Which Factors Are Associated with Distal Pancreatectomy Outcomes' Optimization with the Application of an Enhanced Recovery After Surgery Program?

Background: Distal pancreatectomy (DP) represents the best therapeutic option for patients with body-tail pancreatic neoplasms (PNs). The enhanced recovery after surgery protocol is widely used for treating patients with PN to speed up postoperative recovery. This study aims to describe our institute's experience in the application of fast recovery protocol in a cohort of patients treated with DP, identifying predictors facilitating a decrease in the length of hospital stay. Patient and Methods: Were retrospectively enrolled 60 consecutive cases of DP performed from January 2016 to June 2022 in patients treated with enhanced recovery protocol, 25% of them were treated with spleen preserving procedure. Single-variable logistic regression models were used to evaluate the potential association between patient characteristics and the probability of postoperative complications. Standard linear regression models were used for length of stay, number of postoperative days (PODs) from surgery to full bowel function recovery, and PODs to the interruption of intravenous analgesia administration. Results: Thirty-four (57%) patients underwent open surgery and 26 (43%) laparoscopic surgery. Patients who underwent laparoscopic surgery and spleen-preserving procedures experienced a lower complication rate (P = .037), shorter length of stay, and time of analgesic requirements. With single-variable logistic regression models patients treated with laparoscopic surgery had statistically significant higher recovery times in terms of nasogastric tube removal (P = .004) and early enteral nutrition (P = .001). Conclusion: Continual refinement with enhanced recovery protocol for treating PN patients based on perioperative counseling and surgical decision-making is crucial to reduce patient morbidity and time for recovery.

How important is the role of iterative liver direct surgery in patients with hepatocellular carcinoma for a transplant center located in an area with a low rate of deceased donation?

Introduction: Hepatocellular carcinoma (HCC) accounts for nearly 90% of primary liver cancers, with estimates of over 1 million people affected by 2025. We aimed to explore the impacting role of an iterative surgical treatment approach in a cohort of HCC patients within the Milan criteria, associated with clinical risk factors for tumor recurrence (RHCC) after liver transplant (LT) and loco-regional therapies (LRT), as well as liver resection (LR) and/or microwave thermal ablation (MWTA). Methods: We retrospectively analyzed our experience performed during an 8-year period between January 2013 and December 2021 in patients treated for HCC, focusing on describing the impact on preoperative end-stage liver disease severity, oncologic staging, tumor characteristics, and surgical treatments. The Cox model was used to evaluate variables that could predict relapse risks. Relapse risk curves were calculated according to the Kaplan-Meier method, and the log-rank test was used to compare them. Results: There were 557 HCC patients treated with a first-line approach of LR and/or LRTs (n = 335) or LT (n = 222). The median age at initial transplantation was 59 versus 68 for those whose first surgical approach was LR and/or LRT. In univariate analysis with the Cox model, nodule size was the single predictor of recurrence of HCC in the posttreatment setting (HR: 1.61, 95% CI: 1.05-2.47, p = 0.030). For the LRT group, we have enlightened the following clinical characteristics as significantly associated with RHCC: hepatitis B virus infection (which has a protective role with HR: 0.34, 95% CI: 0.13-0.94, p = 0.038), number of HCC nodules (HR: 1.54, 95% CI: 1.22-1.94, p < 0.001), size of the largest nodule (HR: 1.06, 95% CI: 1.01-1.12, p = 0.023), serum bilirubin (HR: 1.57, 95% CI: 1.03-2.40, p = 0.038), and international normalized ratio (HR: 16.40, 95% CI: 2.30-118.0, p = 0.006). Among the overall 111 patients with RHCC in the LRT group, 33 were iteratively treated with further curative treatment (12 were treated with LR, two with MWTA, three with a combined LR-MWTA treatment, and 16 underwent LT). Only one of 18 recurrent patients previously treated with LT underwent LR. For these RHCC patients, multivariable analysis showed the protective roles of LT for primary RHCC after IDLS (HR: 0.06, 95% CI: 0.01-0.36, p = 0.002), of the time relapsed between the first and second IDLS treatments (HR: 0.97, 95% CI: 0.94-0.99, p = 0.044), and the impact of previous minimally invasive treatment (HR: 0.28, 95% CI: 0.08-1.00, p = 0.051). Conclusion: The coexistence of RHCC with underlying cirrhosis increases the complexity of assessing the net health benefit of ILDS before LT. Minimally invasive surgical therapies and time to HCC relapse should be considered an outcome in randomized clinical trials because they have a relevant impact on tumor-free survival.

