Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. @*Materials and Methods@#To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. @*Results@#Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. @*Conclusion@#We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

Survival Benefit of Perioperative Chemotherapy in Patients with Locally Advanced Gastric Cancer: a Propensity Score Matched Analysis

PURPOSE: It has been reported that the survival of patients with locally advanced gastric cancer (LAGC) is better in East Asia countries than in developed western countries; however, the prognosis of LAGC remains poor. This study aimed to evaluate the effects of perioperative chemotherapy on the long-term survival of East Asia patients with LAGC. MATERIALS AND METHODS: From October 2006 through August 2008, 43 patients with LAGC received perioperative S-1 combined with weekly docetaxel in a phase II study (neoadjuvant group). These patients were matched using propensity scores to patients who underwent surgery without neoadjuvant chemotherapy during the same period (surgery group). The surgical outcomes and long-term survivals were compared between the 2 groups. RESULTS: After matching, 43 and 86 patients were included in the neoadjuvant and surgery groups, respectively, and there was no significant difference in their baseline characteristics. Although the operating time was longer in the neoadjuvant group, there was no significant difference in postoperative complications between the 2 groups. The neoadjuvant group had a significantly higher 5-year overall survival (OS) rate (73.3% vs. 51.1%, P=0.005) and a trend towards higher 5-year progression-free survival (PFS) (62.8% vs. 49.9%, P=0.145). In the multivariate analysis, perioperative chemotherapy was an independent factor for OS, with a hazard ratio of 0.4 (P=0.005) and a marginal effect on the PFS (P=0.054). CONCLUSIONS: Perioperative chemotherapy was associated with better long-term survival without increasing postoperative complications in the setting of D2 surgery for patients with LAGC, suggesting that perioperative chemotherapy can be a therapeutic option in East Asia countries.

Anterior Anorectocolonic Tubular Duplication Presenting as Rectovestibular Fistula in an Infant / 소아외과

Anorectal duplications account for only 5% of gastrointestinal duplications, and cases with involvement of the anal canal are much rarer. Nearly all anorectal duplications are posterior to the rectum; duplications located anterior to the normal rectum are highly unusual, and only a few cases have been reported. We report the case of an anterior anorectocolonic duplication presenting as a rectovaginal fistula in a 2-month-old infant. After diagnosis, the duplication was excised completely without further intestinal complications.

Association of the Extent of Atrophic Gastritis With Specific Dyspeptic Symptoms

BACKGROUND/AIMS: It remains unclear whether atrophic gastritis can affect dyspeptic symptoms. We aimed to investigate whether the extent of atrophic gastritis is associated with specific dyspeptic symptoms. METHODS: Consecutive adults in a routine health-checkup program were enrolled in the study. The extent of atrophic gastritis was classified into 3 groups based on the Kimura-Takemoto criteria; the gastritis with no or little atrophy (group A: C0), the gastritis with atrophy mainly in the antrum (group B: C1 and C2), and the gastritis with atrophy in the large area of the corpus (group C: C3 and O). Upper gastrointestinal symptoms were categorized into "typical reflux symptoms," "epigastric pain syndrome (EPS)-related symptoms," and "postprandial distress syndrome (PDS)-related symptoms." RESULTS: A total of 1827 patients (1009 males, mean age 45.1 years) were included in the analysis. The subgroups of atrophic gastritis were as follows: group A (n = 1218, 66.7%), group B (n = 392, 21.4%), and group C (n = 217, 11.9%). Typical reflux, EPS-related, and PDS-related symptoms were present in 10.5%, 19.8%, and 16.2% of the subjects, respectively. PDS-related and EPS-related symptoms were significantly more prevalent in the group C of male patients and the group B of female patients, respectively, compared with other groups. PDS-related and EPS-related symptoms were independently associated with the group C in males (OR, 2.123; 95% CI, 1.090-4.136) and the group B in females (OR, 2.571; 95% CI, 1.319-5.025), respectively. CONCLUSIONS: The extent of atrophic gastritis appears to affect the generation of specific dyspeptic symptoms in a gender-dependent manner.

Lessons from the Initial Experience of Laparoscopic Liver Resection

PURPOSE: This study was conducted to evaluate the initial experience of 24 cases of laparoscopic liver resection by a single surgeon to determine its feasibility and report perioperative complications associated with this technique. METHODS: A retrospective analysis of data from 24 patients who received attempted laparoscopic liver resections for primary liver tumors from November 2008 to April 2012 was conducted. Sixteen benign and eight primary malignant lesions were included. The patient's electronic medical records including age, gender, underlying disease, past medical history, type of operations, operative time, complications, conversion rates, and length of hospital stay were reviewed. RESULTS: The mean age of the patients was 52.6 years and the mean operation time was 263.7 minutes. The overall morbidity was 12.5% and the mortality was zero. One case was converted to open surgery (4.2%), while intraoperative transfusion was conducted in four cases. The types of operations included left hepatectomy (n=12, 50%; 3 with CBD exploration), left lateral sectionecectomy (n=4, 16.7%; 1 with cholecystectomy), partial hepatectomy for benign tumor (n=3, 12.5%: 1 with cholecystectomy), right hepatectomy (n=1, 4.1%), S6 segmentectomy (n=1, 4.1%), and tumorectomy (n=3, 12.5%). The mean estimated blood loss during operation was 375.3 cc and the postoperative hospital stay was 7.7 days. Additionally, one intraoperative complication and two postoperative complications occurred (12.5%). There was no postoperative mortality. CONCLUSION: The results of this study indicate that laparoscopic surgery with HBP training is suitable for laparoscopic liver resection. However, to ensure safety of the liver resection and the advantages of laparoscopic surgery, a thorough understanding of hepatic anatomy and elaborate surgical planning is essential.

Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

BACKGROUND/AIMS: Adipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH). The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP), and retinol-binding protein-4 (RBP-4) in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH. METHODS: Polymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps. RESULTS: Patients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively). Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05). CONCLUSIONS: NASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

The Examination of the Acute Vascular Changes Due to Smoking Using Second Derivative of Photoplethysmogram / 가정의학회지

BACKGROUND: Although smoking is the major risk factor for atherosclerosis under the age of 40, the smoking rate of adolescent and young adult has been is increasing. In case of young adults, there is no available clinical indices reflecting harmful effects of smoking. The aim of this study was to investigate whether any second derivative of photoplethysmogram (SDPTG) index can be used as a clinical index of acute effects of smoking. METHODS: Twenty smoking and eighteen never-smoking males ages between 20-39 without medical history of atherosclerotic disease nor peripheral vascular diseases were selected for this study. We investigated the life styles and risk factors of atherosclerosis through a questionnaire, laboratory test and physical examination. We measured SDPTG at baseline, 3, 5, 10, 15, and 20 minutes for smokers after smoking and walking and for never-smokers after walking. Repeated measures ANOVA and ANCOVA were used for analysing the changes of SDPTG according to time. RESULTS: The heart rate and blood vessel tension (BVT) were different between the smokers and never-smokers after adjusting age, fasting blood sugar, body mass index, depression, and exercise (P < 0.05, P < 0.05, respectively). In contrast to never-smokers, heart rate of smokers at 3 minutes after smoking was increased for 10.1 per minute (P < 0.001) and higher than never-smokers until 15 minutes (P < 0.05). BVT in smokers was decreased at 3 minutes (P < 0.05) from baseline and lower than never-smokers at 3 minutes (P < 0.05). Differential pulse wave index, stress power, remained blood volume, and the changes of these indices according to time were not significantly different between the two groups. CONCLUSION: BVT and heart rate reflected the acute effect of smoking on blood vessels and could be used to provide motivation to quit smoking and make people more concerned about their own health especially to the young smokers who has no symptoms yet.

A case of myocardial infarction during pregnancy / 대한산부인과학회지

Recently, the incidence of hypertension (HT) and coronary artery disease is increasing because of the change of diet and life pattern. But, coronary artery disease is relatively uncommon in young women of pregnant age. The trend towards delayed marriage and child-bearing may results in an increasing number of women with coronary heart disease. Myocardial infarction complicates approximately 1 in 20,000 pregnancies. Myocardial infarction in pregnancy carries substantial maternal and fetal risks. Overall maternal mortality rate is 21% to 35% and the fetal mortality rate is 13%. Importantly, the maternal mortality rate approaches 50% when women deliver within 2 weeks of the initial MI event. We experienced a case of pregnancy with acute myocardial infarction (AMI) and chronic HT. The patient had a myocardial attack at gestational age 36(+5) weeks and medical treatment was administered. Labor inuction was begun at gestational age 39+3 weeks and the patient delivered by spontaneous vaginal delivery. We report this case with a brief review of the concerned literatures.

A Case of Ectopic Pregnancy in a Previous Cesarean Scar / 대한산부인과학회지

Implantation of a pregnancy within the scar of a previous cesarean delivery is a very rare form of ectopic pregnancy. However, this type of ectopic pregnancy is considered to be a life-threatening condition because of the very high risk of uterine rupture and uncontrollable hemorrhage. Unfortunately, optimal treatment have not been established. We present here a case of ectopic pregnancy in the previous cesarean scar treated with combined systemic and local intra-amniotic methotrexate successfully.

A Case of Early Fetal Testicular Regression Syndrome / 대한산부인과학회지

A 29-year-old phenotypic female with 46,XY genotype presented with primary amenorrhea, no breast development, no axillary hair, no pubic hair, and clitomegaly. The vagina was blind pouch. The vagina and urethra shared same outlet. Plasma follicle-stimulating hormone (FSH) was in the normal range for female subject. Plasma luteinizing-hormone (LH) and testosterone were elevated. Plasma estradiol (E2) level was markedly low. At laparoscopy, no uterus, only vestigial remnants of fallopian tube was seen and very small streak gonad was found. According to the pathologic report, they were remnant of Mullerian duct and salpinx ("right adnexa") and streak gonad with vas deference ("left adnexa"). On the basis of the clinical, genotypic, and endocrine feature, the patient was diagnosed as testicular regression syndrome. We present it with brief review of literature.

Excitatory Effects of 5-Hydroxytryptamine on the Resting Activity of Medial Vestibular Nuclear Neurons in the Rat / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study was aimed to investigate the effects of 5-Hydroxytryptamine (5-HT) on the spontaneous activity of medial vestibular nuclear neurons of the rat. MATERIALS AND METHOD: Sprague-Dawley rats aged 14 to 16 days were anesthetized with ether and decapitated. After enzymatic digestion, the brainstem portion of medial vestibular nuclear neuron was obtained by micropunching. The dissociated neurons were transferred into a recording chamber mounted on an inverted microscope and spontaneous action potentials were recorded by standard patch-clamp techniques. RESULTS: The response of medial vestibular nuclear neurons to 5-HT applied in the recording chamber was not uniform. The spontaneous action potentials were increased in 10 cells, decreased in 3 cells and not altered in 2 of 15 cells. The spike width of the neurons was not affected by 5-HT. The spike frequency and resting membrane potential of these cells were increased by 5-HT. The depth of afterhyperpolarization was decreased by 5-HT. CONCLUSION: These results suggest 5-HT increases spontaneous firing of the medial vestibular nuclear neurons by altering the afterhyperpolarization.