Contact endoscopy as a novel technique for intra-operative identification of normal pituitary gland and adenoma.

Intraoperative distinction of pituitary adenoma from normal gland is critical in maximizing tumor resection without compromising pituitary function. Contact endoscopy provides a noninvasive technique that allows for real-time in vivo visualization of differences in tissue vascularity. Two illustrative cases of endoscopic endonasal approaches (EEAs) for resection of pituitary adenoma illustrate the use of contact endoscopy in identifying tumor from gland and differentiating a thin section of normal gland draped over the underlying tumor, thereby allowing for safe extracapsular tumor resection. Contact endoscopy may be used as an adjunct for intraoperative, in vivo differentiation of pituitary gland and adenoma. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21199.

Comparison of a Handheld Device vs Endotracheal Tube-Based Neuromonitoring for Recurrent Laryngeal Nerve Stimulation.

OBJECTIVE: To measure the effect of thyroidectomy difficulty on intraoperative neuromonitoring false loss of signal (LOS) and to compare intraoperative endotracheal tube-based neuromonitoring (ETNM) and Checkpoint palpation-based direct stimulation (pDS) signals with postoperative laryngoscopy. We hypothesized that pDS has higher a positive predictive value for postdissection confirmation of recurrent laryngeal nerve function than ETNM and that this difference is accentuated with increasing thyroidectomy difficulty. STUDY DESIGN: Prospective single-arm cross-sectional study comparing ETNM and pDS for patients undergoing hemi-, total, or completion thyroidectomy from July 2018 to March 2020. SETTING: Single-surgeon series at a tertiary care hospital. METHODS: Percentage concordance and positive and negative predictive values were measured. Each thyroidectomy was assigned a validated thyroidectomy difficulty score, and recorded recurrent laryngeal nerve signals were compared with postoperative vocal fold mobility. RESULTS: Percentage concordance was 90.09%. Positive and negative predictive values were 0.19 (95% CI, 0.09-0.31) and 1.0 for ETNM and 0.59 (95% CI, 0.35-0.82) and 1.0 for pDS. The difference in positive predictive value was significant (0.40 [95% CI, 0.33-0.47], P < .001). False LOS rates for ETNM and pDS were 13.19% versus 3.30% (9.89% [95% CI, 1.80%-18.62%], P = .0155), 44.11% versus 0% (44.11% [95% CI, 25.80%-60.54%], P < .001), and 73.33% versus 13.33% (60% [95% CI, 24.76%-78.46%], P = .001) for the second through fourth thyroidectomy difficulty score quartiles, respectively. False LOS with ETNM was linearly correlated with increasing difficulty (R2 = 0.97). CONCLUSION: ETNM was subject to high rates of postdissection false LOS that increased with thyroidectomy difficulty score. pDS is a reliable alternative that has higher positive predictive value than ETNM, particularly in more challenging cases such as those with posteriorly fixed thyroid cancers and fibrotic glands. EVIDENCE LEVEL: 2.

CD147 is increased in HCC cells under starvation and reduces cell death through upregulating p-mTOR in vitro.

Transarterial chemoembolization (TACE) is the standard of care for treatment of intermediate hepatocellular carcinoma (HCC), however, key molecules involved in HCC cell survival and tumor metastasis post-TACE remain unclear. CD147 is a member of the immunoglobulin superfamily that is overexpressed on the surface of HCC cells and is associated with malignant potential and poor prognosis in HCC patients. In this study, using an Earle's Balanced Salt Solution medium culture model that mimics nutrient deprivation induced by TACE, we investigated the regulation of CD147 expression on HCC cells under starvation conditions and its functional effects on HCC cell death. During early stages of starvation, the expression of CD147 was considerably upregulated in SMMC7721, HepG2 and HCC9204 hepatoma cell lines at the protein levels. Downregulation of CD147 by specific small interfering RNA (siRNA) significantly promoted starvation-induced cell death. In addition, CD147 siRNA-transfected SMMC7721 cells demonstrated significantly increased levels of both apoptosis and autophagy as compared to cells transfected with control siRNA under starvation conditions, whereas no difference was observed between the two treatment groups under normal culture conditions. Furthermore, silencing of CD147 resulted in a remarkable downregulation of phosphorylated mammalian target of rapamycin (p-mTOR) in starved SMMC7721 cells. Finally, the combined treatment of starvation and anti-CD147 monoclonal antibody exhibited a synergistic HCC cell killing effect. Our study suggests that upregulation of CD147 under starvation may reduce hepatoma cell death by modulating both apoptosis and autophagy through mTOR signaling, and that CD147 may be a novel potential molecular target to improve the efficacy of TACE.

