Objective: To examine the efficacy of MSH6 and PMS2 immunohistochemistry (IHC) as a screening method for Lynch syndrome in endometrial cancer patients. Methods: Through multidisciplinary discussions, an institutional MSH6 and PMS2 IHC-initiated cascade test (MSH6, PMS2 IHC→microsatellite instability [MSI] assay→germline mismatch repair [MMR] gene sequencing) was developed to screen for Lynch syndrome in endometrial cancer patients. Testing was performed on a consecutive cohort of 218 newly diagnosed endometrial cancer patients who underwent surgery at a tertiary hospital in the Republic of Korea between August 2018 and December 2020. The number of MMR deficiencies (MSH6 or PMS2 loss in IHC) and results of subsequent tests (MSI assay and germline MMR gene sequencing) were examined. Results: MMR deficiency was detected in 52 of the 218 patients (24.0%). Among these 52 patients, 34 (65.0%) underwent MSI testing, of which 31 (91.0%) exhibited high MSI. Of the 31 patients with MSI-high status, 15 (48.0%) underwent germline MMR gene sequencing. Subsequently, Lynch syndrome was diagnosed in five patients (33.0%). Conclusion Lynch syndrome screening using MSH6 and PMS2 IHC-initiated cascade testing is a viable strategy in the management of endometrial cancer. A simplified strategy (MSH6 and PMS2 IHC→germline MMR gene sequencing) was proposed because most women with MMR deficiencies exhibited high MSI.

Objective: The need to perform genetic sequencing to diagnose the polymerase epsilon exonuclease (POLE) subtype of endometrial cancer (EC) hinders the adoption of molecular classification. We investigated clinicopathologic and protein markers that distinguish the POLE from the copy number (CN)-low subtype in EC. Methods: Ninety-one samples (15 POLE, 76 CN-low) were selected from The Cancer Genome Atlas EC dataset. Clinicopathologic and normalized reverse phase protein array expression data were analyzed for associations with the subtypes. A logistic model including selected markers was constructed by stepwise selection using area under the curve (AUC) from 5-fold cross-validation (CV). The selected markers were validated using immunohistochemistry (IHC) in a separate cohort. Results: Body mass index (BMI) and tumor grade were significantly associated with the POLE subtype. With BMI and tumor grade as covariates, 5 proteins were associated with the EC subtypes. The stepwise selection method identified BMI, cyclin B1, caspase 8, and X-box binding protein 1 (XBP1) as markers distinguishing the POLE from the CN-low subtype. The mean of CV AUC, sensitivity, specificity, and balanced accuracy of the selected model were 0.97, 0.91, 0.87, and 0.89, respectively. IHC validation showed that cyclin B1 expression was significantly higher in the POLE than in the CN-low subtype and receiver operating characteristic curve of cyclin B1 expression in IHC revealed AUC of 0.683. Conclusion BMI and expression of cyclin B1, caspase 8, and XBP1 are candidate markers distinguishing the POLE from the CN-low subtype. Cyclin B1 IHC may replace POLE sequencing in molecular classification of EC.

PURPOSE: The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility. MATERIALS AND METHODS: In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting. CONCLUSION: Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.
Demography ; Drug Therapy ; Fallopian Tubes* ; Female ; Humans ; Ovarian Neoplasms ; Reproducibility of Results

PURPOSE: Despite the benefits of minimally invasive surgery for cervical cancer, there are a lack of randomized trials comparing laparoscopic radical hysterectomy and abdominal radical hysterectomy. We compared morbidity, cost of care, and survival between abdominal radical hysterectomy and laparoscopic radical hysterectomy for cervical cancer. MATERIALS AND METHODS: We used the Korean nationwide database to identify women with cervical cancer who underwent radical hysterectomy from January 1, 2011 to December 31, 2014. Patients who underwent abdominal radical hysterectomy were compared to those who underwent laparoscopic radical hysterectomy. Perioperative morbidity, the use of adjuvant therapy, and survival were evaluated after propensity score balancing. RESULTS: We identified 6,335 patients, including 3,235 who underwent abdominal radical hysterectomy and 3,100 who underwent laparoscopic radical hysterectomy. The use of laparoscopic radical hysterectomy increased from 46.1% in 2011 to 51.8% in 2014. Patients who were younger, had a more recent year of diagnosis, and were treated in the metropolitan area were more likely to undergo a laparoscopic procedure (p < 0.001). Compared to abdominal radical hysterectomy, laparoscopic radical hysterectomy was associated with lower rates of complication, fewertransfusions, a shorter hospital stay, less adjuvant therapy, and reduced total medical costs (p < 0.001). Laparoscopic surgery was associated with a better overall survival than abdominal operation (hazard ratio, 0.74; 95% confidence interval, 0.64 to 0.85). CONCLUSION: In the postdissemination era, laparoscopic radical hysterectomy was associated with more favorable morbidity profiles, a lower cost of care, and comparable survival than abdominal radical hysterectomy.
Diagnosis ; Female ; Humans ; Hysterectomy ; Laparoscopy ; Length of Stay ; Minimally Invasive Surgical Procedures ; Propensity Score ; Uterine Cervical Neoplasms

