Conservative management of a delayed esophagomediastinal fistula after endoscopic submucosal dissection: A case report

Abstract

BACKGROUND

In this report, we summarize our experience with conservative management in a rare case of delayed perforation with mediastinal fistula formation following endoscopic submucosal dissection (ESD) for long-segment circumferential early esophageal cancer.

CASE SUMMARY

The patient had developed a delayed perforation with formation of mediastinal fistula following ESD. A multidisciplinary conservative regimen was implemented, consisting of targeted long-term antimicrobial therapy, repeated low-pressure sinus tract irrigation, continuous sinus and thoracic closed drainage, and early enteral nutrition support guided by nutrition specialists. Meticulous nursing care was continued for more than 50 days, following which the fistula healed and the patient was discharged successfully.

CONCLUSION

Systematic multidisciplinary conservative management combining infection control, adequate fistula drainage, and nutritional support can achieve complete healing of delayed ESD-related esophagomediastinal fistula in selected stable patients.

Key Words: Endoscopic submucosal dissection; Esophagomediastinal fistula; Delayed perforation; Conservative management; Fistula drainage; Case report

Core Tip: We report a rare case of severe, ultra-late esophagomediastinal fistula occurring on postoperative day 23 following circumferential endoscopic submucosal dissection. Instead of emergency thoracic surgery, we adopted a multidisciplinary conservative strategy with three core pillars: (1) Culture-guided, long-term antimicrobial infection control; (2) Prolonged low-pressure sinus tract irrigation and closed drainage; and (3) Early jejunal enteral nutrition. Joint participation of gastroenterology, infectious disease, thoracic surgery, radiology and nutrition teams optimized clinical decision making. This multidisciplinary approach was useful in achieving complete fistula healing, demonstrating that systematic non-operative management is a viable and effective option for selected patients, precluding the risks of major surgery. Clinicians should maintain high vigilance for ultra-late delayed perforation after full-circumferential esophageal endoscopic submucosal dissection, with serial postoperative monitoring to exclude sepsis and occult mediastinal infection.

INTRODUCTION

Endoscopic submucosal dissection (ESD) is a minimally invasive technique used in the treatment of early gastrointestinal cancers. ESD offers the advantages of en bloc resection of large lesions, reduced risk of residual or recurrent disease, and availability of complete pathological specimens[1]. However, the procedure is technically complex, time-consuming, and carries a relatively high risk of complications, with perforation being the most serious complication[2]. Delayed perforation is a particularly insidious complication of esophageal ESD and can lead to serious, potentially life-threatening sequelae such as mediastinal emphysema and empyema[3]. Due to its serious nature, this complication is rarely managed conservatively, and reports of conservative treatment are rare both domestically and internationally[4,5].

Even though ESD is classified as minimally invasive, circumferential resection of long esophageal segments significantly elevates perforation risk. Early recognition and continuous postoperative monitoring are critical to exclude sepsis and progressive mediastinal contamination; missed delayed perforation may lead to fatal diffuse mediastinitis. Due to its high mortality risk, this complication is traditionally managed with emergency surgical intervention, and standardized conservative treatment protocols are rarely reported both domestically and internationally.

In this report, we present a case in which a multidisciplinary conservative approach that included standardized antimicrobial infection control was used to successfully manage early esophageal cancer complicated by delayed perforation and mediastinal fistula following ESD.

CASE PRESENTATION

Chief complaints

Chest tightness, dyspnea, and persistent fever for 1 day on postoperative day 23 after esophageal ESD.

History of present illness

The patient was a 72-year-old man with known hypertension, well-controlled with medication. He was admitted for the treatment of early esophageal cancer diagnosed over one month back. Preoperative gastroscopy revealed a lesion located at a distance of 33-39 cm from the incisors and involving the entire esophageal circumference (Figure 1A). On December 5, 2022, ESD was performed using the double-tunnel technique combined with snare-assisted traction for complete en bloc resection (Figure 1B-D). The total procedure time was 115 minutes. Careful inspection by the surgeon during and immediately after resection did not reveal obvious injury to the muscular layer, as confirmed by subsequent histopathological examination of the resection specimen. To prevent stricture formation, 40 mg of triamcinolone acetonide was injected into the submucosa around the resection wound. Following the operation, fasting, acid suppression, mucosal protectants, and fluid therapy were initiated. A liquid diet was started 48 hours after the procedure. Additionally, multipoint submucosal injections of triamcinolone acetonide (40 mg per session, mixed with saline) were administered on post-ESD days 7 and 14 (December 12 and 19, 2022) for stricture prophylaxis (Figure 1E and F). The patient remained stable during the recovery period.

