Background: Primary hypertrophic osteoarthropathy (PHO) is a rare disease related to HPGD and SLCO2A1 gene mutation. Gastrointestinal involvement of PHO is even rarer with unknown pathogenesis. Clinical features of GI complication in PHO mimics other auto-immune based bowel entities, such as inflammatory bowel diseases and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE). We aimed to analyze the clinical, genetic, radiological and pathological features of Chinese patients with PHO and determine the difference between PHO patients presenting with and without GI involvement. Methods: We reported two PHO cases with gastrointestinal involvement and reviewed all the studies of PHO in Chinese population published from January 1, 2000, to April 30, 2018. Clinical and genetic presentations of PHO in Chinese patients were analyzed. We compared the characteristics of those patients with gastrointestinal involvement against those without. Results: The two patients were both males with complete-form PHO for more than 10 years. GI related symptoms included diarrhea, chronic gastrointestinal hemorrhage, incomplete intestinal obstruction, anemia, and edema, which were unresponsive to etoricoxib treatment. Radiological examinations revealed segmental intestinal stenosis and thickened intestinal wall. Endoscopic findings included multiple ulcers and mucosal inflammation. Both patients had mutations of SLCO2A1 according to sequence analysis. The surgical pathology revealed chronic inflammation involving the intestinal mucosa and submucosa, similar to histological changes in CMUSE. According to the systemic review of 158 Chinese patients with PHO, 17.2% had gastrointestinal involvement, including peptic ulcer, gastric polyps, hypertrophic gastritis, and segmental intestinal stenosis. Patients with gastrointestinal involvement were more likely to have anemia (40.0% vs. 4.5%, P < 0.001), hypoalbuminemia (16.7% vs. 0.9%, P = 0.003), and myelofibrosis (19.0% vs. 0.9%, P = 0.002) than those without. Most patients with gastrointestinal complication had SLCO2A1 mutation (86.7%, 13 /15). Conclusions: Digestive tract involvement is uncommon in patients with PHO and often presents with anemia, and hypoalbuminemia resulted from intestinal inflammation. The intestinal pathologic characteristics are distinct from Crohn’s disease but similar to CMUSE. Mutations in SLCO2A1 might be the pathogenic cause of GI involvement of PHO. NSAIDs may not be effective for PHO patients with gastrointestinal complications.

Gastroblastoma is an extremely rare stomach tumor that primarily presents in adolescent and early adulthood, with a biphasic cell morphology of epithelioid and spindle cells. In light of its similarity to other childhood blastomas, it has been named gastroblastoma. Few patients showed a potential of metastasis and recurrence, however, most of the reported cases were alive, with no evidence of the disease after surgical treatment. Commonly, MALAT1-GLI1 fusion has been considered to be the most relevant mutation. Herein, we present a case of an asymptomatic 58-year-old man who happened to find a submucosal gastric mass during a gastroscope and received endoscopic submucosal excavation (ESE). He turned out to have a gastroblastoma with a novel PTCH1::GLI2 fusion confirmed by Sanger sequencing. The patient was discharged two days after ESE without any complication and was recurrence-free during his one-year follow-up. According to the previous literature and our own experience, in cases with characteristic histopathology and immunohistochemistry patterns, a diagnosis of gastroblastoma should be considered even without a MALAT1-GLI1 fusion. Gastroblastoma pursues a favorable clinical outcome and endoscopic therapy could be an effective alternative treatment choice.

