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In major hepatectomies performed under SHVE, ischemic preconditioning appears to attenuate apoptotic response of the liver remnant, possibly through alteration of inflammatory and oxidative pathways.

Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF.14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n57), which received post-operative intravenous infusion of DFX (14.5 mg?kg ?h -1 until completion of 24 h), and a control group (n57). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A 2 activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA 2 , platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals.DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA 2 and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and prevents alveolar space collapse.

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Objective: GHRH is secreted by the hypothalamus and, upon binding to specific GHRH receptors in the pituitary, stimulates growth hormone (GH) production and release from the pituitary. In addition to this neuroendocrine action, accumulated evidence implies additional roles for GHRH in carcinogenesis in non-pituitary tissues. In vitro and in vivo studies have shown that splice variant 1 (SV1) of the GHRH receptor, which is widely expressed in non-pituitary tissues and cancers, can mediate the proliferative effects of GHRH. The aim of the present study was to investigate the operation of an autocrine stimulatory loop between GHRH and SV1 in primary breast tumors. Design: Fifty-three primary breast tumors were evaluated for GHRH and SV1 expression. Methods: Expression of GHRH and SV1 was assessed by immunohistochemistry using anti-GHRH SV95 and anti-SV1 2317/5 polyclonal antibodies. Results: About 40% of the specimens tested express GHRH and/or SV1 (approx. 25% each), while in 35% of these positive specimens co-expression of these antigens was detected (P , 0.01). Furthermore, a correlation of GHRH, but not SV1, expression was detected in lobular compared with ductal carcinomas. Conclusions: These results constitute the first demonstration for the expression of GHRH and SV1 in primary breast cancers, and provide evidence for the operation of an autocrine stimulatory loop between GHRH and SV1 in primary cancers. Our findings indicate that GHRH analogs could have diagnostic and therapeutic applications for the management of breast cancer.European Journal of Endocrinology 151 391-396

We present a 57-year-old man with Zollinger-Ellison syndrome who had undergone total gastrectomy 12 years previously. At that time, a cystic mass in the left lobe of the liver was palpated but was not removed. The patient currently had high serum gastrin levels. Abdominal ultrasound, CT and MR images showed a well defined liver mass with solid and cystic components. The lesion was resected and a primary hepatic carcinoid tumour was diagnosed. Post-operatively, serum gastrin levels were normal. A primary liver carcinoid may appear as multicystic liver mass with solid components. Careful exclusion of a primary tumour elsewhere is required to establish the diagnosis of this rare entity.

Liver resections are frequently associated with significant ischemia-reperfusion (I-R) injury of the liver remnant. The aim of this study was to investigate whether deferoxamine (DFO) can ameliorate I-R injury during major hepatectomies performed under vascular exclusion of the liver in a porcine model. Twelve female domestic pigs were divided into control (n = 6) and DFO treatment (n = 6) groups and subjected to 150 min. liver ischemia followed by 70% hepatectomy and 24 hours reperfusion. Pigs in the DFO group received a continuous intravenous infusion of 100 mg/kg DFO. Liver remnant injury was evaluated by liver function tests, hepatic histology as well as serum and liver tissue malondialdehyde (MDA) concentrations. Deferoxamine-treated animals had reduced total bilirubin, gamma-glutamyl transferase and ammonia levels as well as hepatocyte necrosis and oxidative injury. In a subsequent randomized clinical trial using DFO for I-R protection during major liver surgery, preliminary results revealed amelioration of hepatocellular damage, oxidative and inflammatory serum markers and apoptotic response in liver remnant biopsies.

In an experimental pig model that combines liver resection with prolonged ischemia, iron chelation during reperfusion of the remnant liver is associated with improvement of several parameters of oxidative stress, lung injury and arterial oxygenation.