1.Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients
Wonyoung CHOI ; Yun-Hee KIM ; Sang Myung WOO ; Yebeen YU ; Mi Rim LEE ; Woo Jin LEE ; Jung Won CHUN ; Sung Hoon SIM ; Heejung CHAE ; Hyoeun SHIM ; Keun Seok LEE ; Sun-Young KONG
Cancer Research and Treatment 2023;55(4):1077-1086
Purpose:
Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.
Materials and Methods:
Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.
Results:
We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients.
Conclusion
Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.
2.Effects of Particulate Matter Exposure on the Eustachian Tube and Middle Ear Mucosa of Rats
Hyun Min LEE ; Youn-Suk SON ; Hyang-Sook KIM ; Joo-Young KIM ; Seok-Hyun KIM ; Jung Hee LEE ; Sung-Won CHOI ; Se-Joon OH ; Soo-Keun KONG ; Moo Jin BAEK ; Il-Woo LEE
Clinical and Experimental Otorhinolaryngology 2023;16(3):225-235
Objectives:
. Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats.
Methods:
. Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR).
Results:
. In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1β significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01).
Conclusion
. The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.
3.Outcomes of Endoscopic Tympanoplasty for Large Perforations: A Multicenter Retrospective Study in South Korea
Sung-Won CHOI ; Il Joon MOON ; Ji Eun CHOI ; Woo Seok KANG ; In Seok MOON ; Soo-Keun KONG ; Hyong Ho CHO ; Il-Woo LEE ; Jong Woo CHUNG ; Dong Gu HUR ; Jong Dae LEE
Clinical and Experimental Otorhinolaryngology 2023;16(2):125-131
Objectives:
. Endoscopic tympanoplasty (ET) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility for the treatment of tympanic membrane (TM) perforations. However, the literature on surgical outcomes for large TM perforations is lacking and limited to small series. This study aimed to evaluate the clinical benefits of ET for large TM perforations.
Methods:
. This retrospective cohort study was conducted at nine tertiary referral hospitals in South Korea, where 252 patients who underwent ET as primary surgery from September 2019 to August 2021 were included. The outcome measures included the graft success rate and pre- and postoperative audiometric data.
Results:
. In 239 patients, the graft success rate of ET for large or subtotal perforations was 86.2% (206 patients), while the graft failure rate was 13.8% (33 patients). The graft failure rate was directly correlated with surgical techniques, including overlay and medial or lateral underlay tympanoplasty (P=0.027). Lateral underlay tympanoplasty showed the most favorable results. Sex, laterality, etiology, site and size of perforation, operation time, and graft materials did not vary significantly between the graft success and failure groups (P>0.05). The mean air-bone gap (ABG) improved significantly in both groups (graft success group: 10.0±0.6 dB and graft failure group: 7.7±0.3 dB; P<0.001). However, the ABG improvement did not significantly differ between the groups. Analysis of covariance revealed that the postoperative 500-Hz bone conduction threshold improved after successful ET (adjusted coefficient, –11.351; 95% confidence interval, –21.491 to –1.212; P=0.028).
Conclusion
. This study involved the largest population to date of large TM perforations treated by ET. The study findings suggest that ET is feasible and effective in treating large TM perforations.
4.Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy
Bang Wool EOM ; Joongyub LEE ; In Seob LEE ; Young-Gil SON ; Keun Won RYU ; Sung Geun KIM ; Hyoung-Il KIM ; Young-Woo KIM ; Seong-Ho KONG ; Oh Kyoung KWON ; Ji-Ho PARK ; Ji Yeong AN ; Chang Hyun KIM ; Byoung-Jo SUH ; Hong Man YOON ; Myoung Won SON ; Ji Yeon PARK ; Jong-Min PARK ; Sang-Ho JEONG ; Moon-Won YOO ; Geum Jong SONG ; Han-Kwang YANG ; Yun-Suhk SUH ; Ki Bum PARK ; Sang-Hoon AHN ; Dong Woo SHIN ; Ye Seob JEE ; Hye-Seong AHN ; Sol LEE ; Jae Seok MIN ; Haejin IN ; Ahyoung KIM ; Hoon HUR ; Hyuk-Joon LEE ;
Cancer Research and Treatment 2021;53(3):763-772
Purpose:
Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.
Results
The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
5.Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy
Bang Wool EOM ; Joongyub LEE ; In Seob LEE ; Young-Gil SON ; Keun Won RYU ; Sung Geun KIM ; Hyoung-Il KIM ; Young-Woo KIM ; Seong-Ho KONG ; Oh Kyoung KWON ; Ji-Ho PARK ; Ji Yeong AN ; Chang Hyun KIM ; Byoung-Jo SUH ; Hong Man YOON ; Myoung Won SON ; Ji Yeon PARK ; Jong-Min PARK ; Sang-Ho JEONG ; Moon-Won YOO ; Geum Jong SONG ; Han-Kwang YANG ; Yun-Suhk SUH ; Ki Bum PARK ; Sang-Hoon AHN ; Dong Woo SHIN ; Ye Seob JEE ; Hye-Seong AHN ; Sol LEE ; Jae Seok MIN ; Haejin IN ; Ahyoung KIM ; Hoon HUR ; Hyuk-Joon LEE ;
Cancer Research and Treatment 2021;53(3):763-772
Purpose:
Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.
