Risk factors for incident anemia of chronic diseases: A cohort study.

OBJECTIVE: Anemia of chronic disease (ACD) refers to hypoproliferative anemia in the context of acute or chronic activation of the immune system. There is a paucity of prospective data addressing the risk factors for ACD development. An association between common chronic diseases and ACD was examined cross-sectionally and longitudinally. METHOD: A cohort of 265,459 healthy participants without ACD at baseline were prospectively followed annually or biennially. RESULTS: During average follow-up period of 62 months, 4,906 participants developed ACD (incidence rate 3.58 per 1000 person-years). Multivariable-adjusted hazard ratio (HR) [95% confidence interval (CI)] for incident ACD comparing estimated glomerular filtration rate 30-60 and < 30 vs. ≥ 60 ml/min/1.73 m2 were 3.93 [3.18-4.85] and 39.11 [18.50-82.69]; HRs [95% CI] for ACD comparing prediabetes and diabetes vs. normal were 1.19 [1.12-1.27] and 2.46 [2.14-2.84], respectively. HRs [95% CI] for incident ACD comparing body-mass-index (BMI) of < 18.5, 23-24.9 and ≥ 25 vs. 18.5-22.9 kg/m2 were 0.89 [0.78-1.00], 0.89 [0.80-0.99] and 0.78 [0.66-0.91], respectively. HRs [95% CI] for incident ACD comparing prehypertension and hypertension vs. normal were 0.79 [0.73-0.86] and 1.10 [0.99-1.23], respectively. Metabolic syndrome, hypertension, chronic liver disease, and chronic obstructive pulmonary disease were not associated with incident ACD. CONCLUSIONS: The severity of chronic kidney disease and diabetic status were independently associated with an increased incidence of ACD, whereas prehypertension and an increasing BMI were significantly associated with decreased risk of ACD.

Efficacy and safety of Viscum album extract (Helixor-M) to treat malignant pleural effusion in patients with lung cancer.

PURPOSE: Manifestations of malignant pleural effusions (MPEs) are alleviated by local therapies as well as by systemic treatment. After 2009, when commercial use of talc was discontinued in Korea, we have used Helixor-M, which is derived from the European mistletoe (Viscum album), as an alternative sclerosing agent for pleurodesis. We aimed to evaluate the efficacy and safety of Helixor-M for controlling MPE. METHODS: Between 2009 and 2015, we consecutively enrolled 52 patients with lung cancer, who underwent pleurodesis to treat MPE and were analyzed retrospectively. On day 1, 100 mg of Helixor-M was instilled via pleural catheter. If the procedure was not effective, it was repeated every other day up to five times, and the dose increased each time by 100 mg. The primary study outcome was reappearance of pleural effusion at 1 month after the last pleurodesis procedure. RESULTS: The median age of patient was 63 years, and 77% of the 52 patients were male. About 85% of pleural effusions were found to be malignant by cytogenetic analysis. Forty-two (81%) patients were evaluable for recurrence of MPE. The 1-month recurrence rate was 48% (20/42). Among the 20 patients who developed recurrent MPE, 6 required therapeutic thoracentesis. Thirteen (25%) patients experienced procedure-related pain requiring medication. Eight (15%) had fever > 38 °C. CONCLUSIONS: Our results suggest that a pleurodesis with Helixor-M was an effective and tolerable procedure for controlling MPE in lung cancer patients.

Impact of Epidermal Growth Factor Receptor Mutation on Clinical Outcomes of Nintedanib Plus Docetaxel in Patients with Previously Treated Non-Small Cell Lung Cancer from the Korean Named Patient Program.

OBJECTIVES: Anti-angiogenic agents are reported to exert clinical activity on epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancers. We evaluated the clinical outcomes of nintedanib and docetaxel in refractory NSCLC according to EGFR mutation status during the Korean nintedanib named patient program. METHODS: Docetaxel was administered either 75 or 37.5 mg/m2 on D1, D8 q every 3 weeks for 4-6 cycles plus nintedanib 200 mg orally twice daily until disease progression or unacceptable toxicity. RESULTS: Sixty-two patients were enrolled for study. Twenty-eight patients with activating EGFR mutations progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy and 25 out of 28 patients showing progression after platinum doublet chemotherapy were enrolled. The objective response rate was 29% and median PFS and OS were 3.9 months and 11.7 months. Based on the EGFR mutation status, the objective response rate was 39.3 vs. 21.9% (EGFR mut(+) vs. EGFR mut(-), p = 0.142) and median PFS was 6.5 vs. 3.3 months (EGFR mut(+) vs. EGFR mut(-), p = 0.009). No treatment-related deaths were reported. The most frequent drug-related adverse events (AE) were neutropenia (53.2%) and diarrhea (37.1%). Treatment in 12 patients (19.3%) was permanently discontinued due to AEs without disease progression. CONCLUSIONS: Our data indicated that nintedanib-docetaxel combination could be considered to be effective treatment in EGFR TKI-resistant EGFR mutant NSCLC.

