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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 4  |  Page : 156-159

A retrospective cohort study of 304 patients with gastrointestinal stromal tumors in mackay memorial hospital


1 Department of General Surgery, Mackay Memorial Hospital, Taipei, Taiwan
2 Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan

Date of Submission11-Mar-2020
Date of Decision28-Apr-2020
Date of Acceptance04-May-2020
Date of Web Publication1-Dec-2020

Correspondence Address:
Dr. Po- Chun Wang
Department of General Surgery, Mackay Memorial Hospital, No. 92, Sec. 2, Zhongshan N. Rd., Taipei 10449
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCRP.JCRP_10_20

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  Abstract 


Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs often occur in middle-aged and older individuals. The main morphologic type of GISTs is the spindle cell type. Immunohistochemistry and genotyping can help to identify GISTs from other subgroups of sarcoma. Materials and Methods: This retrospective study collected 304 patients over a 10-year period (from January 2009 to June 2019) who were diagnosed with GISTs based on the pathological database of our hospital. We retrospectively analyzed the clinical manifestations and treatment strategies. Results: Anemia or gastrointestinal bleeding was the most common symptom (36.5%), followed by gastrointestinal discomfort (32.6%) and incidental findings (21.4%). Ruptured tumors with hollow organ perforation increased the mortality risk. Liver metastasis and peritoneal seeding were the most two common patterns of recurrence. GISTs arising in adults are characterized by the near-universal expression of CD117/KIT antigen. Early surgery with margin-free resection is the best strategy for GISTs without metastasis. Routine lymph node dissection is not recommended. Laparoscopic surgery is feasible and safe for GISTs in the gastrointestinal tract. Endoscopic submucosal dissection to treat GISTs is suitable for small tumors with very low-to-intermediate risk in the stomach. Postoperative treatment with tyrosine kinase inhibitors can prolong recurrence-free survival after surgery. Conclusion: Surgical resection is the preferred treatment for patients without metastasis. Administration of tyrosine kinase inhibitors such as imatinib is recommended for unresectable, metastatic, or recurrent GISTs. Postoperative follow-up by computed tomography to detect early recurrence is recommended.

Keywords: Endoscopic submucosal dissection, gastrointestinal stromal tumor, tyrosine kinase inhibitors


How to cite this article:
Wang PC, Wu PS. A retrospective cohort study of 304 patients with gastrointestinal stromal tumors in mackay memorial hospital. J Cancer Res Pract 2020;7:156-9

How to cite this URL:
Wang PC, Wu PS. A retrospective cohort study of 304 patients with gastrointestinal stromal tumors in mackay memorial hospital. J Cancer Res Pract [serial online] 2020 [cited 2021 Apr 20];7:156-9. Available from: https://www.ejcrp.org/text.asp?2020/7/4/156/301903




  Introduction Top


Gastrointestinal stromal tumors (GISTs) are the most common malignant subepithelial neoplasms of the gastrointestinal tract and are most often located in the stomach and proximal small intestine; however, they also can occur in any portion of the alimentary tract and occasionally in the omentum, mesentery, and peritoneum.[1],[2],[3],[4] GISTs are submucosal tumors that can grow to a huge size before causing symptoms. The most common symptoms of GISTs are gastrointestinal bleeding, including acute melena and hematemesis with anemia, weakness, and abdominal pain, fullness and distension.[5] Previous studies have shown that 15%–30% of patients with GISTs are asymptomatic, and that their GISTs are found incidentally during health examinations or surgery for treatment of other diseases.[6]

The incidence of other primary neoplasms in GIST patients is relatively high. Previous studies over the past decade have reported annual incidence rates of 7–19 cases per million population. A study of 6142 cases between 2001 and 2011 reported an incidence of 0.68 per 100,000. [2,7]

The main morphologic types of GISTs are the spindle cell type (70%), epithelial cell type (20%), and mixed type (10%) [Figure 1].[8],[9] Pathologically, the diagnosis of a GIST relies on morphology and immunohistochemistry. A diagnosis can also be made by the presence of KIT/CD117 or CD34 positivity. If the tumor is negative for CD117, CD34, desmin, and S-100, additional tests including discovered on GIST 1 (DOG1) staining or a mutation search of the CD117 or platelet-derived growth factor receptor-α genes are useful to diagnose GISTs.[9],[10] GISTs are considered to be a potentially malignant tumor and are classified as very low, low, intermediate, or high risk.[6] The metastatic risk of GISTs has been reported to increase with the tumor size irrespective of the mitotic count.[11]
Figure 1: Pathological diagnosis of gastrointestinal stromal tumor by immunohistochemistry and genotyping[9]

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The prognosis of this disease is associated with the tumor size and mitotic index. Surgical resection is the standard treatment for patients without metastasis.[12],[13],[14],[15] Tyrosine kinase inhibitors such as imatinib mesylate are the first-line standard therapy for unresectable, metastatic, or recurrent GISTs.[9],[16] When the patients have disease progression despite imatinib treatment or are unable to tolerate adverse events, sunitinib malate can serve as second-line treatment.[17] Regorafenib can be used as third-line therapy.[18]


  Methods Top


We searched medical records according to The International Statistical Classification of Diseases and Related Health Problems 10th Revision, ICD-10 code and pathological database of our hospital to identify all patients with GISTs from January 2009 to June 2019. Data including the patient's gender, age, time of first diagnosis, histological type, tumor size, mitotic figure <5 or ≥5 per 50 high-power fields, and immune histochemistry characteristics (CD117, CD34, DOG-01, smooth muscle actin, and S-100) were recorded. We also reviewed treatment strategies and patients with recurrence or metastasis to evaluate the interval to recurrence and location of the metastasis.

