Poor Mobilization-Associated Factors in Autologous Hematopoietic Stem Cell Harvest.

Peripheral blood stem cell transplantation (PBSCT) is an important therapeutic measure for both hematologic and non-hematologic diseases. For PBSCT to be successful, sufficient CD34+ cells need to be mobilized and harvested. Although risk factors associated with poor mobilization in patients with hematologic diseases have been reported, studies of patients with non-hematologic diseases and those receiving plerixafor are rare. To identify factors associated with poor mobilization, data from autologous PBSC harvest (PBSCH) in 491 patients were retrospectively collected and analyzed. A multivariate analysis revealed that in patients with a hematologic disease, an age older than 60 years (odds ratio [OR] 1.655, 95% confidence interval [CI] 1.049-2.611, p = 0.008), the use of myelotoxic agents (OR 4.384, 95% CI 2.681-7.168, p < 0.001), and a low platelet count (OR 2.106, 95% CI 1.205-3.682, p = 0.009) were associated with poor mobilization. In patients with non-hematologic diseases, a history of radiation on the pelvis/spine was the sole associated factor (OR 12.200, 95% CI 1.934-76.956, p = 0.008). Among the group of patients who received plerixafor, poor mobilization was observed in 19 patients (19/134, 14.2%) and a difference in the mobilization regimen was noted among the good mobilization group. These results show that the risk factors for poor mobilization in patients with non-hematologic diseases and those receiving plerixafor differ from those in patients with hematologic diseases; as such, non-hematologic patients require special consideration to enable successful PBSCH.

Comparison of Optical Genome Mapping With Conventional Diagnostic Methods for Structural Variant Detection in Hematologic Malignancies.

Background: Structural variants (SVs) are currently analyzed using a combination of conventional methods; however, this approach has limitations. Optical genome mapping (OGM), an emerging technology for detecting SVs using a single-molecule strategy, has the potential to replace conventional methods. We compared OGM with conventional diagnostic methods for detecting SVs in various hematologic malignancies. Methods: Residual bone marrow aspirates from 27 patients with hematologic malignancies in whom SVs were observed using conventional methods (chromosomal banding analysis, FISH, an RNA fusion panel, and reverse transcription PCR) were analyzed using OGM. The concordance between the OGM and conventional method results was evaluated. Results: OGM showed concordance in 63% (17/27) and partial concordance in 37% (10/27) of samples. OGM detected 76% (52/68) of the total SVs correctly (concordance rate for each type of SVs: aneuploidies, 83% [15/18]; balanced translocation, 80% [12/15] unbalanced translocation, 54% [7/13] deletions, 81% [13/16]; duplications, 100% [2/2] inversion 100% [1/1]; insertion, 100% [1/1]; marker chromosome, 0% [0/1]; isochromosome, 100% [1/1]). Sixteen discordant results were attributed to the involvement of centromeric/telomeric regions, detection sensitivity, and a low mapping rate and coverage. OGM identified additional SVs, including submicroscopic SVs and novel fusions, in five cases. Conclusions: OGM shows a high level of concordance with conventional diagnostic methods for the detection of SVs and can identify novel variants, suggesting its potential utility in enabling more comprehensive SV analysis in routine diagnostics of hematologic malignancies, although further studies and improvements are required.

Re-evaluation of a Fibrillin-1 Gene Variant of Uncertain Significance Using the ClinGen Guidelines.

