Efficacy of quadruple therapy with clarithromycin based on faecal molecular antimicrobial susceptibility tests as first-line treatment for Helicobacter pylori infection: a protocol of a single-centre, single-blind, randomised clinical trial in China.

INTRODUCTION: Helicobacter pylori is the most well-known risk factor for gastric cancer. Antibiotic resistance is the main reason for the failure of H. pylori eradication, and understanding the antibiotic resistance before treatment may be the main determinant of successful eradication of H. pylori. This study aims to evaluate the efficacy and safety of quadruple therapy based on faecal molecular antimicrobial susceptibility tests for the first-line eradication of H. pylori infection. METHODS AND ANALYSIS: This is a single-centre, single-blind, randomised controlled trial, enrolling 855 patients with H. pylori infection. Patients are randomised to three groups for a 14-day treatment: group A: amoxicillin- and clarithromycin-based bismuth-containing quadruple therapy (BQT) (rabeprazole 10 mg, amoxicillin 1 g, clarithromycin 500 mg and colloidal bismuth 200 mg two times per day); group B: clarithromycin medication history-based BQT (rabeprazole 10 mg, amoxicillin 1 g, furazolidone 100 mg (with clarithromycin medication history)/clarithromycin 500 mg (without clarithromycin medication history) and colloidal bismuth 200 mg two times per day); group C: antimicrobial susceptibility test-based BQT (rabeprazole 10 mg, amoxicillin 1 g, clarithromycin 500 mg (clarithromycin-sensitive)/furazolidone 100 mg (clarithromycin resistant) and colloidal bismuth 200 mg two times per day). The primary end point is the eradication rate. The secondary end points are the incidence of adverse events and compliance. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Second Affiliated Hospital, School of Medicine, Zhejiang University (Number 20230103). The results will be published in the appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05718609.

Short-term outcomes and intermediate-term follow-up of Helicobacter pylori infection treatment for naïve patients: a retrospective observational study.

OBJECTIVES: To explore the outcomes of Helicobacter pylori infection treatments for naïve patients in the real-world settings. DESIGN: A retrospective observational study. SETTING: Single tertiary level academic hospital in China. PARTICIPANTS: We identified patients initially receiving quadruple therapy for H. pylori infection from 2017 to 2020 in whom eradication was confirmed (n=23 470). PRIMARY OUTCOME: Efficacy of different initial H. pylori infection treatments. SECONDARY OUTCOME: Results of urea breath test (UBT) after H. pylori eradication. RESULTS: Among 23 470 patients who received initial H. pylori treatment, 21 285 (90.7%) were treated with amoxicillin-based regimens. The median age of the patients decreased from 2017 to 2020 (45.0 vs 39.0, p<0.0001). The main treatments were therapies containing amoxicillin and furazolidone, which had an eradication rate of 87.6% (14 707/16 784); those containing amoxicillin and clarithromycin had an eradication rate of 85.5% (3577/4182). The date of treatment, age, antibiotic regimen and duration of treatment showed correlations with the failure of H. pylori eradication in a multivariable logistic regression analysis. Finally, positive UBT results after eradication clustered around the cut-off value, in both the 13C-UBT and 14C-UBT. CONCLUSIONS: The major H. pylori infection treatments for naïve patients were those containing amoxicillin and furazolidone, which offered the highest eradication rate. The date of treatment, age, antibiotic regimen and duration of treatment were risk factors for the failure of H. pylori eradication. Additionally, positive UBT results after eradication clustered around the cut-off value.

High-Fat Diet Enhances the Liver Metastasis Potential of Colorectal Cancer through Microbiota Dysbiosis.

Obesity, metabolic changes, and intestinal microbiota disruption significantly affect tumorigenesis and metastasis in colorectal cancer (CRC). However, the relationships among these factors remain poorly understood. In this study, we found that a high-fat diet (HFD) promoted gut barrier dysfunction and inflammation in the colorectum and liver. We further investigated gut microbiota changes through 16S rRNA sequencing of faecal samples from HFD-fed rats and CRC hepatic metastasis patients and found an abundance of Desulfovibrio (DSV). DSV could also induce barrier dysfunction in the colorectum and inflammation in the colorectum and liver, suggesting that it contributes to the formation of a microenvironment conducive to CRC tumorigenesis and metastasis. These findings highlight that HFD-induced microbiota dysbiosis, especially DSV abundance, could promote CRC initiation and metastasis.

The roles of connective tissue growth factor in the development of anastomotic esophageal strictures.

