Autologous cell immunotherapy (IGV-001) with IGF-1R antisense oligonucleotide in newly diagnosed glioblastoma patients.

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).

ExPert ConsEnsus on the management of Advanced clear-cell RenaL celL carcinoma: INDIAn Perspective (PEARL-INDIA).

In advanced Renal Cell Carcinoma (aRCC), systemic therapy is the mainstay of treatment, with no or little role for surgery in these patients. Tyrosine kinase inhibitors (TKIs) and immune-oncological (IOs) therapies, either alone or in combination, are recommended in these patients depending on patient and tumour factors. The sequencing of therapies is critical in RCC because the choice of subsequent line therapy is heavily dependent on the response and duration of the previous treatment. There are additional barriers to RCC treatment in India. Immunotherapy is the cornerstone of treatment in ccRCC, but it is prohibitively expensive and not always reimbursed, effectively putting it out of reach for the vast majority of eligible patients in India. Furthermore, in advanced RCC (particularly the clear cell variety), Indian oncologists consider the disease burden of the patients, which is particularly dependent on the quantum of the disease load, clinical symptoms, and performance status of the patient, before deciding on treatment. There are no India-specific guidelines for clear cell RCC (ccRCC) treatment or the positioning and sequencing of molecules in the management of advanced ccRCC that take these country-specific issues into account. The current consensus article provides expert recommendations and treatment algorithms based on existing clinical evidence, which will be useful to specialists managing advanced ccRCC.

Imaging score for differentiation of meningioma grade.

PURPOSE: We sought to establish a comprehensive imaging score indicating the likelihood of higher WHO grade meningiomas pre-operatively. METHODS: All surgical intracranial meningioma patients at our institution between 2014 and 2018 underwent retrospective chart review. Preoperative MRI sequences were reviewed, and imaging features were included in the score based on statistical and clinical significance. Point values for each significant feature were assigned based on the beta coefficients obtained from multivariate analysis. The imaging score was calculated by adding up the points, for a total score of 0 to 5. The predictive ability of the score to identify higher-grade meningiomas was evaluated. RESULTS: Ninety patients, 50% of whom had a postoperative diagnosis of WHO grade II meningioma, were included. The mean age for the population was 59.9 years and 70% were female. Tumor volume ≥ 36.0 cc was assigned 2 points, presence of irregular tumor borders was assigned 2 points, and presence of peritumoral edema was assigned 1 point. The probability of having a WHO grade II meningioma was 0% with a score of 0, 25.0% with a score of 1, 38.5% with a score of 2, 65.4% with a score of 3, and 83.3% with a score of 4 or greater. A threshold of ≥ 3 points achieved a recall of 0.80, precision of 0.73, F1-score of 0.77, accuracy of 0.76, and AUC of 0.82. CONCLUSION: The proposed imaging scoring system had good predictive capability for WHO grade II meningiomas with good discrimination and calibration. External validation is needed.

Medical Malpractice and Trigeminal Neuralgia: An Analysis of 49 Cases.

PURPOSE: Our study fills the vacancy of litigation research related to trigeminal neuralgia management, giving health care providers the information needed to understand the potential litigious outcomes that follow treatment methods. METHODS: We queried the Westlaw database to identify litigation cases related to trigeminal neuralgia management. Key variables extracted included medical complaints, trial outcomes, and demographics. Continuous variables were compared between cases in favor of defendant and cases in favor of plaintiff using t-test or Wilcoxon rank sum test. Categorial variables were compared using χ2 or Fisher exact test. RESULTS: About 49 cases met the inclusion criteria-for those cases surgical complications (42.9%) were cited as the most common reasons for malpractice claims. Cranial nerve deficits (34.7%) were the most frequent postoperative complaints. Verdicts ruled in favor of the plaintiff in 26.5% of cases with a mean payout of $1,982,428.46. Dentists were included in the most cases, 63.3%, and the average payout was $415,908, whereas neurosurgeons were involved in 20.4% of cases with an average payout of $618,775. Cases with verdicts in favor of the plaintiff were more likely to be older than cases with verdicts in favor of the defendant (P = .03). CONCLUSIONS: Over one-half of cases resulted in verdicts in favor of the defendant with surgical complications cited as the most common reason for litigation. Dentistry was the most common individual clinical specialty for defendants, whereas neurosurgery contributed to the largest average payout based on specialty (for n > 1). Cranial nerve deficits were the most common plaintiff postoperative complaints. These analyses may help doctor teams involved in management of trigeminal neuralgia to have a more informed discussion with the patient at every visit so that such litigations may be avoided.

