Eradicating Helicobacter pylori via 13C-urea breath screening to prevent gastric cancer in indigenous communities: a population-based study and development of a family index-case method.

OBJECTIVE: Screening and eradication of Helicobacter pylori help reduce disparities in the incidence of gastric cancer. We aimed to evaluate its acceptability and feasibility in the indigenous communities and develop a family index-case method to roll out this programme. DESIGN: We enrolled residents aged 20-60 years from Taiwanese indigenous communities to receive a course of test, treat, retest and re-treat initial treatment failures with the 13C-urea breath tests and four-drug antibiotic treatments. We also invited the family members of a participant (constituting an index case) to join the programme and evaluated whether the infection rate would be higher in the positive index cases. RESULTS: Between 24 September 2018 and 31 December 2021, 15 057 participants (8852 indigenous and 6205 non-indigenous) were enrolled, with a participation rate of 80.0% (15 057 of 18 821 invitees). The positivity rate was 44.1% (95% CI 43.3% to 44.9%). In the proof-of-concept study with 72 indigenous families (258 participants), family members of a positive index case had 1.98 times (95% CI 1.03 to 3.80) higher prevalence of H. pylori than those of a negative index case. The results were replicated in the mass screening setting (1.95 times, 95% CI 1.61 to 2.36) when 1115 indigenous and 555 non-indigenous families were included (4157 participants). Of the 6643 testing positive, 5493 (82.6%) received treatment. According to intention-to-treat and per-protocol analyses, the eradication rates were 91.7% (89.1% to 94.3%) and 92.1% (89.2% to 95.0%), respectively, after one to two courses of treatment. The rate of adverse effects leading to treatment discontinuation was low at 1.2% (0.9% to 1.5%). CONCLUSION: A high participation rate, a high eradication rate of H. pylori and an efficient rollout method indicate that a primary prevention strategy is acceptable and feasible in indigenous communities. TRIAL REGISTRATION NUMBER: NCT03900910.

Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands.

OBJECTIVE: Although mass eradication of Helicobacter pylori has been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear. DESIGN: Mass eradication of H. pylori infection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalent H. pylori infection. Test positives for the 13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively. RESULTS: After six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates of H. pylori fell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, p<0.001) and 25% (95% CI -14% to 51%, p=0.18), respectively. No significant changes were noted in the incidence rates of other digestive tract cancers or the antibiotic resistance rate of H. pylori. CONCLUSION: Population-based eradication of H. pylori has significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period. TRIAL REGISTRATION NUMBER: NCT00155389.

Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese Nationwide Colorectal Cancer Screening Program.

OBJECTIVES: Interval colorectal cancer (CRC) after colonoscopy may affect effectiveness and cost-effectiveness of screening programmes. We aimed to investigate whether and how faecal haemoglobin concentration (FHbC) of faecal immunochemical testing (FIT) affected the risk prediction of interval cancer (IC) caused by inadequate colonoscopy quality in a FIT-based population screening programme. DESIGN: From 2004 to 2009, 29 969 subjects underwent complete colonoscopy after positive FIT in the Taiwanese Nationwide CRC Screening Program. The IC rate was traced until the end of 2012. The incidence of IC was calculated in relation to patient characteristics, endoscopy-related factors (such adenoma detection rate (ADR)) and FHbC. Poisson regression analysis was performed to assess the potential risk factors for colonoscopy IC. RESULTS: One hundred and sixty-two ICs developed after an index colonoscopy and the estimated incidence was 1.14 per 1000 person-years of observation for the entire cohort. Increased risk of IC was most remarkable in the uptake of colonoscopy in settings with ADR lower than 15% (adjusted relative risk (aRR)=3.09, 95% CI 1.55 to 6.18) and then higher FHbC (µg Hb/g faeces) (100-149: aRR=2.55, 95% CI 1.52 to 4.29, ≥150: aRR=2.74, 95% CI 1.84 to 4.09) with adjustment for older age and colorectal neoplasm detected at baseline colonoscopy. Similar findings were observed for subjects with negative index colonoscopy. CONCLUSIONS: Colonoscopy ICs arising from FIT-based population screening programmes were mainly influenced by inadequate colonoscopy quality and independently predicted by FHbC that is associated with a priori chance of advanced neoplasm. This finding is helpful for future modification of screening logistics based on FHbC.

Evolution of in vitro cow's milk protein-specific inflammatory and regulatory cytokine responses in preterm infants with necrotising enterocolitis.

