Cancer-risk by family history and mismatch-repair mutation in Lynch syndrome

Abstract

Introduction: Surveillance of Lynch syndrome (LS) is recommended to reduce cancer-risk. There is an increased awareness that cancer-risk may vary with mismatch-repair mutation and family history. However, gene-specific and family-specific surveillance are not recommended. Therefore, we aimed to estimate the cumulative incidence of lesions and to assess the cancer-risk by family history and mismatch-repair mutation (MMR).

Methods: Single-centre retrospective cohort of all individuals (n?=?241) in a specialized institution was conducted.

Results: Forty-eight percent of individuals inherited MSH2 mutations, 32% MLH1, 15% MSH6 and 5% PMS2. The calculated cumulative incidence for any cancer increased with age. By age 70, the cumulative incidence for low-risk, high-risk adenomas and CRC was estimated at 66.6%, 57.7% and 25.7%, respectively. By age 70, the cumulative incidence of endometrial cancer (EC), gastric cancer and urinary tract cancer was estimated at 17.3%, 3.3% and 12.6%, respectively. MLH1 and MSH2 mutation carriers had lower mean age of CRC diagnosis than MSH6 and PMS2 [MLH1:44(CI95% 38–50); MSH2:43(CI95% 40–47); MSH6:52(CI95% 45–59); PMS2:46(CI95% 35–57)]. The risk of EC was higher when family history was present (RR = 2.39, CI95%[1.3;4.6]). MSH6 mutation carriers had higher risk of EC comparative to other MMR mutation carriers (RR = 1.9, p?=?.09). The risk of urinary tract cancer was higher with MSH2 (RR = 8.4, CI95%[2.7;25.9]) and positive family history (RR = 10.8, CI95%[1.4;82.8]).

Conclusion: This cohort demonstrates the effectiveness of LS surveillance and suggests possible tailored surveillance strategies by gene mutation and family history.     

Impact of mismatch repair deficiency on tumour regression grade after neoadjuvant chemotherapy in localized gastroesophageal adenocarcinoma

BackgroundThe use of neoadjuvant chemotherapy (NAC) in patients with mismatch repair (MMR) deficient (dMMR) localized gastric and oeso-gastric junction (OGJ) adenocarcinoma is subject of debate. Histological response assessment might help to better evaluate the impact of dMMR on response to NAC.MethodsPatients with localized gastric/OGJ adenocarcinoma resected after NAC were retrospectively identified. MMR protein expression status was assessed by immunohistochemistry. The primary objective was the frequency of histological responders to NAC defined by tumour regression grade (TRG) using Mandard's (TRG1-2) and Becker's (TRG1) classifications, according to the MMR status.ResultsIn total, 247 patients with 43 dMMR and 204 pMMR gastric/OGJ adenocarcinoma were identified. Among dMMR tumours, 18 (42%) arose from the OGJ. Histological response (Becker TRG1-2) was observed for 28% and 35% of dMMR and pMMR tumours, respectively (p = 0.35). Similar results were observed with Mandard classification. With a median follow-up of 37.5 months, median disease-free and overall survival were not reached for the dMMR group.ConclusionHistological response after NAC in patients with localized dMMR gastric/OGJ adenocarcinoma is not statistically different to those with pMMR tumours. This study provides additional data for the discussion about avoiding NAC in patients with dMMR gastric/OGJ adenocarcinomas.     

Perinatal and familial risk factors for irritable bowel syndrome in a Swedish national cohort

Objective: Studies of the importance of perinatal factors for the development of irritable bowel syndrome (IBS) are sparse. We conducted a large national cohort study to examine perinatal and familial risk factors for IBS.

Material and methods: A national cohort of 1,963,685 persons who were born in Sweden in 1973–1992 (identified from the Swedish Birth Registry) were followed up for adult (18 years and older) IBS incidence in the Swedish Patient Register through 2010 (maximum age 38 years). There were 24,633 IBS cases in 46,784,296 person-years of follow-up.

