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Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

  • Petric, Militza;Martinez, Santiago;Acevedo, Francisco;Oddo, David;Artigas, Rocio;Camus, Mauricio;Sanchez, Cesar
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10277-10280
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    • 2015
  • Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

Hypofractionated Radiotherapy for Breast Cancers - Preliminary Results from a Tertiary Care Center in Eastern India

  • Nandi, Moujhuri;Mahata, Anurupa;Mallick, Indranil;Achari, Rimpa;Chatterjee, Sanjoy
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2505-2510
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    • 2014
  • Background: The standard radiotherapy (RT) fractionation practiced in India and worldwide is 50Gy in 25 fractions over 5 weeks to the chest wall or whole breast followed by tumour bed boost in case of breast conservation (BCS). A body of validated data exists regarding hypofractionation in breast cancer. We here report initial results for 135 patients treated at our center with the START-B type of fractionation. Materials and Methods: From May 2011 till July 2012, women with all stages of breast cancer (excluding metastatic), who had undergone BCS or mastectomy were planned for 40Gy in 15 fractions over 3weeks to chest wall/whole breast and supraclavicular fossa (where indicated) followed by tumour bed boost in BCS patients. Planning was done using Casebow's technique. The primary end point was to assess the acute toxicity and the cosmetic outcomes. Using cosmetic scales; patients were assessed during radiotherapy and at subsequent follow up visits with the radiation oncologist. Results: Of the 135 patients, 62 had undergone BCS and 73 mastectomy. Median age of the population was 52 years. Some 80% were T1&T2 tumours in BCS whereas most patients in mastectomy group were T3&T4 tumours (60%). 45% were node negative in BCS group whilst it was 23% in the mastectomy group. Average NPI scores were 3.9 and 4.9, respectively. Most frequently reported histopathology report was infiltrating ductal carcinoma (87%), grade III being most common (58%), and 69% were ER positive tumours, and 30% were Her 2 Neu positive. Triple negative tumours accounted for 13% and their mean age was young (43 yrs.) The maximum acute skin toxicity at the end of treatment was Grade 1 in 94% of the mastectomy grouppatients and 71% in BCS patients. Grade 2 toxicity was 6% in mast group and 23% in BCS group. Grade 3 was 6% in BCS group, no grade 3 toxicity in mastectomy patients and there was no grade 4 skin toxicity in any case. Post RT at 1 month; 39% of BCS patients had persisting Grade I skin reaction which was only 2% in mastectomy patients. At 3 months post RT, 18% patients had persisting hyperpigmentation. At 6 months 8% patients had persisting erythema in the BCS group only. Some 3% BCS and 8% mastectomy patients had lymph edema till the date of evaluation. Cosmetic outcome in BCS patients remained good to excellent 6 months post surgery and radiotherapy. 1 patient of BCS and 3 patients of mast had developed metastatic disease at the time of evaluation. Conclusions: Hypofractionated RT is well tolerated in Indian population with reduced acute skin toxicity and good cosmetic outcome. Regimens such as these should be encouraged in other centers to increase machine output time. The study is on-going to assess long term results.

Angiogenesis Markers in Breast Cancer - Potentially Useful Tools for Priority Setting of Anti-Angiogenic Agents

  • Keyhani, Elahe;Muhammadnejad, Ahad;Behjati, Farkhondeh;Sirati, Fereidoon;Khodadadi, Faranak;Karimlou, Masoud;Moghaddam, Fatemeh A.;Pazhoomand, Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7651-7656
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    • 2013
  • Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

A Study on Adhesion Characteristics and Physical Properties of Animal Glue Added Genipin (제니핀을 첨가한 아교의 접착 특성과 물성 변화 연구)