Donor Simvastatin Treatment Is Safe and Might Improve Outcomes After Liver Transplantation: A Randomized Clinical Trial.

BACKGROUND: The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study. METHODS: SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective tial aiming to compare the safety and efficacy of preoperative brain-dead donors' treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d posttransplant; secondary end-points were severe complications. RESULTS: The trial enrolled 58 adult patients (18-65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% ( P = 0.016) and 89.66% ( P = 0.080) at 90 d and 86.21% ( P = 0.041) and 86.2% ( P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group ( P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d ( P = 0.017), ( P = 0.015) in the simvastatin group. CONCLUSIONS: Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory.

Risk factors for bile leakage after liver resection for neoplastic disease.

Biliary leakage (BL) remains the most frequent and feared complication after hepatoresective surgery. Placement of the abdominal drainage at the end of liver surgery remains controversial due to the delicate balance between risks and potential benefits in case of BL. The study was aimed to detect possible risk factors for BL occurrence after liver surgery. We enrolled all oncologic patients who underwent liver resection from June 2016 to March 2021. BL was diagnosed according to the ISGLS definition. We have examined demographic characteristics of the patients, type of neoplasia, presence of cirrhosis, neoadjuvant chemotherapy and type of intervention. Uni- and multivariable analyses were performed to assess the predictive value of potential predictor of BL. A total of 379 patients were enrolled in the study, 16 (4.2%) of which developed BL. Among others, at univariate analysis the occurrence of BL was found to be associated with bilio-digestive anastomosis (OR: 9.75, C.I. 2.7-34.7, p < 0.001) and neoadjuvant chemotherapy (OR: 0.09, C.I 0.01,-0.88, p = 0.039). Multivariable analysis selected the body mass index (OR: 1.21, 95%C.I.: 1.04-1.41, p = 0.015), anatomical resection (OR: 8.35, 95% C.I.: 2.01-34.74, p = 0.004), and blood loss (OR: 1.09, 95%C.I.: 1.05-1.13, p < 0.001). Identification of patients at greater risk of BL can help in the choice of positioning the drainage at the end of liver surgery.

Recurrent graft failure secondary to portal vein steal syndrome: a case report with an unusual indication for a third liver transplant.

BACKGROUND: Portal vein shunt is common in chronic hepatic diseases and after a liver transplant. Ensuring a satisfactory portal flow is essential to support a rapid liver recovery, of paramount importance to meet the recipient's metabolic needs. CASE PRESENTATION: We report the case of a 32-year-old female undergoing a third liver transplant due to recurrence of graft failure secondary to portosystemic shunting. The patient, affected with biliary atresia, was first transplanted in 2009 with a right split liver graft. The clinical course was complicated by biliary stenosis of the Roux-en-Y anastomosis and multiple episodes of acute rejection treated with steroid boluses, plastic dilation of the biliary anastomosis, and biliary catheter placement. Unfortunately, in 2017 a liver biopsy showed an autoimmunity with histological evidence of ANA 1:80 (granular and nucleolar pattern). This was a contributing factor of liver function impairment, leading to the need to perform a second liver transplant, complicated by an acute rejection, with only a partial response to steroid therapy. Due to the further worsening of the liver function (MELD: 40, Child-Pugh: C11), the patient was relisted for a liver transplant. After five days, she received her third liver transplant, with an entire graft of an AB0 identical group. Intraoperative exploration revealed multiple collaterals and large splenocaval shunts, with a significant alteration of the portal flow and hypertension, isolated and closed with a vascular stapler to restore the graft's regular portal vein flow. CONCLUSIONS: In patients listed for a liver transplant, portal steal syndrome should be identified prior to the transplant. Our recommendation is to consider intraoperative or perioperative closure of the portal collateral varices.

