Non-cirrhotic Liver Research Articles

Benign hepatocellular nodules: What have we learned using the patho-molecular classification

Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors that develop most frequently in females and in non-cirrhotic livers. HCA are prone to bleed and to transform into hepatocellular carcinoma (HCC). Four major subgroups of HCA have been thus far identified: HNF1α mutated HCA, inflammatory HCA (IHCA), β-catenin mutated HCA (b-HCA and b-IHCA), based on mutations in specific oncogenes and tumor suppressors. B-HCA and b-IHCA are strongly associated with HCC transformation. Benign hepatocellular tumors can be classified using immunohistochemistry (LFABP, CRP, GS, b-catenin). Analysis of HCA phenotypes has led to the identification of patients at risk of HCC transformation and therefore improved the indications provided by invasive and non-invasive diagnostic techniques, such as biopsies and MRI. These recent advances have broadened the clinical scope of HCA in various conditions, such as their presence in males, in obese patients, in patients suffering from liver vascular disorders, genetic diseases. However, specific immunohistochemistry has shown limitations particularly for the identification of b-HCA, thereby, outlining the importance of molecular studies to improve the diagnosis/prognosis of HCA. If evaluation of prognosis and treatment has benefited from these advances, much more needs to be done to obtain guidelines for good clinical practice.

Is a fluorescence navigation system with indocyanine green effective enough to detect liver malignancies?

Although several reports have shown the efficacy of a fluorescence navigation system (FNS) with indocyanine green (ICG) to detect liver malignancies during hepatectomy, the real accuracy of this procedure is not yet clear. This study aimed to analyze the actual efficacy of ICG-FNS in cirrhotic and non-cirrhotic livers. Ten cirrhotic whole livers explanted from liver transplant recipients and 23 non-cirrhotic livers from patients who underwent hepatectomy for various kinds of liver tumors were investigated with ICG-FNS. All surgical specimens were analyzed macroscopically and pathologically. In the patients with a cirrhotic liver, most nodules illuminated by ICG-FNS were diagnosed as regenerative nodules pathologically. The positive predictive value was 5.4%. There was a significant difference in positive predictive value to detect malignant liver tumors between cirrhotic liver and non-cirrhotic liver (5.4% vs 100%, P < 0.0001). In the non-cirrhotic livers, 11 of 33 (32.4%) tumors were not recognized by ICG-FNS through the liver surface before resection. There was a significant difference in the depth from the liver surface to tumor between illuminated nodules and non-illuminated nodules (1.5 mm vs 11.6 mm, P < 0.01). It is necessary to know the limitation of ICG-FNS when detecting liver malignancies in both cirrhotic and non-cirrhotic livers.

Impact of liver cirrhosis on liver enhancement at Gd-EOB-DTPA enhanced MRI at 3 Tesla

PurposeThe purpose of this study was to assess differences in enhancement effects of liver parenchyma between normal and cirrhotic livers on dynamic, Gd-EOB-DTPA enhanced MRI at 3T. Materials and methods93 patients with normal (n=54) and cirrhotic liver (n=39; Child–Pugh class A, n=18; B, n=16; C, n=5) underwent contrast-enhanced MRI with liver specific contrast media at 3T. T1-weighted volume interpolated breath hold examination (VIBE) sequences with fat suppression were acquired before contrast injection, in the arterial phase (AP), in the late arterial phase (LAP), in the portal venous phase (PVP), and in the hepatobiliary phase (HBP) after 20min. The relative enhancement (RE) of the signal intensity of the liver parenchyma was calculated for all phases. ResultsMean RE was significantly different among all evaluated groups in the hepatobiliary phase and with increasing severity of liver cirrhosis, a decreasing, but still significant reduction of RE could be shown. Phase depending changes of RE for each group were observed. In case of non-cirrhotic liver or Child–Pugh Score A cirrhosis mean RE showed a significant increase between AP, LAP, PVP and HBP. For Child–Pugh B+C cirrhosis RE increased until PVP, however, there was no change in case of B cirrhosis (p=0.501) and significantly reduced in case of C cirrhosis (p=0.043) during HBP. ConclusionRE of liver parenchyma is negatively affected by increased severity of liver cirrhosis, therefore diagnostic value of HBP could be limited in case of Child Pugh B+C cirrhosis.

