Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors.

BACKGROUND: The aim of this clinical trial was to compare Fluorescein-stained intraoperative confocal laser endomicroscopy (CLE) of intracranial lesions and evaluation by a neuropathologist with routine intraoperative frozen section (FS) assessment by neuropathology. METHODS: In this phase II noninferiority, prospective, multicenter, nonrandomized, off-label clinical trial (EudraCT: 2019-004512-58), patients above the age of 18 years with any intracranial lesion scheduled for elective resection were included. The diagnostic accuracies of both CLE and FS referenced with the final histopathological diagnosis were statistically compared in a noninferiority analysis, representing the primary endpoint. Secondary endpoints included the safety of the technique and time expedited for CLE and FS. RESULTS: A total of 210 patients were included by 3 participating sites between November 2020 and June 2022. Most common entities were high-grade gliomas (37.9%), metastases (24.1%), and meningiomas (22.7%). A total of 6 serious adverse events in 4 (2%) patients were recorded. For the primary endpoint, the diagnostic accuracy for CLE was inferior with 0.87 versus 0.91 for FS, resulting in a difference of 0.04 (95% confidence interval -0.10; 0.02; P = .367). The median time expedited until intraoperative diagnosis was 3 minutes for CLE and 27 minutes for FS, with a mean difference of 27.5 minutes (standard deviation 14.5; P < .001). CONCLUSIONS: CLE allowed for a safe and time-effective intraoperative histological diagnosis with a diagnostic accuracy of 87% across all intracranial entities included. The technique achieved histological assessments in real time with a 10-fold reduction of processing time compared to FS, which may invariably impact surgical strategy on the fly.

Lumbar Spondylodiscitis Mimicking Cholecystitis: A Case Report and Review of Literature.

BACKGROUND: Lower back pain is a frequent cause of emergency department visits and one of the leading causes of the disease burden worldwide. The purpose of this case report and literature review was to discuss atypical abdominal entities mimicking spinal diseases typically presenting with lower back pain. METHODS: A 79-year-old man presented with lower back pain and urinary incontinence after receiving a non-image-guided lumbar infiltration treatment 4 weeks prior to admission. The magnetic resonance imaging (MRI) highlighted multisegmental hyperintensities in the intervertebral disk spaces of the lumbar spine indicative for spondylodiscitis. Antibiotic treatment over a week did not lead to significant clinical improvement. Blood cultures, cardiologic, otorhinolaryngologic, and dental examinations turned out negative for a focus of infection. A computed tomography (CT) guided biopsy was indicated after discontinuation of antibiotic treatment for less than 24 hours. Rapid clinical deterioration with concomitant onset of abdominal pain resulted in the diagnosis of cholecystitis, which required cholecystectomy. We performed a systematic literature review using the Pubmed database for the keywords "spondylodiscitis," "spine," "abdominal," and "cholecystitis," to identify abdominal diseases that mimic spine pathologies and spinal diseases that mimic abdominal pathologies. RESULTS: No other report in English literature of cholecystitis associated with initial onset of lower back pain was identified. Eighteen reports referred to abdominal conditions that mimic spinal diseases, among them a patient with cyclic lumbar back pain who received a lumbar spinal fusion who, after persisting symptoms led to further diagnostic procedures, was ultimately diagnosed with endometriosis. Spinal symptoms included paraplegia and urinary incontinence as results of acute aortic pathologies. Eleven reports presented spinal pain mimicking abdominal conditions including abdominal pain and diarrhea as well as have had surgical procedures such as an appendectomy before the spinal condition was discovered. CONCLUSION: Clinical symptoms of the spine such as lower back pain can be unspecific and lead to false conclusions in the presence of concomitant pathologies in MRI. Only clinical deterioration in our case patient prompted correction of the diagnosis on day 7. Initial workup for alternative common infectious foci such as lung and urinary tract was performed, but further abdominal workup despite the absence of abdominal symptoms may have led to an earlier diagnosis. Our literature review found several cases of misdiagnosed spinal and abdominal conditions. Some had undergone unnecessary surgical procedures before the right diagnosis was made. Because of the high incidence of symptoms such as lumbar back pain and abdominal pain, considering optimal patient care as well as economic aspects, it would be essential to conduct an interdisciplinary clinical management to avoid errors in the early stage of diagnostics.

Optimized Intraoperative Imaging for Stereotactic Planning with a Multiaxial Robotic C-arm System: Technical Note and Case Series.

BACKGROUND: The preoperative preparation of the planning dataset for frame-based stereotactic brain biopsy is often associated with logistical effort and burden on the patient. Intraoperative imaging modalities need to be investigated to overcome these limitations. OBJECTIVE: The objective of the study was to develop and apply a new method for the intraoperative acquisition of the planning dataset with the multiaxial robotic C-arm system Artis zeego. METHODS: An indication-customized dose-reduced protocol for Artis zeego was developed and implemented into the workflow. A sample of 14 patients who had undergone intraoperative imaging with Artis zeego was analyzed. A sample of 10 patients with conventional preoperative imaging by cranial computed tomography (CT) was used as a control group. Outcomes were compared with regard to target deviation, diagnostic value of the biopsies, complications, and procedure time. RESULTS: In all patients, a suitable intraoperative planning dataset could be acquired with Artis zeego. Total procedure time was shorter for the Artis zeego group (p = 0.01), whereas time in the operating room area was longer in the Artis zeego group (p = 0.04). Biopsy results were diagnostic in 12 patients (86%) in the Artis zeego group and in 8 patients (80%) in the control group. There were no significant differences in target size, trajectory length, or target deviation. CONCLUSION: Intraoperative imaging for frame-based stereotactic brain biopsy with Artis zeego is an easy and feasible method. Accuracy is comparable to conventional CT, whereas radiation exposure could be additionally reduced. It allows a significant reduction of the total procedure length and improves the comfort for the patient and staff.