Figure 1 Surgical procedure and postoperative multipoint steroid injections for stricture prevention. A: Lesion located 33-39 cm from incisors, involving the entire circumference; B: Double-tunnel technique and snare traction providing adequate exposure of the wound, reducing complications; C: Postoperative wound intact without muscular layer injury; D: Resected specimen en bloc; E: Multipoint submucosal triamcinolone injection one week post-endoscopic submucosal dissection (December 12, 2022); F: Multipoint submucosal triamcinolone injection two weeks post-endoscopic submucosal dissection (December 19, 2022).

History of past illness

Chronic hypertension for 10 years, well controlled with oral antihypertensive agents; no diabetes mellitus or chronic renal/hepatic dysfunction; preoperative serum albumin 38 g/L, without hypoalbuminemia.

Personal and family history

Forty pack-year smoking history, smoking cessation 10 years prior to admission; no history of alcohol abuse; no family history of esophageal malignancy or gastrointestinal fistula disease.

Physical examination upon admission

Temperature 38.7 °C, heart rate 96 beats/minute, respiratory rate 24 breaths/minute, blood pressure 128/76 mmHg; bilateral lower lung crackles on lung auscultation; mild tenderness over the substernal region without rebound tenderness or subcutaneous emphysema; no tachycardia or hypotension suggestive of septic shock.

Laboratory examinations

White blood cell count 14.2 × 10⁹/L, neutrophil percentage 87.3%, C-reactive protein 118 mg/L, procalcitonin 2.1 ng/mL consistent with bacterial infection; serum albumin 33 g/L, indicating mild malnutrition secondary to inflammatory stress; renal and liver function test results within normal limits.

Imaging examinations

Chest computed tomography (postoperative day 23): (1) Esophageal wall defect communicating with mediastinal space; (2) Mediastinal inflammatory exudate; (3) Bilateral pleural effusion; and (4) Pulmonary consolidation (Figure 2A).

Figure 2 Chest computed tomography and follow-up gastroscopy upon clinical deterioration (December 28, 2022). A: Chest computed tomography showing esophagomediastinal fistula and pleural effusion; B: Yellowish-white purulent secretion at the original surgical site; C: Fistula opening approximately 0.6 cm in diameter, 43 cm from nasal verge; D: Abundant yellow secretion within the sinus tract; E: Nasogastric tube placed in the sinus tract (approximately 5 cm from fistula), connected to negative suction for drainage, alongside jejunal feeding tube placed in the duodenum.

Emergency gastroscopy: Yellowish-white purulent secretions covering the ESD wound; a 0.6-cm-wide fistula opening 43 cm from the nasal verge with pus-filled sinus tract (Figure 2B-E).

MULTIDISCIPLINARY EXPERT CONSULTATION

Multidisciplinary team consultation including gastroenterology, thoracic surgery, infectious disease, clinical nutrition and radiology departments was performed immediately after fistula diagnosis. Infectious disease specialists guided full antimicrobial therapy as per the institutional microbiology protocols followed at the hospital. Nutrition specialists formulated enteral feeding regimens. Thoracic surgeons evaluated surgical indications and supported closed thoracic drainage placement.

Chronological clinical timeline

December 5, 2022: Circumferential esophageal ESD performed, total operation time 115 min; no intraoperative muscular layer injury identified.

December 7, 2022: Liquid diet initiated 48 hours postoperatively.

December 12, 2022 (post-ESD day 7): First multipoint submucosal triamcinolone injection for stricture prophylaxis.

December 19, 2022 (post-ESD day 14): Second multipoint submucosal triamcinolone injection.

December 28, 2022 (post-ESD day 23): (1) Onset of fever, chest tightness and dyspnea; and (2) Computed tomography (CT) + gastroscopy confirm esophagomediastinal fistula.

December 28, 2022: (1) Jejunal feeding tube, sinus drainage tube and thoracic closed drainage tube placed; and (2) Empirical intravenous antibiotics initiated.

January 11, 2023 (post-ESD day 37): (1) Two-week follow-up gastroscopy; and (2) Sinus tract irrigation continued with minimal drainage output.

January 18, 2023: (1) Three consecutive days with zero drainage volume; and (2) Repeat chest CT showed complete absorption of pleural effusion, all drainage tubes removed.

January 25, 2023 (post-ESD day 51): (1) Final gastroscopy confirmed fistula scarring and full healing; and (2) Patient discharged.

February 25, 2023 (1-month follow-up): Endoscopic esophageal stenosis detected, four sessions of intermittent balloon dilation completed sequentially.

The 3-month, 6-month, 9-month follow-up: Serial gastroscopies without tumor recurrence or recurrent stenosis.

FINAL DIAGNOSIS

The final diagnosis was delayed esophagomediastinal fistula following ESD for esophageal lesions. This diagnosis was confirmed based on postoperative fever and chest distress, endoscopic and CT evidence of esophageal wall defect with mediastinal communication, and local infectious manifestations.

