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.

Adenoma Detection Rate and Colorectal Cancer Risk in Fecal Immunochemical Test Screening Programs : An Observational Cohort Study.

BACKGROUND: Colorectal cancer (CRC) screening programs based on fecal immunochemical tests (FITs) represent the standard of care for population-based interventions. Their benefit depends on the identification of neoplasia at colonoscopy after FIT positivity. Colonoscopy quality measured by adenoma detection rate (ADR) may affect screening program effectiveness. OBJECTIVE: To examine the association between ADR and postcolonoscopy CRC (PCCRC) risk in a FIT-based screening program. DESIGN: Retrospective population-based cohort study. SETTING: Fecal immunochemical test-based CRC screening program between 2003 and 2021 in northeastern Italy. PATIENTS: All patients with a positive FIT result who had a colonoscopy were included. MEASUREMENTS: The regional cancer registry supplied information on any PCCRC diagnosed between 6 months and 10 years after colonoscopy. Endoscopists' ADR was categorized into 5 groups (20% to 39.9%, 40% to 44.9%, 45% to 49.9%, 50% to 54.9%, and 55% to 70%). To examine the association of ADR with PCCRC incidence risk, Cox regression models were fitted to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Of the 110 109 initial colonoscopies, 49 626 colonoscopies done by 113 endoscopists between 2012 and 2017 were included. After 328 778 person-years follow-up, 277 cases of PCCRC were diagnosed. Mean ADR was 48.3% (range, 23% and 70%). Incidence rates of PCCRC from lowest to highest ADR group were 13.13, 10.61, 7.60, 6.01, and 5.78 per 10 000 person-years. There was a significant inverse association between ADR and PCCRC incidence risk, with a 2.35-fold risk increase (95% CI, 1.63 to 3.38) in the lowest group compared with the highest. The adjusted HR for PCCRC associated with 1% increase in ADR was 0.96 (CI, 0.95 to 0.98). LIMITATION: Adenoma detection rate is partly determined by FIT positivity cutoff; exact values may vary in different settings. CONCLUSION: In a FIT-based screening program, ADR is inversely associated with PCCRC incidence risk, mandating appropriate colonoscopy quality monitoring in this setting. Increasing endoscopists' ADR may significantly reduce PCCRC risk. PRIMARY FUNDING SOURCE: None.

Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients.

OBJECTIVE: Autoimmune gastritis (AIG) is an immunomediated disease targeting parietal cells, eventually resulting in oxyntic-restricted atrophy. This long-term follow-up study aimed at elucidating the natural history, histological phenotype(s), and associated cancer risk of patients with AIG consistently tested H. pylori-negative (naïve H. pylori-negative subjects). DESIGN: Two-hundred eleven naïve H. pylori-negative patients (tested by serology, histology, molecular biology) with AIG (F:M=3.15:1; p<0.001) were prospectively followed up with paired biopsies (T1 vs T2; mean follow-up years:7.5 (SD:4.4); median:7). Histology distinguished non-atrophic versus atrophic AIG. Atrophy was further subtyped/scored as non-metaplastic versus metaplastic (pseudopyloric (PPM) and intestinal (IM)). Enterochromaffin-like-cell (ECL) status was categorised as diffuse versus adenomatoid hyperplasia/dysplasia, and type 1 neuroendocrine tumours (Type1-NETs). RESULTS: Over the long-term histological follow-up, AIG consistently featured oxyntic-predominant-mononuclear inflammation. At T1, PPM-score was greater than IM (200/211 vs 160/211, respectively); IM scores increased from T1 to T2 (160/211 to 179/211), with no changes in the PPM prevalence (T1=200/211; T2=201/211). At both T1/T2, the prevalence of OLGA-III-stage was <5%; no Operative Link on Gastritis Assessment (OLGA)-IV-stage occurred. ECL-cell-status progressed from diffuse to adenomatoid hyperplasia/dysplasia (T1=167/14 vs T2=151/25). Type1-NETs (T1=10; T2=11) always coexisted with extensive oxyntic-atrophy, and ECL adenomatoid-hyperplasia/dysplasia. No excess risk of gastric or other malignancies was found over a cumulative follow-up time of 10 541 person years, except for (marginally significant) thyroid cancer (SIR=3.09; 95% CI 1.001 to 7.20). CONCLUSIONS: Oxyntic-restricted inflammation, PPM (more than IM), and ECL-cell hyperplasia/neoplasia are the histological AIG hallmarks. Compared with the general population, corpus-restricted inflammation/atrophy does not increase the GC risk. The excess of GC risk reported in patients with AIG could plausibly result from unrecognised previous/current H. pylori comorbidity.

