Establishment of IGF-1 and IGFBP-3 continuous reference percentiles from data of healthy children using three kinds of immunoassay systems.

Background and aims: Appropriate continuous reference intervals (RIs) for serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are important for diagnosing growth hormone deficiency or excess. Material and methods: We retrospectively reviewed serum IGF-1 and IGFBP-3 levels in Korean children aged 0-17 years who were diagnosed as healthy during a short stature workup in the outpatient clinics of three hospitals. IGF-1 and IGFBP-3 levels were measured using various immunoassays, including Liaison XL for IGF-1, an immunoradiometric assay (IRMA) for IGFBP-3 (n = 5522), and Immulite 2000 (n = 3036) and cobas e801 (n = 314). We established RIs from the 2.5th to 97.5th percentile RI curves using the lambda-mu-sigma (LMS) method for each sex group. Results: Pediatric serum continuous IGF-1 and IGFBP-3 reference percentiles by LMS method were found to be immunoassay method-dependent, but aligned relatively well with the manufacturers' RIs. IGFBP-3 levels displayed notable discrepancies among the different immunoassay methods. Conclusion: Age- and sex-specific pediatric LMS based continuous reference intervals are method dependent and they should be calculated for dynamic parameters that show variations throughout childhood.

Evaluation of the Accuracy of Estimated Endpoint Titer of NOVA View in Indirect Immunofluorescent Antinuclear Antibody Testing.

For antinuclear antibody (ANA) screening, the gold standard method is an indirect immunofluorescence assay (IIFA) using HEp-2 cells, and a serial dilution test is needed to determine the endpoint titer. We aimed to evaluate the accuracy of the estimated endpoint titer (eEPT) by the NOVA View system, by comparing it with the EPT by the serial dilution method (dEPT). The endpoint titers of a total of 1518 ANA positive cases with five major patterns including speckled, homogeneous, centromere, nucleolar, and nuclear dots patterns were determined using both the estimation function and the serial dilution method by the NOVA View system. A significant correlation between the light intensity unit (LIU) values and dEPTs was identified in all five patterns with high ρ values, ranging from 0.666 to 0.832. However, the overall exact match rate between dEPT and eEPT was 22.1% (336/1518), with the ±one-titer match rate being highest in the centromere pattern (62.8%, 81/129), and lowest in the homogeneous pattern (37.6%, 200/532). This suggests that while LIU values correlate well with dEPT, there are discrepancies in numerical agreement. Most cases that did not show an exact match, showed one-to-three-titer overestimations by eEPT. Therefore, adjusting eEPT downward significantly improved the concordance rates with dEPTs. Further investigation for an appropriate cutoff of LIU values for determining eEPT should be performed for clinical application and contribution to the standardization of the ANA titer.

Diagnostic Performance of Preoperative Calcitonin and Procalcitonin Tests for Differential Diagnosis of Medullary Thyroid Cancer.

Medullary thyroid cancer (MTC) shows a relatively poor prognosis among thyroid cancers. Though calcitonin has been used as a diagnostic marker for MTC, it has disadvantages including poor sample stability and discrepancies among results by assay. This study aimed to compare the usefulness of preoperative calcitonin and procalcitonin (PCT) in the diagnosis of MTC. Serum calcitonin and PCT levels were measured before thyroidectomy from MTC (n = 23) and other types of thyroid cancers in patients (n = 1308). Diagnostic performances of calcitonin and PCT for discerning MTC were estimated. In a multivariate analysis, preoperative calcitonin level was independently associated with the diagnosis of MTC, whereas PCT was not. Calcitonin and PCT, respectively, exhibited area under the curve values of 0.997 and 0.979 for the diagnosis of MTC, without significant differences. For calcitonin, the sensitivity, specificity, and positive and negative predictive values were 0.957, 0.992, 0.688, and 0.999, respectively, at a cut-off of 7.2 pg/mL. The corresponding values for PCT were 0.913, 0.995, 0.778, and 0.998 at a cut-off of 0.19 ng/mL. Preoperative calcitonin and PCT showed similar diagnostic utility for MTC. Depending on the patient's clinical status and laboratory environment, these tests can be used as complementary methods for detecting MTC.

Development and validation of artificial intelligence models to predict urinary tract infections and secondary bloodstream infections in adult patients.

