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Clinical experience in diagnosis and treatment of malignant gastrointestinal stromal tumors
Kaohsiung Journal of Medical Sciences (2012) 28, 212e215
Available online at www.sciencedirect.com
journal homepage: http://www.kjms-online.com
ORIGINAL ARTICLE
Clinical experience in diagnosis and treatment of malignant gastrointestinal stromal tumors Fan Lin, Jie Cao*, Wei-Li Gu, Shao-Feng Fan, Kun-Ping Li, Hong Du, Guo-Qin Chen, Min-Jie Wen, Li-Hua Dai, Yue-Yuan Lai Department of General Surgery, The First People’s Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou 510180, China Received 8 February 2011; accepted 4 July 2011 Available online 16 February 2012
KEYWORDS Malignant gastrointestinal stromal tumor; Imatinib
Abstract This study investigated the clinical pathologic character of malignant gastrointestinal stromal tumors (MGIST), their treatment with surgery, and evaluated the efficacy of imatinib postoperation. A total of 68 MGIST patients were enrolled. Of these, 27 patients underwent imatinib auxiliary therapy (treatment group) and 41 underwent imatinib therapy (control group). The therapeutic effects on the two groups were compared using c2 test analysis after follow-up of two years. The expressions of CD117, CD34, S100, Vimentin, and alpha smoothmuscle actin (SMA) were detected by immunohistochemistry methods. Of the 68 cases, 28 showed potential MGIST, whereas 40 had MGIST. Haemorrhagia or necrosis, abundant cell, manifest heteromorphism, and caryocinesia were observed in varying degrees. The positive rates of CD117, CD34, Vimentin, S100, and SMA were 89.7% (61/62), 88.2% (60/62), 73.5% (50/62), 41.1% (28/62) and 25.0% (17/62), respectively. The recurrence rate in the treatment group was significantly lower than that in the control group (p < 0.01). We concluded that CD117 and CD34 may be the most valuable markers in the diagnosis of MGIST, and the diagnosis of MGIST depends on the pathology. Surgery is a far better approach in the treatment of such patients, and imatinib is the more efficient target drug in preventing recurrence and metastasis. Copyright ª 2012, Elsevier Taiwan LLC. All rights reserved.
Introduction
* Corresponding author. Department of General Surgery, The First People’s Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou 510180, China. E-mail address: [email protected] (J. Cao).
Gastrointestinal stromal tumors (GIST) are mesenchymal tumors occurring anywhere along the gastrointestinal tract and are believed to originate from the interstitial cells of Cajal. They commonly grow in the stomach or small intestines [1,2]. These lesions have been classified as leiomyomas or leiomyosarcomas because they possess smooth muscle features under light microscopy.
1607-551X/$36 Copyright ª 2012, Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.kjms.2011.10.014
Character of MGIST and imatinib auxiliary therapy Malignant GIST (MGIST) comprises rare mesenchymal tumors originating in the wall of the GI tract. The term “GIST” was first introduced by Mazur and Clark in 1983 [1]. At present, only a few cases of MGIST have been reported [2]. In the present study, 68 cases of MGIST were gathered and analyzed. The clinical effects of imatinib mesylate were observed and assessed as well.
213 conducted using the EnVision (DAKO, Glostrup, Denmark) method. The antibodies used were CD117, CD34, Vimentin, S100, and alpha smooth-muscle actin (SMA) (Zeta). For antigen retrieval, slides were boiled with citrate buffer (0.01 mol/L, pH 6.0) under high pressure for all the antigens.
