The Clinical Utilization of Radiation Therapy in Korea between 2011 and 2015 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to estimate the clinical utilization of radiation therapy (RT) in Korea between 2011 and 2015. MATERIALS AND METHODS: We analyzed the claims data from the Health Insurance Review and Assessment Service to estimate the clinical utilization of RT. The source population consisted of all patients who had any of the International Classification of Diseases 10th revision cancer diagnoses (C00-C97) and those with diagnostic codes D00-D48, who were also associated with at least one of the procedure codes related to RT. RESULTS: The total number of patients who received RT in 2011, 2012, 2013, 2014, and 2015 were 54,810, 59,435, 61,839, 64,062, and 66,183, respectively. Among them, the total numbers of male and female patients were 24,946/29,864 in 2011, 27,211/32,224 in 2012, 28,111/33,728 in 2013, 29,312/34,750 in 2014, and 30,266/35,917 in 2015. The utilization rate of RT in cancer patients has also increased steadily over the same period from 25% to 30%. The five cancers that were most frequently treated with RT between 2011 and 2012 were breast, lung, colorectal, liver, and uterine cervical cancers. However, the fifth most common cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate cancer. More than half of cancer patients (64%) were treated with RT in the capital area (Seoul, Gyeonggi, and Incheon). CONCLUSION: The total number of patients who underwent RT increased steadily from 2011 to 2015 in Korea. The utilization rate of RT in cancer patients is also increasing.

Association between Metformin Use and Survival in Nonmetastatic Rectal Cancer Treated with a Curative Resection: A Nationwide Population Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Metformin is associated with an anticancer effect. However, the effects of metformin in rectal cancer are controversial. This study investigated the impact of metformin on the survival of patients with diabetes mellitus and nonmetastatic rectal cancer who underwent curative surgery. MATERIALS AND METHODS: The database was provided by the Korea Center Cancer Registry and National Health Insurance Service of the Republic of Korea. A cohort of patients with newly diagnosed rectal cancer between 2005 and 2011 was identified. Drug exposure was defined as receiving the oral hypoglycemic agent for at least 90 days over the period from 6 months before the initial diagnosis of rectal cancer to the last follow-up. RESULTS: A total of 4,503 patients were prescribed oral hypoglycemic agents and classified as the diabetic group, of which 3,694 patients received metformin for at least 90 days. Unadjusted analyses showed a significantly higher overall survival (hazard ratio, 0.596; 95% confidence interval, 0.506 to 0.702) and rectal cancer-specific survival (hazard ratio, 0.621; 95% confidence interval, 0.507 to 0.760) in the metformin group than in the nonmetformin group. The adjusted overall survival (hazard ratio, 0.631; 95% confidence interval, 0.527 to 0.755) and cancer-specific survival (hazard ratio, 0.598; 95% confidence interval, 0.479 to 0.746) in the group with a medication possession ratio of 80% or greater was significantly higher than in the group with a medication possession ratio of less than 80%. CONCLUSION: Metformin use is associated with overall and cancer-specific survival in diabetic patients with a nonmetastatic rectal cancer treated with a curative resection.

Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors

PURPOSE: To evaluate the outcomes of stereotactic body radiation therapy (SBRT) for patients with liver oligo-recurrence and oligo-progression from various primary tumors. MATERIALS AND METHODS: Between 2002 and 2013, 72 patients with liver oligo-recurrence (oligo-metastasis with a controlled primary tumor) and oligo-progression (contradictory progression of a few sites of disease despite an overall tumor burden response to therapy) underwent SBRT. Of these, 9 and 8 patients with uncontrollable distant metastases and patients immediate loss to follow-up, respectively, were excluded. The total planning target volume was used to select the SBRT dose (median, 48 Gy; range, 30 to 60 Gy, 3–4 fractions). Toxicity was evaluated using the Common Toxicity Criteria for Adverse Events v4.0. RESULTS: We evaluated 55 patients (77 lesions) treated with SBRT for liver metastases. All patients had controlled primary lesions, and 28 patients had stable lesions at another site (oligo-progression). The most common primary site was the colon (36 patients), followed by the stomach (6 patients) and other sites (13 patients). The 2-year local control and progression-free survival rates were 68% and 22%, respectively. The 2- and 5-year overall survival rates were 56% and 20%, respectively. The most common adverse events were grade 1–2 fatigue, nausea, and vomiting; no grade ≥3 toxicities were observed. Univariate analysis revealed that oligo-progression associated with poor survival. CONCLUSION: SBRT for liver oligo-recurrence and oligo-progression appears safe, with similar local control rates. For liver oligo-progression, criteria are needed to select patients in whom improved overall survival can be expected through SBRT.

