The role of surgery in intracranial PCNSL

This aimed to evaluate the effect of surgery for overall survival (OS) and progression-free survival (PFS) in intracranial primary CNS lymphoma (PCNSL) of all patients diagnosed at a single center. A prospective database at Oslo University Hospital of PCNSL was reviewed over a 12-year period (2003–2014). Seventy-nine patients with intracranial PCNSL were identified. Deep brain involvement was shown in 63 patients. Thirty-two patients underwent craniotomy with resection, while all other patients had a biopsy. Fifty-seven patients were given chemotherapy: 18 were treated with the MSKCC (Memorial Sloan-Kettering Cancer Center) with rituximab, 21 with the MSKCC without rituximab, and 14 within a Nordic prospective phase II protocol. Forty-four patients achieved complete response (CR) and had OS of 46.3 months. Patients who underwent resection had a median OS of 28.6 versus 11.7 months for those who had a biopsy performed. Resection showed an insignificant prolongation of OS. Multivariate analysis confirmed statistical significance of deep brain involvement only (p?<?0.005). Neither chemotherapy regimen, Karnofsky Performance Status (KPS), type of surgery, nor patient age was significant factors for OS or PFS. Resective surgery played no role in significantly improving either OS or PFS and therefore it is not recommended as treatment for PCNSL.     

Vascular hyperpermeability as a hallmark of phacomatoses: is the etiology angiogenesis related to or comparable with mechanisms seen in inflammatory pathways? Part II: angiogenesis- and inflammation-related molecular pathways,tumor-associated macrophages,and possible therapeutic implications: a comprehensive review

Phacomatoses are a special group of familial hamartomatous syndromes with unique neurocutaneous manifestations as well as characteristic tumors. Neurofibromatosis type 2 (NF2) and tuberous sclerosis complex (TSC) are representatives of this family. A vestibular schwannoma (VS) and subependymal giant cell tumor (SGCT) are two of the most common intracranial tumors associated with these syndromes, related to NF2 and TSC, respectively. These tumors can present with an obstructive hydrocephalus due to their location adjacent to or in the ventricles. Remarkably, both tumors are also known to have a unique association with elevated protein concentrations in the cerebrospinal fluid (CSF), sometimes in association with a non-obstructive (communicating) hydrocephalus. Of the two, SGCT has been shown to be associated with a predisposition to CSF clotting, causing a debilitating recurrent shunt obstruction. However, the exact relationship between high protein levels and clotting of CSF remains unclear, nor do we understand the precise mechanism of CSF clotting observed in SGCT. Elevated protein levels in the CSF are thought to be caused by increased vascular permeability and dysregulation of the blood–brain barrier. The two presumed underlying pathophysiological processes for that in the context of tumorigenesis are angiogenesis and inflammation. Both these processes are correlated to the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin pathway which is tumorigenesis related in many neoplasms and nearly all phacomatoses. In this review, we discuss the influence of angiogenesis and inflammation pathways on vascular permeability in VSs and SGCTs at the phenotypic level as well as their possible genetic and molecular determinants. Part I described the historical perspectives and clinical aspects of the relationship between vascular permeability, abnormal CSF protein levels, clotting of the CSF, and communicating hydrocephalus. Part II hereafter describes the different cellular and molecular pathways involved in angiogenesis and inflammation observed in both tumors and explores the existing metabolic overlap between inflammation and coagulation. Interestingly, while increased angiogenesis can be observed in both tumors, inflammatory processes seem significantly more prominent in SGCT. Both SGCT and VS are characterized by different subgroups of tumor-associated macrophages (TAMs): the pro-inflammatory M1 type is predominating in SGCTs, while the pro-angiogenetic M2 type is predominating in VSs. We suggest that a lack of NF2 protein in VS and a lack of TSC1/TSC2 proteins in SGCT significantly influence this fundamental difference between the two tumor types by changing the dominant TAM type. Since inflammatory reactions and coagulation processes are tightly connected, the pro-inflammatory state of SGCT may also explain the associated tendency for CSF clotting. The underlying cellular and molecular differences observed can potentially serve as an access point for direct therapeutic interventions for tumors that are specific to certain phacomatoses or others that also carry such genetic changes.     

Routine placement of subdural drain after burr hole evacuation of chronic and subacute subdural hematoma: a contrarian evidence based approach

The objective of this paper was to evaluate whether available evidence supporting placement of subdural drain placement after evacuation of chronic subdural haematoma (CSDH) is applicable to a cohort of patients managed by us. In this observational cohort study, clinical follow-up was obtained in 166 patients who underwent burr hole evacuation of CSDH without placement of subdural drain followed by 3 days of bed rest. The primary outcome studied was recurrence requiring reoperation. Factors predicting recurrence were also analysed. We compared the patient characteristics and management protocols in our cohort with that in reports supporting drain placement to determine whether such evidence is relevant to our patient group. The mean age of our patients was 58 ± 17 years (range, 1 to 89 years). Sixteen of the 166 (9.6%) patients presented with symptomatic recurrence. The median time to reoperation for recurrence (15 of 16 patients) after the primary procedure was 17 days (range, 2 to 68 days). Antiplatelet and anticoagulant therapy was the only factor that was significantly associated with recurrence (p = 0.01). There were no infective or non-infective complications in our patient cohort. Our patient cohort and outcomes differed from those reporting drain placements in the following parameters: they were a decade younger, all patients received bed rest for 3 days after surgery and the recurrence rate was similar to that reported in the drained groups but significantly less than that reported in the non-drained groups. Routine placement of drain following burr hole evacuation of CSDH should only be done after careful comparison of the patient cohort under consideration and those reporting superior outcomes with drains. Evidence-based medicine supports such an approach.     

Robot guidance for percutaneous minimally invasive placement of pedicle screws for pyogenic spondylodiscitis is associated with lower rates of wound breakdown compared to conventional fluoroscopy-guided instrumentation

Postoperative wound healing can pose a problem in patients undergoing instrumented surgery for pyogenic spondylodiscitis. Robotic guidance allows the minimally invasive placement of pedicle screws in the thoracolumbar spine. We assessed whether using this technique to perform minimally invasive surgery had an impact on wound healing in patients with pyogenic spondylodiscitis when compared to conventional open fluoroscopy-guided surgery. We reviewed charts of 206 consecutive patients who underwent instrumentation for pyogenic spondylodiscitis. The need for wound revision was the primary outcome measure. Patient variables and comorbidities as well as surgical technique (robotic versus fluoroscopy-guided) were analyzed. We also compared fluoroscopy times between the two groups. Multivariate regression analysis was performed to identify predictors of wound breakdown. A total of 206 patients underwent surgery for spondylodiscitis. Robotic surgical assistance was used for percutaneous instrumentation in 47.6% of cases (n = 98). Wound healing problems requiring revision occurred in 30 out of 206 patients (14.6%). Univariate analysis revealed a potential association of wound breakdown with (1) robotic technique, (2) age > 70 years, and (3) the presence of methicillin-resistant Staphylococcus aureus. After multivariate correction however, only robotic technique retained significance with an odds ratio of 0.39 (CI 95% 0.16–0.94; p = 0.035). Wound revision was required in eight out of 98 patients (8.1%) in the robot group and 22/108 (20%) in the conventional surgery group. Fluoroscopy times were significantly lower in the robot group with a mean of 123 ± 86 s in comparison with a mean of 157 ± 99 s in the conventional group (p = 0.014). While initially designed to improve the accuracy of pedicle screw placement, robot-assisted minimally invasive technique had a tangible effect on both radiation exposure and the rate of wound breakdown in patients with pyogenic spondylodiscitis in our large single-center study.     

Neurosurgical management of cavernous malformations located at the foramen of Monro

Cavernous malformations (CMs) located at the foramen of Monro (FM) are relatively rare benign vascular malformations. Knowledge of FM CM is poor. The aims of this study were to describe the incidence, clinical presentation, radiological features, surgical approaches, and neurological outcomes for FM CM patients and to discuss the treatment strategy for this disease. We present a series of nine FM CM patients (four males, five females; mean age 29.3 years) who were treated at a single neurosurgical center. FM CM accounted for 0.56% of the entire series of the central nervous system (CNS) CMs. Headache accompanied by nausea and vomiting was the most common initial symptom (55.6%). The mean preoperative Karnofsky Performance Scale (KPS) score was 84.4 (range 70–100). In all but one patient, the lesions were surgically resected. Postoperatively, two patients developed obstructive hydrocephalus, and one experienced motor aphasia and right hemiparesis. At the time of discharge, the KPS score improved to a mean of 88.9. Follow-up period after diagnosis was 18 to 131 months (mean 69.7 months); all the patients were considered to be in excellent clinical condition. FM CMs are rare and challenging lesions; they have a female predilection. The most common clinical manifestations of FM CM are the symptoms of mass effect. The seizure risk of FM CMs seems to be significantly lower than that of general intraventricular CMs. Early surgical intervention should be offered to symptomatic cases, and gross total resection is associated with favorable neurological outcomes.     

