Computer-assisted liver tumor surgery using a novel semiautomatic and a hybrid semiautomatic segmentation algorithm.

We developed a medical image segmentation and preoperative planning application which implements a semiautomatic and a hybrid semiautomatic liver segmentation algorithm. The aim of this study was to evaluate the feasibility of computer-assisted liver tumor surgery using these algorithms which are based on thresholding by pixel intensity value from initial seed points. A random sample of 12 patients undergoing elective high-risk hepatectomies at our institution was prospectively selected to undergo computer-assisted surgery using our algorithms (June 2013-July 2014). Quantitative and qualitative evaluation was performed. The average computer analysis time (segmentation, resection planning, volumetry, visualization) was 45 min/dataset. The runtime for the semiautomatic algorithm was <0.2 s/slice. Liver volumetric segmentation using the hybrid method was achieved in 12.9 s/dataset (SD ± 6.14). Mean similarity index was 96.2 % (SD ± 1.6). The future liver remnant volume calculated by the application showed a correlation of 0.99 to that calculated using manual boundary tracing. The 3D liver models and the virtual liver resections had an acceptable coincidence with the real intraoperative findings. The patient-specific 3D models produced using our semiautomatic and hybrid semiautomatic segmentation algorithms proved to be accurate for the preoperative planning in liver tumor surgery and effectively enhanced the intraoperative medical image guidance.

Overexpression of CDT1 Is a Predictor of Poor Survival in Patients with Hepatocellular Carcinoma.

BACKGROUND: Genomic instability is a common feature in hepatocellular carcinoma. Deregulation of replication licensing factors has been shown to trigger DNA damage response contributing to genomic instability. Overexpression of DNA replication licensing factors chromatin licensing and DNA replication factor 1 (CDT1) and minichromosome maintenance complex component 7 (MCM7) has been previously reported in several human cancers. The aim of the present study was to evaluate the expression and prognostic significance of CDT1 and MCM7 in association with DNA damage response markers and p53 in patients with hepatocellular carcinoma. METHODS: Expression of CDT1, MCM7, p-H2A histone family member X (H2AX), phospho-ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia rad3-related (ATR) substrate, and p53 was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded surgical specimens from 111 patients who underwent hepatectomy for hepatocellular carcinoma. Statistical analysis was performed to evaluate associations between the studied proteins, clinicopathological parameters, and patient survival. RESULTS: CDT1 expression correlated with p-H2AX (p = 0.038), while MCM7 correlated with p-H2AX and phospho-ATM/ATR substrate (p < 0.001). Increased CDT1 expression was associated with higher tumor grade (p = 0.006) and tumor-node-metastasis (TNM) stage (p = 0.033). High CDT1 expression correlated significantly with reduced overall survival (60.8 and 26.5 % vs 82.8 and 53.0 %, for low CDT1 expression, at 2 and 5 years, respectively, p = 0.012) and was identified by multivariate analysis as an independent predictor of poor overall survival (p = 0.049). CONCLUSIONS: Overexpression of CDT1 and MCM7 in hepatocellular carcinoma correlates with DNA damage response, and CDT1 overexpression is a significant prognostic biomarker in hepatocellular carcinoma.

Gangrenous Cholecystitis Related to Transcatheter Arterial Chemoembolization (TACE) Treatment for Hepatocellular Carcinoma.

A 69-year-old male with a history of hepatitis B-induced cirrhosis underwent segmental liver resection for hepatocellular carcinoma. At his 12-month follow-up, local recurrence in segment VII was diagnosed, measuring 7.8 by 6.2 cm, with irregular margins and the presence of a tumor thrombus in the portal vein. After evaluation by the multidisciplinary liver team, the patient underwent transcatheter arterial chemoembolization with drug-eluting beads. Forty-eight hours after his discharge, the patient presented with gangrenous cholecystitis and he underwent an uneventful cholecystectomy. Cholecystitis is a well-documented complication of transcatheter arterial chemoembolization due to inadvertent reflux of the embolic material into the cystic artery. However, super selective embolization significantly reduces the risk of cholecystitis. In most cases, management is conservative and only severe cases require further intervention.

Giant malignant insulinoma.

Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed.

"True" duct-to-mucosa pancreaticojejunostomy, with secure eversion of the enteric mucosa, in Whipple operation.