The use of normothermic machine perfusion to rescue liver allografts from expanded criteria donors.

The use of expanded criteria donors is one of the strategies used to overcome the gap between the demand for organs and the number of donors. Physicians debate the extent to which marginal grafts can be used. In recent years, normothermic machine perfusion (NMP) has been used to test liver viability before transplantation. Grafts underwent NMP whenever histological steatosis was > 40% or there were at least three Eurotransplant criteria for expanded criteria donor (ECD). We used NMP to test 19 grafts, 3 from donation after type 3 controlled cardiac death (DCD), and 16 from donation after brain death (DBD). Only two grafts from DBD were not transplanted, because perfusion proved they were not suitable (total of 17 transplanted grafts of 19 tested grafts). Kaplan-Meier survival estimates at 30, 90, 180, and 1 year after transplant were all 94% (95% CI 84-100%); estimated 3-years survival was 82% (95% CI 62-100%). Overall survival rates did not differ from those of patients transplanted with non-perfused grafts from an ECD. In our experience, the use of very marginal grafts preventively tested by NMP does not negatively influence the patient's outcome, and increases the number of transplants in low donation areas.

Liver Transplantation for Unresectable Intrahepatic Cholangiocarcinoma: The Role of Sequencing Genetic Profiling.

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive primary liver tumor, characterized by a range of different clinical manifestations and by increasing incidence and mortality rates even after curative treatment with radical resection. In recent years, growing attention has been devoted to this disease and some evidence supports liver transplantation (LT) as an appropriate treatment for intrahepatic cholangiocarcinoma; evolving work has also provided a framework for better understanding the genetic basis of this cancer. The aim of this study was to provide a clinical description of our series of patients complemented with Next-Generation Sequencing genomic profiling. From 1999 to 2021, 12 patients who underwent LT with either iCCA or a combined hepatocellular and cholangiocellular carcinoma (HCC-iCCA) were included in this study. Mutations were observed in gene activating signaling pathways known to be involved with iCCA tumorigenesis (KRAS/MAPK, P53, PI3K-Akt/mTOR, cAMP, WNT, epigenetic regulation and chromatin remodeling). Among several others, a strong association was observed between the Notch pathway and tumor size (point-biserial rhopb = 0.93). Our results are suggestive of the benefit potentially derived from molecular analysis to improve our diagnostic capabilities and to devise new treatment protocols, and eventually ameliorate long-term survival of patients affected by iCCA or HCC-iCCA.

Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection.

BACKGROUND: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. METHODS: 124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan-Meier estimators. RESULTS: Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan-Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24-47) and to 51% (95% C.I.: 35-62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91-4.24, p = 0.085), serum bilirubin levels (HR: 5.32, 95%C.I.: 2.07-13.69, p = 0.001), number of nodules (HR: 1.63, 95%C.I.: 1.12-2.38, p = 0.011) and size of the larger nodule (HR: 1.11, 95%C.I.: 1.03-1.18, p = 0.004). Time-to-recurrence analysis showed that loss of heterozygosity in the PTEN loci (involved in the PI3K/AKT/mTOR signaling pathway) was significantly associated with a lower risk of HCC recurrence (HR: 0.35, 95%C.I.: 0.13-0.93, p = 0.036). CONCLUSIONS: multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.

ERAS Protocol for Perioperative Care of Patients Treated with Laparoscopic Nonanatomic Liver Resection for Hepatocellular Carcinoma: The ISMETT Experience.

