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Background: The relationship between paraspinal muscle degeneration and low back pain (LBP), disability, and structural changes has been investigated in the literature, but it is still a matter of debate. We differentiated paraspinal muscle magnetic resonance imaging by quality and quantity, focusing on fatty infiltration (FI) and paraspinal muscles cross-sectional area (CSA) from T12 to S1 in patients with and without chronic LBP. We aimed to determine whether paraspinal muscle quantity (CSA) and quality (FI) are positively associated with LBP or degenerative/spinopelvic changes in the spine., Methods: Between 2018 and 2021, we prospectively enrolled 205 patients aged between 18 to 65 years, of whom 153 patients had chronic back pain (back pain group) and 52 patients did not have chronic back pain (no back pain group), and collected clinicodemographic, structural, and spinopelvic data. We correlated these data with paraspinal muscle FI and CSA from T12 to S1. Multivariate models were run to highlight associations between pain, disability, or degenerative and spinopelvic parameters., Results: Age was not associated with increased FI but consistently with decreased CSA values. After adjusting for age, sex, and body mass index, FI was associated with an increased risk of back pain (OR, 8.80; 95% CI, 1.9-39.79; P = 0.006) and high disability scores (OR, 3.41; 95% CI, 1.12-10.30; P = 0.030). Decreased CSA was associated with reduced disc height ( P < 0.001), while FI and CSA did not associate with abnormal spinopelvic parameters., Conclusions: FI on paraspinal muscle highly correlates with back pain and disability but was not found in structural and degenerative changes in the lower back., Clinical Relevance: Findings from this study are clinically relevant for patient counseling and rehabilitation strategies., Level of Evidence: 2b., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Background: Maximum safe resection for eloquent areas glioblastomas (GBMs) is the greatest tumor resection achievable without causing neurological deficits. This study aims to assess, through quantitative volumetric analysis, the outcomes of patients with eloquent areas GBMs and correlate the extent of resection (EOR), based on MRI T1-contrast enhanced (CE) and T2- fluid-attenuated inversion recovery (FLAIR) sequences, with patient outcomes and overall survival., Methods: We prospectively collected and analyzed patients with a diagnosis of primary GBM located in an eloquent area operated between January 2012 and April 2018. We examined 295 consecutive patients' records with GBM and identified 82 eloquent GBMs who met inclusion criteria. We stratified our patients by type of treatment-awake surgery (AS) and general anesthesia (GA) craniotomies. The kind of treatment was correlated with EOR, focusing on exeresis over the limit of the contrast-enhanced signal intensity, including both T1-CE and T2-FLAIR MRI signal alterations., Results: The overall mean EOR value was higher in AS than in GA on T1-CE (P value: 0.010) and T2-Flair MRI images (P value: 0.007). Also, patients who had at least 30% of T2-FLAIR signal resection (EOR≥30%) had a significantly lower risk of death and recurrence (P value: 0.020), independent of residual T1-CE tumor volume., Conclusions: Extensive T2-Flair resection and AS improve overall survival and reduce risk of recurrence while simultaneously minimizing surgical and medical complications among patients with GBMs in eloquent areas.