BACKGROUND: Postoperative pancreatic fistula (POPF) due to anastomotic leak is often associated with significant morbidity and mortality. The aim of this study was to present an improved anastomotic technique for Whipple operation, which we call "true" duct-to-mucosa anastomosis (DMA)-pancreaticojejunostomy. METHODS: A novel enteric mucosal eversion at the point of the jejunostomy is constructed prior to the anastomosis with the pancreatic duct in order to enhance sealing. This technique was tested in a series of 38 patients (study group) and compared to the technique used in the preceding 35 patients who served as controls. RESULTS: The incidence of POPF was significantly lower in the study group compared to controls: 7.9 % (3/38) vs 34.3 % (12/35), respectively (P = 0.008, odds ratio 6.1). All POPFs in the study group were International Study Group on Pancreatic Fistula (ISGPF) grade A, while in the control group POPFs ISGPF grade B and C occurred in 17.1 %. Additionally, median (interquartile range) postoperative hospitalization was reduced in the study group [16 (14-21) days] compared to controls [20 (16-27) days, P = 0.005]. CONCLUSIONS: The "true" DMA technique appears to be one of the safest techniques reported to date. The modifications presented herein can easily be adopted by experienced surgeons already performing other techniques of duct-to-mucosa anastomosis.

Expression of claudins-1, -4, -5, -7 and occludin in hepatocellular carcinoma and their relation with classic clinicopathological features and patients' survival.

BACKGROUND: Occludin and claudins are integral constituents of tight junction proteins and are de-regulated in various malignancies, including hepatocellular carcinoma (HCC). This study investigated whether expression of claudins 1, 4, 5, 7 and occludin may be used as prognostic markers for overall and disease-free survival in patients with HCC after hepatectomy. PATIENTS AND METHODS: The study included 67 hepatectomy specimens obtained from an equal number of patients with HCC who underwent partial hepatectomy at the Patras University Hospital for therapeutic reasons. Ten normal liver tissues were used as controls. Expression of claudins 1, 4, 5, 7 and occludin in liver tissues was assessed by immunochemistry. Clinicopathological features were also available for each case. RESULTS: Expression of claudins 1, 4, 5, 7 and occludin was significantly increased in HCC specimens compared to non-neoplastic liver tissues and normal controls (p<0.001 in each case) Moreover, there was a statistically significant association between low level of claudin-4 and advanced tumor grade (p=0.03). Down-regulation of claudin-1 was associated with low overall survival in univariate survival analysis (p=0.049) and Kaplan-Meier analysis (p=0.04). Multivariate analysis showed that the claudin-4 level was an independent factor for survival prognosis (p=0.01). In addition, down-regulation of claudin-4 expression was associated with increased recurrence rate and low disease-free survival rate in univariate analysis (p=0.038), Kaplan-Meier plot (p=0.013) and multivariate analysis (p=0.013). A low level of claudin-5 and high level of claudin-7 levels were independent negative prognostic factors according to multivariate analysis (p=0.015 and 0.009, respectively). CONCLUSION: The present study demonstrates that high expression of claudins 1, 4, 5 and down-regulation of claudin-7 are positive prognostic markers and are associated with good outcome and increased survival rates. Moreover, an increase in claudin-4 expression may serve as an independent positive prognostic factor for low recurrence rate after hepatectomy.

The prognostic value of frozen section preimplantation graft biopsy in the outcome of renal transplantation.

INTRODUCTION: Preimplantation biopsy provides a window on the state of the renal allograft. In this study, the prognostic value of frozen section preimplantation graft biopsy was estimated and compared to regularly processed formalin-fixed biopsy. MATERIALS AND METHODS: Seventy-four renal allograft recipients were studied. The degree of glomerulosclerosis, acute tubular necrosis, interstitial fibrosis, arteriosclerosis, and arteriolosclerosis was rapidly estimated in frozen sections and correlated to the renal function in the immediate posttransplantation period and 3 months thereafter. The histological changes were also examined in paraffin-embedded sections. RESULTS: The histological changes observed in rapidly processed frozen sections were comparable to those observed on regularly processed sections and their differences did not reach statistical significance. Glomerulosclerosis and arteriolosclerosis were underestimated, whereas acute tubular necrosis and interstitial fibrosis were overestimated, in the frozen sections compared to permanent ones, but those differences were not statistically significant. Immediate graft function was observed in 45 patients (61%). Delayed graft function was more frequently observed among recipients with donor age above 60 years (57% vs. 32%). Serum creatinine 3 months after transplantation was above 2 mg/dL in 33 recipients (44.5%) and was positively correlated to the degree of tubular necrosis (p = 0.04) and donor age (p = 0.03). Donor age was correlated to the degree of arteriolosclerosis (p < 0.01). CONCLUSIONS: Frozen section preimplantation biopsy gives reliable information for the situation of the graft that is related to the outcome of renal transplantation.

