Comparison of Genetic Profiles and Prognosis of High-Grade Gliomas Using Quantitative and Qualitative MRI Features: A Focus on G3 Gliomas

Objective@#To evaluate the association of MRI features with the major genomic profiles and prognosis of World Health Organization grade III (G3) gliomas compared with those of glioblastomas (GBMs). @*Materials and Methods@#We enrolled 76 G3 glioma and 155 GBM patients with pathologically confirmed disease who had pretreatment brain MRI and major genetic information of tumors. Qualitative and quantitative imaging features, including volumetrics and histogram parameters, such as normalized cerebral blood volume (nCBV), cerebral blood flow (nCBF), and apparent diffusion coefficient (nADC) were evaluated. The G3 gliomas were divided into three groups for the analysis: with this isocitrate dehydrogenase (IDH)-mutation, IDH mutation and a chromosome arm 1p/19q-codeleted (IDHmut1p/19qdel), IDH mutation, 1p/19q-nondeleted (IDHmut1p/19qnondel), and IDH wildtype (IDHwt). A prediction model for the genetic profiles of G3 gliomas was developed and validated on a separate cohort. Both the quantitative and qualitative imaging parameters and progression-free survival (PFS) of G3 gliomas were compared and survival analysis was performed. Moreover, the imaging parameters and PFS between IDHwt G3 gliomas and GBMs were compared. @*Results@#IDHmut G3 gliomas showed a larger volume (p = 0.017), lower nCBF (p = 0.048), and higher nADC (p = 0.007) than IDHwt. Between the IDHmut tumors, IDHmut1p/19qdel G3 gliomas had higher nCBV (p = 0.024) and lower nADC (p = 0.002) than IDHmut1p/19qnondel G3 gliomas. Moreover, IDHmut1p/19qdel tumors had the best prognosis and IDHwt tumors had the worst prognosis among G3 gliomas (p < 0.001). PFS was significantly associated with the 95th percentile values of nCBV and nCBF in G3 gliomas. There was no significant difference in neither PFS nor imaging features between IDHwt G3 gliomas and IDHwt GBMs. @*Conclusion@#We found significant differences in MRI features, including volumetrics, CBV, and ADC, in G3 gliomas, according to IDH mutation and 1p/19q codeletion status, which can be utilized for the prediction of genomic profiles and the prognosis of G3 glioma patients. The MRI signatures and prognosis of IDHwt G3 gliomas tend to follow those of IDHwt GBMs.

Prognostic Value of Dynamic Contrast-Enhanced MRI-Derived Pharmacokinetic Variables in Glioblastoma Patients: Analysis of Contrast-Enhancing Lesions and Non-Enhancing T2 High-Signal Intensity Lesions

Objective@#To evaluate pharmacokinetic variables from contrast-enhancing lesions (CELs) and non-enhancing T2 high signal intensity lesions (NE-T2HSILs) on dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in glioblastoma (GBM) patients. @*Materials and Methods@#Sixty-four GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. We analyzed the pharmacokinetic variables of the volume transfer constant (Ktrans) and volume fraction of extravascular extracellular space within the CEL and NE-T2HSIL of the entire tumor. Univariate and multivariate Cox regression analyses were performed using preoperative clinical characteristics, pharmacokinetic variables of DCE MR imaging, and postoperative molecular biomarkers to predict PFS. @*Results@#The increased mean Ktrans of the CEL, increased 95th percentile Ktrans of the CELs, and absence of methylated O6- methylguanine-DNA methyltransferase promoter were relevant adverse variables for PFS in the univariate analysis (p = 0.041, p = 0.032, and p = 0.083, respectively). The Kaplan-Meier survival curves demonstrated that PFS was significantly shorter in patients with a mean Ktrans of the CEL > 0.068 and 95th percentile Ktrans of the CEL > 0.223 (log-rank p = 0.038 and p = 0.041, respectively). However, only mean Ktrans of the CEL was significantly associated with PFS (p = 0.024; hazard ratio, 553.08; 95% confidence interval, 2.27–134756.74) in the multivariate Cox proportional hazard analysis. None of the pharmacokinetic variables from NE-T2HSILs were significantly related to PFS. @*Conclusion@#Among the pharmacokinetic variables extracted from CELs and NE-T2HSILs on preoperative DCE MR imaging, the mean Ktrans of CELs exhibits potential as a useful imaging predictor of PFS in GBM patients.

