Surgical technique: Posterior retropleural thoracotomy for resection of a T10 dumbbell schwannoma.

Background: Myelopathy and nerve root dysfunction resulting from the imperceptible growth of intraspinal schwannomas have been well documented.[1] Thoracic spine schwannomas, in particular, have exceptional growth potential due to the presence of the posterior mediastinum and retropleural spaces accommodating insidious and often subclinical tumor expansion.[5] Extraspinal extension of these lesions, however, poses a distinct challenge for surgeons.[3,4]. Case Description: Here, we provide a two-dimensional intraoperative video demonstrating the technical nuances concerning maximally safe resection of a partially cystic thoracic dumbbell schwannoma having extraspinal extension with associated bony remodeling of the T10 vertebral body and neural foramen in a middle-aged male. A posterolateral approach with T8-T12 fusion, retropleural thoracotomy, facetectomies, and pediculectomies allowed for gross total resection. No intraoperative or postoperative complications were observed, and the parietal pleura was kept intact throughout the surgery. In addition, the patient continued to have improved symptoms and was ambulatory at 6-month follow-up. Conclusion: Gross total resection of a partially cystic thoracic dumbbell schwannoma was achieved without complications. Our use of a preoperative three-dimensional reconstruction for surgical planning,[2] intraoperative ultrasound,[6] and a durable instrumentation construct were essential for a successful outcome. Moreover, great care was taken to avoid violating the tumor-parietal pleura plane, which would have resulted in postoperative respiratory complications.

A rare case of multifocal craniospinal leptomeningeal melanocytoma: A case report and scoping review.

Introduction: Leptomeningeal melanocytomas are rare tumours originating from neural crest derived melanocytes. They are usually solitary and presentation with multifocal meningeal melanocytoma is very rare and indicative of potentially more aggressive behaviour. This case report and scoping review sought to evaluate the presentation, and key radiological features that can help differentiate multifocal meningeal melanocytoma from other differentials and provide a discussion of the key management and prognostic points once these tumours are diagnosed. Case presentation: A 26 year old male presented with neck pain radiating to both shoulders and subjective weakness in left shoulder movement. MRI demonstrated a large enhancing C2-C3 intradural-extramedullary lesion with further lesions at the T7/T8 level, left cerebellopontine angle and midline suprachiasmatic region. Whilst the imaging appearances were initially thought be indicative of a phacomatosis such as NF2-related schwannomatosis, surgical excision of the cervical tumour confirmed a melanocytic tumour of leptomeningeal origin, consistent with multifocal meningeal melanocytoma. Patient made a good post-operative recovery and remains under half yearly radiological surveillance, with repeat MRI 6 months after surgery demonstrating subtle growth of the untreated intracranial and spinal lesions. Literature review and conclusions: This is the first description, to our knowledge, of a multifocal meningeal melanocytoma associated with both cerebellopontine angle and suprasellar lesions. This case and included scoping review highlight the need to consider this rare diagnosis whenever multifocal craniospinal lesions are encountered, and the need to consider aggressive management through surgical resection and adjuvant craniospinal radiotherapy once these tumours are diagnosed.

Transcription factor support for the dual embryological origin of the sternocleidomastoid and trapezius muscles.

The embryological origin of the trapezius and sternocleidomastoid muscles has been debated for over a century. To shed light on this issue, the present anatomical study was performed. Five fresh frozen human cadavers, three males and two females, were used for this study. Samples from each specimen's trapezius and sternocleidomastoid were fixed in 10% formalin and placed in paraffin blocks. As Paired like homeodomain 2 (Pitx2) and T-box factor 1(Tbx1) have been implicated in the region and muscle type regulation, we performed Tbx1 and Pitx2 Immunohistochemistry (IHC) on these muscle tissue samples to identify the origin of the trapezius and sternocleidomastoid muscles. We have used the latest version of QuPath, v0.4.3, software to quantify the Tbx and Pitx2 staining. For the sternocleidomastoid muscle, for evaluated samples, the average amount of positively stained Tbx1 and Pitx2 was 25% (range 16%-30%) and 18% (range 12%-23%), respectively. For the trapezius muscles, for evaluated samples, the average amount of positively stained Tbx1 and Pitx2 parts of the samples was 17% (range 15%-20%) and 15% (14%-17%), respectively. Our anatomical findings suggest dual origins of both the trapezius and sternocleidomastoid muscles. Additionally, as neither Pitx2 nor Tbx1 made up all the staining observed for each muscle, other contributions to these structures are likely. Future studies with larger samples are now necessary to confirm these findings.

