A Histopathological Study of Endoscopic Gastroduodenal Biopsies in Cases of Anaemia

A HISTOPATHOLOGICAL STUDY OF ENDOSCOPIC GASTRODUODENAL BIOPSIES IN CASES OF ANAEMIA

BY

MAJ (DR) V D DANGWAL

SYNOPSIS FOR REGISTRATION OF SUBJECT FOR

DISSERTATION

TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

IN PARTIAL FULFILLMENT OF REGULATIONS FOR

THEAWARD OF

DOCTOR OF MEDICINE

IN

PATHOLOGY

DEPARTMENT OF PATHOLOGY

COMMAND HOSPITAL AIR FORCE BANGALORE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
TO BE SUBMITTED IN DUPLICATE
1. / NAME OF THE CANDIDATE AND ADDRESS / MAJ (DR) V D DANGWAL
DEPARTMENT OF PATHOLOGY
COMMAND HOSPITAL (AIR FORCE) BANGALORE KARNATAKA
2. / NAME OF THE INSTITUTION / COMMAND HOSPITAL (AIR FORCE)
BANGALORE - 560007
3. / COURSE OF THE STUDY AND SUBJECT / M.D. PATHOLOGY
4. / DATE OF ADMISSION TO THE COURSE / JULY 2013
5. / TITLE OF THE TOPIC / A HISTOPATHOLOGICAL STUDY OF ENDOSCOPIC GASTRODUODENAL BIOPSIES IN CASES OF ANAEMIA
6. / BRIEF RESUME OF INTENDED WORK / APPENDIX A
7. / MATERIALS AND METHODS / APPENDIX B
8. / LIST OF REFERENCES / APPENDIX C
9. / SIGNATURE OF THE CANDIDATE
10 / REMARKS OF THE GUIDE
11.1 / NAME AND DESIGNATION
OF GUIDE / GP CAPT (DR) MRS VANMALINI TEWARI
PROFESSOR AND HOD
DEPARTMENT OF PATHOLOGY
COMMAND HOSPITAL AIR FORCE
BANGALORE
11.2 / SIGNATURE
11.3 /

CO GUIDE

/ GP CAPT (DR) BHASKAR NANDI
PROFESSOR AND SENIOR ADVISOR
DEPARTMENT OF MEDICINE AND GASTROENTEROLOGY
COMMAND HOSPITAL AIR FORCE
BANGALORE
11.4 / SIGNATURE
11.5 / HEAD OF THE DEPARTMENT / GP CAPT (DR) MRS VANMALINI TEWARI
PROFESSOR AND HOD
DEPARTMENT OF PATHOLOGY
COMMAND HOSPITAL AIR FORCE
BANGALORE
11.6 / SIGNATURE
12.1 / REMARKS OF DEAN AND PRINCIPAL
12.2 / SIGNATURE

APPENDIX ‘A’

6. BRIEF RESUME OF INTENDED WORK.

6.1. INTRODUCTION AND NEED FOR THE STUDY:

Anemia is a universal problem involving individuals of all ages and both sexes. There is a paucity of studies on unexplained anemia from urban india where socio-economic conditions is different and hence the cause of anemia is expected to be different.

The most common cause of anemia is nutritional Iron deficiency anemia (IDA). Chronic gastrointestinal (GI) bleeding is a leading cause of the Iron deficiency anemia (IDA).Anemia resulting from gastrointestinal bleeding is a common feature of many gastrointestinal conditions, several of which may be asymptomatic, including tumours of thegastrointestinal tract . In addition, IDA is now one of the most common presenting features of coeliac disease, which can be managed by dietary compliance. Therefore to establish a cause is essential for adequate management. The investigations are often unpleasant and demanding on patients.

Although GI biopsy is not a part of standard work up for anemia, a possibility of it being included in the investigation protocol for anemia is being explored in this study to find out if any correlation exists between GI causes frequently encountered in patients with anemia vis a vis degree of anemia, age at detection, any other co-morbidities etc.

