1. MEDICAL GRANDROUNDS ERNEST JOEL SAMACO M.D. FEBUARY 1, 2007
GOOD MORNING
MEDICAL GRANDROUNDS
ERNEST JOEL SAMACO M.D.
FEBUARY 1, 2007

2. A.G. 51 MALE MARRIED CATHOLIC EMPLOYEE KAWIT CAVITE
GENERAL DATA
A.G.
51 MALE
MARRIED
CATHOLIC
EMPLOYEE
KAWIT CAVITE

3. CHIEF COMPLAINT
ABDOMINAL PAIN

4. Objectives
To present a case of a female patient with a giant malignant gastrointestinal stromal tumor of the jejunum
To discuss the approach to patients with abdominal pain - its evaluation and management
To discuss the management of gastrointestinal stromal tumor.

5. HISTORY OF PRESENT ILLNESS
Three month5 day hx abdominal fullness
appetite irregular bowel movement
(-) nausea, vomiting, fever
(-)early satiety,melena,hematochezia
, domperidone 10mg 2 tab
+ consult AMD
Imp: Acid Peptic Disease
PFA: Ileus
Ranitidine 1 tab BID x 1week
Pineverium bromide x 3 days
Domperidone 10 mg TID

6. PFA Reflex Ileus Right Pelvic Calcification R/O Distal
Calculus in the distal end of the right ureter

7. Two month + still with abdominal fullness
occassional crampy RUQ abdominal pain, PS 7-8/10
re-consulted AMD
s/p gastroscopy
dx duodenal ulcer; negative H.pyolri
Esomeprazole 20mg BID; domperidone 10mgTID ac; rebamipide 100mg TID ac
symptoms improved
Irrectable abdominal pain
None responsive to medication
American Gastro recomendadtion egd >45
Colonoscopy was not done because the symptoms does not indicative to do colonoscopy
Hisotpath biopsy was not done because

8. Night PTAabdominal pain 10/10 localized at the LUQ
One monthrecurrence abdominal fullness Repeat gastroscopy done showed healing duodenal ulcer, gastritis Esomeprazole 40mg OD x 4 wk
2 weeks PTAprogressive bloatedness constipation
Night PTAabdominal pain 10/10
localized at the LUQ
associated with severe bloatedness and nausea
Persistence of symptoms prompted consult

9. Review of Systems (-) fever (-) chest pain (-) cough (-) DOB
(-) easy fatigability (-) urinary changes
(+) weight loss

10. Past Medical History
(+) HPN, HBP: 160/100 NBP: 130/90 on metoprolol 50mg 1/2 tab BID and valsartan+HCTZ 160/2.5mg OD
(-) DM
(-) PTB, Bronchial Asthma, allergies
(-) previous surgery
Denies use of NSAID

11. Family History (-) HPN, DM, Asthma (-) Cancer Personal Social History
(-) smoker
(-) drinker
No food preference
Denies exposure to chemicals

12. Physical Exam Conscious coherent, not in CRD
BP: 130/90 HR: 76 RR: 20 T36.2
Ht 5’8” Wt 188 lbs BMI 28.9
SHEENT: anicteric sclerae, pink palpebral conjunctivae, No CLAD, flat neck veins
C/L: no spider naevi noted, symmetric chest expansion, clear breath sounds
Heart: adynamic precordium, distinct heart sounds, NRRR, no murmur.

