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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.

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).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.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.With further refinement and validation in prospective multicentre studies, MRI-based linear measurements can help predict response assessment in SBRT-treated spinal metastases.

Introduction: According to WHO, 190 million reproductive-aged women are affected by endometriosis. Using self-care interventions has a significant impact on managing endometriosis-related pain. Despite the enormous potential of different endometriosis applications, the medical professionals’ role has been neglected in the process of app development. This study aimed to extract the requirements for developing a mobile-based app for self-care of endometriosis patients through an overview of the literature, and validate them according to the expert gynecologists’ point of view.Materials and Methods: This cross-sectional descriptive study was carried out in two steps. First, endometriosis-related articles were reviewed. Second, a researcher-made questionnaire (Cronbach’s alpha = 0.98) was designed to validate the identified information elements. Elements that obtained at least an average score of 3.2 (60%) out of 5-point Likert scale, were considered practicable elements for designing the app.Results: Based on the literature review, 36 studies were retrieved and 126 data elements were extracted. The elements were classified into six categories including electronic health record, educational materials, follow-up, pain management, nutritional diet, and lifestyle. All data elements except “using traditional opioids/drugs” were verified.Conclusion: In this study, a minimum data set was achieved for designing an endometriosis mobile app. Due to the lack of international standards for designing health apps, the results of this research can be beneficial for the design and development of any other apps. Investment in this study would improve the quality of care thereby reducing the burden and cost of endometriosis.

There is a lack of research on the analysis of per-user traffic in cellular networks, for deriving and following traffic-aware network management. \textcolor{black}{In fact, the legacy design approach, in which resource provisioning and operation control are performed based on the cell-aggregated traffic scenarios, are not so energy- and cost-efficient and need to be substituted with user-centric predictive analysis of mobile network traffic and proactive network resource management.} Here, we shed light on this problem by designing traffic prediction tools that utilize standard machine learning (ML) tools, including long short-term memory (LSTM) and autoregressive integrated moving average (ARIMA) on top of per-user data. We present an expansive empirical evaluation of the designed solutions over a real network traffic dataset. Within this analysis, the impact of different parameters, such as the time granularity, the length of future predictions, and feature selection are investigated. As a potential application of these solutions, we present an ML-powered Discontinuous reception (DRX) scheme for energy saving. Towards this end, we leverage the derived ML models for dynamic DRX parameter adaptation to user traffic. The performance evaluation results demonstrate the superiority of LSTM over ARIMA in general, especially when the length of the training time series is high enough, and it is augmented by a \textit{wisely}-selected set of features. Furthermore, the results show that adaptation of DRX parameters by online prediction of future traffic provides much more energy-saving at low latency cost in comparison with the legacy cell-wide DRX parameter adaptation., IEEE Transactions on Green Communications and Networking, 2021. arXiv admin note: text overlap with arXiv:1906.00939

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.

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.

Aims The rising prevalence of metabolic syndrome has made it a major health concern. Chronic occupational exposure to organic solvents affects different systems of the body. This study aimed to investigate the association between exposure to organic solvents and the prevalence of metabolic syndrome in petroleum refinery workers. Method This study was conducted in 2019–2020 on workers employed in an Iranian petroleum refinery. The demographic and occupational information on the participants was obtained using the interview method. Their height, weight, and blood pressure were measured by the occupational health team, and fasting blood samples were taken from them to measure the paraclinical parameters. Results In this study, 1009 petroleum refinery workers were analyzed. The prevalence of metabolic syndrome in workers was 20.1% and it was about two times higher in exposed workers (CI 95%: 1.61–3.35) compared to non-exposed ones. Factors associated with the prevalence of metabolic syndrome include age, higher BMI, exercise, and longer exposure to organic solvents. Conclusion Findings of this study suggested that exposure to organic solvents is associated with increased prevalence of metabolic syndrome (the highest association was observed with elevated serum triglycerides). Besides, longer exposure to organic solvents increased the risk of developing metabolic syndrome.

Non-neoplastic brainstem (BS) lesions span a wide range of pathologies, including abscesses, encephalitis, demyelinating disorders, paraneoplastic and connective tissue diseases (CTDs), and vasculitis. In many cases, the underlying etiology is readily apparent, and a specific treatment can be initiated at the time of presentation. This concerns, for example, patients with known multiple sclerosis who develop symptoms or signs of BS dysfunction. When this is not the case, the initial diagnostic approach is dependent on the clinical setting and paraclinical findings. When dealing with space-occupying lesions, the initial focus is to differentiate BS tumors from abscesses or pseudo-tumoral inflammatory lesions. Early distinction between neoplastic and non-neoplastic lesions will help avoid unnecessary surgery and its potential complications. With encephalitic lesions, the focus shifts towards excluding a life-threatening condition such as infectious BS encephalitis. Establishing an early preliminary diagnosis in this setting is essential in order to choose the most appropriate empiric treatment. Whatever the scenario is, in depth knowledge of non-neoplastic disorders of the brainstem and their epidemiological, clinical, biological and imaging features is essential to guide the diagnostic approach. This chapter will address the various infectious and inflammatory disorders of the brainstem, with a particular emphasis on their clinical presentation, key radiological and laboratory findings, and general principles of management.

