Pancreatic ductal adenocarcinoma (PDAC) regional nodal disease at standard lymphadenectomy: is MRI accurate for identifying node-positive patients?

OBJECTIVE: To determine the accuracy of qualitative and quantitative MRI features for the diagnosis of pathologic regional lymph nodes at standard lymphadenectomy in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: All adult patients with pancreatic MRI performed from 2011 to 2021 within 3 months of a pancreaticoduodenectomy were eligible for inclusion in this single-center retrospective cohort study. Regional nodes at standard lymphadenectomy were independently reviewed by two fellowship-trained abdominal radiologists for the following qualitative features: heterogeneous T2 signal, round shape, indistinct margin, peri-nodal fat stranding, and restricted diffusion greater than the spleen. Quantitative characteristics including primary tumor size, largest node short- and long-axes length, number of regional nodes, absolute apparent diffusion coefficient (ADC) values, and ADC node-to-spleen signal index were assessed. Analysis was at the patient-level with surgical pathology as the reference standard. RESULTS: Of 75 patients, 85% (64/75) were positive for regional nodal disease on histopathology. None of the qualitative variables evaluated on MRI was associated with pathologic nodes. Median primary tumor maximum diameter was slightly larger for patients with pathologic nodes compared to those without (18 mm (10-42 mm) vs 16 mm (9-22 mm), p = 0.027). None of the other quantitative features was associated with pathologic nodes. Radiologist opinion was not associated with pathologic nodes (p = 0.520). Interobserver agreement was fair (kappa = 0.257). CONCLUSIONS: Lymph node morphologic features and radiologist opinion using MRI are of limited value for diagnosing PDAC regional nodal disease. Improved diagnostic techniques are needed given the prognostic implications of pathologic lymph nodes in these patients. KEY POINTS: • Multiple lymph node morphologic features routinely assessed on MRI for malignancies elsewhere in the body are likely not applicable when assessing for pancreatic ductal adenocarcinoma nodal disease. • Interobserver agreement for the presence or absence of pancreatic ductal adenocarcinoma lymph node morphologic features on MRI is fair (kappa = 0.257). • Many more lymph nodes are resected at PDAC standard lymphadenectomy than are detectable on MRI, median 25 vs 5 (p < 0.001), suggesting improved diagnostic techniques are needed to identify PDAC nodal disease.

Evaluating compliance of extended venous thromboembolism prophylaxis following abdominopelvic surgery for cancer: A multidisciplinary quality improvement project.

BACKGROUND AND OBJECTIVES: Despite quality evidence supporting postoperative extended venous thromboembolism prophylaxis (eVTEp) following abdominopelvic cancer surgery, baseline use of eVTEp at our institution was 3%. Our project aim was to improve the proportion of patients prescribed eVTEp following surgery for gynecologic, hepatobiliary, and colorectal cancers by a 30% absolute increase. METHODS: We performed an interrupted time series study using quality improvement methodology. Postoperative order sets, pre-printed prescriptions, process checklists, and multimodal education were introduced. Process and outcome data were collected and analyzed on statistical process control charts. RESULTS: We included 324 patients with gynecologic and hepatobiliary cancers. Despite efforts to include them, the colorectal team did not participate. The monthly mean order set-use was 58% (SD = 14%), by specialty: gynecology 79%, hepatobiliary 47%. The proportion of patients prescribed eVTEp increased from 3% to 70% (SD = 14%). The target goal was surpassed and sustained by both cohorts. Patient compliance was 73% (n = 117/160, SD = 16%). Of those who stopped eVTEp early, 45% (n = 14/31) objected because of the injectable nature. Bleeding events were infrequent (0.6%, n = 2/324). CONCLUSIONS: Three process changes and multimodal education resulted in a significant increase in eVTEp use. Failure to identify improvement champions limited project expansion to colorectal patients. Patient compliance was largely limited by the injectable nature of the medication.

Weight Loss Following Hepatopancreatobiliary Surgery. How Much is Too Much? A Retrospective Cohort Study.

Background & Aims. Postoperative weight loss is common following hepato-pancreato-biliary (HPB) surgical resections; however, the extent of weight loss and the association with poor outcomes have not been well described. We assessed the average percentage of weight loss and risk factors associated with sustained postoperative weight loss. Materials and Methods. We enrolled patients undergoing major HPB surgical resections from 2011-2016 at a single institution. We evaluated percent change in weight postoperatively, incidence of complications, and nutritional clinical markers at 1, 3, and 6 months postoperatively compared to preoperative baseline. We used multiple logistic regression to evaluate factors associated with significant weight loss (>10% from baseline) at 3 months from surgery. Results. Among 262 patients undergoing HPB surgery, liver surgery patients lost 2.5% of baseline weight at 3 months postoperatively but regained baseline weight by 6 months. Pancreatic surgery patients lost 7.7% at 3 months and were unable to recover their baseline weights at 6 months. Forty-three (16%) patients had major postoperative complications including abdominal abscess (5.3%) and anastomotic leak (3.8%). Patients who experienced major postoperative complications had a greater percentage weight loss at 3 months compared to those without major complications: median 11% (interquartile range (IQR): 7%-15%) vs 4% (IQR: 0%-8%), P < .001. In the multivariable analysis, major postoperative complications were associated with significant weight loss at 3 months (OR 3.39, 95% CI 1.38-8.33). Conclusions. Due to the association of weight loss and major postoperative complications, patients who experience significant weight loss (>10% from baseline) may benefit from nutritional assessment for dietary intervention.

