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86 Case Report Kitasato Med J 2015; 45: 86-89 Received 29 October 2014, accepted 5 January 2015 Correspondence to: Masahiko Watanabe, Department of Surgery, Kitasato University School of Medicine 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan E-mail: [email protected] Laparoscopic resection of a small-bowel gastrointestinal stromal tumor (GIST): a case report Satoru Ishii, 1 Takatoshi Nakamura, 1 Keita Kojima, 1 Atsuko Tsutsui, 1 Hirohisa Miura, 1 Takeo Sato, 1 Shi-Xu Jiang, 2 Masahiko Watanabe 1 1 Department of Surgery, Kitasato University School of Medicine 2 Department of Pathology, Kitasato University School of Medicine Gastrointestinal stromal tumor (GIST) of the small bowel is a relatively rare submucosal tumor that is often difficult to diagnose preoperatively. The only effective treatment is complete tumor resection. We describe a patient with a small-bowel GIST in whom laparoscopy was useful for diagnosis and treatment. The patient was a 65-year-old woman who underwent laparoscopic partial resection of the small intestine for a well-demarcated, solid mass arising in the ileum, measuring about 6 cm in diameter. The resected mass measured 5.5 cm in diameter and was immunohistopathologically positive for c-Kit and negative for CD34, with a Ki-67 labeling index of <1%. A moderate-risk GIST of the small bowel was diagnosed. The use of laparoscopy permitted extensive examination of the abdominal cavity through a small incision and allowed the lesion to be resected using a minimal number of skin incisions, placed at appropriate sites. As of 3 years after surgery, there is no evidence of recurrence. Key words: small-bowel submucosal tumor, gastrointestinal stromal tumor (GIST), laparoscopic surgery Introduction he anatomic characteristics of small-bowel tumors with extraluminal growth often lead to difficulty in diagnosis and treatment. Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor arising in the gastrointestinal tract or mesentery. Approximately 25% of GISTs occur in the small bowel. 1,2 We describe our experience with a patient who had a small-bowel GIST that could be resected laparoscopically. Case Report The patient was a 65-year-old woman who was referred to our hospital because of an abdominal mass, detected on a gynecologic examination. The abdomen was flat, with no palpable tumor or tenderness. Blood tests showed no abnormalities. Contrast-enhanced computed tomography of the abdomen revealed a hypovascular mass contiguous with the intestinal wall in the pelvic cavity (Figure 1). A small-bowel series showed a submucosal tumor-like shadow defect (Figure 2). The lesion could not be identified on enteroscopy. A small- bowel submucosal tumor was diagnosed. The differential diagnosis included GIST, schwannoma, leiomyoma, desmoid tumor, and a solitary fibrous tumor. Laparoscopic surgery was performed. A 2-cm incision T Figure 1. A contrast-enhanced computed tomographic scan of the abdomen, showing a mass, about 6 cm in diameter, in the lower small intestine. There was no evidence of peritoneal metastasis, liver metastasis, or lymph-node metastasis.

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Page 1: Laparoscopic resection of a small-bowel gastrointestinal ... · The only effective treatment is complete tumor resection. We describe a patient with a small-bowel GIST in whom laparoscopy

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 Case Report Kitasato Med J 2015; 45: 86-89 

Received 29 October 2014, accepted 5 January 2015Correspondence to: Masahiko Watanabe, Department of Surgery, Kitasato University School of Medicine1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, JapanE-mail: [email protected]

Laparoscopic resection of a small-bowel gastrointestinal stromaltumor (GIST): a case report

Satoru Ishii,1 Takatoshi Nakamura,1 Keita Kojima,1 Atsuko Tsutsui,1 Hirohisa Miura,1

Takeo Sato,1 Shi-Xu Jiang,2 Masahiko Watanabe1

1 Department of Surgery, Kitasato University School of Medicine2 Department of Pathology, Kitasato University School of Medicine