Technical nuances for the resection of cervical dumbbell schwannomas.

The majority of spinal nerve sheath tumors are within the intradural/extramedullary compartment. A subset of these tumors develop extraforaminal components that gradually expand into potential spaces. Herein, the authors provide a 2D video demonstrating the technical nuances concerning resection of cervical dumbbell schwannomas with extraspinal extension. Although nerve sheath tumors with large extraforaminal extension are often associated with complications and pose unique challenges to surgeons, circumferential exposure with intradural exploration allows for gross-total resection and nerve root preservation, without need for adjuvant treatments. The use of intraoperative ultrasound, neurophysiological monitoring, Doppler imaging, and meticulous surgical techniques aided to circumvent complications.

Combining Procedural and Behavioral Treatments for Chronic Low Back Pain: A Pilot Feasibility Randomized Controlled Trial.

Individual treatments for chronic low back pain (CLBP) have small magnitude effects. Combining different types of treatments may produce larger effects. This study used a 2×2 factorial randomized controlled trial (RCT) design to combine procedural and behavioral treatments for CLBP. The study aims were to: (1) assess feasibility of conducting a factorial RCT of these treatments; and (2) estimate individual and combined treatment effects of (a) lumbar radiofrequency ablation (LRFA) of the dorsal ramus medial branch nerves (vs. a simulated LRFA control procedure) and (b) Activity Tracker-Informed Video-Enabled Cognitive Behavioral Therapy program for CLBP (AcTIVE-CBT) (vs. an educational control treatment) on back-related disability at 3 months post-randomization. Participants (n=13) were randomized in a 1:1:1:1 ratio. Feasibility goals included an enrollment proportion ≥30%, a randomization proportion ≥80%, and a ≥80% proportion of randomized participants completing the 3-month Roland-Morris Disability Questionnaire (RMDQ) primary outcome endpoint. An intent-to-treat analysis was used. The enrollment proportion was 62%, the randomization proportion was 81%, and all randomized participants completed the primary outcome. Though not statistically significant, there was a beneficial, moderate-magnitude effect of LRFA vs. control on 3-month RMDQ (-3.25 RMDQ points; 95% CI: -10.18, 3.67). There was a significant, beneficial, large-magnitude effect of AcTIVECBT vs. control (-6.29, 95% CI: -10.97, -1.60). Though not statistically significant, there was a beneficial, large effect of LRFA+AcTIVE-CBT vs. control (-8.37; 95% CI: -21.47, 4.74). We conclude that it is feasible to conduct an RCT combining procedural and behavioral treatments for CLBP.

Age, Sex, and BMI Differences Related to Repairable Meniscal Tears in Pediatric and Adolescent Patients.

