Occurrence of gastric cancer and carcinoids in atrophic gastritis during prospective long-term follow up.

OBJECTIVE: Atrophic gastritis (AG) is a risk condition for gastric cancer and type I gastric carcinoids. Recent studies assessing the overall risk of gastric cancer and carcinoids in AG at long-term follow up are lacking. This study aimed to investigate in a prospective cohort of AG patients the occurrence of gastric cancer and carcinoids at long-term follow up. METHODS: A total of 200 AG patients from a prospective cohort (67% female, median age 55 years) with a follow up of 7.5 (range: 4-23.4) years were included. Inclusion criteria were presence of AG and at least one follow-up gastroscopy with biopsies at ≥4 years after AG diagnosis. Follow-up gastroscopies at 4-year intervals were performed. RESULTS: Overall, 22 gastric neoplastic lesions were detected (crude incidence 11%). Gastric cancer was diagnosed in four patients at a median follow up of 7.2 years (crude incidence 2%). Eleven type I gastric carcinoids were detected at a median follow up of 5.1 years (crude incidence of 5.5%). In seven patients, six low-grade and one high-grade dysplasia were found. The annual incidence rate person-year were 0.25% (95% confidence interval [CI]: 0.067-0.63%), 0.43% (95% CI: 0.17-0.89%), and 0.68% (95% CI: 0.34-1.21%) for gastric cancer, dysplasia, and type I-gastric carcinoids, respectively. The incidence rates of gastric cancer and carcinoids were not different (p = 0.07). CONCLUSION: This study shows an annual incidence rate of 1.36% person-year for gastric neoplastic lesions in AG patients at long-term follow up. AG patients are similarly exposed to gastric cancer and type I gastric carcinoids.

Gastric cancer in patients with type I gastric carcinoids.

BACKGROUND: Atrophic body gastritis (ABG) is associated with both type I gastric carcinoids (T1-GCs) and intestinal-type gastric cancer. The occurrence of gastric cancer in ABG patients with type I gastric carcinoids has not yet been described. AIM: To describe the occurrence at follow-up of gastric cancer in ABG patients with type I gastric carcinoid in a retrospective case series in a single tertiary referral center. METHODS: Between 1994 and 2012, 17 new cases of T1-GCs were diagnosed among a cohort of ABG patients in a single tertiary referral center for ABG. The clinical charts of these 17 T1-GC patients were retrospectively evaluated for the occurrence of gastric cancer at follow-up (median 4.2 years, range 0.5-13). RESULTS: In 4 (23.5 %)/17 T1-GCs patients (3 females, age 40-78 years), gastric cancer occurred (median follow-up 5.9 years, range 5.1-13). Three cases were intestinal-type adenocarcinomas and one a signet-ring cell diffuse gastric cancer, localized in three cases in the antrum. In two patients, it was detected on random biopsies during follow-up gastroscopy; in the other two, gastroscopy was performed because of new symptoms. All patients with gastric cancer had associated autoimmune features (pernicious anemia, autoimmune thyroid disease and a spared antrum) compared to 77, 46 and 54 % of those without gastric cancer, although statistical significance was not reached. CONCLUSIONS: This case series shows that in patients with T1-GCs, gastric cancer may frequently occur at long-term follow-up. Thus, these patients should be monitored by a long-term surveillance program, including an accurate bioptic sampling of the antral mucosa.

Updated features associated with type 1 gastric carcinoids patients: a single-center study.

