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DOI 10.1007/s10147-017-1201-3
ORIGINAL ARTICLE
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Vol.:(0123456789)
Int J Clin Oncol
incidence of advanced ESCN may be lower and the present consumption was estimated as the average number of grams
overall survival rate may have improved from those of past of pure ethanol ingested per drinking day. Smoking was cal-
reports. culated according to the Brinkman index (the number of
The objective of this study was to investigate the preva- cigarettes smoked per day multiplied by the number of total
lence of ESCN and the impact on the overall survival rate of smoking years). The primary tumor was grouped by location
HNC patients in recent years. We retrospectively examined (oral cavity, epipharynx, oropharynx, hypopharynx, larynx).
such questions using the medical data of the HNC patients Tumor stage was classified according to TNM classification
who had undergone EGDS at our institute. of the Union for International Cancer Control, 6th edition
[15].
Patients and methods
Statistical analysis
Patients
Continuous variables were described by medians and ranges;
categorical variables were described by counts and percent-
We retrospectively reviewed the medical records of HCN
ages. All patient data were compared based on whether
patients who had undergone EGDS at our institute between
patients had ESCN. Continuous variables were compared
October 2005 and September 2012. Patients were selected
using the Wilcoxon rank-sum test. Categorical variables
for this study according to the following criteria:
were compared with the chi-square test when appropriate;
otherwise, a Fisher’s exact test was used. Cumulative inci-
i. At the time of an HCN diagnosis, patients underwent
dences of overall survival of HNC patients, with or without
staging workups, including oral cavity inspection,
ESCN, were calculated by the Kaplan–Meier method, with
endoscopic examination of the pharynx and larynx,
the date of the first EGDS at our institute as the starting
computed tomography (CT) and/or magnetic reso-
point, and differences were assessed with the log-rank test.
nance imaging of the head and neck, and whole-body
The prognostic factors that were shown to be significant in
fluorodeoxyglucose–positron emission tomography.
a univariate Cox regression analysis were also tested with a
ii. For those patients with HCN who underwent EGDS,
multivariate Cox regression analysis. We used the analysis
EGDS were performed with an upper gastrointestinal
to examine hazard ratio (HR) of the HNC patients, with the
high-resolution magnifying endoscope (GIF-Q240Z,
95% confidence interval (CI). We conducted all statistical
GIF-H260Z; Olympus Medical Systems, Tokyo,
analyses using SPSS version 20 (SPSS, Chicago, IL, USA).
Japan).
All statistical tests were two tailed, and significance was
iii. After treatment for HCN, CT and EGDS were per-
defined as p < 0.05. This study was approved by the institu-
formed annually to check for the recurrence of disease
tional review board of Mie University Hospital.
and to survey for ESCN.
We analyzed the prevalence of ESCN in HNC patients, its Baseline characteristics of patients with HNC
association with patient baseline characteristics (sex, age,
toxic habits such as smoking and alcohol drinking, loca- During the study period, a total of 226 patients fulfilled
tion of HNC, staging of HNC, location of second primary the eligibility criteria for this study (Table 1). Of the 226
malignancies, initial treatment for HNC), the difference in patients, 194 (85.8%) were male; the median age was 68
therapeutic outcomes of HNC patients with and without years (range, 33–89 years). The median amount of daily
ESCN, and the prognostic value of the presence of ESCN alcohol intake was 22 g (range, 0–220 g) and the median
in HNC patients. Brinkman index was 606 (range, 0–2560). Considering
The data of HNC patients with ESCN were divided into the location of the HNC, 40 lesions (17.7%) were found
two groups, depending on whether patients had synchronous in the oral cavity, 12 lesions (5.3%) in the epipharynx, 42
or metachronous ESCN. Synchronous ESCN was defined lesions (18.6%) in the oropharynx, 74 lesions (32.7%) in the
as developing at the same time, or within 6 months before hypopharynx, and 58 lesions (25.7%) in the larynx. Sixty-
and after a diagnosis of HNC. For development before and seven patients (29.6%) had localized disease (stage I, II),
after 6 months, the ESCN was considered metachronous. In and 159 patients (70.4%) had locally advanced or metastatic
cases of HNC with multiple ESCNs, the ESCN stage was disease (stage III, IV). Twenty-three patients (10.2%) had
defined according to the most advanced lesion. Alcohol second primary malignancies other than ESCN (gastric
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Int J Clin Oncol
Table 1 Patient background and comparison between those with and without ESCN
Characteristics Total (n = 226) Without ESCN (n = 192) With ESCN (n = 34) p*
ESCN esophageal squamous cell neoplasia, HNC head and neck cancer
* Chi-square or Fisher’s exact tests were used for sex, site of primary tumor, clinical stage, second primary tumor except ESCN, and initial treat-
ment for HNC; Wilcoxon rank-sum tests were used for age, alcohol intake, and Brinkman index
a
Amount of alcohol intake converted to ethanol value
cancer, lung cancer, colon cancer, hepatocellular carcinoma, treatment for HNC was significantly lower in patients with
and prostate cancer). ESCN (14.7% vs. 35.0%, p = 0.030).
For HNC treatment, radiotherapy fields included the
lesion; the daily fractional radiation dose was 2 gray (Gy), Characteristics of ESCN lesions
administered 5 days per week, for all patients. The standard
total radiation dose for HNC was 70 Gy. Chemotherapy for The characteristics of ESCN lesions are shown in Table 2.