The clinical utilization of radiation therapy in Korea between 2009 and 2013

PURPOSE: The purpose of this study was to estimate the clinical utilization of radiation therapy (RT) in Korea between 2009 and 2013. MATERIALS AND METHODS: We analyzed open claims data from the Health Insurance Review and Assessment Service. The subjects were patients who had diagnostic codes C00-C97 or D00-D48 according to the 10th revision of the International Classification of Diseases, with procedure codes indicating RT treatment. RESULTS: The total number of patients who received RT in 2009, 2010, 2011, 2012, and 2013 were 45,571, 49,593, 54,671, 59,172, and 61,485, respectively. Among them, the total numbers of male and female patients were 20,780/24,791 in 2009, 22,711/26,882 in 2010, 24,872/29,799 in 2011, 27,101/32,071 in 2012, and 27,941/33,544 in 2013. The five cancers that were most frequently treated with RT between 2009 and 2012 were breast, lung, colorectal, liver, and uterine cervical cancers. However, the fifth most common cancer treated with RT that replaced uterine cervical cancer in 2013 was prostate cancer. The three leading types of cancer among the male patients were lung, colorectal, and liver cancers, whereas in female patients, they were breast, uterine cervical, and lung cancers. The type of cancer most commonly treated by RT was cancer of the central nervous system in patients aged 20 years or less, breast cancer in patients aged 30-50 years, and lung cancer in patients aged 60 years or more. CONCLUSION: Data from this study provided the clinical utilization of RT in Korea between 2009 and 2013.

The Clinical Status of Radiation Therapy in Korea in 2009 and 2013 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to estimate the clinical status of radiation therapy (RT) in Korea. MATERIALS AND METHODS: We analyzed open claims data from the Health Insurance Review and Assessment Service (HIRA). The subjects were patients with malignant neoplasms who had procedure codes concerning RT in 2009 and 2013. RESULTS: The total numbers of patients who underwent RT in 2009 and 2013 were 42,483 and 56,850, respectively. The numbers of men and women were 20,012 and 22,471 in 2009 and 26,936 and 29,914 in 2013, respectively. The five most frequent RT sites were metastatic, breast, gastrointestinal, thoracic, and gynecologic cancers in 2009, and metastatic, breast, gastrointestinal, thoracic and head and neck cancers in 2013. The three leading types of cancer among men were metastatic, gastrointestinal, and thoracic, and breast, metastatic, and gynecologic among women. According to age, the most common treatment site was the central nervous system for those aged 20 years or less, the breast for those in their 30s to 50s, and metastatic sites for those in their 60s or older. CONCLUSION: Data from this study provide an overview of the clinical status of RT in Korea.

Academic Trend and Clinical Status of Radiotherapy for Hepatobiliary Cancer Over the Past 20 Years in Korea

BACKGROUND/AIMS: To analyze the future trends through the status of radiotherapy in the hepatobiliary cancer in Korea and related articles published in the world. METHODS: Science citation index (SCI) and science citation index expanded (SCIE) articles, published in the 20 years from 1995 until 2014, were searched that contain the keywords related hepatobiliary cancer and radiotherapy using the Scopus. The incidence of hepatobiliary cancer was analyzed using annual reports from the Korea Central Cancer Registry. The status of radiotherapy was analyzed using data obtained form the Korean Society for Radiation Oncology and the National Health Insurance Service. RESULTS: Total 2,302 papers related radiotherapy for hepatobiliary cancer were searched in the world. By 2014, the cumulative number of papers published by domestic authors was a total 221 pieces. In 1999, total 16,305 hepatobiliary cancer patients were developed, of which 729 patients have been treated with radiotherapy. In 2013, it was expected that total 22,482 hepatobiliary cancer patients would be developed, of which 3,075 patients have been treated with radiotherapy. CONCLUSIONS: Over the past 20 years, South Korea has made clinically and academically remarkable advances in the area of radiotherapy for hepatobiliary cancer. The researchers will continue to announce the results such as an objective status data and published papers in the future.

