Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Background and Objectives: The therapeutic strategy for inflammation and degenerative calcification is of utmost importance for bioprosthetic heart valve (BHV) implanted patients.The purpose of this study was to compare the anti-inflammatory and anti-calcification effects of Entelon150® (grape seed extract), losartan, and rosuvastatin, in a rabbit model of intravascular BHV leaflet implantation in bovine pericardium. Methods: A total of 28 rabbits were implanted with BHV leaflet in the external jugular veins.The Entelon150® group was administered 7.7 mg/kg Entelon150® twice daily for 6 weeks after surgery. The losartan and rosuvastatin groups received 5.14 mg/kg and 1 mg/kg, respectively, once per day. The control group received 1 ml of saline once daily. And then, calcium concentration was measured in the implanted BHV, and histological and molecular analyses were performed on the surrounding tissues. Results: The calcium content of the implanted tissue in the Entelon150® group (0.013±0.004 mg/g) was lower than that in the control group (0.066±0.039 mg/g) (p=0.008). The losartan (0.024±0.016 mg/g, p=0.032) and rosuvastatin (0.022±0.011 mg/g, p=0.032) groups had lower calcium content than the control group, and higher tendency than the Entelon150® group. Immunohistochemistry revealed that the expressions of bone morphogenic protein 2 (BMP2), S-100, and angiotensin II type 1 receptor in the Entelon150® group showed lower tendency than those in the control group. The protein expression levels of BMP2 were reduced in the Entelon150® group compared with those in the control group. Conclusions Entelon150® exhibited a significant effect, similar to other drugs, in reducing calcification and inflammation in the intravascular bovine pericardium.

Purpose: Congenital heart disease (CHD) is a known risk factor for acquired cardiovascular and cerebrovascular diseases. However, available evidence on CHD is limited mostly to Western populations. This study aimed to evaluate the prevalence of vascular events and all-cause mortality in Korean patients with CHD and to further corroborate CHD as a predictor of vascular events and all-cause mortality. Materials and Methods: The claims data of the Korean National Health Insurance Service (NHIS) were retrospectively reviewed. Information regarding diagnostic codes, comorbidities, medical services, income level, and residential area was also collected. Outcomes of interest included stroke, myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular events (MACE). Results: We included 232203 patients with CHD and 3024633 individuals without CHD as a control group through age- and sexmatched 1:10 random sampling. The prevalences of hypertension, congestive heart failure, ischemic heart disease, hyperlipidemia, and atrial fibrillation were significantly higher in the CHD group, which had a more than two-fold higher incidence of vascular events and all-cause mortality, than in the group without CHD. Multivariable models demonstrated that CHD was a significant risk factor for stroke, MI, all-cause mortality, and MACE. Conclusion In conclusion, this nationwide study demonstrates that Korean patients with CHD have a high incidence of comorbidities, vascular events, and mortality. CHD has been established as an important predictor of cardiovascular events. Further studies are warranted to identify high-risk patients with CHD and related factors to prevent vascular events.

The purpose of this study was to evaluate treatment patterns, outcome and prognosticators for patients with leptomeningeal metastases from solid tumor. Medical records of 80 patients from January 1, 2004 to May 31, 2011 were retrospectively reviewed. Most frequent site of origin was the lung (59%) followed by the breast (25%). Most patients were treated with intrathecal chemotherapy (90%) and/or whole brain radiotherapy (67.5%). Systemic therapy was offered to 27 patients (33.8%). Percentage of patients treated with single, dual, and triple modality were 32.5%, 43.8%, and 23.8%, respectively. Median survival was 2.7 months and 1 yr survival rate was 11.3%. Multivariate analysis showed that negative cerebrospinal fluid cytology, fewer chemotherapy regimen prior to leptomeningeal metastases, whole brain radiotherapy, systemic therapy, and combined modality treatment (median survival; single 1.4 vs. dual 2.8 vs. triple 8.3 months, P<0.001) had statistical significance on survival. Subgroup analysis of non-small cell lung cancer (NSCLC) patients showed that targeted therapy had significant independent impact on survival (median survival; 10.5 vs. 3.0 months, P=0.008). Unlike previous reports, survival of patients with NSCLC primary was comparable to breast primary. Furthermore, combined modality treatment for all patients and additionally targeted therapy for NSCLC patients should be considered in the treatment of leptomeningeal metastases from solid tumor.
Adult ; Aged ; Chemoradiotherapy/methods/*mortality/*statistics & numerical data ; Disease-Free Survival ; Female ; Humans ; Male ; Meningeal Neoplasms/mortality/*secondary/*therapy ; Middle Aged ; Neoplasm Recurrence, Local/*mortality/*prevention & control ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Survival Rate ; Treatment Outcome