13. Abdomen: Globular (40.4 inches), normoactive BS, no abdominal bruit, soft, (+)direct tenderness LUQ, (-) rebound tenderness, (-) Murphy’s and Mc Burney’s signs, tympanitic,(-) shifting dullness, (-)organomegaly/mass
Ext: Full equal pulses, Pink nail beds, (-) edema
Rectal: Good sphincter muscles,(-) tenderness, (-)mass, (-) blood on examining finger

14. Salient Features 51 male Abdominal pain (LUQ) Severe bloatedness
Nausea
constipation
(+) weight loss 6 lbs 3 months
PUD S/P EGD
Hypertensive
No family history of cancer
Abdomen: globular (40.4inches), direct tenderness LUQ

15. Admitting Impression Irritable Bowel Sydrome
Acid Peptic Ulcer disease (s/p Gastroscopy 9/06 & 10/06)
Hypertensive Cardiovascular Disease

16. Course in the wards

17. At the ER Diagnostics: CBC, Serum Na, K, lipase, ECG, CXR NPO
IVF: D5MM 1L x 8
Meds: Tramadol 50mg IV q 8
Esomeprazole 40mg IV OD
Metoclopromide 10mg IV q8

18. CBC Serum K: 2.5 (corrected 20 meq IV and kalium durules)
Serum Na: 135
Lipase:16
Urinalysis: Normal
Hgb
14.4
Hct
43.6
RBC
4.8
WBC
10,370
Eos
2.0
Neu
77.0
Lym
14.0 PC
331,000

19. ECG 11/12

20. CXR

21. PFA and CT scan
C/O radiology dept

24. PFA result
Hazziness seen in the hypogastrium extending to the right psoas
Ileus
Abnormal finding in the lower abdomen ct scan colleration was suggested
NGT inserted initial 1250cc yellowish

27. CT Scan whole abdomen
12.7 x 21.9 x 19.5 cm lobulated heterogeneously enhancing abdominopelvic mass, abutting anterior abdominal wall r/o lymphoma , teratoma.
Diverticlosis, sigmopid colon
Areas of consolidation with ground glass opacities lateral and postero-basal segments, right lower lobe and postero-basal segments, left lower lobe. Consider pneumonic process.

28. Interventional radiology referral
Surgery referral
Abdominal mass with signs of obstruction
maintained on NPO
Interventional radiology referral
CT scan aspiration biopsy
Consistent with Gastrointestinal Stromal Tumor
Exploratory Laparotomy with adhesiolysis, Biopsy of mesocolon nodules, Debulking of intrabodominal tumor,with resection of distal jejunum, Appendectomy, end to end anastomosis of distal jejunum
1st hospital day
1250cc initial drain yellowish
A Biopsy done base on the ct scan report to determine what type of tumor because it will determine the course of treatment

29. Slightly sero-sanguinous ascites about 100cc
(+) fleshy friable lobulated tumor apparently invading/arising from small intestine about 6 feet from ligament of trietz with cavity containing abscess
Multiple flabby nodules scattered around mesocolon mesentry and anterior abdominal wall

30. Surgical Pathology Picture
C/O pathology

31. Surgical Pathology Report
Malignant gastrointestinal stromal tumor (CD-117 and Vimentin positive)
Acute Appendicitis with lymphoid hyperplasia
Malignant gastrointestinal stromal tumor, tissues labeled mesocolic nodules
Immunohistochemical Stain
Vimentin (+)
CD117(+) CK (AE1/AE3) (+)

32. Post operatively, the course in the wards were unremarkable.
Referred to Oncology
Suggest to start Imatinib Mesylate 400meqs/day 2-3 weeks post operation
Post operatively, the course in the wards were unremarkable.
Discharged Improved 15th HD

35. 11/15
11/17
11/18
11/22
11/25
hgb
13.8
12.6 12
10.1
hct
41.8
39.1
37.1
32.1
32.6
rbc
4.3
4.1
3.5
wbc
10760
10300
13570
10180
9790
neu 82 85 91 90
lymph 9 8 6 7 13
mono 3 2 pc
307t
262t
535t
616t

36. Abdominal pain/ LUQ Bowel/Colon: IBS Fecal Impaction GB/Pancreas:
Tumor
diverticolosis
GB/Pancreas:
Cholecystolithiasis
Acute pancreatitis
Stomach:
Peptic ulcer
Tumor
ultrasound CT
ERCP
barrium enema
Endoscopy
PFA
Endoscopy
Upper GI Series

