The impact of surgeon's academic leave on surgical outcomes for endoscopic transsphenoidal resection of pituitary tumors.

Background: Endoscopic surgery has become the mainstay of pituitary surgery, but requires comprehensive surgical training. We evaluate the impact of a surgeon's academic leave during endoscopic training on surgical outcomes of patients with pituitary tumors. Methods: This retrospective study reviewed the surgical outcomes of endoscopic transsphenoidal surgery for pituitary tumors performed by a single surgeon. The last 56 surgical cases were performed between July 2010 and August 2014 before academic leave (Phase 1 surgery group), while another 56 consecutive cases were performed between November 2017 and March 2020 immediately after the surgeon's academic leave (Phase 2 surgery group). Demographic and clinical characteristics were collected and compared between the two surgery groups. Results: Overall, most surgical outcomes of endoscopic transsphenoidal surgery were not affected adversely by the period of academic leave. The operative time and length of hospital stay was lower in the Phase 2 surgery group compared to the Phase 1 surgery group (P<0.05). Postoperative tumor residual, intraoperative cerebrospinal fluid (CSF) leaks and reoperation also decreased significantly in the Phase 2 group compared to the Phase 1 group (P<0.05). Similar results were observed in patients operated using a one-hand/mono-nostril and two-hand/one-and-half nostril technique. Conclusions: Academic leave had no negative impact on most surgical outcomes for endoscopic transsphenoidal resection of pituitary tumors. Moreover, a trend toward shorter operative times and length of hospital stays was noted for patients receiving surgery immediately after surgeon's return from leave.

Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005-2018.

Background: This retrospective study aimed to determine the risk of venous thromboembolism (VTE) in patients with PsA after surgery for lumbar degenerative disease (LDD). Methods: The study data of adults aged ≥20 years admitted to U.S. hospitals with diagnoses of LDD and undergoing spinal decompression or fusion between 2005 and 2018 were extracted from the National Inpatient Sample (NIS) database. Patients were further divided into two groups based on a diagnosis of PsA or not via codes ICD-9: 696.0 and ICD-10: L40.50. Patients with missing information were excluded. Propensity score matching (PSM) was employed to enhance comparability between groups. Logistic regression was used to determine associations between PsA and various outcomes, including complications, unfavorable discharge, and prolonged length of stay (LOS). Results: Data on 471,283 patients with LDD was extracted from the NIS database.from 2005 to 2018. Before propensity score matching, patients with PsA had higher proportions of overall morbidity (8.8 % vs. 6.9 %), VTE (1.4 % vs. 0.7 %), and unfavorable discharge (20.8 % vs. 16.9 %). After matching, patients with PsA still had higher VTE incidence and unfavorable discharge proportions. After adjustments, multivariable regression analysis indicated that patients with PsA had a higher risk of unfavorable discharge (aOR: 1.26, 95 % CI: 1.03-1.55) and VTE (aOR: 1.99, 95 % CI: 1.05-3.75). Conclusions: Among patients undergoing surgery for LDD, pre-existing PsA may be associated with increased risks of unfavorable discharge and VTE occurrence. The findings may benefit preoperative risk stratifications before LDD surgeries.

Outcomes of hemorrhagic stroke in patients with autoimmune rheumatic diseases: An analysis of the US Nationwide Inpatient Sample.

AIM: To determine whether and how rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) affect outcomes in patients admitted for hemorrhagic stroke. METHODS: This study screened the Nationwide Inpatient Sample database for adults aged ≥20 years admitted to US hospitals with a principal diagnosis of intracerebral hemorrhage (ICH) between 2005 and 2018. Diagnoses were determined using the International Classification of Diseases, 9th and 10th revisions (ICD-9 and ICD-10) diagnostic codes for ICH (ICD-9: 431, 432; ICD-10: I61, I62). Study outcomes were: (1) in-hospital mortality; (2) unfavorable discharge, defined as transfer to nursing homes or long-term care facilities; and (3) prolonged length of stay (LOS), defined as LOS >75th centile. RESULTS: Associations between comorbid RA, SLE, and SSc and clinical outcomes show a significantly lower risk of in-hospital mortality and prolonged LOS in RA patients. After admissions for ICH, the risk for in-hospital mortality and prolonged LOS was decreased in RA patients, and the risk for unfavorable discharge (long-term care) was reduced in SLE patients. CONCLUSIONS: Among patients admitted to US hospitals for hemorrhagic stroke, patients with RA had decreased risk for in-hospital mortality and prolonged LOS.