BACKGROUND: Traditional culture methods are time-consuming, making it difficult to utilize the results in the early stage of urinary tract infection (UTI) management, and automated urinalyses alone show insufficient performance for diagnosing UTIs. Several models have been proposed to predict urine culture positivity based on urinalysis. However, most of them have not been externally validated or consisted solely of urinalysis data obtained using one specific commercial analyzer. METHODS: A total of 259,187 patients were enrolled to develop artificial intelligence (AI) models. AI models were developed and validated for the diagnosis of UTI and urinary tract related-bloodstream infection (UT-BSI). The predictive performance of conventional urinalysis and AI algorithms were assessed by the areas under the receiver operating characteristic curve (AUROC). We also visualized feature importance rankings as Shapley additive explanation bar plots. RESULTS: In the two cohorts, the positive rates of urine culture tests were 25.2% and 30.4%, and the proportions of cases classified as UT-BSI were 1.8% and 1.6%. As a result of predicting UTI from the automated urinalysis, the AUROC were 0.745 (0.743-0.746) and 0.740 (0.737-0.743), and most AI algorithms presented excellent discriminant performance (AUROC > 0.9). In the external validation dataset, the XGBoost model achieved the best values in predicting both UTI (AUROC 0.967 [0.966-0.968]) and UT-BSI (AUROC 0.955 [0.951-0.959]). A reduced model using ten parameters was also derived. CONCLUSIONS: We found that AI models can improve the early prediction of urine culture positivity and UT-BSI by combining automated urinalysis with other clinical information. Clinical utilization of the model can reduce the risk of delayed antimicrobial therapy in patients with nonspecific symptoms of UTI and classify patients with UT-BSI who require further treatment and close monitoring.

Calf Circumference as an Indicator for Cystatin C Testing in Hospitalized Elderly Male Patients for Detecting Hidden Renal Impairment.

Serum creatinine is used to measure the estimated glomerular filtration rate (eGFR); however, it is influenced by muscle mass and may therefore overestimate renal function in patients with sarcopenia. We examined calf circumference (CC) as a convenient muscle mass evaluation tool that can potentially indicate the need to test for cystatin C instead of creatinine in elderly inpatients. We retrospectively reviewed the electronic health record of 271 inpatients aged 65 or over. CC was determined by measuring the thickest part of the nondominant calf. eGFRcys and eGFRcr were calculated using cystatin C and creatinine levels, respectively. We evaluated optimum CC cutoff values using the eGFRcys/eGFRcr ratio for detecting hidden renal impairment (HRI, defined as eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2). CC showed a significant positive correlation with the eGFRcys/eGFRcr ratio in both sexes. The areas under the receiver operating characteristic curve were 0.725 and 0.681 for males and females, respectively. CC cutoffs with a sensitivity or specificity of 90% or 95% might be used to detect HRI in males. In conclusion, utilizing the optimum cutoff, CC could be a cost-effective screening tool for detecting HRI in elderly male patients using cystatin C as an add-on test.

Muscle mass has a greater impact on serum creatinine levels in older males than in females.

Background and aims: We analyzed the effects of age and sex on the relationship between muscle mass and serum creatinine levels in an apparently healthy population, including older adults. Materials and methods: We retrospectively evaluated 1,502 individuals from the Korea National Health and Nutrition Examination Survey (KNHANES) and 4,586 individuals from the Health Check (HC) groups. We utilized data from the KNHANES and HC groups on serum creatinine levels and skeletal muscle mass index (SMI), determined using dual X-ray absorptiometry or bioelectric impedance analysis. Results: A significant negative correlation between SMI and age was observed in both the KNHANES and HC groups in males but not in females. In males, serum creatinine levels showed a significant negative correlation with age in both the KNHANES (r = -0.522, P < 0.0001) and HC groups (r = -0.451, P < 0.0001). In females, there was no significant correlation between serum creatinine levels and age in the KNHANES (r = -0.016, P = 0.5985) and HC group (r = -0.011, P = 0.5618). Conclusions: Serum creatinine levels decrease more significantly in older males than in older females due to sex-specific muscle mass decline.

A single-center experience on long-term clinical performance of a rapid SARS-CoV-2 Antigen Detection Test, STANDARD Q COVID-19 Ag Test.