Background: Liver resection (LR) remains the best therapeutic option for patients with early-stage hepatocellular carcinoma (HCC) with preserved hepatic function and who are not eligible for liver transplantation. After its inception, the enhanced recovery after surgery (ERAS) protocol was widely used for treating patients with liver cancer, although there are still no clear indications for improving upon it in both open and laparoscopic surgery. Objective: This study aims to describe our institute's experience in the application of the ERAS protocol in a cohort of HCC patients, and to explore possible factors that could have an impact on postoperative outcomes. Materials and Methods: We retrospectively analyzed our experience with LR performed from September 2017 to January 2020 in patients treated with ERAS protocol, focusing on describing impact on postoperative nutrition, analgesic requirements, and length of hospitalization. Demographics, operative factors, and postoperative complications of patients were reviewed. Results: During the study period, 89 HCC patients were eligible for LR, and 75% of patients presented with liver cirrhosis. The most prevalent among etiologic factors was hepatitis C virus infection (53 patients out of 89, 60%), followed by nonalcoholic steatohepatitis (18 patients, 20%). The median age was 70 years. Liver cirrhosis did not have an impact on postoperative course of patients. Patients who underwent laparoscopic surgery and nonanatomic LR experienced low complication rates, shorter length of stay, and shorter time of intravenous analgesic requirements. Conclusions: Continual refinement with ERAS protocol for treating HCC patients based on perioperative counseling and surgical decision-making is crucial to guarantee low complication rates, and reduce patient morbidity and time for recovery.

Laparoscopic Microwave Thermal Ablation for the Treatment of Hepatocellular Carcinoma in Chronic Hepatic Patients.

Background: Laparoscopic microwave thermal ablation (LMWTA) is a well-established alternative treatment to liver resection for treatment of liver tumors. The aim of this study was to describe our experience in LMWTA for hepatocellular carcinoma (HCC) in chronic hepatic patients. Materials and Methods: A study group of 61 consecutive HCC patients treated with LMWTA from January, 2013 to May, 2020 were considered for this study. Patient characteristics, liver function test, operational characteristics, and complications were recorded. Results: Of the 61 patients who underwent LMWTA, median age was 64 (interquartile range [IQR]: 58-71) years, mean body mass index was 26.2 (IQR: 23.2-29.4); 44 patients (72%) presented with an hepatitis C virus etiology, 46 (75%) were Child-Pugh Class A, median model for end-stage liver disease (MELD) score was 8.0 (IQR: 7.0-9.4). Viral infection was confirmed to be the most important risk factor in determining progressive cirrhotic evolution with HCC expression. Conclusions: LMWTA is a safe alternative treatment to traditional surgery, and can be combined with surgery.

Impact of Extended-Criteria Donor Liver Grafts on Benchmark Metrics of Clinical Outcome After Liver Transplantation: A Single Center Experience.

BACKGROUND: The adoption of extended criteria for donors remains the best strategy to widen the pool of available liver graft against the chronic shortage of donors. Benchmarking in liver transplantation (LT) offers the unprecedented opportunity to compare clinical outcome measures to a set of validated reference values. We aimed to evaluate the impact of marginal grafts usage in a cohort of low-risk benchmark cases from an area with a very low rate of deceased donation. METHODS: A cohort of low-risk benchmark cases was identified from all adult patients who underwent LT at our center. Among these patients, those transplanted with a graft from an extended-criteria donor (ECD) were identified. Benchmark metrics (length of hospital and intensive care unit stay, incidences of mortality, graft loss, and postoperative complication) were compared with benchmark cutoffs and between the 2 groups. RESULTS: Two hundred forty-five patients satisfied the inclusion criteria, 146 (60%) of whom received an organ from an ECD. Overall, all benchmark metrics where within the cutoffs limits, except for graft loss (14% vs 11%) and mortality (10% vs 9% 1 year after LT). The ECD group was associated with more grade III complications (60% vs 45%, P = .031), graft loss (18% vs 8%, P = .038), and mortality (14% vs 4%, P = .009). Hepatocellular carcinoma diagnosis was found to be associated with less mortality (odds ratio = 0.42, P = .048). CONCLUSION: While ECD graft usage is associated with slightly worse prognosis, our experience suggests that their use can be considered safe, especially when matched on hepatocellular carcinoma recipients.

