Reviewer's report
Title:Risk Factors for Second Primary Malignancy of Esophagus in Newly
Diagnosed Head and Neck Cancer Patients: A Case-Control Study
Version: 2Date:19 August 2013
Reviewer: Keisuke Hori
Reviewer's report:
Comments to the Author
Title: Risk Factors for Second Primary Malignancy of Esophagus in Newly
Diagnosed Head and Neck Cancer Patients: A Case-Control Study by
Chen-Shuan Ch, et al.
General comments
This prospective study examines possible risk factors for synchronous
esophageal neoplasia on patients of head and neck cancer, and diagnostic ability
of white light imaging (WLI), magnified endoscopy with narrow band imaging
(NBI-ME), and iodine dye endoscopy for esophageal neoplasia. The study is
overall well written, however, several issues should be answered.
Specific comments
Major
#1 Authors included LGIN in the esophagus as an event of second malignant
legions in esophagus. HGIN or SCC, or previously, high grade dysplasia or SCC
usually has been reported as an event for report of the synchronous and
metachronous multiple malignant legions in the esophagus and head and neck
legion [1-5]. LGIN is usually recognized as the risk of developing multiple
cancers, and it is not usually recognized as an event of second primary
malignancy. I think that additional risk analysis for developing HGIN or SCC is
necessary. But the analysis including multivariate analysis seems to be difficult
from the view of the sample size. Otherwise, authors need to reconsider the title
name including malignancy, and describe the reason why LGINs are included as
an event and difference with previous reports.
#2 Magnified endoscopy with narrow-band imaging (NBI-ME) has been reported
to be useful for detection of early-stage squamous cell cancer or HGIN of these
legions [2, 3, 6-8]. Both finding of brownish discoloration of mucosa and
abnormal epithelial capillary pattern has been reported to be useful for
differentiate HGIN or SCC from LGIN or non neoplastic legions. When iodine die
used after ME-NBI, many LGINs with NBI-ME negative thought to be detected.
Previous report for neoplastic regions including LGINs have not used iodine die
after ME-NBI, then high ratio of sensitivity was observed [9]. But in comparison
with iodine die, sensitivity of NBI-ME for neoplastic regions including LGINs
thought to be low if both finding of brownish discoloration of mucosa and
abnormal epithelial capillary pattern regarded as positive.
As for previous report of NBI-ME using iodine die for detecting legions including
LGINs and non neoplastic legions for reference, Takenaka et al. show that the
sensitivity for esophageal SCC and HGIN was 90.9%, specificity was 95.4%, and
accuracy was 95.1% in comparison with iodine die [2]. In the study of Ishihara et
al., sensitivity and specificity in diagnosing HGIN and SCC from brownish dots
and brownish epithelium visible on NBI were 85 and 79 %, respectively[7].
Authors need to describe the diagnostic criteria of NBI-ME more strictly with
adequate citation regarding esophageal neoplasm including LGIN. Mochizuki et
al. reported that 20/35 legions of LGIN had Brownish dots and 17/35 legions of
LGIN had Brownish epithelium[8] Have authors differentiated neoplasm including
LGIN from non neoplastic legions with both of the two findings or one or more of
the two findings of (1) brownish discoloration of mucosa, and (2) abnormal
epithelial capillary pattern as positive? If both of two findings positive regarded as
neoplasia including LGIN, difference with previous report must be described.
#3 Discussion for the discrepancy between the results of the univariate and
multivariate analyses for the association between location of head and neck
cancer and esophageal neoplasia is insufficient. Authors set the oral cavity as
reference of location of head and neck cancer. Therefore, the reason why
hypopharyngeal and laryngeal cancer have significant high odds ratio in
univariate analysis which were not significant risk factors in multivariate analysis
in comparison with cancer in the oral cavity need to be described. Table 1 and 2
seems to show that strong associations between hypopharyngeal, laryngeal
cancer and esophageal neoplasm in univariate analysis affected by alcohol
consumption which highly associated with both of hypopharyngeal, laryngeal and
esophageal cancer in multivariate analysis. Authors already have shown the
associations of risk factors for the esophageal neoplasm and alcoholic
metabolism. Citation of high prevalence of alcohol consumption and
hypopharryngeal and laryngeal cancer in comparison with oral cancer is needed.
This will explain the discrepancy between the results of the univariate and
multivariate analyses.
Minor
#1 Authors must show the reason why LGIN had to be resected. LGIN is usually
thought to have the risk of malignant transformation, but readers may think such
legions are not require immediate treatment and close follow up are adequate.
