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1.  Efficacy of the Mineral Oil and Hyaluronic Acid Mixture Eye Drops in Murine Dry Eye 
To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE).
Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining.
There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group.
The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE.
PMCID: PMC4369516  PMID: 25829831
Dry eye; Hyaluronic acid; Mineral oil; Ocular surface
2.  Chemotherapy for colorectal cancer in the elderly 
Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the elderly. However, elderly patients with CRC tend to be under-presented in clinical trials and undertreated in clinical practice. Advanced age alone should not be the only criteria to preclude effective therapy in elderly patients with CRC. The best guide about optimal cancer treatment can be provided by comprehensive geriatric assessment. Elderly patients with stage III colon cancer can enjoy the same benefit from adjuvant chemotherapy with 5-fluorouracil/leucovorin or capecitabine as younger patients, without a substantial increase in toxicity. With conflicting results of retrospective studies and a lack of data available from randomized studies, combined modality treatment should be used with great caution in elderly patients with locally advanced rectal cancer. Combination chemotherapy can be considered for older patients with metastatic CRC. For elderly patients who are frail or vulnerable, however, monotherapy or a stop-and-go strategy may be desirable. The use of targeted therapies in older patients with metastatic CRC appears to be promising in view of their better efficacy and toxicity. Treatment should be individualized based on the nature of the disease, the physiologic or functional status, and the patient’s preference.
PMCID: PMC4419056  PMID: 25954089
Adjuvant chemotherapy; Colorectal cancer; Elderly; Palliative chemotherapy; Review
3.  Comparison of RECIST 1.0 and RECIST 1.1 in Patients with Metastatic Cancer: A Pooled Analysis 
Journal of Cancer  2015;6(4):387-393.
Background:We conducted this pooled analysis to investigate the impact of RECIST 1.1 on the selection of target lesions and classification of tumor response, in comparison with RECIST 1.0.
Methods: We searched MEDLINE and EMBASE for articles with terms of RECIST 1.0 or RECIST 1.1. We looked into all abstracts and virtual meeting presentations from the conferences of ASCO and ESMO between 2009 and 2013.
Results: There were six articles in the literature comparing the clinical impacts of RECIST 1.0 and RECIST 1.1 in patients with metastatic cancer. A total of 359 patients were recruited from the six trials; 217 with non-small cell lung cancer, 61 with gastric cancer, 58 with colorectal cancer, and 23 with thyroid cancer. The number of target lesions by RECIST 1.1 was significantly lower than that by RECIST 1.0 (P<0.001). Because of new lymph node criteria, fourteen patients (3.1%) had no target lesions when adopting RECIST 1.1. RECIST 1.1 showed high concordance with RECIST 1.0 in the assessment of tumor responses (k = 0.903). Sixteen patients (4.8%) showed disagreement between the two criteria.
Conclusion: This pooled study demonstrated that RECIST 1.1 showed a highly concordant response assessment with RECIST 1.0 in patients with metastatic cancer.
PMCID: PMC4349880  PMID: 25767610
RECIST 1.0; RECIST 1.1; Target lesion; Tumor response
4.  Comparison of the RECIST 1.0 and RECIST 1.1 in Non-Small Cell Lung Cancer Treated with Cytotoxic Chemotherapy 
Journal of Cancer  2015;6(7):652-657.
Background : The impact of the RECIST 1.1 on the selection of target lesions and assessment of tumor response was not evaluated in patients with advanced NSCLC who received cytotoxic chemotherapy.
Methods: We reviewed medical records of patients with advanced NSCLC who received first-line chemotherapy between January 2004 and December 2013 and compared the selection of target lesions and tumor responses using the two RECIST versions.
Results: A total of 88 patients who had at least one target lesion according to the RECIST 1.0 were included in the study. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0. When adopting the RECIST 1.1 instead of the RECIST 1.0, 40 patients (45.4%) showed a decrease in the number of target lesions. Three patients no longer had target lesion because of the new lymph node (LN) criteria of the RECIST 1.1. Tumor responses showed a high level of concordance between the RECIST 1.0 and RECIST 1.1, with a kappa value of 0.912. Four patients (4.5%) showed disagreement of tumor responses between the two criteria, which were all due to the change of the LN criteria.
Conclusion: The RECIST 1.1 showed a high level of concordance with the RECIST 1.0 in the assessment of tumor response in advanced NSCLC patients treated with cytotoxic chemotherapy. The new LN criteria were the major cause of the reduction of target lesions and reclassification of the tumor response.
PMCID: PMC4466415  PMID: 26078796
RECIST 1.0; RECIST 1.1; Lung cancer; Chemotherapy; Target lesion
5.  The Assessment of Tumor Response by Measuring the Single Largest Lesion per Organ in Metastatic Tumors: A Pooled Analysis of Previously Reported Data 
Journal of Cancer  2015;6(2):169-176.
