PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

BACKGROUND/AIMS: To evaluate the diagnostic value of contrast (SonoVue(R)) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses. METHODS: CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass characterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI. RESULTS: The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with kappa values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a kappa value of 0.765. CONCLUSIONS: If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses.
Adult ; Aged ; Contrast Media/diagnostic use ; Female ; Humans ; Liver Diseases/pathology/radiography/*ultrasonography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Sensitivity and Specificity ; Tomography, X-Ray Computed

Gallbladder (GB) cancer occurs predominately as a biliary tract malignant tumor. It generally has a very poor prognosis, and early detection is often difficult. A variety of carcinogens have been implicated as an important cause for GB cancer. Benzene is a well-known carcinogen for hematologic malignancy, and its casual relationship with GB cancer has been suggested. We report a case of two patients who had operated a laundry cleaning facility together and later simultaneously got GB cancer after prolonged benzene exposure.
Adenocarcinoma/*diagnosis/etiology/ultrasonography ; Benzene/*toxicity ; Female ; Gallbladder Neoplasms/*diagnosis/etiology/ultrasonography ; Humans ; Laundering ; Male ; Middle Aged ; Positron-Emission Tomography and Computed Tomography ; Tomography, X-Ray Computed

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.
Adult ; Aged ; Aged, 80 and over ; Anorexia/chemically induced ; Antineoplastic Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/pathology ; Diarrhea/chemically induced ; Disease-Free Survival ; Fatigue/chemically induced ; Female ; Hand-Foot Syndrome/etiology ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/*drug therapy/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nausea/chemically induced ; Neoplasm Invasiveness ; Niacinamide/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/adverse effects/*therapeutic use ; Portal Vein/*pathology ; Proportional Hazards Models ; Tomography, Spiral Computed ; Venous Thrombosis/*drug therapy/pathology

BACKGROUND/AIMS: Achalasia is a rare esophageal motility disorder. Recently, a novel endoscopic technique, peroral endoscopic myotomy (POEM), was introduced as an alternative treatment for achalasia. We report the results and short term outcomes of POEM for patients with achalasia. METHODS: POEM was performed in 13 patients with achalasia. The procedure consisted of creating a submucosal tunnel followed by endoscopic myotomy of circular muscle bundles. The mucosal entry was closed by conventional hemostatic clips. A validated clinical symptom score (Eckardt score) and high resolution manometry were used to evaluate the outcomes. RESULTS: Both the clinical score of achalasia, as well as the resting lower esophageal sphincter (LES) pressure, were significantly reduced after POEM. Mean posttreatment Eckardt score was 0.4+/-0.7, compared to 6.4+/-1.9 prior to the treatment (p=0.001). The mean pretreatment and posttreatment LES pressure was 30.3 and 15.3 mm Hg, respectively (p=0.007). Following POEM, symptomatic relief from dysphagia without reflux symptoms was observed in all patients (13/13). No serious complications related to POEM were encountered. CONCLUSIONS: Based upon our initial experience, the authors believe that POEM is a feasible, safe, and effective treatment and may possibly substitute established treatments of refractory achalasia.
Deglutition Disorders ; Esophageal Achalasia ; Esophageal Motility Disorders ; Esophageal Sphincter, Lower ; Humans ; Manometry ; Muscles

Schwannomas of the gastrointestinal (GI) tract are rare subepithelial tumors comprising approximately 3.3% to 12.8% of all mesenchymal tumors of the GI tract. On endoscopic ultrasound (EUS) they are seen as hypoechoic tumors arising most commonly from the 4th proper muscle layer. Although EUS helps to distinguish tumor characteristics, tissue sampling is required for differentiation with other more common tumors such as GI stromal tumors. Both EUS-guided fine needle aspiration and EUS-guided trucut biopsy (EUS-TCB) can be used for tissue sampling. However, only EUS-TCB allows core biopsy and a high yield of immunohistochemical staining. We report a case of a gastric schwannoma diagnosed by EUS-TCB.
Biopsy ; Biopsy, Fine-Needle ; Gastrointestinal Tract ; Muscles ; Neurilemmoma

Copper is an essential trace element for numerous vital enzymes. Recently, copper can be used clinically as assessing the disease activity, prognosis, therapeutic effect and early prediction of recurrence in patient with neoplasia. But overloading of copper can cause fatal outcome. Copper intoxication is usually encountered following accidental ingestion or suicidal intoxication. A 43-year old male was admitted because of epigastric pain and hematuria after ingestion of the copper hydroxide and organophosphate for suicidal purpose. The laboratory findings showed that the serum and urinary copper concentration are elevated, then the acute renal failure, hemolytic anemia and liver injury progressed. With conservative management, the hemolytic anemia was improved, but disseminated intravascular coagulation with sepsis and respiratory failure by pneumonia were developed, and then finally expired on the eighth hospital days. We experienced a case of a patient who presented with acute renal failure, hemolytic anemia and liver injury after ingestion of copper, and we reported with review of literature.
Acute Kidney Injury ; Adult ; Anemia, Hemolytic ; Copper* ; Disseminated Intravascular Coagulation ; Eating ; Fatal Outcome ; Hematuria ; Humans ; Liver ; Male ; Pneumonia ; Prognosis ; Recurrence ; Respiratory Insufficiency ; Sepsis

