Boram Lee

Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma

The success of crizotinib in ALK-positive patients has elicited efforts to find new oncogenic fusions in lung cancer. These efforts have led to the discovery of novel oncogenic fusion genes such as ROS1 and RET. However, the molecular and clinicopathologic characteristics associated with RET or ROS1 fusion, compared with ALK fusion-positive lung cancer, remain unclear. We accordingly analyzed the clinicopathologic characteristics of RET- and ROS1-fusion-positive lung adenocarcinomas. We further performed immunohistochemistry and fluorescence in situ hybridization analysis (FISH) in 15 cases of RET and 9 cases of ROS1 fusion tumors by identified NanoString’s nCounter screening. RET fusion-positive patients were younger in age, never-smokers, and in early T stage; ROS1 fusion-positive patients had a higher number of never-smokers compared with patients with quintuple-negative (EGFR−/KRAS−/ALK−/ROS1−/RET−) lung adenocarcinoma. Histologically, RET and ROS1 fusion tumors share the solid signet-ring cell and mucinous cribriform pattern, as previously mentioned in the histology of ALK fusion tumors. Therefore, it can be presumed that fusion gene-associated lung adenocarcinomas share similar histologic features. In immunohistochemistry, the majority of 15 RET and 9 ROS1 fusion-positive cases showed positivity of more than moderate intensity and cytoplasmic staining for RET and ROS1 proteins, respectively. In FISH, the majority of RET and ROS1 rearrangement showed two signal patterns such as one fusion signal and two separated green and orange signals (1F1G1O) and an isolated 3′ green signal pattern (1F1G). Our study has provided not only characteristics of fusion gene-associated histologic features but also a proposal for a future screening strategy that will enable clinicians to select cases needed to be checked for ROS1 and RET rearrangements based on clinicohistologic features.

Comparison of operator radiation exposure between C-arm and O-arm fluoroscopy for orthopaedic surgery

The O-arm system has recently been introduced and has the capability of combined two-dimensional (2-D) fluoroscopy imaging and three-dimensional computed tomography imaging. In this study, an orthopaedic surgical procedure using C-arm and O-arm systems in their 2-D fluoroscopy modes was simulated and the radiation doses to susceptible organs to which operators can be exposed were investigated. The experiments were performed in four configurations of the location of the X-ray source and detector. Shielding effects on the thyroid surface and the direct exposure delivered to the surgeons hands were also compared. The results obtained show that the O-arm delivered higher doses to the sensitive organs of the operator in all configurations. The thyroid shield cut-off 89 % of the dose in the posteroanterior configuration of both imaging systems. Thus, the operators need to pay more attention to managing radiation exposure, especially when using the O-arm system.

Pyloric Gland Adenoma in Lynch Syndrome

The prevalence of gastric cancer associated with Lynch syndrome (LS) is highly variable, and the underlying histologic pathway or molecular mechanisms remain unclear. From 1995 to 2012, 15 patients had been treated for both gastric and colonic adenocarcinomas and diagnosed as LS. In all cases, pathologic review, immunohistochemical analysis for mismatch-repair proteins, and microsatellite instability (MSI) tests were performed. To confirm LS, germline mutation tests and multiplex ligation-dependent probe amplification were performed. All gastric and colonic carcinomas were MSI-high and lost expressions of MLH1/PMS2 in 11 (73%) cases and MSH2/MSH6 in 4 (27%) cases. Remarkably, in a patient with LS and germline mutation of MLH1 gene, pyloric gland adenoma (PGA) transformed to adenocarcinoma during follow-up. In 2 additional cases, PGA was found adjacent to advanced gastric cancers. All PGAs in LS patients were MSI-high and lost expression of mismatch-repair proteins (MLH1/PMS2 in 2 cases and MSH2/MSH6 in 1 case), whereas none of the 14 sporadic PGAs was MSI-high or had lost expression of mismatch-repair proteins. On the basis of these observations, although very rare, we suggest the possibility that PGA may be a precursor lesion to gastric adenocarcinoma in LS and that the mismatch-repair deficient pathway of carcinogenesis is involved early in the gastric carcinogenesis pathway.

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center

Purpose The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. Materials and Methods The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. Results The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. Conclusion The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Clinicopathologic characteristics of EGFR , KRAS , and ALK alterations in 6,595 lung cancers

Background EGFR, KRAS, and ALK alterations are major genetic changes found in non-small cell lung cancers (NSCLCs). Testing advanced lung adenocarcinoma tumors for these three genes is now standard care. The purpose of this study was to investigate the clinicopathologic expression pattern of these three genes in East Asian NSCLC patients. Patients and methods We conducted a retrospective study of all patients tested for mutations of these three genes at a single institute in Korea between 2006 and 2014. Study data were extracted from electronic medical records. Univariate and multivariate logistic regression analyses were used to measure associations between clinicopathologic features and alterations of EGFR, KRAS, and ALK. Results We detected 12 EGFR-mutated tumors with additional mutations in KRAS (N=6, 0.1%) or ALK (N=6, 0.1%). General clinicopathologic characteristics of tumors with EGFR, KRAS, or ALK mutations were similar to previous reports. Patients having EGFR L858R point mutations were older than patients having EGFR exon 19 deletions. EGFR G719X point mutations were more common in men and smokers than exon 19 deletions or L858R point mutations. Tumors having KRAS G12C mutations were less often of mucinous type than those with G12D or G12V, mutations. Conclusions This is the largest three gene molecular epidemiology study in East Asian NSCLC patients. Each genetic alteration was associated with distinct clinicopathologic characteristics. Furthermore, different age and sex are associated with different subtypes of EGFR and KRAS mutations.

