Background/aims: The appropriate number of band ligations during the first endoscopic session for acute variceal bleeding is debatable. We aimed to compare the technical aspects of endoscopic variceal ligation (EVL) in patients with variceal bleeding according to the number of bands placed per session. Methods: We retrospectively reviewed multicenter data from patients who underwent EVL for acute variceal bleeding. Patients were classified into minimal EVL (targeting only the foci with active bleeding or stigmata of recent bleeding) and maximal EVL (targeting potential bleeding sources in addition to the aforementioned targets) groups. The primary endpoint was 5-day treatment failure. The secondary endpoints were 30-day rebleeding, 30-day mortality, and intraprocedural adverse events. Results: Minimal EVL was associated with lower rates of hypoxia and shock during EVL than maximal EVL (hypoxia, 0.9% vs 2.9%; shock, 1.3% vs 3.4%). However, treatment failure was higher in the minimal EVL group than in the maximal EVL group (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.41). Age ≥60 years, Model for End-Stage Liver Disease score ≥15, Child-Turcotte-Pugh classification C, presence of hepatocellular carcinoma, and systolic blood pressure <90 mm Hg at initial presentation were also associated with treatment failure. In contrast, 30-day rebleeding and 30-day mortality did not differ between the minimal and maximal EVL groups. Conclusions Given that minimal EVL was associated with a high risk of treatment failure, maximal EVL may be a better option for variceal bleeding. However, the minimal EVL strategy should be considered in select patients because it does not affect 30-day rebleeding and mortality.

PURPOSE: p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets. MATERIALS AND METHODS: Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA. RESULTS: Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine. CONCLUSION: PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer.
Cell Line* ; Cell Proliferation ; Cell Survival ; Equilibrative Nucleoside Transporter 1 ; Humans ; p21-Activated Kinases ; Pancreatic Neoplasms* ; Phosphotransferases* ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; RNA, Small Interfering ; Up-Regulation

PURPOSE: The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. MATERIALS AND METHODS: Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m2, and the dose of HM30181A was escalated from 30-210 mg/m2. RESULTS: A total of twenty-four patients were enrolled. Only one patient experienced a dose-limiting toxicity-a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m2 of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m2 and the area under the curve of plasma concentration-time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m2. The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m2. The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m2. Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. CONCLUSION: The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m2.
Absorption ; Humans ; Maximum Tolerated Dose ; Neutropenia ; P-Glycoprotein* ; Paclitaxel* ; Pharmacokinetics ; Plasma

We report a case of Caplan's Syndrome, which presented as multiple pulmonary nodules. A 58-year-old male was admitted to hospital due to multiple pulmonary nodules. In addition, the patient presented with multiple arthritis, and dyspnea on exertion. Rheumatoid arthritis had been diagnosed 35 years ago. The patient had worked as a stonemason for 20 years. Computed Tomography (CT) revealed numerous well-defined tiny nodules scattered in both lungs, which was suspicious of miliary tuberculosis or malignancy. The patient was started on antituberculous medications and referred to our hospital. First, a transbronchial lung biopsy was performed, which showed no evidence of granuloma. It was our opinion that the biopsy was insufficient, and a follow-up video-associated thoracoscopy was performed. The pathological report determined necrotizing granulomatous inflammation and silicosis on background. According to imaging studies, pathologic reports, and clinical symptoms, we concluded that the patient had Caplan's syndrome. We controlled his rheumatic medications, and instructed him to avoid exposure to hazardous dust.
Arthritis ; Arthritis, Rheumatoid ; Biopsy ; Caplan Syndrome ; Dust ; Dyspnea ; Follow-Up Studies ; Granuloma ; Humans ; Inflammation ; Lung ; Male ; Middle Aged ; Multiple Pulmonary Nodules ; Silicosis ; Thoracoscopy ; Tuberculosis, Miliary

