Polydopamine Adhesion: Catechol, Amine, Dihydroxyindole, and Aggregation Dynamics.

While polydopamine (PDA) possesses the surface-independent adhesion property of mussel-binding proteins, significant differences exist between them. Particularly, PDA's short and rigid backbone differs from the long and flexible protein sequence of mussel-binding proteins. Given that adhesion relies on achieving a conformal contact with large surface coverage, PDA has drawbacks as an adhesive. In our study, we investigated the roles of each building block of PDA to build a better understanding of their binding mechanisms. Initially, we anticipated that catecholamine oligomers form specific binding with substrates. However, our study showed that the universal adhesion of PDA is initiated by the solubility limit of growing oligomers by forming agglomerates, complemented by multiple binding modes of catechol. Notably, in the absence of amines, poly(catechol) either remained in solution or formed minor suspensions without any surface coating, underscoring the essential role of amines in the adhesion process by facilitating insoluble aggregate formation. To substantiate our findings, we induced poly(catechol) aggregation using quaternized poly(4-vinylpyridine) (qPVP), leading to subsequent surface adhesion upon agglomerate formation.

Factors associated with oral hygiene compliance in patients treated with radiation therapy for head and neck cancer.

BACKGROUND: Patients who are oral hygiene noncompliant (OHNC) are more likely to lose teeth after radiation therapy (RT) for head and neck cancer (HNC), which increases the risk of developing osteoradionecrosis. A previous study revealed that patients who were OHNC at baseline (BL) who became oral hygiene compliant during follow-up had the best tooth-failure outcomes. The purpose of this study was to identify factors associated with oral hygiene compliance (OHC), overall, and among those who were BL OHNC. METHODS: This was an observational, prospective, cohort study of 518 patients with HNC assessed before RT and at post-RT follow-up visits every 6 months for 2 years. Patient and treatment-related information was collected at BL and during follow-up, including self-reported OHC. OHC was defined as toothbrushing at least twice daily and flossing at least once daily. RESULTS: Of the 296 patients who self-reported being BL OHNC, 44 (14.9%) became oral hygiene compliant at all follow-up visits. Among this group, those who had dental insurance (P = .026), surgery before RT (P = .008), limited mouth opening before RT (P = .001), compliant fluoride use (P = .023), primary RT site of oral cavity (P = .004), and primary surgical site of larynx and hypopharynx (P = .042) were more likely to become oral hygiene compliant post-RT. CONCLUSIONS: The reasons for the cohort of patients with HNC in this study being OHNC are multifaceted and relate to socioeconomic factors and cancer characteristics. PRACTICAL IMPLICATIONS: Finding ways to increase OHC and fluoride use among patients with HNC who are at greatest risk of being OHNC should be explored.

Incidence and treatment outcomes of ovarian carcinosarcoma from the national cancer registry of Korea.

OBJECTIVE: To investigate the incidence and survival outcomes of ovarian carcinosarcoma in Korea between 1999 and 2018. METHODS: Patients diagnosed with ovarian carcinosarcoma between 1999 and 2018 were identified from the Korea Central Cancer Registry (KCCR) and their information was collected. Age-standardized incidence rates (ASRs), annual percent changes (APC), and relative survival rates of ovarian carcinosarcoma were calculated and compared to those of epithelial ovarian cancer. RESULTS: According to the KCCR, 458 cases of ovarian carcinosarcoma were detected, and accounted for 1.5% (458/30,679) of all epithelial ovarian cancers in Korea between 1999 and 2018. The ASR of ovarian carcinosarcoma between 1999 and 2018 was 0.064 per 100,000 women. The incidence rate of ovarian carcinosarcoma increased during the study period, with an ASR of 0.029 per 100,000 in 1999 and 0.073 per 100,000 in 2018. The APC of ovarian carcinosarcoma during 1999-2018 was 5.86 (p<0.001). The median overall survival (OS) of patients with ovarian carcinosarcoma was 39 months, and the 5-year OS rate was 42.5%. Among ovarian carcinosarcomas, patients with localized stages showed better clinical outcomes than those with regional or distant stages (5-year OS, 60.8%, 57.9%, and 32.8%, respectively; p<0.001). In addition, younger (<50 years) patients showed better OS than older (≥50 years) patients (5-year OS, 52.6% vs. 40.2%; p<0.001). CONCLUSION: Our nationwide registry-based study demonstrated that the incidence of ovarian carcinosarcoma increased from 1999 to 2018 in Korea. Patients with advanced-stage disease and older age (≥50 years) had poorer survival outcomes.

