Background: Acute deterioration of patients in general wards often leads to major adverse events (MAEs), including unplanned intensive care unit transfers, cardiac arrest, or death. Traditional early warning scores (EWSs) have shown limited predictive accuracy, with frequent false positives. We conducted a prospective observational external validation study of an artificial intelligence (AI)-based EWS, the VitalCare - Major Adverse Event Score (VC-MAES), at a tertiary medical center in the Republic of Korea. Methods: Adult patients from general wards, including internal medicine (IM) and obstetrics and gynecology (OBGYN)—the latter were rarely investigated in prior AI-based EWS studies—were included. The VC-MAES predictions were compared with National Early Warning Score (NEWS) and Modified Early Warning Score (MEWS) predictions using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and logistic regression for baseline EWS values. False-positives per true positive (FPpTP) were assessed based on the power threshold. Results: Of 6,039 encounters, 217 (3.6%) had MAEs (IM: 9.5%, OBGYN: 0.26%). Six hours prior to MAEs, the VC-MAES achieved an AUROC of 0.918 and an AUPRC of 0.352, including the OBGYN subgroup (AUROC, 0.964; AUPRC, 0.388), outperforming the NEWS (0.797 and 0.124) and MEWS (0.722 and 0.079). The FPpTP was reduced by up to 71%. Baseline VC-MAES was strongly associated with MAEs (P<0.001). Conclusions The VC-MAES significantly outperformed traditional EWSs in predicting adverse events in general ward patients. The robust performance and lower FPpTP suggest that broader adoption of the VC-MAES may improve clinical efficiency and resource allocation in general wards.

Background/Aims: There are no definite guidelines for the management of gastric lesions diagnosed as indefinite for dysplasia (IND) by endoscopic forceps biopsy (EFB). Therefore, this study aimed to evaluate the clinical outcomes of gastric IND and predictive factors for gastric neoplasm. Methods: This study included 457 patients with a first diagnosis of gastric IND by EFB between January 2005 and December 2013. Patient characteristics and endoscopic and pathological data were reviewed and compared. Results: Of the 457 gastric IND patients, 128 (28%) were diagnosed with invasive carcinoma, 21 (4.6%) with high-grade dysplasia, 31 (6.8%) with low-grade dysplasia, and 277 (60.6%) as negative for dysplasia. Of lesions observed, 180 (39.4%) showed upgraded histology. Multivariate analysis revealed that surface erythema (odds ratio [OR], 2.804; 95% confidence interval [CI], 1.741 to 4.516), spontaneous bleeding (OR, 2.618; 95% CI, 1.298 to 5.279), lesion size ≥ 1 cm (OR, 5.762; 95% CI, 3.459 to 9.597), and depressed morphology (OR, 2.183; 95% CI, 1.155 to 4.124) were significant risk factors for high-grade dysplasia or adenocarcinoma. The ORs associated with 2 and ≥ 3 risk factors were 7.131 and 34.86, respectively. Conclusions Precautions should be taken in the management of gastric IND patients, especially when risk factors, including surface erythema, spontaneous bleeding, lesion size ≥ 1 cm, and depressed morphology are present. Considering the combined effect of the presence of multiple risk factors on the incidence of high-grade dysplasia or adenocarcinoma, endoscopic resection should be recommended if a gastric IND patient has at two or more of these factors.

Purpose: Under the South Korea’s unique health insurance structure, any new surgical technology must be evaluated first by the government in order to consider whether that particular technology can be applied to patients for further clinical trials as categorized as ‘New Health Technology,’ then potentially covered by the insurance sometime later. The aim of this meta-analysis was to assess the safety and efficacy of transanal total mesorectal excision (TaTME) for rectal cancer, activated by the National Evidence-based Healthcare Collaborating Agency (NECA) TaTME committee. Methods: We systematically searched Ovid-MEDLINE, Ovid-Embase, Cochrane, and Korean databases (from their inception until August 31, 2019) for studies published that compare TaTME with laparoscopic total mesorectal excision (LaTME). End-points included perioperative and pathological outcomes. Results: Sixteen cohort studies (7 for case-matched studies) were identified, comprising 1,923 patients (938 TaTMEs and 985 LaTMEs). Regarding perioperative outcomes, the conversion rate was significantly lower in TaTME (risk ratio, 0.19; 95% confidence interval, 0.11–0.34; P < 0.001); whereas other perioperative outcomes were similar to LaTME. There were no statistically significant differences in pathological results between the 2 procedures. Conclusion Our meta-analysis showed comparable results in preoperative and pathologic outcomes between TaTME and LaTME, and indicated the benefit of TaTME with low conversion. Extensive evaluations of well-designed, multicenter randomized controlled trials are required to come to unequivocal conclusions, but the results showed that TaTME is a potentially beneficial technique in some specific cases. This meta-analysis suggests that TaTME can be performed for rectal cancer patients as a ‘New Health Technology’ endorsed by NECA in South Korea.

