Preoperative frailty assessment in older patients with colorectal cancer: use of clinical and radiological tool.

PURPOSE: The Memorial Sloan Kattering Frailty Index (MSK-FI) and the Skeletal Muscle Index (SMI) have recently gained attention as markers of frailty and decreased physiologic reserve, and are promising as predictors of adverse postoperative outcomes in patients undergoing oncologic surgery. The objective of this study was to establish the prognostic accuracy of these indexes in a cohort of patients with colorectal cancer subjected to surgical intervention. METHODS: We performed an observational study including all patients older than 60 years, subjected to colorectal cancer surgery between January 2010 and May 2020, and stratified our cohort based on the presence of frailty, as defined by MSK-FI ≥ 3. Computed tomography was used to calculate SMI, using a standardized institutional protocol. A multivariable analysis was used to study the association between these novel indexes with adverse postoperative outcomes in our cohort. RESULTS: A total of 216 patients were included. Among these, 56 (26%) qualified as frail and 132 (62%) had a low SMI. On multivariable analysis (adjusted by patient and intraoperative characteristics), frailty was associated with increased risk of having a major postoperative complication (OR 29.78, 95%CI 10.36-85.71) and increased admission to the intensive care unit (OR 4.99, 95%CI 1.55-16.06), while both frailty and low SMI were associated with prolonged length of stay (OR 11.22, 95%CI 8.91-13.53 and OR 0.14, 95% CI 0.06-0.20, respectively). CONCLUSION: MSK-FI ≥ 3 and low SMI are associated with adverse postoperative outcomes in elderly patients undergoing colorectal cancer surgery. Implementing this practical tool in routine clinical practice, may help identify patients that would benefit from surgical prehabilitation and preoperative optimization to improve outcomes.

Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology.

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.

How strong is the evidence to support statins repurposing for the treatment of cirrhosis?

In this editorial, we briefly mention the studies that support the use of statins to change the natural history of liver cirrhosis, alongside potential biases and flaws that need to be considered when analyzing data. The key message that we want to communicate is that even if current evidence is somehow compelling, it is limited, mostly from observational studies, and in general not enough to formally recommend the prescription of statins in patients with cirrhosis as disease-modifying agents. Finally, we also mention some important facts about the safety of statins in the context of patients with underlying liver disease.

The neutrophil-lymphocyte ratio as a predictor of steroid response in patients with severe ulcerative colitis: a retrospective cohort study.

In this study we assessed the neutrophil-lymphocyte ratio (NLR) as a predictor of steroid non-response (SNR) in patients with acute severe ulcerative colitis and found a NLR on day 3 (NLR-3) >6.1 as a suitable cutoff point to identify SNR (OR 3.44, 95%CI 1.22-9.66) with sensitivity, specificity, positive predictive value, negative predictive value, and AUROC of 66.75, 63.2%, 35.9%, 86%, and 0.650, respectively. A model including bowel movements, albumin levels, and a NLR-3>6.1 had an AUC of 0.812 to predict SNR, with acceptable calibration.

Economic evaluation of long-term albumin use in cirrhosis patients from the Mexican healthcare system perspective.

INTRODUCTION AND OBJECTIVES: Liver cirrhosis is a major public health issue associated with high morbidity and mortality. The ANSWER trial showed that long-term human albumin (LTA) infusions led to significant reduction of complications and mortality in patients with uncomplicated ascites. The present study aimed to assess the incremental cost of cirrhosis patients treated with LTA plus standard medical treatment (SMT) versus those treated with SMT from the perspective of the Mexican Social Security Institute (IMSS). MATERIAL AND METHODS: Cost of illness for patients with cirrhosis and grade 2-3 ascites treated with SMT or with SMT and LTA (following the treatment regimen from ANSWER) over a one-year period was estimated according to the IMSS perspective. Rates of treatments, complications and hospitalizations were based on results from the ANSWER trial. Unit costs from IMSS were gathered from public sources and transformed to 2020 Mexican $ (Mex$). RESULTS: The use of LTA is estimated to require additional annual expenditure derived from the pharmacological cost of human albumin and by the follow up visits required for LTA administration (Mex$28,128). However, this cost may potentially be counterbalanced by the reduction in paracentesis, cirrhosis-related complications and hospitalizations which would lead to cost savings of Mex$33,417 per patient/year. CONCLUSIONS: Based on the ANSWER trial results, our study suggests that LTA may result in improved clinical outcomes and reduced costs for the IMSS when administered to cirrhosis patients with uncomplicated ascites.