Background: Marfan syndrome (MFS) is caused by fibrillin-1 gene (FBN1) variants. Mutational hotspots and/or well-established critical functional domains of FBN1 include cysteine residues, calcium-binding consensus sequences, and amino acids related to interdomain packaging. Previous guidelines for variant interpretation do not reflect the features of genes or related diseases. Using the Clinical Genome Resource (ClinGen) FBN1 variant curation expert panel (VCEP), we re-evaluated FBN1 germline variants reported as variants of uncertain significance (VUSs). Methods: We re-evaluated 26 VUSs in FBN1 reported in 161 patients with MFS. We checked the variants in the Human Genome Mutation Database, ClinVar, and VarSome databases and assessed their allele frequencies using the gnomAD database. Patients' clinical information was reviewed. Results: Four missense variants affecting cysteines (c.460T>C, c.1006T>C, c.5330G>C, and c.8020T>C) were reclassified as likely pathogenic and were assigned PM1_strong or PM1. Two intronic variants were reclassified as benign by granting BA1 (stand-alone). Four missense variants were reclassified as likely benign. BP5 criteria were applied in cases with an alternate molecular basis for disease, one of which (c.7231G>A) was discovered alongside a pathogenic de novo COL3A1 variant (c.1988G>T, p.Gly633Val). Conclusions: Considering the high penetrance of FBN1 variants and clinical variability of MFS, the detection of pathogenic variants is important. The ClinGen FBN1 VCEP encompasses mutational hotspots and/or well-established critical functional domains and adjusts the criteria specifically for MFS; therefore, it is beneficial not only for identifying pathogenic FBN1 variants but also for distinguishing these variants from those that cause other connective tissue disorders with overlapping clinical features.

Nonfamilial VACTERL-H Syndrome in a Dizygotic Twin: Prenatal Ultrasound and Postnatal 3D CT Findings.

Background: VACTERL association is a widely known congenital malformation that includes vertebral, anal, cardiac, tracheoesophageal, renal, and limb anomalies. Patients with VACTERL and hydrocephalus appear to form a distinct group, both genetically and phenotypically, and their condition has been called VACTERL-H syndrome. Most cases of VACTERL-H have been reported postnatally, as VACTER-H syndrome is difficult to diagnose prenatally. Case Presentation: Here, we report a case of VACTERL-H syndrome in a dichorionic and diamniotic twin diagnosed prenatally by ultrasonography and confirmed postnatally by three-dimensional computed tomography (3D CT). A 34-year-old multiparous female was referred to our institution at 31 + 3 weeks gestation for suspected fetal ventriculomegaly. Detailed examinations using two-dimensional and Doppler ultrasounds revealed hydrocephalus, bilateral dysplastic upper arms, radial aplasia, unilateral pulmonary agenesis, dextrocardia with right atrial enlargement, a unilateral hypoplastic ectopic kidney, a single umbilical artery, a tracheoesophageal fistula with a small stomach, polyhydramnios, and anal atresia. Findings from the postnatal 3D CT aligned with the prenatal diagnosis, showing upper-limb agenesis, dextrocardia with pulmonary hypoplasia, tracheoesophageal fistula, imperforate anus, and colon dilatation. The affected 1390-g male twin had an unaffected 1890-g female twin sister and a healthy 6-year-old brother. Conclusions: Upon encountering fetuses with multiple anomalies, including ventriculomegaly, a small stomach with polyhydramnios, an abnormally positioned heart, and upper-limb abnormalities, clinicians should perform systematic ultrasonographic examinations to detect associated anomalies and be aware of VACTERL-H syndrome.

Efficacy of a continuous wound infiltration system for postoperative pain management in gynecologic patients who underwent single-port access laparoscopy for adnexal disease.

Introduction: Single-port access (SPA) laparoscopy requires only one incision, unlike conventional laparoscopy. However, its umbilical incision is larger than that of conventional laparoscopy and can be vulnerable to postoperative pain. This study aimed to evaluate whether simultaneous use of a continuous wound infiltration (CWI) system and intravenous patient-controlled analgesia (IV PCA) effectively decreases surgical site pain in patients who underwent SPA laparoscopy due to gynecologic adnexal disease. Methods: A total of 371 patients who underwent SPA laparoscopy and who received IV PCA or CWI was retrospectively reviewed (combined group [CWI + IV PCA, n = 159] vs. PCA group [IV PCA only, n = 212]). To evaluate postoperative pain management, the numeric rating scale (NRS) pain score after surgery, total amount of fentanyl administered via IV PCA, and additional pain killer consumption were collected. Results: The NRS scores at 12 h (1.90 ± 1.11 vs. 2.70 ± 1.08, p < 0.001) and 24 h (1.82 ± 0.82 vs. 2.11 ± 1.44, p = 0.026) after surgery were significantly lower in the combined group than in the PCA group. The total amount of PCA fentanyl was significantly smaller in the combined group than in the PCA group (p < 0.001). The total quantity of rescue analgesics was smaller in the combined group than in the PCA group (p < 0.05). Conclusion: Combined use of the CWI system and IV PCA is an effective postoperative pain management strategy in patient who underwent SPA laparoscopy for adnexal disease.