Accurate measurements of liver stiffness using shear wave elastography in children and young adults and the role of the stability index

PURPOSE: The purpose of this study was to evaluate the usefulness of the stability index (SI) in liver stiffness measurements using shear wave elastography (SWE) in children. METHODS: A total of 29 children and young adults (mean age, 16.1 years; range, 8 to 28 years; 11 boys and 18 girls) who underwent liver stiffness measurements using SWE under free-breathing and breath-holding conditions were included in our study. Ten SWE measurements were acquired in each of four groups: free-breathing and breath-holding, and with and without using the SI. The failure rate of acquisition of SI values over 90% was calculated in each group. To evaluate variability in the SWE measurements, the standard deviation, coefficient of variation, and percentage of unreliable measurements were compared. Intraobserver agreement and the optimal minimal number of measurements were calculated using intraclass correlation coefficients. RESULTS: A failure to acquire SI values over 90% was observed in 17% of the scans in the free-breathing group and in 7% of the scans in the breath-holding group. In both groups, utilizing the SI led to a significantly lower standard deviation and coefficient of variation. When using the SI, the percentage of unreliable measurements decreased from 16.7% to 8.3% in the free-breathing group and 14.8% to 0% in the breath-holding group. With the use of the SI, intraobserver agreement increased and the optimal minimal number of repeated measurements decreased in both the free-breathing and breath-holding groups. CONCLUSION: Utilization of the SI in the measurement of liver SWE in children reduced measurement variability and increased reliability in both free-breathing and breath-holding conditions.

Non Small Cell Carcinoma Metastasis to Meningioma

"Tumor-to-tumor" metastasis is a rare event; meningioma has been reported as the most common primary intracranial tumor to harbor cancer metastases. Several hypotheses have been previously proposed to explain this occurrence, but the exact mechanism by which these metastases develop into meningiomas is not yet understood. Magnetic resonance imaging and spectroscopy have been valuable diagnostic tools, but preoperative diagnosis of metastasis to meningioma remains highly difficult. We present a case report of a metastasis of non-small cell lung cancer into an intracranial meningioma.

Application of Tyramide Signal Amplification (TSA) Both to Biochip Platform and to the Immunoelectron Microscopy to Label Proteins within the Organelle / 대한해부학회지

The tyramide signal amplification (TSA) technique, based on the ability of HRP to catalyze the deposition of tyramide onto the surrounding proteins, has been proved to detect scarce tissue antigens. In this study we applied this technique to a biochip platform and an immunocytochemistry at the electron microscopic level. First, in the optical fluorescence sensing, the signal was amplified by Dako Envision(TM) (goat anti-mouse immunoglobulins IgG conjugated to peroxidase labelled-dextran polymer) and tyramide-Cy3, which was then compared to the non-amplified control using goat antimouse IgG-Cy3 conjugate instead. The result showed that the tyramide method produced a more sensitive signal than the control method. Secondly, in the pre-embedding immunocytochemistry, we investigated to see whether it is possible to label proteins within a organelle in the cell using the TSA method. The signal was amplified by a primary antibody, a biotinylated secondary antibody, streptavidin-HRP, biotinyl-tyramide, and streptavidinnanogold followed by silver enhancement and gold toning. Then, this protocol was compared to the non-amplified or simple protocol that does not include the steps of streptavidin-HRP and biotinyl-tyramide. With the TSA protocol, the labeling for a membrane bound antigen (gp100) that is known to be exclusively localized to melanosomes in melanocyte, was tested in a melanoma cell line (G361) and found to be highly sensitive and more enhanced than with the simple protocol. Moreover, the gold particles were well localized to the subcellular structures or melanosomes both in the TSA and simple protocols, which indicates that resolution of the signals remains high. Control experiment with omission of the primary antibody demonstrated that background levels or nonspecific bindings are negligible. This result showed that the TSA method can be successfully applied to label the intra-organelle protein that is known to be labeled only in the specific fixation condition with the optimal permeability.

