Ville Vuorinen

Debulking or biopsy of malignant glioma in elderly people - a randomised study.

Summary.Background: Patients with radiologically (MRI and/or CT images) suspected malignant glioma is referred to radiotherapy after craniotomy and resection of the tumour or after diagnostic biopsy. Patients with poor preoperative status and elderly patients are diagnosed more often by biopsy and treated by radiotherapy rather than by craniotomy and tumour resection. However, based on previous retrospective studies it is not possible to conclude which procedure is better for elderly patients. Thus a prospective study comparing these two procedures with elderly patients was planned. Methods: 30 patients older than 65 years with radiologically (CT and/or MRI) obvious malignant glioma were randomised into two groups: I) stereotactic biopsy and II) open craniotomy and resection of the tumour. Nineteen patients were diagnosed to have grade IV glioma and four patients grade III glioma. Seven out of 30 (23%) were followed in the “intention-to-treat” group with diagnosis of stroke (n=3), metastasis (n=2), malignant lymphoma (n=1) and one with out histological diagnosis. Patients with histologically verified malignant glioma (grade III–IV) were diagnosed by stereotactic biopsy (n=13) or by open craniotomy and resection (n=10) and all the patients were referred to radiotherapy. Survival and time of deterioration were followed. Findings: The overall median survival time was 146 (95% CI 89–175) days after the procedure. The estimated median survival time was 171 (95% CI 146–278) days after the craniotomy versus 85 (95% CI 55–157) days after the biopsy (p=0.035). The estimated survival time was 2.757 times longer (95% CI 1.004–7.568, p=0.049) after craniotomy. However, there was no significant difference in the time of deterioration between these two treatments (p=0.057). Amount of radiotherapy given had a significant effect on survival (p=0.001). Interpretation: Longer survival time is achieved after open craniotomy and resection of tumour. However, overall benefit of open surgery to patient seems to be modest, while time of deterioration did not differ between two treatment groups. Our results support previous studies on the benefit of radiotherapy in the treatment of malignant glioma.

The endoneurial response to neurolytic agents is highly dependent on the mode of application.

BACKGROUND AND OBJECTIVES The variability and predictability of neurolytic neural blocks were studied using an experimental rat sciatic nerve model. The goal of the study was to compare endoneurial and clinical responses to commonly used neurolytic agents. METHODS The sciatic nerves of 80 rats were treated either with intra- or perineural injections of 7% phenol-aqua, anhydrous glycerol, or 5% phenol-glycerol. Lidocaine and saline injections were used as controls. Muscle function and trophic changes of the hind limbs were evaluated, and samples for morphologic analysis were taken 1, 2, 4, and 8 weeks after the injections. RESULTS Intra- and perineural injections of 7% phenol-aqua resulted in gross endoneural damage of the sciatic nerve and hind limb paresis. Perineural 5% phenol-glycerol and anhydrous glycerol injections caused subperineural damage with slight paresis; gross endoneural damage and noticeable paresis were present only after intraneural injections. When 7% phenol-aqua was compared to other neurolytic agents, the differences in the lesion size (P < .0001) were statistically significant after perineural injections. Regeneration occurred in a stereotypic fashion in all neurolytic groups. Axonal sprouts were noted at the injured area 2 weeks after intraneural and 1 week after perineural injections. Motor function had partially recovered at 8 weeks. CONCLUSION There were no differences in the effects of clinically used neurolytic agents after intraneural injections. Although the perineurally applied 7% phenol-aqua induced marked endoneural damage, the destructive effect of glycerol and phenol-glycerol injections seemed to be prevented by the perineurium; phenol-glycerol and glycerol treatments induced subperineural damage only after perineural injections. The ability to penetrate the perineurium favors the use of 7% phenol-aqua in peripheral perineural blocks when complete neurolysis is the goal.

A glass fiber-reinforced composite - bioactive glass cranioplasty implant: A case study of an early development stage implant removed due to a late infection.

This case study describes the properties of an early development stage bioactive glass containing fiber-reinforced composite calvarial implant with histology that has been in function for two years and three months. The patient is a 33-year old woman with a history of substance abuse, who sustained a severe traumatic brain injury later unsuccessfully treated with an autologous bone flap and a custom-made porous polyethylene implant. She was thereafter treated with developmental stage glass fiber-reinforced composite - bioactive glass implant. After two years and three months, the implant was removed due to an implant site infection. The implant was analyzed histologically, mechanically, and in terms of chemistry and dissolution of bioactive glass. Mechanical integrity of the load bearing fiber-reinforced composite part of the implant was not affected by the in vivo period. Bioactive glass particles demonstrated surface layers of hydroxyapatite like mineral and dissolution, and related increase of pH was considerably less after two and three months period than that for fresh bioactive glass. There was a difference in the histology of the tissues inside the implant areas near to the margin of the implant that absorbed blood during implant installation surgery, showed fibrous tissue with blood vessels, osteoblasts, collagenous fibers with osteoid formation, and tiny clusters of more mature hard tissue. In the center of the implant, where there was less absorbed blood, only fibrous tissue was observed. This finding is in line with the combined positron emission tomography - computed tomography examination with (18F)-fluoride marker, which demonstrated activity of the mineralizing bone by osteoblasts especially at the area near to the margin of the implant 10 months after implantation. Based on these promising reactions found in the bioactive glass containing fiber-reinforced composite implant that has been implanted for two years and three months, calvarial reconstruction with the presented material appears to be a feasible method.

Uptake of 4-borono-2-[18F]fluoro-L-phenylalanine in sporadic and neurofibromatosis 2-related schwannoma and meningioma studied with PET.

