Rectal linitis plastica as the first presentation of metastatic lobular breast cancer: an endoscopic ultrasound diagnosis.

Gastrointestinal tract is an uncommon site of breast cancer metastasis. Rectal linitis plastica (RLP) is a rare presentation of rectal neoplasia, both primary and secondary, and refers to a diffuse infiltration of the wall by an infiltrating carcinoma. Diagnostic assessment of RLP may be challenging since cross-sectional imaging and endoscopic findings may be nonspecific, and endoscopic biopsies are frequently non-diagnostic due to the submucosal disease localization. Endoscopic ultrasound (EUS) with fine needle biopsy (FNB) is widely used for the diagnostic assessment of sub-epithelial lesions of upper and lower gastrointestinal tract. However, data about the use of EUS in case of rectal linitis plastica are very poor. We present a case of rectal metastasis as the first presentation of lobular breast cancer, presenting as rectal linitis plastica and diagnosed with EUS-FNB.

Endoscopic ultrasound diagnostic gain over computed tomography and magnetic resonance cholangiopancreatography in defining etiology of idiopathic acute pancreatitis.

BACKGROUND: About 10%-30% of acute pancreatitis remain idiopathic (IAP) even after clinical and imaging tests, including abdominal ultrasound (US), contrast-enhanced computed tomography (CECT) and magnetic resonance cholangiopancreatography (MRCP). This is a relevant issue, as up to 20% of patients with IAP have recurrent episodes and 26% of them develop chronic pancreatitis. Few data are available on the role of EUS in clarifying the etiology of IAP after failure of one or more cross-sectional techniques. AIM: To evaluate the diagnostic gain after failure of one or more previous cross-sectional exams. METHODS: We retrospectively collected data about consecutive patients with AP and at least one negative test between US, CECT and MRCP, who underwent linear EUS between January 2017 and December 2020. We investigated the EUS diagnostic yield and the EUS diagnostic gain over different combinations of these cross-sectional imaging techniques for the etiologic diagnosis of AP. Types and frequency of EUS diagnosis were also analyzed, and EUS diagnosis was compared with the clinical parameters. After EUS, patients were followed-up for a median of 31.5 mo to detect cases of pancreatitis recurrence. RESULTS: We enrolled 81 patients (63% males, mean age 61 ± 18, 23% with previous cholecystectomy, 17% with recurrent pancreatitis). Overall EUS diagnostic yield for AP etiological diagnosis was 79% (20% lithiasis, 31% acute on chronic pancreatitis, 14% pancreatic solid or cystic lesions, 5% pancreas divisum, 5% autoimmune pancreatitis, 5% ductal abnormalities), while 21% remained idiopathic. US, CECT and MRCP, taken alone or in combination, led to AP etiological diagnosis in 16 (20%) patients; among the remaining 65 patients, 49 (75%) obtained a diagnosis at EUS, with an overall EUS diagnostic gain of 61%. Sixty-eight patients had negative US; among them, EUS allowed etiological diagnosis in 59 (87%). Sixty-three patients had a negative CECT; among them, 47 (74%) obtained diagnosis with EUS. Twenty-four had a negative MRCP; among them, 20 (83%) had EUS diagnosis. Twenty-one had negative CT + MRCP, of which 17 (81%) had EUS diagnosis, with a EUS diagnostic gain of 63%. Patients with biliary etiology and without previous cholecystectomy had higher median values of alanine aminotransferase (154 vs 25, P = 0.010), aspartate aminotransferase (95 vs 29, P = 0.018), direct bilirubin (1.2 vs 0.6, P = 0.015), gamma-glutamyl transpeptidase (180 vs 48, P = 0.006) and alkaline phosphatase (150 vs 72, P = 0.015) Chronic pancreatitis diagnosis was more frequent in patients with recurrent pancreatitis at baseline (82% vs 21%, P < 0.001). During the follow-up, AP recurred in 3 patients, one of which remained idiopathic. CONCLUSION: EUS is a good test to define AP etiology. It showed a 63% diagnostic gain over CECT + MRCP. In suitable patients, EUS should always be performed in cases of IAP. Further prospective studies are needed.

SARS-CoV-2 in inflammatory bowel disease population: Antibodies, disease and correlation with therapy.

