Investigator

Yong Beom Kim

Seoul National University

YBKYong Beom Kim
Papers(12)
Changes in Epithelial…Association of cul-de…Clinical practice gui…High-throughput viabl…Clinical guidelines f…Practice guidelines f…Clinical practice gui…Aspiration biopsy ver…Risk factors of progr…Clinicopathologic and…Clinical evaluation o…Clinical practice gui…
Collaborators(10)
Dong Hoon SuhKidong KimJae Hong NoMyong Cheol LimBanghyun LeeWoo Yeon HwangEun Ji NamYun Hwan KimBo Seong YunByung Su Kwon
Institutions(8)
Seoul National Univer…Seoul National Univer…National Cancer CenterInha UniversityKyung Hee University …Yonsei University Col…Ewha Women's Universi…Cha University Ilsan …

Papers

Changes in Epithelial Ovarian Cancer Recurrence and Survival According to Treatment Paradigm Shifts

ABSTRACT Aim To evaluate oncologic outcomes in patients with epithelial ovarian cancer (EOC) amid evolving surgical and systemic therapy paradigms. Methods This retrospective cohort study included patients diagnosed with EOC from June 2003 to December 2020 at a single tertiary center, grouped by diagnosis period. Overall survival (OS) and progression‐free survival (PFS) were analyzed using the Kaplan–Meier and Cox regression analyses. Results A total of 763 patients were classified as 2003–2008 (Group 1, n  = 101), 2009–2013 (Group 2, n  = 207), and 2014–2020 (Group 3, n  = 455), reflecting changes in cytoreductive surgery and targeted therapies (bevacizumab and PARP inhibitors). Early‐stage diagnoses increased over time without statistical significance (Stage I–II: Group 1, 37.6% vs. Group 3, 46.6%; p  = 0.200). Group 2 showed greater use of interval debulking surgery (IDS), higher complete cytoreduction rates, and more first‐line chemotherapy cycles (all p  < 0.001). Group 3 represented the introduction of targeted therapies ( p  < 0.001 for both). IDS with residual (< 1 cm) was associated with poorer outcomes than complete/optimal primary debulking surgery (PDS) (hazard ratio 2.94, 95% confidence interval 1.5–5.8). Despite unchanged PFS, the 5‐year OS improved from 64.0% to 82.5% among patients with advanced‐stage disease ( p  = 0.024). Conclusions Over two decades, with the advent of targeted therapies, complete cytoreduction (especially in PDS) has increased. Although the use of IDS also increased, residual disease (< 1 cm) after IDS was associated with poorer outcomes. While PFS remained unchanged, 5‐year OS significantly improved among patients with advanced‐stage disease diagnosed in the most recent period.

Association of cul-de-sac seeding with intraperitoneal tumor burden in advanced ovarian cancer (CIEL, KGOG 4003)

To evaluate the relationship between tumor seeding in the cul-de-sac, assessed by transvaginal or transrectal ultrasound, and intraperitoneal tumor burden in advanced ovarian cancer. We prospectively enrolled 101 patients scheduled for surgery due to suspected or newly diagnosed ovarian, fallopian tube, or peritoneal cancer at three hospitals in Korea (Feb 2022-Dec 2023). Five were excluded for missing ultrasound or surgery, and eleven for benign or other malignancies. Preoperative ultrasound was used to assess cul-de-sac tumor seeding, categorized as no seeding, reticulonodular, serosal, or mass seeding. Intraperitoneal tumor burden was evaluated using the Peritoneal Cancer Index (PCI) and Fagotti score. Associations with bowel surgery and residual tumors >1 cm were also analyzed. Eighty-five patients were included; 28 received neoadjuvant chemotherapy. Cul-de-sac seeding was classified as no seeding (42 %), reticulonodular (14 %), serosal (18 %), or mass (26 %). Higher PCI and Fagotti scores correlated with more severe seeding. Intraoperative confirmation of seeding was seen in 69 % of cases. Bowel surgery was less frequent in patients without seeding. No significant differences were found in residual tumors >1 cm between groups. Cul-de-sac tumor seeding identified by transvaginal or transrectal ultrasound may reflect intraperitoneal tumor burden and could help predict surgical complexity in advanced ovarian cancer.

