Neurosurgical resection of multiple brain metastases: outcomes, complications, and survival rates in a retrospective analysis.

PURPOSE: This study investigates the outcomes of microsurgical resection of multiple brain metastasis (BMs). METHODS: This retrospective, monocentric analysis included clinical data from all consecutive BM patients, who underwent simultaneous resection of ≥ 2 BMs between January 2018 and May 2023. Postoperative neurological and functional outcomes, along with perioperative complications, as well as survival data were evaluated. RESULTS: A total of 47 patients, with a median age of 61 years (IQR 48-69), underwent 73 craniotomies (median 2; range 1-3) for resection of 104 BMs. Among patients, 80.8% presented with symptomatic BMs, causing focal neurological deficits in 53% of cases. Gross total resection was achieved in 87.2% of BMs. Karnofsky Performance Scale (KPS) scores improved in 42.6% of patients, remained unchanged in 46.8%, and worsened in 10.6% after surgery. Perioperative complications were observed in 29.8% of cases, with transient complications occurring in 19.2% and permanent deficits in 10.6%. The 30-days mortality rate was 2.1%. Logistic regression identified eloquent localization (p = 0.036) and infratentorial craniotomy (p = 0.018) as significant predictors of postoperative complications. Concerning overall prognosis, patients with permanent neurological deficits post-surgery (HR 11.34, p = 0.007) or progressive extracranial disease (HR: 4.649; p = 0.006) exhibited inferior survival. CONCLUSION: Microsurgical resection of multiple BMs leads to clinical stabilization or functional improvement in most patients. Although transient complications do not affect overall survival, the presence of persistent neurological deficits (> 3 months post-surgery) and progressive extracranial disease negatively impact overall survival. This highlights the importance of careful patient selection for resection of multiple BMs.

Efficacy and safety of cysto-ventricular catheter implantation for space-occupying cysts arising from glioma and brain metastasis: a retrospective study.

BACKGROUND: Cysto-ventricular catheters (CVC) have emerged as promising treatment option for cystic craniopharyngioma and arachnoid cysts, but their effectiveness in treating cysts originating from glioma or brain metastasis (BM) remains limited. This study aimed to analyze the efficacy of CVC in patients with glioma and BM as well as procedure-associated morbidity. METHODS: This single-center retrospective study included all patients treated with CVC placement for acquired space-occupying cysts deriving from previously treated glioma or BMs between 1/2010 and 12/2021. RESULTS: A total of 57 patients with a median age of 47 years (IQR 38-63) were identified. Focal neurological deficits were the predominant symptoms in 60% of patients (n = 34), followed by cephalgia in 14% (n = 8), and epileptic seizures in 21.1% (n = 12). Accurate CVC placement was achieved in all but one case requiring revision surgery due to malposition. Three months after CVC implantation, 70% of patients showed symptomatic improvement. Multivariate logistic regression analysis identified the development of space-occupying cysts later in the course of the disease (OR 1.014; p = 0.04) and a higher reduction of cyst-volume postoperatively (OR 1.055; p = 0.05) were significant predictors of postoperative symptomatic improvement following CVC placement. Local cyst recurrence was observed in three cases during follow-up MRI after an average time of 5 months (range 3-9 months). Further complications included secondary malresorptive hydrocephalus in three cases and meningeosis neoplastica in one patient. CONCLUSIONS: Stereotactic implantation of CVC is an efficient treatment option for patients suffering from symptomatic space-occupying cysts from BMs or glioma, independently from their CNS WHO grade. However, a vigilant approach is crucial regarding potential complications and treatment failures.

Evaluation of surgical treatment strategies and outcome for cerebral arachnoid cysts in children and adults.