Trends in the incidence and survival outcomes of endometrial cancer in Korea: a nationwide population-based cohort study.

OBJECTIVE: To evaluate trends in the incidence and survival outcomes of endometrial cancer (EC) based on the year of diagnosis, stage, age, and histologic types. METHODS: Women with primary EC diagnosed between 1999 and 2018, and who were followed up with until 2019, were identified from the Korea Central Cancer Registry using the International Classification of Diseases, 10th revision. The age-standardized rates (ASRs) of incidence, annual percent changes (APCs), and survival were estimated according to age, stage, histology, and year of diagnosis. RESULTS: The ASR for EC increased from 2.38 per 100,000 in 1999 to 7.29 per 100,000 in 2018 across all histologic types (APCs of 9.82, 15.97, and 7.73 for endometrioid, serous, and clear cell, respectively, p<0.001). There were significant differences in the 5-year survival rates based on histology (90.9%, 55.0%, and 68.5% for endometrioid, serous, and clear cell, respectively, p<0.001), stage (93.4%, 77.0%, and 31.0% for localized, regional, and distant, respectively, p<0.001), and age (93.0% for <50 years and 80.6% for ≥50 years, p<0.001). The 5-year survival was significantly better in the group diagnosed between 2000 and 2018 (85.9%) than that in the 1999-2008 group (83.3%) (p<0.001). This trend was only observed for endometrioid cancer (p<0.001). CONCLUSION: The incidence of EC increased across the all 3 subtypes. Survival of patients with endometrioid histology improved over the past two decades, but remained static for serous or clear cell histology. Healthcare strategies to prevent EC incidence in at-risk populations and apply effective treatments for high-risk histology are needed.

Characteristics of second primary breast cancer after ovarian cancer: a Korea central cancer registry retrospective study.

Background: Second primary cancer has become an important issue among cancer survivors. This study sought to determine the differences in clinicopathologic outcomes between second primary breast cancer (SPBC) after ovarian cancer and primary breast cancer (PBC) in the Republic of Korea. Methods and materials: We searched the Korea Central Cancer Registry and identified 251,244 breast cancer cases that were diagnosed between 1999 and 2017. The incident rate and standardized incidence ratio (SIR) were calculated. Demographic and clinical characteristics and overall survival (OS) rates were estimated according to age, histological type, and cancer stage. Results: Among the 228,329 patients included, 228,148 were patients with PBC, and 181 patients had SPBC diagnosed after ovarian cancer (OC). The mean ages at diagnosis were 56.09 ± 10.81 years for SPBC and 50.65 ± 11.40 years for PBC. Patients with SPBC were significantly less likely than patients with PBC to receive adjuvant radiotherapy (14.92% vs. 21.92%, p = 0.02) or adjuvant chemotherapy (44.75% vs. 55.69%, p < 0.01). Based on the age-standardized rate (ASR), the incidence of SPBC after OC was 293.58 per 100,000 ovarian cancer patients and the incidence of PBC was 39.13 per 100,000 women. The SIR for SPBC was 1.27 (1.09-1.46, 95% Confidence interval) in the patients overall. The 5-year OS rates were 72.88% and 89.37% for SPBC and PBC (p < 0.01). The OS rate in SPBC decreased significantly with advanced stage and older age. Conclusion: The incidence of breast cancer is about 1.27 times higher in ovarian cancer patients than in healthy people. The survival outcomes were worse for SPBC than for PBC and were related to older age and advanced stage. Active screening for breast cancer is necessary in ovarian cancer patients.

Exocrine pancreatic cancer as a second primary malignancy: A population-based study.