EMMPRIN regulates tumor growth and metastasis by recruiting bone marrow-derived cells through paracrine signaling of SDF-1 and VEGF.

EMMPRIN, a cell adhesion molecule highly expressed in a variety of tumors, is associated with poor prognosis in cancer patients. Mechanistically, EMMPRIN has been characterized to contribute to tumor development and progression by controlling the expression of MMPs and VEGF. In the present study, by using fluorescently labeled bone marrow-derived cells (BMDCs), we found that the down-regulation of EMMPRIN expression in cancer cells reduces tumor growth and metastasis, and is associated with the reduced recruitment of BMDCs. Further protein profiling studies suggest that EMMPRIN controls BMDC recruitment through regulating the secretion of soluble factors, notably, VEGF and SDF-1. We demonstrate that the expression and secretion of SDF-1 in tumor cells are regulated by EMMPRIN. This study reveals a novel mechanism by which EMMPRIN promotes tumor growth and metastasis by recruitment of BMDCs through controlling secretion and paracrine signaling of SDF-1 and VEGF.

Novel microcatheter-based intracarotid delivery approach for MCAO/R mice.

The intra-arterial (IA) model by microcatheter administration was an effective way to deliver drugs or cells to the brain. All of these models were carried out introduced in rat rather than mice for the difficult and technically challenging due to their small caliber. In 2014, Alejandro Santillan first introduced this model in mice and we found that most of the operational steps were similar with the middle cerebral artery occlusion and reperfusion (MCAO/R) model. We attempted to combine these two techniques into a single model in mice and discovered that this technique was indeed possible. In our work, 12C57Bl/6J male mice were carried on middle cerebral artery occlusion for 60min and then the intra-arterial microcatheter was placed into the internal carotid artery (ICA) from the external carotid artery (ECA). GFP-Luc-Pro labeled mNSCs were infused through the microcatheter and then the blood flow perfusion was reestablished subsequently. The results showed that all 12 mice were carried on successfully the model of middle cerebral artery occlusion, and the placement of the microcatheter and the mNSCs perfusion were completed smoothly without exception. Which means that it is logical to combine the two models into one in order to facilitate studying of stroke. Meanwhile, during the dissection, we found the variation of occipital artery (OA) was noticeable and we classified first time this variation into four categories to attempt to protect the OA.

Epistaxis and pituitary apoplexy due to ruptured internal carotid artery aneurysm embedded within pituitary adenoma.

Epistaxis due to ruptured internal carotid artery (ICA) aneurysm embedded within a pituitary adenoma (PA) has seldom been reported in the literature. Here we want to elaborate the incidence, mechanisms, clinical manifestations, and treatment strategy for this condition. The first survived case of a patient with epistaxis and pituitary apoplexy due to ruptured aneurysm embedded within PA was reported and the literature was reviewed. A 53-year-old male patient presented to our institution with sudden onset epistaxis and progressive vision loss. Neurological examination revealed bilateral ptosis and dilated unresponsive pupils. A CT scan showed a large mass in the pituitary fossa with bony erosion. MRI revealed a large pituitary tumor and abnormal signal intensity in the tumor. No aneurysm was noted during the pre-operative MR angiography. Abundant arterial bleeding suddenly occurred during urgent transsphenoidal surgery. Digital subtraction angiography confirmed the presence of a 14 mm unexpected saccular aneurysm of right ICA in the cavernous sinus with the dome protruding into the sella turcica. Balloon test occlusion of the right ICA was undertaken and permanent occlusion was performed. The patient recovered well and received bromocriptine and thyroid hormone replacement therapy during the follow-up period. At 14-month followup, the patient had no neurological deficits, no features of ischaemia relating to the right ICA therapeutic occlusion. Our case indicated that epistaxis and pituitary apoplexy could be due to the rupture of an ICA aneurysm embedded in a PA. Clinical suspicion should remain high when evaluating any case of epistaxis and pituitary apoplexy. Optimal treatment should take into consideration individual features of the tumor, aneurysm, and patient. Making the correct diagnosis as well as identifying an appropriate management strategy is critical in the care of such patients.