Adaptation to hypoxia and consequent pro-inflammatory gene expression of prostate and breast carcinomas have been implicated in the progression toward cancer malignant phenotype. Only partial data are available for the human tumor glioblastoma multiforme (GBM). The aim of our study was to analyze the hypoxic and pro-inflammatory microenvironment in GBMs and to demonstrate that in a stem/progenitor cell line derived from human glioblastoma (GBM-SCs), hypoxia activates a coordinated inflammatory response, evidencing an invasive and migratory phenotype. From each of 10 human solid glioblastomas, clinically and histopathologically characterized, we obtained three surgical samples taken from the center and the periphery of the tumor, and from adjacent host normal tissue. Molecular and morphological analyses were carried out using quantitative real-time PCR and western blot (WB). GBM stem and differentiated cells were incubated under hypoxic conditions and analyzed for pro-inflammatory gene expression and for invasive/migratory behavior. A panel of selected representative pro-inflammatory genes (RAGE and P2X7R, COX2, NOS2 and, PTX3) were analyzed, comparing tumor, peritumor and host normal tissues. Tumors containing leukocyte infiltrates (as assessed using CD45 immunohistochemistry) were excluded. Selected genes were overexpressed in the central regions of the tumors (i.e. in the more hypoxic areas), less expressed in peripheral regions, and poorly expressed or absent in adjacent normal host tissues. Western blot analysis confirmed that the corresponding pro-inflammatory proteins were also differently expressed. Hypoxic stem cell lines showed a clear time-dependent activation of the entire panel of pro-inflammatory genes as compared to differentiated tumor cells. Biological assays showed that invasive and migratory behavior was strengthened by hypoxia only in GBM stem cells. In human solid glioblastoma we have observed a coordinated overexpression of a panel of pro-inflammatory genes as compared to host normal tissue. We have also evidenced a similar pattern of overexpressed genes in GBM-SCs after hypoxic treatment, showing also a gain of invasive and migratory function that was lost when these stem cells differentiated. We suggest that, as has been previously described for prostatic and mammary carcinoma, in human glioblastoma acquisition of a proinflammatory phenotype may be relevant for malignant progression.
26 November 2021 in European Journal of Orthopaedic Surgery & Traumatology
Background: Normal pressure hydrocephalus (NPH) is characterized by the triad of dementia, gait disturbance and urinary incontinence, all potentially reversible following a ventriculoperitoneal shunt (VPS). This study aims to evaluate the clinical outcomes of shunting in normal pressure hydrocephalus following a new standardized protocol. Methods: This study is designed according to the STROBE guidelines. Demographical, clinical, surgical and radiological data were collected from May 2015 to November 2019. Gait, balance and incontinence data based on the NPH European scale were collected before and after one, six and twelve months of treatment with a VPS. Clinical symptoms and changes of the stoke volume, measured on phase-contrast MRI, were used to evaluate improvement after VPS surgery. Results: One hundred and eighty-one consecutive patients met the inclusion criteria. The mean age was 73.1 years (59–86) and mean follow-up was 38.3 months (13–50). The gait (58.5 ± 14.3 to 70.1 ± 13.4, p < 0.001), the balance (66.7 ± 21.5 to 71.7 ± 22.1, p = 0.001), continence domain (69.9 ± 20.5 to 76 ± 20, p = 0.002) scores and neuropsychological scales showed a statistically significant improvement over the follow-up. The overall improvement after 12 months was present in 91.2% of patients. An overall complication rate of 8.8% and a reoperation rate of 9.4% were recorded, respectively. Conclusions: Surgical treatment by VPS for NPH improves symptoms in most patients, when accurately selected. A standardized protocol and a multidisciplinary team dedicated to this disorder is needed to achieve an early and correct diagnosis of NPH. Follow-up with stroke volume measurement is a valuable tool for the early diagnosis of shunt malfunction or the need for valve adjustment.