Surgical Outcome and Evaluation of Strategies in the Management of Growth Hormone-Secreting Pituitary Adenomas After Initial Transsphenoidal Pituitary Adenectomy Failure.

Acromegaly is a systemic disease that requires multidisciplinary treatment to achieve the best clinical outcome. This study aimed to evaluate the outcomes of the endoscopic transsphenoidal approach (TSA) as the primary treatment for somatotroph adenomas and further investigate patients who had suboptimal surgical results. This retrospective study included 83 patients with somatotroph adenomas treated by TSA at our institution from 1999 to 2010. Biochemical remission was defined as hGH <1 and <2.5 ng/ml. Factors associated with failure of TSA and strategy of secondary treatments for refractory and recurrent disease were analyzed. The mean age of patients was 41.1 ± 11.3 years, and the mean follow-up time was 54.2 ± 44.3 months. Approximately 44.5% of patients had residual tumors after TSA. Larger tumor size, higher GH level before the operation, and the existence of residual tumors were associated with TSA failure. Forty-one patients had an inadequate response to TSA or a recurrent lesion, and of these patients, 37 had residual tumor after TSA. Octreotide results in good outcomes in the treatment of DGSA patients, and SRS/EXRT generates good results in treating patients who receive second treatments when remission cannot be reached 6 months after TSA operation.

Endoscopic transsphenoidal surgery for resection of pituitary macroadenoma: A retrospective study.

BACKGROUND: The endoscopic transsphenoidal approach is an efficient minimally invasive procedure for removal of pituitary tumors that can be accomplished through a one-hand or two-hand approach. The one-hand procedure through one nostril is more intuitive for surgeons, but maneuvering the instruments can be restrictive. The two-hand procedure using a one-and-half nostril approach provides more precise manipulation. This study aimed to compare the surgical outcomes of one-hand/mono-nostril and two-hand/one-and-half nostril surgeries for resection of large pituitary tumors by a single neurosurgeon. MATERIALS AND METHODS: The surgical data of 78 consecutive cases with pituitary macroadenoma (diameter >1 cm) were reviewed retrospectively. Altogether, 30 cases received one-hand/mono-nostril surgery, while 48 cases received two-hand/one-and-half nostril surgery. Postoperative outcomes of the two operations were compared. RESULTS: The operative time, hospital stay, residual rate of pituitary macroadenoma, visual field, surgical complications, and re-operative rates were slightly improved in the two-hand/one-and-half nostril surgery group compared with that in the one-hand/mono-nostril surgery group (all p>0.05). However, postoperative hypopituitarism was less frequent (1/48; 2.0%) with the two-hand/one-and-half nostril approach than with the mono-nostril approach (p = 0.004). Similar surgical outcomes were found in all patients with either small or large pituitary tumors, except that the difference in postoperative improvement in visual field change reached statistical significance (p = 0.044). CONCLUSION: A single-surgeon endoscopic endonasal transsphenoidal surgery with two-hand/one-and-half nostril approach is an effective and safe procedure for removal of large pituitary tumors.

Aggressive cytoreduction and multiple subpial cortical transections may obtain good surgical outcomes in refractory epilepsy with multiple epileptic foci.

BACKGROUNDS: Epilepsy surgery is the most efficacious therapeutic modality for patients with medical refractory epilepsy, especially resective surgery. However, the variable etiologies and multiple epileptic foci are usually associated with the outcomes. The aim of this study was to demonstrate that combination of different intervention procedures might be an alternative option for patients of refractory epilepsy. METHODS: We retrospectively analyzed pre-operative and post-surgical outcomes in 30 patients who received epilepsy surgery between January 1, 2010 and December 31, 2014 at Chang Gung Memorial Hospital (CGMH), Linkou, according to Engel's classification. RESULTS: Twenty-six of the 30 patients (86.7%) had good outcomes, sum of class I and class II after epilepsy surgery. The good outcome rate of our complicated group was 80.0% (12/15), compared to 93.3% (14/15) in the simple group, but no significant differences between the two groups (p = 0.569). Four patients whose epileptic foci involved eloquent area and received multiple subpial cortical transection, and good outcome rate was 75% (3/4). At last, six patients had previously failed epilepsy surgery and received a reoperation, with a good outcome rate of 83.3% (5/6). CONCLUSION: After complete pre-surgical evaluation and combined interventional procedures, the patients with refractory epilepsy had satisfactory outcomes and few neurological complications. Moreover, re-operation can improve the outcome in some patients who previously failed epilepsy surgery.

