Introduction

Esophageal cancer is known to be a strongly male dominant disease. However, the gender differences have not been well understood. We aimed to evaluate the differences between male and female esophageal cancer in Korean population.

Aims & Methods

We retrospectively analyzed patients confirmed as esophageal cancer in Asan Medical Center between January 2005 and December 2015. The clinical features of patients, histopathologic characteristics of tumor, treatment response, and survival were investigated between male and female patients respectively.

Results

A total of 2,068 patients were analyzed. The median age was younger in female (62 years; interquartile range [IQR] 38-85) than male (64 years, IQR 37–90), and the male to female ratio was 13.4:1. Squamous cell carcinoma was major pathologic type (99.0% in male and 93.1% in female), however, the proportion of adenocarcinoma was higher in female than male (5.6% vs. 0.8%, p<0.001). Female patients smoked less (22.2% vs. 86.5%, p<0.001) and drank less alcohol (26.4% vs 89.9%, p<0.001) than male patients. Female had upper and middle esophagus dominant tumor location (75.0%), whereas middle and lower dominant in male (81.7%). Multivariate analysis showed that gender (Hazard ratio [HR], 0.77; 95% CI, 0.60 to 0.99; p=0.044), age (HR, 1.03; 95% CI, 1.02 to 1.03; p<0.001), and advanced tumor stage (stage 4, HR, 14.3; 95% CI, 8.43 to 24.4; p<0.001) were independent prognostic factors for overall survival. The 5-year overall survival rate of female was higher than those of male (53.5% vs. 44.5%, p=0.038). Cancer recurrence rate in complete remission patients were significantly lower in female than male (15.3% vs. 25.1%, p=0.03).

Conclusion

The gender is an independent prognostic factor for esophageal cancer, with favorable survival outcomes in female than male. Further research is warranted to determine the cause of prognostic difference in esophageal cancer in male and female.

Disclosure

There is no conflict of interest.

Introduction

When esophageal cancer is diagnosed at an advanced stage, it requires a highly invasive treatment, and its prognosis is poor. Although the number of endoscopic examinations has been increasing globally, esophageal cancer is still difficult to diagnose at an early stage. The rapidly increasing number of endoscopic examinations performed over a short period might influence diagnostic performance. Accessing the association between calendar month and esophageal cancer detection rates might improve policy and guide institutional support.

Aims & Methods

We aimed to evaluate the association between the increased number of examinations over a certain period and esophageal cancer detection rates (EDR) among a large population in the Korean National Cancer Screening Program (KNCSP). We performed a retrospective population-based study using the KNCSP database for gastric cancer between 2015 and 2019. We included 28,032,590 Koreans aged ≥40 years. We assessed monthly EDR and performed a negative binomial regression model and least square mean evaluation to evaluate the association between the screening month and EDR.

Results

In total, 28,032,590 subjects underwent upper endoscopy, according to KNCSP. The monthly number of subjects who underwent examinations was the highest in December (n=4,819,606, 17.2%). EDR tended to decrease towards the end of the year, and EDR was the lowest in December 2015 – 2019 (0.06 – 0.08). In the multivariable logistic model, the association of calendar month with detected cancer remained after adjusting for other confounding factors (December 2015: odds ratio, 0.58; 95% CI, 0.43 – 0.79; P < .001; 2016: odds ratio, 0.51; 95%CI, 0.38 – 0.67; P < .001). The age group adjusted the calendar month, and the predicted detection rate significantly decreased at the end of the year compared with the beginning of the year in 2015, 2016, and 2017 respectively.

Conclusion

In the KNCSP, the workload of endoscopists increased excessively, with an increasing number of examinations towards the end of the year, as demonstrated by decreased EDR during this period.

Clinical Case Summary

A 65-year old man visited our hospital for abdominal pain. Esophagogastroduodenoscopy showed an area of fainted redness in the right upper thoracic esophagus. Narrow band imaging (NBI) detected a demarcated area with brownish dots. Intrapapillary capillary loops (IPCL) implied that the carcinoma had not invaded the deep submucosa. The entire lesion showed no stains by 1% Lugol’s iodine solution. Therefore, endoscopic submucosal dissection (ESD) was conducted under general anesthesia with endotracheal intubation. Labeling, submucosal injection, mucosal incision were performed according to surgical protocols. During dissection, however, a depression was observed in the left of the cancer lesion. Submucosal and muscular defects appeared in the depression edge, which indicated a shallow pulsion diverticulum under the lesion. We proceeded cautiously the dissection to separate the submucosa from the adventitia. ESD was successfully completed without perforation. To prevent postoperative perforation, we placed a covered esophageal stent. Post-ESD CT showed mild mediastinal emphysema. No other adverse events were observed and the patient was discharged at five days after ESD. The esophageal stent was removed at one month after ESD without perforation, stenosis or bleeding. Histopathological examination showed a well-differentiated squamous cell carcinoma within the mucosa without lympho-vascular invasion, suggesting a low risk of recurrence without additional treatment. Esophageal cancer that involves diverticula is extremely rare. The thin wall of diverticulum is easily to be perforated, bringing a great challenge to endoscopic resection. The location of an esophageal diverticulum in the cancer lesion is critical to its outcome.In conclusion, we reported a rare case of a superficial esophageal cancer with an esophageal diverticulum, which was invisible before the ESD. The cancer was successfully removed by ESD with no perforation.

