H. pylori is related to NAFLD but only in female: A Cross-sectional Study.

Background: Recently, an increasing number of studies have focused on the extragastrointestinal effects of Helicobacter pylori (H. pylori), including metabolic syndrome, fatty liver, and rheumatic and skin diseases. Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease worldwide that conveys a heavy economic burden on patients and society. The aim of this study was to investigate the relationship between H. pylori and NAFLD and to identify potential influencing factors. Methods: We conducted a cross-sectional study of individuals who had undergone regular physical examinations at the Beijing Shijitan Hospital Health Examination Center from July to October 2018. We evaluated the associations between NAFLD and NAFLD with H. pylori infection and related serum markers using multiple linear regression and logistic regression. Results: There were significant relationships between H. pylori infection status and NAFLD in females (P=0.034) but not in males (P=0.795) according to Fisher's exact test. The association persisted after further adjustment for metabolic variables, gastrin factors, and liver enzymes. Waist-to-Hip Ratio, Body Mass Index, triglycerides, High-density lipoprotein cholesterol, glucose, uric acid, alkaline phosphatase, and Alanine aminotransferase are related to NAFLD after adjusting for age or interaction between biochemical indexes. Conclusion: H. pylori infection is related to NAFLD in female patients. The relationship between H. pylori and NAFLD may be mediated by markers of lipid metabolism and glycometabolism.

H. Pylori is related to osteoporosis but only in premenopausal female: a cross-sectional study.

BACKGROUND: Recently, an increasing number of studies have focused on the extra-gastrointestinal effects of Helicobacter pylori (H. pylori), including metabolic syndrome, fatty liver, and rheumatic and skin diseases. Osteoporosis is an asymptomatic disease that can eventually lead to fractures and has a significant impact on the quality of life of elderly individuals. Sex is an influential factor that plays a crucial role in the development of osteoporosis. The aim of this study was to investigate the relationship between H. pylori infection and osteoporosis and to identify potential influencing factors. METHODS: We conducted a cross-sectional study of individuals older than 50 years old, who had undergone regular physical examinations at the Beijing Shijitan Hospital Health Examination Center from July to October 2018. We evaluated the associations of osteopenia and osteoporosis with H. pylori infection and related serum markers by using multiple linear regression and logistic regression. Then, we analysed the correlation between sex and potential serum biomarkers. RESULTS: There were significant relationships between H. pylori infection status and bone density in premenopausal females but not in males (P = 0.381) according to Fisher's exact test. In females, H. pylori positivity (OR = 0.132, P = 0.023), Body Mass Index (BMI) (OR = 28.163, P = 0.021), and homocysteine (HCY) (OR = 17.218, P = 0.045) were associated with osteoporosis. Calcium had a trend but no statistically significant (OR = 0.060, P = 0.076) relationship with osteoporosis. Furthermore, the waist-to-hip ratio (OR = 5.783, P = 0.029), BMI (OR = 0.152, P = 0.014) and triglyceride levels (OR = 0.201, P = 0.036) were significantly different by sex, after adjusting for age as a confounder. CONCLUSION: H. pylori positivity, BMI and HCY are associated with osteoporosis in premenopausal females. Chronic inflammation may be involved in the relationship between H. pylori and osteoporosis.

Prognostic and predictive value of angiogenesis-associated serum proteins for immunotherapy in esophageal cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved patient survival in multiple cancers. However, therapy response in esophageal cancer is limited to subgroups of patients and clinically useful predictive biomarkers are lacking. METHODS: We collected a series of plasma samples from 91 patients with esophageal cancer before and after ICI treatment. The Olink Immuno-Oncology panel (92 proteins) with proximity extension assays was used to detect the dynamic changes in plasma and potential biomarkers associated with treatment outcomes. We screened all survival-related proteins and established a risk score model to better predict the prognosis and treatment response in patients with esophageal cancer immunotherapy. RESULTS: We found that 47 out of 92 quantified proteins had significant changes in plasma levels during ICI treatment (p<0.050), and these changed proteins were involved in immune-related reactions, such as intercellular adhesion and T-cell activation. Notably, the baseline levels of three angiogenesis-related proteins (IL-8, TIE2, and HGF) were significantly associated with the survival outcomes of patients treated with ICIs (p<0.050). According to these prognostic proteins, we established an angiogenesis-related risk score, which could be a superior biomarker for ICI response prediction. In addition, antiangiogenic therapy combined with ICIs significantly improved overall survival compared with ICI monotherapy (p=0.044). CONCLUSIONS: An angiogenesis-related risk score based on three proteins (IL-8, TIE2, and HGF) could predict ICI response and prognosis in patients with esophageal cancer, which warrants verification in the future. Our study highlights the potential application of combining ICIs and antiangiogenic therapy and supports Olink plasma protein sequencing as a liquid biopsy method for biomarker exploration.

Clinical efficacy and identification of factors confer resistance to afatinib (tyrosine kinase inhibitor) in EGFR-overexpressing esophageal squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal squamous cell carcinoma (ESCC) patients, but anti-EGFR treatments offer limited survival benefits. Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC. This proof-of-concept, phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients (n = 41) with EGFR overexpression (NCT03940976). The study met its primary endpoint, with a confirmed objective response rate (ORR) of 39% in 38 efficacy-evaluable patients and a median overall survival of 7.8 months, with a manageable toxicity profile. Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2 (NTRK2) was negatively associated with afatinib sensitivity and might serve as a predictive biomarker, irrespective of EGFR expression. Notably, knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment. Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

HAIC as a potential therapy for esophageal cancer patients with liver metastasis: a retrospective cohort study.