BACKGROUND: Ampullary cancer is a malignant lesion in the pancreatobiliary system with a relatively good prognosis because of its slow growth, early appearance of symptoms and high resectability. Hndoscopic retrograde cholangiopancreaticography(ERCP) is an important and useful method in the diagnosis of ampullary cancer because it identifies the location of lesions endoseopically and by opacification of the bilio-pancreatic ducts and allows confirmation by biopsy, But the diagnostic accuracy of endoscopic forcep biopsy was variable according to the macroscopic appearance of ampullary cancer. In unexposed type ampullary cancer, biopsy after endoscopic sphincterotomy or intraluminal cannulatian biopsy has been recommended because the cancer tissue was either not visible at all or barely visible from the lumen of the duodenum. The purpose of this study was to evaluate the contribution of endoscopic sphincterotomy to the diagnosis of ampullary cancer and to compare the clinical eharasteristics of unexposed type ampullary cancer with those of exposed type ampullary cancer. METHOD: Thirty-one cases of the ampullary cancers over the past 5 years were reviewed. Macroscopically, thirty one ampullary cancers were classified into two types. The unexposed type ampullary cancer was defined normal ampullary mucosa with or without protruding. The exposed type ampullary cancer was defined abnormal ampullary mucosa including nodular, ulcerative, nodulo-ulcerative and polypoid appearance. Ampullary cancers were diagnosed preoperatively by forcep biopsy, biopsy after endoscopic sphincterotomy, or brushing cytology. RESULT: The proportion of unexposed type in ampullary cancer was 29%(9 cases). There were no differences of age, sex, diagnostic clue, distal common bile duct(CBD) shape and CBD dilatation by ERCP between unexposed and exposed type ampullary cancers. The serum bilirubin, alkaline phosphatase and GGT were lower in unexposed type comparting with exposed type. The unexposed ampullary cancers could be diagnosed with biopsy after endoscopic sphincterotomy except one case. Biopsy samples were successfully obtained immediately after sphincterotomy in 3 patients and a few days (3 days later-1 month later) after sphincterotomy in 5 patients. CONCLUSION: Weconsider the possibility of unexposed ampullary cancer in cases of jaundice or duct dilatation with normal ampullary cancer in cases of jaundice or duct dilatation with normal ampulla mucosa and should perform biopsy after endoscopic sphincterotomy.
Alkaline Phosphatase ; Bile ; Bilirubin ; Biopsy ; Cholangiopancreatography, Endoscopic Retrograde ; Diagnosis ; Dilatation ; Duodenum ; Humans ; Jaundice ; Mucous Membrane ; Prognosis ; Sphincterotomy, Endoscopic ; Surgical Instruments ; Ulcer

-D- is a very rare haplotype which determines D without C, c, E or e and exalted D activity. The extremely rare homozygote propositi(-D-/-D-) are usually ascertained through their immune antibodies which react with red cells of all common Rh phenotypes. Authors experienced a woman with -D- phenotype for the first time in Korea. She had a history of abortion and intrauterine fetal death. She delivered a baby with severe hemolytic disease of the newborn at the third pregnancy. In spite of intensive medical interventions, the baby died of hydrops fetalis. An immune antibody to high incidence Rh antigen, namely anti-Hro, was demonstrated in the woman's serum. Family study revealed that all of the family had -D- gene complex and one of her sisters also was -D-homozygote. The sister also had anti-Hro in the serum.
Antibodies ; Female ; Fetal Death ; Haplotypes ; Homozygote ; Humans ; Hydrops Fetalis ; Incidence ; Infant, Newborn* ; Korea ; Phenotype* ; Pregnancy ; Siblings

The incidence of traumatic rupture of the tracheobronchial tree has been increased considerably with advent of widespread mechanization and high speed era. Rupture of the bronchus is an unusual result of nonpenetrating trauma to chest. Early diagnosis and primary repair not only restore normal lung function but also avoid difficulties and complications associated with delayed diagnosis and repair. These complications are pneumonia, atelectasis and lung abscess secondary to the bronchial obtruction. We experienced a case of partial rupture on left main bronchus caused by nonpenetrating blunt chest trauma with rib fractures 1 year ago. He was suffered from progressively developing dyspnea on exercise and treated as bronchial asthma at other hospital. Bronchoscopic finding was the narrowed lumen of left main bronchus at 1cm from carina by web-like membrane. We confirmed by bronchogram and repaired by end to end anastomosis, which is rare delayed finding in bronchial rupture without pulmonary complications. We report a case of nonpenetrating traumatic bronchial rupture, manifested by bronchial web in bronchoscopy.
Asthma ; Bronchi ; Bronchoscopy* ; Delayed Diagnosis ; Dyspnea ; Early Diagnosis ; Incidence ; Lung ; Lung Abscess ; Membranes ; Pneumonia ; Pulmonary Atelectasis ; Rib Fractures ; Rupture* ; Thorax* ; Trees