Background: The RECIST 1.1 adopted a total of five target lesions to be measured, with a maximum of two lesions per organ. To the best of our knowledge, the criterion of two target lesions per organ in the RECIST 1.1 is arbitrary and has not been supported by any objective evidence. Recently, we reported that the modified RECIST 1.1 (measuring the single largest lesion in each organ) showed a high level of concordance with the original RECIST 1.1 in patients with advanced or metastatic non-small cell lung cancer (NSCLC), gastric cancer (GC), and colorectal cancer (CRC). However, each study had a major limitation of a small number of patients.
Methods: We conducted a pooled analysis using the data from the three individual studies to improve statistical power. Tumor responses were compared according to the RECIST 1.1 and modified RECIST 1.1 (mRECIST 1.1).
Results: A total of 153 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included in this pooled study: 64 with NSCLC, 51 with GC, and 38 with CRC. Regardless of primary sites, the number of target lesions according to the mRECIST 1.1 was significantly lower than that according to the RECIST 1.1 (P<0.001). The assessment of tumor responses showed a high concordance between the two criteria (k = 0.908). Only eight patients (5.2%) showed disagreement in the tumor response assessment between the two criteria. The overall response rates of chemotherapy were not significantly different between the two criteria (33.3% versus 33.3%, P=1.0).
Conclusions: The modified RECIST 1.1 was comparable to the original RECIST 1.1 in the tumor response assessment of patients with advanced or metastatic NSCLC, GC, and CRC. Our results suggest that it may be possible to measure the single largest lesion per organ for assessing tumor response in clinical practice.
PMCID: PMC4280400  PMID: 25561982
RECIST 1.1; modified RECIST 1.1; Target lesion; Tumor response; Single-lesion measurement
6.  The Factors Affecting Pain Pattern after Arthroscopic Rotator Cuff Repair 
Clinics in Orthopedic Surgery  2014;6(4):392-400.
We evaluated the factors that affect pain pattern after arthroscopic rotator cuff repair.
From June 2009 to October 2010, 210 patients underwent arthroscopic rotator cuff repair operations. Of them, 84 patients were enrolled as subjects of the present study. The evaluation of postoperative pain was conducted by visual analog scale (VAS) scores during postoperative outpatient interviews at 6 weeks, 3 months, 6 months, and 12 months. The factors that were thought to affect postoperative pain were evaluated by dividing into three categories: preoperative, operative, and postoperative.
Pain after arthroscopic rotator cuff repair surgery showed a strictly decreasing pain pattern. In single analysis and multiple regression tests for factors influencing the strictly decreasing pain pattern, initial VAS and pain onset were shown to be statistically significant factors (p = 0.012, 0.012, 0.044 and 0.028, respectively). With regard to the factors influencing lower than average intensity pain pattern for each period, the stiffness of internal rotation at 3 months postoperatively was shown to be a statistically significant factor in single and multiple regression tests (p = 0.017 and p = 0.004, respectively).
High initial VAS scores and the acute onset of pain affected the strictly decreasing postoperative pain pattern. Additionally, stiffness of internal rotation at postoperative 3 months affected the higher than average intensity pain pattern for each period after arthroscopic rotator cuff repair.
PMCID: PMC4233217  PMID: 25436062
Arthroscopy; Rotator cuff repair; Stiffness; Postoperative pain; Visual analog scale
7.  Ideal number of target lesions per organ to measure in metastatic colorectal cancer 
Oncology Letters  2014;8(4):1896-1900.
The Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guideline states that the two largest lesions per organ should be measured as target lesions for assessment of the tumor response. This criterion is considered to be arbitrary and, to the best of our knowledge, has not been supported by any objective evidence. The present study hypothesized that measuring the single largest lesion in each organ into which the cancer had metastasized (termed the modified RECIST; mRECIST 1.1) may yield the same response classification as measuring the two target lesions per organ (as per the RECIST 1.1 guideline). The medical records of patients with metastatic colorectal cancer (CRC), who received first-line chemotherapy between January 2004 and June 2013 were reviewed. The tumor responses of the patients were compared according to the two criteria using computed tomography. A total of 38 patients were included in the present study, all of whom had at least two target lesions in any one organ according to the RECIST 1.1 guidelines. When adopting the mRECIST 1.1, rather than the RECIST 1.1, 18 patients (47.4%) demonstrated an increase in the rate of change of the sum of the tumor measurements. The overall response rates of chemotherapy were 39.4% and 34.2% according to the RECIST 1.1 and the mRECIST 1.1, respectively, and the difference between the two criteria was not identified to be significantly different (P=0.226). The tumor response showed near perfect agreement between the RECIST 1.1 and mRECIST 1.1 criteria (κ=0.905). Only two patients (5.3%) showed a disagreement with regard to the tumor responses between the two criteria. Therefore, it was identified that the mRECIST 1.1 showed a high level of concordance with the original RECIST 1.1 guidelines in the tumor response assessment of metastatic CRC patients to chemotherapy. The present results indicate that the mRECIST 1.1, with a decreased number of target lesions to be measured, may be more convenient in clinical practice for the assessment of tumor response.