Some reasons, such as comparative higher risk of malignant transformation with
citation of previous report of mild to moderate dysplasia[10], or the possibility that
the lesions of diagnosed as LGIN under biopsy turn out to be HGIN after
resection, are needed.
#2 Diagnostic performances in Table 3 are difficult to understand and necessary
data are not included. Please show the data as follows; number of biopsied or
resected legions (total), number of diagnosed as neoplastic legions (total, WLI,
NBI-ME, LC), number of detected neoplastic legions (total, WLI, NBI-ME, LC),
and diagnostic performance of Sensitivity, Specificity, and Accuracy (WLI,
NBI-ME, LC).
1 Shimizu Y, Omori T, Yokoyama A, et al. Endoscopic diagnosis of early
squamous neoplasia of the esophagus with iodine staining: high-grade
intra-epithelial neoplasia turns pink within a few minutes. J Gastroenterol Hepatol
2008;23:546-50.
2 Takenaka R, Kawahara Y, Okada H, et al. Narrow-Band Imaging Provides
Reliable Screening for Esophageal Malignancy in Patients With Head and Neck
Cancers. The American journal of gastroenterology 2009;104:2942-48.
3 Muto M, Minashi K, Yano T, et al. Early detection of superficial squamous cell
carcinoma in the head and neck region and esophagus by narrow band imaging:
a multicenter randomized controlled trial. J Clin Oncol 2010;28:1566-72.
4 Hori K, Okada H, Kawahara Y, et al. Lugol-voiding lesions are an important risk
factor for a second primary squamous cell carcinoma in patients with
esosphageal cancer or head and neck cancer. The American journal of
gastroenterology 2011;106:858-66.
5 Wang WL, Lee CT, Lee YC, et al. Risk factors for developing synchronous
esophageal neoplasia in patients with head and neck cancer. Head & neck
2011;33:77-81.
6 Ishihara R, Takeuchi Y, Chatani R, et al. Prospective evaluation of
narrow-band imaging endoscopy for screening of esophageal squamous
mucosal high-grade neoplasia in experienced and less experienced
endoscopists. Dis Esophagus 2010;23:480-6.
7 Ishihara R, Inoue T, Uedo N, et al. Significance of each narrow-band imaging
finding in diagnosing squamous mucosal high-grade neoplasia of the esophagus.
J Gastroenterol Hepatol 2010;25:1410-5.
8 Mochizuki Y, Saito Y, Kobori A, et al. Magnified endoscopy combined with
narrow band imaging of minimal superficial esophageal neoplasia-indicators to
differentiate intraepithelial neoplasias. J Gastrointest Cancer 2012;43:599-606.
9 Lee CT, Chang CY, Lee YC, et al. Narrow-band imaging with magnifying
endoscopy for the screening of esophageal cancer in patients with primary head
and neck cancers. Endoscopy 2010;42:613-9.
10 Wang GQ, Abnet CC, Shen Q, et al. Histological precursors of oesophageal
squamous cell carcinoma: results from a 13 year prospective follow up study in a
high risk population. Gut 2005;54:187-92.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Risk Factors for Second Primary Malignancy of Esophagus in Newly
Diagnosed Head and Neck Cancer Patients: A Case-Control Study
Version: 2Date:19 August 2013
Reviewer: Keisuke Hori
Reviewer's report:
Comments to the Author
Title: Risk Factors for Second Primary Malignancy of Esophagus in Newly
Diagnosed Head and Neck Cancer Patients: A Case-Control Study by
Chen-Shuan Ch, et al.
General comments
This prospective study examines possible risk factors for synchronous
esophageal neoplasia on patients of head and neck cancer, and diagnostic ability
of white light imaging (WLI), magnified endoscopy with narrow band imaging
(NBI-ME), and iodine dye endoscopy for esophageal neoplasia. The study is
overall well written, however, several issues should be answered.
Specific comments
Major
#1 Authors included LGIN in the esophagus as an event of second malignant
legions in esophagus. HGIN or SCC, or previously, high grade dysplasia or SCC
usually has been reported as an event for report of the synchronous and
metachronous multiple malignant legions in the esophagus and head and neck
legion [1-5]. LGIN is usually recognized as the risk of developing multiple
cancers, and it is not usually recognized as an event of second primary
malignancy. I think that additional risk analysis for developing HGIN or SCC is
necessary. But the analysis including multivariate analysis seems to be difficult
from the view of the sample size. Otherwise, authors need to reconsider the title
name including malignancy, and describe the reason why LGINs are included as
an event and difference with previous reports.