  • Lee, Jun Ho;Yu, Ji A;Chung, Yong Jae
    • Journal of Conservation Science
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    • v.34 no.3
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    • pp.157-166
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    • 2018
  • In this study, gelatin binding ability was increased by adding cross linking agent to improve adhesive characteristic of animal glue. Animal glue added genipin measured gel strength and viscosity, the structural analysis, the color retention degree, elution degree, and rupture strength. And the water resistance and ultraviolet light resistance with the addition of genipin were compared. As a result of the study, the gel strength and viscosity increased with the amount of genipin. As a result of the structural analysis, in gelatin, the absorption peak of the triple structure of collagen structurally stabilized was observed. As a result of the color retention degree, the film was observed because of the lowered brightness. The amount of elution glue was increased with addition of genipin at $50^{\circ}C$ distilled water condition and rupture strength has increased with the amount of genipin. In the water resistance and light fastness, there was no appearance before and after deterioration due to the addition of genipin. Based on the results of this study, it confirmed the adhesive characteristics of animal glue added genipin and examined the experimental method applicable for animal glue. After the addition of genipin, flexibility, re-solving, adhesive force, and curing speed, which are unique characteristics of glue, can be improved without disappearing, so it is expected that it will be applicable to production of animal glue and conservation of cultural heritage when homogeneous glue is secured.

The Efficacy of P2Y12 Reactive Unit to Predict the Periprocedural Thromboembolic and Hemorrhagic Complications According to Clopidogrel Responsiveness and Safety of Modification of Dual Antiplatelet Therapy : A Meta-Analysis

  • Kim, Hyun Jung;Oh, Jae Sang;Park, Sukh Que;Yoon, Seok Mann;Ahn, Hyeong Sik;Kim, Bum Tae
    • Journal of Korean Neurosurgical Society
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    • v.63 no.5
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    • pp.539-549
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    • 2020
  • The efficacy of P2Y12 reaction unit (PRU) of VerifyNow still remains as a controversial issue in neurointervention. So we investigated the usefulness of PRU of VerifyNow to predict the peri-procedural thromboembolic events (TE) and hemorrhagic events (HE). And we evaluated the safety of modified dual antiplatelet therapy (DAPT) or triple antiplatelet therapy (TAPT) for clopidogrel hyporesponders. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus on August 19 2018. Data was collected the 1) incidence of TE between clopidogrel responder and clopidogrel hypo-responder, 2) incidence of HE between clopidogrel hyper-responder and clopidogrel responder and hypo-responder, and 3) incidence of TE and HE between modified DAPT or TAPT and standard DAPT in clopidogrel hypo-responder. High cut-off value of PRU was defined as PRU >40% or <220. Fifteen studies were enrolled. Clopidogrel responder showed lower incidence of TE than hypo-responder (risk ratio [RR], 0.32; 95% confidence interval [CI], 0.17-0.61; p<0.001). With the high cut-off value of PRU, clopidogrel responder showed more lower incidence of TE than hypo-responder (RR, 0.11; 95% CI, 0.02-0.45; p=0.002). The incidence of periprocedural HE have higher on clopidogrel hyper-responder than clopidogrel responder and hypo-responder (RR, 4.26; 95% CI, 1.10-16.44; p=0.04; I2=66%). The incidence of periprocedural TE after changing regimen of DAPT for clopidogrel hypo-responder have a tendency to reduce, but there was no significant difference between modified DAPT or TAPT group and standard DAPT group (p>0.05). The incidence of periprocedural HE after changing regimen of DAPT for clopidogrel hypo-responder was no significant difference between modified DAPT or TAPT group and standard DAPT group (p>0.05). PRU is a useful tool as a predictor of peri-procedural TE or HE on neurointervention. PRU has a threshold effect of cut-off value to predict the peri-procedural TE. Modified DAPT or TAPT to prevent TE in clopidogrel hypo-responders could not reduce the incidence of TE. We should investigate the further research about modification of regiment on neurointervention.

Annual report of thoracic and cardiovascular surgery in Korea [II] (흉부외과 진료통계( II ) -1992년-)