Incomplete Intestinal Metaplasia Is Rare in Autoimmune Gastritis.

BACKGROUND: Incomplete intestinal metaplasia (IM) is reportedly associated with higher gastric cancer (GC) risk than its complete variant. AGA Guidelines recommend including IM subtyping in routine pathology reports. This study assesses the prevalence of complete versus incomplete IM in gastric conditions with different GC risks. METHODS: IM subtyping (complete vs. incomplete) and grading (IM extension: G1: ≤30%; G2: >30%) were assessed in 386 patients with IM + ve gastric biopsy sets that included both antral and oxyntic samples. Cases were categorized as: (a) IM foci in otherwise normal mucosa (n = 59); (b) Helicobacter pylori gastritis (n = 138); (c) reactive gastropathy (141); and (d) autoimmune atrophic gastritis (AIG, n = 48). Odds ratios (OR) and their 95% CI were used in comparing the prevalence of incomplete IM and the correlation between subtype and IM extension. RESULTS: Incomplete IM was present in 37.7% of patients with H. pylori gastritis, 8.3% of those with AIG 5.0% of those with reactive gastropathy, and none of those with otherwise normal mucosa. Incomplete IM was strongly associated with more extensive (G2-IM) mucosal intestinalization (OR = 6.69; 95% CI = 2.77-9.40). CONCLUSION: Incomplete IM is significantly more prevalent in conditions (H. pylori gastritis) known to carry a higher risk of GC and is strongly associated with its extension. The low prevalence of incomplete IM in AIG (8.3%) and reactive gastropathy (5.2%) is in keeping with the low GC risk associated with these conditions.

Non-compliance with colonoscopy after a positive faecal immunochemical test doubles the risk of dying from colorectal cancer.

BACKGROUND: The risk of colorectal cancer (CRC) among subjects with a positive faecal immunochemical test (FIT) who do not undergo a colonoscopy is unknown. We estimated whether non-compliance with colonoscopy after a positive FIT is associated with increased CRC incidence and mortality. METHODS: The FIT-based CRC screening programme in the Veneto region (Italy) invited persons aged 50 to 69 years with a positive FIT (>20 µg Hb/g faeces) for diagnostic colonoscopy at an endoscopic referral centre. In this retrospective cohort study, we compared the 10-year cumulative CRC incidence and mortality among FIT positives who completed a diagnostic colonoscopy within the programme (compliers) and those who did not (non-compliers), using the Kaplan-Meier estimator and Cox-Aalen models. RESULTS: Some 88 013 patients who were FIT positive complied with colonoscopy (males: 56.1%; aged 50-59 years: 49.1%) while 23 410 did not (males: 54.6%; aged 50-59 years: 44.9%).The 10-year cumulative incidence of CRC was 44.7 per 1000 (95% CI, 43.1 to 46.3) among colonoscopy compliers and 54.3 per 1000 (95% CI, 49.9 to 58.7) in non-compliers, while the cumulative mortality for CRC was 6.8 per 1000 (95% CI, 5.9 to 7.6) and 16.0 per 1000 (95% CI, 13.1 to 18.9), respectively. The risk of dying of CRC among non-compliers was 103% higher than among compliers (adjusted HR, 2.03; 95% CI, 1.68 to 2.44). CONCLUSION: The excess risk of CRC death among those not completing colonoscopy after a positive faecal occult blood test should prompt screening programmes to adopt effective interventions to increase compliance in this high-risk population.

Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report.

Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.

Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction.

OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

Organ donation from patients with a rare disease is often safe: the italian guidelines.

