GOOD MORNING MEDICAL GRANDROUNDS ERNEST JOEL SAMACO M.D. FEBUARY 1, 2007.
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Transcript of GOOD MORNING MEDICAL GRANDROUNDS ERNEST JOEL SAMACO M.D. FEBUARY 1, 2007.
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GOOD MORNING
MEDICAL GRANDROUNDS
ERNEST JOEL SAMACO M.D.
FEBUARY 1, 2007
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GENERAL DATA
A.G.
51 MALE
MARRIED
CATHOLIC
EMPLOYEE
KAWIT CAVITE
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CHIEF COMPLAINT
ABDOMINAL PAIN
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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.
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HISTORY OF PRESENT ILLNESS
• Three month5 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
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PFA
•Reflex Ileus
•Right Pelvic Calcification R/O Distal
Calculus in the distal end of the right ureter
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• 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
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• One monthrecurrence abdominal fullness Repeat gastroscopy done
showed healing duodenal ulcer, gastritis Esomeprazole 40mg OD x 4 wk
• 2 weeks PTAprogressive bloatedness constipation
• Night PTAabdominal pain 10/10 localized at the LUQ associated with severe
bloatedness and nausea• Persistence of symptoms prompted
consult
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Review of Systems
(-) fever (-) chest pain
(-) cough (-) DOB
(-) easy fatigability (-) urinary changes
(+) weight loss
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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
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Family History• (-) HPN, DM, Asthma• (-) Cancer
Personal Social History• (-) smoker• (-) drinker• No food preference• Denies exposure to chemicals
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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.
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• 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
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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
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Admitting Impression
1. Irritable Bowel Sydrome
2. Acid Peptic Ulcer disease (s/p Gastroscopy 9/06 & 10/06)
3. Hypertensive Cardiovascular Disease
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Course in the wards
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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
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• 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
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ECG 11/12
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CXR
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PFA and CT scan
• C/O radiology dept
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• PFA result• Hazziness seen in the hypogastrium
extending to the right psoas• Ileus
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• 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.
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• 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
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• 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
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Surgical Pathology Picture
• C/O pathology
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• 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) (+)
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• 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
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11/12 11/15 11/17 11/18 11/19 11/20 11/22 11/25 Na 138 136 134 132 134 136 K 2.5/2.9 3 3.5 4.9 3.7 3.4 4.1 BUN 9 8 15 11 17 24 Crea 1.2 0.8 0.8 0.9 1.0 1.0 Albumin 2.3 3.1 2.8 3.0
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11/15 11/17 11/18 11/22 11/25
hgb 13.8 12.6 12 10.1 10.1
hct 41.8 39.1 37.1 32.1 32.6
rbc 4.3 4.1 3.5 3.5
wbc 10760 10300 13570 10180 9790
neu 82 85 91 90 85
lymph 9 8 6 7 13
mono 8 6 3 3 2
pc 307t 262t 262t 535t 616t
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Stomach:Stomach:
Peptic ulcerPeptic ulcer
TumorTumor
GB/Pancreas:GB/Pancreas:
CholecystolithiasisCholecystolithiasis
Acute pancreatitisAcute pancreatitis
Bowel/Colon:Bowel/Colon:
IBSIBS
Fecal ImpactionFecal Impaction
TumorTumor
diverticolosisdiverticolosis
EndoscopyEndoscopy
Upper GI SeriesUpper GI Series
ultrasoundultrasound
CT CT
ERCPERCP
barrium enemabarrium enema
EndoscopyEndoscopy
PFAPFA
Abdominal pain/ LUQAbdominal pain/ LUQ
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FINAL DIAGNOSIS
1.GASTROINTESTINAL STROMAL TUMOR2. INTESTINAL OBSTRUCTION 2 TO JEJUNAL
TUMOR3. S/P EXPLORATORY LAPOROTOMY WITH
COMPLEX ADHENOLYSIS AND DEBULKING OF TUMOR AND JEJUNAL RESECTION
4. Hypertension Stage II
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DISCUSSION
1. Indication for Endoscopy and Colonoscopy
2. Management of Gastrointestinal Stromal Tumor
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Indications for EGD
American Society for Gastrointestinal Endoscopy. Appropriate use of gastrointestinal endoscopy. Gastrointestinal Endoscopy 2006;52:831-7.
