Gastric Carcinoma in Autoimmune Gastritis: A Histopathologic and Molecular Study.

Patients with autoimmune gastritis (AIG) have a 13-fold risk of developing type-1 neuroendocrine tumors, whereas the risk for gastric adenocarcinoma is still uncertain. Here we describe the clinicopathologic and molecular features of a series of gastric carcinomas (GC) arising in the context of AIG. A total of 26 AIG-associated GC specimens were collected from 4 Italian Institutions. Immunohistochemistry for MUC1, MUC2, MUC5AC, MUC6, CDX2, HER2, PD-L1, CLDN18, mismatch repair (MMR) proteins, and p53 and EBV-encoded RNA (EBER) in situ hybridization were performed. Histologic and immunohistochemical features were jointly reviewed by 5 expert gastrointestinal pathologists. Next-generation sequencing analysis (TrueSight Oncology 500, Illumina) of 523 cancer-related genes was performed on 19 cases. Most tumors were diagnosed as pT1 (52%) and they were located in the corpus/fundus (58%) and associated with operative link for gastritis assessment stage II gastritis (80.8%), absence of parietal cells, complete intestinal metaplasia, and enterochromaffin-like-cell micronodular hyperplasia. Only 4 (15.4%) GCs were diagnosed during follow-up for AIG. The following histotypes were identified: 20 (77%) adenocarcinomas; 3 (11%) mixed neuroendocrine-non-neuroendocrine neoplasms, and 2 (8%) high-grade solid adenocarcinomas with focal neuroendocrine component, 1 (4%) adenocarcinoma with an amphicrine component. Overall, 7 cases (27%) showed MMR deficiency, 3 (12%) were positive (score 3+) for HER2, 6 (23%) were CLDN18 positive, and 11 (42%) had PD-L1 combined positive score ≥ 10. EBER was negative in all cases. Molecular analysis revealed 5/19 (26%) microsatellite instability (MSI) cases and 7 (37%) tumor mutational burden (TMB) high. The most frequently altered genes were TP53 (8/19, 42%), RNF43 (7/19, 37%), ERBB2 (7/19, 37% [2 amplified and 5 mutated cases]), ARID1A (6/19, 32%), and PIK3CA (4/19, 21%). In summary, AIG-associated GCs are often diagnosed at low stage in patients with longstanding misrecognized severe AIG; they often display a neuroendocrine component or differentiation, have relatively higher rates of MMR deficiency, and TMB high.

Clinical outcomes of diverticular disease in young adults: results from a tertiary referral center.

Introduction: Diverticular disease (DD), commonly associated with the elderly, is becoming more prevalent among younger individuals. This retrospective study aimed to evaluate the differences in the natural history and outcomes between young and old patients with DD. Methods: Adult patients with DD diagnosed between 2010 and 2022 at an Italian tertiary referral center were enrolled, and their demographic and clinical data were retrieved. The patients were categorized as young or old based on the 25th percentile of the population's age at diagnosis. Univariate and multivariate analyses were performed to assess the association between the collected variables and the age of disease presentation. Additionally, survival analyses were conducted to evaluate the association between the age of diagnosis and clinical outcomes at follow-up, including disease recurrence, hospital access, surgery, and death. Results: A total of 220 DD patients (with a median age of 66 years, IQR 55-74, and a female-to-male ratio of 1.4:1) were included in the study, comprising 54 patients receiving a diagnosis before the age of 49 years (young DD patients) and 166 patients diagnosed after the age of 49 years (old DD patients). Male sex (57 vs. 36%, p < 0.01), smoking (38 vs. 14%, p < 0.01), and alcohol consumption (54 vs. 38%) were highly prevalent in young patients. The complications at the time of diagnosis, particularly abscesses and free perforations, occurred more frequently in younger patients (p = 0.04). Moreover, young DD patients experienced a higher rate of hospitalization and surgical intervention (p = 0.01 and p = 0.04, respectively) over a median follow-up period of 5 years. Conclusion: Preventive strategies and prompt diagnosis are crucial in young patients with DD for achieving better disease outcomes and preventing complications.

