Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial / 대한뇌졸중학회지

Background@#and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. @*Methods@#Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. @*Results@#One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. @*Conclusions@#Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

Interobserver variation in target volume for salvage radiotherapy in recurrent prostate cancer patients after radical prostatectomy using CT versus combined CT and MRI: a multicenter study (KROG 13-11)

PURPOSE: To investigate interobserver variation in target volume delineations for prostate cancer salvage radiotherapy using planning computed tomography (CT) versus combined planning CT and magnetic resonance imaging (MRI). MATERIALS AND METHODS: Ten radiation oncologists independently delineated a target volume on the planning CT scans of five cases with different pathological status after radical prostatectomy. Two weeks later, this was repeated with the addition of planning MRI. The volumes obtained with CT only and combined CT and MRI were compared, and the effect of the addition of planning MRI on interobserver variability was assessed. RESULTS: There were large differences in clinical target volume (CTV) delineated by each observer, regardless of the addition of planning MRI (9.44–139.27 cm³ in CT only and 7.77–122.83 cm³ in CT plus MRI) and no significant differences in the mean and standard deviation of CTV. However, there were decreases in mean volume and standard deviation as a result of using the planning MRI. CONCLUSION: This study showed substantial interobserver variation in target volume delineation for salvage radiotherapy. The combination of planning MRI with CT tended to decrease the target volume and the variation.

The Effect of Sleep Disordered Breathing on Olfactory Functions: Analysis by Apnea-Hypopnea Index

OBJECTIVES: One hypothesis of obstructive sleep apnea syndrome (OSAS) is that long-standing snoring vibrations and hypoxia of the nerves cause a local neuropathy in the upper airway during sleep. The aim of this study was to investigate olfactory function in subjects comprising snorers and untreated subjects with OSAS, and to correlate data with polysomnographic parameters. METHODS: Sixty-nine patients were evaluated for snoring from January 2010 to December 2013. The mild group (apneahypopnea index [AHI]<15) consisted of 19 subjects, and the moderate-severe group (AHI≥15) consisted of 50 subjects. Exclusion criteria were conductive olfactory dysfunction, previous tonsil or soft palatal surgery, central sleep apnea, and medications that are known to affect peripheral nerves. Nocturnal polysomnography and olfactory function test such as Korean version of Sniffin’s stick test I, II (KVSS I, II) were performed. RESULTS: There was a significant difference in body mass index, average oxygen saturation (SaO2), lowest SaO2, average snoring duration, and KVSS I, II between the two groups. AHI was related to odor threshold score, and average SaO2 was related to odor discrimination score. But, odor identification score showed no relation with AHI and average SaO2 except for age. Average SaO2 and AHI were closely related to the function of smell. CONCLUSION: Hypoxia and low nasal airflow caused by OSAS may have an effect on the olfactory function. On comparison between the two groups, patients with a high AHI, especially those with OSAS, had an olfactory dysfunction. Also, low average oxygen is the main risk factor in determining the olfactory function. In people with OSAS, the possibility of olfactory dysfunction should be considered and an olfactory function test should be performed.

Unexpected Bleeding Following Endoscopic Sinus Surgery Leading to the Rare Diagnosis of Acquired Haemophilia A / 대한이비인후과학회지

We report a case of acquired hemophilia A following endoscopic sinus surgery. The patient was a 64-year-old man whose preoperative activated partial thromboplastin time (aPTT) was slightly prolonged. He underwent endoscopic sinus surgery for chronic rhinosinusitis with nasal polyp. Nasal bleeding occurred spontaneously on the postoperative day 3. The aPTT was prolonged at 58.9 s, with factor VIII activity of 21% and a positive factor VIII inhibitor. Treatment with factor VIII and methylprednisolone resulted in remission within 1 month. This is the first of such case reported in Korea; the patient was treated by recombinant factor VIII replacement and steroid therapy.

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.

