Study of the Intersegmental Veins Between S5 and S8 Based on 3D Reconstruction.

BACKGROUND: Anatomic resection (AR) is a surgical method for treating hepatocellular carcinoma, and identifying intersegmental planes between segments 5 (S5) and 8 (S8) remains challenging. This study aims to find reliable intersegmental veins (IVs) between them as anatomical landmarks using 3D reconstruction analysis. METHODS: We retrospectively evaluated 57 patients who underwent multidetector-row CT scans from September 2021 to January 2023. The portal vein watershed of S5 and S8 and hepatic veins were reconstructed using 3D reconstruction analysis software. We counted and analyzed the IVs running within the intersegmental plane between S5 and S8, examined their features, and analyzed the location of the junctions between IVs and middle hepatic veins (MHVs). RESULTS: Among the 57 patients, 43 patients (75.4%) had IVs between S5 and S8. Most patients (81.4%) had a single IV joining the MHV, while 13.9% had two IVs, one joining the MHV and the other joining the right hepatic vein (RHV). The majority of IV-MHV junctions were found in the lower part of the MHVs. The most clearly identifiable junctions between the IVs and MHVs occurred slightly below the midpoint of the horizontal planes of the second hepatic portal and the center of the gallbladder bed. CONCLUSION: Our study identified IVs between S5 and S8 in the liver as potential anatomical landmarks during AR for hepatocellular carcinoma surgery. We found three types of IVs and provided insights on how to locate their junctions with MHVs for easier surgical navigation. However, individual anatomical variations must be considered, and preoperative 3D reconstruction and personalized surgical planning are crucial for success. More research with larger sample sizes is needed to validate our findings and establish the clinical significance of these IVs as landmarks for AR.

Identification of potential core genes at single-cell level contributing to pathogenesis of pancreatic ductal adenocarcinoma through bioinformatics analysis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) prognosis has not improved over the last decades because of the lack of effective diagnostic and therapeutic methods in the early stage of the disease. METHODS: Several gene expression profiles were downloaded from the Expression Omnibus (GEO) database. We calculated the differentially expressed mRNAs (DEGs) and miRNAs (DEmiRs). Then, we constructed a miRNA-mRNA regulatory network by using the miRWalk database. For the DEGs regulated by DEmiRs, we introduced GEPIA to confirm these DEGs' expression and effect on overall survival. We used other GEO datasets and mRNA-miRNA target databases to validate these DEGs and their relationship with DEmiRs. All these potential core DEGs regulated by DEmiRs were also analyzed at the single-cell level to confirm their cell type source. RESULTS: CCNB2 and KCNN4, which were regulated by several micro RNAs, showed relatively high expression levels in PDAC patients and significant association with worse overall survival. Furthermore, we identified many DEGs at single-cell level and found that 10 oncogenes were significantly upregulated in type 2 ductal cell type, thereby further demonstrating that type 2 ductal cells might be major sources of malignant cells and are valuable therapeutic targets in PDAC. CONCLUSIONS: Our data added some new insights into the molecular mechanism of PDAC and may be helpful for finding potential biomarkers for diagnosis. These discovery at single-cell level may also be useful for developing new therapeutic targets for PDAC patients.

Management and outcomes of patients for non-functioning pancreatic neuroendocrine tumours: a multi-institutional analysis.

BACKGROUND: To analysed the short- and long-term outcomes of patients who underwent surgical resection for non-functioning pancreatic neuroendocrine tumours (NF-PNETs) to gain insights into treatment approaches for this rare and heterogeneous entity. METHODS: All patients who underwent surgical resection for NF-PNETs at The Second Affiliated Hospital of Guangzhou Medical University, and West China Hospital, Sichuan University, from 2009 to 2019 were retrospectively reviewed. The data of patients was including perioperative management, pathologic analysis and follow-up. RESULTS: A total of 119 cases with histologically or cytologically confirmed NF-PNETs, The mean age of the patients was 52, and 56.3% were female. Twenty-three patients received post-operative adjuvant therapy, and five of nine (55.6%) patients with distant metastasis showed recurrence 14(60.9%) G2/G3 patients without distant metastasis received post-operative therapy with octreotide. Of these 14 patients, 3 (21.4%) revealed recurrence. Univariate analysis indicated that symptoms (P = 0.03), tumour size >4 cm (P = 0.029), ENETS stages III-IV (P < 0.001), positive lymph nodes (P < 0.001), vascular/perineural invasion (P < 0.001), and pathology grade G2 were associated with significantly higher risks of recurrence; age, gender, surgery type, and tumour location were not. Multivariate analysis revealed that positive lymph nodes (P < 0.001), vascular/peripheral invasion (P < 0.001), and pathology grade G3 (P = 0.03) are significant prognostic factors of tumour recurrence. CONCLUSION: Positive lymph nodes, vascular/peripheral invasion and pathology grade G3 were related to recurrence of NF-PNETs. Lymph node resection is recommend when FNA biopsy indicates pathology grade G3 for patients with NF-PNETs.