Treatment
Patients and methods Patients A total of 68 patients with MGIST were diagnosed in the First People’s Municipal Hospital of Guangzhou, Guangdong Provincial People’s Hospital and the First Affiliated Hospital of Guangzhou Medical College from March 1994 to March 2010. The current study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of First People’s Hospital of Guangzhou. Written consent was obtained from all participating patients. The diagnoses of all the cases were pathologically defined. Of the 68 patients, 31 were male and 37 female with an average age of 55.3 years (from 32 to 73). Tumor sites included gastric cardia (32 cases, 47.1%), small intestine (20 cases, 29.4%), colon or rectum (7 cases, 10.3%), omentum (5 cases, 7.3%), and mesenterium (4 cases, 5.9%). Symptoms that occurred since admission into the study lasted from 3 days to 2 years. Of these, 10 patients were diagnosed with symptoms for less than 1 month, 40 patients for a period of 1e6 months, and 18 patients were diagnosed with symptoms for a period greater than or equal to 6 months. The primary clinical symptoms were abdominal pain (36, 53.3%), abdominal mass (11, 16.7%), pale appearance (22, 16.7%), melena (17, 26.1%), abdominal distension (13, 19.1 %), weakness (7, 10.2 %), eating difficulty (7, 10.2 %), sickness and vomiting (7, 10.2 %), anorexia (5, 7.4 %), constipation (5, 7.4 %), diarrhea (3, 4.6 %), and ascites (3, 4.6 %).
Identification of MGIST According to methods described by Miettinen et al. [3], GIST are divided into benign stromal tumor (no malignant indicator), potential malignant stromal tumor (one of any potential malignant indicators), and definite malignant stromal tumor (one of any definite malignant indicators or at least two potential malignant indicators). The definite malignant indicators are the distant metastasis (identified by pathology) and adjacent organ invasion. The potential malignant indicators are as follows: (1) tumor diameter greater than 5.5 cm; (2) mitoses greater than 5/50 HPF or any intestinal stromal tumor where mitosis occurs; (3) evident necrosis of the tumor; (4) atypical nuclei; (5) heavy cell density; (6) mucosa lamina propria and blood vessel invasion that can be observed under microscope; and (7) any epithelial stromal tumors showing acinar or cellular sphere structure.
All 68 patients with MGIST underwent different surgical procedures, as follows: 30 cases of partial gastrectomy, two cases of total gastrectomy, 20 cases of partial enterectomy, seven cases of partial colectomy, five cases of omentum resection, and four cases of partial mesenterectomy. All patients underwent radical resection and had no residual tumors. The patients were randomly divided into two groups: 27 underwent the imatinib auxiliary therapy (treatment group) and 41 patients underwent surgery without imatinib therapy (control group).
Statistical analysis The analyses presented in the current paper are explorative. Differences in the treatment procedures or the use of cytostatic drugs in different subgroups were evaluated by means of a two-sided Chi-square test. A p value of less than 0.05 was considered statistically significant.
Results Frequency and clinical features Of the 68 patients, 28 cases were diagnosed with potential MGIST with tumor diameters ranging from 3.2 cm to 7.2 cm (mean of 5.3 cm). The cut surfaces were hoar or grayish yellow, and the tumors were solid or hemorrhaging, showing cystic changes. The other 40 cases were diagnosed with MGIST with tumor diameters ranging from 3.0 cm to 25.0 cm (mean of 9.2 cm). The cut surfaces were finetextured, fish-like, and possessed an abundance of cells. Some lesions were invaded or migrated locally (22 cases invaded adjacent organs, 4 cases migrated into the liver, 14 cases showed no invasion or metastasis). Atypical mitoses were significant. Hemorrhage and necrosis were also observed (Fig. 1).
Immunohistochemical analysis Of the 68 patients with MGIST, 61 cases were positive for CD117 (89.7%), 60 cases expressed CD34 protein (88.2%), and 50 cases were positive for Vimentin (73.5%). In addition, 28 cases were positive for S100 (41.1%), and only 17 cases expressed SMA protein (25.0%).
Treatment and follow-up Immunohistochemistry Paraffin wax-embedded sections were stained with hematoxylin and eosin. Immunohistochemical analysis was
All the patients received primary tumor resection, and no one died immediately after surgery. The follow-up periods ranged from 3 months to 5 years, and 17 of the patients died
214
Figure 1. necrotics.