Recurrence of Hepatocellular Carcinoma in Noncirrhotic Liver After Hepatectomy

Hepatocellular carcinoma in noncirrhotic liver (HCCNC) is rare. This tumor has a particular epidemiology and presentation, and it requires specific treatment, compared with HCC in cirrhotic liver. The aims of this study were to determine the survival and recurrence rates, prognostic factors, and optimum treatment of HCCNC and to propose a follow-up protocol for patients who have undergone surgery for HCCNC. This study included 131 patients who underwent surgical treatment for HCCNC from January 1992 to December 2010. Survival and recurrence rates were evaluated, and the prognostic factors and characteristics of recurrence were analyzed. Pathologic characteristics of the tumors and the nontumoral liver were examined. The mean survival time was 67.9 months. The 5- and 10-year overall survival rates were 72.9 and 36.7 %, respectively. In all, 54 patients (41.2 %) developed recurrence at a median interval of 30.96 months. Of these recurrences, 31.5 % occurred during the first year, and 24.1 % occurred more than 5 years after surgery. Macro- or microvascular invasion and tumor size >5 cm were significantly associated with a poor survival rate. The predictive factors for recurrence were multiple tumors, tumor diameter >5 cm, and satellite nodules. Patients who underwent surgical treatment for recurrence had a significantly longer survival time than those who did not (p < 0.0292). Recurrence is the most common cause of death after hepatectomy for HCC, and patients should undergo careful, long-term follow-up. Early detection and treatment of recurrence with curative intent should improve the prognosis of these patients.

Hydatid cyst

Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors that develop most frequently in females and in non-cirrhotic livers. HCA are prone to bleed and to transform into hepatocellular carcinoma (HCC). Four major subgroups of HCA have been thus far identified: HNF1α mutated HCA, inflammatory HCA (IHCA), β-catenin mutated HCA (b-HCA and b-IHCA), based on mutations in specific oncogenes and tumor suppressors. B-HCA and b-IHCA are strongly associated with HCC transformation. Benign hepatocellular tumors can be classified using immunohistochemistry (LFABP, CRP, GS, b-catenin). Analysis of HCA phenotypes has led to the identification of patients at risk of HCC transformation and therefore improved the indications provided by invasive and non-invasive diagnostic techniques, such as biopsies and MRI. These recent advances have broadened the clinical scope of HCA in various conditions, such as their presence in males, in obese patients, in patients suffering from liver vascular disorders, genetic diseases. However, specific immunohistochemistry has shown limitations particularly for the identification of b-HCA, thereby, outlining the importance of molecular studies to improve the diagnosis/prognosis of HCA. If evaluation of prognosis and treatment has benefited from these advances, much more needs to be done to obtain guidelines for good clinical practice.

Long-term follow-up after resection of thyroid metastases from hepatocellular carcinoma in noncirrhotic liver

Thyroid metastasis from hepatocellular carcinoma (HCC) is rare, and has poor prognosis. We report the case of a 62-year-old woman seen at our clinic because of the occurrence of a slightly painful abdominal mass. At that time, alpha-fetoprotein concentration was very high, reaching 49,831.7 ng/mL. Abdominal ultrasound showed a heterogeneous mass in segment IV of the liver, which was diagnosed as HCC upon MRI. The patient underwent surgical resection and histological analysis of the specimen confirmed HCC. Metastases to the thyroid were detected 17 months after liver resection. Although the presence of metastases indicates advanced disease, thyroidectomy was performed, since no other distant metastases were detected. In fact, the patient is doing well 3 years after thyroidectomy and regular imaging exams showed no tumor recurrence. Current alpha-fetoprotein concentration is 8 ng/mL. In conclusion, thyroid metastasis from HCC is uncommon and short-term survival is expected. However, surgical resection should be encouraged, especially in the case of solitary metastases.