37. FINAL DIAGNOSIS 1.GASTROINTESTINAL STROMAL TUMOR
2. INTESTINAL OBSTRUCTION 2 TO JEJUNAL TUMOR
3. S/P EXPLORATORY LAPOROTOMY WITH COMPLEX ADHENOLYSIS AND DEBULKING OF TUMOR AND JEJUNAL RESECTION
4. Hypertension Stage II

38. DISCUSSION Indication for Endoscopy and Colonoscopy
Management of Gastrointestinal Stromal Tumor

39. Indications for EGD American Society for Gastrointestinal Endoscopy.
Our patient is presented with chronic abdominal pain and underwent gastroscopy. For the benefit of the residents, I would like to discuss he indication of egd and colonoscopy for academic purposes.
American Society for Gastrointestinal Endoscopy.
Appropriate use of gastrointestinal endoscopy.
Gastrointestinal Endoscopy 2006;52:831-7.

40. EGD is generally indicated for evaluating:
A.Upper abdominal symptoms that persist despite an appropriate
trial of therapy
B.Upper abdominal symptoms associated with other symptoms
or signs suggesting serious organic disease (e.g., anorexia and
weight loss) or in patients >45 years old
C.Dysphagia or odynophagia
D.Esophageal reflux symptoms that are persistent or recurrent
despite appropriate therapy
E.Persistent vomiting of unknown cause
G.Familial adenomatous polyposis syndromes
H.For confirmation and specific histologic diagnosis of
radiologically demonstrated lesion
I.GI bleeding
J.When sampling of tissue or fluid is indicated
K.In patients with suspected portal hypertension to
document or treat esophageal varices

41. L.To assess acute injury after caustic ingestion
M.Banding or sclerotherapy of varices
N.Removal of foreign bodies
O.Removal of selected polypoid lesions
P.Placement of feeding or drainage tubes
Q.Dilation of stenotic lesions (e.g., with transendoscopic
balloon dilators or dilation systems using guidewires)
R.Management of achalasia
T.Palliative treatment of stenosing neoplasms

42. Colonoscopy Indications*
American Society for Gastrointestinal Endoscopy.
Appropriate use of gastrointestinal endoscopy.
Gastrointest Endosc 2006;52:831-7.

43. A..Evaluation on barium enema or other imaging study of an abnormality
that is likely to be clinically significant, such as a filling defect or stricture
B..Evaluation of unexplained gastrointestinal bleediNG
C.Unexplained iron deficiency anemia
D..Screening and surveillance for colonic neoplasia
1.Screening of asymptomatic, average-risk patients for colonic neoplasia
2.Examination to evaluate the entire colon for synchronous cancer or
neoplastic polyps in a patient with treatable cancer or neoplastic polyp
3.Colonoscopy to remove synchronous neoplastic lesions at or around
time of curative resection of cancer followed by colonoscopy at 3 years
and 3-5 years thereafter to detect metachronous cancer
4.After adequate clearance of neoplastic polyp(s) survey at
3- to 5-year intervals

44. 6.In patients with ulcerative or Crohn's pancolitis 8 or more years’
5.Patients with significant family history
a..Hereditary nonpolyposis colorectal cancer:
colonoscopy every 2 years beginning at the earlier
of age 25 years or 5 years younger than the earliest
age of diagnosis of colorectal cancer.
Annual colonoscopy should begin at age 40 years.
b.Sporadic colorectal cancer before age 60 years:
colonoscopy every 5 years beginning at age 10 years earlier than
the affected relative or every 3 years if adenoma is found
6.In patients with ulcerative or Crohn's pancolitis 8 or more years’
duration every 1-2 years with systematic biopsies to detect
dysplasia
E.Clinically significant diarrhea of unexplained origin F.Intraoperative identification of a lesion not apparent
at surgery

