• Journal of Korean Neurosurgical Society
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• v.67 no.1
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• pp.84-93
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• 2024

Objective : We aimed to examine trends in critically ill neurology-neurosurgery (NNS) patients who were admitted to the intensive care unit (ICU) in South Korea and identify risk factors for in-hospital mortality after ICU admission in NNS patients. Methods : This nationwide population-based retrospective cohort study enrolled adult NNS adult patients admitted to the ICU from 2010 to 2019 extracted from the National Health Insurance Service in South Korea. The critically ill NNS patients were defined as those whose main admission departments were neurology or neurosurgery at ICU admission. The number of ICU admission, age, and total cost for hospitalization from 2010 to 2019 in critically ill NNS patients were examined as trend information. Moreover, multivariable logistic regression modeling was used to identify risk factors for in-hospital mortality among critically ill NNS patients. Results : We included 845474 ICU admission cases for 679376 critically ill NNS patients in South Korea between January 1, 2010 to December 31, 2019. The total number of ICU admissions among NNS patients was 79522 in 2010, which increased to 91502 in 2019. The mean age rose from 62.8 years (standard deviation [SD], 15.6) in 2010 to 66.6 years (SD, 15.2) in 2019, and the average total cost for hospitalization per each patient consistently increased from 6206.1 USD (SD, 5218.5) in 2010 to 10745.4 USD (SD, 10917.4) in 2019. In-hospital mortality occurred in 75455 patients (8.9%). Risk factors strongly associated with increased in-hospital mortality were the usage of mechanical ventilator (adjusted odds ratio [aOR], 19.83; 95% confidence interval [CI], 19.42-20.26; p<0.001), extracorporeal membrane oxygenation (aOR, 3.49; 95% CI, 2.42-5.02; p<0.001), and continuous renal replacement therapy (aOR, 6.47; 95% CI, 6.02-6.96; p<0.001). In addition, direct admission to ICU from the emergency room (aOR, 1.38; 95% CI, 1.36-1.41; p<0.001) and brain cancer as the main diagnosis (aOR, 1.30; 95% CI, 1.22-1.39; p<0.001) are also potential risk factors for increased in-hospital mortality. Conclusion : In South Korea, the number of ICU admissions increased among critically ill NNS patients from 2010 to 2019. The average age and total costs for hospitalization also increased. Some potential risk factors are found to increase in-hospital mortality among critically ill NNS patients.

• Progress in Medical Physics
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• v.25 no.2
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• pp.79-88
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• 2014

The dose distributions within the real volumes of tumor targets and critical organs during internal target volume-based intensity-modulated radiation therapy (ITV-IMRT) for liver cancer were recalculated by applying the effects of actual respiratory organ motion, and the dosimetric features were analyzed through comparison with gating IMRT (Gate-IMRT) plan results. The ITV was created using MIM software, and a moving phantom was used to simulate respiratory motion. The doses were recalculated with a 3 dose-volume histogram (3DVH) program based on the per-field data measured with a MapCHECK2 2-dimensional diode detector array. Although a sufficient prescription dose covered the PTV during ITV-IMRT delivery, the dose homogeneity in the PTV was inferior to that with the Gate-IMRT plan. We confirmed that there were higher doses to the organs-at-risk (OARs) with ITV-IMRT, as expected when using an enlarged field, but the increased dose to the spinal cord was not significant and the increased doses to the liver and kidney could be considered as minor when the reinforced constraints were applied during IMRT plan optimization. Because the Gate-IMRT method also has disadvantages such as unsuspected dosimetric variations when applying the gating system and an increased treatment time, it is better to perform a prior analysis of the patient's respiratory condition and the importance and fulfillment of the IMRT plan dose constraints in order to select an optimal IMRT method with which to correct the respiratory organ motional effect.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.2
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• pp.355-362
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• 2014