BACKGROUND: Guidelines recommend to cease inflammatory bowel disease (IBD) biologic therapy during coronavirus disease 2019 (COVID-19). AIM: To investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody positivity in an IBD cohort, COVID-19 disease severity and to evaluate the correlation with clinical/therapeutic variables. METHODS: Prospective observational cohort study. IBD patients were tested for SARS-CoV-2 IgG. Data on COVID-19 disease, demographics/therapeutics and clinical features of the IBD population were collected. IgG ≥ 7 was set for SARS-CoV-2 antibody positivity. Throat swab was performed in cases of IgG positivity. Correlations between antibody positivity or COVID-19 symptoms and therapeutic/clinical data were assessed. RESULTS: In total, 103 IBD patients were enrolled. Among them, 18.4% had IgG ≥ 7. Multivariate analysis of antibody positivity correlated only with IBD treatment. For IgG ≥ 7, the odds ratio was 1.44 and 0.16 for azathioprine and mesalazine, respectively, vs biologic drugs (P = 0.0157 between them). COVID-19 related symptoms were reported in 63% of patients with IgG positivity. All but one patient with COVID-19 symptoms did not require ceasing IBD treatment or hospitalization. IBD treatment and body mass index correlated with COVID-19 disease development with symptoms. CONCLUSION: The IBD population does not have a higher risk of severe COVID-19. The relative risk of having SARS-CoV-2 antibodies and symptoms was higher for patients taking azathioprine, then biologic therapy and lastly mesalazine. None of the patients under biologic therapy developed severe COVID-19.

Gastric per-oral endoscopic myotomy: Indications, technique, results and comparison with surgical approach.

Gastroparesis is a chronic disease of the stomach that causes a delayed gastric emptying, without the presence of a stenosis. For 30 years the authors identified pylorospasm as one of the most important pathophysiological mechanisms determining gastroparesis. Studies with EndoFLIP, a device that assesses pyloric distensibility, increased the knowledge about pylorospasm. Based on this data, several pyloric-targeted therapies were developed to treat refractory gastroparesis: Surgical pyloroplasty and endoscopic approach, such as pyloric injection of botulinum and pyloric stenting. Notwithstanding, the success of most of these techniques is still not complete. In 2013, the first human gastric per-oral endoscopic myotomy (GPOEM) was performed. It was inspired by the POEM technique, with a similar dissection method, that allows pyloromyotomy. Therapeutical results of GPOEM are similar to surgical approach in term of clinical success, adverse events and post-surgical pain. In the last 8 years GPOEM has gained the attention of the scientific community, as a minimally invasive technique with high rate of clinical success, quickly prevailing as a promising therapy for gastroparesis. Not surprisingly, in referral centers, its technical success rate is 100%. One of the main goals of recent studies is to identify those patients that will respond better to the therapies targeted on pylorus and to choose the better approach for each patient.

Liver-side of inflammatory bowel diseases: Hepatobiliary and drug-induced disorders.

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases (IBD), both in Crohn's disease and ulcerative colitis (UC), and therefore represent a diagnostic challenge. Immune-mediated conditions include primary sclerosing cholangitis (PSC) as the main form, variant forms of PSC (namely small-duct PSC, PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis) and granulomatous hepatitis. PSC is by far the most common, presenting in up to 8% of IBD patients, more frequently in UC. Several genetic foci have been identified, but environmental factors are preponderant on disease pathogenesis. The course of the two diseases is typically independent. PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies. Risk of cholangiocarcinoma is significantly increased in PSC, as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis. No disease-modifying drugs are approved to date. Thus, PSC management is directed against symptoms and complications and includes medical therapies for pruritus, endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease. Other non-immune-mediated hepatobiliary disorders are gallstone disease, whose incidence is higher in IBD and reported in up to one third of IBD patients, non-alcoholic fatty liver disease, pyogenic liver abscess and portal vein thrombosis. Drug-induced liver injury (DILI) is an important issue in IBD, since most IBD therapies may cause liver toxicity; however, the incidence of serious adverse events is low. Thiopurines and methotrexate are the most associated with DILI, while the risk related to anti-tumor necrosis factor-α and anti-integrins is low. Data on hepatotoxicity of newer drugs approved for IBD, like anti-interleukin 12/23 and tofacitinib, are still scarce, but the evidence from other rheumatic diseases is reassuring. Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD, and adequate screening and vaccination is warranted. On the other hand, hepatitis C reactivation does not seem to be a real risk, and hepatitis C antiviral treatment does not influence IBD natural history. The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis, but it is of paramount importance to make a quick and accurate diagnosis, as it may influence the therapeutic management.

Clinical features and natural history of idiopathic peptic ulcers: a retrospective case-control study.