Medical malpractice and meningiomas: an analysis of 47 cases.

OBJECTIVE: Among medical practices, surgical fields, including neurosurgery, are at a high risk for medical malpractice litigation. With meningiomas contributing to 10% of the total neurosurgery litigation cases, the aim of this study was to identify demographic characteristics, reasons for litigation, and surgical complications commonly reported in these cases. This analysis serves to increase neurosurgeons' awareness of factors associated with medical malpractice litigation. METHODS: The online legal database Westlaw was utilized to query public litigation cases related to the medical management of meningiomas between December 1985 and May 2020. Variables extracted included the following: plaintiff and defendant demographics, litigation category, plaintiff medical complaints, and trial outcomes. The authors compared these characteristics between cases with decisions in favor of the defendant and those with decisions in favor of the plaintiff. RESULTS: A total of 47 cases met the inclusion criteria. Failure to diagnose (68.1%) was the most common type of malpractice claim, and surgical complications (19.1%), motor weakness (33%), and financial loss (33%) were cited as the most common postoperative complaints. Individual specialties that most often required defense due to malpractice claims were radiology (21.7%) and neurosurgery (19.6%). The jury verdict was in favor of the defense in 51.1% of cases and in favor of the plaintiff in 27.7% of cases. A settlement was reached in 19.1% of cases. The mean payout for a verdict in favor of the plaintiff was $3,409,650.22, while the mean payout for settlements was $867,555.56. The greatest average payout for specialties was in neurosurgery at $3,414,400, followed by radiology at $3,192,960. Cases with a verdict in favor of the plaintiff were more likely to involve an internal medicine physician as a defendant (p = 0.007). CONCLUSIONS: Over one-half of the cases resulted in a defendant's verdict with failure to diagnose cited as the most common reason for litigation. Radiology and neurosurgery were the most common specialties for legal cases and also had some of the largest average payouts based on specialty. Motor weakness and financial loss were the most common plaintiff postoperative complaints. These findings may inform surgeons on active measures to take, such as increasing focus on diagnostic accuracy and reducing specific postoperative complaints, such as motor weakness, through risk management and prophylactic measures, to reduce unfavorable legal outcomes.

Shared Decision-Making and Medicolegal Aspects: Delivering High-Quality Cancer Care in India.

It is often difficult for people with cancer to make decisions for their care. The aim of this review is to understand the importance of shared decisionmaking (SDM) in Indian clinical scenario and identify the gaps when compared to practices in the Western world. A systematic search (2000-2019) was executed in Medline and Google Scholar using predefined keywords. Of the approximate 400 articles retrieved, 43 articles (Indian: 5; Western: 38) were selected for literature review. Literature review revealed the paucity of information on SDM in India compared to the Western world data. This may contribute to patientreported physical or psychological harms, life disruptions, or unnecessary financial costs. Western world data demonstrate the involvement and sharing of information by both patient and physician, collective efforts of the two to build consensus for preferred treatment. In India, involvement of patients in the planning for treatment is largely limited to tertiary care centers, academic institutes, or only when the cost of therapy is high. In addition, cultural beliefs and prejudices impact the extent of participation and engagement of a patient in disease management. Communication failures have been found to strongly correlate with the medicolegal malpractice litigations. Research is needed to explore ways to how to incorporate SDM into routine oncology practice. India has a high unmet need towards SDM in diagnosis and treatment of cancer. Physicians need to involve patients or their immediate family members in decision making, to make it a patient-centric approach as well. SDM enforces to avoid uninformed decisionmaking or a lack of trust in the treating physician's knowledge and skills. Physician and patient education, development of tools and guiding policies, widespread implementation, and periodic assessments may advance the practice of SDM.

Is EGFR really a therapeutic target in head and neck cancers?

Epidermal growth factor receptor (EGFR) is overexpressed in 90% to 100% of squamous cell carcinoma of the head and neck (SCCHN). The overexpression of EGFR and its ligand transforming growth factor is associated with poorer survival. EGFR inhibitors such as Cetuximab (Erbitux) have shown a significant antitumoral effect in SCCHN and has improved locoregional control and as well as survival. Even though there was some success with Cetuximab, work with other EGFR inhibition has not been very fruitful and not really shown any promise. Mechanism of action of Cetuximab could be immune-mediated rather than EGFR inhibition and EGFR may not necessarily be a therapeutic target in SCCHN.

