INTRODUCTION:Colonic diverticulosis is the most common structural abnormality of the colon in developed countries, with an increasing global prevalence. Approximately 20-25% of affected individuals develop symptoms, collectively referred to as diverticular disease. Given its wide clinical spectrum, evolving pathophysiological insights and growing disease burden, updated guidance is essential. METHODS:This International Consensus, developed by 32 experts from 14 countries through a structured Delphi process based on the PICO framework and GRADE methodology, provides evidence-based recommendations across five domains: epidemiology and pathogenesis; clinical features; diagnosis; medical therapy; and surgical management. RESULTS:Key statements define diverticulosis as the presence of diverticula without symptoms and diverticular disease as diverticula associated with symptoms or complications. High dietary fibre intake is protective whereas smoking, obesity and the use of non-steroidal anti-inflammatory drugs, corticosteroids, opioids or immunotherapy increase risk. Imaging is essential in suspected acute diverticulitis: ultrasound may be appropriate in experienced hands, while CT remains preferred for complicated cases. Diverticulosis itself requires no treatment. In symptomatic uncomplicated diverticular disease, dietary fibre, selected probiotics, mesalazine and rifaximin may help relieve symptoms. Routine antibiotic use is not recommended for acute uncomplicated diverticulitis, and elective surgery should be individualised, prioritising quality of life considerations over episode count. CONCLUSIONS:These Consensus statements aim to standardise and optimise the diagnosis, management and prevention of diverticular disease across diverse healthcare systems, while highlighting research priorities such as microbiome characterisation, genetic risk profiling and long-term outcomes of selective antimicrobial and surgical strategies.

The optimal treatment for recurrent glioblastoma (rGBM) remains controversial. We explore the impact of re-surgical resection, compared to solely oncological treatment, in a cohort of isocitrate dehydrogenase (IDH) wild-type rGBM. A retrospective cohort study included adult patients diagnosed with IDHwt rGBM. At recurrence, patients recieved re-surgical resection (re-surgery group - RSG) or further oncological treatments (chemo-radiation group - CRG). Overall survival (OS) and progression-free survival (PFS) were analyzed. A Cox regression model was performed to identify variables related to outcomes. Furthermore, to minimize possible study design-related bias, a propensity score analysis was applied. Additionally, subgroup analysis to explore the role of adjuvant therapies was performed. In a cohort of 104 patients with rGBM, 44 patients received re-surgical resection. Patients in RSG experienced a longer OS compared to CRG (21 vs. 12 months, p < 0.001); a shorter survival in the CRG was confirmed at the propensity score analysis (HR 2.16, p = 0.004). The median cohort PFS was 4 months. The PFS was similar between the RSG and CRG (6 vs. 4 months). The variables associated with OS were: age, subventricular zone involvement, repeated chemotherapy. The variables associated with PFS were: extent of resection at first surgery, MGMT methylation, no adjuvant therapies, and delayed radiotherapy. At the subgroup analysis, re-irradiation was not associated with OS or PFS benefit in the RSG; adjuvant chemo-radiation therapy offers a survival advantage compared to standard adjuvant chemotherapy in the CRG. Re-surgical resection offers a significant survival benefit compared to the sole adjuvant treatment in patients with IDHwt rGBM.

BACKGROUND AND AIMS:Chronic atrophic gastritis (CAG) is a known precancerous condition that can lead to the development of gastric cancer (GC). Low serum pepsinogen (PG) I levels have been proposed as a non-invasive marker for chronic atrophic gastritis of the stomach body, but the adequate upper cut-off for diagnosis remains controversial, as values ranging from 30 to 50 mcg/L are currently considered as a "grey zone". We aimed to identify patients with chronic atrophic gastritis (CAG) of the stomach body amongst subjects with PG-I levels ranging between 30 and 50 mcg/L by means of a proton pump inhibitor (PPI) challenge. METHODS:We selected 102 patients with baseline PG-I <60 mcg/L in whom upper gastrointestinal endoscopy with protocol biopsies staged according to OLGA system had been performed. Subsequently, all patients underwent a PPI challenge (consisting of PG-I testing after taking Esomeprazole 40 mg daily for 1 week). This population was divided into 5 groups according to PG-I levels: group A (PG-I< 30 mcg/L); group B (PG-I: 31-35 mcg/L); group C (PG-I: 36-40 mcg/L); group D (PG-I: 41-50 mcg/L); group E (PG-I: 51-60 mcg/L). By using the ROC curve, a cut-off of 30% increase from baseline PG-I was chosen. RESULTS:A statistically significant relationship between PG-I levels and OLGA staging was found, being 100% in the group of PG-I < 30mcg/L. Based on the value of the cut-off of 30% (calculated by ROC curve) corresponding to the delta increase between PG-I baseline value and after a one-week full dose of PPI, the positive predictive value was 95%, the negative predictive value 86%, the sensitivity 83% and the specificity 96%. CONCLUSIONS:The use of the PPI challenge allows to identify subjects with CAG showing pepsinogen I values ranging between 30 and 50 mcg/L.