Results: After adjusting for potential confounders, significant risk factors for IBS included caesarean (HR?=?1.10, 95% confidence interval [CI] 1.05–1.11, p?p?=?.02), being second in birth order (HR?=?1.04, 95%CI 1.01–1.08, p?=?.01), foetal growth ≥1 SD (HR?=?1.06, 95%CI 1.00–1.11, p?=?.05), young maternal age (<20 years) (HR=?1.09, 95%CI 1.02–1.17, p?=?.02), maternal marital status (divorced/widowed) (HR?=?1.12, 95%CI 1.08–1.17, p?p?=?.01), maternal education of 12–14 years (HR?=?1.06, 95%CI 1.01–1.11, p?=?.03), parental history of IBS (HR?=?1.54, 95%CI 1.42–1.66, p?p?p?=?.02). Protective factors were male sex (HR?=?0.36, 95%CI 0.35–0.37, p?p?=?.03).

Conclusions: In this large cohort study, several perinatal and familial factors were associated with an increased risk of IBS independently, suggesting that perinatal and familial factors may play an important long-term role in the aetiology of IBS.     

Are prematurity and environmental factors determinants for developing childhood-onset systemic lupus erythematosus?

Objective: The objective of this study is to evaluate the influence of exposure to air pollutants and inhalable environmental elements during pregnancy and after birth until childhood-onset systemic lupus erythematosus(cSLE) diagnosis.

Methods: This case–control study comprised 30 cSLE patients and 86 healthy controls living in the Sao Paulo metropolitan area. A structured and reliable questionnaire (kappa index for test-retest was 0.78) assessed demographic data, gestational and perinatal-related-factors, and exposure to inhalable elements during pregnancy and after birth (occupational exposure to inhalable particles and/or volatile vapor, and/or tobacco, as well as, the presence of industrial activities or gas stations near the home/work/daycare/school). Tropospheric pollutants included: particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), ozone (O₃) and carbon monoxide (CO).

Results: The median current age was similar between cSLE patients and healthy controls [16.0 (5–21) versus 15.0 (4–21) years, p?=?.32], likewise the frequency of female gender (87% versus 78%, p?=?.43). The frequencies of prematurity (30% versus 6%, p?=?.001), maternal occupational exposure during pregnancy (59% versus 12%, p?p?p?=?.008) were significantly higher in cSLE patients compared with controls. In a multivariate analysis regarding the gestation period, maternal occupational exposure (OR 13.5, 95% CI 2.5–72.4, p?=?.002), fetal smoking (OR 8.6, 95%CI 1.6–47, p?=?.013) and prematurity (OR 15.8, 95%CI 1.9–135.3, p?=?.012) remained risk factors for cSLE development. Furthermore, exposure to secondhand smoking during pregnancy and after birth (OR 9.1, 95%CI 1.8–42.1, p?=?.002) was also a risk factor for cSLE development.

Conclusions: Prematurity and environmental factors were risk factors for developing cSLE.     

Percutaneous endoscopic gastrostomy: dealing with the issue of dislodgement

Abstract

Introduction: Percutaneous Endoscopic Gastrostomy (PEG) is accepted as an efficient method to provide long-term enteral nutrition. PEG accidental dislodgement (device exteriorization confirmed by expert evaluation) rate is high and can lead to major morbidity.

Objective: To identify independent risk factors for PEG accidental dislodgement.

Methods: Retrospective, single-center study, including consecutive patients submitted to PEG procedure, for 38 consecutive months. Every patient had 12?months minimum follow-up after PEG placement. Univariate analysis selected variables with at least marginal association (p?<?.15) with the outcome variable, PEG dislodgement, which were included in a logistic regression multivariate model. Discriminative power was assessed using area under curve (AUC) of the receiver operating curve (ROC).

Results: We included 164 patients, 67.7% (111) were female, mean age was 81?years. We report 59 (36%) PEG dislodgements, of which 13 (7.9%) corresponded to early dislodgements. The variables with marginal association were hypoalbuminemia (p?=?.095); living at home (p?=?.049); living in a nursing home (p?=?.074); cerebrovascular disease (CVD) (p?=?.028); weight change of more than 5?kg, either increase or decrease (p?=?.001); psychomotor agitation (p?<?.001); distance inner bumper-abdominal wall (p?=?.034) and irregular appointment follow-up (p?=?.149). At logistic multivariate regression, the significant variables after model adjustment were CVD OR 4.8 (CI 95% 2.0–11.8), weight change OR 4.7 (CI 95%1.6–13.9) and psychomotor agitation OR 18.5 (CI 95% 5.2–65.6), with excellent discriminative power (AUC ROC 0.797 [CI95% 0.719–0.875]).