PurposeMeningiomas and schwannomas associated with neurofibromatosis 2 (NF2) are difficult to control by microsurgery and stereotactic radiotherapy alone. Boron neutron capture therapy (BNCT) is a chemically targeted form of radiotherapy requiring increased concentration of boron-10 in tumour tissue. PET with the boron carrier 4-borono-2-[18F]fluoro-L-phenylalanine ([18F]FBPA) allows investigation of whether 4-borono-L-phenylalanine (BPA) concentrates in NF2 tumours, which would make BNCT feasible.MethodsWe studied dynamic uptake of [18F]FBPA in intracranial meningiomas (n=4) and schwannomas (n=6) of five sporadic and five NF2 patients. Tracer input function and cerebral blood volume were measured. [18F]FBPA uptake in tumour and brain was assessed with a three-compartmental model and graphical analysis. These, together with standardised uptake values (SUVs), were used to define tumour-to-brain [18F]FBPA tissue activity gradients.ResultsModel fits with three parameters K1 (transport), k2 (reverse transport) and k3 (intracellular metabolism) were found to best illustrate [18F]FBPA uptake kinetics. Maximum SUV was two- to fourfold higher in tumour as compared with normal brain and independent of NF2 status. The increased uptake was due to higher transport of [18F]FBPA in tumour. In multiple-time graphical analysis (MTGA, Gjedde-Patlak plot) the tumour-to-brain [18F]FBPA influx constant (Ki -MTGA) ratios varied between 1.8 and 5.4 in NF2-associated tumours while in sporadic tumours the ratio was 1–1.4.Conclusion[18F]FBPA PET offers a viable means to evaluate BPA uptake in meningiomas and schwannomas in NF2. Based on our results on tumour uptake of [18F]FBPA, some of these benign neoplasms may be amenable to BNCT.

Presenting symptoms of glioma in adults

Studies on the presenting symptoms of glioma in adults in the age of readily available MRI imaging are scarce. This study investigates presenting symptoms of glioma and assesses the correlations of the presenting symptoms with patient age and histopathological class of the tumor.

Somatostatin receptor 2A in gliomas: Association with oligodendrogliomas and favourable outcome

Somatostatin receptor subtype 2A (SSTR2A) is a potential therapeutic target in gliomas. Data on SSTR2A expression in different glioma entities, however, is particularly conflicting. Our objective was to characterize SSTR2A status and explore its impact on survival in gliomas classified according to the specific molecular signatures of the updated WHO classification. In total, 184 glioma samples were retrospectively analyzed for SSTR2A expression using immunohistochemistry with monoclonal antibody UMB-1. Double staining with CD68 was used to exclude microglia and macrophages from analyses. SSTR2A staining intensity and its localization in tumor cells was evaluated and correlated with glioma entities and survival. Diagnoses included 101 glioblastomas (93 isocitrate dehydrogenase (IDH) -wildtype, 3 IDH-mutant, 5 not otherwise specified (NOS)), 60 astrocytomas (22 IDH-wildtype, 37 IDH-mutant, 1 NOS), and 23 oligodendrogliomas (19 IDH-mutant and 1p/19q-codeleted, 4 NOS). SSTR2A expression significantly associated with oligodendrogliomas (79% SSTR2A positive) compared to IDH-mutant or IDH-wildtype astrocytomas (27% and 23% SSTR2A positive, respectively), and especially glioblastomas of which only 13% were SSTR2A positive (p < 0.001, Fishers exact test). The staining pattern in glioblastomas was patchy whereas more homogeneous membranous and cytoplasmic staining was detected in oligodendrogliomas. Positive SSTR2A was related to longer overall survival in grade II and III gliomas (HR 2.7, CI 1.2–5.8, p = 0.013). In conclusion, SSTR2A expression is infrequent in astrocytomas and negative in the majority of glioblastomas where it is of no prognostic significance. In contrast, oligodendrogliomas show intense membranous and cytoplasmic SSTR2A expression, which carries potential diagnostic, prognostic, and therapeutic value.

Cranioplasty After Severe Traumatic Brain Injury: Effects of Trauma and Patient Recovery on Cranioplasty Outcome

Background In patients with severe traumatic brain injury (sTBI) treated with decompressive craniectomy (DC), factors affecting the success of later cranioplasty are poorly known. Objective We sought to investigate if injury- and treatment-related factors, and state of recovery could predict the risk of major complications in cranioplasty requiring implant removal, and how these complications affect the outcome. Methods A retrospective cohort of 40 patients with DC following sTBI and subsequent cranioplasty was studied. Non-injury-related factors were compared with a reference population of 115 patients with DC due to other conditions. Results Outcome assessed 1 day before cranioplasty did not predict major complications leading to implant removal. Successful cranioplasty was associated with better outcome, whereas a major complication attenuates patient recovery: in patients with favorable outcome assessed 1 year after cranioplasty, major complication rate was 7%, while in patients with unfavorable outcome the rate was 42% (p = 0.003). Of patients with traumatic subarachnoid hemorrhage (tSAH) on admission imaging 30% developed a major complication, while none of patients without tSAH had a major complication (p = 0.014). Other imaging findings, age, admission Glasgow Coma Scale, extracranial injuries, length of stay at intensive care unit, cranioplasty materials, and timing of cranioplasty were not associated with major complications. Conclusion A successful cranioplasty after sTBI and DC predicts favorable outcome 1 year after cranioplasty, while stage of recovery before cranioplasty does not predict cranioplasty success or failure. tSAH on admission imaging is a major risk factor for a major complication leading to implant removal.