HNC consisted of cisplatin only, 5-fluorouracil plus cispl- Thirty-eight ESCNs were detected in 34 patients: 30 patients
atin, or S-1 only. One hundred and four patients (46.0%) had 1 lesion, and 4 patients had 2 lesions each. Thirty-three
had undergone chemoradiation therapy as initial treatment synchronous and 5 metachronous ESCNs were diagnosed in
for HNC. this study. Of the 38 ESCN lesions, 31 (81.6%) were early
ESCN (stage 0, I). These results demonstrated that ESCNs
were likely to be an earlier-stage neoplasia than HNC.
Comparison with characteristics of HNC patients
with or without ESCN Treatment characteristics for patients with ESCN
There were 192 patients with HNC without ESCN (85.0%) Treatments for HNC patients with ESCN are shown in
and 34 patients with HNC and with ESCN (15.0%) (Table 1). Table 3. Of 34 patients with ESCN, 10 patients (29.4%)
Comparing the characteristics of HNC patients, the amount underwent endoscopic resection for ESCN and 10 patients
of alcohol intake (44 vs. 20 g, p = 0.007) and location of (29.4%) underwent simultaneous chemoradiation therapy.
cancer in the hypopharynx (55.9% vs. 28.6%, p = 0.003) Radiotherapy fields for ESCN included the lesion. The daily
were significantly greater in patients with ESCN compared fractional radiation dose was 2 Gy, administered 5 days per
to those without ESCN. On the other hand, use of surgical week to all patients. The standard total radiation dose for
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Int J Clin Oncol
Table 2 Characteristics of esophageal squamous cell neoplasia The median follow-up period was 29.8 months (range,
(ESCN) 0–98.0 months). During the follow-up period, 17 (50.0%) of
No. of ESCN (%) HNC patients with ESCN and 57 (29.7%) of HNC patients
without ESCN died. Figure 1 shows the overall survival
Single/double
curves of HNC patients without or with ESCN. The median
Single 30 (78.9)
survival period for HNC patients without ESCN was not
Double 8 (21.1)
reached; that for those with ESCN was 45 months. The
Synchronous/metachronous
3-year survival rates for HNC patients with or without
Synchronous 33 (86.8)
ESCN were 53% and 70%, respectively. Kaplan–Meier curve
Methacronous 5 (13.2)
analysis using a log-rank test showed that the presence of
Clinical stage of ESCN (UICC 6th)
ESCN (p = 0.029) was associated with a greater probability
Stage 0 11 (29.0)
of a shorter overall survival period.
Stage I 20 (52.6)
We conducted univariate and multivariate analyses using
Stage II 5 (13.2)
a Cox regression analysis with a time-dependent covariate
Stage III 1 (2.6)
(Table 4). This analysis also identified a more advanced
Stage IV 1 (2.6)
clinical stage (HR = 2.15; 95% CI = 1.18–3.93; p = 0.012)
ESCN esophageal squamous cell neoplasia, UICC Union for Interna- and the presence of ESCN (HR = 1.73; 95% CI = 1.00–2.97;
tional Cancer Control p = 0.049) as significant and independent determinants of
the overall survival period.
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radiation field of the lung and the adverse effects, resulting for an endoscopic screening protocol. Ann Otol Rhinol Laryngol
in a reduced survival rate [24, 25]. In our series, the major- 101:105–112
8. Muto M, Hironaka S, Nakane M et al (2002) Association of mul-
ity of HNC patients with synchronous ESCN underwent tiple Lugol-voiding lesions with synchronous and metachronous
simultaneous chemoradiation therapy. Of the HNC patients esophageal squamous cell carcinoma in patients with head and
with synchronous ESCN, a definite CRT-related death was neck cancer. Gastrointest Endosc 56:517–521
observed in a patient with radiation pneumonitis; moreover, 9. Su YY, Chen WC, Chuang HC et al (2013) Effect of routine
esophageal screening in patients with head and neck cancer.
the late complications of CRT were hidden as HNC-related JAMA Otolaryngol Head Neck Surg 139:350–354
deaths. In fact, ESCN patients who received simultaneous 10. Wang WL, Lee CT, Lee YC et al (2011) Risk factors for develop-
CRT tended to show a shorter overall survival period after ing synchronous esophageal neoplasia in patients with head and
analysis using a log-rank test in our study (p = 0.10; data neck cancer. Head Neck 33:77–81
11. Hung SH, Tsai MC, Liu TC et al (2013) Routine endoscopy for
not shown). esophageal cancer is suggestive for patients with oral, oropharyn-
The present study had several limitations. First, patients geal and hypopharyngeal cancer. PLoS One 8:e72097
were enrolled in a single center. The findings reported here 12. Chen MC, Huang WC, Chan CH et al (2010) Impact of second
should be confirmed in a multicenter study. A second limita- primary esophageal or lung cancer on survival of patients with
head and neck cancer. Oral Oncol 46:249–254
tion was that the study design was retrospective: we relied 13. León X, Quer M, Diez S et al (1999) Second neoplasm in patients
on medical records for patient data. Furthermore, the choice with head and neck cancer. Head Neck 21:204–210
of treatment regimen depended on the managing physicians. 14. Chu PY, Chang SY, Huang JL et al (2010) Different patterns of
The foregoing factors would have contributed to biases in second primary malignancy in patients with squamous cell carci-
noma of larynx and hypopharynx. Am J Otolaryngol 31:168–174
the present study. 15. Sobin LH, Wittekind C (2002) TNM classification of malignant
In conclusion, ESCN is associated with a high incidence tumours, 6th edn. Wiley, Hoboken
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Conflict of interest The authors declare that they have no conflict neck cancer. Gut Liver 9:159–165
of interest. 19. Cooper JS, Porter K, Mallin K et al (2009) National Cancer Data-
base report on cancer of the head and neck: 10-year update. Head
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