#2 Magnified endoscopy with narrow-band imaging (NBI-ME) has been reported
to be useful for detection of early-stage squamous cell cancer or HGIN of these
legions [2, 3, 6-8]. Both finding of brownish discoloration of mucosa and
abnormal epithelial capillary pattern has been reported to be useful for
differentiate HGIN or SCC from LGIN or non neoplastic legions. When iodine die
used after ME-NBI, many LGINs with NBI-ME negative thought to be detected.
Previous report for neoplastic regions including LGINs have not used iodine die
after ME-NBI, then high ratio of sensitivity was observed [9]. But in comparison
with iodine die, sensitivity of NBI-ME for neoplastic regions including LGINs
thought to be low if both finding of brownish discoloration of mucosa and
abnormal epithelial capillary pattern regarded as positive.
As for previous report of NBI-ME using iodine die for detecting legions including
LGINs and non neoplastic legions for reference, Takenaka et al. show that the
sensitivity for esophageal SCC and HGIN was 90.9%, specificity was 95.4%, and
accuracy was 95.1% in comparison with iodine die [2]. In the study of Ishihara et
al., sensitivity and specificity in diagnosing HGIN and SCC from brownish dots
and brownish epithelium visible on NBI were 85 and 79 %, respectively[7].
Authors need to describe the diagnostic criteria of NBI-ME more strictly with
adequate citation regarding esophageal neoplasm including LGIN. Mochizuki et
al. reported that 20/35 legions of LGIN had Brownish dots and 17/35 legions of
LGIN had Brownish epithelium[8] Have authors differentiated neoplasm including
LGIN from non neoplastic legions with both of the two findings or one or more of
the two findings of (1) brownish discoloration of mucosa, and (2) abnormal
epithelial capillary pattern as positive? If both of two findings positive regarded as
neoplasia including LGIN, difference with previous report must be described.
#3 Discussion for the discrepancy between the results of the univariate and
multivariate analyses for the association between location of head and neck
cancer and esophageal neoplasia is insufficient. Authors set the oral cavity as
reference of location of head and neck cancer. Therefore, the reason why
hypopharyngeal and laryngeal cancer have significant high odds ratio in
univariate analysis which were not significant risk factors in multivariate analysis
in comparison with cancer in the oral cavity need to be described. Table 1 and 2
seems to show that strong associations between hypopharyngeal, laryngeal
cancer and esophageal neoplasm in univariate analysis affected by alcohol
consumption which highly associated with both of hypopharyngeal, laryngeal and
esophageal cancer in multivariate analysis. Authors already have shown the
associations of risk factors for the esophageal neoplasm and alcoholic
metabolism. Citation of high prevalence of alcohol consumption and
hypopharryngeal and laryngeal cancer in comparison with oral cancer is needed.
This will explain the discrepancy between the results of the univariate and
multivariate analyses.
Minor
#1 Authors must show the reason why LGIN had to be resected. LGIN is usually
thought to have the risk of malignant transformation, but readers may think such
legions are not require immediate treatment and close follow up are adequate.
Some reasons, such as comparative higher risk of malignant transformation with
citation of previous report of mild to moderate dysplasia[10], or the possibility that
the lesions of diagnosed as LGIN under biopsy turn out to be HGIN after
resection, are needed.
#2 Diagnostic performances in Table 3 are difficult to understand and necessary
data are not included. Please show the data as follows; number of biopsied or
resected legions (total), number of diagnosed as neoplastic legions (total, WLI,
NBI-ME, LC), number of detected neoplastic legions (total, WLI, NBI-ME, LC),
and diagnostic performance of Sensitivity, Specificity, and Accuracy (WLI,
NBI-ME, LC).
1 Shimizu Y, Omori T, Yokoyama A, et al. Endoscopic diagnosis of early
squamous neoplasia of the esophagus with iodine staining: high-grade
intra-epithelial neoplasia turns pink within a few minutes. J Gastroenterol Hepatol
2008;23:546-50.
2 Takenaka R, Kawahara Y, Okada H, et al. Narrow-Band Imaging Provides
Reliable Screening for Esophageal Malignancy in Patients With Head and Neck
Cancers. The American journal of gastroenterology 2009;104:2942-48.
3 Muto M, Minashi K, Yano T, et al. Early detection of superficial squamous cell
carcinoma in the head and neck region and esophagus by narrow band imaging:
a multicenter randomized controlled trial. J Clin Oncol 2010;28:1566-72.
4 Hori K, Okada H, Kawahara Y, et al. Lugol-voiding lesions are an important risk
factor for a second primary squamous cell carcinoma in patients with
esosphageal cancer or head and neck cancer. The American journal of
gastroenterology 2011;106:858-66.