BACKGROUND: The incidence of meniscus tears and ACL tears in pediatric patients continues to rise, bringing to question the risk factors associated with these injuries. As meniscus tears are commonly repaired in pediatric populations, the epidemiology of repairable meniscus tears is an important for consideration for surgeons evaluating treatment options. PURPOSE: To describe meniscal tear patterns in pediatric and adolescent patients who underwent meniscal repair across multiple institutions and surgeons, as well as to evaluate the relationship between age, sex, and body mass index (BMI) and their effect on the prevalence, type, and displacement of repaired pediatric meniscal tears. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Data within a prospective multicenter cohort registry for quality improvement, Sport Cohort Outcome Registry (SCORE), were reviewed to describe repaired meniscal tear patterns. All consecutive arthroscopic meniscal repairs from participating surgeons in patients aged <19 years were analyzed. Tear pattern, location, and displacement were evaluated by patient age, sex, and BMI. A subanalysis was also performed to investigate whether meniscal tear patterns differed between those occurring in isolation or those occurring with a concomitant anterior cruciate ligament (ACL) injury. Analysis of variance was used to generate a multivariate analysis of specified variables. Sex, age, and BMI results were compared across the cohort. RESULTS: There were 1185 total meniscal repairs evaluated in as many patients, which included 656 (55.4%) male and 529 (44.6%) female patients. Patients underwent surgery at a mean age of 15.3 years (range, 5-19 years), with a mean BMI of 24.9 (range, 12.3-46.42). Of the 1185 patients, 816 (68.9%) had ACL + meniscal repair and 369 (31.1%) had isolated meniscal repair. The male patients underwent more lateral tear repairs than the female patients (54.3% to 40.9%; P < .001) and had a lower incidence of medial tear repair (32.1% vs 41.4%; P < .001). Patients with repaired lateral tears had a mean age of 15.0 years, compared with a mean age of 15.4 years for patients with repaired medial or bilateral tears (P = .001). Higher BMI was associated with "complex" and "radial" tear repairs of the lateral meniscus (P < .001) but was variable with regard to medial tear repairs. CONCLUSION: In pediatric and adolescent populations, the data suggest that the surgical team treating knees with potential meniscal injury should be prepared to encounter more complex meniscal tears, commonly indicated in those with higher BMI, while higher rates of lateral meniscal tears were seen in male and younger patients. Future studies should analyze correlates for meniscal repair survival and outcomes in this pediatric cohort undergoing knee surgery.

Raman hyperspectral imaging coupled to three-dimensional discriminant analysis: Classification of meningiomas brain tumour grades.

Meningiomas remains a clinical dilemma. They are the commonest "benign" types of brain tumours and, although being typically benign, they are divided into three WHO grades categories (I, II and III) which are associated with the tumour growth rate and likelihood of recurrence. Recurrence depends on extend of surgery as well as histopathological diagnosis. There is a marked variation amongst surgeons in the follow-up arrangements for their patients even within the same unit which has a significant clinical, and financial implication. Knowing the tumour grade rapidly is an important factor to predict surgical outcomes and adequate patient treatment. Clinical follow up sometimes is haphazard and not based on clear evidence. Spectrochemical techniques are a powerful tool for cancer diagnostics. Raman hyperspectral imaging is able to generate spatially-distributed spectrochemical signatures with great sensitivity. Using this technique, 95 brain tissue samples (66 meningiomas WHO grade I, 24 meningiomas WHO grade II and 5 meningiomas that reoccurred) were analysed in order to discriminate grade I and grade II samples. Newly-developed three-dimensional discriminant analysis algorithms were used to process the hyperspectral imaging data in a 3D fashion. Three-dimensional principal component analysis quadratic discriminant analysis (3D-PCA-QDA) was able to distinguish grade I and grade II meningioma samples with 96% test accuracy (100% sensitivity and 95% specificity). This technique is here shown to be a high-throughput, reagent-free, non-destructive, and can give accurate predictive information regarding the meningioma tumour grade, hence, having enormous clinical potential with regards to being developed for intra-operative real-time assessment of disease.

Genome-wide methylation analyses identifies Non-coding RNA genes dysregulated in breast tumours that metastasise to the brain.

Brain metastases comprise 40% of all metastatic tumours and breast tumours are among the tumours that most commonly metastasise to the brain, the role that epigenetic gene dysregulation plays in this process is not well understood. We carried out 450 K methylation array analysis to investigate epigenetically dysregulated genes in breast to brain metastases (BBM) compared to normal breast tissues (BN) and primary breast tumours (BP). For this, we referenced 450 K methylation data for BBM tumours prepared in our laboratory with BN and BP from The Cancer Genome Atlas. Experimental validation on our initially identified genes, in an independent cohort of BP and in BBM and their originating primary breast tumours using Combined Bisulphite and Restriction Analysis (CoBRA) and Methylation Specific PCR identified three genes (RP11-713P17.4, MIR124-2, NUS1P3) that are hypermethylated and three genes (MIR3193, CTD-2023M8.1 and MTND6P4) that are hypomethylated in breast to brain metastases. In addition, methylation differences in candidate genes between BBM tumours and originating primary tumours shows dysregulation of DNA methylation occurs either at an early stage of tumour evolution (in the primary tumour) or at a later evolutionary stage (where the epigenetic change is only observed in the brain metastasis). Epigentic changes identified could also be found when analysing tumour free circulating DNA (tfcDNA) in patient's serum taken during BBM biopsies. Epigenetic dysregulation of RP11-713P17.4, MIR3193, MTND6P4 are early events suggesting a potential use for these genes as prognostic markers.

