Clinicopathologic Analysis of Pituitary Adenoma: A Single Institute Experience

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke''s cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

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Cynomorium songaricum extract enhances novel object recognition, cell proliferation and neuroblast differentiation in the mice via improving hippocampal environment

Background

Increasing numbers of reports show the beneficial effects of listening to Mozart music in decreasing epileptiform discharges as well as seizure frequency in epileptic children. There has been no effective method to reduce seizure recurrence after the first unprovoked seizure until now. In this study, we investigated the effect of listening to Mozart K.448 in reducing the seizure recurrence rate in children with first unprovoked seizures.

Methods

Forty-eight children who experienced their first unprovoked seizure with epileptiform discharges were included in the study. They were randomly placed into treatment (n?=?24) and control (n?=?24) groups. Children in the treatment group listened to Mozart K.448 daily before bedtime for at least six months. Two patients in the treatment group were excluded from analysis due to discontinuation intervention. Finally, forty-six patients were analyzed. Most of these patients (89.1%) were idiopathic in etiology. Seizure recurrence rates and reduction of epileptiform discharges were compared.

Results

The average follow-up durations in the treatment and control groups were 18.6?±?6.6 and 20.1?±?5.1 months, respectively. The seizure recurrence rate was estimated to be significantly lower in the treatment group than the control group over 24 months (37.2% vs. 76.8%, p?=?0.0109). Significant decreases in epileptiform discharges were also observed after 1, 2, and 6 months of listening to Mozart K.448 when compared with EEGs before listening to music. There were no significant differences in gender, mentality, seizure type, and etiology between the recurrence and non-recurrence groups.

Conclusions

Although the case number was limited and control music was not performed in this study, the study revealed that listening to Mozart K.448 reduced the seizure recurrence rate and epileptiform discharges in children with first unprovoked seizures, especially of idiopathic etiology. We believe that Mozart K.448 could be a promising alternative treatment in patients with first unprovoked seizures and abnormal EEGs. Further large-scaled study should be conducted to confirm the effect.

Trial registration

NCT01892605, date: June-19-2013     

A wireless power transmission system for implantable devices in freely moving rodents

Reliable wireless power delivery for implantable devices in animals is highly desired for safe and effective experimental use. Batteries require frequent replacement; wired connections are inconvenient and unsafe, and short-distance inductive coupling requires the attachment of an exterior transmitter to the animal’s body. In this article, we propose a solution by which animals with implantable devices can move freely without attachments. Power is transmitted using coils attached to the animal’s cage and is received by a receiver coil implanted in the animal. For a three-dimensionally uniform delivery of power, we designed a columnar dual-transmitter coil configuration. A resonator-based inductive link was adopted for efficient long-range power delivery, and we used a novel biocompatible liquid crystal polymer substrate as the implantable receiver device. Using this wireless power delivery system, we obtain an average power transfer efficiency of 15.2 % (minimum efficiency of 10 % and a standard deviation of 2.6) within a cage of 15 × 20 × 15 cm³.     

Effects of strobe light stimulation on postnatal developing rat retina

The nature and intensity of visual stimuli have changed in recent years because of television and other dynamic light sources. Although light stimuli accompanied by contrast and strength changes are thought to have an influence on visual system development, little information is available on the effects of dynamic light stimuli such as a strobe light on visual system development. Thus, this study was designed to evaluate changes caused by dynamic light stimuli during retinal development. This study used 80 Sprague-Dawley rats. From eye opening (postnatal day 14), half of the rats were maintained on a daily 12-h light/dark cycle (control group) and the remaining animals were raised under a 12-h strobe light (2 Hz)/dark cycle (strobe light-reared group). Morphological analyses and electroretinogram (ERG) were performed at postnatal weeks 3, 4, 6, 8, and 10. Among retinal neurons, tyrosine hydroxylase-immunoreactive (TH-IR, dopaminergic amacrine cells) cells showed marked plastic changes, such as variations in numbers and soma sizes. In whole-mount preparations at 6, 8, and 10 weeks, type I TH-IR cells showed a decreased number and larger somata, while type II TH-IR cells showed an increased number in strobe-reared animals. Functional assessment by scotopic ERG showed that a-wave and b-wave amplitudes increased at 6 and 8 weeks in strobe-reared animals. These results show that exposure to a strobe light during development causes changes in TH-IR cell number and morphology, leading to a disturbance in normal visual functions.     

