The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma

PURPOSE: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. MATERIALS AND METHODS: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. RESULTS: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A or C-->T) rather than a transversion mutation (G-->T or G-->C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. CONCLUSION: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.

Reasons for Investigators to Participate Industry Sponsored Clinical Trials

BACKGROUND: It is getting more difficult to involve appropriate investigators in clinical trials. Knowing what investigators want from sponsor initiated clinical trials would help industry cooperate with investigators more efficiently. This study aims to describe the incentives for investigators choosing to participate or not and perform well in sponsored clinical trials. METHODS: Investigators who have participated in GSK sponsored clinical trials were interviewed face-to-face or through e-mail using the standardized questionnaire. Investigators were asked to choose five items and determine the ranking or those five items. RESULTS: Questionnaires answered by 122 investigators were collected. The top three incentives were "Academic merit" (108, 88.5 %), "Expectation of treatment potentially helpful to patient" (101, 82.8 %), and "Access to new treatments" (92, 75.4 %). The disincentives and the factors affecting an investigator's performance were analyzed separately because of the different questionnaire between investigators for medicine and vaccine. Investigators for medicine choose as disincentives "Insufficient time" (43, 61.4 %), "Difficult protocol" (41, 58.6 %), and "Adverse event concerns" (41, 58.6 %). Vaccine investigators pointed out "Limited support staff" (41, 78.8 %), "Insufficient time" (40, 76.9 %), and "Difficult blood sampling" (333, 63.5 %) as disincentives. Factors adversely affecting an investigator's performance showed similar results to those of disincentives. CONCLUSION: Investigators focused on academic curiosity and patients and insufficient time mostly inhibits them from participating and performing clinical trials. Our results would help industry cooperate with investigators more efficiently, finally making companies perform clinical trials more effectively.

A case of nephrogenic systemic fibrosis after gadolinium-based contrast agent injection / 대한내과학회지

Nephrogenic systemic fibrosis is a rare multisystemic disorder mainly affecting the skin and joints in patients with underlying renal insufficiency exposed to gadolinium-based contrast. We report a patient who had renal insufficiency caused by multiple myeloma and developed nephrogenic systemic fibrosis after exposure to gadolinium-based contrast for the first time in Korea.

Treatment Outcomes of Sunitinib Treatment in Advanced Renal Cell Carcinoma Patients: A Single Cancer Center Experience in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The retrospective study was performed to assess the efficacy and toxicity profiles of sunitinib in Korean patients with metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: Between January 2005 and December 2008, 76 Korean patients with recurrent/metastatic RCC who received sunitinib were retrospectively reviewed. The primary end point was progression-free survival and the secondary end points were overall survival and response rate. We also assessed the toxicities associated with sunitinib treatment. RESULTS: Of the 76 patients, 69 (90.1%) were diagnosed with clear cell RCC. The median progression-free survival and overall survival were 7.2 and 22.8 months, respectively in overall patients. Sixty-two patients (81.6%) received 50 mg 4 week and 2 week off schedule, and 14 patients (18.4%) received 37.5 mg daily on a daily continuous schedule. The objective response rate and disease control rate were 27.6% and 84.2%, respectively. A dose reduction or reduction in dose due to adverse events occurred in 76% of the patients, whereas 11% of the patients had discontinued treatment. Other common laboratory abnormalities were increased serum creatinine (75.6%), elevated alanine aminotransferase (71.0%), neutropenia (61.8%), anemia (69.7%), and increased aspartate aminotrasferase (53.3%). Grade 3/4 toxicities occurred as follows: thrombocytopenia (38.2%), fatigue (10.5%), stomatitis (10.5%), and hand-foot syndrome (9.2%). CONCLUSION: Our results indicate that sunitinib treatment is effective and tolerable for ecurrent/metastatic RCC patients in Korea. Further studies with prognostic or biochemical factors are needed to clarify the different toxicity profiles of this study.

