• Title/Summary/Keyword: Clinical progression

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Immunohistochemical Study of Phosphatase and Tensin Homolog Deleted on Chromosome Ten in Gefitinib Treated Nonsmall Cell Lung Cancer Patients (폐암 조직에서의 PTEN 발현 정도와 Gefitinib의 반응율과의 관계)

  • Lee, Sung Yong;Lee, Ju Han;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.5
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    • pp.473-479
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    • 2005
  • Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

The Immunohistochemical Analysis for the Expression of Survivin, HSP, and Bcl-2 in Non-small Cell Lung Carcinoma (비소세포폐암에서 Survivin, HSP 및 Bcl-2 발현에 관한 면역조직화학적 분석)

  • Hong, Hyun-Ju;Hong, Seok-Gyun;Lee, Kye-Young;Kim, Woo-Ho;Lee, Choon-Taek;Yoo, Chul-Gyu;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.441-452
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    • 2002
  • Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.

The Clinical Significance of Cathepsin D and p53 Expression in Locally Advanced Rectal Cancer (국소진행된 직장암에서 Cathepsin D와 p53 발현의 임상적 의의)

  • Kim, Jun-Sang;Lee, Sheng-Jin;Kim, Jin-Man;Cho, Moon-June
    • Radiation Oncology Journal
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    • v.26 no.1
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    • pp.56-64
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    • 2008
  • Purpose: Cathepsin D(CD) is a lysosomal acid proteinase that is related to malignant progression, invasion, and a poor prognosis in several tumors. The aim of this study was to evaluate the prognostic clinical significance of CD and p53 expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer who were treated with preoperative chemoradiation. Materials and Methods: Eighty-nine patients with locally advanced rectal cancer(cT3/T4 or N+) were included in this study. Preoperative chemoradiation consisted of a dose of 50.4 Gy of pelvic radiation and two concurrent cycles of administration of 5-fluorouracil and leucovorin. Surgery was performed six weeks after chemoradiation. CD and p53 expression in pretreatment formalin-fixed paraffin-embedded tumor biopsy specimens were assessed by immunohistochemical staining using a CD and p53 monoclonal antibodies. The threshold value for a positive stain in tumor tissue and stromal cells was 1+ intensity in 10% of the tumors or stromal cells, respectively. Results: Positive CD expression was found in 57(64%) of the tumors and 32(35%) of the stromal cell specimens. There was no association with CD expression of the tumor or stromal cells and patient characteristics. There was a correlation between tumor CD expression with stromal cell CD expression(p=0.01). Overexpression of p53 was not a significant prognostic factor. The 5-year overall survival(OS) and disease-free survival(DFS) rates were not different between tumor CD-negative and positive patient biopsy samples(69% vs. 65%, 60% vs. 61%, respectively). The 5-year OS rates in the tumor-negative/stromal cell-negative, tumor-negative/stromal cell-positive, tumor-positive/stromal cell-negative and tumor-positive/stromal cell-positive biopsy samples were 75%, 28%, 62%, and 73%, respectively. Stromal cell staining only without positive tumor staining demonstrated the worst overall survival prognosis for patients(p=0.013). Conclusion: Overexpression of p53 in rectal biopy tissue was not associated with prognostic significance. In the pretreatment biopsy specimens, an exclusive increase in CD expression in stromal cells without tumor expression was related to poor overall survival in patients with locally advanced rectal cancer treated with preoperative chemoradiation.

The Clinical Usefulness of Cystatin C in Evaluating Renal Function in Children with Various Renal Diseases (다양한 신질환을 가진 소아에서 Cystatin C 검사의 임상적 유용성)