Effectiveness of dose-escalated topiramate monotherapy and add-on therapy in neurosurgery-related epilepsy: A prospective study.

BACKGROUND: Lesional and symptomatic causes of epilepsy are the most common neurological disorders of the brain. Topiramate effectively controls newly diagnosed epilepsy and refractory focal seizures, but high-dose topiramate does not improve seizure control. This study aimed to evaluate the clinical efficacy and safety of dose-escalated topiramate as first-line monotherapy and add-on therapy in patients with neurosurgery-related epilepsy. MATERIAL AND METHODS: A total of 55 neurosurgical patients with epilepsy were divided into monotherapy and add-on therapy groups and both groups received topiramate via the dose-escalation method. The primary efficacy outcomes were seizure-free rate and seizure response rate. Adverse events and seizure frequency were recorded. RESULTS: The seizure response rate in the first month of monotherapy was significantly better than that of add-on therapy (89% vs 65%, P < .05), but no significant differences were found in seizure response rates between the 2 groups after 2 months of treatment. Both monotherapy and add-on therapy were effective in controlling seizures, with mean seizure frequency of 0.725 vs 0.536 and seizure-free rate of 88% vs 78.6%. Both treatments showed good improvement of seizure frequency in patients without tumor. The efficacy of monotherapy was better than that of add-on therapy (80% vs 29.2%) in patients with body mass index (BMI) ≤24. However, add-on therapy was better than monotherapy (76.7% vs 21.4%) in patients with BMI > 24. Dizziness (25.5%) and headache (16.4%) were the most common adverse events. No severe adverse event such as cognitive impairment was observed. CONCLUSIONS: Dose-escalated topiramate monotherapy and add-on therapy demonstrate good efficacy and safety, with fewer adverse events in seizure control in neurosurgical patients.

Three-Dimensional Volumetric Changes and Clinical Outcomes after Decompression with DIAM™ Implantation in Patients with Degenerative Lumbar Spine Diseases.

Background and objectives: The prevalence of degenerative lumbar spine diseases has increased. In addition to standard lumbar decompression and/or fusion techniques, implantation of interspinous process devices (IPDs) can provide clinical benefits in highly selected patients. However, changes in spinal structures after IPD implantation using magnetic resonance imaging (MRI) have rarely been discussed. This volumetric study aimed to evaluate the effect of IPD implantation on the intervertebral disc and foramen using three-dimensional assessment. Materials and Methods: We retrospectively reviewed patients with lumbar degenerative disc diseases treated with IPD implantation and foraminotomy and/or discectomy between January 2016 and December 2019. The mean follow-up period was 13.6 months. The perioperative lumbar MRI data were processed for 3D-volumetric analysis. Clinical outcomes, including the Prolo scale and visual analog scale (VAS) scores, and radiographic outcomes, such as the disc height, foraminal area, and translation, were analyzed. Results: Fifty patients were included in our study. At the one-year follow-up, the VAS and Prolo scale scores significantly improved (both p < 0.001). The disc height and foraminal area on radiographs also increased significantly, but with limited effects up to three months postoperatively. MRI revealed an increased postoperative disc height with a mean difference of 0.5 ± 0.1 mm (p < 0.001). Although the mean disc volume difference did not significantly increase, the mean foraminal volume difference was 0.4 ± 0.16 mm3 (p < 0.05). Conclusions: In select patients with degenerative disc diseases or lumbar spinal stenosis, the intervertebral foramen was enlarged, and disc loading was reduced after IPD implantation with decompression surgery. The 3D findings were compatible with the clinical benefits.

CCM1 and CCM2 variants in patients with cerebral cavernous malformation in an ethnically Chinese population in Taiwan.

