Mohamed El-Sadany

DNA ploidy of liver biopsies from patients with liver cirrhosis and hepatocellular carcinoma: a flow cytometric analysis

Flow cytometric DNA analysis was used to assess cellular kinetics of needle liver biopsies from patients with liver cirrhosis and hepatocellular carcinoma (HCC). An abnormal DNA content was shown in 44.5% of liver cirrhosis cases and in 78.6% of tumor sites. The number of proliferating cells (S + G2M%) was significantly increased in cirrhotic liver (P < 0.05). Dysplasia was found in 66% of cirrhotic specimens. All negative dysplasia specimens showed a diploid pattern while 69% of positive dysplastic specimens were aneuploid (P < 0.001). In conclusion, cell proliferation, aneuploidy and liver cell dysplasia are important indicators in liver cirrhosis for the development of HCC.

DNA ploidy and liver cell dysplasia in liver biopsies from patients with liver cirrhosis.

There is controversy among pathologists when assessing the presence or absence of liver cell dysplasia in liver biopsies taken from cirrhotic patients. The objective of the present study was to determine the DNA ploidy pattern of hepatocytes of patients with liver cirrhosis and its relationship to liver cell dysplasia. A total of 48 male patients diagnosed with liver cirrhosis based on clinical, laboratory and histopathological criteria were included in the study. A liver biopsy was taken from each patient; one part of the biopsy was subjected to histopathology, and the other to flow cytometry. The histopathological examination revealed liver cell dysplasia in 60% of patients with liver cirrhosis (62% of them had large cell dysplasia [LCD] and 38% had small cell dysplasia [SCD]). Abnormal DNA content (aneuploidy) was found in 81.5% of positive liver cell dysplasia specimens and found only in 11.1% of negative liver cell dysplasia specimens, with a statistically significant difference (P<0.001). Aneuploidy was found more commonly in LCD but without significant difference (P>0.05) in comparison with SCD. In conclusion, SCD (similar to LCD) is also associated with aneuploidy and elevated DNA index, and may carry the same risk for progression to hepatocellular carcinoma.

Dysregulation of blood lymphocyte subsets and natural killer cells in schistosomal liver cirrhosis and hepatocellular carcinoma.

Abstract.Immunological factors are important in the pathogenesis of a wide spectrum of hepatobiliary diseases. Using flow cytometry, we determined the changes in lymphocyte subsets and natural killer cells in 123 individuals (81 patients with liver disease and 42 healthy volunteers). The liver diseases included periportal fibrosis (PPF, 10 patients), liver cirrhosis (LC, 31 patients), and hepatocellular carcinoma (HCC, 40 patients). Schistosomiasis and viral hepatitis B and C were the putative etiological agents of liver diseases. Immunophenotyping by indirect immunofluorescence was conducted using monoclonal antibodies to CD3 (T-lymphocytes), CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T-cells), and CD57 (natural killer cells) cell surface markers. Immunophenotyping of PPF patients showed no significant changes in all markers compared with the healthy controls. However, there was a significant decrease (P<0.01) in CD3 and CD4 T-cells, and a highly significant increase (P<0.001) in CD57 T-cells in patients with LC or HCC. In addition, LC and HCC patients showed no significant change in CD8 T-cells compared with controls. In conclusion, the progression of liver diseases is associated with a dysregulation of cellular immune responses. T-lymphocytes and natural killer cells may play a role in the immunopathogenesis of liver cirrhosis and HCC.

The impact of portopulmonary hypertension on intraoperative right ventricular function of living donor liver transplant recipients.

BACKGROUND: Portopulmonary hypertension (PPH) burdens a right ventricle (RV) already exposed to physiologic stress during liver transplantation. The magnitude of the impact of PPH on RV function, especially early reperfusion, has not been evaluated adequately by prospective controlled trials. In this study, we prospectively quantified the impact of PPH on the RV function in living donor liver transplant recipients. METHODS: Twenty patients undergoing living donor liver transplant were stratified based on mean pulmonary artery pressure (mPAP) into a control group (mPAP <25 mm Hg) and a PPH group (mPAP ≥25 mm Hg). Standard anesthetic technique and monitoring were used. Fiberoptic pulmonary artery catheters enabled to measure RV ejection fraction (RVEF) were used. Hemodynamics were recorded after induction of anesthesia, the end of hepatectomy, before portal unclamping, 5 and 30 minutes after reperfusion, and at skin closure. RESULTS: The PPH group had significantly lower RVEF, stroke volume, and higher central venous pressure and RV end-diastolic volume index after portal unclamping versus the controls. Pulmonary vascular resistance index and mPAP were significantly higher throughout the operation in the PPH group, but RV stroke work index did not differ significantly between groups. RVEF was significantly reduced in the PPH group after reperfusion compared with baseline, but the control group did not experience such a reduction. CONCLUSIONS: Mild to moderate PPH was associated with reduced RVEF during liver transplantation, especially after reperfusion, likely because of a reduced RV contractile reserve in PPH patients. This reduction in RVEF was clinically well tolerated by patients with mild to moderate PPH.

