Current Perspectives in Atrophic Gastritis.

PURPOSE OF THE REVIEW: Atrophic gastritis is a complex syndrome with gastric atrophy as a common trait. Helicobacter pylori infection and autoimmunity are the two main contexts in which it develops. It is slightly symptomatic, affects various aspects of general health, and remains a predisposing factor for gastric cancer. This review will update current knowledge and progress on atrophic gastritis. RECENT FINDINGS: Atrophic gastritis affects mostly adults with persistent dyspepsia, deficient anemia, autoimmunity disease, long-term proton pump inhibitor use, and a family history of gastric cancer. Gastric biopsies, expressed as Sydney system grade and OLGA/OLGIM classifications, represent the gold standard for diagnosis and cancer risk stage, respectively. Recently, electronic chromoendoscopy has allowed "targeted biopsies" of intestinal metaplasia. The associated hypochlorhydria affects the gastric microbiota composition suggesting that non-Helicobacter pylori microbiota may participate in the development of gastric cancer. Physicians should be aware of multifaceted clinical presentation of atrophic gastritis. It should be endoscopically monitored by targeted gastric biopsies. Autoimmune and Helicobacter pylori-induced atrophic gastritis are associated with different gastric microbial profiles playing different roles in gastric tumorigenesis.

Flash on gut microbiome in gestational diabetes: a pilot study.

Pregnancy induces a deep modification of women's gut microbiota composition. These changes may influence hormonal and metabolic factors, increasing insulin resistance and leading to hyperglycaemia in susceptible women. Data on 29 women in pregnancy showed insignificant reductions in the Bacteroidetes/ Firmicutes ratio in women with (n. 14) and without (n. 15) gestational diabetes (GDM). Gut microbiota compositions at the genera and species level were further analysed in ten pregnant women with and ten without GDM (9 samples were excluded due to low DNA quality/quantity), showing differences in functionally specific patterns affecting host energy dietary polysaccharide metabolism pathways. According to our results, gut microbiome alteration may play a role in GDM pathogenesis through an increase of gut permeability and higher intestinal energetic balance.

Improving basic skills in celiac-like disease diagnosis: a case report.

BACKGROUND: The diagnosis of Coeliac disease (CD) requires a combination of sign/symptoms, positivity of specific antibodies and duodenal histological evidence of villous atrophy. Duodenal villous atrophy, despite representing the CD landmark, is not specific since it is found in many gastrointestinal disorders. Giardiasis is one of the most common human intestinal protozoan infestations in industrialized countries whose histological duodenal mucosa damage could mimic that of CD. The present report shows how a wise clinical and laboratory assessment led us shortly to a correct diagnosis. CASE PRESENTATION: A 42-year-old outpatient woman without previous significant gastrointestinal diseases, was referred with dyspeptic symptoms, fatigue and mild diarrhea from 4 months. Her first investigations including immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (anti-tTG) and stool parasitological and cultural analysis were negative. An esophagogastroduodenoscopy (EGDS) showed no mucosal alteration. But histology demonstrated a Helicobacter Pylori (HP) pan-gastritis while duodenal mucosa showed villous atrophy consistent with a diagnosis of CD Marsh type 3b. While on gluten-free diet (GFD) the patient didn't experience any improvement of symptoms. Duodenal biopsies were then reviewed showing the presence of trophozoites of Giardia on the luminal surface of the duodenal wall and at the same time, a second stool examination revealed the presence of trophozoites and cysts of Giardia. Treated with metronidazole, 500 mg twice daily for 6 days the patient reduced diarrhea after few days. After about 2 months of GFD she was invited to discontinue it. At the same time stool examination was repeated with negative results. She subsequently performed eradication for Hp with triple therapy (Pylera®). Around 6 months later, the patient did not complain any gastrointestinal symptoms. Serological tests were normal and at a follow-up EGDS, duodenal mucosa had normal histology with normal finger-like villi and absence of Giardia trophozoites. CONCLUSION: This case report shows how CD diagnosis can sometimes be manifold. Intestinal villous atrophy alone may not automatically establish a diagnosis of CD. In the present case the clinical scenario could be fully explained by giardiasis. Indeed, different diagnostic tools and a multi-step approaches have been used to determine the final correct diagnosis.

Laparoscopic resection of large gastric GISTs: feasibility and long-term results.

BACKGROUND: Laparoscopy is the procedure of choice for the resection of gastric Gastrointestinal stromal tumors (GISTs) smaller than 2 cm; there is still debate regarding the most appropriate operative approach for larger GISTs. The aims of this study were to evaluate the safety and long-term efficacy of laparoscopic resection of gastric GISTs larger than 2 cm. METHODS: Between 2007 and 2011, we prospectively enrolled all patients affected by gastric GIST larger than 2 cm. Exclusion criteria for the laparoscopic approach were the presence of metastases and the absence of any involvement of the esophago-gastric junction, the pyloric canal, or any adjacent organ. Final diagnosis of GIST was confirmed by histological and immunohistochemical analysis. Follow-up assessment included abdominal CT scans every 6 months for the first 2 years and yearly thereafter. RESULTS: Twenty-four consecutive patients were enrolled. Twenty-one patients (87.5%) were symptomatic. The most common symptoms were gastrointestinal bleeding and abdominal pain. The mean tumor size was 5.51 cm (range 2.5-12.0 cm). GISTs were located in the lesser curvature in five cases (20.8%), in the greater curvature in seven cases (29.1%), in the posterior wall in one case (4.1%), in the anterior wall in eight cases (33.3%), and in the fundus in 3 cases (12.5%). Laparoscopic resection was possible in all cases and took on average of 55 min (range 30-105 min). Median blood loss was 24 ml. No major intraoperative complications were observed. Mortality rate was 0%. Median postoperative stay was 3 days. No patients were lost to follow-up. No recurrences occurred after a median follow-up period of 75 months. CONCLUSION: Although larger randomized controlled trials comparing different surgical strategies for large gastric GISTs are warranted, our study supports the evidence that laparoscopic resection of gastric GISTs is feasible, safe, and effective on long-term clinical outcome even for lesions up to 12 cm.

In Elderly Anemic Patients without Endoscopic Signs of Bleeding Are Duodenal Biopsies Always Necessary to Rule Out Celiac Disease?

Iron-deficiency anemia in the elderly may be due to numerous gastrointestinal conditions. Anemia is frequent in celiac disease (CD); however, the use of routine duodenal biopsies, independently of age or serology, is debated. To determine the diagnostic yield of routine duodenal biopsies in adult and elderly patients with no bleeding anemia, a cross-sectional study analyzing 7968 gastroscopies (2017−2020) was performed; 744 were for anemia and 275 were excluded (GI bleeding or without duodenal biopsies). Of the 469 included patients, clinical, endoscopic, and histological features were analyzed in groups with or without histopathological changes in the duodenal mucosa (DM). Univariate/multivariate analyses were performed. Of the 469 patients, 41 (8.7%) had DM histopathological changes, 12 (2.6%) had CD, 26 (5.5%) had duodenal intraepithelial lymphocytosis (DIL), and 3 had (0.6%) other conditions. They were younger compared to patients with normal DM. DM histopathology was significantly inversely correlated with age group, with prevalences of 27%, 20%, 12.5%, 10%, and 2.5%, in the <40−50, 51−60, 61−70, 71−80, and >80-year age groups, respectively (p = 0.0010). Logistic-regression models showed that anemic patients aged >60, >70, or >80 years with endoscopically normal DM had a progressively three- to four-fold higher probability of having normal duodenal histology. In adults, anemic patients without bleeding, age and endoscopically normal DM are predictors of normal DM histology. In >70-year anemic patients, negligible DM pathology was found. The results suggest that routine duodenal biopsies are questionable in elderly anemic patients

Prevalence of Segmental Colitis Associated with Colonic Diverticulosis in a Prospective Cohort of Patients Who Underwent Colonoscopy in a Tertiary Center.

