achalasia is a chronic esophageal motility disorder associated with esophageal retention of foods and fluids , bacterial overgrowth , and impaired clearance of regurgitated gastric contents .
these factors usually lead to chronic inflammation of the esophageal mucosa , which potentially increases the risk of hyperplasia , dysplasia , and esophageal cancer [ 2 , 3 ] .  
esophageal squamous cell carcinomas in achalasia patients have been investigated previously . in a large cohort
followup study , wychulis et al .   analyzed 1,318 patients and found a 7-fold increased risk of esophageal squamous cell carcinomas in achalasia patients compared to the general population .
despite some contradictory data [ 57 ] , achalasia is generally accepted as a condition associated with an increased risk for developing esophageal squamous cell carcinoma [ 8 , 9 ] .
chromoendoscopy with lugol 's staining remains the gold standard technique for detecting superficial esophageal squamous cell carcinoma [ 10 , 11 ] .
although lugol 's staining is a simple and low - cost method , instillation of its solution may lead to complications , such as hypersensitivity to iodine , laryngitis , and pneumonitis , as well as frequent painful sensations and nausea [ 1215 ] .
kondo et al .   demonstrated a significant reduction in retrosternal discomfort with the use of sodium thiosulfate .
an alternative technique such as narrow - band imaging for  optical staining  would be desirable , especially because it is a simpler technique and has no known complications .
narrow - band imaging technology may be useful for detecting squamous cell carcinomas of the pharynx and esophagus .
muto et al .   and yoshida et al .   observed morphological pattern changes in intrapapillary capillary loops .
these patterns can be useful for diagnosing squamous cell carcinomas and even to predict lesion extension .
various reports of early - stage pharyngeal and esophageal squamous cell carcinomas identified with narrow - band imaging technology can be found in the literature . without using imaging magnification , muto et al .   diagnosed a superficial squamous cell carcinoma of the pharynx , which appeared as a small and well - defined brownish area .
watanabe et al . , who also used narrow - band imaging without magnification , found six pharyngeal squamous cell carcinomas , and goda et al .  
found an esophageal squamous cell carcinoma that was not identified by conventional endoscopy ( obscure lesion ) .
recently , our group demonstrated that narrow - band imaging performs as well as lugol 's chromoendoscopy for the detection of esophageal squamous cell carcinoma in patients with head and neck cancer .
the aim of this study was to compare narrow - band imaging technology with lugol 's staining during endoscopic examination of the esophagus for the detection of high - grade intraepithelial neoplasias and superficial squamous cell carcinomas in patients with esophageal achalasia .
this was a cross - sectional study , and esophageal mucosal examination was analyzed in a sequential approach divided into three phases .
the first phase was with white light , the second phase was with narrow - band imaging , and the final phase was with lugol 's staining . at the end of each phase ,
the patients were submitted to an endoscopic procedure , and it was performed under conscious sedation with midazolam and fentanyl .
only one senior endoscopist ( edson ide ) performed all of the endoscopic procedures . at the first phase ,
if there were lesions , they were mapped using the anterior , posterior , right , and left esophageal walls and the distance up to anterior incisors as references .  
the second phase involved the use of narrow - band imaging assessment of the esophageal mucosa . at this moment ,
mucosa , which is green independent of changes in surface or vascular texture . in the third phase ,
lugol 's staining was performed by spraying 20cc of a 2% lugol 's solution at esophageal mucosa .
after the staining , white - colored areas were suspected of being neoplasia , in contrast with brown or brownish  normal  areas .  
the operator took biopsies of every suspicious lesion detected by any phase of the study .
biopsies were only performed after lugol 's staining was completed , and , after mucosal examination and biopsy , a volume of 20cc of a 0.5% sodium thiosulfate solution was instilled to remove lugol 's solution in order to reduce spasm and pain .
complications due to lugol 's solution were registered including laryngitis , chemical pneumonitis , hypersensitivity , and anaphylactic shock .  
the size and macroscopic shape of the lesions were evaluated according to the paris classification   for superficial esophageal lesions .
topography was divided into cervical ( up to 5  cm of cricopharyngeus muscle ) , thoracic , and abdominal esophagus . from october 2006 to february 2007
, 48 consecutive patients with achalasia were referred to the gastrointestinal endoscopy unit of a tertiary academic center for early esophageal cancer detection .