  • Sun, Kyung;Kwak, Young-Tae;Kim, Hyoung-Mook
    • Journal of Chest Surgery
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    • v.26 no.3
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    • pp.163-169
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    • 1993
  • This is the result of the annual statistic analysis of thoracic and cardiovascular surgical cases in 1992 Korea. Overall 17, 520 cases of surgery [11, 732 cases of thoracic surgery by 54 institutes / 5, 788 cases of cardiovascular surgery by 48 institutes] were done. 1. Tumor [N=2, 532] : Lung was the most frequently involved organ by tumor [54.9%],and the remainders were mediastinum [16.2%] / esophagus [14.8%] / chest wall [11.7%] / tracheobronchus [1.3%] / pleura [1.1%] in order. Of 1, 082 cases of primary lung cancer surgery,the frequency of cell type was squamous [62.6%] / adeno [21.6%] / small cell [7.1%] / large cell [2.7%]. Of 411 cases of mediastinal tumor surgery,the frequency of cell type was neurogenic [28.8%] / thymoma [27.6%] / teratoma [17.7%] / congenital cystic [17.2%]. Of 376 cases of esophageal tumor surgery,primary cancer were the most [85.4%]. 2. Infection [N=3, 157] : Pleura was the most frequently involved organ [59.0%],and the remainders were lung [31.3%] / chest wall [8.6%] / mediastinum [1.1%] in order. 3. Miscellaneous [N=6, 043] : Lung and pleural disease esp. pneumothorax [85.1%] was the most frequent surgical indication. The remainders were chest wall anomaly [3.4%] / benign esophageal disease [3.4%] / diaphragmatic pathology [2.4%] / myasthenia [1.4%] in order. Of 85 cases of thymectomy for myasthenia gravis,thymoma was noted in 58.8%. 1. Congenital heart disease [N=3, 363] : The ratio of noncyanotic to cyanotic heart disease was 3:1. Of 2, 516 cases of noncyanotic heart disease,the frequency of disease entity was VSD [44.1%] / ASD [26.0%] / PDA [19.4%] / PS [3.3%],and that of 847 cases of cyanotic heart disease was TOF [29.4%] / ECD [15.6%] / TGA [9.7%] / DORV [7.6%]. Overall mortalities were 2.1% in noncyanotic and 12.2% in cyanotic heart surgery. 2. Acquired heart disease [N=1, 929] : Of 1, 422 cases of valvular surgery,single mitral pathology was the most frequent candidate [48.0%],and total 1, 574 prosthetic valves which were mainly mechanical [95.6%] were used. Of 376 cases of coronary surgery,triple vessel was the most [35.9%],and the frequency of bypassing grafts was great saphenous vein [52.9%] / internal mammary artery [44.7%] / artificial vessel [2.4%]. Overall mortalities were 3.4% in valvular and 4.5% in coronary surgery. 3. Pericardium,Cardiac tumor,Arrhythmia,Aortic aneurysm,Assist device,and Pacemaker : There were no specific changes compared to previous survey1]. This nation-wide inquiry will be continued and reported annually by KTCS Society.

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Long-term clinical results of the xenograft cardiac valves (이종조직판막의 장기임상성적)

  • 김종환
    • Journal of Chest Surgery
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    • v.20 no.2
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    • pp.289-299
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    • 1987
  • A total of 1,239 patients had cardiac valve replacement using 1,514 substitute valves at Seoul National University Hospital from 1968 to 1986. Of the total substitute vales, 84.9% were the glutaraldehyde-treated xenograft valves. Six hundred ninety-four patients who had 820 bioprosthetic tissue valves were studied for their clinical characteristics. They were a total and consecutive cases to the end of the study. Four hundred sixty-four patients had the lonescu-Shiley pericardial valves: MVR 291, AVR 66 and MVR+AVR 107; 163 had the Hancock porcine valves; 46 had the Angell-Shiley porcine valves; and 21 had the Carpentier-Edwards porcine valves. Five hundred forty patients underwent single valve replacement: MVR 460, AVR 76 and TVR 4; 154 had multiple valve replacement: MVR+AVR 141, MVR+TVR 12 and one triple valve replacement. Additional surgery was necessary in 22.3% of the cases. Operative mortality rate within 30 days of surgery was 6.77% for the total patients: 5.2% and 4.2% with MVR, 13.6% and 12.5% with AVR, and 7.5% and 7.4% with MVR+AVR using the lonescu and the Hancock valves respectively. A linealized annual late mortality rate was 2.56%/patient-year. Six hundred forty-three operative survivors were followed up for a total of 1482.7 patient-years [a mean 27.7 months], and the follow-up rate was 67.7%. The Idealized complication rates were: 2.02% emboli/patient-year, 0.94% bleeding/patient-year, 1.21% endocarditis/patient-year, and 3.84% overall valve failure/patient-year. A linealized rate of primary tissue failure was 0.87%/patient-year. Actuarial survival rates including the operative mortality were: 87.8*2.6%, 82.3*4.9% and 82.2*4.7% with MVR, AVR and MVR+AVR using the lonescu valves at 4 years after surgery respectively; and they were 88.0*4.1% with MVR at 8 years, 82.3*4.9% with AVR at 4 years and 84.9*7.0% with MVR+AVR at 6 years after surgery using the Hancock valves respectively. Probabilities of freedom from thromboembolism were 89.8*6.3% with MVR using the lonescu valves at postoperative 5 years and 89.2*3.8% with MVR using the Hancock valves at postoperative 7 years, and 93.3*3.9% with AVR using the lonescu valves at postoperative 5 years. None had embolic complication after AVR using the Hancock valves. Probabilities of freedom from valve failure [according to the Stanford criteria] were 81.0*7.1% with MVR using the lonescu valves at postoperative 4 years and 57.4*12.5% with MVR using the Hancock valves at postoperative 9 years. These clinical results prove the excellent antithrombogenicity of the glutaraldehyde-treated xenograft substitute valves and confirm the previously speculated rate of tissue failure. At the present situation, it may be concluded that there is a room for the further development of more durable bioprosthetic valves.

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Behcet`s Syndrome with Aortic Aneurysm: A Case Report (Bechet`s 병과 합병된 상부대동맥류: 치험 1례 보고)

  • Gang, Jeong-Ho;Lee, Jeong-Ho;Yu, Hoe-Seong
    • Journal of Chest Surgery
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    • v.10 no.1
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    • pp.98-105
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    • 1977
  • A 36 year old blindman, engineer was admitted with chief complaints of hemoptysis, recurrent sore throat, pyoderma in genital organ, uveitis and thrombophlebitis for 10 years. Above the chief complaints were remission or exacerbation during hospitalization. Physicalexamination showed that left radial, ulnar & brachial pulse was not palpable. No bruit or murmur was obtained over the mass. Neurologic examination revealed no significant finding.On admission, chest P-A showed hen egg sized round & oval compact hazy density on left upper lung field. Bronchogram revealed no pathological finding and Lt. tomogram showed well define large,ovoid mass density in the superior mediastinum. Fluoroscopy finding showed nonpulsatile on left upper lung field. Pre-op. aortography was not taken, under the impression of lung Ca. rule out .sortie aneurysm, exploratory operation was performed through the 2nd intercostal space, Lt. It was performed that the mass was ascending sortie aneurysm of saccular type. Direct aneurysmectomy with multiple figure of eight suture were done without any prosthetic graft. Post-op. control I.V.C graphy showed completely obstruction sign. Postopcontrol aortography revealed good surgical result. Final, histopathological answered non-specific sortie aneurysm, saccular type. Post-op. courses were uneventful except mild neurologic disturbance with subclavian steal syndrome and associated with both lower leg pitting edema due to inferior vena cava obstruction. After op, 3 month later, discharged to home, with big systemic problem. Behcet`s syndrome reviewed with related literatures. The coexistence of mouth and genital ulceration with hypopyon mentioned by hippocrates and described by various workers in the early part of this century was first defined as a syndrome by Behcet in 1937. In 1937 Behcet described a chronic relapsing triple symptom complex of oral ulceration, genital ulceration, and ocular inflammation. The place of the syndrome as part of a systemic disorder in now clearer, and the under lying pathology appears to be a vasculitis. The disease runs a- chronic course, blindness being the greatest disability and control nervous system involvement a cause of death. Thrombophlebitis is fairly frequent, france et al [1951] giving an incidence of 25% and Dowling [1961] 12%, superficial thrombophlebitis migrans and thrombosis of large veins, including venae cavae [Thomas, 1947: Boolukos 1960] are recorded. Little attention has been paid to arterial involvement. Mishima et al. [1961] described resection cf an aortic aneurysm in a 38 year old man with Behcet`s syndorme. Mounsey in a clinicopathological conference described a case [Brit, med. J., 1966] of ruptured aortic aneurysm in Bechcet`s syndrome treated by aorto-iliac graft. Also, Shikano and Oshima et al [1963] recorded two aneyrysm of smaller arteries. Unfrequently, aortic aneurysm was presumed to be secondary to osteomyelitis of the lumber spine, though the possible association between aortic aneurysm and Behcet`s syndrome was raised. A further case is reported here, in which ascending aortic aneurysm with Behcet`s Ds. appeared to form part of this generalized disease. This is a case report of surgical experience of Behcet`s Ds. with ascending aortic aneurysm which had nearly all the typical clinical features. Above mentioned and was reviewed with related literatures.

