slagelse, Denmark. PATIENTS: Patients without diabetes planned for elective surgery for colon cancer were included. INTERVENTIONS: Patients received metformin 500mg three times a day or placebo for 20 days before and 10 days after surgery. MAIN OUTCOME MEASURES: Blood glucose levels were measured several times daily until the end of postoperative day two. The main outcome measures were the percentage of patients who experienced at least one blood glucose measurement above 7.7 and 10 mmol/l, respectively. Rates of complications within 30 days of surgery and Quality of recovery-15 scores were also recorded. RESULTS: Of the 48 included patients, 21 (84.0%) in the placebo group and 18 (78.3%) in the metformin group had at least one blood glucose measurement above 7.7 mmol/l (p = 0.72), and 13 (52.0%) patients in the placebo group had a measurement above 10.0 mmol/l versus 5 (21.7%) in the metformin group, (p = 0.04). No differences in complication rates or Quality of recovery-15 scores were seen. LIMITATIONS: The number of patients in the study was too low to detect a possible difference in postoperative complications. Blood glucose was measured as spot measurements instead of continuous surveillance. CONCLUSIONS: In patients without diabetes, metformin significantly reduced the percentage of patients experiencing postoperative hyperglycemia as defined as spot blood glucose measurements above 10 mmol/l after elective colon cancer surgery. See Video Abstract.

Perioperative Metformin Treatment to Reduce Postoperative Hyperglycemia After Colon Cancer Surgery: A Randomized Clinical Trial.

BACKGROUND: Surgery induces a stress response, causing insulin resistance that may result in postoperative hyperglycemia, which is associated with increased incidence of complications, longer hospitalization, and greater mortality. OBJECTIVE: This study examined the effect of metformin treatment on the percentage of patients experiencing postoperative hyperglycemia after elective colon cancer surgery. DESIGN: This was a randomized, double-blind, placebo-controlled trial. SETTINGS: The study was conducted at Slagelse Hospital in Slagelse, Denmark. PATIENTS: Patients without diabetes planned for elective surgery for colon cancer were included. INTERVENTIONS: Patients received metformin (500 mg 3× per day) or placebo for 20 days before and 10 days after surgery. MAIN OUTCOME MEASURES: Blood glucose levels were measured several times daily until the end of postoperative day 2. The main outcome measures were the percentage of patients who experienced at least 1 blood glucose measurement >7.7 and 10 mmol/L, respectively. Rates of complications within 30 days of surgery and Quality of Recovery-15 scores were also recorded. RESULTS: Of the 48 included patients, 21 patients (84.0%) in the placebo group and 18 patients (78.3%) in the metformin group had at least 1 blood glucose measurement >7.7 mmol/L ( p = 0.72), and 13 patients (52.0%) in the placebo group had a measurement >10.0 mmol/L versus 5 patients (21.7%) in the metformin group ( p = 0.04). No differences in complication rates or Quality of Recovery-15 scores were seen. LIMITATIONS: The number of patients in the study was too low to detect a possible difference in postoperative complications. Blood glucose was measured as spot measurements instead of continuous surveillance. CONCLUSIONS: In patients without diabetes, metformin significantly reduced the percentage of patients experiencing postoperative hyperglycemia, as defined as spot blood glucose measurements >10 mmol/L after elective colon cancer surgery. See Video Abstract . TRATAMIENTO PERIOPERATORIO CON METFORMINA PARA REDUCIR LA HIPERGLUCEMIA POSOPERATORIA DESPUS DE LA CIRUGA DE CNCER DE COLON ENSAYO CLNICO ALEATORIZADO: ANTECEDENTES:La cirugía induce una respuesta de estrés que causa resistencia a la insulina que puede resultar en hiperglucemia posoperatoria. La hiperglucemia posoperatoria se asocia con una mayor incidencia de complicaciones, una hospitalización más prolongada y una mayor mortalidad.OBJETIVO:Este estudio examinó el efecto del tratamiento con metformina en el porcentaje de pacientes que experimentaron hiperglucemia posoperatoria después de una cirugía electiva de cáncer de colon.DISEÑO:Este fue un ensayo aleatorio, doble ciego y controlado con placebo.AJUSTES:El estudio se realizó en el Hospital Slagelse, Slagelse, Dinamarca.PACIENTES:Se incluyeron pacientes sin diabetes planificados para cirugía electiva por cáncer de colon.INTERVENCIONES:Los pacientes recibieron 500 mg de metformina tres veces al día o placebo durante 20 días antes y 10 días después de la cirugía.PRINCIPALES MEDIDAS DE RESULTADO:Los niveles de glucosa en sangre se midieron varias veces al día hasta el final del segundo día postoperatorio. Las principales medidas de resultado fueron el porcentaje de pacientes que experimentaron al menos una medición de glucosa en sangre por encima de 7,7 y 10 mmol/l, respectivamente. También se registraron las tasas de complicaciones dentro de los 30 días posteriores a la cirugía y las puntuaciones de Calidad de recuperación-15.RESULTADOS:De los 48 pacientes incluidos, 21 (84,0%) en el grupo placebo y 18 (78,3%) en el grupo metformina tuvieron al menos una medición de glucosa en sangre superior a 7,7 mmol/l (p = 0,72), y 13 (52,0%) los pacientes del grupo de placebo tuvieron una medición superior a 10,0 mmol/l frente a 5 (21,7%) en el grupo de metformina (p = 0,04). No se observaron diferencias en las tasas de complicaciones ni en las puntuaciones de Calidad de recuperación-15.LIMITACIONES:El número de pacientes en el estudio fue demasiado bajo para detectar una posible diferencia en las complicaciones posoperatorias. La glucosa en sangre se midió mediante mediciones puntuales en lugar de vigilancia continua.CONCLUSIONES:En pacientes sin diabetes, la metformina redujo significativamente el porcentaje de pacientes que experimentaron hiperglucemia postoperatoria, definida como mediciones puntuales de glucosa en sangre por encima de 10 mmol/l después de una cirugía electiva de cáncer de colon . (Traducción-Dr Yolanda Colorado ).