BACKGROUND: Hydroxyethyl starch (HES) effectively restores plasma volume and thereby enhances microcirculation and tissue oxygenation at the expense of coagulation impairment. These effects are related to molecular weight, substitution and C2:C6 ratio. But, most of the studies regarding coagulation impairment in cardiac surgeries were performed in patients undergoing cardiopulmonary bypass which significantly causes coagulation derangements. Therefore, we have evaluated the effects of 2 different HES solutions on tissue oxygenation and postoperative bleeding in patients undergoing off-pump coronary artery bypass surgery (OPCAB). METHODS: Forty four patients were prospectively enrolled. After the induction of anesthesia, either HES 130/0.4 (V group) or 200/0.5 (H group) were infused for fluid therapy to maintain predetermined urine output, cardiac index and filling pressure up to 16 h after the surgery. Tissue oxygenation profiles and respiratory parameters were recorded after induction of anesthesia, completion of distal anastomosis and sternum closure, upon admission at intensive care unit, and 4 h thereafter. The amounts of chest tube drainage, transfusion and fluid balance were measured up to 16 h after the surgery. RESULTS: Patients' demographic data were similar between the groups. Tissue oxygenation profiles, respiratory parameters, hemodynamics, and time to extubate were not different between the groups. However, chest tube drainage and transfusion requirements were significantly less in the V group. CONCLUSIONS: In OPCAB, 6% HES 130/0.4 causes less postoperative bleeding and transfusion requirement and has a comparable efficacy on hemodynamic stability, pulmonary function and tissue oxygenation when compared to 6% HES 200/0.5.
Anesthesia ; Cardiac Output ; Cardiopulmonary Bypass ; Chest Tubes ; Coronary Artery Bypass, Off-Pump* ; Drainage ; Fluid Therapy ; Hemodynamics ; Hemorrhage* ; Humans ; Intensive Care Units ; Microcirculation ; Molecular Weight ; Oxygen* ; Plasma Volume ; Prospective Studies ; Starch* ; Sternum ; Water-Electrolyte Balance

Purpose: This multiinstitutional study was to investigate the accuracy of the Kattan nomograms for the prediction of recurrence after definitive surgery for renal cell carcinoma (RCC) in Korean patients and develop a nomogram revised to complement the shortcomings. Materials and Methods: Clinical and pathological data of 1,866 patients with RCC who had been followed for at least 2 years after surgery in each participating institutes were reviewed as well as evidence of disease recurrence, defined to include local recurrence and distant metastasis. Accuracy of the Kattan nomograms' predictability in tumors 7cm or less was tested by calculating the area under the receiver-operating characteristics curve (AUC) and actuarial recurrence-free survival by Kaplan- Meier method. We used the Cox proportional hazard analysis to identify significant variables and develop prediction nomogram, and internally validated by bootstrapping method. Mean follow-up was 56.5 months (24-184). Results: Recurrence occurred in 12.5% of the patients and correlated with the pathological stage, with 4.3%, 7.9%, 15.0%, 22.6%, 38.4%, 58.3% for stages T1a, T1b, T2, T3a, T3b/c and T4, respectively (p<0.001). The AUC of the Kattan nomograms was 0.276. Factors significantly predictive of recurrence were T stage (p<0.0001), presentation (p=0.006), preoperative hemoglobin (p=0.023) and gender (p=0.032). Actuarial 60-month recurrence- free survival was 87.9% and using the prognostic factors, nomogram predicting 60-month recurrence-free survival was constructed. Conclusions: Korean nomogram complementing the preexisting nomograms for the prediction of recurrence-free survival after definitive surgery for RCC has been constructed, which may be useful in patient prognostication, counseling and follow-up planning.
Academies and Institutes ; Area Under Curve ; Carcinoma, Renal Cell* ; Complement System Proteins ; Counseling ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; Neoplasm Metastasis ; Nomograms* ; Recurrence

BACKGROUND: This prospective phase II study assessed the efficacy and toxicity of the combination of carboplatin, ifosfamide and etoposide for previously untreated patients with extensive-disease small cell lung cancer (ED-SCLC). METHODS: Patients with ED-SCLC received a combination chemotherapy with carboplatin AUC 6.0 on day 1, ifosfamide 1200 mg/m2 on day 1-3, and etoposide 100 mg/m2 on day 1-3. RESULTS: Forty-one patients received a median of six cycles of chemotherapy. A complete response was seen in 5 patients and a partial response was seen in 33 patients (overall response 95%). The median duration of the response was 5.1 months (95% CI; 3.4-6.8 months). The median time to progression and overall survival were 7.4 months (95% CI; 6.1-8.6 months) and 10.7 months (95% CI; 6.9-14.6 months), respectively, providing the one-year survival rate of 43.9%. Grade 3~4 anemia, neutropenia and thrombocytopenia occurred in 14%, 7% and 6% in a total of 212 cycles, respectively. Non-hematologic toxicities were generally mild and manageable. No treatment related death was observed. CONCLUSIONS: The combination chemotherapy of carboplatin, etoposide and ifosfamide showed an effective response rate and acceptable toxicity.
Anemia ; Area Under Curve ; Carboplatin* ; Drug Therapy* ; Drug Therapy, Combination ; Etoposide* ; Humans ; Ifosfamide* ; Neutropenia ; Prospective Studies ; Small Cell Lung Carcinoma* ; Survival Rate ; Thrombocytopenia

