Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis.
Animals ; Apolipoproteins E/genetics/physiology ; Atherosclerosis/*drug therapy ; Cytokines/metabolism ; Disease Models, Animal ; Drug Synergism ; Ginkgo biloba/*chemistry ; Humans ; Macrophages/cytology/drug effects ; Male ; Mice ; Mice, Nude ; Plant Extracts/*administration & dosage/chemistry ; Reactive Oxygen Species/*metabolism ; Tetrazoles/*administration & dosage

BACKGROUND: Sleep is an essential restorative physiologic phenomenon. Impaired sleep results in significant negative effect to the health. Symptoms like sleep initiation difficulty, frequent awakening, severe snoring have related to poor sleep quality. We studied frequency and compared the characteristics of common sleep disorders at family practice. METHODS: We surveyed patients over 18 years of age and their guardians who visited 16 familial practices for 6 days. We investigated sleep characteristics, frequency of sleep disorder and associated factors by questionnaires and analyzed by frequency analysis, Spearman's correlation coefficient, multiple logistic regression. RESULTS: We enrolled 1,117 participants. Older participants were more likely to report early sleep onset and off time, short sleep duration. Mean number of awakening during a typical night is 1.69. Female complained difficulties in initiation and maintenance of sleep more than male. A total of 32.5% had these insomnia symptoms and related to hypertension, stroke, stress, arthralgia, depression, urological disorder. 31.1% had excessive daytime sleepiness, related to stress, arthralgia, depression. Loud snoring and gasp for breath showed positive correlation between male, high BMI. Disrupted sleep over 3 times was related to old age, female, diabetes, hypertension, stroke, stress, arthralgia, depression. Restless leg syndrome were high in elderly, high BMI, stress, arthralgia and depression. CONCLUSION: About one in three who visit in primary medical practice have sleep disorder symptoms like insomnia, daytime fatigue, snoring. 3% of them have gasp for breath, 8% have restless leg syndrome.
Aged ; Arthralgia ; Depression ; Family Practice ; Fatigue ; Female ; Humans ; Hypertension ; Leg ; Male ; Prevalence ; Sleep Wake Disorders ; Sleep Initiation and Maintenance Disorders ; Snoring ; Stroke

OBJECTIVE: To evaluate the efficacy of taxane and platinum-based chemotherapy guided by extreme drug resistance assay (EDRA) in patients with epithelial ovarian cancer. METHODS: Thirty-nine patients were enrolled, who were diagnosed as epithelial ovarian cancer, tubal cancer or primary peritoneal carcinoma and received both debulking surgery and EDRA in Asan Medical Center between August 2004 and August 2006. Another thirty-nine patients were enrolled, who did not receive EDRA as control. Paclitaxel 175 mg/m2 and carboplatin AUC 5 were administered as primary combination chemotherapy to both EDRA group and the control group. In the EDRA group, paclitaxel was replaced by docetaxel 75 mg/m2 if a patient showed extreme drug resistance (EDR) to paclitaxel and not to docetaxel. Carboplatin was replaced by cisplatin 75 mg/m2 if a patient showed EDR to carboplatin and not to cisplatin. If only one drug showed low drug resistance (LDR), it was allowed to add another drug which showed LDR such as gemcitabine 1,000 mg/m2. CT scan was performed every three cycles and CA-125 was checked at each cycle. RESULTS: There was no significant difference in overall response rate between EDRA group and the control group (84.5% vs. 71.8%, p=0.107). However, 93.8% of patients in EDRA group did not show EDR to at least one drug and its response rate was significantly higher than that of the control group (93.3% vs. 71.8%, p=0.023). CONCLUSION: we could choose a combination of taxane and platinum which did not show EDR and could obtain a good response in the patients with ovarian cancer.
Area Under Curve ; Biological Assay ; Bridged Compounds ; Carboplatin ; Cisplatin ; Deoxycytidine ; Drug Resistance ; Drug Therapy, Combination ; Humans ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Paclitaxel ; Platinum ; Taxoids

