Sporadic and MEN1-related gastrinoma and Zollinger-Ellison syndrome: differences in clinical characteristics and survival outcomes.

PURPOSE: Gastrinoma with Zollinger-Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features. METHODS: Consecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort. RESULTS: Of 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively. CONCLUSION: MEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.

Meta-analysis: nonsteroidal anti-inflammatory drugs in biliary colic.

BACKGROUND: Biliary colic is a common manifestation of cholelithiasis, developing in about one-third of patients. Even if nonsteroid anti-inflammatory drugs (NSAIDs) have widely been used to relieve biliary pain, there is a lack of systematic review of treatments on this issue. AIM: To assess the potential benefits in terms of both pain control and reduction of complications, and the potential harms of NSAIDs in patients with biliary colic. METHODS: Data from randomised clinical trials (RCTs) comparing NSAIDs with no treatment, placebo or other drugs in patients with biliary colic, were collected from Medline and Embase. The outcome measures were expressed as odds ratio and relative risk and then pooled using fixed or random-effect models. RESULTS: Eleven RCTs involving 1076 subjects (268 men, 808 women; 18-86 years), including 442 controls were analysed. In comparison with placebo, NSAIDs led to a significantly higher proportion of patients with complete pain relief (RR 3.77, 95%CI 1.65-8.61; I(2) : 73%) and a significantly lower rate of complications (RR 0.53, 95% CI 0.31-0.89; I(2) : 35%). In comparison with other drugs, NSAIDs were more efficacious in controlling pain than spasmolytics (RR 1.47, 95% CI 1.03-2.10; I(2) : 55%); there was no difference between NSAIDs and opioids (RR 1.05, 95% CI 0.82-1.33; I(2) : 74%). CONCLUSIONS: In patients with biliary colic NSAIDs are the first-choice treatments as they control pain with the same efficacy of opioids and significantly reduce the proportion of patients with severe complications. However, the lack of high-quality RCTs and the presence of consistent heterogeneity among studies may partially flaw these results.

Chromogranin A levels in chronic liver disease and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the relevant cause of death in patients with compensated cirrhosis. Alpha-fetoprotein (AFP) is used for screening HCC, with limited success. AIM: We evaluated plasma chromogranin A (CgA) as a marker of HCC. PATIENTS: CgA plasma levels and AFP serum levels were prospectively measured in 30 patients with HCC, 14 with cirrhosis, 79 with chronic hepatitis and 65 controls. METHODS: CgA was measured with an enzyme-linked immunosorbent assay (DAKO A/S Glostrup, Denmark). AFP was measured by electrochemiluminoimmunoassay (Elecsys, Roche S.p.A., Italy). RESULTS: CgA levels were significantly higher in the three groups of patients than in controls and in patients with HCC they were significantly higher than in chronic hepatitis patients [median 44.5 (interquartile range 21-145.9)U/L vs. 15.3 (10.9-29.25)U/L, p<0.001]. AFP values were above the upper reference limit in 75% of patients with HCC, 50% of cirrhotic patients and 11% of chronic hepatitis patients (p<0.005). CgA values significantly correlated with AFP levels (r(s)=0.42, p<0.0001). The overall diagnostic accuracy of CgA was 75% (CI 66-82), with a sensitivity of 70% (CI 50.6-85.2) and a specificity of 67% (CI 55.9-76.3). CONCLUSIONS: Despite the evidence of higher CgA levels in patients with HCC, this test has low-diagnostic accuracy. Its pathophysiological meaning remains unknown, even if it could suggest an endocrine phenotype of HCC.