The use of AFP and DCP as serum biomarkers to differentiate between hepatocellular carcinoma and intrahepatic cholangiocarcinoma in non-cirrhotic livers.

e15162 Background: Differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) can be challenging in patients without evidence of liver cirrhosis. Definitive diagnosis is based on tissue biopsy. We investigated if the use of serum biomarkers could help differentiate between these two types of malignancies, thereby avoiding the risks associated with biopsy. Methods: Patients with cholangiocarcinoma and HCC were recruited from Queen Elizabeth Hospital, Birmingham, UK; blood samples were collected at time of diagnosis. Two biomarkers, alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were measured in the serum samples from 56 patients with cholangiocarcinoma and 35 patients with HCC without evidence of liver cirrhosis. Of the 56 patients with cholangiocarcinoma, 17 were intrahepatic and 39 were extrahepatic. Results: 17 ICC and 35 HCC were included in the analysis. The levels of AFP and DCP were much higher in HCC as compared to ICC. The median AFP was 64.6 (IQR 10.9, 3564.2) in HCC as compared to 3 (IQR 2.4, 3.9) in ICC. Similarly, the median DCP was 215.41 (IQR 22.46, 692.53) in HCC as compared to 0.33 (IQR 0.16, 1.08) in ICC. Stepwise logistic regression was performed using both biomarkers. Log- DCP remained significant at 95% level in predicting HCC from ICC, giving an AUC of 0.96. Conclusions: In patients with a non-cirrhotic liver and radiological evidence of cancer, measurement of serum AFP and DCP level may help differentiate between HCC and ICC. In this study, DCP is the most useful discriminator between HCC and ICC. Further prospective studies should be done with larger sample sizes to validate the use of AFP and DCP as diagnostic biomarkers in this clinical setting.

Etiologic influence on chromosomal aberrations in European hepatocellular carcinoma identified by CGH

Previous studies suggest different pathways in the molecular development of hepatocellular carcinoma (HCC). We investigated the pattern of chromosomal imbalances in HCC depending on the type of underlying liver disease as detected by comparative genomic hybridization in 67 cases of primary HCC occurring in non-cirrhotic livers (n=30), in liver cirrhosis (LC) related to alcohol intake (n=9), cryptogenic or metabolic changes (n=11), and chronic viral hepatitis B or C (n=17). HCC were treated by liver resection in 48 patients and transplantation in 19 patients. The 10-year disease-free and overall survival rates were 51% and 68%, respectively. The copy number changes occurring in more than 10% of cases were gains at 8q (55%), 1q (49%), 7q (15%), 7p (13%), 6p (12%), and 20q (12%), as well as losses at 8p (55%), 4q (33%), 6q (33%), 13q (25%), 14q (24%), 17p (22%), 16q (19%), 1p (18%), 18q (16%), 9p (13%), 10q (13%), 4p (12%), and 9q (12%). HCC arising in alcoholic LC showed a different pattern with significantly fewer net changes (p=0.008), particularly fewer chromosomal gains (p=0.008) and fewer breakpoints (p=0.003) compared to the other investigated HCC subgroups. Future clinical studies should evaluate the prognostic relevance of these findings.

Non‐alcoholic fatty liver disease contributes to hepatocarcinogenesis in non‐cirrhotic liver: A clinical and pathological study

