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.

Introduction

Endoscopic submucosal dissection (ESD) is recommended as a treatment modality for early gastric cancer because it allows organ-sparing, curative en-bloc resection, and complete histopathological evaluation. Although many endoscopists are interested in learning how to perform ESD, the procedure requires a high level of expertise and is technically challenging, especially for less experienced endoscopists.

Aims & Methods

This study aimed to investigate the single-operator learning curve and clinical outcomes of consecutive gastric ESDs. Eight hundred-eleven gastric ESDs were performed between March 2016 and December 2022. The learning curve for ESD was evaluated using the cumulative sum (CUSUM) method to analyze the number of ESDs required for achieving proficiency.

Results

Of the enrolled patients, 310 (40.9%) cases were diagnosed with early gastric cancer. Overall en-bloc resection rates, R0 resection, and curability is 98.6%, 96.3%, and 93.7%, respectively. The median ESD speed was 18.1 cm2/h (IQR 12.2 – 25.3). ESD speed was slower than average in the upper third (9.9 cm2/h), presence of submucosal fibrosis (11.0 cm2/h) and the presence of subcutaneous fat (11.1 cm2/h), and faster than 20 cm2/h in the lower third (20.2 cm2/h) and lesion sized > 3 cm (23.6 cm2/h). According to the existing literature, the proficiency benchmark is defined as en-bloc resection >90%, R0 resection and >80%, and resection speed >9 cm2/h. However, since the first case satisfies all the existing benchmarks, we should establish a new definition of speed among benchmarks. In the changes of resection speed, we defined 16.5 cm2/h as a benchmark for ESD speed, which is the median value of the rapidly changing slope, and the CUSUM curve revealed that 156 cases were needed to achieve proficiency.

Conclusion

Due to the development of endoscopic equipment, a higher level of ESD proficiency benchmark is required. One hundred sixty-five cases were required to attain a higher technical level of successful performance in gastric ESD.

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

Safe and effective sedation are important factors when performing gastrointestinal endoscopy. However, clinicians should be cautious when using sedatives in older patients because of their decreased physiological reserves. Remimazolam is an ultrashort active benzodiazepine that has attracted attention because of its efficacy. This study aimed to determine the safety and efficacy of remimazolam compared with midazolam as a sedative for diagnostic upper gastrointestinal endoscopy in older patients aged ≥65 years.

Aims & Methods

We randomly assigned patients aged ≥65 years who were scheduled for diagnostic upper gastrointestinal endoscopy. The average induction time, average recovery time, and side effect profile of patients who received remimazolam as a sedative were compared with those of patients who received midazolam.

Results

Patients who received remimazolam had shorter average induction (102.0 sec vs. 327.5 sec, p<0.001) and recovery times (5.8 min vs. 13.4 min, p<0.001) than those who received midazolam. No significant difference in side effect profiles was observed between the groups.

Conclusion

In performing upper gastrointestinal endoscopy in older patients, remimazolam can be a good alternative sedative to midazolam, whether used as monotherapy or in combination therapy.

References

Kilpatrick GJ, McIntyre MS, Cox RF, et al. CNS 7056: a novel ultra-short-acting Benzodiazepine. Anesthesiology 2007;107:60-6.
Borkett KM, Riff DS, Schwartz HI, et al. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg 2015;120:771-80.
Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol 1990;10:244-51.

Introduction

Twenty-five years have passed since the development of endoscopic submucosal dissection (ESD), and it has become widely used as the first-line treatment for early-stage esophageal and gastric cancers with low risk of lymph node metastasis. However, due to the anatomical complexity and technical difficulty, the application of ESD for hypopharyngeal cancer remains limited.

Aims & Methods

A total of 151 lesions in 106 patients with hypopharyngeal cancer who underwent ESD at the Department of Endoscopy, Saku Central Hospital Advanced Care Center from June 2006 to March 2025 were retrospectively reviewed to evaluate treatment outcomes. Cases of recurrence after chemoradiotherapy were excluded. ESD Procedure
All procedures were performed under general anesthesia with intubation. A hook knife J was used to perform circumferential incisions with the Autocut mode of the VIO 3000 or VIO 3. Submucosal dissection was carried out using Endocut I and spray coagulation. For traction and improved visualization, Clip line technique was used.

