Unveiling the intrinsic role of malnutrition in patients with Crohn's disease undergoing major surgery using entropy balancing weighting analysis.

The negative role of malnutrition in patients with Crohn's disease is known; however, many coexisting disease-related factors could cause misinterpretation of the real culprit. This study aimed to describe the role of malnutrition using a novel methodology, entropy balancing. This was a retrospective analysis of consecutive patients undergoing elective major surgery for Crohn's disease, preoperatively screened following the European Society for Clinical Nutrition guidelines. Two-step entropy balancing was applied to the group of malnourished patients to obtain an equal cohort having a null or low risk of malnutrition. The first reweighting homogenised the cohorts for non-modifiable confounding factors. The second reweighting matched the two groups for modifiable nutritional factors, assuming successful treatment of malnutrition. The entropy balancing was evaluated using the d-value. Postoperative results are reported as mean difference or OR, with a 95 % CI. Of the 183 patients, 69 (37·7 %) were at moderate/high risk for malnutrition. The malnourished patients had lower BMI (d = 1·000), Hb (d = 0·715), serum albumin (d = 0·981), a higher lymphocyte count (d = 0·124), Charlson Comorbidity Index (d = 0·257), American Society of Anaesthesiologists (d = 0·327) and Harvey-Bradshaw scores (d = 0·696). Protective loop ileostomy was more frequently performed (d = 0·648) in the malnourished group. After the first reweighting, malnourished patients experienced a prolonged length of stay (mean difference = 1·9; 0·11, 3·71, days), higher overall complication rate (OR 4·42; 1·39, 13·97) and higher comprehensive complication index score (mean difference = 8·9; 2·2 15·7). After the second reweighting, the postoperative course of the two groups was comparable. Entropy balancing showed the independent role of preoperative malnutrition and the possible advantages obtainable from a pre-habilitation programme in Crohn's disease patients awaiting surgery.

Frailty assessment can predict textbook outcomes in senior adults after minimally invasive colorectal cancer surgery.

AIM: Colorectal cancer (CRC) surgery can be associated with suboptimal outcomes in older patients. The aim was to identify the correlation between frailty and surgical variables with the achievement of Textbook Outcome (TO), a composite measure of the ideal postoperative course, by older patients with CRC. METHOD: All consecutive patients ≥70years who underwent elective CRC-surgery between January 2017 and November 2021 were analyzed from a prospective database. To obtain a TO, all the following must be achieved: 90-day survival, Clavien-Dindo (CD) < 3, no reintervention, no readmission, no discharge to rehabilitation facility, no changes in the living situation and length of stay (LOS) ≤5days/≤14days for colon and rectal surgery respectively. Frailty and surgical variables were related to the achievement of TO. RESULTS: Four-hundred-twenty-one consecutive patients had surgery (97.7% minimally invasive), 24.9% for rectal cancer, median age 80 years (range 70-92), median LOS of 4 days (range 1-96). Overall, 288/421 patients (68.4%) achieved a TO. CD 3-4 complications rate was 6.4%, 90-day mortality rate was 2.9%. At univariate analysis, frailty and surgical variables (ileostomy creation, p = 0.045) were related to. However, multivariate analysis showed that only frailty measures such as flemish Triage Risk Screening Tool≥2 (OR 1.97, 95%CI: 1.23-3.16; p = 0.005); Charlson Index>6 (OR 1.61, 95%CI: 1.03-2.51; p = 0.036) or Timed-Up-and-Go>20 s (OR 2.06, 95%CI: 1.01-4.19; p = 0.048) independently predicted an increased risk of not achieving a TO. CONCLUSION: The association between frailty and comprehensive surgical outcomes offers objective data for guiding family counseling, managing expectations and discussing the possible loss of independence with patients and caregivers.

Years of Life Lost for Older Patients After Colorectal Cancer Diagnosis.

BACKGROUND: An aging population combined with an increased colorectal cancer (CRC) incidence in the older population will increase its prevalence in the elderly, questioning how many years of life are lost (YLLs) in these patients. PATIENTS AND METHODS: Data from 32,568 Dutch CRC patients ≥ 80 years were used to estimate the number of YLLs after diagnosis, using a reference age-, sex- and year-of-onset-matched cohort derived from national life tables. YLLs were additionally adjusted by comorbidities. Number needed to treat (NNT) was used as measure of surgical effect size. RESULTS: Surgery was applied in 74.9% of patients leading to 1.3 YLLs, being superior in 86.1% of cases with respect to alternative therapies (YLLs 4.8 years) and resulting in a number of two patients needed to operate to achieve one positive outcome. YLLs and NNTs depended on CRC stage, patient' age and comorbidities. For Stage I-II patients in the best clinical conditions (80-85 years without comorbidities), YLLs increased up to 4.1 years after surgery and up to 8.8 years without surgery (NNT 3). For Stage III patients, the NNT of surgery varied between 2 when they were in the best clinical conditions and 4 when they were older with high comorbidities. In Stage IV patients, the NNT ranged between 6 and 31. CONCLUSIONS: YLLs represents a novel approach to evaluate CRC prognosis. Stage I-III surgical patients can have a life expectancy similar to that of general population, being the NNT of surgery reasonably small compared with alternatives. Personalized comorbidity data are needed to confirm present findings.