Initial titration with 200 µg fentanyl buccal tablets: a retrospective safety analysis in Korean cancer patients.

BACKGROUND/AIMS: Managing breakthrough pain (BTP) is important for many cancer patients because of the rapid onset and unpredictable nature of the pain episodes. Fentanyl buccal tablets (FBTs) are a rapid-onset opioid indicated for BTP management. However, FBT titration is needed to optimize BTP management. In this study, we aimed to evaluate the safety and efficacy of initiating 200 µg FBTs in Korean cancer patients. METHODS: A retrospective analysis of medical records was performed on all advanced cancer patients treated with FBTs for BTP between October 2014 and July 2015. Patients who received initial doses of 200 µg FBTs for at least 3 days and cases in which FBT was available at doses of 200, 400, and 800 µg were included. RESULTS: A total of 56 patients with a median age of 62 years (range, 32 to 80) were analyzed, 61% of whom were male. The median and mean values of morphine equivalent daily doses were 60 mg/day (range, 15 to 540) and 114.8 ± 124.8 mg/day, respectively. The most frequent effective doses of FBT were 200 µg (41 patients, 74%) and 400 µg (12 patients, 21%). Three patients (5%) could not tolerate 200 µg of FBT and discontinued treatment. Nausea, vomiting, somnolence, and dizziness were the most frequent treatment-related adverse events (AEs), and all AEs were grade 1 (mild) or 2 (moderate). CONCLUSIONS: FBT at the initial 200 µg dosage was well-tolerated and effective as a BTP management strategy in Korean cancer patients. Further prospective studies are needed to determine appropriate initiating doses of FBT in Korean patients with opioid tolerance.

Multicenter, cross-sectional observational study of the impact of neuropathic pain on quality of life in cancer patients.

PURPOSE: Neuropathic cancer pain (NCP) is a common and potentially debilitating symptom in cancer patients. We investigated the prevalence of NCP, as well as its management and association with QOL. METHODS: Cancer patients with pain ≥1 on the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique (DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and pain severity or NCP and QOL, while controlling for variables relevant to QOL, were then analyzed. RESULTS: A total of 2003 patients were enrolled in this survey; the prevalence of NCP was 36.0% (n = 722, 95% CI, 32.5-39.5). We found that NCP in cancer patients was closely correlated to a higher pain severity (BPI-SF; 4.96 ± 1.94 versus 4.24 ± 2.02, p < 0.001), and in patients with NCP, pain more severely interfered with daily living, as compared to those without NCP (BPI-SF; 4.86 ± 2.71 versus 4.41 ± 2.87, p < 0.001). Patients with NCP also had worse QOL than those without NCP, as measured by EQ-5D index score (0.47 ± 0.30 vs. 0.51 ± 0.30, p = 0.005), and this was confirmed using multivariate analysis (p < 0.001), even after controlling for other variables such as age, sex, disease stage, cancer duration, radiotherapy, chemotherapy, and comorbidities. Importantly, adjuvant analgesics were used in less than half of patients with NCP (n = 358, 46.4%). CONCLUSIONS: We found that NCP in cancer patients was significantly associated with a worsened QOL, and current management is inadequate. Therefore, future research aimed at developing improved strategies for management of NCP is required.

Practice Patterns Regarding Multidisciplinary Cancer Management and Suggestions for Further Refinement: Results from a National Survey in Korea.