BACKGROUND: Small cell lung cancer (SCLC) is very sensitive to both chemotherapy and radiation therapy. In limited disease of SCLC, the addition of radiation therapy to chemotherapy improves survival and decrease local relapse over chemotherapy alone. This study evaluated the response rate, duration of response, overall survival and toxicity for the combination of etoposide, ifosfamide, carboplatin given concurrently with thoracic irradiation in limited SCLC. METHODS: Twenty eight patients with histologically proven SCLC who have a measurable disease and previously untreated, were enrolled in this study. Each cycle consisted of VP-16 100 mg/m2 IV days 1~3, ifosfamide 1,200 mg/m2 IV days 1~3 with mesna, carboplatin AUC 6 IV day 1. Cycles were repeated every 21days. Patients received a total of median 6,000 cGy thoracic radiation therapy (180~200 cGy/day) starting on the first day of chemotherapy. Prophylactic cranial irradiation was given to complete remission after chemoradiotherapy. RESULTS: The overall response rate in 27 evaluable patients was 93% (41% of complete response, 52% of partial response). The median time to progression was 10.3 months. The median disease free survival was 18.4 months in patients with complete response. The median overall survival was 16.7 months in all evaluable patients. Hematologic toxicities (> or = Grade3) of 129 cycles of chemotherapy were leukopenia in 38% and fever with infection in 26%. Nonhematologic toxicities (> or = Grade2) of evaluable 27 patients included alopecia in 11%, post-irradiation esophagitis in 44% and pneumonitis in 11%. CONCLUSIONS: VIC combination chemotherapy with concurrent thoracic irradiation is effective in limited SCLC. It's maior toxicity is myelosuppression.
Alopecia ; Area Under Curve ; Carboplatin* ; Chemoradiotherapy ; Cranial Irradiation ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination* ; Esophagitis ; Etoposide* ; Fever ; Humans ; Ifosfamide* ; Leukopenia ; Mesna ; Pneumonia ; Recurrence ; Small Cell Lung Carcinoma*

PURPOSE: evaluate the effectiveness of minimally invasive plate osteosynthesis (MIPO) in unstable fractures of the distal tibia. MATERIALS AND METHODS: From March 2001 to December 2003, 21 cases with unstable fractures of the distal tibia were treated with MIPO technique and followed for at least one year. Eighteen cases were extra-articular and three cases were intra-articular fractures. According to AO classification, six cases were 42-A, four 42-B, one 42-C, seven 43-A, and three 43-C. There was only one case of Gustilo-Anderson type II open fracture. We reviewed the results of fracture healing, axial and rotational deformity, ankle motion, and complications RESULTS: All fractures were healed in an average of 16.1 weeks (range, 11 to 24 weeks). There was only one case of 7-degree posterior angular deformity, but no cases of rotational malalignment. Recovery of ankle motion was satisfactory in all patients within 5-degree loss of motion. Subcutaneous abscess was developed in one case after fracture healing and cured by a drainage with implant removal. CONCLUSION: Although MIPO technique is technically more demanding than the traditional open technique, MIPO technique is an effective method for unstable fractures of the distal tibia because it minimizes incidence of soft-tissue compromise and infection and provides good fracture healing.
Abscess ; Ankle ; Classification ; Congenital Abnormalities ; Drainage ; Fracture Healing ; Fractures, Open ; Humans ; Incidence ; Intra-Articular Fractures ; Tibia*

Choriocarcinoma is one of the malignant tumors of trophoblastic cells characterized by the secretion of human chorionic gonadotrophin (hCG) (1-3). Cutaneous metastasis is a rare presentation of choriocarcinoma but a poor prognostic sign because it is associated only with widespread disease (3-5). A 52-yr-old female complaining of dyspnea for 2 months, presented with fingertip sized erythematous nodules on the left side of the neck and the right side of the upper back of 1 month duraton. She has suffered from Behcet's disease since 1999. Microscopic examination of a nodule of upper back demonstrated biphasic pattern of cytotrophoblasts and hCG-positive syncytiotrophoblasts, and the typical histologic features of choriocarcinoma. She was referred to the gynecological oncology department. After 17 cycles of combination chemotherapy, the serum hCG level has fallen from 700,000 to under 2.0 mIU/mL and the skin lesions have almost disappeared. However, after 3 months, total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed due to elevated serum hCG level (4,447.7 mIU/mL), and she is scheduled to receive post-operative adjuvant chemotherapy.
Choriocarcinoma/blood/*pathology ; Chorionic Gonadotropin/blood ; Female ; Humans ; Middle Aged ; Pregnancy ; Skin Neoplasms/*secondary ; Uterine Neoplasms/blood/*pathology