Hepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis.

Chronic hepatitis C virus (HCV) infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even "similar" causes, such as hepatitis B virus- (HBV-) related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.

Proteasome inhibitors: possible novel therapeutic strategy for ischemia-reperfusion injury?

INTRODUCTION: The ubiquitin-proteasome system (UPS) is responsible for the degradation of misfolded or damaged proteins, regulating inflammatory processes and cell cycle progression. The aim of this article is to summarize the currently available data regarding the possible utility of proteasome inhibitors (PIs) in the treatment of ischemia-reperfusion injury (IRI). AREAS COVERED: Data were reviewed from the published literature using the Medline database. The effect of PIs on IRI is dependent on the dosage, time of administration (prior to or post IRI induction), the affected organ, and the experimental model used. Undoubtedly, in most cases PIs' application resulted in attenuated IRI, although it was uniformly shown that inhibition of the UPS prior to ischemic preconditioning (IPC) abolished the protective effect of IPC in IRI. Mechanism of action involves several pathways, including nuclear factor kappa-B (NF-κB) inactivation, antineutrophil action, decreased intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression, and the cytoprotective proteins eNOS, heme oxigenase 1 and hsp70 up-regulation. EXPERT OPINION: Current data are limited, but appear promising with regard to PI consideration as an effective future therapeutic strategy for IRI. Nevertheless, further investigation is required in terms of safety and validation of the appropriate for each agent dosage, in order to establish their possible contribution in human IRI.

Synchronous primary epithelial tumors of the pancreas.

INTRODUCTION: Pancreatic incidentalomas are diagnosed at increased rates due to advanced pancreatic imaging. Coexistence of such lesions with another pancreatic pathology, however, is uncommon and their management might be perplexed by the anatomical location and the histological features of the lesion. PRESENTATION OF CASE: A patient with obstructive jaundice was diagnosed with adenocarcinoma of the pancreatic head and underwent routine pancreatic imaging (CT) which revealed the coexistence of a small cystic lesion at the pancreatic body. Further investigation with MRCP and ERCP was unable to confirm a benign lesion and total pancreatoduodenectomy was performed. Histological examination showed a rare type of mixed serous-mucinous cystadenoma of borderline malignancy at the pancreatic body coexistent with an adenocarcinoma of the pancreatic head. DISCUSSION: Coexistence of a peripheral pancreatic cystic tumor with a ductal adenocarcinoma of the pancreatic head is a very rare incidence in medical literature. The management of the peripheral lesion is not straightforward and there can be uncertainty as to the extent of the pancreatic resection that may be required. CONCLUSION: Appropriate preoperative imaging has a significant impact on the definitive management of synchronous pancreatic tumors. Implications of a common pathogenetic pathway are also raised for this rare occurrence of two primary epithelial pancreatic tumors.

Surgical control of life-threatening post-ERCP bleeding with a gelatin matrix-thrombin hemostatic agent.

INTRODUCTION: Several conventional techniques have been developed in order to control surgical bleeding. Their greatest disadvantage, though, is their inability to control bleeding in areas where access is very difficult. In such cases the application of topical hemostatic agents may prove particularly useful. PRESENTATION OF CASE: We describe the case of an 82-year old patient with life-threatening post-ERCP bleeding which was intraoperatively controlled with infusion of a topical gelatin matrix-thrombin hemostatic agent into the distal portion of the common bile duct. DISCUSSION: Most iatrogenic cases of post-ERCP bleeding occur at the site of sphincterotomy at the level of the ampulla of Vater and may be relatively easily controlled by repeat endoscopy and local hemostatic measures. More rarely, however, significant and difficult to control bleeding may occur within the lower portion of the common bile duct (CBD) where routine hemostatic techniques may prove unsuccessful. Under these circumstances, we successfully employed a novel hemostatic technique using a gelatin matrix-thrombin agent in a patient with life-threatening bleeding after ERCP. CONCLUSION: This novel technique might prove particularly useful for bleeding control in surgically challenging anatomical areas such as the lower portion of the CBD.

Current treatment for colorectal liver metastases.

Surgical resection offers the best opportunity for survival in patients with colorectal cancer metastatic to the liver, with five-year survival rates up to 58% in selected cases. However, only a minority are resectable at the time of diagnosis. Continuous research in this field aims at increasing the percentage of patients eligible for resection, refining the indications and contraindications for surgery, and improving overall survival. The use of surgical innovations, such as staged resection, portal vein embolization, and repeat resection has allowed higher resection rates in patients with bilobar disease. The use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Ablative techniques have gained wide acceptance as an adjunct to surgical resection and in the management of patients who are not surgical candidates. Current management of colorectal liver metastases requires a multidisciplinary approach, which should be individualized in each case.

Barrett's esophagus with high-grade dysplasia: focus on current treatment options.