Background: Full-endoscopic spine surgery (FESS) indications already cover degenerative, infectious, and neoplastic diseases. This study aimed to use a bibliometric search and meta-analysis of the highest-quality studies in the last 20 years to determine the quantity and quality of FESS research, geographic distribution, and the outcomes for lumbar conditions., Methods: Articles on FESS published from 2000 to 2022 were screened and assessed through Web of Science, PubMed, and Scopus. Also, databases were searched for longitudinal studies to pool in a meta-analysis of patients undergoing FESS for lumbar conditions. After stratifying the risk of bias and having collected the studies of the highest quality, we included the proportion of patients with a satisfactory outcome and intraoperative and postoperative adverse events after the analysis of lumbar spine conditions., Results: A total of 728 articles were identified by the bibliographic search. Between 2000 and 2021, the published articles increased 21-fold. Most were from China (70.15%), followed by South Korea (19.5%). Most were retrospective (68.3%) and regarding treatment of lumbar disease (86.4%). Fifty studies, including 34,828 patients, were pooled in the meta-analysis. More than 85% of patients experienced satisfactory improvement in each of different lumbar conditions. Major adverse events were <2%; recurrence and postoperative dysesthesia rates were within those reported for open or mini-invasive procedures., Conclusions: This study may fill research gaps on FESS and lead to adequately designed studies. Our meta-analysis showed that FESS for lumbar diseases is a procedure with satisfactory outcomes and low rates of adverse events., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Different procedures have been used for the treatment of lumbar juxtafacet cysts (JFCs). Recently, full-endoscopic cyst excision has been suggested as a reasonable alternative. We performed a meta-analysis to assess the overall rates of favorable outcomes and adverse events for each available treatment and determine the outcome and complication rates concerning spine stability., Methods: Multiple databases were searched for English-language studies involving adult patients with lumbar JFCs who had been followed for more than 6 months. Outcomes included the proportion of patients with a satisfactory outcome. Adverse events included recurrence and revision rates as well as intraoperative complications. We further stratified the analysis based on the spine's condition (degenerative listhesis vs without degenerative listhesis)., Results: A total of 43 studies, including 2226 patients, were identified. Over 80% of patients experienced satisfactory improvement after surgical excision but only 66.2% after percutaneous cyst rupture and aspiration. Overall, recurrence and revision rates were almost double in patients with preoperative degenerative listhesis at the cyst level, especially in the minimally invasive group (2.1% vs 31.3% and 6.8% vs 13.1%, respectively). The rate of full-endoscopic satisfactory outcomes was approximately 90%, with low rates of adverse events (<2%)., Conclusion: We analyzed the outcome and adverse event rates for each kind of available treatment for JFC. Full endoscopy has outcomes and rates of adverse events that overlap with open and minimally invasive approaches., Level of Evidence: 2A., Competing Interests: Financial Disclosures and Conflicts of Interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2022 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Objective: Although evidence and descriptions of the central canal (CC) along the medulla oblongata and the spinal cord have been provided by several anatomical and radiological studies, a clear picture and assessment of the opening of the CC, or apertura canalis centralis (ACC), into the fourth ventricle is lacking, due to its submillimetric size and hidden position in the calamus scriptorius., Methods: The authors reviewed all of their cases in which patients underwent ventricular transaqueductal flexible endoscopic procedures and selected 44 cases in which an inspection of the region of the calamus scriptorius had been performed and was suitable for study inclusion. Patients were divided into different groups, based on the presence or absence of a chronic pathological process involving the fourth ventricle. In each case, the visual appearance of the opening of the CC of the ACC was classified as no evidence (A0), indirect evidence (A1), or clear evidence (A2). Morphometric measurements were inferred from surrounding structures and the size of surgical tools visible in the field., Results: The opening of the CC could be clearly observed in all cases (A1 4.5%, A2 95.5%). In normal cases, a lanceolate shape along the median sulcus was most frequently found, with an average size of 600 × 250 µm that became rounded and smaller in size in cases of hydrocephalus. The distance between the caudal margin of the ACC and the obex was about 1.8 mm in normal cases, 2.1 mm in cases of obstructive hydrocephalus, and 1 mm in cases of normal pressure hydrocephalus. The two wings of the area postrema, variable in size and shape, were sited just caudal to the opening., Conclusions: A flexible scope inserted through the cerebral aqueduct can approach the hidden calamus scriptorius like a pen fits into an inkpot. With this privileged viewpoint, the authors provide for the first time, to their knowledge, a clear and novel vision of the opening of the CC in the fourth ventricle, along with the precise location of this tiny structure compared to other anatomical landmarks in the inferior triangle.

