Introduction

According to the 2022 edition of the Japanese guideline for esophageal cancer, the necessity of additional treatment for muscularis mucosa/submucosa (MM/SM1) esophageal squamous cell carcinoma is comprehensively decided after endoscopic treatment. At our hospital, esophageal endoscopic submucosal dissection (ESD) is performed using a scissor-type knife, which is considered highly safe; however, few studies have reported its long-term outcomes. Therefore, the study aimed to compare the short- and long-term outcomes of esophageal ESD treatment using a scissor-type knife for MM/SM1 cancer and epithelium/lamina propria mucosae (EP/LPM) cancers in our hospital.

Aims & Methods

Patients diagnosed with esophageal squamous cell carcinomas who underwent ESD at our hospital between December 2009 and November 2019 were recruited, followed up for >3 years, and classified into two groups: 61 patients with 91 lesions diagnosed as EP/LPM cancer (group A) and 22 patients with 22 lesions diagnosed as MM/SM1 cancer (group B). Short- and long-term outcomes were compared. In all cases, only scissor-type knives were used.

Results

The mean ages were 69 ± 8.9 and 70 ± 8.8 years in groups A and B, respectively. Gender (male/female) was 78/13 and 20/2 patients in groups A and B, respectively. The mean tumor sizes were 16.8 ± 11.3 and 26.8 ± 18.1 mm in groups A and B, respectively, with significant differences (p = 0.0011). The R0 resection rates were 100% in both groups; lymphovascular invasion was observed in two cases with pT1a-MM cancers and one case with pT1b-SM1 cancer. Chemoradiation therapy (CRT) was added to one case with pT1a-MM cancer and two with pT1b-SM1 cancers, and only chemotherapy was added to one case with pT1a-MM cancer. The average observation period was 55 ± 30 and 60 ± 38 months in groups A and B, respectively, and no local recurrence was observed in either group. Lymph node recurrence was observed in one case with pT1a-MM cancer with lymphovascular invasion who received chemotherapy alone and one with pT1b-SM1 cancer with lymphovascular invasion who received CRT. Twenty-five and nine patients in groups A and B died from other diseases, respectively, but only one SM1 case with lymph node recurrence was the primary cancer death. The overall survival rate (3 years) was 80.2% and 77.3% (p = 0.85), and the disease-specific survival rate (3 years) was 100% and 95.5% (p = 0.30) in groups A and B, respectively.

Conclusion

The short-term outcomes of ESD for MM/SM1 cancer using a scissors-type knife were as good as those for EP/LPM cancer, and no local recurrence occurred even in the long-term outcomes. In addition, pT1a-MM tumors without lymphovascular invasion have progressed without recurrence and were considered appropriate as ESD-adaptive lesions.

Introduction

Patients with multiple Lugol-voiding lesions (mLVLs) in esophageal squamous cell carcinoma (ESCC) were known to have an increased risk of metachronous ESCC or pharyngeal and laryngeal squamous cell carcinoma (PLSCC) following endoscopic resection (ER), necessitating intensive endoscopic surveillance. The Japan Esophageal Cohort study, a multicenter prospective study evaluating the cumulative incidence of metachronous ESCC after esophageal ER, demonstrated that ER was selected as the initial treatment for most newly detected metachronous ESCC (72/74 patients). However, in clinical practice, ESCC or PLSCC outside the indications for ER are occasionally detected. Additionally, patients with mLVLs are known to have a high risk of developing other secondary primary cancers, nonetheless, the long-term clinical course in this population remains unclear.

Aims & Methods

The aim of this retrospective study was to evaluate the long-term prognosis of patients with mLVLs after endoscopic submucosal dissection (ESD) for superficial ESCC. This study included patients with mLVLs who underwent ESD for primary ESCC at our institution between April 2008 and August 2016. The exclusion criteria were patients with non-curative resection after ESD requiring additional treatment, such as submucosal invasion, positive vertical margins (pVM1), or lymphovascular invasion (LVI), and patients with a follow-up period of less than one year. After esophageal ESD, endoscopic surveillance was conducted every six months to one year, and metachronous cancers were considered for treated if detected. The cumulative incidence of metachronous ESCC and PLSCC, as well as the cumulative incidence of metachronous major ESCC and PLSCC, and overall survival (OS) were evaluated. Major ESCC were defined as lesions outside the indications for ER or those in which ER was performed resulting in a non-curative resection. Major PLSCC were defined as lesions outside the indications for ER or endoscopic laryngopharyngeal surgery (ELPS), or those in which ER or ELPS were performed resulting in pVM1 or LVI.