Conclusion: PEG is a common procedure and accidental dislodgement is a frequent complication. CVD, psychomotor agitation and weight change >5?kg increase the risk of this complication and should be seriously considered when establishing patients’ individual care requirements.     

Factors predictive of gastroesophageal reflux disease and esophageal motility disorders in patients with non-cardiac chest pain

Background: Patients with non-cardiac chest pain (NCCP) are referred for esophageal motility testing and pH monitoring since gastroesophageal reflux disease (GERD) and esophageal motility disorders are frequently encountered in these patients. Our aim was to determine the prevalence and distribution of these disorders and to identify predictors of abnormal esophageal function testing.

Methods: We performed a retrospective study of NCCP patients who presented after a negative cardiac evaluation and underwent esophageal manometry, esophageal pH monitoring and upper endoscopy from January 2010 to January 2017.

Key results: In a total of 177 patients, esophageal motility disorders were diagnosed in 31% and GERD in 35% of the patients. The most common diagnoses were ineffective esophageal motility (IEM) in 14.1%, jackhammer esophagus in 6.8%, diffuse esophageal spasm in 5.1% and achalasia in 2.3% patients. Older age [for every 5-year increment, odds ratio (OR) 1.2 (95% confidence intervals (CI) 1.00–1.3) p?=?.047] and dysphagia [OR 3.8 (95% CI, 1.9–7.5) p?p?=?.032] was predictive of GERD. Abnormal esophageal testing was associated with male gender [OR 2.2 (95% CI, 1.04–4.6) p?=?.039], older age [for every 5-year increment, OR 1.2 (95% CI, 1.03–1.3) p?=?.016] and Caucasian race [OR 3.1 (95% CI, 1.1–8.7) p?Conclusions: Approximately two thirds of patients presenting with NCCP have GERD or esophageal motility disorders. Esophageal function testing in NCCP should be considered in older patients, men, Caucasians and those presenting with dysphagia.     

Lipids,glucose and iron metabolic alterations in chronic hepatitis C after viral eradication – comparison of the new direct-acting antiviral agents with the old regimens

Background: Hepatitis C virus (HCV) is a unique virus which interacts with cholesterol, iron and insulin metabolism. There is limited data on the effects of direct-acting antiviral agents (DAAs) on metabolic profiles. We aimed at evaluating the behavior of metabolic risk factors of chronically HCV-infected patients after sustained virologic response (SVR), comparing the outcomes with the new DAAs versus the old treatment regimen Peg-interferon?±?ribavirin.

Methods: A total of 178 patients who achieved SVR and completed one year of follow-up were prospectively included in this study: group 1 with 105 patients treated with DAAs and group 2 with 73 patients treated with old regimens. Outcomes included lipid, glucose and iron metabolism variation after SVR.

Results: There was a significant increase in total cholesterol in both groups (group 1: p?p?p?=?.015, 95% CI: ?0.33–0.04) in group 1 and increased (p?=?.014, 95% CI: 0.07–0.59) in group 2. LDL levels increased in group 1 (p?=?.029, 95% CI: 0.05–0.88), but no significant variation was found in group 2. No significant variation in HDL, fast glucose and iron was seen in both groups. There was a significant increase of HOMA (p?=?.002, 95% CI: 0.17592–0.72317) only in group 2. Ferritin serum levels significantly decreased (p?Conclusion: Patients who have achieved SVR may have increased risk of cardiovascular outcomes due to development of hyperlipidemia and insulin resistance.     

Diagnostic accuracy of a quantitative faecal immunochemical test vs. symptoms suspected for colorectal cancer in patients referred for colonoscopy

Abstract

Objective: Determine diagnostic accuracy of a quantitative faecal immunochemical haemoglobin test (QuikRead go^® FIT, Orion Diagnostica Oy) in symptomatic patients referred for colonoscopy, at various cut-offs and for one or two tests.

Methods: Patients referred to four endoscopy units in mid-Sweden between 2013 and 2017 provided information on lower abdominal symptoms and faecal samples from two separate days prior to colonoscopy.