Survival Analysis for Patients with Hepatocellular Carcinoma according to Stage, Liver Function and Treatment Modalities / 대한간학회지

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is 3rd leading cause of cancer in Korea and the prognosis for HCC patients is poor. For assessing the present treatment outcome, this study analyzed the three-year survival rate (3-YSR) and the prognostic factors for patients with HCC in Korea. METHODS: Between November 2000 and December 2003, 905 patients with HCC who were diagnosed and treated at the National Cancer Center Korea were enrolled in this study. The clinical variables, tumor characteristics and survival periods were analyzed. RESULTS: The mean age of all patients was 56.2+/-10.3 years and 732 (80.9%) patients were male (M:F=4.2:1). 508 (56.1%) patients died and the median survival period was 15.3 months. The overall 3-YSR of the patients with modified UICC stage I, II, III, IVa and IVb were 67.4%, 65.2%, 30.7%, 9.0% and 5.0%, respectively. The modified UICC stage could not differentiate stage I from II, and stage IVa from IVb, on the 3-YSR. The 3-YSR of the Child-Pugh class A patients with modified UICC stage I or II was 85.4% by surgical resection and it was 69.6% by transcatheter chemoembolization (TACE), respectively (P= .461), and those values for patients with stage III were 49.2% and 36.8%, respectively (P=.081). As compared with systemic chemotherapy or conservative therapy, TACE increased the survival rate more for the Child-Pugh class A patients with stage IV. The independent prognostic factors were serum AFP, portal vein thrombosis, the Child-Pugh classification and the stage of HCC. CONCLUSIONS: This follow-up study will be helpful in assessing the results of treatments for HCC and it will provide data for the establishment of a more effective treatment strategy.

The Adverse Effect of Indirectly Diagnosed Portal Hypertension on the Complications and Prognosis after Hepatic Resection of Hepatocellular Carcinoma / 대한간학회지

<0.01). The cumulative 3-year recurrence-free survival rate showed no statistical difference between the two groups. However, the cumulative 3-year survival rate was significantly higher in the non-portal hypertension group (82.8% vs. 53%, respectively, P=0.014). CONCLUSION: Indirectly diagnosed portal hypertension is correlated with the development of complications and poor prognosis after the surgical resection of HCC.

Extrahepatic Metastasis of Hepatocellular Carcinoma to the Nasal Cavity Manifested as Massive Epistaxis: A Case Report / 대한간학회지

Extrahepatic metastasis of hepatocellular carcinoma (HCC) is not infrequently found during the later stage, regarding that the autopsy report described its prevalence to be up to 50%. The most frequent sites are known to be the abdominal lymph nodes, lung and bone. However, metastasis to the nasal cavity and paranasal sinuses has been seldom reported, and to out knowledge, there is no Korean report describing extrahepatic metastasis of HCC to these sites. Recently we experienced a case of extrahepatic metastasis of HCC to the nasal cavity in a 50 year-old man with massive epistaxis refractory to conservative treatment. He was found to have a mass of soft tissue attenuation occupying the right nasal cavity at CT, which was biopsy-proven as metastatic HCC. Epistaxis was successfully treated by transcatheter arterial embolization.

