RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1.NAME OF THE CANDIDATE AND ADDRESS / Dr.MEKALA.L,
FLAT NO.2,SUNDARI APTS,NO.5 BANK STREET, KILPAUK,CHENNAI 600010
2.ADDRESS FOR CORRESPONDENCE / ROOM NO.452,TRIVENI GIRLS HOSTEL, M.S.RAMAIAH MEDICAL COLLEGE, MSR NAGAR, BANGALORE 560054
3.NAME OF THE INSTITUTION / M.S.RAMAIAH MEDICAL COLLEGE, BANGALORE
4.COURSE OF STUDY / MD PATHOLOGY
5.DATE OF ADMISSION TO COURSE / 31/05/2012
6.TITLE OF THE TOPIC / Incidence and spectrum of clinico pathological changes of Barrett’s esophagus among reflux esophagitis cases detected by Narrow Band Imaging

7. BRIEF RESUME OF INTENDED WORK

7.1 NEED FOR THE STUDY

Barrett’s esophagus (BE) is defined as the replacement of the normal squamous epithelium of the loweresophagus by metaplastic columnar epithelium.Itis a consequence of prolonged gastroesophagealreflux disease (GERD) and is increasing inincidence1. BE is a precancerous condition whichpredisposes to the development of esophageal adenocarcinoma. The major reason to evaluate patients with long standing GERD is to recognize BE and hence enhance the early detection of esophageal adenocarcinoma.

The present recommended strategy for BE surveillance is for endoscopists to carry out random four quadrant biopsies every 1–2 cm. This approach is however fraught with problems as sampling error can frequently occur as only 3.5% of a given 2 cm BE segment is sampled missing out the other 96.5%2.

Standard endoscopic imaging provides little detail of the mucosal surface making it difficult to distinguish specialized intestinal epithelium from gastric type metaplasia or to recognize dysplastic epithelium. Better imaging modalities have the potential to improve detection of Barrett's esophagus and surveillance for dysplasia and cancer.

Narrow-band imaging (NBI) is an optical technology that modifies the centre wavelength and bandwidth of an endoscope’s light into narrow-band illumination of 415 ± 30 nm. NBI markedly improves capillary pattern contrast and can be used to visualize microvessel morphological changes in superficial neoplastic lesions.This is a promising method for the diagnosis of early gastrointestinal tumors3.

7.2 REVIEW OF LITERATURE

In Asian countries, most cases of esophageal carcinomas are squamous cell carcinomas, not adenocarcinomas. Recently, however, the increase in the number of Barrett’s esophagus cases with subsequent adenocarcinoma has become worrisome in Asian countries, as the number of patients with GERD has been increasing in these countries4. One reason for the low prevalence of BE and adenocarcinoma in Asia may be that BE cases are mainly short-segment (<3 cm). However, as with long-segment Barrett’s esophagus (LSBE; >3 cm), some short-segment Barrett’s esophagus (SSBE) cases also show malignant potential4..Reports of a gradually increasing incidence of BE in Asia suggest that particular attention should be paid to these patients.

According toreports from Western countries, the prevalence of BE(histologically confirmed by the presence of goblet cell metaplasia/specialized columnar epithelium), LSBE, and SSBE is 1.6–25.0%, 0.5–7.2%, and 1.1–17.2%, respectively4.In these reports, most of the patients were Caucasian.LSBE prevalence in Asia is extremely low (<1.0% of all BE patients in most reports). In contrast, SSBE prevalence in Asia is greater than 96% of all BEpatients4.

The only characteristic feature of ‘specialized’ intestinal Barrett’s mucosa is the presence of goblet cells.1These cells are usually easily visualized on routinely stained sections. However, these goblet cells in all cases produce acidic mucins. Accordingly, it has been proposed that systematic staining of biopsies of the gastro eosophageal junction with AlcianBlue(AB) could be of interest to demonstrate rare positive goblet cells, which may indicate SSBE.1

In a prospective singlecentre study involving 21 patients [75 areas, corresponding NBI and White Light Endoscopy(WLE) images]with BE,mucosal patterns (pit pattern and microvascular morphology) were evaluated for their image quality on a visual analogue scale (VAS) of 1-10 by five expert endoscopists. The overall pit and microvasculature quality was significantly higher for NBI, pit: NBI=6, WLE=4.5, p < 0.001; microvasculature: NBI=7.3, WLE=4.9, p < 0.001. This translated into a superior prediction of histology (Sn: NBI: 88.9, WLE: 71.9, p < 0.001). For the prediction of dysplasia, NBI was superior to WLE (chi square=10.3, p < 0.05). The overall kappa agreement among the five endoscopists for NBI and WLE, respectively, was 0.59 and 0.31 (p < 0.001).5This study concluded that NBI is superior to WLE in the prediction of histology in BE, with good reproducibility. This novel imaging modality could be an important tool for surveillance of patients with BE.

A singlecentre study in India showed the prevalence of BE in reflux esophagitis cases to be 23.6%6. Out of 55 patients with symptoms ofGERD, 13 cases were diagnosed asBE. There were 8 males and 5 females. Majority of the patients (77%) were between 20-40 years of age. At endoscopy, in 84.6% patients, lesions were in the form of islands of red mucosa. On histology examination, in 6 cases, squamous epithelium was replaced by intestinal epithelium containing goblet cells and in 7 cases it was replaced by gastric epithelium. Associated dysplasia was not seen in any of the case, while one case showed associated adenocarcinoma.