these patients usually participate in a surveillance protocol , which consists of upper gastrointestinal endoscopy with associated esophageal lugol 's staining every 3 years .
inclusion criteria were indications to take part in the surveillance protocol for patients with achalasia , despite any treatment ( e.g. , pharmacologic , endoscopic dilation , and surgical cardiomyotomy ) they had undergone previously .
exclusion criteria were as follows : clinical conditions that prevented upper gastrointestinal endoscopy examination or lugol 's staining ; previous history of allergic reaction to iodine ; esophageal stasis that could not be cleared by endoscopic procedures ; and endoscopic detection of an ulcerated , infiltrative , or stenotic lesion .
this study was approved by the ethics committee of the university of so paulo medical school .
an exera ii evis 180 gif180 videogastroscope ( olympus , tokyo , japan ) with high resolution ( 1,080  dpi ) , 1.5-fold magnification , and narrow - band imaging technology was used .
histology was performed by a senior pathologist , who was aware of the endoscopic suspicion of esophageal squamous cell carcinoma .
the lesions were classified in accordance with the revised vienna classification . in the absence of lamina propria invasion ,
noninvasive neoplastic lesions were divided into two groups based on the degree of intraepithelial neoplasia : low grade and high grade .
high - grade dysplasia , intraepithelial carcinoma , and carcinoma in situ were considered equivalent entities .
whenever the lamina propria of the mucosa was invaded , the lesion was referred to as intramucosal carcinoma . in this study , only findings of high - grade intraepithelial neoplasia ( carcinoma in situ ) and intramucosal carcinoma of squamous cells were considered true positives for esophageal squamous cell carcinoma . values and 95% confidence intervals were calculated for sensitivity , specificity , positive predictive value , negative predictive value , accuracy , and positive and negative likelihood ratios .
of the 48 patients enrolled , five were excluded : one because he had an advanced malignant esophageal lesion that was easily detected by conventional endoscopy , three because they had esophageal stasis , and one because of a prior history of allergy to iodine . of the remaining 43 patients ,
the 43 patients underwent all stages of the protocol of investigation for this study ( figure 1 ) .
narrow - band imaging and lugol 's staining found seven and nine suspected lesions , respectively .
conventional endoscopy revealed one superficial lesion with a flat morphology ( 0-iib according to paris classification ) , which was also detected by narrow - band imaging and lugol 's staining ( figure 2 ) .
this lesion proved to be an esophageal neoplasia ( squamous cell carcinoma in situ ) , sized 15  mm in diameter , and was located in the thoracic esophagus .  
of the seven lesions found by narrow - band imaging , histopathology revealed that one was normal mucosa , five were esophagitides , and one was squamous cell carcinoma in situ .
of the nine lesions found by lugol 's staining , histopathology revealed that eight were esophagitides and one was squamous cell carcinoma in situ .
the performance of narrow - band imaging was similar to that obtained by lugol 's staining .
sensitivity and negative predictive value were 100% for both methods , and the specificity was 85.7% ( 75.1%96.3% ) for narrow - band imaging and 81% ( 69.1%92.8% ) for lugol 's staining .
diagnostic performances for conventional endoscopic examinations , narrow - band imaging , and lugol 's staining are presented in table 2 . in the lugol 's staining group
the present study selected patients with achalasia as an increased - risk group for esophageal squamous cell carcinoma .
these patients usually present with delayed esophageal emptying , and they report worsening of these symptoms due to development of an obstructive tumor at late stages . without surveillance , esophageal carcinoma is usually diagnosed in advanced stages with poor prognosis .
the lugol 's staining technique is based on the presence of large amounts of glycogen in the squamous epithelium , which stains intensely with iodine ; in contrast , dysplastic and carcinoma cells contain little or no glycogen , which results in no staining [ 15 , 2527 ] .
thus , upper gastrointestinal endoscopy with lugol 's staining is still considered the best method for the diagnosis and delimitation of superficial esophageal squamous cell carcinoma [ 2729 ] .
however , lugol 's solution irritates the mucosa and may lead to retrosternal chest pain and discomfort , because of its alcoholic nature .
its utilization is limited by other factors , namely , hypersensitivity to iodine and the risk of chemical esophagitis , laryngitis , and bronchopneumonia .
several authors have reported necrosis and injury to the esophageal and gastric mucosa caused by hypersensitivity to lugol 's solution [ 30 , 31 ] .
