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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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
18.  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
19.  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
20.  Adjuvant Chemotherapy and Survival of Elderly Korean Patients with Breast Carcinoma 
Journal of Breast Cancer  2012;15(3):296-305.
The available research work on types of treatment and the efficacy of adjuvant chemotherapy in older Korean patients is insufficient. Henceforth, this report assessed treatment patterns and the relationship between chemotherapy and survival in elderly Korean breast cancer patients.
We identified women over 55 years of age diagnosed with breast cancer from the period 1995 to 2006. Clinicopathologic features and treatment methods were compared for three groups divided on the basis of age: 55 to 59 years, 60 to 69 years, and over 70 years old. The effects of chemotherapy on survival were compared overall and individually for each group.
A total of 832 patients over 55 years of age were included in the present investigation. No statistical differences were observed between the three age groups in clinicopathologic features including tumor size, grade, and stage. However, patients in the elderly group received mastectomy more often when compared to the younger groups (p<0.001). In contrast, there was a decline in radiation treatment and chemotherapy with older age (p<0.001). Overall, patients who received chemotherapy had a significantly increased breast cancer specific survival and overall survival rate when compared to the non-chemotherapy groups (p=0.022). Among the estrogen receptor positive group, no statistical significance was achieved in the survival benefit of chemotherapy. However, in estrogen receptor-negative patients, overall, the chemotherapy groups showed a better survival rate than the non-chemotherapy patients and a similar trend was observed in each age group except in the group comprising of 70 years old patients.
This study describes the survival benefit of adjuvant chemotherapy in Korean patients over 55 years of age, especially in hormone receptor-negative patients. Hence, based on the results of the present report and considering the similarity of clinicopathologic features between age groups, it is proposed that age alone should not be a determinant factor of treatment methods.
PMCID: PMC3468783  PMID: 23091542
Aged; Breast; Carcinoma; Chemotherapy; Survival
21.  Invasive Pleomorphic Lobular Carcinoma of the Breast: Clinicopathologic Characteristics and Prognosis Compared with Invasive Ductal Carcinoma 
Journal of Breast Cancer  2012;15(3):313-319.
Invasive pleomorphic lobular carcinoma (IPLC) is a very rare and distinct morphological variant of invasive lobular carcinoma (ILC), characterized by nuclear atypia and pleomorphism contrasted with the cytologic uniformity of ILC. This study evaluated clinicopathologic characteristics and prognosis of IPLC compared with invasive ductal carcinoma (IDC).
We retrospectively reviewed the medical records of 35 patients with IPLC and 6,184 patients with IDC, not otherwise specified. We compared the clinicopathologic characteristics, relapse-free survival (RFS) and disease specific survival (DSS) of patients who were surgically treated between January 1997 and December 2010.
Patients with IPLC presented at an older age with larger tumor size, worse histologic grade, higher rates of N3 stage, more multifocal/multicentric tumors, and more nipple-areolar complex involvement than those of patients with IDC. During the follow-up period, the IPLC group experienced five cases (14.3%) of disease recurrence and three cases (8.6%) of disease specific mortality compared with 637 cases (10.4%) of recurrence and 333 cases (5.4%) of disease specific mortality in the IDC group. Univariate analysis using the Kaplan-Meier method revealed that the IPLC group showed a significantly poorer prognosis than that of the IDC group (RFS, p=0.008; DSS, p<0.001). However, after adjusting for clinicopathologic factors, a multivariate analysis showed no statistical differences in RFS (p=0.396) and DSS (p=0.168) between the IPLC and the IDC groups.
Our data suggest that patients with IPLC present with poor prognostic factors such as large tumor size, poor histologic grade and advanced stage at diagnosis. These aggressive clinicopathologic characteristics may result in poor clinical outcomes. Although our study could not link IPLC histology to poor prognosis, considering the aggressive characteristics of IPLC, early detection and considerate treatment, including proper surgical and adjuvant intervention, could be helpful for disease progression and survival.
PMCID: PMC3468785  PMID: 23091544
Breast; Lobular carcinoma; Prognosis
22.  Endoscopic Treatment of Duodenal Bleeding Caused by Direct Hepatocellular Carcinoma Invasion with an Ethanol Injection 
Gut and Liver  2012;6(1):122-125.
We report a case of a man who developed duodenal bleeding caused by direct hepatocellular carcinoma (HCC) invasion, which was successfully treated with endoscopic ethanol injection. A 57-year-old man with known HCC was admitted for melena and exertional dyspnea. He had been diagnosed with inoperable HCC a year ago. Urgent esophagogastroduodenoscopy (EGD) showed two widely eroded mucosal lesions with irregularly shaped luminal protruding hard mass on the duodenal bulb. Argon plasma coagulation and Epinephrine injection failed to control bleeding. We injected ethanol via endoscopy to control bleeding two times with 14 cc and 15 cc separately without complication. Follow-up EGD catched a large ulcer with necrotic and sclerotic base but no bleeding evidence was present. He was discharged and he did relatively well during the following periods. In conclusion, Endoscopic ethanol injection can be used as a significantly effective and safe therapeutic tool in gastrointestinal tract bleeding caused by HCC invasion.
