GASTROINTESTINAL STROMAL

TUMORS (GISTS)
SURGICAL MANAGEMENT UPDATE
2009

Warko Karnadihardja
 INTRODUCTION
 GISTs are the commonest mesenchynal tumors in the GIT
 Worldwide incidence + 15 per million
Steijfer S et al : Nat Clin Pract Oncol.2008.5; 102-111
 Hirota et al (1998) investigated molecular biology :
 A mutation in the juxtamembrane domain of CD117 (c-
kit) resulted in constitutive activation (gain-of-function)
of the c-kit receptor tyrosine kinase
 This mutation is present in 90% of GISTs, and one-third of
GISTs lacking c-kit mutations have a mutation in a related
tyrosine kinase, platelet-derived growth factor receptor α
(PDGRFA)
Heinrich ML et al Science 2003, 299: 708-710
 INTRODUCTION-2
 Kindblom et al (1998) and Sircar et al (1999) GISTs
share a common percussor with the interstitial cells
of Cajal, which regulate autonomous gut
peristalsis and are intercalated between the
longitudinal and circular layer of muscularis
propria throughout the GIT
 GISTs occur most commonly in the stomach (60%)
followed by : small intestine (25%), colon and
rectum (10%) and esophagus (5%)
 TYROSINE KINASE INHIBITOR (TKI)

 In 2001, a multicenter study reported the efficacy and

safety of TKI : imatinib mesylate (STI 571) for treating
pts with advanced GISTs
Joen sun H et al : N Engl J Med 2001, 344;1052-1056
Demetri GD et al : N Engl J med 2002, 347, 472-480
 Since then, various TKIs have been developed, with the
concept of targeted molecular therapy for cancer
Gold JS, De Matteo RP : Ann Surg 2006, 244, 176-184
 A large proportion of pts with a primary localized GIST
do not require TKIs; they require adequate surgical
resection
 POPULATION BASED DATA
BEFORE THE TKI ERA
 From the USA ( Tran T et al: 1458 cases, 1992-2000)
and Sweden (Nilson B et al, 2005), indicate:
 50%-60% of tumors are localized at the time of
diagnosis
 Complete removal of tumor can be achieved in 95%
of pts with non-metastatic disease
 In contrast, curative resection (RO) is possible only a
small minority of pts presenting with recurrent or
metastatic disease
 Such pts had a median survival of only 12 months
before the introduction of imitinib mesylate
Dematteo RP et al : Ann Surg 2000, 231, 51-58
 THE PRESENT ARTICLE