Position statement on the use of albumin in liver cirrhosis.

Cirrhosis is characterised by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Characteristic of this is the increase in pro-inflammatory cytokines and pro-oxidant molecules which are determining factors in the development of multiple organ dysfunction. In the early development of cirrhosis, splanchnic arterial vasodilation, activation of vasoconstrictor systems (renin-angiotensin-aldosterone) and the sympathetic nervous system (noradrenaline) bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic inflammation present in the patient with cirrhosis. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic and endothelial stabilising properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options in patients with cirrhosis, from the compensated then decompensated phases to multiple organ dysfunction. Its recognised uses in spontaneous bacterial peritonitis, post-paracentesis circulatory dysfunction, acute kidney injury and hepatorenal syndrome are fully validated, and a treatment option has opened up in decompensated cirrhosis and in acute-on-chronic liver disease.

The Educational Quality of Laparoscopic Right Hemicolectomy Videos on YouTube.

Introduction. Surgical technique videos are an important part of surgical fellows' education. YouTube has been identified as the preferred source of educational videos among trainees. The aim of this article is to objectively evaluate the quality of the 50 most viewed videos on YouTube concerning right laparoscopic hemicolectomy using LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS). We hypothesized that the number of likes or views will not necessarily reciprocate with the educational content. Materials and methods. This observational study started with a YouTube search under the words "laparoscopic right hemicolectomy", "right colectomy", and "right hemicolectomy". The 50 most viewed videos with an English title were chosen. Video characteristics and LAP-VEGaS score were analyzed by four colorectal surgery fellows from a tertiary center in Mexico City. Results. Right hemicolectomy videos were reviewed; there was no correlation between the LAP-VEGaS score and the view ratio, the like ratio, or the video power index. The LAP-VEGaS score was significantly higher among videos uploaded by medical associations, journals, or commercial when compared with videos uploaded by doctors/physicians or academic associations. Conclusion. Educational quality in right laparoscopic hemicolectomy videos did not reciprocate with their educational quality, but it agrees significantly with the video uploading source. Low educational quality was identified among the videos underscoring the need to endorse peer-reviewed video channels.

Statins and Liver Cancer in Cirrhosis: The Most Relevant Questions Are Still Unanswered.

ABSTRACT: Several observational studies have shown an association between statin use and lower incidence of liver cancer. However, several potential biases limit a causal interpretation that could lead to a recommendation of statin prescription to patients with cirrhosis in the absence of a cardiovascular indication. Ongoing randomized trials will soon provide a clearer picture on the efficacy and safety of statins for preventing liver cancer and other complications of cirrhosis.

