Autologous parathyroid gland in left-brachioradialis transplantation: A single-center study and long-term follow-up.

Parathyroid gland transplantation into the sternocleidomastoid muscle is effective, but it is not possible to confirm transplant survival with this method. In this study, we evaluated parathyroid autotransplantation into the brachioradialis muscle and its survival rate. OBJECTIVES: To evaluate autologous parathyroid gland left forearm brachioradial muscle transplantation and its survival rate. SUMMARY BACKGROUND DATA: The most commonly used transplantation site is the sternocleidomastoid muscle, but transplant survival cannot be confirmed using this method. Autologous parathyroid gland left forearm brachioradial muscle transplantation solves this problem, and we evaluate the transplant survival using this method. METHODS: We followed-up patients who underwent thyroidectomy and autologous parathyroid left forearm brachioradial muscle transplantation in our center from September 2013 to January 2018. The last follow-up date was January 2021; all enrolled patients underwent at least 3 years of follow-up. We calculated the transplant survival rate at several time points. RESULTS: We evaluated 238 transplanted cases, for which the long-term survival rate was 85.7% (204/238), and the short-term survival rate was 86.1% (205/238). Sixty-five cases had two parathyroid glands transplanted into the left forearm brachioradialis muscle. The long-term survival rate was 92.3% (60/65), and the short-term survival rate was 95.4% (62/65). CONCLUSIONS: Autologous parathyroid gland left brachioradialis transplantation is a reliable, measurable method with good survival rate, and we recommend this method for consideration for transplanting parathyroid glands in thyroidectomy.

LXR activation potentiates sorafenib sensitivity in HCC by activating microRNA-378a transcription.

Sorafenib resistance is a major obstacle to the treatment of advanced hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) are multifunctional regulators of gene expression with profound impact for human disease. Therefore, better understanding of the biological mechanisms of abnormally expressed miRNAs is critical to discovering novel, promising therapeutic targets for HCC treatment. This study aimed to investigate the role of miR-378a-3p in the sorafenib resistance of HCC and elucidate the underlying molecular mechanisms. Methods: A novel hub miR-378a-3p was identified based on miRNA microarray and bioinformatics analysis. The abnormal expression of miR-378-3p was validated in different HCC patient cohorts and sorafenib-resistant (SR) HCC cell lines. The functional role of miR-378a-3p and its downstream and upstream regulatory machinery were investigated by gain-of-function and loss-of-function assays in vitro and in vivo. Interactions among miR-378a-3p, LXRα, and IGF1R were examined by a series of molecular biology experiments. Then, the clinical relevance of miR-378a-3p and its targets were evaluated in HCC samples. HCC patient-derived xenograft (PDX) model was used to assess the therapeutic value of LXRα and its downstream miR-378a-3p. Results: miR-378a-3p expression was frequently reduced in established sorafenib-resistant HCC cell lines. The decreased miR-378a-3p levels correlated with poor overall survival of HCC patients following sorafenib treatment. miR-378a-3p overexpression induced apoptosis in SR HCC cells, whereas miR-378a-3p silencing exerted the opposite effects. IGF1R was identified as a novel target of miR-378a-3p. Furthermore, the primary miR-378 level was not consistent with its precursor miRNA level in SR HCC cells, which was attributed to the downregulation of exportin5 (XPO5) and subsequently reduced nuclear export of precursor miR-378 and restrained maturation of miR-378-3p. In this context, we combined an agonist GW3965 of liver X receptor alpha (LXRα), which functioned as a transcription activator of miRNA-378a, and its activation re-sensitized sorafenib-resistant cells to sorafenib treatment in vitro and in vivo. Conclusions: Our finding suggested decreased expression of XPO5 prevents maturation of miR-378a-3p, which leaded to the overexpression of IGF-1R and counteracted the effects of sorafenib-induced apoptosis. LXRα was able to activate miRNA-378a-3p transcription in HCC cells and could be a potential combinable treatment strategy with sorafenib to suppress HCC progression.

Perioperative outcomes comparing laparoscopic with open repeat liver resection for post-hepatectomy recurrent liver cancer: A systematic review and meta-analysis.