F. Lin et al.
The morphological characteristics of metastatic MGIST cells. (A) nuclear fission ; (B) cell atypia; (C) hemorrhagic
within 2 years. Of those patients that suffered metastasis or recurrence, 33 were in the control group, together with 6 from the treatment group (x2 Z 22.3, p < 0.05). The data are shown in Table 1.
Discussion According to the new histological classification of tumors, mesenchymal tumor originates from muscles of nervous type. Some stromal tumors may have been diagnosed with leiomyoma of stomach [4]. Stromal tumors can be classified
Table 1 Comparison of clinical data between control and treatment groups (c2 test). Group
Control (n Z 41)
Treatment (n Z 27)
p
Gender male female
19 22
12 15
>0.05
Age (y)
47.3 14.15
49.87 15.37
>0.05
Tumor position stomach small intestine colorectal omentum mesenterium
21 11 4 3 2
11 9 3 2 2
>0.05
9 18 100% 6
<0.05 <0.05 <0.01
3
<0.05
Tumor malignant degree potential MGIST 19 MGIST 22 Rate of follow-up 100% metastasis and 33 recurrence within 5 years death 14
MGIST Z malignant gastrointestinal stromal tumor.
into smooth muscle, nerve tissue, as well as biphasic differentiating and undifferentiating type. GIST was named from pathology or molecular pathology, whereas MGIST possessed the characters of c-kit genetic mutation and activation. CD117 and CD34 are highly expressed in MGIST, whereas S100 and SMA are relatively lower. The immunohistochemistry results showed that CD117 and CD34 had positive rates of 89.7% and 88.2%, respectively, consistent with previous reports [5,6]. All symptoms of MGIST patients are generally nonspecific. The main pathological evidence comprises large tumor volume, invasive growth, and more mitoses (over 5/ 50 HPF). Cassier [7] et al. reported that the prognosis of MGIST is poor, and the median survival period is 5 years. In the current work, a total of 35 out of 50 cases of MGIST located in the small intestine received complete resection but only 43% of the complete resection group suffered local recurrence. In addition, 57% suffered distant metastasis within 2 years after surgery with a 5-year survival rate of 43%. The 5-year survival rate of the incomplete resection group was barely 7%. Finally, 34 patients died of tumor recurrence [8]. At present, imatinib, a molecular targeting drug aiming at c-kit gene, has shown advantages in the treatment of MGIST [9]. Many known diseases are attributed to the aberration of the signal transduction pathways in cells, especially protein tyrosine kinase (PTK) P. Over activation of PTK occurs in some malignant tumors and hyperplastic benign tumors, and the inhibition of PTK activity can cure hyperplastic diseases. Imatinib is a kind of PTK inhibitor that can suppress c-kit gene of the platelet-derived growth factor receptor and stem cell factor receptor, inhibiting the biochemical reactions conducted by those two receptors without affecting the signal transmissions conducted by other simulating factors, such as epidermal growth factor and insulin [10]. There were 17 cases of death in the present study, including 14 from the control group and three from the treatment group. Pierie et al. [11] divided 125 cases of GIST
Character of MGIST and imatinib auxiliary therapy into muscle-originated, nerve-originated, c-kit negative, and c-kit positive cases. The tumors of c-kit positive are bigger, more invasive, and result in more necrosis and hemorrhage compared with the other groups. The survival periods and qualities of this group are also poorer. All 68 cases in the present study were treated with primary tumor resection and followed up for 3 months to 2 years. In all, 33 patients from the control group and six cases from the treatment group suffered metastasis or recurrence, suggesting that surgery alone might lead to an unsatisfactory long-term prognosis [12,13].