The COVID-19 pandemic in Korea has dynamically changed with the occurrence of more easily transmissible variants. A rapid and reliable diagnostic tool for detection of SARS-CoV-2 is needed. While RT-PCR is currently the gold standard for detecting SARS-CoV-2, the procedure is time-consuming and requires expert technicians. The rapid antigen detection test (RADT) was approved as a confirmatory test on 14 March 2022 due to rapid dissemination of the Omicron variant. The benefits of the RADT are speed, simplicity, and point-of-care feasibility. The aim of our study was to evaluate the clinical performance of RADT compared to RT-PCR in a single center over 15 months, fully covering the SARS-CoV-2 'Variants of Concern (VOC).' A total of 14,194 cases was simultaneously tested by RT-PCR and RADT from January 2021 to March 2022 in Gangnam Severance Hospital and were retrospectively reviewed. PowerChek SARS-CoV-2, Influenza A&B Multiplex Real-time PCR Kit, and STANDARD Q COVID-19 Ag Test were used. Positive rates, sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were estimated for five periods (3 months/period). Receiver operator characteristic curve (ROC) analysis was performed, and Spearman's rank test assessed the correlation between RT-PCR Ct values and semi-quantitative RADT results. The overall positive rate of RT-PCR was 4.64%. The overall sensitivity and specificity were 0.577 [95% confidence interval (CI) 0.539-0.614] and 0.991 [95% CI 0.989-0.993], respectively. ROC analysis resulted in an area under the curve of 0.786 (P < 0.0001, Yuden's index = 0.568). The PCR positive rates were estimated as 0.11%, 0.71%, 4.51%, 2.02%, and 13.72%, and PPV was estimated as 0.045, 0.421, 0.951, 0.720, and 0.798 in Periods 1, 2, 3, 4, and 5, respectively. A significant and moderate negative correlation between PCR Ct values and semi-quantitative RADT results was observed (Spearman's ρ = - 0.646, P < 0.0001). The RADT exhibited good performance in specimens with low Ct values (Ct ≤ 25.00) by RT-PCR. The PPV was significantly higher in Periods 3 and 5, which corresponds to rapid dissemination of the Delta and Omicron variants. The high PPV implies that individuals with a positive RADT result are very likely infected with SARS-CoV-2 and would require prompt quarantine rather than additional RT-PCR testing. The sensitivity of 0.577 indicates that RADT should not replace RT-PCR. Nonetheless, given the high PPV and the ability to track infected persons through rapid results, our findings suggest that RADT could play a significant role in control strategies for further SARS-CoV-2 variants.

Associations of Perioperative Red Blood Cell Transfusion With Outcomes of Kidney Transplantation in Korea Over a 16-Year Period.

BACKGROUND: This study investigated the associations between transfusion of different types of red blood cell (RBC) preparations and kidney allograft outcomes after kidney transplantation (KT) over a 16-year period in Korea using a nationwide population-based cohort. METHODS: We investigated the reported use of RBCs during hospitalization for KT surgery, rejection, and graft failure status using nationwide data from the National Health Information Database (2002-2017). The associations between the type of perioperative RBC product and transplant outcomes were evaluated among four predefined groups: no RBC transfusion, filtered RBCs, washed RBCs, and packed RBCs (pRBCs). RESULTS: A total of 17,754 KT patients was included, among which 8,530 (48.0%) received some type of RBC transfusion. Of the patients who received RBC transfusion, 74.9%, 19.7%, and 5.4% received filtered RBCs, pRBCs, or washed RBCs, respectively. Regardless of the type of RBC products, the proportions of acute rejection and graft failure was significantly greater in patients receiving transfusion (P < 0.001). Cox proportional hazards regression analyses showed that the filtered RBC and pRBC groups were significantly associated with both rejection and graft failure. The washed RBC group also had hazard ratios greater than 1.0 for rejection and graft failure, but the association was not significant. Rejection-free survival of the pRBC group was significantly lower than that of the other groups (P < 0.001, log-rank test), and graft survival for the no RBC transfusion group was significantly greater than in the other groups (P < 0.001, log-rank test). CONCLUSION: Perioperative RBC transfusion was associated with poor graft outcomes. Notably, transfusion of pRBCs significantly increased transplant rejection. Therefore, careful consideration of indications for RBC transfusion and selection of the appropriate type of RBCs is necessary, especially for patients at high risk of rejection or graft failure.

Establishment of muscle mass-based indications for the cystatin C test in renal function evaluation.