Malignant brainstem gliomas in adults: clinicopathological characteristics and prognostic factors.

Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the natural history, presentation, imaging, molecular characteristics, prognostic factors, and appropriate treatments. A total of 34 patients were identified, consisting of 22 anaplastic astrocytomas (AAs) and 12 glioblastomas (GBMs). The overall median survival for all patients was 25.8 months, with patients having GBMs experiencing significantly worse survival (12.1 vs. 77.0 months, p = 0.0011). The majority of tumors revealed immunoreactivity for EGFR (93.3 %) and MGMT (64.7 %). Most tumors also exhibited chromosomal abnormalities affecting the loci of epidermal growth factor receptor (92.9 %), MET (100 %), PTEN (61.5 %), and 9p21 (80 %). AAs more commonly appeared diffusely enhancing (50.0 vs. 27.3 %) or diffusely nonenhancing (25.0 vs. 0.0 %), while GBMs were more likely to exhibit focal enhancement (54.6 vs. 10.0 %). Multivariate analysis revealed confirmed histopathology for GBM to significantly affect survival (HR 4.80; 95 % CI 1.86-12.4; p = 0.0012). In conclusion, adult malignant BSGs have an overall poor prognosis, with GBM tumors faring significantly worse than AAs. As AAs and GBMs have differing imaging characteristics, tissue diagnosis may be necessary to accurately determine patient prognosis and identify molecular characteristics which may aid in the treatment of these aggressive tumors.

Endovascular treatment of a spinal dural arteriovenous malformation (DAVF).

We present a case of a patient with rapid loss of motor strength in his lower extremities. He became bedridden with bowel and bladder incontinence, and developed saddle anesthesia. MRI of the lumbar spine showed edema in the conus medullaris and multiple flow voids within the spinal canal. A spinal angiogram showed a dorsal Type I spinal AVF. This was treated successfully with Onyx 18 (eV3, Irvine, CA). The patient showed rapid post-procedure improvement, and at discharge from the hospital to a rehabilitation center he was fully ambulatory. At 3-year follow-up, the patient was found to ambulate without difficulty. He also had improved saddle anesthesia, and he was voiding spontaneously. There was no evidence of flow voids on repeat MRI of the lumbar spine. The video can be found here: http://youtu.be/SDYNIGNQIW8 .

Transcirculation balloon-assisted stent-supported coil embolization of a basilar tip aneurysm.

We present the case of a balloon-assisted, stent-supported coil embolization of a basilar tip aneurysm. Initially, a balloon extending from the basilar artery into the right PCA was placed. However, even with a more proximal purchase, coils were found to impinge on the left PCA. Subsequently, a transcirculation approach was performed, where the left posterior communicating artery was utilized as a conduit for balloon support and the coils were embolized from the ipsilateral vertebral artery. However, after this transcirculation approach was completed, there was a coil tail extruding from the aneurysm. The balloon was then removed over an exchange wire and a horizontal stent advanced, spanning the entire neck of the aneurysm, eliminating the extruded coil. The video can be found here: http://youtu.be/bMbtZoPnYvo .

Reverse pedicle-based greater saphenous neuro-veno-fasciocutaneous flap for reconstruction of lower leg and foot.

INTRODUCTION: Paucity of soft tissue available locally for reconstruction of defects in leg and foot presents a challenge for reconstructive surgeon. The use of reverse pedicle-based greater saphenous neuro-veno-fasciocutaneous flap in reconstruction of lower leg and foot presents a viable alternative to free flap and cross-leg flap reconstruction. The vascular axis of the flap is formed by the vessels accompanying the saphenous nerve and the greater saphenous vein. We present here our experience with reverse saphenous neurocutaneous flap which provides a stable cover without the need to sacrifice any important vessel of leg. PATIENTS AND METHODS: The study is conducted from March 2003 through Dec 2009 and included a total of 96 patients with defects in lower two-thirds of leg and foot. There are 74 males and 22 females. Distal pivot point was kept approximately 5-6 cm from tip of medial malleolus, thus preserving the distal most perforator, and the flap is turned and inserted into the defect. Donor site is covered with a split thickness skin graft. Postoperative follow-up period was 6 weeks to 6 months. RESULT: The procedure is uneventful in 77 cases. Infection is observed in 14 cases. Partial flap necrosis occurs in 2 cases. Total flap necrosis is noted in 3 cases. CONCLUSION: Reverse pedicle saphenous flap can be used to reconstruct defects of lower one-third leg and foot with a reliable blood supply with a large arc of rotation while having minimal donor site morbidity.