Impact of Italian Score for Organ Allocation System on Deceased Donor Liver Transplantation: A Monocentric Competing Risk Time-to-Event Analysis.

BACKGROUND: Liver transplantation (LT) is the only definitive and curative treatment for patients with end-stage liver disease and hepatocellular carcinoma. We aimed to evaluate the impact of the Italian score for organ allocation (ISO) in terms of the waiting-list mortality, probability of LT, and patient survival after LT. PATIENT AND METHODS: All of the adult patients on the waiting list for LT at our institute from January 2014 to December 2017 were included in the study. The probabilities of death while on the waiting list, dropout from the list, and LT were compared by means of cumulative incidence functions, in a competing risk time-to-event analysis setting. Uni- and multivariable logistic regression models were used to estimate and compare the probability of death and to find potential risk factors for waiting-list death. RESULTS: There were 286 patients on the waiting list for LT during the study period, 122 of whom entered the waiting list prior to the implementation of ISO (Group A) and 164 afterward (Group B). Group A had 62 transplants, and Group B had 116 transplants. Group B showed a lesser probability of death (P = .005) and a greater probability of transplant (P < .001) compared to Group A. In the 2 groups, post-transplant survival was similar. CONCLUSION: Based on preliminary clinical experience from a single transplant center, the ISO allocation system demonstrated an overall reduced probability of patient death while on the waiting list without impairing post-LT survival, suggesting that the ISO system might represent an improved method of organ allocation, with a more beneficial distribution of livers.

Role of Allelic Imbalance in Predicting Hepatocellular Carcinoma (HCC) Recurrence Risk After Liver Transplant.

BACKGROUND One of the most controversial problems for liver transplantation in patients affected by hepatocellular carcinoma (HCC) remains the lack of an oncologic staging system to predict cancer recurrence after liver transplantation (LT). We analyzed allelic imbalance (AI) in 19 microsatellites, and assessed the post-LT HCC recurrence risk. MATERIAL AND METHODS Seventy-one patients were included; 18 had tumor recurrence within 5 years post-transplant. Molecular analysis was done in the primary HCC and peripheral blood samples: a total of 19 microsatellites was used to assess AI. Specific AI was evaluated when outside of range value between 0.66 and 1.5. Based on data in the literature, we grouped the 19 microsatellites into 4 panels. We calculated the fractional allelic imbalance (FAI) to make comparisons between different panels including different subsets of microsatellites. RESULTS We report that AI was associated with HCC recurrence in 3 main loci (D3S2303, D9S251, and D9S254). Tumor recurrence was associated only with 2 specific panels with 9 microsatellites previously reported to be associated with high risk for HCC recurrence. Our data show that fractional allelic imbalance (FAI) index has good negative ability to predict HCC recurrence (Panel 2: negative predictive value of 95%). CONCLUSIONS AI analysis could have prognostic value in risk management of HCC recurrence after LT, especially for early recurrence.

Liver Perfusate Natural Killer Cells From Deceased Brain Donors and Association With Acute Cellular Rejection After Liver Transplantation: A Time-to-Rejection Analysis.