OBJECTIVE: The best treatment strategies for cerebral arachnoid cysts (CAC) are still up for debate. In this study, we present CAC management, outcome data, and risk factors for recurrence after surgical treatment, focusing on microscopic/endoscopic approaches as compared to minimally invasive stereotactic procedures in children and adults. METHODS: In our single-institution retrospective database, we identified all patients treated surgically for newly diagnosed CAC between 2000 and 2022. Microscopic/endoscopic surgery (ME) aimed for safe cyst wall fenestration. Stereotactic implantation of an internal shunt catheter (STX) to drain CAC into the ventricles and/or cisterns was used as an alternative procedure in patients aged ≥ 3 years. Treatment decisions in favor of ME vs. STX were made by interdisciplinary consensus. The primary study endpoint was time to CAC recurrence (TTR). Secondary endpoints were outcome metrics including clinical symptoms and MR-morphological analyses. Data analysis included subdivision of the total cohort into three distinct age groups (AG1, < 6 years; AG2, 6-18 years; AG3, ≥ 18 years). RESULTS: Sixty-two patients (median age 26.5 years, range 0-82 years) were analyzed. AG1 included 15, AG2 10, and AG3 37 patients, respectively. The main presenting symptoms were headache and vertigo. In AG1 hygromas, an increase in head circumference and thinning of cranial calvaria were most frequent. Thirty-five patients underwent ME and 27 STX, respectively; frequency did not differ between AGs. There were two (22.2%) periprocedural venous complications in infants (4- and 10-month-old) during an attempt at prepontine fenestration of a complex CAC, one with fatal outcome in a 10-month-old boy. Other complications included postoperative bleeding (2, 22.2%), CSF leaks (4, 44.4%), and meningitis (1, 11.1%). Overall, clinical improvement and significant volume reduction (p = 0.008) were seen in all other patients; this did not differ between AGs. Median follow-up for all patients was 25.4 months (range, 3.1-87.1 months). Recurrent cysts were seen in 16.1%, independent of surgical procedure used (p = 0.7). In cases of recurrence, TTR was 7.9 ± 12.7 months. Preoperative ventricular expansion (p = 0.03), paresis (p = 0.008), and age under 6 years (p = 0.03) were significant risk factors for CAC recurrence in multivariate analysis. CONCLUSIONS: In patients suffering from CAC, both ME and STX can improve clinical symptoms at low procedural risk, with equal extent of CAC volume reduction. However, in infants and young children, CAC are more often associated with severe clinical symptoms, stereotactic procedures have limited use, and microsurgery in the posterior fossa may bear the risk of severe venous bleeding.

Risk-benefit analysis of surgical treatment strategies for cystic craniopharyngioma in children and adolescents.

Objective: Treatment strategies for craniopharyngiomas are still under debate particularly for the young population. We here present tumor control and functional outcome data after surgical treatment focusing on stereotactic and microsurgical procedures for cystic craniopharyngiomas in children and adolescents. Methods: From our prospective institutional database, we identified all consecutive patients less than 18 years of age who were surgically treated for newly-diagnosed cystic craniopharyngioma between, 2000 and, 2022. Treatment decisions in favor of stereotactic treatment (STX) or microsurgery were made interdisciplinary. STX included aspiration and/or implantation of an internal shunt catheter for permanent cyst drainage. Microsurgery aimed for safe maximal tumor resections. Study endpoints were time to tumor recurrence (TTR) and functional outcome including ophthalmological/perimetric, endocrinological, and body-mass index (BMI) data. Results: 29 patients (median age 9.9 yrs, range 4-18 years) were analyzed. According to our interdisciplinary tumor board recommendation, 9 patients underwent stereotactic treatment, 10 patients microsurgical resection, and 10 patients the combination of both. Significant volume reduction was particularly achieved in the stereotactic (p=0.0019) and combined subgroups (p<0.001). Improvement of preoperative visual deficits was always achieved independent of the applied treatment modality. Microsurgery and the combinational treatment were associated with higher rates of postoperative endocrinological dysfunction (p<0.0001) including hypothalamic obesity (median BMI increase from 17.9kg/m2 to 24.1kg/m2, p=0.019). Median follow-up for all patients was 93.9 months (range 3.2-321.5 months). Recurrent tumors were seen in 48.3% and particularly concerned patients after initial combination of surgery and STX (p=0.004). In here, TTR was 35.1 ± 46.9 months. Additional radiation therapy was found indicated in 4 patients to achieve long-lasting tumor control. Conclusion: In children and adolescents suffering from predominantly cystic craniopharyngiomas, stereotactic and microsurgical procedures can improve clinical symptoms at low procedural risk. Microsurgery, however, bears a higher risk of postoperative endocrine dysfunction. A risk-adapted surgical treatment concept may have to be applied repeatedly in order to achieve long-term tumor control even without additional irradiation.

