Early and advanced gastric cancer during follow-up of apparently benign gastric ulcer: significance of the presence of epithelial dysplasia

One hundred and forty-four patients with apparently benign gastric ulcer were endoscopically followed up in order to evaluate the outcome of the lesion. Particular attention was given to: (a) detect possible delay in diagnosing gastric cancer; (b) ascertain the frequency of association with epithelial dysplasia; (c) establish the role of markers, such as serum pepsinogen group I (PGI), and gastric juice CEA in predicting gastric ulcer evolution. Endoscopic and bioptic check-ups were carried out during the first year at 3, 6 and 12 months after endoscopic healing of the ulcer, and then at every symptomatic recurrence. Ten patients (6.9%) were found to present histological evidence of malignancy (within 3 months in six cases, between 6 and 12 months in three cases, and after 41 months in the rest). Four cases were early gastric cancers, and six had shown dysplastic changes of the mucosa at the edge or scar of the ulcer. Serum PGI levels were not significantly different in gastric cancer patients, while gastric juice CEA levels were sharply increased compared to those of gastric ulcer patients: nine out of ten patients had values above normal range. These data suggest that: (a) there may be some delay in diagnosing gastric carcinoma, and gastric ulcer patients should be controlled routinely more than once; (b) the presence of dysplasia indicates the need for prolonged follow-up, because of the high risk of association with or evolution into gastric cancer, and because of the higher number of early gastric cancer detections that this protocol allows; (c) further support in monitoring patients "at risk" may be afforded by gastric juice CEA determination.     

Extended lymphadenectomy (D2) in patients with early gastric cancer.

AIMS: To investigate the survival benefit of extended lymphadenectomy (D2) in EGC patients in one European Institution. METHODS: A review was made of our prospective gastric database from January 1980 to December 2001. Of 527 patients with primary gastric adenocarcinoma, 119 with EGC underwent potentially curative resection (R0) with D2 lymphadenectomy. RESULTS: There were two post-operative deaths. Of the 117 evaluable cases, 96 were classified as N0 and 21 as N+, with metastases in the perigastric lymph nodes (level 1) in 13, and beyond this site (level 2) in eight. Five-year survival was 85.9 and 83.0% in N0 and N+ patients, respectively. During a median follow-up of 90 months, five of the eight patients with level 2 metastases died of recurrent disease and three were alive. The estimated survival benefit for 119 patients with EGC was 2.5% (3/119 cases). CONCLUSIONS: In patients with EGC, metastases to level 2 are rare. Our results indicate that D2 lymphadenectomy has a limited survival benefit and that in these cases a less extensive lymphadenectomy (D1) could be performed.     

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

Oxidative damage,pro-inflammatory cytokines,TGF-αand c-myc in chronic HCV-related hepatitis and cirrhosis

AIM: To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-αand c-myc. METHODS: The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TIMF-α, IL-1β, TGF-αand c-myc in liver specimens was detected by semi-quantitative comparative RT-PCR. RESULTS: TNF-αlevels were significantly higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1βwas higher in cirrhosis patients (P=0.05). A significant correlation was found between TNF-αand staging (P=0.05) and between IL-1βlevels and grading (P=0.04). c-myc showed a significantly higher expression in cirrhosis patients (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients (P=0.05) and in HCV genotype 1 (P=0.03). Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype (P=0.04) and grading (P=0.007). Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-αexpression and HCV genotype (P=0.02). CONCLUSION: In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-αlevels. As HCV-related liver damage progresses, TNF-αlevels drop while IL-1βand c-myc levels increase, which may be relevant to liver carcinogenesis.     

Circulating prostaglandin E2: a novel potential prognostic biomarker in patients with hepatocellular carcinoma

Clinical and Experimental Medicine - We aimed to explore the activation of monoacylglycerol lipase (MAGL)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis in hepatocellular carcinoma (HCC),...     

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)     

Clinical markers of slow healing and relapsing gastric ulcer.