References

1. Watanabe S, Matsuda, K. Arima K, et.al. Detection of subclinical disorders of the hypopharynx and larynx by gastrointestinal endoscopy. Endoscopy. 1996; 28(3): 295-298.
2. Herbella, Fernando A M et al. Are idiopathic and Chagasic achalasia two different diseases? Digestive diseases and sciences vol. 49,3 (2004): 353-60.
3. Shinwa, T, Takashi T, Yoshiko O, et al. Esophageal diverticulum exposed during endoscopic submucosal dissection of superficial cancer. World J Gastroenterol. 2015 March 14;21(10):3121-3126.

Disclosure

All authors declare that there is no conflict of interest.

Introduction

Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer in eastern Asia and Africa. Diagnosis at early stage is crucial to reduce the mortality of ESCC. Currently, esophagogastroduodenoscopy (EGD) is the golden standard for screening ESCC, however, the patient compliance rate has been low due to the invasiveness and high cost of EGD. Thus, there is an unmet need for the development of diagnostic modality that enables non-invasive early detection of ESCC.

Aims & Methods

The purpose of this study is to construct a urinary exosomal miRNA panel as a least invasive test that can detect ESCC with high accuracy and validate its performance in a prospective cohort enriched with early ESCC. We prospectively collected urine samples from 161 ESCC patients and 180 healthy controls (HC) at five institutions from September 2019 to March 2023. Exosomes were extracted from urine specimens by polymer precipitation method, and exosomal miRNAs were subjected for comprehensive expression analysis by small RNA seq. Of the 341 total samples, 309 samples (90.6%) that passed the QC check were selected for subsequent data-analysis. In the training cohort (100 samples of ESCC and 98 samples of HC), we measured the expression of 328 miRNAs to identify candidate biomarker miRNAs. A miRNA diagnostic panel was constructed using machine learning analysis, and diagnostic performance was evaluated using a 5-fold cross-validation method. In the validation cohort (50 samples of ESCC and 61 samples of HC), the diagnostic performance of the urinary miRNA diagnostic panel was verified with blind to clinical information.

Results

In the RNAseq analysis of the training cohort (ESCC; mean age 68.2 years, 77.9% male; HC; mean age 58.1 years, 76.3% male), 33 out of 328 miRNAs were differentially expressed between ESCC and HC. Out of the 33 dysregulated miRNAs, 21 were upregulated and 12 were down-regulated. A multi-miRNA biomarker panel composed of miRNAs that were individually significant and non-significant between ESCC and HC had a diagnostic performance of AUC 0.89 (95% CI 0.84 to 0.94) by 5-fold cross-validation. In the validation cohort (ESCC; mean age 63.0 years, 78.0% male, median size 32mm, Stage I/II/III/IV 54/10/26/10%, HC; mean age 51.0 years, 52.5% male), The diagnostic performance of the miRNA diagnostic panel was AUC 0.85(95% CI 0.80 to 0.90), with a sensitivity of 84%, specificity of 73.8%, and accuracy of 78.4% at a pre-defined cutoff value. There was no confounding of diagnostic performance by age, gender, BMI, history of alcohol consumption or smoking. The sensitivity by clinical stage of ESCC was 88.9/80.0/77.8/80% for Stage I/II/III/IV.

Conclusion

We developed and validated a urinary exosomal miRNA diagnostic panel, which may be a new non-invasive diagnostic method that contributes to the early detection of ESCC.

Disclosure

Tomonori Yano received research funding from Craif Inc.

Introduction

Esophageal cancer (EC) exhibits a disproportionate burden in low- and middle-income regions. Magnesium, a critical regulator of metabolic and inflammatory pathways, has been implicated in chronic diseases such as diabetes and cardiovascular disorders. Preclinical studies suggest that magnesium deficiency promotes oxidative stress and systemic inflammation, processes central to cancer progression. However, evidence directly linking magnesium metabolism disorders with esophageal cancer risk remains limited. The Magnesium Depletion Score (MDS), a validated tool integrating diuretic use, proton pump inhibitors, renal dysfunction, and heavy alcohol consumption, offers a novel approach to evaluate magnesium status. The study aims to elucidate the potential mechanisms by which magnesium metabolism may influence the development of esophageal cancer and to provide a scientific basis for future preventive and intervention strategies.

