{'fraction_non_alphanumeric': 0.033011681056373796, 'fraction_numerical': 0.03339258506856272, 'mean_word_length': 4.999238385376999, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Effectiveness of screening endoscopy for esophageal squamous cell carcinoma in Japanese males

Abstract Background Esophageal squamous cell carcinoma (ESCC) has a poor prognosis; therefore, early detection is essential. In Japan, more than 90% of esophageal cancers are ESCC. Endoscopy is effective to detect ESCC in the early stage, but there is a limited number of reports examining its efficacy and effectiveness. Objective This study aimed to evaluate the efficacy of screening endoscopy for detecting ESCC. Methods This retrospective study analyzed the prevalence of ESCC, annual transition of prevalence, and the stage of each ESCC among 128,520 medical check‐up patients who underwent esophagogastroduodenoscopy from April 2015 to March 2020 at Yamanashi Koseiren Health Care Center. Furthermore, a case‐control study utilized the multivariate logistic regression analysis was performed to assess the risk factor of ESCC. Results Among a total of 128,520 subjects, 42 ESCC patients were detected, with 95.2% being diagnosed at early stages. Annual prevalence in males was 0.015% (2/13,122) in 2015, 0.044% (6/13,562) in 2016, 0.044% (6/13,676) in 2017, 0.074% (10/13,488) in 2018%, and 0.11% (16/14,386) in 2019. ESCC prevalence has been increasing each year. A significant increase was observed between 2015 and 2018 (p = 0.039). ESCC prevalence was 0.102% (25/24,272) when focusing on males aged over 50 years with a history of smoking and drinking. Regarding the case‐control study, the multivariate logistic regression analysis revealed smoking (p = 0.044), mean corpuscular volume (MCV) (p = 0.0018), and severe gastric atrophy (p = 0.048) as positively correlated with ESCC. Conclusion In conclusion, ESCC has been increasing in our center from 2015 to 2019, and the prevalence has been approaching that of gastric cancer in 2019 in male subjects. ESCC can be detected efficiently by targeting males with high MCV who have a history of drinking and smoking.


INTRODUCTION
Esophageal carcinoma (EC) is the seventh most common cancer worldwide, with more than 570,000 cases diagnosed annually. Also, it ranks as the sixth most aggressive cancer, with mortality exceeding 500,000 deaths worldwide. 1 There are two major types of EC: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). In Western countries, the incidence of EA has been increasing, whereas that of ESCC has been decreasing. 2 However, in Japan, according to the graph of national estimates of age-adjusted morbidity of esophageal cancer, the age-adjusted morbidity of esophageal cancer is gradually increasing, especially for men. More than 90% of esophageal cancer in Japan is ESCC. The Japanese National Cancer Center has recently demonstrated that 9571 males and 2048 females (11,619 in total) died of ESCC in 2019 and that the 5 year survival rate was 41.5% (male 40.6%, female 45.9%) among newly diagnosed cases from 2009 to 2011. 3 The poor prognosis of ESCC is attributed to late detection of most lesions, that is, in their advanced stages; therefore, early detection is essential to treat and cure ESCC.
Thus, we examined the annual changes in ESCC prevalence at our health care center by age group and evaluated the efficacy and effectiveness of screening endoscopy for detecting early esophageal cancer. Then, we conducted a multivariate logistic regression analysis to assess the following risk factors: male sex, alcohol consumption, cigarette smoking, MCV, body mass index (BMI), and gastric atrophy.

MATERIALS AND METHODS
This retrospective study included medical check-up patients aged over 50 who underwent esophagogastroduodenoscopy (EGD) from April 2015 to March 2020 at Yamanashi Koseiren Health Care Center to analyze ESCC prevalence, annual prevalence transition, and the stage of each ESCC. Screening endoscopy was intended for the early detection of gastric cancer. All cases were only among health checkup protocol and they did not have symptoms that required EGD diagnosis.
The endoscopes used were OLYMPUS ® GIF-Q260, GIF-H290, GIF-XP260N, GIF-XP290N, or FUJIFILM ® EG-L580NW7. We used white light and Narrow Band Imaging for the OLYMPUS ® endoscope and white light and Blue Laser Imaging for the FUJIFILM ® endoscope.
We did not use lugol staining systematically; it was only used when we suspected cancer. EC prevalence was analyzed by age group and year. Additionally, we performed a case-control study to investigate risk factors, specifically alcohol drinking, cigarette smoking, MCV, and gastric atrophy. We defined habitual alcohol drinking as the consumption of >20 g of pure alcohol per day. Gastric atrophy was measured by endoscopy using Kimura-Takemoto classification: atrophy was defined as C-II, C-III, or Open type, while severe atrophy was defined as O-II, III. The degree of atrophic gastritis is classified using the Kimura-Takemoto classification based on endoscopic findings and is based on the grading of the atrophic boundary extending from the gastric angle to the gastric body. 4 With regard to the case-control study, the controls were those who underwent the medical check-up in our center from 2015 to 2019 and had no localized lesions in the upper gastrointestinal tract that matched gender and age. There were no patients and control people who were suffering from liver cirrhosis. We conducted univariate and multivariate logistic regression analyses. Statistical analysis was performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing). More precisely, it is a modified version of R commander designed to add statistical functions frequently used in biostatistics. 5  � Endoscopy is effective to detect ESCC in the early stage, but there is a limited number of reports examining its efficacy and effectiveness.      investigating lesions discovered, including ESCC. Therefore, it is possible that the learning curve could be influenced by these conferences and be involved in finding lesions.
Most of the subjects were men with a history of alcohol drinking or cigarette smoking, both of which are the two major risk factors for ESCC. 9 When focused on males aged over 50 years with a history of In this study, we targeted a group of people who underwent medical examination with high smoking and drinking rates, and in such a group, atrophic gastritis can be promoted, and the risk of ESCC is also increased. 16 Atrophic gastritis is a condition in which the mucous membrane of the stomach is chronically inflamed, inducing the loss of parietal cells. Most atrophic gastritis is caused by H.pylori infection in Japan, 17 and parietal cell destruction in atrophic gastritis leads to gastric hyposecretion. Particularly, profound hypochlorhydria is a cause of non-cardiac gastric cancer, 18 which causes bacterial overgrowth in the stomach, resulting in the formation of carcinogens, such as nitrosamines 19,20 and acetaldehyde. 21,22 These carcinogens also form DNA adducts. 20,23 Therefore, it is highly probable that carcinogens and DNA adducts produced in the stomach reach the esophagus through reflux and venous plexus, which further induces the formation of ESCC.
In conclusion, ESCC has been increasing, and its prevalence has been approaching that of GC in 2019 in male subjects. Therefore, screening endoscopy should be considered to be an effective measure for early detection of ESCC. Hence, ESCC can be detected efficiently by targeting males with high MCV who have a history of drinking and smoking.
for the English language review.

CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.

DATA AVAILABILITY STATEMENT
The dataset generated during the current study are not publicly available but are available from the corresponding author on reasonable request.