TREATMENT

Antimicrobial infection control

Immediately after fistula diagnosis, broad-spectrum intravenous empirical antibiotics were administered: Piperacillin-tazobactam 4.5 g every 8 hours combined with metronidazole 0.5 g every 12 hours, covering aerobic oropharyngeal flora and mediastinal anaerobes. Culture of purulent secretion from the sinus tract was positive for Streptococcus viridans, fully susceptible to β-lactam antibiotics. Infectious disease specialists recommended de-escalation to single-agent piperacillin-tazobactam after culture results. The total duration of intravenous antimicrobial therapy was 23 days; antibiotics were discontinued after normalized inflammatory markers and complete resolution of purulent sinus drainage.

Sinus tract irrigation and multi-site closed drainage

A nasogastric drainage tube was positioned 5 cm proximal to the fistula orifice for continuous low-pressure negative-pressure drainage. Slow, low-flow normal saline irrigation was performed twice daily under endoscopic guidance to evacuate pus without mediastinal infection spread. A thoracic drainage tube was placed to drain pleural effusion. Irrigation and drainage were sustained for 23 days until three consecutive days of zero drainage output.

Nutritional support

A jejunal feeding tube was positioned in the duodenal horizontal segment to establish early enteral nutrition, avoiding oral food passage through the esophageal fistula. High-protein enteral formulas were administered to maintain positive nitrogen balance, correct hypoalbuminemia, and promote mucosal tissue repair.

Supportive and symptomatic treatment

Intravenous proton-pump inhibitors for acid suppression, mucosal protective agents, standardized drainage tube nursing care, with monitoring of vital signs for fever.

OUTCOME AND FOLLOW-UP

All drainage tubes were removed, oral soft diet was gradually reintroduced, and the patient was discharged without acute infectious complications (Figure 3A). After 51 days of inpatient conservative management, follow-up gastroscopy on January 25, 2023 demonstrated complete scar formation at the fistula site with no residual sinus tract (Figure 3B). Chest CT showed full resolution of pleural effusion without pneumomediastinum (Figure 3C).

Figure 3 Follow-up examination after one week of drainage and images showing fistula healing. A: Gastroscopy at the 2-week follow-up showing a well-positioned esophageal drainage tube; B: Gastroscopy on January 25, 2023 showing scar formation at the fistula site, confirming healing; C: Repeat chest computed tomography showing no significant effusion or pneumothorax, with pleural effusion largely absorbed.

One month after discharge, routine gastroscopy revealed severe esophageal stenosis that could not be traversed by the standard endoscope. Four sessions of intermittent endoscopic balloon dilation were completed to relieve dysphagia. Serial gastroscopy follow-up at 3 months, 6 months, and 9 months postoperatively showed no recurrence of tumor or esophageal stricture. Thus, emergency thoracic surgery was avoided in this patient, with no long-term mediastinal infectious sequelae and satisfactory quality of life.

DISCUSSION

Our patient underwent ESD for the treatment of long-segment circumferential early esophageal cancer. Following the procedure, he developed delayed perforation and mediastinal fistula formation, a rare and serious complication. Large lesion size, deep dissection, poor local blood supply, and postoperative steroid injections have been implicated as contributing factors for the occurrence of this complication[6]. Management of delayed perforation is often difficult due to the insidious nature of the accompanying symptoms, which can result in potential misdiagnosis or delayed diagnosis[3]. The occurrence of mediastinal infection and pleural effusion over and above perforation further increases the severity of the condition, making it a therapeutic challenge.

Benefits and risks of post-ESD steroid injection for circumferential esophageal lesions

The risk of stricture following ESD for circumferential esophageal lesions has been reported to be extremely high, at over 90%[6,7]. A widely used measure to prevent stricture formation is the administration of submucosal steroid injection (e.g., triamcinolone acetonide), which primarily acts by inhibiting collagen synthesis and inflammatory responses, thereby reducing fibrotic tissue hyperplasia[8,9]. In the present case, the administration of multiple triamcinolone injections did indeed delay stricture formation to some extent. However, the development of strictures despite these preventive measures in this case highlights the importance of recognizing that steroids may inhibit tissue repair and delay wound healing, particularly after extensive circumferential resection, because of the thinning of the submucosal and muscle layers. Furthermore, steroid injections can mask the signs of infection, which in turn can lead to delayed recognition of potentially severe complications such as mediastinal fistula. Therefore, in cases of long-segment circumferential lesions, the benefits of steroid injections must be carefully weighed against the possible risks. Additionally, clinicians should consider the combined use of diverse strategies such as oral steroids and endoscopic dilation, coupled with enhanced postoperative imaging follow-up.