Results: In all, 5.4% (13/242) patients had colorectal cancer (CRC). For one FIT at cut-off 10?µg Hb/g faeces, sensitivity for CRC was 92% (95% CI 78–100%) and specificity 77% (95% CI 72–83%); equal to 74%; 95% CI 68–80 (178/242) colonoscopies potentially avoidable and one CRC missed. Based on the maximal outcome of two FITs, sensitivity was 100%, specificity 71% (66–77%) and 68%; 95% CI 62–74 (160/237) colonoscopies potentially avoidable. Among 17% (42/242) patients with one FIT of >200?µg Hb/g faeces, 85% (11/13) had CRC. Positive predictive values of FIT varied 16.9–26.2% depending on cut-off and one or two FITs, whereas NPVs were 99% and above in all scenarios.

In 60 patients reporting rectal bleeding, one FIT at cut-off 10?µg Hb/g discriminated well between CRC and other conditions (p?=?.001). In regression models, FIT was more important than age, sex and all symptoms.

Conclusion: One or two FITs in symptomatic patients referred for colonoscopy imply powerful risk stratification abilities for CRC, even among patients reporting rectal bleeding. Larger studies in various settings will clarify how to make the best use of this opportunity.

Trial registration: Clinicaltrails.gov NCT 02491593     

Biliary tract malignancies: a population-based study on incidence,prognosis and management of patients

Background: Biliary tract malignancies are uncommon and few population-based studies are available.

Methods: This nationwide population-based study in Iceland included all patients diagnosed with intra- and extrahepatic cholangiocarcinoma, gallbladder and ampullary cancer from 1984 to 2012. Patients were identified through the Icelandic Cancer Registry. Clinical information was obtained from patient records.

Results: Overall 245 patients were identified: 38 had intrahepatic cholangiocarcinoma, 66 extrahepatic cholangiocarcinoma, 73 gallbladder cancer (GBC) and 68 ampullary cancer. Overall incidence for bile tract malignancies was 1–3 per 100,000 person-years and less than 1 by sub-type. The overall bile tract malignancies in males increased from 1.3 (95% CI 0.8–1.8) to 2.5 (1.9–3.1) per 100,000 inhabitants. The incidence of GBC among females decreased from 1.1 (0.7–1.5) to 0.5 (0.2–0.7). Surgery decreased for extrahepatic cholangiocarcinoma (56 to 23%, p?=?.027), ampullary cancer (80 to 48%, p?=?.03) and overall bile tract cancer (61 to 32%, p?p?Conclusions: Overall incidence of bile tract malignancies increased in males and GBC decreased in women. Long-term survival is poor and did not improve despite changes in treatment.     

Factors for improving the diagnostic efficiency of the rapid urease test from the gastric corpus

Objective: This study aimed to evaluate the optimal biopsy site for Helicobacter pylori detection by comparing the results of rapid urease test (RUT) between the gastric corpus and the antrum.

Methods: A biopsy specimen from each subject was obtained from the corpus and from the antrum. For each subject, the two specimens were separately immersed in two different RUT kits. Positive reaction times were measured at 20?minutes and 1, 3, and 24?hours. If either of the two RUT kits showed a positive reaction, H. pylori infection was confirmed.

Results: A total of 310 H. pylori-infected subjects were eligible for study inclusion. Compared with the antrum, positive RUT reaction times in the corpus were shorter when the degree of gastric atrophy was moderate or severe (p?=?.001 and p?p?=?.021) and severe gastric atrophy (OR?=?2.41; 95% CI?=?1.13–5.13; p?=?.023). Also, severe gastric atrophy was an independent factor associated with positive RUT reaction only in the corpus (OR?=?5.12; 95% CI?=?1.55–16.88; p?=?.007).

Conclusions: In subjects aged ≥50 years or with severe gastric atrophy, biopsy of the corpus mucosa optimized the efficiency of H. pylori detection through a faster positive RUT reaction.     

Prognostic significance of granulomas in children with Crohn’s disease

Objectives: Granulomas have long been considered the histological hallmark of Crohn's disease (CD). Currently, there is considerable dispute with regards to their prognostic implications. We aimed to determine the effect of granulomas on phenotypic features and disease's long-term outcomes in a large cohort of pediatric CD patients.

Materials and methods: Medical records of pediatric CD patients diagnosed at the Schneider Children’s Medical Center were reviewed retrospectively. Patients were categorized into two groups based on the presence or absence of granulomas at diagnosis. Baseline characteristics included anthropometric, clinical, laboratory, radiological and endoscopic data. Outcome measures included flares, hospitalizations, biological therapy and surgery.

