1.Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13)
Dong-Hoe KOO ; Minkyu JUNG ; Yeul Hong KIM ; Hei-Cheul JEUNG ; Dae Young ZANG ; Woo Kyun BAE ; Hyunki KIM ; Hyo Song KIM ; Choong-kun LEE ; Woo Sun KWON ; Hyun Cheol CHUNG ; Sun Young RHA
Cancer Research and Treatment 2024;56(4):1136-1145
Purpose:
Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials and Methods:
Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity.
Results:
RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D.
Conclusion
A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.
2.Outcomes of Hip Arthroplasty in Patients with Preoperative Thrombocytopenia
Jong Jin GO ; Minji HAN ; Tae Woo KIM ; Byung Kyu PARK ; Jung-Wee PARK ; Young-Kyun LEE
Clinics in Orthopedic Surgery 2024;16(5):711-717
Background:
Thrombocytopenia is a condition where platelet counts are below the normal range (< 150 ×103 /µL), resulting in a higher risk of bleeding and affecting the results of hip arthroplasty. We assessed the impact of preoperative platelet counts on the clinical results of patients who underwent hip arthroplasty.
Methods:
Between April 2003 and March 2023, 437 patients (451 hips), who had preoperative thrombocytopenia of less than 150 ×103 /µL platelets, underwent hip arthroplasty. Preoperative platelet levels were categorized into severe thrombocytopenia (< 50 ×103 /µL) and non-severe thrombocytopenia (50–149 ×103 /µL). Total blood loss, operation time, requirement of transfusion, amount of transfusion, duration of surgical wound oozing, length of hospital stay, mortality rate at 1 year after surgery, and any complication were compared between the 2 groups.
Results:
No notable differences were observed in the surgery time or the total amount of blood loss between the groups. The requirement of transfusion and the amount of transfused blood were higher in the severe thrombocytopenia group. Prolonged oozing was found in around 18% in both groups, while periprosthetic joint infections occurred in 3 of the non-severe thrombocytopenia group. No significant difference was noted in the duration of hospital stay (25.6 ± 18.3 days vs. 19.4 ± 16.6 days, p = 0.067) and 1-year mortality (22.2% vs. 11.8%, p = 0.110).
Conclusions
Hip arthroplasties are safe for patients with low platelet counts and do not lead to prolonged hospital stays. On the other hand, patients with severe thrombocytopenia tend to need blood transfusions more frequently than those with less severe thrombocytopenia.
3.Reliability of the 2018 Revised Version of AO/OTA Classification for Femoral Shaft Fractures
Jung-Wee PARK ; Woo-Lam JO ; Byung Kyu PARK ; Jong Jin GO ; Minji HAN ; Sungha CHUN ; Young-Kyun LEE
Clinics in Orthopedic Surgery 2024;16(5):688-693
Background:
The Arbeitsgemeinschaft für Osteosynthesefragen (AO) and the Orthopaedic Trauma Association (OTA) classification system for diaphyseal fracture has been recently revised to refine and enhance the accuracy of fracture categorization. This study aimed to investigate the interobserver reliability of the new AO/OTA classification and to compare it with the older version in femoral shaft fractures.
Methods:
We retrospectively analyzed 139 patients (mean age, 43.8 ± 19.5 years; 92 men and 47 women) with femoral shaft fractures who were treated from 2003 to 2017. Four well-trained observers independently classified each fracture following the previous and revised AO/OTA classification system. We calculated the Fleiss kappa for the interobserver reliability.
Results:
The previous classification showed the kappa value of 0.580 (95% confidence interval [CI], 0.547–0.613), and the revised version showed 0.528 (95% CI, 0.504–0.552). Both the old and the revised versions showed moderate reliability.
Conclusions
Our study highlights the moderate interobserver reliability of both the previous and new AO/OTA classification systems for diaphyseal femur fractures. These findings emphasize the importance of standardized systems in clinical decision-making and underscore the need for ongoing education and collaboration to enhance fracture classification.
4.Survival Outcomes Based on Axillary Surgery in Ductal Carcinoma In Situ:A Nationwide Study From the Korean Breast Cancer Society
Bong Kyun KIM ; Joohyun WOO ; Jeeyeon LEE ; Eunhye KANG ; Soo Yeon BAEK ; Seokwon LEE ; Hyouk Jin LEE ; Jina LEE ; Woo Young SUN ;
Journal of Breast Cancer 2024;27(1):1-13
Purpose:
In total mastectomy (TM), sentinel lymph node biopsy (SLNB) is recommended but can be omitted for breast-conserving surgery (BCS) in patients with ductal carcinoma in situ (DCIS). However, concerns regarding SLNB-related complications and their impact on quality of life exist. Consequently, further research is required to evaluate the role of axillary surgeries, including SLNB, in the treatment of TM. We aimed to explore the clinicopathological factors and outcomes associated with axillary surgery in patients with a final diagnosis of pure DCIS who underwent BCS or TM.
