Expression of cyclo-oxygenase-2 and yap/taz in hepatocellular carcinoma in untreated and treated hepatitis C virus patients.

The pathogenesis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) differs according to whether prior treatment with interferon (IFN) vs. direct-acting antiviral agents (DAAs) was administered. Cyclo- oxygenase-2 (COX-2), yes-associated protein 1 (YAP), and transcriptional co-activator with PDZ-binding motif (TAZ) play a crucial role in hepatocarcinogenesis. However, their roles in untreated or treated HCV-related HCC development have not been clarified. Therefore, we performed an immunohistochemical study and stained tissue from 83 HCV-related HCC cases using antibodies against COX-2, YAP, and TAZ and correlated their expression with the clinicopathological characteri stics and survival data. The cases were subdivided into 3 groups based on prior HCV treatment. In the 3 groups, COX-2 was significantly higher in HCC tissue compared with adjacent non-tumour liver tissue. However, the expression of YAP/TAZ was not significantly different between HCC and adjacent non-tumour tissue. We further grouped HCC cases into YAP+/TAZ+ and YAP-/TAZ- cases. In the YAP+/TAZ+ cases, COX-2 was significantly associated with tumour size, tumour multifocality, and late pathologic stage. No significant difference was observed in COX-2 and TAZ expression as a result of IFN or DAA treatment; however, YAP was significantly higher in IFN-treated HCC. Cyclo-oxygenase-2 overexpression may play a role in late HCC development, while YAP/TAZ could play an early role in HCC progression. Sustained expression of combined YAP/TAZ could mediate the poor prognostic role of COX-2.

THE BENEFICIAL VALUES OF TRANSOESOPHAGEAL DOPPLER IN INTRAOPERATIVE FLUID GUIDANCE VERSUS STANDARD CLINICAL MONITORING PARAMETERS IN INFANTS UNDERGOING KASAI OPERATION.

BACKGROUND: Fluid overload in infants can result from inappropriate volume expansion (VE). The aim of this work was to evaluate the beneficial values of Transoesophageal Doppler TED in intraoperative fluid guidance versus standard clinical monitoring parameters in infants undergoing Kasai operation. METHODS: Forty infants scheduled for Kasai procedure were randomly allocated into two groups (Doppler and clinical group). In Doppler group decided to provide VE (10-30 m1/kg of Hydroxyethyl starches HES) when the index stroke volume decreased by ≥ 15% from the baseline value, in clinical group, hemodynamic variables triggering colloid administration mean arterial blood pressure (MAP) less than 20% below baseline or central venous pressure (CVP) < 5 cmH2O in both groups: Ringer's acetate was infused at constant rate (6 m 1/kg/h). Standard and TED-derived data were recorded before and after VE. Follow up the postoperative outcome and hospital stay. RESULTS: There were significantly lower mean volume of HES (42.85 ± 3.93 versus 84 ± 14.29 ml) and percent of infants required it (30% versus 90%) associated with earlier tolerance to oral feeding (2 ± 0.66 versus 3.4 ± 0.51), shorter hospital stay (5.30 ± 0.47 versus 6.7 ± [symbols: see text] days) and lower rate of chest infection (15% versus 30%) in Doppler group than clinical group. There was no difference between the two studied groups regarding heart rate, MAP. CONCLUSIONS: TED guided intraoperative fluid intake in infants undergoing Kasai operation optimize fluid consumption and improve outcome associated with shorter hospital stay.

THE BENEFICIAL VALUES OF TRANSOESOPHAGEAL DOPPLER IN INTRAOPERATIVE FLUID GUIDANCE VERSUS STANDARD CLINICAL MONITORING PARAMETERS IN INFANTS UNDERGOING KASAI OPERATION.