Outcomes of stereotactic body radiotherapy for unresectable primary or recurrent cholangiocarcinoma

PURPOSE: To report the results of stereotactic body radiotherapy (SBRT) for unresectable primary or recurrent cholangiocarcinoma. MATERIALS AND METHODS: From January 2005 through August 2013, 58 patients with unresectable primary (n = 28) or recurrent (n = 30) cholangiocarcinoma treated by SBRT were retrospectively analyzed. The median prescribed dose was 45 Gy in 3 fractions (range, 15 to 60 Gy in 1-5 fractions). Patients were treated by SBRT only (n = 53) or EBRT + SBRT boost (n = 5). The median tumor volume was 40 mL (range, 5 to 1,287 mL). RESULTS: The median follow-up duration was 10 months (range, 1 to 97 months). The 1-year, 2-year overall survival rates, and median survival were 45%, 20%, and 10 months, respectively. The median survival for primary group and recurrent group were 5 and 13 months, respectively. Local control rate at 1-year and 2-year were 85% and 72%, respectively. Disease progression-free survival rates at 1-year and 2-year were 26% and 23%, respectively. In univariate analysis, ECOG performance score (0-1 vs. 2-3), treatment volume ( or =50 mL), and pre-SBRT CEA level ( or =5 ng/mL) were significant in overall survival rate. In multivariate analysis, ECOG score (p = 0.037) and tumor volume (p = 0.030) were statistically significant. In the recurrent tumor group, patients with >12 months interval from surgery to recurrence showed statistically significant higher overall survival rate than those with or =grade 3 complications. CONCLUSION: SBRT can be considered as an effective local modality for unresectable primary or recurrent cholangiocarcinoma.

The influence of serum substituents on serum-free Vero cell conditioned culture media manufactured from Dulbecco's modified Eagle medium in mouse embryo culture

OBJECTIVE: This study was conducted to examine the influences of supplementation of the serum substituents and available period of serum-free Vero cell conditioned media (SF-VCM) manufactured from Dulbecco's modified Eagle medium cultured with Vero cells for in vitro development of mouse preimplantation embryos. METHODS: A total of 1,099 two-cell embryos collected from imprinting control region mice were cultured in SF-VCM with 10% and 20% human follicular fluid (hFF), serum substitute supplement (SSS), and serum protein substitute (SPS). Development of embryos was observed every 24 hours. Results between different groups were analyzed by chi-square test, and considered statistically significant when P-value was less than 0.05. RESULTS: The rates of embryonic development cultured in SF-VCM supplemented with serum substituents were significantly higher compare with serum-free group (P < 0.05). The rates of embryonic development after 48 hours (morula< or =) and 96 hours (blastocyst< or =) were significantly higher in 20% SSS and 10% SPS than in 20% hFF supplementation (P < 0.05). And the rates of embryonic development after 96 hours (hatching blastocyst< or =) were significantly higher in 10% SPS (94.5%) than in 20% SSS (82.6%) and 20% hFF supplementation (68.5%). The rates of embryonic development according to storage period of the SF-VCM supplemented with 10% SPS showed no significant difference between control, 2 weeks and 4 weeks group. However developmental rate in 6 weeks storage group was significantly lower than other groups. CONCLUSION: The rate of embryonic development after 96 hours (hatching blastocyst< or =) was significantly higher in SF-VCM supplemented with 10% SPS. And storage period of media up to 4 weeks did not affect on embryonic development.