Correlations between preoperative statin treatment with short- and long-term survival following colorectal cancer surgery: a propensity score-matched national cohort study.

INTRODUCTION: The pleiotropic effects of statins have attracted considerable attention in oncological treatment. Several preclinical and epidemiological studies have highlighted their potential anti-tumor properties in patients with colorectal cancer, although results have been conflicting. This study aimed to examine the association between statin exposure before colorectal cancer surgery with long and short-term survival outcomes. METHODS: This retrospective propensity score-adjusted study was conducted on a Danish cohort of patients who underwent elective curative-intended surgery for stage I-III colorectal cancer in 2008-2020, using four national patient databases. The primary and secondary outcomes were overall, 90-day, and disease-free survival. Propensity scores were calculated using all available data to match patients with and without statin exposure in a 1:1 ratio. RESULTS: Following propensity score matching, 7120 patients were included in the primary analysis. The median follow-up time was 5 years. A Cox proportional hazards model showed no statistically significant difference in overall survival between patients with or without statin exposure 365 days before surgery (HR 0.93, 95% CI 0.85-1.02) and no association with 90-day survival (OR 0.91, 95% CI 0.76-1.10). However, a subgroup analysis examining a 90-day exposure before surgery found a statistically significant association with increased overall survival (HR 0.85, 95% CI 0.77-0.93). CONCLUSION: Although a subgroup of patients with a preoperative exposure time of 90 days showed statistically significant better overall survival, we found no statistically significant association between statin exposure 1 year before colorectal cancer surgery and overall survival.

Associations between pre-operative cholesterol levels with long-term survival after colorectal cancer surgery: a nationwide propensity score-matched cohort study.

