Liquid biopsy using extracellular vesicle–derived DNA in lung adenocarcinoma

Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%–60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult. Extracellular vesicles (EVs) are ideal carriers of cancer biomarkers, as cancer cells secret an abundance of EVs, and the contents of tumor cell-originated EVs reflect the molecular and genetic composition of parental cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and tumor-specific oncogenic mutant DNAs. For these reasons, liquid biopsy using EV DNA has the potential to overcome issues arising from tissue shortages associated with small biopsies, which are often seen in lung cancer patients, and the biopsy product can be used in other diagnostic methods, such as epidermal growth factor receptor (EGFR) mutation testing and next-generation sequencing (NGS). A higher sensitivity can be achieved when EV DNAs obtained from bronchoalveolar lavage fluid (BALF) are used rather than those from blood. BALF, when obtained close to the tumor site, is a promising liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the tumor microenvironment, and provides increased diagnostic sensitivity when compared to blood.

Risk factors for primary lung cancer among never-smoking women in South Korea: a retrospective nationwide population-based cohort study

Background/Aims@#We performed a large-scale, retrospective, nationwide, cohort study to investigate the risk factors for lung cancer among never-smoking Korean females. @*Methods@#The study data were collected from a general health examination and questionnaire survey of eligible populations conducted between January 1, 2003 and December 31, 2004; the data were acquired from the tailored big data distribution service of the National Health Insurance Service. After a 1-year clearance period, 5,860,922 of 6,318,878 never-smoking female participants with no previous history of lung cancer were investigated. After a median follow-up of 11.4 years, 43,473 (0.74%) participants were defined as “newly diagnosed lung cancer”. @*Results@#After adjusting for all variables at baseline, the variables older age, lower body mass index (BMI), less exercise, frequent alcohol drinking, meat-based diet, rural residence, and previous history of cancer were associated with a higher incidence of lung cancer. Low BMI (< 18.5 kg/m2: hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.27 to 1.40) was a significant independent risk factor; as BMI decreased, HR increased. Negative associations between BMI and lung-cancer development were also observed after controlling for age (p for trend < 0.001). Drinking alcohol one to two times a week (HR, 1.25; 95% CI, 1.21 to 1.28) and eating a meat-based diet (HR, 1.08; 95% CI, 1.01 to 1.15) were associated with lung-cancer incidence. @*Conclusions@#Modifiable baseline characteristics, such as BMI, exercise, alcohol consumption, and diet, are risk factors for lung-cancer development among never- smoking females. Thus, lifestyle modifications may help prevent lung cancer.

Current status and future perspectives of liquid biopsy in non-small cell lung cancer

With advances in target therapy, molecular analysis of tumors is routinely required for treatment decisions in patients with advanced non-small cell lung cancer (NSCLC). Liquid biopsy refers to the sampling and analysis of circulating cell-free tumor DNA (ctDNA) in various body fluids, primarily blood. Because the technique is minimally invasive, liquid biopsies are the future in cancer management. Epidermal growth factor receptor (EGFR) ctDNA tests have been performed in routine clinical practice in advanced NSCLC patients to guide tyrosine kinase inhibitor treatment. In the near future, liquid biopsy will be a crucial prognostic, predictive, and diagnostic method in NSCLC. Here we present the current status and future perspectives of liquid biopsy in NSCLC.

Liquid biopsy using extracellular vesicle–derived DNA in lung adenocarcinoma

Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%–60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult. Extracellular vesicles (EVs) are ideal carriers of cancer biomarkers, as cancer cells secret an abundance of EVs, and the contents of tumor cell-originated EVs reflect the molecular and genetic composition of parental cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and tumor-specific oncogenic mutant DNAs. For these reasons, liquid biopsy using EV DNA has the potential to overcome issues arising from tissue shortages associated with small biopsies, which are often seen in lung cancer patients, and the biopsy product can be used in other diagnostic methods, such as epidermal growth factor receptor (EGFR) mutation testing and next-generation sequencing (NGS). A higher sensitivity can be achieved when EV DNAs obtained from bronchoalveolar lavage fluid (BALF) are used rather than those from blood. BALF, when obtained close to the tumor site, is a promising liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the tumor microenvironment, and provides increased diagnostic sensitivity when compared to blood.

Efficacy of Afatinib in a Previously-Treated Patient with Non-Small Cell Lung Cancer Harboring HER2 Mutation: Case Report

Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined especially in eastern populations. We provide evidence of clinical benefit of afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously failed cytotoxic chemotherapy and gefitinib treatment. Next-generation sequencing of the tumor tissue revealed a HER2 exon 20 mutation (c.2437A > G), which has never been reported. The patient was treated with afatinib for more than four months. She showed rapid radiologic response within a month, and maintained stable state until the last dose of afatinib.

Right Ventricular Myocardial Infarction due to Right Coronary Artery Total Occlusion Originating From the Distal Left Circumflex Artery

An isolated single coronary artery is rare but often associated with other congenital cardiac malformations and myocardial ischemia. We report a rare case of right ventricular myocardial infarction due to total occlusion of the right coronary artery originating from the distal left circumflex artery.