Hepatocellular carcinoma (HCC) is a major complication of cirrhosis and has been increasing in incidence in recent years. Fatty liver disease is an increasingly common cause of chronic liver disease, and there have been several case reports of HCC in patients with non-cirrhotic fatty liver disease. However, there is limited data from systematic studies with histological confirmation of the presence of both the HCC and the non-cirrhotic fatty liver disease. We studied the occurrence of fatty liver disease and the associated demographic, clinical, and pathological characteristics of a large cohort of patients with HCC in non-cirrhotic livers. Patients with intrahepatic cholangiocarcinoma (CC) occurring in non-cirrhotic livers and diagnosed during the same time period were used as the comparison group. Significant steatosis in the nontumor liver had a statistically significant association with HCC, being present in 54% (85/157) of HCC compared with 27% (32/120) of CC (P < 0.0001). Steatohepatitis was present in 15% (24/157) of HCC and 1% (2/120) of CC (P = 0.0014). Furthermore, HCC was more prevalent in cases with higher grades of steatosis. In addition, the recently described intratumoral steatohepatitic morphology of HCC (SH-HCC) was also associated with significant steatosis in nontumor liver, with significant steatosis being present in 89% with SH-HCC compared with 50% without SH-HCC (P = 0.0162). Finally, SH-HCC was increasingly more prevalent in patients with higher grades of nontumor steatosis. Taken together, these findings suggest a strong association between fatty liver disease and HCC in non-cirrhotic livers.

Lack of correlation between the antibody to hepatitis B core antigen and survival after surgical resection for hepatitis C virus-related hepatocellular carcinoma

The impact of antibodies to hepatitis B core antigen (anti-HBc) on survival after curative surgical resection (SR) for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to examine the relationship between anti-HBc positivity and survival of HCV-related HCC patients who underwent curative SR. A total of 222 patients with HCV-related, hepatitis B surface antigen (HBsAg)-negative HCC who underwent curative SR were analyzed. They included 119 anti-HBc-positive patients (53.6%) and 103 anti-HBc-negative patients (46.4%). Overall survival (OS) and recurrence-free survival (RFS) rates were compared between the two groups. The median follow-up periods in the anti-HBc-positive and anti-HBc-negative groups were 3.4 years (range, 0.3-10.9 years) and 3.2 years (range, 0.5-10.9 years), respectively. The 1-, 3- and 5-year cumulative OS rates were 88.8, 70.2 and 50.0%, respectively, in the anti-HBc-positive group and 95.8, 77.1 and 61.7% in the anti-HBc-negative group (P=0.300). The corresponding RFS rates were 68.7, 33.0 and 20.0%, respectively, in the anti-HBc-positive group and 74.4, 38.5 and 16.5% in the anti-HBc-negative group (P=0.482). Multivariate analyses identified serum albumin ≥3.8 g/dl (P=0.005) and the presence of microvascular invasion (P<0.001) as independent factors linked to OS, and interferon therapy after surgery (P=0.011), α-fetoprotein ≥40 ng/ml (P=0.030) and the presence of microvascular invasion (P<0.001) were significant predictors linked to RFS. In subgroup analyses according to maximum tumor size and background liver disease in terms of OS and RFS, no significant difference between the anti-HBc-positive and anti-HBc-negative groups was observed except in patients with non-cirrhotic liver in terms of RFS. In conclusion, anti-HBc-positivity is not a useful predictor for survival of patients with HCV-related HCC after curative SR.

Does the cost of care differ for patients with fee-for-service vs. capitation of payment? A case–control study in gastroenterology

There is growing evidence to demonstrate overuse of medical resources in fee for service (FFS) payment models (in which physicians are reimbursed according to volume of care provided) compared to capitation payment models (in which physicians receive a fixed salary regardless of level of care provided). In this medical centre, patients with and without insurance are admitted through the same access point (emergency room) and cared for by the same physicians. Therefore, apart from insurance status, all other variables influencing delivery of care are similar for both patient groups. However, physician reimbursement differs for both groups: FFS for patients with private insurance (i.e. the admitting physician's reimbursement escalates progressively with each day that the patient spends in hospital) and base salary irrespective of care provided for patients with universal insurance (capitation payment model). All admitting physicians are aware of the patient's insurance status and the duration of hospitalization is at the discretion of the admitting physician. This study aimed to compare cost of care of patients with and without insurance admitted to a teaching hospital with a primary gastroenterology or hepatology (GIH) diagnosis. All hospital inpatients admitted between January 2008 and December 2009 with a primary GI-related diagnosis related group (DRG) were identified. Patients were classified as uninsured (state-funded) or privately insured. Only DRGs with at least five patients in both the insured and uninsured patient groups were analyzed to ensure a precise estimate of inpatient costs. Patient level costing (PLC) was used to express the total cost of hospital care for each patient; PLC comprised a weighted daily bed cost plus cost of all medical services provided (e.g. radiology, pathology tests) calculated according to an activity-based costing approach, cost of medications were excluded. An overall mean cost of care per patient was calculated for both groups. All costs were discounted to 2009 values. In total, 630 patients were admitted with one of 11 GIH DRGs, 181 (29 %) with private insurance. Pooled mean cost of care was higher for uninsured (6,781 euros/patient) compared to insured patients (6,128 euros/patient). Apart from patients with 'non-cirrhotic non-alcoholic liver disease (non-complex)' in whom mean cost was higher for insured patients, there were no significant differences in mean cost of care nor mean patient age for insured and uninsured groups for any other diagnoses. Inpatient hospital costs were equivalent for patients with and without private health insurance when care was provided in a single hospital. Provision of care for all patients in a common hospital setting regardless of health insurance status may reduce disparities in healthcare utilization.