Introduction: A dura mater substitute in decompressive craniectomies must protect the brain while providing a dissection plane between the cortex and myocutaneous layer. The human amniotic membrane (AM) has anti-inflammatory, wound healing, and differentiation properties. We tested AM properties as a dural substitute by comparing the outcomes to biological ones., Methods: We prospectively collected data on 25 patients who randomly underwent decompressive craniectomy with lyophilized AM patches and 25 in which biological substitutes were utilized between 2015 and 2019. The AM was laid with the epithelial side facing the brain because of the anti-adhesive proprieties, while the chorion facing the myocutaneous flap. We collected data on demographics, neurological status, comorbidities, and surgical outcomes. Additionally, we created a score - dura mimicking score- and reviewed postoperative imaging and pathological specimens., Results: The majority (96%) of AM grafts were integrated into native dura. Thirteen patients scored as excellent and 11 good on our "dura mimicking score", showing tissue integration ability but no cerebral cortex adhesion. The histopathological analysis showed that AM had thick plates of dense fibrous tissue with small reactive vessels, reactive fibroblasts, and lymphocytes infiltrate. The AM group's first outcomes were not different from the biological substitute patients but higher integration rate to the dura and less adhesion to the myocutaneous flap in AM patients., Conclusions: We documented the anti-adhesive, protective, and integrative properties of AM dural substitute patches in patients who underwent decompressive craniectomies, comparing the intraoperative differences and postoperative outcomes to biological dural substitutes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) had been combined into a single classification until 2016. Recurrence and metastases rates are still understudied, especially for spinal SFT/HPCs. Here, we describe CNS SFT/HPCs and predictors for recurrence, metastases, and death, in spinal and intracranial SFT/HPCs, separately. We collected data from studies with patient-level data available on primary SFT/HPCs from multiple online databases. Clinico-demographic data, surgical outcomes, recurrence, metastases, and death rates were abstracted. We used logistic and Cox regression models to identify predictors for recurrence, metastases, and death for spinal and intracranial SFT/HPCs. Twenty-nine studies (368 patients) were included. Higher histological grade and subtotal resection were associated with recurrence (p values < 0.05), while higher histological grade and recurrence (p values < 0.005) were associated with metastases formation. Time to recurrence (p < 0.005) and metastases (p < 0.001) formation were shorter for spinal SFT/HPCs. Death rates were higher among intracranial SFT/HPC patients (p value = 0.001). Among patients with higher histological grade, rates of metastases formation were different between intracranial and spinal SFT/HPCs. Risk of metastases was higher in the first 5 years from surgery for both intracranial and spinal SFT/HPCs. Meningeal SFT/HPCs patients have high rates of recurrence and metastasis, which occur mostly within the first 5 years after diagnosis. Spinal and intracranial SFT/HPCs show similar behavior, but spinal SFT/HPCs tend to develop metastases and recurrences in a shorter interval of time. Careful follow-up for spinal SFT/HPCs should be considered because spinal cases seem to be slightly more aggressive and require more attention.

Objective: Opto-chiasmatic (OC) cavernous malformations are sporadic lesions that are often misdiagnosed clinically and radiologically. Presenting symptoms range from incidental findings to the more frequent and dramatic "chiasmal apoplexy." The present study aims to evaluate the potential role of arachnoidal membranes of the basal cisterns in the onset of OC apoplexy. A possible mechanism resembling a compartment syndrome is discussed through the description of two cases of bleeding cavernomas., Methods: We describe clinical, radiological, intraoperative findings in two cases of young patients presenting with OC apoplexy from bleeding cavernoma. The first was a 38-year-old man diagnosed with optic neuritis at the first episode of visual acuity deterioration. The second patient was a 22 -year-old woman who suffered two OC apoplexy episodes from a recurrence, which also presented with bleeding., Results: Both patients were operated on via pterional craniotomy and presented a postoperative improvement of visual symptoms. The second patient experienced deterioration 30 months after surgical resection due to rebleeding from a recurrence and required a second operation. Follow-up revealed a good recovery of visual disturbances; MRI at 6 and 3 years showed in both patients an apparent complete removal of the cavernous malformations., Conclusion: The cisternal environment where OC cavernous malformations develop and the paradigm of a compartment syndrome could explain the clinical presentation variability. This very rare subset of cavernomas would benefit from a classification system using ad hoc neuroimaging protocols and consistent indications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Purulent intracranial infections are threatening conditions. Different surgical approaches have been described, respecting the rationale of evacuating the fluid component of the purulent collection. Emerging evidence supports the use of the endoscope for the treatment of cerebral abscesses and subdural empyemas; especially the peculiarities of flexible endoscopes could potentially offer a more effective and conclusive management as compared with the drainage through catheters. We describe our experience in the treatment of intracranial purulent collections with flexible endoscopy, comparing it with the most recent literature., Methods: Ten patients affected by intracranial suppuration were treated with endoscopy at our institution. The neurosurgical technique is thoroughly described. The related literature is reviewed, providing a comprehensive overview on the endoscopic treatment of intracranial suppuration so far., Results: All the patients had a good clinical outcome, with no peri-operative complications. The postoperative scans showed significant radiological improvement, with important reduction of the pus volume. In all cases, the microbiological cultures showed positivity., Conclusions: In our experience, the use of the flexible scope proved feasible and effective in the treatment of intracranial purulent collections. Visual awareness of the internal capsule is not limited to a direct inspection of the fluid pus; it rather allows an active removal of the more solid (and perhaps more microbiologically significant) fibrinoid component, and also assists in final bleeding control and in assessing the extent of the evacuation. The steering capabilities of the fiberscope are particularly suitable for such purposes, allowing sampling the solid internal layer of the pyogenic membrane, and potentially shedding light on the actual clinical significance of this component of the abscess.

Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Irene Troncon et al.)

Objective: Despite the technological advancements of neurosurgery, the posterior part of the third ventricle has always been the "dark side" of the ventricle. However, flexible endoscopy offers the opportunity for a direct, in vivo inspection and detailed description of the posterior third ventricle in physiological and pathological conditions. The purposes of this study were to describe the posterior wall of the third ventricle, detailing its normal anatomy and surgical landmarks, and to assess the effect of chronic hydrocephalus on the anatomy of this hidden region., Methods: The authors reviewed the video recordings of 59 in vivo endoscopic explorations of the posterior third ventricle to describe every identifiable anatomical landmark. Patients were divided into 2 groups based on the absence or presence of a chronic dilation of the third ventricle. The first group provided the basis for the description of normal anatomy., Results: The following anatomical structures were identified in all cases: adytum of the cerebral aqueduct, posterior commissure, pineal recess, habenular commissure, and suprapineal recess. Comparing the 2 groups of patients, the authors were able to detect significant variations in the shape of the adytum of the cerebral aqueduct and in the thickness of the habenular and posterior commissures. Exploration with sodium fluorescein excluded the presence of any fluorescent area in the posterior third ventricle, other than the subependymal vascular network., Conclusions: The use of a flexible scope allows the complete inspection of the posterior third ventricle. The anatomical variations caused by chronic hydrocephalus might be clinically relevant, in light of the commissure functions.

Introduction: Orbitocranial wooden foreign body (OWF) penetrations are rare but challenging occurrences that may violate the intracranial space resulting in brain damage and hemorrhagic, as well as infectious, complications. Moreover, there is a specific subset of cases of OWF penetrations that are particularly challenging to treat. Although there are well-defined management guidelines for pure intraorbital localization, there is not yet a defined treatment protocol for foreign bodies reaching the intracranial space. However, their removal performed either directly or through craniotomy, is often easily attainable given the condition that all necessary precautions are accounted for., Evidence Acquisition: After having treated a 48-year-old man with a transorbital OWF penetration injury at our neurosurgical department, we systematically reviewed the last 15 years of literature to define and summarize the best management strategy. Multiple databases were searched for case reports and case series involving patients with intraorbital and transorbital OWF penetration injuries. For each study, we extracted data on age, sex, imaging modality, type of wood (processed vs. unprocessed), location of periorbital and intracranial entry site, treatment type ("pull and see" or "open and see"), antibiotic therapy, and complications., Evidence Synthesis: We classified transorbital OWFs into two categories: transorbital with only cavernous sinus involvement and transorbital with more extensive intracranial involvement. We described what we believed was the most appropriate management conduct in each case., Conclusions: Grounded on our experience and on the review of the literature, we suggest, based on the anatomical localization of the OWF, a classification system for OWFs which is coupled with a tailored treatment strategy for each case. These suggestions are made to provide surgeons with direction on the correct management of such rare but challenging occurrences.