MRI vs. CT for the Detection of Liver Metastases in Patients With Pancreatic Carcinoma: A Comparative Diagnostic Test Accuracy Systematic Review and Meta-Analysis.

BACKGROUND: The detection of liver metastases is important for pancreatic cancer curative treatment eligibility. The data suggest that magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for the diagnosis of pancreatic cancer liver metastases. However, MRI is not currently recommended in multiple published guidelines. PURPOSE: To perform a comparative diagnostic test accuracy systematic review and meta-analysis comparing CT and MRI for pancreatic cancer liver metastases detection. STUDY TYPE: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and multiple radiology society meeting archives were searched until November 2018. Comparative design studies reporting on liver CT and MRI accuracy for detection of pancreatic cancer liver metastases in the same cohort were included. FIELD STRENGTH: 1.5T or 3.0T. ASSESSMENT: Demographic, methodologic, and diagnostic test accuracy data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. STATISTICAL TESTS: Accuracy metrics were obtained using bivariate random-effects meta-analysis. The impact of different covariates on accuracy estimates was assessed using a meta-regression model. Covariates included modality, study design, tumor characteristics, risk of bias, and imaging protocols. RESULTS: Fourteen studies including 987 patients with pancreatic cancer (205 with liver metastases) were included. Sensitivity for CT and MRI was 45% (confidence intervals [95% CI] 21-71%) and 83% (95% CI 74-88%), respectively. Specificity for CT and MRI was 94% (95% CI 84-98%) and 96% (95% CI 93-97%), respectively. The greater observed sensitivity of MRI was preserved in the meta-regression model (P = 0.01), while no difference in specificity was detected (P = 0.16). CT sensitivity was highest for triphasic and quadriphasic examinations compared to single phase or biphasic protocols (P = 0.03). Most studies were at high risk of bias. DATA CONCLUSION: MRI is more sensitive than CT for pancreatic cancer liver metastases detection, accounting for confounding variables. Consideration of this finding in clinical practice guidelines is recommended. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Hypovascular pancreas head adenocarcinoma: CT texture analysis for assessment of resection margin status and high-risk features.

OBJECTIVES: To determine if CT texture analysis features are associated with hypovascular pancreas head adenocarcinoma (PHA) postoperative margin status, nodal status, grade, lymphovascular invasion (LVI), and perineural invasion (PNI). METHODS: This Research Ethics Board-approved retrospective cohort study included 131 consecutive patients with resected PHA. Tumors were segmented on preoperative contrast-enhanced CT. Tumor diameter and texture analysis features including mean, minimum and maximum Hounsfield units, standard deviation, skewness, kurtosis, and entropy and gray-level co-occurrence matrix (GLCM) features correlation and dissimilarity were extracted. Two-sample t test and logistic regression were used to compare parameters for prediction of margin status, nodal status, grade, LVI, and PNI. Diagnostic accuracy was assessed using receiver operating characteristic curves and Youden method was used to establish cutpoints. RESULTS: Margin status was associated with GLCM correlation (p = 0.012) and dissimilarity (p = 0.003); nodal status was associated with standard deviation (p = 0.026) and entropy (p = 0.031); grade was associated with kurtosis (p = 0.031); LVI was associated with standard deviation (p = 0.047), entropy (p = 0.026), and GLCM correlation (p = 0.033) and dissimilarity (p = 0.011). No associations were found for PNI (p > 0.05). Logistic regression yielded an area under the curve of 0.70 for nodal disease, 0.70 for LVI, 0.68 for grade, and 0.65 for margin status. Optimal sensitivity/specificity was as follows: nodal disease 73%/72%, LVI 72%/65%, grade 55%/83%, and margin status 63%/66%. CONCLUSIONS: CT texture analysis features demonstrate fair diagnostic accuracy for assessment of hypovascular PHA nodal disease, LVI, grade, and postoperative margin status. Additional research is rapidly needed to identify these high-risk features with better accuracy. KEY POINTS: • CT texture analysis features are associated with pancreas head adenocarcinoma postoperative margin status which may help inform treatment decisions as a negative resection margin is required for cure. • CT texture analysis features are associated with pancreas head adenocarcinoma nodal disease, a poor prognostic feature. • Indicators of more aggressive pancreas head adenocarcinoma biology including tumor grade and LVI can be diagnosed using CT texture analysis with fair accuracy.