Introduction Colonic diverticulosis is the most common structural abnormality of the colon in developed countries, with an increasing global prevalence. Approximately 20-25% of affected individuals develop symptoms, collectively referred to as diverticular disease. Given its wide clinical spectrum, evolving pathophysiological insights and growing disease burden, updated guidance is essential. Methods This International Consensus, developed by 32 experts from 14 countries through a structured Delphi process based on the PICO framework and GRADE methodology, provides evidence-based recommendations across five domains: epidemiology and pathogenesis; clinical features; diagnosis; medical therapy; and surgical management. Results Key statements define diverticulosis as the presence of diverticula without symptoms and diverticular disease as diverticula associated with symptoms or complications. High dietary fibre intake is protective whereas smoking, obesity and the use of non-steroidal anti-inflammatory drugs, corticosteroids, opioids or immunotherapy increase risk. Imaging is essential in suspected acute diverticulitis: ultrasound may be appropriate in experienced hands, while CT remains preferred for complicated cases. Diverticulosis itself requires no treatment. In symptomatic uncomplicated diverticular disease, dietary fibre, selected probiotics, mesalazine and rifaximin may help relieve symptoms. Routine antibiotic use is not recommended for acute uncomplicated diverticulitis, and elective surgery should be individualised, prioritising quality of life considerations over episode count. Conclusions These Consensus statements aim to standardise and optimise the diagnosis, management and prevention of diverticular disease across diverse healthcare systems, while highlighting research priorities such as microbiome characterisation, genetic risk profiling and long-term outcomes of selective antimicrobial and surgical strategies.

Background. Gastrointestinal severe adverse events such as ulceration and perforation have been reported for sodium or calcium polystyrene sulfonate and sevelamer. Howewer, their role in the pathogenesis is unclear. Chronic kidney disease is a well known risk factor, while the role of hypertension and/or diabetes is uncertain. Methods. A meta-analysis of the published literature was conducted to review the clinical features, risk factors and histopathological findings of patients who experienced gastrointestinal adverse events after administration of polystyrene sulfonate or sevelamer. Results. The meta-analysis indicated that patients were more likely to show necrosis and/ or perforation when the resin used was polystyrene sulfonate compared to sevelamer (p < 0.001). Death was more likely in patients taking polystyrene sulfonate compared to sevelamer (p < 0.001). Discussion. The results show that sevelamer is more likely to lead to inflammation or ulceration in the gastrointestinal tract than polystyrene sulfonate, which is more likely to be associated with severe gastrointestinal adverse events such as necrosis and/or perforation. Polystyrene sulfonate is significantly associated with death compared to sevelamer.

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.

BACKGROUND Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover, whether prokinetics or barrier drugs used alongside PPIs are more effective remains under debate. OBJECTIVES The aim of the study was to assess the efficacy of different therapeutic approaches to GERD treatment. MATERIAL AND METHODS We enrolled 211 grade A reflux esophagitis patients who consented to participate in this non-randomized, open-label trial. The study consisted of 6 sequentially administered medical treatments for GERD, lasting 2 months, with a 3-week washout period between each drug schedule: Group A: PPI (esomeprazole 40 mg/day before breakfast); Group B: mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, 3 times daily after a meal); Group C: prokinetics (levosulpiride 25 mg or domperidone 10 mg, 3 times daily before a meal); Group D: barrier drug (alginate 3 times daily after a meal); Group E: PPI (esomeprazole 40 mg/day before breakfast) and mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, before sleep); Group F: PPI (esomeprazole 40 mg/day before breakfast) and prokinetics (levosulpiride 25 mg or domperidone 10 mg before lunch and dinner). Symptoms were evaluated using the visual analogue scale (VAS) and global symptomatic score (GSS), as follows: heartburn: 0-3; retrosternal chest pain: 0-3; regurgitation: 0-3. RESULTS All but 2 treatments (groups C and D) significantly improved VAS and GSS, with group E showing the most significant GSS improvement. Group C had the highest number of dropouts due to treatment failure and reported more side effects. CONCLUSION Using PPIs and mucosal protective drugs resulted in significant symptom alleviation. However, the administration of prokinetics caused higher dropouts due to treatment failure.