Background/Aims: There are no definite guidelines for the management of gastric lesions diagnosed as indefinite for dysplasia (IND) by endoscopic forceps biopsy (EFB). Therefore, this study aimed to evaluate the clinical outcomes of gastric IND and predictive factors for gastric neoplasm. Methods: This study included 457 patients with a first diagnosis of gastric IND by EFB between January 2005 and December 2013. Patient characteristics and endoscopic and pathological data were reviewed and compared. Results: Of the 457 gastric IND patients, 128 (28%) were diagnosed with invasive carcinoma, 21 (4.6%) with high-grade dysplasia, 31 (6.8%) with low-grade dysplasia, and 277 (60.6%) as negative for dysplasia. Of lesions observed, 180 (39.4%) showed upgraded histology. Multivariate analysis revealed that surface erythema (odds ratio [OR], 2.804; 95% confidence interval [CI], 1.741 to 4.516), spontaneous bleeding (OR, 2.618; 95% CI, 1.298 to 5.279), lesion size ≥ 1 cm (OR, 5.762; 95% CI, 3.459 to 9.597), and depressed morphology (OR, 2.183; 95% CI, 1.155 to 4.124) were significant risk factors for high-grade dysplasia or adenocarcinoma. The ORs associated with 2 and ≥ 3 risk factors were 7.131 and 34.86, respectively. Conclusions Precautions should be taken in the management of gastric IND patients, especially when risk factors, including surface erythema, spontaneous bleeding, lesion size ≥ 1 cm, and depressed morphology are present. Considering the combined effect of the presence of multiple risk factors on the incidence of high-grade dysplasia or adenocarcinoma, endoscopic resection should be recommended if a gastric IND patient has at two or more of these factors.

Purpose: Under the South Korea’s unique health insurance structure, any new surgical technology must be evaluated first by the government in order to consider whether that particular technology can be applied to patients for further clinical trials as categorized as ‘New Health Technology,’ then potentially covered by the insurance sometime later. The aim of this meta-analysis was to assess the safety and efficacy of transanal total mesorectal excision (TaTME) for rectal cancer, activated by the National Evidence-based Healthcare Collaborating Agency (NECA) TaTME committee. Methods: We systematically searched Ovid-MEDLINE, Ovid-Embase, Cochrane, and Korean databases (from their inception until August 31, 2019) for studies published that compare TaTME with laparoscopic total mesorectal excision (LaTME). End-points included perioperative and pathological outcomes. Results: Sixteen cohort studies (7 for case-matched studies) were identified, comprising 1,923 patients (938 TaTMEs and 985 LaTMEs). Regarding perioperative outcomes, the conversion rate was significantly lower in TaTME (risk ratio, 0.19; 95% confidence interval, 0.11–0.34; P < 0.001); whereas other perioperative outcomes were similar to LaTME. There were no statistically significant differences in pathological results between the 2 procedures. Conclusion Our meta-analysis showed comparable results in preoperative and pathologic outcomes between TaTME and LaTME, and indicated the benefit of TaTME with low conversion. Extensive evaluations of well-designed, multicenter randomized controlled trials are required to come to unequivocal conclusions, but the results showed that TaTME is a potentially beneficial technique in some specific cases. This meta-analysis suggests that TaTME can be performed for rectal cancer patients as a ‘New Health Technology’ endorsed by NECA in South Korea.

Artifacts ; Blood Buffy Coat ; Gene Frequency ; Hematologic Tests ; High-Throughput Nucleotide Sequencing ; Humans ; Mass Screening ; Ovarian Neoplasms ; Sensitivity and Specificity ; Tissue Preservation

Objective: A simultaneous detection of germline and somatic mutations in ovarian cancer (OC) using tumor materials is considered to be cost-effective for BRCA1/2 testing. However, there are limited studies of the analytical performances according to various sample types. The aim of this study is to propose a strategy for routine BRCA1/2 next-generation sequencing (NGS) screening based on analytical performance according to different sample types. Methods: We compared BRCA1/2 NGS screening assay using buffy coat, fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) from 130 samples. Results: The rate of repeated tests in a total of buffy coat, FF and FFPE was 0%, 8%, and 34%, respectively. The accuracy of BRCA1/2 NGS testing was 100.0%, 99.9% and 99.9% in buffy coat, FFPE and FF, respectively. However, due to the presence of variant allele frequency (VAF) shifted heterozygous variants, tumor materials (FFPE and FF) showed lower sensitivity (95.5%–99.0%) than buffy coat (100%). Furthermore, FFPE showed 51.4% of the positive predictive value (PPV) on account of sequence artifacts. When performed in the post-filtration process, PPV was increased by approximately 20% in FFPE. Buffy coat showed 100% of sensitivity, specificity and accuracy in BRCA1/2 NGS test. Conclusions On the comparison of the analytical performance according to different sample types, the buffy coat was not affected by sequencing artifacts and VAF shifted variants. Therefore, the blood test should be given priority in detecting germline BRCA1/2 mutation, and tumor materials could be suitable to detect somatic mutations in OC patients without identifying germline BRCA1/2 mutation.