furthermore , esophageal chromoendoscopy with lugol 's staining significantly increases the length of the examination period .
narrow - band imaging enhances the visualization of superficial capillaries , as well as mucosal surface structure , and has an effect similar to that of chromoendoscopy .
moreover , narrow - band imaging does not have the limitations of lugol 's staining chromoendoscopy and could be considered as a potential alternative method for the detection of esophageal squamous cell carcinoma .  
few studies have evaluated the capacity of narrow - band imaging without magnification to detect esophageal squamous cell carcinoma .
watanabe et al .   found that narrow - band imaging was more likely 2 folds than conventional white - light evaluation to detect pharyngeal squamous cell carcinoma . in a multicenter study that compared narrow - band imaging with conventional white - light evaluation ,
when lugol 's staining chromoendoscopy was compared with narrow - band imaging with image magnification , the sensitivity was the same ( 92.3% ) , but narrow - band imaging had a higher specificity ( 91.7% versus 72.2% ) . in our study , we compared lugol 's staining with narrow - band imaging technology without magnification .
many medical centers do not have the resources for magnification ; therefore , the aim of this study was to determine whether narrow - band imaging alone would suffice to detect small and superficial neoplasias of the esophagus .
narrow - band imaging and lugol 's staining identified one esophageal neoplasia that was also detected by conventional white - light examination . both methods had 100% sensitivity and negative predictive value .
although narrow - band imaging without magnification had a higher specificity for detecting early squamous cell neoplasias in the esophagus , it was similar to lugol 's staining : 85.7% ( 75.1%96.3% ) and 81% ( 69.1%92.8% ) , respectively . in a study of patients with head and neck squamous cell carcinomas employing the same methodology , ide et al
. observed similar results when they compared narrow - band imaging without magnification with lugol 's staining .
takenaka et al . [ 33 , 34 ] found that the sensitivity of narrow - band imaging for detecting esophageal squamous cell carcinoma and high - grade intraepithelial neoplasia was 90.9% ( 58.7%99.8% ) , the specificity was 95.4% ( 90.398.3% ) , and the accuracy was 95.1% ( 90.1%98.0% ) .  
narrow - band imaging without magnification and lugol 's staining had equivalent performances ; this indicates that narrow - band imaging is a potential surveillance method for patients with esophageal achalasia .  
a sequential approach was adopted in which the standard endoscopy , narrow - band imaging , and the lugol 's staining were employed by the same operator in the same patient .
this setting might have affected the results since the operator possessed prior information after each phase of endoscopic procedure .
furthermore , this methodology was used in similar studies [ 31 , 33 , 34 ] . in conclusion ,
the results obtained with narrow - band imaging technology without magnification were comparable with those obtained with lugol 's staining for the screening of esophageal squamous cell carcinoma in patients with achalasia .
although narrow - band imaging does not have the risks and technical difficulties associated with lugol 's staining , larger multicenter studies are necessary in order to analyze the cost and benefits of this technology and to determine whether narrow - band imaging could replace lugol 's staining for screening of early - stage esophageal squamous cell carcinoma .
 chromoendoscopy with lugol 's staining remains the gold standard technique for detecting superficial scc . 
 an alternative technique , such as narrow - band imaging ( nbi ) , for  optical staining  would be desirable , since nbi is a simpler technique and has no known complications . in this study 
 , we compare nbi without magnification and chromoendoscopy with lugol 's staining for detecting high - grade dysplasia and intramucosal esophageal squamous cell carcinoma ( scc ) in patients with achalasia . this was a prospective observational study of 43 patients with achalasia referred to the gastrointestinal endoscopy unit of the hospital of clinics , so paulo , university medical school , brazil , from october 2006 to february 2007 . 
 conventional examinations with white light , nbi , and lugol staining were consecutively performed , and the suspected lesions were mapped , recorded , and sent for biopsy . 
 the results of the three methods were compared regarding sensitivity , specificity , accuracy , positive predictive value , negative predictive value , positive likelihood value , and negative likelihood value . 
 of the 43 patients , one was diagnosed with esophageal squamous cell carcinoma , and it was detected by all of the methods . 
 nbi technology without magnification has high sensitivity and negative predictive value for detecting superficial esophageal squamous cell carcinoma , and it has comparable results with those obtained with lugol 's staining . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion