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.

GSK3 Restrains Germinal Center B Cells to Form Plasma Cells.

B cells in the germinal center (GC) are programmed to form plasma cells (PCs) or memory B cells according to signals received by receptors that are translated to carry out appropriate activities of transcription factors. However, the precise mechanism underlying this process to complete the GC reaction is unclear. In this study, we show that both genetic ablation and pharmacological inhibition of glycogen synthase kinase 3 (GSK3) in GC B cells of mice facilitate the cell fate decision toward PC formation, accompanied by acquisition of dark zone B cell properties. Mechanistically, under stimulation with CD40L and IL-21, GSK3 inactivation synergistically induced the transcription factors Foxo1 and c-Myc, leading to increased levels of key transcription factors required for PC differentiation, including IRF4. This GSK3-mediated alteration of transcriptional factors in turn facilitated the dark zone transition and consequent PC fate commitment. Our study thus reveals the upstream master regulator responsible for interpreting external cues in GC B cells to form PCs mediated by key transcription factors.

Bobby sox homolog regulates tooth root formation through modulation of dentin sialophosphoprotein.

Tooth root development occurs through the interaction of multiple growth factors and transcription factors expressed in Hertwig's epithelial root sheath (HERS) and dental mesenchyme. Previously, we demonstrated that bobby sox homolog (Bbx) regulates odontoblast differentiation of human dental pulp stem cells. Here, we generated Bbx knockout (Bbx-/- ) mice to address the functional role of Bbx in tooth formation. During tooth development, Bbx was expressed in both dental epithelium and mesenchyme. However, molar and incisor morphology in Bbx-/- mice at postnatal Day 0 (P0) exhibited no prominent abnormalities compared with their wild-type (Bbx+/+ ) littermates. Until P28, the crown morphology in Bbx-/- mice was not distinctively different from Bbx+/+ littermates. Meanwhile, the length of the mandibular base in Bbx-/- mice was notably less at P28. Compared with Bbx+/+ mice, the mesial and distal root lengths of the first molar were reduced by 21.33% and 16.28% at P14 and 16.28% and 16.24% at P28, respectively, in Bbx-/- mice. The second molar of Bbx-/- mice also showed 10.16% and 6.4% reductions at P28 in the mesial and distal lengths, compared with Bbx+/+ mice, respectively. The gene expression analysis during early tooth root formation (P13) showed that the expression of dentin sialophosphoprotein (Dspp) was significantly decreased in Bbx-/- mice. Collectively, our data suggest that Bbx participates in tooth root formation and might be associated with the regulation of Dspp expression.

Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities.

BACKGROUND: Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. METHODS: The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan. RESULTS: It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types. CONCLUSIONS: Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.

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.

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.

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.

Inhibitory effect of oolonghomobisflavan B on osteoclastogenesis by suppressing p38 MAPK activation.

Suppression of differentiation and/or function of osteoclasts is considered an effective therapeutic strategy for osteolytic bone diseases such as periodontitis and osteoporosis. Evidence regarding the health benefits of oolong tea consumption is accumulating, and tea polyphenols have various pharmacological properties such as anti-cancer and anti-diabetes effects. In this study, we investigated the effect of oolonghomobisflavan B (OFB), a polyphenolic compound in oolong tea, on osteoclast differentiation. OFB suppressed receptor activator of nuclear factor-κB (RANKL)-induced formation of tartate-resistant acid phosphatase-positive multinuclear cells without cytotoxicity. OFB also significantly attenuated p38 phosphorylation, which is essential for RANKL-induced osteoclastogenesis, and inhibited the expressions of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) and osteoclast-specific target genes, including dendritic cell-specific transmembrane protein and cathepsin K. Our findings suggest that OFB exhibits an anti-osteoclastogenic activity by inhibiting RANKL-mediated p38 activation, which is useful for the prevention and treatment of osteolytic bone diseases.

Second primary cancer after primary peritoneal, epithelial ovarian, and fallopian tubal cancer: a retrospective study.

