Exploration of preventive treatment for high risk patients with metachronous multiple esophageal squamous cell carcinoma: A case report

Abstract

BACKGROUND

Metachronous multiple esophageal squamous cell carcinomas (ESCCs) may occur in some patients after endoscopic resection. Multiple dysplastic lesions in the esophagus increase risk of multiple squamous cell carcinomas (SCCs). Endoscopic imaging technology such as narrow band imaging (NBI), can detect early SCC. Lugol chromoendoscopy is also the conventional standard technique for detecting superficial ESCC. However, little is known about the interval from the first SCC to the metachronous SCC. Effective methods to prevent multiple metachronous SCCs are needed in survivors of esophageal SCC.

CASE SUMMARY

A 56-year-old man showed a slightly elevated reddish area in the middle thoracic esophagus at 30 cm from the incisors on gastroscopy for routine examination. Esophageal mucosa lesion was about 2.5 cm. NBI and magnifying gastroscopy confirmed intra-epithelial papillary loop type B-1 according to the Japan Esophageal Society Classification. Lugol chromoendoscopy was used to evaluate the dysplastic squamous epithelium in the esophagus. Biopsy pathology revealed severe dysplastic squamous epithelium. Computed tomography showed no lymph node metastasis. His complete blood test and tumor markers were within reference values. He had no history of alcohol consumption and smoking. Mucosal lesion was dissected by endoscopic submucosal dissection (ESD). Postoperative pathological results showed moderately differentiated squamous carcinoma. No cancer thrombus was seen in the vasculature, and the surrounding cut edge was not involved. The patient underwent radiotherapy within 2 months after ESD. The multiple Lugol-voiding lesions disappeared, and enhanced chest computed tomography revealed no lymph node metastasis.

CONCLUSION

This is the first case of multiple dysplastic lesions of esophagus cured by radiotherapy. Radiotherapy after minimally invasive endoscopic treatment might be a safe and effective optional therapeutic strategy to prevent metachronous multiple esophageal SCCs.

Key Words: Multiple dysplastic lesions; Metachronous multiple esophageal squamous cell carcinomas; Lugol-voiding lesions; Lugol chromoendoscopy; Radiotherapy; Case report

Core Tip: The grade of Lugol-voiding lesions is associated with risk of metachronous squamous cell carcinomas (SCCs). Effective methods to prevent metachronous multiple SCCs are needed in survivors of esophageal squamous cell carcinomas. We present the first case of multiple dysplastic lesions of esophagus cured by radiotherapy. This case indicated that radiotherapy after endoscopic submucosal dissection might be a safe and effective optional therapeutic strategy to prevent metachronous multiple esophageal SCCs.

INTRODUCTION

Squamous dysplasia is believed to be a pre-neoplastic lesion of squamous cell carcinomas (SCCs) and it is easily identified as Lugol-voiding lesions (LVL) on Lugol chromoendoscopy[1,2]. Many patients with esophageal SCC have multiple LVLs in the esophageal mucosa[3,4]. LVL is graded according to the number of LVL per endoscopic view (A = no lesion; B = 1 to 9 Lesions; C ≥ 10 Lesions). Some studies have shown that higher grade of LVL carries a high risk of metachronous multiple esophageal SCCs[5]. Effective methods are needed to prevent metachronous multiple SCCs. Here we present a case of multiple dysplastic lesions of esophagus cured by radiotherapy.

CASE PRESENTATION

Chief complaints

A 56-year-old man complained of right upper abdominal pain for 2 days.

History of present illness

The patient had a history of diabetes.

History of past illness

The patient had no history of hypertension, hepatitis, tuberculosis, and trauma.

Personal and family history

The patient had no personal or family history of tumours.

Physical examination

Physical examination was negative.

Laboratory examinations

The blood tests and tumor markers were all within reference ranges.

Imaging examinations

A slightly elevated reddish area in the middle thoracic esophagus at 30 cm from the incisors was revealed by gastroscopy (Figure 1A). Narrow band imaging (NBI) and magnification gastroscopy showed intra-epithelial papillary loop type B-1 (Figure 1B). According to the grade of LVL, more than 10 Lesions per endoscopic view are defined as Grade C (Figure 1C). Biopsy pathology revealed severe dysplastic squamous epithelium (Figure 1D). Computed tomography showed no lymph node metastasis (Figure 1E and F).

Figure 1 Imaging examinations. A: Gastroscopy showing a slightly elevated reddish area; B: Narrow band imaging (NBI) magnifying gastroscopy findings; C: More than 10 Lesions were found per endoscopic view and defined as grade C; D: Biopsy pathology findings; E: Computed tomography in the venous phase; F: Computed tomography in the arterial phase; G: Postoperative pathological results; H: Endoscopic submucosal dissection (ESD) scar under the white light; I: ESD scar under NBI; J: Titanium clips were used for accurate marking on oral and anal sides for multiple Lugol-voiding lesions (LVL) ranges; K: Clinical target volume; L: Multiple LVL disappeared.

FINAL DIAGNOSIS

Prophylactic radiotherapy can reduce the occurrence of multiple metachronous esophageal cancer.