Hepamet Fibrosis Score in Nonalcoholic Fatty Liver Disease Patients in Mexico: Lower than Expected Positive Predictive Value.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been associated with different negative outcomes in the presence of advanced fibrosis. The Hepamet Fibrosis Score (HFS), a recently described noninvasive score, has shown excellent performance for the detection of advanced fibrosis. The aim of this study was to assess its performance in a Mexican population with NAFLD. METHODS: This was a retrospective cross-sectional study performed in 222 patients with biopsy-proven NAFLD, of whom 33(14%) had advanced fibrosis. We retrieved clinical data from each patient's medical record to compute the HFS, the NAFLD Fibrosis Score (NFS), and the Fibrosis-4 (FIB-4), and assess their performance. RESULTS: When considering the models as continuous variables, the area under the receiving operating characteristics curve of the HFS(0.758) was not different from that of the NFS(0.669, p = 0.09) or FIB-4(0.796, p = 0.1). The HFS had a sensitivity, specificity, positive and negative predictive values of 76.7% (95% CI 57.7-90.1), 90.1% (95% CI 85-93.9), 36.7% (95% CI 19.9-56.1), and 94.3% (95% CI 88.5-97.7), respectively. Indeterminate results (i.e., gray area) were more common with FIB-4 and HFS when compared with NFS [139(63%) and 122(55%) vs 80(36%), p < 0.001]. The variables that were associated with misclassification using the HFS were diabetes [OR 3.40 (95% CI 1.42-8.10), p = 0.006] and age [OR 1.06 (95% CI 1.01-1.11), p = 0.01]. CONCLUSION: The HFS showed sensitivity and specificity similar to that reported in the original publication; however, the positive predictive value was 36.7% at a pretest probability of 14%. The role of the HFS in prospective studies and in combination with other methods should be further explored.

Selective Internal Radiation Therapy for Hepatocellular Carcinoma Across the Barcelona Clinic Liver Cancer Stages.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common lethal cancer, and there is a need for effective therapies. Selective internal radiation therapy (SIRT) has been increasingly used, but is not supported by guidelines due to a lack of solid evidence. AIMS: Determine the efficacy and safety of SIRT in HCC across the Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C. METHODS: Consecutive patients that received SIRT between 2006 and 2016 at two centers in Canada were evaluated. RESULTS: We analyzed 132 patients, 12 (9%), 62 (47%), and 58 (44%) belonged to BCLC stages A, B, and C; mean age was 61.2 (SD ± 9.2), and 89% were male. Median survival was 12.4 months (95% CI 9.6-16.6), and it was different across the stages: 59.7 (95% CI NA), 12.8 (95% CI 10.2-17.5), and 9.3 months (95% CI 5.9-11.8) in BCLC A, B, and C, respectively (p = 0.009). Independent factors associated with survival were previous HCC treatment (HR 2.01, 95% CI 1.23-3.27, p = 0.005), bi-lobar disease (HR 2.25, 95% CI 1.30-3.89, p = 0.003), ascites (HR 1.77, 95% CI 0.99-3.13, p = 0.05), neutrophil-to-lymphocyte ratio (HR 1.11, 95% CI 1.02-1.20, p = 0.01), Albumin-Bilirubin (ALBI) grade-3 (HR 2.69, 95% CI 1.22-5.92, p = 0.01), tumor thrombus (HR 2.95, 95% CI 1.65-5.24, p < 0.001), and disease control rate (HR 0.62, 95% CI 0.39-0.96, p = 0.03). Forty-four (33%) patients developed severe adverse events, and ALBI-3 was associated with higher risk of these events. CONCLUSIONS: SIRT has the potential to be used across the BCLC stages in cases with preserved liver function. When using it as a rescue treatment, one should consider variables reflecting liver function, HCC extension, and systemic inflammation, which are associated with mortality.

Frailty index as a predictive preoperative tool in the elder population undergoing major abdominal surgery: a prospective analysis of clinical utility.

