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Background: Total hip arthroplasty (THA) is an effective surgery for patients with end-stage hip joint degenerative arthritis. This study aimed to determine peri-operative factors that impact the length of stay (LOS) and design a formula to predict LOS in patients undergoing THA., Methods: This cross-sectional study was performed from September 2019 to January 2020. For this study, all patients who underwent THA over a period of 12 years since 2005 were included in the study. Data about the LOS and several variables including demographic variables, surgery-related variables, transfusion, intensive care unit (ICU) admission, past drug history, comorbidities, and laboratory data, were gathered. Qualitative variables are presented as numbers (%), and quantitative variables are presented as mean Mann± standard deviation. Mann Whitney test , Kruskal-Wallis test, and Spearman's rank correlation test were also used., Results: A total of 524 patients were included in the study; 12 were excluded .261 (51%) were female and 251(49%) male. The mean age was 56.13±17.04 years. In the univariate analysis, the day of admission, surgery indication, transfusion, diabetes mellitus, oral anti-diabetic drugs, American Society of Anesthesiology (ASA) score, preoperative hemoglobin (Hb) level, and type of prosthesis showed significant relation with LOS. Significant variables entered to zero truncated negative binomial regression. Among them, the day of admission, ASA score, preoperative Hb level, and type of prosthesis showed significant relation with LOS ( P < 0.05) and were used for model design., Conclusion: Preoperative Hb level, ASA score, day of admission, and prosthesis type have an impact on LOS and can predict LOS in patients who are candidates for THA., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)

Objective: Pelvic access is a challenging matter in abdominal hysterectomy especially in obese patients and presence of pelvic adhesions. Uterus manipulators (UM) have been used in a number of studies on laparoscopic approach to improve surgical performance. This study aimed to assess the impact of UM application on the operation time and blood loss in total abdominal hysterectomy (TAH) for benign diseases., Materials and Methods: Forty-one patients aged 34 to 56 years were enrolled for abdominal hysterectomy - 20 as the case group (hysterectomy with UM application) and 21 as the control group (conventional hysterectomy). In the case group, UM was used after uterus artery ligation during TAH. The control group underwent traditional TAH., Results: The mean operation time was significantly less in TAH with UM compared to traditional TAH (90.23 ± 10.54 minutes vs. 140.5 ± 16.61 minutes; p-value<0.001). The mean decline between preoperative and 12-hour postoperative hemoglobin was 0.74 ± 0.23 mg/dL in the TAH with UM group and 1.65± 1.02 mg/dL in the traditional TAH group (p-value<0.001). Also, no difference was detected in intra- and post-operative complications., Conclusion: The current study showed that, using UM is beneficial in total abdominal hysterectomy by decreasing the operative time and blood loss., Competing Interests: Conflict of Interests Authors declare no conflict of interests., (Copyright © 2023 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Purpose: To establish reporting adherence to the Checklist for Artificial Intelligence in Medical Imaging (CLAIM) in diagnostic accuracy AI studies with the highest Altmetric Attention Scores (AAS), and to compare completeness of reporting between peer-reviewed manuscripts and preprints. Methods: MEDLINE, EMBASE, arXiv, bioRxiv, and medRxiv were retrospectively searched for 100 diagnostic accuracy medical imaging AI studies in peer-reviewed journals and preprint platforms with the highest AAS since the release of CLAIM to June 24, 2021. Studies were evaluated for adherence to the 42-item CLAIM checklist with comparison between peer-reviewed manuscripts and preprints. The impact of additional factors was explored including body region, models on COVID-19 diagnosis and journal impact factor. Results: Median CLAIM adherence was 48% (20/42). The median CLAIM score of manuscripts published in peer-reviewed journals was higher than preprints, 57% (24/42) vs 40% (16/42), P < .0001. Chest radiology was the body region with the least complete reporting ( P = .0352), with manuscripts on COVID-19 less complete than others (43% vs 54%, P = .0002). For studies published in peer-reviewed journals with an impact factor, the CLAIM score correlated with impact factor, rho = 0.43, P = .0040. Completeness of reporting based on CLAIM score had a positive correlation with a study's AAS, rho = 0.68, P < .0001. Conclusions: Overall reporting adherence to CLAIM is low in imaging diagnostic accuracy AI studies with the highest AAS, with preprints reporting fewer study details than peer-reviewed manuscripts. Improved CLAIM adherence could promote adoption of AI into clinical practice and facilitate investigators building upon prior works.

