BACKGROUND: We examined the feasibility of a full-length gene analysis for the drug resistance-related genes inhA, katG, rpoB, pncA, rpsL, embB, eis, and gyrA using ion semiconductor next-generation sequencing (NGS) and compared the results with those obtained from conventional phenotypic drug susceptibility testing (DST) in multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates. METHODS: We extracted genomic DNA from 30 pure MDR-TB isolates with antibiotic susceptibility profiles confirmed by phenotypic DST for isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA), amikacin (AMK), kanamycin (KM), streptomycin (SM), and fluoroquinolones (FQs) including ofloxacin, moxifloxacin, and levofloxacin. Enriched ion spheres were loaded onto Ion PI Chip v3, with 30 samples on a chip per sequencing run, and Ion Torrent sequencing was conducted using the Ion AmpliSeq TB panel (Life Technologies, USA). RESULTS: The genotypic DST results revealed good agreement with the phenotypic DST results for EMB (Kappa 0.8), PZA (0.734), SM (0.769), and FQ (0.783). Agreements for INH, RIF, and AMK+KM were not estimated because all isolates were phenotypically resistant to INH and RIF, and all isolates were phenotypically and genotypically susceptible to AMK+KM. Moreover, 17 novel variants were identified: six (p.Gly169Ser, p.Ala256Thr, p.Ser383Pro, p.Gln439Arg, p.Tyr597Cys, p.Thr625Ala) in katG, one (p.Tyr113Phe) in inhA, five (p.Val170Phe, p.Thr400Ala, p.Met434Val, p.Glu812Gly, p.Phe971Leu) in rpoB, two (p.Tyr319Asp and p.His1002Arg) in embB, and three (p.Cys14Gly, p.Asp63Ala, p.Gly162Ser) in pncA. CONCLUSIONS: Ion semiconductor NGS could detect reported and novel amino acid changes in full coding regions of eight drug resistance-related genes. However, genotypic DST should be complemented and validated by phenotypic DSTs.
Amikacin ; Clinical Coding ; Complement System Proteins ; DNA ; Drug Resistance* ; Ethambutol ; Fluoroquinolones ; Isoniazid ; Kanamycin ; Levofloxacin ; Mycobacterium tuberculosis* ; Mycobacterium* ; Ofloxacin ; Pyrazinamide ; Rifampin ; Semiconductors* ; Streptomycin

Prophylactic para-aortic lymphadenectomy is not recommended in curable advanced gastric cancer. However, there are few reports on therapeutic para-aortic lymphadenectomy after palliative chemotherapy in far advanced gastric cancer. We report three cases of laparoscopy-assisted gastrectomy with para-aortic lymphadenectomy after palliative chemotherapy for the first time in Korea. Three gastric cancer patients with isolated para-aortic lymph node (PAN) metastasis showed partial response to capecitabine-based chemotherapy, and laparoscopy-assisted gastrectomy with para-aortic lymphadenectomy was performed with curative intent. The mean total operation time was 365 minutes (range, 310 to 415 minutes), and the mean estimated blood loss was 158 mL (range, 125 to 200 mL). The mean number of retrieved PAN was 9 (range, 8 to 11), and all pathologic results showed no metastasis of para-aortic region. All patients recovered and were discharged without any significant complications.
Gastrectomy ; Humans ; Korea ; Laparoscopy ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis ; Stomach Neoplasms

Patent ductus arteriosus (PDA) is a rare clinical finding in adult patients. Considering the increase in cases of PDA discovered incidentally on echocardiograms at young ages, and the life-shortening effect of PDA, it is rare to diagnose PDA in old patients. We report a case of an 80-year-old patient who experienced symptoms of congestive heart failure showed findings suggestive of PDA in echocardiogram and confirmed the diagnosis through a cardiac catheterization and a coronary angiography. After percutaneous occlusion of PDA with an Amplatzer duct occlusion device, symptoms related to congestive heart failure improved.
Adult ; Aged ; Cardiac Catheterization ; Cardiac Catheters ; Coronary Angiography ; Ductus Arteriosus, Patent ; Estrogens, Conjugated (USP) ; Heart Failure ; Humans

The generally accepted treatment for infected aortic aneurysms involves open surgical resection and debridement, with in situ or extra-anatomical bypass. Occasionally, endovascular management can be substituted for the standard operation dependent on the patient's condition. We report the case of an 81-year-old female with a ruptured infected aortic aneurysm and sepsis, successfully treated endovascularly. She had been on oral antibiotics for one year and is doing well 2 years after discharge.
Aged, 80 and over ; Aneurysm, Ruptured ; Anti-Bacterial Agents ; Aortic Aneurysm ; Debridement ; Female ; Humans ; Sepsis