Results
The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
6.Extratympanic Observation of Middle and Inner Ear Structures in Rodents Using Optical Coherence Tomography
Se-Joon OH ; Il-Woo LEE ; Soo-Geun WANG ; Soo-Keun KONG ; Hong-Ki KIM ; Eui-Kyung GOH
Clinical and Experimental Otorhinolaryngology 2020;13(2):106-112
Objectives:
. This study aimed to investigate whether optical coherence tomography (OCT) provides useful information about the microstructures of the middle and inner ear via extratympanic approach and thereby could be utilized as an alternative diagnostic technology in ear imaging.
Methods:
. Five rats and mice were included, and the swept-source OCT system was applied to confirm the extent of visibility of the middle and inner ear and measure the length or thickness of the microstructures in the ear. The cochlea was subsequently dissected following OCT and histologically evaluated to compare with the OCT images.
Results:
. The middle ear microstructures such as ossicles, stapedial artery and oval window through the tympanic membrane with the OCT could be confirmed in both rats and mice. It was also possible to obtain the inner ear images such as each compartment of the cochlea in the mice, but the bone covering bulla needed to be removed to visualize the inner ear structures in the rats which had thicker bulla. The bony thickness covering the cochlea could be measured, which showed no significant differences between OCT and histologic image at all turns of cochlea.
Conclusion
. OCT has been shown a promising technology to assess real-time middle and inner ear microstructures noninvasively with a high-resolution in the animal model. Therefore, OCT could be utilized to provide additional diagnostic information about the diseases of the middle and inner ear.
7.Hearing Outcome According to the Intratympanic Steroid Injection Starting Timing in Combined Intratympanic and Oral Steroid Treatment for Idiopathic Sudden Sensorineural Hearing Loss
Hyun Min LEE ; Da Hee PARK ; Dong Jo KIM ; Sung Won CHOI ; Se Joon OH ; Soo Keun KONG ; Il Woo LEE
Korean Journal of Otolaryngology - Head and Neck Surgery 2020;63(10):448-457
Background and Objectives:
The combined intratympanic and oral steroid treatment has been accepted as effective treatment strategy for idiopathic sudden sensorineural hearing loss (ISSNHL). However, the treatment protocol of combined treatment for ISSNHL has not been established. In this study, we investigated whether hearing outcome differed according to different starting timing of intratympanic steroid injection (ITSI) in combined treatment for ISSNHL.Subjects and Method Tertiary academic referral center-based retrospective medical records of idiopathic 144 ISSNHL patients who received combined treatment from January 2015 to April 2018 were reviewed. All patients underwent a 2-week oral systemic steroid treatment and multiple ITSI. The hearing results of 3 months after treatment were compared according to the timing of ITSI.
Results:
The mean pure tone audiogram gain was 24.3±23.6 dB. When Siegel’s criteria was applied, the overall rate of hearing improvement was 63.9% (92/144). The rate of hearing improvement was significantly higher in women (p=0.043) statistically, and there was a statistically significant lower rate of recovery in the former history of hearing loss (p<0.01) or otitis media (p<0.01). Moreover, the shorter the delay between symptom onset and initial ITSI, greater the statistical significance of hearing recovery rate became (p<0.01).
Conclusion
The result of this study suggests that early ITSI during combined intratympanic and oral steroid treatment increases the chance of hearing recovery.
8.The pattern of postoperative quality of life following minimally invasive gastrectomy for gastric cancer: a prospective cohort from Korean multicenter robotic gastrectomy trial
Jong-Ho CHOI ; Sang-Uk HAN ; Han-Kwang YANG ; Young-Woo KIM ; Keun Won RYU ; Joong-Min PARK ; Ji Yeong AN ; Min-Chan KIM ; Sungsoo PARK ; Kyo Young SONG ; Sung Jin OH ; Seong-Ho KONG ; Byoung Jo SUH ; Dae Hyun YANG ; Tae Kyung HA ; Hyoung-Il KIM ; Woo Jin HYUNG ; Hyuk-Joon LEE
Annals of Surgical Treatment and Research 2020;99(5):275-284
Purpose:
Quality of life (QOL) has become important in the trend of emphasizing patient satisfaction. This study aimed to evaluate the QOL in patients who underwent laparoscopic or robotic gastrectomy for gastric cancer.
