High Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia

Our central hypothesis is that HRME can improve the efficiency and clinical impact of
endoscopic screening and surveillance of esophageal squamous cell neoplasia by providing
in-vivo optical biopsies comparable to standard histology. Specifically, HRME will allow more
detailed evaluation of Lugol's abnormal areas, allowing selective biopsy or removal of
neoplastic mucosa. We hypothesize that this will improve the accuracy and diagnostic yield of
mucosal sampling.

We also hypothesize the HRME will provide additional, more accurate information regarding the
presence of neoplasia that will impact upon the physician's decision to obtain a mucosal
biopsy or perform endoscopic therapy (endoscopic mucosal resection or ablation). This could
potentially minimize the number of unnecessary biopsies and enable the physician to perform
endoscopic therapy at the time of the initial examination, rather than delaying endoscopic
treatment to another procedure following pathologic confirmation of the initial biopsies.

Primary Aims:

1. To compare the efficiency of HRME + Lugol's chromoendoscopy (HRME + LC) to that of
Lugol's chromoendoscopy alone (LC) for the diagnosis of esophageal squamous cell
neoplasia. Efficiency will be defined as:

1. Diagnostic Yield: The number of neoplastic biopsies/total number of biopsies
obtained in patients who receive biopsies.

2. 'Patients saved': # patients who receive no biopsies

3. Procedure time: Total procedure time in the HRME-LC arm compared to the LC arm.

2. To prospectively determine the potential clinical impact of HRME + Lugol's
chromoendoscopy (HRME-LC) to Lugol's Chromoendoscopy (LC) by determining if HRME changes
the decision to perform endoscopic therapy (endoscopic mucosal resection or ablation) or
perform a mucosal biopsy.

3. To prospectively compare the performance characteristics of HRME-LC to LC for the
prediction of squamous esophageal neoplasia in flat mucosa and mucosal lesions using
histopathology as the gold standard:

(a) To determine the sensitivity, specificity, positive and negative predictive value
for the identification of neoplasia on a per biopsy and per patient analysis

4. To determine the cost-effectiveness of HRME-LC to LC alone for the endoscopic screening
and surveillance of esophageal squamous neoplasia in the US and China.

Inclusion Criteria:

All inclusive outpatients undergoing routine (standard of care) Lugol's chromoendoscopic
evaluation for suspected or known squamous cell neoplasia will be enrolled as well as any
outgoing patients referred to the clinic with any prior history of squamous cell dysplasia
and/or neoplasia will also be considered eligible as they will serve as study population
for the surveillance group.

Exclusion Criteria:

- Allergy or prior reaction to the fluorescent contrast agent proflavine

- Patients who are unable to give informed consent

- Known advanced squamous cell carcinoma of the distal esophagus, or dyplastic/suspected
malignant esophageal lesion greater than or equal to 2cm in size not amenable to
endoscopic therapy

- Patient unable to undergo routine endoscopy with biopsy:

- women who are pregnant or breastfeeding

- prothrombin time greater than 50% of control; PTT greater than 50 sec, or INR greater
than 2.0

- inability to tolerate sedated upper endoscopy due to cardio-pulmonary instability or
other significant medical issues