Medical malpractice and epidural hematomas: a retrospective analysis of 101 cases in the United States.

Background: Neurosurgeons face particularly high rates of litigation compared to physicians in other fields. Malpractice claims are commonly seen after mismanagement of life-threatening medical emergencies, such as epidural haematomas. Due to the lack of legal analysis pertaining to this condition, the aim of this study is to identify risk factors associated with litigation in cases relating to the diagnosis and treatment of epidural haematomas. Materials and methods: Westlaw Edge, an online database, was used to analyze malpractice cases related to epidural haematomas between 1986 and 2022. Information regarding plaintiff demographics, defendant specialty, reason for litigation, trial outcomes, and payouts for verdicts and settlements were recorded. Comparative analysis between cases that returned a jury verdict in favour of the plaintiff versus defendant was completed. Results: A total of 101 cases were included in the analysis. Failure to diagnose was the most common reason for litigation (n = 64, 63.4%), followed by negligent care resulting in an epidural haematoma (n = 44, 43.6%). Spine surgery (n = 29, 28.7%), trauma (n = 28, 27.7%), and epidural injection/catheter/electrode placement (n = 21, 20.8%) were the primary causes of haematomas. Neurosurgeons (n = 18, 17.8%) and anesthesiologists (n = 17, 16.8%) were the two most common physician specialties cited as defendants. Most cases resulted in a jury verdict in favour of the defense (n = 54, 53.5%). For cases ending in plaintiff verdicts, the average payout was $3 621 590.45, while the average payment for settlements was $2 432 272.73. Conclusion: Failure to diagnose epidural haematomas is the most common reason for malpractice litigation, with neurosurgeons and anesthesiologists being the most common physician specialties to be named as defendants. More than half of all cases returned a jury verdict in favour of the defense and, on average, settlements proved to be more cost-effective than plaintiff verdicts.

Medical malpractice and cerebrospinal fluid shunts: An analysis of 36 cases.

Many physicians, particularly neurosurgeons, face malpractice claims during their career. The aim of this paper is to identify which factors increase the risk of litigation and influence legal outcomes relating to cerebrospinal fluid shunt management. Westlaw, an online legal database, was used to identify all medico-legal cases pertaining to cerebrospinal fluid shunts. Information regarding plaintiff demographics, defendant specialties, reasons for litigation, and trial outcomes were analysed. Thirty-six cases met criteria for inclusion. Most cases returned a defence verdict (44.4%), with delayed treatment or failure to appropriately treat patients with shunts the most common reason for litigation (66.7%). The average plaintiff verdict payout was $4,888,136.75 and average settlement $1,362,307.69. Delay or failure to treat resulted in the largest average payouts for plaintiff verdicts and settlements ($5,329,299.14 and $1,531,500.00, respectively).

Endoscopic Transclival Approach for Evacuation of Retroclival Hematoma: 2-Dimensional Operative Video.

Retroclival hematomas are a rare entity, presenting anteriorly to the brainstem in the epidural, subdural, or subarachnoid space. Although those that develop in the epidural space often arise from trauma, subdural retroclival hematomas frequently occur spontaneously in the setting of coagulopathy, aneurysm rupture, or pituitary apoplexy, with many cases having an unknown etiology.1-4 Although most are treated with conservative management, surgical intervention is preferred for those presenting with evidence of brainstem compression, hydrocephalus, worsening neurological deficits, and clinical deterioration.5 In this report, we present the case of a 75-year-old woman with a medical history of mitral regurgitation, nonischemic cardiomyopathy, and atrial fibrillation on warfarin presenting with 4 days of temporoparietal headaches and double vision. On examination, the patient demonstrated right abducens and hypoglossal nerve palsies. Computed tomography revealed a subdural hemorrhage within the retroclival cistern, extending into the dorsal inferior aspect of the C2 vertebral body, resulting in posterior displacement of the pons, medulla, and proximal cervical spinal cord. Spinal and cerebral angiograms did not show evidence of any vascular malformation. An endoscopic transclival approach was selected for hematoma evacuation. Key surgical steps included harvesting of nasoseptal flap, endoscopic transnasal approach to the sellar/subsellar space, transclival drilling, retroclival hematoma evacuation, and clival reconstruction. The patient tolerated the procedure well and was discharged 15 days postoperatively with resolution of prior cranial nerve deficits. Postoperative computed tomography imaging revealed complete retroclival hematoma evacuation. At her 3-month follow-up, the patient remained neurologically intact with imaging confirming no residual subdural hematoma. Institutional Review Board approval was obtained for this submission (2018-9379). Patient consent was not obtained as personal identifying information was kept confidential, following guidelines set forth by Institutional Review Board requirements.