PURPOSE: The purpose of this study was to evaluate the clinical and radiological outcomes after total hip arthroplasty using the S-ROM modular system for osteonecrosis of the femoral head, and to compare the results between the groups using metal-on-metal articulation and ceramic-on-ceramic articulation. MATERIALS AND METHODS: Sixty-six patients (78 hips) with osteonecrosis of the femoral head were evaluated after primary total hip arthroplasty between January 2001 and December 2004, using an S-ROM proximal modular femoral stem. The average follow-up was 77 months (range, 60 to 122 months) and all patients were followed for more than five years. RESULTS: The average Harris hip score improved from 53 points to 88.5 points at the final follow-up. At the latest radiologic evaluation, sixty-seven stems had bony ingrowth stability, and 10 stems had stable fibrous ingrowth. However, one stem had diffuse extensive osteolysis and loosening, which was revised at 9 years. Postoperative complications included 4 cases of heterotrophic ossificiation, 1 case of linear fracture after insertion of the femoral stem, 1 case of dislocation, 2 cases of infection, and 1 case of extensive osteolysis and loosening. There were 3 cases of revision and Kaplan-Meier survivorship analysis with revision estimated at a 95.7% chance of survival for the femoral component during 122 months. CONCLUSION: Our study showed that total hip arthroplasty using the S-ROM modular system with metal-on-metal articulation or ceramic-on-ceramic articulation had favorable clinical and radiological mid- to long-term results.
Arthroplasty ; Dislocations ; Follow-Up Studies ; Head ; Hip ; Humans ; Osteolysis ; Osteonecrosis ; Postoperative Complications ; Survival Rate

The purpose of our study was to determine the most accurate analytic method to define in vitro chemosensitivity, using clinical response as reference standard in prospective clinical trial, and to assess accuracy of adenosine triphosphate-based chemotherapy response assay (ATP-CRA). Forty-eight patients with chemo-naive, histologically confirmed, locally advanced or metastatic gastric cancer were enrolled for the study and were treated with combination chemotherapy of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 for maximum of six cycles after obtaining specimen for ATP-CRA. We performed the receiver operator characteristic curve analysis using patient responses by WHO criteria and ATP-CRA results to define the method with the highest accuracy. Median progression free survival was 4.2 months (95% confidence interval [CI]: 3.4-5.0) and median overall survival was 11.8 months (95% CI: 9.7-13.8) for all enrolled patients. Chemosensitivity index method yielded highest accuracy of 77.8% by ROC curve analysis, and the specificity, sensitivity, positive and negative predictive values were 95.7%, 46.2%, 85.7%, and 75.9%. In vitro chemosensitive group showed higher response rate (85.7% vs. 24.1%) (P=0.005) compared to chemoresistant group. ATP-CRA could predict clinical response to paclitaxel and cisplatin chemotherapy with high accuracy in advanced gastric cancer patients. Our study supports the use of ATP-CRA in further validation studies.
Adenosine Triphosphate/*analysis ; Adult ; Aged ; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Cisplatin/administration & dosage ; Drug Screening Assays, Antitumor/*methods ; Female ; Humans ; Korea ; Male ; Middle Aged ; Outcome Assessment (Health Care)/methods ; Paclitaxel/administration & dosage ; Reproducibility of Results ; Sensitivity and Specificity ; Stomach Neoplasms/*diagnosis/*drug therapy/metabolism ; Treatment Outcome

OBJECTIVE: The objective of this study is to evaluate the safety and the clinical efficacy of the laparoscopic myomectomy through analyzing several operation factors. METHODS: There were 185 cases of laparoscopic myomectomy between January 2004 and December 2008 at the department of obstetrics and gynecology in Hanyang University Guri Hospital. Retrospectively many factors of the operation were analyzed. The factors include the size, number and type of the myoma, BMI (body mass index), operation method, operation time, and complication and the prognosis of the operation. RESULTS: For the type of myomas, 115 (62.2%) cases were intramural myomas, 38 (20.5%) cases were subserosal types and 32 (17.3%) cases were mixed types. The average diameter of the biggest myoma was 6.67+/-0.16 cm (range, 2.5~15 cm) and the average number of the myoma was 2.07+/-0.15 (range, 1~15). Previous operation history and pelvic adhesion did not show correlation with the operation time. The size, type and number of myoma and the operation methods showed correlation with the operation time. According to myoma size and number, we divided the cases into two groups, low risk group (122 cases) and high risk group (63 cases). The analysis showed that post-operation hemoglobin drop (2.89+/-0.10 g/dL vs. 4.03+/-0.23 g/dL) and blood transfusion amount (2.89+/-0.10 pints vs. 4.03+/-0.23 pints) as well as the operation time (137.58+/-4.37 min vs. 193.73+/-9.88 min) showed noticeable increase in the high risk group. CONCLUSION: This statistics show that laparoscopic myomectomy is now being applied to patients with larger and more myomas. Factors affecting operation time were the weight of myomas, number of myomas, type of myomas, number of trocars and methods of resected myomas removal. Also, operation time and post-operative hemoglobin drop increased in the high risk group.
Blood Transfusion ; Gynecology ; Hemoglobins ; Humans ; Laparoscopy ; Myoma ; Obstetrics ; Prognosis ; Retrospective Studies ; Surgical Instruments