References [1] Stamatakos M, Douzinas E, Stefanaki C, Safioleas P, Polyzou E, Levidou G, et al. Gastrointestinal stromal tumor. World J Surg Oncol 2009;1:61. [2] Hopkins TG, Marples M, Stark D. Sunitinib in the management of gastrointestinal stromal tumours (GISTs). Eur J Surg Oncol 2008;34:844e50. [3] Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): definition, occurrence, pathology, differential diagnosis and molecular genetics. Pol J Pathol 2003;54:3e24. [4] Crosby JA, Catton CN, Davis A, Couture J, O’Sullivan B, Kandel R, et al. Malignant gastrointestinal stromal tumours of the small intestine: a review of 50 cases from a prospective database. Ann Surg Oncol 2001;8:50e9.
215 [5] Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577e80. [6] Miettimen M, Lasota J. Gastrointestinal stromal tumorsd definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001;438:1e12. [7] Cassier PA, Blay JY. Molecular response prediction in gastrointestinal stromal tumors. Target Oncol 2010;5:29e37. [8] Nishida T, Nakamura J, Taniquch M, Hirota S, Ito T, Kitamura Y, et al. Clinicopathological features of gastricstromal tumors. Exp Clin Cancer Res 2000;19:417e25. [9] Demetric GD, Mehren MV, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Eng J Med 2002;347:472e80. [10] Hirota S, Isozaki K. Pathology of gastrointestinal stromal tumors. Pathol Int 2006;56:1e9. [11] Pierie JP, Choudry U, Mazknnsky A, Yeap BY, Souba WW, Ott MJ. The effect of surgery and grade on outcome of gastrointestianal stromal tumors. Arch Surg 2001;136:383e9. [12] Huse DM, von Mehren M, Lenhart G, Joensuu H, Blanke C, Feng W, et al. Cost effectiveness of imatinib mesylate in the treatment of advanced gastrointestinal stromal tumours. Clin Drug Investig 2007;27:85e93. [13] Frolov A, Chanwan S, Ochs M, Arnoletti JP, Pan ZZ, Favorova O, et al. Response markers and the molecular mechanisms of action of Gleevec in gastrointestinal stromal tumours. Mol Cancer Ther 2003;2:699e709.
Available online at www.sciencedirect.com
journal homepage: http://www.kjms-online.com
ORIGINAL ARTICLE
Clinical experience in diagnosis and treatment of malignant gastrointestinal stromal tumors Fan Lin, Jie Cao*, Wei-Li Gu, Shao-Feng Fan, Kun-Ping Li, Hong Du, Guo-Qin Chen, Min-Jie Wen, Li-Hua Dai, Yue-Yuan Lai Department of General Surgery, The First People’s Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou 510180, China Received 8 February 2011; accepted 4 July 2011 Available online 16 February 2012
KEYWORDS Malignant gastrointestinal stromal tumor; Imatinib
Abstract This study investigated the clinical pathologic character of malignant gastrointestinal stromal tumors (MGIST), their treatment with surgery, and evaluated the efficacy of imatinib postoperation. A total of 68 MGIST patients were enrolled. Of these, 27 patients underwent imatinib auxiliary therapy (treatment group) and 41 underwent imatinib therapy (control group). The therapeutic effects on the two groups were compared using c2 test analysis after follow-up of two years. The expressions of CD117, CD34, S100, Vimentin, and alpha smoothmuscle actin (SMA) were detected by immunohistochemistry methods. Of the 68 cases, 28 showed potential MGIST, whereas 40 had MGIST. Haemorrhagia or necrosis, abundant cell, manifest heteromorphism, and caryocinesia were observed in varying degrees. The positive rates of CD117, CD34, Vimentin, S100, and SMA were 89.7% (61/62), 88.2% (60/62), 73.5% (50/62), 41.1% (28/62) and 25.0% (17/62), respectively. The recurrence rate in the treatment group was significantly lower than that in the control group (p < 0.01). We concluded that CD117 and CD34 may be the most valuable markers in the diagnosis of MGIST, and the diagnosis of MGIST depends on the pathology. Surgery is a far better approach in the treatment of such patients, and imatinib is the more efficient target drug in preventing recurrence and metastasis. Copyright ª 2012, Elsevier Taiwan LLC. All rights reserved.