Although a disease is defined as rare when it has a prevalence of less than 1:2000, the overall prevalence of rare diseases in the population is greater than 1%. Among potential organ donors, a similar frequency is observed. To date, guidelines have not been established, and operational decisions have been made empirically, case- by-case, based on the experience and expertise of clinicians. For this reason, the Italian Superior Health Council (CSS) has appointed a working Group to address "patients with a rare disease as potential organ donors," with the aim of devising recommendations for the management of transplant cases in which the donors have a rare disease. This group evaluated 493 diseases (10% of all rare diseases, including over 95% of patients with a rare disease) to deliver a technical report dealing with the suitability of organ donation and transplantation, with a focus on the organs most frequently used, including kidney, liver, heart, lung, and pancreas. This work has made it clear that a rare disease "per se" does not contraindicate organ donation at all. Indeed, in donors affected by a rare disease, almost 80% of the organs are suitable for transplantation, approximately 7% are unsuitable, and approximately 14% are suitable as non-standard with an acceptable risk.

Pepsinogen II in gastritis and Helicobacter pylori infection.

BACKGROUND AND AIM: In the gastric mucosa, pepsinogen II (PgII) is produced/secreted by glands in the mucus-secreting antral and cardia compartments, but also by the chief cells and the oxyntic glands. Increasing PgII serum levels are associated with the whole spectrum of gastric inflammatory diseases, including gastritis induced by Helicobacter pylori (H. pylori). This review critically addresses the clinical value of PgII serology for assessing gastric mucosal inflammation, and as a marker of H. pylori status, in both H. pylori-positive patients and after eradication therapy. RESULTS: A search in PubMed/Scopus records yielded 39 out of 1190 published scientific studies meeting the selection criteria for this study. In the studies considered, PgII levels were significantly associated with non-atrophic gastric inflammatory lesions (p-values: 0.025-0.0001). H. pylori-positive patients had significantly higher PgII levels than H. pylori-negative individuals (p-values: 0.o5-0.0001). While a significant drop in serum PgII levels is consistently reported in H. pylori-eradicated patients (p-values: from 0.05 to 0.0001), inconsistencies in the related negative and positive predictive values significantly lower the clinical reliability of PgII testing by comparison with other available non-invasive tests. CONCLUSIONS: PgII serology may provide clinically useful information on gastric inflammatory diseases, particularly if they are non-atrophic. PgII serology is inconsistent, however, for the purposes of distinguishing patients whose H. pylori eradication therapy is successful from those who remain infected.

Renal cell carcinoma: the population, real world, and cost-of-illness.

BACKGROUND: The RCC treatment landscape has evolved dramatically over the past decade. The purpose of this study is to present a real-world data estimation of RCC's cost-of-illness for this tumour's clinical pathway. METHODS: This investigation is a population-based cohort study using real-world data, which considers all RCC incident cases diagnosed in Local Unit 6 of the Province of Padua in 2016 and 2017 as registered by the Veneto Cancer Registry. Data on drug prescriptions, the use of medical devices, hospital admissions, and visits to outpatient clinics and emergency departments were collected by means of administrative databases. We evaluated the costs of all healthcare procedures performed in the 2 years of follow-up post-RCC diagnosis. The overall and annual average real-world costs per patient, both as a whole and by single item, were calculated and stratified by stage of disease at diagnosis. RESULTS: The analysis involved a population of 148 patients with a median age of 65.8 years, 66.22% of whom were male. Two years after diagnosis, the average total costs amounted to €21,429 per patient. There is a steady increment in costs with increasing stage at diagnosis, with a total amount of €41,494 spent 2 years after diagnosis for stage IV patients, which is 2.44 times higher than the expenditure for stage I patients (€17,037). In the first year, hospitalization appeared to be the most expensive item for both early and advanced disease. In the second year, however, outpatient procedures were the main cost driver in the earlier stages, whereas anticancer drugs accounted for the highest costs in the advanced stages. CONCLUSIONS: This observational study provides real-world and valuable estimates of RCC's cost-of-illness, which could enable policymakers to construct dynamic economic cost-effectiveness evaluation models based on real world costs' evaluation.

Young immigrant women and cervical cancer screening: participation and lesions detected at the first screening round.