Operative Risk Assessment of Degenerative Spinal Disorder Comparing with Total Hip Replacement

STUDY DESIGN: Retrospective study. OBJECTIVES: To assess the operative risks and complications of posterior decompression and fusion for degenerative spine disorders, we compared single level posterior decompression and posterolateral fusion of lumbar spine with total hip arthroplasty which have been evaluated in many reports and articles on complications and operative risks. SUMMARY OF LITERATURE REVIEW: There has been no study comparing the relative risks of spinal surgery with total hip arthroplasty. MATERIALS AND METHODS: One hundred and thirty-six subjects (mean age 69.6 years) who received single level posterior decompression and posterolateral fusion for degenerative lumbar disorders from February 2000 to May 2010 were selected as group A, and 136 subjects (mean age 67.2 years) who received total hip arthroplasty during the same period were selected as group B. A comparative analysis was performed according to age, gender, pre-operative ASA status based on their underlying medical conditions, total operative time, blood loss, hospitalization period, incidence of major and minor complications and functional recovery at the time of final follow up using retrospective and statistical manners from medical records and radiologic evaluations. RESULTS: The total operative time and blood loss were longer in group A with statistical significance (P<0.01). Major complications were frequent in group B with 16 cases and in group A with 6 cases (P<0.05). There were no significant differences in the total hospitalization period, incidence of minor complications and post-operative functional recovery. CONCLUSIONS: The present study revealed no increased operative risks for surgery for degenerative lumbar disorders compared with total hip arthroplasty in similar age groups.

Development of an Offline Based Internal Organ Motion Verification System during Treatment Using Sequential Cine EPID Images / 의학물리

Verification of internal organ motion during treatment and its feedback is essential to accurate dose delivery to the moving target. We developed an offline based internal organ motion verification system (IMVS) using cine EPID images and evaluated its accuracy and availability through phantom study. For verification of organ motion using live cine EPID images, a pattern matching algorithm using an internal surrogate, which is very distinguishable and represents organ motion in the treatment field, like diaphragm, was employed in the self-developed analysis software. For the system performance test, we developed a linear motion phantom, which consists of a human body shaped phantom with a fake tumor in the lung, linear motion cart, and control software. The phantom was operated with a motion of 2 cm at 4 sec per cycle and cine EPID images were obtained at a rate of 3.3 and 6.6 frames per sec (2 MU/frame) with 1,024x768 pixel counts in a linear accelerator (10 MVX). Organ motion of the target was tracked using self-developed analysis software. Results were compared with planned data of the motion phantom and data from the video image based tracking system (RPM, Varian, USA) using an external surrogate in order to evaluate its accuracy. For quantitative analysis, we analyzed correlation between two data sets in terms of average cycle (peak to peak), amplitude, and pattern (RMS, root mean square) of motion. Averages for the cycle of motion from IMVS and RPM system were 3.98+/-0.11 (IMVS 3.3 fps), 4.005+/-0.001 (IMVS 6.6 fps), and 3.95+/-0.02 (RPM), respectively, and showed good agreement on real value (4 sec/cycle). Average of the amplitude of motion tracked by our system showed 1.85+/-0.02 cm (3.3 fps) and 1.94+/-0.02 cm (6.6 fps) as showed a slightly different value, 0.15 (7.5% error) and 0.06 (3% error) cm, respectively, compared with the actual value (2 cm), due to time resolution for image acquisition. In analysis of pattern of motion, the value of the RMS from the cine EPID image in 3.3 fps (0.1044) grew slightly compared with data from 6.6 fps (0.0480). The organ motion verification system using sequential cine EPID images with an internal surrogate showed good representation of its motion within 3% error in a preliminary phantom study. The system can be implemented for clinical purposes, which include organ motion verification during treatment, compared with 4D treatment planning data, and its feedback for accurate dose delivery to the moving target.

Clinical Usefulness of Implanted Fiducial Markers for Hypofractionated Radiotherapy of Prostate Cancer / 대한방사선종양학회지