7.3 OBJECTIVES OF THE STUDY

1) To determine the incidence of Barrett’s esophagus in cases of clinically suspected reflux esophagitis confirmed by High Definition endoscopy with Narrow Band Imaging in a tertiary care hospital over a period of 2 years.(June 2012-May 2014)

2) To study the spectrum of clinico-pathological changes in Barrett’s esophagus.

3)To determine the correlation between length of the inflamed segment of reflux esophagitis and BE and categorize as SSBE and LSBE.

8. MATERIALS AND METHODS

8.1 SOURCE OF DATA

Biopsy of reflux esophagitis cases done by Narrow Band Imaging received for routine histopathological evaluation from the Department of Gastroenterology,M.S.Ramaiah Memorial Hospital, Bangalore, from June 2012 to May 2014 will be the source of data for the study.

8.2 METHOD OF COLLECTION OF DATA

Age and sex of all the patients undergoing High Definition endoscopy with Narrow Band Imaging for suspected gastroesophageal reflux disease and NBI guided biopsy of Barrett’s lesion, will be noted.The endoscopic criteria for diagnosis of reflux esophagitis will be based on Los Angeles classification and endoscopic diagnosis of Barrett’s esophagus will be based on Prague endoscopic criteria.The gross appearance and length of the lesion while doing endoscopy will be noted.The biopsy specimen will be received in the Pathology Department in 10% formalin and fixed for 2-3 hours.After conventional processing,paraffin sections of 5 micrometre thickness will be stained by haematoxylin and eosin(H & E) for histopathology study.Slides of squamous epithelium will be analyzed for histologic features of Barrett’s esophagus.Thepresence of goblet cells will be used as criteria for intestinal metaplasia.Metaplastic columnar epithelium (gastric or specialized columnar epithelium),dysplasia and carcinomawill also be noted.In all cases diagnosed as BE, special staining with AlcianBlue-Periodic Acid Schiff at pH 2.5 will be done to confirm the presence of acidic mucin in the goblet cells.

8.3 INCLUSION CRITERIA

Patients with symptoms of gastro esophageal reflux disease for over 6 months not responding to symptomatic treatment with no sustained relief will be included in the study

8.4 EXCLUSION CRITERIA

Patients with esophageal carcinoma, history of upper gastrointestinal surgery, esophageal varicesand unwillingness to give informed consent will be excluded from the study.

8.5 SAMPLE SIZE DETERMINATION

From the literature review, it was observed that the prevalence of Barrett’s esophagus in cases of reflux esophagitis in a study in India was found to be 23.6%6.We need a sample of 311 to get a similar result with a precision of 95% confidence and 20% relative presicion.

8.6 STATISTICAL ANALYSIS

Descriptive statistics of Barrett’s esophagus and its spectrum of clinicopathologicalchanges (age and sex of the patient, endoscopic findings,presence of intestinal and gastric metaplasia,,association with dysplasia and adenocarcinoma)will be analyzed and expressed in terms of percentage and its 95% confidence intervals will be analysed.The relationship between length of the inflammation seen by endoscopy and BE will be analysed using chi square.

8.7DOES THE STUDY REQUIRE ANY OTHER INVESTIGATIONS OR INTERVENTIONS TO BE CONDUCTED ON HUMANS OR ANIMALS?

Endoscopy,biopsy and histopathological examination will be performed as a part of routine protocol for treatment, pathological assessment and planning further management. No additional investigations or interventions will be done specially for the purpose of the dissertation.

8.8HAS ETHICAL CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION?

Yes

9.REFERENCES

1.Fle´jou JF and SvrcekM. Barrett’soesophagus—a pathologist’s view. Histopathology 2007;50:3–14.

2. Singh R, Nordeen N, Shanmuganathan G, Thurairajah PH and Bhat YM. Current consensus for role of NBI in diagnosis of superficial neoplasia in the upper digestive tract.Digestive Endoscopy 2011;23:83–85.

3.Emura F, Saito Y, Ikematsu H.Narrow-band imaging optical chromocolonoscopy: Advantages and limitations. World J Gastroenterology 2008;14(31): 4867-72.

4.Amano Y, KinoshitaY.Barrett Esophagus: Perspectives on Its Diagnosis and Management in Asian Populations.Gastroenterology and Hepatology 2008;4:45-53.

5.Singh.R et al. Comparison of high-resolution magnification narrow-band imaging and white-light endoscopy in the prediction of histology in Barrett's oesophagus.Scandinavian Journal of Gastroentrology 2009;44(1):85-92.

6.Punia RS, Arya S, Mohan H, Duseja A, Bal A. Spectrum of clinico-pathological changes in Barrett oesophagus. Journal Assoc Physicians India 2006;54:187-189.

10.SIGNATUREOF THE CANDIDATE
11. REMARKS OF THE GUIDE / Barrett’s esophagus is a premalignant condition commonly associated with Gastro Esophageal Reflux Disease.It can now be detected by visualizing abnormal vascular patterns by using special scope called Narrow Band Imaging.Hence it is useful in early detection and studying its incidence in GERD.
12.(a) NAME AND DESIGNATION OF THE GUIDE / DR.MANGALA GOURI.S.R,
PROFESSOR OF PATHOLOGY
(b) SIGNATURE OF THE GUIDE
(c) NAME AND DESIGNATION OF THE CO-GUIDE / DR.SATYAPRAKASH B.C,
SENIOR PROFESSOR OF GASTROENTEROLOGY
(d) SIGNATURE OF THE CO-GUIDE
(e) HEAD OF THE DEPARTMENT / DR.K.C.MAHADEVA
(f) SIGNATURE OF THE H.O.D
(g) REMARKS OF CHAIRMAN AND PRINCIPAL
(h) SIGNATURE OF THE PRINCIPAL