Diagnostic Delay of Celiac Disease in Childhood.

Importance: The extent and factors associated with risk of diagnostic delay in pediatric celiac disease (CD) are poorly understood. Objectives: To investigate the diagnostic delay of CD in childhood, and to assess factors associated with this delay. Design, Setting, and Participants: Multicenter, retrospective, cross-sectional study (2010-2019) of pediatric (aged 0-18 years) patients with CD from 13 pediatric tertiary referral centers in Italy. Data were analyzed from January to June 2023. Main Outcomes and Measures: The overall diagnostic delay (ie, the time lapse occurring from the first symptoms or clinical data indicative of CD and the definitive diagnosis), further split into preconsultation and postconsultation diagnostic delay, were described. Univariable and multivariable linear regression models for factors associated with diagnostic delay were fitted. Factors associated with extreme diagnostic delay (ie, 1.5 × 75th percentile) and misdiagnosis were assessed. Results: A total of 3171 patients with CD were included. The mean (SD) age was 6.2 (3.9) years; 2010 patients (63.4%) were female; and 10 patients (0.3%) were Asian, 41 (1.3%) were Northern African, and 3115 (98.3%) were White. The median (IQR) overall diagnostic delay was 5 (2-11) months, and preconsultation and postconsultation diagnostic delay were 2 (0-6) months and 1 (0-3) month, respectively. The median (IQR) extreme overall diagnostic delay (586 cases [18.5%]) was 11 (5-131) months, and the preconsultation and postconsultation delays were 6 (2-120) and 3 (1-131) months, respectively. Patients who had a first diagnosis when aged less than 3 years (650 patients [20.5%]) showed a shorter diagnostic delay, both overall (median [IQR], 4 [1-7] months for patients aged less than 3 years vs 5 [2-12] months for others) and postconsultation (median [IQR], 1 [0-2] month for patients aged less than 3 years vs 2 [0-4] months for others). A shorter delay was registered in male patients, both overall (median [IQR], 4 [1-10] months for male patients vs 5 [2-12] months for female patients) and preconsultation (median [IQR], 1 [0-6] month for male patients vs 2 [0-6] months for female patients). Family history of CD was associated with lower preconsultation delay (odds ratio [OR], 0.59; 95% CI, 0.47-0.74) and lower overall extreme diagnostic delay (OR, 0.75; 95% CI, 0.56-0.99). Neurological symptoms (78 patients [21.5%]; OR, 1.35; 95% CI, 1.03-1.78), gastroesophageal reflux (9 patients [28.1%]; OR, 1.87; 95% CI, 1.02-3.42), and failure to thrive (215 patients [22.6%]; OR, 1.62; 95% CI, 1.31-2.00) showed a more frequent extreme diagnostic delay. A previous misdiagnosis (124 patients [4.0%]) was more frequently associated with gastroesophageal reflux disease, diarrhea, bloating, abdominal pain, constipation, fatigue, osteopenia, and villous atrophy (Marsh 3 classification). Conclusions and Relevance: In this cross-sectional study of pediatric CD, the diagnostic delay was rather short. Some factors associated with risk for longer diagnostic delay and misdiagnosis emerged, and these should be addressed in future studies.

Clinical and atopic features of patients with primary eosinophilic colitis: an Italian multicentre study.

