Augmenter of liver regeneration (ALR), which is critically important in liver regeneration and hepatocyte proliferation, is highly expressed in cirrhotic livers and hepatocellular carcinomas (HCC). In the current study, the functional role of ALR in hepatocancerogenesis was analyzed in more detail. HepG2 cells, in which the cytosolic 15 kDa ALR isoform was reexpressed stably, (HepG2-ALR) were used in migration and invasion assays using modified Boyden chambers. Epithelial-mesenchymal transition (EMT) markers were determined in HepG2-ALR cells in vitro and in HepG2-ALR tumors grown in nude mice. ALR protein was quantified in HCC and nontumorous tissues by immunohistochemistry. HepG2-ALR, compared with HepG2 cells, demonstrated reduced cell motility and increased expression of the epithelial cell markers E-cadherin and Zona occludens-1 (ZO-1), whereas SNAIL, a negative regulator of E-cadherin, was diminished. Matrix metalloproteinase MMP1 and MMP3 mRNA expression and activity were reduced. HepG2-ALR cell-derived subcutaneously grown tumors displayed fewer necrotic areas, more epithelial-like cell growth and fewer polymorphisms and atypical mitotic figures than tumors derived from HepG2 cells. Analysis of tumor tissues of 53 patients with HCC demonstrated an inverse correlation of ALR protein with histological angioinvasion and grading. The 15 kDa ALR isoform was found mainly in HCC tissues without histological angioinvasion 0. In summary the present data indicate that cytosolic ALR reduces hepatoma cell migration, augments epithelial growth and, therefore, may act as an antimetastatic and EMT reversing protein.
Benign liver tumors are being detected more frequently due to the widespread use of ultrasound and complementary methods and due to improvements in diagnostic accuracy. In the case of a reliable diagnosis of asymptomatic hemangioma or focal nodular hyperplasia surgery is not indicated. Hepatic adenoma of considerable size should be resected primarily based on the risk of rupture. Improvements in diagnostic imaging as well as the optimization of surgical procedures with extremely low complication rates permit an individualized management strategy founded on evidence-based algorithms. In the case of an equivocal diagnosis, we advocate low-risk tumor resection instead of tumor biopsy due to the inherent complication rates of hemorrhage or tumor-cell dissemination and possible misleading histology.
Augmenter of liver regeneration (ALR), which is critically important in liver regeneration and hepatocyte proliferation, is highly expressed in cirrhotic livers and hepatocellular carcinomas (HCC). In the current study, the functional role of ALR in hepatocancerogenesis was analyzed in more detail. HepG2 cells, in which the cytosolic 15 kDa ALR isoform was reexpressed stably, (HepG2-ALR) were used in migration and invasion assays using modified Boyden chambers. Epithelial-mesenchymal transition (EMT) markers were determined in HepG2-ALR cells in vitro and in HepG2-ALR tumors grown in nude mice. ALR protein was quantified in HCC and nontumorous tissues by immunohistochemistry. HepG2-ALR, compared with HepG2 cells, demonstrated reduced cell motility and increased expression of the epithelial cell markers E-cadherin and Zona occludens-1 (ZO-1), whereas SNAIL, a negative regulator of E-cadherin, was diminished. Matrix metalloproteinase MMP1 and MMP3 mRNA expression and activity were reduced. HepG2-ALR cell-derived subcutaneously grown tumors displayed fewer necrotic areas, more epithelial-like cell growth and fewer polymorphisms and atypical mitotic figures than tumors derived from HepG2 cells. Analysis of tumor tissues of 53 patients with HCC demonstrated an inverse correlation of ALR protein with histological angioinvasion and grading. The 15 kDa ALR isoform was found mainly in HCC tissues without histological angioinvasion 0. In summary the present data indicate that cytosolic ALR reduces hepatoma cell migration, augments epithelial growth and, therefore, may act as an antimetastatic and EMT reversing protein.
ObjectivesA significant number of patients with colorectal cancer are presented with various conditions requiring surgery in an oncologically palliative setting. We performed this study to identify risk factors for early outcome after surgery to facilitate the decision-making process for therapy in a palliative disease.MethodsWe performed a retrospective chart review of 142 patients who underwent palliative surgery due to locally advanced, complicated, or advanced metastatic colorectal carcinoma between January 2010 and April 2018 at the “Elbland” Medical Center Riesa. We performed a logistic regression analysis of 43 factors to identify independent predictors for complications and mortality.ResultsSurgery included resections with primary anastomosis (n=31; 21.8%) or discontinuous resections with colostomy (n=38; 26.8%), internal bypasses (n=27; 19.0%) and stoma formation only (n=46; 32.4%). The median length of hospitalization was 12 days (2–53 days), in-hospital morbidity was 50.0% and the mortality rate was 18.3%. Independent risk factors of in-hospital morbidity were age (HR: 1.5, p=0.046) and various comorbidities of the patients [obesity (HR: 1.8, p=0.036), renal failure (HR: 1.6, p=0.040), diabetes (HR: 1.6, p=0.032), alcohol abuse (HR: 1.3, p=0.023)] as well as lung metastases (HR: 1.6, p=0.041). Arteriosclerosis (HR: 1.4; p=0.045) and arterial hypertension (HR: 1.4, p=0.042) were independent risk factors for medical complications in multivariate analysis. None of the analyzed factors predicted the surgical morbidity after the palliative procedures. Emergency surgery (HR: 10.2, p=0.019), intestinal obstruction (HR: 9.2, p=0.006) and ascites (HR: 5.0, p=0.034) were multivariate significant parameters of in-hospital mortality.ConclusionsPalliatively treated patients with colorectal cancer undergoing surgery show high rates of morbidity and mortality after surgery. In this retrospective chart review, independent risk factors for morbidity and in-hospital mortality were identified that are similar to patients in curative care. An adequate selection of patients before palliative operation should lead to a better outcome after surgery. Especially in patients with intestinal obstruction and ascites scheduled for emergency surgery, every effort should be made to convey these patients to elective surgery by interventional therapy, such as a stent or minimally invasive stoma formation.
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