PURPOSE: The geriatric population has increased considerably in the last decades. Such increases come along with new challenges for surgical practitioners, who now face a risen number of frail patients in need of major operations. The value of frailty indexes in this setting has been discussed recently. This study assessed the modified Rockwood frailty index (mRFI) as a predictive tool for postoperative complications in older adults subjected to major abdominal operations and correlated it with other scores widely utilized for this purpose. METHODS: We performed a prospective study utilizing the mRFI including all patients older than 65 years subjected to major abdominal surgery between May 2017 and May 2019 in a third-level academic center. A comparison between frail (mRFI >0.25) and non-frail patients (mRFI <0.25) was performed. We performed logistic regression to identify predictors of postoperative complications and 30-day mortality. We analyzed the correlation between mRFI and ACS-NSQIP, P-POSSUM, PMP, and Charlson score risk calculators. RESULTS: One hundred forty patients were included in our study, of whom 49 (35%) were identified as frail. Frail patients demonstrated significantly prolonged hospital stay (p<.0001), ICU admission rates (p=0.004), hospital readmissions (p=0.007), and higher mortality rates (p=0.02). Our univariate analysis associated frailty (mRFI>0.25), ASA >III, increased age, and BMI with postoperative complications. In our multivariate analysis, frailty remained an independent predictor for postoperative complications (OR 6.38, 95% CI [2.45-16.58], p<0.001). Frailty was also associated with length of stay (LOS) regardless of the type of surgery (OR 3.35, 95% CI [0.37-6.33], p= 0.03). mRFI>0.25 demonstrated a sensitivity (Se) of 70% and specificity (Sp) 67% with area under the curve (AUC) 0.75 for perioperative complications, Se 69% and Sp 70% with AUC 0.74 for ICU admissions, and Se 83% and Sp 68% with AUC 0.83 for mortality. CONCLUSION: Frail patients demonstrated significantly prolonged hospital stay, ICU admission rates, hospital readmissions, and higher mortality rates. mRFI is an independent predictor for perioperative complications with a Se of 70% and Sp 67% and AUC 0.75.

Influence of Muscle Mass Area and Visceral Obesity on 30-day Mortality After Colorectal Surgery with Primary Anastomosis.

BACKGROUND: Muscle mass and visceral fat may be assessed at the level of the third lumbar vertebra (L3) in computed tomography (CT). Both variables have been related with adverse surgical outcomes. OBJECTIVE: The objective of the study was to study the association of skeletal muscle index (SMI) and visceral fat area (VFA) with 30-day mortality in colorectal surgery. METHODS: This is a retrospective cohort study conducted at a tertiary referral hospital in Mexico City. Patients who underwent colorectal surgery with primary anastomosis from January 2007 to December 2018 were included in the study. Their preoperative CT scans were analyzed with the NIH ImageJ software at the level of the third lumbar vertebra to determine their SMI (L3-SMI) and the VFA. Logistic regression analysis (adjusted by surgery anatomical location) was used to determine the association between these variables and surgical 30-day mortality. RESULTS: A total of 548 patients were included; 30-day mortality was 4.18% (23 patients). On univariable analysis, L3-SMI, low SMI, anastomosis leak, pre-operative albumin, estimated blood loss, age, steroid use, Charlson comorbidity index score >2, and type of surgery were associated with 30-day mortality. On multivariable analysis, low SMI remained an independent risk factor with an odds ratio of 4.74, 95% confidence interval 1.22-18.36 (p = 0.02). CONCLUSION: Low SMI was found to be an independent risk factor for 30-day mortality in patients submitted to colorectal surgery with a primary anastomosis, whether for benign or malignant diagnosis. VFA was not associated with 30-day mortality.

Non-Invasive Prediction of High-Risk Varices in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis.

BACKGROUND: Baveno-VI guidelines recommend that patients with compensated cirrhosis with liver stiffness by transient elastography (LSM-TE) <20 kPa and platelets >150,000/mm(3) do not need an esophagogastroduodenoscopy (EGD) to screen for varices, since the risk of having varices needing treatment (VNT) is <5%. It remains uncertain if this tool can be used in patients with cholestatic liver diseases (ChLDs): primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These patients may have a pre-sinusoidal component of portal hypertension that could affect the performance of this rule. In this study we evaluated the performance of Baveno-VI, expanded Baveno-VI (LSM-TE <25 kPa and platelets >110,000/mm(3)), and other criteria in predicting the absence of VNT. METHODS: This was a multicenter cross-sectional study in four referral hospitals. We retrospectively analyzed data from 227 patients with compensated advanced chronic liver disease (cACLD) due to PBC (n = 147) and PSC (n = 80) that had paired EGD and LSM-TE. We calculated false negative rate (FNR) and number of saved endoscopies for each prediction rule. RESULTS: Prevalence of VNT was 13%. Baveno-VI criteria had a 0% FNR in PBC and PSC, saving 39 and 30% of EGDs, respectively. In PBC the other LSM-TE-based criteria resulted in FNRs >5%. In PSC the expanded Baveno criteria had an adequate performance. In both conditions LSM-TE-independent criteria resulted in an acceptable FNR but saved less EGDs. CONCLUSIONS: Baveno-VI criteria can be applied in patients with cACLD due to ChLDs, which would result in saving 30-40% of EGDs. Expanded criteria in PBC would lead to FNRs >5%.

Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis.

BACKGROUND & AIMS: Two major body compartments, skeletal muscle and adipose tissue, exhibit independent functions. We aimed to explore the prognostic significance of skeletal muscle, visceral and subcutaneous adipose tissue, according to sex, in patients with cirrhosis assessed for liver transplantation (LT). METHODS: CT images taken at the 3rd lumbar vertebra from 677 patients were quantified for three body composition indexes (cm2/m2), visceral adipose tissue index, subcutaneous adipose tissue index (SATI), and skeletal muscle index (SMI). Cox proportional and competing-risk analysis hazard models were conducted to assess associations between mortality and body composition. RESULTS: The majority of patients were male (67%) with a mean age of 57 ±â€¯7 years, model for end-stage liver disease (MELD) score of 14 ±â€¯8 and mean body mass index of 27 ±â€¯6 kg/m2. Despite similar body mass index between the sexes, male patients had greater SMI (53 ±â€¯12 vs. 45 ±â€¯9 cm2/m2), whereas SATI (67 ±â€¯52 vs. 48 ±â€¯37 cm2/m2) was higher in females (p <0.001 for each). In sex stratified multivariate analyses after adjustment for MELD score and other confounding variables, SATI in females (hazard ratio [HR] 0.99; 95% CI 0.98-1.00; p = 0.01) and SMI in males (HR 0.98; 95% CI 0.96-1.00; p = 0.02) were significant predictors of mortality. Female patients with low SATI (<60 cm2/m2) had a higher risk of mortality (HR 2.06; 95% CI 1.08-3.91; p = 0.03). Using competitive risk analysis in female patients listed for LT, low SATI was also an independent predictor of mortality (subdistribution HR 2.80; 95% CI 1.28-6.12; p = 0.01) after adjusting for MELD, and other confounding factors. CONCLUSIONS: A lower SATI is associated with higher mortality in female patients with cirrhosis. Subcutaneous adipose tissue has a favorable metabolic profile - low SATI may reflect depletion of this major energy reservoir, leading to poor clinical outcomes. LAY SUMMARY: We looked at the importance of two of the main body compartments, skeletal muscle and adipose tissue (fat) on the prognosis of males and females with end-stage liver disease. Lower amounts of subcutaneous fat but not visceral fat (around internal organs), are associated with higher mortality in female patients with end-stage liver disease. However, low skeletal muscle predicts mortality in male patients with end-stage liver disease.

Association between Low Testosterone Levels and Sarcopenia in Cirrhosis: A Cross-sectional Study.

