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Background: Autoimmune gastritis (AIG) is an infrequent disease predisposing to both neuroendocrine tumours and cancer. This study aimed to evaluate whether pH measurement of gastric juice allows accurate exclusion of the presence of AIG in real time so that gastric mucosa sampling on normal-appearing mucosa may be avoided. Methods: This study enrolled patients diagnosed with AIG and matched controls (ratio 1:5) who underwent upper endoscopy with standard gastric mucosa sampling and real-time, gastric juice pH assessment. A threshold of pH less than 4.5 was adopted as cut-off to rule out the presence of a feature of AIG. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), overall accuracy, positive likelihood ratio (LR+), and negative likelihood ratio (LR−) were calculated. Results: Data of 40 patients (M/F: 19/21; mean age: 58 years, range: 18–89) with AIG and 212 matched controls were evaluated. Among AIG patients, the feature of atrophy/metaplasia of the oxyntic mucosa was staged as mild in 9 cases, moderate in 9, and severe in the remaining 22 patients. Gastric juice analysis showed a pH value >4.5 in 29 (72.5%) patients and 12 (5.7%) controls. Sensitivity, specificity, accuracy, PPV, NPV, LR+, and LR− were 73% (95% CI = 0.57–0.84), 94% (95% CI = 0.90–0.97), 71% (95% CI = 0.64–0.74), 95% (95% CI = 0.93–0.97), 91% (95% CI = 0.87–0.95), 12.9 (95% CI = 7.19–23.03), and 0.29 (95% CI = 0.18–0.48), respectively. The histological assessment of false-negative cases showed the presence of only mild-moderate atrophy of oxyntic mucosa in 6 (54.5%) cases, and severe in the others. Conclusions: Our data found that real-time pH evaluation of gastric juice allows ruling out AIG with a very high NPV, but further studies are needed.

Background and aim: Guidelines suggest endoscopic resection for rectal neuroendocrine tumors (rNETs) < 10 mm, but the most appropriate resection technique is unclear. In real-life clinical practice, the endoscopic removal of unrecognized rNETs can take place with “simple” techniques and without preliminary staging. The aim of the current study is to report our own experience at a referral center for both neuroendocrine neoplasms and endoscopy. Methods: Retrospective analyses of polypectomies were performed at the Humanitas Research Hospital for rNETs (already diagnosed or previously unrecognized). Results: A total of 19 patients were included, with a median lesion size of 5 mm (range 3–10 mm). Only five lesions were suspected as NETs before removal and underwent endoscopic ultrasound (EUS) before resection, being removed with advanced endoscopic techniques. Unsuspected rNETs were removed by cold polypectomy in eleven cases, EMR in two, and biopsy forceps in one. When described, the margins were negative in four cases, positive in four (R1), and indeterminate in one. The median follow-up was 40 months. A 10 mm polypoid lesion removed with cold snare polypectomy (G2 R1) needed subsequent surgery. Eighteen patients underwent EUS after a median time of 6.5 months from resection. The EUS identified local recurrence after 14 months in a 7 mm polypoid lesion removed with cold snare polypectomy (G1 R1); the lesion was treated with cap-assisted EMR. For all the other lesions, the follow-up was negative. Conclusions: When rNETs are improperly removed without prior staging, caution must be exercised. The data from our cohort suggest that even if inappropriate resection had happened, patients may be safely managed with early EUS evaluation.

Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms of the bile ducts and represents the second most common hepatic cancer after hepatocellular carcinoma; it is sub-classified as intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA), the latter comprising both perihilar cholangiocarcinoma (pCCA or Klatskin tumor), and distal cholangiocarcinoma (dCCA).The global incidence of CCA has increased worldwide in recent decades. Chronic inflammation of biliary epithelium and bile stasis represent the main risk factors shared by all CCA sub-types.When feasible, liver resection is the treatment of choice for CCA, followed by systemic chemotherapy with capecitabine. Liver transplants represent a treatment option in patients with very early iCCA, in referral centers only. CCA diagnosis is often performed at an advanced stage when CCA is unresectable. In this setting, systemic chemotherapy with gemcitabine and cisplatin represents the first treatment option, but the prognosis remains poor.In order to ameliorate patients’ survival, new drugs have been studied in the last few years. Target therapies are directed against different molecules, which are altered in CCA cells. These therapies have been studied as second-line therapy, alone or in combination with chemotherapy. In the same setting, the immune checkpoints inhibitors targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), have been proposed, as well as cancer vaccines and adoptive cell therapy (ACT). These experimental treatments showed promising results and have been proposed as second- or third-line treatment, alone or in combination with chemotherapy or target therapies.

Celiac disease (CD) is a common systemic disorder that results from an abnormal response of human immunity to gluten intake, affecting the small intestine. In individuals who carry a genetic susceptibility, CD is triggered by environmental factors, including viral infections and dysbiosis of the gut microbiota. The gut microbiome is essential in controlling the immune system, and recent findings indicate that changes in the gut microbiome may contribute to various chronic immune disorders, such as CD through mechanisms that still require further exploration. Some bacteria exhibit epitopes that mimic gliadin and may enhance an immune response in the host. Other bacteria, including Pseudomonas aeruginosa, may work in conjunction with gluten to trigger and escalate intestinal inflammation. The microbiota may also directly influence antigen development through the production of immunogenic or tolerogenic gluten peptides or directly influence intestinal permeability through the release of zonulin. Finally, the gut microbiome can impact intestinal inflammation by generating proinflammatory or anti-inflammatory cytokines and metabolites. It is crucial to consider the impact of genetic factors (specifically, HLA-DQ haplotypes), perinatal elements such as birth mode, type of infant feeding, and antibiotic and infection exposure on the composition of the early intestinal microbiome. According to the available studies, the gut microbiome alterations associated with CD tend to exhibit a decreased presence of beneficial bacteria, including some anti-inflammatory Bifidobacterium species. However, some controversy remains as some reports have found no significant differences between the gut microbiomes of individuals with and without CD. A better understanding of the gut microbiome’s role in the development of CD would greatly benefit both prevention and treatment efforts, especially in complicated or treatment-resistant cases. Here, we have attempted to summarize the available evidence on the relationship between the gut microbiota and CD, with a particular focus on potential therapeutic targets.