INTRABEAM intraoperative radiotherapy combined with portal vein infusion chemotherapy for treating hepatocellular carcinoma with portal vein tumor thrombus.

BACKGROUND: Portal vein tumor thrombus (PVTT) is common in hepatocellular carcinoma (HCC). Recent studies indicate that more aggressive treatments, including surgical resection or locoregional treatment, may benefit selected HCC patients with PVTT. External radiation therapy and infusion chemotherapy were found to achieve good outcomes; however, the use of low-energy x-ray radiation system (INTRABEAM), intraoperative radiation therapy, and portal vein infusion chemotherapy for PVTT has not been reported. We present a case of HCC with PVTT. The patient underwent hemihepatectomy and thrombectomy along with intraoperative radiotherapy (IORT) using a portable INTRABEAM radiation system. Subsequently, to treat PVTT, portal vein infusion chemotherapy with FOLFOX (leucovorin [Folinic acid], fluorouracil, and oxaliplatin) regimen was administered. There were no obvious post-operative complications. After 20 months follow-up period, no obvious tumor recurrence had been observed, and PVTT gradually disappeared completely. CONCLUSIONS: IORT using the INTRABEAM radiation system combined with portal vein infusion chemotherapy is promising for select patients with PVTT.

Using the new INTRABEAM mobile intraoperative radiotherapy system during surgery for pancreatic cancer: a case report.

BACKGROUND: Pancreatic cancer is one of the most common fatal malignancies and has a poor prognosis. Surgical treatment is the most important treatment method, but there is a low rate of radical excision; moreover, the postoperative recurrence rate is high, with a local recurrence rate greater than 50%. The usefulness of intraoperative radiotherapy for pancreatic cancer has previously been examined. However, prior research was based on the traditional high-energy electron beam, which causes serious radiation toxicity. Therefore, the tumor radiation dose was limited, subsequently limiting the effect. In contrast, there is also a low-energy X-ray radiation system called INTRABEAM®. Use of INTRABEAM has been applied clinically, but the treatment effect of INTRABEAM in pancreatic cancer has not been reported. CASE PRESENTATION: We present a case of a 56-year-old Chinese man with local advanced pancreatic cancer with invasion of the coeliac trunk artery and origin of the portal vein. He underwent distal pancreatectomy and splenectomy along with intraoperative radiotherapy using a portable INTRABEAM radiation system. The radiotherapy dose was 10 Gy and irradiation time was 27.4 minutes. There were no obvious postoperative complications. His abdominal pain was alleviated after surgery, and no obvious tumor recurrence has been observed in short-term follow-up. CONCLUSIONS: We believe that it is safe to apply intraoperative radiotherapy using the INTRABEAM radiation system in pancreatic cancer. This approach appears promising for further future development.

A novel mouse model of orthotopic extrahepatic cholangiocarcinoma confirmed with molecular imaging.

BACKGROUND: Cholangiocarcinoma (CCA) is the second most common primary hepatic malignancy in humans. Although early-stage CCA can be managed with surgery, CCA is considered incurable at advanced stages and results in poor quality of life and overall survival. A good orthotopic CCA animal model is essential to perform basic studies investigating CCA in order to understand the molecular pathways that underlie cancer development, and to develop new therapies for the prevention and treatment of CCA. However, to the best of our knowledge, orthotopic extrahepatic CCA animal models have not yet been reported in the literature. METHODS: In this study, we established an orthotopic extrahepatic CCA model in mice using a two-step surgical procedure. RESULTS: The characteristics of this model were confirmed using molecular imaging and histological analysis. CONCLUSIONS: We believe that this CCA animal model, which can be established quickly, easily, and with good reproducibility, will help guide research on novel diagnostic and treatment strategies for extrahepatic CCA.

MiR-324-5p Suppresses Hepatocellular Carcinoma Cell Invasion by Counteracting ECM Degradation through Post-Transcriptionally Downregulating ETS1 and SP1.