Incidence of Splanchnic Vein Thrombosis After Abdominal Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Abdominal surgery may increase the risk of splanchnic vein thrombosis (SVT). We determined the incidence of SVT after abdominal surgery and identified groups at highest risk. MATERIALS AND METHODS: MEDLINE and Embase were searched for clinical studies evaluating the incidence of postoperative SVT after abdominopelvic surgery. Study selection, data abstraction, and risk of bias assessment were carried out independently by two reviewers. Clinical heterogeneity was explored by subgroup analyses (i.e., type of intra-abdominal procedure and organ group). RESULTS: Of 5549 abstracts screened, 48 were analyzed. Pooled incidence of SVT (n = 50,267) was 2.68% [95% confidence interval (CI), 2.24 to 3.11] (1347 events), I2 = 96%. Pooled incidence of SVT in high-risk procedures were splenectomy with devascularization (24%), hepatectomy in patients with cirrhosis (9%), and pancreatectomy with venous resection (5%). Pooled incidence of symptomatic and asymptomatic SVT was 1.02% (95% CI: 0.97% to 1.07%) and 0.98% (95% CI 0.88% to 1.07%), respectively. Most common causes of SVT-related mortality were irreversible thrombosis, bowel ischemia, liver failure, and gastrointestinal bleed. Most studies included were at a high risk of bias due to lack of prospective data collection and lack of SVT screening for all participants. CONCLUSIONS: Incidence of SVT after abdominal surgery is low but remains a relevant complication. Patients undergoing procedures involving surgical manipulation of the venous system and splenectomy are at the highest risk. Given the life-threatening risks associated with SVT, there is a need for larger prospective studies on the incidence and impact of SVT after abdominal surgery.

Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey.

BACKGROUND: We examined surgeon practice intentions and barriers to performing simultaneous resections for colorectal cancer with synchronous liver metastases. METHODS: We electronically surveyed North American surgeons who provide colorectal cancer care with a pilot-tested questionnaire. Four clinical scenarios of increasing complexity were presented. Perceived outcomes of and barriers to simultaneous resection were assessed on a 7-point Likert scale. We compared results between general and hepatobiliary surgeons. RESULTS: Responses (rate 20%, 234/1166) included 50 general and 134 hepatobiliary surgeons. High likelihood scores for support of simultaneous resection among general and hepatobiliary surgeons, respectively, included the following for: minor liver and low complexity colon, 83% and 98% (p < 0.001); minor liver and rectal resection, 57% and 73% (p = 0.042); complex liver and low complexity colon resection, 26% and 24% (p = 0.858); and, complex liver and rectal resection, 11% and 7.0% (p = 0.436). Among hepatobiliary surgeons, the most common barriers to simultaneous resections were patient comorbidities and lung metastases, whereas certain general surgeons additionally identified transfer of care. CONCLUSIONS: Surgeon support for simultaneous resection was high for cases with minor hepatectomy, and low for cases involving major hepatectomy. These results suggest that clinical trials should involve patients with limited disease to evaluate post-operative complications and cost.

Adjuvant Chemotherapy With or Without Biologics Including Antiangiogenics and Monoclonal Antibodies Targeting EGFR and EpCAM in Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Adjuvant therapy for early-stage colorectal cancer improves survival. Biologic agents have shown promise as adjuncts to chemotherapy in metastatic colon cancer, but the effect on earlier stage cancer remains unclear. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the additive effect of biologic agents to adjuvant chemotherapy on survival in colorectal cancer (all comers and subpopulations defined by microsatellite instability, BRAF and KRAS status, and stage). Only randomized controlled trials published between 2002 and 2017 in MEDLINE, EMBASE, and CENTRAL were included. The control arm: chemotherapy alone, the intervention arm: chemotherapy with biologic agents. OUTCOMES: overall survival (OS) and disease-free survival. RESULTS: Six trials including 10,754 patients were included. OS (hazard ratio [HR] 2.55, 95% confidence interval [CI] 2.15-3.03) and disease-free survival (HR 2.54, 95% CI 2.25-2.87) were significantly worse in the intervention arm. High heterogeneity was explained by subgroup analysis of different biologic agents (bevacizumab versus others); however, results still showed harm in the intervention arm across subgroups. Bevacizumab was associated with improved OS in patients with microsatellite instability (HR 0.58, 95% CI 0.36-0.92); this was the only indication of benefit for a biomarker-defined subpopulation. Analyses by tumor stage failed to demonstrate advantage with use of a biologic agent; however, it explained heterogeneity. CONCLUSIONS: The addition of biologic agents to adjuvant chemotherapy in the treatment of high-risk stage II and III colorectal cancer is associated with worse survival outcomes. The only subgroup of patients that may benefit from the addition of bevacizumab to adjuvant chemotherapy is those with microsatellite unstable tumors.