High-Grade Glioma Recurrence Is Delayed in Hispanic Patients despite Severe Social Vulnerability: A Retrospective Cohort Study.

High-grade gliomas (HGGs; WHO grade III or IV) are the most common and lethal brain malignancy. Patients of Hispanic ethnicity are diagnosed with HGGs earlier than non-Hispanic patients, but they exhibit improved HGG survival following diagnosis. Either environmental or biological factors could explain this survival benefit. We aimed to determine if post-diagnosis advantages would still be present in Hispanic patients with high social vulnerability, an environmental condition predisposing patients to poor oncologic outcomes. HGG outcomes were retrospectively assessed in a cohort of 22 Hispanic patients and 33 non-Hispanic patients treated for HGGs from 2015 to 2020 at a single institution that serves a highly vulnerable region. Compared to non-Hispanic patients, Hispanic patients demonstrated higher social vulnerability index scores (96.8 + 0.7 vs. 76.3 + 4.6; *** p = 0.0002) and a 14-month longer interval between diagnosis and recurrence (19.7 + 5.9 (n = 13) vs. 5.5 + 0.6 months (n = 19); ** p = 0.001). In only those patients with more aggressive IDH-1 wildtype tumors (glioblastoma), Hispanic ethnicity still related to a longer time before recurrence (15.8 + 5.9 months (n = 9); 5.5 + 0.6 months (n = 18); * p = 0.034), and in a multivariate analysis, Hispanic ethnicity predicted time-to-recurrence (* p = 0.027) independent of patient age, functional status, MGMT gene methylation, or treatments received. Therefore, environmental factors, specifically social vulnerability, did not obscure the post-diagnosis benefits associated with Hispanic ethnicity. In future experiments, basic studies should be prioritized which investigate the cellular or genetic mechanisms underlying this ethnicity effect on HGG progression in the hopes of improving care for these devastating malignancies.

The Effect of Preoperative Cabergoline on Prolactinoma Fibrosis: A Case Series.

Introduction Prolactinomas are a common intracranial neoplasm and constitute most pituitary tumors. Although patients can present with variable hormone dysregulation and symptom severity, the use of dopamine agonists remains a first-line treatment. While bromocriptine has been found to increase tumor fibrosis, the effect of cabergoline on collagen deposition has been disputed. The aim of this article is to understand the influence of cabergoline on tumor fibrosis prior to resection. Case Presentations Four male patients who underwent prolactinoma resection were included in this report. The average age was 39.8 years (range: 26-52 years). Pre-treatment prolactin levels ranged from 957.8 to 16,487.4 ng/mL. Three patients received cabergoline for at least 1 month prior to surgery (treatment range: 1-6 months). One patient had surgery without prior cabergoline use. Pathology reports confirmed each tumor to be of lactotroph origin. For each sample, Masson's trichrome staining was performed and the percentage of sample fibrosis was quantified using an artificial intelligence imaging software. Among those who received preoperative cabergoline, the extent of tumor fibrosis was in the range of 50 to 70%. In contrast, specimen fibrosis was approximately 15% without cabergoline use. Conclusion This report demonstrates that a short duration of preoperative cabergoline can cause significant prolactinoma fibrosis. Understanding the effect of cabergoline on tumor consistency prior to surgery is essential as increased fibrosis can lead to more difficult tumor removal, reduce the extent of resection, and increase surgical complications. Considering these effects, further studies regarding the use of surgery prior to cabergoline for prolactinoma management are warranted.

Primary Pituitary Abscess: Two Case Reports.

Introduction Pituitary abscess is a rare disorder that represents a small fraction of all pituitary lesions. In this report, we present two additional cases with unique features to promote awareness and prompt surgical intervention. Case Presentations A 42-year-old male presented with headache, photophobia, subjective fever, dizziness, imbalance, nausea, and vomiting. A pituitary hormone panel confirmed hypothyroidism and suggested central hypogonadism and secondary adrenal insufficiency. Magnetic resonance imaging (MRI) showed a large sellar mass measuring 2.5 cm × 1.8 cm × 1.6 cm (CC × XT × AP). A 76-year-old woman presented with several months of headaches and unsteady gait in the setting of a known previously asymptomatic sellar lesion, measuring 1.8 cm × 1.2 cm × 1.5 cm (XT × CC × AP). Repeat MRI demonstrated possible hemorrhage within the lesion. In both cases, a preliminary diagnosis of pituitary macroadenoma was made, but transsphenoidal surgery revealed an encapsulated abscess; cultures obtained from the abscesses stained for gram-positive bacteria. Conclusion Pituitary abscess is a rare, potentially life-threatening disorder that may be easily mistaken for other sellar lesions. In this review, we contribute two additional cases of pituitary abscesses to increase awareness and emphasize the importance of proper diagnosis and management.

