Introduction: Glioblastoma multiforme (GBM) is a highly malignant glial tumor, affecting men more often than women. The reason for this gender-specific predominance remains unclear, raising the question whether these effects are subject to hormonal control. The purpose of this study was to examine the expression of estrogen receptor alpha (ERα) and aromatase in human GBM tissue samples in relation to patient survival and furthermore to investigate the effect of standard chemotherapy in combination with estradiol treatment on glioblastoma tumor cell lines in vitro. Methods: 60 tissue samples (31 male, 29 female) of GBM patients were analysed with immunohistochemistry for ERα and aromatase for survival analyses. The cell lines LN18 and LN229 were treated with 17β-estradiol (E2) in different dosing regimens and the cell viability was measured with MTT assay. After estradiol pre-treatment Temozolomide was added and tested again. Results: High expression of ERα and aromatase in the GBM tissue samples was associated with significantly longer survival times of GBM patients, regardless of gender and body-mass-index. The treatment with high concentrations of estradiol resulted in lower tumor cell viability, compared to control. The cells significantly showed a stronger sensitivity against Temozolomid (TMZ) after estradiol pre-treatment. Conclusion: ERα-expression of glial tumour cells seems to play an important prognostic role as a biomarker in GBM, as well as the expression of the enzyme Aromatase. The combined treatment of GBM with standard chemotherapy and estradiol may be beneficial to patient’s survival.

(1) Background: As resection of trigeminal schwannomas is challenging, due to anatomical involvement of the anterior, middle and posterior fossa, the appropriate approach is important. We report our experience with surgical resection of trigeminal schwannomas by simple and classic skull-base approaches. (2) Methods: We performed a retrospective single-center study including patients who underwent surgery for trigeminal schwannoma tumors between June 2007 and May 2020, concentrating on surgical technique, extent of resection, postoperative outcome and complications. (3) Results: We included 13 patients (median age 57.5 with range of 36-83 years, 53.8% (7/13) female. The most common preoperative clinical presentations were facial pain in six (46.2%), hypoacusis in four (30.8%), trigeminal nerve hypesthesia in 11 (V1 46.2% (6/13), V2 (61.5% (8/13), V3 46.2% (6/13)) and headache in three (23.1%) patients. In three cases, the tumor was resected in a two-stage technique. The intradural subtemporal approach was performed in six cases, the extradural technique in two cases, the retrosigmoid approach in five cases, a Kawase approach in two cases and the transnasal endoscopic approach in one case. The gross total resection rate was 76.9% (10/13) and the median follow-up time 24.0 (0–136) months. Three (23.1%) patients developed postoperative anesthesia in at least one branch of the trigeminal nerve. Trigeminal motor function was preserved in 11 (84.6%) patients. Ten of the 11 patients (76.9%) who reported decreased gustation, cerebellar ataxia, visual impairment, or headache improved postoperatively. Two (15.4%) patients exhibited minimal facial palsy (House and Brackmann II–III), which resolved during the follow-up. The total adverse event rate requiring surgical intervention during follow-up was 7.7%. Surgery-related mortality was 0%. (4) Conclusions: Trigeminal schwannomas are rare benign lesions with intra- and extracranial extension. Considering the low operative morbidity and satisfying functional outcome, gross total resection of trigeminal schwannomas is achievable by classic, but also individually tailored approaches. More invasive or combined techniques were not needed with meticulous surgical planning.

Background: Colorectal mixed adenoneuroendocrine carcinomas (MANECs) are clinically highly aggressive neoplasms. MANECs are composed of variable adenocarcinoma components combined with morphologically distinct neuroendocrine carcinoma components, which are confirmed by synaptophysin immunohistochemistry, the gold standard marker of a neuroendocrine differentiation. However, the biological behavior of adenocarcinomas that express synaptophysin but do not show a typical neuroendocrine morphology remains unclear. Methods: We investigated synaptophysin expression in 1002 conventional colorectal adenocarcinomas and correlated the results with clinicopathological characteristics and patient survival and compared the survival characteristics of synaptophysin expression groups to MANECs. Results: Synaptophysin expression in conventional colorectal adenocarcinomas was associated with a shortened disease-free survival (p = 0.037), but not with overall survival or disease-specific survival (DSS) in univariate analyses and without any survival impact in multivariate analyses. Patients with “true” MANECs, on the other hand, showed a significantly shorter survival than all conventional adenocarcinomas with or without synaptophysin expression in uni- and multivariate analyses (e.g., multivariate DSS: p < 0.001, HR: 5.20). Conclusions: Our study demonstrates that synaptophysin expression in conventional colorectal adenocarcinomas, in contrast to MANECs, is not associated with a significantly poorer clinical outcome when compared to adenocarcinomas without synaptophysin expression. Furthermore, our data suggest that conventional adenocarcinomas with a diffuse synaptophysin expression should not be classified as MANECs, also strongly arguing that synaptophysin testing should be reserved for carcinomas with an H&E morphology suggestive of a neuroendocrine differentiation.