Introduction
* Corresponding author. Department of General Surgery, The First People’s Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou 510180, China. E-mail address: [email protected] (J. Cao).
Gastrointestinal stromal tumors (GIST) are mesenchymal tumors occurring anywhere along the gastrointestinal tract and are believed to originate from the interstitial cells of Cajal. They commonly grow in the stomach or small intestines [1,2]. These lesions have been classified as leiomyomas or leiomyosarcomas because they possess smooth muscle features under light microscopy.
1607-551X/$36 Copyright ª 2012, Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.kjms.2011.10.014
Character of MGIST and imatinib auxiliary therapy Malignant GIST (MGIST) comprises rare mesenchymal tumors originating in the wall of the GI tract. The term “GIST” was first introduced by Mazur and Clark in 1983 [1]. At present, only a few cases of MGIST have been reported [2]. In the present study, 68 cases of MGIST were gathered and analyzed. The clinical effects of imatinib mesylate were observed and assessed as well.
213 conducted using the EnVision (DAKO, Glostrup, Denmark) method. The antibodies used were CD117, CD34, Vimentin, S100, and alpha smooth-muscle actin (SMA) (Zeta). For antigen retrieval, slides were boiled with citrate buffer (0.01 mol/L, pH 6.0) under high pressure for all the antigens.
Treatment
Patients and methods Patients A total of 68 patients with MGIST were diagnosed in the First People’s Municipal Hospital of Guangzhou, Guangdong Provincial People’s Hospital and the First Affiliated Hospital of Guangzhou Medical College from March 1994 to March 2010. The current study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of First People’s Hospital of Guangzhou. Written consent was obtained from all participating patients. The diagnoses of all the cases were pathologically defined. Of the 68 patients, 31 were male and 37 female with an average age of 55.3 years (from 32 to 73). Tumor sites included gastric cardia (32 cases, 47.1%), small intestine (20 cases, 29.4%), colon or rectum (7 cases, 10.3%), omentum (5 cases, 7.3%), and mesenterium (4 cases, 5.9%). Symptoms that occurred since admission into the study lasted from 3 days to 2 years. Of these, 10 patients were diagnosed with symptoms for less than 1 month, 40 patients for a period of 1e6 months, and 18 patients were diagnosed with symptoms for a period greater than or equal to 6 months. The primary clinical symptoms were abdominal pain (36, 53.3%), abdominal mass (11, 16.7%), pale appearance (22, 16.7%), melena (17, 26.1%), abdominal distension (13, 19.1 %), weakness (7, 10.2 %), eating difficulty (7, 10.2 %), sickness and vomiting (7, 10.2 %), anorexia (5, 7.4 %), constipation (5, 7.4 %), diarrhea (3, 4.6 %), and ascites (3, 4.6 %).
Identification of MGIST According to methods described by Miettinen et al. [3], GIST are divided into benign stromal tumor (no malignant indicator), potential malignant stromal tumor (one of any potential malignant indicators), and definite malignant stromal tumor (one of any definite malignant indicators or at least two potential malignant indicators). The definite malignant indicators are the distant metastasis (identified by pathology) and adjacent organ invasion. The potential malignant indicators are as follows: (1) tumor diameter greater than 5.5 cm; (2) mitoses greater than 5/50 HPF or any intestinal stromal tumor where mitosis occurs; (3) evident necrosis of the tumor; (4) atypical nuclei; (5) heavy cell density; (6) mucosa lamina propria and blood vessel invasion that can be observed under microscope; and (7) any epithelial stromal tumors showing acinar or cellular sphere structure.