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EGD is generally indicated for evaluating:A.Upper abdominal symptoms that persist despite an appropriate trial of therapyB.Upper abdominal symptoms associated with other symptoms or signs suggesting serious organic disease (e.g., anorexia and weight loss) or in patients >45 years oldC.Dysphagia or odynophagiaD.Esophageal reflux symptoms that are persistent or recurrent despite appropriate therapyE.Persistent vomiting of unknown causeG.Familial adenomatous polyposis syndromesH.For confirmation and specific histologic diagnosis of radiologically demonstrated lesionI.GI bleedingJ.When sampling of tissue or fluid is indicatedK.In patients with suspected portal hypertension to document or treat esophageal varices
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L.To assess acute injury after caustic ingestionM.Banding or sclerotherapy of varicesN.Removal of foreign bodiesO.Removal of selected polypoid lesionsP.Placement of feeding or drainage tubesQ.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
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Colonoscopy Indications*
American Society for Gastrointestinal Endoscopy. Appropriate use of gastrointestinal endoscopy. Gastrointest Endosc 2006;52:831-7.
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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 polyp3.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
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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
dysplasiaE.Clinically significant diarrhea of unexplained originF.Intraoperative identification of a lesion not apparent at surgery
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G.Treatment of bleeding from such lesions as vascular malformation, ulceration, neoplasia, and polypectomy site H.Foreign body removalI.Excision of colonic polypJ.Decompression of acute nontoxic megacolon or sigmoid volvulusK.Balloon dilation of stenotic lesionsL.Palliative treatment of stenosing or bleeding neoplasmsM.Marking a neoplasm for localization
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Management of Gastrointestinal Stromal
Tumor
CONSENSUS MEETING FOR MANAGEMENT OF GISTREPOST OF THE GIST CONSENSUS CONFERENCEMARCH 2004 UNDER THE AUSPICES OF ESMOAnnals of Oncology 2005 16(4);566-578
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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%).
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• 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)
Histologic Criteria for GIST
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• 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 10-20 months with unresectable disease
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Is molecular biology for KIT and PDGFR mutation a diagnostic or research procedure for GIST?
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• 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
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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
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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
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• 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
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Adjuvant treatment with Imatinib: WHEN?
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• 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
Imatinib
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Neo-adjuvant treatment with imatinib:
WHEN?
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• 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
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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
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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
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Optimal Dose
• 400mg/day is currently recommended• No overall survival improvement (400 and
800mg)• Superiority of progression-free survival in
800mg
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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
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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
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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
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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
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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
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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
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Condition Rule in Rule out
Peptic ulcer Abdominal painDiagnosed by EGD
appendicitis Crampy abdominal pain; Nausea; Leukocytosis
Gnawing;Anorexia, (-) rovsing;obturatot; psoas; mcburney sign
Cholicystitis Abdominal distentionLeukocytosis
(-) murphy’s RUQFever
pancreatits Abdominal pain/distentionNausea
Non radiating (-) cullens sign(-) Turner signNormal lipase
IBS Recurrent abdominal pain; bloatness; altered stool form
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Rule in Rule out
Intestinal obstruction Crampy abdominal pain; distention; constipation; Leucocytosis
(-) borborygmi; vomitingObstipation;SingultusDiarrhea;blood per rectum; Stepladder pattern PFA
tumors
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NA:138 BILI T: 1.4K: 2.9 UA : 4.7CL: 94 TP: 5.7Trig: 82 ALB: 2.3LDH: 304 CHOL: 168SGOT: 92 UREA: 9.0SGPT: 64 CREA:1.1PHOS: 2.9 CPK: 176CALC: 8.8 GLOB: 3.4ALK P: 233 A/G : 0.70
•SPEC 19 (11/12/06)