45. G.Treatment of bleeding from such lesions as vascular
malformation, ulceration, neoplasia, and polypectomy
site
H.Foreign body removal
I.Excision of colonic polyp
J.Decompression of acute nontoxic megacolon or
sigmoid volvulus
K.Balloon dilation of stenotic lesions
L.Palliative treatment of stenosing or bleeding neoplasms
M.Marking a neoplasm for localization

46. Management of Gastrointestinal Stromal Tumor
Report of GIST Consensus Conference of March 2004 under ESMO
CONSENSUS MEETING FOR MANAGEMENT OF GIST
REPOST OF THE GIST CONSENSUS CONFERENCE
MARCH 2004 UNDER THE AUSPICES OF ESMO
Annals of Oncology (4);

47. Introduction 1983 describes as tumors in GIT and Mesentery
Characterized by specific histological and immunohistochemical pattern
Median age of 60 year old
Incidence of 10 cases per 1 million which approxiately 1/3 are malignant
Male predominance
The stomach is the most common site for GITS, with the small bowel being the second most frequent location
GITS tumor constitutes 1%-3% of all gastric tumors and develop from the intestinal cell of Cajal ( or pacemaker cells)
They maybe benign or malignant and presents with GI bleeding (40%), abdominal mass (40%), or abdominal pain (20%).

48. Histologic Criteria for GIST
Spindle cell (70%)
Epitheliod type (20%)
Mixed cell type (10%)
Immunohistochemical staining
CD 117 (+ in 95% cases)
CD34 (+ in 70% cases)
Smooth muscle actin (+ in 40% cases)
PS100 (+ in 5% cases)
Desmin (+ in 2% cases)

49. Prognositc value of grading is unclear
GIST from small intestine worse prognosis compared to gastric GIST
5 Year survival rate approximately 35-65% among patient complete resection
Median survival months with unresectable disease

50. Is molecular biology for KIT and PDGFR mutation a diagnostic or research procedure for GIST?
KIT is a type III tyrosine receptor. KIT is required for the development of the intertitial cell of Cajal wjicj are the pacemaker of gut.

51. Intra-abdominal tumors suspected to be GIST in which CD117 is negative should be considered for molecular analysis for KIT or PRGFR mutation
Mutation screening
Formalin fixed paraffin embedded
Frozen tumor sample

52. Recommended Imaging Study for GISTCT
Choice in suspected abdominal mass/biopsy
Staging and surgical planning
MRI
Rectal GIST
Fluorine 18 flurodeoxyglucose (FDR) positron emission tomography (PET)
Early detection of tumor response to Imatinib treatment is required
Images suspected to be metastatic
Not mandatory

53. Laparoscopic surgery should be avoided
Standard Treatment
Biopsy
Preoperative Biopsy
Tumors are fragile and bleed easily
Intraabdominal Biopsy
Discourage because of risk of tumor spill
Complete resection of visible and microscopic disease should be done in established GIST ( avoiding the occurrence of tumor rupture and achieving negative margine)
Laparoscopic surgery should be avoided
Higher risk of tumor rupture

54. Resection vs watchful waiting
Lymphadenectomy
Rarely metastisize to local regional lymph nodes
Is warranted only for evident nodal involvement
Resection vs watchful waiting
All GIST potentially malignant
All GIST need to be resected but not all intramural lesion are GIST, thus preoperative pathological diagnosis should be obtained

55. Adjuvant treatment with Imatinib: WHEN?

56. Imatinib Not considered as adjuvant therapy Remains investigational
A tyrosine kinase inhibitor blocking most mutated-activated KIT and PDRGFR
Not considered as adjuvant therapy
Remains investigational
Might be able to eradicate microscopic disease but reduce the efficacy of treatment of recurrent GIST
Not recommended in patients with localized GIST