Eosinophilic colitis (EC) is the rarest among primary eosinophilic gastrointestinal disorders (EGID). EC is underdiagnosed due to its blurred and proteiform clinical manifestations. To explore the clinical and atopic characteristic of EC adult patients, the diagnostic delay, and relapse-associated factors, by comparison with patients with eosinophilic esophagitis (EoE) and irritable bowel syndrome (IBS). EC patients followed-up at four clinics were included, and clinical, histopathological, and laboratory data were retrieved. As control groups, age-matched patients with EoE and IBS were recruited. Allergy tests included skin prick test and serum specific IgE. Diagnostic delay was assessed. Overall, data from 73 patients were retrieved, including 40 with EC (median age 39 years IQR 22.5-59, F:M 2.1:1), 12 with EoE (F:M ratio: 1:5), and 21 with IBS (F:M ratio: 1:0.9). The most common features in EC patients were female sex (67.5%), atopy (77.5%), abdominal pain/distention (70%), diarrhoea (77.5%), and faecal calprotectin elevation (22.5%). Blood eosinophils were elevated in EoE, but not in EC (p < 0.001), while ECP did not differ across the three groups (p = 0.4). The frequency of allergen sensitization reached 25% of patients. Several frequent pan-allergens for this region were present. The overall diagnostic delay was 10 months (IQR 4-15). Factors contributing to a greater diagnostic delay were atopy, weight loss, and a previous misdiagnosis. EC is mostly a diagnosis of exclusion, burdened by a substantial diagnostic delay. In female patients the presence of allergen sensitization, abdominal symptoms and faecal calprotectin elevation should raise the suspicion of EC.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis-Current Treatment and Monitoring.

The present document constitutes Part 2 of the EoETALY Consensus Statements guideline on the diagnosis and management of eosinophilic esophagitis (EoE) developed by experts in the field of EoE across Italy (i.e., EoETALY Consensus Group). Part 1 was published as a different document, and included three chapters discussing 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history and 3) diagnosis of EoE. The present work provides guidelines on the management of EoE in two final chapters: 4) treatment and 5) monitoring and follow-up, and also includes considerations on knowledge gaps and a proposed research agenda for the coming years. The guideline was developed through a Delphi process, with grading of the strength and quality of the evidence of the recommendations performed according to accepted GRADE criteria.This document has received the endorsement of three Italian national societies including the Italian Society of Gastroenterology (SIGE), the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). The guidelines also involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

Recent advances in intestinal fibrosis.

Despite many progresses have been made in the treatment of inflammatory bowel disease, especially due to the increasing number of effective therapies, the development of tissue fibrosis is a very common occurrence along the natural history of this condition. To a certain extent, fibrogenesis is a physiological and necessary process in all those conditions characterised by chronic inflammation. However, the excessive deposition of extracellular matrix within the bowel wall will end up in the formation of strictures, with the consequent need for surgery. A number of mechanisms have been described in this process, but some of them are not yet clear. For sure, the main trigger is the presence of a persistent inflammatory status within the mucosa, which in turn favours the occurrence of a pro-fibrogenic environment. Among the main key players, myofibroblasts, fibroblasts, immune cells, growth factors and cytokines must be mentioned. Although there are no available therapies able to target fibrosis, the only way to prevent it is by controlling inflammation. In this review, we summarize the state of art of the mechanisms involved in gut fibrogenesis, how to diagnose it, and which potential targets could be druggable to tackle fibrosis.

The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis - Definition, Clinical Presentation and Diagnosis.

Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.

Diagnostic delay in symptomatic uncomplicated diverticular disease: an Italian tertiary referral centre study.

The magnitude of the diagnostic delay of symptomatic uncomplicated diverticular disease (SUDD) is unknown; we aimed to evaluate SUDD diagnostic delay and its risk factors. SUDD patients diagnosed at a tertiary referral centre were retrospectively enrolled (2010-2022). Demographic and clinical data were retrieved. Overall, patient-, and physician-dependant diagnostic delays were assessed. Univariate and multivariate analyses were fitted to identify risk factors for diagnostic delay. Overall, 70 SUDD patients (median age 65 years, IQR 52-74; F:M ratio = 1.6:1) were assessed. The median overall diagnostic delay was 7 months (IQR 2-24), patient-dependant delay was 3 months (IQR 0-15), and physician-dependant delay was 1 month (IQR 0-6). Further, 25% of patients were misdiagnosed with irritable bowel syndrome (IBS). At multivariate analysis, previous misdiagnosis was a significant risk factor for overall and physician-dependant diagnostic delay (OR 9.99, p = 0.01, and OR 6.46, p = 0.02, respectively). Also, a high educational level (> 13 years) was associated with a greater overall diagnostic delay (OR 8.74 p = 0.02), while previous abdominal surgery was significantly associated to reduced physician-dependant diagnostic delay (OR 0.19 p = 0.04). To conclude, SUDD may be diagnosed late, IBS being the most frequent misdiagnosis. Timely diagnosis is crucial to tackle the burden of SUDD on patients and healthcare.