Backgrounds/Aims: Although cancer survivors are at higher risk of developing second primary malignancies, cancer surveillance strategies for them have not yet been established. This study aimed to identify first primary cancers that had high risks of developing second primary exocrine pancreatic cancer (EPC). Methods: Data on individuals diagnosed with primary cancers between 1993 and 2017 were obtained from the Korea Central Cancer Registry. The standardized incidence ratios (SIRs) of second primary EPCs were analyzed according to the primary tumor sites and follow-up periods. Results: Among the 3,205,840 eligible individuals, 4,836 (0.15%) had second primary EPCs, which accounted for 5.8% of the total EPC patients in Korea. Between 1 and 5 years after the diagnosis of first primary cancers, SIRs of second primary EPCs were increased in patients whose first primary cancers were in the bile duct (males 2.99; females 5.03) in both sexes, and in the small intestine (3.43), gallbladder (3.21), and breast (1.26) in females. Among those who survived 5 or more years after the diagnosis of first primary cancers, SIRs of second primary EPCs were elevated in patients whose first primary cancers were in the bile duct (males 2.61; females 2.33), gallbladder (males 2.29; females 2.22), and kidney (males 1.39; females 1.73) in both sexes, and ovary (1.66) and breast (1.38) in females. Conclusions: Survivors of first primary bile duct, gallbladder, kidney, ovary, and female breast cancer should be closely monitored for the occurrence of second primary EPCs, even after 5 years of follow-up.

Investigation of changes in DNA methylation associated with alterations in gene expression resulting in differences between lean and obese adipogenesis.

DNA methylation (DNAm) is an important epigenetic regulator controlling various cellular activities, including cell proliferation and differentiation. In the present work, we examined alterations in DNAm associated with obesity using methylome and transcriptome data from 27 purified adipocytes (ACs) and 7 preadipocytes (preACs) in human visceral adipose tissue (VAT) samples. We identified differentially methylated probes (DMPs) using two methods: (i) DMPs that were obtained from a comparison of the DNAm levels between AC and preAC samples (AGDMPs) and (ii) DMPs that were obtained from a comparison of the DNAm levels between obese and lean AC samples (ACDMPs). These two classes of DMPs were obtained to identify a relationship between adipogenesis and obesity. We also investigated how hyper and hypomethylation of the promoter and/or gene body differentially affected changes in gene expression by estimating the odds ratios (ORs) of changes in gene expression without DMPs in the background. Interestingly, the magnitude of DNAm alterations during AC differentiation was greater under lean conditions than under obese conditions. In conclusion, several adipogenesis-related genes were affected by complicated methylation changes and ultimately cause differences in gene expression in ACs under lean and obese conditions.

Incidence and treatment outcomes of uterine cervical cancer in Korea 1999-2018 from the national cancer registry.

OBJECTIVE: To describe the incidence and survival outcomes of uterine cervical cancer during 1999-2018. METHODS: Patients who were diagnosed with cervical cancer during 1999-2018 were identified in the Korea Central Cancer Registry. Age-standardized incidence rates (ASRs) and annual percent changes (APCs) were calculated. Survival rates by histology, year of diagnosis (1999-2008 vs. 2009-2018), stage, and age at diagnosis were analyzed. RESULTS: The absolute incidence of cervical cancer decreased over 20 years from 4,488 in 1999 to 3,500 in 2018, with an APC of -3.42% (p<0.0001). While ASR of squamous cell carcinoma (SCCA) more than halved from 13.27 per 100,000 in 1999 to 6.16 in 2018 (APC, -4.04%), adenocarcinoma continued to rise (ASR, 1.30 per 100,000 to 1.92; APC, 1.52%; p<0.0001). Patients with adenocarcinoma were younger than those with SCCA (mean, 49.9±12.7 vs. 52.9 ±14.6 years; p<0.0001). Five-year survival rate of cervical cancer patients overall was 78.0%. Adenocarcinoma had poorer survival than SCCA (5-year survival rate, 76.8% vs. 79.8%; p<0.0001). There was no survival difference between patients who were diagnosed between 1999-2008 and 2009-2018. Earlier-stage disease had better survival (5-year survival rate for localized, regional, and distant disease, 90.0% vs. 69.9% vs. 26.5%; p<0.0001). Younger patients aged <50 years had better survival than those aged ≥50 years (87.1% vs. 69.8%; p<0.0001). CONCLUSION: The incidence of SCCA of the uterine cervix declined while adenocarcinoma continued to increase slowly but significantly from 1999 to 2018 in Korea. Adenocarcinoma was diagnosed at a younger age, but had poorer survival outcome than SCCA.

Adipocyte differentiation between obese and lean conditions depends on changes in miRNA expression.