Outstanding Characteristics of Birt-Hogg-Dube Syndrome in Korea.

Birt-Hogg-Dube (BHD) is a rare genetic disorder characterized by multiple lung cysts, typical skin manifestations, and renal tumors. We prospectively enrolled thirty-one subjects from four South Korean institutions with typical lung cysts, and next-generation sequencing was conducted. We prospectively enrolled thirty-one subjects from four Korean institutions with typical lung cysts. Next-generation sequencing was performed to investigate mutations in the following genes: FLCN, TSC1, TSC2, CFTR, EFEMP2, ELN, FBLN5, LTBP4, and SERPINA1. BHD was diagnosed in 11 of the 31 enrolled subjects (35.5%; FLCN mutations). Notably, we identified three novel mutations (c.1098G>A, c.139G>T, and c.1335del) that have not been previously reported. In addition to FLCN mutations, we also observed mutations in CFTR (16.1%), LTBP4 (9.7%), TSC2 (9.7%), TSC1 (3.2%), ELN (3.2%), and SERPINA1 (3.2%). According to a systematic review of 45 South Korean patients with BHD, the prevalence of pneumothorax (72.7%) was greater in South Korea than in the rest of the world (50.9%; p = 0.003). The prevalence of skin manifestations (13.6%) and renal tumors (9.1%) was lower in Korea than in the rest of the world, at 47.9% [p < 0.001] and 22.5% [p = 0.027], respectively). This study confirmed a significant prediction model for BHD based on age, number of lung cysts (>40), and maximal diameter of lung cysts (>2 cm) regardless of skin manifestations and renal tumors. Importantly, three novel mutations (c.1098G>A, c.139G>T, and c.1335del) were identified. In conclusion, South Korean patients with BHD display characteristics that are different from those observed in patients of other nationalities. Detailed characterization of lung cysts is needed to define BHD, especially in South Korea, even if patients do not present with skin or renal lesions.

Cost-Effectiveness Analysis of Three Diagnostic Strategies for the Detection of EGFR Mutation in Advanced Non-Small Cell Lung Cancer.

Background: In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutation testing of tumor tissue should be conducted at diagnosis. Alternatively, circulating tumor DNA can be used to detect EGFR mutation. We compared the cost and clinical effect of three strategies according to the application of the EGFR test. Methods: Decision models were developed to compare the cost-effectiveness of tissue-only, tissue-first, and plasma-first diagnostic strategies as first- and second-line treatments for NSCLC from the perspective of the Korean national healthcare payer. Progression-free survival (PFS), overall survival (OS), and direct medical costs were assessed. A one-way sensitivity analysis was performed. Results: The plasma-first strategy correctly identified numerous patients in the first- and second-line treatments. This strategy also decreased the cost of biopsy procedures and complications. Compared with that when using the other two strategies, the plasma-first strategy increased PFS by 0.5 months. The plasma-first strategy increased OS by 0.9 and 1 month compared with that when using the tissue-only and tissue-first strategies, respectively. The plasma-first strategy was the least expensive first-line treatment but the most expensive second-line treatment. First-generation tyrosine kinase inhibitor and the detection rate of the T790M mutation in tissues were the most cost-influential factors. Conclusions: The plasma-first strategy improved PFS and OS, allowing for a more accurate identification of candidates for targeted therapy for NSCLC and decreased biopsy- and complication-related costs.