 Is based on a Pub Med search of the English

literature from 1998 to 2008 for references
continuing the terms : “ gastrointestinal stromal
tumors” and” surgery”
 What follows is a review and critical assessment of
existing surgical strategies for GISTs according to
tumor location
 RATIONALE FOR ASPECIFIC
SURGICAL MANAGEMENT
 GISTs are not like carcinomas
 Specific features of GISTs:
1. Metastases commonly develop in the liver and
peritoneum, but are extremely rare in locoregional
lymph modes
2. GISTs typically show a tending to grow opposite the
intestinal lumen, or towards the abdominal cavity
3. Even when overtly malignant, they have a tending to
displace, but not to invade, surrounding organs
4. They are soft, fragile tumors, when rupture within the
abdomen during surgery, with significant risk of
subsquent peritoneal dissemination
 THE AIM OF SURGERY
 To achieve complete gross resection with negative
histological margins
 Lymphadenectomy in unnecessary
 GISTs of duodenum : pancreas-sparing procedures
 Extraluminal growth of these tumors enhances the
possibility of using minimal invasive techniques
Gervaz P, Huber O, Morel P : Br J Surg.2009, 96: 567-578
MANAGEMENT OF GISTs IN
VARIOUS ORGAN SYSTEMS
 ESOPHAGUS
 In the esophagus, the commonest of mesenchynal tumors are
leiomyomas, which are 3 times as common as GISTs
Meittinem M et al, Ann J Surg Pathal 2000, 24,211-222
 Their endoscopic and radiological appearance being similar,
leiomyomas and GISTs should be differentiated before surgery using
immunohistochemical staining for c-kit (endoscopic vs guided FNA)
Zhu X, et al: World J Gastroenteral 2007, 13: 768-773
 Blum et al (2007) recommended local resection, restricted to small (< 2
cm) of esophageal GISTs, with the condition that negative margins of
resection can be obtained
 Larger tumors or those located close to GE junction are best treated by
Ivor Lewis esophagectomy, as there is no need for regional
lymphadenectomy
 STOMACH
 The stomach is the commonest site for GIST
development
 In a series of 1765 pts, GI bleeding was the most
frequent presentation, and prognosis was usually good
 The overall tumor-specific mortality was 17% and <
2% for tumors smaller than 10 cm
 Even tumors > 10 cm with a low mitotic count were
associated with a low risk (12%) of developing
subsquent metastatic disease
 Recommendation:
 Limited gastric resection with clear margin
 Avoid tumor rupture
Heinrich MC, Corless CL : J Surg Oncol 2005, 90: 195-207
 LESSER CURVATURE AND
GE JUNCTION
 GISTs located near the GE junction are rare and
may be difficult to resect with adequate margins
 In a series of 111 pts with gastric GISTs:
An JY et al (2007) reported a 42% local recurrence rate
 Limited resection is the preferred procedure using
“cut and sew” technique and reconstruction over
esophageal bougie with the aim of preserving
patient of GE junction
 Larger tumors may benefit from neoadjuvant
imitinib therapy to downsize the tumor volume,
making a complete resection easier and safer
Large GIST of Stomach displace without infiltrating the head of
pancreas (black arrow). A distal gastrectomy was performed
GREATER CURVATURE AND FUNDUS
 Most GISTs in this location are approached laparoscopically
and treated with wedge or sleeve resection depending on
tumor size
 In Japan: 2/3 of pts had wedge resection
 in Mayo Clinic : series of 191 GISTs resected between 1978-
2004, + 1/3 of tumors were located within the greater
curvature, mostly removed by laparoscopic wedge resection
 Longterm laparoscopic wedge resection:
 Novitsky et al (2006): 92% disease free survival rate in
50 pts, mean follow-up 36
 Choi et al (2007): no recurrences or liver metastasis in 23
pts
 GISTs located on the posterior wall can be excised using
transgastric approach
 ANTRUM (Prepyloric)
 A minority of GISTs can be safety resected
laparoscopically using a “cut and sew” technique
according to the size of tumors