Purpose: The reasons why a specific subset of glioblastoma (GBM) patients survive longer than others is still unclear. This study analyzed a cohort of long-term and very-long-term GBM survivors to determine which genetic alterations or patient's characteristics influence survival time., Methods: We retrospectively reviewed a cohort of GBM patients treated at our institution over the last 20 years, stratifying patients in three groups: those with a survival time ≥ 36 months and < 120 months (LTS), ≥120 months (VLTS), and < 36 months, respectively. Clinical (age, sex, focality, resection degree, Karnofsky performance status), and immunohistochemical and molecular data (Ki-67 expression and multiple genes alterations) were collected. We then utilized principal component analysis, logistic regression, and Cox proportional hazard models to identify those variables associated with survival., Results: Younger age at presentation (HR = 0.36, 95% CI 0.21-0.67, p = .001), and MGMT promoter [(MGMTp), methylated, HR = 0.57, CI 0.34-0.96, p = .034) were associated with higher odds of VLTS survival. The multivariate analysis showed how the combination of younger age (< 50 years), Ki-67 < 10%, and the coexistence of TERTp not mutated, MGMTp methylated, and IDH1/2 mutated in the same patient are also associated with higher odds of survival (HR = 0.10, CI 0.01-0.74, p = .025)., Conclusions: We confirmed younger age at presentation and MGMTp methylation as the only independent factors associated with VLTS. The exceptional survival of our VLTS patients is probably associated with different, still understudied, gene mutations, or with the coexistence of multiple factors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: The choice between sitting and prone position to access the infratentorial space in a suboccipital craniotomy is still a matter of debate. The comparisons in terms of complications and outcome of both positions are scarce, and the pediatric population is indeed more infrequent in these in scientific reviews. In this paper, we assess intraoperative and postoperative complications and neurological outcome in pediatric patients undergoing posterior cranial fossa surgery for pilocytic astrocytoma in sitting and prone position respectively., Methods: We retrospectively analyzed 30 consecutive patients undergoing surgery for cerebellar pilocytic astrocytoma at the two neurosurgical units referring to the University of Padova Medical School from 1999 to 2017. Preoperative, intraoperative, and postoperative data were retrieved from our medical archives., Results: The statistical analysis did not show any differences between the two groups in terms of preoperative, intraoperative, and postoperative data. The neurological status at last follow-up was similar in both groups of patients., Conclusions: Our results suggest that both sitting and prone position can be considered safe in suboccipital craniotomies. Further studies are needed to show if there are possible differences between these positions for other frequent pediatric tumors such as medulloblastomas and ependymomas.

Objective: Surgical management of spinal dysraphism often requires the use of dural substitutes. Amniotic membrane (AM) has drawn the interest of clinicians for its valuable concentration of cytokines and factors capable of promoting wound healing, re-epithelialization, inhibiting fibrosis and regulating angiogenesis. These beneficial qualities could make AM an interesting dural substitute for spina bifida repair. In this study, we describe the use of banked homologous AM as a dural substitute for the repair of spinal dysraphism in newborns. Our purpose is to test the mechanical characteristics, as well as the safety and effectiveness of AM in preventing postoperative complications and re-tethering., Methods: The AM patch was carefully detached from the chorion of donors undergoing caesarean section, rinsed in saline solution, and cryopreserved in liquid nitrogen. Five newborns were treated using AM: three affected by open spinal dysraphism and two by spina bifida occulta. The AM patch was used as a dural substitute with two different positions and purposes: the amnion-side down covering the placode to prevent adhesions or placed extradurally facing the dura to avoid scarring and facilitating the sliding of the dural sac itself under the extradural tissue layers., Results: No adverse events occurred, and the surgical wounds healed without complications. MRI scans taken at 3 and 6 months after surgery showed a satisfying de-tethering of the spinal cord with no obvious evidence of new adherence formation., Conclusions: We present a multimodal interposition technique using AM as a reconstructive and anti-adhesive tissue for the treatment of open myelomeningocele (MMC) and lipomeningocele (LMC) treatment. In our experience, AM proved its efficacy in restoring the dural sac integrity without complications. We support the use of AM as a promising dural substitute, speculating on how the use of AM could potentially change reconstructive strategies for spinal dysraphism.

Spindle cell oncocytoma (SCO) is a rare pituitary tumor, classified as a WHO grade I neoplasm. Due to its rarity, SCO is often preoperatively misdiagnosed as a pituitary macroadenoma. In the present study we report two recent cases of SCO, a 61-year-old male and a 65-year-old female presenting at Treviso General Hospital between March 2014 and April 2015. Tumor resection was achieved by endoscopic transsphenoidal approach but massive hemorrhagic events hampered surgery, endangering the patient's life in both cases. Both tumors featured fascicles of spindle cells with eosiniphilic cytoplasm expressing vimentin, S-100 and thyroid transcription factor-1 (TTF-1). The diagnosis of SCO was confirmed by second opinion in both cases. Extensive review of available literature, about 30 cases from 2002 to 2015, provided valuable clinical data for preoperative diagnosis and surgical removal of SCO tumors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Osteoblastomas are rare, benign bone tumors mainly arising from the long bones and the posterior vertebral arches. Skull localizations account for approximately 15% of cases. A total amount of thirty cases involving the temporal bone are reported in the literature. Clinical presentation of temporal osteoblastomas often includes local pain and swelling, while 7 th and 8 th cranial nerve impairment is rare. We report the novel finding of increase intracranial pressure syndrome secondary to dominant transverse-sigmoid sinus junction compression caused by a small temporal bone osteoblastoma. Excision of the tumor with the restoration of venous flow in the sigmoid sinus was followed by a prompt clinical improvement. In the management of patients with a venous sinus compression, restoration of venous drainage should be a priority., Competing Interests: There are no conflicts of interest.

Background: Current evidence suggests that endometrial-derived stem cells, spilled in the peritoneal cavity via retrograde menstruation, are key players in the establishment of endometriotic lesions. The aim of this study was to determine the presence and distribution of the stemness-related factors OCT4, SOX15, TWIST1 and DCAMLK1 in women with and without endometriosis., Methods: Immunohistochemical analysis was used to determine stromal and epithelial expression of OCT4, SOX15, TWIST1 and DCAMLK1 in endometriosis patient (EP) endometrium (n = 69) and endometriotic tissue (n = 90) and in control endometrium (n = 50). Quantitative Real-Time PCR of OCT4, SOX15 TWIST1 and DCAMLK1 was performed in paired samples of EP endometrium and endometriotic tissue. Co-immunofluorescence staining was performed for OCT4 and SOX15. For statistical analyses we used unpaired t-test, Fisher combination test and Spearman test. For paired analyses, paired t-test and McNemar test were used., Results: We detected a significant correlation between the expression of the established stem cell marker OCT4 and the stemness-related markers SOX15 (p < 0.001) and TWIST1 (p = 0.002) but not DCAMLK1. We showed a colocalization of SOX15 and OCT4 in epithelial and stromal cells of endometriotic tissue by coimmunofluorescence. A concordant expression of OCT4 and SOX15 in the same sample was observed in epithelial cells of the endometriotic tissue (71.7%). The expression of stemness-related factors was not associated with proliferative or secretory phase of the menstrual cycle in endometriosis patients but was found to be differentially expressed during the menstrual cycle in the control group. Increased expression of epithelial OCT4, SOX15 and TWIST1 was detected in endometriotic tissue compared to EP endometrium in paired (p = 0.021, p < 0.001 and p < 0.001) and unpaired analysis (p = 0.040, p < 0.001 and p = 0.001)., Conclusion: Our findings support the hypothesis that upregulation of stem cell-related factors contribute to the establishment of endometriotic lesions., Trial Registration: The study was approved by the institutional review board (545/2010 on 6th of May 2014) of the Medical University of Vienna ( http://ethikkommission.meduniwien.ac.at/fileadmin/ethik/media/dokumente/register/alle&#95;2010.pdf ).

Purpose: Although the utility of the sitting position is undisputed for biomechanical and ergonomic reasons, it has been debated in recent years for its risks, particularly venous air embolism (VAE). In order to reduce the hemodynamic effect of VAE, we changed the composition of the surgical field air partially replacing nitrogen with carbon dioxide (CO2) that better dissolves in human tissues., Methods: First, we tested our method on a test dummy in the sitting position. Infrared CO2 sensors were placed close to the wound opening and on the facial mask of the surgeon. An oxygen sensor was connected to a computer for data recording (ALTAIR(®), MSA Safety). This model showed that 10 L/min CO2 flow provides efficient air displacement, maintaining safety for the surgeon. We reproduced the above-described surgical field environment in ten consecutive cases of posterior fossa surgery performed in the sitting position. A homogeneous group of ten patients operated in the sitting position with standard setting environment was used for control. We intraoperatively monitored VAE with trans-esophageal echocardiography (TEE), end-tidal CO2 (ETCO2), CO2 arterial pressure (PaCO2), and hemodynamic changes., Results: Although the percentage of VAE was 70% in both groups, hemodynamic effects occurred in 10% of cases in the study group and in 40% of cases in the control group., Conclusions: Our preliminary study shows that a CO2-enriched sitting position surgical microenvironment significantly reduces the hemodynamic effects of VAE, more likely because arterial CO2 emboli are more soluble and consequently much better tolerated than air emboli.