Telehealth and Rural-Urban Differences in Receipt of Pain Care in the Veterans Health Administration.

OBJECTIVE: Examine changes in specialty pain utilization in the Veterans Health Administration (VHA) after establishing a virtual interdisciplinary pain team (TelePain). DESIGN: Retrospective cohort study. SETTING: A single VHA healthcare system, 2015-2019. SUBJECTS: 33,169 patients with chronic pain-related diagnoses. METHODS: We measured specialty pain utilization (in-person and telehealth) among patients with moderate to severe chronic pain. We used generalized estimating equations to test the association of time (pre- or post-TelePain) and rurality on receipt of specialty pain care. RESULTS: Among patients with moderate to severe chronic pain, the reach of specialty pain care increased from 11.1% to 16.2% in the pre- to post-TelePain periods (adjusted odds ratio [aOR]: 1.37, 95% confidence interval [CI]: 1.26-1.49). This was true of both urban patients (aOR: 1.62, 95% CI: 1.53-1.71) and rural patients (aOR: 1.16, 95% CI: 0.99-1.36), although the difference for rural patients was not statistically significant. Among rural patients who received specialty pain care, a high percentage of the visits were delivered by telehealth (nearly 12% in the post-TelePain period), much higher than among urban patients (3%). CONCLUSIONS: We observed increased use of specialty pain services among all patients with chronic pain. Although rural patients did not achieve the same degree of access and utilization overall as urban patients, their use of pain telehealth increased substantially and may have substituted for in-person visits. Targeted implementation efforts may be needed to further increase the reach of services to patients living in areas with limited specialty pain care options.

Multicenter study evaluating factors associated with treatment outcome for low back pain injections.

BACKGROUND: There has been a worldwide surge in interventional procedures for low back pain (LBP), with studies yielding mixed results. These data support the need for identifying outcome predictors based on unique characteristics in a pragmatic setting. METHODS: We prospectively evaluated the association between over two dozen demographic, clinical and technical factors on treatment outcomes for three procedures: epidural steroid injections (ESIs) for sciatica, and sacroiliac joint (SIJ) injections and facet interventions for axial LBP. The primary outcome was change in patient-reported average pain intensity on a numerical rating scale (average NRS-PI) using linear regression. For SIJ injections and facet radiofrequency ablation, this was average LBP score at 1 and 3 months postprocedure, respectively. For ESI, it was average leg pain 1- month postinjection. Secondary outcomes included a binary indicator of treatment response (success). RESULTS: 346 patients were enrolled at seven hospitals. All groups experienced a decrease in average NRS-PI (p<0.0001; mean 1.8±2.6). There were no differences in change in average NRS-PI among procedural groups (p=0.50). Lower baseline pain score (adjusted coefficient -0.32, 95% CI -0.48 to -0.16, p<0.0001), depressive symptomatology (adjusted coefficient 0.076, 95% CI 0.039 to 0.113, p<0.0001) and obesity (adjusted coefficient 0.62, 95% CI 0.038 to 1.21, p=0.037) were associated with smaller pain reductions. For procedural outcome, depression (adjusted OR 0.94, 95% CI 0.91, 0.97, p<0.0001) and poorer baseline function (adjusted OR 0.59, 95% CI 0.36, 0.96, p=0.034) were associated with failure. Smoking, sleep dysfunction and non-organic signs were associated with negative outcomes in univariate but not multivariate analyses. CONCLUSIONS: Identifying treatment responders is a critical endeavor for the viability of procedures in LBP. Patients with greater disease burden, depression and obesity are more likely to fail interventions. Steps to address these should be considered before or concurrent with procedures as considerations dictate. TRIAL REGISTRATION NUMBER: NCT02329951.

Cervical avulsion during induced labour: diagnosis, intraoperative management and postoperative course.

