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 ).

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.

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.

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.

Evaluation of a real-life experience with a digital fluid balance monitoring technology.

BACKGROUND: Innovations in healthcare technologies have the potential to address challenges, including the monitoring of fluid balance. OBJECTIVE: This study aims to evaluate the functionality and accuracy of a digital technology compared to standard manual documentation in a real-life setting. METHODS: The digital technology, LICENSE, was designed to calculate fluid balance using data collected from devices measuring urine, oral and intravenous fluids. Participating patients were connected to the LICENSE system, which transmitted data wirelessly to a database. These data were compared to the nursing staff's manual measurements documented in the electronic patient record according to their usual practice. RESULTS: We included 55 patients in the Urology Department needing fluid balance charting and observed them for an average of 22.9 hours. We found a mean difference of -44.2 ml in total fluid balance between the two methods. Differences ranged from -2230 ml to 2695 ml, with a divergence exceeding 500 ml in 57.4% of cases. The primary source of error was inaccurate or omitted manual documentation. However, errors were also identified in the oral LICENSE device. CONCLUSIONS: When used correctly, the LICENSE system performs satisfactorily in measuring urine and intravenous fluids, although the oral device requires revision due to identified errors.

Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate.

Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.

The impact of platelets on the metastatic potential of tumour cells.

In cancer, activation of platelets by tumor cells is critical to disease progression. Development of precise antiplatelet targeting may improve outcomes from anticancer therapy. Alongside a distinct shift in functionality such as pro-metastatic and pro-coagulant properties, platelet production is often accelerated significantly early in carcinogenesis and the cancer-associated thrombocytosis increases the risk of metastasis formation and thromboembolic events. Tumor-activated platelets facilitate the proliferation of migrating tumor cells and shield them from immune surveillance and physical stress during circulation. Additionally, platelet-tumor cell interactions promote tumor cell intravasation, intravascular arrest, and extravasation through a repertoire of adhesion molecules, growth factors and angiogenic factors. Particularly, the presence of circulating tumor cell (CTC) clusters in association with platelets is a negative prognostic indicator. The contribution of platelets to the metastatic process is an area of intense investigation and this review provides an overview of the advances in understanding platelet-tumor cell interactions and their contribution to disease progression. Also, we review the potential of targeting platelets to interfere with the metastatic process.

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.

Remote ischaemic preconditioning on gene expression and circulating proteins after subacute laparoscopic cholecystectomy: randomized clinical trial.

BACKGROUND: Surgical stress may lead to postsurgical hypercoagulability, endothelial dysfunction and systemic inflammation, which can impact on patient recovery. Remote ischaemic preconditioning is a procedure that activates the body's endogenous defences against ischaemia and reperfusion injury. Studies have suggested that remote ischaemic preconditioning has antithrombotic, antioxidative and anti-inflammatory effects. The hypothesis was that remote ischaemic preconditioning reduces surgery-induced systemic stress response. METHOD: During a 24-month period (2019-2021), adult patients undergoing subacute laparoscopic cholecystectomy due to acute cholecystitis were randomized to remote ischaemic preconditioning or control. Remote ischaemic preconditioning was performed less than 4 h before surgery on the upper arm. It consisted of four cycles of 5 min ischaemia and 5 min reperfusion. The gene expression of 750 genes involved in inflammatory processes, oxidative stress and endothelial function was investigated preoperatively and 2-4 h after surgery in both groups. In addition, changes in 20 inflammation- and vascular trauma-associated proteins were assessed preoperatively, 2-4 h after surgery and 24 h after surgery. RESULTS: A total of 60 patients were randomized. There were no statistically significant differences in gene expression 2-4 h after surgery between the groups (P > 0.05). Remote ischaemic preconditioning did not affect concentrations of circulating proteins up to 24 h after surgery (P > 0.05). CONCLUSION: The study did not demonstrate any effect of remote ischaemic preconditioning on expression levels of the chosen genes or in circulating immunological cytokines and vascular trauma-associated proteins up to 24 h after subacute laparoscopic cholecystectomy in patients with acute cholecystitis.

Interprofessional clinical reasoning education.