Deep Neural Network for Differentiation of Brain Tumor Tissue Displayed by Confocal Laser Endomicroscopy.

BACKGROUND: Reliable on site classification of resected tumor specimens remains a challenge. Implementation of high-resolution confocal laser endoscopic techniques (CLEs) during fluorescence-guided brain tumor surgery is a new tool for intraoperative tumor tissue visualization. To overcome observer dependent errors, we aimed to predict tumor type by applying a deep learning model to image data obtained by CLE. METHODS: Human brain tumor specimens from 25 patients with brain metastasis, glioblastoma, and meningioma were evaluated within this study. In addition to routine histopathological analysis, tissue samples were stained with fluorescein ex vivo and analyzed with CLE. We trained two convolutional neural networks and built a predictive level for the outputs. RESULTS: Multiple CLE images were obtained from each specimen with a total number of 13,972 fluorescein based images. Test accuracy of 90.9% was achieved after applying a two-class prediction for glioblastomas and brain metastases with an area under the curve (AUC) value of 0.92. For three class predictions, our model achieved a ratio of correct predicted label of 85.8% in the test set, which was confirmed with five-fold cross validation, without definition of confidence. Applying a confidence rate of 0.999 increased the prediction accuracy to 98.6% when images with substantial artifacts were excluded before the analysis. 36.3% of total images met the output criteria. CONCLUSIONS: We trained a residual network model that allows automated, on site analysis of resected tumor specimens based on CLE image datasets. Further in vivo studies are required to assess the clinical benefit CLE can have.

Risk Factors and Management of Incidental Durotomy in Lumbar Interbody Fusion Surgery.

STUDY DESIGN: This is a retrospective study analysis. OBJECTIVE: In this retrospective study we evaluated risk factors for incidental durotomy and its impact on the postoperative course. SUMMARY OF BACKGROUND DATA: Lumbar interbody fusion (LIF) is increasingly applied for the treatment of degenerative instability. A known complication is incidental durotomy. MATERIALS AND METHODS: A cohort of 541 patients who underwent primary LIF surgery between 2005 and 2015 was analyzed. Previous lumbar surgery, age, surgeon's experience, intraoperative use of a microscope, and the number of operated levels were assessed and the risk for incidental durotomy was estimated using the Log-likelihood test and Wald test, respectively. The association of incidental durotomy and outcome parameters was analyzed using the quantile regression model. RESULTS: In 77 (14.2%) patients intraoperative cerebrospinal fluid (CSF) fistula was observed. Previous lumbar surgery (P<0.001), number of operated levels (P=0.03), and surgeon's experience (P=0.01) were significantly associated with incidental durotomy. Incidental durotomy was significantly associated with a prolonged bed rest (P<0.001), hospital stay (P=0.041), and an increased use of postoperative antibiotics (P<0.001). Eleven of 77 patients with incidental durotomy (14.3%) developed postoperative CSF fistula of whom 10 (91%) needed revision surgery for dural repair. CONCLUSIONS: We could identify important risk factors for incidental durotomy in LIF surgery. In patients who had undergone previous lumbar surgery and those with multilevel disease particular precaution is required. Furthermore, we were able to verify the morbidity associated with CSF fistula as shown by increased immobilization and follow-up surgeries for postoperative CSF fistula which emphasizes the importance to develop strategies to minimize the risk for incidental durotomy.

Prognostic factors and long-term survival in surgically treated brain metastases from non-small cell lung cancer.

OBJECTIVE: Brain metastases (BMs) are the most common malignant brain tumors in adults. Despite multimodal treatment options such as microsurgery, radiotherapy and chemotherapy, prognosis still remains very poor. Non-small cell lung cancer (NSCLC) constitutes the most common source of brain metastases. In this study, prognostic factors in this patient population were identified through an in-depth analysis of clinical parameters of patients with BMs from NSCLC. PATIENTS AND METHODS: Clinical data of 114 NSCLC cancer patients who underwent surgery for BMs at the University Hospital Heidelberg were retrospectively reviewed for age, gender, type of treatment, time course of the disease, presence of neurologic symptoms, Karnofsky Performance Status (KPS), smoking history, presence of extracranial metastases at initial diagnosis of NSCLC, number, location and size of brain metastases. Univariate and multivariate survival analyses were performed using the Log-rank test and Cox' proportional hazard model, respectively. RESULTS: Median survival time from surgery for BMs was 11.2 months. 18.4% (21 of 114) patients were long-term survivors (>24 months; range 26.3-75.1 months). Age, gender, size and number of intracranial metastases were not significantly associated with patient survival. Univariate analysis identified complete resection, postoperative whole brain radiotherapy (WBRT) and a preoperative KPS of >80% as positive prognostic factors. Infratentorial location and presence of extracranial metastases were shown to be negative prognostic factors. Surgery for the primary tumor was associated with a superior patient outcome both in univariate and multivariate analyses. CONCLUSION: Our data strongly suggest that surgical treatment of the primary tumor and complete resection of brain metastases in NSCLC patients followed by WBRT improve survival. Moreover, long-term survivors (>2 years) were more frequent than previously reported.