Prenatal Diagnosis of Fetal Obstructed Hemivagina and Ipsilateral Renal Agenesis (OHVIRA) Syndrome.

Background: Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome, also known as Herlyn-Werner-Wunderlich syndrome, is a rare syndrome characterized by the triad of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Most cases of OHVIRA have been reported in adolescents or adults. Gartner duct cysts, including those manifesting as vaginal wall cysts, are also rare. Fetal OHVIRA syndrome and Gartner duct cysts are difficult to diagnose. Case Presentation: Here, the authors report a case of combined OHVIRA and Gartner duct cyst diagnosed prenatally by ultrasonography, along with a brief review of the relevant published reports. A 30-year-old nulliparous female was referred to our institution at 32 weeks' gestation for fetal right kidney agenesis. Detailed ultrasonographic examinations using 2D, 3D, and Doppler ultrasounds revealed hydrocolpometra, and uterus didelphys, with a normal anus and right kidney agenesis. Conclusions: When encountering female fetuses with ipsilateral renal agenesis or vaginal cysts, clinicians should be aware of OHVIRA syndrome and Gartner duct cysts and perform systematic ultrasonographic examinations for other genitourinary anomalies.

Characteristic Chest Computed Tomography Findings for Birt-Hogg-Dube Syndrome Indicating Requirement for Genetic Evaluation.

Background: Chest computed tomography (CT) findings are important for identifying Birt−Hogg−Dube (BHD) syndrome. However, the predictive power of classical criteria for chest CT findings is weak. Here, we aimed to identify more specific chest CT findings necessitating genetic examination for FLCN gene mutations. Methods: From June 2016 to December 2017, we prospectively enrolled 21 patients with multiple bilateral and basally located lung cysts on chest CT with no other apparent cause, including cases with and without spontaneous primary pneumothorax. All enrolled patients underwent FLCN mutation testing for diagnosis confirmation. Results: BHD was diagnosed in 10 of 21 enrolled patients (47.6%). There were no differences in clinical features between the BHD and non-BHD groups. Maximal cyst diameter was significantly greater in the BHD group (mean ± standard deviation; 4.1 ± 1.1 cm) than in the non-BHD group (1.6 ± 0.9 cm; p < 0.001). Diversity in cyst size was observed in 100.0% of BHD cases and 18.2% of non-BHD cases (p = 0.001). Morphological diversity was observed in 100.0% of BHD cases and 54.6% of non-BHD cases (p = 0.054). Areas under the receiver operating characteristic curves for predicting FLCN gene mutations were 0.955 and 0.909 for maximal cyst diameter and diversity in size, respectively. The optimal cut-off value for maximal diameter FLCN mutations prediction was 2.1 cm (sensitivity: 99%; specificity: 82%). Conclusions: Reliable chest CT features suggesting the need for FLCN gene mutations screening include variations in cyst size and the presence of cysts > 2.1 cm in diameter, predominantly occurring in the bilateral basal lungs.

Comparison of Homologous Recombination Repair Gene Next-Generation Sequencing Analysis in Patients With Metastatic Castration-Resistant Prostate Cancer Between Local and Central Laboratories in Korea.