  • Kim, Khi-Joo;Kim, Joung-A;Shin, Jae-Il;Hwang, You-Sik;Cheung, Il-Chun;Lim, Jong-Baeck;Lee, Jae-Seung
    • Childhood Kidney Diseases
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    • v.11 no.2
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    • pp.161-167
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    • 2007
  • Purpose : GFR(glomerular filtration rate) is a fundamental parameter in detecting renal impairment and predicts the progression of renal disease. Because serum creatinine has several disadvantages, serum cystatin C has been recently proposed as a new endogenous marker for GFR. We compared serum cystatin C with creatinine and creatinine clearance to investigate the clinical usefulness of cystatin C. Methods : We retrospectively analyzed 46 patients(60 case numbers) who had various renal diseases and classified them into 3 groups according to creatinine clearance(Group 1 : CrCl <40 mL/min/$1.73m^2$, Group 2 : CrCl 40-60 mL/min/$1.73m^2$, Group 3 CrCl >60 mL/min/$1.73m^2$). We measured serum creatinine, cystatin C and creatinine clearance and also analyzed the correlations among them. Results : Serum cystatin C and creatinine showed a similar correlation to creatinine clearance (r=0.685, r=0.640, respectively) and showed similar diagnostic accuracy in detecting decreased GFR(AUC, cystatin C 0.829 vs. creatinine 0.826, P=0.848). Serum cystatin C showed a greater sensitivity for detecting a decreased GFR than creatinine in Group 2 and 3(Group 1 : 100% vs. 100%, Group 2 : 70% vs. 35%, Group 3 : 46% vs. 15%). Conclusions : Serum cystatin C could be a useful endogenous marker for GFR and would be superior to serum creatinine in early detection of renal impairment in pediatric patients with renal diseases.

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Independent Prognostic Value of the Fascin Expression in Patients with Esophageal Cancer (식도암에 있어서 Fascin의 발현과 예후와의 상관관계에 대한 연구)

  • Choi, Pill-Jo;Jeong, Sang-Seok;Bang, Jung-Heui;Cho, Kwang-Jo;Woo, Jong-Soo;Roh, Mee-Sook
    • Journal of Chest Surgery
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    • v.41 no.1
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    • pp.74-81
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    • 2008
  • Background: Fascin is an actin-bundling protein that induces membrane protrusions and it increases cell motility in various transformed cells. Esophageal cancer is one of the most lethal malignancies, and it exhibits extensive local invasion or frequent regional lymph node metastasis even after curative surgery. We investigate the expression of fascin by performing immunohistochemistry to evaluate the clinical characteristics and prognostic significance of its expression in esophageal cancer patients. Material and Method: Immunochemistry for fascin was performed on 76 tumor samples from 76 patients who underwent esophageal cancer operations. The expression levels of fascin in the 76 esophageal cancer tissues were compared with those in the corresponding normal esophageal epithelium. The fascin-positive samples were defined as those showing more than 75% of fascin-positive cells. Result: Overall, a fascin positive expression was detected in 39 (51.3%) out of the total 76 cases. The tumors with positive fascin expression tended to more frequently show a higher stage (p=0.030), and a higher T-factor (p=0.031). The prognosis of the fascin negative group was significantly better than that of the fascin positive group (p=0.004). Multivariate analysis revealed that lymphovascular invasion and the fascin expression were independent prognostic factors. Conclusion: Fascin was expressed in 513% of the esophageal cancer tissues and a positive expression of fascin was associated with more advanced tumor progression and recurrence. Our study suggests that the fascin expression may be an independent prognostic factor for an unfavorable clinical course few those patients suffering with esophageal cancer.

A Case of the Shoulder-Hand Syndrome Caused by a Crush Injury of the Shoulder (견관절부 외상후 발생된 Shoulder-Hand Syndrome)