Cerebral cavernous malformation (CCM) is a vascular malformation characterized by clustered enlarged capillary-like channels in the central nervous system. The genes harboring variants in patients with CCM include CCM1/Krev interaction trapped-1, CCM2/MGC4607, and CCM3/programmed cell death protein 10. We aimed to identify pathogenic variants in an ethnic Chinese population in Taiwan. We recruited 95 patients with multiple CCMs or a single lesion with a relevant family history. Sanger sequencing was performed for 41 patients. Variants were identified using sequence alignment tools, and the clinical significance of these variants was determined using American College of Medical Genetics and Genomics standards and guidelines. Several pathogenic variants were found in six patients, including three unrelated patients and three affected members of one family. Two novel pathogenic variants leading to early truncation comprised a deletion variant in exon 18 of CCM1 (c.1846delA; p.Glu617LysfsTer44) and an insertion variant in exon 4 of CCM2 (c.401_402insGCCC; p.Ile136AlafsTer4). One novel pathogenic splice site variant was c.485 + 1G > C at the beginning of intron 8 of CCM1. In this study, we identified novel variants related to CCM in an ethnically Chinese population in Taiwan.

Adjuvant Radiation Therapy Compared with Observation Alone for Postoperative Residual Nonfunctional Pituitary Adenomas.

OBJECTIVE: The management of residual nonfunctional pituitary tumors after surgical resection remains controversial. In this study, we compared the prognosis of postoperative radiation therapy and observation only in patients with residual nonfunctional pituitary adenoma and reviewed the long-term complications after radiation therapy. METHODS: We retrospectively analyzed 90 patients who underwent surgery for nonfunctional pituitary adenomas from January 2008 to April 2012. Residual tumors were classified by size, location, and pathologic staining. Tumor progression was defined as volume progression ≥15% with or without clinical symptoms. Postoperative radiation therapy was performed <1 year after the last surgery. We compared the progression and 3-year and 5-year progression-free survival between the observation group and postoperative radiation therapy group. Postradiation complications including hypopituitarism, diabetes insipidus, deterioration in visual field or acuity, cranial nerve palsy, and hydrocephalus were also analyzed. RESULTS: More of the patients who received postoperative radiation therapy had a tumor progression-free survival of ≥3 years than did those who did not receive postoperative radiation therapy. Postoperative radiation therapy was significantly beneficial for the patients with a tumor size ≥3 cm or with tumors in the cavernous sinus. The most frequent complication after radiation therapy was hypopituitarism and a few cases had third cranial nerve palsy; however, there were no significant relationships with radiation therapy. CONCLUSIONS: In this study, immediate radiation therapy after tumor resection was an effective and relatively safe treatment for residual or progressive nonfunctional pituitary adenomas. Moreover, the long-term complications of radiation therapy were mild.

Correlations between clinical hormone change and pathological features of pituicytoma.

PURPOSE: Pituicytoma is a rare low-grade glioma arising from the pituicytes of the posterior pituitary. To date, the clinical and pathological correlates of pituicytoma have not been investigated. This study was thus designed to examine the correlation between pituicytoma and the normal pituitary gland. METHODS: The records of patients who underwent pituitary surgery at Chang Gung Memorial Hospital in Linkou, Taiwan between 2000 and 2016 were reviewed. Patients who received a pathological diagnosis of pituicytoma were included; however, those with inadequate specimens for pathological study were excluded. Clinical information, including patients' presenting symptoms, serum hormone levels, neuroimages, and specimens, were collected. Hematoxylin and eosin stains and immunohistochemical (IHC) stains were performed for differential diagnosis. RESULTS: Among the 1532 patients who underwent pituitary surgery, nine (0.59%) received a pathological diagnosis of pituicytoma. Two patients were excluded due to inadequate specimens. Among the seven remaining patients, six presented with hormone changes. The IHC stains revealed that pituicytoma has no secretory function; however, the resected pituitary glands showed positive results for hormone change. Coexisting pituicytoma and adrenocorticotropic hormone adenoma were identified in one patient with a diagnosis of Cushing disease. CONCLUSIONS: Pituicytoma revealed a negative endocrine secretory function through IHC staining. Additionally, pituicytoma is associated with hypersecretion of the pituitary gland both clinically and pathologically. Diagnosing pituicytoma before pathological confirmation is difficult because the tumour may present with hormone dysfunction. Therefore, IHC staining of specimens is useful to exclude the possibility of coexisting pituicytoma and pituitary adenoma.

Changes of cerebrospinal fluid protein concentrations and gait patterns in geriatric normal pressure hydrocephalus patients after ventriculoperitoneal shunting surgery.