Results

The study included 116 patients (109 men, 7 women), with a mean age at diagnosis of 67.7 years (range: 40–92). Synchronous multiple pharyngeal cancers were found in 25 patients and metachronous in 13. A total of 156 lesions were resected: 10 by endoscopic mucosal resection (EMR) and 146 by ESD.
Tumor locations were as follows: oropharynx (7 lesions), hypopharynx (149 lesions), primarily in the piriform sinus (135) and posterior cricoid area (14). Of these, 6 extended to the epiglottis and 5 to the aryepiglottic fold.
Detailed Results

1. Tumor size: mean maximum diameter was 14.5 mm (range: 1–51; resection specimen size: 27.4 mm (5–90). Depth of invasion: EP in 92 lesions (59%) and SEP in 64 (41%). Mean invasion depth from the surface was 712 µm (range: 150–2600). Macroscopic types: 0-I (7), 0-IIa (53), 0-IIb (92), 0-IIc (4). Histology: squamous cell carcinoma (SCC) in 155 lesions, neurofibroma in 1. En bloc resection rate was 100%. Lateral margins: positive in 6, negative in 150. Deep margins: negative in all cases.
2. Adverse events: delayed bleeding (1), aspiration pneumonia (2), and stricture (1).
3. Local recurrence: observed in one SEP case with lymphatic involvement.
4. Pre-ESD metachronous cancers: esophagus: 42, stomach:17, colon:1.
5. Post-ESD metachronous cancers: esophagus:22, hypopharynx:13 and stomach:10.
6. Prognosis: Mean follow-up was 84.9 months (range: 5–222). There were 5 deaths from primary disease, 10 from other diseases, and 8 from other malignancies. All 5 primary disease-related deaths had ly1 and died due to lymph node, pulmonary, or hepatic metastases.
7. Among 11 cases with extension to the aryepiglottic fold or epiglottis, tracheostomy was performed in 8 and nasotracheal intubation in 2 cases.

Conclusion

ESD for hypopharyngeal cancer demonstrated a high rate of local control and was an effective treatment option. Even in cases with extension to the aryepiglottic fold or epiglottis, safe procedures were possible with tracheostomy. For cases with positive lympho-vascular involvement, the risk of lymph node and distant metastases warrants consideration of additional treatment. Metachronous multiple cancers in the hypopharynx, esophagus, and stomach occurred in 40% of patients, emphasizing the importance of postoperative surveillance.

Introduction

Endoscopic submucosal dissection (ESD) has become a common treatment method for superficial esophageal cancer, allowing complete resection and accurate postoperative pathological evaluation, especially for relatively larger lesions^{1, 2}. However, resection of larger lesions, especially circumferential lesions, can be time-consuming and challenging. The resected tissue can obstruct the esophageal lumen, leading to limited working space and poor visibility, thereby increasing the risk of adverse events such as perforation and muscular injury³. In recent years, several auxiliary traction techniques have been emerged, including positional adjustment traction, hemostatic clip elastic band traction, snare traction, line traction, and magnet anchor traction, which significantly improve the visibility of the submucosal layer during dissection and enhance the efficiency of the procedure ^4-5. Among these techniques, snare traction allows bidirectional traction through "push and pull" maneuvers, offering flexibility and practicality in clinical practice. However, due to the difficulty and limited cases of circumferential esophageal ESD, there is currently no published literature demonstrating the advantages of snare traction-assisted ESD over traditional ESD techniques.

Aims & Methods

This study aims to investigate the efficacy and safety of snare traction assisted ESD for the management of circumferential superficial esophageal cancer. A total of 68 patients who underwent ESD for circumferential superficial esophageal cancer were included in this study. All the patients were divided into two groups based on whether the snare traction was used or not; the snare traction group (S-ESD, group n=35) and the control group (C-ESD, group n=33).

Results

There was no significant difference in the size of the resected area between the groups [21.98 (18.30, 27.00) cm² vs 24.00 (15.28, 30.72) cm², P=0.976]. The snare traction group had a shorter dissection time [92.00 (74.00, 121.00) min vs 110.00 (92.50, 137.00) min, P=0.017] and a faster resection speed [0.28±0.13 cm²/min vs 0.22±0.11cm²/min, P=0.040] compared to the control group. There were no statistically significant differences between the two groups in terms of hospital stay, cost, en bloc resection rate, R0 resection rate, curative resection rate，bleeding rate, perforation rate, stricture rate, and recurrence rate (P>0.05).

Conclusion

Snare traction-assisted ESD is a safe and efficient approach for the treatment of circumferential superficial esophageal cancer. Its advantages includes shorter procedure so the anesthesia requirement, clear operative filed view, improved mucosal dissection efficiency, simple, and easily accessible equipment.

References

1 Ishihara R, Arima M, Iizuka T et al. Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer. Dig Endosc. 2020; 32: 452-93.
2 Draganov PV, Wang AY, Othman MO, Fukami N. Aga institute clinical practice update: Endoscopic submucosal dissection in the united states. Clin Gastroenterol Hepatol. 2019; 17: 16-25.e1.
3 Zhang W, Zhai Y, Chai N et al. Endoscopic submucosal tunnel dissection and endoscopic submucosal dissection for large superficial esophageal squamous cell neoplasm: Efficacy and safety study to guide future practice. Surg Endosc. 2018; 32: 2814-21.
4 Fukami N. What we want for esd is a second hand! Traction method. Gastrointest Endosc. 2013; 78: 274-6.
5 Jin P, Yu Y, Fu KI, Yu DL, Li AQ, Sheng JQ. A new traction method with use of the snare as a "second hand" during endoscopic submucosal dissection. Endoscopy 2015; 47 Suppl 1 UCTN: E286-7.