Mini-laparotomy cholecystectomy versus laparoscopic cholecystectomy: which way to go?

PURPOSE: The aim of this paper is to report the results of a prospective clinical trial investigating traditional laparoscopic cholecystectomy versus "mini-lap" cholecystectomy in a tertiary care University Hospital. MATERIALS AND METHODS: This is a prospective, randomized, single-center observational study. Forty-four patients were allocated in each group; patients in group L underwent laparoscopic cholecystectomy, whereas patients in group M had open "mini-laparotomy" cholecystectomy with a small incision through the rectus abdominis muscle. RESULTS: The operation lasted significantly longer in group L compared with group M, whereas patients of group L had a shorter hospital stay. There was no difference between groups regarding postoperative day on which patients commenced eating. There was no significant difference between groups regarding doses of analgesics used during surgery or in the recovery room. However, patients in group M used significantly more opioids in the postoperative period. Time to resume normal activity was significantly shorter in group L. A very good aesthetic result was obtained in 97.7% of patients in group L and 77.3% of patients in group M. CONCLUSIONS: Cholecystectomy through a mini-laparotomy incision is a lower-cost, versatile, and safe alternative to laparoscopic cholecystectomy.

Hepatocellular carcinoma in hepatectomized patients: biologic and therapeutic implications.

UNLABELLED: The macroscopic and microscopic features of 60 hepatocellular carcinomas (HCC) were investigated and correlated with patients' disease-free survival. PATIENTS AND METHODS: The study included 60 HCCs removed, by partial hepatectomy, from an equal number of patients. In these tumors, several macroscopic and microscopic features were assessed, graded and correlated with disease-free survival. RESULTS: HCCs begin as small, well-differentiated tumors that have an increased proliferation rate and neovascularization. Vascular invasion, which is the strongest predictor of disease recurrence, correlated significantly with tumor number and size, the predominant and worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence of macroscopic or large vessel invasion, the largest tumor size (p = 0.006), apoptosis/mitosis ratio (p = 0.03) and number of tumors (p = 0.04) were independent predictors of disease-free survival. CONCLUSION: This study showed that, in humans, the prognosis of HCC depends on several biological factors. Aggressive biological behavior (vascular invasion and recurrence) correlated significantly with: a) alterations in the apoptosis/mitosis ratio and b) architectural and cellular alterations.

The potential role of TGFbeta1, TGFbeta2 and TGFbeta3 protein expression in colorectal carcinomas. Correlation with classic histopathologic factors and patient survival.

PURPOSE: This study investigates the expression of tumor growth factors TGFbeta1, TGFbeta2 and TGFbeta3 in tissue material from patients with colorectal carcinoma and evaluates their correlation with known prognostic markers and patient survival. PATIENTS AND METHODS: The study included 124 patients with colorectal carcinoma. According to the TNM classification of malignant tumors, 26 tumors were identified as being stage I, 30 stage II, 48 stage III, and 20 stage IV, whereas 106 tumors were low-grade and 18 high-grade malignancies. On paraffin sections, the streptavidin-biotin technique using antibodies against TGFbeta1, TGFbeta2 and TGFbeta3 was applied. Morphological and immunohistochemical results were correlated with clinicopathologic parameters. RESULTS: TGFbeta1 protein was expressed in 88 out of 124 (71%) carcinomas, whereas TGFbeta2 and TGFbeta3 proteins were detected in all tumors examined. Normal colonic mucosal epithelial cells expressed TGFbeta2 (significantly less as compared to neoplastic cells; p < 0.01) and TGFbeta3 (p > 0.05 compared to neoplastic cells), but not TGFbeta1. Statistical analysis revealed a higher expression of TGFbeta1 in low-grade carcinomas (p = 0.009) and a higher presence of TGFbeta2 in advanced tumors (p = 0.008). TGFbeta1 expression was related with increased disease-free and overall survival (p < 0.05 each). The presence of TGFbeta2 was correlated with worse prognosis (p < 0.05). Cox analysis revealed that besides tumor grade and stage, TGFbeta1 expression constituted an independent prognostic factor. CONCLUSION: This study shows that in adenocarcinomas of the colon, there is a differential expression of TGFbeta1, TGFbeta2 and TGF3. TGFbeta1 may be implicated in the pathogenesis of these tumors, since it is expressed only in neoplastic but not in normal cells. TGFbeta1 is related with an increased disease-free and overall survival and constitutes an independent prognostic factor. In advanced stages, TGFbeta2 seems to be involved in tumor progression and is related with worse prognosis.