The Clinical Report of 1,078 Cases of Hepatocellular Carcinomas: National Cancer Center Experience / 대한간학회지

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the third leading cause of cancer and the 5 year survival rate is 9.6% in Korea. To develop a strategy for surveillance and treatments, we studied the recent clinical characteristics of HCC diagnosed at single institution in Korea, where is in an endemic area of chronic hepatitis B. METHODS: One thousand and seventy eight patients with HCC who visited the National Cancer Center between June 2001 and December 2003 were retrospectively studied. RESULTS: The male/female ratio was 4.5:1. The mean age of the patients was 56.3 years. 74.2% of patient had hepatitis B virus (HBV) infections, 8.6% had hepatitis C virus (HCV) infections, 6.9% of the patients abused alcohol and 10.3% of the patients had non-B non-C considered as the etiologic factors of their HCC. Only 10.0% of patients had a tumor sized 2 cm or less and 53.3% of patients had a large tumor over 5 cm in diameter. 33.2% of patients had a single tumor. At the time of diagnosis, the modified UICC staging was as follows: 6.5%, 20.1%, 30.9%, 25.2% and 17.3% in stages I, II, III, IVa and IVb, respectively. The initial treatment performed was transcatheter arterial chemoembolization (48.2%), radiofrequency ablation (1.5%), hepatic resection (11.2%), systemic chemotherapy (7.5%), radiotherapy (2.1%), and conservative medical treatments (29.5%). The mean number of treatments was 1.65. The response rates to the initial treatments were 27.9% (complete response), 23.6% (partial response), 7.5% (minimal response), 14.2% (stable disease), and 30.4% (progressive disease). CONCLUSIONS: HBV infection is a major etiologic factor for Korean HCC patients. Most cases are still in advanced stages and these cases responded poorly to any treatments. The national surveillance program and its guideline for HCC are expected to improve the survival of HCC patients.

A case of spontaneous rupture of hepatic angiomyolipoma / 대한내과학회지

Hepatic angiomyolipoma (AML) is a very rare neoplasm compared to that of the kidney. Few of these occurred in symptomatic patients and showed intratumoral hemorrhagic foci. The spontaneous rupture of AML is a rare complication that occurs most commonly in the kidney. Only two cases of spontaneous rupture of hepatic AML treated surgically have been published. We now report a case of a 39-year-old woman with chronic hepatitis B and spontaneous rupture of hepatic AML mimicking hepatocellular carcinoma, which was successfully treated by transcather arterial chemoembolization. To our knowledge, this is the first reported case of ruptured hepatic AML treated successfully by transarterial embolization.

A Case of Primary Leiomyosarcoma of the Inferior Vena Cava Treated by Surgical Resection and Reconstruction with Synthetic Graft Replacement / 대한소화기학회지

Leimyosarcoma of the inferior vena cava (IVC) is a rare tumor, with about 200 cases reported in the world literature. There were 5 cases reported in Korea. We report a case of primary leiomyosarcoma of the inferior vena cava in a 50 year-old woman who presented with a heterogenous enhancing mass within IVC on CT scan and MRI scan. The tumor expanded the IVC with displacement of the adjacent structures. The patient underwent ultrasound guided percutaneous biopsy which was consistent with leiomyosarcoma. The patient was treated by surgical resection and synthetic graft replacement of the inferior vena cava and postoperative external beam radiation therapy. We report the case of leiomyosarcoma of the inferior vena cava with a review of relevant literatures.

Impairment of diastolic function in newly diagnosed non-insulin-dependent diabetes mellitus / 대한내과학회지