Venous Thromboembolic Events Following Major Pelvic and Abdominal Surgeries for Cancer: A Prospective Cohort Study.

OBJECTIVE: The aim of this study was to evaluate the incidence and risk factors for post-hospital discharge venous thromboembolism (VTE) following abdominal cancer surgery without post-discharge prophylaxis. METHODS: This was a single-center, prospective cohort study. Patients were evaluated at 1, 3, and 6 months from surgery for the presence of proximal deep vein thrombosis (DVT; screening ultrasound at 1 month and questionnaire at each visit). Cumulative VTE incidence with 95% confidence interval (CI) was estimated using Kaplan-Meier methods, and multivariable analysis was performed using a Cox proportional hazards model. RESULTS: Of 284 patients enrolled, 79 (28%) underwent colorectal laparotomy, 97 (34%) underwent hepatobiliary laparotomy, 100 (35%) underwent gynecological laparotomy, and 8 (3%) underwent exploratory laparotomy without resection. All patients received pre- and postoperative inpatient prophylaxis. The cumulative incidence of VTE at 1 month was 0.35% (95% CI 0.05-2.48), 2.5% at 3 months (95% CI 1.19-5.15), and 7.2% at 6 months (95% CI 4.72-10.97). Screening ultrasound performed 4 weeks after surgery in 50% of patients was negative for thrombosis in all cases. Event distribution was similar according to the type of surgery (open/laparoscopic) and type of cancer. Seventeen (6.6%) patients died (95% CI 3.5-9.4) (two had a VTE-related death). Postoperative chemotherapy and Caprini score were significantly associated with VTE [hazard ratios 3.77 (95% CI 1.56-9.12) and 1.17 (95% CI 1.02-1.34), respectively]. CONCLUSION: The incidence of post-hospital discharge proximal DVT and/or symptomatic VTE following abdominal and pelvic cancer surgery appears to be low. The cumulative number of events increased at 6 months, but this was likely due to additional risk factors that were not related to surgery. Postoperative chemotherapy increases the risk of VTE.

Effect of PET before liver resection on surgical management for colorectal adenocarcinoma metastases: a randomized clinical trial.

IMPORTANCE: Patients with colorectal cancer with liver metastases undergo hepatic resection with curative intent. Positron emission tomography combined with computed tomography (PET-CT) could help avoid noncurative surgery by identifying patients with occult metastases. OBJECTIVES: To determine the effect of preoperative PET-CT vs no PET-CT (control) on the surgical management of patients with resectable metastases and to investigate the effect of PET-CT on survival and the association between the standardized uptake value (ratio of tissue radioactivity to injected radioactivity adjusted by weight) and survival. DESIGN, SETTING, AND PARTICIPANTS: A randomized trial of patients older than 18 years with colorectal cancer treated by surgery, with resectable metastases based on CT scans of the chest, abdomen, and pelvis within the previous 30 days, and with a clear colonoscopy within the previous 18 months was conducted between 2005 and 2013, involving 21 surgeons at 9 hospitals in Ontario, Canada, with PET-CT scanners at 5 academic institutions. INTERVENTIONS: Patients were randomized using a 2 to 1 ratio to PET-CT or control. MAIN OUTCOMES AND MEASURES: The primary outcome was a change in surgical management defined as canceled hepatic surgery, more extensive hepatic surgery, or additional organ surgery based on the PET-CT. Survival was a secondary outcome. RESULTS: Of the 263 patients who underwent PET-CT, 21 had a change in surgical management (8.0%; 95% CI, 5.0%-11.9%). Specifically, 7 patients (2.7%) did not undergo laparotomy, 4 (1.5%) had more extensive hepatic surgery, 9 (3.4%) had additional organ surgery (8 of whom had hepatic resection), and the abdominal cavity was opened in 1 patient but hepatic surgery was not performed and the cavity was closed. Liver resection was performed in 91% of patients in the PET-CT group and 92% of the control group. After a median follow-up of 36 months, the estimated mortality rate was 11.13 (95% CI, 8.95-13.68) events/1000 person-months for the PET-CT group and 12.71 (95% CI, 9.40-16.80) events/1000 person-months for the control group. Survival did not differ between the 2 groups (hazard ratio, 0.86 [95% CI, 0.60-1.21]; P = .38). The standardized uptake value was associated with survival (hazard ratio, 1.11 [90% CI, 1.07-1.15] per unit increase; P < .001). The C statistic for the model including the standardized uptake value was 0.62 (95% CI, 0.56-0.68) and without it was 0.50 (95% CI, 0.44-0.56). The difference in C statistics is 0.12 (95% CI, 0.04-0.21). The low C statistic suggests that the standard uptake value is not a strong predictor of overall survival. CONCLUSIONS AND RELEVANCE: Among patients with potentially resectable hepatic metastases of colorectal adenocarcinoma, the use of PET-CT compared with CT alone did not result in frequent change in surgical management. These findings raise questions about the value of PET-CT scans in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00265356.