We report the presentation, operative management and follow-up of a 31-year-old nulliparous woman who experienced a cervical avulsion injury (CAI) during labour. The woman was induced with dinoprostone gel, followed by oxytocin infusion and had a prolonged active phase. During the second stage, fetal decelerations were noted and the consultant asked to make a plan for delivery. When assessing to perform a midpelvic instrumental delivery, a cord of tissue was felt below the fetal head. A caesarean delivery was recommended based on this finding. After delivery, injuries to the broad ligament, posterior lower uterine segment vagina and cervix were repaired. The cervix was retained with the intent that some tissue be salvaged. At 6-week follow-up, transvaginal ultrasound confirmed blood flow in the cervical tissue, though cervical insufficiency was suspected on clinical examination. Our findings reinforce the seriousness of CAI and support conservative surgical management as opposed to trachelectomy or hysterectomy.

Rare Case of Multiple Intradural Extramedullary Spinal Schwannomas With Intramedullary Extension.

Spinal schwannomas are benign WHO grade I nerve sheath tumors that account for nearly 30% of all spinal neoplasm. Typically, these lesions are intradural extramedullary in location and are composed entirely of well-differentiated eosinophilic Schwann cells. Intramedullary schwannomas, however, are extremely rare due to the lack of Schwan cells in the normal spinal cord and represent 1% of all the spinal schwannoma population. The presence of such an intramedullary component makes diagnosis challenging as imaging features may resemble other intramedullary neoplastic entities. Here, we describe a case of a 56-year-old male patient who presented with an 18-month history of intermittent right-sided mid-thoracic pain secondary to multiple intradural extramedullary spinal schwannoma with intramedullary extensions. We also review the literature pertaining to the condition.

Bringing chronic-pain care to rural veterans: A telehealth pilot program description.

Opioid-related harms disproportionately affect rural communities. Recent research-based policy changes have called for reductions in opioid prescribing and substitution of safe and effective alternatives to opioids for treating chronic pain, but such alternatives are often difficult to access in rural areas. Telehealth services can help address this disparity by bringing evidence-based, biopsychosocial chronic-pain services to rural and underserved patients with chronic pain. This article describes a 2-year pilot project for delivering chronic-pain care by pain specialists from central hubs at Veterans Health Administration (VA) medical centers to spokes at VA community-based outpatient clinics (CBOCs). The VA Puget Sound Pain Telehealth pilot program offered pain education classes, cognitive-behavioral therapy groups, opioid-safety education, and acupuncture education. The program delivered 501 encounters to patients from 1 hub to 4 CBOC spoke sites from 2016 to 2018, and supported training, administration, equipment acquisition, and grant-writing. The quality-improvement project was rolled out using existing local resources. We present initial findings about the patients who utilized Pain Telehealth, share lessons learned, and discuss future directions for expansion. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Comparing patterns of care and outcomes after operative management of complications after bariatric surgery at MBSAQIP accredited bariatric centers and non-bariatric facilities.

BACKGROUND: Many operations for complications after bariatric surgery are performed by surgeons without bariatric expertise at centers without teams who routinely care for bariatric patients. This study sought to evaluate whether bariatric expertise affects patterns of care and perioperative outcomes among patients undergoing operative intervention for complications after bariatric surgery. METHODS: Administrative claims data from the Kentucky Office of Health Policy were queried for inpatients undergoing operative intervention for complications related to bariatric surgery between 2015 and 2018. Patients were stratified with respect to whether or not they underwent surgery at a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) accredited bariatric surgery center (BCE) or not (non-BCE). Groups were compared with respect to demographic, procedural, and outcome variables. RESULTS: BCE patients were more often Caucasian than non-BCE patients (p < 0.001) and have either private insurance or Medicare coverage (p = 0.02). Regarding operative approach, operations were more likely to be performed laparoscopically in BCE (88.5% BCE vs. 80.9% non-BCE, p = 0.007). Length of stay was significantly shorter for BCE patients (median 2 days BCE vs. 3 days non-BCE, p < 0.001), and BCE patients were more likely to be discharged home (85.4% BCE vs. 78.5% non-BCE, p = 0.02). Inpatient mortality and average total charges per patient did not differ significantly between the two groups CONCLUSIONS: Surgical management of complications after bariatric surgery at BCE is associated with greater utilization of minimally invasive techniques, shorter hospital stay, and increased likelihood of routine home discharge. These findings should prompt a review and standardization of care patterns for patients with complications after bariatric surgery aimed at optimizing outcomes and improving value.