BACKGROUND: We have previously reported evidence of in vitro sensitisation to cow's milk protein in peripheral blood mononuclear cells (PBMCs) in preterm infants with necrotising enterocolitis (NEC). In the present study, we document the changes in the PBMC responses to stimulation with mitogen (phytohaemagglutinin) and cow's milk proteins ß-lactoglobulin (ß-lg) and casein over time: from the acute presentation of NEC, to initial recovery (reinitiation of enteral feeds), to full recovery (full feeding). METHODS: Of the 14 preterm infants recruited with acute NEC, 12 were followed until fully enterally fed (2 died during the acute phase). Cytokine secretion (interferon-γ [IFN-γ], interleukin 4, [IL-4], IL-10, and transforming growth factor-ß1 [TGF-ß1]) by PBMCs in response to stimulation by phytohaemagglutinin, ß-lg, and casein was measured by enzyme-linked immunospot in the acute phase and subsequently at recovery and full recovery. RESULTS: The high levels of cytokine secretion (IFN-γ, IL-4, IL-10, and TGF-ß1) observed in response to ß-lg and casein in the acute phase increased by a further 50% to 100% at recovery (P < 0.005). At full recovery (full feeding), however, IFN-γ, IL-4, and IL-10 secretion response had returned to, or below, acute-phase levels, whereas the augmented TGF-ß1 response was maintained (P = 0.005 vs acute level). This response pattern was similar for casein, and did not appear to be influenced by the nature of the feed used following NEC (breast milk/formula/hydrolysed formula). CONCLUSIONS: The evolution of the cytokine response profile in parallel with the clinical recovery from NEC is consistent with a putative role for TGF-ß1 in regulation of inflammation, and possibly also oral tolerance.

Iatrogenic Neonatal Esophageal Perforation: A European Multicentre Review on Management and Outcomes.

BACKGROUND: The aim of this multicenter retrospective study and literature review was to review management and outcomes of neonatal esophageal perforation (NEP). METHODS: Protocol data were collected from four European Centers on gestational age, factors surrounding feeding tube insertion, management and outcomes. RESULTS: The 5-year study period (2014-2018) identified eight neonates with median gestational age of 26 + 4 weeks (23 + 4-39) and median birth weight 636 g (511-3500). All patients had NEP from enterogastric tube insertions, with the perforation occurring at median 1st day of life (range 0-25). Seven/eight patients were ventilated (two/seven-high frequency oscillation). NEP became apparent on first tube placement (n = 1), first change (n = 5), and after multiple changes (n = 2). Site of perforation was known in six (distal n = 3, proximal n = 2 and middle n = 1). Diagnosis was established by respiratory distress (n = 4), respiratory distress and sepsis (n = 2) and post-insertion chest X-ray (n = 2). Management in all patients included antibiotics and parenteral nutrition with two/eight receiving steroids and ranitidine, one/eight steroids only and one/eight ranitidine only. One neonate had a gastrostomy inserted, while in another an enterogastric tube was orally successfully re-inserted. Two neonates developed pleural effusion and/or mediastinal abscess requiring chest tube. Three neonates had significant morbidities (related to prematurity) and there was one death 10 days post-perforation (related to prematurity complications). CONCLUSIONS: NEP during NGT insertion is rare even in premature infants after evaluating data from four tertiary centers and reviewing the literature. In this small cohort, conservative management seems to be safe. A larger sample size will be necessary to answer questions on efficacy of antibiotics, antacids and NGT re-insertion time frame in NEP.

In vitro cow's milk protein-specific inflammatory and regulatory cytokine responses in preterm infants with necrotizing enterocolitis and sepsis.

Enteral feeding with cow's milk formula is associated with neonatal necrotizing enterocolitis (NEC) and sepsis. Dietary antigen sensitization may play a role in promoting and/or sustaining inflammation in both conditions. Aiming at investigating cow's milk protein (CMP)-specific cytokine responses in preterm infants with NEC and sepsis, 14 babies with NEC, 14 matched healthy controls, and 10 septic controls were recruited. Unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) secreting IFN-γ, IL-4, IL-10, and TGF-ß1 were counted by the single-cell enzyme-linked immunospot (ELISPOT) assay. During the acute phase of NEC, patients showed a general pattern of a high level of cytokine secretion both when unstimulated and stimulated by mitogen [phytohaemagglutinin (PHA)] and CMPs: beta-lactoglobulin (ß-lg) and casein. These responses were more marked to ß-lg for IFN-γ, IL-4, and IL-10 than TGF-ß1. Cytokine responses in sepsis were lower than in NEC (lowest in healthy controls, with a minimal TGF-ß1 response). At term, lower frequencies of cytokine-secreting cells were elicited than during the acute phase, except for TGF-ß1 secreting cells, which increased at term (in response to PHA and CMPs) particularly following not only NEC but also sepsis.

Thoracoscopic Repair of Congenital Diaphragmatic Hernia in Preterm Neonate at 1 Kilogram.

We report the first successful primary thoracoscopic repair of congenital diaphragmatic hernia (CDH) in a preterm infant born at 28 weeks of gestation weighing 1,043 g. Left-sided CDH was incidentally diagnosed on postnatal chest X-ray on day 1. The neonate subsequently underwent thoracoscopic repair with primary closure of the defect on day 8 weighing 1,150 g. Intraoperative arterial blood gas monitoring including end tidal carbon-dioxide remained within normal range throughout. Postoperative recovery was uneventful. One year neurodevelopmental outcome was normal for age with no CDH recurrence.