57. Neo-adjuvant treatment with imatinib:
WHEN?

58. No data supports
Not recommended outside clinical trials
Unresectable GIST may be treated with preoperative imatinib in an attempt to achieve cytoreduction and organ presevation
Radiotherapy as neo-adjuvant or adjuvant treatment not documented

59. Follow up after resection of primary tumor
No reliable data in published literature could support specific recommendation (whether beneficial or not)
Proposal
High and Intermediate risk
Tumors >5cm or mitotic index >5/50hpf
CT scan every 3-4 months for 3 years
Then every 6 months until 5 years
Low or very low risk
Tumors <5cm or mitotic index <5/50 hpf
CT scan every 6 months for 5 years

60. When should imatinib treatment be initiated in patient with advanced GIST?
For unresectable and/or metastatic disease,
immediate treatment is recommended
Disease spread to peritoneal surface or
to the liver (metastasis), imatinib mesylate
is the therapy of choice after resection

61. Optimal Dose 400mg/day is currently recommended
No overall survival improvement (400 and 800mg)
Superiority of progression-free survival in 800mg

62. Duration imatinib treament with advanced GIST
Imatinib interruption after 1 year is associated with high risk of relapse
Continues until progression, intolerance or patient refusal

63. Standard imaging strategy for advanced tumor
FDG PET highly sensitive in detecting early tumor response
CT scan imaging modality of choice in response evaluation
MRI option for liver metastasis
Ultrasound is currently under investigation

64. Surgical resection of residual metastasis in patient in whom advanced disease is controlled by imatinib?
No current data indicate that surgery alone may cure advanced GIST
Imatinib should not be interrupted because of risk of tumor re-growth

65. Sunitinib
Sugen, Biotech company focused on kinase inhibitors in oncology in 1999
FDA approved January 2006
Sutent (previously known as SU11248)
Inhibits signaling through multiple receptor tyrosine kinase, including PDGF and VEGF receptors
Inhibits mutationally activated kit kinase
Diarrhea, hypertension, skin discoloration, mucositis, fatique, hypothyroidism, neutropenia, thrombocytopenia, dec LV EF
Wikipedia.org.sunitinib

66. Evaluation of malignancy and prognosis in 113 cases in Northern Italy
GIST represent are rare but well recognizable disease
Risk of aggressive behavior is high >50%
Finding that after radical surgery all tumors relapse
American Society of Clinical Oncology
2004 ASCO Annual meeting

67. A Giant Malignant GIST of the Stomach: A Case Report
63/F, severe anemia, large abdominal mass on CT scan surgical resection done, later diagnosed with GIST on imatinib mesylate
Phil Journal Internal Medicine 43:75-78 March -April 2005

68. Condition Rule in Rule out Peptic ulcer Abdominal pain
Diagnosed by EGD
appendicitis
Crampy abdominal pain; Nausea; Leukocytosis
Gnawing;
Anorexia, (-) rovsing;obturatot; psoas; mcburney sign
Cholicystitis
Abdominal distention
Leukocytosis
(-) murphy’s RUQ
Fever
pancreatits
Abdominal pain/distention
Nausea
Non radiating
(-) cullens sign
(-) Turner sign
Normal lipase
IBS
Recurrent abdominal pain; bloatness; altered stool form

69. Rule in Rule out Intestinal obstruction
Crampy abdominal pain; distention; constipation; Leucocytosis
(-) borborygmi; vomiting
Obstipation;Singultus
Diarrhea;blood per rectum; Stepladder pattern PFA
tumors

70. SPEC 19 (11/12/06) NA:138 BILI T: 1.4 K: 2.9 UA : 4.7
CL: 94 TP: 5.7
Trig: 82 ALB: 2.3
LDH: 304 CHOL: 168
SGOT: 92 UREA: 9.0
SGPT: 64 CREA:1.1
PHOS: 2.9 CPK: 176
CALC: 8.8 GLOB: 3.4
ALK P: 233 A/G : 0.70