Cancer is a complex, heterogeneic, and dynamic disease involving multiple gene-environment interactions, and affecting numerous biological pathways. As such, the development of reliable and robust non-invasive platforms constitutes a vital step toward realizing the potential of precision medicine. Distant metastases harbor unique genomic characteristics that are not detectable in the corresponding primary tumor of the same patient, and metastases located at different sites show considerable intra-patient heterogeneity. Thus, the analysis of the resected primary tumor alone or, if possible, re-evaluation of tumor characteristics based on the biopsy of the most accessible metastasis, may not reveal sufficient information for treatment decisions. Here, we propose that this dilemma can be solved by a new diagnostic concept: liquid biopsy, that is, the analysis of therapeutic targets and drug resistance-conferring gene mutations in or on circulating tumor cells (CTCs). Finally, the analysis of the resected primary tumor alone may provide misleading information with regard to the characteristics of metastases, the key target for systemic anticancer therapy. Liquid biopsies are noninvasive tests using blood or fluids that detect CTCs or the products of tumors, such as fragments of nucleotides or proteins that are shed into biological fluids from the primary or metastatic tumors. Such biopsies are expected to be informative or easily accessible tools to provide comprehensive information regarding cancers beyond conventional biopsies. Thus, this review addresses the use of CTCs in cancer detection, diagnosis and monitoring and discusses the direction of its clinical application in cancer patient care.
Biopsy ; Diagnosis ; Early Detection of Cancer ; Gene-Environment Interaction ; Humans ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Nucleotides ; Patient Care ; Population Characteristics ; Precision Medicine

Radiomics handles imaging biomarker from high-throughput feature extraction through complex pattern recognition that is difficult for human to process. Recent medical paradigms are rapidly changing to personalized medicine, including molecular targeted therapy, immunotherapy, and theranostics, and the importance of biomarkers for these is growing day by day. Even though biopsy continues to gold standard for tumor assessment in personalized medicine, imaging is expected to complement biopsy because it allows whole tumor evaluation, whole body evaluation, and non-invasive and repetitive evaluation. Radiomics is known as a useful method to get imaging biomarkers related to intratumor heterogeneity in molecular targeted therapy as well as one-size-fits-all therapy. It is also expected to be useful in new paradigms such as immunotherapy and somatostatin receptor (SSTR) or prostate-specific membrane antigen (PSMA)-targeted theranostics. Radiomics research should move to multimodality (CT, MR, PET, etc.), multicenter, and prospective studies from current single modality, single institution, and retrospective studies. Image-quality harmonization, intertumor heterogeneity, and integrative analysis of information from different scales are thought to be important keywords in future radiomics research. It is clear that radiomics will play an important role in personalized medicine.
Biomarkers ; Biopsy ; Complement System Proteins ; Humans ; Immunotherapy ; Membranes ; Methods ; Molecular Targeted Therapy ; Population Characteristics ; Precision Medicine ; Prospective Studies ; Receptors, Somatostatin ; Retrospective Studies ; Theranostic Nanomedicine ; Weights and Measures

Epidermal growth factor receptor (EGFR)‒tyrosine kinase inhibitors (TKIs) are effective clinical therapeutics for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib, a thirdgeneration EGFR TKI, has proven effective against T790M mutations. However, the vast majority of patients acquire resistance following successful treatment. A 59-year-old female patient with metastatic NSCLC developed resistance after 43 weeks of osimertinib. CancerSCAN of the metastatic liver lesion revealed a EGFR C797G mutation at an allele frequency of 72%, a preexisting T790M mutation (73%) in cis and an exon 19 deletion (87%). Another 53-year-old female patient developed systemic progression after 10 months of osimertinib. CancerSCAN of the lung biopsy identified an EGFR L718Q mutation at an allele frequency of 7%, concomitant PIK3CA E545K (12.90%) and preexisting EGFR L858R (38%), but loss of the T790M mutation. The heterogeneity of osimertinib resistance mechanisms warrants further investigation into novel or combination agents to overcome the rare acquired resistances.
Biopsy ; Carcinoma, Non-Small-Cell Lung* ; Exons ; Female ; Gene Frequency ; Humans ; Liver ; Lung ; Middle Aged ; Phosphotransferases ; Population Characteristics ; Receptor, Epidermal Growth Factor

