[Posted 11/Jul/2024]

AUDIENCE: Gastroenterology, Oncology, Internal Medicine

KEY FINDINGS: While identifying GIST or leiomyoma, the performance of CNN model was robust, which is highlighting its promising role in supporting less-experienced endoscopists and reducing interobserver agreement.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) and leiomyomas are the most common submucosal tumors of the upper digestive tract, and the diagnosis of the tumors is essential for their treatment and prognosis. However, the ability of endoscopic ultrasonography (EUS) which could correctly identify the tumor types is limited and closely related to the knowledge, operational level, and experience of the endoscopists. Therefore, the convolutional neural network (CNN) is used to assist endoscopists in determining GISTs or leiomyomas with EUS.

DETAILS: A model based on CNN was constructed according to GoogLeNet architecture to distinguish GISTs or leiomyomas. All EUS images collected from this study were randomly sampled and divided into training set (n=411) and testing set (n=103) in a ratio of 4:1. The CNN model was trained by EUS images from the training set, and the testing set was utilized to evaluate the performance of the CNN model. In addition, there were some comparisons between endoscopists and CNN models. It was shown that the sensitivity and specificity in identifying leiomyoma were 95.92%, 94.44%, sensitivity and specificity in identifying GIST were 94.44%, 95.92%, and accuracy in total was 95.15% of the CNN model. It indicates that the diagnostic accuracy of the CNN model is equivalent to skilled endoscopists, or even higher than them.

Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Source: Liu, J., Huang, J., Song, Y., et al. (2024). Differentiating Gastrointestinal Stromal Tumors From Leiomyomas of Upper Digestive Tract Using Convolutional Neural Network Model by Endoscopic Ultrasonography. Journal of Clinical Gastroenterology. 2024; 58(6): 574-579. Published: July, 2024. DOI: 10.1097/MCG.0000000000001907.

[Posted 12/Aug/2024]

AUDIENCE: Gastroenterology, Oncology, Internal Medicine

KEY FINDINGS: Cabozantinib demonstrated efficacy in patients who had received prior ICI regimens; survival data for second-line cabozantinib following first-line ICI regimens provide a reference for future clinical trial design. The number of prior lines of treatment may be considered a stratification factor in randomised studies.

BACKGROUND: Prospective data on treatment after immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC) are lacking. Authors conducted a phase II multicentre study on cabozantinib after ICI treatment in HCC.

DETAILS: This is an investigator-initiated, single-arm, clinical trial involving academic centres in Hong Kong and Korea. Key eligibility criteria included diagnosis of HCC, refractoriness to prior ICI-based treatment, and Child-Pugh A liver function. A maximum of two prior lines of therapy were allowed. All patients were commenced on cabozantinib at 60 mg/day. The primary endpoint was progression-free survival (PFS). Forty-seven patients were recruited from Oct 2020 to May 2022; 27 and 20 patients had received one and two prior therapies, respectively. Median follow-up was 11.2 months. The median PFS was 4.1 months (95% CI 3.3-5.3). The median overall survival (OS) was 9.9 months (95% CI 7.3-14.4), and the 1-year OS rate was 45.3%. Partial response and stable disease occurred in 3 (6.4%) and 36 (76.6%) patients, respectively. When used as a second-line treatment (n = 27), cabozantinib was associated with a median PFS and OS of 4.3 (95% CI 3.3-6.7) and 14.3 (95% CI 8.9-NR) months, respectively. The corresponding median PFS and OS were 4.3 (95% CI 3.3-11.0) and 14.3 (95% CI 9.0-NR) months, respectively, for those receiving ICI-based regimens with proven benefits (n = 17). The most common grade 3-4 treatment-related adverse event was thrombocytopenia (6.4%). The median dose of cabozantinib was 40 mg/day. The number of prior therapies was an independent prognosticator (one vs. two; hazard ratio = 0.37; p = 0.03). Prospective data on systemic treatment following prior immune checkpoint inhibitor (ICI) therapy for hepatocellular carcinoma (HCC) are lacking. This phase II clinical trial provides efficacy and safety data on cabozantinib in patients who had received prior ICI-based treatment. Exploratory analyses showed that the performance of cabozantinib differed significantly when used as a second- or third-line treatment. The above data could be used as a reference for clinical practice and the design of future clinical trials on subsequent treatment lines following ICIs.

Copyright © Elsevier Inc. All rights reserved.

