Diffuse gliomas with K27M histone mutations (H3K27M glioma) are generally characterized by a fatal prognosis, particularly affecting the pediatric population. Based on the molecular heterogeneity observed in this tumor type, personalized treatment is considered to substantially improve therapeutic options. Therefore, clinical evidence for therapy, guided by comprehensive molecular profiling, is urgently required. In this study, we analyzed feasibility and clinical outcomes in a cohort of 12 H3K27M glioma cases treated at two centers. Patients were subjected to personalized treatment either at primary diagnosis or disease progression and received backbone therapy including focal irradiation. Molecular analyses included whole-exome sequencing of tumor and germline DNA, RNA-sequencing, and transcriptomic profiling. Patients were monitored with regular clinical as well as radiological follow-up. In one case, liquid biopsy of cerebrospinal fluid (CSF) was used. Analyses could be completed in 83% (10/12) and subsequent personalized treatment for one or more additional pharmacological therapies could be recommended in 90% (9/10). Personalized treatment included inhibition of the PI3K/AKT/mTOR pathway (3/9), MAPK signaling (2/9), immunotherapy (2/9), receptor tyrosine kinase inhibition (2/9), and retinoic receptor agonist (1/9). The overall response rate within the cohort was 78% (7/9) including one complete remission, three partial responses, and three stable diseases. Sustained responses lasting for 28 to 150 weeks were observed for cases with PIK3CA mutations treated with either Gojo et al.Personalized Treatment of H3K27M Glioma miltefosine or everolimus and additional treatment with trametinib/dabrafenib in a case with BRAFV600E mutation. Immune checkpoint inhibitor treatment of a case with increased tumor mutational burden (TMB) resulted in complete remission lasting 40 weeks. Median time to progression was 29 weeks. Median overall survival (OS) in the personalized treatment cohort was 16.5 months. Last, we compared OS to a control cohort (n = 9) showing a median OS of 17.5 months. No significant difference between the cohorts could be detected, but long-term survivors (>2 years) were only present in the personalized treatment cohort. Taken together, we present the first evidence of clinical efficacy and an improved patient outcome through a personalized approach at least in selected cases of H3K27M glioma.

Lesions of obturator nerve are rare. Tumours and mainly malignant schwannoma of this nerve are extremely rare. The authors describe an unusual case of a gigantic schwannoma of the obturator nerve in 69 year old woman. Due to tumour expansion in the proximal part of the thigh MRI was performed and demonstrated extensive tumour originating most probably from the obturator nerve. The patient had no neurological symptoms. Biopsy from the lesion was taken at the Department of Orthopaedics with the following conclusion: malignant schwannoma. The patient received neoadjuvant chemotherapy due to diffuse metastatic spread on the chest X ray, after which metastatic spread subsided. The main lesion reduced its size by 1 cm. In 4 months after biopsy the patient was referred for operation to neurosurgery. The tumour was removed along its borders and except of minimal weakness of adduction of the right thigh there was no neurological deterioration. She was subsequently referred for further care to oncology and radiotherapy. The goal of this work is to emphasize the extremely rare occurrence of tumours of this nerve and suggest therapeutic options (Fig. 4, Ref. 11).

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Several methods of carpal tunnel syndrome (CTS) surgery have been described. The open approach is regarded as the gold standard, however there are also many critics of this technique. Due to the fact that results of open surgery are often quite disappointing -about 60 % of patients have scar pain or so called pillar pain in the hypothenar and thenar eminences following surgery, we have therefore, turned our interests to less invasive techniques. In the past 12 years, we have accumulated vast experience in CTS surgery, which is a very frequent procedure in our department. Other than the classic open approach, we have obtained experience in the so called "twin incision technique" (1) "flexor carpi radialis approach" (20) and the uniportal (single portal) endoscopic approach (9). Endoscopy is our favoured technique (system Wolf). In most cases of mild or moderate EMG findings, using the endoscopic technique we were able to achieve superior patient satisfaction rates.Intracarpal pressure (ICP) measurement has a long history. The accepted normal ICP range in healthy individuals is between 3-6 mmHg in the neutral wrist position and up to 20-60 mmHg during extension (21). The positive results of certain groups, especially studies done by Japanese authors have led us to further improve our results. In our study, a Codman sensor, typically used for the measurement of intracranial pressure was used to measure intracarpal pressure. The main reason for ICP measurement was to evaluate the relationship between peroperative intracarpal pressure, the level of decompression and pre/postoperative EMG findings. In addition, the effect of different hand positions and anatomical location on ICP was assessed. Summary: Endoscopic carpal tunnel syndrome surgery is a modern minimally invasive method of carpal tunnel decompression. However, the method does also have its critics, who emphasize that there is an increased rate of complications in comparison to open procedures. To further improve and optimize results of endoscopic surgery we used an intracarpal pressure sensor to verify the effect of carpal tunnel decompression. The endoscopic single portal approach was used in all cases. Median nerve conduction studies were performed prior to and 3 months after surgery. Two groups, those with pressure studies and those without, were then compared according to several EMG parameters such as: median nerve distal motor latency, amplitude of motor response, sensory nerve conduction velocity to the index finger, and amplitude of sensory nerve action potential. In both groups, we observed similarly significant improvements in all conduction parameters, except the amplitude of motor response, which did not change in either group, i.e. no difference in postoperative EMG between the two groups was observed. Despite this fact, intracarpal pressure measurement is still useful in localising the point in which the median nerve is compressed and provides valuable functional information on the level decompression achieved. Material and Methods Surgery TH...