RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

Low Colorectal Cancer Risk After Resection of High-Risk Pedunculated Polyps.

BACKGROUND: Post-fecal immunochemical test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas. Due to an expected higher risk of colorectal cancer (CRC), postpolypectomy surveillance is recommended, generating a substantially increased load on endoscopy services. The aim of our study was to investigate postpolypectomy CRC risk in a screening population of FIT+ subjects after resection of low-risk adenomas (LRAs) or high-risk adenomas (HRAs). METHODS: We retrieved data from a cohort of patients undergoing postpolypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were postpolypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia, and location of the index lesion. We adopted as comparators FIT+/colonoscopy-negative and FIT- patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables. RESULTS: Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had an LRA, and 22,709 (26.0%) an HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.92-1.53) was not increased compared with the FIT+/colonoscopy-negative group, while for HRAs a significant increase in CRC incidence (HR, 1.53; 95% CI, 1.14-2.04) was found. The presence of 1 or more risk factors among proximal location, nonpedunculated morphology, and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR, 1.85; 95% CI, 1.36-2.52). Patients with only distal pedunculated polyps without high-grade dysplasia, representing 39.2% of HRA, did not have increased risk compared with the FIT- group (HR, 0.87; 95% CI, 0.59-1.28). CONCLUSIONS: CRC incidence is significantly higher in patients with HRAs diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without high-grade dysplasia, an observation that could potentially reduce the burden of surveillance in FIT programs.

Cutaneous melanoma in older patients.

BACKGROUND: In industrialized countries, the aging population is steadily rising. The incidence of cutaneous malignant melanoma (CMM) is highest in old people. This study focuses on the clinicopathological profile of CMM and indicators of diagnostic-therapeutic performance in older patients. METHODS: This retrospective population-based cohort study included 1,368 incident CMM, as recorded in 2017 by the Regional Veneto Cancer Registry (Northeast Italy). Older subjects were defined as ≥ 80, old as 65-79, and adults as < 65 years of age. The strength of association between pairs of variables was tested by Cramer's-V. Using age groups as the dependent variable, ordered logistic regression was fitted using the clinicopathological CMM profiles as covariates. In each of the three age-groups, the indicators of clinical performance were computed using the Clopper-Pearson exact method. RESULTS: Compared to patients aged younger than 80 years (1,187), CMM in older patients (181; 13.2%) featured different CMM topography, a higher prevalence of ulcers (43.3% versus 12.7%; p < 0.001), a higher Breslow index (p < 0.001), a lower prevalence of tumor-infiltrating lymphocytes (64.4% versus 76.5%, p < 0.01), and a more advanced pTNM stage at clinical presentation (p < 0.001). Elderly patients with a positive sentinel-lymph node less frequently underwent sentinel- lymph node biopsy and lymphadenectomy (60.0% versus 94.2%, and 44.4% versus 85.5%, respectively; p < 0.001). CONCLUSIONS: In older CMM patients, the clinicopathological presentation of CMM shows a distinctive profile. The present results provide critical information to optimize secondary prevention strategies and refine diagnostic-therapeutic procedures tailored to older patients.

Cutaneous melanoma in adolescents and young adults.

BACKGROUND: Cutaneous malignant melanoma (CMM) ranks among the five most common cancers in young people in high-income countries and it features peculiar clinicopathological traits. Very few studies have addressed the quality of care and the costs for adolescents and young adults (AYA) population. OBJECTIVE: To provide a comprehensive epidemiological and clinicopathological profile of CMM in AYA. The study also addresses the cost-of-illness and the diagnostic-therapeutic performance indicators by patient age category. METHODS: This population-based cohort study included 2435 incident CMM (age range 15-65 years; age 15-39 = 394; age 40-65 = 2041), as recorded in 2015, 2017 and 2019 by the Regional Veneto Cancer Registry (Italy). Cramer's-V tested the strength of association between pairs of variables. The Kaplan-Meier method was used to test the association between age and survival rate. The clinical performance indicators were computed using the Clopper-Pearson exact method. RESULTS: In AYA patients (16.2%), CMM incidence rates increased significantly from 1990 to 2019. Low-stage CMM (p = 0.007), radial growth pattern (p = 0.026) and lower Clark levels (p = 0.007) prevailed; males had less advanced malignancies (p = 0.003), with the trunk as the most common primary site (67.5%); the lower limbs (32.6%) were the most common primary site for females (p < 0.001). Overall survival was better in AYA than adults. No significant difference was detected in the clinical management of the two age groups, with the only exception of the margin in wide local excision. The care costs were lower in AYA (€195.99 vs. €258.94, p = 0.004). CONCLUSION: In AYA patients, the CMM clinicopathological presentation shows a distinctive profile. The present results provide critical information for optimizing primary and secondary prevention strategies and for tailoring diagnostic therapeutic procedures to the peculiar profile of AYA CMM patients.

Host-related low-prevalence gastritides: Epidemiological and clinical characterization.