BACKGROUND: In this retrospective study, data from patients listed in the Korea Central Cancer Registry during 1993-2014 were analysed, to investigate the incidence and survival of second primary cancers (SPCs) after a diagnosis of primary peritoneal, epithelial ovarian, and fallopian tubal (POFT) cancer. METHODS: The standardised incidence ratio (SIR) and survival outcomes of patients with SPCs among POFT cancer survivors were analysed. RESULTS: Among 20,738 POFT cancer survivors, 798 (3.84%) developed SPCs, at an average interval of 5.50 years. SPC risk in POFT survivors (SIR, 1.29) was higher compared to the general population. The most high-risk type of SPC was leukaemia (3.07) followed by the lung and bronchus (1.80), colon (1.58), rectum and rectosigmoid junction (1.42), thyroid (1.34), and breast (1.26). In women aged < 60 years, cancer of the breast (1.30), ascending colon (2.26), and transverse colon (4.07) as SPCs increased. Up to 10 years after POFT cancer treatment, leukaemia risk increased, especially in those < 60 years, with serous histology, and with distant stage, which required aggressive chemotherapy. The median overall survival time was 12.8 years and 14.3 years in women with POFT cancer and SPCs, respectively. Thyroid and breast cancers were favourable prognostic markers among SPCs. CONCLUSIONS: The overall SPC risk increases in POFT cancer survivors, especially in those < 60 years. The cancer risk of breast and the proximal colon increase based on hereditary predisposition, while leukaemia likely develops from aggressive treatment. The median overall survival is favourable in POFT cancer survivors with SPCs.

Risk of second primary Cancer among bladder Cancer patients: a population-based cohort study in Korea.

BACKGROUND: For the expanding population of bladder cancer survivors in Korea, the development of subsequent cancers is a significant concern. Here, we provide the second primary cancer incidence rates and types in Korean patients with bladder cancer. METHODS: Using population-based data from the Korea Central Cancer Registry from 1993 to 2013, we studied the standardized incidence ratios among 48,875 individuals with an initial diagnosis of bladder cancer. Standardized incidence ratios for second primary cancers were evaluated according to age at diagnosis, latency, diagnostic year, and treatment. RESULTS: Over the same period, the overall risk of a second primary cancer was reduced by 6% in patients with bladder cancer compared with the development of a new malignancy in the general population (standardized incidence ratio = 0.94; 95% CI, 0.91-0.97, p < 0.05). For specific cancers, the standardized incidence ratios for stomach, colon, liver, and non-Hodgkin lymphoma were significantly lower in patients with bladder cancer. However, the risk of prostate and kidney cancer in patients with bladder cancer were significantly increased. The risk of lung squamous cell carcinoma and lung adenocarcinoma as second primary cancers was significantly elevated in patients with bladder cancer. CONCLUSION: Korean patients with bladder cancer have a 6% lower risk of developing a second primary cancer. However, they have a higher risk of developing subsequent prostate and kidney cancers, lung squamous cell carcinoma, and lung adenocarcinoma, suggesting the need for continual intensive cancer surveillance among bladder cancer survivors.

Aquatic flower-inspired cell culture platform with simplified medium exchange process for facilitating cell-surface interaction studies.

Establishing fundamentals for regulating cell behavior with engineered physical environments, such as topography and stiffness, requires a large number of cell culture experiments. However, cell culture experiments in cell-surface interaction studies are generally labor-intensive and time-consuming due to many experimental tasks, such as multiple fabrication processes in sample preparation and repetitive medium exchange in cell culture. In this work, a novel aquatic flower-inspired cell culture platform (AFIP) is presented. AFIP aims to facilitate the experiments on the cell-surface interaction studies, especially the medium exchange process. AFIP was devised to capture and dispense cell culture medium based on interactions between an elastic polymer substrate and a liquid medium. Thus, the medium exchange can be performed easily and without the need of other instruments, such as a vacuum suction and pipette. An appropriate design window of AFIP, based on scaling analysis, was identified to provide a criterion for achieving stability in medium exchange as well as various surface characteristics of the petal substrates. The developed AFIP, with physically engineered petal substrates, was also verified to exchange medium reliably and repeatedly. A closed structure capturing the medium was sustained stably during cell culture experiments. NIH3T3 proliferation results also demonstrated that AFIP can be applied to the cell-surface interaction studies as an alternative to the conventional method.