Background: Following success of the phase III PROfound trial, the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib was approved by the US Food and Drug Administration in May 2020 for adult patients with deleterious homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). As locally adopted multigene panel next-generation sequencing (NGS) assays for selecting PARP inhibitor candidates have not been thoroughly evaluated, we compared the analytical performance of the FoundationOne CDx (Foundation Medicine, Inc., Cambridge, MA, USA) (central laboratory) and other NGS assays (local laboratory) with samples from the PROfound trial in Korea. Methods: One hundred PROfound samples (60 HRR mutation [HRRm] cases and 40 non-HRRm cases) were analyzed. The results of HRR gene mutation analysis were compared between the FoundationOne CDx and two other NGS assays [SureSelect Custom Design assay (Agilent Technologies, Inc., Santa Clara, CA, USA) and Oncomine Comprehensive assay (Thermo Fisher Scientific, Inc., Waltham, MA, USA)]. Results: The positive percent agreement for single nucleotide variants (SNVs) and insertion/deletions (indels) between the central laboratory and local laboratory was 98.7%-100.0%. The negative percent agreement and overall percent agreement (OPA) for SNVs and indels between central and local laboratories were both 100%. Compared with that of the FoundationOne CDx assay, the OPA for copy number variations of the Oncomine Comprehensive and SureSelect Custom assays reached 99.8%-100%. Most mCRPC patients harboring a deleterious genetic variant were successfully identified with both local laboratory assays. Conclusions: The NGS approach at a local laboratory showed comparable analytical performance for identifying HRRm status to the FoundationOne CDx assay used at the central laboratory.

Cost-Effectiveness Analysis of Germline and Somatic BRCA Testing in Patients With Advanced Ovarian Cancer.

Background: BRCA testing is necessary for establishing a management strategy for ovarian cancer. Several BRCA testing strategies, including germline and somatic testing, are implemented in clinical practice in Korea. We aimed to comparatively evaluate their cost-effectiveness from patients' perspective. Methods: We developed a decision model comprising five BRCA testing strategies implemented in Korea: (1) germline testing first, followed by somatic tumor testing for patients without a germline variant; (2) somatic testing first, followed by germline testing for patients with a variant detected by somatic testing; (3) both germline and somatic testing; (4) germline testing alone; and (5) somatic testing alone, with no testing as the comparator. One-way sensitivity analysis was conducted to test the uncertainty of key parameters. Results: Assuming a willingness-to-pay of $20,000 per progression-free life-year gain (PF-LYG), all five strategies were considered cost-effective. Strategy 4 was the most cost-effective option, with an incremental cost-effectiveness ratio (ICER) of $2,547.7 per PF-LYG, followed by strategy 1, with an ICER of $3,978.4 per PF-LYG. Even when the parameter values were varied within the possible range, the ICERs of all strategies did not exceed the willingness-to-pay threshold. Conclusions: Considering the importance of knowing a patient's BRCA gene status, germline testing first, followed by somatic testing, may be a reasonable option.

Primary endocrine resistance of ER+ breast cancer with ESR1 mutations interrogated by droplet digital PCR.

We investigated the patterns of recurrence and primary endocrine resistance according to estrogen receptor (ER) alpha gene (ESR1) mutations, as assessed by digital droplet (dd) PCR, in patients with non-metastatic ER+ breast cancer. We collected 121 formalin-fixed paraffin-embedded (FFPE) surgical specimens from ER+ breast cancer patients who had relapsed after surgery. Genomic DNA was extracted from the FFPE samples and ESR1 mutations were evaluated using ddPCR. ESR1 mutations were detected in 9 (7.4%) of 121 primary breast cancer specimens. The median recurrence-free interval and overall survival were significantly lower in patients with ESR1 mutations than in those without. Of the patients treated with ET (N = 98), eight had ESR1 mutations. Of these, six (75.0%) had primary endocrine resistance and two (25.0%) had secondary endocrine resistance. By contrast, only 22 of 90 (24.4%) patients without ESR1 mutations had primary endocrine resistance. A multivariable model showed that an ESR1 mutation is a significant risk factor for primary endocrine resistance. Our findings provide clinical evidence that the presence of rare ESR1 mutant clones identified by ddPCR in primary tumors is associated with primary endocrine resistance in an adjuvant setting.

Application of CRISPR/Cas9-based mutant enrichment technique to improve the clinical sensitivity of plasma EGFR testing in patients with non-small cell lung cancer.