BACKGROUND: The heterogeneity of histological findings in preclinical diet-induced nonalcoholic fatty liver disease (NAFLD) animal models is highly challenging. Here, we aimed to evaluate the feasibility and stability of repeated liver biopsy in NAFLD animal models. METHODS: Heterogeneity of diet-induced NAFLD was evaluated at different time points in 52 high-fat diet (HFD), 35 methionine choline-deficiency diet (MCD), and 166 western diet (WD) induced NAFLD mice. Serial liver biopsies (left lateral, right medial, and left medial lobes) were performed monthly for up to 3 months. Mortality rates and changes in food intake, body weight, and liver enzymes were assessed. RESULTS: At 12 weeks, of the HFD animals, 14% and 30% did not develop steatosis and lobular inflammation, respectively; of the MCD animals, 7% did not develop lobular inflammation; and of the WD animals, 14% and 51% did not develop steatosis and lobular inflammation, respectively. The mortality rate of repeated liver biopsy was 1.62% (2/123 mice died). Repeated liver biopsy can be used to trace disease progression. Although body weight, food intake, and liver enzymes slightly changed after biopsy, all recovered within a week. Repeated liver biopsy did not affect the degrees of inflammation and steatosis of the other liver lobes. CONCLUSION: The diet-induced NAFLD models were quite heterogeneous. Our results suggest that the repeated liver biopsy before treatment was applicable and stable in this NAFLD animal study.
Animals ; Biopsy* ; Body Weight ; Diet ; Diet, High-Fat ; Diet, Western ; Disease Progression ; Eating ; Inflammation ; Liver* ; Methionine ; Mice ; Models, Animal ; Mortality ; Non-alcoholic Fatty Liver Disease* ; Population Characteristics

PURPOSE: This study was undertaken to summarize the published data and to provide more robust estimates regarding the issue of core needle biopsy (CNB) for discriminating thyroid nodules with indeterminate fine-needle aspiration (FNA) results. METHODS: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The sources comprised studies published through November 2017. Original articles that investigated CNB in indeterminate thyroid lesions were searched. A random-effects model was used for statistical pooling of the data. The I2 index was used to quantify the heterogeneity among the studies. The Egger test was carried out to evaluate the possible presence of significant publication bias. Quality assessment of the studies was performed according to QUADAS-2. RESULTS: A total of 205 articles were retrieved, seven were initially selected, and the data of five papers were ultimately pooled in a meta-analysis. The overall cancer rate was 34%. The rate of cancers correctly diagnosed by CNB was 83% (95% confidence interval [CI], 76 to 89), with neither heterogeneity (I2=25%) nor publication bias (Egger test, P=0.918). The rate of benign nodules correctly assessed by CNB was 84% (95% CI, 65 to 97), with significant heterogeneity (I2=93.4%) and publication bias (Egger test, P=0.016). CONCLUSION: Evidence was found that CNB can correctly diagnose the majority of nodules previously read as indeterminate on FNA.
Biopsy, Fine-Needle* ; Biopsy, Large-Core Needle* ; Population Characteristics ; Publication Bias ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule*

BACKGROUND: Longitudinal melanonychia (LM) can be challenging as it may be caused by a wide variety of benign and malignant conditions. However, there are scarce data on LM confirmed by skin biopsy examination in Korean patients. OBJECTIVE: We sought to evaluate the clinical features and histopathologic diagnosis of LM in Korean patients. METHODS: We reviewed the medical records and clinical photographs of patients presenting with LM confirmed by skin biopsy examination between June 2007 and June 2017. RESULTS: Among a total of 75 patients with LM confirmed by skin biopsy examination at our hospital over a period of 10 years, 11 patients (14.7%) had malignant lesions. Common features of malignant lesions were involvement of a single nail, color heterogeneity, Hutchinson's sign, and nail plate dystrophy or ulceration. Common features of benign lesions were a negative Hutchinson's sign and absence of nail plate dystrophy and ulceration. CONCLUSION: This study analyzed the clinical features and histopathologic diagnosis of LM in Korean patients. Our data may contribute to determining the management approach for patients with LM.
Biopsy ; Diagnosis ; Humans ; Medical Records ; Population Characteristics ; Skin ; Ulcer

BACKGROUND/AIMS: Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance. METHODS: We retrospectively analyzed 84 patients with ARDS who met the criteria of the Berlin definition and underwent surgical lung biopsy between January 2004 and December 2013 in three academic hospitals in Korea. We evaluated their histopathologic findings and compared the clinical outcomes. Additionally, the impact of surgical lung biopsy on therapeutic alterations was examined. RESULTS: The histopathologic findings were highly heterogeneous. Of 84 patients undergoing surgical lung biopsy, DAD was observed in 31 patients (36.9%), while 53 patients (63.1%) did not have DAD. Among the non-DAD patients, diffuse interstitial lung diseases and infections were the most frequent histopathologic findings in 19 and 17 patients, respectively. Although the mortality rate was slightly higher in DAD (71.0%) than in non-DAD (62.3%), the difference was not significant. Overall, the biopsy results led to treatment alterations in 40 patients (47.6%). Patients with non-DAD were more likely to change the treatment than those with DAD (58.5% vs. 29.0%), but there were no significant improvements regarding the mortality rate. CONCLUSIONS: The histopathologic findings of ARDS were highly heterogeneous and classic DAD was observed in one third of the patients who underwent surgical lung biopsy. Although therapeutic alterations were more common in patients with non-DAD-ARDS, there were no significant improvements in the mortality rate.
Acute Lung Injury ; Berlin ; Biopsy* ; Humans ; Korea ; Lung Diseases, Interstitial ; Lung* ; Mortality ; Pathology ; Population Characteristics* ; Respiratory Distress Syndrome, Adult* ; Retrospective Studies