The aim of the study was to identify the clinical markers useful in characterising slow healing and relapsing gastric ulcer patients. Ninety nine subjects entered the short term and 79 the long term study (12 months). The following parameters were taken into account: therapy, sex, age, smoking habit, alcohol consumption, analgesic intake, peptic ulcer family history and onset of the disease. Results of the studies were analysed by means of chi 2 test and logistic regression, both in stepwise and in specifying models. Cigarette smoking was found to be the most important risk factor of non-healing (p = 0.04). In women with late onset of the disease, cigarette smoking identified the gastric ulcer subjects at higher risk of non-healing with a predictive probability of 0.4679. Age under 50 years was found to be the most important risk factor of relapsing throughout the entire 12 month follow up period (p = 0.025). In those under 50 years, cigarette smoking and negative peptic ulcer family history in combination, identified the gastric ulcer subjects at higher risk of relapsing, the predicted probability being 0.6027. It is concluded that cigarette smoking is the most important risk factor for non-healing and those who relapse under the age of 50. The possibility of singling out categories of patients more prone not to heal and to relapse suggests new strategies in the management of gastric ulcer disease.     

The Effects of Chronic Ethanol Consumption on Carcinogen Metabolism and on O6-Methylguanine Transferase-Mediated Repair of Alkylated DNA

This article presents a review and update of recent experiments conducted in collaboration with Dr. C. S. Lieber on mechanisms underlying the increased cancer risk associated with alcohol abuse. Ethanol has been found to be a potent inducer of microsomal enzymes involved in carcinogen metabolism in a variety of rat tissues including liver, esophagus, lungs, and intestines. In some of these tissues, ethanol's inductive effect on microsomal cytochrome P-450 enzyme activity may result in enhanced levels of electrophilic metabolites of procarcinogens which are not readily detoxified. In addition, chronic ethanol feeding has been found to depress the activity of O⁶-methylguanine transferase, an enzyme involved in the repair of carcinogen-induced DNA alkylation. The effects of ethanol on carcinogen metabolism and on DNA repair would be expected to enhance the initiation phase of chemically induced cancers.     

Hormonal monitoring of early pregnancy by a direct radioimmunoassay of steroid glucuronides in first morning urine

The usefulness of the direct 4-hour radioimmunoassay of estriol-16-glucuronide (E3G) and pregnanediol-3-glucuronide (P2G) in first morning urine (FMU) for establishing a prognosis of the early pregnancy outcome was evaluated in 106 patients that became pregnant. Microaliquots of FMU were serially assayed from day 3 of the conception cycle until day 80 of pregnancy. The E3G and P2G profiles of 19 pregnancies which terminated in spontaneous abortion with either a diagnosis of the blighted ovum syndrome (n = 11) or presumption of a corpus luteum/trophoblast failure (n = 8) have been compared with those of clinically normal pregnancies (n = 87). Normal pregnancies displayed typical patterns of E3G and P2G development, while variations were observed in abortive events that reflected changes of the fetoplacental unit.     

Direct assay of urinary steroid glucuronides for monitoring the approach of ovulation

The concentrations of estrone-3-glucuronide (E(1)3G) and pregnanediol-3-glucuronide (P(2)3G) in daily samples of early morning urine (EMU) were correlated with the levels of estradiol (E2), progesterone (P) and LH in respective plasma samples. Forty-six menstrual cycles were studied, in order to determine the practical usefulness of the urine assays for detecting: a) an individualized estrogen concentration threshold value, announcing the approach of ovulation. b) an individualized signal provided by P(2)3G in urine from which it can be assumed that ovulation has already occurred. The results showed that the concentration of E2 in plasma, in any day of the cycle, can be precisely inferred from the respective concentration of E(1)3G in EMU. The estimation of the plasmatic P values from those of P(2)3G in EMU had to be based on different factors according to the phase of the cycle, fact that suggests the presence of a phase-related variation in the glucuronization of P metabolites. Considering three consecutive E(1)3G urinary assay results, it was possible to identify a threshold value termed Estrogen-Peak Initiating Rise (E-PIR), which anticipated in 3.02 +/- 0.18 days the occurrence of an LH peak. The attempts to detect the occurrence of ovulation by an individualized urinary P(2)3G signal proved disappointing. The signal was detected, either before, simultaneously or after the LH peak.