Se Ik Kim

Impact of Underweight after Treatment on Prognosis of Advanced-Stage Ovarian Cancer

This study aimed to investigate the impact of underweight status on the prognosis of advanced-stage ovarian cancer. A total of 360 patients with stage III-IV epithelial ovarian cancer were enrolled and divided into three groups by body mass indexes (BMIs): underweight (BMI < 18.5 kg/m2); normal weight to overweight (18.5 kg/m2 BMI < 27.5 kg/m2); obesity (BMI ≥ 27.5 kg/m2). Progression-free survival (PFS), overall survival (OS), CA-125, and neutrophil to lymphocyte ratio (NLR) as a marker reflecting host inflammation and immunity were compared among the three groups according to the three treatment times: at diagnosis; after surgery; and after treatment. Only underweight status after treatment was associated with poor OS in comparison with normal weight to overweight or obesity (mean value, 44.9 versus 78.8 or 67.4 months; P = 0.05); it was also an unfavorable factor for OS (adjusted HR, 2.29; 95% CI, 1.08–4.85). Furthermore, NLR was higher in patients with underweight than in those with obesity after treatment (median value, 2.15 versus 1.47; P = 0.03), in spite of no difference in CA-125 among the three groups at the three treatment times. In conclusion, underweight status after treatment may be a poor prognostic factor in patients with advanced-stage ovarian cancer, which accompanies increased host inflammation and decreased immunity.

Incidence of epithelial ovarian cancer according to histologic subtypes in Korea, 1999 to 2012

Objective To investigate trends in the incidence of epithelial ovarian cancer (EOC), according to histologic subtypes, in Korean women between 1999 and 2012. Methods Data from the Korea Central Cancer Registry recorded between 1999 and 2012 were evaluated. The incidences of EOC histologic subtypes were counted. Age-standardized incidence rates (ASRs) and annual percentage changes (APCs) in incidence rates were calculated. Patient data were divided into three groups based on age (<40, 40 to 59, and >59 years), and age-specific incidence rates were compared. Results Overall, the incidence of EOC has increased. Annual EOC cases increased from 922 in 1999 to 1,775 in 2012. In 1999, the ASR was 3.52 per 100,000 and increased to 4.79 per 100,000 in 2012 (APC, 2.53%; p<0.001). The ASRs in 2012 and APCs between 1999 and 2012 for the four major histologic subtypes were as follows (in order of incidence): serous carcinoma (ASR, 2.32 per 100,000; APC, 4.34%; p<0.001), mucinous carcinoma (ASR, 0.73 per 100,000; APC, –1.05%; p=0.131), endometrioid carcinoma (ASR, 0.51 per 100,000; APC, 1.48%; p=0.032), and clear cell carcinoma (ASR, 0.50 per 100,000; APC, 8.13%; p<0.001). In the sub-analyses based on age, clear cell carcinoma was confirmed as the histologic subtype whose incidence had increased the most since 1999. Conclusion The incidence of EOC is increasing in Korea. Among the histologic subtypes, the incidence of clear cell carcinoma has increased markedly across all age groups since 1999.

Quality of life and sexuality comparison between sexually active ovarian cancer survivors and healthy women

Objective compare quality of life (QoL) and sexual functioning between sexually active ovarian cancer survivors and healthy women. Methods A cross-sectional study was performed in 103 successfully treated ovarian cancer survivors and 220 healthy women. All women had engaged in sexual activity within the previous 3 months, and ovarian cancer survivors were under surveillance after primary treatment without evidence of disease. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Ovarian Cancer Module (EORTC QLQ-OV28), and the Female Sexual Function Index (FSFI). Propensity score matching was used to adjust covariates between the ovarian cancer survivor and healthy women groups. In total, 73 ovarian cancer survivors and 73 healthy women were compared. Results Poorer social functioning (mean, 82.4 vs. 90.9; p=0.010) and more financial difficulties (mean, 16.4 vs. 7.8; p=0.019) were observed among ovarian cancer survivors than among healthy women. Sexuality, both in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain and in terms of interest in sex, sexual activity, and enjoyment of sex (EORTC QLQ-OV28) were similar between the groups. However, vaginal dryness was more problematic in ovarian cancer survivors, with borderline statistical significance (p=0.081). Conclusion Sexuality was not impaired in ovarian cancer survivors who were without evidence of disease after primary treatment and having sexual activities, compared with healthy women, whereas social functioning and financial status did deteriorate. Prospective cohort studies are needed.

Impact of lower limb lymphedema on quality of life in gynecologic cancer survivors after pelvic lymph node dissection.