Mediastinal lymphangiomas are rare benign congenital malformations, but complications can occur, including infection, cystic hemorrhage, superior vena cava syndrome, airway compromise, and chylothorax. Radiologically, lymphangiomas are well-defined masses, with low attenuation ranging from simple to complex fluid and fat. They often encase adjacent mediastinal structures. We present a case of mediastinal lymphangioma in a young female, who presented with recurrent complex pleural effusions, initially thought to represent an empyema and/or necrotic mass. Despite surgical chest tube and interventional radiology drainage, fluid reaccumulated. Upon further review, the interventional and thoracic radiologist concurred that the complex collection was in fact predominantly extra pleural in location. The patient underwent partial resection after it was discovered intraoperatively that the extra pleural cystic mass was contiguous with and extended deeply into the mediastinum. Histopathology confirmed the diagnosis of lymphangioma.

To evaluate uterine scar features after laparoscopic myomectomy (LM) compared with myomectomy performed by laparoscopy initially and then completed with minilaparotomy (LAM).Prospective cohort study.An academic center for advanced endoscopic gynecologic surgery.Sixty-nine symptomatic women who underwent myomectomy between July and December 2018.Patients underwent LM or LAM and 3-month follow-up ultrasonography.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.There were no differences in myometrial scar features after LM compared with after LAM, implying effective suturing via both approaches.

BACKGROUND AND PURPOSE: Recently published North American Imaging in Multiple Sclerosis guidelines call for derivation of a specific radiologic definition of MS WM lesions and mimics. The purpose of this study was to use SWI and magnetization-prepared FLAIR images for sensitive differentiation of MS from benign WM lesions using the morphologic characteristics of WM lesions. MATERIALS AND METHODS: Seventeen patients with relapsing-remitting MS and 18 healthy control subjects were enrolled retrospectively. For each subject, FLAIR and multiecho gradient-echo images were acquired using 7T MR imaging. Optimized postprocessing was used to generate single-slice SWI of cerebral veins. SWI/FLAIR images were registered, and 3 trained readers performed lesion assessment. Morphology, location of lesions, and the time required for assessment were recorded. Analyses were performed on 3 different pools: 1) lesions of >3 mm, 2) nonconfluent lesions of >3 mm, and 3) nonconfluent lesions of >3 mm with no or a single central vein. RESULTS: The SWI/FLAIR acquisition and processing protocol enabled effective assessment of central veins and hypointense rims in WM lesions. Assessment of nonconfluent lesions with ≥1 central vein enabled the most specific and sensitive differentiation of patients with MS from controls. A threshold of 67% perivenous WM lesions separated patients with MS from controls with a sensitivity of 94% and specificity of 100%. Lesion assessment took an average of 12 minutes 10 seconds and 4 minutes 33 seconds for patients with MS and control subjects, respectively. CONCLUSIONS: Nonconfluent lesions of >3 mm with ≥1 central vein were the most sensitive and specific differentiators between patients with MS and control subjects.

Patients with intractable temporal lobe epilepsy (TLE) undergo surgical resection of the anterior temporal lobe. Preoperative assessment of TLE patients involves a multidisciplinary assessment and may involve the use of invasive electroencephalogram (EEG) recording for lateralization of seizure focus in ambiguous cases. Understanding the white matter fibre tracts affected in TLE may assist in preoperative lateralization and planning. We studied pre- and postoperative white matter fibre tract changes in six patients with TLE who underwent surgical resection. Our results indicate that changes in the corpus callosum are highly specific, with the ability to lateralize the epileptogenic side in 100% of our patients (six of six). Contralateral changes were found in all patients with variable involvement of white matter tracts. Postoperatively, most patients (five of six) exhibited further changes to the tracts on the ipsilateral side, with three patients showing contralateral abnormalities. We provide a detailed assessment of pre- and postoperative white matter fibre tracts in patients with TLE and confirm that abnormalities in the ipsilateral corpus callosum may aid in preoperative lateralization and obviate the need for invasive EEG monitoring.