Background: Chronic atrophic gastritis (CAG) alone is a precancerous condition for gastric cancer. Achlorhydria plays an important role in the formation of a class I carcinogen, acetaldehyde. L-cysteine has been claimed to bind acetaldehyde covalently. Symptoms are present in 55% of CAG patients, of whom 70% have upper gastrointestinal complaints. The aim of this study was to investigate the properties of L-cysteine in the modification of symptom patterns in CAG patients. Methods: Consecutive patients with histological diagnosis of CAG (OLGA ≥1 with gastric corpus involvement) were evaluated with serological determination of gastric function, clinical assessment of symptoms using the visual analog score (VAS) and the global symptomatic score (GSS), and considered for therapy with L-cysteine, 300 mg daily. Data regarding symptoms were collected at enrollment and after 3, 6, 12, 18, and 24 months, with an ultimate follow-up of 2 years. Results: A total of 330 patients with CAG were divided in group 1 (77 patients treated with L-cysteine) and group 2 (50 patients who received no specific treatment – control group). A statistically significant improvement in the VAS score (7.8 at baseline vs. 4.5 after 24 months; p < 0.01) was observed in patients treated with L-cysteine, while no significant changes in symptom pattern/intensity were recorded in the 2-year follow-up of untreated patients with CAG. Conclusions: Long-term treatment with L-cysteine provides symptom improvement in CAG patients and might be proposed as maintenance therapy in such patients.

Hydrochloric acid is crucial in gastric physiology. In 1978 cimetidine, the first H2 antagonist of histamine receptors on the gastric parietal cell was introduced into therapy, inducing acid. Lasting the years, several studies focused on the potential relationship between inducing hypo-achlorhydria and risk of developing gastric cancer. In 1988 omeprazole, the first proton pump inhibitor, entered therapy. In 1996, Kuipers underlined the danger of progression of chronic atrophic gastritis in subjects taking PPIs. In 2018, one paper from Korea and an another on from Sweden suggested a possible relationship between long-term PPI therapy and the development of gastric cancer. Over the years, several articles, meta-analyzes and population based  focused on relationship between long-term of PPI use and the onset of gastric cancer, with conflicting results. As reported, the presence of bias in the collection of cases, in particular concerning the evaluation of the H.p. status and presence of atrophic gastritis and intestinal metaplasia in subjects treated with PPI, can lead to noticeable errors in the results and conclusions, as demonstrated in the literature by exhaustive methodological studies of pharmacoepidemiology. A possible bias in the collection of case histories is due to the fact that PPIs are often administered to dyspeptic patients, among which there are patients already carriers of gastric neoplasia: the so-called inverse causality.  Literature data, amended by methodological bias (sampling errors, lack of comparative assessment of Hp status and atrophic gastritis) NOT support a causal relationship between long-term PPIs therapy and the onset of gastric cancer.

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: 0.05-0.0001). 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.

BACKGROUND AND AIM:Barrett's Esophagus represents a condition that predisposes to the development of esophageal adenocarcinoma. The aim of the present study was to analyze the demographic and clinical characteristics of patients with BE, to establish the presence of risk factors for this condition, and to determine the frequency of dysplastic lesions as well as the evolution towards adenocarcinoma under tight endoscopic control.METHODS:In this study, we retrospectively collected and analyzed data from a cohort of patients with Barrett's Esophagus identified through endoscopic records of ULSS7 in Northern Italy, who underwent upper esophagogastroduodenoscopy over a 10-year period from July 2008 to December 2020.RESULTS:A total of 264 patients were identified as having BE and included in the study. Mean follow-up was 6.7 years (range: 3 months-13 years). Demographic characteristics of the study population included mean age of 62.7 years (range 33-90 years), with 62.5% of the study population being aged 60 or older, and a male predominance. Females were significantly older than males (65.7 years, range 37-90 vs 61.9 years, range 33-87, p=0.043, respectively).CONCLUSIONS:The present study confirms the importance of tight endoscopic control in the management of BE, favoring early detection of BE degeneration towards high-grade dysplasia or adenocarcinoma. In a subset of patients with high-risk factors including male sex, cigarette smoking and heavy alcohol intake, it may be worthwhile to consider endoscopic control over time in order to detect the development of BE.

