GOOD MORNING
MEDICAL GRANDROUNDS
ERNEST JOEL SAMACO M.D.
FEBUARY 1, 2007
GENERAL DATA
A.G.
51 MALE
MARRIED
CATHOLIC
EMPLOYEE
KAWIT CAVITE
CHIEF COMPLAINT
ABDOMINAL PAIN
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.
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
PFA
•Reflex Ileus
•Right Pelvic Calcification R/O Distal
Calculus in the distal end of the right ureter
• 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
• 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
Review of Systems
(-) fever
(-) chest pain
(-) cough
(-) DOB
(-) easy fatigability (-) urinary changes
(+) weight loss
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
Family History
• (-) HPN, DM, Asthma
• (-) Cancer
Personal Social History
•
•
•
•
(-) smoker
(-) drinker
No food preference
Denies exposure to chemicals
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.
• 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
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
Admitting Impression
1. Irritable Bowel Sydrome
2. Acid Peptic Ulcer disease (s/p
Gastroscopy 9/06 & 10/06)
3. Hypertensive Cardiovascular Disease
Course in the wards
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
• CBC
Hgb
14.4
Hct
43.6
RBC
4.8
WBC
10,370
Eos
2.0
Neu
77.0
Lym
14.0
PC
331,000
• Serum K: 2.5 (corrected
20 meq IV and kalium
durules)
•Serum Na: 135
•Lipase:16
•Urinalysis: Normal
ECG 11/12
CXR
PFA and CT scan
• C/O radiology dept
• PFA result
• Hazziness seen in the hypogastrium
extending to the right psoas
• Ileus
• 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 posterobasal segments, left lower lobe. Consider
pneumonic process.
• 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
• 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
Surgical Pathology Picture
• C/O pathology
• Surgical Pathology Report
• Malignant gastrointestinal stromal tumor (CD117 and Vimentin positive)
• Acute Appendicitis with lymphoid hyperplasia
• Malignant gastrointestinal stromal tumor,
tissues labeled mesocolic nodules
• Immunohistochemical Stain
• Vimentin (+)
• CD117(+)
CK (AE1/AE3) (+)
• 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
11/12 11/15 11/17
Na
138
136
K
2.5/2.9 3
3.5
BUN 9
8
Crea 1.2
0.8
Albumin 2.3
3.1
11/18 11/19 11/20
134
132
4.9
3.7
15
11
0.8
0.9
2.8
11/22
134
3.4
17
1.0
3.0
11/25
136
4.1
24
1.0
hgb
hct
rbc
11/15
13.8
41.8
wbc
neu
lymph
10760
82
9
mono
pc
8
307t
11/17
12.6
39.1
4.3
10300
85
8
6
262t
11/18
12
37.1
4.1
13570
91
6
3
262t
11/22
10.1
32.1
3.5
10180
90
7
3
535t
11/25
10.1
32.6
3.5
9790
85
13
2
616t
Abdominal pain/ LUQ
Bowel/Colon:
Stomach:
Peptic ulcer
Tumor
GB/Pancreas:
IBS
Cholecystolithiasis
Fecal Impaction
Acute pancreatitis
Tumor
diverticolosis
ultrasound
barrium enema
Endoscopy
CT
Endoscopy
Upper GI Series
ERCP
PFA
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
DISCUSSION
1. Indication for Endoscopy and
Colonoscopy
2. Management of Gastrointestinal
Stromal Tumor
Indications for EGD
American Society for Gastrointestinal Endoscopy.
Appropriate use of gastrointestinal endoscopy.
Gastrointestinal Endoscopy 2006;52:831-7.
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
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
Colonoscopy Indications*
American Society for Gastrointestinal Endoscopy.
Appropriate use of gastrointestinal endoscopy.
Gastrointest Endosc 2006;52:831-7.
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
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
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
Management of
Gastrointestinal Stromal
Tumor
CONSENSUS MEETING FOR MANAGEMENT OF GIST
REPOST OF THE GIST CONSENSUS CONFERENCE
MARCH 2004 UNDER THE AUSPICES OF ESMO
Annals of Oncology 2005 16(4);566-578
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%).
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)
• Prognositc value of grading is unclear
• GIST from small intestine worse
prognosis compared to gastric GIST
• 5 Year survival rate approximately 3565% among patient complete resection
• Median survival 10-20 months with
unresectable disease
Is molecular biology for KIT and PDGFR
mutation a diagnostic or research
procedure for GIST?
• 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
Recommended Imaging Study for GIST
• CT
• 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
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
• 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
Adjuvant treatment with Imatinib: WHEN?
Imatinib
• 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
Neo-adjuvant treatment with imatinib:
WHEN?
• 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
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
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
Optimal Dose
• 400mg/day is currently recommended
• No overall survival improvement (400 and
800mg)
• Superiority of progression-free survival in
800mg
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
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
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
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,Wikipedia.org.sunitinib
dec LV EF
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
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
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
Rule in
Intestinal obstruction Crampy abdominal
pain; distention;
constipation;
Leucocytosis
tumors
Rule out
(-) borborygmi;
vomiting
Obstipation;Singultu
s
Diarrhea;blood per
rectum; Stepladder
pattern PFA
•SPEC 19 (11/12/06)
NA:138
K: 2.9
CL: 94
Trig: 82
LDH: 304
SGOT: 92
SGPT: 64
PHOS: 2.9
CALC: 8.8
ALK P: 233
BILI T: 1.4
UA : 4.7
TP: 5.7
ALB: 2.3
CHOL: 168
UREA: 9.0
CREA:1.1
CPK: 176
GLOB: 3.4
A/G : 0.70