Purpose: To provide evidence towards a quantitative response assessment framework incorporating MRI-based linear measurements for spinal metastasis that predicts outcome following stereotactic body radiation therapy (SBRT)., Methods: Adult patients with de novo spinal metastases treated with SBRT between 2008 and 2018 were retrospectively assessed. The metastatic lesions involving the pedicles, articular processes, lamina, transverse process, spinous process and vertebral body at leach level were measured separately using linear measurements on pre- and all post-SBRT MRIs. The outcome was segment-specific progression (SSP) using SPINO guidelines which was dated to the first clinical documentation of progression, or the date of the associated MRI if imaging was the reason for progression. Random forest analysis for variable selection and recursive partitioning analysis for SSP probability prediction were used., Results: Five Hundred Ninety-three spinal levels (323 patients) from 4081 MRIs were evaluated. The appearance of new T1 hypointensity and increase in Bilsky grade had an odds ratio (OR) of 33.5 and 15.5 for SSP, respectively. Compared to baseline, an increase of > 3 mm in any lesion dimension, combined with a 1.67-fold increase in area, had an OR of 4.6 for SSP. The sensitivity, specificity, positive predictive value, negative predictive value, balanced accuracy and area under the curve of the training model were 96.7%, 89.6%, 28.6%, 99.8%, 93.2% and 0.905 and of the test model were 91.3%, 89.3%, 27.1% 99.6%, 90.3% and 0.933, respectively., Conclusion: With further refinement and validation in prospective multicentre studies, MRI-based linear measurements can help predict response assessment in SBRT-treated spinal metastases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neuroimaging modalities such as computer tomography and magnetic resonance imaging have greatly improved in their ability to achieve higher spatial resolution of neurovascular and soft tissue neuroanatomy, allowing for increased accuracy in the diagnosis of neurological conditions. However, the use of conventional contrast agents that have short tissue retention time and associated renal toxicities, or expensive radioisotope tracers that are not widely available, continue to limit the sensitivity of these imaging modalities. Nanoparticles can potentially address these shortcomings by enhancing tissue retention and improving signal intensity in the brain and neural axis. In this review, we discuss the use of different types of nanotechnology to improve the detection, diagnosis, and treatment of a wide range of neurological diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Faiz, Lam, Chen, Kasper and Salehi.)

Background: There is an association between anterior cerebral artery vessel asymmetry and anterior communicating artery aneurysm, presumably based on flow dynamics. The purpose of this study is to investigate the potential relationship between aortic arch branching patterns and incidence of intracranial aneurysm., Methods: This study included patients scanned over 1 year at our tertiary care center who underwent high-resolution imaging (computed tomography angiography or digital subtracted angiogram) of the head and neck arteries, aortic arch, and superior mediastinum. Exclusion criteria included patients with suboptimal images. Patient age, gender, aortic arch branching pattern, and the presence, location, and number of aneurysms were documented., Results: Among the 1082 patients analyzed, 250 (23%) patients had a variant aortic arch branching pattern, 22 (8.8%) of whom had aneurysms. There were 104 patients with 126 aneurysms, with majority of patients with normal aortic arch branching pattern (n = 82, 79%). The most common variant was a common origin of the left common carotid artery and brachiocephalic trunk with or without direct origin of the left vertebral artery. Twenty-two patients with aneurysms had an aberrant aortic arch (21%), compared to 232 patients without an aneurysm (24%). Fischer exact test showed no statistically significant difference between the incidence of aneurysm with different aortic arch variant groups (two-tailed p-value = 0.715)., Conclusion: To our knowledge, this is the first study to examine the association between aortic arch branching patterns and incidence of intracranial aneurysm. No significant association was found between aortic arch branching pattern and the incidence of intracranial aneurysm.

