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Background De novo malignancies are a major reason of long-term mortalities after liver transplantation. However, they usually receive minimal attention from most health care specialists. The current study aims to evaluate our experience of de novo malignancies after living-donor liver transplantation (LDLT). Methods We reviewed the data of patients who underwent LDLT at our center during the period between May 2004 and December 2018. Results During the study period, 640 patients underwent LDLT. After a mean follow-up period of 41.2 ± 25.8 months, 15 patients (2.3%) with de novo malignancies were diagnosed. The most common de novo malignancies were cutaneous cancers (40%), post-transplantation lymphoproliferative disorders (13.3%), colon cancers (13.3%), and breast cancers (13.3%). Acute cellular rejection (ACR) episodes occurred in 10 patients (66.7%). Mild ACR occurred in 8 patients (53.3%), and moderate ACR occurred in 2 patients (13.3%). All patients were managed with aggressive cancer treatment. The mean survival after therapy was 40.8 ± 26.4 months. The mean overall survival after LDLT was 83.9 ± 52.9 months. Twelve patients (80%) were still alive, and 3 mortalities (20%) occurred. The 1-, 5-, and 10-year overall survival rates after LDLT were 91.7%, 91.7%, and 61.1%, respectively. On multivariate regression analysis, smoking history, operation time, and development of ACR episodes were significant predictors of de novo malignancy development. Conclusions Liver transplant recipients are at high risk for the development of de novo malignancies. Early detection and aggressive management strategies are essential to improving the recipients’ survival.

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., Introduction In adult living donor liver transplantation (LDLT), maintenance of adequate portal inflow is essential for the graft regeneration. Portal inflow steal (PFS) may occur due to presence of huge spontaneous porto-systemic collaterals. A surgical procedure to increase the portal inflow is rarely necessary in adult LDLT. Presentation A 52 years male patient with end-stage liver disease due to chronic hepatitis C virus infection. Preoperative portography showed marked attenuated portal vein and its two main branches, patent tortuous splenic vein, multiple splenic hilar collaterals, and large lieno-renal collateral. He received a right hemi-liver graft from his nephew. Exploration revealed markedly cirrhotic liver, moderate splenomegaly with multiple collaterals and large lieno-renal collateral. Upon dissection of the hepato-duodenal ligament, a well-developed portal vein could be identified with a small mural thrombus. The recipient portal vein stump was anastomosed, in end to end fashion, to the graft portal vein. Doppler US showed reduced portal vein flow, so ligation of the huge lieno-renal collateral that allows steal of the portal inflow. After ligation of the lieno-renal collateral, improvement of the portal vein flow was observed in Doppler US. Discussion There is no accepted algorithm for managing spontaneous lieno-renal shunts before, during, or after liver transplantation, and evidence for efficacy of treatments remains limited. We report a case of surgical interruption of spontaneous huge porto-systemic collateral to prevent PFS during adult LDLT. Conclusion Complete interruption of large collateral vessels might be needed as a part of adult LDLT procedure to avoid devastating postoperative PFS.

Liver 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.Eighty 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 stay RESULTS: Blood 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$760 vs. US$40 P = 0.0001).Spray 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.

Background Living donor liver transplantation (LDLT) is considered a safe alternative to deceased donor liver transplantation (DDLT). In Egypt, DDLT program is still awaited, making LDLT the only hope for patients with end-stage liver disease, mainly due to chronic hepatitis C virus (HCV) infection. The current study is conducted to evaluate our experience of LDLT and discuss the lessons learned from 500 consecutive cases in HCV area. Methods We reviewed the data of patients who underwent LDLT at Gastrointestinal Surgery Center, Mansoura University during the period between May 2004 and March 2017. Results During the study period, 500 cases underwent LDLT at our unit. The median age was 51 years, and most of our cases were males (446, 89.2%) and had HCV infection (453, 90.6%). The median MELD score was 15. Median ICU stay was 5 days, and hospital stay was 22 days. Postoperative morbidities occurred in 220 cases (44%). Early mortality occurred in 69 patients (13.8%), and late mortality occurred in 45 patients (9%). The 1-, 3-, 5-, and 7-year overall survival rates of all cases were 80.9%, 78.2%, 75.7%, and 75%, respectively. Preoperative creatinine, worm ischemia, blood transfusion, ICU stay, postoperative morbidities, and small for size syndrome were independent predictors for overall survival. Conclusions In countries lacking DDLT, LDLT is the only effective alternative. LDLT requires a teamwork to achieve successful outcomes. LDLT should only be performed in centers with the adequate experience to avoid and decrease the hazards related to this procedure.

