Surgical results of 158 petroclival meningiomas with special focus on standard craniotomies.

OBJECTIVE: The goal of this retrospective study is the evaluation of risk factors for postoperative neurological deficits after petroclival meningioma (PCM) surgery with special focus on standard craniotomies. MATERIALS AND METHODS: One-hundred-fifty-eight patients were included in the study, of which 133 patients suffered from primary and 25 from recurrent PCM. All patients were operated on and evaluated concerning age, tumor size, histology, pre- and postoperative cranial nerve (CN) deficits, morbidity, mortality, and surgical complications. Tumor-specific features-e.g., consistency, surface, arachnoid cleavage, and location-were set in a four-grade classification system that was used to evaluate the risk of CN deficits and tumor resectability. RESULTS: After primary tumor resection, new CN deficits occurred in 27.3% of patients. Preoperative ataxia improved in 25%, whereas 10% developed new ataxia. Gross total resection (GTR) was achieved in 59.4%. The morbidity rate, including hemiparesis, shunt-dependence, postop-hemorrhage, and tracheostomy was 22.6% and the mortality rate was 2.3%. In recurrent PCM surgery, CN deficits occurred in 16%. GTR could be achieved in three cases. Minor complications occurred in 20%. By applying the proposed new classification system to patients operated via standard craniotomies, the best outcome was observed in type I tumor patients (soft tumor consistency, smooth surface, plane arachnoid cleavage, and unilateral localization) with GTR in 78.7% (p < 0.001) and 11.9% new CN deficits (p = 0.006). CONCLUSION: Standard craniotomies as the retrosigmoid or subtemporal/pterional approaches are often used for the resection of PCMs. Whether these approaches are sufficient for GTR-and avoidance of new neurological deficits-depends mainly on the localization and intrinsic tumor-specific features.

[Scabies-Renaissance of an ectoparasite infection : Diagnosis and therapy-How to proceed in practice]. / Skabies ­ Renaissance einer Ektoparasitose : Diagnostik und Therapie ­ Vorgehen in der Praxis.

Scabies or mange is currently a common dermatosis in Germany and other countries, and should be more important in health policy. It affects a cross-section of society, including all age groups, from infants to the aged. Locals and people with a migration background both suffer from this highly contagious ectoparasite infection with excessive, predominately nocturnal itching. Clinical diagnosis represents a challenge for the experienced dermatologist due to the variety of dermatosis to be considered in the differential diagnosis. It is still unclear whether treatment failure or the recurrences observed everywhere are due to in vitro and in vivo resistance of the pathogen agent Sarcoptes scabiei against permethrin or ivermectin. Therapeutic errors seem to play a role as often not all direct contact persons are recorded and treated with antiscabious treatment. They form the reservoir for reinfections. In the event of repeated nonresponse to topical (permethrin) and/or oral antiscabious treatment, alternative topical preparations-benzyl benzoate or crotamiton-should be used. Combination with ivermectin is mandatory.

Radiographic assessment of contrast enhancement and T2/FLAIR mismatch sign in lower grade gliomas: correlation with molecular groups.

PURPOSE: With the updated World Health Organization (WHO) 2016 neuropathological diagnostic criteria, radiographic prognostic associations in lower-grade gliomas (LGG, WHO grade II and III) are undergoing re-evaluation. METHODS: We identified 316 LGG patients (151 grade II and 165 grade III) for a combined cohort from three independent databases. We analyzed the preoperative axial FLAIR, axial T2-weighted and post-gadolinium volumetric T1-weighted MR images. The molecular data collected included the status of IDH1/2, TP53, TERT promoter and ATRX mutations, in addition to 1p/19q co-deletions. In a subset of cases (n = 133), we assessed the "T2-FLAIR mismatch" sign. RESULTS: Gliomas were assigned to one of the three molecular groups: Group O (IDH-mutant, 1p/19q co-deleted oligodendrogliomas, n = 95), Group A (IDH-mutant, ATRX inactivated astrocytomas, n = 175) and Group G (IDH wild-type, GBM-like, n = 46). A contrast-enhancing tumor was seen in 98 patients (31%), most frequently in Group G (n = 28/45, 57%), when compared to Group A (n = 49/175, 28%) and Group O (n = 24/95, 25.3%) tumors (p = 0.008 and p = 0.0011, respectively). Consistent with previous reports, T2-FLAIR mismatch was preferentially found in Group A tumors (73.1%, 60 of 82), although its presence was not associated with survival, after controlling for molecular group. False positive mismatch sign was noted in 28.5% (12/42) Group O tumors, but none of the tumors in Group G. A combination of all three factors: age under 40 years at first diagnosis, a tumor size larger than 6 cm and T2-FLAIR mismatch was highly specific for IDH mutant astrocytoma (Group A). CONCLUSION: We identify radiographic correlates of molecular groups in lower-grade gliomas, which join clinical demographic features in defining the characteristic presentation of these tumors. Radiographic correlates of prognosis in LGG require re-evaluation within molecular group.

DMD genomic deletions characterize a subset of progressive/higher-grade meningiomas with poor outcome.

Progressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene as the most common alteration (n = 5, 20.8%), along with alterations of other known X-linked cancer-related genes KDM6A (n =2, 8.3%), DDX3X, RBM10 and STAG2 (n = 1, 4.1% each). DMD inactivation (by genomic deletion or loss of protein expression) was ultimately detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboring DMD inactivation had a shorter overall survival (OS) than their wild-type counterparts [5.1 years (95% CI 1.3-9.0) vs. median not reached (95% CI 2.9-not reached, p = 0.006)]. Given the known poor prognostic association of TERT alterations in these tumors, we also assessed for these events, and found seven patients with TERT promoter mutations and three with TERT rearrangements in this cohort (n = 10, 18.8%), including a recurrent novel RETREG1-TERT rearrangement that was present in two patients. In a multivariate model, DMD inactivation (p = 0.033, HR = 2.6, 95% CI 1.0-6.6) and TERT alterations (p = 0.005, HR = 3.8, 95% CI 1.5-9.9) were mutually independent in predicting unfavorable outcomes. Thus, DMD alterations identify a subset of progressive/high-grade meningiomas with worse outcomes.

Vestibular Schwannoma Surgery: Outcome and Complications in Lateral Decubitus Position versus Semi-sitting Position-A Personal Learning Curve in a Series of 544 Cases over 3 Decades.

OBJECTIVE: To retrospectively evaluate influence of intraoperative positioning (semisitting vs. lateral decubitus) and surgeon's learning curve with regard to functional outcome of patients with vestibular schwannoma. METHODS: This study included 544 patients (median age 57 years) and spanned 3 decades: 1991-1999 (n = 103), 2000-2009 (n = 210), and 2010-2019 (n = 231). Surgery was performed in the lateral decubitus position in 318 patients and the semisitting position in 163 patients. Large T3 and T4 tumors were present in 77% of patients. RESULTS: Complete tumor removal was achieved in 94.3% of patients. A significant reduction in surgery duration and blood loss was observed over 3 decades for T3 (from 325 to 261 minutes, P < 0.001) and T4 (from 440 to 330 minutes, P < 0.001), but not for T1 and T2, tumors. The semisitting position diminished surgical time in T3 and T4 tumors by 1 more hour (P < 0.001). Over 3 decades, facial nerve outcome improved significantly from 59.8% House-Brackmann grade 1-2 in the first decade to 81.7% in the last decade (P < 0.001). Furthermore, hearing was preserved in 45.3%: 23.3% of patients in the first decade and 50.5% in the last decade (P = 0.03). However, neither facial nerve outcome nor hearing preservation significantly differed in patients operated on in the lateral decubitus versus the semisitting position. The most common complication was cerebrospinal fluid leak (6.1%) followed by hemorrhage (3.5%) and pulmonary embolism (2.2%). CONCLUSIONS: Follow-up over 3 decades illustrates a learning curve with significantly improved results. While the semisitting position accelerates the procedure and is associated with reduced blood loss, it does not significantly influence functional outcome.

TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study.

Purpose: We conducted a pilot study to assess the feasibility and the potential implications of detecting TERT promoter (TERTp)-mutant cell-free tumor-derived DNA (tDNA) in the cerebrospinal fluid (CSF) and plasma of glioblastoma patients.Experimental Design: Matched CSF and plasma samples were collected in 60 patients with glial tumors. The CSF collection was obtained during surgery, before any surgical manipulation of the tumor. The extracted tDNA and corresponding tumor DNA samples were analyzed for TERTp and isocitrate dehydrogenase (IDH) hotspot mutations. In addition, the variant allele frequency (VAF) of TERTp mutation in the CSF-tDNA was correlated with tumor features and patients' outcome.Results: Thirty-eight patients had TERTp-mutant/IDH wild-type glioblastomas. The matched TERTp mutation in the CSF-tDNA was successfully detected with 100% specificity (95% CI, 87.6-100%) and 92.1% sensitivity (95% CI, 78.6-98.3%) (n = 35/38). In contrast, the sensitivity in the plasma-tDNA was far lower [n = 3/38, 7.9% (95% CI, 1.6-21.4%)]. We concordantly observed a longer overall survival of patients with low VAF in the CSF-tDNA when compared with patients with high VAF, irrespective of using the lower quartile VAF [11.45%; 14.0 mo. (95% confidence interval, CI, 10.3-17.6) vs. 8.6 mo. (95% CI, 4.1-13.2), P = 0.035], the lower third VAF [13%; 15.4 mo. (95% CI, 11.6-19.2) vs. 8.3 mo. (95% CI, 2.3-14.4), P = 0.008], or the median VAF [20.3%; 14.0 mo. (95% CI, 9.2-18.7) vs. 8.6 mo. (95% CI, 7.5-9.8), P = 0.062] to dichotomize the patients.Conclusions: This pilot study highlights the value of CSF-tDNA for an accurate and reliable detection of TERTp mutations. Furthermore, our findings suggest that high TERTp mutation VAF levels in the CSF-tDNA may represent a suitable predictor of poor survival in glioblastoma patients. Further studies are needed to complement the findings of our exploratory analysis. Clin Cancer Res; 24(21); 5282-91. ©2018 AACR.