Elevated risks of subsequent primary malignancies in patients with thyroid cancer: a nationwide, population-based study in Korea.

BACKGROUND: Thyroid cancer affects relatively young adults, and its overall survival is excellent. With long life expectancy, the development of subsequent cancers is an important concern for survivors of thyroid cancer. The objective of this study was to investigate the incidence and types of second primary malignancies in Korean patients with thyroid cancer. METHODS: The study cohort included 178,844 registrants with thyroid cancer from the Korea Central Cancer Registry (KCCR) database between 1993 and 2010. Standardized incidence ratios (SIRs) were calculated using a statistical software program (SEER*Stat 8.0.4). RESULTS: Among 178,844 patients with thyroid cancer, 2895 (1.6%) were diagnosed with subsequent second primary malignancies. The overall risks of a second primary cancer were elevated by 6% in patients who had thyroid cancer compared with the general population during the same period. The elevated risks for developing second cancers were observed in all sites except the stomach and cervix. The elevated risk of second primary cancers was observed within the first 10 years of follow-up. Leukemia and cancers of the salivary gland, kidney, prostate, lung, and breast had the most significantly elevated risks as secondary cancers and presented as early as during the first 5 years after the initial diagnosis of thyroid cancer. CONCLUSIONS: This is the largest, standardized, population-based study to date using nationwide data from the entire Korean population. The risks of several cancers were elevated significantly during follow-up, thus alerting physicians to pay special attention in their care of patients with thyroid cancer and long-term survivors.

Inhibitory effects of triptolide on titanium particle-induced osteolysis and receptor activator of nuclear factor-κB ligand-mediated osteoclast differentiation.

PURPOSE: We examined the effects of triptolide on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and on titanium (Ti) particle-induced osteolysis. METHODS: To examine the effect of triptolide on osteoclast differentiation, bone marrow macrophages (BMMs) were treated with 100 ng/mL of RANKL and 30 ng/mL of macrophage-colony stimulating factor, or co-cultured with osteoblasts stimulated with 10 nM vitamin D3 and 1 µM prostaglandin E2 in the presence or absence of triptolide (2.8-14 nM). Osteoclast differentiation and activation were assessed using tartrate-resistant acid phosphatase staining, reverse transcriptase-polymerase chain reaction analysis to determine differentiation marker gene expression and pit formation assays. To examine the effect of triptolide on wear debris-induced osteolysis, titanium (Ti) particles were injected into the calvaria of ICR mice. Then, the mice were divided into three groups and were orally administered vehicle, or 16 or 32 µg/kg/day triptolide for ten days, followed by histomorphometric analysis. RESULTS: Triptolide suppressed RANKL-mediated osteoclast differentiation of BMMs in a dose-dependent manner. In a co-culture system, osteoblasts treated with triptolide could not induce osteoclast differentiation of BMMs, which was accompanied by down-regulation of RANKL and up-regulation of osteoprotegrin. Moreover, triptolide significantly inhibited bone resorption, and expression of the bone resorption marker genes. RANKL-induced activation of p38, ERK, and JNK was substantially inhibited by triptolide. Further, in a Ti-induced mouse calvarial erosion model, mice perorally administrated with triptolide showed significant attenuation of Ti-mediated osteolysis. CONCLUSION: Our data indicated that triptolide had an anti-osteoclastic effect and significantly suppressed wear debris-induced osteolysis in mice.

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.

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.

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.

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 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.

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.

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.