PURPOSE: This study was conducted to explore the process and operation of a cancer multidisciplinary team (MDT) after the reimbursement decision in Korea, and to identify ways to overcome the major barriers to effective and sustainable MDTs. MATERIALS AND METHODS: Approximately 1,000 cancer specialists, including medical oncologists, surgical oncologists, radiation oncologists, pathologists, and radiologists in general hospitals in Koreawere invited to complete the survey. The questionnaire covered the following topics: organizational structure of MDTs, candidates for consulting, the clinical decision-making initiative, and responsibility for dealing with legal disputes. RESULTS: We collected a total of 179 responses (18%) from physicians at institutions where an MDT approach was active. A surgical oncologist (91%), internist (90%),radiologist (89%),radiation oncologist (86%), pathologist (71%), and trainees (20%) regularly participated in MDT operations. Approximately 55% of respondents stated that MDTs met regularly. In cases of a split opinion, the physician in charge (69%) or chairperson (17%) made the final decision, and most (86%) stated they followed the final decision. About 15% and 32% of respondents were "very satisfied" and "satisfied," respectively, with the current MDT's operations. Among 38 institutional representatives, 34% responded that the MDT operation became more active and 18% stated an MDT was newly implemented after the reimbursement decision. CONCLUSION: The reimbursement decision invigorated MDT operations in almost half of eligible hospitals. Dissatisfaction regarding current MDTs was over 50%, and the high discordance rates regarding risk sharing suggest that it is necessary to revise the current system of MDTs.

Safety and efficacy of single-agent docetaxel (Taxotere) administered weekly in non-small cell lung carcinoma patients in Korea: An observational study.

BACKGROUND: To investigate the efficacy, safety, and tolerability of weekly docetaxel treatment in advanced non-small cell lung cancer (NSCLC) patients in Korea. METHODS: This prospective observational study included Korean advanced NSCLC patients with Eastern Cooperative Oncology Group performance status <2 who received weekly monotherapy of docetaxel at a dose determined by the physician. Efficacy measurements included tumor response rate, overall survival (OS), progression-free survival, and one-year survival rate. Safety was analyzed through recorded incidences of adverse events (AEs), serious adverse events (SAEs), deaths, and other related safety parameters, along with their toxicity grades. RESULTS: Of 274 patients analyzed, one patient achieved a complete response and 42 partial responses; thus, the overall response rate was 15.7%. The OS rate at baseline and at one-year follow-up was 38.3% and 33.8%, respectively. AEs were reported in 229 (83.6%) patients. The most frequently reported hematologic AE of grade ≥3 was a decrease in neutrophils, with 6.6% of the patients developing neutropenia. In non-hematologic AEs of grade ≥3, the most common were infection with unknown absolute neutrophil count and death not associated with Common Terminology Criteria for Adverse Events (CTCAE) (4.7% each). The most common SAE reported was death, not associated with CTCAE (7.3%). CONCLUSIONS: In Korean patients, the weekly regimen of docetaxel monotherapy was safe and efficacious against advanced NSCLC.

Efficacy and safety of ifosfamide in combination with carboplatin and etoposide in small cell lung cancer.

PURPOSE: Ifosfamide, a potent alkylating agent, is rarely incorporated into small cell lung cancer (SCLC) treatment. The aim of this study was to assess the efficacy and safety of ifosfamide in combination with carboplatin and etoposide (ICE) in previously untreated patients with SCLC. METHODS: From January 2002 to January 2014, we consecutively enrolled 69 patients with SCLC who were treated with ICE as initial chemotherapy at Kangbuk Samsung Hospital. The modified ICE regimen consists of ifosfamide 1200 mg/m(2)/day on days 1, 2, and 3 with mesna, etoposide 80 mg/m(2)/day on days 1, 2, and 3, and carboplatin AUC 6 on day 1. Treatment was repeated every 3 weeks and continued for up to nine cycles. Response assessments were performed every three cycles with computed tomography. RESULTS: Among 69 patients with SCLC, the median age was 69 years (range 51-88 years). Sixteen (23 %) patients had limited disease (LD), and 53 (77 %) had extensive disease (ED). The overall response rate was 73 %. Stable disease rate was 20 %. The median overall survival was 11.3 months [95 % confidence interval (CI) 8.9-14.1] in the overall population, 20.6 months (95 % CI 14.2-21.2) for LD and 9.1 months (95 % CI 7.8-11.6) for ED. The median number of administered cycles was 6 (range 1-9). Grade ≥3 hematological toxicities included neutropenia (34 %), anemia (59 %), and thrombocytopenia (31 %). Grade ≥3 non-hematological toxicities included peripheral neuropathy in 2 %. CONCLUSION: In chemonaïve patients with SCLC, modified ICE is well tolerated and shows favorable efficacy.

Adenocarcinoma has an excellent outcome with pemetrexed treatment in Korean patients: a prospective, multicenter trial.