Liver disease and 30-day mortality after colorectal cancer surgery: a Danish population-based cohort study

BackgroundColorectal cancer (CRC) is common, with surgery as the main curative treatment. The prevalence of chronic liver disease has increased, but knowledge is limited on postoperative mortality in patients with liver disease who undergo CRC surgery. Hence, we examined 30-day mortality after CRC surgery in patients with liver disease compared to those without liver disease.MethodsWe used medical databases to conduct a nationwide cohort study of all patients undergoing CRC surgery in Denmark from 1996 through 2009. We further identified patients diagnosed with any liver disease before CRC surgery and categorized them into two cohorts: patients with non-cirrhotic liver disease and patients with liver cirrhosis. Patients without liver disease were defined as the comparison cohort. Using the Kaplan-Meier method, we computed 30-day mortality after CRC surgery in each cohort. We used a Cox regression model to compute hazard ratios as measures of the relative risk (RR) of death, controlling for potential confounders including comorbidities. In order to examine the impact of liver disease in different subgroups, we stratified patients by gender, age, cancer stage, cancer site, timing of admission, type of surgery, comorbidity level, and non-hepatic alcohol-related disease.ResultsOverall, 39,840 patients underwent CRC surgery: 369 (0.9%) had non-cirrhotic liver disease and 158 (0.4%) had liver cirrhosis. Thirty-day mortality after CRC surgery was 8.7% in patients without liver disease and 13.3% in patients with non-cirrhotic liver disease (adjusted RR of 1.49 95% confidence interval (CI): 1.12-1.98). Among patients with liver cirrhosis, mortality was 24.1%, corresponding to an adjusted RR of 2.59 (95% CI: 1.86-3.61). The negative impact of liver disease on postoperative mortality was found in all subgroups.ConclusionsPre-existing liver disease was associated with a markedly increased 30-day mortality following CRC surgery.

Immunohistochemical characteristics of hepatocellular carcinoma in non-cirrhotic livers

Hepatocellular carcinoma (HCC) typically develops in cirrhotic livers. In the absence of risk factors, for example, cirrhosis or hepatitis B or C virus infection, HCC diagnosis might be difficult. We...

Ecografía Con Contraste Intravenoso Para El Diagnóstico De Las Lesiones Focales En El Contexto Del Hígado No Cirrótico: Análisis Costo-Beneficio

To assess the cost-effectiveness of intravenous contrast enhanced ultrasonography (CEUS) in the diagnosis of focal lesions in the context of non-cirrhotic liver, taking into account the subsequent need to supplement with other methods, computed tomography (CT) or magnetic resonance (MRI).

