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Background and Aims: The optimal management of naïve and not naïve Helicobacter pylori patients remains unclear. Therefore, it is essential to evaluate whether the actual clinical practice mirrors the indications suggested by the guidelines. This study aimed to assess the effectiveness and the safety of the empirical first- and second-line treatments prescribed to patients enroled at Italian centres participating in the European Registry on H. pylori Management (Hp-EuReg)., Methods: The Hp-EuReg is an international multicentre prospective non-interventional registry starting in 2013 aiming to evaluate the management of H. pylori infection by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables assessed included demographics, previous eradication attempts, treatment regimen, effectiveness, and tolerance., Results: Overall, 3723 patients from 2013 to February 2021 were included: 2996 and 727 received an empirical first- and second-line treatment, respectively. According to the modified ITT analysis, among the first-line regimens, only the bismuth quadruple therapy with three-in-one-single capsule (BQT-TSC), the concomitant, and the sequential treatment - all lasting 10 days - achieved an eradication rate >90%. Among the second-line regimens, only the 10-day BQT-TSC reported an effectiveness >90%. High-dose PPI twice daily also significantly increased the effectiveness of some therapies. The BQT-TSC was the regimen with the highest incidence of adverse events., Conclusions: Only quadruple therapies lasting at least 10 days achieved over 90% eradication rates among the empirical first- and second-line regimens. It remains unclear whether high-dose PPI twice daily can improve the efficacy of quadruple treatment., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: α-Fetoprotein (AFP) is a biomarker commonly used in the management of patients with hepatocellular carcinoma (HCC), although the possible determinants of its serum levels in these patients have not been adequately explored. For this study, the authors evaluated the relevance of demographic, clinical, and oncologic factors to the presence of elevated AFP levels in large cohort of patients with HCC., Methods: In 4123 patients with HCC who were managed by the Italian Liver Cancer Group, AFP levels were assessed along with their association with demographic, biochemical, clinical, and oncologic characteristics. Patients were subdivided according to the presence of elevated AFP (ie, >10 ng/mL)., Results: AFP levels were elevated in 62.4% of patients with HCC. Multivariate logistic regression analysis indicated that being a woman (odds ratio [OR], 1.497; 95% confidence interval [95%CI], 1.250-1.793; P < .0001), the presence of cirrhosis (OR, 1.538; 95% CI, 1.050-2.254; P = .027), liver disease with viral etiology (OR, 1.900; 95% CI, 1.589-2.272; P < .0001), an elevated alanine aminotransferase level (OR, 1.878; 95% CI, 1.602-2.202; P < .0001), a low albumin level (OR, 1.301; 95% CI, 1.110-1.525; P = .012), an HCC tumor size >2 cm (OR, 1.346; 95% CI, 1.135-2.596; P = .001), multinodular HCC (OR, 1.641; 95% CI, 1.403-1.920; P < .0001), and the presence of vascular invasion (OR, 1.774; 95% CI, 1.361-2.311; P < .0001) were associated independently with elevated levels of AFP. Both the median AFP level and the proportion of patients who had elevated levels increased with decreasing degrees of HCC differentiation (P < .0001)., Conclusions: Sex and features of chronic liver disease were identified as nontumor characteristics that influence serum AFP levels in patients with HCC. These findings should be taken into account as limitations in interpreting the oncologic meaning of this biomarker in clinical practice., (© 2014 American Cancer Society.)

Background: Over the years, doxorubicin and gemcitabine have been among the most widely used drugs for hepatocellular carcinoma (HCC), with relative efficacy. The authors report the results of a phase 2 study of the combination of gemcitabine plus pegylated liposomal doxorubicin., Methods: Patients with advanced HCC received combination chemotherapy with gemcitabine 1000 mg/m² on Days 1 and 8, followed by pegylated liposomal doxorubicin 30 mg/m² on Day 1. Treatment was repeated every 4 weeks to a maximum of 8 cycles. Primary endpoint was overall response rate, and secondary endpoints were time to disease progression (TTP), overall survival (OS), and toxicity., Results: Forty-one patients were enrolled and were evaluable for response, toxicity, and survival. A total of 194 cycles of treatment were administered. Three (7%) patients had a complete response, and 1 of these patients underwent liver transplantation. Seven (17%) patients had a partial response and, among these patients, 1 patient underwent surgical resection. Among the 31 patients who had initial alpha-fetoprotein levels >400 ng/mL, 20 (64.5%) had a >20% decrease after 2 cycles of treatment. The median TTP and OS were 5.8 and 22.5 months, respectively. Hematologic toxicity was the most common side effect, including neutropenia (17%) and anemia (7%)., Conclusions: The combination of gemcitabine plus pegylated liposomal doxorubicin was active and safe in advanced HCC. Moreover, this treatment induced some complete responses and converted some untreatable HCCs into lesions eligible for resection or transplantation., (© 2010 American Cancer Society.)