PURPOSE: Adjuvant chemoradiation following primary surgery is frequently indicated in patients with stage IB cervical cancer. The aim of this study is to evaluate the role of a magnetic resonance imaging (MRI)-based strategy in avoiding trimodality therapy. MATERIALS AND METHODS: We retrospectively reviewed all patients with stage IB cervical cancer treated initially with primary surgery at Seoul National University Hospital. We suggest an alternative triage strategy in which the primary treatment modality is determined based on preoperative MRI findings. Using this strategy, primary surgery is only indicated when there is no evidence of parametrial involvement (PMI) and lymph node metastasis (LNM) in the MRI results; when there is evidence of either or both of these factors, primary chemoradiation is selected. Assuming that this strategy is applied to our cohort, we evaluate how the rate of trimodality therapy is affected. RESULTS: Of the 254 patients in our sample, 77 (30.3%) had at least one category 1 risk factor (PMI, LNM, positive resection margin) upon pathologic examination. If the MRI-based strategy had been applied to our cohort, 168 patients would have undergone primary surgery and 86 would have undergone primary chemoradiation. Only 25 patients (9.8%) would have required trimodality therapy based on an indication of at least one category 1 pathologic risk factor following radical hysterectomy. CONCLUSION: The inclusion of MRI in the decision-making process for primary treatment modality could have reduced the number of patients requiring trimodality therapy based on the indication of a category 1 risk factor from 30.3% to 9.8% in our cohort.
Chemoradiotherapy ; Cohort Studies ; Humans ; Hysterectomy ; Lymph Nodes ; Magnetic Resonance Imaging* ; Neoplasm Metastasis ; Retrospective Studies ; Risk Factors ; Seoul ; Triage* ; Uterine Cervical Neoplasms*

The 2015 Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, which started with an imported case and spread throughout the country with a total of 186 cases, revealed the vulnerabilities of the health-care system of the country. The situation was compounded by the unique health-care settings in the Republic of Korea, including crowded emergency departments and large numbers of hospital visitors seeking care at multiple hospitals. To assist with the outbreak response, the Ministry of Health and Welfare of the Republic of Korea hosted several international joint missions that provided valuable information and recommendations for MERS control and prevention of future outbreaks. This report briefly summarizes the missions’ outcomes and discusses their positive impacts.

During the Middle East respiratory syndrome (MERS) outbreak in 2015, the Ministry of Health and Welfare (MOHW) of the Republic of Korea provided outbreak information targeting international visitors and foreign residents through multiple channels. The MOHW created a MERS portal website in Korean and English on 10 June 2015; in addition, the existing MOHW website provided English-language press releases beginning 28 May. A toll-free telephone hotline also started service in English on 12 June; it expanded to include 18 other foreign languages on 15 June. This report describes the usage of these multi-language communication channels during this MERS outbreak.