All 68 patients with MGIST underwent different surgical procedures, as follows: 30 cases of partial gastrectomy, two cases of total gastrectomy, 20 cases of partial enterectomy, seven cases of partial colectomy, five cases of omentum resection, and four cases of partial mesenterectomy. All patients underwent radical resection and had no residual tumors. The patients were randomly divided into two groups: 27 underwent the imatinib auxiliary therapy (treatment group) and 41 patients underwent surgery without imatinib therapy (control group).
Statistical analysis The analyses presented in the current paper are explorative. Differences in the treatment procedures or the use of cytostatic drugs in different subgroups were evaluated by means of a two-sided Chi-square test. A p value of less than 0.05 was considered statistically significant.
Results Frequency and clinical features Of the 68 patients, 28 cases were diagnosed with potential MGIST with tumor diameters ranging from 3.2 cm to 7.2 cm (mean of 5.3 cm). The cut surfaces were hoar or grayish yellow, and the tumors were solid or hemorrhaging, showing cystic changes. The other 40 cases were diagnosed with MGIST with tumor diameters ranging from 3.0 cm to 25.0 cm (mean of 9.2 cm). The cut surfaces were finetextured, fish-like, and possessed an abundance of cells. Some lesions were invaded or migrated locally (22 cases invaded adjacent organs, 4 cases migrated into the liver, 14 cases showed no invasion or metastasis). Atypical mitoses were significant. Hemorrhage and necrosis were also observed (Fig. 1).
Immunohistochemical analysis Of the 68 patients with MGIST, 61 cases were positive for CD117 (89.7%), 60 cases expressed CD34 protein (88.2%), and 50 cases were positive for Vimentin (73.5%). In addition, 28 cases were positive for S100 (41.1%), and only 17 cases expressed SMA protein (25.0%).
Treatment and follow-up Immunohistochemistry Paraffin wax-embedded sections were stained with hematoxylin and eosin. Immunohistochemical analysis was
All the patients received primary tumor resection, and no one died immediately after surgery. The follow-up periods ranged from 3 months to 5 years, and 17 of the patients died
214
Figure 1. necrotics.
F. Lin et al.
The morphological characteristics of metastatic MGIST cells. (A) nuclear fission ; (B) cell atypia; (C) hemorrhagic
within 2 years. Of those patients that suffered metastasis or recurrence, 33 were in the control group, together with 6 from the treatment group (x2 Z 22.3, p < 0.05). The data are shown in Table 1.
Discussion According to the new histological classification of tumors, mesenchymal tumor originates from muscles of nervous type. Some stromal tumors may have been diagnosed with leiomyoma of stomach [4]. Stromal tumors can be classified
Table 1 Comparison of clinical data between control and treatment groups (c2 test). Group
Control (n Z 41)
Treatment (n Z 27)
p
Gender male female
19 22
12 15
>0.05
Age (y)
47.3 14.15
49.87 15.37
>0.05
Tumor position stomach small intestine colorectal omentum mesenterium
21 11 4 3 2
11 9 3 2 2
>0.05
9 18 100% 6
<0.05 <0.05 <0.01
3
<0.05
Tumor malignant degree potential MGIST 19 MGIST 22 Rate of follow-up 100% metastasis and 33 recurrence within 5 years death 14
MGIST Z malignant gastrointestinal stromal tumor.