 If not feasible (size > 3 cm) : distal gastrectomy

whether laparoscopically or hand assisted

 Tumor with φ > 10 cm : resected by laparotomy

 DUODENUM
 GISTs account + 30% of all primary duodenal tumors and
present in the vast majority of pts with GI bleeding
 Commonest procedures: segmental resection, wedge
resection and Whipple’s operation
 Duodenal GISTs have a wide range of aggressiveness, from
small indolent tumours to overt sarcomas
 In summary:
 Wedge resection for tumors < 1 cm as long as they are
located > 2 cm away from ampulla of Vater
 Segmental duodenectomy : tumors > 3 cm on D3/D4,
with a side to side duodenojejunostomy opposite to the
ampulla
 Whipple’s procedure : the best option for peri ampullary
GISTs, or large tumors of D1/D2
 SMALL BOWEL-1
 The small intestine is the second commonest
location of GISTs and as early as 1999 clinicians
suspected this anatomical site to be associated with
poor prognosis
Emory TS et al : Am J Surg Pathed, 1999, 23; 82-87
 Despite conflicting data from post-imitinib era
gastric and small bowel GISTs with similar size and
mitotic activity have a strikingly different prognosis
(49% vs 11%) tumor-related mortality
Keun Park C et al : Am J Surg 2008, 247: 1011-1018
Miettinem M, Lasota J, Semm Diagn Pathol, 2006, 23 : 70-83
 SMALL BOWEL-2
 A series from a single tertiary cancer centre in the pre-
imatinib era clearly confirmed that small bowel GISTs
are aggressive tumors, with overall disease free
survival rates of 59%, 24% and 18% at 1,3 and 5
years ( Crosby JA et al 2001)
 Most pts present with bleeding and in one series 28%
had non-elective procedures for either severe
hemorrhage or tumor perforation
 WW TJ et al : BMC gastroenterology 2006, 6, 29
 Segmental resection of the small bowel without
lymphadenectomy, is the recommended treatment for
jejunal and ileal GISTs
 SMALL BOWEL-3
 Many pts with small bowel GISTs present with
anemia secondary to occult GI bleeding
 GISTs was the most frequent tumor type (32%)
detected in a series of 5129 pts who had video
capsule endoscopy
(Rondenotti E et al: Endoscopy 2008, 40; 488-495)
 Larger tumors ( > 5 cm) which are usually detected
by CT Scan, and those located close to the
duodenojejunal function require a laparotomy
approach
 VIDEO CAPSUL ENDOSCOPY VS
DOUBLE BALLOON ENDOSCOPY
 Three major drawbacks of video capsul endoscopy
1. There is a lack of biopsy capability
2. There is a lack of precise information regarding
tumor location within the small bowel
3. There is a risk of missing lessions, because of their
tendency to grow extra luminal
 Double balloon endoscopy to be superior to video
capsule endoscopy:
 Possibilities of obtaining biopsies (D0/lymphoma)
 Tattooing the site of GIST to make perioperative
location easy during laparoscopic resection for
small GISTs of jejunum and ileum
 COLON
 Less than 5% of GISTs are located in the colon
 Colonic GISTs must be distinguished from leiomyomas
originating from the muscularis mucosal, which are
benign
Miettinen M et al : Mod Pathal 2001, 14:9500-956
 Most pts present with relatively bulky tumors causing
pain and bleeding
 Segmental colectomy without LN dissection is
recommended strategy
 The prognosis is poor, especially for tumors with high
mitotic count
 RECTUM
 According to Miettinen group, the rectum is the 3rd
commonest site for GISTs, 5%-10% of all tumors

 Symptoms : bleeding on peritoneal pain or

discomfort

 New adjuvant therapy with imatinib may play role

in downsizing large pelvic GISTs, especially when
tumor is in the vicinity of the anal sphincters
 METASTATIC GI STROMAL TUMORS

 As many as 40% of pts after resections of a

primary localized tumor will eventually develop
recurrent disease, mostly in the liver and
peritoneum
 Before imatinib, the median survival of these pts
was 19 mo with a 25% 5-year survival rate (Gold
JS.2007)
 One series has reported the outcome of 60 pts who
had surgery for recurrent or metastatic GIST
between 1982 and 1995: median survival of 15
mo
 NEOADJUVANT IMITINIB
MESYLATE THERAPY
 In the absence of high level, rely on 3
variables
Tumor resectability
Extent of procedure needed to achieve
RO resection
Expected functional outcome
 CONCLUSION
 Surgical management of these sarcomas
should be tailored according to the tumor
location and morphological characteristics
 Clinical decision making for marginally
resectable on locally advanced GISTs
requires multidisciplinary approach
expertise
 Surgery for metastatic but initially TKI-
responces, GISTs is still under investigation
 CT-SCAN
BULAN JUNI
 LAPAROTOMI
 Tumor capsulated mudah dibebaskan dari
pankreas, lien dinding belakang abdomen tetapi
melekat dengan dinding belakang korpus
lambung sekitar 7 cm. Diputuskan dilakukan eksisi
sekitar 2 cm dari batas perlekatan tumor.
Pancreatico duodenectomy

1980 ; Male, 14 years, Bandung

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