  • Jeon, Jae-Soo;Lee, Sung-Keun;Song, Hoo-Bin;Kim, Sun-Jong;Park, Wook;Kim, Sung-Yell
    • The Korean Journal of Pain
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    • v.2 no.2
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    • pp.155-166
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    • 1989
  • Bonica defined, that reflex sympathetic dystrophy (RSD) may develop pain, vasomotor abnoramalities, delayed functional recovery, and dystrophic changes on an affected area without major neurologic injury following trauma, surgery or one of several diseased states. This 45 year old male patient had been crushed on his left shoulder by a heavily laden rear car, during his job street cleaning about 10 years ago (1978). At first the pain was localizea only to the site of injury, but with time, it spreaded from the shoulder to the elbow and hand, with swelling. X-ray studies in the local clinic, showed no bone abnormalities of the affected site. During about 10 years following the injury, the had recieved several types of treatments such as nonsteroidal analgesics, steroid injections into the glenoidal cavity (10 times), physical therapy, some oriental herb medicines, and acupuncture over a period of 1~3 months annually. His shoulder pain and it's joint dysfunction persisted with recurrent paroxysmal aggrevation because of being mismanaged or neglected for a sufficiently long period these fore permiting progression of the sympathetic imbalance. On July 14 1988 when he visited our clinic. He complained of burning, aching and had a hyperpathic response or hyperesthesia in touch from the shoulder girdle to the elbow and the hand. Also the skin of the affected area was pale, cold, and there was much sweating of the axilla and palm, but no edema. The shoulder girdle was unable to move due to joint pain with marked weakness. We confirmed skin temperatures $5^{\circ}C$ lower than those of the unaffected axilla, elbow and palm of his hand, and his nails were slightly ridged with lateral arching and some were brittle. On X-ray findings of both the shoulder AP & lateral view, the left humerus and joint area showed diffuse post-traumatic osteoporosis and fibrous ankylozing with an osteoarthritis-like appearance. For evaluating the RSD and it's relief of pain, the left cervical sympathetic ganglion was blocked by injecting 0.5% bupivacaine 5 ml with normal saline 5 ml (=SGB). After 15 minutes following the SGB, the clinical efficacy of the block by the patients subjective score of pain intensity (=PSSPI), showed a 50% reduction of his shoulder and arm pain, which was burning in quality, and a hyperpathic response against palpation by the examiner. The skin temperatures of the axilla and palm rose to $4{\sim}5^{\circ}C$ more than those before the SGB. He felt that his left face and upper extremity became warmer than before the SGB, and that he had reduced sweating on his axilla and his palm. Horner's sign was also observed on his face and eyes. But his deep shoulder joint pain was not improved. For the control of the remaining shoulder joint pain, after 45 minutes following the SGB, a somatic sensory block was performed by injecting 0.5% bupivacaine 6 ml mixed with salmon calcitonin, $Tridol^{(R)}$, $Polydyn^{(R)}$ and triamcinolone into the fossa of the acromioclavicular joint region. The clinical effect of the somatic block showed an 80% releif of the deep joint pain by the PSSPI of the joint motion. Both blocks, as the above mentioned, were repeated a total of 28 times respectively, during 6 months, except the steroid was used just 3 times from the start. For maintaining the relieved pain level whilst using both blocks, we prescribed a low dose of clonazepam, prazocin, $Etravil^{(R)}$, codeine, etodolac micronized and antacids over 6 months. The result of the treatments were as follows; 1) The burning, aching and hyperpathic condition which accompanied with vaosmotor and pseudomotor dysfunction, disappeared gradually to almost nothing, within 3 weeks from the starting of the blocks every other day. 2) The joint disability of the affected area was improved little by little within 6 months. 3) The post-traumatic osteoporosis, fibrous ankylosis and marginal sclerosis with a narrowed joint, showed not much improvement on the X-ray findings (on April 25, 1989) 10 months later in the follow-up. 4) Now he has returned to his job as a street cleaner.

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Correlation between Clinicopathology and Expression of HSP70, BAG1 and Raf-1 in Human Diffuse Type Gastric Carcinoma (미만형 위암에서 임상병리학적 인자와 Hsp70, BAG1과 Raf-1 발현간의 상관성)