Evaluation of the Various Artificial Skin Substitutes Implanted onto Nude Mice

PURPOSE: The purpose of this study is to evaluate the remodeling process of the various skin substitutes in 4th and 6th weeks following the transplantation when transplanted onto nude mice. METHODS: Three types of artificial skin substitutes, such as PLGA scaffold with keratinocyte sheets(group 1), acellular human dermis(Surederm(TM)) and keratinocyte sheet(group 2), bioengineered skin(Neoderm(TM))(group 3), were applied to the wound on nude mice. All mice were killed in 2, 4 weeks and/or 6 weeks after grafting and tissue samples were harvested from the back of mice. The changes in wound size, degree of angiogenesis, formation of basement membrane and epidermis, density of collagen fibers and neural restoration were examined. RESULTS: There was no significant changes in wound size among the three groups. However, the size of wound decreased in the non-substituted group due to contracture. Degree of angiogenesis and systhesis of collagen or neurofilaments were mostly increased in bioengineered skin(Neoderm(TM))(group 3), followed by acellular human dermis(Surederm(TM)) and keratinocyte sheet(group 2), PLGA scaffold with keratinocyte sheets (group 1). However, group 3 and group 2 showed similar thickness of basement membrane and epidermis. CONCLUSION: We found that degree of angiogenesis, formation of basement membrane and skin appendages, density of collagen fibers and neurofilaments can be the categories to evaluate the success of artificial skin substitution in early stages.

Accessory Earlobe Malformation

A rare auricular malformation with an accessory earlobe is presented, and its method of correction is described. After review of literature, there has not been any previous report of such malformation. Relevant embryologic correlations are discussed. A 13-years-old girl is presented with a bilateral ear deformity that was present since birth. Two bulging masses below both ears and mild indentation of upper lobules were noticed. Bulging masses were removed and indented upper lobules were augmented by composite graft using these soft tissue. The pixie earlobes were also corrected using superiorly based flap of the lobe border. The external ear of the human develops from a fusion of six small hillocks at the region of the first and second branchial arches of the embryo. Although the case is limited to one, it is reasonable to presume that the mild depression of the upper lobule might have been caused by a deficiency of the divided hillock 1.

Clinical Experiences of Acrylic Splint on Pediatric Mandile Fracture

The goal of open reduction in mandibular fracture is to restore the underlying bony architecture to its pre-injury position in a stable fashion, with a minimal of aesthetic and functional impairment. Many cases of mandibular fracture are treated by intermaxillary fixation using arch bars after open reduction. In this study, after open reduction of fracture, 23 patients were grouped according to acrylic splint appliction. All patients was younger than 15 years old. Open reduction was performed by miniplate or interosseous wire fixation. After open reduction, 8 patients were applied with acrylic splint and 15 patients were applied with arch bar for intermaxillary fixation. Physical examination and postoperative panoramic x-ray were reviewed for the evaluation of occlusion. In the group where acrylic splint was used, 75% of the patients showed excellent subjective satisfaction and 25% showed good satisfaction. In the group where the acrylic splint was not used, 33% showed excellent and good satisfaction, 27% fair satisfaction and 1 patient showed poor satisfaction. On long-term follow- up, the group where acrylic splint was applied showed better occlusion compared to the group where acrylic splint was not applied.

Simultaneous Reconstruction of the Alar and its Neighboring Area using Bielliptical Flap

It is difficult to repair defects of the alar nasi because of its complex configuration and the structural support which enables to ensure an adequate patency of nasal airway. Furthermore, if the defect is extended to neighboring areas such as the nostril, vestibular floor, and upper lip, proper selection and execution of repair technique is of utmost importance. We considered the alar and perialar area to be two different aesthetic units and so reconstruction of the defect with two regional flaps would yield better result. We designed vertical bielliptical flap as two regional flaps (nasolabial and nasojugal flap). A vertical bielliptical flap commonly based on the perforators from the facial artery on alar groove was developed. With this flap, the defect of the alar and its neighboring area was simultaneously reconstructed. Fuctional and aesthetic result was good.

Simultaneous Reconstruction of the Alar and its Neighboring Area using Bielliptical Flap

It is difficult to repair defects of the alar nasi because of its complex configuration and the structural support which enables to ensure an adequate patency of nasal airway. Furthermore, if the defect is extended to neighboring areas such as the nostril, vestibular floor, and upper lip, proper selection and execution of repair technique is of utmost importance. We considered the alar and perialar area to be two different aesthetic units and so reconstruction of the defect with two regional flaps would yield better result. We designed vertical bielliptical flap as two regional flaps (nasolabial and nasojugal flap). A vertical bielliptical flap commonly based on the perforators from the facial artery on alar groove was developed. With this flap, the defect of the alar and its neighboring area was simultaneously reconstructed. Fuctional and aesthetic result was good.

Biomechanical study on meniscus repair techniques / 대한정형외과학회잡지

No abstract available.