Clinical reasoning is considered one of the most important competencies but is not included in most healthcare curricula. The number and diversity of patient encounters are the decisive factors in the development of clinical reasoning competence. Physical real patient encounters are considered optimal, but virtual patient cases also promote clinical reasoning. A high-volume, low-fidelity virtual patient library thus can support clinical reasoning training in a safe environment and can be tailored to the needs of learners from different health care professions. It may also stimulate interprofessional understanding and team shared decisions. Implementation will be challenged by tradition, the lack of educator competence and prior experience as well as the high-density curricula at medical and veterinary schools and will need explicit address from curriculum managers and education leads.

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.

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.

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.

Predictors for dMMR colorectal cancer in patients with serrated lesions and polyps - A register-based cohort study.

BACKGROUND: Serrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and MLH1 hypermethylation leading to mismatch repair deficient (dMMR) CRC. We investigated predictors of dMMR CRC among patients with co-occurrence of CRC and SP to increase our knowledge on the serrated pathway. METHODS: We used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010-2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR). RESULTS: We included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84]. CONCLUSION: In conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP.

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).

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy: Post Hoc Analysis of the SCOT Randomized Clinical Trial.

Importance: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy. Objective: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival. Design, Setting, and Participants: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024. Intervention: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery. Main Outcomes and Measures: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy. Results: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13). Conclusions and Relevance: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups. Trial Registration: isrctn.org Identifier: ISRCTN59757862.

Re-resection Rates and Disease Recurrence in Crohn's Disease: A Population-based Study Using Individual-level Patient Data.

BACKGROUND AND AIMS: Despite advances in the medical treatment of Crohn's disease [CD], many patients will still need bowel resections and face the subsequent risk of recurrence and re-resection. We describe contemporary re-resection rates and identify disease-modifying factors and risk factors for re-resection. METHODS: We conducted a retrospective, population-based, individual patient-level data cohort study covering 47.4% of the Danish population, including all CD patients who underwent a primary resection between 2010 and 2020. RESULTS: Among 631 primary resected patients, 24.5% underwent a second resection, and 5.3% a third. Re-resection rates after 1, 5, and 10 years were 12.6%, 22.4%, and 32.2%, respectively. Reasons for additional resections were mainly disease activity [57%] and stoma reversal [40%]. Disease activity-driven re-resection rates after 1, 5, and 10 years were 3.6%, 10.1%, and 14.1%, respectively. Most stoma reversals occurred within 1 year [80%]. The median time to recurrence was 11.0 months. Biologics started within 1 year of the first resection revealed protective effect against re-resection for stenotic and penetrating phenotypes. Prophylactic biologic therapy at primary ileocaecal resection reduced disease recurrence and re-resection risk (hazard ratio [HR] 0.58, 95% confidence interval [CI] [0.34-0.99], p = 0.047). Risk factors for re-resection were location of resected bowel segments at the primary resection, disease location, disease behaviour, smoking, and perianal disease. CONCLUSION: Re-resection rates, categorised by disease activity, are lower than those reported in other studies and are closely associated with disease phenotype and localisation. Biologic therapy may be disease-modifying for certain subgroups when initiated within 1 year of resection.

Biofilms and core pathogens shape the tumor microenvironment and immune phenotype in colorectal cancer.

Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the in situ functional implications of host-microbe interactions in CRC are scarce. Therefore, we characterized the influence of CRC core pathogens and biofilms on the tumor microenvironment (TME) in 40 CRC, paired normal, and healthy tissue biopsies using fluorescence in situ hybridization (FISH) and dual-RNA sequencing. FISH revealed that Fusobacterium spp. was associated with increased bacterial biomass and inflammatory response in CRC samples. Dual-RNA sequencing demonstrated increased expression of pro-inflammatory cytokines, defensins, matrix-metalloproteases, and immunomodulatory factors in CRC samples with high bacterial activity. In addition, bacterial activity correlated with the infiltration of several immune cell subtypes, including M2 macrophages and regulatory T-cells in CRC samples. Specifically, Bacteroides fragilis and Fusobacterium nucleatum correlated with the infiltration of neutrophils and CD4+ T-cells, respectively. The collective bacterial activity/biomass appeared to exert a more significant influence on the TME than core pathogens, underscoring the intricate interplay between gut microbiota and CRC. These results emphasize how biofilms and core pathogens shape the immune phenotype and TME in CRC while highlighting the need to extend the bacterial scope beyond CRC pathogens to advance our understanding and identify treatment targets.

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.

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.