1.Comparing the efficacy of combined versus single immune cell adaptive therapy targeting colorectal cancer
Denis Nchang CHE ; NaHye LEE ; Hyo-Jung LEE ; Yea-Won KIM ; Solongo BATTULGA ; Ha Na LEE ; Won-Kook HAM ; Hyunah LEE ; Mi Young LEE ; Dawoon KIM ; Haengji KANG ; Subin YUN ; Jinju PARK ; Daeyoun David WON ; Jong Kyun LEE
Annals of Coloproctology 2024;40(2):121-135
Purpose:
Colorectal cancer (CRC) is the most frequent cancer with limited therapeutic achievements. Recently, adoptive cellular immunotherapy has been developed as an antitumor therapy. However, its efficacy has not been tested in CRC. This study investigated the ability of an immune cell cocktail of dendritic cells (DCs), T cells, and natural killer (NK) cells to overcome immunological hurdles and improve the therapeutic efficacy of cell therapy for CRC.
Methods:
CRC lysate-pulsed monocyte-derived DCs (Mo-DCs), CRC antigen-specifically expanded T cells (CTL), and in vitro-expanded NK cells were cultured from patient peripheral blood mononuclear cells (PBMC). The ability of the combined immune cells to kill autologous tumor cells was investigated by co-culturing the combined immune cells with patient-derived tumor cells.
Results:
The Mo-DCs produced expressed T cell co-stimulating molecules like CD80, CD86, human leukocyte antigen (HLA)-DR and HLA-ABC, at high levels and were capable of activating naive T cells. The expanded T cells were predominantly CD8 T cells with high levels of CD8 effector memory cells and low levels of regulatory T cells. The NK cells expressed high levels of activating receptors and were capable of killing other cancer cell lines (K562 and HT29). The immune cell cocktail demonstrated a higher ability to kill autologous tumor cells than single types. An in vivo preclinical study confirmed the safety of the combined immune cell adaptive therapy showing no therapy-related death or general toxicity symptoms.
Conclusion
The results suggested that combined immune cell adaptive therapy could overcome the limited efficacy of cell immunotherapy.
2.Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data
Kyung-Nam KOH ; Jung Woo HAN ; Hyoung Soo CHOI ; Hyoung Jin KANG ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Kyung Taek HONG ; Jung Yoon CHOI ; Sung Han KANG ; Hyery KIM ; Ho Joon IM ; Seung Min HAHN ; Chuhl Joo LYU ; Hee-Jo BAEK ; Hoon KOOK ; Kyung Mi PARK ; Eu Jeen YANG ; Young Tak LIM ; Seongkoo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Bin CHO ; Meerim PARK ; Hyeon Jin PARK ; Byung-Kiu PARK ; Jun Ah LEE ; Jun Eun PARK ; Soon Ki KIM ; Ji Yoon KIM ; Hyo Sun KIM ; Youngeun MA ; Kyung Duk PARK ; Sang Kyu PARK ; Eun Sil PARK ; Ye Jee SHIM ; Eun Sun YOO ; Kyung Ha RYU ; Jae Won YOO ; Yeon Jung LIM ; Hoi Soo YOON ; Mee Jeong LEE ; Jae Min LEE ; In-Sang JEON ; Hye Lim JUNG ; Hee Won CHUEH ; Seunghyun WON ;
Cancer Research and Treatment 2023;55(1):279-290
Purpose:
Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea.
Materials and Methods:
From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed.
Results:
Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001).
Conclusion
The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.