PURPOSE: To assess the usefulness of implanted fiducial markers in the setup of hypofractionated radiotherapy for prostate cancer patients by comparing a fiducial marker matched setup with a pelvic bone match. MATERIALS AND METHODS: Four prostate cancer patients treated with definitive hypofractionated radiotherapy between September 2009 and August 2010 were enrolled in this study. Three gold fiducial markers were implanted into the prostate and through the rectum under ultrasound guidance around a week before radiotherapy. Glycerin enemas were given prior to each radiotherapy planning CT and every radiotherapy session. Hypofractionated radiotherapy was planned for a total dose of 59.5 Gy in daily 3.5 Gy with using the Novalis system. Orthogonal kV X-rays were taken before radiotherapy. Treatment positions were adjusted according to the results from the fusion of the fiducial markers on digitally reconstructed radiographs of a radiotherapy plan with those on orthogonal kV X-rays. When the difference in the coordinates from the fiducial marker fusion was less than 1 mm, the patient position was approved for radiotherapy. A virtual bone matching was carried out at the fiducial marker matched position, and then a setup difference between the fiducial marker matching and bone matching was evaluated. RESULTS: Three patients received a planned 17-fractionated radiotherapy and the rest underwent 16 fractionations. The setup error of the fiducial marker matching was 0.94+/-0.62 mm (range, 0.09 to 3.01 mm; median, 0.81 mm), and the means of the lateral, craniocaudal, and anteroposterior errors were 0.39+/-0.34 mm, 0.46+/-0.34 mm, and 0.57+/-0.59 mm, respectively. The setup error of the pelvic bony matching was 3.15+/-2.03 mm (range, 0.25 to 8.23 mm; median, 2.95 mm), and the error of craniocaudal direction (2.29+/-1.95 mm) was significantly larger than those of anteroposterior (1.73+/-1.31 mm) and lateral directions (0.45+/-0.37 mm), respectively (p<0.05). Incidences of over 3 mm and 5 mm in setup difference among the fractionations were 1.5% and 0% in the fiducial marker matching, respectively, and 49.3% and 17.9% in the pelvic bone matching, respectively. CONCLUSION: The more precise setup of hypofractionated radiotherapy for prostate cancer patients is feasible with the implanted fiducial marker matching compared with the pelvic bony matching. Therefore, a less marginal expansion of planning target volume produces less radiation exposure to adjacent normal tissues, which could ultimately make hypofractionated radiotherapy safer.

Analysis of changes in dose distribution due to respiration during IMRT

PURPOSE: Intensity modulated radiation therapy (IMRT) is a high precision therapy technique that can achieve a conformal dose distribution on a given target. However, organ motion induced by respiration can result in significant dosimetric error. Therefore, this study explores the dosimetric error that result from various patterns of respiration. MATERIALS AND METHODS: Experiments were designed to deliver a treatment plan made for a real patient to an in-house developed motion phantom. The motion pattern; the amplitude and period as well as inhale-exhale period, could be controlled by in-house developed software. Dose distribution was measured using EDR2 film and analysis was performed by RIT113 software. Three respiratory patterns were generated for the purpose of this study; first the 'even inhale-exhale pattern', second the slightly long exhale pattern (0.35 seconds longer than inhale period) named 'general signal pattern', and third a 'long exhale pattern' (0.7 seconds longer than inhale period). One dimensional dose profile comparisons and gamma index analysis on 2 dimensions were performed RESULTS: In one-dimensional dose profile comparisons, 5% in the target and 30% dose difference at the boundary were observed in the long exhale pattern. The center of high dose region in the profile was shifted 1 mm to inhale (caudal) direction for the 'even inhale-exhale pattern', 2 mm and 5 mm shifts to exhale (cranial) direction were observed for 'slightly long exhale pattern' and 'long exhale pattern', respectively. The areas of gamma index >1 were 11.88%, 15.11%, and 24.33% for 'even inhale-exhale pattern', 'general pattern', and 'long exhale pattern', respectively. The long exhale pattern showed largest errors. CONCLUSION: To reduce the dosimetric error due to respiratory motions, controlling patient's breathing to be closer to even inhaleexhale period is helpful with minimizing the motion amplitude.

Dosimetry by Using EBT2 Film for Total Skin Electron Beam Therapy (TSET) / 의학물리

For treatment of Total Skin Electron beam Therapy (TSET), measurement of dose at various conditions is need on the contrary to usual radiotherapy. When treating TSET with modified Stanford technique based on linear accelerator, the energy of treatment electron beam, the spatial dose distribution and the actual doses deposited on the surface of the patient were measured by using EBT2. The measured energy of the electron beam was agreed with the value that measured by ionization chamber, and the spatial dose distribution at the patient position and the doses at several point on the patient's skin could be easily measured by EBT2 film. The dose on the patient that was measured by EBT2 film showed good agreement with the data measured simultaneously by TLD. With the results of this study, it was proven that the EBT2 film can be one of the useful dosimeter for TSET.

