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Importance: Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear. Objective: To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection. Design, Setting, and Participants: Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization. Interventions: Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia. Main Outcomes and Measures: The primary outcome was receipt of red blood cell transfusion within 7 days of surgery. Results: The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08). Conclusions and Relevance: Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02261415.
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BACKGROUND AND OBJECTIVES: The combination of focused ultrasound (FUS) and chemotherapy is a novel treatment for pancreatic cancer. This paper reviews the literature on this combined therapy. METHODS: The medical literature was searched according to PRISMA guidelines. Inclusion criteria were any study of patients with pancreatic cancer undergoing treatment with FUS and chemotherapy. Data extracted included stage, radiologic response, resection rate, survival, and adverse events. RESULTS: The initial search yielded 212 citations; 10 studies met inclusion criteria (9 retrospective cohorts; 1 randomized trial). A total of 631 patients received FUS + chemotherapy; 63.6% being stage 4, and 29.7% stage 3. Patient selection, FUS parameters, and chemotherapy used were all heterogeneous. Overall survival ranged from 7.4 to 21.6 months, radiologic response rate was 44.1%, and 24.4% of stage 3 patients underwent resection. All four studies with a comparison group demonstrated improved survival. FUS + chemotherapy decreased pain in 69.7% of patients. Severe adverse events occurred in 0.65%. CONCLUSIONS: The literature on combined FUS and chemotherapy for pancreatic cancer is heterogeneous. There is good evidence that adverse events are low, and that it provides effective palliation. There is evidence to suggest oncologic benefit, however, this is subject to selection bias and prospective trials are needed.
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BACKGROUND: Associations between procedure volumes and outcomes can inform minimum volume standards and the regionalization of health services. Robot-assisted surgery continues to expand globally; however, data are limited regarding which hospitals should be using the technology. STUDY DESIGN: Using administrative health data for all residents of Ontario, Canada, this retrospective cohort study included adult patients who underwent a robot-assisted radical prostatectomy (RARP), total robotic hysterectomy (TRH), robot-assisted partial nephrectomy (RAPN), or robotic portal lobectomy using 4 arms (RPL-4) between January 2010 and September 2021. Associations between yearly hospital volumes and 90-day major complications were evaluated using multivariable logistic regression models adjusted for patient characteristics and clustering at the level of the hospital. RESULTS: A total of 10,879 patients were included, with 7567, 1776, 724, and 812 undergoing a RARP, TRH, RAPN, and RPL-4, respectively. Yearly hospital volume was not associated with 90-day complications for any procedure. Doubling of yearly volume was associated with a 17-min decrease in operative time for RARP (95% confidence interval [CI] - 23 to - 10), 8-min decrease for RAPN (95% CI - 14 to - 2), 24-min decrease for RPL-4 (95% CI - 29 to - 19), and no significant change for TRH (- 7 min; 95% CI - 17 to 3). CONCLUSION: The risk of 90-day major complications does not appear to be higher in low volume hospitals; however, they may not be as efficient with operating room utilization. Careful case selection may have contributed to the lack of an observed association between volumes and complications.
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Hospitales de Alto Volumen , Hospitales de Bajo Volumen , Nefrectomía , Complicaciones Posoperatorias , Prostatectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Ontario , Prostatectomía/métodos , Nefrectomía/métodos , Anciano , Hospitales de Alto Volumen/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Hospitales de Bajo Volumen/estadística & datos numéricos , Tempo Operativo , Histerectomía/métodos , Histerectomía/estadística & datos numéricos , AdultoRESUMEN
SummaryThe adoption of robotic surgery has surged globally across multiple surgical specialties, but uptake in Canada has unfolded at a slower pace. Surgical educators and trainees in Canada face potential challenges related to sufficient exposure, experience, and competence in robotic surgical procedures. We conducted a cross-sectional national survey to gain insight into the perspectives of program directors overseeing general surgery residency and fellowship programs on the integration of robotic surgery into Canadian surgical training programs. Despite the presence of robotic surgery platforms at most academic and academic-affiliated hospitals, few trainees have exposure to any robotic surgery. Furthermore, a gap exists between the training provided in robotic surgery and its anticipated relevance to trainees upon graduation. Increased focus on the integration of robotic surgery within general surgical training in Canada is required to equip trainees for their careers.