Computed tomography features associated with operative management for nonstrangulating small bowel obstruction.

BACKGROUND: The management of nonstrangulating small bowel obstruction (SBO) may require surgery, but the need for and timing of surgical intervention isn't always apparent. We sought to determine whether specific features on computed tomography (CT) can predict the necessity for operative management. METHODS: Two radiologists independently reviewed CT scans from all patients admitted to hospital with SBO between 2004 and 2006. We examined the association between radiographic features and operative management by univariate analysis using the χ(2) or Fisher exact test. Significant factors with high concordance between radiologists were entered into a multivariable stepwise logistic regression model. RESULTS: There were 228 patients with SBO, 63 of whom met our inclusion criteria and had CT scans available for review. Three CT features were frequently associated with operative management and had good concordance between radiologists: complete bowel obstruction, small bowel dilation greater than 4 cm and transition point. Transition point was the only significant factor predictive of operative management for SBO on multivariable logistic regression analysis (OR 19, 95% confidence interval 1.8-201, p = 0.014). CONCLUSION: In patients with nonstrangulating SBO, the presence of a transition point on CT scan should alert the surgeon to the increased likelihood that operative management may be required.

CONTEXTE: La prise en charge de l'occlusion du grêle sans étranglement peut nécessiter une chirurgie, mais il n'y a pas de règles claires pour déterminer le bien-fondé et le moment de l'intervention. Nous avons voulu déterminer si certaines caractéristiques spécifiques observées à la tomodensitométrie (TDM) permettent de prédire la nécessité d'une prise en charge chirurgicale. MÉTHODES: Deux radiologistes ont passé en revue de manière indépendante les TDM de tous les patients hospitalisés pour obstruction du grêle entre 2004 et 2006. Nous avons analysé le lien entre les caractéristiques radiographiques et la prise en charge chirurgicale par analyse univariée à l'aide du test du χ2 ou du test exact de Fisher. Les facteurs importants assortis d'une étroite concordance entre les radiologistes ont été intégrés à un modèle de régression logistique multivariée séquentielle. RÉSULTATS: On a dénombré 228 patients atteints d'une occlusion du grêle, dont 63 répondaient à nos critères d'inclusion et pour lesquels on disposait de résultats de TDM à soumettre à l'examen des radiologistes. Trois caractéristiques à la TDM ont fréquemment été associées à la prise en charge chirurgicale, en plus de faire l'objet d'une bonne concordance entre les radiologistes : obstruction intestinale complète, dilatation du grêle de plus de 4 cm et point de transition (ou saut de calibre). Le point de transition a été le seul facteur prédictif important à l'égard de la prise en charge chirurgicale de l'occlusion du grêle à l'analyse de régression logistique multivariée (rapport de cotes 19; intervalle de confiance de 95 %, 1,8­201; p = 0,014). CONCLUSION: Chez les patients qui présentent une occlusion du grêle sans étranglement, la présence d'un point de transition à la TDM devrait indiquer au chirurgien une plus grande probabilité de traitement chirurgical nécessaire.

Tranexamic acid versus placebo to reduce perioperative blood transfusion in patients undergoing liver resection: protocol for the haemorrhage during liver resection tranexamic acid (HeLiX) randomised controlled trial.

INTRODUCTION: Despite use of operative and non-operative interventions to reduce blood loss during liver resection, 20%-40% of patients receive a perioperative blood transfusion. Extensive intraoperative blood loss is a major risk factor for postoperative morbidity and mortality and receipt of blood transfusion is associated with serious risks including an association with long-term cancer recurrence and overall survival. In addition, blood products are scarce and associated with appreciable expense; decreasing blood transfusion requirements would therefore have health system benefits. Tranexamic acid (TXA), an antifibrinolytic, has been shown to reduce the probability of receiving a blood transfusion by one-third for patients undergoing cardiac or orthopaedic surgery. However, its applicability in liver resection has not been widely researched. METHODS AND ANALYSIS: This protocol describes a prospective, blinded, randomised controlled trial being conducted at 10 sites in Canada and 1 in the USA. 1230 eligible and consenting participants will be randomised to one of two parallel groups: experimental (2 g of intravenous TXA) or placebo (saline) administered intraoperatively. The primary endpoint is receipt of blood transfusion within 7 days of surgery. Secondary outcomes include blood loss, postoperative complications, quality of life and 5-year disease-free and overall survival. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating centres and Health Canada (parent control number 177992) and is currently enrolling participants. All participants will provide written informed consent. Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT02261415.