The diagnosis of the pelvic actinomycosis is seldom made preoperatively because of no reliable or specific clinical manifestation which has tendency to mimic advanced gynecological malignancy and the relative infrequency of the disease. To explore the method for improvement of preoperative diagnosis and possibility of avoiding the surgical management of pelvic actinomycosis, we collected and summarized the data of age, parity, state of menopause, history of intrauterine device (IUD) use, symptoms, laboratory findings, radiologic findings, provisional diagnosis and treatment from 14 cases diagnosed pathologically and treated in Hanyang University Hospital from 2000 to 2007. Eleven (78.6%) of 14 cases were IUD users. Most common complaints were lower abdominal pain (71.4%) and vaginal discharge (57.1%) which were followed by fever (28.6%) and back pain (28.6%). Four cases (28.6%) were identified as pelvic actinomycosis before operation and in 3 cases (21.4%) malignancy was provisional preoperative diagnosis. Pelvic actinomycosis was suspected via abdominal computed tomography (CT) or cervicovaginal cytology and confirmed via endometrial biopsy or fine needle aspiration biopsy. Two cases that were diagnosed before operation and received only antibiotics therapy had no recurrence. It was suggested that pelvic actinomycosis could be suspected via abdominal CT and cervicovaginal cytology in IUD users, and endometrial biopsy and fine needle aspiration biopsy may help establish the diagnosis before the operation. Adequate preoperative antibiotics therapy could make extensive exploratory surgery avoided or conservative surgery feasible.
Abdominal Pain ; Actinomycosis ; Anti-Bacterial Agents ; Back Pain ; Biopsy ; Biopsy, Fine-Needle ; Female ; Fever ; Hydrazines ; Intrauterine Devices ; Menopause ; Parity ; Recurrence ; Vaginal Discharge

BACKGROUND/AIMS: The aims of this study were to estimate the frequency of symptoms of gastroesophageal reflux disease and reflux esophagitis, to evaluate the difference in characteristics among groups subdivided by symptoms, and to compare clinical features between a reflux esophagitis group and a non reflux esophagitis group in Chuncheon City. METHODS: A total of 1,011 persons who underwent endoscopy for health check up were enrolled between July 1, 2005, and June 30, 2006. All persons were given a validated, self reported questionnaire, which inquired about the presence, frequency, and severity of typical symptoms (heartburn and acid regurgitation) and atypical symptoms. The questionnaire also inquired about smoking, alcohol intake, and Helicobacter pyroli eradication. The subjects were subdivided into typical symptomatic, atypical symptomatic, no discomfort, and asymptomatic groups. RESULTS: The prevalence of heartburn and acid regurgitation occurring at least weekly was 7.5%. Reflux esophagitis, hiatal hernia, smoking, and alcohol intake were more common in males (p<0.05). Ninety eight cases (9.7%) were endoscopically diagnosed as reflux esophagitis, and sixty nine cases (6.8%) were endoscopically suspected esophageal metaplasia (ESEM). Subjects in the symptomatic group more frequently manifested reflux esophagitis than subjects in the asymptomatic group (p<0.05). CONCLUSIONS: The presence of reflux induced symptoms is related to reflux esophagitis, but the intensity and frequency of symptoms are poor predictors of the presence or severity of endoscopic mucosal breaks.
Barrett Esophagus ; Endoscopy ; Esophagitis ; Esophagitis, Peptic ; Gastroesophageal Reflux ; Heartburn ; Helicobacter ; Hernia, Hiatal ; Humans ; Male ; Metaplasia ; Prevalence ; Self Report ; Smoke ; Smoking ; Surveys and Questionnaires

Transient left ventricular apical ballooning syndrome is also known as takotsubo cardiomyopathy, and this is characterized by transient wall-motion abnormalities involving the left ventricular apex without significant stenosis on the coronary angiogram. We report here on a new variant of transient left ventricular ballooning in which only the mid-ventricle was affected. The patient initially presented with dyspnea and she had wall-motion abnormalities involving the mid-ventricle with hypercontractility of the apical and basal segments in the absence of a significant coronary artery stenosis. Emotional or physical stress or other preceding triggering factors might play a key role in this cardiomyopathy, but the precise etiology remains unknown. So far, the cases of this syndrome have been reported only among the North America Caucasian population and the Japanese population.
Asian Continental Ancestry Group ; Cardiomyopathies ; Constriction, Pathologic ; Coronary Stenosis ; Dyspnea ; Humans ; North America ; Takotsubo Cardiomyopathy