BACKGROUND: The ability to predict which recipients will successfully complete their posttransplant clinical course, which is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates could help identify risk factors portending adverse LT outcomes. METHODS: Liver perfusates were collected during the back-table surgical time after the procurement procedures for donors after brain death. Lymphocytic concentrations and phenotypes were matched with donors after brain death characteristics and indications, timing, surgical techniques, outcomes, and biopsy-proven acute cellular rejections (ACRs) in 46 adult recipients who underwent LT between 2010 and 2014 at our institute. Cox regression models were used to study relevant risk factors in order to estimate hazard ratios for episodes of rejection after LT. RESULTS: Percentage of NK cells was significantly associated with donor age (P = 0.05) and the percentage of NK T cellular subset (P = 0.001). The length of follow-up after LT was 41.0 ± 20.9 months, and 11 (23.9%) recipients experienced biopsy-proven ACR. At time-to-rejection proportional regression analysis, a cutoff value of 33.7% was optimal, with a sensitivity of 1, specificity of 0.57, and positive and negative predictive values of 0.42 and 1, respectively. The liver perfusate NK cell subset was strongly associated with biopsy-proven ACR (hazard ratio, 10.7; P = 0.02). CONCLUSIONS: Liver perfusate cytofluorimetric phenotyping may contribute as a targeted preoperative tool to predict the risk of ACR, and as clinical test in translational studies that aim to improve donor allograft procurement and transplant outcomes.

Author Correction: Binge Drinking among adolescents is related to the development of Alcohol Use Disorders: results from a Cross-Sectional Study.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Binge Drinking among adolescents is related to the development of Alcohol Use Disorders: results from a Cross-Sectional Study.

Binge drinking (BD) is a common pattern of alcohol consumption among adolescents. At present few data are available on the possible relationship between BD and alcohol use disorders (AUD) in adolescents. The aim of this study was to assess the prevalence of BD and relationship between BD behavior and AUD among adolescents. A total of 2704 students attending 10 purposively selected high schools from three Italian provinces were surveyed. Questionnaires regarding socio-demographic data, pattern and amount of alcohol intake, smoking habits, use of illicit drugs, and physical activity were administered. AUD and affective disorders were also evaluated. Alcohol intake was reported by 2126 participants; 1278 reported at least one episode BD in the last year and 715 in the last month. A diagnosis of AUD was made in 165 adolescents. The prevalence of AUD was higher in adolescents that reported BD behavior than in those that did not report BD (11.6% vs 0.9%, respectively; p < 0.0001). Logistic regression showed a positive relationship between a diagnosis of AUD and BD behavior (OR 9.6; 95% CI 4.7-22·9; p < 0.0001). In conclusion alcohol consumption with the pattern of BD among adolescents is highly related to development of AUD.

Non-invasive prediction of esophageal varices by stiffness and platelet in non-alcoholic fatty liver disease cirrhosis.

BACKGROUND & AIMS: Baveno VI and expanded Baveno VI criteria can avoid the need for esophagogastroduodenoscopy (EGD) to screen for varices needing treatment (VNT) in a substantial proportion of compensated patients with viral and/or alcoholic cirrhosis. This multicenter, cross-sectional study aims to validate these criteria in patients with compensated cirrhosis due to non-alcoholic fatty liver disease (NAFLD), accounting for possible differences in liver stiffness measurement (LSM) values between M and XL probes. METHODS: We assessed 790 patients with NAFLD-related compensated cirrhosis who had EGD within six months of a reliable LSM, measured by FibroScan® using M and/or XL probe. Baveno VI and expanded Baveno VI criteria were tested. The main variable used to optimize criteria was the percentage of endoscopies spared, keeping the risk of missing large VNT below a 5% threshold. RESULTS: LSM was measured by both M and XL probes (training set) in 314 patients, while only M or XL probe (validation sets) were used to measure LSM in 338 and 138 patients, respectively. In the training set, use of Baveno VI and expanded Baveno VI criteria reduced the number of EGD by 33.3% and by 58%, with 0.9% and 3.8% of large esophageal varices missed, respectively. The best thresholds to rule-out VNT were identified as platelet count >110,000/mm3 and LSM <30 kPa for M probe, and platelet count >110,000/mm3 and LSM <25 kPa for XL probe (NAFLD cirrhosis criteria). Thus, usage of NAFLD cirrhosis criteria would have led to an absolute reduction in the number of EGD screened patients of 34.7% and 10.5% with respect to Baveno VI and expanded Baveno VI criteria, respectively. CONCLUSION: The new NAFLD cirrhosis criteria, established for the FibroScan probe, can reduce the use of EGD for screening of VNT in NAFLD cirrhosis by more than half, with a chance of missing VNT below 5%. LAY SUMMARY: In non-alcoholic fatty liver disease-related compensated cirrhosis, the expanded Baveno VI criteria work better than the Baveno VI criteria for ruling out the presence of varices needing treatment, sparing unnecessary and invasive screening procedures. New diagnostic criteria for this patient group, based on liver stiffness measurement and platelet count, and optimized for the specific FibroScan® probe used, work better than both Baveno VI and expanded Baveno VI criteria. The accuracy of all non-invasive scoring criteria was lower in non-obese patients.

Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents.

BACKGROUND & AIMS: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. METHODS: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus-associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development. RESULTS: A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P < .001). Seventy-eight patients (3.5%) developed HCC during a mean follow-up of 14 months (range = 6-24 months). At 1 year after exposure to DAAs, HCC developed in 2.1% of patients with Child-Pugh class A with an SVR and 6.6% of patients with no SVR and in 7.8% of patients with Child-Pugh class B with an SVR and 12.4% of patients with no SVR (P < .001 by log-rank test). Albumin level below 3.5 g/dL (hazard ratio = 1.77, 95% confidence interval = 1.12-2.82, P = .015), platelet count below 120 × 109/L (hazard ratio = 3.89, 95% confidence interval = 2.11-7.15, P < .001), and absence of an SVR (hazard ratio = 3.40, 95% confidence interval = 1.89-6.12, P < .001) were independently associated increased risk for HCC. The mean interval from exposure to DAAs to an HCC diagnosis was 9.8 months (range = 2-22 months) and did not differ significantly between patients with (n = 64, 9.2 months) and without (n = 14, 12.0 months) an SVR (P = .11). A larger proportion of patients with an SVR had a single HCC lesion (78% vs 50% without an SVR; P = .009) or an HCC lesion smaller than 3 cm (58% vs 28% without an SVR; P = .07). CONCLUSIONS: In an analysis of data from a large prospective study of patients with hepatitis C virus-associated compensated or decompensated cirrhosis, we found that the SVR to DAA treatment decreased the incidence of HCC over a mean follow-up of 14 months.

Efficacy and tolerability of a plant-based, multi-component cream (Ginetrox®) in vulvovaginal disorders of the genitourinary syndrome during menopause.

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a symptomatic condition including vaginal dryness, irritation, dyspareunia and recurrent urinary tract infections which affects 40-54% of post-menopausal women. Although several estrogen-based therapies are available, it is generally preferable to avoid hormonal therapy, particularly in women with mild symptoms or at risk for estrogen-responsive neoplasia. Therefore, the most common treatment options are over-the-counter vaginal creams for symptomatic relief. METHODS: Thirty-three postmenopausal women suffering from GSM were enrolled in this observational study. A multi-component cream (Ginetrox®, Indena, Milan, Italy) was applied on the vestibular area of the vagina for three months. The primary endpoints were: vaginal burning and/or pain, assessed by Visual Analog Scale and dyspareunia, assessed using the Marinoff Score. As a secondary endpoint, vestibular health was evaluated through a four-point scale. Side effects and adherence to treatment were also recorded. RESULTS: Statistically significant improvement was observed in pain scores and dyspareunia at the end of the treatment compared to baseline values. The vestibular health index significantly decreased after 3 months. Tolerability was acceptable. CONCLUSIONS: This preliminary study suggests that the plant-based, multi-component cream Ginetrox® could be effective and safe in counteracting menopause-related vaginal discomfort symptoms.