Frailty as a Predictor of Postoperative Morbidity and Mortality Following Liver Resection.

BACKGROUND: Liver resection is commonly performed among patients at risk of being frail. Frailty can be used to assess perioperative risk. Thus, we evaluated frailty as a predictor of postoperative complications following liver resection using a validated modified frailty index (mFI). METHODS: A retrospective cohort of consecutive patients undergoing liver resection (2011-2018) were stratified according to the mFI and classified as the following: high (≥.27) and low mFI (<.27). The effect of mFI on postoperative complications (Clavien-Dindo) was evaluated using multiple logistic regression, expressed as odds ratios (OR) and 95% CI. RESULTS: Of 409 patients, 58 (14%) had high mFI. There were no differences in type of liver resection (laparoscopic: 57% vs 55%, P = .766), number of segments resected (3 vs 4, P = .417), or operative time (257 vs 293 minutes, P = .097) between the high and low mFI groups, respectively. High mFI patients had a longer median length of hospital stay (9.5 vs 5 days, P < .001) and higher proportion of postoperative complications (79% vs 46%, P < .001), including minor complications (69% vs 42%, P < .001), major complications (50% vs 13%, P < .001), and 90-day postoperative mortality (12% vs 3.4%, P = .04). On multivariable analysis, longer operating time (OR 1.15, 95% CI, 1.03 to 1.27), higher number of segments resected (OR 1.43, 95% CI, 1.12 to 1.82), and high mFI (OR 6.74, 95% CI, 2.76 to 16.51) were independent predictors of major postoperative complications. DISCUSSION: mFI predicts postoperative outcomes following liver resection and can be used as a risk stratification tool for patients being considered for surgery.

Laparoscopic hepatectomy is safe and effective for the management of patients with colorectal cancer liver metastases in a population-based analysis in Ontario, Canada. A retrospective cohort study.

BACKGROUND: Laparoscopic hepatectomy (LH) has been deemed safe, and, in the case of minor hepatectomy, the standard of care. Short-, long-term outcomes and costs of LH compared with open hepatectomy (OH) in patients with colorectal cancer liver metastases have not been well described at the population level. MATERIALS AND METHODS: Patients diagnosed with colorectal cancer undergoing hepatectomy were included in this population-based retrospective cohort study from 2006- to 2014. Postoperative complications (per Clavien-Dindo) and survival were analyzed using a linear mixed model and Cox-Proportional hazards model respectively. Costs of surgery and the 90-day postoperative period were considered in 2018 Canadian dollars and compared from the perspective of a third-party payer. RESULTS: Over a median follow-up of 56 months, 95% confidence interval (CI): 51 to 68), there were 2991 hepatectomies (OH: 2551 (85%) and LH: 440 (15%)). LH compared to OH was more common for patients >70 years-old (30% vs. 22%, p = 0.004) and for minor hepatectomy (52% vs. 32%, p < 0.001) respectively. By multivariable analyses, OH was associated with similar 90-day mortality (Odds Ratio (OR) 1.05, 95% CI: 0.56-1.97), and overall survival (Hazard Ratio (HR) 1.08, 95% CI: 0.90-1.29), but higher rates of major postoperative complications (OR 1.34, 95% CI: 1.03-1.76), higher cost (median difference $6,163, 95% CI: $3229 to $9096), and longer length of hospital stay (LOS) (mean difference 3.04 days, 95% CI: 2.7 to 3.91). CONCLUSION: LH was associated with lower postoperative complications, shorter LOS, which translated into lower costs to the healthcare system, without differences in postoperative mortality and survival.

Simultaneous versus staged resection for synchronous colorectal liver metastases: A population-based cohort study.

BACKGROUND: Synchronous liver metastases from colorectal cancer may be resected simultaneously with the primary or as a second staged operation. We evaluated trends of resection for synchronous colorectal cancer liver metastases and associated patient outcomes. METHODS: This is a retrospective cohort study that included patients undergoing resection for synchronous colorectal cancer liver metastases from 2006 to 2015 in the province of Ontario, Canada (population 13 million). Simultaneous resections occurred on the same admission, while staged resections occurred less than 6 months apart. Outcomes included postoperative complications, length of hospital stay, and overall survival. Kaplan Meier survival estimates, Cox proportional hazard models and logistic regression were used. RESULTS: Among 2,738 patients undergoing resection for colorectal cancer liver metastases, 1168 (42%) had synchronous disease. Of these, 442 resections were simultaneous (38%) and 776 were staged (62%). The proportion of synchronous disease among patients undergoing resection increased on average 3% per year (p = 0.02). For simultaneous versus staged resection, respectively, median length of hospital stay was shorter (8 vs. 11 days, p < 0.001); rate of major liver resections was lower (17% vs. 65%, p < 0.001), major postoperative complications were similar (28% vs. 23%, p = 0.067), and 90-day post-operative mortality was higher (6% vs. 1%, p < 0.001). Chemotherapy was administered more commonly among patients undergoing staged resections (91% vs. 76%, p < 0.001). Simultaneous resection was associated with a lower median overall survival (40 months, 95%CI 35-46 vs. 78 months, 95%CI 59-86). Risk factors for lower survival included higher comorbidities, right-sided primary and simultaneous resection. CONCLUSION: Simultaneous resection was associated with similar postoperative complications, higher postoperative mortality and poorer long-term survival. Prospective randomized trials can inform the role of simultaneous versus staged resection for synchronous colorectal cancer liver metastases.

