Identification of interleukin-16 production on tumor aggravation in hepatocellular carcinoma by a proteomics approach

BACKGROUND: Cytokines play an important role in the immune response, angiogenesis, cell growth, and differentiation in hepatocellular carcinoma (HCC). OBJECTIVE: We performed a comprehensive study to identify tumor-related cytokines and pathways involved in HCC pathogenesis. METHODS: Cytokine production was evaluated in human HCC tissues and adjacent non-tumor tissues using an antibody-based protein array technique. We compared cytokine expression in HCC tissues with that of hepatic hemangioma (HH), liver metastasis of colorectal cancer, and noncancerous liver tissues from transplantation donors. The protein levels and localization of the candidate cytokines were analyzed by western blotting and immunohistochemistry. RESULTS: Increased expression of interleukin (IL)-1 receptor antagonist, macrophage migration inhibitory factor, and IL-16 was observed in HCC and paired adjacent non-tumor tissues compared with noncancerous livers. In addition, there were increased IL-16 levels in HCC tissues compared with HH. IL-16 treatment significantly increased cell proliferation in vitro. The expression of extracellular signal-regulated kinase (ERK)1/2 and cyclin D1 was markedly increased in cells from two HCC cell lines, Huh7 and HepG2, in a dose- and time-dependent manner. Phosphorylated to total ERK1/2 ratio was increased in Huh7 cells following IL-16 50 ng/ml, but not HepG2 cells. ERK phosphorylation have occurred earlier than protein accumulation at 48 h. Pretreatment with the ERK inhibitor, FR18024, or an anti-IL-16 antibody reduced the increase in IL-16 production in HCC cells. CONCLUSIONS: These results suggest that cell proliferation induced by IL-16 is mediated through the ERK pathway, thus, we identified a new factor associated with HCC tumor growth.

A Nomogram Model for Predicting the Response to Transcatheter Arterial Embolization in Patients With Symptomatic Hepatic Hemangioma

Background: Transcatheter arterial embolization (TAE) is regarded as an effective treatment for patients with symptomatic hepatic hemangioma. However, few studies have evaluated the efficacy of TAE alone for treating hepatic hemangioma. The aim of this study was to identify the factors that influence the response to TAE and formulate a quantitative nomogram to optimize the individualized management of hepatic hemangioma.Methods: We retrospectively studied 276 patients treated with TAE for hepatic hemangioma at our center from January 2011 to December 2019. The full cohort was randomly divided into training and validation cohorts. After assessing the potential predictive factors for the efficacy of TAE in the training cohort, a nomogram model was established and evaluated by discrimination and calibration.Results: During follow-up, the symptom relief rate was 100%. The tumor blood supply (p < 0.001), tumor number (p = 0.004), and tumor size (p = 0.006) were identified as significant predictors of the failure of tumor shrinkage in response to TAE. The nomogram model showed favorable discrimination and calibration, with a C-index of 0.775 (95% CI, 0.705–0.845) in the training cohort, which was further confirmed in the validation cohort (C-index 0.768; 95% CI, 0.680–0.856). The side effects of TAE were relatively minor and included mainly abdominal pain, nausea, vomiting, fever, and the presence of elevated hepatic transaminases.Conclusion: TAE is a safe and effective treatment for symptomatic hepatic hemangioma. The established nomogram performed well for the estimation of the effect of TAE in patients with hepatic hemangioma and can facilitate the selection of patients who would benefit most from the treatment.

Laennec’s approach for laparoscopic anatomical hemihepatectomy

Background Laennec’s capsule has been found for about 200 years. However, laparoscopic anatomical right and left hemihepatectomy (LARH and LALH) using Laennec’s approach are rarely reported. Methods We retrospectively analyzed the technical details and the surgical outcomes of 15 patients who underwent LAH via Laennec’s approach between May 2017 and July 2020. The operation time, intraoperative blood loss, postoperative complications, and hospital stay were recorded and analyzed. Results Four of 15 patients were diagnosed with hepatic hemangioma, 2 had hepatolithiasis, and 9 patients had primary liver cancer. During the surgery, Laennec’s approach was used for LAH without conversion to open surgery. Four patients were treated with LARH, and 11 patients were cured with LALH. The mean age of the patients was 62.1 ± 6.5 years, and four were male. The mean operative time, blood loss, and length of the postoperative hospital stay were 193 ± 49 min, 247 ± 120 mL, and 8.7 ± 2.0 days, respectively. There was no incidence of postoperative bile leakage and bleeding. No mortality occurred. We also demonstrated that Laennec’s capsule does exist around the peripheral hepatic veins with histological confirmation. Conclusions Laennec’s approach is safe and feasible for LAH. Precise isolation of Laennec’s approach based on Laennec’s capsule helps to standardize the surgical techniques for laparoscopic anatomical hepatectomy.