  • Jung, Sang Bong;Lee, Hyoun Wook;Chung, Kyung Tae
    • Journal of Life Science
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    • v.26 no.1
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    • pp.101-108
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    • 2016
  • The aim of this study was to evaluate the relationships between the expression of Heat shock protein70 (HSP70), Raf-1 and Bcl-2-associated athanogene-1 (BAG1) protein in diffuse type gastric carcinoma and examine association of HSP70, Raf-1 and BAG1 expression with various clinic-pathological factors and survival. Heat shock protein70 is induced in the cells in response to various stress conditions, including carcinogens. Overexpression of heat shock protein 70 has been observed in many types of cancer. The proto-oncoprotein Raf is pivotal for mitogen-activated protein kinase (MAPK) signaling, and its aberrant activation has been implicated in multiple human cancers. Overexpression of BAG1 protein has been documented in some type of human cancer. BAG1 has been reported to interact with protein involved with a variety of signal pathway, and regulation of cell differentiation, survival and apoptosis. These interaction partners include HSP70 and Raf-1. The percentage of tumors exhibiting HSP70 positivity was significantly in cases of positive lymph node metastasis (64.9%) compared to cases without lymph node metastasis (35.1%, p=0.007). HS70 expression was correlated with pathological N-stage (p=0.006). Expression of BAG1 was detected in the majority of diffuse type gastric carcinoma tissues (71.7%), especially in younger patients (80% vs 52.6%, p=0.035). Furthermore BAG1 expression was correlated with tumor size (p=0.020). Raf-1 expression was found to be significantly associated with tumor size (p=0.005). The result indicate that HSP70 was significantly correlated the progression of diffuse type gastric cancer. Expression of BAG1 and Raf-1 may be used as diagnostic markers for gastric carcinoma.

Emotional State and Personality Characteristics in Patients with Vitiligo (백반증 환자의 정서상태와 성격특성)

  • Lee, Kyung-Kyu;Lee, Jong-Hyun;Kim, Hyun-Woo;Paik, Ki-Chung;Kim, You-Chan
    • Korean Journal of Psychosomatic Medicine
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    • v.8 no.1
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    • pp.88-97
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    • 2000
  • Objectives : This study was aimed to investigate the emotional state and personality factors of patients with vitiligo, and the impacts of clinical characteristics. Methods : Twenty one patients with vitiligo and 20 normal controls were studied. Beck Depression Inventory(BDI), Spielberg's State and Trait Anxiety Inventory(STAI) and Cattell's 16 Personality Factors Questionnaire(16-PF) were used for assessment. Statistically, t-test, Oneway ANOVA, Mann-Whitney U test and Pearson's correlation test were used. Results : The Results were as follows. 1) The comparison of total score of BDI, state anxiety and trait anxiety between the patients with vitiligo and normal controls were not significantly different. 2) In first-stratum source traits of 16-PF, normal control group was significantly higher than the patients with vitiligo in H-factor(Boldness) and I-factor(Tender-mindedness). In second-stratum source traits of 16-PF, there was no significant difference between the patients with vitiligo and normal control in all factors. 3) According to sex, the comparison of total scores of BDI, STAI between male and female patients with vitiligo were not significantly different. In the comparison of 16-PF, female patients were higher than male patients in I-factor only. 4) As according to age(under and over 30 years of age), the comparison of total scores of BDI, STAI between patients over 30 years of age and under 30 years of age were not significantly different. In the comparison of 16-PF, patients over 30 years of age were higher than patients under 30 years of age in E-, G-, L-, M-, Q2-, Q3-, IND-, SUP-, and CRE-factor. 5) As according to the presence of progression of vitiligo and the presence of visible lesion, the comparison of total scores of BDI, STAI and 16-PF were not significantly different. 6) There were no significant correlation between the duration of the vitiligo and BDI, STAI-S, STAI-T, and 16-PF. Conclusions : There were no significant difference between patients with vitiligo and normal controls on the emotional state and personality characteristics. But patients with vitiligo were more bolder and tender-minded than normal controls on 16-PF. The author propose that methods of treatment to resolve problems of the interpersonal relations will be helpful.

