Download Iron Deficiency Anemia and Colorectal Carcinoma

Iron Deficiency Anemia and
Colorectal Carcinoma
Livia Deda: research, slide summaries, and editing
Linsey Fernandes: research, slides summaries and editing
Gul-e-Rana: research, slide summaries and references
Tim Grainger: research, slide summaries and referencing
Hematology Case 2
Overview
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History
Physical Examination
Lab Investigations: results and interpretation
Assessment: DDx and most likely Dx
Management
Prognosis and Patient education
History
67 year old female with shortness of breath on exertion, easy
fatigability, and lack of energy for the past 2 to 3 months.
Denies GI, or vaginal bleeding.
Denies hemoptysis.
Described a good diet but variable appetite.
Additional Relevant History Questions
❏ Any major surgeries recently? Patient: No.
❏ Can you tell me about your past and recent medical history?
Patient: I have rheumatoid arthritis in my hands and type II
diabetes. I have been experiencing some weight loss (~ 15lbs),
night sweats and fever recently.
❏ What medications and/or supplements are you taking? Patient: I
take Advil or Aleve occasionally for my arthritis, and I am on
metformin for my diabetes.
❏ Can you describe your bowel movements over the past few months?
Patient: I have been having periods of constipation/diarrhea.
❏ Is there a history of GI/stomach cancer in your family? Patient: My
mother died at 60 years of age from colon cancer.
❏ Do you smoke cigarettes or drink alcohol? Patient: Yes, I have been
smoking for the last 40 years; 2-3 cigarettes a day. I also drink 2-3
glasses of brandy every night.
Physical Exam
Skin pallor noted.
The rest of the physical examination is unremarkable.
Laboratory Investigations
RBC 3.72 x 1012/L
Hgb 58 g/L
Hct 0.208
MCV 56.1 fL
MCHC 285 g/L
RDW 0.204
WBC 5.8 x 109/L
Neutrophils 82 %
Leukocytes 13 %
M onlcytes 1 %
E esinophils 4 %
B asophils 0 %
Platelets 387 x 109/L
serum ferritin <10 µg/L
serum iron 4.5 µmol/L
TIBC 127.5 µmol/L
transferrin saturation 4 %
Fecal occult blood negative
Blood smear analysis
RBC morphology
1+ anisocytosis
2+ elliptocytes and target cells
2+ hypochromasia
2+ microcytosis
WBC morphology normal
Platelet morphology normal
Interpretation of Lab Results
(key findings)
❑ CBC shows anemia of hypochromic-microcytic type.
❑ Neutrophilia indicates premature release of myeloid cells
from bone marrow1
❑ ↓ S-Iron, S-ferritin, transferrin saturation and ↑ TIBC
suggests Iron Deficiency Anemia
❑ Peripheral blood film also suggest Iron deficiency is the most
likely cause of anemia
❑ A negative FOBT suggests absent GI bleeding, but a single
negative FOBT does not exclude GI bleed. Sensitivity of a
single FOBT in screening GI bleed is only 30-40%.
Differential Diagnosis
with brief explanation of rationale
1. Occult GI bleed (eg. NSAIDs induced gastritis/peptic ulcer)
Rational: postmenopausal female with iron deficiency anemia,
on NSAIDs with altered appetite.
2. Colorectal Cancer
Rational: 67 yrs, altered appetite, altered bowel habits,
unexplained weight loss, night sweats, fever, FMHx of colon
cancer, diabetes mellitus, smoker and drinker
3. Anemia of chronic inflammatory (ACI)
Rational: rheumatoid arthritis & slightly elevated neutrophil
count; acute/chronic infection and/or disease can alter Fe
hemostasis, RBC half-life, proliferation/differentiation of
progenitor cells.
4. Malabsorption
Rational: age, altered bowel habits (diarrhea)
Most Likely Diagnosis
with brief explanation of rationale
Considering the laboratory results it is reasonable to conclude the
patient is currently experiencing microcytic iron deficient anemia.
