Tumor and GI bleeding : A Case Review

Rajaie Kamarudin P59895 PPUKM

History

❖ Madam WT

❖ 63 Chinese Lady

❖ K/C: COAD (Smoker), under IPR follow up

❖ Complaint of blackish stool for 1 day,

❖ associated with central abdominal discomfort

❖ 26/11/2014

History

❖ history of gastritis > 20 years

❖ + giddines

❖ no history of NSAIDS ingestion

❖ no constituinal symptoms

❖ no family history of cancer

History

❖ Not Working

❖ living with friend

❖ non alcoholic

Social History

Physical examination

❖ Alert conscious

❖ Pale

❖ hydration fair

❖ Spo2 99% (room air)

❖ moderate pulse volume

Physical examination

❖ no palpable cervical, supraclavicular nodes

❖ abdomen soft : there is a vague mass at the left iliac

fossa

❖ Per rectal : fresh maelena

❖ bp : 98/54 106/68 ( after saline bolus)

❖ pulse : 133 108

Biochemical Ix

❖ Hb 7.9

❖ Wcc 8.6

❖ Plt 273

❖ INR 1.02

❖ Urea 6.4 Creatinine 53

❖ Potassium 3.4/Sodium 140

Management

❖ Working Diagnosis & Differential diagnosis?

❖ What to do next?

Management

❖ Hourly Vitals and urine, monitoring

❖ To transfuse 2 pint of pack cell

❖ monitor in acute bay

❖ Nil By Mouth

❖ OGDS

Management

❖ OGDS : normal

❖ Colonoscopy : normal up till caecum, altered blood

throughout the colon but no stigmata of recent bleed

Management

❖ Patient had mild sob

❖ hb 7.9 6.9 10.6

❖ Bp systolic 100-140 & PR : 110-114 overnight

❖ PR : fresh maelena

Day 2 of admission

Management

❖ Imp : Bleeding Tumor

❖ For Exploratory laparatomy & proceed

Intra operative

Intraoperative

❖ Large exophytic tumor arising from the small bowel , 100

cm from DJ junction, 25x25 cm

❖ some part of the tumor was adhered to the posterior

pelvic wall but no involvement of the uterus or adnexa

❖ small bowel resection and primary anastomosis was

done

Management

❖ Post operative patient was nursed in icu, for 1 day

❖ post op was uneventful and patient was discharge at day

5

❖ To See in clinic with HPE review

Management

❖ Differential diagnosis ?

Lorem Ipsum Dolor

Macroscopic : irregular nodular exophytic mass 15x15x8, firm with margin 11 cm . Section

shows haemorraghic and necrotic areas .

Microscopic: malignant spindle cells in storiform pattern with dense cellularity.Malignant

cell display pleomorphic enlarged spindle to oval-shape vesicular with permanent nuclei.

CD117, Vimentin, CD34, DOG -1 are positive, and -ve for SMA, Desmin and s100

Mitotic count 7/50 hpf

Management

❖ Diagnosis : Malignant Gist Tumor

❖ Plan

❖ CT Staging

❖ Refer Oncology for Adjuvant Therapy

Introduction

❖ Its described in the early literature consisted of a heterogenous group

of mesenchymal tumours , involving the GI wall

❖ Hirota S, Isozaki K, Moriyama y et all, gain of function of mutation of

c-kit in human GIST

❖ C-Kit(CD117) is a type III receptor thyrosine kinase that involved in

the development and maintaince of RBC, mast cell, Melanocytes,

germ cells and intertisial cells of Cajal

❖ GIST share morphologic features and express (Oncogenic mutation)

KIT (80-85%) or Platelet Derived Growth Factor PDGFRA 5-7%

GIST (Gastrointestinal Stromal Tumor)

Introduction

❖ its relatively rare neoplasm but most common among

sarcoma of the GI tract.

❖ its account for 5 % of all sarcoma

❖ Can rise in any portion of the GI tract but most common

from the Stomach 60% or the Small bowel 20% and

oesophagus 5%.