PURPOSE: Docetaxel (Taxotere(R)) and capecitabine are used in combination to treat advanced gastric cancer. Thymidine phosphorylase (TP) is an essential enzyme for the activation of capecitabine in tumors. This study sought to identify the best combination therapy with capecitabine and using two different schedules for docetaxel, a TP up-regulator, to enhance capecitabine's efficacy. METHODS: The human gastric cancer cell line SNU-484 was cultured and docetaxel (2 microgram/ml) was added to the 24-well plates that contained 5 x 10(5) cells/well. The total RNA was isolated and RT-PCR was done to identify the TP expression. Four- or five-week-old BALB/c-nu/nu mice were subcutaneously inoculated with the SNU-484 cells. The nude mice were divided into two groups and they were given capecitabine 539 mg/m2 p.o. from days 1 to 14: Group 1 was given docetaxel 15 mg/m2 i.v. on day 1; Group 2 was given docetaxel 7.5mg/m2 on days 1 and 8. Tumor tissues were excised on days 1, 8 and 15 to measure the TP and bcl-2 levels. RESULTS: TP was expressed 2 hours after docetaxel administration. Group 2 had a higher TP concentration in the tumor tissues and a better antitumor effect than did Group 1. There was no difference in the bcl-2 concentration in the two groups. CONCLUSION: These results suggest that docetaxel stimulates the TP expression in tumor tissues and it enhances the antitumor activity of capecitabine. A weekly docetaxel injection with capecitabine administration can be used to treat gastric cancer more effectively than when docetaxel is injected once per cycle. Capecitabine had no bcl-2 suppressive effect in this study.
Animals ; Appointments and Schedules* ; Capecitabine ; Cell Line* ; Heterografts* ; Humans ; Mice ; Mice, Nude* ; RNA ; Stomach Neoplasms* ; Thymidine Phosphorylase* ; Thymidine*

Lateral malleolar bursitis rarely progresses to septic arthritis. In our case, the 27 year old man visited due to progressive left ankle pain, despite the antibiotics treatment of lateral malleolar bursitis. 8 years ago, modified Brostrom procedure was performed owing to chronic ankle instability. Previous surgery altered anatomical structure of lateral ankle bursa, so it may cause the infection to spread to the ankle joint. We reported rare case of secondary septic arthritis caused by lateral malleolar bursitis.
Adult ; Ankle ; Ankle Joint ; Anti-Bacterial Agents ; Arthritis, Infectious* ; Bursitis* ; Humans

Percutaneous approaches, such as percutaneous ethanol injection and radiofrequency ablation, have been most widely used for hepatocellular carcinoma patients who were not eligible for surgery. New technologies to improve the efficacy are currently needed. 166Holmium is a neutron activated radionuclide, and has several beneficial radiophysical characteristics for internal radiation therapy. 166Holmium-Chitosan complex, in which chitosan is chelated with 166Holmium, was developed as a radiopharmaceutical for cancer therapy. We have conducted a pilot study to evaluate the clinical efficacy of transarterial administration of 166Holmium-Chitosan complex in patients with a single and small (< 3 cm) hepatocellular carcinoma. 166Holmium-Chitosan complex, at a dose of 20 mCi per cm of tumor mass-diameter, was administered through the artery that directly fed the tumor. Twelve patients were treated with a median follow-up duration of 26 (range: 12-61) months. The tumor diameter ranged between 1.5 and 2.5 cm. Ten patients (83%) had complete response and two (17%) had partial response. The median complete response duration was not reached. The median AFP level declined from 83.8 to 8.3 ng/mL within 2 months after treatment. No grade III/IV toxicity was observed. Grade I and II toxicities were observed in four patients (2 abdominal pain, 1 fever, and 1 AST/ALT elevation). No toxic death occurred. This preliminary study shows a promising and durable complete response rate with an acceptable safety profile. Further studies with greater accrual of patients are warranted.
alpha-Fetoproteins/metabolism ; Tomography, X-Ray Computed ; Radiopharmaceuticals/administration & dosage/*therapeutic use ; Pilot Projects ; Middle Aged ; Male ; Liver Neoplasms/pathology/radiography/*radiotherapy ; Injections, Intra-Arterial ; Humans ; Female ; Chitosan/administration & dosage/*therapeutic use ; Carcinoma, Hepatocellular/pathology/radiography/*radiotherapy ; Aged ; Adult

OBJECTIVE: The vulvar cancer is an uncommon disease among female population. Because of its rare incidence, sufficient clinical studies have not been accomplished. However, the prevelance of vulvar cancer will continue to increase because of rapid growth of senile population. The goal of this study is to review the clinical outcome and prognosis of patients with vulvar cancer through the analysis of their clinical data. METHODS: We have performed a retrospective clinical study on 23 patients diagnosed with primary invasive vulvar cancer at Asan medical center from May, 1989 to December, 2003. We reviewed demographic data, pathologic findings, treatments, stages, complications, prognosis and survival time. RESULTS: The mean age was 58.9 years. The most common symptoms were palpable mass (69.5%) and itching sense (21.7%). Among the 23 patients, 21 patients have underwent operation, and two patients who refused to receive operation underwent radiotherapy only. 3 of 21 patients who were surgically treated underwent neoadjuvant chemotherapy, and 5 patients, adjuvant radiotherapy. Histopathologically, squamous cell carcinoma (69.5%) was dominant, and 15 patients turned out to have stage II disease or greater (60.8%). Among the 21 patients who have underwent operation, postoperative complications occurred in 8 patients (38.0%) and 4 of them had underwent radical vulvectomy and bilateral groin lymph node dissection. The most common postoperative complication was wound breakdown (23.8%). CONCLUSION: Although surgery is the principal treatment in vulvar cancer, radical vulvectomy and bilateral groin lymph node dissection more often result in complications than other operations such as wide local excision and hemivulvectomy. Considering the mortality and morbidity, the prognosis of vulvar cancer is poor, but early diagnosis and adequate treatment according to each individual will improve the outcome and prognosis of vulvar cancer.
Carcinoma, Squamous Cell ; Chungcheongnam-do ; Drug Therapy ; Early Diagnosis ; Female ; Groin ; Humans ; Incidence ; Lymph Node Excision ; Mortality ; Postoperative Complications ; Prognosis ; Pruritus ; Radiotherapy ; Radiotherapy, Adjuvant ; Retrospective Studies* ; Vulva ; Vulvar Neoplasms* ; Wounds and Injuries