6.2. REVIEW OF LITERATURE:

Anemia is a common, multifactorial condition among adults and it is one of India's major public health problems. The World Health Organization (WHO) definition of Anemia (hemoglobin concentration <12 g/dL in women and <13 g/dL in men) is most often used in epidemiologic studies of adults (1). The prevalence of anaemia was found to range from 30% to 98% in various studies from different regions (2, 3). The prevalence of anemia in males (20-50 years) was 53.2%,with 34.3% suffering from mild, 17.7% from moderate and 1.2% from severe anemia (2).

Common causes of anemia in adults are occult GI blood loss, malabsorption and nutritional (Table 1) Cause of anemia varies with gender and age. There is a paucity of studies on unexplained anaemia from urban india where socio-economic conditions is different and hence the cause of anaemia is expected to be different. There is very limited data on causes of anemia in adult males (2).

Work up for anemia includes

Complete blood count: Hb/PCV/MCV/MCH/MCHC/Reticulocyte count/TLC/DLC/Platelet count.

Smear examination for morphology: size/anisocytosis/polychomasia/poikilocytosis

Stool examination for ova/cyst/occult blood

Test for iron supply /storage : serum iron/ferritin/serum TIBC levels

Urine for hematuria

Table 1: Causes of iron deficiency anemia in adults

1. Low iron in diet

1. Malabsorption

Celiac disease, Gastric resection,
Gut bypass, Bacterial overgrowth,
Whipples disease, Lymphangiectasia

1. Occult GI blood loss

Common: NSAID, Colonic polyp,
Gastric cancer, IBD
IBD, Intestinal parasites
Uncommon: Lymphoma, Peptic ulcer
Meckels divertculum,

Morphological typing of anemia is useful as it not only reduces the differential diagnosis of the cause but also helps in the immediate management of the patient. The morphological typing is done as macrocytic, normocytic normochromic and microcytic hypochromic based on RBC indices

The prevalence of anemia in the elderly has been found to range from 8 to 44 percent, with the highest prevalence in men with 85 years and more. Anemia should not be accepted as an inevitable consequence of ageing and a cause must be found out. Overall, 4–6% of patients with IDA will have coeliac disease, including 4% of premenopausal women. Higher prevalences have been cited. A recent study from Iran showed that a prevalence of up to 15% of patients with IDA had coeliac disease,(5) while in the United States 8.7% of those with IDA had celiac disease.(6) This study also concluded that even if other lesions which may explain IDA are found at endoscopy,a duodenal biopsy should still be performed. A firm

principle is that all patients with IDA should be screened for coeliac disease.

Standard evaluation of a patient with iron deficiency anemia is not sufficient and many patients remain without a diagnosis. Because iron deficiency anemia results from iron loss or defective absorption endoscopy alone is not sufficient and a histopathological evaluation of gastrointestinal tract is essential to look into the various causes which are missed out during work up for anemia

6. 3. OBJECTIVE OF THE STUDY

1. To describe the trend in gastro-duodenal biopsy performed in adult anaemic patients during evaluation of anaemia and to analyze its value for the diagnosis of cause of anaemia in clinical practice.
2. To establish a correlation between various causes of anaemia and results of respective UGIE biopsies.

APPENDIX ‘B’

7 MATERIALS AND METHOD

7.1 SOURCE OF DATA: Gastroduodenal biopsies sent for histopathological evaluation in cases of anemia

STUDY DESIGN: This is a prospective descriptive study along with statistical analysis

STUDY AREA: Command Hospital Air Force, Bangalore

STUDY SUBJECT: 100, consecutive patient, during the study period attending Command Hospital Air Force Bangalore for GI endoscopy and satisfying the inclusion criteria will be studied.

INCLUSION CRITERIA:

1. Patients with Anemia as defined by WHO

Haemoglobin concentration of 13 g/dl or less (men) or

12 g/dl or less (women)

1. Patients undergoing GI endoscopy in Command Hospital Air Force, Bangalore

EXCLUSION CRITERIA

1. Patients who do not have anemia
2. Known haematological abnormalities such ashaemoglobinopathy, Known cause for blood loss such as recent surgery, trauma, or overt gastrointestinal haemorrhage, chronic kidney disease.
3. Patients who have not undergone GI endoscopic biopsy.