Results: Of 289?CD patients diagnosed between 2001 and 2015, 99 patients (34%) had granulomas. Median age of the entire cohort at diagnosis was 14.2 years (females, 42.6%), with a median follow-up of 8.5 years. Patients with granulomas had a significantly higher percentage (47.5% vs. 23.7%, p?=?.001) of upper gastrointestinal involvement and ileo-colonic disease (64.9% vs. 49.5%, p?=?.01). Extraintestinal manifestations were twice as common in patients without granulomas (16.3% vs. 8.1%, p?=?.05). Patients with granulomas were more likely to be hospitalized (HR =1.43, 95% CI: 1.0–2.0) and to receive biologic therapy (HR?=?1.52, 95% CI: 1.1–2.11). Additionally, both of these disease outcomes occurred significantly earlier (p?=?.013 and p?=?.027, respectively). In contrast, patients with granulomas did not exhibit increased risk of flares or bowel resection.

Conclusion: Patients with granulomas exhibited a distinct phenotype at diagnosis and demonstrated a more severe disease course.     

The relationship between social support and health-related quality of life in patients with antiphospholipid (hughes) syndrome

Objective: Antiphospholipid (Hughes) syndrome (APS) is recognised as a systemic autoimmune disease defined by recurrent thromboembolic events and/or pregnancy morbidity. Little is known about the psychological burden of this long-term condition. This study aims to explore the relationship between social support and health-related quality of life (HRQoL) in patients with APS.

Methods: A total of 270 patients with a clinical diagnosis of APS participated in a cross-sectional online questionnaire survey. Data included demographics, disease-related information, social support and HRQoL.

Results: Both perceived and ideal social support were associated with HRQoL in APS. Patients reported receiving insufficient social support. Perceived emotional support was related to physical functioning (B?=?7.77, p?=?.006, 95% CI: 2.25, 13.29); perceived instrumental support was associated with bodily pain (B?=?17.52, p? .001, 95% CI: 11.15, 23.90) and perceived informational support with physical and social functioning (B?=??6.30, p?=?.05, 95% CI: ?12.52, ?0.08; B?=?8.06, p?=?.02, 95% CI: 1.17, 14.94). Ideal emotional support was related to physical and social functioning (B?=?5.80, p?=?.04, 95% CI: 0.26, 11.34; B?=?7.53, p?=?.04, 95% CI: 0.55, 14.51); ideal instrumental support was associated with mental health (B?=?4.73, p?=?.03, 95% CI: 0.38, 9.07) and ideal informational support with vitality (B?=?5.85, p?=?.01, 95% CI: 1.23, 10.46).

Conclusion: Social support was linked to HRQoL in patients with APS. Insufficient social support was associated with limitations in various HRQoL domains. Increasing social support especially through provision of disease-specific education might contribute to improving HRQoL in patients with APS. Patient-tailored interventions addressing psychosocial aspects of living with APS are needed to improve patients’ psychological and physical status.     

Long-term mortality and causes of death in endoscopically verified upper gastrointestinal bleeding: comparison of bleeding patients and population controls

Objective: Upper gastrointestinal bleeding (UGIB) is a common emergency, with in-hospital mortality between 3 and 14%. However, the long-term mortality and causes of death are unknown. We investigated the long-term mortality and causes of death in UGIB patients in a retrospective single-centre case-control study design.

Methods: A total of 569 consecutive patients, aged ≥18 years, admitted to Kuopio University Hospital for their first endoscopically verified UGIB during the years 2009–2011 were identified from hospital records. For each UGIB patient, an age, sex and hospital district matched control patient was identified from the Statistics Finland database. Data on endoscopy procedures, laboratory values, comorbidities and medication were obtained from patient records. Data on deaths and causes of death were obtained from Statistics Finland.

Results: In-hospital mortality of UGIB patients was low at 3.3%. The long-term (mean follow-up 32 months) mortality of UGIB patients was significantly higher than controls (34.1 versus 12.1%, p?<?.001). During the 6 months following UGIB, the risk of death compared to controls was highest (HR 19.2, 95% CI 7.0–52.4, p?<?.001) and remained higher up to 3 years after the bleeding. Beyond 3 years’ follow-up, there was no difference in mortality between the groups (HR 0.7, 95% CI 0.4–1.6, p?=?.436). During the first 3 months after the UGIB episode, mortality was related to gastrointestinal diseases; after 3 months, the causes of death were related to comorbidities and did not differ from causes of death in controls.