BACKGROUND: Heart failure is one of the major cause of premature mortality and morbidity in diabetes mellitus. It has been well recognized that left ventricular diastolic dysfunction caused by autonomic neuropathy, hyperinsulinemia, hyperlipidemia might be a preceding underlying mechanism of heart failure in diabetes. Also, an impairment of diastolic function in early diabetic patients has been reported in some literature. So, we evaluated the diastolic function in newly diagnosed diabetics with echocardiography. METHODS: All patients with newly diagnosed NIDDM in Pundang Cha general hospital from December 1996 to June 1998 were enrolled (n=20). The 20 healthy volunteers comparable for age, sex, body surface area were enrolled as a control group. The echocardiography was performed in all patients before any treatment. Blood pressure, pulse rate, fasting and postprandial sugar and insulin level, serum total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol were also checked in all patients. RESULTS: There were no significant difference in blood pressure, pulse rate, total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol level between both groups. E and A ratio of mitral inflow and peak diastolic velocity of pulmonary vein flow were significantly decreased in NIDDM group compared with control group (p<0.01). But there were no significant difference in left ventricular mass index, isovolumic relaxation time, deceleration time and peak atrial reversal velocity. CONCLUSION: This study demonstrates that an impairment of left ventricular diastolic function occurs early in the NIDDM and investigation of diastolic function should be performed in the clinical evaluation of early diabetic patients.

The study on the histologic findings in the patients of chronic liver disease with normal levels of serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) over 6months / 대한내과학회지

BACKGROUND: Although abnormal serum alanine aminotranferase(ALT) and aspartate aminotransferase (AST) clearly indicates certain disease in the liver, normal reversion of serum ALT and AST during the disease process, after the histologic diagnosis of chronic hepatitis, does not ensure that the patients liver would be normal. We considered a partial remission of chronic hepatitis as the levels of serum ALT and AST were persistently normal over 6 months or more, and studied how the histologic findings in the partial-remitted patients of chronic hepatitis would change. MATERIALS: Twenty-three agreed to rebiopsy in the patients of chronic hepatitis with normal level of serum ALT and AST over 6 months. The histologic findings between the first and second liver-biopsied specimens were compared, and the classification of their morpholgy was translated with Batts and Ludwigs new scoring system of chronic hepatitis divided into grade and stage. RESULTS: The grading scores of the first and second biopsy were 2.70 +/- 0.16 and 1.48 +/- 0.14, respectively, and the grading scores of the second biopsy decreased significantly than of the first biopsy (p=0.000); 18 cases(78.1%) were improved, but none was aggravated. The staging scores of the first and second biopsy were 1.870.19 and 1.430.22, respectively, and the staging scores of the secand biapsy also decreased significantly than of the first biopsy (p=0,020); 14 cases (61.2%) were unchanged, 8 cases (34.5%) were improved, but 1 case (4.3%) was aggravated. The stage-improved cases were 7 in the patients of chronic viral hepatitis B, and 1 in the patient of chronic viral hepatitis C, and viral loads of them disappeared. Three cases (13.0%) of them changed into no fibrosis, and 2 cases of them (8.7%) with severe fibrosis improved to mild fibrosis. But, although the levels of serum ALT and AST were persistently normal over average 16 months, grading and staging scores decreased over 2 points in 21.0% and 13.0%, respectively, and the case of which both grading and staging scores improved to normal was only 4.3%. CONCLUSION: Serum ALT and AST level were well correlated with grading. However, the correlation between serum ALT and AST level and staging was poor, even though the triggering factors of chronic hepatitis had been disappeared. Then, we recommand close follow-up and treatment to lessen the fibrogenic reaction of the liver in them.

Cytologic Features of Endometral Papillary Serous Carchinoma / 대한세포병리학회지

Endometrial papillary serous carcinoma (EPSC) is a distinct variant of endometrial adenocarcinoma that histologically resembles ovarian serous papillary adenocarcinoma and has an aggressive clinical course. Usually, the tumor is diagnosed at the advanced stage. The tumor has well confused with metastatic ovarian tumor of identical histology. Diagnosis of EPSC should be considered when the cervico-vaginal smear reveals numerous papillary clusters of tumor cells with macronucleoli and psammoma bodies. Recently, we have experienced two cases of EPSC diagnosed on cervico-vaginal smears, which revealed characteristic cytologic features including numerous papillary clusters of tumor cells with macronucleoli. The cytologic diagnoses were confirmed on histologic sections.