Gastrointestinal stromal tumor (GIST) of the small bowel is a relatively rare submucosal tumor that isoften difficult to diagnose preoperatively. The only effective treatment is complete tumor resection.We describe a patient with a small-bowel GIST in whom laparoscopy was useful for diagnosis andtreatment. The patient was a 65-year-old woman who underwent laparoscopic partial resection of thesmall intestine for a well-demarcated, solid mass arising in the ileum, measuring about 6 cm indiameter. The resected mass measured 5.5 cm in diameter and was immunohistopathologicallypositive for c-Kit and negative for CD34, with a Ki-67 labeling index of <1%. A moderate-risk GISTof the small bowel was diagnosed. The use of laparoscopy permitted extensive examination of theabdominal cavity through a small incision and allowed the lesion to be resected using a minimalnumber of skin incisions, placed at appropriate sites. As of 3 years after surgery, there is no evidenceof recurrence.

Key words: small-bowel submucosal tumor, gastrointestinal stromal tumor (GIST), laparoscopicsurgery

Introduction

he anatomic characteristics of small-bowel tumorswith extraluminal growth often lead to difficulty in

diagnosis and treatment. Gastrointestinal stromal tumor(GIST) is a mesenchymal tumor arising in thegastrointestinal tract or mesentery. Approximately 25%of GISTs occur in the small bowel.1,2 We describe ourexperience with a patient who had a small-bowel GISTthat could be resected laparoscopically.

Case Report

The patient was a 65-year-old woman who was referredto our hospital because of an abdominal mass, detectedon a gynecologic examination. The abdomen was flat,with no palpable tumor or tenderness. Blood tests showedno abnormalities. Contrast-enhanced computedtomography of the abdomen revealed a hypovascularmass contiguous with the intestinal wall in the pelviccavity (Figure 1). A small-bowel series showed asubmucosal tumor-like shadow defect (Figure 2). The

lesion could not be identified on enteroscopy. A small-bowel submucosal tumor was diagnosed. The differentialdiagnosis included GIST, schwannoma, leiomyoma,desmoid tumor, and a solitary fibrous tumor.Laparoscopic surgery was performed. A 2-cm incision

T

Figure 1. A contrast-enhanced computed tomographic scan ofthe abdomen, showing a mass, about 6 cm in diameter, in thelower small intestine. There was no evidence of peritonealmetastasis, liver metastasis, or lymph-node metastasis.

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was made in the umbilicus, and a camera port (12 mm)was inserted. Laparoscopic examination showed a solidtumor with vascularity and extraluminal growth, locatedabout 240 cm from the terminal ileum (Figure 3). Therewas no invasion of other organs or ascites. On the basisof the above findings, the tumor was initially considereda GIST. The umbilical incision was extended to 6 cm. Awound protector was used to remove the tumor from thebody without contacting the abdominal wall, and thesmall intestine was partially resected. Macroscopically,the tumor was a flat smooth mass, 5.5 cm in diameter,which grew extraluminally (Figure 4). Histopathologicalexamination showed spindle-shaped cells proliferatingin a complex manner, with low cell density and noevidence of tumor necrosis. The number of mitotic figureswas 1 to 3 per 50 high-power fields (HPF). Onimmunostaining (Figure 5), the mass was positive for c-Kit and negative for CD34 and α-SMA, with a Ki-67

Figure 2. Findings on enterography. A protrudinglesion with a flat mucosal surface in the ileum. Thelesion repelled gastrographin.

Figure 3. Laparoscopic findings. A tumor with extraluminalgrowth was located about 240 cm from the terminal ileum. Afterthe lesion was resected in the abdominal cavity, the camera portincision was extended. The lesion was removed from the bodyafter protecting the wound margins.

Figure 4. The surgically resected specimen, showinga submucosal tumor, 5.5 cm in diameter, with no ulceror erosion on the mucosal surface.

A. Hematoxylin and eosin staining (×200),showing a tumor with fascicular and trabecularproliferation of spindle-shaped cells.

B. The tumor was positive for c-Kit (×200).

Figure 5. Histopathological findings

Small-bowel gastrointestinal stromal tumor

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Ishii, et al.

labeling index of 1% or less. A moderate-risk GIST wasdiagnosed. The patient was uneventfully discharged onthe seventh hospital day. As of 3 years after surgery,there has been no evidence of recurrence.