AgNORs count and DNA ploidy in liver biopsies from patients with schistosomal liver cirrhosis and hepatocellular carcinoma

OBJECTIVES Argyrophilic nucleolar organizer regions (AgNOR) proteins are a set of argyrophilic nucleolar proteins that accumulate in highly proliferating cells, whereas their expression is very low in nonproliferating cells. The present study aimed to investigate the potential of DNA flow cytometry (FCM) and AgNORs count in the assessment of cellular kinetics of liver cirrhosis and hepatocellular carcinoma. DESIGN AND METHODS Small-needle liver biopsies (217) were included and were taken from 84 patients with hepatocellular carcinoma (HCC) (one biopsy from tumor lesion and the other from residual nontumor) liver tissues. Only one biopsy was taken from 49 patients with liver cirrhosis. One part of biopsy was subjected to flow cytometry, and the other, to histopathology and AgNORs counting. RESULTS An aneuploidy was shown in 44.5% of liver cirrhosis and in 78.6% of tumor sites. Aneuploid HCC cases showed high AgNORs count compared with diploid cases (3.407+/-1.18 vs. 1.74+/-0.9). An extremely significant increase in AgNORs count in tumor lesion (P<0.001) was found compared with residual liver tissues, liver cirrhosis and normal liver (3.89+/-0.827, 1.49+/-0.52, 1.62+/-0.29, and 1.3+/-0.17, respectively). In liver cirrhosis, dysplasia showed a significant relationship with ploidy (P<0.001) and AgNORs count (P<0.05). CONCLUSION AgNORs count and DNA ploidy analysis of core biopsy specimens are useful in the assessment of cellular kinetics of liver cirrhosis and hepatocellular carcinoma.

Ligation of huge spontaneous porto-systemic collaterals to avoid portal inflow steal in adult living donor liver transplantation: A case-report

Highlights • Maintenance of adequate portal inflow is essential for the graft regeneration in adult LDLT.• Portal inflow steal may occur due to presence of huge spontaneous porto-systemic collaterals.• If the portal inflow to the liver graft is inadequate after adult LDLT, post-transplant impairment of the graft regeneration and eventually graft failure would occur.• A surgical procedure to increase the portal inflow is rarely necessary in adult LDLT.• We report a case of prophylactic surgical interruption of spontaneous huge porto-systemic collateral to prevent PFS during adult LDLT procedure.

Short-term effects of extracorporeal graft rinse versus circulatory graft rinse in living donor liver transplantation. A prospective randomized controlled trial

Living donor liver transplantation has shorter cold ischemia time, less preservative volume, and lower metabolic load compared to transplantation from deceased donors. We investigated the impact of rinsing the graft contents into the systemic circulation on operative course and postoperative outcomes. Donors had right hepatectomy, and grafts were preserved with cold histidine‐tryptophan‐ketoglutarate solution. On ending portal vein anastomosis, grafts were flushed by patients portal blood either through incompletely anastomosed hepatic vein (extracorporeal rinse group, EcRg, n = 40) or into systemic circulation (circulatory rinse group, CRg, n = 40). The primary outcome objective was the lowest mean arterial blood pressure within 5 min after portal unclamping as a marker for postreperfusion syndrome (PRS). Secondary objectives included hemodynamics and early grafts and patients outcomes. Within 5 min postreperfusion, mean arterial blood pressure was significantly lower in the CRg compared to the EcRg, yet this was clinically insignificant. Postoperative graft functions, early biliary and vascular complications, and three‐month survival were comparable in both groups. Rinsing the graft into the circulation increased the incidence of PRS without significant impact on early graft or patient outcome in relatively healthy recipients.

Spray Diathermy Versus Harmonic Scalpel Technique for Hepatic Parenchymal Transection of Living Donor

BackgroundLiver parenchymal transection is the most invasive and challenging part in the living donor operation. The study was planned to compare the safety, efficacy, and outcome of harmonic scalpel versus spray diathermy as a method of parenchymal liver transection in donor hepatectomy.Patient and MethodEighty consecutive patients, who were treated by living donor liver transplantation (LDLT), were included in the study. The study population was divided into two groups according to the method of liver transection: group A by harmonic scalpel (HS) and group B by spray diathermy (SD). The primary outcome was the volume of blood loss during transection. Secondary outcomes were time of transection, number of ligatures needed during transection, pathological changes at cut surface, postoperative morbidities, cost, and hospital stayResultsBlood loss during overall liver transection and in each zone was significantly less in the SD than in the HS group (P = 0.015). The number of ligatures was significantly less in the SD than in the HS group (P = 0.0001). The SD group had significantly higher level of serum bilirubin, serum glutamic pyruvic transaminase (SGPT), and international normalized ratio (INR) levels on postoperative day 3 than the HS group. Lateral tissue coagulation and hepatic necrosis are significantly less in HS group. The overall incidence of postoperative morbidities was the same in both groups. The cost was higher in HS group than SD group (US

AgNORs count and DNA ploidy in liver biopsies from patients with schistosomal liver cirrhosis and hepatocellular carcinoma [Clin. Biochem. 42 (2009) 1616-1620].

760 vs. US

Validity of right ventricular end-diastolic volume as a guide for fluid resuscitation compared with central venous pressure in living donor liver transplantation recipients: a randomized controlled trial

40 P = 0.0001).ConclusionSpray diathermy is an effective method of parenchymal transection with significantly lower blood loss and lower cost compared to HS with no increase in morbidity. HS is associated with earlier recovery of liver functions.