Potential role of bcl-2 and bax mRNA and protein expression in chronic hepatitis type B and C: a clinicopathologic study.

Bcl-2 oncoprotein regulates programmed cell death by providing a survival advantage to rapidly proliferating cells, and bax protein promotes apoptosis by enchanting cell susceptibility to apoptotic stimuli. In this study, we assessed the expression of bcl-2 and bax in liver biopsies from patients with chronic hepatitis (CH) Type B (HBV) and C (HCV). The study comprised 65 liver biopsies from 65 patients with HBV (n = 37) and HCV (n = 28) and 10 normal liver biopsies as controls. The HAI score ranged from 3/18-13/18, and the fibrosis Stage, from 1-6 (7 HBV/10 HCV). Pathologic examination included the following: (1) immunohistochemical stains in paraffin sections for bcl-2 and bax protein expression, (2) Western blot analysis (bcl-2 and bax protein levels evaluation), (3) ISH (detection of bcl-2 and bax mRNA), and (4) ISH (TUNEL-ABI [apoptotic body index]). In CH cases, both bcl-2 and bax protein and mRNA were detected in portal and intralobular lymphocytes and in cholangiolar epithelial cells in interface areas and fibrous bands. Bax protein and mRNA was expressed within hepatocytes and epithelial cells of interlobular ducts in portal tracts. Bcl-2 mRNA was present in periportal hepatocytes only in cases with Stage 5-6 fibrosis. Western blot analysis showed a decreased bcl-2 and an increased bax expression toward advanced fibrotic stages. In CH cases, ABI was reverse correlated with the percentage of bcl-2 expression and was correlated directly with the percentage of bax expression (P <.001). The results of this study suggest that in cases of chronic HBV or HCV infection, bax may be involved in the hepatocyte cycle regulation during infection, whereas its expression in intraportal bile duct epithelium implies that this protein enhances susceptibility of these particular cells to apoptosis. The increased bax expression and ABI in fibrosis Stages 1-5, imply that they are responsible for hepatocytes depletion through apoptosis, during progress of liver fibrosis and fibrous tissue accumulation, until cirrhosis is established. Bcl-2 mRNA expression in periportal hepatocytes only in Stages 5 and 6 suggests that this oncogene is involved in the late stages of progressive liver fibrosis and failure and furthermore that periportal hepatocytes are resistant to apoptosis. Bcl-2 expression, in cholangioles of interface area, suggests that this oncoprotein may be involved in growth regulation of these epithelial cells. Further research is warranted to specify the exact role of apoptosis and apoptotic genes involved in liver fibrosis process in cases of chronic HBV and HCV infection. This may lead to new strategies in the management of human liver disease to prevent the progression to chronic liver failure.

BCL-2 and BAX expression and cell proliferation, after partial hepatectomy with and without ischemia, on cholestatic liver in rats: an experimental study.