Objectives: Peptic ulcer disease (PUD) is still common worldwide and is characterized by high mortality and morbidity. Following the decline of Helicobacter pylori infection, the detection of idiopathic PUD (IPUD) has become more frequent, making diagnosis and treatment more difficult. In this study, the clinical features and natural history of IPUD were analyzed.Methods: This was a retrospective case‒control study conducted in a tertiary care setting (University of Sassari, Italy). Records of 9,212 patients undergoing upper endoscopy from 2002 to 2018 were analyzed. Following the exclusion of H. pylori, NSAIDs, and unusual PUD causes, the remaining were labelled as IPUD. Cases (IPUD) and controls (PUD negative) were compared, adjusting for several covariates through multivariate logistic regression models.Results: Among 380 PUD, 95 were considered IPUD. The proportion rose over the study period in contrast to the decline of H. pylori-PUD. Factors significantly associated with IPUD, after adjusting for all covariates, were age (OR, 3.520; 95% CI, 1.634 - 7.585), male sex (OR, 3.126; 95% CI, 1.888 - 5.176), hospitalization (OR, 2.968; 95% CI, 1.926 - 4.575), and number of medications (OR, 2.808; 95% CI, 1.178 - 6.735). A clinical history positive for PUD was the major risk associated with IPUD (OR, 3.729; 95% CI, 2.050 - 6.785). Patients with IPUD were treated with the highest proton pump inhibitor (PPI) dose for 40-60 days. Follow up endoscopy showed a cure rate of 97.6%.Conclusion: The relative proportion of IPUD is increasing in our population in contrast to the drop of H. pylori-PUD. Treatment with high-dose PPI, and for a long duration, heals IPUD and protects from recurrence.

Overweight: A Protective Factor against Comorbidity in the Elderly.

The aim of this study was to investigate the relationship between body mass index (BMI) categories and comorbidity in 9067 patients (age range 18‒94 years) who underwent upper digestive endoscopy in Northern Sardinia, Italy. The majority of participants (62.2%) had a BMI under 25 kg/m2, overweight was detected in 30.4%, and obesity (BMI ≥ 30 kg/m2) in 7.4% of patients. The most frequent illness recorded was hypertension followed by cardiovascular and liver disease. The multivariate analysis, after adjusting for sex, residence, marital status, smoking habits, occupation and hospitalization detected an association between comorbidity and aging that was statistically significant and progressive. Among patients younger than 60 years (n = 5612) the comorbidity risk was higher for BMI ranging 27.5‒29.9 kg/m2 compared with BMI 25.0‒27.4 kg/m2 (RR = 1.38; 95% CI 1.27‒1.50 vs. RR = 0.86; 95% CI 0.81‒0.90). In patients older than 60 years (n= 3455) the risk was lower for a BMI in the range 27.5-29.9 kg/m2 compared with a BMI in the range 25.0-27.4 kg/m2 (RR = 1.11; 95% CI 1.05‒1.18 vs. RR = 1.28; 95% CI 1.21‒1.35). These results suggest that being moderately overweight is a marker of a healthy aging process and might protect, at least in part, against comorbidity. However, further research is needed to better understand this unexpected finding.

Glucose-6-phosphate dehydrogenase deficiency reduces susceptibility to cancer of endodermal origin.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzyme defect worldwide. There is a growing scientific evidence for a protective role of G6PD deficiency against carcinogenesis. In this retrospective analysis, we tested the hypothesis that G6PD deficiency may reduce the risk of developing cancer in a tissue-specific manner. Material and methods: The study was conducted using data from 11,708 subjects undergoing gastrointestinal endoscopic procedures between 2002 and 2018 and tested for G6PD status in a teaching hospital of Northern Sardinia, Italy. Results: A 40% reduction of risk for cancer of endodermal origin was observed among G6PD-deficient patients compared with subjects with normal enzyme activity (relative risk (RR) 0.61, 95% confidence interval (CI) 0.47-0.80) in both genders, confirmed by multivariable generalized linear regression after adjusting for age, sex, smoking habits, body mass index, diabetes and socio-economic status. The 'protective' effect of G6PD deficiency was larger for gastric cancer (RR 0.41, 95% CI 0.18-0.99), hepatocellular carcinoma (RR 0.48, 95% CI 0.26-0.92) and colorectal cancer (RR 0.72, 95% CI 0.53-0.98), while a non-significant risk was observed for breast, prostate, lung, hematopoietic and metastases (primary site unknown). Conclusions: Our results suggest a reduced susceptibility to develop cancers, mostly of endodermal origin (stomach, colon and liver), but not of ectodermal/mesodermal origin, in carriers of G6PD deficiency. The effects of G6PD deficiency on carcinogenesis need further studies to better understand how cancer cells originating from different germ layers use pentose phosphate pathway to proliferate.