PMCID: PMC4156276  PMID: 25202433
target lesion; Response Evaluation Criteria in Solid Tumors 1.1; tumor response; colorectal cancer
8.  Irinotecan, leucovorin and 5-fluorouracil (modified FOLFIRI) as salvage chemotherapy for frail or elderly patients with advanced gastric cancer 
Oncology Letters  2012;4(4):751-754.
We retrospectively evaluated the efficacy and safety of the modified FOLFIRI regimen in frail or elderly patients with advanced gastric cancer (AGC). We reviewed 24 frail [Eastern Cooperative Oncology Group performance status (ECOG PS) of 2] or elderly (65 years or over) patients with AGC who received the modified FOLFIRI regimen as salvage chemotherapy. Patients received irinotecan 150 mg/m2 and leucovorin (LV) 100 mg/m2 as a 2 h intravenous infusion, followed by 5-fluorouracil (5-FU) 2,000 mg/m2 as a 46 h continuous infusion. Among the 24 patients, 18 (75%) had an ECOG PS of 2, and 11 (45.8%) were aged 65 years or over. A total of 113 cycles were conducted, with a median number of 4 cycles per patient. A total of 3 patients achieved partial response (PR) and 8 demonstrated stable disease (SD). On an intent-to-treat basis, the overall response rate (RR) was 12.5% and the disease control rate (PR and SD) was 45.8%. The median time to progression (TTP) was 2 months [95% confidence interval (CI), 1.9–2.1 months] and the median overall survival (OS) was 5.4 months (95% CI, 4.1–6.7 months). Grade 3–4 hematological toxicities, including neutropenia, anemia and thrombocytopenia, were observed in 6 (25%), 4 (16.7%) and 1 (4.2%) patients, respectively. Additionally, 3 (12.5%) patients developed febrile neutropenia, of which 1 succumbed to pneumonia. Grade 3–4 gastrointestinal toxicities, including nausea, vomiting, diarrhea and mucositis, were observed in 3 (12.5%), 2 (8.3%), 1 (4.2%) and 1 (4.2%) patients, respectively. In conclusion, the modified FOLFIRI regimen as salvage chemotherapy for AGC patients over 65 years of age or with a poor PS was effective and acceptable. These results suggest that this regimen may be an effective option for frail or elderly patients with AGC.
PMCID: PMC3506675  PMID: 23205095
advanced gastric cancer; FOLFIRI; elderly; poor performance status
9.  Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia associated with neuroendocrine carcinoma: A case report 
Oncology Letters  2012;4(1):86-88.
Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is an in vitro phenomenon of EDTA-induced platelet aggregation at room temperature. This phenomenon consists of platelet clumping due to anti-platelet antibodies in blood anticoagulated with EDTA. It has been reported in patients with various diseases, including sepsis, multiple myeloma, acute myocardial infarction and breast cancer. Since unrecognized EDTA-PTCP may lead to inappropriate treatment, it should always be considered as a possible cause in patients with low platelet counts. This study identified a case of transient EDTA-PTCP in a patient with neuroendocrine carcinoma of the stomach. In the present study, a 50-year-old male presented with epigastric pain and a weight loss of 15 kg. The patient presented with EDTA-PTCP and was diagnosed with neuroendocrine carcinoma of the stomach. Following systemic chemotherapy, the tumor showed a marked regression and the EDTA-PTCP disappeared. The mechanism by which this occurred is not clear but an association of EDTA-PTCP with neuroendocrine carcinoma is strongly suggested.
PMCID: PMC3398370  PMID: 22807967
pseudothrombocytopenia; ethylenediaminetetraacetic acid; neuroendocrine carcinoma
10.  Oxaliplatin, 5-fluorouracil and leucovorin (modified FOLFOX-6) as first-line chemotherapy for advanced gastric cancer patients with poor performance status 
Oncology Letters  2011;3(2):425-428.