BACKGROUND AND OBJECTIVES: The diagnostic performance of shear wave elastography (SWE) combined with ultrasound (US) in the differential diagnosis of thyroid nodules was evaluated. MATERIALS AND METHODS: 459 articles were collected using KoreaMed, Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library. The searching words were ‘{(elastography and shear).mp. OR SWE.mp. OR acoustic radiation force impulse.mp. OR ARFI.mp. OR acuson.mp. OR aixplorer.mp.}’. Two authors independently performed article selection and evaluation of the quality of studies with Scottish Intercollegiate Guidelines Network tool. RESULTS: 2582 specimens (thyroid nodules) from 11 studies selected were included in this review. Combined use of US and SWE was reported higher specificity in five literatures, lower specificity in five studies, and no changes in 1 study when compared to US. We performed meta-analysis using data from 10 studies. The pooled sensitivity and specificity of US and SWE group for the differential diagnosis of benign and malignant nodules were 0.91 (I2=83.4%), 0.73 (I2=95.9%). The pooled sensitivity and specificity of US alone group were 0.88 (I2=93.2%), 0.71 (I2=92.7%). CONCLUSION: SWE is not effective in the differential diagnosis of thyroid nodules to minimize unnecessary biopsy of nodules. The included studies showed significant heterogeneity of results.
Acoustics ; Biopsy ; Diagnosis, Differential ; Elasticity Imaging Techniques ; Population Characteristics ; Sensitivity and Specificity ; Thyroid Gland ; Thyroid Nodule ; Ultrasonography

Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy. In this study, we performed whole-exome sequencing for a breast cancer tissue and identified PTEN p.H259fs*7 frameshift mutation. In the plasma DNA (liquid biopsy) analysis by targeted NGS, the same variant initially identified in the tumor tissue was also detected with low variant allele frequency. This mutation was subsequently validated by digital polymerase chain reaction in liquid biopsy. Our result confirm that driver alterations identified in the tumor tissue were detected in liquid biopsy by targeted NGS as well, and suggest that a higher depth of sequencing coverage is needed for detection of genomic alterations in a liquid biopsy.
Biopsy ; Breast Neoplasms* ; Breast* ; DNA* ; Frameshift Mutation ; Gene Frequency ; Plasma* ; Polymerase Chain Reaction ; Population Characteristics

BACKGROUND: The phenotypic heterogeneity of psoriasis could be explained by the alternate activation of either T-helper (Th)-1- or Th-17-related cytokines. However, evidence directly supporting this hypothesis is scarce. OBJECTIVE: To characterize the expression of Th-1- and Th-17-related cytokines according to the morphological psoriasis phenotype: guttate vs. plaque. METHODS: In this study, we enrolled 68 patients exhibiting either guttate or plaque psoriasis, and 10 healthy controls. To avoid age-related bias, age matching was performed for each group. Circulating levels of interferon (IFN)-gamma, interleukin (IL)-1RA, IL-2, IL-12p40, IL-17A, IL-22, and IL-23 were measured with an enzyme-linked immunosorbent assay (ELISA). Psoriasis-affected tissue was obtained through biopsy sampling from the eight patients who exhibited the most typical morphology. Levels of IL-1RA, IL-12p40, IL-17, IL-22, and IL-23 in the psoriasis tissue samples were measured with western blot analysis. RESULTS: ELISAs of the serum samples showed higher levels of inflammatory cytokines such as IL-1RA, IL-2, IL-23, and IFN-gamma in patients with psoriasis than in healthy controls. However, the inflammatory cytokine levels did not differ significantly between guttate and plaque psoriasis patients. Western blot analysis of psoriatic tissue revealed higher protein levels of Th-1- and Th-17-related cytokines in patients than in healthy controls. The levels of IL-12p40 and IL-23 were unexpectedly higher in plaque tissue than in guttate tissue. CONCLUSION: The morphological phenotype of psoriasis does not appear to be determined by a specific activation of either the Th-1 or Th-17 pathway. Rather, the cytokine profile influences disease activity and is altered according to the status of the lesion (early or chronic).
Bias (Epidemiology) ; Biopsy ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interferons ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-12 Subunit p40 ; Interleukin-17 ; Interleukin-2 ; Interleukin-23 ; Interleukins ; Phenotype ; Population Characteristics ; Psoriasis*