In this paper, the performance of non-orthogonal multiple access (NOMA) technique for communication based on finite blocklength (FBL) codes is studied. NOMA, by co-serving multi users has great potential for achieving low-latency and better spectral efficiency rather than conventional orthogonal multiple access (OMA) techniques. Our goal is to have optimal power allocation to attain fair throughput in a DL-NOMA scenario. The optimization problem is formulated and an analytical approach using optimal solution search algorithm is introduced. Performance of the proposed NOMA system is compared with an OMA scheme which is benefiting from optimal power and blocklength allocation as well. Numerical results show that NOMA significantly improves the users’ fair throughput in FBL regime.

Introduction Assessment of patients for temporal lobe epilepsy (TLE) surgery requires multimodality input, including anatomical MRI, neuropsychological evaluation, functional neuroimaging, scalp electroencephalography (EEG) and invasive EEG recordings to ensure optimal surgical planning. Often EEG demonstrates abnormal foci that are not detected on 1.5T MRI. Ultra high-field MRI at 7T provides much improved resolution of the brain. We investigated the utility of 7T MRI to detect potential anatomical abnormalities associated with functional abnormalities detected by scalp and/or invasive EEG recordings. Methods Ultra-high-field data were acquired on a 7T neuroimaging optimized MRI scanner for 13 patients with a history of drug resistant TLE during evaluation for epilepsy surgery. All patients had video-EEG telemetry recordings in our Epilepsy Monitoring Unit. Additionally, 9 patients underwent invasive EEG recordings including subdural and/or depth electrodes. Qualitative evaluation of 7T imaging for scan quality and presence of focal abnormalities detected on EEG was performed. The 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 the clinically suspected TLE in 8 out of 13 cases. Among these, 3 exhibited supportive abnormal 7T MRI abnormalities not detected by the clinical 1.5T MRI. Eleven out of 13 cases had scalp and/or invasive electrode EEG findings with no anatomic correlates on 1.5T or 7T MRI. Findings included IEDs localizing to the contralateral temporal lobe in 6 patients, frontal lobes in 3 patients, and parieto-occipital lobes in 2 patients. Qualitative assessment of 7T images did not reveal any focal anatomical abnormalities to account for the EEG findings in these patients. Conclusion To our knowledge, this is the first study to investigate the utility of 7T MRI in combination with scalp and invasive. Qualitative ultra high-field 7T MRI findings show a moderate concordance with clinical data. However, 7T MRI did not reveal focal anatomical findings to account for all the abnormalities detected by the scalp EEG recordings in patients with temporal lobe epilepsy.

Objectives Ultra high field MRI at 7 T 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 7 T MRI in temporal lobe epilepsy patients with a focus on comparison to histopathology. Methods 7 T 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 1.5 T scans was also performed. Results On the 7 T MRI findings, eight out of 13 cases demonstrated concordance with the clinically suspected TLE. Among these concordant cases, three exhibited supportive abnormal 7 T MRI findings which were not detected by the clinical 1.5 T MRI. Of the ten cases that progressed to epilepsy surgery, seven showed concordance between 7 T 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 1.5 T MRI. Conclusions There was moderate and high concordance between the 7 T imaging findings with the clinical data and histopathology respectively.

ObjectiveTo analyze MRI characteristics of lumbar facet synovial cysts and distinguish those requiring subsequent surgical management for recurrence, after percutaneous synovial cyst rupture.Methods and materialsRetrospective 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.Results24 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.ConclusionsA 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.

Dilation of the cerebral ventricles is a common condition in preterm neonates with intraventricular hemorrhage (IVH). This post hemorrhagic ventricle dilation (PHVD) can lead to lifelong neurological impairment through ischemic injury due to increased intracranial pressure and without treatment, can lead to death. Clinically, 2D ultrasound (US) through the fontanelles ('soft spots') of the patients are serially acquired to monitor the progression of the ventricle dilation. These images are used to determine when interventional therapies such as needle aspiration of the built up cerebrospinal fluid (CSF) ('ventricle tap', VT) might be indicated for a patient; however, quantitative measurements of the growth of the ventricles are often not performed. There is no consensus on when a neonate with PHVD should have an intervention and often interventions are performed after the potential for brain damage is quite high. Previously we have developed and validated a 3D US system to monitor the progression of ventricle volumes (VV) in IVH patients. We will describe the potential utility of quantitative 2D and 3D US to monitor and manage PHVD in neonates. Specifically, we will look to determine image-based measurement thresholds for patients who will require VT in comparison to patients with PHVD who resolve without intervention. Additionally, since many patients who have an initial VT will require subsequent interventions, we look at the potential for US to determine which PHVD patients will require additional VT after the initial one has been performed.

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 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.

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 b-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. Endocrine-Related Cancer (2008) 15 721–743