This study was designed to retrospectively evaluate the efficacy and safety of modified FOLFOX-6 regimen in advanced gastric cancer (AGC) patients with poor performance status (PS). From January 2005 to August 2010, 23 AGC patients with poor PS who received mFOLFOX-6 as first-line chemotherapy were reviewed. Patients received 100 mg/m2 oxaliplatin and 100 mg/m2 leucovorin (LV) as a 2-h intravenous infusion on day 1, followed by 5-fluorouracil (5-FU) at 2000 mg/m2 as a 46-h continuous infusion. A total of 22 patients received more than 3 cycles of chemotherapy and were evaluable for tumor response. Seven patients achieved partial response, giving an overall response rate of 31.8%. The median time to progression and overall survival were 3.5 and 9.2 months, respectively. Grade 3–4 hematological toxicities were noted: neutropenia in four patients (17.4%), anemia in two (8.7%) and thrombocytopenia in one (4.3%). Two patients developed febrile neutropenia and one of these patients succumbed to sepsis. Grade 3–4 gastrointestinal toxicities, such as nausea, vomiting and diarrhea were observed in less than 10% of patients. Peripheral neuropathy was observed in 9 patients (39.1%). In conclusion, the mFOLFOX-6 regimen for AGC patients with poor PS was effective with acceptable toxicity. Our results suggest that this regimen may be an effective option for these patients.
PMCID: PMC3362383  PMID: 22740925
advanced gastric cancer; modified FOLFOX-6; poor performance status
11.  High-Dose Fentanyl Patch for Cancer Pain of a Patient with Cholangiocarcinoma 
We describe here a patient who obtained a good analgesic effect with high-dose fentanyl patches for controlling cancer pain. A 52-year-old man was referred to our hospital because of severe cancer pain that was 7/10 on a numeric rating scale (NRS). He had been diagnosed with locally advanced cholangiocarcinoma 3 months previously. We prescribed weak opioids and an antidepressant, but his pain was not relieved. We introduced strong opioids (transdermal fentanyl patches for the background pain and a short-acting opioid for the breakthrough pain) and his pain was tolerable on 250 µg/hr of fentanyl patches for 3 months. With time, however, his pain intensity became worse and this reached up to 8/10 to 9/10 on the NRS. Percutaneous transhepatic biliary drainage was performed, which did not relieve his pain. We increased gradually the dose of transdermal fentanyl to 1,050 µg/hr (20 patches). At this dose, the patient was mentally alert, with good pain control (NRS 2/10 to 3/10) and no exacerbation of side effects. To the best of our knowledge, we report here on the highest dose of transdermal fentanyl that has been successfully used for treating a patient suffering from visceral cancer pain.
PMCID: PMC2932949  PMID: 20830233
Fentanyl; Neoplasms; Pain; Cholangiocarcinoma
12.  Duodenal Mucosa-Associated Lymphoid Tissue Lymphoma: A Case Report 
Primary duodenal mucosa associated lymphoid tissue (MALT) lymphoma is very rare, and little is known about its clinical course or effective treatment. We describe a case of primary duodenal MALT lymphoma that was resistant to Helicobacter pylori (H. pylori) eradication and regressed after chemotherapy with cyclophosphamide, vincristine, and prednisolone (CVP). A 71-year-old woman was referred to our department because of epigastric pain and dyspepsia. Gastroduodenoscopy revealed an irregular mucosal nodular lesion with ulceration extending from the bulb to the second portion of the duodenum. Histopathological examination of a biopsy specimen disclosed low-grade MALT lymphoma composed of atypical lymphoid cells with lymphoepithelial lesion. Abdominal CT scans revealed 0.5 to 1.5 cm lymph nodes in the peritoneal cavity, suggestive of lymph node metastasis. We successfully eradicated H. pylori but did not see signs of remission. We administered systemic CVP chemotherapy every 3 weeks. After 6 courses of CVP, the patient achieved complete remission and was followed up without recurrence for about a year.
PMCID: PMC2687664  PMID: 18309692
MALT lymphoma; Duodenum; Helicobacter pylori; Chemotherapy
13.  Non-small Cell Lung Cancer Initially Presenting with Intracardiac Metastasis 
Intracardiac metastasis as the initial presentation of malignant neoplasm is very rare. We report here on a 64-year-old man with non-small cell lung cancer (NSCLC) initially presenting with intracardiac metastasis which was identified with 18-F fluorodeoxyglucose positron emission tomography (FDG PET). The patient was admitted with complaints of exertional dyspnea and vague chest discomfort that had developed a few weeks ago. Two-dimensional echocardiography revealed a heart mass attached to its akinetic wall in the right ventricular chamber. CT and MRI demonstrated a large tumor involving the epicardium and myocardium in the right ventricle, and there was a mass in the right lower lobe of the lung along with multiple lymphadenopathies. Cytologic examination of the percutaneous needle aspiration of a lymph node in the anterior mediastinum revealed malignant epithelial cell nests, and this was strongly suggestive of squamous cell carcinoma. Subsequent FDG PET confirmed that the intracardiac mass had an abnormally increased FDG uptake, and again this was strongly suggestive of malignancy. By systemically considering these imaging studies, we were able to diagnose the mass as intracardiac metastasis of NSCLC.