3.A Standardized Pathology Report for Gastric Cancer: 2nd Edition
Young Soo PARK ; Myeong-Cherl KOOK ; Baek-hui KIM ; Hye Seung LEE ; Dong-Wook KANG ; Mi-Jin GU ; Ok Ran SHIN ; Younghee CHOI ; Wonae LEE ; Hyunki KIM ; In Hye SONG ; Kyoung-Mee KIM ; Hee Sung KIM ; Guhyun KANG ; Do Youn PARK ; So-Young JIN ; Joon Mee KIM ; Yoon Jung CHOI ; Hee Kyung CHANG ; Soomin AHN ; Mee Soo CHANG ; Song-Hee HAN ; Yoonjin KWAK ; An Na SEO ; Sung Hak LEE ; Mee-Yon CHO ;
Journal of Gastric Cancer 2023;23(1):107-145
The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements.The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
4.A standardized pathology report for gastric cancer: 2nd edition
Young Soo PARK ; Myeong-Cherl KOOK ; Baek-hui KIM ; Hye Seung LEE ; Dong-Wook KANG ; Mi-Jin GU ; Ok Ran SHIN ; Younghee CHOI ; Wonae LEE ; Hyunki KIM ; In Hye SONG ; Kyoung-Mee KIM ; Hee Sung KIM ; Guhyun KANG ; Do Youn PARK ; So-Young JIN ; Joon Mee KIM ; Yoon Jung CHOI ; Hee Kyung CHANG ; Soomin AHN ; Mee Soo CHANG ; Song-Hee HAN ; Yoonjin KWAK ; An Na SEO ; Sung Hak LEE ; Mee-Yon CHO ;
Journal of Pathology and Translational Medicine 2023;57(1):1-27
The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
5.Definitions of Chronic Obstructive Pulmonary Disease and Chronic Obstructive Pulmonary Disease Exacerbation: A Modified Delphi Survey
Yong Bum PARK ; Jin Hwa LEE ; Seung Won RA ; Hye Yun PARK ; Ji Ye JUNG ; Young Ae KANG ; Chin Kook RHEE ; Deog Kyeom KIM ; Kwang Ha YOO ; Yong Il HWANG ; Seong Yong LIM ; Jae Seung LEE ; Kyung-Wook JO ; Yeon-Mok OH
Tuberculosis and Respiratory Diseases 2023;86(3):196-202
Background:
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) update 2023 proposed new definitions of chronic obstructive pulmonary disease (COPD) and COPD exacerbation. However, an agreement on the definitions has not been made, either internationally or domestically. This study aimed to reach an agreement between experts on the new definitions of COPD and COPD exacerbation in South Korea.
Methods:
A modified Delphi method was used to make an agreement on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023. We performed two rounds of the survey including 15 Korean experts on COPD, asthma, and tuberculosis.
Results:
More than two-thirds of the experts agreed on 12 of the 13 statements related to the definitions of COPD and COPD exacerbation in the two rounds of the survey. The experts agreed on the definitions of COPD and COPD exacerbation that should be revised in line with the definitions proposed by the GOLD update 2023. However, the experts showed an uncertain opinion on the statement that the definition of COPD includes patients with persistent airflow obstruction due to bronchiectasis.
Conclusion
Based on this Delphi survey, experts’ agreement was made on the definitions of COPD and COPD exacerbation proposed by the GOLD update 2023.
6.Glycemic Control and Adverse Clinical Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: Results from KNOW-CKD
Ga Young HEO ; Hee Byung KOH ; Hyung Woo KIM ; Jung Tak PARK ; Tae-Hyun YOO ; Shin-Wook KANG ; Jayoun KIM ; Soo Wan KIM ; Yeong Hoon KIM ; Su Ah SUNG ; Kook-Hwan OH ; Seung Hyeok HAN
Diabetes & Metabolism Journal 2023;47(4):535-546
Background:
The optimal level of glycosylated hemoglobin (HbA1c) to prevent adverse clinical outcomes is unknown in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).
Methods:
We analyzed 707 patients with CKD G1-G5 without kidney replacement therapy and T2DM from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort study. The main predictor was time-varying HbA1c level at each visit. The primary outcome was a composite of development of major adverse cardiovascular events (MACEs) or all-cause mortality. Secondary outcomes included the individual endpoint of MACEs, all-cause mortality, and CKD progression. CKD progression was defined as a ≥50% decline in the estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.
Results:
During a median follow-up of 4.8 years, the primary outcome occurred in 129 (18.2%) patients. In time-varying Cox model, the adjusted hazard ratios (aHRs) for the primary outcome were 1.59 (95% confidence interval [CI], 1.01 to 2.49) and 1.99 (95% CI, 1.24 to 3.19) for HbA1c levels of 7.0%–7.9% and ≥8.0%, respectively, compared with <7.0%. Additional analysis of baseline HbA1c levels yielded a similar graded association. In secondary outcome analyses, the aHRs for the corresponding HbA1c categories were 2.17 (95% CI, 1.20 to 3.95) and 2.26 (95% CI, 1.17 to 4.37) for MACE, and 1.36 (95% CI, 0.68 to 2.72) and 2.08 (95% CI, 1.06 to 4.05) for all-cause mortality. However, the risk of CKD progression did not differ between the three groups.