BACKGROUND: Liver regeneration after partial hepatectomy (PHx) is regulated by several factors that activate or inhibit hepatocyte proliferation. Apoptosis seems to play an important role in cellular proliferation and liver regeneration. This study investigates the expression apoptosis-associated genes bcl-2 and bax, and the presence of apoptosis and cell proliferation after PHx, in normal and jaundiced rats with or without superimposed ischemia. MATERIALS AND METHODS: The study included 50 male Wistar rats assigned into; five groups (10 rats each). On day 0, rats of groups II, IV, and V underwent common bile duct ligation (BDL). On day 10, total liver ischemia (TLI) (occlusion of hepatic artery and portal vein-TLI) for 30 min was performed on animals of group V. When TLI was completed, all 30 animals (of groups I, IV, and V) underwent PHx (68%). Animals of group III underwent only TLI for 30 min. Rats of groups I, IV, and V were sacrificed 24 and 48 h after PHx was completed. Rats of group II were sacrificed 10, 11, and 12 days after BDL. Rats of group III were sacrificed immediately, 24 and 48 h after TLI completion. Liver tissue was obtained and pathologic examination included: (a) H&E stain, (b) in situ hybridization (detection of bcl-2 and bax mRNA) in paraffin sections, (c) Western blot analysis for the evaluation of bcl-2 and bax protein levels, (d) in situ hybridization (TUNEL) for the detection of apoptotic bodies, and (e) immunohistochemical stains (streptavidin-biotin method) in paraffin sections to detect cells that (i) express bcl-2 and bax proteins and (ii) undergo proliferation (Ki67+ cells). Results were expressed following morphometric analysis. RESULTS: Before hepatectomy, bcl-2 (protein or mRNA) levels were higher in jaundiced rats vs controls. Furthermore, bax (protein or mRNA) levels and apoptotic body index (ABI) were higher in cholestatic livers. After hepatectomy, there was an early decrease in the protein and mRNA levels of antiapoptotic gene bcl-2 and a late increase of proapoptotic gene bax and the ABI, compared to controls. Cell proliferation of hepatocytes was lower in group V (BDL + TLI) compared to that of groups II and IV (BDL). CONCLUSIONS: This study shows that apoptosis takes place in cholestatic livers with or without superimposed ischemia and may contribute in the impaired regenerative response observed in livers of jaundiced rats after partial hepatectomy.

Survival for 5 years after repeat liver resections and multimodality treatment for metastatic intestinal leiomyosarcoma: report of a case.

The liver is a common site of metastases from gastrointestinal or retroperitoneal leiomyosarcomas. Although repeat liver resections can prolong survival, to our knowledge, 5-year survival has never been achieved. We report the case of a woman who has survived for 5 years since her first liver resection, during which time five more resections have been performed, in combination with systemic chemotherapy and radiofrequency ablation.

The potential role of bcl-2 mRNA and protein exression in hepatocellular carcinomas.

BACKGROUND: The bcl-2 gene regulates programmed cell death by providing a survival advantage to rapidly proliferating cells. In several malignant tumors bcl-2 presence has been associated with favorable prognosis. In the liver, bcl-2 is expressed in bile ductular cells and tumors of biliary origin. This study investigates the expression of bcl-2 mRNA and protein in hepatocellular carcinomas (HCC). MATERIALS AND METHODS: The study comprised 35 primary HCC resected from 35 patients; 21 males and 14 females, aged from 43-59 years. The tumors were graded according to Edmondson criteria. In 28 cases HCC was developed on the background of cirrhotic liver. In 9 instances the patients received chemoembolization before surgery. The presence of bcl-2 mRNA was assessed on paraffin-embedded, 4 microm-thick sections, using a standard in situ hybridization method with a commercially available bcl-2 probe (Maxim Biotech, USA), while the streptavidin-biotin immunohistochemical technique was employed to detect bcl-2 protein expression using the monoclonal anti-bcl-2 antibody (DAKO, USA). The results were expressed as % of tumor-positive cells following morphometric analysis. RESULTS: The in situ hybridization study revealed bcl-2 mRNA expression in 25 out of 35 (70%) HCC. In addition, bcl-2 mRNA was detected in hyperplastic cholangioles within fibrous septae in the periphery of the tumors. Immunohistochemical staining failed to reveal any bcl-2 protein expression in tumor cells of HCC, whereas hyperplastic cholangioles of the fibrous septae, in the periphery of the tumors and intratumoral lymphocytes displayed a strong-positive cytoplasmic (perinuclear) stain. No significant correlations were recorded between bcl-2 mRNA expression and tumor histological pattern, grade, stage and the use of previous chemoembolization. CONCLUSION: In hepatocellular carcinomas, the bcl-2 gene is frequently present but its protein product is absent. This suggests a post-translational mechanism of bcl-2 protein degradation, indicating that bcl-2 does not play a substantial role in the progress of hepatocellular carcinoma.