Efficacy and safety of sinus tract irrigation with normal saline

As part of the management strategy in this case, local irrigation with normal saline was performed in addition to mediastinal sinus tract drainage; this significantly improved drainage efficacy, relieving the accumulation of purulent secretions. An isotonic solution with good biocompatibility, such as normal saline, effectively dilutes pus and cleanses the sinus tract without irritating the surrounding tissues. Irrigation should be performed under endoscopic or imaging guidance, with strict control of irrigation pressure and speed in order to prevent the undue increase in pressure, which can lead to spread of infection to other mediastinal or pleural compartments. In our case, we employed a low-flow, low-frequency irrigation strategy, which successfully prevented subsequent infection or clinical deterioration; this indicates that the procedure is safe when performed cautiously. Furthermore, irrigation enables the collection of secretion samples for bacterial culture to guide the choice and adjustment of antibiotic therapy.

Critical role of standardized antimicrobial therapy and infection control

Mediastinal contamination from esophageal perforation involves mixed aerobic-anaerobic flora; empirical broad-spectrum antibiotics are mandatory upon fistula diagnosis, with culture-guided de-escalation to minimize antibiotic overexposure. The involvement of infectious disease specialists ensures compliance with institutional microbiology protocols, rational duration of intravenous antibiotics, and timely discontinuation once inflammatory markers normalize. As Theeuwen et al[10] highlighted in their study, complex esophageal perforations represent resource-intensive clinical challenges requiring multimodal infection control as a core treatment pillar, not merely an adjunct to local drainage. Without sustained targeted antimicrobial suppression of mediastinal bacterial infection, persistent purulent secretion impedes the epithelialization of the fistula tract and leads to treatment failure.

Diagnosis and comprehensive management strategy for delayed perforation

Delayed perforation after ESD typically occurs 3-7 days after the operation, commonly presenting with sudden chest pain, fever, dyspnea, and subcutaneous emphysema. In this case, however, the symptoms appeared only on postoperative day 23, which is relatively late; such a delay could easily cause the condition to be misdiagnosed as pulmonary infection or pleural effusion. While CT is the preferred method for diagnosing mediastinal fistula and assessing its extent, gastroscopy enables the direct visualization of the location and size of the fistula. The combined use of both these modalities facilitates early and accurate diagnosis. Apart from ensuring effective drainage and initiating anti-infective therapy, maintenance of nutritional support is crucial. In the present case, early enteral nutrition was achieved via a jejunal feeding tube, whereby it was possible to maintain nitrogen balance as well as prevent gut barrier dysfunction and, consequently, reduce the risk of bacterial translocation.

The value of multidisciplinary collaboration in managing complex sequelae

One of the important factors contributing to the successful management of this case is the close collaboration between members of a multidisciplinary team, including the gastroenterology, thoracic surgery, radiology, and nutrition departments. The team jointly developed an individualized treatment plan that encompassed precise placement of the sinus tract drainage tube, closed thoracic drainage, nutritional support, and subsequent stricture dilation therapy. Additionally, the nursing department played a key role in drain maintenance, irrigation procedures, and patient education. Thus, our experience in this case suggests that integrated care is crucial in the management of complex esophageal complications.

The successful outcome in this case indicates that systematic conservative management is an effective treatment option for selected patients with delayed perforation and mediastinal fistula after ESD. The core principles of this systematic conservative approach include infection control, fistula drainage, and nutritional support. Furthermore, this case also stresses the importance of maintaining high vigilance for delayed perforation following ESD in patients with long-segment or circumferential esophageal lesions. Following ESD, close monitoring of clinical symptoms and timely imaging studies are necessary for early detection and timely intervention.

CONCLUSION

Our experience in this case suggests that although delayed perforation with mediastinal fistula is a severe and serious complication of ESD, adequate fistula healing and satisfactory patient recovery can be achieved with individualized conservative management within a multidisciplinary framework. The success of treatment mainly depends on several key factors: (1) Early diagnosis and intervention: Close monitoring of postoperative symptoms, combined with prompt CT and endoscopic examination, allows for early confirmation of perforation; (2) Combined infection control and mechanical drainage: Culture-guided, long-term antimicrobial therapy paired with low-pressure sinus irrigation and multi-site closed drainage helps eliminate mediastinal purulent accumulation; (3) Nutritional support strategy: Early placement of a jejunal feeding tube helps establish enteral nutrition, maintain positive nitrogen balance, and promote tissue repair; and (4) Individualized rehabilitation plan: Employing endoscopic dilation therapy addresses long-term complications such as esophageal stenosis and improve quality of life.

This case report serves as a valuable reference for the conservative management of severe post-ESD complications and more reports on similar experiences in actual practice are necessary to standardize therapeutic strategies for this entity.