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Internado y Residencia , Procedimientos Quirúrgicos Robotizados , Canadá , Procedimientos Quirúrgicos Robotizados/educación , Humanos , Estudios Transversales , Cirugía General/educación , Encuestas y Cuestionarios , Becas , Competencia Clínica , Educación de Postgrado en Medicina/métodosRESUMEN
BACKGROUND: Surgical resection, the only potentially curative treatment for gallbladder cancer (GBC), entails an extended cholecystectomy with portal lymphadenectomy. Lymph node dissection is a key staging procedure, but its therapeutic value is unclear. Additionally, it is technically challenging and potentially harmful. Methods for better assessment of lymph node status are needed. This report presents a case of indocyanine green (ICG)-guided sentinel lymph node biopsy (SNLB) for a patient with a gallbladder mass suspicious for GBC. METHODS: An 81-year-old woman consulted for abdominal discomfort. Abdominal ultrasound showed an intraluminal gallbladder mass suspicious for GBC. Staging imaging did not show liver invasion, lymphadenopathy, or distant metastasis. Given the woman's advanced age and limited extent of disease, a laparoscopic extended cholecystectomy with an ICG-guided SLNB was performed. Injection of 1 ml of ICG (0.125 mg/mL) into the gallbladder bed was performed using a 22-gauge needle, avoiding direct injection into the gallbladder wall. RESULTS: A near-infrared camera was used to visualize real-time ICG flow through the lymphatic vessels of the gallbladder toward the cystic node. Then, a sentinel lymph node posterolateral to the bile duct (station 12b) was identified. The node was resected and sent for permanent section. The procedure continued with an extended cholecystectomy. Pathology showed an intracholecystic papillary neoplasm with high-grade dysplasia. Cystic and sentinel lymph nodes were negative for malignancy. CONCLUSION: For patients with gallbladder neoplasms, ICG-guided SLNB is a feasible technique that could allow for treatment de-escalation. Further evaluation in clinical trials is needed.
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INTRODUCTION: Loss to follow-up (LTFU) distorts results of randomized controlled trials (RCTs). Understanding trial characteristics that contribute to LTFU may enable investigators to anticipate the extent of LTFU and plan retention strategies. The objective of this systematic review and meta-analysis was to investigate the extent of LTFU in surgical RCTs and evaluate associations between trial characteristics and LTFU. METHODS: MEDLINE, Embase, and PubMed Central were searched for surgical RCTs published between January 2002 and December 2021 in the 30 highest impact factor surgical journals. Two-hundred eligible RCTs were randomly selected. The pooled LTFU rate was estimated using random intercept Poisson regression. Associations between trial characteristics and LTFU were assessed using metaregression. RESULTS: The 200 RCTs included 37,914 participants and 1307 LTFU events. The pooled LTFU rate was 3.10 participants per 100 patient-years (95% confidence interval [CI] 1.85-5.17). Trial characteristics associated with reduced LTFU were standard-of-care outcome assessments (rate ratio [RR] 0.17; 95% CI 0.06-0.48), surgery for transplantation (RR 0.08; 95% CI 0.01-0.43), and surgery for cancer (RR 0.10; 95% CI 0.02-0.53). Increased LTFU was associated with patient-reported outcomes (RR 14.21; 95% CI 4.82-41.91) and follow-up duration ≥ three months (odds ratio 10.09; 95% CI 4.79-21.28). CONCLUSIONS: LTFU in surgical RCTs is uncommon. Participants may be at increased risk of LTFU in trials with outcomes assessed beyond the standard of care, surgical indications other than cancer or transplant, patient-reported outcomes, and longer follow-up. Investigators should consider the impact of design on LTFU and plan retention strategies accordingly.
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Perdida de Seguimiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos/estadística & datos numéricosRESUMEN
INTRODUCTION: Surgical stress results in immune dysfunction, predisposing patients to infections in the postoperative period and potentially increasing the risk of cancer recurrence. Perioperative immunonutrition with arginine-enhanced diets has been found to potentially improve short-term and cancer outcomes. This study seeks to measure the impact of perioperative immunomodulation on biomarkers of the immune response and perioperative outcomes following hepatopancreaticobiliary surgery. METHODS AND ANALYSIS: This is a 1:1:1 randomised, controlled and blinded superiority trial of 45 patients. Baseline and perioperative variables were collected to evaluate immune function, clinical outcomes and feasibility outcomes. The primary outcome is a reduction in natural killer cell killing as measured on postoperative day 1 compared with baseline between the control and experimental cohorts. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating sites and Health Canada (parent control number: 223646). Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov (identifier: NCT04549662). Any modifications to the protocol will be communicated via publications and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04549662.