The institutional review board disclosure

This is a retrospective study of 304 patients in a single medical hospital in the past decade. The institutional review board approved this study (number: 20MMHIS068e) and waiver of informed consent was approved by MacKay Memorial Hospital Institutional Review Board.


  Results Top


A total of 304 patients were included in this retrospective cohort study (male-to-female ratio: 51%:49%). The patients' characteristics are summarized in [Table 1]. GIST was the primary diagnosis in 250 patients (82.2%), 33 patients (10.9%) had recurrence or metastasis of GIST, and 21 patients (6.9%) were diagnosed accidentally when receiving other surgeries (3 for esophageal cancer, 6 for hemicolectomy, 8 for gynecology debulking surgery, 1 for prostate cancer, and 3 for sleeve gastrectomy). Anemia or gastrointestinal bleeding was the most common symptom (36.5%), followed by gastrointestinal discomfort (32.6%) and incidental findings (21.4%).
Table 1: Patient characteristics

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The anatomic distribution of GISTs in the primary diagnosis group was as follows: 177 in the stomach (58.2%), 83 in the small intestinal (27.3%), 17 in the colon (5.6%), and 3 (1.0%) in other unspecified sites [Table 2]. The mean tumor size was 5.7 cm (median: 4 cm and range: 0.2–29 cm) [Table 3].
Table 2: Antomic site of 1st diagnosis of GIST

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Table 3: Tumor characteristics

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A total of 275 patients (90%) received imatinib either before (neoadjuvant; 26 patients) or after (adjuvant; 262 patients) surgical resection. Thirty-three patients (10.9%) had recurrence or metastasis (18 males and 15 females). The mean interval to recurrence or metastasize was 4.14 years (range: 0.5–9 years and median: 2.1 years). Thirty-three patients had recurrent GISTs. Thirteen patients had metastasis to the liver only; 3 patients had metastasis to the liver, colon, and small intestine; 11 patients had seeding to intra-abdominal tissue or retroperitoneum; and 8 patients had recurrence to the gastrointestinal tract [Table 4].
Table 4: Metastatic antomic site of GIST

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During the study period, 6 patients died (2.0%). Five of them died within 3 months after surgery at our facility (mean: 21 days and range: 8–43 days). Among these 5 patients, 3 died of tumor rupture and hollow organ perforation and 2 had metastasis to the liver and colon and died of postoperative sepsis related to anastomosis leakage. One patient survived for over 10 years and died of pneumonia.

The endoscopic submucosal dissection (ESD) technique has been established in recent years [Figure 2]. It provides shorter postoperative hospital stay [Table 5]. In our experience, the ESD method (31 cases) was suitable for small tumors located in the stomach (mean: 1.45 cm, median: 1.2 cm, and range from 0.5 to 4.5 cm), with a very low-to-intermediate risk (22 very low risk, 3 low risk, and 6 intermediate risk).
Figure 2: Shifting paradigm of approaches

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Table 5: Clinical course characteristics

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  Discussion Top


GISTs are the most common sarcoma of the gastrointestinal tract. GISTs arising in adults are characterized by the near universal expression of CD117/KIT antigen. Early diagnosis (early GISTs without metastasis) with early surgical resection is the best chance to obtain a complete cure. The primary surgical goal is to achieve margin-free resection to the greatest extent possible. Routine lymph node dissection is not recommended. Partial resection or segmental resection with anastomosis to preserve organ function is recommended.[19] With the introduction of surgical staplers and energy devices, laparoscopic surgery is feasible and safe for GISTs in the gastrointestinal tract. According to previous studies, it has similar outcomes when compared with traditional open surgery.[20]

The use of ESD to treat GISTs is still under investigation, especially concerning the long-term safety.[21] We found that ESD was associated with shorter hospital stay, better preservation of organ function, and better quality of life after surgery. However, it still has limitation when dealing with large GISTs.