Background and aims: Chronic enteropathy associated with SLCO2A1 gene is a rare intestinal disease caused by loss-of-function SLCO2A1 mutations, with clinical and genetic characteristics remaining largely unknown, especially in Chinese patients. This study aims to reveal clinical and genetic features of Chinese CEAS patients, highlighting the previously unreported or unemphasized characteristics. Methods: We enrolled 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene admitted to Peking Union Medical College Hospital from January 2018 to December 2022. Clinical and genetic data of these patients were collected and analyzed. Results: 58.3% of patients were male, who also had primary hypertrophic osteoarthropathy, whereas female patients did not have primary hypertrophic osteoarthropathy. Apart from common symptoms associated with anemia and hypoalbuminemia, abdominal pain, ileus, diarrhea, and hematochezia were present. 4 of the 5 female patients had early-onset amenorrhea, though the causal relationship remained to be clarified. Endoscopy and computed tomography enterography revealed that lesions can occur in any part of the digestive tract, most commonly in the ileum. Pathology showed multiple superficial ulcers with adjacent vascular dilatation, and loss of SLCO2A1 expression, particularly in gastrointestinal vascular endothelial cells. Genetic analysis confirmed SLCO2A1 mutations in all patients and identified 11 new SLCO2A1 variants for CEAS. Conclusions: This study reports new clinical, pathological, and genetic findings in 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene. This study provides insights into the pathogenesis of this disease. However, studies with larger sample sizes and more in-depth mechanism research are still required.

Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss. This review explores the potential mechanisms underlying the pathogenesis of CEAS, focusing on the role of SLCO2A1 -encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2 (PGE2) levels. Studies have suggested that elevated PGE2 levels contribute to mucosal damage, inflammation, and disruption of the intestinal barrier. The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality, as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS. Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel, targeted therapies.

Ectopic varices and associated bleeding, although rare, pose a significant risk to patients with portal hypertension, carrying a relatively high mortality rate. These varices can occur in various anatomical regions, excluding the gastroesophageal region, which is typically associated with portal vein drainage. The limited data available in the literature, derived mostly from case reports and series, make the diagnosis and treatment of ectopic variceal bleeding particularly challenging. Furthermore, it is crucial to recognize that ectopic varices in different sites can exhibit variations in key decision-making factors such as aetiology and vascular anatomy, severity and bleeding risk and hepatic reserve. These factors significantly influence treatment strategies and underscore the importance of adopting individualized management approaches. Therefore, the objective of this review is to provide a comprehensive overview of the fundamental knowledge surrounding ectopic varices and to propose site-oriented, stepwise diagnosis and treatment algorithms for this complex clinical issue. A multidisciplinary treatment approach is strongly recommended in managing ectopic varices. In addition, to enhance clinical reference, we have included typical case reports of ectopic varices in various sites in our review, while being mindful of potential publication bias.

Background. BRCA1 interacting helicase 1 (BRIP1), an ATP-dependent DNA helicase which belongs to an Iron-Sulfur (Fe-S) helicase cluster family with a DEAH domain, plays a key role in DNA damage and repair, Fanconi anemia, and development of several cancers including breast and ovarian cancer. However, its role in pan-cancer remains largely unknown. Methods. BRIP1 expression data of tumor and normal tissues were downloaded from the Cancer Genome Atlas, Genotype-Tissue Expression, and Human Protein Atlas databases. Correlation between BRIP1 and prognosis, genomic alterations, and copy number variation (CNV) as well as methylation in pan-cancer were further analyzed. Protein-protein interaction (PPI) and gene set enrichment and variation analysis (GSEA and GSVA) were performed to identify the potential pathways and functions of BRIP1. Besides, BRIP1 correlations with tumor microenvironment (TME), immune infiltration, immune-related genes, tumor mutation burden (TMB), microsatellite instability (MSI), and immunotherapy as well as antitumor drugs were explored in pan-cancer. Results. Differential analyses showed an increased expression of BRIP1 in 28 cancer types and its aberrant expression could be an indicator for prognosis in most cancers. Among the various mutation types of BRIP1 in pan-cancer, amplification was the most common type. BRIP1 expression had a significant correlation with CNV and DNA methylation in 23 tumor types and 16 tumor types, respectively. PPI, GSEA, and GSVA results validated the association between BRIP1 and DNA damage and repair, cell cycle, and metabolism. In addition, the expression of BRIP1 and its correlation with TME, immune-infiltrating cells, immune-related genes, TMB, and MSI as well as a variety of antitumor drugs and immunotherapy were confirmed. Conclusions. Our study indicates that BRIP1 plays an imperative role in the tumorigenesis and immunity of various tumors. It may not only serve as a diagnostic and prognostic biomarker but also can be a predictor for drug sensitivity and immunoreaction during antitumor treatment in pan-cancer.