Simultaneous versus staged resection for synchronous colorectal liver metastases: A population-based cost analysis in Ontario, Canada - Health economic evaluation.

BACKGROUND: Simultaneous compared to staged resection of synchronous colorectal cancer liver metastases is considered safe. We aimed to determine their cost implications. STUDY DESIGN: Population-based cohort was generated by linking administrative healthcare datasets in Ontario, Canada (2006-2014). Resection of colorectal cancer and liver metastases within six months was considered synchronous. Cost analysis was performed from the perspective of a third-party payer. Median costs with range were estimated using the log-normal distribution of cost using t-test with a one-year time horizon. RESULTS: Among patients undergoing staged resection (n = 678), the estimated median cost was $54,321 CAD (IQR 45,472 to 68,475) and $41,286 CAD (IQR 31,633 to 58,958) for those undergoing simultaneous resection (n = 390), median difference: $13,035 CAD (p < 0.001). Primary cost driver were all costs related to hospitalization for liver and colon resection, which was higher for the staged approach, median difference: $16,346 CAD (p < 0.001). This was mainly due to a longer median length of hospital stay in the staged vs. simultaneous group (11 vs. 8 days, p < 0.001 respectively), which was not attributable to differences in major postoperative complication rates (23% vs. 28%, p = 0.067 respectively). Other costs, including cost of chemotherapy within six months of surgery ($11,681 CAD vs. $8644 CAD, p = 0.074 respectively) and 90-day re-hospitalization cost ($2155 CAD vs. $2931 CAD, p = 0.454 respectively) were similar between groups. CONCLUSION: Cost of staged resection of synchronous colorectal cancer liver metastases is significantly higher compared to the simultaneous approach, mostly driven by a longer length of hospital stay despite similar postoperative complication rates.

Operative blood loss independently predicts recurrence and survival after resection of hepatocellular carcinoma.

OBJECTIVE: To determine if the degree of blood loss during resection of hepatocellular carcinoma (HCC) is predictive of recurrence and long-term survival. BACKGROUND: Several studies have addressed the impact of blood transfusion on survival and recurrence after liver resection for HCC. However, the independent effect of intraoperative estimated blood loss (EBL) on oncologic outcome is unclear. METHODS: From our prospective database, we identified 192 patients who had a partial hepatectomy for HCC from 1985 to 2002. Clinicopathologic predictors of EBL were identified using logistic regression. Overall survival (OS), disease-specific survival (DSS), and recurrence free survival (RFS) were assessed using the Kaplan-Meier and Cox regression methods. RESULTS: The median patient age was 64 (range, 19-86) and 66% were men. All patients had histologically proven HCC. The median follow-up time was 34 months (range, 1-297). Factors associated with increased EBL on multivariate analysis were male gender, vascular invasion, extent of hepatectomy, and operative time (P < 0.01). EBL and vascular invasion were independent predictors of OS and DSS. Only EBL was significantly associated with RFS on multivariate analysis (P = 0.02). Additionally, we found a significant inverse correlation between increasing levels of EBL and length of DSS (P = 0.01). CONCLUSIONS: The magnitude of EBL during HCC resection is related to biologic characteristics of the tumor as well as the extent of surgery. Increased intraoperative blood loss during HCC resection is an independent prognostic factor for tumor recurrence and death.

Effect of Perioperative Nutritional Supplementation on Postoperative Complications-Systematic Review and Meta-Analysis.