TREATMENT

Endoscopic resection was performed with consent of the patient. Mucosal lesion was completely resected by endoscopic submucosal dissection (ESD). Postoperative pathological results showed moderately differentiated squamous carcinoma, about 1.4 cm × 0.7 cm in size, infiltrated to the muscularis mucosae (Figure 1G). No cancer thrombus was seen in the vasculature, and the surrounding cut edge was not involved.

Patient underwent radiotherapy within 2 months after ESD. We examined patient using Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium of the esophagus before radiotherapy, and found multiple LVLs at 29 cm-40 cm, post-ESD scar at 30 cm-35 cm from the incisors (Figure 1H and I). Titanium clips were used for marking oral and anal sides in multiple LVL ranges (Figure 1J).

Intensity-modulated radiation therapy was delivered by a Varian Synergy linear accelerator (Varian VitalBeam American) with a 6MV X-ray beam. The clinical target volume (CTV) included one tumor bed (CTV1) and multiple LVL (CTV2) (Figure 1K). The planning target volume (PTV) was an additional extension of the caudal and cephalad margin of CTV by 0.3 cm. Standard initial radiation dose of 5040c Gy/28F and 4140cGy/23F were planned for PTV1 and PTV2. The radiation field did not include regional lymph nodes because the probability of metastasis is low in T1a esophageal SCCs (ESCCs). The radiation strategy was designed by an independent radiologist.

OUTCOME AND FOLLOW-UP

Three months after the end of radiotherapy, the multiple LVLs disappeared, evaluated using Lugol chromoendoscopy (Figure 1L). The patient underwent another gastroscopy 8 months after the end of radiotherapy. The multiple LVLs disappeared, and enhanced chest CT did not reveal lymph node metastasis.

DISCUSSION

The 8.5-year follow-up data of 21111 residents from high-incidence areas for ESCC in China, including Linzhou in Henan Province, Cixian in Hebei Province, and Feicheng in Shandong Province, revealed that the cumulative incidence rates of ESCC were 15.5%, 4.5%, and 1.4% among patients with severe dysplasia/carcinoma in situ, moderate dysplasia, and mild dysplasia, respectively[6]. In patients with early esophageal SCC, organs can be preserved by endoscopic curative treatment, but the preserved organs are strongly affected by squamous dysplastic lesion. Prospective study by Katada et al[5], showed the association between the grade of LVL and risk of metachronous SCC. Higher grade of LVL carried a high risk of metachronous multiple esophageal SCC. However, little research has been done to reduce the grade of LVL. Therefore, effective methods to prevent metachronous multiple SCCs are needed in survivors of esophageal SCC. A cohort study analyzed 330 patients newly diagnosed with superficial ESCC. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL[1]. In the past, we could only choose endoscopy for reexamination to detect early esophageal SCC as early as possible. In the screening of high-risk populations for esophageal squamous cell carcinoma, we usually choose NBI and Lugol chromoendoscopy. In the background of LVLs, the influence of some inflammatory lesions increases the difficulty of detecting early esophageal squamous cell carcinoma[7,8]. Therefore, the incidence of multiple synchronous esophageal carcinoma remains high during the follow-up process.

ESD is considered the optimal technique for resecting superficial esophageal lesions; however, its high operational complexity and lengthy learning curve pose significant barriers to widespread adoption. Additionally, the potential complication of post-ESD esophageal stenosis remains a critical issue that must be addressed[9,10]. Radiotherapy induces damage to the DNA of abnormally proliferating cells via ionizing radiation, thereby promoting apoptosis or inhibiting mitosis, particularly in rapidly dividing precancerous cells. The presence of multiple dysplastic lesions in the esophagus is associated with an increased risk of ESCC. Radiotherapy can target abnormally proliferating esophageal cells, preventing their progression to SCC. This mechanism parallels the application of radiotherapy in cervical intraepithelial neoplasia[11], where DNA destruction and inhibition of clonal cell survival eliminate residual proliferative epithelial tissue.

We present the first case of multiple dysplastic lesions of esophagus cured by radiotherapy. After the end of radiotherapy, the multiple LVLs disappeared. This case indicated that radiotherapy after ESD might be a safe and effective optional therapeutic strategy to prevent metachronous multiple esophageal SCC. Radiotherapy primarily accomplishes its therapeutic objective by inducing irreparable damage to the DNA of tumor cells via radiation, ultimately resulting in cell death. However, it may also inflict damage on normal cells, potentially leading to adverse effects such as radiation esophagitis, radiation pneumonitis, radiation-induced cardiac injury, and bone marrow suppression. It is imperative to highlight that the treatment effectiveness may have limitations in individual cases. To further substantiate the safety and efficacy of the therapeutic effect, additional randomized controlled trials with a larger sample size are warranted.

CONCLUSION

The grade of LVL is associated with risk of metachronous multiple esophageal SCCs. Effective methods to prevent metachronous multiple SCC are needed in survivors of esophageal SCC. Radiotherapy after ESD may represent a promising strategy. Further studies are needed to validate its safety and efficacy.

ACKNOWLEDGEMENTS

The authors sincerely thank the presented patient for his willingness to participate in this study.