Minimally invasive third ventriculostomy with stereotactic internal shunt placement for the treatment of tumor-associated noncommunicating hydrocephalus.

BACKGROUND: Intracranial tumors can cause obstructive hydrocephalus (OH). Most often, symptomatic treatment is pursued through ventriculoperitoneal shunt (VS) or endoscopic third ventriculostomy (ETV). In this study, we propose stereotactic third ventriculostomy with internal shunt placement (sTVIP) as an alternative treatment option and assess its safety and efficacy. METHODS: In this single-center, retrospective analysis, clinical symptoms, procedure-related complications, and revision-free survival of all patients with OH due to tumor formations treated by sTVIP between January 2010 and December 2021 were evaluated. RESULTS: Clinical records of thirty-eight patients (11 female, 27 male) with a mean age of 40 years (range 5-88) were analyzed. OH was predominantly (in 92% of patients) caused by primary brain tumors (with exception of 3 cases with metastases). Following sTVIP, 74.2% of patients experienced symptomatic improvement. Preoperative headache was a significant predictor of postoperative symptomatic improvement (OR 26.25; 95% CI 4.1-521.1; p = 0.0036). Asymptomatic hemorrhage was detected along the stereotactic trajectory in 2 cases (5.3%). One patient required local revision due to CSF fistula (2.6%); another patient had to undergo secondary surgery to connect the catheter to a valve/abdominal catheter due to CSF malabsorption. However, in the remaining 37 patients, shunt independence was maintained during a median follow-up period of 12 months (IQR 3-32 months). No surgery-related mortality was observed. CONCLUSIONS: sTVIP led to a significant symptom control and was associated with low operative morbidity, along with a high rate of ventriculoperitoneal shunt independency during the follow-up period. Therefore, sTVIP constitutes a highly effective and minimally invasive treatment option for tumor-associated obstructive hydrocephalus, even in cases with a narrow prepontine interval.

Energy-Reduced Fabrication of Light-Frame Ceramic Honeycombs by Replication of Additive Manufactured Templates.

Ceramic components require very high energy consumption due to synthesis, shaping, and thermal treatment. However, this study suggests that combining the sol-gel process, replica technology, and stereolithography has the potential to produce highly complex geometries with energy savings in each process step. We fabricated light-frame honeycombs of Al2O3, Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT), and BaTiO3 (BT) using 3D-printed templates with varying structural angles between -30° and 30° and investigated their mechanical and piezoelectric properties. The Al2O3 honeycombs showed a maximum strength of approximately 6 MPa, while the BCZT and BaTiO3 honeycombs achieved a d33 above 180 pC/N. Additionally, the BCZT powder was prepared via a sol-gel process, and the impact of the calcination temperature on phase purity was analyzed. The results suggest that there is a large energy-saving potential for the synthesis of BCZT powder. Overall, this study provides valuable insights into the fabrication of complex ceramic structures with improved energy efficiency and enhancement of performance.

Treatment benefit in patients aged 80 years or older with biopsy-proven and non-resected glioblastoma is dependent on MGMT promoter methylation status.

PURPOSE: Glioblastoma is associated with especially poor outcome in the elderly. It is unclear if patients aged ≥80 years benefit from tumor-specific therapy as opposed to receiving best supportive care (BSC) only. METHODS: Patients with IDH-wildtype glioblastoma (WHO 2021), aged ≥80 years, and diagnosed by biopsy between 2010 and 2022 were included. Patient characteristics and clinical parameters were assessed. Uni- and multivariate analyses were performed. RESULTS: 76 patients with a median age of 82 (range 80-89) and a median initial KPS of 80 (range 50-90) were included. Tumor-specific therapy was initiated in 52 patients (68%). 22 patients (29%) received temozolomide monotherapy, 23 patients (30%) were treated with radiotherapy (RT) alone and 7 patients (9%) received combination therapies. In 24 patients (32%), tumor-specific therapy was omitted in lieu of BSC. Overall survival (OS) was longer in patients receiving tumor-specific therapy (5.4 vs. 3.3 months, p < 0.001). Molecular stratification showed that the survival benefit was owed to patients with MGMT promoter methylation (MGMTpos) who received tumor-specific therapy as opposed to BSC (6.2 vs. 2.6 months, p < 0.001), especially to those with better clinical status and no initial polypharmacy. Patients with unmethylated MGMT promoter (MGMTneg) did not benefit from tumor-specific therapy (3.6 vs. 3.7 months, p = 0.18). In multivariate analyses, better clinical status and MGMT promoter methylation were associated with prolonged survival (p < 0.01 and p = 0.01). CONCLUSION: Benefit from tumor-specific treatment in patients with newly diagnosed glioblastoma aged ≥80 years might be restricted to MGMTpos patients, especially to those with good clinical status and no polypharmacy.

Spinal Tuberculosis within the Vertebral Arch Mimicking a Malignant Tumor: Case Report.

BACKGROUND: Spinal tuberculosis is a manifestation of extrapulmonary tuberculosis. The incidence of tuberculosis is low in high-income countries; however, globally, it still remains one of the most frequent fatal infectious diseases. Because of its rarity in developed countries, spinal tuberculosis can be mistaken for malignant tumors of the spine, especially in case of an atypical radiologic manifestation and without pulmonary affection. METHODS: We present the case of a 39-year-old man from South India with quickly progressing gait disturbance and hypesthesia below the Th10 level. Magnetic resonance imaging revealed an osteolytic lesion of the vertebral arch Th2 with central necrosis and compression of the spinal cord altogether highly suspicious for spinal metastasis. RESULTS: After surgical removal of the mass by laminectomy, the patient regained normal neurologic function. Histology revealed a severe granulomatous inflammation and DNAhybridization of polymerase chain reaction (PCR) products detected Mycobacterium tuberculosis-specific DNA in the sample. Biopsy of an enlarged hilar lymphnode allowed us to obtain material to successfully perform a drug resistance test to start specific antimicrobial therapy. CONCLUSION: Spinal tuberculosis, even with atypical radiologic appearance, has to be considered a differential diagnosis in patients with provenance from endemic countries. A multidisciplinary diagnostic approach helps perform antimicrobial susceptibility testing to avoid delaying the start of antibiotic therapy.

Acute Hiccups Detected by Electromyographic Recordings During Resection of a Vestibular Schwannoma.

BACKGROUND AND IMPORTANCE: Intraoperative neuromonitoring (IONM) is routinely used to monitor cranial nerve function during resection of vestibular schwannomas. Sudden movements in the surgical field can be a disturbing factor for the surgeon. IONM can help determine the cause of unexpected patient movements. CLINICAL PRESENTATION: We report the case of a 54-year-old patient who underwent retromastoid craniotomy and resection of a vestibular schwannoma. Toward the end of dissection of the tumor from the lower cranial nerves and brainstem, the patient showed repetitive shoulder elevation. Electroencephalography showed burst suppression, confirming deep sedation and excluding voluntary movements. Free-running electromyography recorded spontaneous, simultaneous, bilateral vocal cord activity that was synchronous with upper body movement. There was simultaneous but smaller activity in the right genioglossus muscle and levator veli palatini, indicative for far-field activity. These IONM findings allowed us to classify the clinical observations as intraoperative hiccups. CONCLUSION: Hiccups during general anesthesia are rare but should be considered as a differential diagnosis of sudden upper body movement. To the best of our knowledge, this is the first reported case of acute hiccups during resection of a vestibular schwannoma. IONM reliably distinguished it from an increase in intraoperative consciousness or accessory nerve activation resulting in shoulder movements.

Intramedullary spinal cord cavernous malformations-association between intraoperative neurophysiological monitoring changes and neurological outcome.