Normal pressure hydrocephalus (NPH) was the first type of dementia ever described that can be treated using ventriculoperitoneal shunting surgery. Three typical clinical symptoms of NPH include gait disturbance, progressive cognitive dysfunction, and urinary incontinence. Although there are articles that have discovered several cerebrospinal fluid (CSF) protein biomarkers associated with NPH; however, studies examining individual and total protein concentrations from the ventricular CSF before and after shunting surgery are lacking. This study used proteomics to calculate the CSF individual and total protein concentrations before, and one week, one month and three months after the shunting surgery. Parameters of cadence, step length, walking speed, and percentages of single- and double-limb support in a gait cycle were measured. Protein concentrations associated with anti-oxidation, aging, and in the prevention of neurotoxic agent production increased by at least 2-folds after the surgery, indicating that the brain may become less susceptible to neurodegeneration. These proteins were alpha-1B-glycoprotein, apolipoproteins A-1 & A-IV, prostaglandin-H2 D-isomerase, alpha-1-antitrypsin, and serotransferrin. In gait analysis, lower cadence, decreased double-limb support, longer step length, and increased single-limb support were observed after the surgery, indicating a more stable walking balance. These changes lasted for a period of at least 3 months. As a result, shunting surgery may be recommended for geriatric patients with confirmed diagnosis of normal pressure hydrocephalus.

Female sex, good performance status, and bevacizumab-induced hypertension associated with survival benefit in Asian patients with recurrent glioblastoma treated with bevacizumab.

AIM: The goals of this study were to assess the activity and safety profile of bevacizumab in Taiwan Chinese patients with recurrent glioblastoma, to determine whether their response differed from that reported in other clinical trials, and to examine potential prognostic factors for survival. METHODS: We retrospectively assessed patients who received bevacizumab for recurrent glioblastoma between 2012 and 2015. Twelve predefined variables and the outcomes of our cohort were analyzed. RESULTS: In total, 76 patients with recurrent glioblastoma were analyzed. The overall response rate was 59.2%, including 19 patients (25.0%) with complete response and 26 patients (34.2%) with partial response. The median progression-free survival and overall survival were 5.2 months (95% confidence interval [CI], 4.6-5.8 months) and 7.8 months (95% CI, 5.8-9.8 months), respectively. Multivariate analysis identified sex and grade 3 posttreatment hypertension (systolic ≥ 160 mmHg or diastolic ≥ 100 mmHg) as the only independent predictive factors for progression-free survival and overall survival. Eastern Cooperative Oncology Group performance status was also found to be independently predictive of improved overall survival. CONCLUSION: We showed good responses using bevacizumab and the progression-free survival and overall survival were comparable with those previously reported. The adverse events of bevacizumab in our study were generally acceptable and manageable. Female sex, good performance status, and grade 3 posttreatment hypertension were suggested to be associated with survival benefits.

Acromegaly determination using discriminant analysis of the three-dimensional facial classification in Taiwanese.

OBJECTIVES: The aim of this study was to assess the size, angles and positional characteristics of facial anthropometry between "acromegalic" patients and control subjects. We also identify possible facial soft tissue measurements for generating discriminant functions toward acromegaly determination in males and females for acromegaly early self-awareness. MATERIAL AND METHODS: This is a cross-sectional study. Subjects participating in this study included 70 patients diagnosed with acromegaly (35 females and 35 males) and 140 gender-matched control individuals. Three-dimensional facial images were collected via a camera system. Thirteen landmarks were selected. Eleven measurements from the three categories were selected and applied, including five frontal widths, three lateral depths and three lateral angular measurements. Descriptive analyses were conducted using means and standard deviations for each measurement. Univariate and multivariate discriminant function analyses were applied in order to calculate the accuracy of acromegaly detection. RESULTS: Patients with acromegaly exhibit soft-tissue facial enlargement and hypertrophy. Frontal widths as well as lateral depth and angle of facial changes were evident. The average accuracies of all functions for female patient detection ranged from 80.0-91.40%. The average accuracies of all functions for male patient detection were from 81.0-94.30%. The greatest anomaly observed was evidenced in the lateral angles, with greater enlargement of "nasofrontal" angles for females and greater "mentolabial" angles for males. Additionally, shapes of the lateral angles showed changes. The majority of the facial measurements proved dynamic for acromegaly patients; however, it is problematic to detect the disease with progressive body anthropometric changes. CONCLUSION: The discriminant functions of detection developed in this study could help patients, their families, medical practitioners and others to identify and track progressive facial change patterns before the possible patients go to the hospital, especially the lateral "angles" which can be calculated by relative point-to-point changes derived from 2D lateral imagery without the 3D anthropometric measurements. This study tries to provide a novel and easy method to detect acromegaly when the patients start to have awareness of abnormal appearance because of facial measurement changes, and it also suggests that undiagnosed patients be urged to go to the hospital as soon as possible for acromegaly early diagnosis.

