Extended endoscopic endonasal approach for resecting anterior intrinsic third ventricular craniopharyngioma.

Background: The surgical treatment of the extended endoscopic endonasal approach (EEEA) is a safe and effective treatment for suprasellar craniopharyngiomas. However, due to damage to the hypothalamus and third ventricle floor (TVF), EEEA is generally regarded as unsuitable in treating intrinsic third ventricle craniopharyngioma (ITVC) that is entirely within the third ventricle. Until now, there have been only a small number of reports using EEEA to treat TVC via a supra-infrachiasmatic approach. Given that the translamina terminalis (TLT) corridor was used in the transcranial subfrontal approach, EEEA via a suprachiasmatic approach may be feasible and practical to treat ITVC. In the current study, we accumulated experience applying the suprachiasmatic translamina terminalis (STLT) corridor for anterior treatment of ITVC. Methods: From March 2016 to December 2020, 14 patients with ITVC in our center were analyzed retrospectively. All patients underwent surgery by EEEA via an STLT corridor. The multilayer reconstruction technique was adopted to achieve skull base reconstruction. Data concerning the patient's tumor resection, vision, hypophyseal hormone, and complications were collected. Results: Gross-total resection was achieved in 13 (92.8%) of14 patients, with achievement of near-total (90%) resection in the remaining 1 patient. Nine cases (64.3%) were papillary craniopharyngiomas, and the other 5 cases were adamantinomatous subtypes. Postoperatively, 3 patients with pituitary insufficiency received hormone replacement therapy. No permanent diabetes insipidus or hypothalamic obesity was found. All pairs showed significant improvement or stability in vision except 1 patient who encountered visual deterioration. No other neurological deficit occurred postoperatively. Observation results for the exudation of nasal tissue and the length of hospitalization were satisfactory. After a mean follow-up period of 26.2 months, tumor recurrence was not observed. Conclusion: TLT is a minimally invasive corridor used in EEEA for treating anterior ITVC without increasing risks of visual and hormonal deficits. The multilayered reconstruction technique we used is a safe and effective method for achieving watertight closure and avoiding cerebrospinal fluid leaks and infection. The endonasal approach via STLT provides a new, safe and efficacious operative strategy that should be considered a surgical alternative in treating ITVC.

Pseudocapsule-Based Resection for Pituitary Adenomas via the Endoscopic Endonasal Approach.

INTRODUCTION: The endoscopic endonasal approach (EEA) is a safe and effective treatment for pituitary adenomas (PAs). Since extracapsular resection (ER) of PAs improves tumor resection and endocrine remission rates, the interface between the pseudocapsule and gland draws increasing attention. However, it is difficult to precisely dissect the tumor along the exact boundary, and complete removal of the tumor increases the risks of normal tissue damage and cerebrospinal fluid (CSF) leakage. In this study, we investigated the extracapsular resection as well as the pseudocapsule histology to evaluate the effectiveness and safety of pseudocapsule-related surgical interventions. METHODS: From December 2017 to December 2019, 189 patients of PAs via EEA in our single center were analyzed retrospectively. The images, operative details, and clinical follow-up of patients were collected. Sixty-four patients underwent pseudocapsule-based ER, and 125 patients also underwent traditional intracapsular resection (IR) with or without intensive excision for FPAs. The clinical characteristics, tumor resection, endocrinological outcomes, and postoperative morbidities of the two groups were compared. Informed consent for publication of our article was obtained from each patient. Histological examination of pseudocapsule was performed using hematoxylin and eosin and reticulin staining. RESULTS: The gross total recession was 62 (96.9%) in the ER group and 107 (85.6%) cases in the IR group, whereas the endocrine remission rate was 29/31 (93.5%) and 40/53 (75.5%) cases, respectively. Anterior pituitary functions were not aggravated postoperatively in any patient, but transient diabetes insipidus (DI) occurred more in the IR group (64.0%) than in ER (48.4%). Pseudocapsule specimens were obtained in 93 patients, and clusters of small cell aggregation were detected in 11 pseudocapsule specimens (11.8%) whereas other patients showed no remarkable developed pseudocapsule. Intraoperative CSF leak occurred more in the ER group (28.1%) than in the IR group (13.6%), but no difference was seen between two groups postoperatively. No case of intracranial hematoma or pituitary crisis occurred in both groups. After a mean follow-up of 22.8 months, tumor recurrence was observed in 4 (2.1%) cases. CONCLUSION: Pseudocapsule-based extracapsular resection of PAs via EEA is an effective and safe procedure to achieve complete resection with high and sustained endocrine remission and without deteriorating pituitary function.