Study on Absorbed Dose Determination of Electron Beam Quality for Cross-calibration with Plane-parallel Ionization Chamber / 의학물리

Absorbed dose to water based protocols recommended that plane-parallel chambers be calibrated against calibrated cylindrical chambers in a high energy electron beam with R50>7 g/cm2 (E> or =16 MeV). However, such high-energy electron beams are not available at all radiotherapy centers. In this study, we are compared the absorbed dose to water determined according to cross-calibration method in a high energy electron beam of 16 MeV and in electron beam energies of 12 MeV below the cross-calibration quality remark. Absorbed dose were performed for PTW 30013, Wellhofer FC65G Farmer type cylindrical chamber and for PTW 34001, Wellhofer PPC40 Roos type plane-parallel chamber. The cylindrical and the plane-parallel chamber to be calibrated are compared by alternately positioning each at reference depth, zref=0.6R50-0.1 in water phantom. The DW of plane-parallel chamber are derived using across-calibration method at high-energy electron beams of 16, 20 MeV. Then a good agreement is obtained the DW of plane-parallel chamber in 12 MeV. The agreement between 20 MeV and 12 MeV are within 0.2% for IAEA TRS-398.

A Study of Radiation Exposure in Proton Therapy Facility / 의학물리

Proton therapy facility, which is recently installed at National Cancer Center in Korea, generally produces a large amount of radiation near cyclotron due to the secondary particles and radioisotopes caused by collision between proton and nearby materials during the acceleration. Although the level of radiation by radioisotope decreases in length of time, radiation exposure problem still exists since workers are easily exposed by a low level of radiation for a long time due to their job assignment for maintenance or repair of the proton facility. In this paper, the working environment near cyclotron, where the highest radiation exposure is expected, was studied by measuring the degree of radiation and its duration for an appropriate level of protective action guide. To do this, we measured the radiation change in the graphite based energy degrader, the efficiency of transmitted beam and relative activation degree of the transmission beam line. The results showed that while the level of radiation exposure around cyclotron and beam line during the operation is much higher than the other radiation therapy facilities, the radiation exposure rate per year is under the limit recommended by the law showing 1~3 mSv/year.

Classification and Treatment of Degenerative Lumbar Spinal Deformity / 대한척추외과학회지

STUDY DESIGN: A retrospective study OBJECTIVE: To categorize and analyze clinical results of degenerative lumbar deformity patients according to the degree of scoliosis and kyphosis. SUMMARY AND LITERATURE REVIEW: A degenerative spinal deformity is classified into a coronal and sagittal deformity. There are some reports about treatment according to each classification but the classification is sometimes inappropriate and the treatment can vary. MATERIALS AND METHODS: From June 1998 to June 2003, 79 patients, who were diagnosed with a degenerative lumbar deformity and underwent conservative or operative treatment, were studied retrospectively. Group I had scoliosis ranging from 10 to 20degrees , and group II had scoliosis > 20degrees Each group was subdivided into A, B, and C according to the lordosis, group A > 30degrees , group B between 20 to 30degrees , and group C 20degrees or lordosis < 20degrees are expected to show more improvement in symptom after surgery than after conservative treatment.

The Usefulness of Blocking Screw in Intramedullary Nail on Proximal Tibial Fracture

PURPOSE: To evaluate the effectiveness of a blocking screw in intramedullary nailing at the tibia proximal shaft fracture. MATERIALS AND METHODS: 63 tibia proximal shaft fractures from January 2000 to December 2002 treated with only intramedullary nailing were referred to as group I, and 8 fractures from January 2003 to December 2003 treated with both intramedullary nailing and the blocking screw were referred to as group II. Retrospective studies were done for group I and II. The incidence of nonunion and the postoperative angular alignments were compared. Malalignment was defined as an angle of 5 degrees anteroposteriorly or mediolaterally. RESULTS: There were 7 nonunion (11%) in group I in compare with none in group II. There were 21 angular malalignments (33%) in group I and 1 in group II (12%) and most of them had valgus deformity or anterior anglulation. No complications were directly due to the use of the Blocking screw. CONCLUSION: The technique of the blocking screw used to be one of the option for proximal tibial nailing at tibial proximal shaft fracture helps to overcome angular malalignments of bones.