We report a case of giant malignant gastrointestinal stromal tumor (GIST) accompanying an advanced gastric adenocarcinoma. A 73-year-old male patient was admitted to our hospital due to epigastric discomfort. In gastrofiberscopic examination, a localized Borrmann III gastric cancer at the lower body and antrum was noted. In endoscopic ultrasonographic examination, T3 hyperechoic advanced gastric cancer lesion and a relatively well-marginated heterogenous hypoechoic huge mass with a size of 10 cm were noted. In abdomen CT findings, localized wall thickening in the gastric antrum and the anterior wall, and a 11-cm-sized large heterogeneously enhancing mass in gastric body, posterior wall were noted. We did a radical subtotal gastrectomy, including a huge mass, with D2 lymph node dissection. Pathologic findings revealed double primary gastric neoplasms (synchronous occurrence of an adenocarcinoma and a huge GIST). Although closely juxtaposed, these two tumors had not merged and were separated by the thin rim of the muscularis propria.
Abdomen ; Adenocarcinoma ; Aged ; Gastrectomy ; Gastrointestinal Stromal Tumors* ; Humans ; Lymph Node Excision ; Male ; Pyloric Antrum ; Stomach Neoplasms* ; Stomach*

OBJECTIVE: To evaluate the outcomes of laparoscopico-vaginal (modified) radical hysterectomy and to compare surgical parameters and recurrence rate of these with those of conventional abdominal radical hysterectomy. METHODS: From October 1997 to March 2002, we have performed 37 cases of LVMRH (laparoscopico- vaginal modified radical hysterectomy) +PLND (pelvic lymph node dissection) and 47 cases of LVRH (laparoscopico-vaginal radical hysterectomy) with paraaortic lymph node sampling +PLND. Inclusion criteria for laparoscopic group were patients with FIGO stage IA1 to IB1 which exocervical mass size was less than 2 cm clinically. As a control group, we selected 46 cases for the MRH group and 96 cases for the RH group. These groups had the same FIGO stage and the same tumor size less than 2 cm or tumor volume calculated by MRI being less than 4.2 cm3, while the age for each group were identically matched with the laparoscopic group. RESULTS: The mean duration of surgery, the number of lymph nodes and the rate of perioperative and postoperative complications were similar in both the laparoscopic and the conventional laparotomy group. The mean duration of hospital stay was significantly shorter in patients treated by laparoscopic surgery (LVMRH vs. MRH; 9 vs. 15, LVRH vs. RH; 13 vs. 21 days). No lymph node metastasis was reported in both LVMRH and MRH group. No recurrences but only one patient in MRH group were found in both groups during the median follow up of 34.5 and 43.5 months, respectively. The positive rates of pelvic lymph node metastasis in both RH groups were similarly 6.4%. Four (8.5%) of 47 LVRH patients and two (2.1%) of 96 RH patients had recurrences. However, in patients who had tumor volume being less than 4.2 cm3, recurrence rate was 2.5% (1/40) and 42.9% (3/7) in those with tumor volume larger than 4.2 cm3. There was one death in a patient with pulmonary metastasis who took LVRH in spite of vigorous chemotherapy. Three year progression free survival rates were 96.7% in LVRH group (tumor volume<4.2 cm3) and 97.9% in RH group (p=0.81). CONCLUSION: Laparoscopic surgery for treatment of early small volume cervical cancer, especially stage IA is safe and effective alternatives in terms of operative morbidity and mortality. However, patients with large volume disease (>4.2 cm3) who were treated by LVRH had higher recurrence rate compared to those by conventional RH. It is concluded that laparoscopic surgery for the treatment of cervical cancer would be better to be limited to patients with early disease who have the largest tumor diameter less than 2 cm or tumor volume less than 4.2 cm3 carefully measured by MRI.
Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Hysterectomy* ; Laparoscopy ; Laparotomy ; Length of Stay ; Lymph Nodes ; Magnetic Resonance Imaging ; Mortality ; Neoplasm Metastasis ; Postoperative Complications ; Recurrence ; Tumor Burden ; Uterine Cervical Neoplasms*