Background: Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose polarity and cell-to-cell contacts and acquire the migratory and invasive abilities of mesenchymal cells. These abilities are thought to be prerequisites for the establishment of endometriotic lesions. A hallmark of EMT is the functional loss of E-cadherin (CDH1) expression in epithelial cells. TWIST1, a transcription factor that represses E-cadherin transcription, is among the EMT inducers. SNAIL, a zinc-finger transcription factor, and its close relative SLUG have similar properties to TWIST1 and are thus also EMT inducers. MYC, which is upregulated by estrogens in the uterus by an estrogen response cis-acting element (ERE) in its promoter, is associated with proliferation in endometriosis. The role of EMT and proliferation in the pathogenesis of endometriosis was evaluated by analyzing TWIST1, CDH1 and MYC expression., Methods: CDH1, TWIST1, SNAIL and SLUG mRNA expression was analyzed by qRT-PCR from 47 controls and 74 patients with endometriosis. Approximately 42 ectopic and 62 eutopic endometrial tissues, of which 30 were matched samples, were collected during the same surgical procedure. We evaluated TWIST1 and MYC protein expression by immunohistochemistry (IHC) in the epithelial and stromal tissue of 69 eutopic and 90 ectopic endometrium samples, of which 49 matched samples were analyzed from the same patient. Concordant expression of TWIST1/SNAIL/SLUG and CDH1 but also of TWIST1 and MYC was analyzed., Results: We found that TWIST1, SNAIL and SLUG are overexpressed (p < 0.001, p = 0.016 and p < 0.001) in endometriosis, while CDH1 expression was concordantly reduced in these samples (p < 0.001). Similar to TWIST1, the epithelial expression of MYC was also significantly enhanced in ectopic endometrium compared to eutopic tissues (p = 0.008). We found exclusive expression of either TWIST1 or MYC in the same samples (p = 0.003)., Conclusions: Epithelial TWIST1 is overexpressed in endometriosis and may contribute to the formation of endometriotic lesions by inducing epithelial to mesenchymal transition, as CDH1 was reduced in ectopic lesions. We found exclusive expression of either TWIST1 or MYC in the same samples, indicating that EMT and proliferation contribute independently of each other to the formation of endometriotic lesions.

Background: This updated analysis of the CECOG/CORE 1.2.002 study investigated the association between clinical outcome and RAS and BRAF mutations in metastatic colorectal cancer (mCRC) patients treated with FOLFOX4 plus cetuximab., Patients and Methods: Available DNA samples from CECOG/CORE 1.2.002 study patients with KRAS exon 2 wild type (wt) (at codons 12 and 13) tumors were screened for mutations at other loci in the KRAS and NRAS (RAS) coding regions by Sanger sequencing, and for BRAF codon 600 mutations by Sanger sequencing and pyrosequencing. Clinical outcome was compared among different mutation subgroups., Results: Of 152 KRAS wt mCRC patients, 148 were evaluable for RAS and BRAF mutation status. Eleven RAS mutations were detected in 10 patients' tumors (7%). BRAF mutations were detected in 14 patients' tumors (9%). RAS and BRAF tumor mutations were mutually exclusive. Compared with patients with RAS wt/BRAF wt tumors (n = 124; median overall survival, 28.5 months), those with RAS mutations (n = 10; median, 16.3 months; hazard ratio, 0.43; 95% confidence interval, 0.20-0.89; P = .020) or BRAF mutations (n = 14; median, 11.7 months; hazard ratio, 0.23; 95% confidence interval, 0.12-0.41; P < .0001) had worse overall survival, which remained significant (P < .04) when adjusting for differences in baseline characteristics among the mutation subgroups., Conclusion: These findings support those from recent studies that RAS and BRAF mutations are associated with poor outcome in patients receiving an epidermal growth factor receptor-targeted monoclonal antibody in combination with oxaliplatin-based chemotherapy. Furthermore, mutation testing should not only include RAS codons 12 and 13 but should also be extended to the entire coding regions., (Copyright © 2015 Elsevier Inc. All rights reserved.)