PURPOSE: Altered lipid metabolism frequently occurs in patients with solid cancers and dyslipidemia has been associated with poorer outcomes in patients with colorectal cancer. This study sought to investigate whether cholesterol levels are associated with clinical outcomes and can serve as survival predictors. METHODS: We conducted a retrospective cohort study with Danish patients diagnosed with colorectal cancer who had surgery with curative intent for UICC stages I to III between 2015 and 2020. Using propensity score adjustment, we matched patients in a 1:1 ratio to examine the impact of total cholesterol (TC) > 4 mmol/L vs. ≤ 4 mmol/L within 365 days prior to surgery on overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 3443 patients were included in the study. Median follow-up time was 3.8 years. Following propensity score matching, 1572 patients were included in the main analysis. There was no statistically significant difference in OS or DFS between patients with TC > 4 mmol/L compared with TC ≤ 4 mmol/L (HR: 0.82, 95% CI, 0.65-1.03, HR: 0.87, 95% CI, 0.68-1.12, respectively.). A subgroup analysis investigating TC > 4 mmol/L as well as low-density lipoprotein (LDL) > 3 mmol/L found a significant correlation with OS (HR: 0.74, 95% CI, 0.54-0.99). CONCLUSION: TC levels alone were not associated with OS or DFS in patients with colorectal cancer. Interestingly, higher TC and LDL levels were linked to better overall survival, suggesting the need for further exploration of cholesterol's role in colorectal cancer. TRIAL REGISTRATION: Not applicable.

Prediction of 30-day, 90-day, and 1-year mortality after colorectal cancer surgery using a data-driven approach.

PURPOSE: To develop prediction models for short-term mortality risk assessment following colorectal cancer surgery. METHODS: Data was harmonized from four Danish observational health databases into the Observational Medical Outcomes Partnership Common Data Model. With a data-driven approach using the Least Absolute Shrinkage and Selection Operator logistic regression on preoperative data, we developed 30-day, 90-day, and 1-year mortality prediction models. We assessed discriminative performance using the area under the receiver operating characteristic and precision-recall curve and calibration using calibration slope, intercept, and calibration-in-the-large. We additionally assessed model performance in subgroups of curative, palliative, elective, and emergency surgery. RESULTS: A total of 57,521 patients were included in the study population, 51.1% male and with a median age of 72 years. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.88, 0.878, and 0.861 for 30-day, 90-day, and 1-year mortality, respectively, and a calibration-in-the-large of 1.01, 0.99, and 0.99. The overall incidence of mortality were 4.48% for 30-day mortality, 6.64% for 90-day mortality, and 12.8% for 1-year mortality, respectively. Subgroup analysis showed no improvement of discrimination or calibration when separating the cohort into cohorts of elective surgery, emergency surgery, curative surgery, and palliative surgery. CONCLUSION: We were able to train prediction models for the risk of short-term mortality on a data set of four combined national health databases with good discrimination and calibration. We found that one cohort including all operated patients resulted in better performing models than cohorts based on several subgroups.

The association of postoperative morbidity and age on 5-year survival after colorectal surgery in the elderly population: a nationwide cohort study.

AIM: This study aimed to evaluate the association of age and postoperative morbidity on 5-year overall survival (OS) after elective surgery for colorectal cancer. METHOD: Patients undergoing elective, curatively intended surgery for colorectal cancer Union for International Cancer Control Stages I-III between January 2014 and December 2019 were selected from four Danish nationwide healthcare databases. Patients were divided into four groups: group I 65-69 years old; group II 70-74 years old; group III 75-79 years old; and group IV ≥80 years old. Propensity score matching was used to reduce potential confounding bias. The primary outcome was the association of age and postoperative morbidity with 5-year OS. The secondary outcome was conditional survival, given that the patient had already survived the first 90 days after surgery. RESULTS: After propensity score matching with a 1:1 ratio, group II contained 2221 patients; group III 952 patients; and group IV 320 patients. There was no significant difference in 5-year OS between group I (reference) and groups II and III (P = 0.4 and P = 0.9, respectively). Patients with severe postoperative complications within 30 days after surgery had a significantly decreased OS (P < 0.01); however, when patients who died within the first 90 days were excluded from the analysis, the differences in 5-year OS were less pronounced across all age groups. CONCLUSION: Postoperative morbidity, and not patient age, was associated with a lower 5-year OS. Long-term survival for patients who experience a complication is similar to patients who did not have a complication when conditioning on 90 days of survival.

Real time organ hypoperfusion detection using Indocyanine Green in a piglet model.