Source: Chan, S. L., Ryoo, B., Mo, F., et al. (2024). Multicentre Phase II Trial of Cabozantinib in Patients With Hepatocellular Carcinoma After Immune Checkpoint Inhibitor Treatment. Journal of Hepatology. 2024; 81(2): 258-264. Published: August, 2024. DOI: 10.1016/j.jhep.2024.03.033.

A Systematic Review and Meta-analysis.

[Posted 24/Jun/2024]

AUDIENCE: Gastroenterology, Pediatric, Internal Medicine

KEY FINDINGS: Authors demonstrated that the CTP classification system is a reliable predictor of ERCP complications in patients with cirrhosis. Consequently, caution should be exercised when performing ERCP in patients classified as CTP class C.

BACKGROUND: Limited objective data exist on the comparison of post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with cirrhosis based on the severity of the disease.

DETAILS: Authors evaluated the effectiveness of the Child-Turcotte-Pugh (CTP) score system in anticipating the risk of post-ERCP complications in patients with cirrhosis. The PubMed, Scopus, Embase, and Cochrane databases were searched from inception through September 2022 to identify studies comparing post-ERCP complications in patients with cirrhosis based on CTP score. Odds ratios (ORs) and their associated 95% CIs were pooled using a random-effect model to calculate effect size. The reference group for analysis was the CTP class C patient group. Seven studies comprising 821 patients who underwent 1068 ERCP procedures were included. The CTP class C patient population exhibited a higher risk of overall post-ERCP adverse events compared with those with class A or B (OR: 2.87, 95% CI: 1.77-4.65, P = 0.00 and OR: 2.02, 95% CI: 1.17-3.51, P = 0.01, respectively). Moreover, CTP class B patients had a significantly higher complication rate than CTP class A patients (OR: 1.62, 95% CI: 1.04-2.53, P = 0.03). However, no statistically significant differences were found in the occurrence of specific types of complications, including bleeding, pancreatitis, cholangitis, perforation, or mortality across the three CTP groups.

Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Source: Alsakarneh, S., Jaber, F., Mohammed, W. Jr., et al. (2024). Applicability of Child-Turcotte-Pugh Score in Anticipating Post-ERCP Adverse Events in Patients With Cirrhosis: A Systematic Review and Meta-analysis. Journal of Clinical Gastroenterology. 2024; 58(6): 554-563. Published: July, 2024. DOI: 10.1097/MCG.0000000000002012.

[Posted 22/May/2024]

AUDIENCE: Gastroenterology, Internal Medicine

KEY FINDINGS: NAFLD and MASLD are similar except individuals with MASLD seem to be older with slightly higher mortality risk, likely owing to cardiometabolic risk factors. Clinical profiles and non-invasive test thresholds were also identical. These data provide evidence that NAFLD and MASLD terminologies can be used interchangeably. For the small proportion of patients with NAFLD who do not meet MASLD criteria, further consideration is needed.

BACKGROUND: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Concern remains regarding whether the evidence generated under the NAFLD definition can be used for MASLD. We compared the clinical profile and outcomes of NAFLD to MASLD using tertiary care- and population-based data.

DETAILS: Comparison data were obtained from our NAFLD database and the National Health and Nutrition Examination Survey (NHANES III). Clinical profiles and non-invasive tests (enhanced liver fibrosis [ELF] score, fibrosis-4 index [FIB-4] and vibration-controlled transient elastography) were compared. Mortality data were obtained from NHANES-National Death Index. All-cause mortality was assessed by Cox proportional hazards regression models and cause-specific mortality by competing risk analysis. There were 6,429 patients in the NAFLD database (age: 54 ± 12 years, 42% male, BMI 35.4 ± 8.3, waist circumference 112 ± 17 cm, 52% type 2 diabetes). Average scores for ELF, FIB-4 and liver stiffness were 9.6 ± 1.2, 1.69 ± 1.24,14.0 ± 11.8 kPa, respectively; 99% met MASLD criteria; 95% met MASLD on BMI only. Predictive accuracy of ELF and FIB-4 were identical between MASLD and NAFLD. We included 12,519 eligible participants from NHANES (age 43.00 years, 47.38% male, 22.70% obese, 7.28% type 2 diabetes, 82.51% >=1 cardiometabolic criteria). Among the NHANES study population, there was excellent concordance between MASLD and NAFLD diagnoses: Cohen's kappa coefficient: 0.968 (95% CI 0.962–0.973) with 5.29% of NAFLD cases not meeting MASLD criteria. After a median follow-up of 22.83 years, there were no mortality differences between MASLD and NAFLD diagnoses (p values >=0.05).

