Andheri East ^ (Genuine) Escort Service Mumbai ₹7.5k Pick Up & Drop With Cash...
Gi tumor
1.
2. History
55 years old male, resident of Chaman,
Balochistan
Presenting complain:
Black stools (melena)- Three months
ago
3. History of presenting complaint:
Complained of black stools for three to four days
three months ago.
Stool was soft in consistency and no history of
constipation or diarrhea
At that time also experienced severe weakness,
dizziness and shortness of breath. Family members
noticed that he seemed pale and weak. Went to
Quetta National Hospital where he was transfused
2 liters of fresh blood (4 packs) anemia
4. • History of melena one year back, but no
weakness at that time
• No history of abdominal discomfort or pain
• No nausea or vomiting
• No dyspepsia or heart burn
• No sour brash
• Did complain of early satiety and loss of
appetite
• Undocumented weight loss
5. Review of systems
• Constitutional: weight loss, generalized
weakness, no fever
• Respiratory: no cough, wheeze, respiratory
difficulty
• Cardiovascular: no tachypnea, dyspnea,
edema
• GU: no urinary complaints
• MSK: No muscle or joints pains
6. Past Medical History
• No HTN or DM
• No history of PUD/Gastritis
• No history of Liver disease, Cirrhosis or Hepatitis
• No history of NSAID use, burns, trauma or
surgeries
7. Medications
• Currently taking Esmoprazole, Motilium
and Gaviscon for three months
• No history of NSAID use
• No history of Iron supplement
• No known allergies to any medications
8. Personal History
• Appetite reduced
• Reduced oily and spicy food in diet
• No change in mood
• Was a shopkeeper in Chaman
• Never smoked or consumed alcohol
9. Physical Examination
• General Physical
• Height: 175 cm, Weight: 63 kg
• BMI: 20.6
• Pulse: 80 BP: 130/90
• Afebrile
• No jaundice or anemia
• No cervical or supraclavicular
lymphadenopathy
10. Systemic Examination
• Chest: Clear, NVB bilaterally
• CVS: S1 + S2 and no added sounds
• Abdomen: soft non tender, GS +ve
• No ascites, hepatosplenomegaly or signs
of CLD
11. Summary
• 55 years of male, no known comorbid,
complaining of melena, weakness, loss of
appetite and weight loss for one year.
• Differentials?
15. Endoscopy (27th July 2013)
• Esophagus: Normal
• GE Junction at 38 cm
• Stomach: Mild erythema with polypoidal mushroom like
growth with central pitting like ulceration seen along the
greater curvature. Biopsy of mass taken
• Duodenum: Normal
16. Biopsy (3rd August 2013)
• Histopathology report:
• Specimen was 0.5 X 0.8 cm in size. Overlying normal gastric
mucosa. Composed of sheets of elongated spindle shaped
cells in short fascicles that stained positive for CD 117 and CD
34. Tissue specimen insufficient to comment on mitotic rate
• Diagnosis: Gastrointestinal Stromal Tumor
17. CT scan (for metastatic work-up)
• Done on 28th August 2013
• Report:
• Soft tissue density on posterior
wall along the greater
curvature of stomach
measuring 5.7 X 6.8 cm
• No evidence of abdominal
lymphadenopathy
• No evidence of ascites or
metastasis to liver, lungs or
bones
19. Sleeve Gastrectomy
On 17th September 2013
Intaoperative findings
• Tumour with endophytic and exophytic
element, 8 x 7 cm
• Freely mobile tumour
• No local invasion
• No ascites or liver metastasis
Procedure
• Midline laporotomy
• Lesser sac opened
• Greater curvature mobilised
• Left gastro-epiploic liagated
• Wedge resection done around tumour
keeping margins 2-3 cm
22. Background
• GISTs are thought to arise from interstitial cells of Cajal (ICC)
• c-kit is a gene that encodes for a transmembrane receptor for
a growth factor termed stem cell factor(scf) expressed by ICC
• Around 95 percent of GISTs result from abnormalities in KIT
pathway
• More than 85% GISTs are associated with a mutations
resulting in overexpression of c-kit gene
• The CD117 antigen is part of the KIT transmembrane receptor
tyrosine kinase (RTK)
23.
24.
25. • Mutations generally occur in the DNA encoding the
intracellular part exon 11 (75%) which has tyrosine kinase
enzyme activity .
• Mutations in the exons 9 and rarely 13 and 17 also result in
uncontrolled KIT signaling.
• Most GIST cells with wildtype (i.e. not mutated) c-kit instead
have a mutation in another gene, PDGFR-α which is a related
tyrosine kinase.
26. Epidemiology
• Incidence vary widely, from 4 to 40 cases per million
population, which corresponds to between 200 and 2000 new
cases per year in England and Wales.
• In the US reported 7-20 cases per million
• Recent epidemiological data from Sweden suggest that the
incidence of GIST is in the region of 15 per million per year.
• Approximately half of new cases of GIST are likely to be
metastatic and/or unresectable on first presentation.
• Although GIST can occur at any age, the mean age of
presentation is between 50 and 70 years.
27. Pathophysiology
• Location:
• Stomach (50-705)
• Small intestine (20-30%)
• Rectum (5-15%)
• Esophagus (<5%)
• Submucosal lesions, can be exophytic or endophytic
• Range in size from smaller than 1 cm to as large as 40 cm
• All GIST tumors are considered to have malignant potential
• GISTs frequently metastasize to liver and peritoneum and
rarely to regional lymph nodes.
28. Outcome
The overall 5-year survival rate ranges from
28-60%.
This can be stratified for patients presenting
with
localized primary
disease with median
survival rate in the
former group is 5
years
metastatic or
recurrent disease
with median survival
rate approximately
10-20 months.