Efficacy and Safety of Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis of Phase III Trials.

AIM/BACKGROUND: After the introduction of sorafenib in the treatment of advanced hepatocellular carcinoma (HCC), different studies tried to evaluate whether other systemic therapies can improve survival. To provide a comprehensive indirect treatment comparison of efficacy and safety of novel drugs, a network meta-analysis (NMA) of phase III randomized controlled trials was performed. METHODS: After pertinent literature search up to November 1, 2016, 6 studies were eligible for the analysis including 4,812 individual patients with advanced HCC: 2,454 received sorafenib, 577 received brivanib, 530 received sunitinib, 514 received linifanib, 358 received sorafenib + erlotinib and 379 received placebo. Frequentist NMA was used to compare treatments within a single analytical framework. RESULTS: NMA showed that sorafenib alone, regardless of combination with erlotinib, and linifanib provide a significant survival advantage over placebo (p < 0.05) but without any significant difference between each other. Conversely, all regimens significantly ameliorate progression-free survival versus placebo (p < 0.05). The rank order of efficacy was: sorafenib ± erlotinib, linifanib, brivanib, sunitinib, and placebo. Sorafenib ± erlotinib was the regimen with the fewest number of adverse events that required discontinuation of treatment, whereas linifanib and brivanib resulted in the most adverse events. The risk-benefit summary identified one cluster of therapies with a similar balance between efficacy and safety which included sorafenib alone or in combination with erlotinib, having, at the same time, the highest efficacy and safety. CONCLUSIONS: Sorafenib remains the best systemic treatment for advanced HCC; linifanib also resulted in survival advantages over placebo but with a lower safety profile.

Adding Liver Stiffness Measurement to the Routine Evaluation of Hepatocellular Carcinoma Resectability Can Optimize Clinical Outcome.

Purpose Liver stiffness (LS) has been shown to be of use in chronic liver disease patients but its utility in surgical judgment still needs to be proven. A decision-making approach was applied to evaluate whether LS measurement before surgery of hepatocellular carcinoma (HCC) can be useful in avoiding post-hepatectomy liver failure (PHLF). Materials and Methods Decision curve analysis (DCA) was applied to 202 HCC patients (2008 - 14) with LS measurement prior to hepatectomy to verify whether the occurrence of PHLF grades B/C should be reduced through a decision-making approach with LS.  Results Within 90 days of surgery, 4 patients died (2 %) and grades B/C PHLF occurred in 29.7 % of cases. Ascites and/or pleural effusion, treatable with medical therapy, were the most frequent complications. DCA showed that using the "expected utility theory" LS measurement can reduce up to 39 % of cases of PHLF without the exclusion of any patient from surgery that duly undergoes an uncomplicated postoperative course. LS measurement does not add any information to normal clinical judgment for patients with a low (< 10 %) risk of PHLF. Conclusion LS measurement can determine a reduction of PHLF under "expected utility theory" fulfilment. However, the degree of PHLF can be minor and "risk seeking" individuals can accept such a risk on the basis of surgical benefits.

Can Current Preoperative Imaging Be Used to Detect Microvascular Invasion of Hepatocellular Carcinoma?

PURPOSE: To determine the accuracy of imaging features, such as tumor dimension, multinodularity, nonsmooth tumor margins, peritumoral enhancement, and radiogenomic algorithm based on the association between imaging features (internal arteries and hypoattenuating halos) and gene expression that the authors called two-trait predictor of venous invasion (TTPVI), in the prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. One hundred twenty-five patients (median age, 63 years; interquartile range, 53-71 years) with a diagnosis of HCC and indications for hepatic resection were included. Two observers independently reviewed radiologic images to evaluate the following features for MVI: maximum diameter, number of lesions, tumor margins, TTPVI, and peritumoral enhancement. Interobserver agreement was checked, and diagnostic accuracy of radiologic features was investigated. RESULTS: The total number of HCC nodules was 140. Large tumor size, nonsmooth tumor margins, TTPVI, and peritumoral enhancement were significantly related to the presence of MVI (P < .05 in all cases and for both observers). Multinodularity was not significantly related (P = .158). Moreover, the diagnostic accuracy of the three "worrisome" radiologic features (nonsmooth tumor margins, peritumoral enhancement, and TTPVI) was associated with tumor size: The negative predictive value of the absence of worrisome features decreased from 0.84 for observer 1 and 0.91 for observer 2 for tumors smaller than 2 cm to 0.56 and 0.71, respectively, for tumors larger than 5 cm, whereas the presence of all three worrisome features returned to a positive predictive value of 0.95 for observer 1 and 0.96 for observer 2 independent of tumor size, with no significant interobserver differences (P > .10). CONCLUSION: "Worrisome" imaging features, such as tumor dimension, nonsmooth tumor margins, peritumoral enhancement, and TTPVI, have high accuracy in the prediction of MVI in HCC.

