Insulin resistance induced by de novo pathway-generated C16-ceramide is associated with type 2 diabetes in an obese population.

BACKGROUND: Obesity and diabetes are two chronic metabolic diseases whose prevalence is increasing at an alarming rate globally. A close association between obesity, diabetes, and insulin resistance has been identified, and many studies have pinpointed obesity as a causal risk factor for insulin resistance. However, the mechanism underlying this association is not entirely understood. In the past decade, ceramides have gained attention due to their accumulation in certain tissues and their suggested role in initiating insulin resistance. This study aims to determine the association of specific ceramides and their major metabolizing enzymes with obesity-associated insulin resistance. METHODS: The samples comprised subcutaneous adipose tissues collected from three cohorts: lean non-diabetic (controls; n = 20), obese-non-diabetic (n = 66), and obese-diabetic (n = 32). Ceramide levels were quantified using LC-MS/MS and mRNA expression level for different enzymes were estimated using real-time PCR-based RNA expression analysis. RESULTS: C16-ceramide (P = 0.023), C16-dihydro-ceramide (P < 0.005), C18-dihydro-ceramide (P = 0.009) and C24-ceramide (P = 0.040) levels were significantly increased in the obese cohort compared to the control group. However, stratification of the obese group revealed a significant increase in the C16-ceramide levels (P = 0.027) and mRNA over expression of the serine palmitoyl transferases enzyme subunit SPT1 (P < 0.005) in the obese-diabetic cohort compared to the obese-non-diabetic cohort. CONCLUSIONS: The present study indicates that C16-ceramide plays a pivotal role in inducing insulin resistance. Overexpression of SPT1 in the obese-diabetic group and its positive correlation with C16-ceramide suggest that C16-ceramide was generated through the de novo pathway.

Large for size in pediatrics liver transplant using left lateral segment grafts: A single center experience.

BACKGROUND: There are still controversies in using the large left lateral segment in pediatrics LT, with the possibility of the problem of LFS grafts, and the use of monosegmental or reduced liver grafts in small infants. This study aimed to evaluate our experience with LFSG in pediatrics LT. METHODS: A cohort retrospective analysis was conducted including pediatric recipients who underwent LT between January 2011 and October 2019. We compared recipients with GRWR ≥ 4% (LFS) vs GRWR < 4% as an average for size grafts. RESULTS: There were 331 pediatric LT, 74 patients with GRWR ≥ 4%, and 257 patients with GRWR < 4%. In the group of LFS grafts, temporary abdominal closure by silicon patch was done in 39 patients (52.7%), 2 patients (2.7%) had postoperative HAT, 3 patients (4.1%) early PVT, 1 patient (1.3%) bile leak, and 3 patients (4.1%) had wound infection, with no significant difference in these complications between the 2 groups. In patients with LFS- grafts, the 1-, 3-, 5-, and 7-year patients survival rates were 94.6%, 91.7%, 91.7%, and 91.7%, respectively, while the survival rates in patients of the other group were 96.1%, 92.6%, 91.9%, and 91.9%, respectively, with no significant difference (p = .85). CONCLUSION: Using LFS graft by left lateral segment in pediatric LT with potential delayed abdominal closure is a safe and feasible option with good outcomes and unnecessary need for graft reduction if performed by an experienced multidisciplinary team.

APRI and FIB-4 indices as diagnostic noninvasive scores for prediction of severe fibrosis in patients with biliary atresia.

Aim of the study: Biliary atresia (BA) is a blockage in the tubes (ducts) that carry bile from the liver to the gallbladder. The aspartate aminotransferase to platelet ratio (APRI), and Fibrosis-4 (FIB-4) scores are commonly used compound surrogates for advanced fibrosis. However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. So, we determined the optimal cutoff values of the APRI and FIB-4 indices in prediction of fibrosis in BA patients. The aim of the study was to evaluate the validity of the APRI and FIB-4 indices in prediction of fibrosis in patients with BA. Material and methods: A cross sectional hospital-based study was conducted on 121 children complaining of BA attending the National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt, during the period from January 2022 to February 2023. Results: The APRI score was significantly higher among neglected BA than BA type II a, BA type III, type II b and type I (p = 0.001). Also FIB-4 was significantly higher among neglected BA than BA type II a, BA type II b, type III and type I (p = 0.001). Receiver operating characteristic (ROC) curve analysis showed that the cutoff point of the APRI score in prediction of fibrosis in patients with BA was 1.29, with sensitivity of 88.6% and specificity of 76.0%, while the cutoff point of FIB-4 in prediction of fibrosis in patients with BA was 9.82 with sensitivity of 89.0% and specificity of 70.0%. Conclusions: Our study confirms that FIB-4 and APRI scores are both able to predict severe fibrosis. APRI score and FIB-4 are good non-invasive alternatives to liver biopsy in the detection of liver fibrosis and its extent in patients with BA.

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.

Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: Given the poor synthetic function of cirrhotic liver, successful resection for patients with hepatocellular carcinoma (HCC) necessitates the ability to achieve resections with tumor free margins. AIM: To validate post hepatectomy liver failure score (PHLF), compare it to other established systems and to stratify risks in patients with cirrhosis who underwent curative liver resection for HCC. METHODS: Between December 2010 and January 2017, 120 patients underwent curative resection for HCC in patients with cirrhosis were included, the pre-operative, operative and post-operative factors were recorded to stratify patients' risks of decompensation, survival, and PHLF. RESULTS: The preoperative model for end-stage liver disease (MELD) score [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (OR = 2.5, 95%CI: 1.5-4.2, P = 0.001) were significant independent predictors of hepatic decompensation after resection. While the preoperative MELD score [hazard ratio (HR) = 1.37, 95%CI: 1.16-1.62, P < 0.001] and different grades of PHLF (grade A: HR = 2.33, 95%CI: 0.59-9.24; Grade B: HR = 3.15, 95%CI: 1.11-8.95; Grade C: HR = 373.41, 95%CI: 66.23-2105.43; P < 0.001) and HCC recurrence (HR = 11.67, 95%CI: 4.19-32.52, P < 0.001) were significant independent predictors for survival. CONCLUSION: Preoperative MELD score and tumor diameter can independently predict hepatic decompensation. While, preoperative MELD score, different grades of PHLF and HCC recurrence can precisely predict survival.

Predictors of Outcome of Living Donor Liver Transplantation for Hepatocellular Carcinoma.

The aim of this work is to study the different factors that affect the outcome of living donor liver transplantation for patients with hepatocellular carcinoma (HCC). Between April 2003 to November 2014, 62 patients with liver cirrhosis and HCC underwent living donor liver transplantation (LDLT) in the National Liver Institute, Menoufia University, Egypt. The preoperative, operative, and postoperative data were analyzed. After studying the pathology of explanted liver; 44 (71 %) patients were within the Milan criteria, and 18 (29 %) patients were beyond Milan; 13 (21.7 %) of patients beyond the Milan criteria were also beyond the University of California San Francisco criteria (UCSF) criteria. Preoperative ablative therapy for HCC was done in 22 patients (35.5 %), four patients had complete ablation with no residual tumor tissues. Microvascular invasion was present in ten patients (16 %) in histopathological study. Seven (11.3 %) patients had recurrent HCC post transplantation. The 1, 3, 5 years total survival was 88.7, 77.9, 67.2 %, respectively, while the tumor-free survival was 87.3, 82.5, 77.6 %, respectively. Expansion of selection criteria beyond Milan and UCSF had no increased risk effect on recurrence of HCC but had less survival rate than patients within the Milan criteria. Microvascular invasion was an independent risk factor for tumor recurrence.

Role of water soluble contrast agents in assigning patients to a non-operative course in adhesive small bowel obstruction.

OBJECTIVES: Adhesive small bowel obstruction (SBO) is a common surgical emergency. It is estimated that at least 60% of SBO are due to post-operative adhesions. Water soluble contrast agents (gastrografin) have been used to identify patients who might be treated non-operatively. This study aims to determine the role of gastrografin in adhesive intestinal obstruction patients. METHODS: In this prospective study, 27 patients admitted between 1(st) August 2004 and 1(st) July 2006 with clinical signs suggestive of postoperative adhesive SBO met the inclusion criteria. After intravenous hydration, nasogastric tube insertion and complete suctioning of the gastric fluid, 100 ml of gastrograsfin was given and plain abdominal radiography was taken 6 hours and 24 hours if the contrast is not seen in the colon. Those in whom the contrast reached the colon in 24 hours were considered to have partial SBO and started oral intake. If gastrografin failed to reach the colon in 24 hours and the patient did not improve in the following 24 hours, laparotomy was performed. RESULTS: Conservative treatment was successful in 31 cases (91%) and 3 (9%) required operation. Patients treated conservatively had short hospital stay (mean=4 days) and tolerated oral feeding with no morbidity or mortality. CONCLUSION: Oral gastrografin helps in the management of patients with postoperative adhesive SBO.

Bilateral paravertebral block in advanced schistosomal liver disease: a prospective study.

BACKGROUND: Surgery in patients with schistosomal liver disease is usually associated with high risks of morbidity and mortality. Bilateral paravertebral block (BPVB) has been advocated as a useful technique for ventral abdominal hernias' repairs. AIM OF THE STUDY: To compare the efficacy of BPVB with general anesthesia (GA) for anterior abdominal wall hernias in advanced schistosomal liver disease patients. PATIENTS AND METHODS: Sixty patients were randomly allocated into two groups to receive either GA or BPVB. Variables were hospital stay, hemodynamic stability, postoperative nausea and vomiting (PONY), postoperative pain measured on a visual analogue scale (VAS) with assessment of the hepatic cell integrity using glutathione S transferase alpha (GSTA) and other liver enzymes. RESULTS: The main significant finding was an apparently significant shorter length of hospital stay following BPVB as compared with GA in patients (P 0.005). CONCLUSIONS: BPVB was superior to GA following abdominal ventral hernia repair in schistosomal liver fibrosis patients.