Are gastric hyperplastic polyps an additional manifestation in celiac disease?: Results from a retrospective study.

Gastric polyps are frequently reported in patients undergoing upper endoscopic procedures. In this retrospective study, the association between hyperplastic polyps and celiac disease in Northern Sardinia was estimated.Age, gender, body mass index, and medications taken in the 2 preceding months, including proton-pump inhibitors (PPIs), H2 receptor blockers (anti-H2), Helicobacter pylori status, endoscopic findings, and histology from charts of patients undergoing esophago-gastro-duodenoscopy were reviewed. Polyps were classified as hyperplastic, fundic gland, inflammatory, and adenomatous.3.7% (423/11379) patients had celiac disease. Prevalence of gastric polyps was 4.2% (3.8% among celiac vs 4.2% nonceliac patients). Inflammatory polyp was the most common histotype (55.8% and 56.2%) followed by fundic gland polyps (31.4% and 43.7%), hyperplastic (8.7% and 0%), and adenomas, in celiac and nonceliac patients, respectively. Fundic gland polyps were more common in PPI users (odds ratio: 4.06) than in nonusers (2.65, P = 0.001) among celiac and nonceliac patients. Age older than 50, female gender, esophago-gastro-duodenoscopy year, and PPI use were associated with the presence of polyps, whereas active H pylori infection was not.Gastric polyps were common in Sardinian patients undergoing esophago-gastro-duodenoscopy. However, the previously reported association between hyperplastic polyps and celiac disease was not confirmed in our study.

Chronic autoimmune disorders are increased in coeliac disease: A case-control study.

Coeliac disease (CD) is an autoimmune disorder of the small bowel associated with increased risk of additional autoimmune diseases (ADs).To investigate the prevalence of ADs in a population of adult coeliac patients.This was a retrospective case-control study. Data from coeliac patients and controls referred to a tertiary center between 2013 and 2016 were collected. The frequency of ADs and the unadjusted and adjusted odds ratios (ORs) for age, gender, disease duration, and body mass index with their 95% confidence intervals (CIs) were evaluated.Two hundred fifty-five patients with CD (median age 37.1 years; 206 women) were matched with 250 controls. ADs were more frequent (35.3%) in coeliac patients than in controls (15.2%). Adjusted ORs for the presence of only 1, at least 1, and more than 1 AD were 3.13 (95% CI 1.81-5.42, P < .0001), 3.31 (95% CI 2.00-5.46, P < .0001), and 3.93 (95% CI 1.49-10.36, P = .006), respectively. Hashimoto thyroiditis was the most prevalent AD (24.3% vs. 10%) OR = 2.55 (95% CI 1.39-4.70, P < .0001), followed by psoriasis (4.3% vs. 1.6%), type 1 diabetes (2.7% vs. 0.4%), and Sjögren syndrome (2.4% vs. 0.4%).These findings suggest a need for a careful surveillance of autoimmune status, especially for Hashimoto thyroiditis in patients with celiac disease.

G6PD Deficiency Does Not Enhance Susceptibility for Acquiring Helicobacter pylori Infection in Sardinian Patients.

BACKGROUND: Subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more susceptible to infections due to impaired leukocyte bactericidal activity. The disorder is common in the Mediterranean area. The aim of this study was to investigate whether G6PD deficiency may be a risk factor for acquiring H. pylori infection. METHODS: We performed a retrospective study. Data from clinical records of 6565 patients (2278 men and 4287 women, median age 51, range 7‒94) who underwent upper endoscopy between 2002 and 2014 were collected. H. pylori status, assessed by histology plus rapid urease test or 13C-urea breath test, and G6PD status were also reported. A multiple logistic regression model was used to investigate the association between G6PD deficiency and H. pylori infection. RESULTS: Enzyme deficiency was detected in 12% (789/6565) of the entire cohort, and more specifically in 8.3% of men and in 14.0% of women. Overall, the proportion of patients positive for H. pylori was 50.6% and 51.5% among G6PD deficient and non-deficient patients (χ² = 0.271; p = 0.315). Moreover, among G6PD-deficient and normal patients the frequency of previous H. pylori infection was similar. After adjustment for age and gender the risk for acquiring H. pylori infection was similar in G6PD-deficient and normal patients. Only age was a strong statistically significant risk predictor. CONCLUSIONS: These results demonstrate for the first time that G6PD deficiency does not enhance patients' susceptibility to acquire H. pylori infection in Sardinia.