29.
30. Clinical Presentation
• Upper GI bleeding: hematemesis or melena in 40-65% of
patients.
• Symptoms of enlarging abdominal mass: abdominal pain,
anorexia, nausea, vomiting, weight loss, epigastric fullness,
and early satiety.
• Overt GI bleeding — 40 percent
• Abdominal mass — 40 percent
• Abdominal pain — 20 percent
31. Work up
Endoscopy with biopsy
• Histologic diagnosis in more than 80% of
cases
• Importance in metastatic or unresectable
disease
CT scan
• tumor invasion to adjacent
structures
• metastasis to liver, omentum, and
peritoneal cavity
Endoscopic ultrasonography:
• Valuable when the diagnosis or location is
in doubt
• most accurate method for distinguishing
leiomyomas from other submucosal lesions
Tumours more likely to
metastasize
• > 5 cm,
• lobulated,
• enhance
heterogeneously
• have mesenteric fat
infiltration,
• ulceration,
• regional
lymphadenopathy
• exophytic growth
pattern
32. Histology
• Light microcopy
• Spindle cells in 70-80%
• Epitheloid aspect in 20-30%
• Mixed
• By light microscopy alone, the distinction among GISTs and
other tumors in the differential diagnosis (particularly
leiomyomas, true leiomyosarcomas, and GI tract
schwannomas) can be difficult
• Important to see for cellular atypia and mitotic rate
33. • Immunohistochemistry
• Positive for CD117 (95%)
• Other possible markers include
CD34 (60-70%), SMA (30-40%),
DOG-1, S-100 protein (5 %),
Desmin (1-2%), and vimentin
Importance of CD117/ cKIT mutation in therapy
34. Staging
Most staging systems employ 3 most
important survival predictors—tumor size,
histologic grade, location of tumor.
Other prognostic factors: cellular atypia, local
invasion, ulceration, non-Kit mutations
35. Lower stage (good
prognosis)
• Mitotic rate less than 5
per 10 high-power
fields (HPF),
• Size smaller than 2 cm
• Stomach
Higher stage (bad
prognosis)
• Mitotic rate greater
than 5 per 10 high-
power fields (HPF),
• Size larger than 5 cm
• Small
intestine/colon/rectum
39. Surgery
Surgical resection remains the treatment of choice and
offers the only chance for cure from GIST
The main operative principle is resection of the tumor
with negative microscopic margins. Wide resection of
the tumor with at least 1-2 cm margin usually the goal
• For small gastric tumors, wedge or segmental resection is
adequate, if technically possible. Larger tumors necessitate
subtotal or total gastrectomy.
• For locally invasive tumors, en bloc resection of adjacent involved
organs, such as colon, spleen, or liver, may be indicated.
40. Medical
The current recommendation by the NCCN is to
consider prescribing imatinib in the adjuvant
setting in any patient with intermediate-risk or
high-risk GIST and to treat for at least 12 months
Sunitinib is a newer tyrosine-kinase inhibitor that
has been shown to provide significant clinical
benefit in imatinib-resistant advanced GIST.
41. Metastatic Disease
• Imatinib treatment at 400 mg/day is recommended as first-
line management of people with KIT (CD117)-positive
unresectable or metastatic gastro-intestinal stromal tumours
(GISTs). (NICE guidelines)
• The two year survival of patients with advanced disease has
risen to 75–80% following imatinib treatment.
• Patients should have been on at least 6 months treatment
• Up to 70% of patients able to undergo an resection with stable
or partially responsive disease enjoy a progression-free
survival as long as 4 years.
Rutkowski et al Surgical treatment of patients with initially inoperable and/or metastatic
gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate.
J Surg Oncol. Mar 15 2006;93(4):304-11.
42.
43. Efficacyandsafetyofimatinibmesylateinadvanced
gastrointestinalstromaltumors
Patients randomly
assigned to receive
a single dose of
400 mg (n = 73) or
600 mg (n = 74) of
imatinib.
Patients received
treatment for a
median of
21 months
The combined
survival rate from
the start of
treatment was 88%
at 1 and 78% at 2-
year follow-up.
Median survival had
not been reached
after 31 months of
follow-up.
Study CSTI571-B2222 is a published ongoing phase II uncontrolled trial of imatinib
treatment in 147 patients (91% of whom were c-KIT-positive) with unresectable
and metastatic GIST, which formed the basis of the license application.
44. “Imatinib induced a sustained objective response in
more than half of patients with an advanced
unresectable or metastatic gastrointestinal stromal
tumor”
45. Safety of Imatinib
• Study CSTI571-B2222 (registration study) reported that at
least one adverse event had been experienced by all 147
patients by 21 months' follow-up.
• A total of 15 (10%) patients withdrew from the study because
of adverse events
• Most commonly reported side effects of imatinib include
nausea, diarrhoea, periorbital oedema, muscle cramps,
fatigue, rash and headache.
• The most common serious adverse events were unspecified
haemorrhage and neutropenia, each event occurring in
approximately 5% of patients.
• Overall, imatinib was well tolerated
46. References
• Bailey and Love's Short Practice of Surgery 25th
Edition Norman S. Williams (Editor), Christopher J.K.
Bulstrode (Editor), P. Ronan O'Connell (Editor)
• CURRENT Diagnosis & Treatment: Surgery, 13e. Edited by
Gerard M. DohertyMedscape
• NCCN Task Force Report: Optimal Management of Patients
with Gastrointestinal Stromal Tumor (GIST)—Update of the
NCCN Clinical Practice Guidelines
http://www.nccn.org/JNCCN/PDF/GIST2007.pdf
• NICE guidelines: Imatinib for the treatment of unresectable
and/or metastatic gastro-intestinal stromal tumours