OBJECTIVES: The objective of this study was to confirm the conformance rate of the actual usage of the clinical pathway (CP) using Electronic Health Record (EHR) log data in a tertiary general university hospital to improve the CP by reflecting real-world care processes. METHODS: We analyzed the application and matching rates of clinicians' orders with predefined CP order sets based on data from 164 inpatients who received appendectomies out of all patients who were hospitalized from August 2013 to June 2014. We collected EHR log data on patient information, medication orders, operation performed, diagnosis, transfer, and CP order sets. The data were statistically analyzed. RESULTS: The average value of the actual application rate of the prescribed CP order ranged from 0.75 to 0.89. The application rate decreased when the order date was factored in along with the order code and type. Among CP pre-operation, intra-operation, post-operation, routine, and discharge orders, orders pertaining to operations had higher application rates than other types of orders. Routine orders and discharge orders had lower application rates. CONCLUSIONS: This analysis of the application and matching rates of CP orders suggests that it is possible to improve these rates by updating the existing CP order sets for routine discharge orders to reflect data-driven evidence. This study shows that it is possible to improve the application and matching rates of the CP using EHR log data. However, further research should be performed to analyze the effects of these rates on care outcomes.
Appendectomy ; Critical Pathways* ; Diagnosis ; Electronic Health Records* ; Humans ; Inpatients

OBJECTIVE: To evaluate the cost-effectiveness of nodal staging surgery before chemoradiotherapy (CRT) for locally advanced cervical cancer in the era of positron emission tomography/computed tomography (PET/CT). METHODS: A modified Markov model was constructed to evaluate the cost-effectiveness of para-aortic staging surgery before definite CRT when no uptake is recorded in the para-aortic lymph nodes (PALN) on PET/CT. Survival and complication rates were estimated based on the published literature. Cost data were obtained from the Korean Health Insurance Review and Assessment Service. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed, including estimates for the performance of PET/CT, postoperative complication rate, and varying survival rates according to the radiation field. RESULTS: We compared two strategies: strategy 1, pelvic CRT for all patients; and strategy 2, nodal staging surgery followed by extended-field CRT when PALN metastasis was found and pelvic CRT otherwise. The ICER for strategy 2 compared to strategy 1 was $19,505 per quality-adjusted life year (QALY). Under deterministic sensitivity analyses, the model was relatively sensitive to survival reduction in patients who undergo pelvic CRT alone despite having occult PALN metastasis. A probabilistic sensitivity analysis demonstrated the robustness of the case results, with a 91% probability of cost-effectiveness at the willingness-to-pay thresholds of $60,000/QALY. CONCLUSION: Nodal staging surgery before definite CRT may be cost-effective when PET/CT imaging shows no evidence of PALN metastasis. Prospective trials are warranted to transfer these results to guidelines.
Chemoradiotherapy/*economics ; Combined Modality Therapy/economics ; Cost-Benefit Analysis ; Female ; Humans ; Laparoscopy/economics ; Lymph Node Excision/*economics/methods ; Lymphatic Metastasis ; Markov Chains ; Multimodal Imaging/economics ; Neoplasm Staging ; Positron-Emission Tomography/economics ; Quality of Life ; Quality-Adjusted Life Years ; Tomography, X-Ray Computed/economics ; Uterine Cervical Neoplasms/*economics/therapy

This study was conducted to evaluate the usefulness of coronary arterial profiles from normal dogs (11 animals) and canines (six dogs) with experimental myocardial infarction (MI) induced by ligation of the left coronary artery (LCA). Blood velocity of the LCA and right coronary artery (RCA) were evaluated following transthoracic pulsed-wave Doppler echocardiography. The LCA was observed as an infundibular shape, located adjacent to the sinus of Valsalva. The RCA appeared as a tubular structure located 12 o'clock relative to the aorta. In normal dogs, the LCA and RCA mean peak diastolic velocities were 20.84 +/- 3.24 and 19.47 +/- 2.67 cm/sec, respectively. The LCA and RCA mean diastolic deceleration times were 0.91 +/- 0.14 sec and 1.13 +/- 0.20 sec, respectively. In dogs with MI, the LCA had significantly (p < 0.01) lower peak velocities (14.82 +/- 1.61 cm/sec) than the RCA (31.61 +/- 2.34 cm/sec). The RCA had a significantly (p < 0.01) rapid diastolic deceleration time (0.71 +/- 0.06 sec) than that found in the LCA (1.02 +/- 0.22 sec) of MI dogs. In conclusion, these profiles may serve as a differential factor for evaluating cardiomyopathy in dogs.
Animals ; Blood Flow Velocity/*veterinary ; Coronary Vessels/surgery/*ultrasonography ; Dog Diseases/*diagnosis ; Dogs/*physiology ; Echocardiography, Doppler, Pulsed/standards/*veterinary ; Female ; Male ; Myocardial Infarction/diagnosis/*veterinary