Victoria Andreu

Ecstasy: A common cause of severe acute hepatotoxicity

BACKGROUND/AIMS Ecstasy is a synthetic amphetamine recently identified as a possible cause of acute liver injury. This drug is consumed by young people and has a marked effect on improving sociability. The extent of ecstasy-associated severe hepatic damage is unknown to date. METHODS The clinical histories of 62 patients with acute liver failure admitted to the Intensive Care Liver Unit between January 1994 and December 1996 were reviewed to assess the frequency, the epidemiological, clinical and histological characteristics and the outcome of ecstasy-induced severe hepatitis. RESULTS Over this period of time, five patients (8%) were admitted because of ecstasy-induced acute liver failure, representing 31% of the cases with drug hepatotoxicity. Ecstasy was the second most common cause of liver injury in patients under the age of 25 years, being 20% in this subset of patients and 36% after ruling out the cases of viral etiology. All the patients had severe liver disease of acute onset, with jaundice, high peak of serum transaminases activity, hypoglycemia and low prothrombin activity, but no hepatic encephalopathy. Full recovery was observed in all cases from 3 to 12 months. CONCLUSIONS Ecstasy is responsible for a relatively high number of cases of acute liver failure in young people. Therefore, the use of this drug should be investigated in all patients with severe hepatitis of unclear origin. Efforts must be made to advise young people of the risks of ecstasy consumption.

Usefulness of laparoscopy with liver biopsy in the assessment of liver involvement at diagnosis of Hodgkin's and non-Hodgkin's lymphomas ☆ ☆☆ ★

BACKGROUND Staging of lymphoma at diagnosis determines therapeutic strategy and disease prognosis. Hepatic involvement, demonstrated by laparotomy or laparoscopy, is frequent in Hodgkins and non-Hodgkins lymphoma. However, it is unclear whether these procedures are still necessary or whether they should be replaced by less invasive techniques. METHODS Laparoscopy-assisted liver biopsies, as well as laboratory studies, bone marrow biopsy, and thoracic and abdominal computed tomography, were performed as an initial staging evaluation in 112 consecutive patients who were diagnosed with Hodgkins or non-Hodgkins lymphoma. RESULTS Hepatic lymphomatous involvement was demonstrated in 18 patients (16%). It was more frequent in non-Hodgkins (24%) than in Hodgkins (8%) lymphomas (p < 0.04) and among stage III and IV (24%) than stage I and 11 (10%) patients (p < 0.05). The laparoscopic finding of white spots or nodules on the liver surface had a 100% specificity in the diagnosis of lymphomatous liver involvement. Conversely, hepatomegaly on both laparoscopy and computed tomography, as well as laboratory studies, had a low sensitivity and specificity. CONCLUSIONS Laparoscopy-assisted liver biopsy was a useful technique to establish hepatic lymphomatous involvement, which was not identified by either computed tomography or laboratory studies.

Incomplete type of intestinal metaplasia has the highest risk to progress to gastric cancer: results of the Spanish follow‐up multicenter study

In high or moderate risk populations, periodic surveillance of patients at risk of progression from gastric precursor lesions (PL) to gastric cancer (GC) is the most effective strategy for reducing the burden of GC. Incomplete type of intestinal metaplasia (IIM) may be considered as the best candidate, but it is still controversial and more research is needed. To further assess the progression of subtypes of IM as predictors of GC occurrence.

Gene expression study and pathway analysis of histological subtypes of intestinal metaplasia that progress to gastric cancer

Background Intestinal metaplasia (IM) is a precursor lesion that precedes gastric cancer (GC). There are two IM histological subtypes, complete (CIM) and incomplete (IIM), the latter having higher progression rates to GC. This study was aimed at analysing gene expression and molecular processes involved in the progression from normal mucosa to IM, and also from IM subtypes to GC. Methodology We used expression data to compare the transcriptome of healthy gastric mucosa to that of IM not progressing to GC, and the transcriptome of IM subtypes that had progressed to GC to those that did not progress. Some deregulated genes were validated and pathway analyses were performed. Results Comparison of IM subtypes that had progressed to GC with those that did not progress showed smaller differences in the expression profiles than the comparison of IM that did not progress with healthy mucosa. New transcripts identified in IM not progressing to GC included TRIM, TMEM, homeobox and transporter genes and SNORD116. Comparison to normal mucosa identified non tumoral Warburg effect and melatonin degradation as previously unreported processes involved in IM. Overexpressed antigen processing is common to both IM-subtypes progressing to GC, but IIM showed more over-expressed oncogenic genes and molecular processes than CIM. Conclusions There are greater differences in gene expression and molecular processes involved in the progression from normal healthy mucosa to IM than from IM to gastric cancer. While antigen processing is common in both IM-subtypes progressing to GC, more oncogenic processes are observed in the progression of IIM.