Aims & Methods

This prospective cohort study included 450,700 UK Biobank participants. The Magnesium Depletion Score (MDS) incorporated diuretic use, proton pump inhibitors, renal function (eGFR-based), and heavy alcohol consumption, categorized as low (0–1), moderate (2), or high (3–5). Multivariable Cox proportional hazards models, adjusted for demographics, socioeconomic factors, BMI, smoking, and alcohol use, assessed associations between MDS and esophageal cancer (EC) incidence (ICD-10: C15) and subtypes. Sensitivity analyses excluded participants with <1–3 years of follow-up. Mediation analyses evaluated inflammatory/metabolic biomarkers (e.g., CRP, HbA1c). Subgroup analyses explored effect modification by age, sex, and lifestyle factors, while restricted cubic splines tested nonlinear relationships. Analyses adhered to STROBE guidelines and utilized R v4.2.3.

Results

Among 450,700 participants (54% female, mean age 56.6 years), 1,572 developed esophageal cancer (EC: 645 adenocarcinomas [EAC], 275 squamous cell carcinomas [ESCC], 905 lower EC). EC cases were predominantly male, older (mean +4.8 years vs. non-EC), and exhibited higher Magnesium Depletion Score (MDS), BMI, smoking rates, and socioeconomic deprivation. EAC patients were more likely overweight/obese (BMI >25), while ESCC patients had higher smoking rates and normal BMI.
Higher MDS was significantly associated with increased EC risk (continuous MDS: HR=1.186, 95% CI:1.102–1.277, P<0.001). Compared to low MDS (0–1), moderate (2) and high MDS (3–5) groups showed 29.6% (HR=1.296, P=0.001) and 63.5% (HR=1.635, P<0.001) higher EC risk, respectively. Similar trends were observed for EAC (HR=1.277, P<0.001) and lower EC (HR=1.158, P=0.003). Sensitivity analyses excluding early-diagnosis cases (1–3 years) confirmed robustness. Associations persisted after adjusting for diabetes, hypertension, and H. pylori.
Stratified analyses revealed stronger MDS-EC associations in males, smokers, alcohol consumers, and overweight/obese individuals (BMI>25). MDS did not correlate with all-cause mortality in EC patients (HR=0.963, P=0.370). Mediation analyses identified inflammatory (C-reactive protein: 1.40%, P=0.013; neutrophils: 4.50%, P=0.003) and metabolic biomarkers (HbA1c: 0.91%, P=0.033; glucose: 0.38%, P=0.047) as partial mediators.

Conclusion

In summary, this study demonstrates a significant positive association between MDS and the risk of esophageal cancer, with an especially pronounced impact observed among overweight or obese individuals, males, and alcohol consumers. The findings support the hypothesis that magnesium metabolism may influence esophageal cancer through multiple mechanisms, including inflammation, metabolic abnormalities, and immune dysfunction.

Introduction

Radiation therapy (Rth) remains an integral part of the multifactorial management of breast cancer (BC). Some reports suggest an increased risk of secondary esophageal cancer (SEC) following Rth for BC, but wide-ranged populational studies on this topic are scarce. We conducted this nationwide registry-based study to analyze the incidence, prognosis, and timing of SEC within BC survivors.

Aims & Methods

We used two high-volume national databases (the National Health Fund Registry and the National Cancer Registry) to identify adult patients with a confirmed diagnosis of primary BC who received oncological treatment either with or without Rth between 2009 and 2019. Those patients were followed-up for the diagnosis of SEC until December 2023. The Fine-Gray competing risk regression models were used to determine and compare the cumulative incidence of SECs in both groups. We applied the Kaplan–Meier method to calculate the 5-year overall survival rates (OS) for SECs in both subsets of BC patients.

Results

We screened 194,598 patients with primary BC, of which 128,625 (66.1%) with available treatment data were included in the final analysis (mean age 61±13yrs.; 99% females). Of these, 89,078 (69%) received Rth within the treatment regime (post-Rth BC) and 39,547 (31%) did not receive Rth (no-Rth BC). The 10-year cumulative incidence of SEC within the post-Rth BC group was 0.06% (95%CI, 0.04%-0.09%), as compared to 0.02% (95%CI, 0.01%-0.04%) within the no-Rth group (Gray test P=.005). In a competing risk model, having received Rth was associated with a >2.5-fold increase in the risk of developing SEC relative to no-Rth BC patients (HR 2.67, 95%CI, 1.27-5.65, P=.010). The median time to SEC occurrence after Rth completion was 3.7 years (interquartile range [IQR], 1.3-6.6). Squamous cell cancers constituted 89% of SECs in the post-Rth BC group, which was higher than within the no-Rth BC group, of which 73% were SCCs. The prognosis of post-Rth SECs was as poor as for no-Rth SECs, with 5-year OS of 23% (95%CI, 14%-37%) and 13% (95%CI, 4.4%-36%), respectively; P=0.3.

Conclusion

Radiotherapy significantly increases the risk of SECs in BC survivors, although the cumulative incidence of this unfavorable event is low. These results raise awareness of SEC after RTH for breast cancer.