BACKGROUND: Microsurgical resection of spinal cord cavernous malformations can be assisted by intraoperative neurophysiological monitoring (IONM). While the clinical outcome after surgical resection has been discussed in several case series, the association of intraoperative IONM changes and detailed neurological outcome, however, has not been analyzed so far. METHODS: Seventeen patients with spinal cavernomas underwent surgery between 02/2004 and 06/2020. Detailed neurological and clinical outcome as well as IONM data including motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) monitoring were retrospectively analyzed. Intraoperative IONM changes were compared to outcome at 3-month and 1-year follow-up in order to identify surrogate parameters for an impending neurological deficit. RESULTS: Compared to the preoperative state, McCormick score at 1-year follow-up remained unchanged in 12 and improved in five patients, none worsened, while detailed neurological examination revealed a new or worsened sensorimotor deficit in 4 patients. The permanent 80% amplitude reduction of MEP and 50% amplitude reduction of SSEP showed the best diagnostic accuracy with a sensitivity of 100% and 67% respectively and a specificity of 73% and 93% respectively. The relative risk for a new neurological deficit at 1-year follow-up, when reversible IONM-deterioration was registered compared to irreversible IONM deterioration, was 0.56 (0.23-1.37) for MEP deterioration and 0.4 (0.18-0.89) for SSEP deterioration. CONCLUSIONS: Reversible IONM changes were associated with a better neurological outcome at follow-up compared to irreversible IONM deterioration during SCCM surgery. Our study favors the permanent 80% amplitude reduction criterion for MEP and 50% amplitude reduction criterion for SSEP for further prospective evaluation of IONM significance and the effectiveness of corrective maneuvers during SCCM surgeries.

Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis.

Carcinoma cells undergo epithelial-mesenchymal transition (EMT); however, contributions of EMT heterogeneity to disease progression remain a matter of debate. Here, we addressed the EMT status of ex vivo cultured circulating and disseminated tumor cells (CTCs/DTCs) in a syngeneic mouse model of metastatic breast cancer (MBC). Epithelial-type CTCs with a restricted mesenchymal transition had the strongest lung metastases formation ability, whereas mesenchymal-type CTCs showed limited metastatic ability. EpCAM expression served as a surrogate marker to evaluate the EMT heterogeneity of clinical samples from MBC, including metastases, CTCs, and DTCs. The proportion of epithelial-type CTCs, and especially DTCs, correlated with distant metastases and poorer outcome of patients with MBC. This study fosters our understanding of EMT in metastasis and underpins heterogeneous EMT phenotypes as important parameters for tumor prognosis and treatment. We further suggest that EpCAM-dependent CTC isolation systems will underestimate CTC numbers but will quantify clinically relevant metastatic cells.

Spatiotemporal patterning of EpCAM is important for murine embryonic endo- and mesodermal differentiation.

Epithelial cell adhesion molecule EpCAM is expressed in pluripotent embryonic stem cells (ESC) in vitro, but is repressed in differentiated cells, except epithelia and carcinomas. Molecular functions of EpCAM, possibly imposing such repression, were primarily studied in malignant cells and might not apply to non-pathologic differentiation. Here, we comprehensively describe timing and rationale for EpCAM regulation in early murine gastrulation and ESC differentiation using single cell RNA-sequencing datasets, in vivo and in vitro models including CRISPR-Cas9-engineered ESC-mutants. We demonstrate expression of EpCAM in inner cell mass, epiblast, primitive/visceral endoderm, and strict repression in the most primitive, nascent Flk1+ mesoderm progenitors at E7.0. Selective expression of EpCAM was confirmed at mid-gestation and perinatal stages. The rationale for strict patterning was studied in ESC differentiation. Gain/loss-of-function demonstrated supportive functions of EpCAM in achieving full pluripotency and guided endodermal differentiation, but repressive functions in mesodermal differentiation as exemplified with cardiomyocyte formation. We further identified embryonic Ras (ERas) as novel EpCAM interactor of EpCAM and an EpCAM/ERas/AKT axis that is instrumental in differentiation regulation. Hence, spatiotemporal patterning of EpCAM at the onset of gastrulation, resulting in early segregation of interdependent EpCAM+ endodermal and EpCAM-/vimentin+ mesodermal clusters represents a novel regulatory feature during ESC differentiation.