PMCID: PMC3891420  PMID: 15906960
Cardiac metastasis; Lung cancer; PET
14.  An Adult with Aplastic Crisis induced by Human Parvovirus B19 as an Initial Presentation of Hereditary Spherocytosis 
The association between aplastic crisis and human parvovirus (HPV) B19 infection is well described in patients with sickle cell anemia. This association has also been described, although much less frequently, in patients with hereditary spherocytosis (HS). However, most cases of aplastic crises in patients with HS and induced by HPV B19 have been reported in children or adolescents. In this paper, we describe an aplastic crisis induced by HPV B19 in an adult with HS. A 34-year-old female presented with presyncope, febrile sensation, and myalgia. The complete blood counts showed severe anemia. The peripheral blood smear revealed spherocytosis with reticulocytopenia and pancytopenia. The direct Coombs' test was negative; the osmotic fragility test was positive. In the bone marrow aspirates, a few giant pronormoblasts with deep blue cytoplasm, pseudopods, and intracellular inclusion bodies were observed. The patient was given eight units of packed red blood cells. HPV B19 infection was proven by the presence of IgM antibodies to HPV B19 and the detection of viral DNA using the PCR technique. To the best of our knowledge, this is the first report in Korea that describes an adult with aplastic crisis presenting initially with HS.
PMCID: PMC3891423  PMID: 15906963
Aplastic crisis; Hereditary spherocytosis; Parvovirus B 19; Pancyopenia
15.  The Clinical Utility of FDG PET-CT in Evaluation of Bone Marrow Involvement by Lymphoma 
Bone marrow biopsy is a standard method for the evaluation of bone marrow infiltration by lymphoma; however, it is an invasive and painful procedure. Fluorodeoxyglucose positron emission tomography–computed tomography (FDG PET-CT) is a noninvasive imaging technique with the potential to detect bone marrow involvement by lymphoma.
Materials and Methods
We retrospectively reviewed medical records of lymphoma patients. All patients were examined by FDG PET-CT and iliac crest bone marrow biopsy for initial staging work-up.
The study population comprised 94 patients (median age, 60 years; 56 males) with Hodgkin’s lymphoma (n=8) or non-Hodgkin’s lymphoma (n=86). Maximum standardized uptake values on the iliac crest of patients with lymphoma infiltrated bone marrow were significantly higher than those of patients with intact bone marrow (2.2±1.2 g/mL vs. 1.3±0.4 g/mL; p=0.001). The calculated values for FDG PET-CT during evaluation of bone marrow involvement were as follows: sensitivity 50%, specificity 96%, positive predictive value 80%, negative predictive value 85%, and positive likelihood ratio (LR+) 11.7. The value of LR+ was 16.0 in patients with aggressive subtypes of non-Hodgkin’s lymphoma (NHL).
FDG PET-CT could not replace bone marrow biopsy due to the low sensitivity of FDG PET-CT for detection of bone marrow infiltration in lymphoma patients. Conversely, FDG PET-CT had high specificity and LR+; therefore, it could be a useful tool for image-guided biopsy for lymphoma staging, especially for aggressive subtypes of NHL. In addition, unilateral bone marrow biopsy could be substituted for bilateral bone marrow biopsy in lymphoma patients with increased FDG uptake on any iliac crest.
PMCID: PMC4506116  PMID: 25648095
Lymphoma; Positron-emission tomography; Bone marrow examination
16.  A Muti-center, Randomized Phase II Study of Oxaliplatin and S-1 versus Capecitabine and Oxaliplatin in Patients with Metastatic Colorectal Cancer 
Journal of Cancer  2015;6(10):1041-1048.
Background: Capecitabine plus oxaliplatin (XELOX) is considered one of the primary chemotherapy regimens for patients with metastatic colorectal cancer (CRC). Oxaliplatin plus S-1 (OS) has also demonstrated significant efficacy in CRC. We performed this randomized phase II study to evaluate the efficacy and toxicity of XELOX versus OS as first-line chemotherapy in patients with metastatic CRC.
Methods: Patients were assigned randomly to receive either OS or XELOX chemotherapy. Oxaliplatin was administered intravenously to all patients at a dose of 130 mg/m2 on day 1. Patients received either S-1 (40 mg/m2) or capecitabine (1,000 mg/m2), twice a day for 2 weeks, followed by a 1-week rest.