In patients with colonic diverticulosis, the prevalence of segmental colitis associated with diverticulosis (SCAD) is debated. The aim of this study was to assess the prevalence of SCAD in consecutive patients with diverticulosis in a single tertiary center. Over a six-month period, consecutive adult patients with colonic diverticulosis were included. Patients with endoscopic signs of interdiverticular mucosal inflammation (erythema, friability, and ulcerations) were considered suspected SCAD and underwent multiple biopsy samplings to confirm diagnosis. Clinical features were collected from diverticulosis and suspected SCAD patients. In total, 367 (26.5%) of 1383 patients who underwent colonoscopy presented diverticulosis. Among diverticulosis patients, 4.3% (n = 16) presented macroscopic signs of interdiverticular mucosal inflammation and were identified as suspected SCAD. Compared to that of patients with diverticulosis, the age of suspected SCAD patients was significantly lower (60 ± 12.9 years (41.0-86.0) vs. 70 ± 10.6 years (38.0-93.0)) (p = 0.047). Among patients with suspected SCAD, one patient received a new diagnosis of Crohn's disease, one had spirochetosis infection, and one presented drug-induced colitis. The remaining patients with suspected SCAD (n = 13) were not confirmed by histology. This observational study suggests that SCAD diagnosis is a challenge in clinical practice due to the heterogeneity of endoscopic findings and lack of stated histological criteria.

A New SMAD4 Splice Site Variant in a Three-Generation Italian Family with Juvenile Polyposis Syndrome.

Juvenile polyposis syndrome (JPS) is an autosomal dominant disorder characterized by hyperplastic polyps in the upper and lower gastrointestinal (GI) tract with a high risk of developing GI cancers. We have described a three-generation Italian family with all the spectrum of SMAD4 phenotype. A multigene panel test was performed on the genomic DNA of the proband by next-generation sequencing, including genes related to hereditary GI tumor syndromes. Molecular analysis revealed the presence of the c.1140-2A>G substitution in the SMAD4 gene, a novel splice variant that has never been described before. Our family is remarkable in that it illustrates the variable expressivity of the SMAD4 phenotype within the same family. The possibility of phenotype variability should also be considered within family members carrying the same mutation. In JPS, a timely genetic diagnosis allows clinicians to better manage patients and to provide early surveillance and intervention for their asymptomatic mutated relatives in the early decades of life.

Isolated intestinal Ganglioneuromatosis: case report and literature review.

BACKGROUND: Intestinal Ganglioneuromatosis (IG) is a rare disorder of the enteric nervous system. In pediatric age it is often associated with genetic syndromes such as Neurofibromatosis 1 (NF1), multiple endocrine neoplasia type 2B (MEN2B) and Cowden syndrome (PTEN mutation), and ganglioneuromas (GNs) may be sometimes the first sign of the disease. Isolated GNs are rare and sporadic. Clinical symptom vary and depend on the size and on the location of the GNs. This disorder affects intestinal motility and it, consequently, causes changes in bowel habits, abdominal pain, occlusive symptoms and rarely lower gastrointestinal bleeding secondary to ulceration of the intestinal mucosa. On the other hand, patients can remain asymptomatic for many years. CASE PRESENTATION: We describe a 9-year-old boy referred to our emergency department for right lower quadrant abdominal pain. No familial history for gastrointestinal disorders. No history of fever or weight loss. At physical examination, he had diffused abdominal pain. Abdominal ultrasonography showed a hypoechoic formation measuring 41.8 mm by 35 mm in the right lower quadrant of the abdomen. Routine blood tests were normal, but fecal occult blood test was positive. Abdominal TC confirmed the hypodense formation, of about 5 cm in transverse diameter, in the right hypochondrium that apparently invaginated in the caecum-last ileal loop. Colonoscopy showed in the cecum an invaginated polypoid lesion of the terminal ileal loop. Laparoscopic resection of the polypoid lesion was performed. Histological diagnosis of the large neoplasm observed in the terminal ileum was diffuse ganglioneuromatosis. NF1, RET and PTEN gene tests resulted negative for specific mutations. At the 1 year follow-up, the patient presented good general condition and blood tests, fecal occult blood test, esophagogastroduodenoscopy, colonoscopy and MR-enterography were negative. CONCLUSIONS: Only few cases are reported in literature of IG in pediatric age. Although rare, the present case suggests that this disorder must be taken in consideration in every patient with GI symptoms such as abdominal pain, constipation, lower intestinal bleeding, in order to avoid a delayed diagnosis.

Skin Manifestations and Coeliac Disease in Paediatric Population.