into smooth muscle, nerve tissue, as well as biphasic differentiating and undifferentiating type. GIST was named from pathology or molecular pathology, whereas MGIST possessed the characters of c-kit genetic mutation and activation. CD117 and CD34 are highly expressed in MGIST, whereas S100 and SMA are relatively lower. The immunohistochemistry results showed that CD117 and CD34 had positive rates of 89.7% and 88.2%, respectively, consistent with previous reports [5,6]. All symptoms of MGIST patients are generally nonspecific. The main pathological evidence comprises large tumor volume, invasive growth, and more mitoses (over 5/ 50 HPF). Cassier [7] et al. reported that the prognosis of MGIST is poor, and the median survival period is 5 years. In the current work, a total of 35 out of 50 cases of MGIST located in the small intestine received complete resection but only 43% of the complete resection group suffered local recurrence. In addition, 57% suffered distant metastasis within 2 years after surgery with a 5-year survival rate of 43%. The 5-year survival rate of the incomplete resection group was barely 7%. Finally, 34 patients died of tumor recurrence [8]. At present, imatinib, a molecular targeting drug aiming at c-kit gene, has shown advantages in the treatment of MGIST [9]. Many known diseases are attributed to the aberration of the signal transduction pathways in cells, especially protein tyrosine kinase (PTK) P. Over activation of PTK occurs in some malignant tumors and hyperplastic benign tumors, and the inhibition of PTK activity can cure hyperplastic diseases. Imatinib is a kind of PTK inhibitor that can suppress c-kit gene of the platelet-derived growth factor receptor and stem cell factor receptor, inhibiting the biochemical reactions conducted by those two receptors without affecting the signal transmissions conducted by other simulating factors, such as epidermal growth factor and insulin [10]. There were 17 cases of death in the present study, including 14 from the control group and three from the treatment group. Pierie et al. [11] divided 125 cases of GIST
Character of MGIST and imatinib auxiliary therapy into muscle-originated, nerve-originated, c-kit negative, and c-kit positive cases. The tumors of c-kit positive are bigger, more invasive, and result in more necrosis and hemorrhage compared with the other groups. The survival periods and qualities of this group are also poorer. All 68 cases in the present study were treated with primary tumor resection and followed up for 3 months to 2 years. In all, 33 patients from the control group and six cases from the treatment group suffered metastasis or recurrence, suggesting that surgery alone might lead to an unsatisfactory long-term prognosis [12,13].
References [1] Stamatakos M, Douzinas E, Stefanaki C, Safioleas P, Polyzou E, Levidou G, et al. Gastrointestinal stromal tumor. World J Surg Oncol 2009;1:61. [2] Hopkins TG, Marples M, Stark D. Sunitinib in the management of gastrointestinal stromal tumours (GISTs). Eur J Surg Oncol 2008;34:844e50. [3] Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): definition, occurrence, pathology, differential diagnosis and molecular genetics. Pol J Pathol 2003;54:3e24. [4] Crosby JA, Catton CN, Davis A, Couture J, O’Sullivan B, Kandel R, et al. Malignant gastrointestinal stromal tumours of the small intestine: a review of 50 cases from a prospective database. Ann Surg Oncol 2001;8:50e9.
215 [5] Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577e80. [6] Miettimen M, Lasota J. Gastrointestinal stromal tumorsd definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001;438:1e12. [7] Cassier PA, Blay JY. Molecular response prediction in gastrointestinal stromal tumors. Target Oncol 2010;5:29e37. [8] Nishida T, Nakamura J, Taniquch M, Hirota S, Ito T, Kitamura Y, et al. Clinicopathological features of gastricstromal tumors. Exp Clin Cancer Res 2000;19:417e25. [9] Demetric GD, Mehren MV, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Eng J Med 2002;347:472e80. [10] Hirota S, Isozaki K. Pathology of gastrointestinal stromal tumors. Pathol Int 2006;56:1e9. [11] Pierie JP, Choudry U, Mazknnsky A, Yeap BY, Souba WW, Ott MJ. The effect of surgery and grade on outcome of gastrointestianal stromal tumors. Arch Surg 2001;136:383e9. [12] Huse DM, von Mehren M, Lenhart G, Joensuu H, Blanke C, Feng W, et al. Cost effectiveness of imatinib mesylate in the treatment of advanced gastrointestinal stromal tumours. Clin Drug Investig 2007;27:85e93. [13] Frolov A, Chanwan S, Ochs M, Arnoletti JP, Pan ZZ, Favorova O, et al. Response markers and the molecular mechanisms of action of Gleevec in gastrointestinal stromal tumours. Mol Cancer Ther 2003;2:699e709.