Discussion

We laparoscopically diagnosed and treated a GIST arisingin the small bowel. The use of laparoscopy permittedextensive examination of the abdominal cavity, andallowed the lesion to be completely resected, using aminimal number of skin incisions.

Small-bowel GISTs most commonly arise in the upperjejunum and the lower ileum. Macroscopically, GISTshave a well-demarcated capsule, with a yellowish-whitecut surface. Histologically, GISTs can be classified asspindle-cell type, epithelioid type, and mixed type.Spindle-cell type GISTs are most common.3,4 Onimmunostaining, more than 90% of GISTs are positivefor c-Kit, and most show strongly positive, nearlyhomogenous staining.5 Mutations in exon 9 of the c-KITgene are often found in the small intestine.6,7 The rate ofpositive staining for CD34 is about 70%. CD34 positivityis thus useful for the diagnosis of c-Kit-negative GISTs.In recent years, DOG-1 (discovered on GIST-1)8

immunostaining has been reported to be useful for thediagnosis of c-Kit-negative GIST, with a higher sensitivityand specificity than c-Kit.8,9 However, about 30% of c-Kit negative GISTs are also negative for DOG-1.Consequently, DOG-1 has also been reported not to bealmighty for the diagnosis of GISTs.9,10 PDGFRA genemutations have been reported in 80% to 90% of all GISTs.Analysis of PDGFRA gene mutations may therefore beuseful in patients with GISTs negative for both c-Kit andCD34.11

Surgical resection is the treatment of choice for small-bowel GISTs. Lymph-node metastasis is rare, and lymph-node dissection is considered unnecessary.12,13

Laparoscopic surgery is indicated for the managementof most small-bowel GISTs, with the exception of far-advanced disease associated with giant tumors orperitoneal dissemination. However, the tumor shouldnot be directly grasped with a forceps or other devicesbecause the intraoperative use of a forceps can damagethe tumor capsule, potentially leading to bleeding anddissemination of tumor cells.

Clinically, GISTs accompanied by invasion andtumor-induced destruction of adjacent organs have ahigher than 90% risk of recurrence and are thereforeclassified as malignant GISTs. Risk is classified on thebasis of two factors, tumor diameter and cell proliferation

activity. Tumors 5 cm or larger in diameter with 5 to 10mitotic figures per 50 HPF and tumors 10 cm or more indiameter with more than 10 mitotic figures per 50 HPFare classified as high risk.14-16 Our patient had a 8-cmtumor with a Ki67 labeling index17 of 1% or less,indicating a moderate risk.

Postoperative adjuvant therapy with imatinib has beenshown to prolong relapse-free survival,18 but is still inclinical trials, and its effectiveness and safety have yet tobe established. Therefore, we did not use imatinib. Inhigh-risk patients, observation by CT every 4 to 6 monthsor adjuvant chemotherapy is recommended. Adjuvantchemotherapy with imatinib was confirmed to be safe 3years after surgery and has also been reported to improverelapse-free survival and overall survival.18,19 As of 3years after surgery, our patient remains free of recurrence.However, close follow-up is considered mandatorybecause the patient was at moderate risk.

Enteroscopy and capsule endoscopy have beenreported to be useful for the diagnosis of small intestinaltumors. However, a definitive diagnosis is often difficultto make before surgery in patients who have tumors withextraluminal growth, similar to our patient. Laparoscopyis beneficial for comprehensive diagnosis and treatmentin such patients. As compared with open surgery,laparoscopic surgery for small intestinal tumors permitsdetailed examination of the entire abdominal cavity andenables appropriate incision sites to be determined,thereby allowing surgery to be completed with a minimalnumber of surgical wounds. Other advantages oflaparoscopic surgery include earlier recovery andprompter return to social activities, minimal invasiveness,and a good esthetic outcome.

We described our experience with a patient who hada small GIST that could be resected laparoscopically.Our findings indicate that laparoscopic surgery is usefulfor the diagnosis and treatment of small-bowel tumorsthat are difficult to definitively diagnose before surgery.