Results

A total of 140 patients were included, with a median age of 69 years (range: 47-86), and 30 patients (21.4%) had a history of head and neck cancer. During the median follow-up of 8.8 years (range: 1.2–15.5), 85 patients (60.7%) developed metachronous ESCC, all of whom were initially treated with ER, and 81 (95.3%) managed with ER alone, including repeated ER. Meanwhile, 35 patients developed metachronous PLSCC, 30 (85.7%) of whom were managed with ELPS alone. The cumulative incidence of metachronous ESCC and PLSCC at 5/10 years was 47.5%/67.1% for ESCC, and 13.8%/35.4% for PLSCC, respectively. The cumulative incidence of metachronous major ESCC and PLSCC at 5/10 years was 0.8%/2.8% for ESCC, and 1.5%/1.5% for PLSCC. Additionally, 30 (21.4%) patients died during follow-up, including progression of superficial metachronous ESCC (n=1) and superficial metachronous PLSCC (n=2) under observation after detection due to poor performance status, recurrences of previously treated PLSCC (n=7), aspiration pneumonia (n=4), hematological malignancies (n=3), tongue cancer (n=2), and others (n=11). The 5- and 10-year OS rates were 92.4%/ 79.5%.

Conclusion

In patients with mLVLs, endoscopic surveillance including pharyngo-laryngeal area following ESD for ESCC enabled early detection of metachronous lesions, the majority of which were successfully treated with ER. However, deaths from other causes were not negligible, highlighting the importance of careful long-term systemic monitoring.

Introduction

Endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) is one of the most challenging endoscopic procedures due to the high risk of bleeding and fibrosis caused by prior treatment of varices. However, due to the small number of such cases, the clinical outcomes of ESD for ESCC with EVs have been reported in only a limited number of cases at single centers^​1-3.

Aims & Methods

We conducted a multicenter, retrospective, cohort study to clarify the safety and efficacy of ESD for ESCC with EVs.Eleven institutions in the Tohoku region of Japan participated in this multicenter, collaborative, retrospective study. We performed endoscopic resection for 3619 patients with esophageal carcinoma at the participating institutions during the period from January 2010 to April 2022. Among those, 30 patients who underwent ESD for ESCC with EVs were recruited for the present study.
Rates of en bloc resection and R0 resection, procedure time and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD.

Results

Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 minutes. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC.

Conclusion

This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

References

1. Sawaguchi M, Jin M, Matsuhashi T, et al. The feasibility of endoscopic submucosal dissection for superficial esophageal cancer in patients with cirrhosis (with video). Gastrointest Endosc 2014;79:681-5.
2. Choi YK, Noh JH, Kim DH, et al. Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis. Clin Endosc 2022;55:381-9.
3. Zhang S, Liu YD, Chai NL, et al. Endoscopic submucosal dissection for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with esophagogastric varices: Ten-year experience from a large tertiary center in China. Gastrointest Endosc 2023 Online ahead of print.

Disclosure

The authors declare that they have no conflicts of interest.

Introduction

Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data on outcomes are derived from Asian studies. Therefore, we aimed to evaluate the short- and long-term outcomes of ESD for patients with early ESCC in a Western cohort.

Aims & Methods

In this retrospective cohort study, patients with early ESCC amendable for ESD were included in four tertiary referral hospitals in the Netherlands between 2012 and 2017. All procedures were performed by experienced endoscopists who were specifically trained in ESD. The decision for and choice of additional treatment following ESD was made on a per-patient basis. For this study, dedicated research fellows collected all relevant data by reviewing the electronic patients files. Data concerning long-term outcomes were checked with general practitioners or referral hospitals, when applicable. Outcomes included technical success, R0 resection (i.e. tumor-free lateral and vertical margins), curative resection (i.e. en-bloc radical resection with histology no more advanced than T1sm1, good differentiation and absence of lymphovascular invasion) and recurrence rates, as well as ESCC-specific and overall survival.