INTRODUCTION: The aim of this study was to investigate the roles of connective tissue growth factor (CTGF) in the development of anastomotic strictures after surgical repair of the esophagus. MATERIAL AND METHODS: Tissues collected from the patients were divided into three groups based on the results of endoscopy and clinical grading. Patients without dysphagia after esophagectomy were used as the control population. The protein levels of CTGF, TGF-ß1, Smad2, and Smad4 were determined by immunohistochemistry (IHC) and western blot analyses, while the mRNA levels of the two growth factors were evaluated by real-time polymerase chain reaction. RESULTS: Compared with the control group, significantly increased (p < 0.01) levels of CTGF and TGF-ß1 protein were observed in the anastomotic stenosis (AS) group, and levels of the two proteins detected by the IHC and western blot analyses were also significantly increased with the increasing severity of stenosis (p < 0.05). The mRNA levels of CTGF and TGF-ß1 in the tissues collected from the patients with stenosis were significantly up-regulated (p < 0.05) as compared with those from the control group. In addition, the levels of Smad2 and Smad4 protein were also significantly increased (p < 0.05) with the increasing severity of stenosis, and the protein levels were positively correlated with the levels of CTGF (r = 0.59, p < 0.05) and TGF-ß1 (r = 0.63, p < 0.05). CONCLUSIONS: Inhibition of CTGF protein or mRNA expression may be a distinctive and effective therapy for the treatment of postoperative anastomotic strictures.

Diameter of involved nerves is a valuable prognostic factor for gastric cancer.

The prognostic role of perineural invasion (PNI) in gastric cancer remains unclear. We hypothesized that the diameter of the tumor-involved nerves might be a useful indicator for prognosis. By labeling nerves and cancer cells in 204 cases of gastric cancer with single or double immunochemistry, we found that 146 cases were PNI positive and that 58 were PNI negative. For each case with PNI, the maximum diameter of the involved nerve was measured microscopically. Then, we correlated this parameter with the patients' 5-year overall survival, and receiver operating curves were used to determine the cutoff value. We found that the optimal cutoff value for predicting 5-year survival was 65 µm (sensitivity 76.9%, specificity 70.0%). Next, all 204 patients were classified into two groups as follows: Group A, PNI-positive cases in which the largest involved nerves were ≥65 µm in diameter (110 cases); Group B, PNI-positive cases in which the largest involved nerves were P˂65 µm and all PNI-negative cases (94 cases). Compared with Group A, Group B had a better 5-year survival (74.5% vs 27.3%) and a better 5-year disease-free survival (63.8% vs 23.6%). Multivariate analysis suggested that a ≥65 µm maximum diameter of the involved nerves was an independent risk factor for both recurrence (P˂0.001) and gastric cancer-related death (P˂0.001) within 5 years. However, if all patients were classified simply based on whether PNI existed (regardless of the nerve size), this did not provide more information than traditional clinicopathological variables. In conclusion, the presence of cancer-involved nerves with a diameter ≥65 µm was a valuable prognostic factor for gastric cancer.

Reevaluating significance of perineural invasion in gastric cancer based on double immunohistochemical staining.

CONTEXT: In gastric cancer, the significance of perineural invasion remains controversial. Detecting perineural invasion with hematoxylin-eosin staining often leads to misdiagnosis. Labeling nerves by immunohistochemistry greatly assists perineural invasion detection, but it might also be misdiagnosed, because scattered cancer cells are difficult to recognize. OBJECTIVE: To reevaluate the significance of perineural invasion in gastric cancer by double immunohistochemical staining that labels both nerves and cancer cells, and to examine agreements on perineural invasion detection between double immunohistochemical staining and single immunochemical staining (to label nerves) or hematoxylin-eosin staining. DESIGN: We evaluated perineural invasion in 160 cases of gastric cancer with double immunohistochemical staining, single immunochemical staining, and hematoxylin-eosin staining, respectively; then we investigated the prognostic significance of perineural invasion. RESULTS: Perineural invasion was detected in 65.0% (104 of 160), 38.1% (61 of 160), and 56.9% (91 of 160) of cases with double immunohistochemical staining, hematoxylin-eosin staining, and single immunohistochemical staining, respectively. Agreement was low between double staining and hematoxylin-eosin staining (κ = .34), and most false reports occurred in diffuse gastric cancer. Agreement between single immunochemical staining and double staining was good (κ = .67), but it declined in diffuse gastric cancer (κ = .28). Perineural invasion was closely associated with other clinicopathologic variables. Although perineural invasion-positive patients had a worse outcome than perineural invasion-negative patients, it was not an independent prognostic factor (P = .11; hazard ratio, 0.637; 95% confidence interval, 0.366-1.110). CONCLUSIONS: Double immunohistochemical staining could improve accuracy of perineural invasion detection in gastric cancer, particularly in the diffuse type. Moreover, perineural invasion predicts a poor outcome in gastric cancer, but it cannot provide more information than traditional clinicopathologic variables.