Purpose: Assessment of patients for temporal lobe epilepsy (TLE) surgery requires multimodality input, including EEG recordings to ensure optimal surgical planning. Often EEG demonstrates abnormal foci not detected on 1.5T MRI. Ultra-high field MRI at 7T provides improved resolution of the brain. We investigated the utility of 7T MRI to detect potential anatomical abnormalities associated with EEG changes., Methods: Ultra-high field data were acquired on a 7T MRI scanner for 13 patients with history of drug resistant TLE who had had EEG telemetry recordings. Qualitative evaluation of 7T imaging for presence of focal abnormalities detected on EEG was performed. Correlation of 7T MRI findings with EEG recordings of focal slowing or interictal epileptic spikes (IEDs), and seizures was performed., Results: Assessment of 7T MRI demonstrated concordance with TLE as determined by the multidisciplinary team in 61.5% of cases (n = 8). Among these, 3 patients exhibited supportive abnormal 7T MRI abnormalities not detected by 1.5T MRI. In patients who underwent surgery, 72.7% had concordant histopathology findings with 7T MRI findings (n = 8). However, qualitative assessment of 7T images revealed focal anatomical abnormalities to account for EEG findings in only 15.4% of patients (n = 2). Other regions that were found to have localized IEDs in addition to the lesional temporal lobe, included the contralateral temporal lobe (n = 5), frontal lobe (n = 3), and parieto-occipital lobe (n = 2)., Conclusion: Ultra-high field 7T MRI findings show concordance with clinical data. However, 7T MRI did not reveal anatomical findings to account for abnormalities detected by EEG.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Study Objective: To evaluate uterine scar features after laparoscopic myomectomy (LM) compared with myomectomy performed by laparoscopy initially and then completed with minilaparotomy (LAM)., Design: Prospective cohort study., Setting: An academic center for advanced endoscopic gynecologic surgery., Patients: Sixty-nine symptomatic women who underwent myomectomy between July and December 2018., Intervention: Patients underwent LM or LAM and 3-month follow-up ultrasonography., Measurements and Main Results: Forty-four patients underwent LM and 25 underwent LAM. Demographic data, intraoperative parameters, and postoperative outcomes were collected. Two-dimensional color Doppler ultrasound was done at a 3-month follow-up to evaluate myomectomy scar features, myometrial thickness, and the presence of and vascularity of a heterogeneous mass. These features were compared with those of the intact myometrium on the opposite wall of the patient's uterus. The 2 groups had similar demographic characteristics, and there were no significant between-group differences in the number, maximum diameter, type, or location of myomas. The mean myometrial thickness at the scar site was 18.9 ± 3.22 mm in the LM group and 19.7 ± 3.50 mm in the LAM group, with no significant difference between the 2 groups. There was no meaningful difference in vascularity between the scar and normal myometrium. Heterogeneous masses were detected in 23% of patients in the LM group and in 24% of those in the LAM group. Other than mean operative time (207 minutes for LM vs 150 minutes for LAM; p < .001) and mean postoperative reduction in hemoglobin (1.77 mg/dL for LM vs 2.35 mg/dL for LAM; p = .023), there were no other statistical differences between the 2 groups. One patient in the LM group experienced a bowel injury resulting from morcellation., Conclusion: There were no differences in myometrial scar features after LM compared with after LAM, implying effective suturing via both approaches., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluates hippocampal pathology through usage of ultra-high field 9.4T ex-vivo imaging of resected surgical specimens in patients who have undergone temporal lobe epilepsy surgery., Method and Materials: This is a retrospective interpretation of prospectively acquired data. MRI scanning of resected surgical specimens from patients who have undergone temporal lobe epilepsy surgery was performed on a 9.4T small bore Varian MR magnet. Structural images employed a balanced steady-state free precession sequence (TrueFISP). Six patients (3 females; 3 males) were included in this study with an average age at surgery of 40.7 years (range 20Y&#95;"60) (one was used as a control reference). Two neuroradiologists qualitatively reviewed the ex-vivo MRIs of resected specimens while blinded to the histopathology reports for the ability to identify abnormal features in hippocampal subfield structures., Results: The hippocampal subfields were reliably identified on the 9.4T ex-vivo scans in the hippocampal head region and hippocampal body region by both neuroradiologists in all 6 patients. There was high concordance to pathology for abnormalities detected in the CA1, CA2, CA3 and CA4 subfields. Detection of abnormalities in the dentate gyrus was also high with detection in 4 of 5 cases. The Cohen's kappa between the two neuroradiologists was calculated at 0.734 SE=0.102., Conclusions: Ex-vivo 9.4T specimen imaging can detect abnormalities in CA1, CA2, CA3, CA4 and DG in both the hippocampal head and body. There was good concordance between qualitative findings and histopathological abnormalities for CA1, CA2, CA3, CA4 and DG., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: To analyze MRI characteristics of lumbar facet synovial cysts and distinguish those requiring subsequent surgical management for recurrence, after percutaneous synovial cyst rupture., Methods and Materials: Retrospective chart review conducted in patients undergoing percutaneous synovial cyst rupture between February 2012 and April 2015. Pre- and post-percutaneous rupture procedure MRI spine studies were serially reviewed. Synovial cyst sizes, T1 and T2 signal characteristics and changes therein, T2 hypointense (or 'dark rim') thickness and change, and changes in the complexity of cyst signals were compared. Operative notes for patients who underwent subsequent surgical removal of recurrent synovial cysts were reviewed., Results: 24 patients received 41 percutaneous synovial cyst rupture procedures, with a technical success rate of 82.9%. There was a significant difference in the mean increased thickness of the T2 hypointense rim on the first post-rupture MRI scan (p=0.0411) between patients requiring subsequent surgery and those who did not. There was a significant difference in the average sizes of synovial cysts before the procedure (p=0.0483) in those requiring subsequent surgery and those who did not. Five complications were noted (12.2%), mostly involving leg pain or weakness. Of the nine patients who underwent subsequent surgery post-synovial cyst rupture, six of the surgeries had recorded difficulty pertaining to scarring and/or adherence of the cyst to dura., Conclusions: A larger increase in thickness of the T2 hypointense rim on the first post-rupture MRI scan and a larger synovial cyst size were associated with the need for subsequent surgical resection., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To provide a more detailed investigation of hippocampal subfields using 7T magnetic resonance imaging (MRI) for the identification of hippocampal sclerosis in temporal lobe epilepsy (TLE)., Materials and Methods: Patients (n = 13) with drug-resistant TLE previously identified by conventional imaging as having hippocampal sclerosis (HS) or not (nine without HS, four HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( R2*) were studied between the two groups. In addition, qualitative assessment at 7T and clinical outcomes were correlated with measured subfield changes., Results: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 (P = 0.001) and CA4+DG (P < 0.001). Volumetry also uncovered subfield atrophy in 33% of patients without HS, which had not been detected using conventional imaging. R2* was significantly lower in the CA4+DG subfields (P = 0.001) and the whole hippocampus (P = 0.029) of HS patients compared to controls but not significantly lower than the group without HS (P = 0.077, P = 0.109). No correlation was found between quantitative volumetry and qualitative assessment as well as surgical outcomes (Sub, P = 0.495, P = 0.567, P = 0.528; CA1, P = 0.104 ± 0.171, P = 0.273, P = 0.554; CA2+CA3, P = 0.517, P = 0.952, P = 0.130 ± 0.256; CA4+DG, P = 0.052 ± 0.173, P = 0.212, P = 0.124 ± 0.204; WholeHipp, P = 0.187, P = 0.132 ± 0.197, P = 0.628)., Conclusion: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T is capable of identifying characteristic patterns of hippocampal atrophy in HS patients; however, difficulty remains in using imaging to identify hippocampal pathologies in cases without HS., Level of Evidence: 2 J. MAGN. RESON. IMAGING 2017;45:1359-1370., (© 2016 International Society for Magnetic Resonance in Medicine.)