High-throughput viable circulating tumor cell isolation using tapered-slit membrane filter-based chipsets in the differential diagnosis of ovarian tumors

Objective To evaluate the diagnostic performance of circulating tumor cells (CTCs) using tapered-slit membrane filter (TSF)-based chipsets for the differential diagnosis of adnexal tumors. Methods A total of 230 women with indeterminate adnexal tumors were prospectively enrolled. The sensitivity, specificity, and accuracy of the CTC-detecting chipsets were analyzed according to postoperative pathological results and compared with those of cancer antigen (CA)-125 and imaging tests. Results Eighty-one (40.3%) benign tumors, 31 (15.4%) borderline tumors, and 89 (44.3%) ovarian cancers were pathologically confirmed. The sensitivity, specificity, and accuracy of CTC-detecting chipsets (75.3%, 58.0%, and 67.1%) for differentiating ovarian cancer from benign tumors were similar to CA-125 (78.7%, 53.1%, and 66.5%), but lower than CT/MRI (94.2%, 77.9%, and 86.5%). “CTC or CA125” showed increased sensitivity (91.0%) and “CTC and CA-125” revealed increased specificity (77.8%), comparable to CT/MRI. CTC detection rates in stage I/II and stage III/IV ovarian cancers were 69.6% and 81.4%, respectively. The sensitivity to detect high-grade serous (HGS) cancer from benign tumors (84.6%) was higher than that to detect non-HGS cancers (68.0%). Conclusion Although the diagnostic performance of the TSF platform to differentiate between ovarian cancer and benign tumors did not yield significant results, the combination of CTC and CA-125 showed promising potential in the diagnostic accuracy of ovarian cancer.

Aspiration biopsy versus dilatation and curettage for endometrial hyperplasia prior to hysterectomy

Abstract Background To compare the diagnostic accuracy of aspiration biopsy and dilatation and curettage (D&C) in patients diagnosed with endometrial hyperplasia prior to hysterectomy. Methods We retrospectively reviewed medical records of 250 patients diagnosed with endometrial hyperplasia by endometrial sampling between July 2003 and March 2020. Endometrial sampling was performed by aspiration biopsy ( n  = 150) or D&C ( n  = 100), followed by hysterectomy within 6 months. Pathological findings of hysterectomy specimens of the two groups were compared to preoperative findings. Results The overall diagnostic concordance between endometrial sampling specimen including D&C and aspiration biopsy, and hysterectomy specimen was 51.0% (51/100) and 41.3% (62/150), respectively. Patients whose preoperative specimen was obtained by D&C were upgraded less significantly than those who underwent aspiration biopsy (21.0% vs 36.7%; P  = 0.008). In particular, significantly fewer patients were upgraded after D&C than after aspiration biopsy in hyperplasia without atypia (12.5% vs 29.0%; P  = 0.028). In addition, when the final pathological upgrade rate to endometrial carcinoma was evaluated between the two methods of endometrial sampling, significantly fewer cases were noted after D&C than after aspiration biopsy (15.0% vs 27.3%; P  = 0.022). Conclusions In our study, D&C more accurately reflected the final diagnosis in patients with endometrial hyperplasia than aspiration biopsy based on the histological examination of hysterectomy specimens. When considering the management strategy for women with an endometrial hyperplasia diagnosis obtained by aspiration biopsy, physicians should consider the significant rate of upgraded diseases with this method of endometrial sampling.

Risk factors of progression to endometrial cancer in women with endometrial hyperplasia: A retrospective cohort study