BACKGROUNDS/AIMS: Hepatic resection has only guaranteed long-term survival in patients with colorectal liver metastasis (CRLM) even in the era of effective chemotherapy. The definite role of neoadjuvant chemotherapy (NCT) is to improve outcomes of unresectable CRLMs, but it its role has not been defined for initially resectable CRLMs (IR-CRLMs). METHODS: We reviewed the medical records of 226 patients, who had been diagnosed and treated for IR-CRLM between 2003 and 2008; the patients had the following pathologies: 10% had more than 4 nodules, 11% had tumors larger than 5 cm, and 61% had synchronous CRMLs. Among these patients, 20 patients (Group Y) were treated with NCT, and 206 (Group N) did not receive NCT according to their physician's preference. The median follow-up time was 34.1 months. RESULTS: The initial surgical plans were changed after NCT to further resection in 20% and to limited resection in 10% of 20 patients. Complication rates of Groups Y (30%) were indifferent from Group N (23%) (p=0.233), but intraoperative transfusions were more frequent in Group N (15%) than in Group Y (5%) (p=0.006). There was one case of hospital mortality (0.44%). Disease-free survival rates in Groups Y and N were 23% and 39%, respectively, and patient survival rates were 42% and 66% (p>0.05). By multivariate analysis, old age (> or =60 years), differentiation of primary tumor (poorly/mucinous), resection margin involvement, and no adjuvant chemotherapy were associated with poor patient survival; the number of CRLMs (> or =4) was associated with poor disease-free survival. CONCLUSIONS: NCT had neither a positive impact nor a negative impact on survival, even with intraoperative transfusion, as observed on operative outcomes for patients with IR-CRLM. Further study is required to elucidate the role of NCT for treatment of patient with IR-CRLMs.
Chemotherapy, Adjuvant ; Disease-Free Survival ; Follow-Up Studies ; Hospital Mortality ; Humans ; Liver ; Medical Records ; Multivariate Analysis ; Neoplasm Metastasis ; Survival Rate

PURPOSE: The Hedgehog (Hh) signaling pathway is important in embryonic development including cell differentiation and proliferation. Recently, activation of this pathway has been implicated in several forms of solid cancers. We investigated sonic hedgehog (Shh) protein expression and its relation to differentiation and clinicopathologic characteristics in thyroid cancer cell lines and tissues. METHODS: FTC-236, FTC-238, and XTC-1. We made tissue microarray slides using 80 thyroid surgical specimen: 40 benign and 40 malignant lesions. Immunohistochemical staining was performed using anti-Shh antibody. mRNA expression of NIS, thyroglobulin, and CD97 were evaluated by RT-PCR. Cyclopamine was used as a Shh signal inhibitor. RESULTS: Shh expression was more prominent in TPC-1, FTC-133, and XTC-1 cell lines than the others. Cyclopamine downregulated CD97 and upregulated thyroglobulin mRNA expression, but did not induce mRNA expression of NIS. Thyroid tissues showed varied expression of Shh in both benign and malignant diseases. Shh expression was detected in 38 of 50 (76%) normal, in 18 of 25 (72%) non-neoplastic benign, in nine of 15 (60%) benign tumors, and in 31 of 40 (77%) malignant tumors. Shh over-expression was significantly less frequent in papillary thyroid carcinomas than in normal or benign thyroid tissues. In addition, Shh protein expression did not relate to clinicopathologic characteristics in papillary thyroid carcinomas. CONCLUSION: Thyroid tissues and cell lines vary in expression of Shh. Cyclopamine can induce redifferentiation in thyroid cancer cell lines. Shh protein expression, however, is unrelated to clinicopathologic characteristics in papillary thyroid carcinomas.
Cell Differentiation ; Cell Line ; Embryonic Development ; Female ; Hedgehog Proteins* ; Hedgehogs ; Pregnancy ; RNA, Messenger ; Thyroglobulin ; Thyroid Gland* ; Thyroid Neoplasms

BACKGROUND: The purpose of this study was to determine whether hand-measured carotid intima-media thickness (IMT) was a reliable and simple tool that could be used to evaluate the severity of stable coronary artery disease (CAD) with normal high-sensitivity C-reactive protein (CRP). MATERIAL AND METHOD: We examined left carotid IMTs in 688 patients with stable CAD and excluded 121 patients with abnormally elevated hs-CRP (> or =0.5 mg/dL). We sought to determine the association between risk factors and the severity of stable CAD and carotid IMT in 567 patients who were divided into lower and higher groups based on the median value. Patients underwent a coronary artery angiogram and had at least significant stenosis (>50% of the original luminal diameter involving one or more major coronary artery). RESULT: Of the 567 patients, 300 (52.9%) were in the lower IMT group and 267 (47.1%) were in the higher IMT group; the median value was 0.76 mm. By multivariable logistic regression analysis, the following groups were different: older age (~49 vs. 70~ years, respectively; OR=6.552), high FBS (~99 vs. 120~ mg/dL; OR=1.713) and severity of CAD (1 vessel vs. 2 vessel disease; OR=1.711, 1 vessel vs. 3 vessel disease; OR=1.714). CONCLUSION: We conclude that there are correlations between increased carotid IMT and severity of CAD in stable angina patients with normal CRP levels.
Angina, Stable ; Atherosclerosis ; C-Reactive Protein ; Carotid Arteries ; Carotid Intima-Media Thickness ; Constriction, Pathologic ; Coronary Artery Disease ; Coronary Vessels ; Glycosaminoglycans ; Humans ; Logistic Models ; Phenobarbital ; Risk Factors