Copyright © Elsevier Inc. All rights reserved.

Source: XXXXX et al. (2024). Clinical Profiles and Mortality Rates Are Similar for Metabolic Dysfunction-Associated Steatotic Liver Disease and Non-Alcoholic Fatty Liver Disease. J Hepatology. 2024; 80(5): 694-701. Published: May, 2024. DOI: 10.1016/j.jhep.2024.01.014.

[Posted 18/Mar/2024]

AUDIENCE: Gastroenterology, Oncology, Internal Medicine

KEY FINDINGS: By using integrative scRNA-seq, spatial transcriptomic analysis and functional assays, authors have uncovered a stem-like cell cluster marked with PTPRO and ASCL2 as the metastatic culprit, whose subpopulations show further different liver or ovary organotropism.

BACKGROUND: Metastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered.

DETAILS: Authors performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). Authors also conducted immunofluorescence staining and functional experiments to examine the mechanism. Integrative analyses of epithelial cells reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O (PTPRO) and achaete scute-like 2 (ASCL2) expression as the metastatic culprit. This cell cluster comprising distinct subpopulations shows distinct liver or ovary metastatic preference. Population 1 (P1) cells with high delta-like ligand 4 (DLL4) and MAF bZIP transcription factor A (MAFA) expression are enriched in primary CRC and oCRC, thus may be associated with ovarian metastasis. P3 cells having a similar expression pattern as cholangiocytes are found mainly in primary CRC and lCRC, presuming to be likely the culprits that specifically metastasise to the liver. Stem-like cells interacted with cancer-associated fibroblasts and endothelial cells via the DLL4-NOTCH signalling pathway to metastasise from primary CRC to the ovary. In the oCRC microenvironment, myofibroblasts provide cancer cells with glutamine and perform a metabolic reprogramming, which may be essential for cancer cells to localise and develop in the ovary.

Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

Source: Li, R., Liu, X., Huang, X., et al. (2024). Single-Cell Transcriptomic Analysis Deciphers Heterogenous Cancer Stem-Like Cells in Colorectal Cancer and Their Organ-Specific Metastasis. Gut. 2024; 73(3): 470-484 .Published: March, 2024. DOI: 10.1136/gutjnl-2023-330243.

[Posted 15/Jan/2024]

AUDIENCE: Gastroenterology, Internal Medicine

KEY FINDINGS: The study extends the understanding of the heterogeneity of EGCA and identifies a functional NNMT+/AQP5+ population that may drive malignant progression in EGCA and could be used for early diagnosis and therapy.

BACKGROUND: Early gastric cardia adenocarcinoma (EGCA) is a highly heterogeneous cancer, and the understanding of its classification and malignant progression is limited. This study explored the cellular and molecular heterogeneity in EGCA using single-cell RNA sequencing (scRNA-seq).

DETAILS: scRNA-seq was conducted on 95,551 cells from endoscopic biopsies of low-grade intraepithelial neoplasia, well/moderately/poorly differentiated EGCA and their paired adjacent nonmalignant biopsy samples. Large-scale clinical samples and functional experiments were employed. Integrative analysis of epithelial cells revealed that chief cells, parietal cells and enteroendocrine cells were rarely detected in the malignant epithelial subpopulation, whereas gland and pit mucous cells and AQP5+ stem cells were predominant during malignant progression. Pseudotime and functional enrichment analyses showed that the WNT and NF-κB signalling pathways were activated during the transition. Cluster analysis of heterogeneous malignant cells revealed that NNMT-mediated nicotinamide metabolism was enriched in gastric mucin phenotype cell population, which was associated with tumour initiation and inflammation-induced angiogenesis. Furthermore, the expression level of NNMT was gradually increased during the malignant progression and associated with poor prognosis in cardia adenocarcinoma. Mechanistically, NNMT catalysed the conversion of nicotinamide to 1-methyl nicotinamide via depleting S-adenosyl methionine, which led to a reduction in H3K27 trimethylation (H3K27me3) and then activated the WNT signalling pathway to maintain the stemness of AQP5+ stem cells during EGCA malignant progression.

Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

Source: Wang Z., Wang Q., Chen C., et al. (2023). NNMT Enriches for AQP5+ Cancer Stem Cells to Drive Malignant Progression in Early Gastric Cardia Adenocarcinoma. Gut. 2024; 73: 63-77. Published: November, 2023. DOI: 10.1136/gutjnl-2022-328408.