7.2 METHODOLOGY

• Complete hemogram and blood counts using Hematology automated analyzers (sysmex XT 2000i)for diagnosing anemia
• Typing of anemia by Peripheral Blood Smears (as per proforma attached)
• UGI endoscopic biopsy using standard FFPE (Formaline Fixed and Paraffin Embedded) method and HPE (Histopathological Examination). Sections will be stained by H&E (Hematoxylin and Eosin) and Toluidine blue and examined under microscope.
• Coeliac disease reporting as per MARSH criteria
• Correlation will be established by standard statistical test (P value)

7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals?

Yes

Upper GI endoscopic biopsy, Complete hemogram and blood counts, serum iron study and PBS.

7.4 Has ethical clearance been obtained from your institution?

yes

APPENDIX‘C’

LIST OF REFERENCES.

1. Blanc B, Finch CA, Hallberg L, et al. Nutritional anaemias. Report of a WHO Scientific Group. WHO Tech Rep Ser. 1968;405: 1-40.
2. Verma P, Singh S, Kumar A, Ghildiyal A,Krishna A. Prevalence of Anaemia in adults with respect to Socio-Demographic status, Blood groups and religion in North Indian population. Int J Bio Med Res 2012;3(4):2441-2447.
3. Gupta VK, Maria AK, Kumar R, Bahia JS, Arora S. Prevalence of Anaemia in adults with respect to Socio-Demographic status, Blood groups and religion in North Indian population. J Clin Diag Res 2011;5(5):1020-1026.
4. Goddard AF, McIntyre AS, Scott BB. Guidelines for the management of iron deficiency anaemia Gut 2000;46(suppl iv):iv1-iv5
5. Zamani F, Mohamadnejad M, Shakeri R et al. Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin. World J. Gastroenterol. 2008; 14; 7381–7385.
6. Grisolano SW, Oxentenko AS, Murray JA et al. The usefulness of routine small bowel biopsies in evaluation of iron deficiency anemia. J. Clin. Gastroenterol. 2004; 38; 756– 760.

COMMAND HOSPITAL AIR FORCEBANGALORE

DEPATMENT OF PATHOLOGY

BIOPSY REPORT

Biopsy NO. B: -

Date of sample: -

Name of Patient: -Relation: -Age: -

Sex: -

Service No.Rank: -Name: -

Unit: -Ward/ OPD

Clinical Diagnosis

Specimen

Gross:

Microscopy

Opinion

Date:Signature of Pathologist

* All Malignancy cases to be registered in MDTC

DEPARTMENT OF PATHOLOGY

COMMAND HOSPITAL AIR FORCE, BANGALORE

PERIPHERAL BLOOD SMEAR REPORT

Date:

PBS No: Patient’s Name: Ward/Dept:

Relation: Ser No: Rank:

Name: Age: Yrs Sex: M/F

Unit:

Diagnosis:

Hb: gm% TLC: /cmm DLC: N %, E %, B: %, M %, L %

Platelet Count: x 105/cmm ESR: mm fall in 1st hour

Complete Haemogram:

TRBC: mil/cmm , PCV: %, MCV: fl, MCH: pg, MCHC: %

Retic: %, AEC: /cumm MISC:

PBS for MP: ICT for MP:

Smear suitable / Poorly prepared / Not Suitable for reporting

RBC series

Size: Normocytic / Microcytic / Macrocytic / Mixed

Chromasia: Normochromic / Hypochromic

Anisocytosis: Nil / Mild / Moderate / Severe

Poikilocytosis: Nil / Mild /Moderate / Severe in the form of pencil cells / Tear drop cells / target cells / macro-ovalocytes / spherocytes / Schistocytes / Others.

Nucleated RBCs: Not seen/ per 100 WBCs

WBC Series

Total count: Appears normal / Increased / Decreased

Sepsis: No changes / Cytoplasmic vacoulation / Toxic granules / Shift to left / Others

Abnormal cells: Nil / Seen

Platelets

Total count: Appears normal / decreased / increased.

Others:

Haemoparasites:

Opinion:

PATIENT CONSENT FORM

Name of the participant: ______

Name of the Principal (Co-) Investigator: ______

Name of the Institution: ______

Documentation of the informed consent

I, … … … … … … … … …. , has read the information in this form (or it has been read to me). I wasfree to ask any questions and they have been answered.