OBJECTIVE: Data on clinical presentation and associated features of patients with type 1 gastric carcinoids (T1-GCs) are scanty. This study aimed to provide detailed data on a series of patients with T1-GCs. MATERIAL AND METHODS: Clinical, laboratory, endoscopic, and histological data were assessed from 31 T1-GCs patients (cross-sectional design), consecutively diagnosed in a tertiary center according to a standardized diagnostic protocol. T1-GCs were diagnosed at baseline or follow-up gastroscopy for atrophic gastritis in 74.2% and 25.8% of patients, respectively. RESULTS: Seventy-one percent of T1-GC patients were female. Age ranged from 23 to 78 (median 58 years). T1-GCs were more frequently diagnosed between 40-49 years (35.5%) and 60-69 years (32.3%) (p = 0.0383). Thyroid disease was present in 54.8% (in 29% autoimmune). All 31 patients had either cobalamin or iron deficiency with or without anemia. Manifest pernicious anemia was present in 67.7% of patients and cobalamin deficiency without anemia in 9.7% patients. Iron deficiency anemia was present in 29% and iron deficiency without anemia in 12.9% of patients. In 48.4% of patients, T1-GCs appeared as polyps, which were single in all cases and had a median size of 4 mm (range 2-15 mm). In patients with polypoid T1-GCs, thyroid disease of autoimmune and nonautoimmune origin (p = 0.0181) was more frequently associated. CONCLUSION: This study shows that T1-GCs may be diagnosed at any age. Autoimmune features are frequently present as well as cobalamin and iron deficiency. The copresence of autoimmune diseases and micronutrient deficiencies should be accurately investigated, in particular in patients with polypoid T1-GCs.

Autosomal dominant Ménétrier-like disease.

BACKGROUND: Familial occurrence of Ménétrier disease is rare and has been reported only in few instances. METHODS: Affected patients from a large pedigree were evaluated at the clinical, endoscopic, and pathological levels. RESULTS: Affected members presented with gastropathy of variable severity but without protein loss. Endoscopy and pathology findings were consistent with Ménétrier disease; however, gastric transforming growth factor α (TGF-α) immunohistochemistry and real-time polymerase chain reaction showed no increase in TGF-α expression. CONCLUSIONS: We describe a unique, 4-generation pedigree with autosomal dominant gastropathy exhibiting the typical clinical, endoscopic, and pathological findings of Ménétrier-like disease, though in the absence of protein loss and with no increase in the levels of gastric TGF-α. Members of this family may be affected by a novel and previously unrecognised hereditary form of gastric hyperplasia.

Alteration of local microflora and α-defensins hyper-production in colonic adenoma mucosa.

BACKGROUND AND AIM: Gut flora/host interactions are fundamental for the maintenance of homeostasis. Evidence of possible regulatory effect of commensal bacteria on proliferative disorders of the colon is mounting. In this study, we explored the hypothesis that precancerous lesions, such as adenomas, present alteration of the local microflora and lead to an overproduction of antibacterial molecules of the innate immunity, namely α-defensins. Thus, the host-bacteria misbalance could represent a potential procarcinogenic factor. METHODS: Biopsies from adenomatous polyps and normal mucosa, in the rectum-sigmoid colon, were collected from 51 patients. Concentration of mucosal bacteria was evaluated by real-time polymerase chain reaction after extraction of total DNA. Total RNA was also extracted, and the defensin α-1, defensin-5, and defensin-6 gene expressions were evaluated by real-time polymerase chain reaction. Immunohistochemical study has been carried out to evaluate protein production and location. Antibacterial activity of adenomatous polyps mucosa was evaluated in vitro. RESULTS: Biopsies from adenomatous polyps had a significant relative reduction of mucosa adherent bacteria compared with normal tissue (20-fold relative reduction, P<0.05). Concomitantly, α-defensin expression and production were significantly increased in adenomas. Adenoma mucosa showed increased antibacterial activity in vitro compared with normal mucosa. CONCLUSIONS: Microflora dysbiosis occurs at the mucosal surface in colonic adenomas, and may represent a potential factor for dysplastic cell proliferation. Further studies are needed to confirm and define the role of this mechanism in colon carcinogenesis and the potential applications in the clinical setting.