24 December 2020 in American Journal of Neuroradiology
BACKGROUND: Endovascular treatment of blister aneurysms is a promising approach, even though they are vascular lesions challenging to treat due to their angioarchitectural characteristics. PURPOSE: Our aim was to investigate clinical and radiologic outcomes after endovascular treatment of ruptured blister aneurysms. DATA SOURCES: PubMed, Ovid MEDLINE, Ovid EMBASE, Scopus, and the Web of Science were screened. STUDY SELECTION: We performed a comprehensive review of the literature from 2010 to 2019 reporting series of patients with blister aneurysms treated with an endovascular approach. DATA ANALYSIS: Event rates were pooled across studies using a random effects meta-analysis. DATA SYNTHESIS: A total of 32 studies reporting on 684 patients (707 aneurysms) were included. Stent placement, stent-assisted coiling, and flow diversion were the most commonly described treatments (282, 256, and 155 patients, respectively). The long-term complete occlusion rate was 76.9% (95% CI, 69.2%–83.9%). The perioperative complication rate was 8.9%, and clinical outcome at final follow-up was mRS <2 in 76.6% (95% CI, 68.2%–84.2%) of patients. The mortality rate was 4.7% (95% CI, 2.30%–7.80%). Among the different techniques, stent-assisted coiling is the one that had the higher rate of immediate occlusion (63.4%); however, the occlusion rate at the final follow-up was comparable among the different techniques. LIMITATIONS: Different techniques were described and data were reported in a nonhomogeneous way, possibly representing a bias in the present study. CONCLUSIONS: This study suggests that endovascular treatment of blister aneurysms is associated with good long-term occlusion rates and reasonable complication and mortality rates. There is no consensus on the best endovascular techniques in blister aneurysm management.
Background: Radiological evidence of adjacent segment disease (ASD) has been reported to have a prevalence of more than 30% and several risk factors have been reported. The aim of this study is to evaluate the clinical and radiological outcomes of patients with symptomatic ASD treated with stand-alone OLIF and compare results with a posterior revision surgery cohort. Methods: This is a retrospective case-control study. Clinical-patient-reported outcomes were obtained at preoperative, postoperative and final follow-up visits using the Short Form (SF-36) scale, the Oswestry Disability Index (ODI) and the visual analog scale (VAS). Radiological measures include lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence-lumbar lordosis (PI-LL) mismatch, segmental coronal Cobb angle and intervertebral disc height (DH). The data are compared with a retrospective series of patients that underwent a posterior revision surgery for ASD. Results: Twenty-eight patients in the OLIF group and 25 patients in the posterior group meet inclusion criteria. The mean ages at the time of the surgery are 65.1 years and 67.5, respectively. The mean follow-up time is 36.1 months (range of 14–56). The clinical outcomes significantly improve from preoperative values from the surgery in both groups. The radiological parameters are significantly improved postoperatively and were maintained at the last follow-up in both groups. A statistically significant difference is observed between the two groups for minor complication rate, length of surgery, blood loss and DH restoration. Conclusions: Stand-alone OLIF is an effective and safe technique with low morbidity and complication rates for the treatment of selected patients with symptomatic ASD following a previous lumbar fusion.
9 March 2018 in Journal of Neurological Surgery Part A: Central European Neurosurgery
Background and Study Objective In surgery for gliomas and brain metastases, preservation of neurologic functions is essential to ensure a good quality of life and the eligibility for adjuvant therapies. This article assesses which factors could influence the functional outcome in patients with lesions located in the motor pathways. Materials and Methods A total of 92 patients with gliomas and metastases involving the motor pathways were studied for concerns regarding quality of life (Karnofsky performance status [KPS] and modified Rankin scale [mRS]) before and after surgical treatment supported by intraoperative neuromonitoring. Patient-related, surgery-related, and lesion-related data were recorded to identify the relationships with postoperative performance status. The relationship between lesions and the corticospinal tract were investigated with preoperative magnetic resonance imaging sequences and tractographic reconstructions. Results Means of preoperative mRS and KPS were 1.91 ± 1.34 and 80.8 ± 20, and at 30 days postoperatively they were 1.93 ± 1.63 and 79.8 ± 24.4, respectively. The better preoperative performance status was a predictor of better outcome in terms of quality of life. Gender showed a statistical association with ∆KPS (p = 0.033) and ∆mRS (p = 0.031). A recurrent lesion was a predictor of poor functional outcome (p= 0.045 for KPS at 30 days).A left-sided lesion showed a statistical association with a lesser improvement with respect to right sided. Complications were associated with a lesser functional improvement (∆mRS, ∆KPS, and clinical improvement: p = 0.001, p = 0.006, and p = 0.003, respectively). Hemorrhagic complications were associated with the worst functional prognosis. Conclusions In our experience, factors associated with worse functional prognosis and quality of life were a poor preoperative performance status, female gender, operating on a recurrent lesion, involvement of the left corticospinal tract, and surgical or medical postoperative complications.