Hepatic arterial infusion (HAI) chemotherapy, first introduced in the 1980s, has gained recognition as an effective locoregional treatment for colorectal liver metastasis (CRLM). Initially used for unresectable liver metastases, HAI’s application has expanded to the adjuvant setting following hepatic resection, with early studies indicating improved hepatic disease-free survival. Recent research demonstrates that combining HAI with modern systemic therapies enhances conversion to resectability and prolongs both recurrence-free and overall survival, even in heavily pretreated patients with diverse RAS mutational statuses. Personalization through approaches like microsatellite instability status and dose modifications further optimize outcomes. However, the complexity of HAI requires expertise across multidisciplinary teams, limiting its widespread adoption to specialized centers. Ongoing clinical trials continue to investigate HAI’s role in CRLM management, highlighting its potential to become a cornerstone of liver-directed therapy. We explore how HAI chemotherapy, in combination with personalized medicine, can advance treatment strategies for metastatic colorectal cancer.

BACKGROUND Pancreatic cancer (PC) is one of the most aggressive malignancies characterized by rapid progression and poor prognosis. The involvement of cancer stem cells (CSCs) and Octamer transcription factor 4 (OCT4) in PC pathobiology is being increasingly recognized. AIM To investigate the role of OCT4 in pancreatic CSCs and its effect on PC cell proliferation, migration, drug sensitivity, and stemness maintenance. METHODS We analyzed OCT4 and CD133 expression in PC tissues and cell lines. BxPC-3 cells were used to assess the effects of OCT4 modulation on cellular behavior. Proliferation, migration, and stemness of BxPC-3 cells were evaluated, and the PI3K/AKT/mTOR pathway was examined to gain mechanistic insights. RESULTS OCT4 and CD133 were significantly overexpressed in PC tissues. OCT4 modulation altered BxPC-3 cell proliferation, invasion, and stemness, with OCT4 overexpression (OV-OCT4) enhancing these properties and OCT4 interference decreasing them. OV-OCT4 activated the PI3K/AKT/mTOR pathway, which correlated with an increase in PC stem cells (PCSC). CONCLUSION OCT4 plays a crucial role in PCSCs by influencing the aggressiveness and drug resistance of PC cells, thus presenting itself as a potential therapeutic target.

BACKGROUND Paraganglioma (PGL) is a neuroendocrine tumor originating from paraganglia that can occur in various locations, such as the head, neck, chest, abdomen, and pelvis. Retroperitoneal PGLs are rare, and recurrent cases in this area are particularly uncommon, posing considerable surgical complexities. Owing to their neuroendocrine activity, PGLs are capable of secreting hormones like catecholamines, thereby presenting significant challenges in hemodynamic management during the perioperative period. CASE SUMMARY We report a 64-year-old man with a recurrent retroperitoneal PGL. The patient underwent retroperitoneal mass resection in 2013, with postoperative pathology revealing a PGL. Regular follow-up was not conducted until April 2024, when a computed tomography scan revealed a huge mass in the retroperitoneum, closely adjacent to the abdominal aorta. Laboratory examinations revealed elevated levels of catecholamines in the patient's blood serum. Upon admission, volume expansion and blood pressure (BP) monitoring were carried out for one week, with catecholamine levels reviewed and normalized. Adequate preoperative preparation was conducted, including central venous access, arterial BP monitoring, and the preparation of vasoactive agents. During tumor resection, the patient experienced acute, significant fluctuations in BP. The timely intervention of the anesthesiologist stabilized the BP, facilitating the successful resection of the tumor which was confirmed as a recurrent PGL. Postoperative follow-up revealed no evidence of tumor residual or recurrence. CONCLUSION PGL recurrence is rare but non-negligible. PGLs adjacent to major arteries complicate surgery, and perioperative hemodynamic stability demands meticulous attention.