Imatinib (a first-line tyrosine kinase inhibitor) can be given after surgery, as many studies have reported that it can prolong recurrence-free survival after surgery.[22] In the present study, the omentum, peritoneal seeding, and liver were the most common GIST metastasis sites, which is compatible with the previous studies.[4],[23]


  Conclusion Top


Tumor size, mitotic rate, and tumor location are the main prognostic determinants. Early surgical resection is the most reliable and curative treatment technique for patients without metastasis. Tumor recurrence tends to be intra-abdominal. The administration of tyrosine kinase inhibitors such as imatinib is recommended for unresectable, metastatic, or recurrent GISTs. Postoperative follow-up by computed tomography (CT) to detect recurrence is crucial. The Japanese clinical practice guidelines for GISTs recommend that GISTs with very low, low, and moderate risks are followed up by CT every 6–12 months, and that high risk and GISTs with metastasis should be followed up by CT every 4 6 months.[9],[23]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: An analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol 2005;100:162-8.  Back to cited text no. 1
    
2.
Ma GL, Murphy JD, Martinez ME, Sicklick JK. Epidemiology of gastrointestinal stromal tumors in the era of histology codes: Results of a population-based study. Cancer Epidemiol Biomarkers Prev 2015;24:298-302.  Back to cited text no. 2
    
3.
Goettsch WG, Bos SD, Breekveldt-Postma N, Casparie M, Herings RM, Hogendoorn PC. Incidence of gastrointestinal stromal tumours is underestimated: Results of a nation-wide study. Eur J Cancer 2005;41:2868-72.  Back to cited text no. 3
    
4.
Hechtman JF, DeMatteo R, Nafa K, Chi P, Arcila ME, Dogan S, et al. Additional primary malignancies in patients with gastrointestinal stromal tumor (GIST): A clinicopathologic study of 260 patients with molecular analysis and review of the literature. Ann Surg Oncol 2015;22:2633-9.  Back to cited text no. 4
    
5.
Masoni L, Gentili I, Maglio R, Meucci M, Ambra GD, Giulio ED, et al. Laparoscopic resection of large gastric GISTs: feasibility and long-term results. Surgical Endoscopy 2014;28:2905-10.  Back to cited text no. 5
    
6.
Tzen CY, Wang JH, Huang YJ, Wang MN, Lin PC, Lai GL, et al. Incidence of gastrointestinal stromal tumor: A retrospective study based on immunohistochemical and mutational analyses. Dig Dis Sci 2007;52:792-7.  Back to cited text no. 6
    
7.
Ducimetière F, Lurkin A, Ranchère-Vince D, Decouvelaere AV, Péoc'h M, Istier L, et al. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One 2011;6:e20294.  Back to cited text no. 7
    
8.
Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: An analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol 2005;100:162-8.  Back to cited text no. 8
    
9.
Nishida T, Blay JY, Hirota S, Kitagawa Y, Kang YK. The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines. Gastric Cancer 2016;19:3-14.  Back to cited text no. 9
    
10.
West RB, Corless CL, Chen X, Rubin BP, Subramanian S, Montgomery K, et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004;165:107-13.  Back to cited text no. 10
    
11.
Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: A clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005;29:52-68.  Back to cited text no. 11
    
12.
Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol 2002;33:459-65.  Back to cited text no. 12
    
13.
US Population Data from the US Census Bureau; 2008. Available from: http://www.census.gov/popest/st ates/NST-ann-est.html. [Last accessed on 2011 Mar 08].  Back to cited text no. 13
    
14.
Nilsson B, Bümming P, Meis-Kindblom JM, Odén A, Dortok A, Gustavsson B, et al. Gastrointestinal stromal tumors: The incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era – A population-based study in western Sweden. Cancer 2005;103:821-9.  Back to cited text no. 14
    
15.
Tryggvason G, Gíslason HG, Magnússon MK, Jónasson JG. Gastrointestinal stromal tumors in Iceland, 1990-2003: The Icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer 2005;117:289-93.  Back to cited text no. 15
    
16.
Li J, Ye Y, Wang J, Zhang B, Qin S, Shi Y, et al. Chinese consensus guidelines for diagnosis and management of gastrointestinal stromal tumor. Chin J Cancer Res 2017;29:281-93.  Back to cited text no. 16
    
17.
Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. Lancet 2006;368:1329-38.  Back to cited text no. 17
    
18.
Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013;381:295-302.  Back to cited text no. 18
    
19.
Demetri GD, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, et al. NCCN Task Force report: Update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw 2010;8 Suppl 2:S1-41.  Back to cited text no. 19
    
20.
Chen K, Zhou YC, Mou YP, Xu XW, Jin WW, Ajoodhea H. Systematic review and meta-analysis of safety and efficacy of laparoscopic resection for gastrointestinal stromal tumors of the stomach. Surg Endosc 2015;29:355-67.  Back to cited text no. 20
    
21.
Inoue H, Ikeda H, Hosoya T, Onimaru M, Yoshida A, Eleftheriadis N, et al. Submucosal endoscopic tumor resection for subepithelial tumors in the esophagus and cardia. Endoscopy 2012;44:225-30.  Back to cited text no. 21
    
22.
Joensuu H, Eriksson M, Hall KS, Hartmann JT, Pink D, Schütte J, et al. One vs. three years of adjuvant imatinib for operable gastrointestinal stromal tumor: A randomized trial. JAMA 2012;307:1265-72.  Back to cited text no. 22
    
23.
Akahoshi K, Oya M, Koga T, Shiratsuchi Y. Current clinical management of gastrointestinal stromal tumor. World J Gastroenterol 2018;24:2806-17.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2]
 
 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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