OBJECTIVE: This prospective multicenter study conducted by the Korean Cancer Study Group evaluated the efficacy and safety of pemetrexed in Korean patients with advanced non-small cell lung cancer (NSCLC) who had prior chemotherapy. PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC in whom prior chemotherapy failed received pemetrexed 500 mg/m(2) every 3 weeks with folic acid and vitamin B12 supplementation until disease progression or the development of intolerable toxicity. Eighty-one patients were enrolled. RESULTS: The overall response rate for 78 evaluable patients was 5.1% [95% confidence interval (CI) 1.4-12.6; partial response 4/78, no complete response]. The disease control rate including complete, partial response and stable disease was 46.2% (36/78, 95% CI 34.8-57.8). With a median 8.7 months follow-up, the median time to progression was 3.1 months (95% CI 1.17-5.03) and the median overall survival (OS) was 7.8 months (95% CI 5.19-10.35). The median OS for patients with adenocarcinoma histology was 18.7 months compared to 6.1 months for non-adenocarcinoma. In a multivariate analysis, Eastern Cooperative Oncology Group performance status 0-1 [hazards ratio (HR)=0.331, 95% CI 0.135-0.814] and adenocarcinoma (HR=0.504, 95% CI 0.283-0.899) were independent factors for prolongation of overall survival. CONCLUSIONS: Pemetrexed monotherapy has promising efficacy in patients with advanced NSCLC as a second-line therapy with less hematologic and non-hematologic toxicity, especially in those with adenocarcinoma histology.

The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test.

BACKGROUND & AIMS: Systemic chemotherapy may damage gastrointestinal epithelium. Mucositis is associated with increased intestinal permeability (IP). It is known that IP test with chromium 51-ethylene diaminetetra-acetate (51Cr-EDTA) is a useful tool to assess the mucositis. Oral glutamine supplements (OGS) may have a role in the prevention of chemotherapy-induced mucositis/stomatitis. The aim of this study was to characterize the relationship between the urinary excretion of 51Cr-EDTA and the severity of mucositis, and the effect of OGS on 5-fluorouracil/leucovorin (FU/LV)-induced mucositis/stomatitis. METHODS: Fifty-one patients with advanced or metastatic cancer received FU/LV chemotherapy. The control group included 18 healthy volunteers. IP was assessed via the measurement of 51Cr-EDTA urinary excretion after oral challenge, on days 7 after the discontinuation of chemotherapy. Of the 51 patients, 22 patients received OGS (30 g/day) and 29 received only best supportive care (BSC). Glutamine supplementation continued for 15 days. It was initiated at least 3 days before the beginning of chemotherapy. Mucositis/stomatitis was graded according to version 3.0 of the Common Terminology Criteria for Adverse Events. RESULTS: In the chemotherapy group, the median (25 percentile, 75 percentile) IP test score was significantly higher than those of the control group [6.78% (4.63, 10.66) vs. 2.17% (1.38, 2.40), P<0.001]. The severity of stomatitis was significantly correlated with IP test scores (r=0.898, P<0.001). In the OGS group, the median IP test score was significantly lower than that of the BSC group [4.69% (3.10, 6.48) vs. 8.54% (6.48, 15.31), P<0.001]. A mucositis/stomatitis of grade 2-4 was observed in two patients of the OGS group (9%), and in 11 patients (38%) in the BSC group (P<0.001). CONCLUSIONS: The IP test may be a useful tool in the evaluation of mucositis/stomatitis. OGS may exert a protective effect on FU/LV-induced mucositis/stomatitis. Further studies, however, will be necessary to define the role of glutamine supplementation in FU/LV-induced mucositis/stomatitis.

Ovarian granulosa cell tumor presenting as Meigs' syndrome with elevated CA125.

Herein, a rare case of ovarian granulosa cell tumor, presenting as Meigs' syndrome, with elevated carbohydrate antigen 125 (CA125), is reported. A 69-year-old woman was admitted for the investigation of abdominal fullness and dyspnea. A preoperative examination revealed a huge pelvic tumor and an abdominopelvic magnetic resonance image (MRI) assumed ovarian cancer. A chest computed tomography (CT) scan revealed pleural effusion. A laparotomy confirmed the huge mass to be an ovarian tumor. A total abdominal hysterectomy (TAH), with a bilateral salpingo-oophorectomy (BSO) and partial omentectomy, was performed. Although short-term intrathoracic drainage was required, the hydrothorax and ascites rapidly resolved in the postoperative period.

The relationship between the serum intercellular adhesion molecule-1 level and the prognosis of the disease in lung cancer.