Background: The life expectancy of a patient with hepatocellular carcinoma (HCC) in cirrhosis is hard to predict, making it difficult to decide whether a certain treatment is indicated and what to say to the patient regarding prognosis. A new score recently has been proposed, which includes the parameters involved in the Child-Pugh stage, plus macroscopic tumor morphology, alpha-fetoprotein levels, and the presence or absence of portal thrombosis. The score has been validated in internal control series, but its general applicability has yet to be confirmed. The authors compared the discriminatory ability of the Cancer of the Liver Italian Program (CLIP) score with those of the Okuda and TNM staging systems and the Child-Pugh classification in a group of cirrhotic patients with HCC, diagnosed and followed up by their unit., Methods: One hundred fifty-four patients with histologically ascertained HCC in cirrhosis were recruited (median age, 62.5 years; male/female ratio, 122/32) and prospectively followed up. Staging was performed at the baseline using the Child-Pugh, Okuda, TNM, and CLIP systems., Results: The CLIP score was able to predict survival better than the Okuda or TNM staging system, as confirmed by the Kaplan-Meier comparison of survival curves and by the Cox regression analysis, with a median survival rate of 31, 27, 13, 8, 2, and 2 months in patients with CLIP Stages 0, I, II, III, IV, and V-VI, respectively. The Child-Pugh classification performed as well as the Okuda. The predictive capacity of CLIP score was confirmed in the subgroup of patients undergoing chemoembolization. Overall, the survival rate in the authors' series was higher than predicted on the basis of previous reports., Conclusions: The CLIP score, which is based on simple features of the patient and of the tumor, can accurately identify patients with different prognoses, particularly in the early phases of HCC, thus representing a useful tool in the management of the disease and of the affected patient.

Background: Cathepsin B (CATB) and cathepsin L (CATL), which are cysteine proteases, urokinase-(UPA) and tissue-type plasminogen activator (TPA), both serine proteases, and their inhibitor type-1 (PAI-1) are believed to play an important role in colorectal carcinoma (CRC) invasion and metastasis. The objective of this study was to measure CATB, CATL, UPA, TPA, and PAI-1 in the same cancerous tissue (CANCER) and in tissues obtained from a tumor free area (NORMAL) to compare their respective prognostic roles in patients with CRC., Methods: CANCER and NORMAL samples were obtained from 60 CRC patients undergoing surgery (36 males and 24 females; mean age, 63.8 years [range, 27-85 years]). The antigen concentrations were measured using an enzyme-linked immunoadsorbent assay method. The CANCER tissue also was examined in terms of major histomorphologic parameters such as differentiation, vascular invasion, degree of necrosis, and mucus production., Results: Significantly higher antigen levels were found: 1) in CANCER versus NORMAL (with respect to CATL, UPA, and PAI-1, with significantly lower levels for TPA); 2) in CRC with versus without metastasis (CATB, CATL, and PAI-1); 3) in poorly versus well differentiated CRC (UPA and PAI-1); and 4) in advanced Dukes stages (PAI-1). CATB and CATL significantly correlated with UPA and PAI-1. Finally, CATL (P = 0.0001), UPA (P = 0.006), PAI-1 (P = 0.006), Dukes stage (P = 0.0001), presence of metastases (P = 0.003), and vascular invasion (P = 0.03) had a significant prognostic impact., Conclusions: The simultaneous up-regulation of cysteine and serine proteases in CRC confirms their role in colorectal tumor biology and particularly in the process of invasion and metastasis. Together with Dukes stage, determinations of CATL, UPA, and PAI-1 have a major prognostic impact in patients with CRC., (Copyright 1999 American Cancer Society.)