BACKGROUND: Approximately 50%-60% of secondary resistance to primary EGFR- tyrosine kinase inhibitors (TKI) therapy is caused by acquired p.Thr790Met (T790M) mutation; however, highly fragmented, low-quantity circulating tumor DNA is an obstacle for detecting mutations. Therefore, more sensitive mutation detection techniques are required. Here, we report a new mutant enrichment technology, the CRISPR system combined with post-polymerase chain reaction (PCR) cell-free DNA (cfDNA) (CRISPR-CPPC) to detect the T790M mutation using droplet digital PCR (ddPCR) from cfDNA. METHODS: The CRISPR-CPPC process comprises the following three steps: (1) cfDNA PCR, (2) assembly of post-PCR cfDNA and CRISPR/CRISPR associated protein 9 complex, and (3) enrichment of the target DNA template. After CRISPR-CPPC, the target DNA was detected using ddPCR. We optimized and validated CRISPR-CPPC using reference cfDNA standards and cfDNA from patients with non-small cell lung cancer who underwent TKI therapy. We then compared the detection sensitivity of CRISPR-CPPC assay with the results of real-time PCR and those of ddPCR. RESULTS: CRISPR-CPPC aided detection of T790M with 93.9% sensitivity and 100% specificity. T790M mutant copies were sensitively detected achieving an approximately 13-fold increase in the detected allele frequency. Furthermore, positive rate of detecting a low T790M copy number (< 10 copies/mL) were 93.8% (15/16) and 43.8% (7/16) for CRISPR-CPPC assay and ddPCR, respectively. CONCLUSIONS: CRISPR-CPPC is a useful mutant enrichment tool for the sensitive detection of target mutation. When tested in patients with progressive disease, the diagnostic performance of CRISPR-CPPC assay is exceptionally better than that of any other currently available methods.

Association between TP53 mutation and high 21-gene recurrence score in estrogen receptor-positive/HER2-negative breast cancer.

We investigated the association between TP53 mutation and 21-gene recurrence score (RS) in ER-positive/HER2-negative breast cancer (BC) using data from 141 patients who underwent TP53 sequencing and Oncotype DX® tests. We detected TP53 mutations in 18 (12.8%) patients. Most patients with TP53 mutation had a high 21-gene RS (≥26). The average 21-gene RS was higher in TP53 mutant tumors. Multivariate analysis showed that mutated TP53 is an independent factor for a high 21-gene RS. Mutated TP53 remained closely associated with high 21-gene RS in patients with low pathological risk (n = 103). In the ER+/PR+/HER2-negative subset (n = 356) of The Cancer Genome Atlas, the non-luminal A intrinsic subtype was more prevalent in the group with mutant TP53. mRNA levels of p53-regulated senescence gatekeeper and cell cycle-related genes were increased in BC with mutated TP53. Mutational analysis of TP53 helped identify endocrine-resistant tumors.

Comparison of IL-6 measurement methods with a special emphasis on COVID-19 patients according to equipment and sample type.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine associated with various diseases, including coronavirus disease (COVID-19). Although IL-6 levels can be assessed using serum samples, use of the AFIAS (Boditech Med Inc.) automated immunoassay analyzer enables quick and simple measurement of IL-6 levels in both serum and whole blood specimens. This study aimed to assess the correlation between IL-6 measurements obtained from the AFIAS IL-6 assay and Elecsys IL-6 assay (Roche Diagnostics). Additionally, utilization of the AFIAS IL-6 assay was evaluated. METHODS: The IL-6 levels from 113 serum samples quantified using two assay systems were evaluated for their degree of correlation. Meanwhile, the linearity, analytical sensitivity, and precision/reproducibility of the AFIAS IL-6 assay were also assessed. RESULTS: Quantification of IL-6 with the AFIAS IL-6 and Elecsys IL-6 assays showed excellent agreement (kappa 0.802) and were found to be correlated (y = -0.2781 + 1.068x; 95% confidence interval: 1.007-1.124). AFIAS IL-6 showed good analytical performances. IL-6 levels were significantly higher in deceased patients compared to those with non-complicated disease and those who were intubated (p = 0.002 and p < 0.0001, respectively). Finally, IL-6 levels more accurately predicted poor prognosis in patients, than did C-reactive protein (area under the curve, 0.716 vs. 0.634). CONCLUSION: The overall analytical performance of the AFIAS assay was comparable to that of the Elecsys IL-6 assay. In light of the ongoing COVID-19 pandemic, the AFIAS may be an attractive tool for measuring IL-6 levels.