Celiac disease (CD) is an immune-mediated enteropathy caused by gluten ingestion, affecting approximately 1% of the worldwide population. Extraintestinal symptoms may be present as the first signs of CD, years before the CD diagnosis is made. A great variety of extraintestinal manifestations may be associated with CD. Cutaneous manifestations represent the main extraintestinal manifestations, with dermatitis herpetiformis being the most common in patients with CD. In adults, it has been demonstrated that the role of a gluten-free diet is crucial not only for the recovery of signs and symptoms associated with CD but also for cutaneous manifestations, which often improve after gluten avoidance. In children with CD, the association with skin disorders is well documented regarding dermatitis herpetiformis, but studies considering other dermatological conditions, such as psoriasis and atopic dermatitis, are few. The prevalence and manifestations of dermatological disorders in celiac children are often different from those in adults, explaining the gap between these populations. In addition, the therapeutic role of a gluten-free diet in the improvement in skin alterations is not fully understood in children and in adult population except for dermatitis herpetiformis. Therefore, cutaneous CD symptoms need to be known and recognized by physicians despite their specialties to improve early CD diagnosis, which is critical for a better prognosis. This review describes the current scientific evidence on skin manifestations associated with CD in the pediatric population.

Dieulafoy lesion: two pediatric case reports.

BACKGROUND: Massive gastrointestinal bleeding in children is uncommon. Dieulafoy lesion is an uncommon disease which may lead to massive and repeated upper gastrointestinal hemorrhage. We report two cases of gastric Dieulafoy lesion successfully treated with either band ligation or endoscopic hemoclipping. CASE PRESENTATION: First case report: A previously healthy 18-month-old female infant with E. coli sepsis, pneumonia and respiratory failure with bilateral pneumothorax requiring chest drainage. Over a few days, the patient presented hematemesis and melena with progressively worsening anemia. The esophagogastroduodenoscopy revealed an arterial vessel with eroded apex located between the body and the fundus of the stomach. Two elastic bands were applied which resulted in resolution of hematemesis and melena and improvement of the anemia. Second case report: A 8-year-old male was admitted to our department with sudden massive hematemesis and melena. Clinical examination revealed anemia (hemoglobin, 6.8 g/dl). Esophagogastroduodenoscopy revealed a mucosal erosion with visible vessel located along the small curvature, close to the antrum. Three hemostatic clips were placed on the Dieulafoy lesion and hemostasis was obtained. CONCLUSIONS: we showed that, similar to gastric DL in adult patients,, gastric DL in pediatric patients can be successfully treated with endoscopic therapy, and both hemoclipping and band ligation are suitable techniques.

Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities.

Corynebacterium jeikeium is a commensal bacterium that colonizes human skin, and it is part of the normal bacterial flora. In non-risk subjects, it can be the cause of bad body smell due to the generation of volatile odorous metabolites, especially in the wet parts of the body that this bacterium often colonizes (i.e., groin and axillary regions). Importantly, in the last few decades, there have been increasing cases of serious infections provoked by this bacterium, especially in immunocompromised or hospitalized patients who have undergone installation of prostheses or catheters. The ease in developing resistance to commonly-used antibiotics (i.e., glycopeptides) has made the search for new antimicrobial compounds of clinical importance. Here, for the first time, we characterize the antimicrobial activity of some selected frog skin-derived antimicrobial peptides (AMPs) against C. jeikeium by determining their minimum inhibitory and bactericidal concentrations (MIC and MBC) by a microdilution method. The results highlight esculentin-1b(1-18) [Esc(1-18)] and esculentin-1a(1-21) [Esc(1-21)] as the most active AMPs with MIC and MBC of 4-8 and 0.125-0.25 µM, respectively, along with a non-toxic profile after a short- and long-term (40 min and 24 h) treatment of mammalian cells. Overall, these findings indicate the high potentiality of Esc(1-18) and Esc(1-21) as (i) alternative antimicrobials against C. jeikeium infections and/or as (ii) additives in cosmetic products (creams, deodorants) to reduce the production of bad body odor.

Eosinophilic Esophagitis in Children: Clinical Findings and Diagnostic Approach.

Eosinophilic esophagitis (EoE) is an emerging chronic immune and antigen-mediated clinicopathologic disease. During the last 2 decades, the incidence of this condition in children has increased significantly, thanks to practitioners for creating the awareness and higher use of diagnostic endoscopy. We have analysed paediatric literature on EoE focusing on the epidemiology, pathophysiology, clinical findings and diagnostic approach. EoE is pathogenically related to a Th2 inflammation characterized by a mixed IgE and non-IgEmediated reaction to food and/or environmental agents. This leads to esophageal dysfunction and remodeling accompanied by subepithelial fibrosis. EoE can be presented with several range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or feeding refusal in infants and toddlers, as well as heartburn, dysphagia and food bolus impaction in older children and adults. The diagnostic suspicion is based on the presence of chronic symptoms of esophgeal dysfunction and esophageal eosinophilia characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field). In this review, we will provide an update on clinical presentation and diagnostic approach to EoE in children. We emphasized on the relevant aspects of the new clinical condition termed "PPI responsive esophageal eosinophilia", as entities distinct from EoE and the role of PPI trial in the diagnostic workup, therefore we proposed a new diagnostic algorithm.