Accurate preoperative prediction of lymph node metastasis is crucial for developing clinical management strategies for patients with esophageal cancer. In this letter, we present our insights and opinions on a new nomogram proposed by Xu et al . Although this research has great potential, there are still concerns regarding the small sample size, limited consideration of biological complexity, subjective image segmentation, incomplete image feature extraction and statistical analyses. Furthermore, we discuss how to achieve more robust and accurate predictive performance in future research.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a common malignancy in China, often diagnosed at an advanced stage, with poor prognosis. Standard treatments such as definitive chemoradiotherapy offer limited survival benefits. Recent advances in immune checkpoint inhibitors combined with chemotherapy have shown promise, but their effectiveness and safety in conjunction with radiotherapy for unresectable ESCC require further exploration. AIM To assess the safety and effectiveness of induction chemoimmunotherapy followed by definitive radiotherapy or concurrent chemoradiotherapy (CCRT) in locally advanced unresectable ESCC. METHODS This retrospective study included 80 patients with locally advanced unresectable ESCC who underwent induction chemoimmunotherapy followed by definitive radiotherapy, recruited from Zhejiang Cancer Hospital. All patients received 2-4 cycles of chemotherapy plus programmed cell death 1/programmed cell death ligand 1 inhibitor, were re-evaluated to be inoperable, then received definitive radiotherapy or CCRT. Primary endpoint was treatment safety and tolerance. SPSS 26.0 software was used for data analysis. Th Kaplan-Meier method was used for survival analysis. RESULTS Thirty-seven (46.3%) patients received CCRT and 43 (53.7%) received radiotherapy alone. The most common treatment-related adverse events included radiation esophagitis (32/80, 40.0%) and anemia (49/80, 61.3%), with 22 (27.5%) experiencing grade ≥ 3 adverse events. No treatment-related deaths occurred. After median follow-up of 16.5 months, the median progression-free survival (PFS) was 14.2 months, and median overall survival (OS) was 19.9 months. The 1-year and 2-year PFS and OS were 55.8% and 31.6%, and 67.5% and 44.1%, respectively. Patients with partial response had better outcomes than those with stable disease: 1-year PFS 69.4% vs 43.9% (P = 0.011) and OS 83.2% vs 48.8% (P = 0.007). Induction therapy effectiveness and immunotherapy maintenance were independent prognostic factors for OS. CONCLUSION Chemotherapy combined with programmed cell death 1/programmed cell death ligand 1 inhibitor followed by definitive radiotherapy or CCRT in patients with locally advanced ESCC was safe and effective.

BACKGROUND Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare tumors originating from neuroendocrine cells. Due to lack of neuroendocrine symptoms and specific radiographic characteristics, PHNETs are challenging to differentiate from other liver tumors. CASE SUMMARY This case involved a 67-year-old male who was admitted with a discovered hepatic mass and a suspicious lung lesion. Primary hepatic carcinoma was initially speculated based on the characteristic magnetic resonance imaging findings. The patient underwent a laparoscopic right partial hepatectomy, and subsequent immunohistochemical examination revealed a HNET. To exclude other potential origins, a positron emission tomography-computed tomography scan and gastrointestinal endoscopy were performed, leading to a final diagnosis of PHNETs. Then we conducted a literature review using the PubMed database, identifying 99 articles and 317 cases related to PHNETs. The characteristics, diagnostic methods, and treatment of PHNETs have been described. Finally, we elaborate on the presumed origins, pathological grades, clinical features, diagnosed methods, and treatments associated with PHNETs. CONCLUSION The diagnosis of PHNETs was primarily an exclusionary process. A definitive diagnosis of PHNETs relied mainly on immunohistochemical markers (chromogranin A, synaptophysin, and cluster of differentiation 56) and exclusion of primary foci in other organs. Radical surgery was the preferred treatment for early-stage tumors.

BACKGROUND Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. In cases of metastatic CRC (mCRC) that are resistant to conventional chemotherapy-based treatments, the efficacy of available therapeutic options is typically low. CRC exhibiting overexpression or amplification of the human epidermal growth factor receptor 2 (HER2) gene has shown responsiveness to HER2-targeted therapies. CASE SUMMARY We present the case of a 69-year-old woman diagnosed with mCRC with an NRAS p.G12V mutation and microsatellite stability, identified through tumor sequencing, along with HER2 overexpression detected by immunohistochemistry. She exhibited an excellent response to disitamab vedotin-containing therapy. To our knowledge, this is the first reported case of mCRC with HER2 overexpression and an NRAS p.G12V mutation achieving a remarkable clinical response to anti-HER2 therapy. CONCLUSION Disitamab vedotin demonstrates promising anti-tumor effects in HER2-overexpressing mCRC, offering patients an additional treatment option.

