Surgical Treatment of Pineal Region Tumors: An 18 year-Experience at a Single Institution.

BACKGROUND: The pineal tumor was once considered as a restricted area for surgery. Such cases are rare, with many different opinions on surgical treatment. This study aimed to review our experience of tumor treatment in the pineal region and explore the optimal treatment strategy. METHODS: The clinical data of 72 patients with pineal tumors from January 1997 to May 2015 (18 years) were retrospectively analyzed. Preoperative preparation, pathology type, tumor resection rate, surgical approach, and follow-up outcomes were used as the indicators to evaluate the treatment efficacy. RESULTS: The Krause approach was used in 46 cases, the Poppen approach in 10 cases, and the transcallosal-lateral ventricle-choroid fissure approach in 16 cases. The postoperative pathological results were as follows: 24 cases of germinoma, 11 of teratoma, 15 of glioma, 6 of meningioma, 11 of Pineocytoma, 2 of cholesteatoma, 2 of cavernous hemangioma, and 1 of choriocarcinoma. Further, the study included 64 cases of total surgical resections, 8 of subtotal resections, and 2 deaths. The follow-up period was from 7 months to 10 years. Further, 51 (70.8%) patients were followed up. The multivariate regression model showed that the surgical method and the pathological type contributed significantly to predicting outcomes. CONCLUSIONS: The type of pathology, extent of excision, and surgical approach had a significant impact on the prognosis of patients. The transcallosal-lateral ventricle-choroid fissure approach for large and medium-sized pineal tumors near the posterior part of the third ventricle had good efficacy.

Anti-P0 Antibody-Conjugated Nanoscale Contrast Agent Targeting the Myelin Sheath for Intraoperative Visible Delineation of Cranial Nerves.

The preservation of cranial nerves is a major problem that surgeons encounter when resecting a tumor in the posterior cranial fossa. Most cranial nerve injuries occur because the tight adhesion between the tumor capsule and cranial nerves renders the nerves indistinguishable. In this study, a nerve-specific nanoscale contrast agent was developed for visually distinguishing cranial nerves from the tumor surface in real time. To enable the contrast agent to specifically bind peripheral nerves, a previously reported biodegradable multiblock polyurethane nanoparticle (BMPU NP) was conjugated with an antibody against myelin protein zero (MPZ, P0), which is expressed on myelin sheaths in peripheral nerve fibers. Coomassie brilliant blue G (CB) was encapsulated into the BMPU NP for visual contrast. The CB-BMPU NP specifically stained mouse peripheral nerve fibers blue when directly applied to the nerve surface ex vivo and in vivo. The CB-BMPU NP also achieved satisfactory visual contrast of the trigeminal nerve in a mouse nerve-tissue adhesion model. This study offers new insights for the development of intraoperatively applied nerve-specific contrast agents for delineating cranial nerves adhered to tumors.

Application of technical strategies for surgical management of adult intrinsic pontine gliomas: a retrospective series.

OBJECT: The authors retrospectively analyzed the surgical treatment of adult intrinsic pontine gliomas in their department, and to enhance the understanding of technical strategies to treat this disease. METHODS: 7 patients with intrinsic pontine gliomas were recruited for this study, between January 2011 and June 2013. All patients underwent preoperative MRI and Diffusion Tensor Imaging Fiber Tracking (DTI-FT). In addition, multimodal Intraoperative Neuromonitoring (IOM) and Intraoperative Neuronavigation were also applied during microsurgery. RESULTS: 7 patients with intrinsic pontine gliomas were treated at the West China Hospital of Sichuan University. Mean age, mean duration of symptoms prior to diagnosis, and mean duration of follow-up average time were 38.0 years, 2.0 months, and 23.4 months, respectively. The main presentations were progressive cranial nerve deficits and long tract signs. Total resection was achieved in 3 patients, subtotal resection in 2, and partial resection in 2. Postoperative pathological examination revealed: astrocytoma (WHO II) in 4 cases, anaplastic oligoastrocytoma (AO, WHO III) in one case, and anaplastic astrocytoma (AA, WHO III) in two cases. Postoperative radiotherapy were administered to all patients, and 4 patients with astrocytoma (WHO II) rejected chemotherapy. After 11-39 months of follow-up, patient symptoms were resolved or stable without aggravation except one patient died because of rapidly progressive glioma at 11 months after operation. MRI in other patients showed residual tumor size to be unchanged or without obviously recurrence. CONCLUSION: Combining preoperative MRI with preoperative DTI-FT, surgery can be better assessed and the operation for adult intrinsic pontine gliomas can be maximally and safely resected with the aid of Multimodal IOMs and Intraoperative Navigation during microsurgery.

Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.

BACKGROUND: Subarachnoid hemorrhage is a common and dangerous disease with an unfavorable prognosis. Patients with poor-grade subarachnoid hemorrhage (Hunt & Hess Grades 4-5) are unconscious on admission. Because of the high mortality and disability rate associated with poor-grade subarachnoid hemorrhage, it is often treated conservatively. Timing of surgery for poor-grade aneurysmal subarachnoid hemorrhage is still controversial, therefore this study aims to identify the optimal time to operate on patients admitted in poor clinical condition. METHODS/DESIGN: Ninety-nine patients meeting the inclusion criteria were randomly assigned into three treatment groups. The early surgery group received operation within 3 days after onset of subarachnoid hemorrhage (day of SAH = day 1); the intermediate surgery group received operation from days 4 to 7, and surgery was performed on the late surgery group after day 7. Follow-up was performed 1, 3, and 6 months after aneurysm clipping. Primary indicators of outcome included the Extended Glasgow Outcome Scale and the Modified Rankin Scale, while secondary indicators of outcome were assessed using the Barthel Index and mortality. DISCUSSION: This is the first prospective, single-center, observer-blinded, randomized controlled trial to elucidate optimal timing for surgery in poor-grade subarachnoid hemorrhage patients. The results of this study will be used to direct decisions of surgical intervention in poor-grade subarachnoid hemorrhage, thus improving clinical outcomes for patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-12002917.

[Microsurgical management of adult brainstem gliomas under the DTI and intraoperative nuclei mapping: a retrospective analysis of 19 cases].

OBJECTIVE: To explore the role of DTI-Tractography and intraoperative nuclei mapping in microsurgery of adult brainstem gliomas. METHODS: Nineteen patients with adult brainstem gliomas were recruited for this study in our hospital from 2010 to 2012. The role of DTI-Tractography and intraoperative nuclei mapping in the microsurgery was retrospectively reviewed. RESULTS: Two patients underwent almost total resection, while 11 patents underwent subtotal resection and 6 patients underwent partial resection. Neurological functions improved or remained stable in 14 patients (73.7%) after surgery; whereas, 5 patients (26.3%) experienced deteriorated or transitory new symptoms. Follow-up visits found that 17 patients (89.5%)had improved or stable neurological functions. CONCLUSION: DTI-Tractography and intraoperative nuclei mapping provides great support to the choice of surgical approach and the determination of degree of resection. It helps achieve maximal safe resection of adult brainstem gliomas.

Von Hippel-Lindau disease manifesting disseminated leptomeningeal hemangioblastomatosis: surgery or medication?

We report the case of a 46-year-old man with von Hippel-Lindau (VHL) disease, manifesting disseminated leptomeningeal hemangioblastomatosis. The patient initially presented with a solitary hemangioblastoma in the right cerebellum. Later, he was diagnosed with VHL disease and underwent several surgical procedures in the following 14 years. But the prognosis was poor. Recently, the hemangioblastomatosis disseminated along leptomeninges involving both brain and spine. We aim to analyze the possible reason for the leptomeninges dissemination, discuss the imaging characteristics of this rare disease with ominous manifestation and propose the optimal strategy for treatment. We think the optimal treatment strategy should be surgical biopsy and surgical decompression. A long-term follow-up is inevitable. Antiangiogenic medication might be the hope for remission of this disease.