Gastrointestinal endoscopy can be safely performed during pandemic SARS-CoV-2 infection in Central Italy.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious; gastrointestinal endoscopies are considered risky procedures for the endoscopy staff. Data on the SARS-CoV-2-exposure/infection rate of gastrointestinal endoscopy staff is scarce. This study aimed to assess the SARS-CoV-2-exposure/infection rate among gastrointestinal endoscopists/nurses performing gastrointestinal endoscopies before and after the adoption of specific prevention measures. PATIENTS AND METHODS: Cross-sectional study in a teaching hospital (Rome, Central Italy) on retrospective data (9 March-15 April 2020) of consecutive gastrointestinal endoscopies, characteristics of procedures, patients and endoscopy staff, SARS-CoV-2-exposure/positivity of patients and staff before and after adoption of prevention measures. Exposed staff tested for SARS-CoV-2 by nasopharyngeal swabs(RNA-PCR) and serology. RESULTS: A total of 130 gastrointestinal endoscopies were performed in 130 patients (age 66 ± 14 years, 51% women, 51% inpatients, 56.9% lower). A total of 12 (9.2%) patients were SARS-CoV-2-positive and 14(10.8%) had a high risk of potential infection. Of the endoscopy staff (n = 16, 5 endoscopists, 8 nurses and 3 residents), 14 (87.5%) were exposed to SARS-CoV-2-infected and 16 (100%) to potentially infected patients. 3/5 and 5/5 endoscopists were exposed to actual and potential, 1/3 and 3/3 residents to actual and potential and 8/8 nurses to actual and potential infection, respectively. None of the staff was found to be infected with SARS-CoV-2. None experienced fever or any other suspicious symptoms of coronavirus disease 2019. Before the adoption of prevention measures, more endoscopists/nurses were in the endoscopy room than after (3.5 ± 0.6 vs. 2.1 ± 0.3, P < 0.0001). CONCLUSIONS: Despite supposed high infection risk, gastrointestinal endoscopies may be safe for the endoscopy staff during the SARS-CoV-2 pandemic.

New PRSS1 and common CFTR mutations in a child with acute recurrent pancreatitis, could be considered an "Hereditary" form of pancreatitis ?

BACKGROUND: acute recurrent pancreatitis is a complex multigenic disease, the diagnosis is even more difficult when this disease develops in a child. CASE PRESENTATION: a 6-years old boy, hospitalized with epigastric pain radiating to the back showed high serum levels of serum amylase, lipase, CRP and erythrosedimentation rate. Several similar milder episodes of pain, followed by quick recovery and complete disappearance of symptoms were reported during the previous 13 months. The child was medically treated and after 7 days with normal clinic and laboratory tests was discharged with a hypolipidic diet. All the known aetiologic hypotheses were excluded by anamnestic investigation, clinical observation and biochemical evaluation, whereas, anatomic abnormality were excluded by a secretin stimulated magnetic resonance (MRI). At the last follow-up visit, (11 months later), the child showed a normal body weight and anthropometric profile, without further abdominal pain. Mutation screening for coding regions of PRSS1, SPINK1, CFTR and the new hereditary pancreatitis-associated chymotrypsin C (CTRC) genes showed a novel variation, c.541A > G (p.S181G), in the exon 4 of PRSS1 gene and the classical CF p.F508del mutation in the CFTR. Both mutations were present in his clinically normal mother and absent in the patient's father. CONCLUSIONS: this report extend the spectrum of PRSS1 mutations, however, the absence of family history of pancreatitis leaves the present case without the hallmark of the hereditary origin of pancreatitis. At the present knowledge it can be only stated that the combined genotype CFTR (F508del)/PRSS1 (S181G) is associated to a mild phenotype of acute recurrent pancreatitis in this child without any further conclusion on its pathogenetic role or prediction on the course of the disease.

Somatostatin receptor subtypes 2 and 5 are associated with better survival in well-differentiated endocrine carcinomas.

The majority of gastroenteropancreatic well-differentiated endocrine carcinomas (WDEC) express somatostatin receptors (SSTR). To correlate the expression of SSTR subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) with clinicopathological features and survival in a group of WDEC patients, 42 WDEC tissue specimens from 33 patients were analysed. All patients were treated with somatostatin analogues and had a median follow-up period of 45 months (range 6-196). Neither SSTR2 and SSTR5 expression nor Ki-67 level alone correlated with survival. A significantly better survival rate was observed in patients with tumours expressing SSTR2, SSTR5 and Ki-67 <2%, compared to those with SSTR2- and SSTR5-negative tumours and Ki-67 >or=2% (p < 0.038), with 5-year survival rates of 91 vs. 43%, respectively. Expression of SSTR2 and SSTR5 appears to play a positive prognostic role, possibly correlated with the high affinity that the available somatostatin analogues display for these 2 specific SSTR subtypes.

