Duodenal gist (gastrointestinal stromal tumor)

1. Presentor: Dr. Ved Prakash Sah

2.  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

3.  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 +

4.  No h/o abdominal distension, vomiting, constipation &
obstipation
 No h/o jaundice
 No h/o awareness of lump abdomen

5.  No known comorbities
 No h/o any previous surgery
 No h/o blood transfusion
 Vegetarian diet
 Non-smoker, non-alcoholic

6.  No h/o similar illness in any family members
 No h/o any malignancy in any family members

7.  General examination
◦ Pallor+/ icterus / cyanosis / clubbing / generalized lymphadenopathy /
pedal edema
◦ No supraclavicular LAP
 Vitals
◦ PR: 88/min
◦ BP: 110/70mmHg
◦ RR: 18/Min
◦ Afebrile

8.  Scaphoid
 Soft
 No lump palpable
 No Free Fluid
 Bowel sounds +
 PR examination – normal

9. 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

10.  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

11.  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

20.  Polypoidal partially exophytic
enhancing growth involving D1 and
D2 part of duodenum with hypodense
areas within (Necrosis) with extent as
described , likely s/o duodenal GIST

21.  f/s/o Gastrointestinal stromal tumour (GIST)
 Tumor compromising of spindle cells seen
 Immunostains for SMA & C-kit are positive &
chromogranin is negative

22. D2 GIST

23.  APPREPD (Antrum preserving pyloric ring
excision pancreaticoduodenectomy) +
External pancreatic stent +
PJ+HJ+GJ+FJ+perianastomotic drain

24.  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 peritumoral
collateralls
 CBD-1 cm in diameter
 Pancreas-soft, MPD-1.5mm in diameter
 SMV, Portal vein free from tumor mass

26. Whipple’s specimen
◦ Duodenal GIST High grade
◦ 12x9x5 cm
◦ Mitosis >5/50 hpf
◦ LN 0/9
◦ All resection limit free

36. Pancreatic shaved off
margin
CBD margin
Periportal CHA

37. Distal Proximal

38. C kit SMA
Ki Ki

39.  Duodenum : Gastrointestinal stromal tumor,
high malignant potential

40.  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)

41.  6 weeks postop
 Pt is planned for adjuvant imatinib therapy

42. DISCUSSION

43.  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)

44.  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

45.  By Hirota and colleagues in 1998
 Pathophysiology- gain of excess function at the
tyrosine kinase receptor (KIT) on the cell membrane

46. 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

47.  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

48.  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.

49. 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.

50.  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.

51.  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

52.  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

53.  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

54. I. Local resection (LR)
1. Wedge resection
2. Segmental resection
II. Pancreaticoduodenectomy (PD)

55.  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

56. A- Wedge resection with primary suture
B- Segmental resection with primary anastomosis

57.  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 duodenal
gastrointestinal stromal tumors. Annals of surgical oncology.
2014 Oct 1;21(11):3429-38.

59. 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 on
oncological 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

60.  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 duodenal
gastrointestinal stromal tumors. Annals of surgical oncology.
2014 Oct 1;21(11):3429-38.

61.  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

62.  No role of radiotherapy and conventional cytotoxic
chemotherapy
 Biologic agents
◦ Imatinib Mesylate
◦ Sunitinib Malate

63.  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!

64.  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


65. Prognosis is mainly dependent on malignant status,
which is determined by size and mitotic rate (Fletcher
scale)

66.  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