BACKGROUND: Preserving sufficient oxygen supply to the tissue is fundamental for maintaining organ function. However, our ability to identify those at risk and promptly recognize tissue hypoperfusion during abdominal surgery is limited. To address this problem, we aimed to develop a new method of perfusion monitoring that can be used during surgical procedures and aid surgeons' decision-making. METHODS: In this experimental porcine study, thirteen subjects were randomly assigned one organ of interest [stomach (n = 3), ascending colon (n = 3), rectum (n = 3), and spleen (n = 3)]. After baseline perfusion recordings, using high-frequency, low-dose bolus injections with weight-adjusted (0.008 mg/kg) ICG, organ-supplying arteries were manually and completely occluded leading to hypoperfusion of the target organ. Continuous organ perfusion monitoring was performed throughout the experimental conditions. RESULTS: After manual occlusion of pre-selected organ-supplying arteries, occlusion of the peripheral arterial supply translated in an immediate decrease in oscillation signal in most organs (3/3 ventricle, 3/3 ascending colon, 3/3 rectum, 2/3 spleen). Occlusion of the central arterial supply resulted in a further decrease or complete disappearance of the oscillation curves in the ventricle (3/3), ascending colon (3/3), rectum (3/3), and spleen (1/3). CONCLUSION: Continuous organ-perfusion monitoring using a high-frequency, low-dose ICG bolus regimen can detect organ hypoperfusion in real-time.

Small bowel anastomosis in emergency surgery.

BACKGROUND: Emergency laparotomy is associated with a high morbidity and mortality rate. The decision on whether to perform an anastomosis or an enterostomy in emergency small bowel resection is guided by surgeon preference alone, and not evidence based. We examined the risks involved in small bowel resection and anastomosis in emergency surgery. METHODS: A retrospective study from 2016 to 2019 in a university hospital in Denmark, including all emergency laparotomies, where small-bowel resections, ileocecal resections, right hemicolectomies and extended right hemicolectomies where performed. Demographics, operative data, anastomosis or enterostomy, as well as postoperative complications were recorded. Primary outcome was the rate of bowel anastomosis. Secondary outcomes were the anastomotic leak rate, mortality and complication rates. RESULTS: During the 3.5-year period, 370 patients underwent emergency bowel resection. Of these 313 (84.6%) received an anastomosis and 57 (15.4%) an enterostomy. The 30-day mortality rate was 12.7% (10.2% in patients with anastomosis and 26.3% in patients with enterostomy). The overall anastomotic leak rate was 1.6%, for small-bowel to colon 3.0% and for small-bowel to small-bowel 0.6%. CONCLUSION: A primary anastomosis is performed in more than eight out of 10 patients in emergency small bowel resections and is associated with a very low rate of anastomotic leak.

Postoperative recovery in peroral versus intravenous antibiotic treatment following laparoscopic appendectomy for complicated appendicitis: a substudy of a cluster randomized cluster crossover non-inferiority study.

BACKGROUND: Acute appendicitis is the most common cause of abdominal pain requiring surgery, usually managed with laparoscopic appendectomy. In Denmark, the standard postoperative treatment for complicated cases involves intravenous antibiotics. This study compares peroral versus intravenous antibiotics in the context of fast-track surgery and Enhanced Recovery After Surgery (ERAS) protocols. Our objective is to evaluate the impact of peroral versus intravenous antibiotics on patient-reported outcomes following laparoscopic appendectomy for complicated appendicitis. METHODS: This was a sub-study within a broader Danish cluster-randomized non-inferiority trial conducted at Zealand University Hospital, focusing on adult patients undergoing laparoscopic appendectomy for complicated appendicitis. Participants were randomized into two groups: one receiving a three-day course of peroral antibiotics and the other intravenous antibiotics after surgery. Recovery quality was assessed on the third postoperative day using the Quality of Recovery-15 (QoR-15) questionnaire. RESULTS: The study included 54 patients, 23 in the peroral and 31 in the intravenous groups. The peroral group reported significantly better recovery outcomes, with higher QoR-15 scores (mean difference of 12 points, p < 0.001). They also experienced shorter hospital stays, averaging 47 h less than the intravenous group (p < 0.001). No significant differences between the groups were observed in readmissions or severe postoperative complications. CONCLUSIONS: Peroral antibiotic administration after laparoscopic appendectomy for complicated appendicitis significantly improves patient recovery and reduces hospital stay compared to intravenous antibiotics. These results advocate a potential shift towards peroral antibiotic use in postoperative care, aligning with ERAS principles. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04803422.