Studies on development of serum-free conditioned media using Vero cells and DMEM with controlled concentration of glucose and pyruvate / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to examine in vitro development of early preimplantation mouse embryos in various kind of serum-free conditioned media (SF-VCM) manufactured from DMEM cultured with Vero Cells. METHODS: A total of 846 two-cell mouse embryos were cultured in different kind of SF-VCM. SF-VCMs were divided into SF-VCM-10, -30 and -50 by media volume using DMEM #1 media, and divided into SF-VCM #1, #2 and #3 by controlled concentration of glucose and pyruvate (manufactured by DMEM #1: mixed three volume of DMEM-G (DMEM with glutamine without glucose and pyruvate) and one volume of DMEM-GGP (DMEM with glutamine, glucose, pyruvate), #2: mixed same volume of DMEM-G and DMEM-GGP and #3: mixed one volume of DMEM-G and three volume of DMEM-GGP, respectively). Experimental groups were mainly added 10% SSS, and 20% hFF was added to only Control group co-cultured with Vero cells. Development of embryos was observed every 24 hours. Results between different groups were analyzed using Chi-square test, and considered statistically significant when P-value was less than 0.05. RESULTS: In vitro developmental rate by each cleavage stages of mouse embryos cultured in SF-VCMs with a various volumes were significantly (P<0.05) higher in SF-VCM-30 (morula< or =: 97.2%, Blastocyst (BL)< or =: 97.2%, Hatching BL< or =: 82.2%) than other groups. In the rate of development on in vitro co-culture vs. a various SF-VCMs manufactured by DMEM controlled concentration of glucose and pyruvate, Group I (SF-VCM #1) was higher than other groups in each cleavage stages (morula< or =: 98.1%, Blastocyst (BL)< or =: 97.1%, hatching BL< or =: 81.7%, respectively). Moreover, specially, in the developmental rate into the hatching blastocyst < or = after 96 hours in vitro culture, Group I (81.7%) was significantly higher than control group (67.6%, P<0.05). CONCLUSION: SF-VCM #1 manufactured by volume of 30 mL DMEM #1 media cultured in vitro for 48 hours in 250 mL flask was the most effective on in vitro developmental rate of mouse preimplantation embryos. Therefore, it is expected that SF-VCM #1 has application to human IVF-ET.

The Usefulness of 18F-FDG PET/CT for Predicting the Response of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiation Therapy / 대한방사선종양학회지

PURPOSE: This study aimed at assessing the value of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) for predicting the response of locally advanced rectal cancer to neoadjuvant CRT. MATERIALS AND METHODS: Between August 2006 and January 2008, we prospectively enrolled 20 patients with locally advanced rectal cancer and who were treated with neoadjuvant CRT at the Korea Institute of Radiological and Medical Sciences. The treatment consisted of radiation therapy and chemotherapy, and this was followed by curative resection 6 weeks later. All the patients underwent 18F-FDG PET/CT both before CRT and 6 weeks after completing CRT. The measurements of the FDG uptake (SUV(max)), the absolute difference (DeltaSUV(max)) and the percent SUV(max) difference (response index, RI(SUV)) between the pre- and post-CRT 18F-FDG PET/CT scans were assessed. The measurements of the metabolic volume, the absolute difference (Delta metabolic volume) and the percent metabolic volume difference (response index, RI(metabolic volume)) were also assessed. RESULTS: Of the 20 patients who underwent surgery, 11 patients (55%) were classified as responders according to Dworak's classification. The post-CRT SUV(max) was significantly lower than the pre-CRT SUV(max). However, there were no significant differences in the SUV(max) and the metabolic volume reduction between the responders and non-responders. We used a minimum SUV(max) reduction of 67% as the cut-off value for defining a response, with a sensitivity of 45.5%, a specificity of 88.9%, a positive predictive value of 77% and a negative predictive value of 53.8%. CONCLUSION: Although there were no statistically significant results in this study, other studies have revealed that 18F-FDG PET/CT has the potential to assess the tumor response to neoadjuvant CRT in patients with locally advanced rectal cancer.

Accelerated Hyperfractionated Radiotherapy for Locally Advanced Uterine Cervix Cancers / 대한방사선종양학회지

PURPOSE: To assess the efficacy of the use of accelerated hyperfractionated radiotherapy (AHRT) for locally advanced uterine cervix cancers. MATERIALS AND METHODS: Between May 2000 and September 2002, 179 patients were identified with FIGO stage IIB, IIIB, and IVA cancers. Of the 179 patients, 45 patients were treated with AHRT (AHRT group) and 134 patients were treated with conventional radiotherapy (CRT group), respectively. Patients undergoing the AHRT regimen received a dose of 30 Gy in 20 fractions (1.5 Gyx2 fractions/day) to the whole pelvis. Subsequently, with a midline block, we administered a parametrial boost with a dose of 20 Gy using 2 Gy fractions. Patients also received two courses of low-dose-rate brachytherapy, up to a total dose of 85~90 Gy to point A. In the CRT group of patients, the total dose to point A was 85~90 Gy. The overall treatment duration was a median of 37 and 66 days for patients that received AHRT and CRT, respectively. Statistical analysis was calculated by use of the Kaplan-Meier method, the log-rank test, and Chi-squared test. RESULTS: For patients that received cisplatin-based concurrent chemotherapy and radiotherapy, the local control rate at 5 years was 100% and 79.2% for the AHRT and CRT group of patients, respectively (p=0.028). The 5-year survival rate for patients with a stage IIB bulky tumor was 82.6% and 62.1% for the AHRT group and CRT group, respectively (p=0.040). There was no statistically significant difference for severe late toxicity between the two groups (p=0.561). CONCLUSION: In this study, we observed that treatment with AHRT with concurrent chemotherapy allows a significant advantage of local control and survival for locally advanced uterine cervix cancers.