BACKGROUND: Perioperative carbohydrate loading, increased protein intake, and immunonutrition may decrease postoperative complications. Studies on the topic have led to controversial results. METHODS: We searched Medline, EMBASE, and CENTRAL up to August 2018 for randomized trials comparing the effect of perioperative nutritional supplements (intervention) versus control on postoperative complications in patients undergoing gastrointestinal cancer surgery. Secondary outcomes included infectious complications and length of hospital stay (LOS). Random effects model was used to estimate the pooled risk ratio (RR) of treatment effects. Pooled mean difference (MD) was used to compare LOS. Heterogeneity was assessed using I2. Sources of heterogeneity were explored through subgroup analysis by nutritional supplementation protocol, type of surgery, and type of nutritional supplement. Risk of bias and quality of the evidence were assessed. RESULTS: Of 3951 articles, we identified 56 trials (n = 6370). Perioperative nutrition was associated with a lower risk of postoperative complications (RR 0.74, 95% confidence interval (CI) 0.69-0.80); postoperative infections (RR 0.71, 95% CI 0.64-0.79, n = 4582); and postoperative non-infectious complications (RR 0.79, 95% CI 0.71-0.87, n = 4883). There were no significant heterogeneity outcomes analyzed (I2 = 14%, 1%, and 7%, respectively). LOS was shorter for the intervention group, MD - 1.58 days; 95% CI - 1.83 to - 1.32; I2 = 89%). Subgroup analysis did not identify sources of heterogeneity. The quality of evidence for postoperative complications was high and for LOS was moderate. CONCLUSION: Perioperative nutritional optimization decreases the risk of postoperative infectious and non-infectious complications. It also decreases LOS in patients undergoing gastrointestinal cancer surgery, but these findings should be taken with caution given the high heterogeneity.

Does the Addition of Biologic Agents to Chemotherapy in Patients with Unresectable Colorectal Cancer Metastases Result in a Higher Proportion of Patients Undergoing Resection? A Systematic Review and Meta-analysis.

BACKGROUND: Surgical resection provides the best opportunity for cure for metastatic colorectal cancer. Whether addition of a biologic agent to chemotherapy improves the rate of conversion from unresectable to resectable disease remains uncertain. We carried out a systematic review of the literature and meta-analysis to define the impact of biologic agents on resection. METHODS: We searched Medline, Embase, CENTRAL, and PubMed for randomized controlled trials published up until April 2017 comparing chemotherapy and biologics (intervention) vs. chemotherapy alone (control) in treatment-naïve patients with unresectable metastatic colorectal cancer. Study selection, data abstraction, risk of bias, and quality of evidence assessment were performed in duplicate. Random-effects meta-analysis was used to estimate the pooled odds ratio (OR) for resection rate and corresponding confidence interval (CI). RESULTS: Nine studies, including a total of 4345 patients, were analyzed. Seven studies assessed epithelial growth factor receptor (EGFR)-directed monoclonal antibodies, and two used antiangiogenic agents. The addition of a biologic agent to chemotherapy was associated with higher resection rate (OR 1.47, 95% CI 1.07-2.02; resection rate 8.4 vs. 6.1%). Subgroup analysis based on mechanism of action of drugs showed benefit for resection rate only with EGFR-directed agents (OR 1.70, 95% CI 1.10-2.64). Heterogeneity among studies was low (I 2  = 34%). CONCLUSIONS: The addition of biologic agents to systemic chemotherapy in patients with initially unresectable metastatic colorectal cancer improved resection rate. The optimal biologic agent for this outcome cannot yet be determined.

Postoperative complications in elderly patients following pancreaticoduodenectomy lead to increased postoperative mortality and costs. A retrospective cohort study.

BACKGROUND: Complications frequently occur after pancreaticoduodenectomy. Patients undergoing pancreaticoduodenectomy tend to be older; age and postoperative complication may be associated. To clarify this association, we compared postoperative outcomes in patients undergoing pancreaticoduodenectomy based on age group. We aimed to determine whether we could identify an age cutoff where the incidence and cost of postoperative complications starts increasing and potentially outweigh the potential benefits of pancreaticoduodenectomy. MATERIALS AND METHODS: We built a retrospective cohort of consecutive patients undergoing pancreaticoduodenectomy at one institution from 2011 to 2017. Demographics, operative data and costs were obtained from hospital and administrative databases. A restricted cubic spline regression analysis was performed to graphically identify the age in which the comprehensive complication index (CCI) substantially increased. Cost analysis was undertaken from the perspective of a third-party payer. Differences in costs between age groups were tested using t-test. RESULTS: Among 440 patients, the CCI became significantly higher at the age cutoff of 72 (median 21 in the older vs. 12 in the younger group, P = 0.014). Postoperative complications (74% vs. 64%, P = 0.038), and mortality (8% vs. 3%, P = 0.016) were also significantly higher in the older age group; mostly driven by pneumonia (11% vs. 6%, P = 0.097), myocardial infarction (12% vs. 4%, P < 0.002) and urinary tract infection (18% vs. 5%, P = 0.003). Median length of hospital stay was also longer for the older age group (10 vs. 8 days, P = 0.002). Total mean cost was significantly higher in the older age group ($38,225 CAD vs. $29,771 CAD). CONCLUSIONS: In our cohort of patients, after age 72, pancreaticoduodenectomy is associated with significantly more postoperative complications and deaths which translated in longer hospital stay and higher costs. This information may help patients and surgeons make informed decisions.