Enders Kwok Wai Ng

Background Atrophic gastritis (AG) and intestinal metaplasia (IM) were proven precancerous status in the development of gastric cancer (GC). Traditionally, AG and IM were assessed by histology of biopsy specimens. Recently, endoscopic mapping of AG and IM emerged as an alternative method of risk stratification that allows real-time assessment. It is unclear which method most accurately predicts the risk of GC. We, therefore, conducted this prospective case-control study to compare the accuracy of endoscopic and histological assessment tools of AG and IM in the prediction of GC development. Methods Patients undergoing elective diagnostic gastroscopy would be recruited into gastric cancer group and control group. The endoscopy would be performed by endoscopists with sufficient training in recognition of endoscopic AG and IM. Patterns and severity of AG and IM would be compared according to histological and endoscopic classifications. Endoscopic scoring of AG would be assessed according to the Kyoto Classification of Gastritis and Kimura-Takemoto Classification. Endoscopic staging of IM would be based on the EGGIM classification. The presence of ‘regular appearance of collecting venules (RAC)’ would be documented as well. Histological assessments of AG and IM were performed following the OLGA and OLGIM systems respectively through random biopsies taken according to Sydney protocol. Results From December 2019 to May 2022, 98 patients were recruited: 46 in GC and 52 in control group. OLGIM, EGGIM scores and absent of RAC were statistically significant associated with the presence of gastric cancer. The odds ratios for predicting presence of GC were 24.677 [95% CI 3.105–196.127 (pConclusions The odds ratios in correlation with GC were highest with OLGIM III/IV and EGGIM 5–10. The odds ratio of invisibility of RAC was also statistically significant. These should be considered the best risk stratification tools for predicting GC.

Objectives: The COVID‐19 pandemic has raised concerns on whether colonoscopies (CS) carry a transmission risk. The aim was to determine whether CS are aerosol‐generating procedures.Methods: This was a prospective observational trial including all patients undergoing CS at the Prince of Wales Hospital from 1 June to 31 July 2020. Three particle counters were placed 10 cm from each patient’s anus and near the mouth of endoscopists and nurses. The particle counter recorded the number of particles of size 0.3, 0.5, 0.7, 1, 5, and 10 μm. Patient demographics, seniority of endoscopists, use of CO₂ and water immersion technique, and air particle count (particles/cubic foot, dCF) were recorded. Multilevel modeling was used to test all the hypotheses with a post‐hoc analysis.Results: A total of 117 patients were recruited. During CS, the level of 5 μm and 10 μm were significantly higher than the baseline period (P = 0.002). Procedures performed by trainees had a higher level of aerosols when compared to specialists (0.3 μm, P < 0.001; 0.5 μm and 0.7 μm, P < 0.001). The use of CO₂ and water immersion techniques had significantly lower aerosols generated when compared to air (CO₂: 0.3, 0.5, and 0.7 μm: P < 0.001; water immersion: 0.3 μm: P = 0.048; 0.7 μm: P = 0.03). There were no significant increases in any particle sizes during the procedure at the endoscopists' and nurses' mouth. However, 8/117 (6.83%) particle count tracings showed a simultaneous surge of all particle sizes at the patient's anus and endoscopists' and nurses' level during rectal extubation.Conclusion: Colonoscopy generates droplet nuclei especially during rectal extubation. The use of CO₂ and water immersion techniques may mitigate these risks.

Background: Gastric cancer (GC) is one of the most common cancer worldwide. We analyzed the expression of m⁶A regulatory genes in GC cohorts and revealed that YTHDF1 was uniquely upregulated in GC as compared with adjacent normal tissues. In this study, we analyzed the role of YTHDF1 in GC cells and modulation of the tumor immune microenvironment. Methods: Three GC cohorts (cohort 1, n=101; cohort 2, n=278, and the Cancer Genome Atlas cohort, n=375) were analyzed for YTHDF1 expression. Function of YTHDF1 in GC was determined in GC cell lines. Role of YTHDF1 in antitumor immunity was investigated in allograft models. Results: YTHDF1 is upregulated in GC compared with adjacent normal tissues, and high YTHDF1 expression was correlated with poor survival of patients with GC at mRNA (p=0.016) and protein levels (p=0.039). Loss of YTHDF1 in human (AGS, BGC823, MKN74) or mouse (YTN16) GC cell lines inhibited cell growth and colony formation in vitro. Strikingly, syngeneic YTN16 tumors with loss of YTHDF1 underwent complete remission in immunocompetent mice, while a lesser effect was found in immunodeficient mice. Consistently, YTHDF1 loss in GC tumors led to recruitment of mature dendritic cells (DCs) with increased MHCII expression and interleukin-12 (IL-12) secretion, which in turn, promoted CD4⁺ and CD8⁺ T cells infiltration with increased interferon-γ (IFN-γ) secretion. Loss of YTHDF1 mediated the overexpression of IFN-γ receptor 1 and JAK/STAT1 signaling pathway in tumor cells, which might contribute to restored sensitivity to antitumor immunity. In addition, pre-emptive exposure of YTN16 tumors with YTHDF1 loss triggered a potent antitumor immune response on rechallenge with wild-type YTN16 cells, implying that YTHDF1 loss induced a lasting systemic antitumor immunity. Conclusions: YTHDF1 is overexpressed in GC and promotes GC by inducing cell proliferation and repression of DCs-mediated antitumor immune response. YTHDF1 is a promising therapeutic target for GC treatment.

Dear Editor,

Background: Bariatric surgery can be effective in weight reduction and diabetes remission in some patients, but is expensive. The costs of bariatric surgery in patients with obesity and type 2 diabetes mellitus (T2DM) were explored here.Methods: Population-based retrospectively gathered data on patients with obesity and T2DM from the Hong Kong Hospital Authority (2006–2017) were evaluated. Direct medical costs from baseline up to 60 months were calculated based on the frequency of healthcare service utilization and dispensing of diabetes medication. Charlson Co-morbidity Index (CCI) scores and co-morbidity rates were measured to compare changes in co-morbidities between surgically treated and control groups over 5 years. One-to-five propensity score matching was applied.Results: Overall, 401 eligible surgical patients were matched with 1894 non-surgical patients. Direct medical costs were much higher for surgical than non-surgical patients in the index year (€36 752 and €5788 respectively; P < 0·001) mainly owing to the bariatric procedure. The 5-year cumulative costs incurred by surgical patients were also higher (€54 135 versus €28 603; P < 0·001). Although patients who had bariatric surgery had more visits to outpatient and allied health professionals than those who did not across the 5-year period, surgical patients had shorter length of stay in hospitals than non-surgical patients in year 2-5. Surgical patients had significantly better CCI scores than controls after the baseline measurement (mean 3·82 versus 4·38 at 5 years; P = 0·016). Costs of glucose-lowering medications were similar between two groups, except that surgical patients had significantly lower costs of glucose-lowering medications in year 2 (€973 versus €1395; P = 0.012).Conclusion: Bariatric surgery in obese patients with T2DM is expensive, but leads to an improved co-morbidity profile, and reduced length of hospitalization.

Peritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.