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Neoplasias , Humanos , Proyectos de Investigación , Inmunomodulación , Inmunidad , Canadá , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
BACKGROUND: Approximately 15% of patients experience post-hepatectomy liver failure after major hepatectomy. Poor hepatocyte uptake of gadoxetate disodium, a magnetic resonance imaging contrast agent, may be a predictor of post-hepatectomy liver failure. METHODS: A retrospective cohort study of patients undergoing major hepatectomy (≥3 segments) with a preoperative gadoxetate disodium-enhanced magnetic resonance imaging was conducted. The liver signal intensity (standardized to the spleen) and the functional liver remnant was calculated to determine if this can predict post-hepatectomy liver failure after major hepatectomy. RESULTS: In 134 patients, low signal intensity of the remnant liver standardized by signal intensity of the spleen in post-contrast images was associated with post-hepatectomy liver failure in multiple logistic regression analysis (Odds Ratio 0.112; 95% CI 0.023-0.551). In a subgroup of 33 patients with lower quartile of functional liver remnant, area under the curve analysis demonstrated a diagnostic accuracy of functional liver remnant to predict post-hepatectomy liver failure of 0.857 with a cut-off value for functional liver remnant of 1.4985 with 80.0% sensitivity and 89.3% specificity. CONCLUSION: Functional liver remnant determined by gadoxetate disodium-enhanced magnetic resonance imaging is a predictor of post-hepatectomy liver failure which may help identify patients for resection, reducing morbidity and mortality.
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Medios de Contraste , Gadolinio DTPA , Hepatectomía , Fallo Hepático , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Fallo Hepático/etiología , Fallo Hepático/diagnóstico por imagen , Anciano , Factores de Riesgo , Resultado del Tratamiento , AdultoRESUMEN
OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.
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Neoplasias Colorrectales , Trombosis , Tromboembolia Venosa , Humanos , Anticoagulantes/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Hemorragia , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/tratamiento farmacológico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlAsunto(s)
Carcinoma Hepatocelular , Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Arteria Hepática , Natación , Neoplasias Hepáticas/tratamiento farmacológico , Carcinoma Hepatocelular/tratamiento farmacológico , Infusiones Intraarteriales , Quimioterapia Adyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéuticoRESUMEN
BACKGROUND: Robot-assisted surgery has been rapidly adopted. It is important to define the learning curve to inform credentialling requirements, training programs, identify fast and slow learners, and protect patients. This study aimed to characterize the hospital learning curve for common robot-assisted procedures. STUDY DESIGN: This cohort study, using administrative health data for Ontario, Canada, included adult patients who underwent a robot-assisted radical prostatectomy (RARP), total robotic hysterectomy (TRH), robot-assisted partial nephrectomy (RAPN), or robotic portal lobectomy using four arms (RPL-4) between 2010 and 2021. The association between cumulative hospital volume of a robot-assisted procedure and major complications was evaluated using multivariable logistic models adjusted for patient characteristics and clustering at the hospital level. RESULTS: A total of 6814 patients were included, with 5230, 543, 465, and 576 patients in the RARP, TRH, RAPN, and RPL-4 cohorts, respectively. There was no association between cumulative hospital volume and major complications. Visual inspection of learning curves demonstrated a transient worsening of outcomes followed by subsequent improvements with experience. Operative time decreased for all procedures with increasing volume and reached plateaus after approximately 300 RARPs, 75 TRHs, and 150 RPL-4s. The odds of a prolonged length of stay decreased with increasing volume for patients undergoing a RARP (OR 0.87; 95% CI 0.82-0.92) or RPL-4 (OR 0.77; 95% CI 0.68-0.87). CONCLUSION: Hospitals may adopt robot-assisted surgery without significantly increasing the risk of major complications for patients early in the learning curve and with an expectation of increasing efficiency.