Commensal bacteria and "oncologic surveillance": suggestions from an experimental model.

The relationship between resident intestinal flora and colon cancer development are not yet clear. Apoptosis induction could represent a mechanism by which commensal and/or probiotic bacteria could prevent proliferation of dysplastic cells. In the present study, the in vivo and in vitro proapoptotic effect of resident bacteria was evaluated in mouse colon mucosa. Preliminary results suggest that colonic apoptosis induction, by commensal bacteria, could possibly represent a physiologic "oncologic surveillance" mechanism for colonic proliferative disease prevention.

A case of oesophageal ulcer developed after taking homeopathic pill in a young woman.

Oesophageal ulcers occur mainly as a result of gastro-oesophageal reflux disease (GERD). However, pill-induced oesophageal ulcers are a fairly common event. The lesion is mainly due to entrapment of the pill and/or its chemical composition thereof. This case report describes an oesophageal mucosa ulcer occurred in a healthy 35-year old woman who had no previous history of oesophageal disorders and received homeopathic medication. The present case reveals that pill entrapment can occur even in the oesophagus of healthy young individuals and that oesophageal mucosal ulcer can be triggered by substances generally thought devoid of any potentially mucosal aggressive effect.

Endoscopic scores for inflammatory bowel disease in the era of 'mucosal healing': Old problem, new perspectives.

The importance of the endoscopic evaluation in inflammatory bowel disease (IBD) management has been recognized for many years. However, the modalities for reporting endoscopic activity represent an ongoing challenge. To address this, several endoscopic scores have been proposed. Very few have been properly validated, and the use of such tools remains sub-optimal and is mainly restricted to clinical trials. In recent years, a growing emphasis of the concept of 'mucosal healing' as a prognostic marker and therapeutic goal has increased the need for a more accurate definition of endoscopic activity in both ulcerative colitis (UC) and Crohn's Disease (CD). In the present review, the evolution of the challenges related to endoscopic scores in IBD has been analyzed, with particular attention paid to the renewed relevance of endoscopic activity in recent years. Currently, despite the growing relevance of endoscopic activity, evaluating this activity in IBD is still a challenge. The implementation of efficacious endoscopic scores and a better definition of the absence of activity (mucosal healing) are needed.

Endoscopic appearances of polypoid type 1 gastric microcarcinoids by narrow-band imaging: a case series in a referral center.

OBJECTIVE: Narrow-band imaging (NBI) has been associated with high accuracy for the identification of gastric malignant lesions. This study aimed to investigate for the first time the endoscopic NBI appearances of type 1 gastric carcinoids in a consecutive series of patients with atrophic gastritis. METHODS: Seven consecutive patients (five women, median age 61 years) with atrophic gastritis and polypoid type 1 gastric carcinoids were included. After white-light examination, gastric antrum and body were examined by NBI for the examination of polyps and lesions. Digital images of polyps from recorded videos were extracted and reviewed for NBI features. RESULTS: Fifteen polypoid type 1 gastric microcarcinoids (median size 3 mm) were detected in the seven patients; four patients had synchronous lesions. Nine (60%) lesions showed a tubulovillous and six lesions (40%) showed an irregular mucosal pattern; a regular circular pattern was never observed. A light-blue crest was observed on six (40%) lesions. The vascular pattern was irregular in eight (53.3%) microcarcinoids. All six type 1 gastric carcinoids with an irregular mucosal pattern showed an irregular vascular pattern without light-blue crest. Of the nine carcinoids with a tubulovillous mucosal pattern, two had an irregular and seven had a regular vascular pattern. CONCLUSION: Polypoid type 1 gastric microcarcinoids always show an abnormal NBI mucosal surface pattern, but no specific features to distinguish them from other intraepithelial lesions such as intestinal metaplasia, adenomas, or low-grade and high-grade dysplasia are observed. Thus, target biopsies to diagnose the pathological nature of the lesion are advocated.