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A Change of Adrenal Androgen and Cortisol in Kawasaki Disease (가와사끼병에서 부신 안드로겐과 코티솔의 변화)

  • Lee, Sun-Hee;Yu, Jae-Hong;Kil, Hong-Ryang
    • Clinical and Experimental Pediatrics
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    • v.45 no.5
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    • pp.654-658
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    • 2002
  • Purpose : Endocrine and immune systems are connected and interdependent. Adrenal glands play an important role in this network and control the balance between serum levels of dehydroepiandrosterone sulfate(DHEAS) and cortisol. These steroids have an antagonistic effect on the T cell progression into Th1 and Th2 cells and on the induction of correlated interleukins. Therefore we evaluated the role of adrenal androgen and cortisol as immune modulators in Kawasaki disease( KD) with changes of T cell immunity. Methods : From April to August in 2001, we examined serum DHEAS and 24 hour urine free cortisol(F) before administration of immunoglobulin and steroids by radioimmunoassay in 14 KD patients. It's clinical severity was determined by Harada score and coronary lesion. Results : The age of the patient group ranged from 4 months to 4 years; its average age was 2.3 years. Three patients(21.4%) were below 1 year, 2(14.3%) between 1 and 2 years, 5(35.7%) between 2 and 3 years, 4(28.6%) between 3 and 4 years of age. Male to female ratio was 1:1.3. DHEAS was significantly decreased in patients($11.1{\pm}6.0{\mu}g/dL$) more than controls($81.6{\pm}13.3{\mu}g/dL$)(P<0.05). Twenty-four hour urine free cortisol was significantly increased in patients($36.9{\pm}21.9{\mu}g/dL$) more than controls($13.6{\pm}5.5{\mu}g/dL$)(P<0.05). Ratio of DHEAS/F was decreased remarkably in patients($0.33{\pm}0.20$) more than controls($6.65{\pm}2.56$)(P=0.016). There was no difference between ratio of DHEAS/F and Harada score, but its ratio was very low in patients with coronary aneurysm. Conclusion : These data demonstrate that there are changes of DHEAS and cortisol in acute stage of KD and the dis-equilibrium between two steroids may be relevant in the T cell immune response induction of Kawasaki disease. These changes support the use of DHEAS/F ratio as one of the predictive factors of coronary arteries complication.

Gastrointestinal Stromal Tumor (GIST) of the Stomach: Clinicopathologic Analysis and Outcome (위에 발생한 위장관 간질성 종양의 임상병리학적 특성과 치료성적)

  • Ryu Je-Seock;Lee Sung-Ryul;Choi Sae-Byeol;Park Sung-Soo;Lee Ju-Han;Kim Seung-Joo;Kim Chong-Suk;Chae Yang-Seok;Mok Young-Jae
    • Journal of Gastric Cancer
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    • v.5 no.1
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    • pp.40-46
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    • 2005
  • Purpose: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract. GISTs are positive for the expression of c-Kit protein at immunohistochemistry, and their clinical presentations vary. This retrospective study was performed to evaluate the clincopathologic characteristics of GISTs and to define the prognostic factors. Materials and Methods: 40 patients who underwent a complete resection of a GIST during the period $1996\~2003$ at the Department of Surgery, Korea University College of Medicine, were studied. We divided them into low- and high-risk. groups by using tumor size and mitotic count: 23 cases were low risk, and 17 were high risk. Clinicopathologic features, immunohistochemical findings, and prognoses were compared between the low- and the high-risk groups. Results: The mean age of the 40 patients was $61.3\pm11.1$years, and the male-to-female ratio was 1:1.1. There was no significant difference in age and sex between the groups. A comparative analysis revealed tumor size, mitotic count, clinical symptoms, preoperative pathologic diagnosis, ulceration, and necrosis to be variables that had statistically significant differences between the high- and the low-risk groups. In the univariate analysis, tumor size, mitotic count, ulceration, necrosis, and abnormal endoscopic ultrasound findings were associated with disease-free survival, but in the multivariate analysis, mitotic activity was the only independent factor associated with disease-free survival. 8 patients had recurrences during the follow-up period, and four of them were treated with STI-571 (imatinib mesylate, $Gleevec^{(R)}$). The treated patients have survived until now; however, two of non-treated patients died from disease progression. Conclusion: Based on this study, tumor size, ulceration, and necrosis are significant factors affecting survival, and mitotic activity may be a useful prognostic marker. STI-571 may be used in an adjuvant setting because the drug has shown anticancer activity in patients with recurrence or metastasis.

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