Impact of biliary stents on the diagnostic accuracy of EUS-guided fine-needle biopsy of solid pancreatic head lesions: A multicenter study

There is no clear evidence of a negative impact of biliary stents on the diagnostic yield of EUS-guided fine-needle biopsy (EUS-FNB) for diagnosing pancreatic head lesions. We aimed to evaluate the association between the presence of biliary stents and the diagnostic accuracy of EUS-FNB. Materials and Methods: A multicenter retrospective study including all jaundiced patients secondary to pancreatic head masses was performed. Patients were divided into two groups according to the presence of a biliary stent placed before EUS-FNB. Pathological results were classified according to the Papanicolaou classification and compared against the final diagnosis. Diagnostic measures in the two groups were compared. Multivariate logistic regression analyses including potential factors affecting EUS-FNB accuracy were performed. Results: Overall, 842 patients were included, 495 (58.8%) without and 347 (41.2%) with biliary stent. A plastic or a metal stent was placed in 217 (62.5%) and 130 (37.5%) cases, respectively. Diagnostic sensitivity and accuracy were significantly higher in patients without biliary stent than in those with stent (91.9% and 92.1% vs. 85.9% and 86.4%, P = 0.010 At multivariate analyses, lesion size (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.02-1.09, P = 0.01) and presence of biliary stent (OR: 0.51, 95% CI: 0.32-0.89, P = 0.01) were independently associated with diagnostic accuracy. In the subgroup of patients with biliary stent, the type of stent (plastic vs. metal) did not impact EUS-FNB yield, whereas the use of larger bore needles enhanced diagnostic accuracy (OR: 2.29, 95% CI: 1.28-4.12, P = 0.005). Conclusions: In this large retrospective study, an indwelling biliary stent negatively impacted the diagnostic accuracy of EUS-FNB. Preferably, EUS-FNB should precede endoscopic retrograde cholangiopancreatography, especially in the case of small tumors

The role of PNI to predict survival in advanced hepatocellular carcinoma treated with Sorafenib

Background and aims The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). Results A PNI cut-off value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12–76.3) and 6.8 months (95% CI 2.7–24.6) for patients with a high (>31.3) and low (<31.3) PNI, respectively. At both the univariate and the multivariate analysis, low PNI value (p = 0.0004), a 1-unit increase of aspartate aminotransferase (p = 0.0001), and age > 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI <31.3 versus >31.3 was found to be an independent prognostic factor for predicting OS in all the three validation cohorts. Conclusions PNI represents a prognostic tool in advanced HCC treated with first-line Sorafenib. It is readily available and low-cost, and it could be implemented in clinical practice in patients with HCC

Landscape of alcohol-related hepatocellular carcinoma in the last 15 years highlights the need to expand surveillance programs

Background & Aims: Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006–2020) in Italy. Methods: Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006–2010; 2011–2015; 2016–2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Results: Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia, <50% of HCCs were detected by surveillance programmes. The tumour burden at diagnosis was slightly reduced but not enough to change the distribution of the ITA.LI.CA cancer stages. Intra-arterial and targeted systemic therapies increased across quinquennia. A modest improvement in survival was observed in the last quinquennia, particularly after 12 months of patient observation. Cancer stage, HCC treatment, and presence of oesophageal varices were independent predictors of survival. Conclusions: In the past 15 years, modest improvements have been obtained in outcomes of alcohol-related HCC, attributed mainly to underuse of surveillance programmes and the consequent low amenability to curative treatments. Metabolic dysfunction-associated fatty liver disease is a widespread condition in alcohol abusers, but its presence did not show a pivotal prognostic role once HCC had developed. Instead, the presence of oesophageal varices, an independent poor prognosticator, should be considered in patient management and refining of prognostic systems. Impact and Implications: Alcohol abuse is a leading and growing cause of hepatocellular carcinoma (HCC) worldwide and is associated with a worse prognosis compared with other aetiologies. We assessed the evolutionary landscape of alcohol-related HCC over 15 years in Italy. A high cumulative prevalence (78%) of metabolic dysfunction-associated fatty liver disease, with signs of metabolic dysfunction, was observed in HCC patients with unhealthy excessive alcohol consumption. The alcohol + metabolic dysfunction-associated fatty liver disease condition tended to progressively increase over time. A modest improvement in survival occurred over the study period, likely because of the persistent underuse of surveillance programmes and, consequently, the lack of improvement in the cancer stage at diagnosis and the patients’ eligibility for curative treatments. Alongside the known prognostic factors for HCC (cancer stage and treatment), the presence of oesophageal varices was an independent predictor of poor survival, suggesting that this clinical feature should be carefully considered in patient management and should be included in prognostic systems/scores for HCC to improve their performance

Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women

The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10−5) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk

Humoral and haemodynamic interactions between clonidine and nifedipine in human essential hypertension.

Acute administration of nifedipine (NIF), a calcium entry blocker (CEB), in animals reduces the hypotensive effect of clonidine (CLN), an alpha-adrenergic agonist. In order to evaluate possible negative interactions between NIF and CLN in man during chronic treatment with these drugs, 12 patients with mild to moderate uncomplicated essential hypertension received either NIF (20 mg twice daily), CLN (0.25 mg once daily), the two drugs together at the same doses, or their matched placebos for a 2-week period each. NIF (-13.5% versus placebo) and CLN (-10.2% versus placebo) decreased blood pressure significantly and when combined, blood pressure was further decreased (-17.1% versus placebo). Heart rate was increased by NIF and NIF + CLN but unchanged by CLN alone. Plasma renin activity (PRA) tended to increase with NIF, decreased with CLN (P < 0.05) and was unchanged with NIF + CLN. Plasma aldosterone did not vary during any of the phases of the trial. These results indicate that NIF and CLN do not interact negatively on blood pressure control in essential hypertensive subjects

SARS-CoV-2 infection in patients with a normal or abnormal liver

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus causing coronavirus disease 19 (COVID-19), with an estimated 22 million people infected worldwide so far although involving primarily the respiratory tract, has a remarkable tropism for the liver and the biliary tract. Patients with SARS-CoV-2 infection and no antecedent liver disease may display evidence of cytolytic liver damage, proportional to the severity of COVID-19 but rarely of clinical significance. The mechanism of hepatocellular injury is unclear and possibly multifactorial. The clinical impact of SARS-CoV-2 infection in patients with underlying chronic liver disease, a cohort whose global size is difficult to estimate, has been assessed appropriately only recently and data are still evolving. Patients with cirrhosis are at higher risk of developing severe COVID-19 and worse liver-related outcomes as compared to those with non-cirrhotic liver disease. OLT patients have an intermediate risk. Specific interventions in order to reduce the risk of transmission of infection among this high-risk population have been outlined by international societies, together with recommendations for modified treatment and follow-up regimens during the COVID-19 pandemic. When a vaccine against SARS-CoV-2 becomes available, patients with fibrotic liver disease and those with OLT should be considered as prime targets for prophylaxis of COVID-19, as all other highly susceptible subjects

Hemodynamic and humoral interactions between captopril and nifedipine.

Nine patients with uncomplicated essential hypertension received, according to a randomized sequence, captopril (25 mg three times daily), nifedipine (10 mg three times daily), and both drugs for 1 week, with each treatment period separated by a 1-week interval during which a placebo was given. Captopril significantly reduced blood pressure and plasma aldosterone, increased plasma renin activity (PRA), and did not change heart rate. Nifedipine exerted a similar effect on blood pressure and PRA, but it increased heart rate and did not change aldosterone. Captopril plus nifedipine further reduced blood pressure and increased PRA, did not change heart rate, and reduced aldosterone to values similar to those after captopril alone. The hypotensive effect of captopril was highly predictable by basal PRA values, and that of nifedipine by age, while PRA increments induced by captopril were unrelated to those induced by nifedipine. These data indicate that: 1) captopril and nifedipine exert an additive effect on blood pressure and renin; 2) captopril counteracts the heart rate increase induced by nifedipine; 3) nifedipine does not influence the aldosterone inhibition induced by captopril. It is suggested that the association of the two drugs can be usefully employed in the treatment of hypertension