duodenal gist (gastrointestinal stromal tumor)
TRANSCRIPT
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Presentor: Dr. Ved Prakash Sah
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Name: Mr. GS
Age/Sex: 29 Yr/M
Cr no: 2017…..6326
Admission no: 2017….600
Address: Karnal, Haryana
DOA: 05.09.2017
DOSx: 27.09.2017
DOD: 10.10.2017
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Fever x 1 month◦ Low grade, intermittent◦ Not a/w chills & rigors◦ Relieved on medication
Pain abdomen RUQ x 20 days◦ Dull aching, mild in intensity,◦ Non-radiating◦ No aggravating and relieving factors
Generalised weakness x 15 days◦ a/w easy fatiguability but no palpitation, LOC, blackout
LOW & LOA +
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No h/o abdominal distension, vomiting, constipation &
obstipation
No h/o jaundice
No h/o awareness of lump abdomen
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No known comorbities
No h/o any previous surgery
No h/o blood transfusion
Vegetarian diet
Non-smoker, non-alcoholic
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No h/o similar illness in any family members
No h/o any malignancy in any family members
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General examination
◦ Pallor+/ icterus / cyanosis / clubbing / generalized lymphadenopathy /
pedal edema
◦ No supraclavicular LAP
Vitals
◦ PR: 88/min
◦ BP: 110/70mmHg
◦ RR: 18/Min
◦ Afebrile
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Scaphoid
Soft
No lump palpable
No Free Fluid
Bowel sounds +
PR examination – normal
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Pre Op 29/04/17
Hb(g/dL) 9.0
TLC 12800
Platelet 700k
Bil(T/C)mg/dL 0.29/0.04
TP/Alb(g/dL) 8/3.6
OT/PT(U/L) 20/12
ALP(U/L) 129
Na+/K+ 139/4.4
Ur/Cr 17/0.6
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USG Abdomen (01/09/2017)-outside
◦ 10.8x8.2 cm heterogenous lesion with lobulated
margins
◦ Ill defined fat planes between lesion and the inferior
surface of the liver
◦ Lesion causing mass effect on the right kidney
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Stomach◦ Fundus
◦ Body pool of blood present with clots
◦ Antrum-normal
D1D2 jxn: ◦ 3-4 cm large polypoidal mass with overlying
unhealthy mucosa
◦ Sinus opening present through which necrotic material coming out
◦ Extremely friable mass with active blood ooze present
Biopsy taken
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Polypoidal partially exophyticenhancing growth involving D1 and D2 part of duodenum with hypodenseareas within (Necrosis) with extent as described , likely s/o duodenal GIST
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f/s/o Gastrointestinal stromal tumour (GIST)
Tumor compromising of spindle cells seen
Immunostains for SMA & C-kit are positive & chromogranin is negative
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D2 GIST
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APPREPD (Antrum preserving pyloric ring excision pancreaticoduodenectomy) + External pancreatic stent + PJ+HJ+GJ+FJ+perianastomotic drain
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No ascites
No liver/omental/peritoneal deposits
Replaced right hepatic artery arising from SMA
10x12 cm large lobulated mass arising from D2
Extensive large tumour and peritumoralcollateralls
CBD-1 cm in diameter
Pancreas-soft, MPD-1.5mm in diameter
SMV, Portal vein free from tumor mass
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Whipple’s specimen◦ Duodenal GIST High grade
◦ 12x9x5 cm
◦ Mitosis >5/50 hpf
◦ LN 0/9
◦ All resection limit free
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Pancreatic shaved off margin
CBD margin
PeriportalLN
CHA LN
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Distal R/L
Proximal R/L
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C kit SMA
Ki67
Ki67
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Duodenum : Gastrointestinal stromal tumor, high malignant potential
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POD0-1ʘ PRBC transfused
POD1- Elemental feed started via FJ
POD2- PUC removed, self voided
POD3- Pt passed stool, RT removed and orally allowed
POD7- central line removed, ↑ed oral intake
POD8- Drain removed
Discharged on POD12 (27.09.2017)