Objective This study aimed to investigate risk factors of progression to endometrial cancer (EC) in women with non-atypical and atypical endometrial hyperplasia (EH). Methods The data of 62,333 women with EH diagnostic codes from 2007 to 2018 were sourced from the Korean Health Insurance Review and Assessment Service databases. The data from 11,525 women with non-atypical EH and 2,219 women with atypical EH who met the selection criteria were extracted for analysis. Results Risk of EC in women with EH decreased in 40–49 year olds compared to other ages (non-atypical EH: [≤39 vs. 40–49 years] HR, 0.557; 95% CI, 0.439–0.708; P<0.001; [≤39 vs. ≥50 years] P = 0.739; atypical EH: [≤39 vs. 40–49 years] HR, 0.391; 95% CI, 0.229–0.670; P = 0.001; [≤39 vs. ≥50 years] P = 0.712). Risk of EC increased with increase in number of follow-up biopsies in women with non-atypical EH (1 biopsy: HR, 1.835; 95% CI, 1.282–2.629; P = 0.001; ≥2 biopsies: HR, 3.644; 95% CI, 2.585–5.317; P<0.001) and in women receiving ≥2 follow-up biopsies with atypical EH (HR, 3.827; 95% CI, 1.924–7.612; P = 0.001). Time of progression to EC decreased in women ≥50 years old with non-atypical EH compared to other ages (P = 0.004) and showed no differences among ages in women with atypical EH (P = 0.576). Progestational agents were a protective factor for EC in women with non-atypical EH (HR, 0.703; 95% CI, 0.565–0.876; P = 0.002). Conclusions In this claim data analysis, women ≤39 and ≥50 years old with EH were at a high risk for progression to EC, and repeat follow-up biopsy after a diagnosis of EH increased detection of EC. Progestational agents were an effective modality to prevent EC in women with non-atypical EH.

HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP

The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.

Feasibility of extended cycles of neoadjuvant chemotherapy in patients with advanced ovarian cancer in terms of prognosis and surgical outcomes

Objective We aimed to identify the effect of an extended number of neoadjuvant chemotherapy (NAC) cycles on prognosis and surgical morbidity after interval debulking surgery (IDS) in patients with newly diagnosed advanced ovarian cancer. Methods Medical records of patients with advanced ovarian cancer treated with NAC and having undergone IDS were retrospectively reviewed. Clinicopathological factors were compared between two groups: conventional (≤4 cycles) and extended (≥5 cycles) NAC groups. Kaplan–Meier analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS). Results A total of 156 patients were included, 112 patients in the conventional group and 44 patients in the extended NAC group. The extended NAC group had a significantly higher frequency of cancer antigen (CA)-125 normalization after NAC (59.1% vs. 33.9%, P = 0.004), a lower rate of bowel surgery (18.2% vs. 34.8%, P = 0.042), and a lower rate of transfusion during or after IDS (36.4% vs. 59.8%, P = 0.008) as compared to the conventional group. The complete cytoreduction rate after IDS was similar between the groups. In multivariate Cox regression analysis for PFS, radiologically stable and progressive disease after NAC (Hazard ratio [HR], 1.983; 95% Confidence interval [CI], 1.141–3.446; P = 0.015) and gross residual tumor after IDS (HR, 2.054; 95% CI, 1.414–2.983; P < 0.001) were independent risk factors for poor PFS. However, extended NAC cycles were not significantly associated with poor PFS. The median PFS was 19.5 and 16.9 months (P = 0.830), and the 5-year OS was 71.4 and 63.2% (P = 0.677) in the conventional and extended NAC groups, respectively. Conclusion Our study showed that extended NAC cycles were not inferior to conventional NAC cycles in terms of survival in patients with advanced ovarian cancer and reduced surgical morbidity such as bowel surgery and transfusion during or after IDS.

Mutually exclusive antiproliferative effect of cell line‐specific HOX inhibition in epithelial ovarian cancer cell lines: SKOV‐3 vs RMUG‐S

Abstract We aimed to discover cell line‐specific overexpressed HOX genes responsible for chemoresistance and to identify the mechanisms behind HOX‐induced cell line‐specific chemoresistance in EOC. Ten HOX genes and eight EOC cell lines were tested for any cell line‐specific overexpression that presents a mutually exclusive pattern. Cell viability was evaluated after treatment with cisplatin and/or siRNA for cell line‐specific overexpressed HOX genes. Immunohistochemical (IHC) staining for HOXB9 was performed in 84 human EOC tissues. HOXA10 and HOXB9 were identified as cell line‐specific overexpressed HOX genes for SKOV‐3 and RMUG‐S, respectively. Inhibiting the expression of cell line‐specific HOX genes, but not of other HOX genes, significantly decreased cell viability. In SKOV‐3 cells, cell viability decreased to 46.5% after initial 10 µM cisplatin treatment; however, there was no further decrease upon additional treatment with HOXA10 siRNA. In contrast, cell viability did not significantly decrease upon cisplatin treatment in RMUG‐S cells, but decreased to 65.5% after additional treatment with HOXB9 siRNA. In both cell lines, inhibiting cell line‐specific HOX expression enhanced apoptosis but suppressed the expression of epithelial‐mesenchymal transition (EMT) markers such as vimentin, MMP9, and Oct4. IHC analysis showed that platinum‐resistant cancer tissues more frequently had high HOXB9 expression than platinum‐sensitive cancer tissues. HOXB9, which is overexpressed in RMUG‐S but not in SKOV‐3 cells, appeared to be associated with cell line‐specific platinum resistance in RMUG‐S. Inhibiting HOXB9 overexpression in RMUG‐S cells may effectively eliminate platinum‐resistant ovarian cancer cells by facilitating apoptosis and inhibiting EMT.