Determining a multidisciplinary intraoperative strategy in emergency surgery for bowel obstruction and its impact on outcomes.

PURPOSE: Bowel obstruction accounts for around 50% of all emergency laparotomies. A multidisciplinary (MDT) standardized intraoperative model was applied (definitive, palliative, or damage control surgery) to identify patients suitable for a one-step, definitive surgical procedure favoring anastomosis over stoma, when undergoing surgery for bowel obstruction. The objective was to present mortality according to the strategy applied and to compare the rate of laparoscopic interventions and stoma creations to a historic cohort in surgery for bowel obstruction. METHODS: In a retrospective cohort study, we included patients undergoing emergency surgery for bowel obstruction during a 1-year period at two Copenhagen University Hospitals (2019 and 2021). The MDT model consisted of a 30- and 60-min time-out with variables such as functional and hemodynamic status, presence of malignancy, and surgical capabilities (lap/open). Pre-, intra-, and postoperative data were collected to investigate associations to postoperative complications and mortality. Stoma creation rates and laparoscopies were compared to a historic cohort (2009-2013). RESULTS: Three hundred sixty-nine patients underwent surgery for bowel obstruction. Intraoperative surgical strategy was definitive in 77.0%, palliative in 22.5%, and damage control surgery in 0.5%. Thirty-day mortality was significantly lower in the definitive patient population (4.6%) compared to the palliative population (21.7%) (p < 0.000). Compared to the historic cohort, laparoscopic surgery for bowel obstruction increased from 5.0 to 26.4% during the 10-year time span, the rate of stoma placements was reduced from 12.0 to 6.1%, p 0.014, and the 30-day mortality decreased from 12.9 to 4.6%, p < 0.000. CONCLUSION: An intraoperative improvement strategy can address the specific surgical interventions in patients undergoing surgery for bowel obstruction, favoring anastomosis over stoma whenever resection was needed, and help adjust specific postoperative interventions and care pathways in cases of palliative need.

Systemic glucocorticoid exposure and postoperative infection risk in 143,782 appendectomy patients-a Danish longitudinal nationwide study.

BACKGROUND: Glucocorticoids are conventionally associated with increased postoperative infection risk. It is necessary to clarify if preoperative glucocorticoid exposure is associated with postoperative infection in appendectomy patients and if the association is different for open and laparoscopic appendectomies. METHODS: A Danish nationwide study of appendectomy patients between 1996 and 2018. Exposures were defined as high (≥ 5 mg) versus no/low (< 5 mg) glucocorticoid exposure in milligram prednisone-equivalents/day preoperatively. The main outcome was any postoperative infection. Then, 90-day cumulative incidences (absolute risk) and adjusted hazard ratios (relative risk) of the outcome were calculated for high versus no/low glucocorticoid exposure within all appendectomies and within open and laparoscopic subgroups. Propensity-score matching was used for sensitivity analysis. RESULTS: Of 143,782 patients, median age was 29 years, 74,543 were female, and 7654 experienced at least one infection during the 90-day follow-up. The 90-day cumulative incidence for postoperative infection was 5.3% within the no/low glucocorticoid exposure group and 10.0% within the high glucocorticoid exposure group. Compared to no/low glucocorticoid exposure, adjusted hazard ratios for 90-day postoperative infection with high glucocorticoid exposure were 1.25 [95% CI 1.02-1.52; p = 0.03] for all appendectomies, 1.59 [1.16-2.18; p = 0.004] for laparoscopic appendectomies, and 1.09 [0.85-1.40; p = 0.52] for open appendectomies (pinteraction < 0.001). The results were robust to sensitivity analyses. CONCLUSION: Preoperative high (≥ 5 mg/day) glucocorticoid exposure was associated with increased absolute risk of postoperative infections in open and laparoscopic appendectomies. The relative risk increase was significant for laparoscopic but not open appendectomies, possibly due to lower absolute risk with no/low glucocorticoid exposure in the laparoscopic subgroup.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Standardization of the Definition and Surgical Management of Splenic Flexure Carcinoma by an International Expert Consensus Using the Delphi Technique: Room for Improvement?