Genetic variation analysis in a follow-up study of gastric cancer precursor lesions confirms the association of MUC2 variants with the evolution of the lesions and identifies a significant association with NFKB1 and CD14 : Genetic variation and gastric cancer precursor lesions

Gastric carcinogenesis proceeds through a series of gastric cancer precursor lesions (GCPLs) leading to gastric cancer (GC) development. Although Helicobacter pylori infection initiates this process, genetic factors also play a role. We previously reported that genetic variability in MUC2 is associated with the evolution of GCPLs. In order to replicate previous results in an independent sample series and to explore whether genetic variability in other candidate genes plays a role in the evolution of GCPL, genomic DNA from 559 patients with GCPLs, recruited from 9 Spanish hospitals and followed for a mean of 12 years, was genotyped for 141 SNPs in 29 genes. After follow‐up, 45.5% of the lesions remained stable, 37% regressed and 17.5% progressed to a more severe lesion. Genetic association with the evolution of the lesions (progression or regression) was analyzed by multinomial and binomial logistic regression. After correction for multiple comparisons, the results obtained confirmed the inverse association between MUC2 variants and the regression of the lesions. A significant association was also observed between NFKB1 and CD14 variants and the evolution of the lesions; interestingly, this association was with both progression and regression in the same direction, which could reflect the dual role of inflammation in cancer. Stratified analyses according to H. pylori virulence factors indicated some significant and differential effects but none of them passed the FDR test. These results confirm that genetic variability in MUC2, NFKB1 and CD14 may have a role in the evolution of the GCPLs along time and in gastric carcinogenesis.

Sa1927 Significant Genetic Variability Associated With the Evolution of Gastric Cancer Precursor Lesions in a Spanish Population

Objective Preoperative chemoradiotherapy has recently become common practice in treatment of esophageal cancer with a gain in 5-year survival of 10-15%. However, a significant proportion of patients do not respond well and experiencing unnecessary severe side-effects. Accurate risk-stratification of patients using informative biomarkers before therapy may help to avoid unnecessary morbidity due to ineffective treatment. The aim of this study was to investigate the correlation between the expression of SOX2 and P53 in pre-treatment tumor biopsies and grade of pathological tumor response in resected specimen of patients with esophageal adenocarcinoma (EAC) treated with neoadjuvant chemoradiotherapy (nCRT). Methods All EAC patients who received nCRT according to the CROSS regimen followed by esophagectomy, between January 2003 and July 2011 at the Erasmus University Medical Center, were included. SOX2 and P53 protein expression was visualized by immunohistochemistry on all pre-treatment tumor biopsies and scored independently by two investigators who were blinded for clinical outcome. Aberrant expression was defined as negative expression of SOX2 and overexpression or complete loss of P53 expression. The overall Tumor Regression Grade (TRG) was evaluated using the modified Mandard scoring system. Patients with TRG 1 or TRG 2 were classified as major responders (ie, 10% of tumor cells remaining). Results In total 77 patients were included. Forty (53%) patients had a major pathological response (TRG 1-2) and 37 (47%) a minor response (TRG 3-4). In pre-treatment biopsies aberrant SOX2 and P53 expression was seen in 40% (31/77) and 83% (64/77), respectively. A major response was significantly associated with an aberrant SOX2 expression (OR 3.9, 95% CI: 1.5 10.2, p=0.005) and aberrant p53 expression (OR 4.5, 95% CI: 1.15 18.2, p=0.031). Aberrant expression of both biomarkers increased the probability of a major response in the individual patient (OR of 5.6; 95% CI: 2.1 14.9, p= 0.001), with a sensitivity of 68%, specificity of 73% and a positive predictive value of 73%. Conclusion SOX2 and P53 expression in the pre-treatment biopsies predict response to nCRT in patients with EAC. These biomarkers might help to identify patients who are likely to benefit most from this multimodality treatment.