Long-Term Natural History of Autoimmune Gastritis: Results From a Prospective Monocentric Series.

INTRODUCTION: The natural history of autoimmune gastritis (AIG) has been poorly described. In this study, we report the long-term natural history and clinical clustering of the full spectrum of AIG, from the potential to the complicated stage. METHODS: Prospective single-center study conducted in a tertiary referral center. Patients with AIG at any stage (0 = potential; 1 = early; 2 = florid; 3 = severe; and 4 = complicated) were enrolled (January 2000-December 2022). The histopathological evolution, the clinical presentation, and the correlates of evolution of potential AIG were assessed. RESULTS: Four hundred ninety-eight patients with AIG (mean age 56.7 ± 15.2 years, F:M ratio 2.5:1) were included, of whom 93 experienced potential AIG. The maximum disease duration was 27 years (median 18, interquartile range 14-23), while the overall median follow-up was 52 months (interquartile range 12-95). Age was significantly lower in stage 0 compared with that in the other stages. Accidental histologic evidence and hematologic findings were the most common clusters of diagnosis. The overall median rate of progression was 7.29 per 100 persons/yr (95% confidence interval [CI] 6.19-8.59), while the stage-specific rates of progression were 10.85 (stage 0; 95% CI 7.75-15.18), 14.83 (stages 1-2; 95% CI 11.89-18.49), and 2.68 (stage 3; 95% CI 1.88-3.84). Newly onset neoplastic complications at follow-up occurred in 41/483 patients (8.5%; 23 neuroendocrine tumors and 18 epithelial dysplasia). No cases of adenocarcinoma were noticed. Male sex was associated with a greater likelihood of evolving from potential AIG to overt AIG. DISCUSSION: AIG is a progressive disorder, with a virtually absent risk of gastric adenocarcinoma. Patients with potential AIG should be monitored because they carry a high risk of evolving into overt AIG.

A Clinicopathologic Comparison Between Early-Onset and Late-Onset Small Bowel Adenocarcinoma: A Multicenter International Study.

INTRODUCTION: Early-onset small bowel adenocarcinoma (EO-SBA) is a rare and poorly characterized entity. METHODS: This retrospective study conducted on an international multicenter cohort of 208 patients with SBA aimed at comparing clinicopathologic features of EO-SBA (age younger than 50 years at SBA diagnosis) and late-onset SBA (age 50 years or older at SBA diagnosis). RESULTS: The presence of predisposing pathologic conditions was significantly more common in the EO-SBA group compared with that in the late-onset SBA group ( P = 0.003, Fisher exact test; relative risk: 1.50, 95% confidence interval: 1.20-1.86). This difference is mainly due to the significantly higher prevalence of celiac disease among patients with EO-SBA. DISCUSSION: EO-SBA is strongly associated with predisposing conditions, particularly with celiac disease, highlighting the importance of routine screening for celiac disease in patients with EO-SBA.

Haematological sequelae in the post-acute phase of symptomatic SARS-CoV-2 infection.

Many patients surviving SARS-CoV-2 infection suffer from long-term symptoms (long COVID or post COVID) such as shortness of breath, fatigue, loss of taste or smell and cognitive deterioration. However, few data are available concerning blood cell counts and haematological parameters during the post-COVID period. We analysed haematological data from 83 patients previously admitted to the internal medicine unit of our institution because of symptomatic SARS-CoV-2 infection; all data were obtained within 1-12 months from disease onset. A control group of 70 apparently healthy, age- and sex-matched COVID-19 negative individuals was assessed for comparison. Blood cell counts improved in the post-COVID period, but 81% of patients had persistent abnormalities, compared with 50% in the control group, p < 0.001. Most common haematological findings included anaemia (40%), reduced lymphocyte (43%) or eosinophil counts (38%) and low IgM memory B cells and correlated with advanced age, number of chronic comorbidities, female gender, altered renal function, reduced baseline Hb and procalcitonin concentrations and increased RDW. Data on lymphocytes and IgM memory B cells show that impaired immune responses may persist for up to one year in the post-COVID period, possibly contributing to long-term symptoms, especially in female patients.

