Recurrent laryngeal nerve (RLN) injury is an intractable complication of thyroidectomy. Intraoperative nerve monitoring (IONM) was designed to prevent RLN injury. However, the results concerning the protective effect of IONM on RLN injury are still controversial. We searched all eligible databases from 1980 to 2017. Meta-analysis was performed to evaluate the effect of IONM on RLN injury. Sensitivity analysis was also conducted to check the stability of our results. There were 34 studies included in the analysis. Overall analysis found a significant decrease in total injury (RR = 0.68, 95%CI: 0.55 to 0.83), transient injury (RR = 0.71, 95%CI: 0.57 to 0.88), and permanent injury (RD = −0.0026, 95%CI: −0.0039 to −0.0012) with IONM. Subgroup analysis found IONM played a preventive role of total, transient and permanent injury in patients undergoing bilateral thyroidectomy. IONM also reduced the incidence of total and transient injury for malignancy cases. Operations with IONM were associated with fewer total and transient RLN injuries in operation volume < 300 NARs per year and fewer total and permanent RLN injuries in operation volume ≥ 300 NARs per year. The application of IONM could reduce the RLN injury of thyroidectomy. Particularly, we recommend routine IONM for use in bilateral operations and malignancy operations.

IntroductionPostoperative hypocalcemia is the most common complication of thyroidectomy. Incidental parathyroidectomy (IP) was thought to be associated with postoperative hypocalcemia. However, according to previous studies, the risk factors and clinical outcomes of IP remain controversial.MethodsEligible studies were searched in databases including PubMed, Web of Science, and EMBASE from January 1990 to September 2017. Articles focusing on the relationship between IP and postoperative hypocalcemia were included. The risk of publication bias was assessed using Begg’s test and Egger’s regression asymmetry test. Pooled analysis was performed to evaluate the effect of IP on postoperative hypocalcemia and related risk factors. Sensitivity analysis was also conducted to test the stability of our results. The effects of hypocalcemia type, permanent definition, IP incidence, total thyroidectomy, and malignancy operation were also examined using a further subgroup analysis.ResultsThirty-five studies were finally included in the analysis after an exhaustive literature review. Pathology data demonstrate that incidental parathyroidectomy occurred in various locations: intrathyroidal (2.2–50.0%), intracapsular (16.7–40.0%) and extracapsular (15.7–81.1%) regions. Overall, the analysis found that malignancy (RR = 1.60, 95% CI: 1.27 to 2.02; p< 0.0001), central neck dissection (RR = 2.35, 95% CI: 1.47 to 3.75; p = 0.0004), total thyroidectomy (RR = 1.42, 95% CI: 1.20 to 1.67; p< 0.0001) and reoperation (RR = 1.81, 95% CI: 1.20 to 2.75; p = 0.005) were significant risk factors of IP in thyroid surgery. There was an obvious effect of IP on temporary/permanent (RR = 1.59, 95% CI: 1.37 to 1.84; p< 0.0001) and permanent (RD = 0.0220, 95% CI: 0.0069 to 0.0370; p = 0.0042) postoperative hypocalcemia. Sensitivity analysis showed that these results were robust. The subgroup analysis found that IP played a significant role in both biochemical and clinical hypocalcemia in thyroidectomy (p < 0.0001 and p = 0.0003, separately). The association of IP and permanent hypocalcemia using different definitions (6 months or more than 12 months) was also confirmed by the analysis. IP increased the incidence of temporary/permanent and permanent hypocalcemia for cases undergoing total thyroidectomy (40.4% vs 24.8% and 5.8% vs 1.4%, respectively). Thyroidectomy with IP was associated with more permanent hypocalcemia (RR = 3.10, 95% CI: 2.01 to 4.78; p< 0.0001) in malignant cases but was not associated with temporary/permanent hypocalcemia.ConclusionsMalignancy, central neck dissection, total thyroidectomy and reoperation were found to be significant risk factors of IP. IP increases the risk of postoperative hypocalcemia after thyroidectomy. We recommend a more meticulous intraoperative identification of parathyroid gland in thyroidectomy to reduce IP, particularly for total thyroidectomy and malignancy cases.