PMCID: PMC3286730  PMID: 22375182
Endoscopic treatment; Ethanol injection; Duodenal bleeding; Hepatocellular carcinoma
23.  Transgenic Mice Overexpressing Renin Exhibit Glucose Intolerance and Diet-Genotype Interactions 
Numerous animal and clinical investigations have pointed to a potential role of the renin-angiotensin system (RAS) in the development of insulin resistance and diabetes in conditions of expanded fat mass. However, the mechanisms underlying this association remain unclear. We used a transgenic mouse model overexpressing renin in the liver (RenTgMK) to examine the effects of chronic activation of RAS on adiposity and insulin sensitivity. Hepatic overexpression of renin resulted in constitutively elevated plasma angiotensin II (four- to six-fold increase vs. wild-type, WT). Surprisingly, RenTgMK mice developed glucose intolerance despite low levels of adiposity and insulinemia. The transgenics also had lower plasma triglyceride levels. Glucose intolerance in transgenic mice fed a low-fat diet was comparable to that observed in high-fat fed WT mice. These studies demonstrate that overexpression of renin and associated hyperangiotensinemia impair glucose tolerance in a diet-dependent manner and further support a consistent role of RAS in the pathogenesis of diabetes and insulin resistance, independent of changes in fat mass.
PMCID: PMC3538348  PMID: 23308073
adipose tissue; renin-angiotensin system; insulin resistance; angiotensin II
24.  Does Immediate Breast Reconstruction after Mastectomy affect the Initiation of Adjuvant Chemotherapy? 
Journal of Breast Cancer  2011;14(4):322-327.
The frequency of immediate breast reconstruction (IBR) is increasing, and the types of reconstruction used are diverse. Adjuvant chemotherapy is a life-saving intervention in selected high-risk breast cancer patients. The aim of our study was to determine how IBR and type of reconstruction affect the timing of the initiation of chemotherapy.
We obtained data from female breast cancer patients treated by mastectomy with IBR (IBR group) and without IBR (mastectomy only group) who received adjuvant chemotherapy between January 1, 2008, and December 31, 2010. We retrospectively collected data including patient characteristics, disease characteristics, treatment details, and treatment outcomes from our institutional electronic patient database and medical treatment records. The reconstruction types were categorized as deep inferior epigastric perforator (DIEP) flap, latissimus dorsi (LD) flap and tissue expander/implant (TEI).
In total, 595 patients were included in this study. Of these patients, 43 underwent mastectomy with IBR (IBR group) and 552 patients did not undergo reconstruction (mastectomy only group). There was significant difference in the timing of the initiation of chemotherapy between the two groups (p<0.0001). There were no cases of delays of more than 12 weeks. In the IBR group, 20 patients received TEI, 9 patients were treated by the insertion DIEP flaps, and 14 patients were treated by LD flaps. There were no significant differences in the timing of chemotherapy according to the type of reconstruction (p=0.095).
IBR delays the initiation of chemotherapy, but does not lead to omission or significant clinical delay in chemotherapy. Further, the type of reconstruction does not affect the timing of chemotherapy.
PMCID: PMC3268930  PMID: 22323920
Adjuvant chemotherapy; Breast neoplasms; Breast reconstruction
25.  Results from Over One Year of Follow-Up for Absorbable Mesh Insertion in Partial Mastectomy 
Yonsei Medical Journal  2011;52(5):803-808.
Recently, several clinicians have reported the advantages of simplicity and cosmetic satisfaction of absorbable mesh insertion. However, there is insufficient evidence regardint its long-term outcomes. We have investigated the surgical complications and postoperative examination from the oncologic viewpoint.
Materials and Methods
From February 2008 to March 2009, 34 breast cancer patients underwent curative surgery with absorbable mesh insertion in Samsung Medical Center. Patient characteristics and follow up results including complications, clinical and radiological findings were retrospectively investigated.
The mean age of the study population was 50.1±8.9 years old (range 31-82) with a mean tumor size of 3±1.8 cm (range 0.8-10.5), and the excised breast tissue showed a mean volume of 156.1±99.8 mL (range 27-550). Over the median follow-up period of 18±4.6 months (range 3-25), mesh associated complications, including severe pain or discomfort, edema, and recurrent fluid collection, occurred in nine patients (26.5%). In three cases (8.8%), recurrent mastitis resulted in mesh removal or surgical intervention. In the postoperative radiologic survey, the most common finding was fluid collection, which occurred in five patients (16.1%), including one case with organizing hematoma. Fat necrosis and microcalcifications were found in three patients (9.7%).
Absorbable mesh insertion has been established as a technically feasible, time-saving procedure after breast excision. However, the follow-up results showed some noticeable side effects and the oncologic safety of the procedure is unconfirmed. Therefore, we suggest that mesh insertion should be considered only in select cases and should be followed-up carefully.
PMCID: PMC3159934  PMID: 21786446
Breast neoplasms; mastectomy; segmental; absorbable implants

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