The Use of MTT Assay, In Vitro and Ex Vivo, to Predict the adiosensitivity of Colorectal Cancer / 대한방사선종양학회지

PURPOSE: The measurement of radiosensitivity of individuals is useful in radiation therapy. Unfortunately, the measurement of radiation survival using a clonogenic assay, which is the established standard, can be difficult and time consuming. The aim of this study is to compare radiosensitivity results obtained from the MTT and clonogenic assays, and to evaluate whether the MTT assay can be used on clinical specimens. MATERIALS AND METHODS: HCT-8, LoVo, CT-26, and WiDr were the colon cancer cell lines used for this study. The clonogenic assay was performed to obtain the cell survival curves and surviving fractions at a dose of 2 Gy (SF2) as the standard technique for radiosensitivity. Also, the MTT assay was performed for each of the cell lines (in vitro). To simulate clinical specimens, the cell lines were inoculated into nude mice, removed when the tumors reached 1 cm in diameter, and chopped. Next, the tumors were subjected to the same process involved with the MTT assay in vitro. The inhibition rates (IR) of 10 Gy or 20 Gy of irradiation for in vitro and ex vivo were calculated based on the optical density of the MTT assay, respectively. RESULTS: According to SF2 and the cell survival curve, the HCT-8 and WiDr cell lines were more resistant to radiation than LoVo and CT-26 (p<0.05). The IR was measured by in vitro. The MTT assay IR was 17.3%, 21%, 30% and 56.5% for the WiDr, HCT-8, LoVo and CT-26 cell lines, respectively. In addition, the IR measured ex vivo by the MTT assay was 23.5%, 26%, 38% and 53% in the HCT-8, WiDr, LoVo and CT-26 tumors, respectively. CONCLUSION: The radiosensitivity measured by the MTT assay was correlated with the measures obtained from the clonogenic assay. This result highlights the possibility that the MTT assay could be used in clinical specimens for individual radiosensitivity assays.

Distortion of the Dose Profile in a Three-dimensional Moving Phantom to Simulate Tumor Motion during Image-guided Radiosurgery / 대한방사선종양학회지

PURPOSE: Respiratory motion is a considerable inhibiting factor for precise treatment with stereotactic radiosurgery using the CyberKnife (CK). In this study, we developed a moving phantom to simulate three-dimensional breathing movement and investigated the distortion of dose profiles between the use of a moving phantom and a static phantom. MATERIALS AND METHODS: The phantom consisted of four pieces of polyethylene; two sheets of Gafchromic film were inserted for dosimetry. Treatment was planned to deliver 30 Gy to virtual tumors of 20, 30, 40, and 50 mm diameters using 104 beams and a single center mode. A specially designed robot produced three-dimensional motion in the right-left, anterior-posterior, and craniocaudal directions of 5, 10 and 20 mm, respectively. Using the optical density of the films as a function of dose, the dose profiles of both static and moving phantoms were measured. RESULTS: The prescribed isodose to cover the virtual tumors on the static phantom were 80% for 20 mm, 84% for 30 mm, 83% for 40 mm and 80% for 50 mm tumors. However, to compensate for the respiratory motion, the minimum isodose levels to cover the moving target were 70% for the 30~50 mm diameter tumors and 60% for a 20 mm tumor. For the 20 mm tumor, the gaps between the isodose curves for the static and moving phantoms were 3.2, 3.3, 3.5 and 1.1 mm for the cranial, caudal, right, and left direction, respectively. In the case of the 30 mm tumor, the gaps were 3.9, 4.2, 2.8, 0 mm, respectively. In the case of the 40 mm tumor, the gaps were 4.0, 4.8, 1.1, and 0 mm, respectively. In the case of the 50 mm diameter tumor, the gaps were 3.9, 3.9, 0 and 0 mm, respectively. CONCLUSION: For a tumor of a 20 mm diameter, the 80% isodose curve can be planned to cover the tumor; a 60% isodose curve will have to be chosen due to the tumor motion. The gap between these 80% and 60% curves is 5 mm. In tumors with diameters of 30, 40 and 50 mm, the whole tumor will be covered if an isodose curve of about 70% is selected, equivalent of placing a respiratory margin of below 5 mm. It was confirmed that during CK treatment for a moving tumor, the range of distortion produced by motion was less than the range of motion itself.