Impact of proton pump inhibitors on the onset of gastrointestinal immune-related adverse events during immunotherapy.

INTRODUCTION: The gut microbiota (GM) can influence the pathogenesis of immune-mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. METHODS: In this retrospective single-center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). RESULTS: Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty-three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11-56.10, p < 0.000). This HR was confirmed after weighting for the propensity score (HR15.13 95% CI 3.22-71.03, p < 0.000). CONCLUSION: Chronic PPI use is associated with an increased risk of GI irAES.

Role of mucosal immunity and epithelial-vascular barrier in modulating gut homeostasis.

The intestinal mucosa represents the most extensive human barrier having a defense function against microbial and food antigens. This barrier is represented externally by a mucus layer, consisting mainly of mucins, antimicrobial peptides, and secretory immunoglobulin A (sIgA), which serves as the first interaction with the intestinal microbiota. Below is placed the epithelial monolayer, comprising enterocytes and specialized cells, such as goblet cells, Paneth cells, enterochromaffin cells, and others, each with a specific protective, endocrine, or immune function. This layer interacts with both the luminal environment and the underlying lamina propria, where mucosal immunity processes primarily take place. Specifically, the interaction between the microbiota and an intact mucosal barrier results in the activation of tolerogenic processes, mainly mediated by FOXP3+ regulatory T cells, underlying intestinal homeostasis. Conversely, the impairment of the mucosal barrier function, the alteration of the normal luminal microbiota composition (dysbiosis), or the imbalance between pro- and anti-inflammatory mucosal factors may result in inflammation and disease. Another crucial component of the intestinal barrier is the gut-vascular barrier, formed by endothelial cells, pericytes, and glial cells, which regulates the passage of molecules into the bloodstream. The aim of this review is to examine the various components of the intestinal barrier, assessing their interaction with the mucosal immune system, and focus on the immunological processes underlying homeostasis or inflammation.

SARS-CoV-2 infection in patients with inflammatory bowel disease: comparison between the first and second pandemic waves.

BACKGROUND: In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves. METHODS: Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020. RESULTS: We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p < 0.001) and comorbidities (48.9% vs. 38.9%; p < 0.01), and more frequently residing in Northern Italy (73.1% vs. 46.0%, p < 0.001) than patients of the second wave. There were no significant differences between pandemic waves in sex (male: 54.3% vs. 53.3%, p = 0.82) or frequency of active IBD (44.3% vs. 39.0%, p = 0.18). The rates of negative outcomes were significantly higher in the first than second wave: pneumonia (27.8% vs. 11.7%, p < 0.001), hospital admission (27.4% vs. 9.7%, p < 0.001), ventilatory support (11.9% vs. 5.4%, p < 0.003) and death (5.5% vs. 1.8%, p < 0.007). CONCLUSION: Between the first and second SARS-CoV-2 pandemic waves, demographic, clinical and geographical features of IBD patients were different as were the symptoms and outcomes of infection. These differences are likely due to the different epidemiological situations and diagnostic possibilities between the two waves.

Clinical and Histopathological Features of an Italian Monocentric Series of Primary Small Bowel T-Cell Lymphomas.