[Expression of CXCR4 and VEGF in hemangioblastomas of the central nervous system and its relation to tumor angiogenesis].

OBJECTIVE: To evaluate the relationships of CXCR4 (chemokine stromal cell-drived factor-1 receptor) and VEGF (vaseular endothelial growth factor) expression to tumor angiogenesis in hemangioblastomas of the central nervous system. METHODS: The protein expressions of CXCR4 and VEGF were detected by SP immunohistochemical staining in 40 hemangioblastomas. The endothelial cells of blood vessels within the tumor were labeled by CD34, then the microvessel density (MVD) was calculated. RESULTS: Total positive expression rates of CXCR4 and VEGF were 95% (38/40) and 85% (34/40) respectively. The expression rates of CXCR4 and VEGF were found positive obviously in hemangioblastomas compared with the normal cerebellar tissues (P < 0.01). CXCR4 expression was located in the nucleus of tumor stromal cells. VEGF expression was located in the cytoplasm and membrane of tumor stromal cells and some endothelial cells. VEGF has significant positive correlation with the expression level of CXCR4 (r = 0.704, P <0.001). MVD also has significant positive correlation with the expression level of CXCR4 and VEGF (P < 0.001). But there is no significant difference between the cystic and solid tumors, VHL disease and sporadic disease on the expression level of CXCR4, VEGF and MVD (P > 0.05). CONCLUSION: CXCR4 and VEGF may collaborate to induce angiogenesis in hemangioblastomas.

Microsurgery via modified far-lateral approach for giant dumbbell-shaped jugular foramen tumors.

BACKGROUND AND OBJECTIVE: During the resection of jugular foramen tumors via the basic far lateral approach, the jugular foramen tumor area as well as its adjacent structures, especially the intracranial part, can be better exposed, which avoids stripping of the petrous part of temporal bone and displacement of facial nerve, and protects the patient's hearing from damage. However, when applied in tumors developed from ventral to the brain stem and middle fossa, with extracranial tumors, this surgical approach seems to be inadequate and limited. This study was to explore the microsurgical technique and clinical value for treating giant dumbbell-shaped tumors at jugular foramen (JF) via a modified far lateral approach. METHODS: A retrospective analysis was performed in 16 patients with huge dumbbell-shaped tumors at JF which were removed through the modified far lateral approach (suboccipital transjugular-jugular tubercle-jugular process) between January 2001 and December 2008. The process of operation, and pre-and postoperative clinical data were included in the analysis. RESULTS: Gross total tumor removal was achieved in 14 cases, subtotal removal in 1 case, and partial removal in 1 case. Follow-up examinations in most patients demonstrated that the patient with an obvious preoperative deficit had a good recovery. During the follow-up from three months to seven years, 10 (76.9%) cases with lower cranial nerve involvement showed obvious improvement of symptom after operation, 8 (80.0%) cases with facial palsy obtained various degrees of alleviation, and 7 (77.8%) cases with hearing impairment at different levels restored hearing. Two patients developed new lower cranial nerve palsies after operation, and underwent functional rehabilitation in the three-month follow-up. CONCLUSIONS: Modified far lateral approach is helpful for removing the huge tumors at JF, especially for tumors extending to the petroclival region ventral part of pontomedullary junction. It has a higher rate of total resection, preoperative cranial nerve function impairment is expected to restore, and also has the advantage of protecting the facial nerve, labyrinth and vertebral artery structure from unnecessary damage.

Experience of microsurgical treatment of brainstem cavernomas: report of 37 cases.