Glioma grading using apparent diffusion coefficient map: application of histogram analysis based on automatic segmentation

The accurate diagnosis of glioma subtypes is critical for appropriate treatment, but conventional histopathologic diagnosis often exhibits significant intra‐observer variability and sampling error. The aim of this study was to investigate whether histogram analysis using an automatically segmented region of interest (ROI), excluding cystic or necrotic portions, could improve the differentiation between low‐grade and high‐grade gliomas. Thirty‐two patients (nine low‐grade and 23 high‐grade gliomas) were included in this retrospective investigation. The outer boundaries of the entire tumors were manually drawn in each section of the contrast‐enhanced T₁‐weighted MR images. We excluded cystic or necrotic portions from the entire tumor volume. The histogram analyses were performed within the ROI on normalized apparent diffusion coefficient (ADC) maps. To evaluate the contribution of the proposed method to glioma grading, we compared the area under the receiver operating characteristic (ROC) curves. We found that an ROI excluding cystic or necrotic portions was more useful for glioma grading than was an entire tumor ROI. In the case of the fifth percentile values of the normalized ADC histogram, the area under the ROC curve for the tumor ROIs excluding cystic or necrotic portions was significantly higher than that for the entire tumor ROIs (p < 0.005). The automatic segmentation of a cystic or necrotic area probably improves the ability to differentiate between high‐ and low‐grade gliomas on an ADC map. Copyright © 2014 John Wiley & Sons, Ltd.     

The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers

Early gastric cancers (EGCs) precede advanced gastric cancers (AGCs), with a favourable prognosis compared to AGC. To understand the progression mechanism of EGC to AGC, it is required to disclose EGC and AGC genomes in mutational and evolutionary perspectives. We performed whole‐exome sequencing and copy number profiling of nine microsatellite (MS)‐unstable (MSI‐H) (five EGCs and four AGCs) and eight MS‐stable (MSS) gastric cancers (four EGCs and four AGCs). In the cancers, we observed well‐known driver mutations (TP53, APC, PIK3CA, ARID1A, and KRAS) that were enriched in cancer‐related pathways, including chromatin remodelling and tyrosine kinase activity. The MSI‐H genomes harboured ten times more mutations, but were largely depleted of copy number alterations (CNAs) compared to the MSS cancers. Interestingly, EGC genomes showed a comparable level of mutations to AGC in terms of the number, sequence composition, and functional consequences (potential driver mutations and affected pathways) of mutations. Furthermore, the CNAs between EGC and AGC genomes were not significantly different in either MSI‐H and MSS. Evolutionary analyses using somatic mutations and MSI as molecular clocks further identified that EGC genomes were as old as AGC genomes in both MSS and MSI‐H cancers. Our results suggest that the genetic makeup for gastric cancer may already be achieved in EGC genomes and that the time required for transition to AGC may be relatively short. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful in the clinical settings for the molecular diagnosis and therapeutics of gastric cancer patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

High‐risk human papillomavirus load and biomarkers in cervical intraepithelial neoplasia and cancer

The purpose of this study was to examine the implication of high‐risk human papillomavirus (HPV) load in cervical intraepithelial neoplasia (CIN) and cancer, and to detect biomarkers in cervical disease. We conducted high‐risk HPV DNA load and cervical cytology tests in 343 women, cervical tissue biopsy in 143 women, and immunohistochemistry for p16^INK4A, cyclin D1, p53, cyclooxygenase‐2, Ki‐67, GLUT1, hPygopus2, and beta‐catenin. As a result, HPV load [relative light units (RLU) value] was correlated with the histological severity of cervical disease (p < 0.05). In the ‘atypical squamous cells of undetermined significance’ cytology group, 2.385 of HPV load seemed to be the cut‐off value at which ‘benign’ or CIN I can be differentiated from ‘CIN II or more severe’ (AUC = 0.712), but not statistically significant. The relative risk (odds ratio) of p16^INK4A and GLUT1 overexpression increased gradually according to the histological severity of cervical disease. The p16^INK4A showed statistically significant odds ratios in CIN II, CIN III, and cancer; GLUT1, in CIN II and CIN III; hPygopus2, in CIN III; and beta‐catenin, in CIN III and cancer. Conclusively, HPV load, p16^INK4A, and GLUT1 can be instrumental in predicting the severity of HPV‐related cervical disease. The beta‐catenin/hPygopus2 signaling may be involved in proceeding to CIN III.