Increased Alpha-Fetoprotein Serum Level is Predictive for Survival and Recurrence of Hepatocellular Carcinoma in Non-Cirrhotic Livers

Background: Hepatocellular carcinoma (HCC) may be diagnosed in the absence of cirrhosis. However, little is known about prognostic factors for the survival of HCC patients with a non-cirrhotic liver in the absence of well-established risk factors. Method: Survival rates and risk factors for survival and recurrence were analysed in all patients diagnosed between 2000 and 2010 with HCC in a non-cirrhotic liver and in the absence of well-established risk factors. Results: Ninety-four patients were analysed. Treatment with curative intent consisted of surgical resection in 43 patients (46%) and radiofrequency ablation in 4 patients (4%). In patients treated with curative intent and alive 30 days after treatment (n = 40), 1- and 5-year overall survival rates were 95 and 51%, respectively. Patients with a high preoperative α-fetoprotein (AFP) serum level, the presence of microvascular invasion in the resected specimen, a complicated postoperative course and a major resection, due to a greater tumour volume, had a significantly worse outcome and a higher recurrence rate. In multivariate analysis, a high AFP serum level at presentation was significantly associated with recurrence and a worse survival. Conclusion: HCC presenting in a non-cirrhotic liver in the absence of well-established risk factors has a poor prognosis. Increased AFP serum levels are significantly associated with clinical outcome.

Lin's clamp revisited: A safe model for training in liver resection

In 1973, Lin described a simplified technique of hepatic resection using his clamp and crush method. It allowed regional vascular control to reduce blood loss during parenchymal transection. This technique was aimed at avoiding hilar dissection and vascular clamping, thereby preventing ischemic–reperfusion injury of the remnant liver. The objective of our study is to report our experience with Lin's technique and discuss its applicability. The perioperative outcomes of patients who underwent hepatic resection with or without Lin's technique were analyzed. Multiple variables were also used to statistically compare outcomes between patients with a cirrhotic liver and a noncirrhotic one and results of performance by junior surgeons (JSs) and an experienced surgeon (ES). The perioperative outcome in patients undergoing hepatectomy with Lin's technique ( N = 18) showed a significantly shorter transection time, lower blood loss, and shorter hospital stay as compared with patients undergoing hepatectomy without Lin's clamp ( N = 17). Lin's technique was adopted in 29 patients. Eleven and 18 cases were operated on by the JSs and ES, respectively. The transection time was significantly longer in the JS group. Thirteen patients had a noncirrhotic liver whereas 16 patients had cirrhosis. There was no statistically significant difference in the perioperative outcomes between cases operated on by the JS and ES and between cases of patients with cirrhosis and those without cirrhosis. There was no incidence of hepatic failure within 90 days. Lin's technique offers less blood loss, a shorter transection time, and a shorter hospital stay. The application of Lin's technique avoids the need for hilar vascular isolation and hilar clamping. JSs can perform hepatectomy with outcomes comparable to those produced by ESs by applying Lin's technique.

Virtual laparoscopy: Initial experience with three-dimensional ultrasonography to characterize hepatic surface features

ObjectiveTo examine the potential utility of 3D-reconstructed sonograms to distinguish cirrhotic from non-cirrhotic livers by demonstrating hepatic surface characteristics. Materials and methodsA preliminary phantom study was performed to examine the potential resolution of 3D images, recognizing surface irregularities as a difference in height. In a prospective clinical study of 31 consecutive patients with ascites (21 cirrhosis, 10 non-cirrhosis), liver volume data were acquired by transabdominal mechanical scanning. The hepatic surface features of cirrhotic and non-cirrhotic patients were compared by 2 independent reviewers. Intra- and inter-operator/reviewer agreements were also examined. ResultsThe phantom study revealed that 0.4mm was the minimum recognizable difference in height on the 3D sonograms. The hepatic surface image was successfully visualized in 74% patients (23/31). Success depended on the amount of ascites; visualization was 100% with ascites of 10mm or more between the hepatic surface and abdominal wall. The images showed irregularity of the hepatic surface in all cirrhotic patients. The surface appearance was confirmed as being very similar in 3 patients who had both 3D sonogram and liver resection for transplantation. The ability to distinguish cirrhotic liver from non-cirrhotic liver improved with the use of combination of 2D- and 3D-imaging versus 2D-imaging alone (sensitivity, p=0.02; accuracy, p=0.02) or 3D-imaging alone (sensitivity, p=0.03). Intra-/inter-operator and inter-reviewer agreement were excellent (κ=1.0). Conclusion3D-based sonographic visualization of the hepatic surface showed high reliability and reproducibility, acting as a virtual laparoscopy method, and the technique has the potential to improve the diagnosis of cirrhosis.

