Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Background/Aims: Three-dimensional cultures of human pancreatic cancer tissue also known as “organoids” have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research. Methods: Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays. Results: Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy. Conclusions The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research

A sensitive and simple liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of ticagrelor and its active metabolite, AR-C124910XX from 50 µL human plasma using tolbutamide as an internal standard as per regulatory guidelines. Analytes in plasma were extracted by simple protein precipitation using acetonitrile, followed by chromatographic separation with an Acclaim™ RSLC 120 C₁₈ column (2.2 µm, 2.1 × 100 mm) and a gradient acetonitrile-water mobile phase containing 0.1% formic acid within 8 min. Mass spectrometric detection and quantitation were conducted by selected reaction-monitoring on a negative electrospray ionization mode with the following transitions: m/z 521.11 → 361.10, 477.03 → 361.10, and 269.00 → 169.60 for ticagrelor, AR-C124910XX, and tolbutamide, respectively. The lower limit of quantifications was 0.2 ng/mL with linear ranges of 0.2–2,500 ng/mL (r² ≥ 0.9949) for both analytes. All validation data, including selectivity, cross-talk, precision, accuracy, matrix effect, recovery, dilution integrity, stability, and incurred sample reanalysis, were well within acceptable limits. This assay method was validated using K₂-EDTA as the specific anticoagulant. Also, the anticoagulant effect was tested by lithium heparin, sodium heparin, and K₃-EDTA. No relevant anticoagulant effect was observed. This validated method was effectively used in the determination of ticagrelor and its active metabolite, AR-C124910XX, in plasma samples from patients with myocardial infarction.
Heparin ; Humans ; Lithium ; Mass Spectrometry ; Methods ; Myocardial Infarction ; Pharmacokinetics ; Plasma ; Tolbutamide

BACKGROUND/AIMS: There is substantial evidence supporting a role of inflammation in the pathogenesis of colorectal cancer; however, little is known about the association between serum C-reactive protein (CRP) and the risk of colorectal adenoma. This study was conducted to investigate the association between serum CRP and colorectal adenoma risk. METHODS: A retrospective cross-sectional study was performed on first-time screening colonoscopies in asymptomatic subjects who also had their serum CRP level measured during a routine health check-up between September 2006 and September 2009 in Korea. Serum CRP level was compared between high-risk and low-risk adenoma groups and independent predictors of high-risk adenoma were analyzed using multivariate regression analysis. RESULTS: Among the 3,309 eligible patients, the high-risk adenoma group had higher serum CRP levels than the low-risk adenoma group (P=0.000). In addition, patients with a high-risk adenoma were more frequently included in the high CRP group than in the low CRP group (8.6% vs. 4.0%, P<0.001). The prevalence of high-risk adenoma was 3.5 times higher in the highest quartile of CRP level (P=0.000) compared with that in the lowest quartile. In logistic regression analysis, a higher quartile CRP level was found to be an independent risk factor for high-risk adenoma (odds ratio, 1.8; 95% confidence interval, 1.3–2.5; P=0.000). CONCLUSIONS: High CRP level is associated with high-risk adenoma in both men and women. Our data may support the association between chronic inflammation and colorectal neoplasia, which warrants further investigation.
Adenoma* ; C-Reactive Protein* ; Colon ; Colonoscopy ; Colorectal Neoplasms ; Cross-Sectional Studies ; Female ; Humans ; Inflammation ; Korea ; Logistic Models ; Male ; Mass Screening ; Prevalence ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: Western surveillance strategies cannot be directly adapted to the Korean population. The aim of this study was to estimate the risk of metachronous neoplasia and the optimal surveillance interval in the Korean population. METHODS: Clinical and pathological data from index colonoscopy performed between June 2006 and July 2008 and who had surveillance colonoscopies up to May 2015 were compared between low- and high-risk adenoma (LRA and HRA) groups. The 3- and 5-year cumulative risk of metachronous colorectal neoplasia in both groups were compared. RESULTS: Among 895 eligible patients, surveillance colonoscopy was performed in 399 (44.6%). Most (83.3%) patients with LRA had a surveillance colonoscopy within 5 years and 70.2% of patients with HRA had a surveillance colonoscopy within 3 years. The cumulative risk of metachronous advanced adenoma was 3.2% within 5 years in the LRA group and only 1.7% within 3 years in the HRA group. The risk of metachronous neoplasia was similar between the surveillance interval of <5 and ≥5 years in the LRA group; however, it was slightly higher at surveillance interval of ≥3 than <3 years in the HRA group (9.4% vs. 2.4%). In multivariate analysis, age and the ≥3-year surveillance interval were significant independent risk factors for metachronous advanced adenoma (P=0.024 and P=0.030, respectively). CONCLUSIONS: Patients had a surveillance colonoscopy before the recommended guidelines despite a low risk of metachronous neoplasia. However, the risk of metachronous advanced adenoma was increased in elderly patients and those with a ≥3-year surveillance interval.
Adenoma ; Aged ; Colonoscopy ; Colorectal Neoplasms ; Humans ; Multivariate Analysis ; Risk Factors

