Anti-HCV positive hepatocellular carcinoma in cirrhosis : Prevalence, risk factors and clinical features

Recent reports indicate that hepatitis C virus (HCV) may play a role in the pathogenesis of hepatocellular carcinoma in cirrhotics. Using an ELISA test, we evaluated the prevalence of anti-HCV antibodies in 97 patients with hepatocellular carcinoma (HCC) in cirrhosis and in a group of 223 patients, including: 49 patients with HBsAg-positive chronic liver disease (CLD), 42 with alcoholic CLD, 110 with cryptogenic CLD and 22 with post-transfusional HBsAg-negative CLD. All diagnoses were histologically confirmed. Overall, anti-HCV-positive HCC were 64% of the total, with no statistically significant difference with respect to CLD (60.9%). The prevalence of anti-HCV was higher in cryptogenic HCC (80%) than in HBsAg-positive (60%) or alcoholic HCC (42.8%) (p less than 0.005). When HCC and cirrhosis of similar putative etiology were considered, anti-HCV prevalence was significantly higher in HCC than in cirrhosis only in the groups of patients with alcoholic liver damage (60% in HCC vs. 38% in cirrhosis, p less than 0.005). In HBsAg-positive patients, anti-HCV prevalence was twice as high in HCC than in CLD, but the difference was not statistically significant. Overall, anti-HCV prevalence in HCC was significantly higher than in alcoholic or HBsAg-positive CLD (p less than 0.001 and p less than 0.01, respectively) but lower than in cryptogenic CLD (p less than 0.001). Association between anti-HCV and anti-HBc was significantly more prevalent in patients with CLD than in those with HCC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary sclerosing cholangitis (PSC): clinical,laboratory and survival analysis in children and adults

Abstract: Background: Primary sclerosing cholangitis (PSC) is an uncommon disorder, rarely diagnosed in children, moreover, data on its natural history and survival are still lacking. Aim: The study was undertaken to compare clinical, laboratory and survival rates in two series of PSC: one in a pediatric group (group A) and the other in an adult population (group B). Methods: Group A included 9 patients (5 males, 4 females, mean age 10 yrs, range 7–15); group B included 28 patients (19 males, 9 females, mean age 32 years, range 19–60). The mean follow-up was 5.2 years in group A and 6.9 years in group B (range 1–14 years). ERCP and colonos-copy were performed in each case. Survival was analyzed using the Kaplan-Meier method. Results: At presentation children showed significantly higher levels of IgG and AST compared to adults (p<0.05); moreover, interface hepatitis occurred in 50% of children and in 14.2% in adults (p= ns). During follow-up the following major events occurred: oesophageal bleeding (n=2) in group A; progressive liver failure (n=6), cholangiocarcinoma (n=3), colonic cancer (n=1) in group B. Liver transplantation (OLTx) was performed in 4 adults (one died after a retransplantation). No deaths were observed in children. The Kaplan-Meier curve in adults shows a 65% rate of survival at 10 years. Conclusions: The present findings on PSC suggest a more severe activity of the disease in children than in adults at presentation; nonetheless, the prognosis seems to be better in children than in adults. The Mayo score prognostic index does not predict the development of liver/colonic cancer. A poor outcome (defined as death or being listed for OLTx) only occurred in adults.     

Molecular events underlying interleukin‐6 independence in a subclone of the CMA‐03 multiple myeloma cell line

We explored the molecular mechanisms involved in the establishement of CMA‐03/06, an IL‐6‐independent variant of the multiple myeloma cell line CMA‐03 previously generated in our Institution. CMA‐03/06 cells grow in the absence of IL‐6 with a doubling time comparable with that of CMA‐03 cells; neither the addition of IL6 (IL‐6) to the culture medium nor co‐culture with multipotent mesenchymal stromal cells increases the proliferation rate, although they maintain the responsiveness to IL‐6 stimulation as demonstrated by STAT1, STAT3, and STAT5 induction. IL‐6 independence of CMA‐03/06 cells is not apparently due to the development of an autocrine IL‐6 loop, nor to the observed moderate constitutive activation of STAT5 and STAT3, since STAT3 silencing does not affect cell viability or proliferation. When compared to the parental cell line, CMA‐03/06 cells showed an activated pattern of the NF‐κB pathway. This finding is supported by gene expression profiling (GEP) analysis identifying an appreciable fraction of modulated genes (28/308) in the CMA‐03/06 subclone reported to be involved in this pathway. Furthermore, although more resistant to apoptotic stimuli compared to the parental cell line, CMA‐03/06 cells display a higher sensibility to NF‐κB inhibition induced by bortezomib. Finally, GEP analysis suggests an involvement of a number of cytokines, which might contribute to IL‐6 independence of CMA‐03/06 by stimulating growth and antiapoptotic processes. In conclusion, the parental cell‐line CMA‐03 and its variant CMA‐03/06 represent a suitable model to further investigate molecular mechanisms involved in the IL‐6‐independent growth of myeloma cells. © 2013 Wiley Periodicals, Inc.     