Conclusion
This study showed that higher HbA1c levels were associated with an increased risk of MACE and mortality in patients with CKD and T2DM.
7.Fibrinous pleuritis associated with Streptococcus canis in a leopard cat (Prionailurus bengalensis euptilurus)
Min-Gyeong SEO ; Kook-Young HAN ; Sang-Hyun KIM ; Chang Keun KANG ; Jong-Hyun KIM ; Il-Hwa HONG
Journal of Veterinary Science 2023;24(5):e68-
Leopard cat (Prionailurus bengalensis euptilurus) is a small wild cat assessed as an endangered wildlife in Korea. There have been very few reports of their diseases. Herein, we describe fibrinous pleuritis caused by Streptococcus canis infection with excessive pleural effusion, hydropericardium, mild ascites, and liver fibrosis in a leopard cat. S. canis is a commensal microflora in domestic cats and often affects the upper respiratory tract inducing chronic and severe respiratory diseases. However, there is no literature regarding the S. canis in leopard cats. Therefore, we first report fibrinous pleuritis associated with an S. canis infection in a leopard cat.
8.Predictive performance of the new race-free Chronic Kidney Disease Epidemiology Collaboration equations for kidney outcome in Korean patients with chronic kidney disease
Hyoungnae KIM ; Young Youl HYUN ; Hae-Ryong YUN ; Young Su JOO ; Yaeni KIM ; Ji Yong JUNG ; Jong Cheol JEONG ; Jayoun KIM ; Jung Tak PARK ; Tae-Hyun YOO ; Shin-Wook KANG ; Kook-Hwan OH ; Seung Hyeok HAN ;
Kidney Research and Clinical Practice 2023;42(4):501-511
The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). Methods: This study included 2,149 patients with CKD G1–G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). Results: When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922–0.960) and eGFRcr (0.941; 95% CI, 0.922–0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW). Conclusion: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.
9.Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management ofautosomal domInAnt poLycystic kidney disease (ESSENTIAL): short-term outcomes during the titration period
Hyuk HUH ; Yong Soo KIM ; Wookyung CHUNG ; Yong Lim KIM ; Yaerim KIM ; Seungyeup HAN ; Yeonsoon JUNG ; Ki Young NA ; Kyu Beck LEE ; Yun Kyu OH ; Hyeong Cheon PARK ; Seung Hyeok HAN ; Tae Hyun YOO ; Yeong Hoon KIM ; Soo Wan KIM ; Kang Wook LEE ; Hayne Cho PARK ; Sung Gyun KIM ; Hyunsuk KIM ; Chang Hwa LEE ; Kyongtae T. BAE ; Kook Hwan OH ; Curie AHN ; Hyun Jin RYU ; Yong Chul KIM
Kidney Research and Clinical Practice 2023;42(2):216-228
Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods: This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results: After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion: We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.
10.Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group
Kyung Mi PARK ; Keon Hee YOO ; Seong Koo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Hee Young JU ; Hong Hoe KOO ; Chuhl Joo LYU ; Seung Min HAN ; Jung Woo HAN ; Jung Yoon CHOI ; Kyung Taek HONG ; Hyoung Jin KANG ; Hee Young SHIN ; Ho Joon IM ; Kyung-Nam KOH ; Hyery KIM ; Hoon KOOK ; Hee Jo BAEK ; Bo Ram KIM ; Eu Jeen YANG ; Jae Young LIM ; Eun Sil PARK ; Eun Jin CHOI ; Sang Kyu PARK ; Jae Min LEE ; Ye Jee SHIM ; Ji Yoon KIM ; Ji Kyoung PARK ; Seom Gim KONG ; Young Bae CHOI ; Bin CHO ; Young Tak LIM
Cancer Research and Treatment 2022;54(1):269-276
Purpose:
Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea.
Materials and Methods:
Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively.
Results:
Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020).
Conclusion
This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

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