Neurenteric cysts: risk factors and management of recurrence.

BACKGROUND: Neurenteric cysts are rare central nervous system lesions with excellent outcome after total excision. The authors report their experience in the management of these lesions, especially if recurrence occurs. Risk factors of recurrence were analyzed, which have never been reported according to the literature review. METHODS: Twelve patients underwent surgical treatment for neurenteric cysts from April 1998 to July 2015. We retrospectively reviewed the clinical, radiological, operative, and pathological findings for these patients. Correlations between clinical characteristics and recurrence were analyzed. RESULTS: This series included six intracranial and six intraspinal cases. Total resection was achieved in 4 of the 12 cases and partial resection in 8. Six of the patients that underwent partial resection suffered from recurrence, and an additional operation was needed in five. Three of the recurrent intracranial lesions had refractory symptoms and were finally controlled through cyst-peritoneal or ventricle-peritoneal shunts. Risk factors of recurrence were revealed as age ≦30 years old (p = 0.02), subtotal resection in the first operation (p = 0.01), and size of supratentorial NECs >30 ml (p = 0.04). Two-thirds of recurrences occurred in the first 2 years after treatment. CONCLUSIONS: NECs express high recurrence rates when total excision cannot be achieved. The preoperative diagnosis error plays a major role leading to an incorrect surgical strategy and recurrence. MRI with FLAIR and DWI is recommended to improve the preoperative diagnosis. Although timely reoperation is indicated for symptomatic recurrence, adhesion may cause reoperation to become more challenging. C-P or V-P shunts are suggested as the second-line treatment, resulting in excellent prognosis. Patients with mucin-secreting cells noted histologically are susceptible to recurrence.

The Impact of Surgical Experience on Major Intraoperative Aneurysm Rupture and Their Consequences on Outcome: A Multivariate Analysis of 538 Microsurgical Clipping Cases.

The incidence and associated mortality of major intraoperative rupture (MIOR) in intracranial aneurysm surgery is diverse. One possible reason is that many studies failed to consider and properly adjust the factor of surgical experience in the context. We conducted this study to clarify the role of surgical experience on MIOR and associated outcome. 538 consecutive intracranial aneurysm surgeries performed on 501 patients were enrolled in this study. Various potential predictors of MIOR were evaluated with stratified analysis and multivariate logistic regression. The impact of surgical experience and MIOR on outcome was further studied in a logistic regression model with adjustment of each other. The outcome was evaluated using the Glasgow Outcome Scale one year after the surgery. Surgical experience and preoperative Glasgow Coma Scale (GCS) were identified as independent predictors of MIOR. Experienced neurovascular surgeons encountered fewer cases of MIOR compared to novice neurosurgeons (MIOR, 18/225, 8.0% vs. 50/313, 16.0%, P = 0.009). Inexperience and MIOR were both associated with a worse outcome. Compared to experienced neurovascular surgeons, inexperienced neurosurgeons had a 1.90-fold risk of poor outcome. On the other hand, MIOR resulted in a 3.21-fold risk of unfavorable outcome compared to those without it. Those MIOR cases managed by experienced neurovascular surgeons had a better prognosis compared with those managed by inexperienced neurosurgeons (poor outcome, 4/18, 22% vs. 30/50, 60%, P = 0.013).

Corpus callosum involvement and postoperative outcomes of patients with gliomas.