Inclusion of Lactobacillus Reuteri in the Treatment of Helicobacter pylori in Sardinian Patients: A Case Report Series.

Clinical studies have shown that bismuth-containing quadruple therapy given twice a day for 10 to 14 days is effective and safe in the treatment of Helicobacter pylori infection in Sardinia. However, bismuth is no longer available in Italy. To report the effectiveness and tolerability of pantoprazole 20 mg, tetracycline 500 mg, and metronidazole 500 mg given b.i.d. (with the midday and evening meals) for 10 days supplemented with Lactobacillus reuteri (DSM 17938) 10(8)  cfu/tablet once a day for 20 days in patients treated in a routine daily practice setting. H pylori infection was defined as a positive gastric histopathology and/or 13C-Urea Breath Test (UBT) and/or stool antigen testing. Successful eradication was documented by 13C-UBT, and/or stool antigen assay at least 4 weeks post-therapy. Compliance and side effects were recorded after completing treatment. A total of 45 patients (10 men, 35 women; mean age 52.6 years) have completed the treatment regimen with the success rate of 93% (95% confidence interval = 85-99%). Compliance was excellent. Side effects were absent or generally mild.Proton pump inhibitor-tetracycline-metronidazole-L reuteri therapy provided high eradication rates with few side effects and therefore can safely replace bismuth in H pylori treatment. Further studies are needed that include susceptibility testing.

Changing prevalence of Helicobacter pylori infection and peptic ulcer among dyspeptic Sardinian patients.

Over the past 50 years, the prevalence of Helicobacter pylori infection has fallen as standards of living improved. The changes in the prevalence of infection and its manifestations (peptic ulcer disease and gastric mucosal lesions) were investigated in a large cohort of Sardinians undergoing upper endoscopy for dyspepsia. A retrospective observational study was conducted involving patients undergoing endoscopy for dyspepsia from 1995 to 2013. H. pylori status was assessed by histology plus the rapid urease test or 13C-UBT. Gastric mucosal lesions were evaluated histologically. Data including non-steroidal anti-inflammatory drugs (NSAIDs) use and the presence of peptic ulcers were collected. The prevalence of H. pylori was calculated for each quartile and for each birth cohort from 1910 to 2000. 11,202 records were retrieved for the analysis (62.9% women). The overall prevalence of H. pylori infection was 43.8% (M: 46.6% vs. F: 42.0%; P = 0.0001). A dramatic decrease in the prevalence of infection occurred over the 19-year observation period. The birth cohort effect was evident in each category (quartile) reflecting the continuous decline in H. pylori acquisition. Over time, the prevalence of peptic ulcers also declined, resulting in an increase in the proportion of H. pylori negative/NSAID positive and H. pylori negative/NSAID negative peptic ulcers. The prevalence of gastric mucosal changes also declined despite aging. The decline in H. pylori prevalence over time likely reflects the improvement in socioeconomic conditions in Sardinia such that H. pylori infection and its clinical outcomes including peptic ulcer are becoming less frequent even among dyspeptic patients.

Cherry-tree colon: colonoscopic appearance suggesting drug-induced mucosal injury.

Drug-induced damage to the gastrointestinal mucosa has been mainly focused on damage in the upper tract. However, increasing evidence suggests that commonly used drugs may also affect the mucosa of the lower gut, and particularly in the colon. The aim of this study was to report that fairly homogeneous colonoscopic findings, correlate with histological evidence of drug-induced mucosal injury. Charts of patients with the "cherry tree" colonoscopic aspect were reviewed to correlate the endoscopic and histological findings for a possible association with the use of drugs. Data from 29 patients (5 men, 24 women, age range 16-76 years) with the "cherry tree" colonoscopic findings were analyzed. Histology revealed an increase in eosinophils in the left colon in 23 patients, pseudomelanosis coli in 3, and microscopic colitis in 3. The findings were associated with proton pump inhibitors in 19 (65.5 %), non-steroidal anti-inflammatory drugs or statins (3 cases each), and other drugs [4 cases, including estroprogestinics (1), antidepressants (2), and thyroxin (1)]. The "cherry tree" colonoscopic appearance suggests drug-induced colonic damage. Awareness of this association may prevent unnecessary, expensive and time-consuming procedures.