Purpose : When head&neck cancer radiation therapy, thermoplastic mask is applied for patients with fixed. The purpose of this study is to evaluate usefulness of thermoplastic mask for SRS in tomotherapy by conparison with the conventional mask. Materials and Methods : Typical mask(conventional mask, C-mask) and mask for SRS are used to fix body phantom(rando phantom) on the same iso centerline, then simulation is performed. Tomotherapy plan for orbit and salivary glands is made by treatment planning system(TPS). A thick portion and a thin portion located near the treatment target relative to the mask S-mask are defined as region of interest for surface dose dosimetry. Surface dose variation depending on the type of mask was analyzed by measuring the TPS and EBT film. Results : Surface dose variation due to the type of mask from the TPS is showed in orbit and salivary glands 0.65~2.53 Gy, 0.85~1.84 Gy, respectively. In case of EBT film, -0.2~3.46 Gy, 1.04~3.02 Gy. When applied to the S-mask, in TPS and Gafchromic EBT3 film, substrantially 4.26%, 5.82% showed maximum changing trend, respectively. Conclusion : To apply S-mask for tomotherapy, surface dose is changed, but the amount is insignificant and be useful when treatment target is close critical organs because decrease inter and intra fractional variation.

• Progress in Medical Physics
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• v.25 no.3
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• pp.167-175
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• 2014

The purpose of this study is to evaluate the variation of the dose which is delivered to the patients with glottis cancer under IMRT (intensity modulated radiation therapy) by using the 3D registration with CBCT (cone beam CT) images and the DIR (deformable image registration) techniques. The CBCT images which were obtained at a one-week interval were reconstructed by using B-spline algorithm in DIR system, and doses were recalculated based on the newly obtained CBCT images. The dose distributions to the tumor and the critical organs were compared with reference. For the change of volume depending on weight at 3 to 5 weeks, there was increased of 1.38~2.04 kg on average. For the body surface depending on weight, there was decreased of 2.1 mm. The dose with transmitted to the carotid since three weeks was increased compared be more than 8.76% planned, and the thyroid gland was decreased to 26.4%. For the physical evaluation factors of the tumor, PITV, TCI, rDHI, mDHI, and CN were decreased to 4.32%, 5.78%, 44.54%, 12.32%, and 7.11%, respectively. Moreover, $D_{max}$, $D_{mean}$, $V_{67.50}$, and $D_{95}$ for PTV were increased or decreased to 2.99%, 1.52%, 5.78%, and 11.94%, respectively. Although there was no change of volume depending on weight, the change of body types occurred, and IMRT with the narrow composure margin sensitively responded to such a changing. For the glottis IMRT, the patient's weight changes should be observed and recorded to evaluate the actual dose distribution by using the DIR techniques, and more the adaptive treatment planning during the treatment course is needed to deliver the accurate dose to the patients.

• Progress in Medical Physics
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• v.21 no.3
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• pp.298-303
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• 2010

The aim of this study was to compare the dose distribution of intensity modulated radiation therapy (IMRT) with 3 dimensional conformal radiation therapy (3DCRT) in prostate cancer. The IMRT plan and the 3DCRT plan used the 9 fields technique, respectively. In IMRT, tumor dose was a total dose of 66 Gy at 2.0 Gy per day, 5 days a week for 5 weeks. All cases were following the dose volume histogram (DVH) constraints. The maximum and minimum tumor dose constraints were 6,700 cGy and 6,500 cGy, respectively. The rectum dose constraints were <35% over 50 Gy. The bladder dose constraints were <35% over 40 Gy. The femur head dose constraints were <15% over 20 Gy. Tumor dose in the 3DCRT were 66 Gy. In IMRT, the maximum dose of PTV was 104.4% and minimum dose was 89.5% for given dose. In 3DCRT, the maximum dose of PTV was 105.3% and minimum dose was 85.5% for given dose. The rectum dose was 34.0% over 50 Gy in IMRT compared with 63.3% in 3DCRT. The bladder dose was 30.1% over 40 Gy in IMRT compared with 30.6% in 3DCRT. The right femur head dose was 9.5% over 20 Gy in IMRT compared with 17.5% in 3DCRT. The left femur head dose was 10.6% over 20 Gy in IMRT compared with 18.3% in 3 DCRT. The dose of critical organs (rectum, bladder, and femur head) in IMRT showed to reduce than dose of 3DCRT. The rectum dose over 50 Gy in IMRT was reduced 29.3% than 3DCRT. The bladder dose over 40 Gy in IMRT was similar to 3DCRT. The femur head dose over 20 Gy in IMRT was reduced about 7~8% than 3DCRT.

