Secondary Prevention of Epidemic Gastric Cancer in the Model of Helicobacter pylori -Associated Gastritis.

Irrespective of its etiology, long-standing, non-self-limiting gastric inflammation (mostly in Helicobacter pylori-associated cases) is the cancerization ground on which epidemic (intestinal-type) gastric carcinoma (GC) can develop. The natural history of invasive gastric adenocarcinoma encompasses gastritis, atrophic mucosal changes, and intraepithelial neoplasia (IEN). The topography, the extent and the severity of the atrophic changes significantly correlate with the risk of developing both IEN and GC. In recent years, both noninvasive (serological) tests and invasive (endoscopy/biopsy) procedures have been proposed to stratify patients according to different classes of GC risk. As a consequence, different patient-tailored GC secondary prevention strategies have been put forward. This review summarizes the histological features of H. pylori-related gastritis and the natural history of the disease. Histological and serological strategies to assess GC risk as well as the clinical management of atrophic gastritis patients are also discusse

The molecular landscape of colitis-associated carcinogenesis.

In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-α, IL-6, IL-10, IFN-γ), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-κB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters. Most of the molecular dysregulation occurring in sporadic colorectal carcinogenesis is documented in colitis-associated adenocarcinoma too, but marked differences have been established in both their timing and prevalence. Unlike sporadic cancers, TP53 alterations occur early in IBD-related carcinogenesis, while APC dysregulation emerges mainly in the most advanced stages of the oncogenic cascade. From the therapeutic standpoint, colitis-associated cancers are associated with a lower prevalence of KRAS mutations than the sporadic variant. Epigenetic changes, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, are significantly involved in colitis-associated cancer development and progression. The focus now is on identifying diagnostic and prognostic biomarkers, with a view to ultimately designing patient-tailored therapies

MiR-21 up-regulation in ampullary adenocarcinoma and its pre-invasive lesions

Poor information is available on the molecular landscape characterizing the carcinogenetic process leading to ampullary carcinoma. MiR-21 is one of the most frequently up-regulated miRNAs in pancreatic adenocarcinoma, a tumor sharing similar molecular features with ampullary adenocarcinomas (AVCs), above all with the pancreatic-biliary type. We profiled, by in situ hybridization (ISH), miR-21 expression in a series of 26 AVCs, 50 ampullary dysplastic lesions (35 low-grade [LG-IEN] and 15 high-grade [HG-IEN]) and 10 normal duodenal mucosa samples. The same series was investigated by immunohistochemistry for β-catenin, p53 and HER2 expression. HER2 gene amplification was evaluated by chromogenic in situ hybridization. To validate miR-21 ISH results we performed miR-21 qRT-PCR analysis in a series of 10 AVCs and their matched normal samples. All the normal control samples showed a negative or faint miR-21 expression, whereas a significant miR-21 up-regulation was observed during the carcinogenetic cascade (p < 0.001), with 21/26 (80.8%) of cancer samples showing a miR-21 overexpression. In comparison to control samples, a significant overexpression was found in samples of LG-IEN (p =.0003), HG-IEN (p =.0001), and AVCs (p < 0.0001). No significant difference in miR-21 overexpression was observed between LG-IEN, HG-IEN and AVCs. By qRT-PCR analysis, AVCs showed a 1.7-fold increase over the controls (p =.003). P53 was frequently dysregulated in both dysplastic and carcinoma samples (44 out of 76; 57.9%). A 20% (10/50) of dysplastic lesions and 11% (3/26) of carcinomas were characterized by a nuclear localization of β-catenin. Only 2 AVCs (7.7%; both intestinal-type) showed a HER2 overexpression (both 2+), which corresponded to a HER2 gene amplification at CISH analysis. This is the first study demonstrating a miRNA dysregulation in the whole spectrum of ampullary carcinogenesis. MiR-21 overexpression is an early molecular event during ampullary carcinogenesis and its levels increase with the neoplastic progression

Impact of the COVID-19 pandemic on melanoma diagnosis.

Many health-care systems have responded the COVID-19 pandemic by delaying and/or cancelling elective surgical procedures, particularly during the lockdown.1-3 There is a concern that this could have affected the early diagnosis of malignant melanoma (MM) that is critical to improve its prognosis.4,5 The objective of this observational study was to investigate whether a reduction in the incidence of new diagnoses of MM has occurred following the COVID-19 outbreak. All the consecutive histological diagnoses of MM were retrospectively collected in the pathological laboratories of 4 provinces of the Veneto region in northern Italy, namely Verona, Vicenza, Rovigo and Treviso, between 1st March and 31st October 2020 and the same period of 2019. All cases were stratified in three categories according to Breslow thickness: in situ, <1 mm and 651 mm. The date of MM excision was considered for all the time-related analyses. The period March-October 2020 was compared with the same period of 2019

PD-L1 overexpression in ampulla of Vater carcinoma and its pre-invasive lesions

Aims: PD-1/PD-L1 checkpoint immunotherapy has been proposed recently as a promising treatment in relapsed/refractory disease, used eventually in combination with traditional chemotherapy in different cancer settings. To date, no data are available concerning PD-L1 expression in ampulla of Vater carcinoma and its pre-invasive lesions. Methods and results: We assessed the immunohistochemical expression of PD-L1 in a series of 26 ampullary adenocarcinomas, 50 ampullary dysplastic lesions and 10 normal duodenal mucosa samples. Moreover, in all cases DNA mismatch repair proteins status was investigated. PD-L1 was expressed in seven of 26 (26.9%) invasive carcinomas and three of 50 (6.0%) dysplastic samples. Most of the PD-L1-positive tumours (seven of 10) were intestinal-type and poorly differentiated (G3). The number of PD-L1-positive stromal lymphoid cells was significantly higher in dysplastic and invasive lesions than in the normal samples (P = 0.011). Nineteen dysplastic lesions and eight invasive carcinomas did not show any evident epithelial or stromal PD-L1 expression. Four of the carcinomas were mismatch repair-deficient and two of these were PD-L1-positive. Furthermore, mismatch repair-deficient lesions showed a significantly higher average of PD-L1-positive stromal lymphoid cells than those of neoplastic PD-L1-negative samples (62.8 versus 21.6; P < 0.001). Conclusions: The present results suggest a role of the PD-1/PD-L1 axis in ampullary adenocarcinomas, and therefore this may also prompt consideration of checkpoint immunotherapy as a novel promising treatment for these tumours

Programmed cell death-ligand 1 (PD-L1) overexpression in ampulla of Vater carcinoma and its pre-invasive lesions

PD-1/PD-L1 checkpoint immunotherapy has recently been proposed as a promising treatment in relapsed/refractory disease, eventually used in combination with the traditional chemotherapy in different cancer settings. No data are still now available about PD-L1 expression in ampulla of Vater carcinoma and its preinvasive lesions