Gemma Maddalo

Autoimmune gastritis: histology phenotype and OLGA staging

Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis.

Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC).

The serpin squamous cell carcinoma antigen complexed with IgM (SCCA‐IgM) has been reported as a promising serological marker for hepatocellular carcinoma (HCC). We aimed to further evaluate SCCA‐IgM diagnostic accuracy and to determine its prognostic role.

Gastrin: from pathophysiology to cancer prevention and treatment.

Gastrin has been identified as the principal effector of gastric secretion, but several studies have demonstrated its role as a biomarker of cancer risk and as a growth factor for colorectal, stomach, liver, and pancreatic cancer. Hypergastrinemia characterizes autoimmune gastritis, with body and fundic gland atrophy and increased risk for both gastric adenocarcinoma and neuroendocrine tumors. Gastric type I carcinoids develop in the context of autoimmune gastritis because of the stimulus exerted by gastrin on enterochromaffin-like cells and remain gastrin-sensitive for long durations because the removal of hypergastrinemia leads to tumor regression. The treatment of gastric carcinoid is still open to debate, but when the disease frequently relapses, or is multicentric or infiltrating, surgery is advocated or, in the alternative, a costly and long-lasting treatment with long-acting somatostatin analogues is prescribed. A technology allowing the preparation of an immunogen eliciting an immune system response with generation of antibodies against G17 has been developed. This vaccine has been tested in patients with colorectal, pancreatic or advanced gastric cancer. The vaccine has also been used in the treatment of gastric type I carcinoids, and the administration of G17DT in patients harboring these lesions leads to carcinoid regression. Antigastrin vaccination in the treatment of gastrointestinal cancer obviously needs validation, but this immunotherapy may well represent a simple, inexpensive, and active ‘adjuvant’ treatment.

Immunotherapy for gastric premalignant lesions and cancer.

Chronic atrophic gastritis, a precancerous change for gastric cancer, shows a loss of appropriate glands, Helicobacter pylori infection and autoimmune gastritis being the two main etiologic factors. While H. pylori eradication is the mandatory treatment for the former, no etiologic treatment is available for the latter, in which a Th1-type response, modulated by Tregs and Th17 cells, is involved. H. pylori-related atrophic gastritis is a risk factor for gastric adenocarcinoma, while autoimmune atrophic gastritis is also linked to a substantial risk of gastric type I carcinoid, related to the chronic stimulus exerted by hypergastrinemia on enterochromaffin-like cells. Several studies have been published on gastric cancer treatment through an active specific immunotherapy, aimed at improving the immunoregulatory response and increasing the circulating tumor-specific T cells. No study on immunotherapy of carcinoids is available but, in our experience, the administration of an antigastrin 17 vaccine induced carcinoid regression in two out of three patients treated.

Rise and fall of HCV‐related hepatocellular carcinoma in Italy: a long‐term survey from the ITA.LI.CA centres

Hepatitis C virus (HCV) is the leading aetiological factor of HCC in the western world where, overall, its incidence is increasing, despite data suggesting an initial drop in some areas. The aim of this study was to evaluate epidemiology, clinical features and survival of HCV‐related HCC (HCV‐HCC) in a wide time range in Italy.

MINT31 methylation in gastric noninvasive neoplasia: potential role in the secondary prevention of gastric cancer.

Gastric cancer (GC) is still a leading cause of cancer-related death worldwide, and environmental, genetic, and epigenetic DNA changes are involved in the process of gastric carcinogenesis. The objective of this study was to establish the extent of DNA methylation at various CpG islands in GC and in precancerous changes [gastric noninvasive neoplasia (NIN)]. Eighty-one gastric samples were analyzed using methylation-specific PCR at several CpG islands. Thirty-eight samples were obtained at surgery [19 neoplastic (GC) and 19 nonneoplastic cancer-surrounding tissues (sGC)] and 43 at endoscopy (biopsies in 23 NIN patients and 20 controls). Hypermethylation of TPEF (a growth inhibitor), PTGER3 (a prostaglandin receptor isoform), and MINT31 (a promoter locus regulating calcium channels that is involved in p53 mutation) discriminated NIN and GC from normal mucosa, suggesting an early role as initiating events, whereas hypermethylation at ARGHAP20 developed with the progression from NIN to GC. MINT31 hypermethylation predicted persistence or worsening of NIN and cancer development. In conclusion, these data support a progressive accumulation of aberrant methylations in NIN and GC at various CpG islands with distinct time courses. With hypermethylation, the genes involved in regulating the balance between apoptosis and cell proliferation may become silenced and trigger gastric tumorigenesis. Hypermethylation of MINT31 predicted NIN persistence, as well as progression to higher grade or to GC, and might be used as a marker of GC risk.

Interleukin 1β and tumor necrosis factor-α polymorphisms in autoimmune gastritis.

The association between gastric cancer and IL1b polymorphisms, first reported by El-Omar et al. [2] is still debated [3–7]. IL1b polymorphisms have been associated with autoimmune diseases; the cytokine is involved in gastric pathophysiology [8–11] and is therefore, of interest, also in autoimmune gastritis (AIG), a gastric precancerous condition [12]. It is for this reason that we think it is worth to briefly report on the data we obtained comparing cytokine polymorphisms in patients with Helicobacter pylori-related multifocal atrophic gastritis (MAG), with patients with AIG.