OBJECTIVE To evaluate the impact of lower limb lymphedema (LLL) on quality of life (QOL) in cervical, ovarian, and endometrial cancer survivors after pelvic lymph node dissection. STUDY DESIGN A cross-sectional case-control study was performed using the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). In total, 25 women with LLL and 28 women without LLL completed both questionnaires. RESULTS The GCLQ-K total symptom score and scores for swelling-general, swelling-limb, and heaviness were significantly higher in the LLL group than in the control group. In the EORTC QLQ-C30, the LLL group reported more financial difficulties compared to the control group (mean score, 16.0 vs. 6.0; P=0.035). Global health status was poorer in the LLL group with borderline statistical significance (mean score, 62.7 vs. 71.4; P=0.069). Spearmans correlations suggested that global health status in the EORTC QLQ-C30 correlated with the GCLQ-K total symptom score (in the LLL group, R=-0.64, P=0.001; in the control group, R=-0.42, P=0.027). CONCLUSIONS QOL decreases due to LLL-related symptoms and financial difficulty in women with LLL. Well-designed prospective studies are required to confirm these findings.

Comparison of Quality of Life and Sexuality between Cervical Cancer Survivors and Healthy Women

Purpose The purpose of this study is to compare quality of life (QoL) and sexual functioning between sexually active cervical cancer survivors and healthy women. Materials and Methods In this cross-sectional study, propensity-score-matched cervical cancer survivors (n=104) and healthy women (n=104) were compared. All women had engaged in sexual activity within the previous 3 months, and cervical cancer survivors showed no evidence of disease after primary treatment. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Cervical Cancer Module (EORTC QLQ-CX24), and the Female Sexual Function Index (FSFI). Results Significantly higher scores for lymphedema were observed in the cervical cancer survivors group compared with the healthy women group (mean, 20.2 vs. 12.2; p < 0.05). Sexuality, both in terms of sexual activity, sexual enjoyment, and sexual worry (EORTC QLQ-CX24), and in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain (FSFI) were similar between the groups. When the scale of sexual/vaginal functioning in EORTC QLQ-CX24 was divided into individual questions, cervical cancer survivors reported shorter vaginal length than the control group, but without statistical significance (mean, 80.6 vs. 85.4; p=0.077). Conclusion Compared with healthy women, sexuality was not impaired in cervical cancer survivors who showed no evidence of disease after primary treatment and engaging in sexual activity. Further prospective cohort studies are warranted to confirm this finding.

Application of a subcutaneous negative pressure drain without subcutaneous suture: impact on wound healing in gynecologic surgery

OBJECTIVE To evaluate the surgical outcome of a subcutaneous negative pressure drain without subcutaneous suture on wound healing in women undergoing abdominal gynecologic surgery. STUDY DESIGN The medical records of total 322 patients who underwent abdominal surgery, including cytoreductive surgery for ovarian cancer, between March 2010 and January 2013 were reviewed retrospectively. Patients were divided into two groups by the presence of subcutaneous negative pressure drains without subcutaneous suture, or suture without drainage. RESULTS Patients characteristics in the two groups were not statistically different. Among all patients, the 71 patients who had a subcutaneous wound drain achieved a higher rate of clear healing (97.2% vs. 88.8%; p=0.033): 100% vs. 98.0% (not significant) in 126 benign and 95.6% vs. 82.8% (p=0.032) in 196 malignant disease patients. In a multivariate analysis, wound drain placement was an independent prognostic factor affecting the surgical wound outcome; the disruption (OR, 0.100; 95% CI, 0.021-0.485; p=0.004) rate was significantly lower with subcutaneous negative pressure drain. Placement of a subcutaneous negative pressure drain without subcutaneous suture resulted in clinical benefit, such as shorter admission duration (median, 8 vs. 11 days; p=0.021). CONCLUSIONS Application of subcutaneous negative pressure drain is one of the effective and easy ways for clearer wound healing after major gynecologic surgery for malignant disease.

Genomic landscape of ovarian clear cell carcinoma via whole exome sequencing

OBJECTIVE To analyze whole exome sequencing (WES) data on ovarian clear cell carcinoma (OCCC) in Korean patients via the technique of next generation sequencing (NGS). Genomic profiles were compared between endometriosis-associated OCCC (EMS-OCCC) and Non-EMS-OCCC. METHODS We used serum samples and cancer tissues, stored at the Seoul National University Hospital Human Biobank, that were initially collected from women diagnosed with OCCC between 2012 and 2016. In total, 15 patients were enrolled: 5 with pathologically confirmed EMS-OCCC and 10 with Non-EMS-OCCC. We performed NGS WES on 15 fresh frozen OCCC tissues and matched serum samples, enabling comprehensive genomic characterization of OCCC. RESULTS OCCC was characterized by complex genomic alterations, with a median of 178 exonic mutations (range, 111-25,798) and a median of 343 somatic copy number variations (range, 43-1,820) per tumor sample. In all, 54 somatic mutations were discovered across 14 genes, including PIK3CA (40%), ARID1A (40%), and KRAS (20%) in the 15 Korean OCCCs. Copy number gains in NTRK1 (33%), MYC (40%), and GNAS (47%) and copy number losses in TET2 (73%), TSC1 (67%), BRCA2 (60%), and SMAD4 (47%) were frequent. The significantly altered pathways were associated with proliferation and survival (including the PI3K/AKT, TP53, and ERBB2 pathways) in 87% of OCCCs and with chromatin remodeling in 47% of OCCCs. No significant differences in frequencies of genetic alterations were detected between EMS-OCCC and Non-EMS-OCCC groups. CONCLUSION We successfully characterized the genomic landscape of 15 Korean patients with OCCC. We identified potential therapeutic targets for the treatment of this malignancy.