Background: Cirrhosis of viral etiology due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a risk factor for hepatocellular carcinoma (HCC). The current study evaluated the rate of incidence of HCC in patients with compensated cirrhosis of viral etiology., Methods: Two hundred fifty-nine cirrhotic patients (66 hepatitis B surface antigen [HBsAg] positive, 166 HCV positive, and 27 HBsAg/HCV positive) were longitudinally examined every 6 months by serum alpha-fetoprotein test and liver ultrasonography. The rates of incidence of HCC were calculated by the person-years method. The Kaplan-Meier method was used to estimate the cumulative probability of HCC development. Differences in survival time were evaluated by a log rank test. Independent predictors of HCC development were estimated by Cox proportional hazard regression analysis., Results: During a mean follow-up of 64.5 months, HCC developed in 51 (19.7%) patients: in 34 of 166 HCV positive subjects (20.5%) (mean follow-up, 66.3 months), in 6 of 66 of those HBsAg positive (9.1%) (mean follow-up, 55.06 months), and in 11 of 27 of those with dual HBsAg/HCV infection (40.7%) (mean follow-up, 76.4 months). The rate of incidence of HCC per 100 person-years of follow-up was 3.7 in HCV positive subjects, 2.0 in those HBsAg positive, and 6.4 in those with dual infection. Cumulative HCC appearance rates in HBsAg positive, HCV positive, and HBsAg/HCV positive subgroups were 10%, 21%, and 23% at 5 years, 16%, 28%, and 45% at 10 years, and 16%, 40%, and 55% at 13 years, respectively. Multivariate analysis indicated that age >50 years (hazard risk [HR], 4.5; 95% confidence interval [CI] = 2.1-9.4), male gender (HR, 2.8; 95% CI = 1.1-5.3), and HBsAg/HCV coinfection (HR, 2.3; 95% CI = 1.1-4.6) were independent predictors of HCC development., Conclusions: These findings confirm that male gender and more advanced age (>50 years) are risk factors for HCC in patients with cirrhosis. Furthermore, the data indicate that subjects with dual HBsAg/HCV infection are at highest risk for HCC. Surveillance programs for early detection of HCC should focus especially on these patients.

Background: Gastric epithelial dysplasia (GED) in metaplastic mucosa is considered the most advanced preinvasive lesion in the multistep morphogenesis of intestinal-type gastric cancer (GC). The rate of GED's evolution into GC is still under debate and probably is related to pathologic and clinical parameters other than the dysplasia itself. The aim of this study was to evaluate whether clinical aspects (sex and age) and/or morphologic variables (GED grade, coexisting atrophic gastritis) are relevant to the outcome of dysplasia, with a view toward initiating the establishment of a rational follow-up protocol for practical GED management., Methods: Ninety-three patients harboring GED (G1: 56, G2:34, G3:18) were followed for more than 12 months according to a previously-agreed protocol. Regression, progression, or evolution into GC were detected for each grade of GED. Multivariate analysis was used to check the independence of clinical and pathologic variables in the progression of GED into more severe dysplastic lesions and/or as risk factors for evolution into GC., Results: Age, male sex, GED grade and grade of coexisting atrophic gastritis proved independent risk factors for GED progression, with no significant interactions. Only GED grade (G2 and G3) was significantly associated with carcinomatous evolution. In G1-GED, age and the grade of coexisting atrophy proved to be independent risk factors for carcinomatous evolution., Conclusions: In G1-GED, more stringent follow-up should be recommended for older patients with coexisting high grade atrophic gastritis; stringent follow-up is always mandatory for G2-GED; and a surgical approach is justified in G3-GED.

Background: The prognostic relevance of morphology in advanced gastric cancer is well known. Data on tumor cell DNA content are still inadequate and contradictory., Methods: Morphologic parameters and DNA ploidy were evaluated in 76 gastric cancer patients with no extranodal metastases (Stage I, 10 cases; Stage II, 20 cases; and Stage III, 46 cases), using formalin-fixed paraffin-embedded tissue. All cases were followed for at least 6 years after surgery or until death., Results: Among the potential prognostic factors analyzed by Mantel-Cox and generalized Wilcoxon statistics, male sex (P = 0.02), cardiac location of neoplasia (P = 0.02), deeper infiltration of the gastric wall (P = 0.001), vascular neoplastic invasion (P = 0.006), metastatic lymph nodes (P = 0.001), pathologic stage (P = 0.0001), and aneuploidy (P = 0.01) were significantly associated with lower survival rate. Testing of all of the above-mentioned variables by the Cox stepwise multiple regression model disclosed that factors independently associated with survival were stage (P = 0.0001), ploidy (P = 0.0006), and vascular carcinomatous invasion (P = 0.01)., Conclusions: In gastric cancer with no extranodal metastases, DNA ploidy was found to be the most significant prognostic parameter after pathologic stage.