BACKGROUND: Fluid overload in infants can result from inappropriate volume expansion (VE). The aim of this work was to evaluate the beneficial values of Transoesophageal Doppler TED in intraoperative fluid guidance versus standard clinical monitoring parameters in infants undergoing Kasai operation. METHODS: Forty infants scheduled for Kasai procedure were randomly allocated into two groups (Doppler and clinical group). In Doppler group decided to provide VE (10-30 mI/kg of Eydroxyethyl starches HES) when the index stroke volume decreased by ≥ 15% from the baseline value, in clinical group, hemodynamic variables triggering colloid administration mean arterial blood pressure (MAP) less than 20% below baseline or central venous pressure (CVP) < 5 cmH2O in both groups: Ringer's acetate was infused at constant rate (6 m l/kg/h). Standard and TED-derived data were recorded before and after VE. Follow up the postoperative outcome and hospital stay. RESULTS: There were significantly lower mean volume of HES (42.85 ± 3.93 versus 84 14.29 ml) and percent of infants required it (30% versus 90%) associated with earlier tolerance to oral feeding (2 ± 0.66 versus 3.4 ± 0.51), shorter hospital stay (5.30 ± 0.47 versus 6.7 ± 0.92 days) and lower rate of chest infection (15% versus 30%) in Doppler group than clinical group. There was no difference between the two studied groups regarding heart rate, MAP. CONCLUSIONS: TED guided intraoperative fluid intake in infants undergoing Kasai operation optimize fluid consumption and improve outcome associated with shorter hospital stay.

Successful use of venous graft from native liver with hepatocellular carcinoma during living donor liver transplantation with no impact on recurrence rate: A retrospective cohort study.

Introduction: There are still debates regarding using portal vein (PV) from liver with hepatocellular carcinoma (HCC) for vascular reconstruction. This study aimed to assess the feasibility and patency of PV venous graft from an explanted liver with HCC for the reconstruction of the hepatic veins tributaries or PV in living donor liver transplantation (LDLT) and to see if it has any risk on recurrence of HCC. Patient and methods: We conducted a retrospective study on 81 patients with HCC who underwent LDLT from April 2004 to July 2022. Results: Venous graft from native liver PV was used for vascular reconstruction in 31 patients as follows; reconstruction of V5 in 7 patients, V8 in 4 patients, V6 in 3 patients, combined V5 and V8 in 4 patients, V6 with V5/V8 in 5 patients, and as Y shape venous graft for 2 PV reconstruction in 8 patients. The implantation of the new conduit PV graft after reconstruction of the anterior sector tributaries was direct to the IVC in 8 patients, and to the common orifice of the left and middle hepatic veins in 12 patients. The 1 month, 3 months, and 1-year overall patency of the venous graft was 93.5%, 90.3%, and 84%, respectively. Nine patients had recurrent HCC. In multivariate analysis, the independent risk factors for HCC recurrence were AFP >400 ng/mL (HR = 1.47, 95% CI: 1.69-2.31, P = 0.01), moderate/poor differentiated tumor (HR = 3.06, 95% CI: 2.58-6.29, P = 0.02), and microvascular invasion (HR = 2.51, 95% CI: 1.05-1.93, P = 0.01). Using a PV venous graft had no risk factor for HCC recurrence (P = 0.9). Conclusion: The use of PV venous graft of native liver with HCC for venous reconstruction is a feasible and valuable option in LDLT with good patency rates and no risk of HCC recurrence.

Prognostic factors for long-term survival after pancreaticoduodenectomy for periampullary adenocarcinoma. A retrospective cohort study.