Background: We aimed to suggest muscle mass-based criteria for using of the cystatin C test for the accurate estimated glomerular filtration rate (eGFR). Materials and methods: We recruited 138 Korean subjects and evaluated eGFRcr (derived from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) based on creatinine) was compared to eGFRcys based on cystatin C as the reference value. The skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) was used as representative of muscle mass. Calf circumference (CC) was also evaluated. We defined the patients by eGFRcr as those with values of eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2 as the detection of hidden renal impairment (DHRI). Cut-off values were determined based on muscle mass for the cases of DHRI suggesting the criteria of cystatin C test in renal function evaluation. Results: We confirmed significant negative correlation between %difference of eGFRcr from eGFRcys and SMI (r, -0.592 for male, -0.484 for female) or CC (r, -0.646 for male, -0.351 for female). SMI of 7.3 kg/m2 for males and 5.7 kg/m2 for females were suggested to be significant cutoffs for indication of cystatin C test. We also suggested CC would be valuable for cystatin C indication. Conclusion: We suggested the muscle mass-based objective criteria relating to SMI and CC that would indicate the use of cystatin C to evaluate renal function test in sarcopenic cases. Our results highlight the importance of muscle mass-based selection of renal function.

Reactogenicity and Immunogenicity of the ChAdOx1 nCOV-19 Coronavirus Disease 2019 Vaccine in South Korean Healthcare Workers.

PURPOSE: The association between reactogenicity and immunogenicity of the ChAdOx1 nCOV-19 is controversial. We aimed to evaluate this association among South Korean healthcare workers (HCWs). MATERIALS AND METHODS: Participants received two doses of the ChAdOx1vaccine 12 weeks apart. Blood samples were tested for anti-severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) spike protein receptor binding domain antibodies about 2 months after the first and second doses using the Elecsys Anti-SARS-CoV-2 S assay kits. Adverse events were noted using an online self-reporting questionnaire. RESULTS: Among the 232 HCWs, pain (85.78% after the first dose vs. 58.62% after the second dose, p<0.001) was the most prominent local reaction, and myalgia or fatigue (84.05% vs. 53.02%, p<0.001) was the most prominent systemic reaction. The frequency of all adverse events was significantly reduced after the second dose. After the first dose, the anti-SARS-CoV-2 S showed significantly higher titer in the group with swelling, itching, fever, and nausea. Also, the anti-SARS-CoV-2 S titer significantly increased as the grade of fever (p=0.007) and duration of fever (p=0.026) increased; however, there was no significant correlation between immunogenicity and adverse event after the second dose. The group with pain after the first dose showed a greater increase in the anti-SARS-CoV-2 S difference between the second and first doses compared to the group without pain (542.2 U/mL vs. 363.8 U/mL, p=0.037). CONCLUSION: The frequency of adverse events occurring after the first dose of the ChAdOx1 was significantly reduced after the second dose. Interestingly, the elevation of anti-SARS-CoV-2 S titer was significantly increased in the group with pain after the first dose.

Impact of urinary tract infection-causative microorganisms on the progression to bloodstream infection: A propensity score-matched analysis.

OBJECTIVES: We aimed to determine the risk factors for the progression of urinary tract infection (UTI) to bloodstream infection (BSI) and to evaluate the mortality-associated factors in patients with urinary tract-related BSI (UT-BSI). METHODS: A propensity score-matched study was conducted using clinical data from all adult patients with UTIs in two South Korean hospitals. RESULTS: A total of 84,406 patients with UTIs were enrolled. The relative incidence of UTIs caused by Escherichia coli decreased along with an increase in the incidence of Candida species infections during the study period. UTI caused by E. coli, Klebsiella pneumoniae, Staphylococcus aureus, and Candida species had a relatively high rate of progression to BSI. UT-BSI caused by Candida species (adjusted odd ratio 5.67; 95% confidence interval 3.97-8.11; p < 0.001) was significantly associated with high 30-day mortality. CONCLUSIONS: UTI-causative microorganisms were associated with both progression to UT-BSI and 30-day mortality in patients with UT-BSI. Considering the trend of increasing age of patients and more frequent use of indwelling urologic devices, UT-BSIs caused by other microorganisms than E. coli could be a more serious medical burden in the future.

De Novo Cancer Incidence after Kidney Transplantation in South Korea from 2002 to 2017.

Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi's sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients' age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development.