INTRODUCTION: A recent consensus meeting (RE.GA.IN) addressed "host-related, low-prevalence gastritis": eosinophilic (EoG), lymphocytic (Hp-pos_LyG and Hp-neg_LyG), collagenous (CollG), and granulomatous gastritis (GrG). Our study evaluates their clinico-epidemiological characteristics. MATERIALS AND METHODS: We extracted all patients with a diagnosis of EoG, LyG, CollG, and GrG from a clinicopathological database and compared their demographics, clinical and endoscopic characteristics, associated conditions, and clinical awareness to those of all other subjects in the database (controls). RESULTS: There were 1,781,005 unique patients (median age 57 years; 55.7 % female). Hispanics were overrepresented amongst those with Hp-pos_LyG. Subjects with GrG had a high prevalence of erosions and ulcers. Clinical awareness of these conditions was dismal (<1:10,000 patients). Some clinical manifestations were more common in patients with certain gastritides (e.g., vomiting and diarrhea in CollG; anemia in LyG), but none were sufficiently distinctive to suggest a clinical diagnosis. EoG was associated with EoE; LyG had a strong association with celiac disease; CollG with microscopic colitis; and GrG with Crohn disease. CONCLUSIONS: The diagnosis of these gastritides (between <1: in 1,000 and 1 in 5000 subjects) rests on histopathology. They remain poorly characterized and clinically neglected. Yet, their associations may herald other conditions: eosinophilic gastrointestinal diseases (EGID), celiac, and Crohn disease. Patients might benefit from increased detection and characterization.

Geographical and temporal differences in gastric and oesophageal cancer registration by subsite and morphology in Europe.

Background: Gastric and oesophageal cancers pose a serious public health concern. In 2020 a total of 189,031 incident cases (136,038 stomach, 52,993 oesophagus) and 142,508 deaths (96,997 stomach, 45,511 oesophagus) were estimated in Europe. Oesophago-gastric cancers are a heterogeneous disease, with different aetiology and epidemiology for the various topographic subsites and main histopathological types. Topography subsite and morphology is key information to allow differentiating oesophago-gastric cancers. Correct registration and coding of such variables are fundamental in allowing proper description of the epidemiology of different subsites and histopathological types of oesophago-gastric cancers. The aim of this article is to highlight geographical and temporal variability in topography and morphology of oesophago-gastric cancers observed in Europe in the considered period. Methods: Data collected in the framework of the ENCR-JRC (European Commission's Joint Research Centre) data call and feeding the European Cancer Information System (ECIS) were used to assess the variability of topography and morphology registration of gastric and oesophageal cancer in Europe in the period 1995-2014. Malignant cancers of the stomach and the oesophagus were selected following, respectively, topography codes C16 and C15 of the International Classification of Diseases for Oncology, third edition (ICD-O-3). Analyses were performed by subsite, morphology group, year, sex, and European region. Results: A total of 840,464 incident cases occurring in the period 1995-2014 - 579,264 gastric (67.2%) and 276,260 (32.8%) oesophageal carcinomas - was selected for the analysis. Data was recorded by 53 PBCRs (9 based in Northern Europe, 14 in Western Europe, 3 in Eastern Europe and 27 in Southern Europe) from 19 countries. Conclusion: A wide variability in oesophago-gastric cancers topographic subsites and histopathological types patterns was observed, with a corresponding improvement in accuracy of registration in the analysis period. PBCRs are ideally placed to guide the epidemiological evaluations of such a complex group of diseases, in collaboration with clinicians, patients and other public health stakeholders.

Could the mitotic count improve personalized prognosis in melanoma patients?

A number of studies have indicated that the mitotic rate may be a predictive factor for poor prognosis in melanoma patients. The aim of this study was to investigate whether the mitotic rate is associated with other prognostic clinical and anatomopathological characteristics. After adjusting for other anatomopathological characteristics, we then verified the prognostic value of the number of mitoses, determining in which population subgroup this variable may have greater prognostic significance on 3-year mortality. The Veneto Cancer Registry (Registro Tumori del Veneto-RTV), a high-resolution population-based dataset covering the regional population of approximately 4.9 million residents, served as the clinical data source for the analysis. Inclusion criteria included all incident cases of invasive cutaneous malignant melanoma recorded in the RTV in 2015 (1,050 cases) and 2017 (1,205 cases) for which the number of mitoses was available. Mitotic classes were represented by Kaplan-Meier curves for short-term overall survival. Cox regression calculated hazard ratios in multivariable models to evaluate the independent prognostic role of different mitotic rate cut-offs. The results indicate that the mitotic rate is associated with other survival prognostic factors: the variables comprising the TNM stage (e.g., tumor thickness, ulceration, lymph node status and presence of metastasis) and the characteristics that are not included in the TNM stage (e.g., age, site of tumor, type of morphology, growth pattern and TIL). Moreover, this study demonstrated that, even after adjusting for these prognostic factors, mitoses per mm2 are associated with higher mortality, particularly in T2 patients. In conclusion, these findings revealed the need to include the mitotic rate in the histological diagnosis because it correlates with the prognosis as an independent factor. The mitotic rate can be used to develop a personalized medicine approach in the treatment and follow-up monitoring of melanoma patients.