BACKGROUND: Adhesion molecules are related to cell-to-cell interaction and inflammatory interaction. In addition, adhesive interactions between tumor cells and adjacent cells and/or extracellular matrix play important roles in the complex process of tumor growth and development. Among these adhesion molecules, expression of intercellular adhesion molecule-1 (ICAM-1) has been identified in colon cancer, bladder cancer, lung cancer, melanoma, pancreatic cancer and hepatocellular carcinoma. In the current study, we analyzed serum ICAM-1 concentrations to investigate the relationship between the serum ICAM-1 level and prognosis in patients with lung cancer. METHODS: Serum ICAM-1 was measured in 84 patients with lung cancer according to the pathologic type and clinical stage using the ICAM-1 ELISA kit. The Kaplan-Meier method was used to analyse survival time. RESULTS: There was no difference in serum ICAM-1 concentration among the different stages of lung cancer. Furthermore, there was no difference observed between histologic tumor type with regard to serum ICAM-1 concentration. Although the difference was not significant, the overall survival times of patients with a low serum ICAM-1 concentration (< 306 ng/mL) was longer than that of patients with a high concentration (> or = 306 ng/mL) in non-small cell lung cancer patients. CONCLUSION: These results suggest that high levels of serum ICAM-1 reflect poor prognosis for patients with non-small cell lung cancer.

Transcription factors and mitogen-activated protein kinases as molecular targets for chemoprevention with anti-inflammatory phytochemicals.

Chemoprevention refers to the use of nontoxic chemical substances to inhibit, reverse, or retard tumorigenesis. Numerous compounds derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Some anti-inflammatory phytochemicals with cyclooxygenase-2 inhibitory activity have been found to exert chemopreventive properties by targeting intracellular signaling molecules (recently reviewed by Y.-J. Surh, Nature Reviews Cancer, 3: 768-780, 2003). These include mitogen-activated protein kinases and transcription factors, such as NF-kappaB and AP-1.

The relationship between serum VEGF concentration and prognosis of lung cancer.

BACKGROUND: VEGF is an important factor for angiogenesis. Although many previous studies have reported an increased serum VEGF concentration in various malignant tumors, there are few studies on the relationship between serum VEGF concentration and its prognosis. This study investigated whether serum VEGF concentration is a prognostic indicator for lung cancer. METHODS: Using the ELISA kit, we measured the serum VEGF concentrations of 86 patients diagnosed with lung cancer on histologic examination. With a cut off value of 686 pg/mL, the patients were classified as low-concentration (< 686 pg/mL, n=58) or high-concentration (> or = 686 pg/mL, n=28) based on their mean serum VEGF concentration values to compare survival rates, and serum VEGF concentrations for different histologic types and stages. RESULTS: There was no significant difference in serum VEGF concentration based on stage and histologic type between the two groups. Moreover, there was no significant difference in survival rate between the high-concentration and low-concentration groups (p=0.86). CONCLUSION: This study demonstrates that serum VEGF concentration is not associated with the prognosis of lung cancer.

Efficacy of Combination Chemotherapy with Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer.

PURPOSE: To evaluate the efficacy and toxicity of the combination therapy of paclitaxel and cisplatin in advanced, non-small cell, lung cancer patients. MATERIALS AND METHODS: Between December 1997 and September 2001, 37 patients with advanced, non-small cell, lung cancer were enrolled in this study. Patients were treated with paclitaxel (135 mg/m2, 24 hr infusion) and cisplatin (75 mg/m2). The treatments were repeated every 4 weeks. RESULTS: Among the 37 patients enrolled, 21 were treated with paclitaxel and cisplatin as a first-line and 16 patients as a second-line. The median age of the patients was 59. In the first-line group, 10 had stage IIIB and 11 had stage IV, non small cell lung cancer. Of 21 patients in first-line treatment group that could be evaluated, objective responses were observed in 6 patients (response rate: 28.6%, CR: 4.8%, PR: 23.8%). The mediansurvival duration for patients was 48 weeks. With the second-line group, 3 patients showed a partial response (response rate: 18.7%) to treatment, with median survival duration of 44 weeks. Grade 3-4 leukopenia was observed in 27.1% of the first-line, and 23.6% in second- line, treatment groups. CONCLUSION: Combination chemotherapy, with paclitaxel and cisplatin, in non-small cell lung cancer has acceptable toxicities in both first and second-line treatment groups. In terms of efficacy, no superior response was shown for either group. More randomized studies, with a larger group of patients, are required to prove the true efficacy.