Purpose: To detect SARS-CoV-2 RNA in post-mortem human eyes. Ocular symptoms are common in patients with COVID-19. In some cases, they can occur before the onset of respiratory and other symptoms. Accordingly, SARS-CoV-2 RNA has been detected in conjunctival samples and tear film of patients suffering from COVID-19. However, the detection and clinical relevance of intravitreal SARS-CoV-2 RNA still remain unclear due to so far contradictory reports in the literature. Methods: In our study 20 patients with confirmed diagnosis of COVID-19 were evaluated post-mortem to assess the conjunctival and intraocular presence of SARS-CoV-2 RNA using sterile pulmonary and conjunctival swabs as well as intravitreal biopsies (IVB) via needle puncture. SARS-CoV-2 PCR and whole genome sequencing from the samples of the deceased patients were performed. Medical history and comorbidities of all subjects were recorded and analyzed for correlations with viral data. Results: SARS-CoV-2 RNA was detected in 10 conjunctival (50%) and 6 vitreal (30%) samples. SARS-CoV-2 whole genome sequencing showed the distribution of cases largely reflecting the frequency of circulating lineages in the Munich area at the time of examination with no preponderance of specific variants. Especially there was no association between the presence of SARS-CoV-2 RNA in IVBs and infection with the variant of concern (VOC) alpha. Viral load in bronchial samples correlated positively with load in conjunctiva but not the vitreous. Conclusion: SARS-CoV-2 RNA can be detected post mortem in conjunctival tissues and IVBs. This is relevant to the planning of ophthalmologic surgical procedures in COVID-19 patients, such as pars plana vitrectomy or corneal transplantation. Furthermore, not only during surgery but also in an outpatient setting it is important to emphasize the need for personal protection in order to avoid infection and spreading of SARS-CoV-2. Prospective studies are needed, especially to determine the clinical relevance of conjunctival and intravitreal SARS-CoV-2 detection concerning intraocular affection in active COVID-19 state and in post-COVID syndrome.

Background: Despite advances in treatment for brain metastases (BMs), the prognosis for recurrent BMs remains poor and requires further research to advance clinical management and improve patient outcomes. In particular, data addressing the impact of tumor volume and surgical resection with regard to survival remain scarce. Methods: Adult patients with recurrent BMs between December 2007 and December 2022 were analyzed. A distinction was made between operated and non-operated patients, and the residual tumor burden (RTB) was determined by using (postoperative) MRI. Survival analysis was performed and RTB cutoff values were calculated using maximally selected log-rank statistics. In addition, further analyses on systemic tumor progression and (postoperative) tumor therapy were conducted. Results: In total, 219 patients were included in the analysis. Median age was 60 years (IQR 52–69). Median preoperative tumor burden was 2.4 cm³ (IQR 0.8–8.3), and postoperative tumor burden was 0.5 cm³ (IQR 0.0–2.9). A total of 95 patients (43.4%) underwent surgery, and complete cytoreduction was achieved in 55 (25.1%) patients. Median overall survival was 6 months (IQR 2–10). Cutoff RTB in all patients was 0.12 cm³, showing a significant difference (p = 0.00029) in overall survival (OS). Multivariate analysis showed preoperative KPSS (HR 0.983, 95% CI, 0.967–0.997, p = 0.015), postoperative tumor burden (HR 1.03, 95% CI 1.008–1.053, p = 0.007), and complete vs. incomplete resection (HR 0.629, 95% CI 0.420–0.941, p = 0.024) as significant. Longer survival was significantly associated with surgery for recurrent BMs (p = 0.00097), and additional analysis demonstrated the significant effect of complete resection on survival (p = 0.0027). In the subgroup of patients with systemic progression, a cutoff RTB of 0.97 cm³ (p = 0.00068) was found; patients who had received surgery also showed prolonged OS (p = 0.036). Single systemic therapy (p = 0.048) and the combination of radiotherapy and systemic therapy had a significant influence on survival (p = 0.036). Conclusions: RTB is a strong prognostic factor for survival in patients with recurrent BMs. Operated patients with recurrent BMs showed longer survival independent of systemic progression. Maximal cytoreduction should be targeted to achieve better long-term outcomes.

Both positron emission tomography (PET) and magnetic resonance imaging (MRI), including dynamic susceptibility contrast perfusion (DSC-PWI), are crucial for treatment monitoring of patients with high-grade gliomas. In clinical practice, they are usually conducted at separate time points. Whether this affects their diagnostic performance is presently unclear. To this end, we retrospectively reviewed 38 patients with pathologically confirmed glioblastoma (IDH wild-type) and suspected tumor recurrence after radiotherapy. Only patients who received both a PET–MRI (where DSC perfusion was acquired simultaneously with a FET-PET) and a separate MRI exam (including DSC perfusion) were included. Tumors were automatically segmented into contrast-enhancing tumor (CET), necrosis, and edema. To compare the simultaneous as well as the sequential DSC perfusion to the FET-PET, we calculated Dice overlap, global mutual information as well as voxel-wise Spearman correlation of hotspot areas. For the joint assessment of PET and MRI, we computed logistic regression models for the differentiation between true progression (PD) and treatment-related changes (TRC) using simultaneously or sequentially acquired images as input data. We observed no significant differences between Dice overlap (p = 0.17; paired t-test), mutual information (p = 0.18; paired t-test) and Spearman correlation (p = 0.90; paired t-test) when comparing simultaneous PET–MRI and sequential PET/MRI acquisition. This also held true for the subgroup of patients with >14 days between exams. Importantly, for the diagnostic performance, ROC analysis showed similar AUCs for differentiation of PD and TRC (AUC simultaneous PET: 0.77; AUC sequential PET: 0.78; p = 0.83, DeLong’s test). We found no relevant differences between simultaneous and sequential acquisition of FET-PET and DSC perfusion, also regarding their diagnostic performance. Given the increasing attention to multi-parametric assessment of glioma treatment response, our results reassuringly suggest that sequential acquisition is clinically and scientifically acceptable.