Dear Editor,
We reviewed the article entitled: “Analysis of reflux as the
etiology of laryngeal dysplasia progression through a matched
case-control study ”.1 The authors did not find
differences in the level of pepsin, enterokinase and bilirubin in
laryngeal dysplasia (LD) of patients with malignant transformationversus those without transformation. The involvement of reflux in
the development of LD and laryngeal cancers is an important topic and
the realization of such a study is important. However, we wish to draw
attention to many points.
First, it is difficult to know if the included patients with tissue
pepsin really suffered from reflux. The detection of pepsin into the
tissue means that patients had some pharyngeal reflux events the day
before the surgery but cannot confirm the diagnosis. The sensitivity of
pepsin detection in laryngeal tissue depends on the technique and the
material (antibodies), reaching 75 to 85% depending on the type of
reflux (acid versus nonacid).2 Moreover, we
have no detailed information about the immunostaining technique,
limiting the reproducibility of the protocol. The presence of pepsin
into the tissue does not ensure the reflux diagnosis. Thus, for example,
it has been showed that the back flow of gastric content and the deposit
of pepsin into the tissue are influenced by the meals preceding the
sample collection, making the pepsin tissue a poorly reliable marker of
reflux.3 To improve the sensitivity,
authors1 could have performed
hypopharyngeal-esophageal pH-impedance monitoring, which is the only way
to confirm the diagnosis.4
Second, the LD malignant transformation involves many factors such as
tobacco history, environmental factors, genetic, or immune
response.5 The authors did not provide information
about the tobacco history (pack-year data) of groups, which is an
important data to consider the risk of malignant transformation. Even
many years after the tobacco cessation, it is conceivable that patients
with long/more severe history of tobacco consumption may have more cell
mucosa DNA impairments and a higher risk to develop cancer.
Third, the focus on pepsin as the only enzyme associated with malignant
transformation limits the understanding of transformation mechanisms.
More than 50% of patients had mixed or nonacid
reflux,4 in which the activity of pepsin is decreased
regarding the alkaline pH of refluxate. To reliably investigate the
involvement of reflux in the malignant transformation, authors have to
consider the entire content of refluxate, including bile salts and
trypsin.4 Furthermore, bile salts may be involved in
laryngopharyngeal malignant transformation.6
In future studies, reflux has to be diagnosed at the LD diagnosis time
and physicians have to follow the reflux clinical course over the time.
More than 50% of reflux patients had chronic course,4which leads to a potential higher risk to develop cell DNA damage and
lesions. Thus, cross-sectional study design is probably not adequate to
study a disease association involving chronic and repeated exposure.
Acknowledgments: No.