Objectives: Ultra high field MRI at 7T is able to provide much improved spatial and contrast resolution which may aid in the diagnosis of hippocampal abnormalities. This paper presents a preliminary experience on qualitative evaluation of 7T MRI in temporal lobe epilepsy patients with a focus on comparison to histopathology., Methods: 7T ultra high field MRI data, using T1-weighted, T2*-weighted and susceptibility-weighted images (SWI), were acquired for 13 patients with drug resistant temporal lobe epilepsy (TLE) during evaluation for potential epilepsy surgery. Qualitative evaluation of the imaging data for scan quality and presence of hippocampal and temporal lobe abnormalities were scored while blinded to the clinical data. Correlation of imaging findings with the clinical data was performed. Blinded evaluation of 1.5T scans was also performed., Results: On the 7T MRI findings, eight out of 13 cases demonstrated concordance with the clinically suspected TLE. Among these concordant cases, three exhibited supportive abnormal 7T MRI findings which were not detected by the clinical 1.5T MRI. Of the ten cases that progressed to epilepsy surgery, seven showed concordance between 7T MRI findings and histopathology; of these, four cases had hippocampal sclerosis. SWI had the highest concordance with the clinical and histopathological findings. Similar clinical and histopathological concordance was found with 1.5T MRI., Conclusions: There was moderate and high concordance between the 7T imaging findings with the clinical data and histopathology respectively., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of this study is to compare longitudinal two-dimensional (2-D) and three-dimensional (3-D) ultrasound (US) estimates of ventricle size in preterm neonates with posthemorrhagic ventricular dilatation (PHVD) using quantitative measurements of the lateral ventricles. Cranial 2-D US and 3-D US images were acquired from neonatal patients with diagnosed PHVD within 10 min of each other one to two times per week and analyzed offline. Ventricle index, anterior horn width, third ventricle width, and thalamo-occipital distance were measured on the 2-D images and ventricle volume (VV) was measured from 3-D US images. Changes in the measurements between successive image sets were also recorded. No strong correlations were found between VV and 2-D US measurements ([Formula: see text] between 0.69 and 0.36). Additionally, weak correlations were found between changes in 2-D US measurements and 3-D US VV ([Formula: see text] between 0.13 and 0.02). A trend was found between increasing 2-D US measurements and 3-D US-based VV, but this was not the case when comparing changes between 3-D US VV and 2-D US measurements. If 3-D US-based VV provides a more accurate estimate of ventricle size than 2-D US measurements, moderate-weak correlations with 3-D US suggest that monitoring preterm patients with PHVD using 2-D US measurements alone might not accurately represent whether the ventricles are progressively dilating. A volumetric measure (3-D US or MRI) could be used instead to more accurately represent changes.

OBJECT The relationship between headaches, pituitary adenomas, and surgical treatment of pituitary adenomas remains unclear. The authors assessed the severity and predictors of self-reported headaches in patients referred for surgery of pituitary adenomas and evaluated the impact of endoscopic transsphenoidal surgery on headache severity and quality of life (QOL). METHODS In this prospective study, 79 patients with pituitary adenomas underwent endoscopic transsphenoidal resection and completed the Headache Impact Test (HIT-6) and the 36-Item Short Form Health Survey (SF-36) QOL questionnaire preoperatively and at 6 weeks and 6 months postoperatively. RESULTS Preoperatively, 49.4% of patients had mild headache severity, 13.9% had moderate severity, 13.9% had substantial severity, and 22.8% had intense severity. Younger age and hormone-producing tumors predisposed greater headache severity, while tumor volume, suprasellar extension, chiasmal compression, and cavernous sinus invasion of the pituitary tumors did not. Preoperative headache severity was found to be significantly associated with reduced scores across all SF-36 QOL dimensions and most significantly associated with mental health. By 6 months postoperatively, headache severity was reduced in a significant proportion of patients. Of the 40 patients with headaches causing an impact on daily living (moderate, substantial, or intense headache), 70% had improvement of at least 1 category on HIT-6 by 6 months postoperatively, while headache worsened in 7.6% of patients. The best predictors of headache response to surgery included younger age, poor preoperative SF-36 mental health score, and hormone-producing microadenoma. CONCLUSIONS The results of this study confirm that surgery can significantly improve headaches in patients with pituitary adenomas by 6 months postoperatively, particularly in younger patients whose preoperative QOL is impacted. A larger multicenter study is underway to evaluate the long-term effect of surgery on headaches in this patient group.

Background: Bone invasive skull base meningiomas are a subset of meningiomas that present a unique clinical challenge due to brain and neural structure involvement and limitations in complete surgical resection, resulting in higher recurrence and need for repeat surgery. To date, the pathogenesis of meningioma bone invasion has not been investigated. We investigated immunoexpression of proteins implicated in bone invasion in other tumor types to establish their involvement in meningioma bone invasion., Methods: Retrospective review of our database identified bone invasive meningiomas operated on at our institution over the past 20 years. Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1). Differential expression in tumor cell and vasculature was evaluated and comparisons were made between meningioma anatomical locations., Results: MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells. Noninvasive transbasal meningiomas exhibited higher vascular endothelial cell MMP2 immunoexpression compared to invasive meningiomas. We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas. Strong vascular ITGB1 expression extending from the endothelium through the media and into the adventitia was found in a subset of meningiomas., Conclusions: We have demonstrated that key proteins are differentially expressed in bone invasive meningiomas and that the anatomical location of bone invasion is a key determinant of expression pattern of MMP1, OPN, and ITGB1. This data provides initial insights into the pathophysiology of bone invasion in meningiomas and identifies factors that can be pursued as potential therapeutic targets.

Background: Pituitary tumor-transforming gene (PTTG1) has been implicated in several oncogenic processes. The aim of this study was to determine PTTG expression in brain tumors., Materials and Methods: We investigated 88 benign and malignant brain tumors. PTTG immunoexpression was evaluated using a scale of 0 to 3. PTTG immunoexpression was nuclear and cytoplasmic in most tumors, except for medulloblastomas and hemangiopericytomas. Expression was highest in medulloblastomas. Higher grade gliomas including glioblastoma multiforme (GBM) IV and astrocytoma III had the highest level of PTTG expression, whereas low-grade gliomas had the lowest levels of PTTG expression. Hemangiopericytomas had the lowest levels of PTTG immunoreactivity, with meningiomas and schwannomas exhibiting similarly low PTTG levels. Nuclear PTTG immunoreactivity was higher than cytoplasmic in higher-grade tumors., Conclusion: Our results indicate that PTTG immunoexpression is higher in aggressive brain tumors including medulloblastomas, GBM IV, and astrocytoma III, whereas in more benign tumors, PTTG immunoexpression is lower.

Background: O-6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that counteracts chemotherapeutic cytotoxicity of alkylating agents such as temozolomide. Low levels of MGMT expression have been shown to correlate with longer survival in glioma patients treated with temozolomide. The same is true in pituitary adenomas., Objective: We investigated the immunohistochemical expression of MGMT in a variety of corticotroph adenoma subtypes to determine the potential utility of temozolomide as a therapeutic agent., Methods: The tumors consisted of 40 cases of adrenocorticotropin-secreting pituitary tumors in Cushing disease, 12 Crooke cell adenomas, and 7 subtype I silent corticotroph adenomas. Staining for MGMT was assessed by light microscopy; nuclear reactivity was estimated semiquantitatively as present in < 10%, 10% to 25%, 25% to 50%, 50% to 75%, and > 75% of cells., Results: Immunoexpression showed no correlation with patient age, sex, tumor size, invasiveness, or recurrence in patients with Cushing disease. Among adrenocorticotropin-secreting adenomas associated with Cushing disease, most invasive (60%) and recurrent (86%) tumors showed low MGMT immunopositivity, defined as < 25%. Most (75%) Crooke cell adenomas exhibited an MGMT immunoreactivity of ≤ 50%. All subtype I silent corticotroph adenomas showed < 10% MGMT staining., Conclusion: Our descriptive findings of low MGMT expression in adrenocorticotropin-producing pituitary adenomas, particularly aggressive tumors, suggest that they may be suitable candidates for temozolomide therapy.

Many neurosurgical centers use surgical aspirators to remove brain tumor tissue. The resulting aspirate consists of fragmented viable tumor, normal or tumor-infiltrated brain tissue as well as necrotic tissue, depending on the type of tumor. Typically, such fragmented aspirate material is collected but discarded and not included when making the histopathological diagnosis. Whereas the general suitability of surgical aspirate for histological diagnosis and immunohistochemical staining has been reported previously, we have systematically investigated whether the collection and histological examination of surgical aspirate has an impact on diagnosis, in particular on the tumor grading, by providing additional features. Surgical and aspirate specimens from 85 consecutive neurosurgical procedures were collected and routinely processed. Sixty-five of the 85 specimens were intrinsic brain tumors and the remainder consisted of metastatic tumors, meningiomas, schwannomas and lymphomas. Important diagnostic features seen in surgical aspirate were microvascular proliferation (n = 3), more representative necrosis (n = 2), and gemistocytic component (n = 2). In one case, microvasular proliferations were seen in the aspirate only, leading to a change of diagnosis. Collection of surgical aspirate also generates additional archival material which can be microdissected and used for tissue microarrays or for molecular studies., (© 2011 Japanese Society of Neuropathology.)