Results

We included 68 patients (34 males; mean age 69) with a median tumor size of 3cm (range 1-12) and circumferential extent of 50% (range 10-100), in whom ESD was technically successful in 66/68 patients (97%). While en-bloc resection was achieved in 64/66 technically successful ESDs (97%), R0 resection was accomplished in 54/66 patients (82%). Overall, a curative resection was achieved in only 34/66 patients (52%). Among the patients with a non-curative resection, 16/32 (50%) underwent additional treatment receiving either argon plasma coagulation for tumor-positive resection margins (n=1), selective lymph node dissection (n=1), definite chemoradiation therapy (n=4) or esophagectomy ± neoadjuvant chemoradiation therapy (n=10). Endoscopic surveillance was preferred in the other half of patients with a non-curative resection (16/32; 50%) based on significant comorbidities or patient choice. During a median follow-up of 66 months (p25-p75 43-88), 12/66 patients (18%) developed a local recurrence which could be treated endoscopically in most cases (10/12; 83%). Locoregional lymph node metastasis and distant metastasis were observed in 6 (6/66; 9%) and 3 (3/66; 5%) patients, respectively. A total of 30 patients (30/66; 45%) died during follow-up, of which the minority (7/30; 23%) was ESCC-related deaths. The 5-year overall and ESCC-specific survival probability were 64% (95% CI 53-76%) and 88% (95% CI 79-97%), respectively. More importantly, overall survival did not significantly differ between patients with and without curative resections (p = 0.69). In addition, no significant difference was seen for ESCC-specific survival between patients with or without additional treatment after a non-curative resection (p = 0.07).

Conclusion

In this Western cohort with long-term follow-up, the efficacy and safety of ESD for early ESCC was confirmed although the rate of non-curative resections was substantial. Irrespective of non-curative or curative resection, the long-term prognosis of these patients was limited mainly due to competing mortality. Considering additional treatment after a non-curative resection did not influence survival, the potential benefit of adjuvant therapy should be carefully balanced against the risk of dying from another cause than esophageal cancer on an individual basis.

Disclosure

C.N. Frederiks has received speaker's fee from Pentax Medical.
R.E. Pouw is a consultant for MicroTech, and has received speaker’s fee from Medtronic.
J.J.G.H.M. Bergman is a consultant for Medtronic, Cook Medical, and Boston Scientific, and has received research funding from Pentax Medical, C2 Therapeutics, Medtronic, Aqua Medical, Olympus Endoscopy, and Fuji-film.
B.L.A.M. Weusten has received research funding from Pentax Medical, C2 Therapeutics, and Aqua Medical. The remaining authors declare to have no disclosures relevant to this manuscript.

Introduction

Endoscopic submucosal dissection (ESD) has evolved to become a viable treatment option for oesophageal squamous dysplasia (SD) and early squamous cell carcinoma (ESCC). Although enbloc, R0, excision has the potential to yield an endoscopic cure, surgery remains the standard of care in the West. Furthermore, Western data pertaining to endoscopic outcomes is limited. We aimed to assess the efficacy and safety of ESD for SD and ESCC in a single tertiary referral centre.

Aims & Methods

We conducted a prospective observational cohort study over 87 months until November 2023 in consecutive patients undergoing ESD for SD or ESCC. The primary outcomes were enbloc, R0 and curative resection rates. Secondary outcomes included procedure duration, tumor recurrence and adverse events.

Results

112 consecutive patients were referred for treatment and underwent ESD (median age 73 [IQR 68-78]; 50% male; Table 1). Median lesion size was 30 mm (IQR 20-50mm) and Paris IIa was the most common morphology (58.9%). Enbloc resection was achieved in 109 (97.3%) and R0 excision in 87 (77.7%). Curative resection in cases of LGD and HGD, where margins were clear of dysplasia, was 7/11 (63.6%) and 31/34 (91.2%) respectively. In those with T1a/T1b SCC, the curative resection rate was 20/61 (32.8%). In T1a SCC lesions, 11/20 (55.0%) had a curative ESD. Of the remainder, 6/9 were poorly differentiated, 1/9 had LVI, and 2/9 had positive margins (1 deep, 1 peripheral). In T1b SCC lesions, 9/41 were curative (22.0%). The remainder were either poorly differentiated, >T1b-SM1, LVI positive or a combination. In those with T1a/T1b disease, without adverse tumor biology, ESD achieved curative resection in 20/22 (90.9%).
In the 41/61 (67.2%) T1a/T1b patients that did not meet criteria for cure, subsequent treatment included surgery (n=5), radiotherapy (n=5) and chemoradiotherapy (n=1). After MDT discussion, the remaining 30 were managed conservatively, due to advanced age or comorbidities. In these, recurrence occurred in 6/30 patients (1 local, 3 nodal, 2 metastatic) at a median follow up of 12 months (6-18 months). The median hospital length of stay was 1 day (IQR 1-3). Oesophageal strictures occurred in 46 patients (41.1%), requiring a median of 3 dilations (IQR 1-8). There were 2 cases of delayed bleeding. There were no perforations.