Epidemiology

❖ Median age is 60 years old

❖ Most GIST arise sporadically

❖ Hereditary is rare such as Neurofibromatosis type 1, Part

of Carney Triad and Carney -Stratakis Dyad

❖ about 70-80% are Benign and 20-30% are malignant

Incidence

❖ GIST has been reported to 5000-6000 new cases per

year (15-20 per million)

❖ European 11-15 cases per million

Clinical Presentation

❖ GIST commonly arise in the stomach 50-70%, small bowel

25-35%, colon and rectum (5-10%)

❖ Symptomatic 69% Incidental findings during endoscopy or

laparatomy 21 %

❖ bleeding

❖ obstruction, perforation, intussuception

❖ vague abdominal pain

❖ fever

Diagnosis

❖ If suspected or confirmed GIST

is Contrasted enhanced CT

Abdomen and pelvis

❖ MRI may help characterise in

rectal Disease

❖ PET Scan- monitor respons to

therapy but not specific for gist.

Radiographic Study

Diagnosis

❖Endoscopic

❖EUS FNA

❖Biopsy

Usually Fleshy Solid with

haemorrhage or cystic

degeneration

Histopathology

❖ Divided in 2 types

❖ Spindle Cell 70%

❖ Epithelial 20% and Mixed 10%

❖ Immunohistochemical staining CD117, CD 34 and DOG-

1

❖ Divided in 2 types

❖ Spindle Cell 70%

❖ Epithelial 20% and Mixed

10%

Microscopic

Agorithm to diagnose gastrointestinal Stromal tumors

based on immunohistochemistry

Prognostic factor

❖ Tumor size

❖ Mitotic index

❖ Tumos site of origin

Nomogram to predict the probabilities of 2-year and 5-year recurrence-free

survival (RFS). Points are assigned for size, mitotic index, and site of origin by

drawing a line upward from the corresponding values to the Points line. The

sum of these three points, plotted on the Total points line, corresponds to

predictions of 2-year and 5-year RFS. HPF, High-power field.

Risk aggressive behaviour in gist

Fletcher CD, Berman JJ, Corless C, et al: Diagnosis of gastrointestinal stromal tumors: a consensus approach,

Treatment

❖ Primary (Surgery if 2cm or more)

❖ To achieve R0 resection.

❖ Preoperative treatment neoadjuvant?

❖ Adjuvant Therapy ?

RTOG S0132 multicenter using Imatinib as neoadjuvant. 600 mg

per day for 8-12 weeks, 2 years Reccurent free Survival is 83%

Trial Design Dose Eligibility Primary endpoint

ACOSOG

9001Phase iii

400mg OD for

12 mTumor >3 Complete resection

Imatinib 97% vs

Placebo 83% RFS in 1

year

SSGXVIII Phase iii400 mg od for

12/36 month

Tumor 10 cm, Tumor rupture,

, Mitotic count >10, t: >5 m >

5 hpf

36 m 66 % vs 48 % (p<0.01)

5y RFS

OS (92%vs 82%) p=0.02 in

5 year

Trials in Adjuvant Therapy For GIST

Targeted Therapy

❖ Before the advance of TKI Median survival after

recurrence is 18 month

❖ Imatinib commercially as Gleevec or Glivec and Sumatinib

is the choice of treatment

❖ KIT contain 21 types of exon

❖ GIST Pathogenesis loss either Chromosomes 9,11, 13

and 17 exon

❖ best Respon rate is the Exon 11 mutation 72% , exon 9

32%

Side effect

❖ edema

❖ nausea

❖ muscle cramps

❖ diarrhea

❖ headache

❖ dermatitis

❖ anemia

❖ nausea

Advanced Disease

❖ Cryoreductive surgery

❖ Cytoreductive surgery is good in patient with ongoing

response to imatinib but there is no evidence to compare

between surgery vs TKI alone.

❖ There is a progression of drug resistance to Imatinib

Surveillance

❖ Clinic visit with physical assessment

❖ CT scan every 3-6 month first 3-5 years then annually

Conclusion

❖ Principal and only potential curative treatment is Surgery

❖ TKI adjuvant therapy has improve in RFS in 5 years

❖ Imatinib is safely used as a neoadjuvant agents

❖ Need more studies regarding Neoadjuvant and adjuvant

imatinib therapy regarding optimal length and dose of

imatinib.

❖ Cytoreductive Studies me be considered in advanced

disease.

❖Thank You