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6 weeks postop
Pt is planned for adjuvant imatinib therapy
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DISCUSSION
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Represents 0.1-3% of all gastrointestinal (GI)
malignancy but 80% of GI mesenchymal tumors
Term coined in the 1983 by Mazur and Clark
Incidence of 10–20 per million per year
Site
◦ Stomach (60–70 %)
◦ Small intestine (20–25 %) (J>I>D)
◦ Large intestine (5 %)
◦ Oesophagus(‹1 %)
Extragastrointestinal stromal tumors (e-GIST)
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Cells of origin- interstitial cells of Cajal (aka
pacemaker cells of the gut)
◦ Location-normally present in myenteric plexus
◦ Function- coordinates gut peristalsis by assisting the linkage of
smooth muscle cells of the bowel wall with the ANS
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By Hirota and colleagues in 1998
Pathophysiology- gain of excess function at the
tyrosine kinase receptor (KIT) on the cell membrane
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1. KIT mutations (80%)
2. PDGFRA mutations (5-10%)
3. Wild-type GISTs (10-15%)
Markers of GIST
1. CD117 (95%)
2. CD34 (70%)
3. Smooth Muscle Actin
(25%)
4. Desmin (<5%)
5. DOG1
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Tumour size, mitotic count and anatomic location (Gastric<Small
intestine<Rectum) are important prognostic factors
All GISTs have some ability to metastasize and shouldn’t be
considered truly benign
Fletcher et al in 2002 characterized the malignant potential of GIST
Fletcher et al malignant potential of GIST
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Represents 4–5 % of all GISTs & 30% of all primary duodenal tumors
Most common site-D2
Age: >50 yrs (75%)
Sex: M>F
Duodenal Portion Frequency (%)
First 5-25
Second 33-64
Third 22-42
Fourth 8-21
Beltrán MA. Current Management of Duodenal Gastrointestinal Stromal Tumors. Clin Oncol. 2016; 1: 1156.
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S.No. Characteristic Frequency (%)
1. Asymptomatic/incidental finding 9-33
2. Hemorrhage and anemia 22-100
3. Abdominal pain 16-45
4. Palpable abdominal mass 4-18
5. Weight loss 2-14
6. Jaundice 9-11
7. Anorexia 1-9
8. Obstruction 1-3
Beltrán MA. Current Management of Duodenal Gastrointestinal Stromal Tumors. Clin Oncol. 2016;1: 1156.
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At the time of presentation, most tumors are solitary
(89%)
Metastases (hematogenous spread)
◦ Liver-m/c
◦ Peritoneum
Beltrán MA. Current Management of Duodenal Gastrointestinal Stromal Tumors. Clin Oncol. 2016;1: 1156.
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UGIE
◦ Sub-mucosal mass seen as smooth in appearance and as a bulge in the bowel lumen ± ulceration
EUS
◦ Differentiates submucosal GIST mass versus impingement
from surrounding organs like pancreatic mass, pseudocyst
◦ Seen as homogenous, hypoehoic lesion with regular margin
◦ Cystic spaces and irregular margin on EUS s/o malignant GIST
◦ EUS-guided FNA biopsy
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CECT ABDOMEN
◦ Submucosal mass with smooth borders or a rounded
appearance
◦ Exophytic lobulated lesion
◦ Irregular margin, size>10cm, calcification, internal cyst and
central necrosis are suggestive of malignant GIST on CT
PET-CT
◦ Small and metastatic lesion as GIST is FDG-avid
◦ Early assessment of therapeutic response after imatinib therapy
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Surgery is the mainstay of treatment
Surgical principles: 1. Limited intramural extension
Segmental or wedge resection with negative margin
2. Lymphadenectomy not required due to low incidence of lymph node metastasis
3. Avoid tumor spillage
Spillage of tumor cells in the peritoneal cavity - very high risk of peritoneal relapse
1. Complete R0 resection is the treatment of choice
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I. Local resection (LR)
1. Wedge resection
2. Segmental resection
II. Pancreaticoduodenectomy (PD)
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Wedge resection
◦ small (<1 cm) GISTs of the duodenum if they are localized
more than 2 cm from the ampulla of Vater.