Erratum: Improving assessment and management of large non-pedunculated colorectal lesions in a Western center over 10 years: lessons learned and clinical impact.

[This corrects the article DOI: 10.1055/a-1220-6261.].

Enteroscopy in children and adults with inflammatory bowel disease.

Inflammatory bowel disease (IBD) includes Crohn's disease (CD), ulcerative colitis and unclassified entities. CD commonly involves the terminal ileum and colon but at the time of diagnosis it can be confined to the small bowel (SB) in about 30% of the patients, especially in the young ones. Management of isolated SB-CD can be challenging and objective evaluation of the SB mucosa is essential in differentiating CD from other enteropathies to achieve therapeutic decisions and to plan the follow-up. The introduction of cross-sectional imaging techniques and capsule endoscopy (CE) have significantly expanded the ability to diagnose SB diseases providing a non-invasive test for the visualization of the entire SB mucosa. The main CE limitations are the low specificity, the lack of therapeutic capabilities and the impossibility to take biopsies. Device assisted enteroscopy (DAE) enables histological confirmation when traditional endoscopy, capsule endoscopy and cross-sectional imaging are inconclusive and also allows therapeutic interventions such as balloon stricture dilation, intralesional steroid injection, capsule retrieval and more recently stent insertion. In the current review we will discuss technical aspect, indications and safety profile of DAE in children and adults with IBD.

Faecal calprotectin and ultrasonography as non-invasive screening tools for detecting colorectal polyps in children with sporadic rectal bleeding: a prospective study.

BACKGROUND: Colorectal polyps are reported in 6,1% of paediatric colonoscopies and in 12% of those performed for lower gastrointestinal bleeding. Although colonoscopy is widely used in paediatric patients, it requires bowel preparation and general anaesthesia or deep sedation, and in rare cases, it can cause complications. Non-invasive screening techniques able to predict polyps in children with isolated and sporadic rectal bleeding may play a key role in the selection of patients needing colonoscopy. METHODS: We enrolled all children undergoing colonoscopy for isolated and sporadic rectal bleeding to determine the diagnostic accuracy of faecal calprotectin, ultrasonography (US) and digital rectal examination as diagnostic methods for screening colorectal polyps. RESULTS: A total of 26 of 59 enrolled patients (44.1%) had colonic polyps, one patient had multiple polyps, and 23% of children had polyps proximal to the splenic flexure. The diagnostic accuracy of faecal calprotectin for detecting colorectal polyps was 96.6%, with a sensitivity of 100%. False-positive faecal calprotectin was shown in 2 patients with non-steroidal anti-inflammatory drug-related lesions. The diagnostic accuracy of ultrasound was 77.9%. Polyps not seen with ultrasound tended to be relatively smaller (1.5 vs 2.3, p = 0.001) and located in the rectum. The combined use of FC, US and digital rectal examination obtained a specificity and PPV of 100%. CONCLUSIONS: FC combined with US and digital rectal examination is a good and promising non-invasive screening test for detecting colorectal polyps in children with isolated and sporadic rectal bleeding.

Improving assessment and management of large non-pedunculated colorectal lesions in a Western center over 10 years: lessons learned and clinical impact.