Clinical Practice Guidelines for Pre-Analytical Procedures of Plasma Epidermal Growth Factor Receptor Variant Testing.

Standardization of cell-free DNA (cfDNA) testing processes is necessary to obtain clinically reliable results. The pre-analytical phase of cfDNA testing greatly influences the results because of the low proportion and stability of circulating tumor DNA (ctDNA). In this review, we provide evidence-based clinical practice guidelines for pre-analytical phase procedures of plasma epidermal growth factor receptor gene (EGFR) variant testing. Specific recommendations for pre-analytical procedures were proposed based on evidence from the literature and our experimental data. Standardization of pre-analytical procedures can improve the analytical performance of cfDNA testing.

Performance Evaluation of the KRYPTOR Compact PLUS Analyzer-Based B.R.A.H.M.S. CgA â ¡ KRYPTOR Assay for Chromogranin A Measurement.

Numerous immunoassays have been developed to measure the levels of chromogranin A (CgA), a useful biomarker for diagnosing and monitoring generally heterogeneous neuroendocrine tumors (NETs). Here, we evaluated the imprecision and linearity of three such assays: KRYPTOR (ThermoFisher Scientific), NEOLISA (EuroDiagnostica), and CgA-RIA (CisBio), using 123 samples for each assay. The correlation coefficients between the assays were 0.932 (CgA-RIA versus NEOLISA), 0.956 (KRYPTOR versus CgA-RIA), and 0.873 (NEOLISA versus KRYPTOR). KRYPTOR showed good precision, with percent coefficients of variation less than 5% for low and high concentration quality controls. Linearity was maintained over a wide concentration range. Comparison of CgA levels from three disease entities (NETs, non-NET pancreatic tumors, and prostate cancer) and healthy controls showed that patients with NETs had significantly higher CgA levels (n = 57, mean: 1.82 ± 0.43 log ng/mL) than healthy individuals (n = 20, mean: 1.51 ± 0.23 log ng/mL; p = 0.018). No other significant differences between groups were observed. All three immunoassays showed strong correlations in measured CgA levels. Because KRYPTOR operation uses a fully automated random-access system and requires shorter incubation times and smaller sample volumes, the KRYPTOR assay may improve laboratory workflow while maintaining satisfactory analytical performance.

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.

Evaluation of a hybridization capture-based hereditary cancer panel for the ion semiconductor-based next-generation sequencing system.

BACKGROUND: There is an unmet need to use the ThermoFisher Ion sequencing platform with a hybridization capture-based next-generation sequencing(NGS) panel. However, the analytical performance of combining an ion semiconductor-based sequencing system and a hybridization capture-based NGS panel has not been thoroughly evaluated. Therefore, we compared the analytic performance of Illumina's NextSeq and Ion S5 XL using a hybridization capture-based target enrichment method. METHODS: We included 31 clinical samples and NA12878 reference material for comparing two different NGS instruments using a hybridization capture-based panel. The hybridization-based capture hereditary cancer predisposition (HCP) panel was designed for Ion S5 XL Sequencer and Illumina platforms, respectively. RESULTS: We obtained comparable data involving sequencing run metrics and analytical performance of two different NGS systems using a hybridization-based capture panel designed for each NGS platform. The sensitivity, specificity, and accuracy of single-nucleotide variant and indel calling were 97.06%, 100%, and 100% for the Ion S5™ XL system and 98.53%, 100%, and 100% for NextSeq 550Dx platform, respectively. CONCLUSIONS: This study demonstrated that a hybrid capture panel kit can be successfully implemented using the ThermoFisher Scientific Ion S5 XL instrument and offers the opportunity to select a variety of hybridization-based capture panels from various manufacturers.