Table 1

Conclusion

ESD is curative for low and high-grade dysplasia. In a Western setting, ESD offers definitive T-staging and has the potential to yield a cure in almost 33% of T1a and T1b SCC cases. Due to a high risk of disease recurrence, adjuvant therapy should be considered in cases of a non-curative resection.

Introduction

Endoscopic submucosal dissection (ESD) is the preferred treatment for superficial esophageal squamous cell carcinoma (ESCC). However, curative resection is not always achievable for all patients¹. Currently, the curability criteria was inconsistent among different societies^2-3 and may be overly stringent for suggesting additional treatments⁴, which causes dilemmas in clinical decision-making and potential overtreatments in some low-risk cases.

Aims & Methods

The research aim was to develop and validate a risk scoring system to assess curability after ESD for superficial ESCC. This study was based on a nationwide cohort, the China Early Esophageal Cancer Cohort, and all patients were follow-up at least for 3 years. Patients with superficial ESCC undergoing ESD were included, and those with positive horizontal margin, adjuvant chemoradiotherapy, and metachronous esophegeal cance after ESD were excluded. The primary outcome was noncurative resection, defined as either (1) pathological confirmation of residual tumor or lymph node metastasis (LNM) after additional surgery, or (2) identification of local recurrence, LNM, or distant metastasis during follow-up. Data from South and North China were used to develop and validate the scoring system, respectively. Logistic regression analysis was used for model construction, and Kaplan-Meier survival estimates, the C-statistic, and decision curve analysis were employed for performance evaluation.

Results

A total of 1,273 patients with superficial ESCC were included, with 995 for model development and 278 for validation. Multivariable analysis identified 6 independent risk factors for noncurative resection: tumor size ≥30 mm, submucosa invasion, positive vertical margin, lymphatic invasion, vascular invasion, and poor differentiation. For the risk scoring system (ESCC-eCura), lymphatic invasion was assigned as 2 points, and others were assigned as 1 point. In the development cohort, the non-curative resection rates of the low- (≤1 point), intermediate- (2 to 3 points), and high-risk (≥4 points) groups was 4.5%, 16.3%, and 75.0%, respectively. The ESCC-eCura demonstrated a C-statistic of 0.75 (95% condifence interval [CI], 0.69 - 0.81). In the validation cohort, the C-statistic was 0.84 (95% CI, 0.73-0.95), and intermediate- or high-risk groups were significant predictors for subsequent recurrence (hazard ratio [HR] for intermediate-risk group 14.35, 95% CI 4.01-51.35, P<0.001; HR for high-risk group 28.16, 95% CI 4.90-161.83, P<0.001; all compared with the low-risk group). Decision curve analysis also showed acceptable clinical benefits and utility.

Conclusion

This ESCC-eCura scoring system can predict non-curative resection after ESD for superficial ESCC, which offers a practical tool for individualized management. Additiomal treatments should be recommended for patients in ESCC-eCura intermediate- or high-risk groups, while follow-up may be acceptable for the low-risk group.

References

1.Jiang, H., et al., Risk and Pathological Factors of Recurrence after Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis. Gastrointest Endosc, 2024.
2. Kitagawa, Y., et al., Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus, 2023. 20(3): p. 343-372.
3. Pimentel-Nunes, P., et al., Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy, 2022. 54(6): p. 591-622.
4.Liu, Z., et al., Additional Esophagectomy Following Noncurative Endoscopic Resection for Early Esophageal Squamous Cell Carcinoma: A Multicenter Retrospective Study. Ann Surg Oncol, 2021. 28(12): p. 7149-7159.

Disclosure

Nothing to disclose.