Waddell (Nonorganic) Signs and Their Association With Interventional Treatment Outcomes for Low Back Pain.

BACKGROUND: The rising use of injections to treat low back pain (LBP) has led to efforts to improve selection. Nonorganic (Waddell) signs have been shown to portend treatment failure for surgery and other therapies but have not been studied for minimally invasive interventions. METHODS: We prospectively evaluated the association between Waddell signs and treatment outcome in 3 cohorts: epidural steroid injections (ESI) for leg pain and sacroiliac joint (SIJ) injections and facet interventions for LBP. Categories of Waddell signs included nonanatomic tenderness, pain during sham stimulation, discrepancy in physical examination, overreaction, and regional disturbances divulging from neuroanatomy. The primary outcome was change in patient-reported "average" numerical rating scale for pain intensity (average NRS-PI), modeled as a function of the number of Waddell signs using simple linear regression. Secondary outcomes included a binary indicator of treatment response. We conducted secondary and sensitivity analyses to account for potential confounders. RESULTS: We enrolled 318 patients: 152 in the ESI cohort, 102 in the facet cohort, and 64 in the SIJ cohort, having sufficient data for primary analysis on 308 patients. Among these, 62% (n = 192) had no Waddell signs, 18% (n = 54) had 1 sign, 11% (n = 33) had 2, 5% (n = 16) had 3, 2% (n = 7) had 4, and about 2% (n = 6) had all 5 signs. The mean change in average NRS-PI in each of these 6 groups was -1.6 ± 2.6, -1.1 ± 2.7, -1.5 ± 2.5, -1.6 ± 2.6, -1 ± 1.5, and 0.7 ± 2.1, respectively, and their corresponding treatment failure rates were 54% (102 of 192), 67% (36 of 54), 70% (23 of 33), 75% (12 of 16), 71% (5 of 7), and 83% (5 of 6). In the primary analysis, an increasing number of Waddell signs were not associated with a significant decrease in average NRS-PI (coefficient [Coef] = 0.19; 95% confidence interval [CI], -0.43 to 0.05; P = .12). A higher number of Waddell signs were associated with treatment failure, with a 1.35 increased odds of treatment failure per cumulative number of signs (P = .008). CONCLUSIONS: Whereas this study found no consistent relationship between Waddell signs and decreased mean pain scores, a significant relationship between the number of Waddell signs and treatment failure was observed.

Stratifying Brain Tumour Histological Sub-Types: The Application of ATR-FTIR Serum Spectroscopy in Secondary Care.

Patients living with brain tumours have the highest average years of life lost of any cancer, ultimately reducing average life expectancy by 20 years. Diagnosis depends on brain imaging and most often confirmatory tissue biopsy for histology. The majority of patients experience non-specific symptoms, such as headache, and may be reviewed in primary care on multiple occasions before diagnosis is made. Sixty-two per cent of patients are diagnosed on brain imaging performed when they deteriorate and present to the emergency department. Histological diagnosis from invasive surgical biopsy is necessary prior to definitive treatment, because imaging techniques alone have difficulty in distinguishing between several types of brain cancer. However, surgery itself does not necessarily control tumour growth, and risks morbidity for the patient. Due to their similar features on brain scans, glioblastoma, primary central nervous system lymphoma and brain metastases have been known to cause radiological confusion. Non-invasive tests that support stratification of tumour subtype would enhance early personalisation of treatment selection and reduce the delay and risks associated with surgery for many patients. Techniques involving vibrational spectroscopy, such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer diagnostics. In this study, infrared spectra from 641 blood serum samples obtained from brain cancer and control patients have been collected. Firstly, we highlight the capability of ATR-FTIR to distinguish between healthy controls and brain cancer at sensitivities and specificities above 90%, before defining subtle differences in protein secondary structures between patient groups through Amide I deconvolution. We successfully differentiate several types of brain lesions (glioblastoma, meningioma, primary central nervous system lymphoma and metastasis) with balanced accuracies >80%. A reliable blood serum test capable of stratifying brain tumours in secondary care could potentially avoid surgery and speed up the time to definitive therapy, which would be of great value for both neurologists and patients.