PTEN protein expression in malignant pleural mesothelioma.

Malignant pleural mesothelioma is associated with poor prognosis and despite recent advances in chemotherapy, the median survival is still approximately 12 months. Loss of phosphatase and tensin homolog (PTEN) protein expression may lead to constitutive activation of AKT resulting in cell survival and proliferation. Small studies reported that PTEN protein expression is rarely lost in mesothelioma whilst a larger study demonstrated prognostic significance of PTEN protein expression status with absence in 62 % of cases. We aimed to analyse PTEN protein expression in mesothelioma. Immunohistochemical analysis was performed in 86 archival mesothelioma samples to determine the PTEN protein expression status and statistical analysis was performed to identify any prognostic significance. Mesothelial cells in normal pleura demonstrated positive staining for PTEN protein and served as a positive reference. For mesothelioma samples, the expression of PTEN protein was scored as 0 (negative), 1 (intensity less than that of positive normal pleura reference slide) and 2 (intensity equal to or greater than positive normal pleura reference slide). A total of 23/86 (26.7 %) scored 0, 23/86 (26.7 %) scored 1 and 40/86 (46.5 %) scored 2 for PTEN expression. Univariate analysis demonstrated that lack of PTEN expression was not associated with survival. PTEN protein expression was undetectable in 26.7 % of mesothelioma samples; however, no prognostic significance was identified. Absence of PTEN protein may result in activation of the PI3K/AKT/MTOR pathway. Targeting this pathway with inhibitors further downstream of PTEN may provide a potential therapeutic target in selected patients.

Cerebellopontine angle meningiomas: postoperative outcomes in a modern cohort.

OBJECT: Tumors of the cerebellopontine angle (CPA) have always proven difficult for neurosurgeons to optimally manage. Studies investigating the natural history and treatment of vestibular schwannomas have dominated the literature in this regard. Distinguishing meningiomas from schwannomas in this location carries particular importance as each tumor type has certain prognostic and surgical considerations. In this study, the authors have characterized the outcomes of 34 patients surgically treated for CPA meningiomas and have investigated various factors that may affect postoperative neurological function. METHODS: The medical records of patients with CPA meningiomas who underwent surgery from 2005 to 2013 at the Duke University Health System were reviewed. Various patient, clinical, and tumor data were gathered from the medical records including patient demographics, pre- and postoperative neurological examinations, duration of symptoms, procedural details, tumor pathology and size, and treatment characteristics. Differences in continuous variables were then analyzed using the Student t-test while categorical variables were evaluated using the chi-square test. RESULTS: A total of 34 patients underwent surgical treatment for CPA meningiomas during the 8-year period. Jugular foramen invasion was seen in 17.6% of tumors, with nearly half (41.2%) extending into the internal acoustic canal. The most common presenting symptom was hearing loss (58.8%), followed by headache (52.9%) and facial numbness/pain (50.0%). The most common cranial nerve (CN) affected was CN X (11.8%), followed by CNs VI and VII (5.9%). Postoperatively, no patients experienced a decrease in hearing, with only 5.9% of patients experiencing facial nerve palsies. Patients with tumors larger than 3 cm had a significantly higher incidence of permanent CN deficits than those with smaller tumors (45.5% vs 5.9%, respectively; p = 0.011). Also, tumor extension into the jugular foramen was associated with the occurrence of lower CN deficits, none of which occurred in tumors without jugular foramen invasion. Internal acoustic canal tumor extension was not seen to be associated with postoperative complications or CN deficits. CONCLUSIONS: Meningiomas of the CPA are challenging lesions to treat surgically. However, the risk of facial palsy and hearing loss is significantly lower when compared with vestibular schwannomas. Novel methods for preoperative differentiation are needed to appropriately counsel patients on surgical risks. Also, due to the significant potential for neurological deficits, further studies are needed to investigate the utility of radiotherapy for these lesions.