The Clinicopathological Factors That Determine a Local Recurrence of Rectal Cancers That Have Been Treated with Surgery and Chemoradiotherapy / 대한방사선종양학회지

PURPOSE: To evaluate the pathological prognostic factors related to local recurrence after radical surgery and adjuvant radiation therapy in advanced rectal cancer. MATERIALS AND METHODS: Fifty-four patients with advanced rectal cancer who were treated with radical surgery followed by adjuvant radiotherapy and chemotherapy between February 1993 and December 2001 were enrolled in this study. Among these patients, 14 patients experienced local recurrence. Tissue specimens of the patients were obtained to determine pathologic parameters such as histological grade, depth of invasion, venous invasion, lymphatic invasion, neural invasion and immunohistopathological analysis for expression of p53, Ki-67, c-erb, ezrin, c-met, phosphorylated S6 kinase, S100A4, and HIF-1 alpha. The correlation of these parameters with the tumor response to radiotherapy was statistically analyzed using the chi-square test, multivariate analysis, and the hierarchical clustering method. RESULTS: In univariate analysis, the histological tumor grade, venous invasion, invasion depth of the tumor and the over expression of c-met and HIF-1 alpha were accompanied with radioresistance that was found to be statistically significant. In multivariate analysis, venous invasion, invasion depth of tumor and over expression of c-met were also accompanied with radioresistance that was found to be statistically significant. By analysis with hierarchical clustering, the invasion depth of the tumor, and the over expression of c-met and HIF-1 alpha were factors found to be related to local recurrence. Whereas 71.4% of patients with local recurrence had 2 or more these factors, only 27.5% of patients without local recurrence had 2 or more of these factors. CONCLUSION: In advanced rectal cancer patients treated by radical surgery and adjuvant chemo-radiation therapy, the poor prognostic factors found to be related to local recurrence were HIF-1 alpha positive, c-met positive, and an invasion depth more than 5.5 mm. A prospective study is necessary to confirm whether these factors would be useful clinical parameters to measure and predict a radio-resistance group of patients.

Establishment of Culture System for In Vitro Culture of Mouse Pre-antral Follicles: Effect on In Vitro Growth by Thecal-Stromal Cells in Culture Medium without Hormones / 대한산부인과학회잡지

OBJECTIVE: This present study was conducted to examine the effects on in vitro growth of pre-antral mouse follicles by thecal-stromal cells attached to around the follicular membrane in culture medium without hormones. METHODS: Pre-antral follicles (100-130 micro meter) used in our studies were isolated mechanically by fine 30 G needles attached to 1 ml insulin syringe from mice ovaries of 20-25 days old female ICR strain. Isolated pre-antral follicles were divided into three groups by attached status of thecal-stromal cell layers to follicular membrane. Follicular Initial diameters of group I was 112.5 (mean) +/- 6.2 (SD) micro meter (n=31), group II was 112.8 +/- 7.8 micro meter (n=23), and group III was 115.1 +/- 6.5 micro meter (n=27). Divided pre-antral follicles were washed in fresh Ham's F-10 medium and cultured in 20 micro liter droplets of DMEM with glutamine, glucose and pyruvate under mineral oil on the 60 mm culture dish. All experimental media were supplemented with 10% FBS without hormones. Media were exchanged wholly by fresh media every 2 days in culture. Diameters of intrafollicular oocytes and cultured pre-antral follicles were measured using an precalibrated cross ocular micrometer at X200 every day during 6 days in vitro culture. Results were considered statistically significant when p value was less than 0.05 using Student's t-test. RESULTS: The mean and standard deviation (SD) of initial diameters of pre-antral follicles was 113.5 +/- 2.2 micro meter in three groups. Follicular growth rate of group III was significantly (p<0.05) higher in whole culture periods than group I and group II. Rate of follicular growth between group I and group II were not significant difference in culture for 1 to 3 days. However, group II was significantly higher than group I in culture for 4 days. Diameters of grown follicles for 6 days was 155.2 +/- 18.7 micro meter, 196.9 +/- 24.1 micro meter and 284.2 +/- 47.6 micro meter in group I, group II and group III, respectively. Growth rate of intrafollicular oocytes between three groups were not difference and revealed to continuous growth patterns in whole culture periods. Follicular diameter after culture for 7 days were not measured because of disruption of follicular structure or outgrowth of granulosa cells. CONCLUSION: Pre-antral follicles were grown very well in DMEM medium without hormones. Thecal- stromal cells attached to the surface of follicular membrane has acted effectively in vitro growth of follicles.