OBJECTIVE: Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer, which progresses from precursor lesions with no symptom if left untreated. We compared the risk of cervical dysplasia among HPV-positive Korean women based on HPV types and infection patterns. METHODS: We observed participants of a 5-year multicenter prospective cohort study, comprising HPV-positive women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion of the cervix at their enrollment. Follow-ups, comprising cytology and HPV DNA testing results, were included in the final analysis. Incidence was calculated for each infection pattern (persistent infection, incidental infection, and clearance). To investigate cervical dysplasia risk, we used Cox proportional hazard models adjusted for variables that were significantly different among infection patterns. From April 2010 to September 2017, 71 of 1,027 subjects developed cervical dysplasia more severe than high-grade squamous intraepithelial lesion of the cervix. RESULTS: Of these 71 subjects, persistent infection, incidental infection, and clearance were noted in 30, 39, and 2 individuals, respectively. Based on changes in DNA results during follow-up, cumulative incidence was 27.2%, 10.4%, and 0.5% for persistent infection, incidental infection, and clearance, respectively. Compared to clearance, the adjusted hazard ratios for cervical dysplasia were 51.6 and 24.1 for persistent and incidental infections, respectively (p < 0.001). CONCLUSION: Individuals persistently infected with the same HPV types during the follow-up period had the highest risk of severe cervical dysplasia. Hence, it is necessary to monitor HPV types and infection patterns to prevent severe cervical precancerous lesions.
Atypical Squamous Cells of the Cervix ; Cervix Uteri ; Cohort Studies ; DNA ; Female ; Follow-Up Studies ; Human Papillomavirus DNA Tests ; Humans ; Incidence ; Korea ; Papillomavirus Infections ; Proportional Hazards Models ; Prospective Studies ; Republic of Korea ; Risk Factors ; Squamous Intraepithelial Lesions of the Cervix ; Uterine Cervical Dysplasia ; Uterine Cervical Neoplasms

OBJECTIVE: We performed small-scale mutation and large genomic rearrangement (LGR) analysis of BRCA1/2 in ovarian cancer patients to determine the prevalence and the characteristics of the mutations. METHODS: All ovarian cancer patients who visited a single institution between September 2015 and April 2017 were included. Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-range polymerase chain reaction (PCR) were performed to comprehensively study BRCA1/2. The genetic risk models BRCAPRO, Myriad, and BOADICEA were used to evaluate the mutation analysis. RESULTS: In total, 131 patients were enrolled. Of the 131 patients, Sanger sequencing identified 16 different BRCA1/2 small-scale mutations in 20 patients (15.3%). Two novel nonsense mutations were detected in 2 patients with a serous borderline tumor and a large-cell neuroendocrine carcinoma. MLPA analysis of BRCA1/2 in Sanger-negative patients revealed 2 LGRs. The LGRs accounted for 14.3% of all identified BRCA1 mutations, and the prevalence of LGRs identified in this study was 1.8% in 111 Sanger-negative patients. The genetic risk models showed statistically significant differences between mutation carriers and non-carriers. The 2 patients with LGRs had at least one blood relative with breast or ovarian cancer. CONCLUSION: Twenty-two (16.8%) of the unselected ovarian cancer patients had BRCA1/2 mutations that were detected through comprehensive BRCA1/2 genetic testing. Ovarian cancer patients with Sanger-negative results should be considered for LGR detection if they have one blood relative with breast or ovarian cancer. The detection of more BRCA1/2 mutations in patients is important for efforts to provide targeted therapy to ovarian cancer patients.
Breast ; Carcinoma, Neuroendocrine ; Codon, Nonsense ; Female ; Genetic Testing ; Humans ; Korea* ; Multiplex Polymerase Chain Reaction ; Ovarian Neoplasms* ; Ovary ; Polymerase Chain Reaction ; Prevalence

OBJECTIVE: This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). METHODS: We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20–60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. RESULTS: Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08–2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P < 0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01–17.00). CONCLUSION: The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.
Atypical Squamous Cells of the Cervix* ; Cohort Studies* ; Epidemiology ; Female ; Follow-Up Studies ; Human papillomavirus 16* ; Human Papillomavirus DNA Tests ; Humans ; Logistic Models ; Papillomaviridae ; Risk Factors* ; Smoking ; Squamous Intraepithelial Lesions of the Cervix