The effect of sorafenib on liver regeneration and angiogenesis after partial hepatectomy in rats.

BACKGROUND: Liver regeneration is vital for the survival of patients submitted to extensive liver resection as a treatment of hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor of angiogenesis and cell division, both of which are integral components of liver regeneration. We investigated the effect of preoperative treatment with sorafenib, a drug used for the treatment of HCC, on liver regeneration and angiogenesis in healthy rats, after two-thirds partial hepatectomy (PH2/3). METHODS: In total 48 Wistar rats received intragastric injections of sorafenib (30 mg/kg/d) or vehicle, underwent PH2/3, and were sacrificed at 48, 96 or 168 hours after that. The regenerative index of the liver remnant was studied, as well as the mitotic index. DNA synthesis and angiogenesis were estimated by immunohistochemistry for the Ki-67 and CD34 antigens, respectively. RESULTS: Sorafenib reduced significantly the regenerative index at all time points but not the mitotic index at 48, 96 or 168 hours. Deoxyribonucleic acid (DNA) synthesis and angiogenesis were not affected significantly either. CONCLUSIONS: Sorafenib, when administered preoperatively, reduces incompletely and transiently the regeneration of the liver after PH2/3 in rats. This could mean that sorafenib can be used as neoadjuvant treatment of patients with HCC prior to liver resection, but further experimental and clinical studies are needed to establish the safety of this treatment. Hippokratia 2015; 19 (3): 249-255.

Hepatic artery thrombosis after orthotopic liver transplantation: 3 patients with collateral formation and conservative treatment.

Hepatic artery thrombosis (HAT), a serious complication after orthotopic liver transplantation (OLT), can lead to patient death in the absence of revascularization or retransplantation. Herein we have presented clinical characteristics, imaging findings, and long-term outcomes of 3 OLT patients with HAT who were treated conservatively and developed hepatic arterial collaterals. These patients underwent transplantation due to hepatitis B cirrhosis, cryptogenic cirrhosis, or hepatitis C infection and alcoholic disease. They presented with bile duct stenosis and/or a bile leak at 1, 3, and 36 months after transplantation, respectively, and were treated with percutaneous drainage and stent placement, endoscopic retrograde cholangio-pancreatography (ERCP), or reanastomosis of the bile duct over a T tube. HAT was confirmed using multidetector computed tomography (MDCT) 3-dimensional (3D) angiography and Doppler sonography. They survive in good condition with normal liver function at 30, 50, and 42 months after OLT, respectively. Development of collateral arterial circulation to the liver graft was detected with MDCT 3D angiography and Doppler sonography. From our experience with 3 patients and a literature review, we believe that there are a number of patients who experience long-term survival after the diagnosis of irreversible HAT and the development of collaterals. Although this group is at high risk for sepsis and biliary complications, these are usually self-limiting complications due to improved treatment regimens. The development of collateral arterial flow may also be beneficial.

Colorectal carcinoma: contribution of growth pattern on prognosis.

BACKGROUND: Recent studies have reported poor prognosis in colorectal carcinomas with non-polypoid growth pattern. The aim of the present study is to investigate this issue in the patients referred to "Hatzikostas" General Hospital of Messolonghi, Greece. MATERIALS AND METHODS: A total of 13 patients who were treated for primary colorectal adenocarcinoma in a one-year period were studied. Colorectal carcinomas were classified into two types based on the presence or absence of elevation of tumour as compared with adjacent mucosa: polypoid growth (PG-type) and non-polypoid growth (NPG-type) carcinomas. Clinical and tumour histopathologic parameters were analysed. RESULTS: Unlike PG-type carcinomas, NPG-type carcinomas had a high proportion of poorly differentiated adenocarcinoma cells, a high likelihood of being advanced, and a high frequency of lymph node as well as distant metastases at the time of diagnosis. CONCLUSIONS: Colorectal carcinomas with NPG pattern tend to show more malignant characteristics than those with PG pattern, explaining their poorer outcome.

The presence and significance of iron in neoplasia of the colorectum.

BACKGROUND: To investigate the presence and distribution of tissue iron in colon adenomas of all grades of dysplasia as well as colorectal carcinomas of all grades of differentiation. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue blocks from 8 biopsies of colon adenomas and 13 surgical specimens of colorectal carcinoma were studied. Consecutive sections were stained using Perls' stain that demonstrates the presence of ferric iron by staining it blue. RESULTS: Iron was absent in all cases of colon adenoma. On the other hand, iron was present in 9 of the 13 cases of colorectal carcinoma (69.23%), regardless of the degree of differentiation, the location and the stage of development. The iron was stored in mesenchymal cells in the stroma and various types of inflammatory cells. CONCLUSIONS: Our results suggest association of iron presence in the environment of malignant cells. Thus, iron may be a carcinogenic factor, possibly facilitating tumour growth and modulating local immune response.