Expresssion of bcl-2 oncoprotein in cases of acute and chronic viral hepatitis type B and type C: a clinicopathologic study.

The bcl-2 gene is involved in the regulation of programmed cell death by providing a survival advantage to rapidly proliferating cells. This study investigates bcl-2 protein expression in liver biopsies with acute or chronic viral hepatitis B (HBV) or C(HCV). The study comprised 60 liver biopsies with hepatitis B or C. These included 10 biopsies from cases with acute lobular hepatitis (ALH), and 50 with chronic hepatitis (CH). In addition, 10 liver biopsies were used as controls. In CH cases, HAI grade ranged from 3/18 to 15/18, and stage from 1 to 6 (6HBV/8HCV). Immunohistochemical bcl-2 expression was assessed using the streptavidin-biotin method and the presence of apoptotic cells was evaluated by TUNEL method. Immunohistochemical and in situ hybridization (TUNEL) results were expressed following morphometric analysis. In CH cases, bcl-2 was detected in portal and intralobular lymphocytes, and in cholangiolar epithelial cells of the interface area. In ALH and control cases, bcl-2 was expressed only in lymphocytes. Lymphocytic bcl-2 expression was correlated directly with categories A, C and D of HAI (P < 0.001), whereas the degree of fibrosis was reversibly correlated to bcl-2 expression. In conclusion, in cases of chronic hepatitis, bcl-2 expression in cholangioles of interface area suggests that this oncoprotein may be involved in regulation of growth of these epithelial cells.

The effect of ischemia on the regeneration of the cholestatic liver. An experimental study.

BACKGROUND/AIMS: Cholestatic liver is known to be more susceptible to ischemia than normal liver. In this study we assessed the histopathologic features of hepatic ischemic damage and liver regeneration in rats with experimental obstructive jaundice. METHODOLOGY: The study comprised 90 male Wistar rats. These were assigned randomly to 4 groups according to the surgical procedure they underwent: I (n = 10) controls (non-operated), II (n = 10) sham-operated, III (n = 30) occlusion of hepatic artery and portal vein (total liver ischemia), and IV (n = 40) ligation and division of the common bile duct ligation. Rats of group III were sacrificed 15 (IIIa), 30 (IIIb) and 60 min (IIIc) after total liver ischemia was done. Ten days after bile duct ligation, 10 rats of group IV underwent euthanasia, whereas the remaining 30, underwent total liver ischemia and were sacrificed after 15 min (IVb), 30 min (IVc), and 60 min (IVd). Liver wedge biopsies (left anterior lobe) were obtained and histologic examination included hematoxylin and eosin, and immunohistochemical stains for cytokeratin AE1, HEPPAR (hepatocyte paraffin antigen), and antigen Ki67. Immunohistochemical results for Ki67 were expressed following morphometric analysis. RESULTS: Liver sections from category IVa showed large duct obstruction features, and those from group III, ischemic chages including centrilobular hepatocellular swelling and necrosis, hepatocanalicular cholestasis, and mild portal mononuclear/mixed inflammation. Sections from groups IVB, IVc, IVd displayed together changes of large duct obstruction and ischemia, and in categories IVc (bile duct ligation +30 min total liver ischemia), and IVd (bile duct ligation +60 min total liver ischemia) necrosis of the large bile ducts was present. The total liver parenchymal area affected (% necrosis) was higher in categories IVd, and IVc compared to categories IVb (P < 0.05), and IIIc, IIIb, IIIa (P < 0.01). All 60 total liver ischemia-liver biopsies, developed features of liver regeneration that originated from zone 2, extended to zone 1 and occasionally to zone 3. Immunohistochemical stains revealed cells positive to AE1 and cells positive to HEPPAR. Proliferation rate (% Ki67+ cells) was higher in category IIIa compared to categories IIIb, IIIc, IVb, IVc, and IVd (P < 0.05). CONCLUSIONS: Our study shows that liver ischemia induces more severe hepatocyte damage in livers with obstructive cholangiopathy compared to normal ones. Liver regenerative process is mediated mainly by proliferation of non-necrotic cells that express hepatocellular or ductular epithelial features. Proliferation rate of hepatocytes is lower when liver ischemia and obstructive jaundice coexist.