The Expression and Function of the Tumor Necrosis Factor Receptor I (TNFRI), TNFRII, and X-Linked Inhibitor of Apoptosis Genes after Spinal Cord Injury in Rats / 대한척추외과학회지

STUDY DESIGN AND OBJECTIVE: Tumor necrosis factor-alpha(TNF-alpha), a key inflammatory mediator, has been demonstrated in spinal cord injury (SCI). However, the expression of TNF receptors following SCI remains to be identified. To elucidate the expressions of TNF receptor I (TNFRI), TNFRII, XIAP, and their function in SCI, in situ hybridization and RT-PCR were performed in a SCI model. MATERIAL AND METHODS: Sprague-Dawley rats were anesthetized with halothane and laminectomized at the level of the eleventh and twelfth thoracic vertebra. Using a modified New York University Impactor, SCI was induced by dropping a 10 gm weight from a height of 20 mm. The rod of the impactor had a constant circular surface, 3 mm in diameter. After induction of the injury, rats were placed in a temperature and humidity-controlled chamber overnight. RESULTS: The TNFRI gene was not detected in the control rats, but the TNFRII gene was expressed in the neurons in the control rats. The TNFRI gene expression was maximally increased in the spinal cord 1 day after the SCI; however, that of the TNFRII gene occurred 3 days after the SCI. In the white matter, both the TNFRI and TNFRII genes were increased in the oligodendrocytes 3 days after the SCI. The XIAP gene was increased in neurons of the gray matter 1 and 3 days after the SCI, but was not detected in the white matter after the SCI. CONCLUSION: Up-regulation of the expression of TNFRII occurs later than that of TNFRI in the spinal cord after a SCI. TNFR may be related to neuronal survival considering its similar expression pattern to that of XIAP. The results from these studies may lead to alternative therapeutic targets of TNF receptors in spinal cord injury, providing the basis for developing agonist and antagonist systems for TNF receptor subtypes and also for encouraging better strategies for the treatment of spinal cord disorders related to trauma.

Expressions of the p53 and MDM-2 Genes in Primary Chondrosarcoma and Secondary Chondrosarcoma from Osteochondromatosis / 대한정형외과학회잡지

PURPOSE: To evaluate the relationships between mutations of the p53 and MDM-2 proteins in human primary chondrosarcoma and in secondary chondrosarcoma from osteochondromatosis. MATERIALS AND METHODS: From January, 1984 to April, 2000, 33 cases were grouped into three categories: Group I, osteochondromatosis (18 cases), group II, secondary chondrosarcoma (6 cases), group III, primary chondrosarcoma (9 cases). We analysed the expressions of the p53 and MDM-2 proteins. All specimens were embedded in paraffin and stained using the Streptavidin-Biotin peroxidase method with anti-p53 antibody, and DO7 anti-MDM-2 antibody IF2 as monoclonal antibody. RESULTS: The expressions of the p53 and MDM-2 proteins, the pathologic grade of each group, and clinical outcomes were compared and analysed. The expressions of the p53 and MDM-2 proteins in each group were significantly different (p<0.05). However, MDM-2 protein expression was similar between group II and III. Both p53 and MDM-2 protein were expressed most frequently in group III and this was significant. There was an increased manifestation of the p53 and MDM-2 protein in the higher pathologic grade. The 5-year survival rate of patients with a malignant tumor was about 70%. In expired patients, the histologic grade was grade III, and both proteins were expressed, which enabled a relationship to be established between p53 and MDM-2 protein expression and a poorer prognosis. CONCLUSION: In osteochondromatosis, the coexpression of the p53 and MDM-2 proteins was not observed, but isolated p53 or MDM-2 expression was observed in some cases. According to this study, it is helpful as a basic study for early detection of malignant translation of osteochondromatosis. In conclusion, we suggest that the expressions of the p53 and MDM-2 proteins are useful indicators of prognosis.