BACKGROUND: Surgical management of splenic flexure carcinoma remains controversial. OBJECTIVE: This study aimed to establish an expert international consensus on splenic flexure carcinoma management. DESIGN: A 3-round online-based Delphi study was conducted between September 2020 and April 2021. SETTING: The first round included 18 experts from 12 different countries. For the second and third rounds, each expert in the first round was asked to invite 2 more colorectal surgeons (n = 47). Out of 47 invited experts, 89% (n = 42) participated in the second and third rounds of the consensus. INTERVENTIONS: A total of 35 questions were created and sent via the online questionnaire tool. MAIN OUTCOME MEASURES: Levels of recommendation based on voting concordance were graded as follows: more than 75% agreement was defined as strong, between 50% and 75% as moderate, and below 50% as weak. RESULTS: There was moderate consensus on the definition of splenic flexure (55%) as 10 cm from either side where the distal transverse colon turns into the proximal descending colon. Also, experts recommended an abdominopelvic CT scan plus intraoperative exploration (moderate consensus, 72%) for tumor localization and cancer registry. Segmental colectomy was the preferred technique for the management of splenic flexure carcinoma in the elective setting (72%). Moderate consensus was achieved on the technique of complete mesocolic excision and central vascular ligation principles for splenic flexure carcinoma (74%). Only strong consensus was achieved on the surgical approach for minimally invasive surgery (88%). LIMITATIONS: Subjective decisions are based on individual expert clinical experience and not evidence based. CONCLUSIONS: This is the first internationally conducted Delphi consensus study regarding splenic flexure carcinoma. The definition of splenic flexure remains ambiguous. To more effectively compare oncologic outcomes among different cancer registries, guidelines need to be developed to standardize each domain and avoid arbitrary definitions. See Video Abstract at http://links.lww.com/DCR/C143 . ESTANDARIZACIN DE LA DEFINICIN Y MANEJO QUIRRGICO DEL CARCINOMA DE NGULO ESPLNICO ESTABLECIDO POR UN CONSENSO INTERNACIONAL DE EXPERTOS UTILIZANDO LA TCNICA DELPHI ESPACIO PARA MEJORAR: ANTECEDENTES:El tratamiento quirúrgico del cáncer de ángulo esplénico sigue siendo controvertido.OBJETIVO:Establecer un consenso internacional de expertos sobre el manejo del cáncer del ángulo esplénico.DISEÑO:Se condujo un estudio Delphi en línea de 3 rondas entre septiembre de 2020 y febrero de 2021.ESCENARIO:La primera ronda incluyó a 18 expertos de 12 países distintos. Para la segunda y tercera rondas, a cada experto de la primera ronda se le pidió que invitara a 2 cirujanos colorrectales más de su región (n = 47). De los 47 expertos invitados, el 89% (n = 42) participó en la segunda y tercera ronda del consenso.INTERVENCIONES:Se crearon y enviaron un total de 35 preguntas a través de la herramienta de cuestionario en línea.PRINCIPALES MEDIDAS DE RESULTADO:Los niveles de recomendación basados en la concordancia de votos fueron jerarquizados de la siguiente manera: más del 75% de acuerdo se definió como fuerte, entre 50 y 75% como moderado y por debajo del 50% como débil.RESULTADOS:Hubo un consenso moderado sobre la definición de ángulo esplénico (55%) como 10 cm desde cualquier lado donde el colon transverso distal se convierte en el colon descendente proximal. Así también, los expertos recomendaron la tomografía computarizada abdominopélvica más la exploración intraoperatoria (consenso moderado, 72%) para la localización del tumor y el registro del ángulo esplénico. La colectomía segmentaria fue la técnica preferida para el tratamiento del cáncer de ángulo esplénico en el caso de ser electivo (72%). Se logró un consenso moderado sobre la técnica de escisión completa del mesocolon y los principios de ligadura vascular a nivel central para el cáncer de ángulo esplénico (74%). Solo se logró un fuerte consenso sobre el abordaje quirúrgico para la cirugía mínimamente invasiva (88%).LIMITACIONES:Decisiones subjetivas basadas en la experiencia clínica de expertos individuales y no basadas en evidencia.CONCLUSIONES:Este es el primer estudio internacional de consenso Delphi realizado sobre el cáncer de ángulo esplénico. Si bien encontramos un consenso moderado sobre las modalidades de diagnóstico preoperatorio y el manejo quirúrgico, la definición de ángulo esplénico sigue siendo ambigua. Para comparar de manera más efectiva los resultados oncológicos entre diferentes registros de cáncer, se deben desarrollar pautas para estandarizar cada dominio y evitar definiciones arbitrarias. Consulte Video Resumen en http://links.lww.com/DCR/C143 . (Traducción-Dr. Osvaldo Gauto ).