Results: Forty-two patients were assigned to the OS arm and 44 to the XELOX arm. The overall response rate was 33.3% (95% CI, 18.8-47.2) in the OS arm and 40.9% (95% CI, 25.5-54.4) in the XELOX arm (P = 0.230). The disease control rate was significantly higher in the OS arm than the XELOX arm [92.9% (95% CI, 83.7-100) versus 77.3% (95% CI, 64.5-89.4), P = 0.044]. With a median follow up of 17.9 months, the median progression-free survival was 6.1 months in the OS arm and 7.4 months in the XELOX arm, respectively (P = 0. 599). The median survival time was 18.7 months in the OS arm and 20.1 months in the XELOX arm (P = 0.340). The most common grade 3/4 hematologic toxicity was thrombocytopenia in both arms (19.0% for OS and 28.6% for XELOX). Grade 3/4 neutropenia was observed more frequently in the XELOX arm than the OS arm (16.7% vs. 2.4%, P = 0.026).
Conclusion: Both OS and XELOX were effective and well tolerated in patients with metastatic CRC. Our results indicate that the combination of oxaliplatin and S-1 is a possible additional therapeutic strategy for such patients.
PMCID: PMC4565854  PMID: 26366218
Colorectal neoplasm; Oxaliplatin; S-1; Capecitabine; Randomized controlled trial
17.  Adult Multisystem Langerhans Cell Histiocytosis Presenting with Central Diabetes Insipidus Successfully Treated with Chemotherapy 
Endocrinology and Metabolism  2014;29(3):394-399.
We report the rare case of an adult who was diagnosed with recurrent multisystem Langerhans cell histiocytosis (LCH) involving the pituitary stalk and lung who present with central diabetes insipidus and was successfully treated with systemic steroids and chemotherapy. A 49-year-old man visited our hospital due to symptoms of polydipsia and polyuria that started 1 month prior. Two years prior to presentation, he underwent excision of right 6th and 7th rib lesions for the osteolytic lesion and chest pain, which were later confirmed to be LCH on pathology. After admission, the water deprivation test was done and the result indicated that he had central diabetes insipidus. Sella magnetic resonance imaging showed a mass on the pituitary stalk with loss of normal bright spot at the posterior lobe of the pituitary. Multiple patchy infiltrations were detected in both lung fields by computed tomography (CT). He was diagnosed with recurrent LCH and was subsequently treated with inhaled desmopressin, systemic steroids, vinblastine, and mercaptopurine. The pituitary mass disappeared after two months and both lungs were clear on chest CT after 11 months. Although clinical remission in multisystem LCH in adults is reportedly rare, our case of adult-onset multisystem LCH was treated successfully with systemic chemotherapy using prednisolone, vinblastine, and 6-mercaptopurine, which was well tolerated.
PMCID: PMC4192804  PMID: 25309800
Histiocytosis, Langerhans-cell; Drug therapy; Diabetes insipidus
18.  Predictors of high score patient-reported barriers to controlling cancer pain: a preliminary report 
Pain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient’s part can cause major obstacles in pain management.
We evaluated factors associated with patient’s high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory—Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed.
The patients were from nine oncology clinics in university hospitals and a veterans’ hospital in South Korea. The median pain score (0–10 scale) was 4, with a median percentage of pain improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale.
Depression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.
PMCID: PMC3881357  PMID: 23151648
Cancer; Depression; Pain management
19.  Comparison of RECIST version 1.0 and 1.1 in assessment of tumor response by computed tomography in advanced gastric cancer 
Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0 (RECIST 1.0) was proposed as a new guideline for evaluating tumor response and has been widely accepted as a standardized measure. With a number of issues being raised on RECIST 1.0, however, a revised RECIST guideline version 1.1 (RECIST 1.1) was proposed by the RECIST Working Group in 2009. This study was conducted to compare CT tumor response based on RECIST 1.1 vs. RECIST 1.0 in patients with advanced gastric cancer (AGC).
We reviewed 61 AGC patients with measurable diseases by RECIST 1.0 who were enrolled in other clinical trials between 2008 and 2010. These patients were retrospectively re-analyzed to determine the concordance between the two response criteria using the κ statistic.
The number and sum of tumor diameters of the target lesions by RECIST 1.1 were significantly lower than those by RECIST 1.0 (P<0.0001). However, there was excellent agreement in tumor response between RECIST 1.1 and RECIST 1.0 (κ=0.844). The overall response rates (ORRs) according to RECIST 1.0 and RECIST 1.1 were 32.7% (20/61) and 34.5% (20/58), respectively. One patient with partial response (PR) based on RECIST 1.0 was reclassified as stable disease (SD) by RECIST 1.1. Of two patients with SD by RECIST 1.0, one was downgraded to progressive disease and the other was upgraded to PR by RECIST 1.1.
RECIST 1.1 provided almost perfect agreement with RECIST 1.0 in the CT assessment of tumor response of AGC.