The Influences of Different Composition of Glucose and Pyruvate on In Vitro Development of Mouse Preimplantation Embryos in Medium with Glutamine / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to examine the effects on in vitro development of early preimplantation mouse embryos in DMEM medium with glutamine which was controlled by different composition of glucose and pyruvate. METHODS: Four hundred and nineteen mouse 2-cell embryos were cultured in four different media with different composition of glucose and pyruvate for 96 hours. The DMEM-G contained L-glutamine for energy sources was used for control group. Group I embryos were cultured in the medium that mixed one volume of DMEM-GGP contained L-glutamine, D-glucose and sodium pyruvate for energy sources with three volume of DMEM-G, and group II embryos were cultured in the medium that mixed with same volume of DMEM-G and DMEM-GGP, and group III embryos were cultured in DMEM-GGP. RESULTS: At 24 hours, the development into >or=3-cell was significantly higher (por=8-cell was significantly higher in group I (73.1%) than control (44.2%), group II (59.6%) and III (45.8%), and also group II was significantly higher than control and group III. At 48 hours, the development into >or=morula was significantly higher in group I (90.4%) and II (86.5%) than control (73.0%). However, the development into blastocyst, in group III (15.0%) was significantly lower than control, group I and II. At 72 hours, the development into >or=expanded blastocyst was significantly higher in group I (69.2%) than group III (47.7%), and total blastocyst was significantly higher in group I (80.8%) than control (66.3%) and group III (67.3%). At 96 hours, the development into >or=hatching blastocyst was significantly higher in group I (78.8%) than control (61.5%) and group III (57.9%), and also, total blastocyst was significantly higher in group I (85.6%) than control (69.2%) and group III (72.0%). CONCLUSION: The development of early preimplantation mouse embryos cultured in group I medium that mixed one volume of DMEM-GGP with three volume of DMEM-G was better than other groups during the culture period.

Cell-Specific Growth Inhibition of Human Cervical Cancer Cell by Recombinant Adenovirus p53 in vitro and in vivo / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Despite the significance of the p53 adenoviral vector in cancer gene therapy, an advanced strategy for the development of preferential tumor cell-specific delivery and the long-term persistent gene expression control of p53 are required. In this study, the time-course expression patterns of p53 and E6, on cervical cancer cells, were investigated to obtain a molecular level understanding of the cell-dependent tumor growth suppression effects of a recombinant adenovirus expressing p53, both in vitro and in vivo. MATERIALS AND METHODS: The expressions of p53 and E6 in CaSki, SiHa, HeLa, HeLaS3, C33A and HT3 cervical cancer cell lines were examined. After infection with AdCMVp53, the cell growth inhibition was studied via cell count, MTT and Neutral red assays. After transfecting the AdCMVp53 and AdCMVLacZ into the cancer cells-xenografted nude mice, the anti-tumor effects were investigated for one month. RESULTS: The p53 protein levels were more notably expressed in the CaSki and HeLa than in the SiHa and HeLaS3 On day 6, the p53 was only detected in the HeLaS3. In contrast, the p53 expression was highly maintained in the C33A and HT3. The E6 mRNA levels gradually decreased in only the CaSki and HeLa. The growth suppression effects also showed cell-dependent patterns, which were consistent with the reciprocal expression patterns of p53 and E6. After transfection of the AdCMVp53, into the CaSki- and SiHa-xenografted nude mice, the tumor size was remarkably decreased in the SiHa cells as compared to that in the AdCMVLacZ transfected mice, indicating cell-specific growth inhibition patterns. CONCLUSION: The adenovirus-mediated p53 gene transfection was very effective both in vitro and in vivo. Also, the anti-tumor effects were accomplished via the differential role of p53-specific apoptotic cell death, which was dependent on the cervical cancer cell line.