MGMT promoter hypermethylation of aggressive pituitary adenomas and pituitary carcinomas and low protein expression are implicated in improved response to treatment with temozolomide (TMZ). The aim of the present study was to investigate MGMT promoter methylation and immunoexpression in an aggressive subset of pituitary adenomas and carcinomas. Our material consisted of 12 silent subtype 3 (SS3) adenomas, 10 primary carcinomas, and 4 disseminated metastases. Two different tissue samples of 7 of the 12 SS3 adenomas and all carcinomas were analyzed for MGMT promoter methylation and immunohistochemical expression of MGMT. Immunoexpression was assessed semi-quantitatively as a percentage of immunoreactive nuclei. Overall 33% of carcinomas exhibited homogenous MGMT methylation in tumor and metastatic specimens. Low immunohistochemical MGMT expression was noted in 50% of carcinomas. Overall, 42% of the SS3 adenomas exhibited MGMT promoter methylation. MGMT immunostaining was predominantly negative (92%), with homogenous immunostaining results across different samples. Whereas all the methylated SS3 adenomas had low MGMT immunoreactivity, five unmethylated adenomas exhibited absent/low MGMT expression. There was no relationship between methylation status and MGMT immunoexpression was not apparent. MGMT methylation and low immunohistochemical expression seen in a subset of carcinomas and SS3 adenomas, suggesting that a subset of tumors may respond to treatment with TMZ. Heterogeneous MGMT methylation status in SS3 adenomas and the lack of concordance between methylation and immunohistochemical expression of MGMT suggest complex regulatory mechanisms, highlighting the need for improved methods in the research on a correlation between MGMT changes and response to TMZ.

Malignancies lacking specific features of cellular maturation are termed "undifferentiated" and represent 5-10% of all human tumors. They are encountered at a variety of sites but do not, as a rule, arise in the sellar region. A 39-year-old male with a history of testicular seminoma and an unsuccessful biopsy of a third ventricular neoplasm, presented with visual disturbances and memory loss. Light microscopically, the tumor consisted entirely of undifferentiated spindle cells. No germ cell component was noted. An exhaustive immunohistochemical study found immunoreactivity for vimentin and desmin, but for no other myoid markers. Polymerase chain reaction showed no X;18 translocation. Based upon these studies, a diagnosis of "undifferentiated sarcoma" was made. Our case, being highly unusual among reported sellar neoplasms, underscores the difficulties inherent in the differential diagnosis of undifferentiated neoplasms.

Several new markers have shown a capacity to predict the clinicopathological behavior of pituitary neoplasms; these markers have shown potential to correlate with tumor subtype and size and patient age and sex. These various markers are involved in a host of cellular functions, including cell-cycle progression, cell proliferation, apoptosis, cell adhesion, and tumor vascularity. In this companion article to our first review of Ki-67 as a marker of pituitary adenomas, we present and analyze the literature regarding matrix metalloproteinases and their inhibitors (tissue inhibitor metalloproteinases), vascular endothelial growth factor, fibroblast growth factor and its receptor, apoptotic markers and p53, as well as cyclooxygenase-2, galectin-3, and pituitary tumor transforming gene. Some of these markers, such as fibroblast growth factor and fibroblast growth factor receptor and matrix metalloproteinases, show particular promise in their ability to identify pituitary tumors that behave in an aggressive manner. We suggest the need for uniform design and application of methods and standardized criteria for the interpretation of results. A uniform approach will establish clinicopathological utility of emerging markers.

MGMT expression in tumors has been correlated with response to treatment with temozolomide therapy. Few medical therapies are available for Nelson syndrome, and the efficacy of such therapeutics remains limited. The aim of the present study was to assess immunohistochemical expression of MGMT in ACTH-secreting pituitary adenomas of patients with Nelson syndrome. Our material consisted of eight specimens from ACTH-secreting pituitary adenomas of patients with Nelson syndrome. Immunohistochemical staining for MGMT was performed using the streptavidin-biotin-peroxidase complex method. MGMT immunoreactivity was assessed microscopically and recorded as an estimated percentage of nuclear MGMT immunostaining (0 = none, 1=<10%, 2=<25%, 3=<50%, 4=>50%). Five of the eight specimens (65%) exhibited no MGMT immunoreactivity, with two out of eight cases (25%) showing slight MGMT staining (<10%) and one out of eight cases (12%) demonstrating moderate MGMT positivity (<25%). Patient male/female ratio was 3:5, with average patient age being 62.4 (range 57–66). Our findings suggest that temozolomide therapy may be of potential use in patients with Nelson syndrome, as these tumors express absent/low levels of MGMT. Absent or low MGMT staining in brain and other neoplasms has been shown to correlate with successful treatment with temozolomide, and recent reports of aggressive pituitary adenomas suggest similar outcomes.