Adipogenesis is the process by which precursor cells, preadipocytes (preACs), differentiate into adipocytes (ACs). Here, we investigated differentially expressed miRNAs (DEMs) between the two conditions to understand the regulatory role of miRNAs in altering adipogenesis-related mRNAs. A total of 812 and 748 DEMs were obtained in lean and obese conditions, respectively. The up- and downregulated DEMs were highly concordant with each other in both lean and obese conditions; however, DEMs related to adipogenesis in obese conditions were more strongly downregulated than DEMs related to adipogenesis in lean conditions. There were more obese-specific downregulated DEMs than lean-specific downregulated DEMs; in contrast, there were more lean-specific upregulated DEMs than obese-specific upregulated DEMs. Approximately 45% of DEMs were mapped to the list of miRNA-target mRNA pairs when DEMs were matched to the experimentally validated list of miRNA-target mRNA information of miRTarBase. Many of the target mRNAs were differentially expressed genes (DEGs) with functions in processes such as inflammatory responses and fat metabolism. In particular, a total of 25 miRNAs that target three upregulated adipogenesis-associated inflammatory genes (IL-6, TNF-α, and IL-1ß) were commonly altered during adipogenesis. Taken together, our study reveals the types of adipogenesis-related miRNAs that are altered and the degree to which they influence healthy or pathogenic adipogenesis.

Distinct prognosis of biliary tract cancer according to tumor location, stage, and treatment: a population-based study.

Biliary tract cancer (BTC) has been inconsistently identified according to its location in epidemiological and clinical studies. This study retrospectively reviewed the treatment pattern and prognosis of BTC according to tumor location using the Korea Central Cancer Registry data of 97,676 patients with BTC from 2006 to 2017. The proportion of localized and regional Surveillance, Epidemiology, and End Results (SEER) stage was the highest in ampulla of Vater (AoV, 78.2%) cancer, followed by extrahepatic bile duct (BD, 68.3%), gallbladder (GB, 52.6%), and intrahepatic BD (49.5%) cancers. Overall, the "no active anti-cancer treatment" rate was the highest in intrahepatic BD (52.8%), followed by extrahepatic BD (49.5%), GB (39.6%), and AoV cancers (28.9%). The 5-year relative survival rate was the highest in AoV (48.5%), followed by GB (28.5%), extrahepatic BD (19.9%), and intrahepatic BD (10.8%) cancers, which significantly improved over time, except for intrahepatic BD cancer. In the localized and regional stage, older patients had a higher risk of receiving no active anti-cancer treatment in each tumor location after adjusting for period and sex. BTC statistics should be reported separately according to tumor location due to its distinct SEER stage distribution, treatment pattern, and prognosis. Care should be taken in elderly patients to reduce the rate of no active anti-cancer treatment.

Trends in the Incidence and Survival Rates of Primary Ovarian Clear Cell Carcinoma Compared to Ovarian Serous Carcinoma in Korea.

Objective: To compare the incidence and survival rates of primary ovarian clear cell carcinoma (OCCC) and ovarian serous carcinoma (OSC) from a nationwide collected database. Methods: We extracted information of patients with primary OCCC and OSC from the Korea Central Cancer Registry recorded between 1999 and 2018, including age at diagnosis and the Surveillance, Epidemiology, and End Results summary stage. Age-standardized incidence rates (ASRs) and annual percent changes (APCs) were calculated. Baseline characteristics and overall survival (OS) were compared between the OCCC and OSC groups. Results: Overall, the incidence rate of primary OCCC increased markedly from 1999 (ASR, 0.16/100,000) to 2018 (0.76/100,000) (APC, 7.85%; P<0.0001). Patients with OCCC were significantly younger and had early-stage disease more frequently than those with OSC. Patients diagnosed with OCCC before the age of 50 showed better OS than those diagnosed after the age of 50 (P=0.0048). The 5-year OS of the OCCC group did not differ by study period [73.5% (1999-2008) vs. 75.4% (2009-2018), P=0.3187], whereas the 5-year OS of the OSC group improved from 54.4% to 58% (P=0.0003). Conclusions: Our nationwide registry-based study demonstrated that the incidence of OCCC in Korea increased significantly from 1999 to 2018. Early-stage OCCC had a relatively good prognosis, but advanced-stage OCCC had a worse OS than advanced-stage OSC. Therefore, the development of optimal treatment strategies for OCCC is warranted.

First Course of treatment and Prognosis of Exocrine Pancreatic Cancer in Korea from 2006 to 2017.