Conclusions: UGIB patients have three times higher long-term mortality than population controls.     

Stent placement with iodine-125 seeds strand effectively extends the duration of stent patency and survival in patients with unresectable malignant obstructive jaundice

Abstract

Background: This study aimed to compare the treatment outcomes and safety between stent placement with or without Iodine-¹²⁵ (¹²⁵I) seeds strand for patients with unresectable malignant obstructive jaundice (MOJ).

Methods: A total of 84 patients with unresectable MOJ treated in our hospital were retrospectively included and divided into the stent group (n?=?54) undergoing biliary stent placement and the stent?+?seeds group (n?=?30) receiving stent placement with ¹²⁵I seeds strand. The therapeutic outcome, postoperative complications, duration of patient survival and stent patency were compared between groups. Kaplan–Meier survival analysis was performed to compare the duration of patient survival and stent patency between groups. Cox-regression analysis was performed to investigate predictive factors for disease-free survival and overall survival.

Results: The stent?+?seeds group had significantly longer duration of patency (231.57?±?256.54 vs. 110.37?±?120.52) and overall survival (310.57?±?330.54 vs. 173.15?±?219.40) than the stent group (both p?<?.05). In addition, Kaplan–Meier survival analysis confirmed that the stent?+?seeds group had longer duration of patency (log-rank test, p?=?.001) and higher overall survival rate (log-rank test, p?=?.020) than the stent group. Furthermore, Cox-regression analysis demonstrated that treatment methods was an independent factor associated with disease-free survival (HR: 0.36, 95% CI: 0.19–0.70; p?=?.003) and overall survival (HR: 1.01, 95% CI: 1.00–1.01; p?<?.001).

Conclusion: The stent placement with ¹²⁵I seeds strand can significantly improve the primary patency rate and overall survival time in MOJ patients.     

Continuing use of antithrombotic medications for patients with bleeding gastroduodenal ulcer requiring endoscopic hemostasis: a case–control study

Objective: The aim of this study was to compare clinical characteristics and outcomes of bleeding gastroduodenal ulcer between patients taking antithrombotic medications and those not taking antithrombotic medications.

Methods: We performed a case–control study of 346 patients with endoscopically verified bleeding gastroduodenal ulcer, which included 173 cases taking antithrombotic medications throughout peri-bleeding period and 173 age- and sex-matched controls not taking antithrombotic medications.

Results: The cases showed less frequent Helicobacter pylori (H. pylori) infections (45.1% versus 60.7%, p?=?.005), more frequent duodenal location (31.8% versus 19.1%, p?=?.009), and more frequent rebleeding (13.9% versus 5.8%, p?=?.02) than the controls. Multivariate analysis revealed that duodenal location (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.37–6.65) and use of antithrombotic medications (OR 2.47, 95% CI 1.13–5.77) were independent factors for rebleeding. However, there were no differences in clinical outcomes, including final successful endoscopic hemostasis, need for surgical intervention, and mortality between cases and controls. Thromboembolic events did not occur in any cases and controls during the periendoscopic period.

Conclusions: Low prevalence of H. pylori infection, frequent duodenal location, and high rebleeding rate are characteristics of patients with bleeding gastroduodenal ulcer under antithrombotic medications. Continuation of antithrombotic medications can be accepted for bleeding gastroduodenal ulcer.     

Risk factors for surgery in patients with retention of endoscopic capsule

Objectives: Surgery is still the main means for removing retained endoscopic capsules. This study intended to evaluate risk factors for surgery in patients with capsule retention.

Materials and methods: The data of 5348 consecutive capsule endoscopy examinations were retrospectively analyzed. Cox regression analysis was used to evaluate risk factors.