PURPOSE: Graft-Versus-Host Disease (GVHD) is a rare (0.1~2%) but severe complication after liver transplantation (LT). It is the most lethal complication after LT and there are currently no effective preventive or therapeutic measures available. Approximately 90 such cases have been reported in the literature, but only one case has been reported in Korea. METHODS: We performed a retrospective analysis of 767 patients who underwent LT (living donor:deceased donor=554:213) at Seoul National University Hospital, Korea from 1998 to 2009. Four patients (4/767, 0.52%) with histologically proven GVHD were found. The diagnosis of GVHD was made according to observing macrochimerism in the peripheral blood and the affected tissue biopsy. RESULTS: Four patients underwent LT due to Hepatitis B virus-related liver cirrhosis and two of these patients had coexisting hepatocellular carcinoma. Three patients received livers from deceased donors and one received a liver from a live donor. All their blood matching were identical. The first diagnosed case underwent human leukocyte antigen (HLA) typing only after LT and it showed complete one-way donor-recipient HLA matching. The onset of GVHD occurred between 10 days and 55 days after LT. All the patients developed high-grade fever, skin rash, neutropenia, diarrhea and the main signs and symptoms related to GVHD. All the patients died because of sepsis despite intensive treatment. CONCLUSION: GVHD after LT is an extremely rare and fatal complication and it is difficult to diagnose. Therefore, we should perform pre-transplant HLA matching and try to establish an early diagnosis for patients who are clinical suspicious of having GVHD. Further study in this area is needed and physicians need to be alert to detect this malady.
Carcinoma, Hepatocellular ; Chimerism ; Diarrhea ; Early Diagnosis ; Exanthema ; Fever ; Graft vs Host Disease ; Hepatitis B ; Humans ; Korea ; Leukocytes ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Neutropenia ; Retrospective Studies ; Sepsis ; Tissue Donors

PURPOSE: Mutated p53 is a tumor suppressor gene, hMLH1 is a mismatch repair gene, and hypermethylation of hMLH1 follows microsatellite instability (MSI). This research's aim is to investigate mutated p53, inactivated hMLH1 and MSI in gastric cancer and their clinicopathologic implications. METHODS: Between 2003 and 2007, 618 patients underwent curative radical gastrectomy for gastric cancer at Seoul National University Bundang Hospital in Korea. We reviewed their medical charts and the pathologic reports with immunohistochemistry for p53, hMLH1 and polymerase chain reaction for MSI in 509, 499, and 561 cases, respectively. These genetic markers were statistically compared with clinicopathologic features and postoperative survival. RESULTS: The expression ratios of mutated p53, inactivated hMLH1, and MSI were 32.8%, 8.4%, and 8.7%, respectively. Mutation of p53 occurred more frequently in aged group (over 40), differentiated group (against the non-differentiated group), intestinal type, infiltrative type and positive lymph node metastasis group. Inactivated hMLH1 occurred more frequently in aged group, differentiated group, intestinal type and expanding growth type group. MSI was found more frequently in aged group, intestinal type and expanding growth type group. All three genetic markers had no significant associations with the 5-year survival. CONCLUSION: We identified significant relationships between mutated p53, inactivated hMLH1, and MSI with some clinicopathologic features of gastric cancer. However, there were no apparent relationships between p53, hMLH1, and MSI and prognosis.
Aged ; DNA Mismatch Repair ; Gastrectomy ; Genes, Tumor Suppressor ; Genetic Markers ; Humans ; Immunohistochemistry ; Korea ; Lymph Nodes ; Microsatellite Instability ; Microsatellite Repeats ; Neoplasm Metastasis ; Polymerase Chain Reaction ; Prognosis ; Stomach Neoplasms ; Succinimides

Post-transplantation diabetes mellitus (PTDM) is reversible in a considerable number of patients. We examined the prevalence and predictive factors of transient PTDM following liver transplantation. Forty-two of 74 PTDM patients showed the clinical features of transient PTDM. Compared with the persistent PTDM patients, they were characterized by younger age at the time of transplantation (49+/-7 vs. 53+/-8 yr, P<0.05), longer time before the development of PTDM (44+/-59 vs. 13+/-20 days, P<0.05), lower rate of hepatitis c virus seropositivity (0.0 vs. 9.4%, P<0.05), and use of mycophenolate mofetil (59.5 vs. 28.1%, P<0.05). Among these risk factors, age at the time of transplantation is the single independent predictive factor associated with the reversibility of PTDM.
Adult ; Age Factors ; Diabetes Mellitus/diagnosis/*epidemiology ; Female ; Hepacivirus/isolation & purification ; Humans ; *Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Mycophenolic Acid/analogs & derivatives/metabolism ; Predictive Value of Tests ; Prevalence ; Risk Factors