Benefit of negative pressure drain within surgical wound after cytoreductive surgery for ovarian cancer.

Objective The objective of this study was to investigate the efficacy of subcutaneous negative-pressure wound drains on wound healing after cytoreductive surgery for ovarian cancer. Methods A retrospective study was performed on patients who underwent cytoreductive surgery for epithelial ovarian cancer, between 2012 and 2013. The patients were divided into 2 groups, according to using (n = 163) and not using (n = 37) of subcutaneous wound drains, and wound outcomes were analyzed. Results Patients’ characteristics were not statistically different, except for the prolonged operative time in patients with wound drains (median, 395 vs 240 minutes; P = 0.001). A lower rate of wound infection (12.9% vs 27.0%; P = 0.032) was observed in the drain group. In the multivariate analysis, placement of subcutaneous wound drain was an independent prognostic factor for reducing wound complications: disruption (odds ratio [OR], 0.367; 95% confidence interval [CI], 0.145–0.929; P = 0.034) and wound infection (OR, 0.198; 95% CI, 0.068–0.582; P = 0.003). Bowel surgery at the time of cytoreductive surgery and prolonged operative time (≥360 minutes) were also associated with higher rates of disruption (OR, 2.845; 95% CI, 1.111–7.289; P = 0.029) and wound infection (OR, 4.212; 95% CI, 1.273–13.935; P = 0.019), respectively. Conclusions Installation of subcutaneous negative-pressure wound drain is an effective method to achieve clearer wound healing and less wound complications after cytoreductive surgery for ovarian cancer.

Tumor evolution and chemoresistance in ovarian cancer.

Development of novel strategies to overcome chemoresistance is central goal in ovarian cancer research. Natural history of the cancer development and progression is being reconstructed by genomic datasets to understand the evolutionary pattern and direction. Recent studies suggest that intra-tumor heterogeneity (ITH) is the main cause of treatment failure by chemoresistance in many types of cancers including ovarian cancer. ITH increases the fitness of tumor to adapt to incompatible microenvironment. Understanding ITH in relation to the evolutionary pattern may result in the development of the innovative approach based on individual variability in the genetic, environment, and life style. Thus, we can reach the new big stage conquering the cancer. In this review, we will discuss the recent advances in understanding ovarian cancer biology through the use of next generation sequencing (NGS) and highlight areas of recent progress to improve precision medicine in ovarian cancer.

Evaluating Tumor Evolution via Genomic Profiling of Individual Tumor Spheroids in a Malignant Ascites from a Patient with Ovarian Cancer Using a Laser-aided Cell Isolation Technique

Background Epithelial ovarian cancer (EOC) is a silent but mostly lethal gynecologic malignancy. Most patients present with malignant ascites and peritoneal seeding at diagnosis. In the present study, we used a laser-aided isolation technique to investigate the clonal relationship between the primary tumor and tumor spheroids found in the malignant ascites of an EOC patient. Somatic alteration profiles of ovarian cancer-related genes were determined for eight spatially separated samples from primary ovarian tumor tissues and ten tumor spheroids from the malignant ascites using next-generation sequencing. Results We observed high levels of intra-tumor heterogeneity (ITH) in copy number alterations (CNAs) and single-nucleotide variants (SNVs) in the primary tumor and the tumor spheroids. As a result, we discovered that tumor cells in the primary tissues and the ascites were genetically different lineages. We categorized the CNAs and SNVs into clonal and subclonal alterations according to their distribution among the samples. Also, we identified focal amplifications and deletions in the analyzed samples. For SNVs, a total of 171 somatic mutations were observed, among which 66 were clonal mutations present in both the primary tumor and the ascites, and 61 and 44 of the SNVs were subclonal mutations present in only the primary tumor or the ascites, respectively. Conclusions Based on the somatic alteration profiles, we constructed phylogenetic trees and inferred the evolutionary history of tumor cells in the patient. The phylogenetic trees constructed using the CNAs and SNVs showed that two branches of the tumor cells diverged early from an ancestral tumor clone during an early metastasis step in the peritoneal cavity. Our data support the monophyletic spread of tumor spheroids in malignant ascites.