PURPOSE: Surgical procedures using robot-assisted surgery, including pancreatic surgery, have recently become popular. This study aimed to report our initial experiences with distal pancreatectomy procedures using the robot-assisted surgery system. METHODS: The clinical records of 28 patients who underwent robot-assisted distal pancreatectomy (RDP) between July 2012 and January 2016 were reviewed. RESULTS: Of the 28 patients, 5 (17.9%) were male and 23 (82.1%) were female. Their ages ranged from 11 to 78 years, with a median age of 44.5 years. The mean diameter of the pancreatic tumors was 3.6 cm. The median operative time was 192.5 (range, 100~390) minutes, and the median blood loss was 200 (range, 50~1,900) ml. All of the 28 RDPs were successfully completed. Spleen preservation was achieved in 16 (57.1%) patients. Clinically significant postoperative pancreatic fistula was detected in 4 (14.3%) patients. Postoperative complications were evident in 5 (17.9%) of the 28 patients. CONCLUSION: Our experiences suggest that RDP is feasible for patients with benign or borderline tumors at the body or tail of the pancreas. It may be considered as an effective surgical procedure for benign or borderline tumors of the pancreas in the future; however, further studies to confirm this are warranted.
Female ; Humans ; Male ; Operative Time ; Pancreas ; Pancreatectomy* ; Pancreatic Fistula ; Postoperative Complications ; Spleen ; Tail

Pachydermoperiostosis (PDP) is a primary hypertrophic osteoarthropathy characterized by digital clubbing, pachydermia, and periostosis, which is inherited as an autosomal dominant or recessive trait. We report on a patient suffering from bilateral knee arthritis for 6 years who was newly diagnosed as PDP. PDP was confirmed by bilateral digital clubbing, hyperhidrosis, and cutis verticis gyrata, findings of pachydermatosis on the forehead and scalp, X-ray findings of proliferative periostitis. This case indicates that PDP is one of several possible rare diseases that should be considered in patients with undifferentiated arthritis.
Arthritis* ; Forehead ; Humans ; Hyperhidrosis ; Knee ; Osteoarthropathy, Primary Hypertrophic* ; Periostitis ; Rare Diseases ; Scalp

Colonoscopy is the current standard method for evaluation of the colon. The diagnostic accuracy and therapeutic safety of colonoscopy depend on the quality of colonic cleansing and preparation. Generally, all these preparations have been demonstrated to be safe for use in healthy individuals without significant comorbid conditions. Based on safety and efficacy concerns, polyethylene glycol (PEG) is most commonly utilized as a bowel preparation solution for colonoscopy. Adverse events in patients receiving PEG are mostly clinically non-significant. However, fatal adverse events rarely have been shown to occur in the few individuals who experience vomiting or aspiration. Anaphylactic shock associated with ingestion of PEG electrolyte solution is an extremely rare fatal complication, and reported mainly in Western countries. Here, we report the first case of anaphylactic shock following the ingestion of PEG solution in Korea.
Anaphylaxis* ; Colon ; Colonoscopy ; Eating* ; Humans ; Korea ; Polyethylene Glycols* ; Shock ; Vomiting