Possible contribution of artificial neural networks and linear discriminant analysis in recognition of patients with suspected atrophic body gastritis.

AIM: To investigate whether ANNs and LDA could recognize patients with ABG in a database, containing only clinical and biochemical variables, of a pool of patients with and without ABG, by selecting the most predictive variables and by reducing input data to the minimum. METHODS: Data was collected from 350 consecutive outpatients (263 with ABG, 87 with non-atrophic gastritis and/or celiac disease [controls]). Structured questionnaires with 22 items (anagraphic, anamnestic, clinical, and biochemical data) were filled out for each patient. All patients underwent gastroscopy with biopsies. ANNs and LDA were applied to recognize patients with ABG. Experiment 1: random selection on 37 variables, experiment 2: optimization process on 30 variables, experiment 3: input data reduction on 8 variables, experiment 4: use of only clinical input data on 5 variables, and experiment 5: use of only serological variables. RESULTS: In experiment 1, overall accuracies of ANNs and LDA were 96.6% and 94.6%, respectively, for predicting patients with ABG. In experiment 2, ANNs and LDA reached an overall accuracy of 98.8% and 96.8%, respectively. In experiment 3, overall accuracy of ANNs was 98.4%. In experiment 4, overall accuracies of ANNs and LDA were, respectively, 91.3% and 88.6%. In experiment 5, overall accuracies of ANNs and LDA were, respectively, 97.7% and 94.5%. CONCLUSION: This preliminary study suggests that advanced statistical methods, not only ANNs, but also LDA, may contribute to better address bioptic sampling during gastroscopy in a subset of patients in whom ABG may be suspected on the basis of aspecific gastrointestinal symptoms or non-digestive disorders.

Is colonoscopy sufficient for colorectal cancer surveillance in all HNPCC patients?

A 34-year-old male with hereditary non-polyposis colon cancer with a mutation in hMSH2 line is reported. Despite regular colonoscopic follow-up, he developed cecal cancer involving the extraluminal area. Due to sub-occlusive symptoms, the patient was submitted to further colonoscopy, however with no clear evidence of neoplasia. Thin slice multiplanar reconstruction computed tomography CT scan performed thereafter revealed a transmural mass 2.5 cm in size localized near the cecal valve. Discussion is made on the reliability of colonoscopic examinations as well as the need for further investigations in the follow-up of patients at very high risk of right-sided colon cancer, such as male hMSH2 carrier affected by hereditary non-polyposis colon cancer.

Different patterns of 11q allelic losses in digestive endocrine tumors.

Most foregut digestive endocrine neoplasms may be associated with the multiple endocrine type 1 (MEN-1) syndrome. In contrast, midgut/hindgut carcinoids never show such association. To investigate the pathogenetic involvement of the MEN-1 gene and of putative additional oncosuppressor gene(s) distal to it, a comparative analysis of loss of heterozygosity (LOH) at chromosome 11q13 to 11qter was performed in 27 foregut (pancreatic endocrine tumors [PETs]), 23 midgut (ileal and appendiceal), and 3 hindgut (rectal) endocrine tumors. LOH at the MEN-1 gene locus at 11q13 was observed in 52% of the 23 sporadic and in all 4 MEN-1-associated PETs and was found to consistently and continuously span to the most distal marker investigated at 11qter. In contrast, only occasional, discontinuous, and mostly interstitial LOH for 11q markers was observed in ileal (midgut) carcinoids, whereas no LOH was found in all appendiceal (midgut) and rectal (hindgut) carcinoids. The consistent extension of LOH from the MEN-1 region to 11qter in sporadic PETs suggests a mechanism of gene inactivation via chromosomal breakage and complete loss of chromosome 11q; furthermore, these results expand beyond the 11q13 region the search for additional oncosuppressor gene(s) potentially involved in the genesis of these neoplasms. The low frequency, limited extension, and discontinuous distribution of 11q deletions in midgut/hindgut carcinoids suggest that MEN-1 gene is not involved in the pathogenesis of these tumors.

Is proliferative colonic disease presentation changing?