• Reproductive and Developmental Biology
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• v.35 no.1
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• pp.33-45
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• 2011

Heat shock protein 90 (Hsp90) is ATPase-directed molecular chaperon and affects survival of cancer cell. Inhibitory effect of Hsp90 by inducing cell cycle arrest and apoptosis in the cancer cell was reported. However, its role during oocyte maturation and early embryo development is very insufficient. In this study, we traced the effects of Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), on meiotic maturation and early embryonic development in pigs. We also investigated several indicators of developmental potential, including structural integrity, gene expression (Hsp90-, cell cycle-, and apoptosis-related genes), and apoptosis, which are affected by 17-AAG. Then, we examined the roles of Hsp90 inhibitor on viability of primary cells in pigs. Porcine oocytes were cultured in the NCSU-23 medium with or without 17-AAG for 44 h. The proportion of GV arrested oocytes was significantly different between the 17-AAG treated and untreated group (78.2 vs 34.8%, p<0.05). After completion of meiotic maturation, the proportion of MII oocytes was lower in the 17-AAG treated group than in the control group (27.9 vs 71.0%, p<0.05). After IVF, the percentage of penetrated oocytes was significantly lower in the 17-AAG treated group (25.2%), resulting in lower normal pronucleus formation (2PN of 14.6%). Therefore, the inhibition of meiotic progression by Hsp90 inhibitor played a critical role in fertilization status. Porcine embryo were cultured in the PZM-3 medium with or without 17-AAG for 6 days. In result, significant differences in developmental potential were detected between the embryos that were cultured with or without 17-AAG. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) showed that the number of containing fragmented DNA at the blastocyst stage increased in the 17-AAG treated group compared with control (7.5 vs 4.4, respectively). Blastocysts that developed in the 17-AAG treated group had low structural integrity and high apoptotic nuclei than those of the untreated control, resulting in decrease the embryonic qualities of preimplantation porcine blastocysts. The mRNA expressions of cell cycle-related genes were down-regulated in the 17-AAG treated group compared with control. Also, the expression of the pro-apoptotic gene Bax increased in 17-AAG treated group, whereas expression of the anti-apoptotic gene Bel-XL decreased. However, the expression of ER stress-related genes did not changed by 17-AAG. Cultured pESF cells were treated with or without 17-AAG and used for MIT assay. The results showed that viability of pESF cells were decreased by treatment of 17-AAG ($2{\mu}M$) for 24 hr. These results indicated that 17-AAG decreased cell proliferation and increased cell death. Expression patterns Hsp90 complex genes (Hsp70 and p23), cell cycle-related genes (cdc2 and cdc25c) and apoptosis-related genes (Bax and Bcl-XL) were significantly changed by using RT-PCR analysis. The spliced form of pXbp-1 product (pXbp-1s) was detected in the tunicamycin (TM) treated cells, but it is not detected in 17-AAG treated cells. In conclusion, Hsp90 appears to play a direct role in porcine early embryo developmental competence including structural integrity of blastocysts. Also, these results indicate that Hsp90 is closely associated with cell cycle- and apoptosis-related genes expression in developing porcine embryos.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.241-253
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• 1990