(1) I have read and understood this consent form and the information provided to me.

(2) I have had the consent document explained to me.

(3) I have been explained about the nature of the study.

(4) My rights and responsibilities have been explained to me by the investigator.

(5) I have been advised about the risks associated with my participation in the study.

(6) I am aware of the fact that I can opt out of the study at any time without having to give any reason and this will not affect my future treatment in the hospital.

(7) I am also aware that the investigators may terminate my participation in the study at anytime, for any reason, without my consent.

(8) I hereby give permission to the investigators to release the information obtained from me as result of participation in this study to the sponsors, regulatory authorities, Government agencies, and ethics committee. I understand that they may inspect my original records.

(9) My identity will be kept confidential if my data are publicly presented.

(10) If, despite following the instructions, I am physically harmed because of any substance or any procedure as stipulated in the study plan, [my treatment will be carried out free at the investigational site / the sponsor will bear all the expenses], if they are not covered by my insurance agency or by a Government program or any third party.

(11) I have had my questions answered to my satisfaction.

(12) I have decided to be in the research study. I am aware, that if I have any questions during this study, I should contact at one of the addresses listed above. By signing this consent form, I attest that the information given in this document I will be given a copy of this consent document.

Participant’s initials: ____

Investigator Certificate

I certify that all the elements including the nature, purpose and possible risks of the above study as described in this consent document have been fully explained to the subject. In my judgment, the participant possesses the legal capacity to give informed consent to participate in this research and is voluntarily and knowingly giving informed consent to participate,

Signature of the Investigator: ______Dated: ______

Name of the Investigator: ______

CERTIFICATE OF ACCEPTANCE BY THE GUIDE

I, Gp Capt (Dr.) Vanmalini Tewari Professor & HOD, Dept of Pathology, Command Hospital Air Force Bangalore, hereby certify that I accept

Maj (Dr) V D Dangwal as candidate of MD Pathology course. The title of dissertation is as follows:-

A HISTOPATHOLOGICAL STUDY OF ENDOSCOPIC GASTRODUODENAL BIOPSIES IN CASES OF ANAEMIA

He will be under my guidance during the entire period of her study and dissertation work.

Gp Capt (Dr.) Vanmalini Tewari

Professor & HOD

Dept of Pathology

Command Hospital Air Force

Bangalore

CERTIFICATE FROM ETHICAL COMMITTEE

The Committee has examined the scope including the need, objectives, method of data collection and human interventions of the following study to be carried out by Maj (Dr) V D Dangwal, MD student (Department of Pathology) under the guidance of Gp Capt (Dr.) Vanmalini Tewari Professor & HOD Dept of Pathology, and the title of which is:

A HISTOPATHOLOGICAL STUDY OF ENDOSCOPIC GASTRODUODENAL BIOPSIES IN CASES OF ANAEMIA

The committee has no objection for undertaking this study at CommandHospital Air Force Bangalore.

(MS Prakash) ( SC Dash ) (SK Jha) ( H Sahni )

Brig Col Col Gp Capt

Prof and HOD Prof and HOD OIC OIC

Dept of medicine Dept of surgery PG Cell AFMRC

Member Member Member Member Secretary

(S Kaistha) (Shalini Chaudhary) (Dr V Sinha) (Mrs Vasanta Kishore)

Wg Cdr Sqn Ldr Scientist Counsellor

Rep of AFWWA OIC Legal cell Physiologist E support

Member Member Member Member

(M K Bedi)

Air Cmde

AOC

MTC

Chairman Ethical Committee

Command Hospital Air Force

Bangalore– 560007

CERTIFICATE FROM HEAD OF INSTITUTION

Permission is hereby accorded to the student Maj (Dr) V D Dangwal , to undergo MD (Pathology) course being conducted at Command Hospital Air Force Bangalore affiliated to Rajiv Gandhi University of Health Sciences, commencing from June 2013 under guidance of Gp Capt (Dr) Vanmalini TewariProfessor, Dept of Pathology, Command Hospital (AF) Bangalore.

Air Vice Mshl (Dr)RAJVIR BHALWAR

COMMANDANT AND PRINCIPAL

COMMAND HOSPITAL AIR FORCE

BANGALORE – 560007