Hepatic venous pressure gradient in the preoperative assessment of patients with resectable hepatocellular carcinoma.

BACKGROUNDS & AIMS: To assess the relationship existing between hepatic venous pressure gradient (HVPG) and the occurrence of post-hepatectomy liver failure (PHLF) grade B/C after resection of hepatocellular carcinoma (HCC) and persistent worsening of liver function. METHODS: Data from 70 consecutive prospectively enrolled HCC patients undergoing resection were collected and analysed. PHLF grade B/C was defined by the International Study Group of Liver Surgery recommendations. The appearance of unresolved decompensation was also analysed. RESULTS: Postoperative and 90-day mortality were null. The median HVPG value was 9mmHg (range: 4-18) and the median Model for End-stage Liver Disease (MELD) score was 8 (range: 6-14); 34 patients had an HVPG ⩾10mmHg (48.6%). Forty-nine patients had an uneventful (Grade A) postoperative course, including 17 with an HVPG ⩾10mmHg (24.2% of 70 patients). Grade B complications occurred in 20 patients (3 with an HVPG <10mmHg and 17 with an HVPG ⩾10mmHg; p<0.001); only one grade C complication occurred in a patient with an HVPG <10mmHg, subsequently successfully undergoing liver transplantation. Median MELD score returned to preoperative values after a transient postoperative increase, regardless of the HVPG values; after three months, it returned to the preoperative of 8 in patients with an HVPG <10mmHg and of 9 in patients with an HVPG ⩾10mmHg (p=0.077 and 0.076 at paired test, respectively). CONCLUSIONS: The hepatic venous pressure gradient can be used before surgery to stratify the risk of PHLF but the proposed cut-off of 10mmHg excludes approximately one-quarter of the patients who would benefit from surgery without short to mid-term postoperative sequelae.

Cure model survival analysis after hepatic resection for colorectal liver metastases.

BACKGROUND: Statistical cure is achieved when a patient population has the same mortality as cancer-free individuals; however, data regarding the probability of cure after hepatectomy of colorectal liver metastases (CLM) have never been provided. We aimed to assess the probability of being statistically cured from CLM by hepatic resection. METHODS: Data from 1,012 consecutive patients undergoing curative resection for CLM (2001-2012) were used to fit a nonmixture cure model to compare mortality after surgery to that expected for the general population matched by sex and age. RESULTS: The 5- and 10-year disease-free survival was 18.9 and 15.8 %; the corresponding overall survival was 44.3 and 32.7 %. In the entire study population, the probability of being cured from CLM was 20 % (95 % confidence interval 16.5-23.5). After the first year, the mortality excess of resected patients, in comparison to the general population, starts to decline until it approaches zero 6 years after surgery. After 6.48 years, patients alive without tumor recurrence can be considered cured with 99 % certainty. Multivariate analysis showed that cure probabilities range from 40.9 % in patients with node-negative primary tumors and metachronous presentation of a single lesion <3 cm, to 1.5 % in patients with node positivity, and synchronous presentation of multiple, large CLMs. A model for the calculation of a cure fraction for each possible clinical scenario is provided. CONCLUSIONS: Using a cure model, the present results indicate that statistical cure of CLM is possible after hepatectomy; providing this information can help clinicians give more precise answer to patients' questions.

The use of the Hirsch index in benchmarking hepatic surgery research.

BACKGROUND: The Hirsch index (h-index) is recognized as an effective way to summarize an individual's scientific research output. However, a benchmark for evaluating surgeon scientists in the field of hepatic surgery is still not available. METHODS: A total of 3,251 authors who published between 1949 and 2011 were identified using the Scopus identification number. The h-index, the total number of cited document, the total number of citations, and the scientific age were calculated for each author using both Scopus and Google Scholar. RESULTS: The median h-index was 6 and the median scientific age, assessed with Google Scholar, was 19 years. The numbers of cited documents, numbers of citations, and h-indexes obtained from Scopus and Google Scholar showed good correlation with one another; however, the results from the 2 databases were modified in different ways by scientific age. By plotting scientific age against h-index percentiles an h-index growth chart for both Scopus database and Google Scholar was provided. CONCLUSIONS: This analysis provides a first benchmark to assess surgeon scientists' productivity in the field of liver surgery.