HER2-targeted recombinant protein immuno-caspase-6 effectively induces apoptosis in HER2-overexpressing GBM cells in vitro and in vivo.

Glioblastoma multiforme (GBM), which is associated with a high rate of morbidity and mortality, is among the most malignant and treatment-refractory neoplasms in human adults. As GBM is highly resistant to conventional therapies, immunotherapies are a promising treatment candidate. HER2 is an attractive target for GBM immunotherapy, as its expression is highly associated with various types of GBM. We previously reported that a novel HER2-targeted recombinant protein e23sFv-Fdt-casp6 has an antitumor effect on HER2-positive gastric cancer cells. In this study, we established a genetically modified Chinese hamster ovary cell line, which produced and secreted e23sFv-Fdt-casp6 proteins. Following specific binding to and internalization into HER2-overexpressing tumor cells, the e23sFv-Fdt-casp6 protein induced tumor cell apoptosis and inhibited the proliferation of HER2-overexpressing A172 and U251MG cells in vitro, but not in U87MG cells with undetectable HER2. The e23sFv-Fdt-casp6 gene was introduced into severe combined immunodeficient mice bearing human glioblastoma xenografts by using intramuscular injections of a liposome-encapsulated vector. The recombinant protein e23sFv-Fdt-casp6 specifically targeted tumor cells and induced apoptosis, thereby leading to potent inhibition of tumor growth and prolonged the survival time of tumor-bearing mice. We concluded that e23sFv­Fdt­casp6 represents a promising HER2-targeted treatment option for human gliomas.

[Imbalance of immunological functions of Treg and TGF-ß1 aggravated cerebral ischemia damage in mice].

AIM: To investigate the changes of proportion of CD4(+);CD25(+); regulatory T cells (Treg) in Splenocytes and concentration of serum TGF-ß1 in diverse period after transient middle cerebral artery occlusion(tMCAO) in mice and correlation between Treg and TGF-ß1, so as to elucidate their roles in the immunological injury of acute ischemic stroke. METHODS: 60 male Kunming mice were randomly divided into six groups, i.e. sham group (24 h, n=10) and five tMCAO groups(ischemia/reperfusion 12 h, 24 h, 48 h, 72 h and 5 d, n=10/group), amount to six groups. The models of tMCAO were established by modified monofilament method; Neurologic deficit score was performed at each time point after tMCAO, and then, to sacrifice mice and measure the volume of cerebral infarction by TTC staining; the expression of Foxp3 in spleen was observed by frozen section and immunofluorescence method; the proportions of Treg in splenocytes were analyzed by flow cytometry(FCM) and the concentrations of serum TGF-ß1 were measured by ELISA. RESULTS: This study observed that there was obvious immunological injury and it was gradually worse. Similarly, TTC staining indicated that the volume of cerebral infarction gradually enlarged and peaked at 48 h following reperfusion, subsequently, exhibited slight decrease. Neurological function gradually improved after reperfusion. There were positive expressions of Foxp3 in the mice spleens and significant different in every groups. FCM indicated, compared with sham group, the percentage of Treg was decrease at 24 h after ischemia/reperfusion (P<0.05), and recovered normal level at 72 h, and significantly increased at 5 d (P<0.05). The level of serum TGF-ß1 also showed the similar tendency, the concentration of serum TGF-ß1 was lower at 24 h after ischemia/reperfusion than sham group, and recovered to sham's level at 48 h, and was significantly higher at 5 d than sham group (P<0.05). Otherwise, there was a positive correlation between serum level of TGF-ß1 and percentage of Treg. CONCLUSION: The levels of Treg and TGF-ß 1 were decrease in the acute period after ischemia/reperfusion, and they were significant increase in the recovery progress, which closely associated with the change of the ischemia volume. Therefore, Imbalance of Treg and TGF-ß1 is very likely to play an important role in the immunological injury of acute ischemic stroke.