Burning mouth syndrome (BMS) is defined as “idiopathic orofacial pain with intraoral burning or dysesthesia recurring daily for more than 2 hours per day and more than 3 months, without any identifiable causative lesions, with or without somatosensory changes” in International Classification of Orofacial Pain, 2020. Worldwide prevalence of BMS was estimated to be 1.73% in population-based studies, while female and elderly are at higher risk of BMS. The aim of this narrative review is to clarify the main etiopathogenetic factors of BMS investigated so far in the scientific literature. There is growing evidence of an important role of peripheral neuropathology in BMS, supported by immunohistochemical studies which have demonstrated a significant loss of epithelial and subepithelial nerve fibers. Other possible etiopathogenetic factors emerging from literature are laryngopharyngeal reflux and hormonal and salivary changes related to aging and menopause. Finally, the role of the oral microbiota in BMS has not yet been thoroughly investigated. Further studies are necessary to investigate the probably multifactorial etiopathogenesis of primary BMS, a pathology which has a serious impact on the quality of life of our patients, a disease we find ourselves treating without the adequate therapy and the necessary knowledge.

Background and aim Increasing the appropriateness of upper gastrointestinal endoscopy (UGIE) improves the quality of care while containing costs. The aim of this study was to improve the appropriateness of UGIE through a process involving evaluation of prescriptions and the use of a non-invasive alternative. Materials and methods A senior endoscopist evaluated the appropriateness of all outpatient referrals for UGIE and established the proper timing. Referrals were either accepted and programmed, canceled, or substituted by a non-invasive evaluation of gastric function, determining serum levels of gastrin-17 (G17), Pepsinogen I (PGI) and II (PGII), and antibodies against Helicobacter pylori. Results A total of 5102 requests for UGIE examinations were evaluated; 540 (10.4%) were inappropriate and had been prescribed for: gastroesophageal reflux disease (n=307), surveillance with erroneous timing (n=113), dyspepsia (n=66), other indications (n=20), and absence of written indication (n=34). Gastric function was evaluated in 282/540 patients; findings included normal values in 94 patients without proton-pump inhibitor therapy (PPI) and in 48 on PPI, active H pylori infection in 56, previous H pylori infection in 30, GERD in n=50, and atrophic gastritis in n=4. UGIE was performed in the latter 4 cases.  Within 2 years (range 1-22 months) of the initial refusal, 105/504 patients underwent UGIE, with normal endoscopic findings in 71/105 (67.5%), and with no cases of cancer. Conclusions This strategy, based on a strict control of prescriptions, is effective to increase the appropriateness while containing public health costs. The use of gastric function testing improves patient selection for UGIE endoscopy.

BACKGROUND AND AIM:An association between reflux and burning mouth syndrome (BMS) has been proposed. Aims of this study were: 1) to investigate the frequency of BMS in a sample of GERD patients; 2) to measure G17, in a sample of BMS patients; 3) to assess the efficacy of different therapeutical schedules for GERD in BMS patients.METHODS:We divided the study in 3 main steps. In step one, we analyzed 500 consecutive GERD patients' type and frequency of extraesophageal manifestations including BMS. In step two, we collected 124 consecutive BMS patients' symptoms and  G17.  In step three, we evaluate the efficacy of 3 different drugs on BMS.RESULTS:In step one, 204 patients complained heartburn; 31 globus pharyngeus; 52 chronic cough; 54 pharyngitis; 31 postnasal drip; 56 burning mouth symptoms; 34 noncardiac chest pain; 17 asthma and 21 sleep apnea. In step two, 29 patients had G17 ≤ 1 pg/L; 64 patients between 1 and 3; and 31 patients ≥ 3. In step three, 49 patients reported slight benefit with PPI, 75 no benefit. 61 patients reported slight benefit with sodium alginate and sodium bicarbonate, 63 no benefit. 23 reported an almost complete remission with HYCHSA, 26 slight benefit, 33 no benefit.CONCLUSIONS:Prevalence of BMS in GERD patients was similar to that reported for chronic chough and pharyngitis. Low levels of G17 were found in the majority of BMS patients. Finally, we observed a greater benefit from barrier drugs therapy than from PPI therapy in BMS patients. (www.actabiomedica.it).