5 Wang WL, Lee CT, Lee YC, et al. Risk factors for developing synchronous
esophageal neoplasia in patients with head and neck cancer. Head & neck
2011;33:77-81.
6 Ishihara R, Takeuchi Y, Chatani R, et al. Prospective evaluation of
narrow-band imaging endoscopy for screening of esophageal squamous
mucosal high-grade neoplasia in experienced and less experienced
endoscopists. Dis Esophagus 2010;23:480-6.
7 Ishihara R, Inoue T, Uedo N, et al. Significance of each narrow-band imaging
finding in diagnosing squamous mucosal high-grade neoplasia of the esophagus.
J Gastroenterol Hepatol 2010;25:1410-5.
8 Mochizuki Y, Saito Y, Kobori A, et al. Magnified endoscopy combined with
narrow band imaging of minimal superficial esophageal neoplasia-indicators to
differentiate intraepithelial neoplasias. J Gastrointest Cancer 2012;43:599-606.
9 Lee CT, Chang CY, Lee YC, et al. Narrow-band imaging with magnifying
endoscopy for the screening of esophageal cancer in patients with primary head
and neck cancers. Endoscopy 2010;42:613-9.
10 Wang GQ, Abnet CC, Shen Q, et al. Histological precursors of oesophageal
squamous cell carcinoma: results from a 13 year prospective follow up study in a
high risk population. Gut 2005;54:187-92.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Risk Factors for Second Primary Malignancy of Esophagus in Newly
Diagnosed Head and Neck Cancer Patients: A Case-Control Study
Version: 2Date:19 August 2013
Reviewer: Keisuke Hori
Reviewer's report:
Comments to the Author
Title: Risk Factors for Second Primary Malignancy of Esophagus in Newly
Diagnosed Head and Neck Cancer Patients: A Case-Control Study by
Chen-Shuan Ch, et al.
General comments
This prospective study examines possible risk factors for synchronous
esophageal neoplasia on patients of head and neck cancer, and diagnostic ability
of white light imaging (WLI), magnified endoscopy with narrow band imaging
(NBI-ME), and iodine dye endoscopy for esophageal neoplasia. The study is
overall well written, however, several issues should be answered.
Specific comments
Major
#1 Authors included LGIN in the esophagus as an event of second malignant
legions in esophagus. HGIN or SCC, or previously, high grade dysplasia or SCC
usually has been reported as an event for report of the synchronous and
metachronous multiple malignant legions in the esophagus and head and neck
legion [1-5]. LGIN is usually recognized as the risk of developing multiple
cancers, and it is not usually recognized as an event of second primary
malignancy. I think that additional risk analysis for developing HGIN or SCC is
necessary. But the analysis including multivariate analysis seems to be difficult
from the view of the sample size. Otherwise, authors need to reconsider the title
name including malignancy, and describe the reason why LGINs are included as
an event and difference with previous reports.
#2 Magnified endoscopy with narrow-band imaging (NBI-ME) has been reported
to be useful for detection of early-stage squamous cell cancer or HGIN of these
legions [2, 3, 6-8]. Both finding of brownish discoloration of mucosa and
abnormal epithelial capillary pattern has been reported to be useful for
differentiate HGIN or SCC from LGIN or non neoplastic legions. When iodine die
used after ME-NBI, many LGINs with NBI-ME negative thought to be detected.
Previous report for neoplastic regions including LGINs have not used iodine die
after ME-NBI, then high ratio of sensitivity was observed [9]. But in comparison
with iodine die, sensitivity of NBI-ME for neoplastic regions including LGINs
thought to be low if both finding of brownish discoloration of mucosa and
abnormal epithelial capillary pattern regarded as positive.
As for previous report of NBI-ME using iodine die for detecting legions including
LGINs and non neoplastic legions for reference, Takenaka et al. show that the
sensitivity for esophageal SCC and HGIN was 90.9%, specificity was 95.4%, and
accuracy was 95.1% in comparison with iodine die [2]. In the study of Ishihara et
al., sensitivity and specificity in diagnosing HGIN and SCC from brownish dots
and brownish epithelium visible on NBI were 85 and 79 %, respectively[7].
Authors need to describe the diagnostic criteria of NBI-ME more strictly with
adequate citation regarding esophageal neoplasm including LGIN. Mochizuki et
al. reported that 20/35 legions of LGIN had Brownish dots and 17/35 legions of
LGIN had Brownish epithelium[8] Have authors differentiated neoplasm including
LGIN from non neoplastic legions with both of the two findings or one or more of
the two findings of (1) brownish discoloration of mucosa, and (2) abnormal
epithelial capillary pattern as positive? If both of two findings positive regarded as
neoplasia including LGIN, difference with previous report must be described.