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Risk Factors of Morbidity and Mortality after Coronary Artery Bypass Grafting (관상동맥우회로 이식술 후 이환과 사망의 위험요인)

  • 박창률;이응배;전상훈;장봉현;이종태;김규태
    • Journal of Chest Surgery
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    • v.31 no.12
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    • pp.1159-1164
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    • 1998
  • Background: Although operative outcome is progressing due to the development of operative techniques and myocardial protection, some patients face an increased morbidity and mortality. Therefore, it has become increasingly important to predict the operative morbidity and mortality. Material and Method: This retrospective study reports the results of risk factor analysis of morbidity and mortality of 137 consecutive patients who were underwent coronary artery bypass graft surgery(CABG). Preoperative variables were age, sex, preoperative myocardial infarction, operative priority, left ventricular ejection fraction, obesity and triple vessel disease. Postoperative morbidities were arrhythmia, wound infection, cerebral infarction, prolonged postoperative hospitalization, pneumonia, acute renal failure, prolonged use of ventilator and operative death. Result: The mean age of total patients was 56.7 years, from 27 to 74. The overall mortality was 6.6%(9 of 137) with the mortality of 3.9%(5 of 128) for elective operation, and 44.4%(4 of 9) for emergent or urgent cases. The morbidity of patients over 65 years was stastistically higher than that of under 65 years. Sex distribution showed no difference in morbidity, however operative mortality rate was slightly higher in women (5/41, 12.19%) than in men(4/96, 4.17%). Morbidity of emergent or urgent operation was 100%, much higher than that of the elective operation. Mortality of the patients whose left ventricular ejection fraction was under 50% was higher than that of those over 50%. Conclusion: We concluded that the risk factors of morbidity after CABG were old age above 65 years and emergent or urgent operation, and that risk factors of mortality were low left venticular ejection fraction under 50% and emergent or urgent operation.

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Prognostic factors for survivals from first relapse in breast cancer patients: analysis of deceased patients

  • Kim, Haeyoung;Choi, Doo Ho;Park, Won;Huh, Seung Jae;Nam, Seok Jin;Lee, Jeong Eon;Ahn, Jin Seok;Im, Young-Hyuck
    • Radiation Oncology Journal
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    • v.31 no.4
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    • pp.222-227
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    • 2013
  • Purpose: This study was performed to evaluate prognostic factors for survival from first relapse (SFFR) in stage I-III breast cancer patients. Materials and Methods: From June 1994 to June 2008, 3,835 patients were treated with surgery plus postoperative radiotherapy and adjuvant chemotherapy for stage I-III breast cancer at Samsung Medical Center. Among them, a total of 224 patients died by June 2009, and 175 deaths were of breast cancer. Retrospective review was performed on medical records of 165 patients who met the inclusion criteria of this study. Univariate and multivariate analysis were done on survivals according to variables, such as age, stage, hormone status of tumor, disease-free interval (DFI), sites of first failure, number of organs involved by recurrent disease (NOR), application of salvage treatments, and existence of brain or liver metastasis (visceral metastasis). Results: Patients' median overall survival time was 38 months (range, 8 to 123 months). Median SFFR was 17 months (range, 5 to 87 months). Ninety percent of deaths occurred within 40 months after first recurrence. The patients with SFFR ${\leq}1$ year had tendency of triple-negativity, shorter DFI (${\leq}2$ years), larger NOR (>3), visceral metastasis for first relapse than the patients with SFFR >1 year. In multivariate analysis, longer DFI (>2 vs. ${\leq}2$ years), absence of visceral metastasis, and application of salvage treatments were statistically significant prognosticators for longer SFFR. Conclusion: The DFI, application of salvage treatments, and visceral metastasis were significant prognostic factors for SFFR in breast cancer patients.