Objective: We investigated the correlation between immunohistochemical expression of the pituitary tumor transforming gene (PTTG) and pituitary adenoma subtype., Methods: Pituitary adenomas (n = 89) were stained for PTTG using the streptavidin-biotin-peroxidase complex method and a monoclonal PTTG antibody., Results: PTTG staining was found to be cytoplasmic with a pronounced paranuclear expression pattern. Reactivity was highest in growth hormone (GH) adenomas as compared with other tumors, including prolactin (PRL), follicle-stimulating hormone/luteinizing hormone/alpha subunit, as well as adrenocorticotrophic hormone-secreting adenomas. PRL adenomas exhibited the lowest expression levels. Among GH adenomas, untreated tumors demonstrated significantly higher PTTG levels than octreotide-treated examples. Although dopamine agonist-treated PRL adenomas tended to show lower expression levels, statistical significance was not reached., Conclusions: Our finding that PTTG was differentially expressed in pituitary adenoma subtypes suggests a cell-specific function for PTTG. Moreover, treatment of GH adenomas with somatostatin analogues lowered PTTG expression. Further investigation into mechanisms mediating cell-specific expression of PTTG is warranted.

O(6)-Methylguanine-DNA-methyltransferase (MGMT) is a unique protein, which both repairs O(6)-alkylguanine lesions stoichiometrically without a multi-enzymatic pathway and self-inactivates. It has recently been linked to the therapeutic success of alkylating agent chemotherapy, specifically temozolomide treatment. This drug affects the MGMT pathway to induce cell death in tumor tissue. Low levels of functional MGMT have been correlated with success of treatment, while high levels bring about failure of therapy. Expression of MGMT protein varies in normal and tumoral tissue. Furthermore, its epigenetic silencing due to promoter methylation has been linked to its lack of expression in many types of tumor, including gliomas. Great enthusiasm surrounds the utility of this protein in cancer treatment. Not only has there been success in manipulating MGMT levels to enhance alkylating agent therapy, but studies also suggest a possible role of MGMT in protecting hematopoietic cells from the myelosuppressive effects of high-dose chemotherapy. Innovative research into this protein will no doubt be rewarding. This review presents a summary of what is known about this unique protein, including its structure, function in its pathway, polymorphisms, expression in normal and tumoral tissue, relation to alkylating agent therapy, and possible future applications.

KI-67, A MARKER of cellular proliferation, has been studied extensively in pituitary neoplasia. It is of relevance to various clinicopathological parameters, including tumor subtype, size, invasiveness, and recurrence, as well as patient age and sex. Generally, pituitary tumors behaving aggressively have increased Ki-67 labeling indices. Nonetheless, there is considerable overlap in Ki-67 labeling between noninvasive and invasive adenomas as well as between adenomas and pituitary carcinomas. Not only is there no general agreement regarding the relationship of Ki-67 labeling index and tumor invasiveness, but the same is also true of the association with pituitary tumor size, growth fraction, and recurrence. Whereas a number of studies found conclusive associations of Ki-67 labeling indices with aggressive behavior, size, and/or adenoma subtype, others fail to do so. It is evident that discrepant data regarding tumor behavior in part has its basis in nonuniform study criteria. For example, different investigators use varying criteria of tumor invasion and recurrence. Herein, we review the literature relating Ki-67 expression and various other clinicopathological parameters and conclude that uniform definitions and methods, as well as new markers, are key to improved treatment of pituitary tumors.

Pituitary tumor-transforming gene (PTTG) was only recently discovered. Its overexpression occurs in a wide variety of endocrine and non-endocrine tumors, including ones of pituitary, thyroid, ovary, breast, prostate, lung, esophagus, colon, and the central nervous system. It affects tumor invasiveness and recurrence in several systems, functions as a securin during cell cycle progression, and inhibits premature sister chromatid separation. PTTG is involved in multiple cellular pathways, including proliferation, DNA repair, transformation, angiogenesis induction, invasion, and the induction of genetic instability. In thyroid carcinomas, PTTG expression is a marker of invasiveness. PTTG is overexpressed in most pituitary adenomas, where it appears to correlate with recurrence and angiogenesis. Increasing evidence also points to the role of PTTG in endocrine organ development. For example, PTTG knockout mice show defective pancreatic beta-cell proliferation. Herein, we review the current knowledge regarding PTTG-mediated pathways based on evidence from in vivo and in vitro studies as well as knockout mice models. We also summarize the issue of PTTG expression and its correlation with clinicopathologic parameters in patients with neoplasms, particularly of endocrine organs. In addition, we discuss in vitro and in vivo therapeutic models targeting PTTG overexpression.