PURPOSE: Hospital-based clinical studies have limitations in holistic assessment of cancer treatment and prognosis, as they omit out-of-hospital patients including elderly individuals. This study aimed to investigate trends in initial treatment and corresponding prognosis of patients with exocrine pancreatic cancer (EPC) in Korea. MATERIALS AND METHODS: The Korea Central Cancer Registry data of patients with EPC from 2006 to 2017 were retrospectively reviewed. We defined the first course of treatment (FT) as the cancer-directed treatment administered within four months after cancer diagnosis according to the Surveillance, Epidemiology, and End Results (SEER) program. RESULTS: Among 62,209 patients with EPC, localized and regional (LR) SEER stage; patients over 70 years old; and ductal adenocarcinoma excluding cystic or mucinous (DAC) accounted for 40.6%, 50.1%, and 95.9%, respectively. "No active treatment" (NT, 46.5%) was the most frequent, followed by non-surgical FT (28.7%) and surgical FT (22.0%). Among 25,198 patients with LR EPC, surgical FT increased (35.9% to 46.3%) and NT decreased (45.0% to 29.5%) from 2006 to 2017. The rate of surgical FT was inversely related to age (55.1% [< 70 years], 37.3% [70-79 years], 10.9% [≥ 80 years]). Five-year relative survival rates of LR DAC were higher after surgical FT than after NT in localized (46.1% vs. 12.9%) and regional stage (23.6% vs. 4.9%) from 2012 to 2017. CONCLUSION: Less than half of overall patients with LR EPC underwent surgical FT, and this proportion decreased significantly in elderly individuals. Clinicians should focus attention on elderly patients with EPC to provide appropriate medical advice.

Incidence Patterns and Outcomes of Ewing Sarcoma in South Korea (1999-2017): A Retrospective Analysis Using Korea Central Cancer Registry Data.

PURPOSE: Due to low incidence, epidemiologic data of Ewing sarcoma in the Asian population are scarce. We aimed to examine the incidence pattern and outcome of patients with Ewing sarcoma in the Republic of Korea. MATERIALS AND METHODS: Data of patients with Ewing sarcoma diagnosed between 1999 and 2017 were obtained from the Korea Central Cancer Registry (KCCR). Incidence, clinical characteristics, and survival rates were analyzed and compared between different age groups. RESULTS: There were 788 cases (459 males, 329 females), with a median age at diagnosis of 20 years. The age-standardized rate of Ewing sarcoma was 1.01. The number of cases and incidence rates in each age group were as follows: children, 1.6; adolescents and young adults (AYA), 0.93; adults, 0.44; and elderly, 0.53. There were more male cases in children and the AYA group (p < 0.001). Extraskeletal tumors (p < 0.001), primary sites other than extremity (p=0.007), and presence of metastasis at diagnosis (p=0.031) were more frequent in the adults and elderly group. With a median survival time of 78 months, the 5-year overall survival (OS) rate of the entire cohort was 52%. Children fared best (5-year OS, 75%), and the 5-year OS of AYA patients (51%) approximated the OS of the entire cohort. A two-fold difference of 5-year OS was observed between adults and elderly patients (42% vs. 19%). On univariate and multivariate analyses, age ≥ 15 years and presence of metastasis were adverse prognostic factors. CONCLUSION: This was the first epidemiologic study of Ewing sarcoma using the KCCR data. With a similar incidence to other Asian countries, the survival rate was slightly lower than that of Euro-American cases. Collaborative clinical studies are necessary to improve the outcome of Ewing sarcoma in low-incidence populations.

The Neuropeptide Spexin Promotes the Osteoblast Differentiation of MC3T3-E1 Cells via the MEK/ERK Pathway and Bone Regeneration in a Mouse Calvarial Defect Model.