Background and study aims Outcomes of endoscopic assessment and management of large colorectal (CR) non-pedunculated lesions (LNPLs) are still under evaluation, especially in Western settings. We analyzed the clinical impact of changes in LNPL management over the last decade in a European center. Patients and methods All consecutive LNPLs ≥ 20 mm endoscopically assessed (2008-2019) were retrospectively included. Lesion, patient, and resection characteristics were compared among clinically relevant subgroups. Multivariate logistic regression (for predictors of submucosal invasion [SMI] and recurrence), Kaplan-Meier curves and ROC curves (for temporal cut-offs in trends analyses) were used. Results A total of 395 LNPLs were included (30 mm [range 20-40]; SMI = 9.6 %; primary endoscopic resection [ER] = 88.4 %). Pseudo-depression and JNET classification independently predicted SMI beyond single morphologies/location. After complete ER, involvement of ileocecal valve/dentate line, piece-meal resection and high-grade dysplasia independently predicted recurrence. Rates of 5-year recurrence-free, surgery-free and cancer-free survival were 77.5 %, 98.6 % and 100 %, respectively, with 93.8 % recurrences endoscopically managed and no death attributable to ER or CR cancer (versus 3.4 % primary surgery mortality). ROC curves identified the period ≥ 2015 (following Endoscopic Submucosal Dissection [ESD] introduction and education on pre-resective lesion assessment) as associated with improved lesions' characterization, increased en-bloc resection of SMI lesions (87.5 % vs 37.5 %; p = 0.0455), reduced primary surgery (7.5 % vs 16.7 %; p = 0.0072), surgical referral of benign lesions (5.1 % vs 14.8 %; p = 0.0019), and recurrences. Conclusions ESD introduction and educational interventions allowed ER of more complex lesions, offset by increased complementary surgery for complications or intrinsic histological risk. Nevertheless, overall, they have reduced surgery demand and increased appropriateness and safety of LNPL management in our center.

Late recurrence after surgical resection of a pancreatic tumor in von Hippel-Lindau disease.

CONTEXT: Patients with von Hippel-Lindau syndrome, a dominantly inherited familial cancer syndrome, develop a variety of tumors in different organ systems which make the clinical management of these patients complex. CASE REPORT: The long clinical history of a 45-year-old woman started at 22 years of age when she had surgery for a right adrenal pheochromocytoma. Two years later, a pancreaticoduodenectomy was performed to remove a pancreatic mass which turned out to be a pancreatic neuroendocrine tumor. After a long period of relative wellness, 21 years after the surgical resection of her primary pancreatic neuroendocrine tumor, abdominal lymph node metastases of pancreatic neuroendocrine origin occurred. In fact, three abdominal nodules were removed by laparoscopic surgery, and the histological examination showed well-differentiated neuroendocrine tumors with similar immunohistochemical characteristics and Ki67 below 1%. Considering the patient's clinical history, an inherited cause was postulated and multiple endocrine neoplasia type 1 was first investigated, but the result was negative. Then, a missense mutation in exon 3 of the VHL gene (ACT>ATT; Thr157Ile) was found. CONCLUSION: Although no local and/or distant tumor recurrences are usually reported in radically operated on von Hippel-Lindau pancreatic neuroendocrine tumor patients after a median time of five years of follow-up, the present patient had a recurrence after a very long period of time, suggesting that a pancreatic neuroendocrine tumor associated with von Hippel-Lindau syndrome may behave more aggressively than that has previously been described, thus requiring a life-long follow-up.

Occurrence of Acute Oesophageal Necrosis (Black Oesophagus) in a Single Tertiary Centre.

Acute oesophageal necrosis (AON) is a rare condition characterised by the endoscopic finding of diffuse, circumferential, black mucosal pigmentation of the oesophagus, which typically stops at the gastro-oesophageal junction. This observational study aimed to assess the occurrence, clinical characteristics and outcomes of AON in a consecutive endoscopic cohort in a single tertiary university centre. A retrospective analysis of endoscopic data of upper gastrointestinal endoscopy (UGE) was carried out from 2008 to 2018. Out of 25,970 UGE, 16 patients (0.06%) had AON; 75.0% were men with a median age of 75 years. Almost all patients underwent diagnosis during emergency UGE performed for gastrointestinal bleeding, but one patient was diagnosed during elective UGE for persistent vomiting and diarrhoea. All patients reported one or more pre-existing comorbidities and concomitant acute events. Two patients had AON as the first presentation of Zollinger-Ellison syndrome (ZES). One patient developed an oesophageal stenosis, and another patient presented a relapse of AON. Mortality was 50%, but no patient died as a direct consequence of AON. AON is a rare cause of gastrointestinal bleeding diagnosed mainly during emergency UGE. Our study showed that ZES might manifest with this critical presentation, and endoscopists must be aware of this evidence.

Mucosal adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG in the human colonic mucosa: A proof-of-concept study.