Prognosis of pN3 Stage Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to determine the prognosis of pN3 stage gastric cancer patients after they have undergone curative resection, and we also wanted to identify the prognostic factors according to the clinico-pathologic features. MATERIALS AND METHODS: Between January 2000 and December 2004, we retrospectively reviewed the medical records of the patients with histologically confirmed pN3 stage gastric cancer. They underwent both gastrectomy and lymphadenectomy with a curative aim. We categorized the pN3 stage patients into 2 groups; one with pN3 only (pN3M0) and the other with pN3 combined with M1 stage (pN3M1) that included peritoneal seeding, hepatic metastasis or para-aortic LN metastasis. RESULTS: Out of 467 patients with stage IV gastric adenocarcinoma who received surgery, 260 patients underwent curative resection and they were pathologically staged as N3. Among these 260 patients, 78 patients were classified as the pN3/M1 stage. For all the patients, the median follow-up period was 19 months (range: 1~108 months) and the median overall survival time was 16.2 months (95% CI, 14.1~18.3%). The 5-year survival rate of the pN3/M0 group was significantly higher than that of the pN3/M1 group (12.6% vs. 2.6%, respectively, p<0.0001). The identified predictor for a worse prognosis was an advanced T4 stage (HR: 3.38, 95% CI, 1.4~8.3, p=0.008) for the pN3 patients. CONCLUSION: The survival for the pN3 gastric cancer patients after curative gastrectomy was significantly longer in the pN3/M0 group as compared to that of the pN3/M1 group. An advanced T stage was a predictor for a poor prognosis for the pN3 patients. Therefore, diverse treatment strategies for these heterogeneous pN3 gastric cancer patients are needed for improving their survival.

Clinical Value of Ezrin Expression in Primary Osteosarcoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Ezrin is a membrane cytoskeletal linker protein and it is known to be associated with metastasis of primary osteosarcoma. The aim of this study is to determine the relationship between an ezrin expression and several key clinical parameters and to elucidate its potential prognostic value for patients with osteosarcoma. MATERIALS AND METHODS: Seventy patients with histologically confirmed osteosarcoma and who had no distant metastasis were enrolled between 1995 and 2005 at Yonsei Cancer Center, Severance Hospital, Korea. The clinical parameters were retrospectively reviewed and immunohistochemical staining (IHC) for ezrin was performed using the surgically resected specimens. RESULTS: Of the 70 tumor specimens, 39 (55.7%) revealed an ezrin expression. More of an osteoblastic histology and an elevated initial ALP level were observed in the ezrin positive patients than in the ezrin negative patients (p=0.008 and 0.001, respectively). The proportion of patients who favorably responded to neoadjuvant chemotherapy (> or =90% necrosis) was significantly higher in the group of ezrin positive patients than that in the group of ezrin negative patient (72.2% vs 45.2%, respectively, p=0.024). The ezrin positive patients showed more frequent recurrence than did the ezrin negative patients (64.1% vs 35.5%, respectively, p=0.017). The patients with an ezrin expression also demonstrated poorer survival than did those patients without ezrin expression (5-year EFS: 31.7% vs 61.3%, respectively, p=0.023, 5-year OS: 53.4% vs 71.0%, respectively, p=0.022). When comparing EFS according to both an ezrin expression and chemoresponsiveness, there were trends that the ezrin negative/chemoresponsive group showed the best 5-year EFS (71.4%), followed by the ezrin negative/chemoresistant group (52.9%), the ezrin positive/chemoresponsive group (38.1%) and the ezrin positive/chemoresistant group (13.6%). These trends were statistically significant (p=0.036). CONCLUSION: The expression of ezrin by IHC staining was found in 55.7% of the patients with metastasis-free osteosarcoma. Immunoreactivity to ezrin is a negative prognostic factor for survival for the patients suffering with osteosarcoma. Identifying an ezrin expression might offer a valuable piece of information when treating patients with primary osteosarcoma.

A Case of Henoch-Shonlein Purpura Caused by Rifampin / 결핵및호흡기질환

Rifampin is one of the first line drugs for treating tuberculosis, but it might be associated with serious adverse effects, including renal failure. We report here on a case of a 57-year-old patient who developed Henoch-Shonlein purpura during antituberculosis therapy that included rifampin. The patient converted to negative on the AFB smear for tuberculosis two weeks after the initial administration of antituberculosis medication. After treatment for 60 days, this patient was diagnosed with Henoch-Shonlein purpura by the purpura lesion on the lower legs, the leukocytoclastic vasculitis, the renal impairment and the pathological examination. After stopping rifampin, the skin lesions disappeared in about 10 days and his renal function gradually improved. This case study showed that Henoch-Schonlein purpura can be caused by rifampin during antituberculosis therapy and we recommend that the use of rifampin should be restrained when clinical symptoms of Henoch-Shonlein purpura are observed.