BACKGROUND: The neural regulation of bone regeneration has emerged recently. Spexin (SPX) is a novel neuropeptide and regulates multiple biological functions. However, the effects of SPX on osteogenic differentiation need to be further investigated. Therefore, the aim of this study is to investigate the effects of SPX on osteogenic differentiation, possible underlying mechanisms, and bone regeneration. METHODS: In this study, MC3T3-E1 cells were treated with various concentrations of SPX. Cell proliferation, osteogenic differentiation marker expressions, alkaline phosphatase (ALP) activity, and mineralization were evaluated using the CCK-8 assay, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), ALP staining, and alizarin red S staining, respectively. To determine the underlying molecular mechanism of SPX, the phosphorylation levels of signaling molecules were examined via western blot analysis. Moreover, in vivo bone regeneration by SPX (0.5 and 1 µg/µl) was evaluated in a calvarial defect model. New bone formation was analyzed using micro-computed tomography (micro-CT) and histology. RESULTS: The results indicated that cell proliferation was not affected by SPX. However, SPX significantly increased ALP activity, mineralization, and the expression of genes for osteogenic differentiation markers, including runt-related transcription factor 2 (Runx2), Alp, collagen alpha-1(I) chain (Col1a1), osteocalcin (Oc), and bone sialoprotein (Bsp). In contrast, SPX downregulated the expression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1). Moreover, SPX upregulated phosphorylated mitogen-activated protein kinase kinase (MEK1/2) and extracellular signal-regulated kinase (ERK1/2). In vivo studies, micro-CT and histologic analysis revealed that SPX markedly increased a new bone formation. CONCLUSION: Overall, these results demonstrated that SPX stimulated osteogenic differentiation in vitro and increased in vivo bone regeneration via the MEK/ERK pathway.

Osteosarcoma in Adolescents and Young Adults.

The epidemiology of osteosarcoma in adolescents and young adults (AYA) remains unclear. We aimed to assess and compare the clinical features of osteosarcoma between AYA and other age groups. We retrieved osteosarcoma cases diagnosed between 1999 and 2017 from the Korea Central Cancer Registry. We compared survival trends and clinical characteristics between AYA and other age groups. AYA comprised 43.3% (1309/3022) of the osteosarcoma cases. Compared to other age groups, the male-to-female ratio was highest in AYA (1.61:1). The proportion of tumors located in an extremity was 80.3% in AYA, which was lower than in young children (92.5%) or pubertal children (93.8%) but higher than in adults (55.7%) or the elderly (47.5%). As for treatments, 71.2% of AYA received local treatment and systemic chemotherapy, and 28.8% received only local treatment (surgery: 261, radiotherapy: 9, surgery and radiotherapy: 5). The 5-year overall survival (OS) was lower in AYA (68%) than in young children (78%) or pubertal children (73%) but higher than in adults (47%) or the elderly (25%). When AYA were divided into five subgroups by age, patients aged 15-19 years constituted the largest proportion (45.4%, n = 594). Additionally, the proportion of patients with a non-extremity tumor increased in an age-dependent manner, from 10.3% in AYA aged 15-19 years to 35.3% in AYA aged 35-39 years. OS did not significantly differ among the different age subgroups of AYA. The clinical characteristics and OS of the AYA were more similar to those of children than to those of adults. There is a need for cooperation between pediatric and adult oncologists for effective osteosarcoma treatment in AYA.

Incidence and treatment outcomes of ovarian sarcoma compared to epithelial ovarian cancer from the national cancer registry.

PURPOSE: To investigate the incidence and survival outcomes of primary ovarian sarcoma compared to those of epithelial ovarian cancer. METHODS: Data on primary ovarian sarcoma patients (n = 1361) and epithelial ovarian cancer patients (n = 30,366) between 1999 and 2017 were obtained from the Korea Central Cancer Registry, and their respective age-standardized incidence rate (ASR) and relative survival rate were calculated and compared. RESULTS: Based on the ASR, the incidence of epithelial ovarian cancer was 4.75 per 100,000 women, while that of primary ovarian sarcoma was 0.22 per 100,000 women. The ASR ratio was 21.94 without significant change of ASR during the study period. Primary ovarian sarcoma had a better survival curve compared with epithelial ovarian cancer, though the difference was not statistically significant (5 yr overall survival 64.0% vs. 61.5%; p = 0.6030). In addition, among the pure sarcomas, the fibrosarcoma histologic subtype showed the best overall survival, and that of liposarcomas and stromal cell sarcoma were behind that (5 yr overall survival 85.0%, 76.7%, and 72.7%; p < 0.0001). CONCLUSIONS: The incidence of primary ovarian sarcoma is quite low, with an ASR of 0.22/100,000 during the last 20 years. There were no significant differences between survival rates of primary ovarian sarcoma and epithelial ovarian cancer.

Descriptive epidemiology of cancer of unknown primary in South Korea, 1999-2017.