Associations Between Care Bundles and Postoperative Outcomes After Major Emergency Abdominal Surgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: Care bundles were found to improve postoperative outcomes in elective surgery. However, in major emergency general surgery studies show a divergent impact on mortality and length of stay. This meta-analysis aimed to evaluate associations between care bundles and mortality, complications, and length of stay when applied in major emergency general surgery. METHODS: A systematic literature search in PubMed and Embase was performed on the May 1, 2021. Only comparative studies on care bundles in major emergency general surgery were included. Meta-analysis and trial sequential analysis were performed on 30-d mortality. We undertook a narrative approach of long-term mortality, complications, and length of stay. RESULTS: Meta-analysis of 13 studies with 35,771 patients demonstrated that care bundles in emergency surgery were not associated with a significant reduction in odds of 30-d mortality (odds ratio = 0.8, 95% confidence interval 0.62-1.03). Trial sequential analysis confirmed that the meta-analysis was underpowered with a minimum of 78,901 patients required for firm conclusions. Seven studies reported complication rates whereof six reported lower complication rates using care bundles. CONCLUSIONS: Care bundles were reported to decrease postoperative complications in five out of seven studies and seven out of 11 studies reported a shortening in length of stay.

Cardiovascular events after elective colorectal cancer surgery in patients with stage I-III disease with no previous cardiovascular disease.

BACKGROUND: The risk of cardiovascular events in patients treated for colorectal cancer is debated due to diverging results in previous studies. Colorectal cancer and cardiovascular disease share several risk factors such as physical inactivity, obesity, and smoking. Information about confounding covariates and follow-up time are therefore essential to address the issue. This study aims to investigate the risk of new-onset cardiovascular events for patients with stage I-III colorectal cancer receiving elective surgery compared to a matched population. MATERIAL AND METHODS: Using a prospective cohort, we compared cardiovascular events among 876 patients treated with elective surgery for incident stage I-III colorectal cancer diagnosed between January 1st, 2001 and December 31st, 2016 to a cancer-free cohort matched by age, sex, and time since enrollment (N = 3504). Regression analyses were adjusted for lifestyle, cardiovascular risk factors, and comorbidity. Multivariable analyses were used to identify risk factors associated with cardiovascular events in the postoperative (<90 days of elective surgery) and long-term phase (>90 days after elective surgery). RESULTS: After a median follow-up of 3.9 years, the hazard ratio (HR) for incident heart failure was 1.53 (95% CI 1.02-2.28) among patients operated for colorectal cancer. The postoperative risk of myocardial infarction or angina pectoris was associated with the use of lipid-lowering drugs. Long-term risks of cardiovascular events were ASA-score of III+IV and lipid-lowering drugs with HRs ranging from 2.20 to 15.8. Further, the use of antihypertensive drugs was associated with an HR of 2.09 (95% CI 1.06-4.13) for angina pectoris or acute myocardial infarction. Heart failure was associated with being overweight, diabetes, and anastomosis leakage. CONCLUSION: We observed an increased hazard of heart failure in patients operated on for stage I-III colorectal cancer compared to cancer-free comparisons. We identified several potential risk factors for cardiovascular events within and beyond 90 days of elective surgery.