Geomechanical behavior of the reservoir and caprock system at the In Salah CO2 storage project

Almost 4 million metric tons of CO₂ were injected at the In Salah CO₂ storage site between 2004 and 2011. Storage integrity at the site is provided by a 950-m-thick caprock that sits above the injection interval. This caprock consists of a number of low-permeability units that work together to limit vertical fluid migration. These are grouped into main caprock units, providing the primary seal, and lower caprock units, providing an additional buffer and some secondary storage capacity. Monitoring observations at the site indirectly suggest that pressure, and probably CO₂, have migrated upward into the lower portion of the caprock. Although there are no indications that the overall storage integrity has been compromised, these observations raise interesting questions about the geomechanical behavior of the system. Several hypotheses have been put forward to explain the measured pressure, seismic, and surface deformation behavior. These include fault leakage, flow through preexisting fractures, and the possibility that injection pressures induced hydraulic fractures. This work evaluates these hypotheses in light of the available data. We suggest that the simplest and most likely explanation for the observations is that a portion of the lower caprock was hydrofractured, although interaction with preexisting fractures may have played a significant role. There are no indications, however, that the overall storage complex has been compromised, and several independent data sets demonstrate that CO₂ is contained in the confinement zone.In Salah is an industrial-scale carbon capture and storage project located in central Algeria. Between 2004 and 2011, 3.8 million metric tons of CO₂ were injected into an anticlinal structure at ∼1,800 m depth. Storage integrity at the site is provided by a massive, 950-m-thick caprock that sits above the injection interval (Fig. 1). It consists of a number of low-permeability units that work together to limit vertical fluid migration. These are grouped into main caprock units, providing the primary seal, and lower caprock units, providing an additional buffer and some secondary storage capacity.Open in a separate windowFig. 1.Stratigraphic column with interval depths at well KB-502. Depth is given as meters of true vertical depth below the rotary table (m TVD brt) of the drilling rig, a common elevation datum in the oil and gas industry.In June 2011, injection operations halted at the site to allow reevaluation of the injection strategy (1). At the time, several monitoring observations suggested that pressure, and probably CO₂, had migrated vertically into the lower portion of the caprock. Although there are no indications that overall storage integrity has been compromised, these observations raise interesting questions about the geomechanical behavior of the reservoir and lower caprock system.Several hypotheses have been put forward by various groups to explain these observations. These include fault leakage, flow through preexisting fractures, or the possibility that injection pressures hydraulically fractured a portion of the lower seal (2–13). In this work, we evaluate these hypotheses in light of the available data. We suggest that the most likely explanation for the observed behavior is that the lower caprock was hydrofractured, although interaction with preexisting fractures may have played a significant role. Previous studies by Bissell and colleagues (4) and Oye and colleagues (8) have shown that injectivity and microseismic data show indications of fracturing behavior, at least in the reservoir and possibly in the overburden. Here, we use well data to constrain the state of stress in the reservoir and lower caprock, providing strong support for the hydrofracture hypothesis.This work also highlights those monitoring and analysis methods that have been most useful for understanding the field behavior, as well as lessons learned and potential improvements. This perspective can guide future carbon storage projects.     

Evaluation of sexual function in sexually active women 1 year after transvaginal NOTES: a prospective cohort study of 106 patients

Purpose

The primary objective of this prospective cohort study was to investigate sexual function, quality of life and patient satisfaction in sexually active women 1 year after transvaginal hybrid natural orifice transluminal endoscopic surgery (NOTES).

Patients and methods

This prospective single-centre cohort study included sexually active female patients after transvaginal hybrid NOTES cholecystectomy or anterior resection. Sexual life impairment and quality of life were assessed by the Gastrointestinal Quality of Life Index (GIQLI) prior and 1 year after surgery. Patient satisfaction was assessed as well as the sexual function 1 year postoperatively using the validated German version of the Female Sexual Function Index (FSFI-D).

Results

Between September 2008 and December 2009, 106 sexually active women after transvaginal hybrid NOTES cholecystectomy or anterior resection were identified. Sexual life significantly improved (GIQLI scores 3.2?±?1.0 preoperatively vs. 3.7?±?0.7 1 year postoperatively, P?<?0.001), and painful sexual intercourse (3.3?±?1.0 vs. 3.6?±?0.7, P?=?0.008) decreased post-surgery. The mean FSFI-D total score after transvaginal NOTES was 28.1?±?4.6, exceeding the cutoff for sexual dysfunction defined as 26. Four (4.5 %) out of 88 patients who answered this question were not satisfied with the transvaginal hybrid NOTES procedure.

Conclusions

This prospective cohort study of female sexual function after transvaginal NOTES provides compelling evidence that the transvaginal access is safe and associated with high satisfaction rate.