OBJECTIVES: to evaluate if the country of origin affects participation and outcomes of cervical cancer screening. DESIGN: retrospective cohort study. SETTING AND PARTICIPANTS: all Italian and foreign women resident in the Veneto region (North-Eastern Italy) who were born between 1986 and 1992 and who had been invited for the first time through the screening programme between 2011 and 2017 were identified and included in the survey. MAIN OUTCOME MEASURES: participation to screening was calculated along with the detection of Cervical Intraepithelial Neoplasia (CIN) grade 2 or 3 and of carcinoma, by citizenship. RESULTS: 96,105 (77.5%) Italians and 27,958 (22.5%) foreign women were included. Overall, the adjusted participation was 53.3%, with large differences among the geographical study areas. The value was highest for Italian women (56.4%), while women with other citizenships showed lower attendance: 45.5% for Eastern Europe, 44.8% for Sub Saharan Africa, 40.0% for Northern Africa, 38.5% for Central and Southern America, and 36.5% for Asia. The detection of CIN2+ was higher for women from Central and Southern America (23.0‰) or from Eastern Europe (17.9‰), while it was lower for those from Italy (11.9‰), Northern Africa (7.5‰), Sub-Saharan Africa (6.6‰), and from Asia (2.5‰) (p<0.001). CONCLUSIONS: cervical screening programmes should identify and face the barriers to participation of foreign women. This is particularly important for women from geographic areas with a high prevalence of disease, such as Central and Southern America and Eastern Europe.

Colorectal cancer incidence and mortality after negative fecal immunochemical tests by age 70: A prospective observational study.

Limited endoscopy capacity usually represents the main barrier to the extension of screening to subjects older than 70, given the high positivity rate in this age group. We assessed CRC incidence and mortality by number of previous negative fecal immunochemical tests (FIT) among subjects turning 70. We selected persons aged 70 years who had received their last screening invitation when they were 68 or 69 years old within the population-based screening program in the Veneto region of Italy. Subjects with a positive FIT were excluded. We calculated 10-year cumulative CRC incidence and mortality in cohorts of subjects having performed zero, one, two or three negative FITs over the last three screening rounds before turning 70. Out of 117 858 subjects included in the study (46.4% men), 33.7% had never participated in screening (zero negative FITs), 23.3% had had one-negative FIT, 20.1% two-negative FITs and 22.9% three negative FITs. The 10-year cumulative CRC incidence was 29.7 per 1000 subjects with zero FITs, and respectively, 14.5, 11.7 and 9.6 per 1000 subjects with one, two and three negative FITs. The corresponding figures for 10-year cumulative mortality were 9.3, 3.5, 2.2 and 2.1 per 1000 in the four study cohorts. Figures were roughly double for men than for women for all the study cohorts. In order to use more efficiently limited endoscopy resources, and to minimize the potential harms related to false positive results in the elderly, screening among people aged 70 to 74 might be restricted to those with zero previous negative FITs.

Diagnosis of digestive system tumours.

The WHO Classification of Tumours provides the international standards for the classification and diagnosis of tumours. It enables direct comparisons to be made between different countries. In the new fifth edition, the series has gone digital with the launch of a website as well as a series of books, known widely as the WHO Blue Books. The first volume to be produced is on the classification of Digestive System tumours, replacing the successful 2010 version. It has been rewritten and updated accordingly. This article summarises the major diagnostic innovations that have occurred over the last decade and that have now been incorporated in the classification. As an example, it incorporates the recently proposed classification of neuroendocrine tumours, based on the recognition that neuroendocrine tumours and carcinomas differ substantially in the genetic abnormalities that drive their growth, findings relevant to treatment selection and outcome prediction. Several themes have emerged during the production process. One is the importance of the progression from hyperplasia to dysplasia to carcinoma in the evolution of the malignant process. Advances in imaging techniques and endoscopy have resulted in enhanced access to precancerous lesions in the gastrointestinal and biliary tract, necessitating both changes in classification schema and clinical practice. Diagnosis of tumours is no longer the sole purview of pathologists, and some patients now receive treatment before tissue is obtained, based on clinical, radiological and liquid biopsy results. This makes the classification relevant to many disciplines involved in the care of patients with tumours of the digestive system.

Mid-term trends and recent birth-cohort-dependent changes in incidence rates of cutaneous malignant melanoma in Italy.

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe.

Prevalence of Gastric Intestinal Metaplasia in a Multiethnic US Veterans Population.