PMCID: PMC3872539  PMID: 24385696
Response Evaluation Criteria in Solid Tumors guideline version 1.0 (RECIST 1.0); Response Evaluation Criteria in Solid Tumors guideline version 1.1 (RECIST 1.1); gastric cancer; tumor response
20.  Cushing syndrome in pregnancy secondary to adrenal adenoma 
Obstetrics & Gynecology Science  2013;56(6):400-403.
We report a case of Cushing syndrome secondary to adrenal adenoma presenting with hypertension and oligohydramnios during pregnancy. The tumor was confirmed by magnetic resonance imaging at 28 week 3 day weeks of pregnancy and was removed surgically at 29 week 1 day weeks of gestation. After surgery, hypertension subsided and amniotic fluid volume returned to normal range. The gravid woman subsequently delivered a healthy infant at term.
PMCID: PMC3859012  PMID: 24396819
Adrenocortical adenoma; Adrenalectomy; Cushing syndrome; Oligohydramnios; Pregnancy
21.  A Phase II Study to Evaluate the Efficacy of Ramosetron, Aprepitant, and Dexamethasone in Preventing Cisplatin-Induced Nausea and Vomiting in Chemotherapy-Naïve Cancer Patients 
Combination therapy with aprepitant, serotonin receptor antagonist, and steroids improves the complete response rate of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). However, it is not known whether ramosetron is suitable for administration in combination with aprepitant. Therefore, we conducted a multicenter, open-label, prospective, phase II study in order to assess the efficacy and tolerability of combination therapy with ramosetron, aprepitant, and dexamethasone (RAD) for prevention of cisplatin-based CINV in chemotherapy-naïve patients with solid cancers.
Materials and Methods
Forty-one patients with various solid cancers (31 male and 10 female; median age, 59 years) who received treatment with highly emetogenic chemotherapy (median cisplatin dose, 70 mg/m2; range 50 to 75 mg/m2) were enrolled in this study. Oral aprepitant (125 mg on day 1; 80 mg on days 2 and 3), intravenous ramosetron (0.6 mg on day 1), and oral dexamethasone (12 mg on day 1; 8 mg on days 2-4) were administered for prevention of CINV.
The complete response (no emesisand retching and no rescue medication) rate was 94.9% in the acute period (24 hours post-chemotherapy), 92.3% in the delayed period (24-120 hours post-chemotherapy), and 92.3% in the overall period (0-120 hours). The absolute complete response (complete response plus no nausea) rate was 74.4% in the acute period, 51.3% in the delayed period, and 46.2% in the overall period. There were no grade 3 or 4 toxicities related to these antiemetic combinations.
RAD regimen is a safe and effective antiemetic treatment for prevention of CINV in patients receiving highly emetogenic chemotherapy.
PMCID: PMC3804728  PMID: 24155675
Aprepitant; Dexamethasone; Ramosetron; Chemotherapy-induced nausea and vomiting
22.  Experience of treatment of patients with granulomatous lobular mastitis 
To present the author's experience with various treatment methods of granulomatous lobular mastitis (GLM) and to determine effective treatment methods of GLM.
Fifty patients who were diagnosed with GLM were classified into five groups based on the initial treatment methods they underwent, which included observation (n = 8), antibiotics (n = 3), steroid (n = 13), drainage (n = 14), and surgical excision (n = 12). The treatment processes in each group were examined and their clinical characteristics, treatment processes, and results were analyzed respectively.
Success rates with each initial treatment were observation, 87.5%; antibiotics, 33.3%; steroids, 30.8%; drainage, 28.6%; and surgical excision, 91.7%. In most cases of observation, the lesions were small and the symptoms were mild. A total of 23 patients underwent surgical excision during treatment. Surgical excision showed particularly fast recovery, high success rate (90.3%) and low recurrence rate (8.7%).
The clinical course of GLM is complex and the outcome of each treatment type are variable. Surgery may play an important role when a lesion is determined to be mass-forming or appears localized as an abscess pocket during breast examination or imaging study.
PMCID: PMC3699681  PMID: 23833753
Breast; Granulomatous mastitis; Treatment; Excision
23.  Clinical Results Associated with Changes of Posterior Tibial Slope in Total Knee Arthroplasty 
The purpose of this retrospective study is to investigate the effect of posterior tibial slope (PTS) on clinical results in total knee replacement arthroplasty (TKA).
Materials and Methods
We analyzed 801 knees in 768 patients who underwent TKA using a cruciate-retaining prosthesis for osteoarthritis from July 2003 to July 2009. PTS was measured on simple X-ray films and patients were divided into 5 groups, according to the change in PTS that was calculated by subtracting the preoperative from the postoperative PTS: group 1, >3°; group 2, 3° to 1°; group 3, 1° to -1°; group 4, -1° to -3°; and group 5, <-3°. We analyzed the correlations between the change in PTS and clinical results, such as Knee Society knee score, Knee Society functional score, Feller patella score, Kujala score, visual analog scale score, range of motion, and complications.
