Liver perivascular epithelioid cell tumor in a patient with systemic lupus erythematosus.

INTRODUCTION: Perivascular epithelioid cell tumor (PECOMA) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers showing a benign course,although malignant tumors have also been reported. To date there are approximately 33 cases of published hepatic pecomas. PRESENTATION OF CASE: We describe a 47-year-old man with a 27-year past medical history of systemic lupus erythematosus (SLE) who underwent left liver lobectomy due to a liver pecoma. His postoperative course complicated with infection, thrombosis of hepatic artery and liver ischemia as well as drug fever. DISCUSSION: Treatment protocol especially for hepatic PECOMA has not reached a consensus although surgical resection is the preferred therapy. CONCLUSION: This is the first case of coexistence of liver pecoma and SLE.

Pancreatic resection for renal cell carcinoma metastasis: An exceptionally rare coexistence.

INTRODUCTION: Pancreatic metastases are uncommon and only found in a minority of patients with widespread metastatic disease at autopsy. The most common primary cancer site resulting in pancreatic metastases is the kidney, followed by colorectal cancer, melanoma, breast cancer, lung carcinoma and sarcoma. PRESENTATION OF CASE: Herein, we report a 63-year-old male patient who presented -3.5 years after radical nephrectomy performed for renal cell carcinoma (RCC)-with a well-defined lobular, round mass at the body of the pancreas demonstrated by abdominal Magnetic Resonance Imaging (MRI). The patient underwent distal pancreatectomy combined with splenectomy and cholecystectomy. Histopathological examination revealed clusters of epithelial clear cells, immunohistochemically positive for RCC marker, and negative for CD10 and CA19-9. A final diagnosis of clear RCC metastasizing to pancreas was obtained in view of the past history of RCC, microscopy and the immunoprofile. This was the second metachronous disease recurrence after a previous metastatic involvement of the liver, developed 19 months from the initial diagnosis. The patient has remained well at a 6 month follow up post-resection. DISCUSSION: Solitary pancreatic metastases may be misdiagnosed as primary pancreatic cancer. However, imaging including computed tomography (CT) and MRI, may discriminate between them. Surgical procedures could differentiate solitary metastasis from neuroendocrine neoplasms. The optimal resection strategy involves adequate resection margins and maximal tissue preservation of the pancreas. CONCLUSION: Recently, an increasing number of surgical resections have been performed in selected patients with limited metastatic disease to the pancreas. In addition, a rigid follow-up scheme, including endoscopic ultrasound (EUS) and CT is essential give patients a chance for a prolonged life.

Glycine maintains mitochondrial activity and bile composition following warm liver ischemia-reperfusion injury.

BACKGROUND AND AIM: Experimental studies have shown protective effect by the non-essential amino acid glycine to liver ischemia-reperfusion (I/R) injury but the mechanism of action is unknown. METHODS: A rabbit model of hepatic lobar I/R was used. Three groups of animals (n=6) were studied: Sham group (laparotomy alone), ischemia reperfusion (I/R) group (1 h of liver lobar ischemia and 6 h of reperfusion), and a glycine I/R group (intravenous glycine 5 mg/kg prior to the I/R protocol). Systemic and hepatic hemodynamics, degree of liver injury (bile flow, transaminases), hepatic microcirculation, mitochondrial activity (redox state of cytochrome oxidase), bile composition and cytokines (tumor necrosis factor-α and interleukin-8) were measured during the experiment. RESULTS: Glycine administration increased portal blood flow, bile production, hepatic microcirculation and maintained cytochrome oxidase activity as compared with the I/R group during reperfusion. Glycine also reduced bile lactate surge and stimulated acetoacetate release in bile during reperfusion versus the I/R group. Cytokine levels (tumor necrosis factor-α, interleukin-8) and hepatocellular injury (aspartate aminotransferase and alanine aminotransferase) were significantly reduced by glycine administration. CONCLUSION: Intravenous glycine administration reduces liver warm I/R injury by reducing the systemic inflammatory response, and maintaining cellular energy production.

Intracellular oxygenation and cytochrome oxidase C activity in ischemic preconditioning of steatotic rabbit liver.