BACKGROUND & AIMS: There is a need to identify individuals with gastric intestinal metaplasia, a precursor to gastric cancer, so they can be offered screening and surveillance. We examined the prevalence of gastric intestinal metaplasia, detected by upper endoscopy biopsy analysis, in different race and ethnic subgroups. We also investigated the extent to which Helicobacter pylori infection, with or without acute and chronic gastritis, accounts for observed associations between race or ethnicity and risk of gastric intestinal metaplasia. METHODS: We used data from a cross-sectional study of consecutively recruited patients at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, from February 2008 to August 2013. All participants completed a study questionnaire on sociodemographic and clinical characteristics and underwent upper endoscopy with gastric mapping (7 biopsy sites). Cases were classified as having gastric intestinal metaplasia if intestinal metaplasia was detected in 1 or more noncardia gastric biopsies; noncases were participants without evidence of gastric intestinal metaplasia. We used logistic regression models to estimate odds ratios (ORs) and 95% CI values to examine the association between race or ethnicity and gastric intestinal metaplasia and performed a mediation analysis to determine whether H pylori and gastritis affected observed associations. RESULTS: We included 415 cases with gastric intestinal metaplasia and 1764 noncases. The prevalence of gastric intestinal metaplasia was highest among Hispanic patients (29.5%; 95% CI, 23.7%-36.1%), followed by African American (25.5%; 95% CI, 22.4%-28.9%) and non-Hispanic white patients (13.7%; 95% CI, 11.9%-15.7%). After we adjusted for age, sex, and smoking, African American (OR, 1.87; 95% CI, 1.44-2.44) and Hispanic race or ethnicity (OR, 2.32; 95% CI, 1.61-3.34) and H pylori infection (OR, 3.65; 95% CI, 2.79-4.55) were associated with an increased risk of gastric intestinal metaplasia. H pylori infection alone accounted for 33.6% of the association of race or ethnicity with gastric intestinal metaplasia, and 55.5% of the association when combined with acute and chronic gastritis. CONCLUSIONS: Hispanic and African American patients have an increased risk for gastric intestinal metaplasia, determined by upper endoscopy biopsy analysis, compared with non-Hispanic white patients. This increase in risk was partially independent of H pylori infection.

Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas.

BACKGROUND: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. PATIENTS AND METHODS: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability. RESULTS: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status. CONCLUSIONS: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.

Prevalence of Barrett's esophagus and performance of societal screening guidelines in an unreferred primary care population of U.S. veterans.

BACKGROUND AND AIMS: Less than 10% of patients diagnosed with esophageal adenocarcinoma have a pre-existing Barrett's esophagus (BE) diagnosis, possibly because of suboptimal performance of guidelines. We examined the prevalence of BE in a previously unscreened primary care population and the potential yield of practice BE screening guidelines. METHODS: This was a retrospective analysis of a prospective cross-sectional study of consecutively recruited unreferred patients from primary care clinics who underwent study upper endoscopy. We examined the performance of BE screening guidelines of the European Society of Gastrointestinal Endoscopy (ESGE), British Society of Gastroenterology (BSG), American Society for Gastrointestinal Endoscopy (ASGE), American College of Gastroenterology (ACG), American Gastroenterological Association (AGA), and our own modification of guidelines. RESULTS: We identified 44 BE cases and 469 control subjects (prevalence, 8.6%). Among 371 patients without GERD symptoms, 25 (6.7%) had BE. The AGA guidelines requiring ≥2 BE risk factors had sensitivity of 100% and specificity of only .2%, whereas ACG, ASGE, ESGE, and BSG guidelines (all requiring GERD first) had low sensitivities (38.6%-43.2%), specificities ranging from 67.4% to 76.5%, and area under the receiver operating curve (AUROC) of .50 to .60. Our 2-pronged approach depending on presence or absence of GERD symptoms but with other risk factors achieved sensitivity of 81.8%, specificity of 51.2%, and AUROC of .66. CONCLUSIONS: Over half of BE cases were without frequent GERD symptoms, but virtually all had at least 1 known BE risk factor. Practice guidelines requiring GERD symptoms have low sensitivity, whereas those not requiring GERD have low specificity. We have proposed a screening guideline with better use of known risk factors.