Pathologic discrepancies between colposcopy-directed biopsy and loop electrosurgical excision procedure of the uterine cervix in women with cytologic high-grade squamous intraepithelial lesions

To investigate pathologic discrepancies between colposcopy-directed biopsy (CDB) of the cervix and loop electrosurgical excision procedure (LEEP) in women with cytologic high-grade squamous intraepithelial lesions (HSILs). We retrospectively identified 297 patients who underwent both CDB and LEEP for HSILs in cervical cytology between 2015 and 2018, and compared their pathologic results. Considering the LEEP to be the gold standard, we evaluated the diagnostic performance of CDB for identifying cervical intraepithelial neoplasia (CIN) grades 2 and 3, adenocarcinoma in situ, and cancer (HSIL+). We also performed age subgroup analyses. Among the study population, 90.9% (270/297) had pathologic HSIL+ using the LEEP. The diagnostic performance of CDB for identifying HSIL+ was as follows: sensitivity, 87.8%; specificity, 59.3%; balanced accuracy, 73.6%; positive predictive value, 95.6%; and negative predictive value, 32.7%. Thirty-three false negative cases of CDB included CIN2,3 (n=29) and cervical cancer (n=4). The pathologic HSIL+ rate in patients with HSIL- by CDB was 67.3% (33/49). CDB exhibited a significant difference in the diagnosis of HSIL+ compared to LEEP in all patients (p<0.001). In age subgroup analyses, age groups <35 years and 35-50 years showed good agreement with the entire data set (p=0.496 and p=0.406, respectively), while age group ≥50 years did not (p=0.036). A significant pathologic discrepancy was observed between CDB and LEEP results in women with cytologic HSILs. The diagnostic inaccuracy of CDB increased in those ≥50 years of age.

Perioperative outcomes in patients with very low‐risk endometrial cancer undergoing surgery without lymph node dissection: Results from KGOG 2021

AbstractAimTo evaluate the perioperative outcomes of patients with endometrial cancer meeting the Korean Gynecologic Oncology Group (KGOG) criteria who underwent surgery without lymph node dissection.MethodsThis study included 153 patients who met the KGOG criteria: (1) endometrioid histology, (2) myometrial invasion &lt;50%, (3) tumor confined to the corpus, (4) no lymph node &gt;1 cm, and (5) serum CA125 ≤ 35 U/mL. The patients underwent surgery without lymph node dissection at 11 hospitals in Korea between February 2020 and May 2024. Perioperative outcomes were collected prospectively.ResultsAmong the 153 patients, 89 (58%) underwent surgery without lymph node removal, while 64 (42%) underwent surgery with lymph node removal. Minimally invasive surgery was performed in &gt;90% of cases, with a conversion rate to laparotomy of 1%. The mean surgery time was 109.37 ± 37.67 min. Estimated blood loss was minimal (93.74 ± 93.13 mL), with a mean hemoglobin drop of 1.32 ± 1.01 g/dL. Transfusions were required in only three patients (2%). Postoperative hospital stays exceeded 2 days in 51% of cases. Lymph node metastasis was observed in just one case (1%). Adverse events included 52 grade 1 and 2 grade 2 events (e.g., headache, paresthesia). Patients undergoing lymph node removal (primarily sentinel lymph node biopsy) had significantly longer surgery times and postoperative hospital stays compared to those without lymph node removal.ConclusionSurgery without lymph node dissection demonstrated excellent perioperative outcomes and minimal adverse events in patients meeting KGOG criteria.

9Works
20Papers
59Collaborators
Endometrial NeoplasmsOvarian NeoplasmsUterine Cervical NeoplasmsNeoplasm Recurrence, LocalNeoplasm StagingCell Line, TumorApoptosis