Study on Development of Mouse Preimplantation Embryos in Culture Media with Different Composition of Energy Sources / 대한산부인과학회잡지

OBJECTIVE: The objective of this study was to examine the effect on development of mouse preimplantation embryos in culture media with different composition of energy sources in vitro culture. METHODS: Two hundred and seventy one two-cell embryos were cultured in four different culture system for 96 hours. Group I (n=61) was cultured in DMEM-G (DMEM with glutamine) only, groupII (n=64) was cultured in DMEM-GGP (DMEM with glutamine, glucose and pyruvate) only, group III (n=72) was cultured for 48 hours in DMEM-G and then transferred to DMEM-GGP and group IV (n=74) was cultured for 48 hours in DMEM-GGP and then transferred to DMEM-G. Development of embryos in each group was observed every 24 hours. RESULTS: After 24 hours, the rate of development > or = 3-cell was significantly higher in groupII (87.5%) and IV (86.5%) compared with group I (59.0%) and III (62.5%). After 48 hours, the rate of development into > or = morula stage was significantly higher in GroupII (79.7%) and IV (86.5%) compared with group I (34.4%) and III (37.5%). After 72 hours, the rate of development into blastocyst was significantly higher in group IV (74.3%) compared with group I (49.2%) and III (45.8%). After 96 hours, the rate of development into > or = expanded blastocyst was significantly higher in group IV (70.3%) compared with group I (32.8%),II (53.1%), and group III (40.3%). CONCLUSION: Mouse preimplantation embryos development was the most effective in culture system with DMEM-GGP for 48 hours and then transferred to DMEM-G.

Total Laparoscopic Hysterectomy using Modified Bae's Uterine Elevator / 대한산부인과학회잡지

OBJECTIVE: Hysterectomy is one of the most common gynecological operations. The objective of this study was to introduce a new uterine elevator for total laparoscopic hysterectomy. METHODS: Bae's uterine elevator was modified for laparoscopic hysterectomy. Modified Bae's uterine elevator was 5 cm longer than original one and handle was modified to vertical position and stopper, silicon tube and silicon adapter for colpotomizer was installed on the shaft. Three hundred and fifty seven cases of total laparoscopic hysterectomies using modified Bae's uterine elevator were performed from Jan 1999 to Jun 2000. RESULTS: Mean age of the patients was 41.8, operation time was 48.3 minutes and uterine weight was 245.5 gm. Leiomyoma was the most common cause of hysterectomies (70.9%), and followed by adenomyosis (16.2%), endometriosis (7.6%). There were no major operative complications such as vascular, bladder, ureter or intestinal injuries. CONCLUSIONS: Three hundred and fifty seven cases of total laparoscopic hysterectomies using modified Bae's uterine elevator were performed successfully without any major complications. Modified Bae's uterine elevator was very convenient for uterine manipulation during total laparoscopic hysterectomy.

Prophylactic antibiotics in elective cesarean section / 대한산부인과학회잡지

OBJECTIVE: To evaluate effectiveness of short-course administration of prophylactic antibiotics in elective cesarean section compared with multiple, long-course administration. METHODS: Forty women undergoing elective cesarean section had prophylactic antibiotics administration preoperatively and 2 times more within 24 hours after operation. Forty women was control group who had antibiotics administration postoperatively 5 or 6 times with multiple regimens and 7 days more per oral. Postpartum complications including febrile morbidity, endometritis, wound infection, urinary tract infection were recorded, as were the duration of hospital stay and need for therapeutic antibiotics. RESULTS: Postpartum complications including febrile morbidity, endometritis, wound infection and urinary tract infection had no difference between two groups significantly. Also, their hospital stay had no difference significantly. CONCLUSION: Prophylactic and short-course antibiotics administration in elective cesarean section is considered to have no difference in comparison with multiple, long-course post-operative administration. Short- course prophylactic antibiotics administration will reduce side effect of drugs and resistance. Also it will provide better cost effectiveness.