#3 Discussion for the discrepancy between the results of the univariate and
multivariate analyses for the association between location of head and neck
cancer and esophageal neoplasia is insufficient. Authors set the oral cavity as
reference of location of head and neck cancer. Therefore, the reason why
hypopharyngeal and laryngeal cancer have significant high odds ratio in
univariate analysis which were not significant risk factors in multivariate analysis
in comparison with cancer in the oral cavity need to be described. Table 1 and 2
seems to show that strong associations between hypopharyngeal, laryngeal
cancer and esophageal neoplasm in univariate analysis affected by alcohol
consumption which highly associated with both of hypopharyngeal, laryngeal and
esophageal cancer in multivariate analysis. Authors already have shown the
associations of risk factors for the esophageal neoplasm and alcoholic
metabolism. Citation of high prevalence of alcohol consumption and
hypopharryngeal and laryngeal cancer in comparison with oral cancer is needed.
This will explain the discrepancy between the results of the univariate and
multivariate analyses.
Minor
#1 Authors must show the reason why LGIN had to be resected. LGIN is usually
thought to have the risk of malignant transformation, but readers may think such
legions are not require immediate treatment and close follow up are adequate.
Some reasons, such as comparative higher risk of malignant transformation with
citation of previous report of mild to moderate dysplasia[10], or the possibility that
the lesions of diagnosed as LGIN under biopsy turn out to be HGIN after
resection, are needed.
#2 Diagnostic performances in Table 3 are difficult to understand and necessary
data are not included. Please show the data as follows; number of biopsied or
resected legions (total), number of diagnosed as neoplastic legions (total, WLI,
NBI-ME, LC), number of detected neoplastic legions (total, WLI, NBI-ME, LC),
and diagnostic performance of Sensitivity, Specificity, and Accuracy (WLI,
NBI-ME, LC).
1 Shimizu Y, Omori T, Yokoyama A, et al. Endoscopic diagnosis of early
squamous neoplasia of the esophagus with iodine staining: high-grade
intra-epithelial neoplasia turns pink within a few minutes. J Gastroenterol Hepatol
2008;23:546-50.
2 Takenaka R, Kawahara Y, Okada H, et al. Narrow-Band Imaging Provides
Reliable Screening for Esophageal Malignancy in Patients With Head and Neck
Cancers. The American journal of gastroenterology 2009;104:2942-48.
3 Muto M, Minashi K, Yano T, et al. Early detection of superficial squamous cell
carcinoma in the head and neck region and esophagus by narrow band imaging:
a multicenter randomized controlled trial. J Clin Oncol 2010;28:1566-72.
4 Hori K, Okada H, Kawahara Y, et al. Lugol-voiding lesions are an important risk
factor for a second primary squamous cell carcinoma in patients with
esosphageal cancer or head and neck cancer. The American journal of
gastroenterology 2011;106:858-66.
5 Wang WL, Lee CT, Lee YC, et al. Risk factors for developing synchronous
esophageal neoplasia in patients with head and neck cancer. Head & neck
2011;33:77-81.
6 Ishihara R, Takeuchi Y, Chatani R, et al. Prospective evaluation of
narrow-band imaging endoscopy for screening of esophageal squamous
mucosal high-grade neoplasia in experienced and less experienced
endoscopists. Dis Esophagus 2010;23:480-6.
7 Ishihara R, Inoue T, Uedo N, et al. Significance of each narrow-band imaging
finding in diagnosing squamous mucosal high-grade neoplasia of the esophagus.
J Gastroenterol Hepatol 2010;25:1410-5.
8 Mochizuki Y, Saito Y, Kobori A, et al. Magnified endoscopy combined with
narrow band imaging of minimal superficial esophageal neoplasia-indicators to
differentiate intraepithelial neoplasias. J Gastrointest Cancer 2012;43:599-606.
9 Lee CT, Chang CY, Lee YC, et al. Narrow-band imaging with magnifying
endoscopy for the screening of esophageal cancer in patients with primary head
and neck cancers. Endoscopy 2010;42:613-9.
10 Wang GQ, Abnet CC, Shen Q, et al. Histological precursors of oesophageal
squamous cell carcinoma: results from a 13 year prospective follow up study in a
high risk population. Gut 2005;54:187-92.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests.
assistant