Her anemia may be related to malignancy in her lower GI causing a
slow bleed. She exhibits key risk factors for colorectal cancer:
❏ > 50 yrs old
❏ history of altered appetite, weight loss, fever, night sweats
❏ FMHx of colon cancer
❏ smoking/drinking
❏ diabetes mellitus
Her test results show severe anemia, incompatible with a diagnosis
of ACI. She has no history of gastritis, peptic ulcers and denies
hemoptysis however; considering her NSAIDs use, we need to ruleout upper GI bleed.
Pathophysiology
Colorectal Carcinoma (CRC) causing Anemia
As the tumour grows in size it becomes highly vascularized and is
susceptible to hemorrhage. Tumors may become quite large and
the passage of feces alone may also cause bleeding. Additionally
large tumors can perforate the intestinal wall.2
Approximately 20% of patients with colon cancer experience GI
bleeding, specifically cecal and ascending colon tumors can cause
up to 9ml daily blood loss.2
CRC Pathophysiology
Chromosomal Instability Pathway (CIP) is the most common in CRC
❑ Activation of KRAS (proto-onco gene)
❑ De-activation of three tumour suppressor genes:
APC, p53, Chromosome 18 (loss of heterozygosity)3
Management
We would first discuss the following diagnostic tools/options
with the patient:4,5
1. Colonoscopy = generally considered the gold standard.
2. Barium enema = sensitivity ≈ 50%
3. CT colonography
4. Biopsy for definitive diagnosis
5. Carcinoembryonic Antigen (CEA) serum marker
6. Upper GI endoscopy: to rule out upper GI bleed
Staging Investigations
CT scan abdomen pelvis, Chest, Liver MRI, Liver enzymes, Liver
Function tests, Bone Scan, CT head only if lesions suspected.4,5
Treatment
Arrange referral to a surgeon and oncologist
Surgical excision is the mainstay of treatment for colon cancer
Chemotherapy indicated in patients with advanced disease.
Radiation - In case of advanced disease.5,6
Prognosis/ Patient Education
Prognosis
Overall 5 years survival rate for colorectal carcinoma is
approximately 65% but it varies greatly with age, presence of other
prognostic factors such as CEA and tumor grade.2,7
Patient education
• Your symptoms are most likely due to Iron deficiency Anemia
(IDA). Most probable cause of IDA for your age, medical history
and test results is a GI bleed – for which we need to find the
source with further investigations.
• We will arrange an appointment with Gastroenterologist.
• We will arrange a follow up meeting to discuss your
Colonoscopy results and treatment options.
• You may need a referral to an Oncologist or Surgeon depending
on results of colonoscopy.7
References
1. Howard MR, Hamilton PJ. Haematology: An Illustrated Colour
Text. 4th ed. London, UK: Churchill Livingstone Elsevier; 2013.
2. Dennis J Ahnen, MD Finlay A Macrae, MD Johanna Bendell, MD.
Clinical presentation, diagnosis, and staging of colorectal cancer.
http://www.uptodate.com/home (accessed 18 January 2015).
3. Armaghany T, Wilson JD, Chu Q, Mills G. Genetic Alterations in
Colorectal Cancer. Gastrointestinal Cancer Research. 2012 Jan
5(1): 19-27.
4. Stern, SDC. Cifu AS, Altkorn D. Symptoms to Diagnosis: An
evidence Based Guide. 2nd ed. New York City; 2010.
5. Bowers N, Gawad N. General Surgery. In: Vojvodic M, Young A,
editors. Toronto Notes. 30th ed. Toronto: Type & Graphics Inc.
2014
References
6. Longmore M, Wilkinson I, Davidson E, Foulkes A, Mafi A.
Oxford Handbook of Clinical Medicine. 9th ed. Oxford: Oxford
University Press; 2010.
7. Canadian Cancer Society. Prognosis and survival for colorectal
cancer. https://www.cancer.ca/en/?region=on (accessed 19
January 2014).