Methods:
A prospective trial was performed involving patients who underwent laparoscopic or robotic gastrectomy for primary gastric cancer at 11 hospitals in Korea. Within this comparative trial, QOL, postoperative pain, and long-term complications were exanimated. The quality-of-life questionnaire (QLQ)-C30 and QLQ-STO22 developed by the European Organization for Research and Treatment of Cancer were used for the QOL survey. We compared the data after dividing it into several types of characteristics as follows; device (robotic or laparoscopic), operation type, pathological stage, and sex.Biased components were extracted by logistic regression analysis. Propensity score matching was applied to the data set with the biased components.
Results:
In total, 434 patients (211 for laparoscopic surgery and 223 for robotic surgery) were enrolled, out of which 321 patients who responded to both preoperative and postoperative surveys were selected for analysis. Robotic gastrectomy was not different from laparoscopic gastrectomy with respect to postoperative QOL. Distal gastrectomy showed better scores than total gastrectomy in terms of role functioning, social functioning, fatigue, nausea/vomiting, pain, dyspnea, constipation, financial difficulties, dysphagia, eating restrictions, anxiety, taste, and body image. Male patients showed better scores on the 19 scales compared to female patients.
Conclusion
Robotic and laparoscopic approaches for gastric cancer surgery did not differ from each other with respect to QOL. Distal gastrectomy resulted in better QOL than total gastrectomy.
9.Development of a Korean-Type Qualitative Case History Tinnitus Questionnaire.
Se Joon OH ; Eui Kyung GOH ; Soo Keun KONG ; Shi Nae PARK ; June CHOI ; Hyun Min LEE ; Seung Chul HA ; Il Woo LEE
Korean Journal of Otolaryngology - Head and Neck Surgery 2018;61(4):182-192
BACKGROUND AND OBJECTIVES: Qualitative and quantitative data of tinnitus are both important to obtain necessary information for assessing tinnitus evaluation. But contrary to quantitative questionnaire, qualitative data is not standardized in Korea. This study aimed to standardize the qualitative data of tinnitus by developing a Korean-type integrated qualitative tinnitus questionnaires. SUBJECTS AND METHOD: A cross-sectional survey of Korean otolaryngologists was performed. The questionnaires were administered to otologists who were registered as participants in the tinnitus study group of otology research interest group (ORIG). RESULTS: Most of the otologists (100% of responders) have used the quantitative tinnitus questionnaire measurement (90.5%), but only 76% have used qualitative tinnitus questionnaire. From the responses of otologists who regularly use qualitative questionnaire, 25 items were adopted from the 35 item list. Questionnaire items were selected according to the frequency of listed items in the individual lists. CONCLUSION: We made a qualitative questionnaire consisting of 25 items that were essential and widely accepted. We expect this work will integrate and standardize qualitative tinnitus questionnaires in Korea.
Cross-Sectional Studies
;
Korea
;
Methods
;
Otolaryngology
;
Public Opinion
;
Qualitative Research
;
Tinnitus*
10.Anatomical Relationships between Eustachian Tube and Internal Carotid Artery Using Computed Tomography.
Jae Hoon JUNG ; Eui Kyung GOH ; Il Woo LEE ; Jae Hwan JUNG ; Se Joon OH ; Soo Keun KONG
Korean Journal of Otolaryngology - Head and Neck Surgery 2015;58(12):848-854
BACKGROUND AND OBJECTIVES: It is important to figure out the location between the internal carotid artery (ICA) and the Eustachian tube (ET) for conducting safe ET surgery. Using computed tomography (CT), this study was aimed to evaluate the anatomical relationship between ET and ICA according to age and gender. SUBJECTS AND METHOD: Contrast enhanced CT scans of the paranasal sinus taken between January 2005 and December 2010 were reviewed retrospectively. A total of 216 patients (432 ears) were enrolled. In each patient, we measuresed the distance from the anterior cushion of torus tubarius to ICA (AC-ICA), the distance from the posterior cushion of torus tubarius to ICA (PC-ICA), the distance from the Rosenmuller fossa to ICA, the shortest distance from ET lumen to ICA (ET-ICA), and the angle between the imaginary lines from the orifice of ET to the posterior end point of nasal septum to point ICA (ET-NS-ICA). Patients were divided into 10 groups based on age difference of 15-years. RESULTS: For the female patients aged 65 to 80 years old, AC-ICA, PC-ICA were closest from the nasopharynx. For this group, at p<0.05, the distances of AC-ICA, PC-ICA and ET-ICA showed a negative correlation with increasing age, whereasET-NS-ICA (p<0.05) showed a positive correlation, indicating a tendency of medicalization with increased age. CONCLUSION: The distance between ET and ICA represents a variety of distribution according to gender and age. When performing a surgery for the nasopharyngeal portion of ET, the surgeon should be aware of the location of ICA in the preoperative CT findings.
Carotid Artery, Internal*
;
Eustachian Tube*
;
Female
;
Humans
;
Medicalization
;
Nasal Septum
;
Nasopharynx
;
Retrospective Studies
;
Tomography, X-Ray Computed

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