Rapid analysis of disease state in liquid human serum combining infrared spectroscopy and "digital drying".

In recent years, the diagnosis of brain tumors has been investigated with attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy on dried human serum samples to eliminate spectral interferences of the water component, with promising results. This research evaluates ATR-FTIR on both liquid and air-dried samples to investigate "digital drying" as an alternative approach for the analysis of spectra obtained from liquid samples. Digital drying approaches, consisting of water subtraction and least-squares method, have demonstrated a greater random forest (RF) classification performance than the air-dried spectra approach when discriminating cancer vs control samples, reaching sensitivity values higher than 93.0% and specificity values higher than 83.0%. Moreover, quantum cascade laser infrared (QCL-IR) based spectroscopic imaging is utilized on liquid samples to assess the implications of a deep-penetration light source on disease classification. The RF classification of QCL-IR data has provided sensitivity and specificity amounting to 85.1% and 75.3% respectively.

Discrimination of fresh frozen non-tumour and tumour brain tissue using spectrochemical analyses and a classification model.

Introduction: In order for brain tumours to be successfully treated, maximal resection is beneficial. A method to detect infiltrative tumour edges intraoperatively, improving on current methods would be clinically useful. Vibrational spectroscopy offers the potential to provide a handheld, reagent-free method for tumour detection.Purpose: This study was designed to determine the ability of both Raman and Fourier-transform infrared (FTIR) spectroscopy towards differentiating between normal brain tissue, glioma or meningioma.Method: Unfixed brain tissue, which had previously only been frozen, comprising normal, glioma or meningioma tissue was placed onto calcium fluoride slides for analysis using Raman and attenuated total reflection (ATR)-FTIR spectroscopy. Matched haematoxylin and eosin slides were used to confirm tumour areas. Analyses were then conducted to generate a classification model.Results: This study demonstrates the ability of both Raman and ATR-FTIR spectroscopy to discriminate tumour from non-tumour fresh frozen brain tissue with 94% and 97.2% of cases correctly classified, with sensitivities of 98.8% and 100%, respectively. This decreases when spectroscopy is used to determine tumour type.Conclusion: The study demonstrates the ability of both Raman and ATR-FTIR spectroscopy to detect tumour tissue from non-tumour brain tissue with a high degree of accuracy. This demonstrates the ability of spectroscopy when targeted for a cancer diagnosis. However, further improvement would be required for a classification model to determine tumour type using this technology, in order to make this tool clinically viable.

Spectrochemical differentiation of meningioma tumours based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy.

Meningiomas are the commonest types of tumours in the central nervous system (CNS). It is a benign type of tumour divided into three WHO grades (I, II and III) associated with tumour growth rate and likelihood of recurrence, where surgical outcomes and patient treatments are dependent on the meningioma grade and histological subtype. The development of alternative approaches based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy could aid meningioma grade determination and its biospectrochemical profiling in an automated fashion. Herein, ATR-FTIR in combination with chemometric techniques is employed to distinguish grade I, grade II and grade I meningiomas that re-occurred. Ninety-nine patients were investigated in this study where their formalin-fixed paraffin-embedded (FFPE) brain tissue samples were analysed by ATR-FTIR spectroscopy. Subsequent classification was performed via principal component analysis plus linear discriminant analysis (PCA-LDA) and partial least squares plus discriminant analysis (PLS-DA). PLS-DA gave the best results where grade I and grade II meningiomas were discriminated with 79% accuracy, 80% sensitivity and 73% specificity, while grade I versus grade I recurrence and grade II versus grade I recurrence were discriminated with 94% accuracy (94% sensitivity and specificity) and 97% accuracy (97% sensitivity and 100% specificity), respectively. Several wavenumbers were identified as possible biomarkers towards tumour differentiation. The majority of these were associated with lipids, protein, DNA/RNA and carbohydrate alterations. These findings demonstrate the potential of ATR-FTIR spectroscopy towards meningioma grade discrimination as a fast, low-cost, non-destructive and sensitive tool for clinical settings. Graphical abstract Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was used to discriminate meningioma WHO grade I, grade II and grade I recurrence tumours.