BACKGROUND: Cancers of unknown primary (CUPs) are tumors found after metastasizing from unidentified primary sites; these tumors generally have unknown treatment strategies, expected treatment results, and prognosis. We assessed the epidemiological characteristics of CUPs in Korea. METHODS: We extracted records for 1999 through 2017 from the Korea Central Cancer Registry using the International Statistical Classification of Diseases and Related Health Problems (10th revision) codes for CUP as defined by the International Agency for Research on Cancer. Age-standardized rates and relative survival rates were calculated. RESULTS: The CUPs constituted 2.1 % of the total number of cancer registrations in 1999, declining to 0.7 % in 2017. The incidence rate decreased for both sexes (5.35 to 2.20 for men, 3.15 to 1.77 for women). Patients aged 80 years and older had the highest incidence rate at 40.2, and 86.3 % of CUPs occurred in those 50 years of age or older. The cases of retroperitoneum and peritoneum sites increased over time. Cases diagnosed by microscopic methods and death certification only were 62.3 % and 7.9 %, respectively. The malignant neoplasm of the retroperitoneum and peritoneum and unknown primary site had the highest and lowest survival rates, respectively. The 5-year relative survival rate increased over time from 14.2 % (1999-2002) to 27.3 % (2013-2017). CONCLUSIONS: Our analysis of data from the Korea Central Cancer Registry found decreasing rates of CUP, although with consistent disparities by patient age and sex. Advancements in diagnostic technology may be decreasing the number of CUP diagnoses. Expanding the amount of information recorded in the registry may further improve diagnostic accuracy.

Protective Effect of Ciclopirox against Ovariectomy-Induced Bone Loss in Mice by Suppressing Osteoclast Formation and Function.

Postmenopausal osteoporosis is closely associated with excessive osteoclast formation and function, resulting in the loss of bone mass. Osteoclast-targeting agents have been developed to manage this disease. We examined the effects of ciclopirox on osteoclast differentiation and bone resorption in vitro and in vivo. Ciclopirox significantly inhibited osteoclast formation from primary murine bone marrow macrophages (BMMs) in response to receptor activator of nuclear factor kappa B ligand (RANKL), and the expression of genes associated with osteoclastogenesis and function was decreased. The formation of actin rings and resorption pits was suppressed by ciclopirox. Analysis of RANKL-mediated early signaling events in BMMs revealed that ciclopirox attenuates IκBα phosphorylation without affecting mitogen-activated protein kinase activation. Furthermore, the administration of ciclopirox suppressed osteoclast formation and bone loss in ovariectomy-induced osteoporosis in mice and reduced serum levels of osteocalcin and C-terminal telopeptide fragment of type I collagen C-terminus. These results indicate that ciclopirox exhibits antiosteoclastogenic activity both in vitro and in vivo and represents a new candidate compound for protection against osteoporosis and other osteoclast-related bone diseases.

Incidence and outcomes of malignant ovarian germ cell tumors in Korea, 1999-2017.

OBJECTIVE: Malignant ovarian germ cell tumor (MOGCT) is a rare ovarian malignancy accounting for less than 5% of all ovarian cancers. We aimed to evaluate the incidence, survival, and subsequent malignancies after the diagnosis of MOGCT. METHODS: Data from the Korea Central Cancer Registry were used to identify MOGCTs between 1999 and 2017. The age-standardized rates (ASRs), 5-year relative survival rates (RSR) and standardized incidence ratio (SIR) for subsequent cancer after diagnosis of MOGCT were estimated. RESULTS: Of 2125 cases of newly diagnosed MOGCTs, 596 (28.0%) were diagnosed with dysgerminoma and 1529 (72.0%) with non-dysgerminoma. The ASR per 100,000 women-years was 0.539; ASR slightly increased over the study period (annual percent change [APC] = 1.01%; p = 0.02). There was an increase and decrease in the incidence of MOGCTs in the age groups 0-19 years (APC = 1.96%; p < 0.01) and ≥ 50 years (APC = -6.51%; p < 0.01), respectively. Patients with dysgerminoma showed significantly higher RSR than patients with non-dysgerminoma (98.0% vs. 94.9%, p < 0.01). Patients aged ≥50 years showed worst 5-year RSR (68.7%) than patients aged 0-19 years (97.8%) and 20-34 years (96.4%) (p < 0.01). The overall SIR for a subsequent cancer occurrence was 2.07, with the most frequent site of subsequent primary cancer being the thyroid (SIR = 2.78). CONCLUSIONS: Our data demonstrated an excellent prognosis of MOGCTs among Korean women. There was a slight increase in MOGCT prevalence, which was more pronounced among those aged <19 years. After MOGCT diagnosis, the risk of developing a subsequent malignancy was doubled compared with the general population.