BACKGROUND: Mild to moderate steatotic livers are used as marginal donors in liver transplantation. Very little is known about the mechanisms of ischemia reperfusion (IR) injury (IRI) in fatty liver. This study aimed to establish whether cytochrome oxidase C (COX) activity is compromised by IRI in fatty liver and whether ischemic preconditioning (IPC) can protect COX activity. METHODS: New Zealand rabbits were fed on a high-cholesterol diet for 8 weeks to induce moderate hepatic steatosis. Three groups were tested. The IR group underwent 60 minutes of ischemia, followed by 7 hours of reperfusion. The IPC group (IPC + IR) underwent 5 minutes of ischemia, followed by 10 minutes of reperfusion and then 60 minutes of ischemia and 7 hours of reperfusion. The control group (sham) underwent the same surgical procedure, but ischemia was not induced. Deoxyhemoglobin, oxyhemoglobin, and change in the redox state of COX was continuously monitored in vivo by near-infrared spectroscopy. COX and citrate synthase (CS) activity assays were carried out on liver biopsy specimens in vitro. Bile was collected continuously during the procedure and analyzed using proton nuclear magnetic resonance spectroscopy. RESULTS: The IR group had decreased COX activity and tissue oxygenation represented by deoxyhemoglobin, oxyhemoglobin, COX, and elevated redox ratios of lactate/pyruvate and ß-hydroxybutarate/acetoacetate in vivo and a decrease in COX and CS activity in vitro. The IPC + IR group showed higher levels of all measured parameters in vivo and showed a smaller decrease in COX and CS activity in vitro. CONCLUSION: This study shows that IRI affects COX activity in fatty livers. This is attenuated by IPC.

The role of thiols in liver ischemia-reperfusion injury.

Thiol-containing compounds have an essential role in many biochemical reactions due to their ability to be easily oxidised and then quickly regenerated. Main representatives are glutathione, lipoic acid and thioredoxin which are synthesised de novo in mammalian cells. N-acetylcysteine and Bucillamine are synthetic thiols which have been administered in experimental and clinical studies for treatment of conditions associated with oxidative stress. Ischemia and reperfusion (I/R) injury is characterised by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. I/R occurs in a variety of clinical settings such as liver resection, organ transplantation, haemorrhagic shock with fluid resuscitation, heart surgery, myocardial infarction followed by reperfusion and laparoscopic surgery. In these circumstances, the administration of antioxidant agents such as thiols, could provide protection from the harmful effects of I/R injury. However, the ability of thiol compounds to reduce free radicals is associated with the formation of thiyl radicals and the rate and efficiency of removal of thiyl radicals has a critical effect on antioxidant or prooxidant actions of thiols in the cells. The aim of this review is to present the mechanisms by which thiols act as antioxidants and signalling molecules and the experimental and clinical evidence regarding their role in I/R injury with a particular emphasis on liver I/R. The current evidence suggests that thiols ameliorate I/R injury and that their clinical significance should be further evaluated in large scale randomised clinical trials.

N-Acetylcysteine ameliorates the late phase of liver ischaemia/reperfusion injury in the rabbit with hepatic steatosis.

Steatotic livers are highly susceptible to I/R (ischaemia/reperfusion) injury and, therefore, the aim of the present study was to evaluate the in vivo effect of NAC (N-acetylcysteine) on hepatic function in the early and initial late phase of warm liver I/R injury in steatotic rabbits. Twelve New Zealand White rabbits were fed a high-cholesterol (2%) diet. The control group (n=6) underwent lobar liver ischaemia for 1 h, followed by 6 h of reperfusion. In the treated group receiving NAC (n=6), an intravenous infusion of NAC was administered prior to and during the 6 h reperfusion period. Systemic and hepatic haemodynamics were monitored continuously. ALT (alanine aminotransferase) activity and bile production were measured. NMR spectroscopy was used to analyse bile composition. Oxidation of DHR (dihydrorhodamine) to RH (rhodamine) was used as a marker of production of reactive oxygen and nitrogen species. Moderate centrilobular hepatic steatosis was demonstrated by histology. The results showed that NAC administration significantly improved portal flow, hepatic microcirculation, bile composition and bile flow after 5 h of reperfusion. NAC administration was also associated with less hepatocellular injury, as indicated by ALT serum activity, and decreased the oxidation of DHR to RH. In conclusion, NAC administration decreased the extent of I/R injury in the steatotic liver, particularly during the late phase of reperfusion.