Corpus callosum involvement is associated with poorer survival in high grade glioma (HGG), but the prognostic value in low grade glioma (LGG) is unclear. To determine the prognostic impact of corpus callosum involvement on progression free survival (PFS) and overall survival (OS) in HGG and LGG, the records of 233 glioma patients treated from 2008 to 2011 were retrospectively reviewed. Preoperative magnetic resonance (MR) images were used to identify corpus callosum involvement. Age, sex, preoperative Karnofsky performance scale, postoperative Eastern Cooperative Oncology Group (ECOG) score and extent of resection (EOR) were evaluated with respect to PFS and OS. The incidence of corpus callosum involvement was similar among HGG (14 %) and LGG (14.5 %). Univariate analysis revealed that PFS and OS were significantly shorter in both WHO grade II and grade IV glioma with corpus callosum involvement (both, p < 0.05). Multivariate analysis showed that grade II glioma with corpus callosum involvement have shorter PFS (p = 0.03), while EOR, instead of corpus callosum involvement (p = 0.16), was an independent factor associated with PFS in grade IV glioma (p < 0.05). Corpus callosum involvement was no longer significantly associated with OS after adjusting age, gender, EOR, preoperative and postoperative performance status (p = 0.16, 0.17 and 0.56 in grade II, III and IV gliomas, respectively). Corpus callosum involvement happened in both LGG and HGG, and is associated with lower EOR and higher postoperative ECOG score both in LGG and HGG. Corpus callosum involvement tends to be an independent prognostic factor for PFS in LGG, but not for OS in LGG or in HGG.

Differentiation of brain abscesses from glioblastomas and metastatic brain tumors: comparisons of diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MR imaging before and after mathematic contrast leakage correction.

PURPOSE: To compare the diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MRI before and after mathematic contrast leakage correction in differentiating pyogenic brain abscesses from glioblastomas and/or metastatic brain tumors. MATERIALS AND METHODS: Cerebral blood volume (CBV), leakage-corrected CBV and leakage coefficient K2 were measured in enhancing rims, perifocal edema and contralateral normal appearing white matter (NAWM) of 17 abscesses, 19 glioblastomas and 20 metastases, respectively. The CBV and corrected CBV were normalized by dividing the values in the enhancing rims or edema to those of contralateral NAWM. For each study group, a paired t test was used to compare the K2 of the enhancing rims or edema with those of NAWM, as well as between CBV and corrected CBV of the enhancing rims or edema. ANOVA was used to compare CBV, corrected CBV and K2 among three lesion types. The diagnostic performance of CBV and corrected CBV was assessed with receiver operating characteristic (ROC) curve analysis. RESULTS: The CBV and correction CBV of enhancing rim were 1.45±1.17 and 1.97±1.01 for abscesses, 3.85±2.19 and 4.39±2.33 for glioblastomas, and 2.39±0.90 and 2.97±0.78 for metastases, respectively. The CBV and corrected CBV in the enhancing rim of abscesses were significantly lower than those of glioblastomas and metastases (P = 0.001 and P = 0.007, respectively). In differentiating abscesses from glioblastomas and metastases, the AUC values of corrected CBV (0.822) were slightly higher than those of CBV (0.792). CONCLUSIONS: Mathematic leakage correction slightly increases the diagnostic performance of CBV in differentiating pyogenic abscesses from necrotic glioblastomas and cystic metastases. Clinically, DSC perfusion MRI may not need mathematic leakage correction in differentiating abscesses from glioblastomas and/or metastases.

Transglutaminase 2 expression is increased as a function of malignancy grade and negatively regulates cell growth in meningioma.

Most meningiomas are benign, but some clinical-aggressive tumors exhibit brain invasion and cannot be resected without significant complications. To identify molecular markers for these clinically-aggressive meningiomas, we performed microarray analyses on 24 primary cultures from 21 meningiomas and 3 arachnoid membranes. Using this approach, increased transglutaminase 2 (TGM2) expression was observed, which was subsequently validated in an independent set of 82 meningiomas by immunohistochemistry. Importantly, the TGM2 expression level was associated with increasing WHO malignancy grade as well as meningioma recurrence. Inhibition of TGM2 function by siRNA or cystamine induced meningioma cell death, which was associated with reduced AKT phosphorylation and caspase-3 activation. Collectively, these findings suggest that TGM2 expression increases as a function of malignancy grade and tumor recurrence and that inhibition of TGM2 reduces meningioma cell growth.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

IMPORTANCE: The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. OBJECTIVE: To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. MAIN OUTCOMES AND MEASURES: Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. RESULTS: The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease. CONCLUSIONS AND RELEVANCE: This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.