High-grade dysplasia (HGD) in Barrett's esophagus (BE) is the critical step before invasive esophageal adenocarcinoma. Although its natural history remains unclear, an aggressive therapeutic approach is usually indicated. Esophagectomy represents the only treatment able to reliably eradicate the neoplastic epithelium. In healthy patients with reasonable life expectancy, vagal-sparing esophagectomy, with associated low mortality and low early and late postoperative morbidity, is considered the treatment of choice for BE with HGD. Patients unfit for surgery should be managed in a less aggressive manner, using endoscopic ablation or endoscopic mucosal resection of the entire BE segment, followed by lifelong surveillance. Patients eligible for surgery who present with a long BE segment, multifocal dysplastic lesions, severe reflux symptoms, a large fixed hiatal hernia or dysphagia comprise a challenging group with regard to the appropriate treatment, either surgical or endoscopic.

Global financial crisis and surgical practice: the Greek paradigm.

Apart from the significant implications of recent financial crisis in overall health indices and mortality rates, the direct effect of health resources redistribution in everyday clinical practice is barely recognized. In the case of Greece, health sector reform and health spending cuts have already had a major impact on costly interventions, particularly in surgical practice. An increase in utilization of public health resources, lack of basic and advanced surgical supplies, salary deductions, and emerging issues in patient management have contributed to serious dysfunction of a public health system unable to sustain current needs. In this context, significant implications arise for the surgeons and patients as proper perioperative management is directly affected by reduced public health funding. The surgical community has expressed concerns about the quality of surgical care and the future of surgical progress in the era of the European Union. Greek surgeons are expected to support reform while maintaining a high level of surgical care to the public. The challenge of cost control in surgical practice provides, nevertheless, an excellent opportunity to reconsider health economics while innovation through a more traditional approach to the surgical patient should not be precluded. A Greek case study on the extent of the current situation is presented with reference to health policy reform, serving as an alarming paradigm for the global community under the pressure of a profound financial recession.

Eph-A2 and Eph-A4 expression in human benign and malignant thyroid lesions: an immunohistochemical study.

BACKGROUND: Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, metastasis and angiogenesis. The aim of the present study was to evaluate the clinical significance of Eph-A2 and Eph-A4 expression in human benign and malignant thyroid lesions. MATERIAL/METHODS: Eph-A2 and Eph-A4 protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 131 patients with benign and malignant lesions. RESULTS: Eph-A2 was significantly overexpressed in malignant compared to benign thyroid lesions (p<0.001). Papillary carcinoma cases presented significantly increased Eph-A2 expression compared to those with hyperplasia nodules (p<0.001). Eph-A4 expression was not differentiated between cases with malignant or benign thyroid lesions. Papillary carcinoma cases presented significantly increased Eph-A4 expression compared to those with hyperplasia nodules (p=0.006). In the subgroup of malignant thyroid lesions, Eph-A2 and Eph-A4 expression was not associated with TNM stage, capsular, lymphatic or vascular invasion. CONCLUSIONS: The present data suggest that Eph-A2, but not Eph-A4, overexpression may be associated with the malignant transformation of thyroid neoplasia. Further studies conducted on cohorts including a higher proportion of patients with advanced nodal and metastatic disease are recommended to draw definite conclusions on the clinical significance of Eph proteins in thyroid neoplasia.

Nonmelanoma skin cancer after renal transplantation: a single-center experience in 1736 transplantations.

BACKGROUND: Renal transplantation is associated with an increased incidence of nonmela-noma skin cancer (NMSC) caused by immunosuppression. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), the two major histological types of NMSC, exhibit more aggressive biological and clinical courses in renal transplant recipients (RTRs), with higher rates of recurrence and mortality than in the general population. METHODS: We retrospectively analyzed our experience of NMSC in 1736 renal transplantations performed over a 25-year period. All cases of skin cancer after renal transplantation were included except those of skin cancer resulting from melanoma and mesenchymal skin tumors. RESULTS: In our series, the overall incidence of NMSC after transplantation was 2.2% (n = 39), and SCC represented the most frequent skin malignancy (64.1%), followed by BCC (17.9%), Bowen's disease (10.2%), basosquamous carcinoma (5.1%), and a rare case of invasive sebaceous carcinoma (2.6%). A shift to newer immunosuppressive regimens after the initial diagnosis of NMSC had been implemented in eight cases (20.5%). The recurrence rate after initial treatment was 41% (n = 16), and distant metastatic disease was diagnosed in 15.4% (n = 6) of NMSC patients. The NMSC-specific mortality rate was 25.6% (n = 10). CONCLUSIONS: Nonmelanoma skin cancer remains a significant source of morbidity and mortality in RTRs, and post-transplant surveillance should be increased.

Platelet-activating factor in liver injury: a relational scope.

The hepatocyte, the main cellular component of the liver, exhibits variable susceptibility to different types of injury induced by endogenous or exogenous factors. Hepatocellular dysfunction or death and regeneration are dependent upon the complicated interactions between numerous biologically active molecules. Platelet-activating factor (PAF) seems to play a pivotal role as the key mediator of liver injury in the clinical and experimental setting, as implied by the beneficial effects of its receptor antagonists. A comprehensive up-to-date overview of the specific functional and regulatory properties of PAF in conditions associated with liver injury is attempted in this review.