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Procedimientos Quirúrgicos Robotizados , Masculino , Adulto , Femenino , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios de Cohortes , Curva de Aprendizaje , Prostatectomía/efectos adversos , Hospitales , Ontario , Resultado del TratamientoRESUMEN
The resection margin status is a significant surgical prognostic factor for the long-term outcomes of patients undergoing pancreaticoduodenectomy (Whipple procedure). As a result, surgeons frequently rely on intraoperative consults (IOCs) involving frozen sections to evaluate margin clearance during these resections. Nevertheless, the impact of this practice on final margin status and long-term outcomes remains a topic of debate. This study aimed to assess the impact of IOCs on the clearance rate of resection margins following Whipple procedure and distal pancreatectomy. A retrospective database review of all patients who underwent Whipple procedure or distal pancreatectomy at our institution between 2018 and 2020 was performed to evaluate the utility of IOCs by gastrointestinal surgeons and its correlation with final postoperative surgical margin status. A significant variation in the frequency of IOC requests for margins among surgeons was noted. However, the use of frozen section analysis for intraoperative margin assessment was not significantly associated with the clearance rate of final post-operative margins. More frequent use of IOC did not result in higher final margin clearance rate, an important prognostic factor following Whipple procedure.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Arteria Hepática , Infusiones Intraarteriales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
BACKGROUND: An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies. METHODS: Using SurveyMonkeyTM, a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice. RESULTS: Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI. CONCLUSIONS: Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials.
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BACKGROUND: Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres moving away from using epidural analgesia, there is the need to evaluate alternative opiate sparing techniques for postoperative analgesia. We sought to determine if rectus sheath catheters (RSCs) had an opiate sparing and analgesic effect compared with standard care alone (opiate analgesia). METHODS: We conducted a retrospective pre- and postintervention cohort study of patients undergoing pancreaticoduodenectomy at a single tertiary academic hospital in Toronto, Canada, between April 2018 and December 2019. All patients undergoing a pancreaticoduodenectomy were eligible for inclusion. Among the 101 patients identified, 84 (61 control, 23 RSCs) were analyzed after exclusion criteria were applied (epidural analgesia, admission to intensive care intubated or reintubated within the first 96 hours). The pre-intervention group received a semi-standardized course of analgesics, including intravenous hydromorphone, acetaminophen, ketamine, with or without nonsteroidal anti-inflammatory, and with or without intravenous lidocaine; the latter 2 drugs were at the individual anesthesiologist and surgeon's preference. For the postintervention group, the same course of analgesics were used, with the addition of RSCs. These were inserted at the end of the operation, with a loading dose of ropivacaine administered and followed by a programmed intermittent bolus regime for 72-96 hours. The primary outcome measure was total postoperative opiate consumption (oral morphine equivalents). Secondary outcomes included pain scores (numeric rating scale) and treatment-related adverse effects. RESULTS: Opiate consumption (oral morphine equivalents) at 96 hours was significantly lower (median 188 mg, interquartile range [IQR] 112-228 v. 242.4 mg, IQR 166.8-352) with and without RSC, respectively (p = 0.01). The RSC group used significantly less opiates at each time point from 24 hours postoperatively, with no significant difference in pain scores between the groups and no significant catheter-related complications. CONCLUSION: The use of RSCs was associated with significant reductions in postoperative opiate consumption. Given the ease of placement and management, with minimal complications, RSCs should be incorporated into a course of postoperative multimodal analgesia. A large scale randomized controlled trial should be conducted to further investigate these findings.