References

1. Miettinen M, Majidi M, Lasota J. Pathology anddiagnostic criteria of gastrointestinal stromal tumors(GISTs): a review. Eur J Cancer 2002; 38 (Suppl 5):S39-51.

2. DeMatteo RP, Lewis JJ, Leung D, et al. Two hundredgastrointestinal stromal tumors: recurrence patternsand prognostic factors for survival. Ann Surg 2000;231: 51-8.

3. Mazur MT, Clark HB. Gastric stromal tumors:Reappraisal of histogenesis. Am J Surg Pathol 1983;7: 507-19.

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4. Rosai J. Stromal tumors. Ackerman's SurgicalPathology, 8th edition. St. Louis: Mosby-Year Book;1996; 645-7.

5. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinalstromal tumors. Science 1998; 279: 577-80.

6. Miettinen M, Lasota J. Gastrointestinal stromaltumors-def in i t ion , c l in ica l , h is to logica l ,immunohistochemical, and molecular geneticfeatures and differential diagnosis. Virchows Arch2001; 438: 1-12.

7. Heinrich MC, Rubin BP, Longley BJ, et al. Biologyand genetic aspects of gastrointestinal stromal tumors:KIT activation and cytogenetic alterations. HumPathol 2002; 33: 484-95.

8. West RB, Corless CL, Chen X, et al. The novelmarker, DOG1, is expressed ubiquitously ingastrointestinal stromal tumors irrespective of KITor PDGFRA mutation status. Am J Pathol 2004;165: 107-13.

9. Espinosa I, Lee CH, Kim MK, et al. A novelmonoclonal antibody against DOG1 is a sensitiveand specific marker for gastrointestinal stromaltumors. Am J Surg Pathol 2008; 32: 210-8.

10. Liegl-Atzwanger B, Fletcher JA, Fletcher CD.Gastrointestinal stromal tumors. Virchows Arch2010; 456: 111-27.

11. Hirota S, Ohashi A, Nishida T, et al. Gain-of-functionmutations of platelet-derived growth factor receptoralpha gene in gastrointestinal stromal tumors.Gastroenterology 2003; 125: 660-7.

12. Corless CL, McGreevey L, Haley A, et al. KITmutations are common in incidental gastrointestinalstromal tumors one centimeter or less in size. Am JPathol 2002; 160: 1567-72.

13. Ng EH, Pollock RE, Munsell MF, et al. Prognosticfactors influencing survival in gastrointestinalleiomyosarcomas. Implications for surgicalmanagement and staging. Ann of Surg 1992; 215:68-77.

14. Hasegawa T, Yokoyama R, Lee YH, et al. Prognosticrelevance of a histological grading system using MIB-1 for adult soft-tissue sarcoma. Oncology 2000; 58:66-74.

15. Hasegawa T, Yamamoto S, Nojima T, et al. Validityand reproducibility of histologic diagnosis andgrading for adult soft-tissue sarcomas. Hum Pathol2002; 33: 111-5.

16. Fletcher CD, Berman JJ, Corless C, et al. Diagnosisof gastrointestinal stromal tumors: A consensusapproach. Hum Pathol 2002; 33: 459-65.

17. Hasegawa T, Yamamoto S, Yokoyama R, et al.Prognostic significance of grading and stagingsystems using MIB-1 score in adult patients withsoft tissue sarcoma of the extremities and trunk.Cancer 2002; 95: 843-51.

18. DeMatteo RK, Owzar KR, Maki R, et al. Adjuvantimatinib mesylate increases recurrence free survival(RFS) in patients with completely resected localizedprimary gastrointestinal stromal tumor (GIST): NorthAmerican Intergroup Phase III trial ACOSOG Z9001.2007 ASCO Annual Meetings.

19. Joensuu H. Tweleve versus 36 months of adjuvantimatinib (IM) as treatment of operable GIST with ahigh risk of recurrence: Final results of a randamizedtrial (SSGXVIII/AIO). J Clin Oncol 2011; 29 (18Suppl); 775s.

Small-bowel gastrointestinal stromal tumor