Sorafenib (SORA), a multi kinase inhibitor, is the standard first-line targeted therapy approved by the Food and Drug Administration for advanced hepatocellular carcinoma (HCC). However, emerging evidence from clinical practice indicates that SORA alone has only moderate antitumor effects and could not completely inhibit the progression of the disease. Therefore, it is very necessary and urgent to develop novel combination therapy to improve the clinical outcomes of SORA. The pharmacological study on the chemosensitizing effects of natural products has become a hotspot in recent years, which is commonly thought to be a potential way to improve the effectiveness of drugs in clinical use. Berbamine (BBM) has potential sensitizing effects in multiple chemotherapies and target therapy. However, it remains unclarified whether the combination of BBM and SORA as a treatment could exert a synergistic effect on HCC cell lines. In this study, we first investigated whether BBM can increase the sensitivity of HCC cell lines to SORA. The results revealed that the combination of BBM and SORA could synergistically inhibit the growth of two HCC cell lines and promoted their apoptosis. Mechanistically, our results showed that BBM exerted a dose-dependent inhibitory effect on the basal and IL-6-induced STAT3 activation of HCC cell lines. In addition, the combined treatment of BBM and SORA synergistically suppressed STAT3 phosphorylation at Tyr705 and knockdown of STAT3 abolished the sensitization effect of BBM, indicating that BBM’s sensitization effect is mainly mediated by its inhibition of STAT3. These findings identify a new type of natural STAT3 inhibitor and provide a novel approach to the enhancement of SORA efficacy by blocking the activation of STAT3.

PurposeControversies exist for which treatment is optimal for early hepatocellular carcinoma (HCC): radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT). We compared outcomes between treatments as first-line therapy for HCC patients measuring up to 5 cm or different cancer risk groups.Patients and methodsThe Surveillance, Epidemiology, and End Results database was retrieved for HCC patients treated with RFA, SR, or LT between 2004 and 2015. The effects of three treatments were compared using propensity score, inverse probability of treatment weights adjustment, and instrumental variable analysis for overall survival (OS) and competing risks regression models for disease-specific survival (DSS). We also evaluated whether the effect of treatments varied according to baseline clinical characteristics by locally weighted regression method.ResultsOf 7664 patients, RFA and SR yielded worse OS (HR 1.67, CI 1.43–1.70, P<0.001; HR 1.43, CI 1.40–1.67, P<0.001) and DSS (HR 2.00, CI 1.10–3.30, P<0.011; HR 2.50, CI 2.00–3.30, P<0.001) than LT. In patients with small tumors, SR may confer more survival benefits than RFA (HR>1) for different tumor sizes measuring up to 5 cm and may be an appropriate first-line treatment. Additionally, RFA has more survival benefits compared with SR (HR 0.83, CI 0.53–1.25) for those patients with low tumor risk and good general health condition (without any prognostic risk factors). However, those patients with a predicted 5-year overall mortality risk >30% seem to benefit more for SR than RFA.ConclusionDue to a shortage of donors, RFA and SR can be applied as either primary management of HCC or as a bridging therapy for LT. Furthermore, SR is an effective option for patients with different HCC tumor size. However, RFA could achieve comparable survival benefits with SR for patients without any risk factors.

PurposeLangerhans cell histiocytosis (LCH) is a rare clonal disorder of Langerhans antigen-presenting cells. However, thyroid LCH involvement is relatively rare. We present the first case of spontaneous thyroid hemorrhage due to LCH progression and discuss the clinical features, diagnosis, and treatments of thyroid LCH in a literature review.MethodsClinical data were collected. Previously published articles on thyroid LCH involvement were reviewed to assess the clinical features, diagnosis, and treatments for thyroid LCH.ResultsA 54-year-old female presented with a multi-system LCH, affecting the uterus, liver, pituitary gland, and thyroid gland. Clinical stability was achieved after systemic chemotherapy. After 7 years of regular follow up, the patient complained of a sudden painful neck swelling and progressive dyspnea. Computed Tomography revealed bilateral goiter with hematoma, and the patient was diagnosed with spontaneous thyroid bleeding based on her clinical symptoms and radiological findings. The patient was incubated to relieve airway compromise and partial thyroidectomy was performed for definitive treatment. Pathological evaluation further confirmed the diagnosis of thyroid LCH. The patient recovered well after surgery.ConclusionSpontaneous thyroid bleeding due to thyroid LCH progression is extremely rare. Treatments for LCH vary depending on the severity of the disease. We suggest that, for patients with multi-system LCH with thyroid lesion, long-term active surveillance of thyroid hormone concentrations, and thyroid gland volume is required. Physicians should be alert of the potentially life-threatening spontaneous thyroid hemorrhage when aggravated diffuse goiter and hypothyroidism appear. Further investigation is required to establish the guidelines for thyroid LCH treatment.