BACKGROUND: Cavernomas are rare in the brainstem and account for 18-35% of central nervous cavernomas and can cause recurrent hemorrhages, devastating neurological deficits and mortality. OBJECTIVES: To summarize the experience of microsurgical treatment of brainstem cavernomas and to investigate curative effect of microsurgical treatment of brainstem cavernomas. MATERIALS AND METHODS: A retrospective analysis clinical data of 37 patients with brainstem cavernomas seen between 2003 and 2007. The analysis included age distribution, hemorrhage rates, clinical presentation, location of the lesions, and preoperative and postoperative Karnofsky Performance Scale (KPS) scores. The surgical indications, the timing of surgery and the surgical techniques were also assessed. RESULTS: All the 37 patients received microsurgical resections, there was no surgery-related mortality. Histopathological examination confirmed the diagnosis of cavernoma. Postoperatively, 20 patients had functional improvement, 15 patients had no change in the neurological status, and two patients deteriorated. Early surgery was associated with better outcomes. Mean followed up period was 21.5 months (range 6-36 months). During the follow-up 20 patients had resumed activities of daily living (KPS scores of 90-100), 10 patients were able to self-care with some efforts (KPS scores of 70-80), five patients needed considerable assistance (KPS score of 50-60) and two patients suffered hemiparesis (KPS scores of 40). None of the patient had recurrent hemorrhage. CONCLUSIONS: Brainstem cavernomas can safely be resected. Successful resection of brainstem cavernomas can be achieved by optimal surgical approaches, feasible entry zone and meticulous microsurgical techniques. The goal of surgical intervention should be the total resection of the lesion without any deteriorative in the neurological deficits.

[Expression of CD147 and MMP-2 in human gliomas and its correlations with prognosis].

OBJECTIVE: To investigate the expressions of CD147 and MMP-2 in human gliomas and to study the relationship between their expression and prognosis. METHODS: Immunohistochemistry SP methods were applied to detect the expression of CD147 and MMP-2 in 50 cases of gliomas and RT-PCR also applied to analyze the expression level of CD147 mRNA. The relationship between the expression level and the glioma prognosis were analyzed statistically depends on the follow-up investigation of the disease development. RESULTS: The positive rates of CD147 and MMP-2 in human gliomas were 72. 0% and 78. 0%, and coexpression of CD147 and MMP-2 in gliomas was 70. 0%. CD147 protein was positively correlated with the expression of MMP-2 protein (r =0. 737, P<0. 01). CD147 mRNA expression was also detected in low and high grade gliomas by RT-PCR, but their expression levels were obviously enhanced in high grade gliomas. There was a significant difference in each grade gliomas. The higher expression of CD147, the shorter survival time of the patients. The variations were significant statistically. CONCLUSION: There was positive correlation between the expressions of CD147, MMP-2 in human gliomas and the degree of malignancy and prognosis. CD147 and MMP-2 may be a prognostic factor of human gliomas and targets for chemotherapeutical strategies.

[An experimental research on tumor metastasis treated by chicken homologous matrix metalloproteinase-2 vaccine combined with low-dose cisplatin].

OBJECTIVE: To evaluate the cooperating effect on whether the chicken homologous matrix metalloproteinase-2 (c-MMP-2) vaccine combined with low-dose cisplatin (DDP) can enhance the treatment efficacy of tumor metastasis. METHODS: The eukaryotic expression plasmid encoding chicken homologous MMP-2 was constructed by recombinant DNA technique. In this experiment, the lung metastasis model of murine colon adenocarcinoma (C26) was established in 6- to 8- weeks of age female BALB/c mice, and then treated with 0.9% NaCl solution (NS), DDP, c-MMP-2, or c-MMP-2 combined DDP. The number of tumor metastasis nodules on murine lung surface was counted and the lungs were weighed after the completion of above treatments. The tumor microvessel density (MVD) and cell apoptosis were evaluated by immunohistochemical and TUNEL methods. The titer and type of autoantibodies against MMP-2 in serum of mice were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with three other control groups, the combined treatment group significantly decreased the number of tumor metastasis nodules on lung surface and markedly the weight of murine lungs. The immunohistochemical analysis of tumor demonstrated a decreased MVD and a higher apoptosis cell rate happening to the combined treatment group. Autoantibodies against MMP-2 in serum of mice were, by ELISA, found in c-MMP-2 group and c-MMP-2 combined DDP group. CONCLUSION: The antitumor effect of DDP can be potentiated by c-MMP-2. Thus the combination of c-MMP-2 and DDP results in an additive effect on the treatment of tumor metastasis.