INTRODUCTION AND AIM: Sarcopenia is an independent predictor of mortality in cirrhosis. Hypogonadism is common in cirrhosis and has been associated with sarcopenia in non-cirrhotic chronic liver disease populations. The aim of this study is to investigate if sarcopenia is associated with low testosterone levels in patients with cirrhosis. MATERIAL AND METHODS: This is a retrospective analysis of prospectively collected data of 211 cirrhotic patients undergoing evaluation for liver transplantation. Sarcopenia was defined by computed tomography (CT) scan using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning testosterone levels were obtained in all patients. RESULTS: Of the 211 patients, sarcopenia was noted in 94 (45%). Testosterone levels were lower in sarcopenic patients (10.7 ± 1.1 vs. 13.7 ± 1.4 nmol/L, p = 0.03) and hypotestosteronemia was more frequent in them too (34 vs. 16%, p = 0.004). In males, those with sarcopenia had lower testosterone levels (14.6 ± 1.4 vs. 21.9 ± 1.8, p = 0.002), and the corresponding frequency of hypotestosteronemia (42 vs. 19%, p = 0.006) was also higher. There were no significant differences in female patients. There was a weak correlation between L3 SMI and testosterone levels (r 0.37, p < 0.001). On multivariable regression analysis including sex, body mass index (BMI), hypotestosteronemia, MELD and etiology of cirrhosis, only hypotestosteronemia (RR 2.76, p = 0.005) and BMI (RR 0.88, p < 0.001) were independently associated with sarcopenia. CONCLUSION: Low testosterone levels are associated with sarcopenia in male cirrhotic patients. The potential therapeutic effect of testosterone to reverse sarcopenia in these patients warrants evaluation in future trials.

Beta-blockers in patients with advanced liver disease: Has the dust settled?

Nonselective beta-blockers (NSBBs) have been the backbone for the treatment of portal hypertension in cirrhosis for the last 3 decades. A publication in 2010 of a prospective observational study suggested that NSBBs could increase mortality in patients with refractory ascites. This opened a controversy about the safety and efficacy of NSBBs in patients with advanced liver disease and led to the publication of a large corpus of observational data assessing the safety of NSBBs in patients with advanced cirrhosis. In this article, we briefly review the clinical pharmacology of NSBBs, the pathophysiological basis for the underlying benefits and harms of NSBBs in advanced cirrhosis, and the evidence in favor and against the use of NSBBs in specific scenarios. Finally, we summarize the current recommendations and propose areas of opportunity for future research. Liver Transplantation 23 1058-1069 2017 AASLD.

High Dietary Magnesium Intake is Significantly and Independently Associated with Higher Insulin Sensitivity in a Mexican-Mestizo Population: A Brief Cross-Sectional Report.

BACKGROUND: Magnesium acts as a cofactor in many intracellular reactions including phosphorylation of the insulin receptor; therefore, its imbalance can potentially cause insulin resistance. Low serum magnesium concentration has been associated with the development of metabolic syndrome and type 2 diabetes mellitus. OBJECTIVE: To study the association between the daily dietary magnesium intake and insulin resistance estimated by the homeostatic model assessment of insulin resistance and homeostatic model assessment 2, as well as insulin sensitivity estimated by the Matsuda index. METHODS: In a university affiliated medical center, 32 participants (22 women, 10 men) that had an indication for testing for type 2 diabetes mellitus with an oral glucose tolerance test were enrolled in this cross-sectional, comparative study. Clinical and biochemical evaluations were carried out including an oral glucose tolerance test. Hepatic insulin resistance index, homeostatic model assessment 2, homeostatic model assessment of insulin resistance, and Matsuda insulin sensitivity were calculated for each participant. They were asked to recall their food ingestion (24 hours) of three days of the past week, including a weekend day; magnesium intake was calculated according to the food nutritional information. RESULTS: The low dietary magnesium intake group (< 4.5 mg/kg/day) had a higher two-hour insulin concentration after an oral glucose tolerance test compared to those with high dietary magnesium (119.5 [73.0-190.6] vs. 63.5 [25.4-114.2]; p = 0.008), and insulin sensitivity assessed by the Matsuda index was higher in the high dietary magnesium intake group (4.3 ± 3.1 vs. 2.4 ± 1.5; p = 0.042). In multiple linear regression analysis a higher dietary magnesium intake was independently associated (ß = 4.93; p = 0.05) with a better insulin sensitivity estimated by the Matsuda index. CONCLUSIONS: Our results suggest that higher magnesium intake is independently associated with better insulin sensitivity in patients at risk for type 2 diabetes mellitus.