Results: Seventy-seven patients (1.4%) had capsule retention. Spontaneous passage occurred in 16 patients, of which 14 were asymptomatic. Successful retrieval by double-balloon enteroscopy (DBE) was achieved in 14 patients, of which 11 did not need surgery during clinical follow-up. A total of 50 patients underwent surgery. The cumulative rates of surgery were 44.2%, 53.2%, 55.8%, 62.3% and 64.9% at 1, 3, 6, 12 and 60 months after capsule retention, respectively. Intestinal obstruction [hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.12–3.76; p?=?.020] and overt small bowel bleeding (HR 2.01, 95%CI 1.08–3.71; p?=?.027) during capsule retention were independently associated with an increased risk for surgery. Specific treatment for primary disease (HR 0.22, 95%CI 0.07–0.74, p?=?.014) and successful endoscopic retrieval (HR 0.20, 95%CI 0.06–0.66; p?=?.008) were independently associated with a decreased risk for surgery.

Conclusions: For asymptomatic patients, specific medical treatment for primary disease can be maintained until the capsule spontaneously passes or symptoms appear. For patients with slight abdominal pain, DBE can be performed. For patients with intestinal obstruction or overt small bowel bleeding, early surgical consultation should be considered.     

Gastropathy in patients with Wilson disease

Abstract

Background: Gastrointestinal symptoms are common in patients with Wilson disease (WD) and may be related to the disease itself or to adverse drug reactions (ADRs).

Aim: To investigate gastroscopy findings in patients with WD and to analyze the risk of gastropathy in the context of different manifestations and treatments of WD as well as Helicobacter pylori infection status.

Methods: This cross-sectional study included patients diagnosed or monitored for WD between 2007 and 2017. All enrolled patients were examined with gastroscopy and checked for infection with a urease test. Based on predominant manifestations, WD was classified as pre-symptomatic, hepatic (only liver symptoms) or neurological. Patients were divided into three treatment groups: untreated, treated with d-penicillamine (DPA) or zinc sulfate therapy.

Results: Of 115 patients, 58 were male and the median age was 30 years. Gastropathy was observed in 65.2% of all patients. Factors that increased the risk of gastropathy were zinc sulfate (odds ratio [OR]?=?3.01; 95% confidence interval [CI]: 1.12–8.09, p?=?.03), H. pylori infection (OR?=?2.96; 95%CI: 1.34–6.56, p?=?.01) and neurological manifestations (OR?=?2.55; 95%CI: 1.16–5.60, p?=?.02). In total, 9.6% of patients had gastric or duodenal ulcers and 29.6% had esophageal varices but no difference was seen by treatment status. In multivariate analysis, zinc sulfate remained associated with higher risk of gastropathy compared with no treatment (OR?=?4.57; 95%CI: 1.21–17.19; p?=?.03) and DPA (OR?=?6.28; 95%CI: 1.43–27.56; p?=?.01).

Conclusions: Our results show that gastropathy in WD may be influenced by the treatment used.

• Keypoints

• In a retrospective study of 115 patients with Wilson’s disease, gastric injury was frequent.

• Patients receiving zinc sulfate had increased gastropathy risk compared with those receiving no treatment or d-penicillamine.

     

Children with untreated coeliac disease have sub-clinical cardiac dysfunction: a longitudinal observational analysis

Introduction: We assessed cardiac function (CF) in celiac disease (CD) patients and the effect of gluten-free diet (GFD) on CF.

Methods: Prospective evaluation of CF using conventional and tissue doppler echocardiography in 50 CD patients (age 4.2?±?1.1 years) at diagnosis and after a year of GFD (group 1), 100 CD children (group 2; 47 compliant and 53 non-compliant) in follow-up and 25 healthy controls.

Results: Untreated CD (n?=?50) children had larger left ventricle end diastolic dimension (35.33?±?0.87 vs. 32.90?±?0.91 mm; p?=?.04), reduced (<55%) left ventricular ejection fraction (20% vs. 0%; p?=?.01) and a higher (>0.6) myocardial performance index (MPI, 66% vs. 0%; p ≤ .01) as compared to controls. Re-evaluation after one year with good dietary compliance showed changes in isovolumic relaxation time (72.5?±?4.2 vs. 50.62?±?2.69; p?=?.0001) and deceleration time (121.05?±?10.1 vs. 99.87?±?8.5; p?=?.02), reflecting improved cardiac diastolic function. GFD compliant patients had lower MPI than non-compliant (0.60?±?.03 vs. 0.66?±?.08; p?=?.04), reflecting improvement in load-independent echocardiographic parameters.

Conclusions: Subclinical cardiac dysfunction is common in CD children at diagnosis. Improvement

in echocardiographic parameters occurs with GFD and non-compliant children continue to have

persistent cardiac dysfunction.