Background: The aim of the present study was to dissect the clinical outcome of GB patients through the integration of molecular, immunophenotypic and MR imaging features. Methods: We enrolled 57 histologically proven and molecularly tested GB patients (5.3% IDH-1 mutant). Two-Dimensional Free ROI on the Biggest Enhancing Tumoral Diameter (TDFRBETD) acquired by MRI sequences were used to perform a manual evaluation of multiple quantitative variables, among which we selected: SD Fluid Attenuated Inversion Recovery (FLAIR), SD and mean Apparent Diffusion Coefficient (ADC). Characterization of the Tumor Immune Microenvironment (TIME) involved the immunohistochemical analysis of PD-L1, and number and distribution of CD3+, CD4+, CD8+ Tumor Infiltrating Lymphocytes (TILs) and CD163+ Tumor Associated Macrophages (TAMs), focusing on immune-vascular localization. Genetic, MR imaging and TIME descriptors were correlated with overall survival (OS). Results: MGMT methylation was associated with a significantly prolonged OS (median OS = 20 months), while no impact of p53 and EGFR status was apparent. GB cases with high mean ADC at MRI, indicative of low cellularity and soft consistency, exhibited increased OS (median OS = 24 months). PD-L1 and the overall number of TILs and CD163+TAMs had a marginal impact on patient outcome. Conversely, the density of vascular-associated (V) CD4+ lymphocytes emerged as the most significant prognostic factor (median OS = 23 months in V-CD4high vs. 13 months in V-CD4low, p = 0.015). High V-CD4+TILs also characterized TIME of MGMTmeth GB, while p53mut appeared to condition a desert immune background. When individual genetic (MGMTunmeth), MR imaging (mean ADClow) and TIME (V-CD4+TILslow) negative predictors were combined, median OS was 21 months (95% CI, 0–47.37) in patients displaying 0–1 risk factor and 13 months (95% CI 7.22–19.22) in the presence of 2–3 risk factors (p = 0.010, HR = 3.39, 95% CI 1.26–9.09). Conclusion: Interlacing MRI–immune–genetic features may provide highly significant risk-stratification models in GB patients.

Background Early colorectal cancer (ECC) is defined as T1NXM0 colorectal cancer (CRC). Although a non-negligible number of T1-CRCs presents metastatic lymph-nodes, local excision is increasingly proposed as alternative to radical resection. Several criteria have been suggested to identify low-risk T1-CRC, but recommendations on this topic are still heterogeneous. This study aims to identify criteria associated with N+ T1-CRC, to select patients to undergo (or not) local excision. Methods A retrospective analysis of demographic, clinical, and histology criteria of 122 consecutive T1-CRC patients undergoing radical resection at Parma University Hospital between 2000 and 2018 has been performed. Results Lymph-node metastasis (LNM) was observed in 15/122 patients (12.3%). No LNM was observed among well-differentiated (G1) tumors (0/37), while 10/65 (15.4%) G2 cases as well as 5/20 (25%) G3 patients presented LNM. G1 was associated with absence of LNM ( p = 0.013). After excluding G1 patients, the rate of N + T1-CRC was 17.6% (15/85). LNM was observed in 4/8 (50%) patients with lymphovascular invasion (LVI) and in 11/77 (14.2%) without LVI. LVI resulted being associated with LNM ( p < 0.042). LNM was reported in 28.3% of cases with a tumor infiltration >4.25 mm (13/46), compared to 5.1% in cases with an infiltration ≤4.25 mm (2/39) ( p = 0.012). In Cox regression analysis, the higher hazard ratio (HR) was reported for the LVI + and infiltration >4.25 mm (HR 24.849). Conclusions In patients with ECC (pT1NXM0), good differentiation (G1), absence of lymphovascular invasion (LVI-), and tumor radial infiltration ≤4.25 mm may allow performing local resection and avoiding radical surgery.