Segmental duodenectomy
◦ large (>3 cm) tumors located in the third or fourth or first
portions of the duodenum.
Cavallaro et al. Int J Surg. 2012
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A- Wedge resection with primary sutureB- Segmental resection with primary anastomosis
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Indicated if:
1. Tumor size (≥5 cm)
2. Tumors with high mitotic count ≥5/50 HPF
3. Location
1. proximity to the ampulla of Vater in D2
2. Medial wall of duodenum
4. Invasion or adherence to adjacent organs
Chok AY et al. A systematic review and meta-analysis comparing pancreaticoduodenectomy versus limited resection for duodenalgastrointestinal stromal tumors. Annals of surgical oncology.
2014 Oct 1;21(11):3429-38.
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S.No Local resection (LR) Pancreatiocodudenectomy (PD)
PROS
1. Simpler to perform Negative margin
2. Decreased perioperative morbidity
Appropriate for lesion in medial wall and close to ampulla of vater
3. Does not compromise ononcological outcomes(depends on tumor biology)
CONS
1. Higher positive margin (16% vs 5%)
Higher postop morbidity (48% vs 20%)
Reconstruction can be difficult because of undilated duct
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LR was found to be associated with
1. Lower recurrence rate
2. Better DFS
3. Lower rate of distant metastasis
Reason: Selection bias
(And it was not due to the type of resection because larger and higher-risk tumors were subjected to PD)
Chok AY et al. A systematic review and meta-analysis comparing pancreaticoduodenectomy versus limited resection for duodenalgastrointestinal stromal tumors. Annals of surgical oncology.
2014 Oct 1;21(11):3429-38.
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Recurrence rate:40-50%
◦ Depends on tumor size, site, mitotic rate, surgical margin and
tumor rupture
Follow up
◦ H&P , and CT scan q3-6 months for 3 to 5 years f/by annually
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No role of radiotherapy and conventional cytotoxic
chemotherapy
Biologic agents
◦ Imatinib Mesylate
◦ Sunitinib Malate
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MOA-Binds to the tyrosine kinase receptor preventing phosphorylation
Uses: First line of therapy◦ Recurrent, locally invasive, metastatic GIST◦ In adjuvant setting if T>3 cm(ACOSOG trial by DeMatteo et al in
2009)
S/E◦ Periorbital edema (m/c) -74%◦ Diarrhoea-45%◦ Myalgia-40%◦ Rashes-30%◦ Headache-25%◦ Bleeding-5% , most worrisome, when used in neoadjuvant setting
Dose? How long? Imatinib resistance!
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MOA-inhibits multiple receptor tyrosine kinases, including KIT, PDGFRs (alpha and beta), VEGF receptor 1, -2, and -3
USE: as a second-line therapy◦ GIST pts refractory to imatinib or unable to tolerate imatinib
S/E◦ Fatigue, diarrhea, abdominal pain, nausea, hand-foot skin
reaction, mucositis, hypertension, hypothyroidism
Other kinase inhibitors◦ Regorafenib◦ Nilotinib◦ Sorafenib◦ Masitinib◦ Valatinib◦ Dasatinib◦ Pazopanib
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Prognosis is mainly dependent on malignant status,
which is determined by size and mitotic rate (Fletcher
scale)
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Duodenal GIST are fairly rare
Complete R0 resection is the treatment of choice
Due to the complex anatomy of the duodenum, local
resections are not always feasible
PD remains a good alternative for large tumors and
tumors in the vicinity of the ampulla of Vater
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