Liver resection for hepatocellular carcinoma in patients without cirrhosis

Background:

Data on liver resection for hepatocellular carcinoma (HCC) without cirrhosis are sparse. The present study was conducted to evaluate the indications and results of liver resection for HCC with regard to safety and efficacy.

Methods:

Data for patients who had liver resection for HCC without cirrhosis between January 1996 and March 2011 were retrieved retrospectively using a prospective database containing information on all patients who underwent hepatectomy for HCC. Patient and tumour characteristics were analysed for influence on overall and disease‐free survival to identify prognostic factors by univariable and multivariable analysis.

Results:

The 1‐, 3‐ and 5‐year overall survival rates after resection with curative intent for HCC without cirrhosis were 84, 66 and 50 per cent respectively. Disease‐free survival rates were 69, 53 and 42 per cent respectively. The 90‐day mortality rate was 4·5 per cent (5 of 110 patients). Surgical radicality and growth pattern of the tumour were independent prognostic factors for overall survival. Disease‐free survival after resection with curative intent was independently affected by growth pattern and by the number and size of tumour nodules.

Conclusion:

Liver resection for HCC without cirrhosis carries a low perioperative risk and excellent long‐term outcome if radical resection is achieved. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Targeting the vascular endothelial growth factor in hematologic malignancies

There exists increasing evidence that apart from solid tumors, angiogenic growth factors also play important roles in the development and/or maintenance of hematolymphoid malignancies. Thus, in these cancers, angiogenesis and bone marrow microvessel density often correlate with prognosis and disease burden. Several reports speculated on the role of angiogenesis and the resulting possible therapeutic options in hematologic malignancies. The most prominent angiogenic factor, vascular endothelial growth factor (VEGF), is expressed in a number of established leukemic cell lines as well as in freshly isolated human leukemias and lymphomas, and several human leukemias express VEGF receptor 1 and/or VEGF receptor 2. VEGF/VEGF‐receptor interactions are also involved in proliferation, migration, and survival of leukemic cells by autocrine and paracrine mechanisms. As a consequence, a possible drugable effect by inhibiting VEGF signaling in different hematologic malignancies has been discussed. This review focuses on angiogenesis‐independent effects of VEGF on survival and proliferation of leukemic or lymphoma cells and on possible therapeutic approaches using anti‐VEGF/VEGF‐receptor therapies to inhibit proliferation or induce apoptosis of malignant cells in hematologic diseases.     

Treatment with mesenchymal stromal cells is a risk factor for pneumonia-related death after allogeneic hematopoietic stem cell transplantation

We performed a retrospective cohort study to find out whether the use of reduced‐intensity conditioning (RIC) might reduce the risk of early death from pneumonia. Pneumonia‐associated deaths were evaluated in 691 hematopoietic stem cell transplantation (HSCT) patients. The majority had a hematological malignancy (n = 504) and an HLA‐matched donor (n = 584). RIC was given to 336 patients and myeloablative conditioning (MAC) to 355. Data concerning radiology, culture and autopsy results were evaluated together with risk factors for death related to pneumonia within or after 100 d after HSCT (early and overall pneumonia). In 60 patients, pneumonia contributed to death (early n = 17). The cumulative incidence of early pneumonia‐related death was 2.8% and 2.1% in MAC and RIC patients, respectively. The cumulative incidence of overall pneumonia‐related death was 8.2% and 10.5%, respectively. In 40 patients, (67%) an etiology could be established, with 19 patients having proven or probable mold infection. In the multivariate analyses, acute graft‐versus‐host disease (GVHD) grades II–IV, cytomegalovirus (CMV) infection and having received mesenchymal stromal cells (MSCs) were factors associated with overall pneumonia‐related death. Bacteremia and a previous HSCT were associated with early pneumonia‐related death. RIC did not reduce the incidence of early death associated with pneumonia. Acute GVHD II–IV, CMV infection and MSC treatment were factors associated with pneumonia‐related death. Mold infection was the most common contributor to pneumonia‐related death in HSCT patients.     

Genetic loci on chromosomes 4q25, 7p31, and 12p12 are associated with onset of lone atrial fibrillation before the age of 40 years

Background

Three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 have been associated with atrial fibrillation (AF) in genome-wide association studies (GWAS). Five additional loci have been associated primarily with the PR interval and subsequently with AF. We aimed to investigate if 8 single nucleotide polymorphisms (SNPs), representing the 8 genomic loci previously linked with AF in genome-wide association studies, were associated with early-onset lone AF.

Methods

We included 209 patients with early-onset lone AF, and a control group consisting of 534 individuals free of AF. The 8 SNPs were genotyped using TaqMan assays (Applied Biosystems, Foster City, CA).

Results

Three SNPs were found to be significantly associated with early-onset lone AF: rs2200733 closest to PITX2 (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.27; P = 0.004), rs3807989 near to CAV1 (OR 1.35; 95% CI, 1.06-1.72; P = 0.015), and rs11047543 near to SOX5 (OR 1.70; 95% CI, 1.18-2.44; P = 0.004). When correcting for multiple testing, rs2200733 and rs11047543 were still significantly associated with AF.

Conclusions

Three SNPs, rs2200733 (4q25), rs3807989 (7p31), and rs11047543 (12p12), were associated with early-onset lone AF. All 3 SNPs are positioned close to genes that in previous studies have been demonstrated to be important for cardiac morphology/development, thereby suggesting a link between these SNPs and structural heart disease. Our results however, indicate that variants in these 3 loci are associated with AF through mechanisms that do not involve major structural abnormalities in the heart.     

Major surgery in a neutropenic patient undergoing allogeneic stem cell transplantation for high risk myelofibrosis

Certain homeostatic functions are particularly important to the success of extensive surgery. For example metabolic homeostasis, inflammation and tissue repair, coagulation and immune defense against infection are all of great importance. In patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT), the ability to mount adequate inflammatory responses is severely impaired. Thrombocytopenia is common making coagulation inadequate for any kind of invasive procedure, let alone extensive surgery. For this reason, abdominal surgery in neutropenic patients is associated with very high mortality rates of between 50 and 70 % [1]. Here, we describe a patient with high-risk myelofibrosis who required extensive abdominal surgery during the aplastic phase only 7 days after ASCT due to severe abdominal hemorrhage. This patient’s successful recovery shows that extensive surgery is possible even during the aplastic phase after ASCT. Interestingly, we also found that radical splenectomy 7 days after stem cell transplantation did not lead to any significant loss of infused stem cells.     

Eosinophil associated genes in the inflammatory bowel disease 4 region: Correlation to inflammatory bowel disease revealed

AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP).METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn’s disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5’-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP^® system as described by the manufacturer. Statistical tests for calculations of results were χ² test, Fisher’s exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant.RESULTS: The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject’s genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29%,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of ≥ 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in μg/10⁶ eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes.CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.