Primary liver sarcomatous carcinoma: Report of two cases and review of the literature

Primary liver sarcomatous carcinomas (PLSCs) are very aggressive tumors. They are characterized by a fast clinical course, and therefore need a prompt histological diagnosis.Here, we report two cases of PLSC. One arises in a non-cirrhotic liver and the other in cirrhosis, with differences in onset and histological features. Special emphasis is put on the expression of albumin and HCC markers, and their possible usefulness in the diagnosis. The English literature of the last 20 years was revised (92 cases).Immunohistochemistry was performed manually or automatically; in situ hybridization (ISH) technique for albumin mRNA detection was carried out.The sarcomatoid components in both cases were immunoreactive for K8/18, Glutamine Synthetase and EZH2, and negative for Glypican 3, SMA, caldesmon, desmin, DOG-1, CD34, CD31, CD117, CD56, and alpha-fetoprotein. The detection of albumin mRNA by ISH was negative in the sarcomatoid component in both cases.PLSC represents a diagnostic challenge for pathologists, especially in its “pure” form: neither albumin mRNA detection nor HCC markers are useful for the diagnosis: positivity for K8/18 and the negativity for the mesenchymal markers seem to represent the main tools for the histological diagnosis.

Cholangitis and multiple liver abscesses after percutaneous ethanol injection (PEI) for recurrent hepatocellular carcinoma (HCC)

Percutaneous ablation procedures are minimally invasive treatments for unresectable early stage hepatocellular carcinoma (HCC). These techniques are usually safe, but rare and even fatal complications have been described. We present a fatal result after percutaneous ethanol injection (PEI) for the treatment of a recurrent HCC in a non-cirrhotic liver, with subsequent development of diffuse cholangitis and multiple liver abscesses. Although percutaneous drainage and intensive antibiotic treatment were employed, the patient finally died. We discuss about the etiology and the physiopathology of this rare complication in which the therapeutic options are limited and usually unsuccessful.

Molecular and metabolic changes in human liver clear cell foci resemble the alterations occurring in rat hepatocarcinogenesis

Activation of the AKT/mTOR and Ras/MAPK pathways and the lipogenic phenotype occurs in both a rat model of insulin-induced hepatocarcinogenesis and in human hepatocellular carcinoma (HCC). In the rat model, activation of these pathways is evident within the earliest morphologic detectable alterations, i.e., clear cell foci (CCF) of altered hepatocytes. CCF have also been described in the human liver, but molecular and metabolic alterations within these foci remain to be determined. A collection of human liver specimens was examined using electron microscopy, histology, enzyme- and immunohistochemistry, and molecular analysis. Human data were compared to rat preneoplastic CCF and HCC induced by N-nitrosomorpholine administration. CCF occurred in ∼33% of extrafocal tissues of human non-cirrhotic livers. Electron microscopy showed massive glycogen storage within CCF, largely due to the reduced activity of the glycogenolytic enzyme glucose-6-phosphatase. Hepatocytes in CCF overexpressed the insulin receptor and glucose transporter proteins. AKT/mTOR and Ras/MAPK pathways as well as enzymes of glycolysis, de novo lipogenesis, beta-oxidation, and cholesterol synthesis were upregulated, both in human CCF, and in CCF and HCC of N-nitrosomorpholine-treated rats. The Ki-67 proliferation index was 2-fold higher in human CCF than in extrafocal tissue. The high degree of similarity between human CCF and pre-neoplastic lesions from experimental models of hepatocarcinogenesis in terms of morphologic, molecular and metabolic features suggests a low-grade dysplastic nature of these lesions in human non-cirrhotic livers.