Age-group-specific reference intervals for anti-Müllerian hormone and its diagnostic performance for polycystic ovary syndrome in a Korean population.

BACKGROUND: We established age-group-specific reference intervals for serum anti-Müllerian hormone (AMH) levels in a Korean population and investigated the effectiveness of AMH assay for polycystic ovary syndrome (PCOS) diagnosis. METHODS: We analyzed serum levels of AMH, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) from 1540 Korean women. Subjects were divided into three groups: healthy, benign gynecologic diseases, and PCOS. Age-group-specific reference intervals and AMH diagnostic performance were estimated. RESULTS: The PCOS group had a median AMH level of 7.0 µg/L, which was higher than for the healthy (1.8 µg/L) and the benign gynecologic diseases (2.7 µg/L) groups. The upper 97.5% reference limits for age groups 12-20 years, 21-34 years, and 35-46 years were 13.2 µg/L, 15.8 µg/L, and 6.6 µg/L, respectively. The area under the curve (AUC) values to estimate AMH ability to discriminate PCOS from healthy women for each age group were 0.741, 0.785, and 0.789, respectively. AUCs for LH/FSH were 0.719, 0.672, and 0.590. CONCLUSIONS: The better diagnostic ability of AMH over LH/FSH in women of late childbearing ages indicates that age and other clinical characteristics should be considered when interpreting these test results.

Prediction of urine culture results by automated urinalysis with digital flow morphology analysis.

To investigate the association between the results of urinalysis and those of concurrent urine cultures, and to construct a prediction model for the results of urine culture. A total of 42,713 patients were included in this study. Patients were divided into two independent groups including training and test datasets. A novel prediction algorithm, designated the UTOPIA value, was constructed with the training dataset, based on an association between the results of urinalysis and those of concurrent urine culture. The diagnostic performance of the UTOPIA value was validated with the test dataset. Six variables were selected for the equation of the UTOPIA value: age of higher UTI risk [odds ratio (OR), 2.069125], female (OR, 1.400648), nitrite (per 1 grade; OR, 3.765457), leukocyte esterase (per 1 grade; OR, 1.701586), the number of WBCs (per 1 × 106/L; OR, 1.000121), and the number of bacteria (per 1 × 106/L; OR, 1.004195). The UTOPIA value exhibited an area under the curve value of 0.837 when validated with the independent test dataset. The UTOPIA value displayed good diagnostic performance for predicting urine culture results, which would help to reduce unnecessary culture. Different cutoffs can be used according to the clinical indication.

Outcomes of kidney transplantation over a 16-year period in Korea: An analysis of the National Health Information Database.

BACKGROUND: This study investigated the outcomes of kidney transplantation (KT) over a 16-year period in Korea and identified risk factors for graft failure using a nationwide population-based cohort. METHODS: We investigated the Korean National Health Insurance Service-National Health Information Database. Health insurance claims for patients who underwent KT between 2002 and 2017 were analyzed. RESULTS: The data from 18,331 patients who underwent their first KT were reviewed. The percentage of antithymocyte globulin (ATG) induction continuously increased from 2.0% in 2002 to 23.5% in 2017. Rituximab began to be used in 2008 and had increased to 141 patients (9.6%) in 2013. Acute rejection occurred in 17.3% of all patients in 2002 but decreased to 6.3% in 2017. The rejection-free survival rates were 78.8% at 6 months after KT, 76.1% after 1 year, 67.5% after 5 years, 61.7% after 10 years, and 56.7% after 15 years. The graft survival rates remained over 80% until 12 years after KT, and then rapidly decreased to 50.5% at 16 years after KT. In Cox's multivariate analysis, risk factors for graft failure included being male, more recent KT, KT from deceased donor, use of ATG, basiliximab, or rituximab, tacrolimus use as an initial calcineurin inhibitor, acute rejection history, and cytomegalovirus infection. CONCLUSIONS: ATG and rituximab use has gradually increased in Korea and more recent KT is associated with an increased risk of graft failure. Therefore, meticulous preoperative evaluation and postoperative management are necessary in the case of recent KT with high risk of graft failure.

Perioperative blood usage and therapeutic plasma exchange in kidney transplantation during a 16-year period in South Korea.