Methods:
We retrospectively analyzed large-scale data from the Korean Breast Cancer Society registration database, highlighting on patients diagnosed with pure DCIS who underwent surgery and were categorized into two groups: BCS and TM. Patients were further categorized into surgery and non-surgery groups according to their axillary surgery status. The analysis compared clinicopathological factors and outcomes according to axillary surgery status between the BCS and TM groups.
Results:
Among 18,196 patients who underwent surgery for DCIS between 1981 and 2022, 11,872 underwent BCS and 6,324 underwent TM. Both groups leaned towards axillary surgery more frequently for large tumors. In the BCS group, clinical lymph node status was associated with axillary surgery (odds ratio, 11.101; p = 0.003). However, in the TM group, no significant differences in these factors were observed. Survival rates did not vary between groups according to axillary surgery performance.
Conclusion
The decision to perform axillary surgery in patients with a final diagnosis of pure DCIS does not affect the prognosis, regardless of the breast surgical method.Furthermore, regardless of the breast surgical method, axillary surgery, including SLNB, should be considered for high-risk patients, such as those with large tumors. This may reduce unnecessary axillary surgery and enhance the patients’ quality of life.
5.Fracture Liaison Service in Korea: 2022 Position Statement of the Korean Society for Bone and Mineral Research
Jae-Young LIM ; Young Yul KIM ; Jin-Woo KIM ; Seongbin HONG ; Kyunghoon MIN ; Jaewon BEOM ; Byung-Ho YOON ; Sang Yoon LEE ; Sung Hye KONG ; Jun-Il YOO ; Myung Sook PARK ; Jae-Hwi NHO ; Sangbong KO ; Min Wook JOO ; Dong Hwan KIM ; Chan Ho PARK ; Tae-Young KIM ; Seil SOHN ; So Young PARK ; A Ram HONG ; Young Joo KWON ; Sung Bae PARK ; Young-Kyun LEE ; Nam Hoon MOON ; Bo Ryun KIM ; Yongsoon PARK ; Yonghan CHA ; Yong-Chan HA
Journal of Bone Metabolism 2023;30(1):31-36
Osteoporosis and osteoporotic fractures cause socioeconomic concerns, and medical system and policies appear insufficient to prepare for these issues in Korea, where the older adult population is rapidly increasing. Many countries around the world are already responding to osteoporosis and osteoporotic fractures by adopting fracture liaison service (FLS), and such an attempt has only begun in Korea. In this article, we introduce the operation methods for institutions implementing FLS and characteristics of services, and activities of the FLS Committee for FLS implementation in the Korean Society for Bone and Mineral Research. In addition, we hope that the current position statement will contribute to the implementation of FLS in Korea and impel policy changes to enable a multidisciplinary and integrated FLS operated under the medical system.
6.Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG ;
Journal of Gastric Cancer 2023;23(1):3-106
Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
7.Effect of Total Hip Arthroplasty on Ipsilateral Lower Limb Alignment and Knee Joint Space Width: Minimum 5-Year Follow-up
Yun Seong CHOI ; Jung-Wee PARK ; Tae Woo KIM ; Kee Soo KANG ; Young-Kyun LEE ; Kyung-Hoi KOO ; Chong Bum CHANG
Journal of Korean Medical Science 2023;38(20):e148-
Background:
This study aimed to 1) assess the effect of total hip arthroplasty (THA) on coronal limb alignment, namely, the hip–knee–ankle angle (HKA), 2) identify factors that determine changes in the HKA, and 3) determine whether alignment changes influence the knee joint space width.
Methods:
We retrospectively evaluated 266 limbs of patients who underwent THA. Three types of prostheses with neck shaft angles (NSAs) of 132°, 135°, and 138° were used. Several radiographic parameters were measured in the preoperative and final radiographs (at least 5 years after THA). A paired t-test was used to confirm the effect of THA on HKA change.Multiple regression analysis was performed to identify radiographic parameters related to HKA changes following THA and changes in knee joint space width. Subgroup analyses were performed to reveal the effect of NSA change on the HKA change, and the proportion of total knee arthroplasty usage and changes in radiographic parameters between maintained joint space and narrowed joint space groups were compared.
Results:
The preoperative mean HKA was 1.4° varus and increased to 2.7° varus after THA.This change was related to changes in the NSA, lateral distal femoral angle, and femoral bowing angle. In particular, in the group with a decrease in NSA of > 5°, the preoperative mean HKA was largely changed from 1.4° varus to 4.6° varus after THA. The prostheses with NSA of 132° and 135° also led to greater varus HKA changes than those with an NSA of 138°. Narrowing of the medial knee joint space was related to changes in the varus direction of the HKA, decrease in NSA, increase in femoral offset.
Conclusion
A large reduction in NSA can lead to considerable varus limb alignment after THA, which can have adverse effects on the medial compartment of the ipsilateral knee.
8.Modified Charlson comorbidity index as a survival prediction tool for older patients after liver transplantation
Jiho CHOI ; Eun-Woo CHOI ; YoungRok CHOI ; Su young HONG ; Sanggyun SUH ; Kwangpyo HONG ; Eui Soo HAN ; Jeong-moo LEE ; Suk Kyun HONG ; Nam-Joon YI ; Kwang-Woong LEE ; Kyung-Suk SUH
Annals of Surgical Treatment and Research 2023;104(6):358-363
Purpose:
An increasing number of older patients now undergo liver transplantation (LT). Although the overall outcomes in older patients are not different from those of younger patients, there is no tool to predict LT prognosis in older patients.We hypothesized that a modified Charlson comorbidity index (mCCI) and 5-factor modified frailty index (mFI-5) can predict outcomes in older patients after LT.
Methods:
This retrospective study included 155 patients (aged >65 years) who underwent LT at Seoul National University Hospital. The recipients were subcategorized into 2 groups based on the mCCI score and mFI-5: the low (0–1) and high (2–5) mCCI groups, and low (≤0.4) and high (>0.4) mFI-5 groups. The independent effect of each variable on post-LT survival was determined using the mCCI subgroup, age at transplantation, sex, Child-Turcotte-Pugh score, model for end-stage liver disease (MELD) score, and mFI-5 subgroup.
Results:
The high-mCCI group (41 patients) showed significantly lower 1- and 3-month and 1-, 3-, and 5-year survival than the low-mCCI group. Using the Cox regression model, the mCCI, sex, and MELD score remained significant. The mFI-5 was not a significant factor to predict patients’ survival.
Conclusion
The mCCI and MELD scores could be used to predict post-LT survival in older patients.
9.Donor sex and donor-recipient sex disparity do not affect hepatocellular carcinoma recurrence after living donor liver transplantation
Rak Kyun OH ; Shin HWANG ; Gi-Won SONG ; Chul-Soo AHN ; Deok-Bog MOON ; Tae-Yong HA ; Dong-Hwan JUNG ; Gil-Chun PARK ; Young-In YOON ; Woo-Hyoung KANG
Annals of Surgical Treatment and Research 2023;105(3):133-140
Purpose:
Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center.
Methods:
This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%).
Results:
Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374).
Conclusion
Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.
10.Hip Fractures in Centenarians: Functional Outcomes, Mortality, and Risk Factors from a Multicenter Cohort Study
Byung-Woong JANG ; Jin-Woo KIM ; Jae-Hwi NHO ; Young-Kyun LEE ; Jung-Wee PARK ; Yong-Han CHA ; Ki-Choul KIM ; Jun-Il YOO ; Jung-Taek KIM ; Kyung-Hoi KOO ; You-Sung SUH
Clinics in Orthopedic Surgery 2023;15(6):910-916
Background:
Increasing longevity has caused the very old population to become the fastest-growing segment. The number of centenarians (over 100 years old) is increasing rapidly. Fractures in the elderly lead to excessive medical costs and decreased quality of life with socioeconomic burdens. However, little research has thoroughly examined the functional outcomes and mortality of hip fractures in centenarians.
Methods:
This is a retrospective observational study. Sixty-eight centenarian hip fracture patients were admitted to the 10 institutions from February 2004 to December 2019. Fifty-six patients with 1-year follow-up were finally included. The following data were obtained: sex, age, body mass index, Charlson comorbidity index value on the operation day, Koval’s classification for ambulatory ability, type of fracture, the time interval from trauma to surgery, American Society of Anesthesiologists grade, surgery-related complications, and duration of hospital stay. Postoperative Koval’s classification (at 1 year after surgery) and information about death were also collected. Multivariate analysis was performed to analyze the risk factors affecting mortality 1 year after surgery.
Results:
Mortality rates were 26.8% at 6 months and 39.3% at 1 year. The 90-day mortality was 19.6%, and one of them (2.1%) died in the hospital. The 1-year mortality rates for the community ambulatory and non-community ambulatory groups were 29% and 52%, respectively. Only 9 (16.1%) were able to walk outdoors 1 year after surgery. The remaining 47 patients (83.9%) had to stay indoors after surgery. Multivariate analysis demonstrated that the pre-injury ambulatory level (adjusted hazard ratio, 2.884; p = 0.034) was associated with the risk of mortality.
Conclusions
We report a 1-year mortality rate of 39.3% in centenarian patients with hip fractures. The risk factor for mortality was the pre-injury ambulatory status. This could be an important consideration in the planning of treatment for centenarian hip fracture patients.

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