Based on the discovery that human β-defensin-1 (hBD-1) triggers autophagy in colon cancer cells and inhibits proliferation, we proposed the consideration of its druggability. As a protein, its stability, targetability and bioavailability must be improved. Compared with the traditional medicinal chemistry technology, nanotechnology is more economical for increasing the druggability of hBD-1 and can be readily scaled up. Here, we propose an immunoliposome system containing hBD-1 to improve its stability and bioavailability. To enhance its targetability, anti-epidermal growth factor receptor (EGFR) antibodies were conjugated to the liposomal bilayer to produce immunoliposomes that can target EGFR, which is highly expressed in colon cancer cells. Although more studies are needed to support clinical trials and large-scale manufacturing, these immunoliposomes have great potential as therapeutics. Thus, immunoliposomes are suitable nanovesicles to improve the druggability of hBD-1; however, additional basic and translational research of these systems is warranted.

BACKGROUND Colorectal cancer (CRC) is a prevalent malignant tumor characterized by a high mortality rate, with significant challenges persisting in the identification and management of its metastatic stage. The role of checkpoint kinase 1 (CHEK1), a cell cycle checkpoint kinase, in CRC has not been fully clarified. We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells, indicating its potential as a novel therapeutic target for CRC therapy. AIM To investigate the expression and function of CHEK1 in CRC, this study utilizes single-cell RNA sequencing and tissue microarray data. METHODS Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset, and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues. We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expression in CRC. Molecular docking experiments were performed to explore the interaction between CHEK1 and the potential drug nitidine chloride (NC), as well as to investigate the influence of CHEK1 on CRC cell proliferation. RESULTS We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC, with marked upregulation of its mRNA levels in CRC tissues. Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues, and the receiver operating characteristic curve demonstrated high accuracy (area under the curve = 0.964) for CHEK1 as a biomarker. Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC (standard mean difference = 1.81, P < 0.01), with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88, respectively. Molecular docking studies indicated that NC specifically targeted CHEK1, while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation. CONCLUSION Upregulation of CHEK1 promotes CRC cell proliferation. However, the dataset's diversity is limited, requiring further investigation into its specific mechanisms.

BACKGROUND Hepatocellular carcinoma (HCC) is a difficult cancer to manage due to its highly invasive and metastatic nature. AIM To investigate the molecular function of transmembrane channel-like 5 (TMC5) in vitro and in vivo , with the objective of identifying novel diagnosis and treatment targets for HCC. METHODS The expression of TMC in cancer and normal tissues, along with its correlation with HCC prognosis, was analyzed using the GENT2, GEPIA database, and Human Protein Atlas. COX analysis was conducted to assess the relationship between TMC5 expression and overall survival in TCGA-LIHC patients. Further experiments were conducted to investigate the effect of TMC5 in cancer progression through loss- and gain-of-function assays in vitro and in vivo . RESULTS Bioinformatics revealed that TMC5 expression was generally higher in tumors than in normal tissues, and its expression was associated with poorer patient survival outcomes. TMC5 expression in HCC tissues and cells was consistent with the results of the bioinformatics analysis. Suppression of TMC5 expression reduced migration, invasion, and proliferation, while also decreasing the expression of epithelial-mesenchymal transition (EMT)-associated molecules in MHCC97-LM3 cells. Conversely, higher TMC5 expression significantly increased cell migration, invasion, proliferation, and EMT in MHCC97 L cells. TMC5 knockdown significantly decreased both the formation and spread of nodules in liver tissue, whereas TMC5 overexpression promoted them. CONCLUSION Our study provides compelling evidence that TMC5 is highly expressed in HCC and drives cancer progression through the activation of EMT-mediated invasion. TMC5 could represent a valuable molecular target for the diagnosis and treatment of HCC.