Methods: This was a single-arm historical cohort study of ESCC patients with synchronous or heterochronous LM between December 2014 and July 2021 at the Department of Gastrointestinal Oncology. The patients were treated with HAIC for LM, and regular image assessments were performed according to the judgment of the interventional physician. Liver progression-free survival (PFS), liver objective response rate (ORR), liver disease control rate (DCR), overall survival (OS), adverse events (AEs), treatment information, and basic characteristics were observed retrospectively. Results: Overall, a total of 33 patients were enrolled in this study. All included patients received catheterized HAIC therapy, with a median of three (ranging from 2 to 6) sessions. The treatment response of liver metastatic lesions included partial response (PR) in 16 (48.5%) patients, stable disease (SD) in 15 (45.5%) patients, and progressive disease (PD) in two (6.1%) patients, for an ORR of 48.5% and a DCR of 93.9%. The median liver PFS was 4.8 months (95% confidence interval (CI): 3.0-6.6 months), and the median OS was 6.4 months (95% CI: 6.1-6.6 months). Patients who achieved PR at the liver metastasis site after HAIC were more likely to have a longer OS than those who achieved SD or PD. Grade 3 AEs occurred in 12 patients. The most common grade 3 AE was nausea, occurring in 10 (30.0%) patients, followed by abdominal pain in three (9.1%) patients. Only one patient showed grade 3 elevation of alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and one patient suffered from grade 3 embolism syndrome AEs. Grade 4 adverse events, followed by abdominal pain, occurred in one patient. Conclusion: Hepatic arterial infusion chemotherapy might be an option as a regional therapy for ESCC patients with LM, as it is acceptable and tolerable.

Using genotype to assist clinical surveillance: a retrospective study of Chinese familial adenomatous polyposis patients.

Without treatment, familial adenomatous polyposis (FAP) patients will inevitably develop colorectal cancer (CRC) during lifetime. Yet, surgical trauma is a high risk of desmoid tumor (DT), one of the main causes of death in FAP patients. So far, the timing for colectomy is primarily based on the clinician's experience and the patient's preference; most patients undergo surgery at mid-20's. In this study, we analyzed the germline mutation distribution in 35 FAP patients from different families, 16 of them diagnosed with DTs. We also investigated the association between the molecular alterations and the clinicopathological features. Capture-based targeted sequencing using a panel of 520 genes was performed on tumor tissue and paired normal mucosa or white blood cells from 18 FAP probands who were initially diagnosed with CRC. Of all 35 FAP patients, 30 (85.7%) of them harbored germline APC mutations scattered from codon 161 to 1578. The mutations in the 16 DT patients scattered from codon 457 to 1578. All three patients with the mutation at the 3' of 1444 codon were diagnosed with DT. The percentage of high-risk DT (stage III or IV) harboring mutations at the 5' of 1062 or 1062-1578 was 14.3% and 77.8%, respectively, and all three patients with 3' of 1399 codon mutation had high risk. In addition, by using public database, we compared 140 FAP patients with DT to all 1880 FAP patients on the Leiden Open Variation Database and found that the odd ratio of DT in codon 159 to 495 was 0.34, while in codon 1310 to 2011 was 2.36. Compared to sporadic CRCs, the somatic spectrum of FAP CRCs was similar to the early onset CRCs, with higher TP53 (94.1%) and lower somatic APC mutations (65.7%), but the KRAS mutation rate was the highest (58.5%). One of the 18 FAP CRCs was identified as microsatellite instability-high (MSI-H), with tumor mutation burden (TMB) of 115.65 mut/Mb. Given that no TP53 mutations were detected in the low- and high-grade adenomas, ctDNA TP53 sequencing might be used for the close monitoring before FAP colectomy. In conclusion, except mutations at the 5' end of APC (5' to 495), all FAP patients need to consider the risk of DT after colectomy. The chance of life-threating DTs was higher in patients with 3' 1062 codon mutation and peaked in patients with 3' 1399 codon mutation. Scheduled monitoring of TP53 ctDNA is proposed to be a novel tool for optimizing the operation time.

Correlation between narrow-band imaging endoscopy results and hPTTG expression indicated by angiogenensis and its distribution in the initial phase of colorectal adenoma-carcinoma sequence.

The aim of the present study was to investigate the correlation between vascular characteristics under narrow band imaging endoscopy (NBI) and the expression of angiogenic factors of colorectal carcinoma and adenoma, and to evaluate the feasibility and validity of NBI in vivo visualizing angiogenesis. Patients with colorectal polyps, which were pathologically confirmed as early carcinoma, adenoma and hyperplastic polyp, were recruited and examined by NBI. The endoscopic vascular pattern was classified by Showa classification. Immunohistochemical staining was performed by cluster of differentiation (CD34), microvessel density (MVD) and Human Pituitary Tumor-Transforming Gene (hPTTG). The histologic results were compared with the vascular pattern under NBI. Overall, 83 colorectal lesions including 9 intramucosal colorectal carcinomas, 44 adenomas (18 tubular adenomas, 26 tubulovillous adenomas) and 30 hyperplastic polyps were recruited and examined by NBI. A higher proportion (88.6%, 47/53) of intramucosal carcinomas and adenomas were more likely to have the dense pattern (DP) or network pattern (NP), while that of hyperplastic polyps was only 30.0% (9/30). There was an obvious increase in the MVD-CD34 counting from hyperplastic polyps, to adenoma to carcinoma, and a significant difference among the three groups as well. Also, a clear difference can be seen in the expression of hPTTG, which was expressed more in carcinoma than in adenoma and HP group (P < 0.05). Conclusion: NBI might be a useful tool as in vivo visualizing angiogenesis. hPTTG expression in colorectal adenoma and carcinoma is related to angiogenesis.