The gastrointestinal (GI) tract is the most common extranodal site of occurrence of non-Hodgkin lymphomas. Most GI lymphomas are of B-cell lineage, while T-cell lymphomas are less frequent. The aim of our retrospective study was to depict the clinical-pathological profile of a series of patients affected by intestinal T-cell lymphomas (ITCL) and possibly define hallmarks of these neoplasms. A total of 28 patients were included: 17 enteropathy-associated T-cell lymphomas (EATL), 5 monomorphic epitheliotropic T-cell lymphomas (MEITL), 3 indolent T-cell lymphoproliferative disorders of the gastrointestinal tract (ITCLDGT), and 3 intestinal T-cell lymphomas not otherwise specified (ITCL-NOS). Celiac disease (CD) was diagnosed in around 70% of cases. Diagnosis of EATL showed a significant correlation with CD30 expression, whereas MEITL with angiotropism and CD56 positivity. ITCLDGT cases showed plasma cells infiltration. Peripheral lymphocytosis, the absence of a previous diagnosis of CD, an advanced Lugano clinical stage, and the histological subtype ITCL-NOS were significantly associated with worse survival at multivariate analysis. Our findings about the epidemiological, clinical, and histopathological features of ITCL were in line with the current knowledge. Reliable prognostic tools for these neoplasms are still lacking but according to our results lymphocytosis, diagnosis of CD, Lugano clinical stage, and histological subtype should be considered for patient stratification.

Dietary Strategies in Adult Patients with Eosinophilic Esophagitis: A State-of-the-Art Review.

Allergen-free diets are a specific and effective anti-inflammatory therapy for eosinophilic esophagitis. They should be carried out by a multidisciplinary team to reduce side effects and improve adherence. According to recent guidelines and expert opinions, empirical diets with a reduced number of eliminated food categories and a step-up approach are the most encouraged strategy to reduce the number of endoscopies to identify food trigger(s) and maximize clinical results and adherence. Despite the fact that allergy testing-based diets are not recommended at a population level, geographical sensitization patterns may play a role in some patients in specific areas, such as in Southern and Central Europe.

Immunotherapy with Pru p 3 for food allergy to peach and non-specific lipid transfer protein: a systematic review.

BACKGROUND: Non-specific lipid-transfer protein (nsLTP) is a pan-allergen in the plant world, and a cause of significant concern as food allergen in the Mediterranean area, due to its general heat- and acid-resistance and hence the risk of severe allergic reactions. Pru p 3, the peach nsLTP, is considered the primary sensitizer to this allergen family and this allergy is usually persistent. Allergen-free diet and acute treatment of manifestations are the main recognized management goals in food allergy. MAIN TEXT: The role of immunotherapy for treating food allergy in adult patients is controversial, but immunotherapy for Pru p 3 could potentially represent a relevant therapeutic strategy. We systematically searched databases for studies assessing the role of immunotherapy Pru p 3 in food allergy. Overall, nine studies were included. Immunotherapy with Pru p 3 appears to be effective and with a good safety profile in both peach and LTP allergy for some foods, such as peanut, in both RCT and real-life studies. CONCLUSIONS: Immunotherapy with Pru p 3 is a possible treatment option for food allergy to the peach LTP in the Mediterranean area, although at present have not reached routinary clinical practice. Larger studies are needed to confirm these findings and identify predictive biomarkers.

Mismatch repair deficiency as prognostic factor for stage III small bowel adenocarcinoma: A multicentric international study.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare cancer with an aggressive behavior. No study has specifically addressed the putative prognostic role of mismatch repair status in stage III SBAs. AIMS: We aimed to investigate whether mismatch repair deficiency is associated with cancer-specific survival in a Western cohort of patients with stage III SBAs. METHODS: In this retrospective multicentric international cohort study, we enrolled 70 patients who underwent surgically resection for stage III SBAs and we analyzed the frequency of mismatch repair deficiency, tested by immunohistochemistry for mismatch repair proteins and by polymerase chain reaction for microsatellite instability, and its association with cancer-specific survival and other clinic-pathologic factors. RESULTS: We found sixteen (23%) patients with mismatch repair deficient adenocarcinoma, without discordance between immunohistochemical and polymerase chain reaction for microsatellite instability analyses. Mismatch repair deficiency proved to be associated with a better outcome both at univariable analysis (hazard ratio: 0.28, 95% confidence interval: 0.08-0.91, p: 0.035) and in bivariable models adjusted for patient age or gender, tumor site, pT4 stage, tumor budding, and perineural invasion. CONCLUSION: This study highlights the importance of testing mismatch repair status to improve prognostic stratification in stage III SBAs.