Presentor: Dr. Ved Prakash Sah

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

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 +

No h/o abdominal distension, vomiting, constipation &

obstipation

No h/o jaundice

No h/o awareness of lump abdomen

No known comorbities

No h/o any previous surgery

No h/o blood transfusion

Vegetarian diet

Non-smoker, non-alcoholic

No h/o similar illness in any family members

No h/o any malignancy in any family members

General examination

◦ Pallor+/ icterus / cyanosis / clubbing / generalized lymphadenopathy /

pedal edema

◦ No supraclavicular LAP

Vitals

◦ PR: 88/min

◦ BP: 110/70mmHg

◦ RR: 18/Min

◦ Afebrile

Scaphoid

Soft

No lump palpable

No Free Fluid

Bowel sounds +

PR examination – normal

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

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

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

Polypoidal partially exophyticenhancing growth involving D1 and D2 part of duodenum with hypodenseareas within (Necrosis) with extent as described , likely s/o duodenal GIST

f/s/o Gastrointestinal stromal tumour (GIST)

Tumor compromising of spindle cells seen

Immunostains for SMA & C-kit are positive & chromogranin is negative

D2 GIST

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

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

Whipple’s specimen◦ Duodenal GIST High grade

◦ 12x9x5 cm

◦ Mitosis >5/50 hpf

◦ LN 0/9

◦ All resection limit free

Pancreatic shaved off margin

CBD margin

PeriportalLN

CHA LN

Distal R/L

Proximal R/L

C kit SMA

Ki67

Ki67

Duodenum : Gastrointestinal stromal tumor, high malignant potential

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)

6 weeks postop

Pt is planned for adjuvant imatinib therapy

DISCUSSION

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)

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

By Hirota and colleagues in 1998

Pathophysiology- gain of excess function at the

tyrosine kinase receptor (KIT) on the cell membrane

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

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

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.

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.

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.

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

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

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

I. Local resection (LR)

1. Wedge resection

2. Segmental resection

II. Pancreaticoduodenectomy (PD)

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

A- Wedge resection with primary sutureB- Segmental resection with primary anastomosis

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.

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

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.

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

No role of radiotherapy and conventional cytotoxic

chemotherapy

Biologic agents

◦ Imatinib Mesylate

◦ Sunitinib Malate

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!

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

Prognosis is mainly dependent on malignant status,

which is determined by size and mitotic rate (Fletcher

scale)

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