Duodenal gist (gastrointestinal stromal tumor)

Duodenal gist (gastrointestinal stromal tumor)

1. DUODENAL GIST 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 Index Case

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 + Clinical History

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

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

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

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

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

9. INVESTIGATIONS 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 Investigations

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 UGIE (08/09/17)

12. 9.9x5.9x6.9 cm polypoidal partially exophytic enhancing growth in D2 & part of D1 No significant luminal compromise Fat planes with adjacent liver segment is illdefined Posteriorly abutting anterior surface of right kidney Increased mesenteric vascularity locally Rest of the visualised bowel loops are grossly unremarkable CECT Abdomen(11/09/17)-M19942/17

13. CECT ABDOMEN 11/9/2017

14. RADIOLOGICAL IMPRESSION 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

15. f/s/o Gastrointestinal stromal tumour (GIST) Tumor compromising of spindle cells seen Immunostains for SMA & C-kit are positive & chromogranin is negative Duodenal biopsy (S-24931/17)

16. D2 GIST Diagnosis

17. APPREPD ( Antrum preserving pyloric ring excision pancreaticoduodenectomy ) + External pancreatic stent + PJ+HJ+GJ+FJ+perianastomotic drain Surgery ( DOSx : 27.09.2017)

18. 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 Intraop findings

19. Cut Section Image

20. Whipple’s specimen Duodenal GIST High grade 12x9x5 cm Mitosis >5/50 hpf LN 0/9 All resection limit free HPR (S-27046/2017)

21. Pancreatic shaved off margin CBD margin Periportal LN CHA LN

22. Distal R/L Proximal R/L

23. C kit SMA Ki 67 Ki 67

24. Duodenum : Gastrointestinal stromal tumor, high malignant potential

25. 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) Post op period

26. 6 weeks postop Pt is planned for adjuvant imatinib therapy Follow Up

27. DISCUSSION

28. Represents 0.1-3% of all gastrointestinal (GI) malignancy but 80% of GI mesenchymal tumors Term coined in the 1983 by Mazur and Clark I ncidence of 10–20 per million per year Site S tomach (60–70 %) Small intestine (20–25 %) (J>I>D) L arge intestine (5 %) Oesophagus (‹1 %) Extragastrointestinal stromal tumors (e-GIST) Gastrointestinal stromal tumor (GIST)

29. 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 GIST…

30. B y Hirota and colleagues in 1998 Pathophysiology- gain of excess function at the tyrosine kinase receptor (KIT) on the cell membrane Molecular mechanism of carcinogenesis

31. KIT mutations (80%) PDGFRA mutations (5-10%) Wild-type GISTs (10-15%) MUTATIONS Markers of GIST CD117 (95%) CD34 (70%) Smooth Muscle Actin (25%) Desmin (<5 %) DOG1

32. 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 Predictors of malignancy in GIST Fletcher et al malignant potential of GIST

33. Represents 4–5 % of all GISTs & 30% of all primary duodenal tumors Most common site-D2 Age: >50 yrs (75%) Sex: M>F Duodenal GISTs 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.

34. 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 Clinical presentation Beltrán MA. Current Management of Duodenal Gastrointestinal Stromal Tumors. Clin Oncol . 2016 ; 1: 1156.

35. At the time of presentation, most tumors are solitary (89 %) Metastases ( hematogenous spread) Liver-m/c Peritoneum Clinical presentation Beltrán MA. Current Management of Duodenal Gastrointestinal Stromal Tumors. Clin Oncol . 2016 ; 1: 1156.

36. 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 Diagnosis

37. 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 IMAGING

38. Surgery is the mainstay of treatment Surgical principles: Limited intramural extension Segmental or wedge resection with negative margin Lymphadenectomy not required due to low incidence of lymph node metastasis Avoid tumor spillage Spillage of tumor cells in the peritoneal cavity - very high risk of peritoneal relapse Complete R0 resection is the treatment of choice TREATMENT

39. Local resection (LR) Wedge resection Segmental resection Pancreaticoduodenectomy (PD) Surgical options

40. Local Resection 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

41. Local resection (LR) A- Wedge resection with primary suture B- Segmental resection with primary anastomosis

42. I ndicated if: T umor size (≥5 cm ) T umors with high mitotic count ≥5/50 HPF Location proximity to the ampulla of Vater in D2 Medial wall of duodenum Invasion or adherence to adjacent organs Pancreaticoduodenectomy 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.

43. Pancreaticoduodenectomy (PD)

44. S.No Local resection (LR) Pancreatiocodudenectomy (PD) PROS 1. Simpler to perform Negative margin 2. Decreased perioperative morbidity Appropriate for lesion in m edial 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 LR versus PD

45. LR was found to be associated with Lower recurrence rate B etter DFS 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) LR versus 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.

46. 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 Duodenal GIST

47. No role of radiotherapy and conventional cytotoxic chemotherapy Biologic agents Imatinib Mesylate Sunitinib Malate Adjuvant therapy

48. 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! BIOLOGIC AGENT- Imatinib

49. 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   BIOLOGIC AGENT- Sunitinib

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

51. Take home message 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