Predictors for a further local in-brain progression after re-craniotomy of locally recurrent cerebral metastases

Treatment of recurrent cerebral metastases is an emerging challenge due to the high local failure rate after surgery or radiosurgery and the improved prognosis of patients with malignancies. A total of 36 patients with 37 metastases who underwent surgery for a local in-brain progression of a cerebral metastasis after previous metastasectomy were retrospectively analyzed. Degree of surgical resection on an early postoperative MRI within 72 h after surgery was correlated with the local in-brain progression rate and overall survival. Complete surgical resection of locally recurrent cerebral metastases as confirmed by early postoperative MRI could only be achieved in 37.8%. Detection of residual tumor tissue on an early MRI following recurrent metastasis surgery correlated with further local in-brain progression when defining a significance level of p?=?0.05 but not after ?idák or Bonferroni significance level correction for multiple testing: However, definite local tumor control could finally be achieved in 91.9% after adjuvant therapy. Overall survival after recurrent metastasectomy was significantly higher as predicted by diagnosis-specific graded prognostic assessment (12.9?±?2.3 vs. 8.4?±?0.7 months; p?<?0.0001). However, our series involved a limited number of heterogeneous patients. A larger, prospective, and controlled study is required. Considering the adequate local tumor control achieved in the vast majority of patients, surgery of recurrent metastases may represent one option in a multi-modal treatment approach of patients suffering from locally recurrent cerebral metastases.     

Shunt overdrainage syndrome: review of the literature

Shunt overdrainage in patients with hydrocephalus still represents a challenge for neurosurgeons, in part due to the lack of agreement or uniformity concerning the entity. Important problems exist relating to the real incidence of the entity, its definition, classification, and the pathophysiological theories behind the various treatment strategies proposed. Recent reports have suggested that the evidence about overdrainage and its consequences is not so robust as presumed. Consequently, the topic requires more detailed examination. In this review, we comment on all the main facets related with shunt overdrainage.     

The Combination of icariin and constrained dynamic loading stimulation attenuates bone loss in ovariectomy‐induced osteoporotic mice

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increasing the risk of fracture. Icariin (ICA) as a phytoestrogen shows osteogenic effects, and the mechanical stimulation has been demonstrated the improving effect on osteoporosis. The objective of this study was to investigate the effect of ICA in combination with constrained dynamic loading (CDL) stimulation on osteoporosis in ovariectomized (OVX) mice. The serum hormone levels, bone turnover markers, trabecular architecture, ulnar biomechanical properties, and the expression of osteoblast‐related gene (alkaline phosphatase, ALP; osteocalcin, OCN; bone morphogenetic protein‐2, BMP‐2; Collagen I (α1), COL1; osteoprotegerin, OPG) and osteoclast‐related genes (receptor activators of NF‐κB ligand, RANKL; tartrate‐resistant acid phosphatase, TRAP) were analyzed. The results showed that ICA + CDL treatment could increase the osteocalcin (20.85%), estradiol levels (20.61%) and decrease the TRAP activity (26.27%) significantly than CDL treatment. The combined treatment attenuated bone loss and biomechanical decrease more than single use of CDL treatment. ICA + CDL treatment significantly up‐regulated the level of osteoblast‐related gene expression and down‐regulated the osteoclast‐related genes expression; moreover, the combined treatment increased the ratio of OPG/RANKL significantly compared to ICA (72.83%) or CDL (65.63%) treatment alone. The present study demonstrates that icariin in combination with constrained dynamic loading treatment may have a therapeutic advantage over constrained dynamic loading treatment alone for the treatment of osteoporosis, which would provide new evidence for the clinical treatment of osteoporosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1415–1424, 2018.