Characteristics of Cognitive Impairment in Patients With Post-stroke Aphasia

Objective To analyze cognitive functions of post-stroke aphasia patients compared to patients having right hemispheric stroke and left hemispheric lesions without aphasia, and to look for a relationship between cognitive deficits and aphasia severity. Methods Thirty-six patients with right hemispheric stroke (group 1), 32 with left hemispheric lesion without aphasia (group 2), and 26 left hemispheric stroke patients with aphasia (group 3) completed a set of tests in the computerized neurocognitive function batteries for attention, executive function and intelligence and Korean version of Western Aphasia Battery. Data analyses explored cognitive characteristics among the three groups and the correlation between cognitive deficits and aphasia severity. Results Right hemispheric and left hemispheric stroke patients without aphasia showed similar findings except for digit span forward test. Cognitive tests for working memory and sustained attention were significantly impaired in the aphasic patients, but intelligence was shown to be similar in the three groups. Significant correlation between cognitive deficit and aphasia severity was only shown in some attention tests. Conclusion Cognitive deficits may be accompanied with post-stroke aphasia and there are possible associations between language and cognitive measures. Therefore, detection and treatment towards coexisting cognitive impairment may be necessary for efficient aphasia treatment.

Dose area product measurement for diagnostic reference levels and analysis of patient dose in dental radiography

In this study, diagnostic reference levels (DRLs) were suggested and patient doses were analysed through the dose-area product value in dental radiography. In intraoral radiography, at three sites, i.e. molar, premolar and incisor on the maxilla and acquired third quartile values: 55.5, 46 and 36.5 mGy cm(2), respectively, were measured. In panoramic, cephalometric and cone beam computed tomography, the values were 120.3, 146 and 3203 mGy cm(2) (16 × 18 cm), respectively. It has been shown that, in intraoral radiography, the patient dose changes proportionally to the value of mA s, but the change in extraoral radiography in response to mA s could not be confirmed. The authors could confirm, however, the difference in dose according to the manufacturer in all dental radiography examinations, except for panoramic radiography. Depending on the size of hospital, there were some differences in patient dose in intraoral radiography, but no difference in patient dose in extraoral radiography.

Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases

Background: Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy. Methods: In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features. Results: All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had KRAS mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation. Conclusions: EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

Dose evaluation of selective collimation effect in cephalography by measurement and Monte Carlo simulation.

Recently, simulations based on the Monte Carlo code have been increasingly applied for physics phenomena, patient dose and quality assurance of radiation systems. The objective of this study was to use Monte Carlo simulation and measurement to verify dose and dose reduction in cephalography. The collimator was constructed with 3-mm thick lead plate, and attached to the tube head to remove regions of disinterest in the radiation field. A digital phantom patient was constructed to evaluate patient dose. In addition, detectors of pixel size 1×1 cm² and 0.1×0.1 cm² were constructed to check collimator location. The effective dose according to International Commission on Radiological Protection 103 was calculated with and without collimation. The effective doses for simulation with and without collimation were 5.09 and 11.32 µSv, respectively. The results of the calculated effective dose show 61.7 % reduction of field area and 55 % of effective dose. The Monte Carlo simulation is a good evaluation tool for patient dose.

Dose reduction and image quality assessment in MDCT using AEC (D-DOM & Z-DOM) and in-plane bismuth shielding

Since computed tomography (CT) was introduced about 40 y ago, its use has continuously grown, resulting in the increase of the CT dose. Therefore, an awareness of the CT dose and its potential complications has led to the development of several dose-reduction strategies. One of the strategies is automatic exposure control (AEC), which modulates radiation intensity depending on the patient size, z-axis thickness (Z-DOM) or angular thickness (D-DOM). Another dose-reduction method is the in-plane bismuth shield which attenuates radiation to reduce the CT doses of the tissues underneath the shield. We evaluated and compared the dose reduction and image quality of CT for various dose-reduction techniques. The result showed that both AEC and the in-plane shield reduced the CT dose effectively and the combined method of AEC and in-plane shielding reduced the CT dose more than the single use of AEC or in-plane shields. The dose reduction using Z-DOM was normally higher than that using D-DOM. The image quality of CT dramatically degraded when the in-plane shield was directly attached to the phantom without using AEC. In order to effectively reduce CT dose without the significant degradation of the image quality, the in-plane shield should be placed 1 cm apart from the patient with applying AEC control.