BACKGROUND: Periampullary adenocarcinoma (PAAC) had a poor prognosis, and pancreaticoduodenectomy (PD) remains the only potentially curative treatment. The study aimed to identify the impact of different clinicopathological factors on long-term survival following PD for PAAC. PATIENTS AND METHODS: This study is a retrospective cohort study for the patients who underwent PD for pathologically proven PAAC from January 2010 to January 2019. Statistical analysis was done using Cox regression multivariate analyses for independent risk factors for survival. RESULT: There were 137 patients with PAAC who underwent PD, 79 patients (57.7%) underwent pylorus-preserving PD. Pancreatico-jejunostomy was done in 108 patients (78.8%). The primary analysis showed that risk factors for poor long-term survival include patients with co-morbidities like hypertension or ischemic heart disease, Carbohydrate Antigen 19-9 > 400U/ml, tumor size > 3 cm, poor tumor differentiation, positive lymph nodes invasion, lymphovascular invasion, and Perineural invasion. Multivariate analysis demonstrated that large tumor size > 3 cm (HR: 0.177, 95%CI: 0.084-0.374, P = 0.002), poorly differentiated tumor (HR: 0.059, 95%CI: 0.020-0.0174, P = 0.016), and perineural invasion in the pathological study (HR: 0.101, 95%CI: 0.046-0.224, P = 0.006) were independent risk factors for poor 5-years survival. The prognosis was better in ampullary adenocarcinoma (5-year survival was 42.1%) than pancreatic adenocarcinoma (5-year survival was 24.3%). The 1, 3, 5 and 7-year overall survival rates were 84.5%, 57.4%, 35.9% and 20.1% respectively. CONCLUSION: It seems from the current study that Tumor size > 3 cm, poor tumor differentiation, and Perineural invasion were independent predictors of poor survival in patients with PAAC.

Total tumor volume as a prognostic value for survival following liver resection in patients with hepatocellular carcinoma. Retrospective cohort study.

BACKGROUND: Total tumor volume (TTV) can provide a simplified parameter in describing the tumor burden by incorporating the size and number of tumor nodules into one continuous variable. The aim of the study was to evaluate the prognostic value of TTV in resection of hepatocellular carcinoma (HCC). METHODS: Patients who underwent liver resection for HCC between 2012 and 2017 were retrospectively analyzed. Patients were divided into a group with TTV ≤65.5 cm³ (which nearly equal to a single tumor with a diameter of 5 cm), and another group with TTV > 65.5 cm³. RESULTS: Two hundred and four patients were included in this study (108 patients had TTV ≤ 65.5cm3, and 96 patients had TTV > 65.5 cm³). Ninety patients (44.1%) were within Milan and 114 patients (55.9%) were beyond Milan criteria. Eighteen patients (15.8%) of beyond Milan criteria had TTV ≤ 65.5 cm³, with a median survival of 32 months which is comparable to a median survival of patients with TTV< 65.5 cm³ (38 months, P = 0.38). TTV-based Cancer of Liver Italian Program (CLIP) score gained the highest value of likelihood ratio 114.7 and the highest Concordance-index 0.73 among other prognostic scoring and staging systems. In multivariate analysis, independent risk factors for diminished survival were serum AFP level >400 ng/ml, TTV >65.5 cm³, microvascular invasion, postoperative decompensation (all P values < 0.05). CONCLUSION: TTV is a feasible prognostic measure to describe the tumor burden in patients with HCC. TTV-CLIP score may provide good prognostic value for resection of HCC than other staging systems.

Impact of Inter-Laboratory Variability on Model of End-Stage Liver Disease (MELD) Score Calculation.

BACKGROUND The model for end-stage liver disease (MELD) is a laboratory-based scoring system for assessing the severity of liver disease. Since 16 December 2006, MELD-based organ allocation for liver transplantation (LT) has been established in Germany to prioritize the sickest patients. The present study was designed to evaluate the effect of using different laboratories on the calculated MELD score, despite the use of mandatory round-robin testing for comparable of inter-laboratory results. MATERIAL AND METHODS Blood samples were taken from 10 patients with liver disease. Bilirubin, creatinine, and INR were measured in 6 different laboratories. The patients' MELD scores were calculated and the inter-laboratory variability was compared. RESULTS The highest discrepancy between the laboratories was 5 MELD score points and the highest inter-laboratory difference for bilirubin, INR, and creatinine was 4.6, 1.2, and 0.99 mg/dl, respectively. Pairwise comparison of the laboratory values showed a significant inter-laboratory difference (p<0.05). CONCLUSIONS Results clearly demonstrate, for the first time, that liver allocation for LT in Germany is based on nationwide noncomparable laboratory readouts for the MELD score.