BACKGROUND: The frequency of kidney transplantation (KT) is increasing. Blood transfusion plays an important role in the success of KT. Therapeutic plasma exchange (TPE) is also used for desensitisation in ABO-incompatible KT and treatment of antibody-mediated rejection. MATERIALS AND METHODS: We analysed red blood cell (RBC), platelet, and fresh frozen plasma (FFP) usage and the number of TPE procedures performed during the hospitalisation of KT patients from 2002 to 2017 using the Korean National Health Insurance Service-National Health Information Database. RESULTS: A total of 18,331 KT patients were included in this study. The number of transfused RBCs continued to increase from 4,806 units in 2002-2005 to 12,390 units in 2014-2017. However, the average number of RBCs transfused per patient decreased from 2.17 to 1.79 units. Estimated platelet usage increased from 4,259 units in 2002-2005 to 11,519 units in 2014-2017, and the proportion of filtered platelets increased from 72.6% to 83.4% during the same period. There was a huge increase in the total number of FFP units used, from 2,255 units in 2002-2005 to 51,531 units in 2014-2017. The number of TPE procedures performed also increased from 296 to 6,479 during the same period. Patients with acute rejection accounted for 8.8% of all KT patients, and more RBC and FFP were used for these patients and a greater number of TPE procedures were performed compared to those who did not experience rejection. DISCUSSION: Blood usage and TPE have increased steadily with the increasing numbers of KTs. Therefore, continuous efforts are needed to ensure appropriate perioperative blood preparation and usage for KT patients.

Carbohydrate antigen 19-9 elevation without evidence of malignant or pancreatobiliary diseases.

Although carbohydrate antigen 19-9 (CA 19-9) may be elevated in benign diseases, elevated CA 19-9 may cause a fear of cancer and unnecessary follow-up studies. Research on how to approach systematically in this case is very limited. The purpose of this study was to analyze the clinical features and the causes of CA 19-9 elevation without evidence of malignant or pancreatobiliary diseases. We retrospectively reviewed the medical records of patients who had CA 19-9 elevation (≥80 U/mL) and were found to be unrelated to cancer after follow-up. After exclusion, 192 patients were included in this study. The median level of CA 19-9 was 136.5 U/mL. The causes of CA 19-9 elevation were determined in 147 (76.6%) patients, and that was unknown in 45 (23.4%). The estimated causative diseases were hepatic diseases in 63 patients, pulmonary diseases in 32, gynecologic diseases in 38, endocrine diseases in 13, and spleen disease in 1. Of 45 patients with unknown cause, 35 had normalization of CA 19-9 and 10 had persistently elevated CA 19-9. In conclusion, CA 19-9 elevation without malignancies or pancreatobiliary diseases should be systematically evaluated and followed up. We suggest an algorithm to investigate the causes and follow up these patients.

Diagnostic performance of CA 125, HE4, and risk of Ovarian Malignancy Algorithm for ovarian cancer.

OBJECTIVE: We evaluated the diagnostic performance of CA 125, HE4, and ROMA for ovarian cancer in Koreans and set optimal cutoffs. METHOD: Serum levels of HE4 and CA 125 and the ROMA score were determined in 762 patients with benign gynecological disease and 70 with ovarian cancer. Receiver operating characteristic curves were constructed to calculate the areas under the curve (AUC). CA 125, HE4, and ROMA exhibiting maximum Youden index were determined, respectively, as the optimal cutoffs, and sensitivity and specificity were evaluated by applying those cutoffs. RESULTS: In benign diseases, CA 125 significantly increased in patients with uterine myoma, adenomyosis, endometrial pathology, or endometriosis, but HE4 only increased in patients with adenomyosis. For the diagnosis of ovarian cancer, the combination of CA 125, HE4, and age showed the highest AUC value of 0.892 in the premenopausal group, and ROMA demonstrated the best diagnostic performance, with an AUC of 0.935 in postmenopausal patients. When the optimal cutoff values for CA 125 and HE4 were applied, the sensitivities of CA 125, HE4, and ROMA in premenopausal women were all the same at 0.714, while the specificities were 0.841, 0.974, and 0.972, respectively. In the postmenopausal group, the sensitivities of these markers were 0.857, 0.804, and 0.929, and the specificities were 0.836, 0.887, and 0.800, respectively. CONCLUSION: Although all markers demonstrated good diagnostic performance, they varied depending on the pathologic types of benign diseases and ovarian cancer. For accurate diagnosis of ovarian cancer, CA 125, HE4, and ROMA should be used complementarily.