This study aimed to clarify the role of Orosomucoid 1 (ORM1) in the development and therapy resistance in hepatocellular carcinoma (HCC). The mRNA expression level of ORM1 was analyzed via integrative analysis of Gene Express Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The protein expression level of ORM1 in our cohort was determined using immunohistochemistry. Correlation analysis was used to investigate the relationship between ORM1 expression and clinical parameters. The Cell Counting Kit-8 assay was used to clarify the role of ORM1 in HCC malignant behaviors, including cell growth and sorafenib sensitivity, in vitro. The results indicated that ORM1 was significantly downregulated in the hepatic cancer cells compared to that in the non-cancerous cells. However, it was upregulated in microvascular invasion samples, especially in the cancer embolus compared to that in the surrounding tumor cells. Though Kaplan-Meier analysis did not show an association of ORM1 expression with the overall survival rates of HCC patients, univariate analysis indicated that ORM1 expression was highly correlated with tumor grade and stage. An in vitro assay also revealed that downregulation of ORM1 led to the suppression of tumor growth and enhancement of sorafenib sensitivity without epithelial-to-mesenchymal transition (EMT) alteration, which was consistent with our bioinformatic analysis. Hence, ORM1 played a key role in HCC tumorigenesis and may serve as a potential target for the development of therapeutics against HCC in the future.

The incidence of pancreatic ductal adenocarcinoma (PDAC) has been on the rise in recent years; however, its clinical diagnosis and treatment remain challenging. Although surgical resection remains the only chance for long-term patient survival, the likelihood of initial resectability is no higher than 20%. Neoadjuvant therapy (NAT) in PDAC aims to transform the proportion of inoperable PDACs into operable cases and reduce the likelihood of recurrence to improve overall survival. Ongoing phase 3 clinical trial aims to validate the role of NAT in PDAC therapy, including prolongation of survival, increased R0 resection, and a higher proportion of negative lymph nodes. Controversies surrounding the role of NAT in PDAC treatment include applicability to different stages of PDAC, chemotherapy regimens, radiation, duration of treatment, and assessment of effect. This review aims to summarize the current progress and controversies of NAT in PDAC.

Perihilar cholangiocarcinoma (PHCC) is an aggressive biliary malignancy originating from the epithelial cells of the bile duct, typically located in the extrahepatic biliary tree, proximal to the cystic duct. PHCC often presents with a rapid onset of jaundice. While radical surgical resection remains the only curative treatment, only a minority of patients are eligible due to early metastasis and challenges associated with preoperative evaluations. Comprehensive treatments, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, are crucial for managing PHCC. However, in advanced stages, complications such as cholestatic liver injury, malnutrition, and biliary infections pose significant obstacles to these treatments. Therefore, biliary drainage (BD) is essential in the management of PHCC. In addition to external drainage methods like percutaneous transhepatic biliary drainage (PTBD), endoscopic biliary drainage (EBD), particularly endoscopic retrograde cholangiopancreatography (ERCP), offer an effective option for internal drainage, which is more physiologically compatible and better tolerated. Furthermore, the integration of various endoscopic techniques has expanded the management of PHCC beyond mere drainage. Techniques such as radiofrequency ablation (RFA), photodynamic therapy (PDT), and endoscopic ultrasound (EUS) based methods present new therapeutic avenues, albeit with variable results. This review aims to summarize current advancements and ongoing debates in the field of endoscopic treatment for unresectable PHCC.