Thirty-two-year trends of cancer incidence by sex and cancer site in the Veneto Region from 1987 to 2019.

Background: This observational study considers the sex-specific incidence of the most incident cancers as recorded in the population-based Veneto Regional Cancer Registry over a period of more than 30 years (1987-2019). Methods: The Veneto Regional Cancer Registry collected data for the time interval 1987-2019. Significant changes in incidence trends calculated on age-standardized incidence rates (Annual Percent Change-APC) were identified by join point regression analysis. Results: Overall, the incidence trend for all cancers decreased in males and remained stable in females. In nine cancer sites, the incidence trends showed consistent differences by sex (oral cavity, esophagus, colon rectum and anus, liver, larynx, lung, cutaneous malignant melanoma, bladder, and thyroid gland). Other malignancies did not show significant sex-related differences (stomach, pancreas, biliary tract, kidney/urinary tract, central nervous system, multiple myeloma, non-Hodgkin lymphoma, and leukemia). Conclusion: In the period 1987-2019, this study revealed sex-related differences in cancer incidence trends. Over time, cancer incidence remained higher in males, with a decreasing epidemiological impact, plausibly resulting from prevention campaigns against environmental cancer risk factors, as tobacco and alcohol. Conversely, a significant decrease was not observed in the incidence trend in females. These findings contribute essential insights for profiling the epidemiological map of cancer in a large Italian population, allowing comparison with other European cancer epidemiology studies and providing updated data supporting sex-related primary and secondary cancer prevention strategies.

Ductular reaction and hepatocyte ballooning identify patients with fibrosing cholestatic hepatitits after liver transplantation / La reacción ductular y la balonización de los hepatocitos permiten identificar a los pacientes con hepatitis colestásica fibrosante

Introduction: Diagnosis of severe hepatitis C recurrence is based on analytical and histological criteria but there is little information about their correlation. Aim: To assess the accuracy of laboratory criteria for the diagnosis of fibrosing cholestatic hepatitis (FCH). Patients and methods: Retrospective analysis of prospectively collected data form HCV positive patients who underwent liver transplantation (LT) between 2000 and 2014 in two European university hospitals. Patients were classified according to laboratory criteria such as FCH, cholestatic hepatitis (CH) and non-cholestatic acute hepatitis (NCAH). Histological characteristics were also evaluated. Results: Seventy patients with acute HCV recurrence within the first year after LT with an available liver biopsy were included in the study. Most patients were male (70%) with a median age of 58 years (50-64) and infected with genotype 1b (71.4%). Median time from LT to diagnosis of recurrence was 2.96 months (2.1-5.3). Thirty-nine patients were classified as FCH, 21 as CH and 10 as NCAH. Marked hepatocyte ballooning and ductular reaction were associated with the presence of FCH with an OR of 4.66 (p=0.047) and 20.58 (p=0.025), respectively. Considering liver biopsy as the gold standard, the sensitivity, specificity, positive and negative predictive values of the analytical criteria were 0.8, 0.5, 0.3 and 0.9, respectively. However, correlation between histological and analytical criteria was poor (k=0.033). Discussion: Analytical criteria may be used to rule out the presence of FCH, but a biopsy is mandatory to confirm the diagnosis. Ductular reaction and hepatocyte ballooning were independent predictors of FCH

Introducción: El diagnóstico de la recurrencia grave de la hepatitis C se basa en criterios histológicos y analíticos. Sin embargo, existe poca información respecto su correlación. Objetivo: Evaluar la precisión de los criterios analíticos el diagnóstico de la hepatitis colestásica fibrosante (HCF). Pacientes y métodos: Análisis retrospectivo de pacientes con una recidiva grave precoz del virus de la hepatitis C (VHC) tras el trasplante hepático (TH) en 2 hospitales universitarios europeos entre 2000-2014. Los pacientes se clasificaron según criterios analíticos en HCF, hepatitis colestásica (HC) y hepatitis aguda no colestásica (HANC). Las características histológicas también fueron evaluadas. Resultados: Se incluyeron 70 pacientes que desarrollaron una recurrencia grave del VHC en el primer año tras TH con una biopsia hepática disponible. La mayoría eran varones (70%) con mediana de edad de 58 años (50-64) y genotipo 1b (71,4%). La mediana de tiempo desde el TH hasta el diagnóstico de la recurrencia fue de 2,96 meses (2,1-5,3). Treinta y nueve pacientes fueron clasificados como HCF, 21 como HC y 10 como HANC. La balonización intensa y reacción ductular se asociaron con HCF con una OR de 4,66 (p=0,047) y 20,58 (p=0,025), respectivamente. Considerando la biopsia hepática como gold standard, la sensibilidad, especificidad y valores predictivos positivo y negativo de los criterios analíticos fueron 0,8, 0,5, 0,3 y 0,9, respectivamente. Sin embargo, la correlación entre ambos fue escasa (k=0,033). Discusión: Los criterios analíticos podrían utilizarse para descartar la presencia de HCF, pero la biopsia sigue siendo obligatoria para el diagnóstico. La reacción ductular y la balonización son predictores de HCF