Background Living liver donors represent a special group of patients. They are healthy individuals who are exposed to a major surgery, in which the dominant liver proportion is extracted as a graft. Of all potential donor-related morbidities, posthepatectomy liver dysfunction (PHLD) is the most significant as it may be directly related to donor mortality. We aimed to review our data of adult living donor liver transplantation (LDLT) utilizing the right hemiliver grafts to determine the incidence and potential predictors for the development of PHLD, defined according to the International Study Group of Liver Surgery. Methods We reviewed the data of all adult living donors who underwent right hemihepatectomy during the period between May 2004 and 2016. Results During the study period, 434 cases underwent right hemihepatectomy for adult LDLT. We divided our cases into 2 groups according to the occurrence of PHLD. A significant lower residual liver volume and percentage were noted in PHLD group. Longer intensive care unit stay and hospital stay, and more postoperative morbidities, were observed in PHLD group. PHLD occurred in 50 cases (11.5%), and most of them were grade A (47 cases [10.8%]). Two cases (0.5%) had grade B requiring diuretic therapy, and 1 case (0.2%) had grade C requiring ultrasound guided tube drainage and surgical exploration finally. Conclusions We should not underestimate the risks of liver donation surgery, especially when utilizing the right hemiliver graft. Donor safety should be ensured by accurate preoperative volumetric assessment of the remnant liver and remnant liver volume limitations must be strictly followed.

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 patient's 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 graft's and patient's 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.

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

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

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.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.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 (P0.001) 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 (P0.001) and AgNORs count (P0.05).AgNORs count and DNA ploidy analysis of core biopsy specimens are useful in the assessment of cellular kinetics of liver cirrhosis and hepatocellular carcinoma.

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 (P0.05) 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.

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.

The diagnosis of liver diseases induced by hepatitis B virus (HBV) is supported by the detection of HBV surface antigen (HBsAg) in serum. The present study aimed to investigate the presence of HBV deoxyribonucleic acid (DNA) in patients with liver cirrhosis using a polymerase chain reaction (PCR) based on primers derived from the pre-S1 and pre-core regions. HBsAg was detected in 10 of 48 patients (21%), total anti-hepatitis B core antigen (HBc) antibodies in 54%, anti-hepatitis B e antigen (HBeAg) in 14.6%, anti-HBc immunoglobulin M in 8%, and anti-HBs in 26%; none had detectable HBeAg. HBV DNA was detected in 73% of the cirrhotic patients. All cirrhotic patients with HBsAg also had HBV DNA; HBV DNA was detected in 64.5% of those without HBsAg. We conclude that the clearance of HBsAg does not necessarily indicate termination of viraemia in patients with liver cirrhosis and the detection of HBV DNA using a PCR based on primers from the pre-S1 and pre-core regions should be included in the diagnosis of HBV infection.

Background Fluid transfusion inflects major impact on graft and renal functions in living donor liver transplantation. Major hemodynamic swinging renders intraoperative preload assessment crucial yet difficult task. In this prospective randomized double-blind controlled trial, we examined the validity of right ventricular end-diastolic volume (RVEDV) as a preload indicator compared with central venous pressure (CVP) in recipients of living donor liver grafts. Patients and methods A total of 21 patients included in the study were randomly allocated into either the RVEDV group ( n = 11) or the CVP group ( n = 10) on the basis of the trigger for operative fluid resuscitation. Basal value for both right ventricular end-diastolic volume index (RVEDVI) and CVP was recorded after laparotomy. Fluids (albumin 4% or Voluven) were given in boluses of 250 ml when the triggering parameter decreased by 20% of its basal value. Hemodynamic data were recorded after laparotomy (basal), at the end of hepatectomy, before portal unclamping, 15 min after portal unclamping, and at skin closure. Total fluids infused, blood loss, early graft, and patient's outcomes were also recorded. Results Both groups were similar with respect to demographic and operative data. Fluids infused were significantly higher in the RVEDVI group compared with the CVP group. Cardiac output and stroke volume were significantly higher in the RVEDVI than in the CVP group starting at end of hepatectomy and thereafter. Urine output was significantly less in the CVP group compared with the RVEDVI group. Hypotensive episodes were greater in the CVP group compared with the RVEDVI group. RVEDVI and CVP did not correlate at any time point. No intergroup differences were observed with respect to early graft functions, serum creatinine, blood urea, ICU stay, 28th day graft, and patient survival. Conclusion RVEDV appears to be a more sensitive preload indicator and a trigger for fluid resuscitation compared with CVP; however, patient monitoring with either parameter did not significantly affect the patient outcome.