BACKGROUND: Repeat laparoscopic hepatectomy (LRH) offers an option for recurrent tumors in liver remnants following an initial liver resection of recurrent hepatocellular carcinoma (HCC), colorectal liver metastasis (CRLM) and cholangiocellular carcinoma (CCC), showing advantages in some outcomes. The objective of the study was to evaluate the feasibility, safety, and potential benefits of LRH in comparison with repeat open hepatectomy (ORH) for recurrent liver cancer. METHODS: A systematic review was performed in compliance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) and AMSTAR (Assessing the methodological quality of systematic reviews) guidelines. We performed a systematic search of PubMed, Embase, Cochrane Library, and Web of Science to identify studies that compared LRH with ORH from inception to September 30, 2019. Outcomes of interest included operation time, intraoperative estimated blood loss, length of hospital stay, complication rate, transfusion and R0 resection rate. The protocol was registered with the PROSPERO register of systematic reviews. RESULTS: 10 retrospective observational studies were suitable for this analysis, involving 767 patients with 334 undergoing LRH (43.5%) and 433 undergoing ORH (56.5%). Compared with ORH, LRH had less intraoperative blood loss (SMD = -1.03; 95% CI: 1.48~-0.59, P < 0.001), less overall postoperative complications (OR = 0.40; 95% CI: 0.16-0.99, P = 0.048), less major complications (OR = 0.31, 95% CI: 0.15-0.62, P = 0.001), shorter hospital stay (SMD = -0.98; 95% CI: 1.41~-0.54, P < 0.001) and higher R0 resection rate (OR = 2.30, 95% CI: 1.39-3.81, P = 0.001). It was comparable in operation time (WMD = -7.66; 95% CI: 52.50-37.19, P = 0.738), transfusion rate (OR = 0.33; 95% CI:0.11-1.05, P = 0.060), and mortality (OR = 0.76; 95% CI: 0.27-2.18, P = 0.615) between LRH and ORH. CONCLUSION: Our results indicate that LRH is a safe and effective technique. Benefits, especially less intra-operative blood loss, less complications rate, shorter hospital stay and higher R0 resection, might be offered in the laparoscopic approach.

CYP450-mediated mitochondrial ROS production involved in arecoline N-oxide-induced oxidative damage in liver cell lines.

BACKGROUND: IARC has classified the betel nut as a human environmental carcinogen. Previous studies have found that arecoline (AR) is the major alkaloid present in the saliva of betel quid chewers. Saliva contains a large content of AR which has been further shown to cause mutation of oral mucosa cells, resulting in oral cancer. Whereas, to date, there are only few studies reported the hepatotoxicity associated with arecoline and betel nut chewing. Therefore, the main purpose of this study was to determine the toxic effects of AR and its oxidative metabolite, arecoline N-oxide (ARNO), in normal liver cell lines. METHODS: The cytotoxic, genotoxic, and mutagenic effects were detected by crystal violet staining, alkaline comet assay, and Salmonella mutagenicity test, respectively. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2-DCFDA assay. RESULTS: Our results demonstrated that ARNO exerted higher cytotoxicity, DNA damage, and mutagenicity than its parent compound arecoline in liver cells. Antioxidants, such as N-acetylcysteine, Trolox, and penicillamine, strongly protected liver cells from ARNO-induced DNA damage and ROS production. Furthermore, co-treatment with Mito-TEMPO also effectively blocked ARNO-induced ROS production in liver cells. Besides antioxidants, co-treatment with 1-aminobenzotriazole and methimazole nearly completely suppressed ARNO-induced ROS production in liver cells. CONCLUSIONS: Our data suggest that arecoline ingested from the habit of chewing betel quid can be primarily oxidized to ARNO, thereby enhancing its toxicity through increased ROS production. Considering the excellent protective effects of both mitochondria-targeted antioxidant and CYP450 inhibitor on ARNO-induced ROS production in liver cells, mitochondria CYP450-mediated metabolism of ARNO may be a key mechanism. Collectively, our results provide novel cellular evidence for the positive connection between habitual betel quid chewing and the risk for liver damage.