331 patients of stage IIb uterine cervix cancer trated by radiation alone at Kosin Medical Center between June 1980 and Dec. 1985 were analysed to determine parameters of radiotherapy associated to disease states. Survival rate was highest among the reported ($82.8{\%}$ for crude and $82.4{\%}$ for disease free survival). Pelvic control rate in 6 weeks after the end of radiotherapy was $93.6{\%}$ in the patients treated with ICR following total pelvic radiation and $71.6{\%}$ with small field additional external irradiation. 5 year survival rate in those who achieved pelvic control was $98.9{\%}$ and $12.9{\%}$ in those who had pelvic failure and/or metastasis after radiation. The survival rate figured maximal $88.5{\%}$ with dosage of $7500{\~}8500$ cGy to point A with acceptable incidence of complications ($4.9{\%}$) but without increasing survival above it and minimal $74.1{\%}$ with dosage of less than 6500 cGy. The treatment failure was counted $18.7{\%}$ (62 of 331 patients): Local failure $72.6{\%}$ (45 of 62 patients), locoregional failure $3.2{\%}$ (2 of 62 patients) and distant failure $24{\%}$ (15 of 62 patients). Late complications were found in 50 patients ($15.1{\%}$) and $42{\%}$ of them was rectal bleeding and stenosis. The dose of 8500 cGy to point A was found to be critical for complication and $70{\%}$ of complications occurred above it and was more serious one such as fistula. Rectal complications were developed above rectal dose 6500 cGy and bladder complication above bladder dose 7500 cGy. Major cause of death was cachexia due to locoregional failure ($73.7{\%}$ of death), next was due to metastasis to lung, liver and bone, and only 3 patients died of complication of intestinal perforations and obstruction. In conclusion higher external radiation dose for a bulky uterine cervix and barrel shaped uterus was essential for local control.

• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.213-219
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• 2009

Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.

• The Journal of Korean Society for Radiation Therapy
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• v.31 no.2
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• pp.33-41
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• 2019

Purpose: The purpose of this study is to improve the reduction of coverage of PTVs adjacent to organ at risk (OAR) by setting up overlapping Planning Target Volume (PTV) during Volumetric Modulated Arc Therapy(VMAT). Materials and Methods: In patients who received Whole Brain, Gall Bladder and Rectum radiation therapy, We compared the cover change, maximum dose, Homogenicity Index and Conformity Index of PTV and also compared the maximum dose and average dose change of Organ At Risk by organizing treatment plans that are not applied overlaped PTV and treatment plans that are applied overlaped PTV in areas where coverage is insufficient. Results: overage of treatment plans with overlapping PTVs was increased in all patients, and overall coverage was also increased in each of the four patients. The maximum dose for PTV was increased in five patients, and the Homogenicity Index and Conformity Index for all patients did not differ much. The maximum dose of the lens was increased by 1.12 times, and the maximum dose was decreased in two patients for brain stem. The mean dose of the eyeball was increased by a maximum of 1.15 times, and there was no significant difference between both parotid gland. In case of gallbladder cancer patients, the mean dose in the liver and colon was decreased, and the mean dose in the duodenum was increased. In the case of rectal cancer patients, the mean dose was reduced for both femur and bladder set as OARs. The overall MU was shown to be similar in four patients, excluding one. Conclusion: If the critical dose of OAR is considered and used properly, I think it is a useful way to improve coverage of PTV.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7825-7829
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• 2015

Background: Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum B2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. Materials and Methods: In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. B2M levels were measured in serum with a fully-automated IMX system. Results: The mean serum B2M level of Group (1) was $4.25{\pm}1.48{\mu}g/ml$., Group (2) was $7.48{\pm}3.04$, Group (3) was $6.62{\pm}2.49$ and Group (4) was $1.62{\pm}0.63$. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis ($7.48{\pm}3.04$) and HCC groups ($6.62{\pm}2.49$) than the HCV group ($4.25{\pm}1.48$) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB andWBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%.The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Conclusions: Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.