There was no statistically significant intergroup difference; however, Feller patella score and Kujala score were significantly different in groups 2 and 3. There were no complications, such as progressive loosening of implants, fractures of polyethylene inserts and wears.
Clinically meaningful improvement was observed in all patients after TKA. Groups 2 and 3 (3° to -1°) showed significant improvement compared to the other groups.
PMCID: PMC3597842  PMID: 23508238
Total knee replacement; Arthroplasty; Knee; Posterior tibial slope
24.  Validation of a Web-Based Tool to Predict the Ipsilateral Breast Tumor Recurrence (IBTR! 2.0) after Breast-Conserving Therapy for Korean Patients 
Journal of Breast Cancer  2013;16(1):97-103.
IBTR! 2.0 is a web-based nomogram that predicts the 10-year ipsilateral breast tumor recurrence (IBTR) rate after breast-conserving therapy. We validated this nomogram in Korean patients.
The nomogram was tested for 520 Korean patients, who underwent breast-conserving surgery followed by radiation therapy. Predicted and observed 10-year outcomes were compared for the entire cohort and for each group, predefined by nomogram-predicted risks: group 1, <3%; group 2, 3% to 5%; group 3, 5% to 10%; group 4, >10%.
In overall patients, the overall 10 year predicted and observed estimates of IBTR were 5.22% and 5.70% (p=0.68). In group 1, (n=124), the predicted and observed estimates were 2.25% and 1.80% (p=0.73), in group 2 (n=177), 3.95% and 3.90% (p=0.97), in group 3 (n=181), 7.14% and 8.80% (p=0.42), and in group 4 (n=38), 11.66% and 14.90% (p=0.73), respectively.
In a previous validation of this nomogram based on American patients, nomogram-predicted IBTR rates were overestimated in the high-risk subgroup. However, our results based on Korean patients showed that the observed IBTR was higher than the predicted estimates in groups 3 and 4. This difference may arise from ethnic differences, as well as from the methods used to detect IBTR and the healthcare environment. IBTR! 2.0 may be considered as an acceptable nomogram in Korean patients with low- to moderate-risk of in-breast recurrence. Before widespread use of this nomogram, the IBTR! 2.0 needs a larger validation study and continuous modification.
PMCID: PMC3625777  PMID: 23593089
Breast neoplasms; Nomograms; Radiotherapy; Recurrence; Validation studies
25.  Subcongenic analysis of tabw2 obesity QTL on mouse chromosome 6 
BMC Genetics  2012;13:81.
We previously established a congenic mouse strain with TALLYHO/Jng (TH) donor segment on chromosome 6 in a C57BL/6 (B6) background that harbors an obesity quantitative trait locus, tabw2. The B6.TH-tabw2 congenic mice developed increased adiposity that became exacerbated upon feeding a high fat-high sucrose (HFS) diet. To fine map the tabw2, in this study we generated and characterized subcongenic lines with smaller TH donor segments.
We fixed four subcongenic lines, with maximum size of donor segment retained in the lines ranging from 10.8 – 92.5 Mb. For mapping, all the subcongenic mice, along with B6.TH-tabw2 congenic and B6-homozygous control mice were fed either chow or HFS diets, and their post-mortem fat pads were weighed. Mice were also characterized for energy expenditure, respiratory exchange ratio, locomotor activity, and food intake. As previously reported, B6.TH-tabw2 congenic mice showed a significantly larger fat mass than controls on both diets. On chow, a subcongenic line retaining the distal region of the TH donor congenic interval exhibited significantly larger fat mass than B6-homozygous controls, and comparable that to B6.TH-tabw2 congenic mice. Two nested subcongenic lines within that region suggested that the effect of tabw2 on obesity could be attributed to at least two subloci. On HFS diets, on the other hand, all the subcongenic mice had significantly larger fat mass than controls without genotype differences, but none of them had fat mass as large as the original congenic mice. This possibly implicates that further genetic complexity involves in the effect of tabw2 on diet-induced obesity. Significantly reduced locomotor activity was exhibited in B6.TH-tabw2 congenic and subcongenic mice compared to controls when animals were fed HFS diets. B6.TH-tabw2 congenic mice, but not subcongenic mice, also had significantly increased food intake on HFS diets.
It appears that at least two subloci explaining the tabw2 effect under chow feeding map to the distal region of the congenic interval, whereas the diet-induced obesity mediated by tabw2 is attributed to more complex genetic mechanism.
PMCID: PMC3519667  PMID: 23025571

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