Objectives: The aim of this work was to investigate the immunohistochemical expression of nestin, a member of the intermediate filament family, in adenohypophysial vasculature during development and progression of pituitary infarction., Methods: Forty-five nontumorous adenohypophyses and 34 pituitary adenomas of various types, all exhibiting acute or healing infarcts, were examined immunohistochemically using the streptavidin-biotin-peroxidase complex method., Results: In both adenohypophyses and pituitary adenomas without infarction, nestin was expressed in only a few capillaries and endothelial cells. In acute infarcts without a vascular response, no nestin was demonstrable within necrotic capillaries (50 cases). In organizing infarcts, newly formed vessels spreading into necrotic zones showed nestin expression in all capillaries and practically every endothelial cell (25 cases). In the hypocellular, fibrotic scar phase, only a few vessels (4) were apparent, and immunoreactivity was focal and mild., Conclusions: Nestin is strongly expressed in newly formed capillaries and is downregulated when infarcts transform to fibrous tissue. Nestin expression may provide valuable insight into the process of pituitary angiogenesis.

Purpose: Approximately 25% of patients with traumatic brain injury (TBI) may develop partial or complete hypopituitarism. The causative mechanisms involved in its development are not clear. To the authors' knowledge, there have been no recent morphologic studies of the pituitary following TBI., Methods: To characterize the resultant histologic changes, this study investigated the pituitaries of 42 patients who died following a motor vehicle accident, all from the Mayo Tissue Registry. Twelve patients died instantly at the scene of the accident (Group I) whereas 30 survived between 3 hours and 7 days (Group II). All pituitary specimens were obtained at autopsy, formalin-fixed and paraffin-embedded. Hematoxylin-eosin sections cut in horizontal or sagittal plane were examined light-microscopically., Results: No infarction was noted in the pituitary specimens from group I. In group II, 13 of 30 (43%) showed acute infarcts of varying size. The extent of infarction in group II ranged from focal to sub-total necrosis involving 90% of the adenohypophysis., Conclusions: Underlying adenohypophysial pathology in patients dying after TBI is acute infarction. Loss of large numbers of adenohypophysial cells causes reduced secretion of adenohypophysial hormones and may contribute to post-traumatic hypopituitarism.

We report here the case of a 21-year-old woman with a large sellar tumor, extending to the suprasellar area associated with growth hormone deficiency, hypogonadism, hypocorticism, and hyperprolactinemia. Transsphenoidal surgery was performed, and histologic, immunohistochemical, and electron microscopic study lead to the diagnosis of granular cell tumor. These tumors are, in most cases, very small and are found incidentally at autopsy of older patients. Our case is exceptional because the tumor developed in a young woman, extended to the suprasellar region, and caused clinical symptoms.

Objective: The purpose of this article is to define the relations of the symphysis pubis and capsular tissues to the adductor and rectus abdominis soft-tissue attachments on cadaver dissection and correlate with MRI of the anterior pelvis., Subjects and Methods: Seventeen cadavers (8 males and 9 females; mean age, 80 years) were dissected bilaterally. Rectus abdominis and adductor muscles were traced to the pubis and further attachments to the pubic symphysis were defined. Ten asymptomatic (mean age, 17; age range, 16.5-29 years) male athletes underwent 1.5-T MRI of the anterior pelvis with two surface microcoils (each 42 mm in diameter). An axial T2-weighted turbo spin-echo (TSE) sequence (TR/TE, 2,609/106; voxel size, 0.4 mm) was obtained. Axial and sagittal 3D T1-weighted fast-field echo (FFE) sequences (25/4.9; voxel size, 0.3 mm) were obtained. Sequences were repeated incorporating fat suppression and i.v. gadolinium. The relation of the symphysis pubis, disk, and capsular tissues to the insertions of the rectus abdominis, adductor muscles, and gracilis were independently evaluated by two experienced radiologists blinded to all clinical details., Results: In all 17 cadaver specimens, the adductor longus and rectus abdominis attached to the capsule and disk of the symphysis pubis, whereas the adductor brevis had an attachment to the capsule in seven specimens and the gracilis in one. All adductor tendons attached to the pubis. In all 10 athletes, the adductor longus and rectus abdominis bilaterally contributed to the capsular tissues and disk. This was only the case for the adductor brevis in four athletes. No other tendons involved the capsular tissues., Conclusion: Cadaver and MRI findings show an intimate relationship between the adductor longus; rectus abdominis; and symphyseal cartilage, disk, and capsular tissues.

Bihormonal or plurihormonal pituitary tumors produce two or more hormones different in chemical composition, immunoreactivity, and clinical significance. Immunohistochemical and electron microscopic investigations and more recently molecular-genetic studies have provided conclusive evidence of the production of multiple hormones by pituitary adenomas. Most frequently, they produce GH, PRL, TSH, and/or alpha-subunit of the glycoprotein hormones. Other uncommon combinations may also be apparent. We report the case of a 40-yr-old acromegalic man with a pituitary macroadenoma. The pituitary tumor was removed by transsphenoidal surgery. Histological, immunohistochemical, electron microscopic, and immunoelectron microscopic examinations revealed that the tumor contains multiple hormones (GH, LH, and alpha subunit) and transcription factors. The application of different reagents yielded different patterns of positivity indicating that the validity of some common immunohistochemical reagents must be re-evaluated.