AIM: To compare the site, age and gender of cases of colorectal cancer (CRC) and polyps in a single referral center in Rome, Italy, during two periods. METHODS: CRC data were collected from surgery/pathology registers, and polyp data from colonoscopy reports. Patients who met the criteria for familial adenomatous polyposis, hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study. Overlap of patients between the two groups (cancers and polyps) was carefully avoided. The χ² statistical test and a regression analysis were performed. RESULTS: Data from a total of 768 patients (352 and 416 patients, respectively, in periods A and B) who underwent surgery for cancer were collected. During the same time periods, a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies (428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B). A proximal shift in cancer occurred during the latter years for both sexes, but particularly in males. Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio (OR) 3.31, 95%CI: 2.00-5.47; P < 0.0001). A similar proximal shift was observed for polyps, particularly in males (OR 1.87, 95%CI: 1.23-2.87; P < 0.0038), but also in females (OR 1.62, 95%CI: 0.96-2.73; P < 0.07). CONCLUSION: The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade, particularly in males.

Reversal of atrophic body gastritis after H. pylori eradication at long-term follow-up.

BACKGROUND: The effect of Helicobacter pylori treatment on the potential reversal of atrophic body gastritis (ABG) is controversial. Body atrophy reversal was evaluated in a cohort of H. pylori-negative and treated H. pylori-positive ABG patients. METHODS: Observational long-term follow-up cohort study including 300 ABG patients with at least one follow-up gastroscopy with three biopsies from the antrum and three from the body performed no earlier than 1 year after diagnosis was included. H. pylori was diagnosed by Giemsa-stain and serology. H. pylori-positive patients (n = 192) were treated with bismuth-based triple regimen. RESULTS: After a mean follow-up of 5.2 years, body atrophy reversal was observed in 42/300 patients (14%). Body atrophy reversal occurred more frequently in patients treated for H. pylori than in H. pylori-negative ones (21.3% vs 0.9%, p < 0.00001) and was observed between 2 and 8 years after treatment in 52% of cases. Predictive factors for body atrophy reversal at Cox-regression analysis were mild atrophy (HR 2.14; 95% CI 1.12-4.1), moderate-severe inflammation (HR 5.3; 95% CI 1.64-17.3), and absence of intestinal metaplasia (HR 2.4; 95% CI 1.2-4.8). CONCLUSION: Body atrophy reversal was observed in about 20% of ABG patients treated for H. pylori infection, and about 50% of reversals occurred during long-term follow-up.

HLA-DRB1*03 and DRB1*04 are associated with atrophic gastritis in an Italian population.

BACKGROUND: Atrophic gastritis (AG) is often considered an autoimmune disorder and is associated with other autoimmune diseases. HLA-DRB1 alleles are often associated with autoimmune diseases, however HLA-DRB1 genotyping data in AG patients are lacking. The objective of the study was to evaluate the prevalence of HLA-DRB1 in AG patients. METHODS: The occurrence of HLA-DRB1 alleles was assessed in 89 Italian AG patients (69.1% female) and 313 controls (47.3% females). Genomic DNA was extracted from peripheral venous blood, PCR-coamplified for HLA-DRB1 and typed using a reverse line-blot assay. RESULTS: Compared to controls, prevalence of HLA-DRB1*03 (28.1% vs. 15.9%, p=0.01) and HLA-DRB1*04 (25.8% vs. 14.4%, p=0.01) was greater in AG patients, conferring an OR of 2.05 and 2.07, respectively. HLA-DRB1*01 occurred more frequently in controls than in AG patients (11.5% vs. 3.4%, p=0.01) conferring an OR of 0.27. AG patients carrying the HLA-DRB1*03 or *04 alleles were characterised by having more frequently autoimmune thyroid disease (70.4% vs. 42.2%, p=0.01) and intestinal metaplasia (86.4% vs. 62.2%, p=0.01). CONCLUSIONS: In our population, over 50% of AG patients carry the HLA-DRB1*03 or *04 alleles associated with autoimmune diseases, suggesting that this subset of AG patients has a genetic predisposition to autoimmunity.