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Alcaloides Opiáceos , Humanos , Alcaloides Opiáceos/uso terapéutico , Analgésicos Opioides , Estudios Retrospectivos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios de Cohortes , Pancreaticoduodenectomía/efectos adversos , Resultado del Tratamiento , Analgésicos , Morfina/uso terapéutico , Complicaciones Posoperatorias , Catéteres/efectos adversosRESUMEN
OBJECTIVE: To establish the association between bactibilia and postoperative complications when stratified by perioperative antibiotic prophylaxis. BACKGROUND: Patients undergoing pancreatoduodenectomy experience high rates of surgical site infection (SSI) and clinically relevant postoperative pancreatic fistula (CR-POPF). Contaminated bile is known to be associated with SSI, but the role of antibiotic prophylaxis in mitigation of infectious risks is ill-defined. METHODS: Intraoperative bile cultures (IOBCs) were collected as an adjunct to a randomized phase 3 clinical trial comparing piperacillin-tazobactam with cefoxitin as perioperative prophylaxis in patients undergoing pancreatoduodenectomy. After compilation of IOBC data, associations between culture results, SSI, and CR-POPF were assessed using logistic regression stratified by the presence of a preoperative biliary stent. RESULTS: Of 778 participants in the clinical trial, IOBC were available for 247 participants. Overall, 68 (27.5%) grew no organisms, 37 (15.0%) grew 1 organism, and 142 (57.5%) were polymicrobial. Organisms resistant to cefoxitin but not piperacillin-tazobactam were present in 95 patients (45.2%). The presence of cefoxitin-resistant organisms, 92.6% of which contained either Enterobacter spp. or Enterococcus spp., was associated with the development of SSI in participants treated with cefoxitin [53.5% vs 25.0%; odds ratio (OR)=3.44, 95% CI: 1.50-7.91; P =0.004] but not those treated with piperacillin-tazobactam (13.5% vs 27.0%; OR=0.42, 95% CI: 0.14-1.29; P =0.128). Similarly, cefoxitin-resistant organisms were associated with CR-POPF in participants treated with cefoxitin (24.1% vs 5.8%; OR=3.45, 95% CI: 1.22-9.74; P =0.017) but not those treated with piperacillin-tazobactam (5.4% vs 4.8%; OR=0.92, 95% CI: 0.30-2.80; P =0.888). CONCLUSIONS: Previously observed reductions in SSI and CR-POPF in patients that received piperacillin-tazobactam antibiotic prophylaxis are potentially mediated by biliary pathogens that are cefoxitin resistant, specifically Enterobacter spp. and Enterococcus spp.
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Profilaxis Antibiótica , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/tratamiento farmacológico , Profilaxis Antibiótica/métodos , Pancreaticoduodenectomía/efectos adversos , Cefoxitina/uso terapéutico , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Combinación Piperacilina y Tazobactam/uso terapéutico , Estudios Retrospectivos , Antibacterianos/uso terapéuticoRESUMEN
Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.
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Cefoxitina , Sepsis , Masculino , Adulto , Humanos , Anciano , Cefoxitina/uso terapéutico , Piperacilina/uso terapéutico , Pancreaticoduodenectomía/efectos adversos , Fístula Pancreática/tratamiento farmacológico , Ácido Penicilánico/uso terapéutico , Antibacterianos/uso terapéutico , Combinación Piperacilina y Tazobactam/uso terapéutico , Infección de la Herida Quirúrgica/prevención & control , Sepsis/tratamiento farmacológicoRESUMEN
Introduction: Contrast-enhanced MRI is routinely performed as part of preoperative work-up for patients with Colorectal Cancer Liver Metastases (CRLM). Radiomic biomarkers depicting the characteristics of CRLMs in MRI have been associated with overall survival (OS) of patients, but the reproducibility and clinical applicability of these biomarkers are limited due to the variations in MRI protocols between hospitals. Methods: In this work, we propose a generalizable radiomic model for predicting OS of CRLM patients who received preoperative chemotherapy and delayed-phase contrast enhanced (DPCE) MRIs prior to hepatic resection. This retrospective two-center study included three DPCE MRI cohorts (n=221) collected between January 2006 and December 2012. A 10-minute delayed Gd-DO3A-butrol enhanced MRI discovery cohort was used to select features based on robustness across contrast agents, correlation with OS and pairwise Pearson correlation, and to train a logistic regression model that predicts 3-year OS. Results: The model was evaluated on a 10-minute delayed Gd-DO3A-butrol enhanced MRI validation cohort (n=121), a 20-minute delayed Gd-EOB-DTPA (n=72) cohort from the same institute, and a 5-minute delayed Gd-DTPA cohort (n=28) from an independent institute. Two features were selected: minor axis length and dependence variance. The radiomic signature model stratified high-risk and low-risk CRLM groups in the Gd-DO3Abutrol (HR = 6.29, p = .007), Gd-EOB-DTPA (HR = 3.54, p = .003) and Gd-DTPA (HR = 3.16, p = .04) validation cohorts. Discussion: While most existing MRI findings focus on a specific contrast agent, our study shows the potential of MRI features to be generalizable across main-stream contrast agents at delayed phase.