AIM: To investigate the adhesion and anti-inflammatory effects of Lactobacillus rhamnosus GG (LGG) in the colonic mucosa of healthy and ulcerative colitis (UC) patients, both in vivo and ex vivo in an organ culture model. METHODS: For the ex vivo experiment, a total of 98 patients (68 UC patients and 30 normal subjects) were included. Endoscopic biopsies were collected and incubated with and without LGG or LGG-conditioned media to evaluate the mucosal adhesion and anti-inflammatory effects [reduction of tumor necrosis factor alpha (TNFα) and interleukin (IL)-17 expression] of the bacteria, and extraction of DNA and RNA for quantification by real-time (RT)-PCR occurred after the incubation. A dose-response study was performed by incubating biopsies at "regular", double and 5 times higher doses of LGG. For the in vivo experiment, a total of 42 patients (20 UC patients and 22 normal controls) were included. Biopsies were taken from the colons of normal subjects who consumed a commercial formulation of LGG for 7 d prior to the colonoscopy, and the adhesion of the bacteria to the colonic mucosa was evaluated by RT-PCR and compared with that of control biopsies from patients who did not consume the formulation. LGG adhesion and TNFα and IL-17 expression were compared between UC patients who consumed a regular or double dose of LGG supplementation prior to colonoscopy. RESULTS: In the ex vivo experiment, LGG showed consistent adhesion to the distal and proximal colon in normal subjects and UC patients, with a trend towards higher concentrations in the distal colon, and in UC patients, adhesion was similar in biopsies with active and quiescent inflammation. In addition, bioptic samples from UC patients incubated with LGG conditioned media (CM) showed reduced expression of TNFα and IL-17 compared with the corresponding expression in controls (P < 0.05). Incubation with a double dose of LGG increased mucosal adhesion and the anti-inflammatory effects (P < 0.05). In the in vivo experiment, LGG was detectable only in the colon of patients who consumed the LGG formulation, and bowel cleansing did not affect LGG adhesion. UC patients who consumed the double LGG dose had increased mucosal concentrations of the bacteria and reduced TNFα and IL-17 expression compared with patients who consumed the regular dose (48% and 40% reduction, respectively, P < 0.05). CONCLUSION: In an ex vivo organ culture model, LGG showed consistent adhesion and anti-inflammatory effects. Colonization by LGG after consumption for a week was demonstrated in vivo in the human colon. Increasing the administered dose increased the adhesion and effectiveness of the bacteria. For the first time, we demonstrated that LGG effectively adheres to the colonic mucosa and exerts anti-inflammatory effects, both ex vivo and in vivo.

Clinical management of endoscopically resected pT1 colorectal cancer.

Background Implementation of colorectal cancer (CRC) screening programs increases endoscopic resection of polyps with early invasive CRC (pT1). Risk of lymph node metastasis often leads to additional surgery, but despite guidelines, correct management remains unclear. Our aim was to assess the factors affecting the decision-making process in endoscopically resected pT1-CRCs in an academic center. Methods We retrospectively reviewed patients undergoing endoscopic resection of pT1 CRC from 2006 to 2016. Clinical, endoscopic, surgical treatment, and follow-up data were collected and analyzed. Lesions were categorized according to endoscopic/histological risk-factors into low and high risk groups. Comorbidities were classified according to the Charlson comorbidity index (CCI). Surgical referral for each group was computed, and dissociation from current European CRC screening guidelines recorded. Multivariate analysis for factors affecting the post-endoscopic surgery referral was performed. Results Seventy-two patients with endoscopically resected pT1-CRC were included. Overall, 20 (27.7 %) and 52 (72.3 %) were classified as low and high risk, respectively. In the low risk group, 11 (55 %) were referred to surgery, representing over-treatment compared with current guidelines. In the high risk group, nonsurgical endoscopic surveillance was performed in 20 (38.5 %) cases, representing potential under-treatment. After a median follow-up of 30 (6 - 130) months, no patients developed tumor recurrence. At multivariate analysis, age (OR 1.21, 95 %CI 1.02 - 1.42; P  = 0.02) and CCI (OR 1.67, 95 %CI 1.12 - 3.14; P  = 0.04) were independent predictors for subsequent surgery. Conclusions A substantial rate of inappropriate post-endoscopic treatment of pT1-CRC was observed when compared with current guidelines. This was apparently related to an overestimation of patient-related factors rather than endoscopically or histologically related factors.