Hepatocellular carcinoma (HCC) is one of the common malignancies, which is highly metastatic and the third common cause of cancer deaths in the world. The invasion and metastasis of cancer cells is a multistep and complex process which is mainly initiated by extracellular matrix (ECM) degradation. Aberrant expression of microRNA has been investigated in HCC and shown to play essential roles during HCC progression. In the present study, we found that microRNA-324-5p (miR-324-5p) was downregulated in both HCC cell lines and tissues. Ectopic miR-324-5p led to the reduction of HCC cells invasive and metastatic capacity, whereas inhibition of miR-324-5p promoted the invasion of HCC cells. Matrix metalloproteinase 2 (MMP2) and MMP9, the major regulators of ECM degradation, were found to be downregulated by ectopic miR-324-5p, while upregulated by miR-324-5p inhibitor. E26 transformation-specific 1 (ETS1) and Specificity protein 1 (SP1), both of which could modulate MMP2 and MMP9 expression and activity, were presented as the direct targets of and downregulated by miR-324-5p. Downregulation of ETS1 and SP1 mediated the inhibitory function of miR-324-5p on HCC migration and invasion. Our study demonstrates that miR-324-5p suppresses hepatocellular carcinoma cell invasion and might provide new clues to invasive HCC therapy.

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits hepatoma cell growth via downregulation of SEPT2 expression.

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis and low therapeutic efficacy. Recent studies have demonstrated the therapeutic prospect of peroxisome proliferator-activated receptor-γ (PPARγ) cancer angiogenesis. However, the action mechanisms remain elusive. In the present study, by using mass spectrometry, we found that PPARγ ligand rosiglitazone (RGZ) could regulate HCC cell growth by influencing various downstream factors and pathways. Among the altered proteins, septin 2 (SEPT2) was found to exhibit oncogenic function. PPARγ overexpression could inhibit the expression of SEPT2, thus blocking the promoting effects of SEPT2 on HCC cell proliferation, invasion and its inhibitory effect on cell apoptosis. Further studies also indicated that SEPT2 promoted HCC cell growth via upregulation of matrix metalloproteinase (MMP)-2 and -9, and simultaneously inhibited the cleavage of caspase-3, -7, and -9. Interestingly, the effects of SEPT2 on the above factors could be suppressed by PPARγ overexpression, suggesting that PPARγ could inhibit HCC cell growth via regulating the expression and blocking the oncogenic function of SEPT2. Taken together, these results provide new evidence for the action mechanisms of PPARγ in carcinogenesis of HCC, and upon further investigation, PPARγ could be developed as a new target for the treatment of liver cancer.

Rosiglitazone enhances 5-fluorouracil-induced cell growth inhibition in hepatocellular carcinoma cell line Hep3B.

BACKGROUND AND OBJECTIVE: Rosiglitazone is a peroxisome proliferators-activated receptor gamma (PPARgamma) ligand, which inhibits tumor growth by activating PPARgamma signaling pathways. Fluorouracil (5-FU) is one of the commonly used chemotherapeutic drugs. However, patients develop drug resistance of 5-FU over time. The aim of this study was to investigate whether rosiglitazone can enhance 5-FU-induced cell growth inhibition and to explore its potential mechanisms. METHODS: Cell viability was measured using MTT assay. Protein expression levels were detected by Western blot analysis. Small interference RNA was utilized to knockout PPARgamma and PTEN in Hep3B cells. RESULTS: After 48 h of treatment with 10, 20, and 40 µmol/L rosiglitazone, the viability of Hep3B cells was (78.0 ± 2.7)%, (37.3 ± 8.1)%, and (19.8 ± 2.2)%, respectively (compared with control group, P values were all < 0.001). After 48 h of treatment with 10 µmol/L 5-FU, the viability of Hep3B cells was about (82.6 ± 3.9)%. When cells were treated with 10 µmol/L 5-FU in combination with either 10, 20 or 40 µmol/L rosiglitazone, the cell viability was (51.6 ± 5.4)%, (14.8 ± 4.2)%, and (8.5 ± 0.9)%, with corresponding q value of 1.36, 1.23, and 1.19, respectively. These data suggested that the two drugs had synergic effect in inhibiting Hep3B cell growth, which was further confirmed in an in vivo mice model. Subsequent investigations showed that rosiglitazone activated PPARgamma signaling pathways and increased the expression of PTEN. CONCLUSIONS: Rosiglitazone enhances 5-FU-induced cell growth inhibition of Hep3B cells.