Management of anastomotic leakage in upper gastrointestinal tract after oncologic surgery: Role of fully covered metallic stents

Abstract

BACKGROUND

Upper gastrointestinal anastomotic leakage (AL) is a life-threatening condition with high mortality rates and one of the most feared complications following surgery. Due to its challenging clinical management, a multidisciplinary approach is recommended. In the last decades, endoscopic devices and technical advancements have provided less invasive therapeutic alternatives to surgery. However, evidence on the best approach is still lacking. This study investigated the efficacy of fully covered self-expandable metallic stents (FCSEMS) in upper gastrointestinal tract AL management, in the oncology setting.

AIM

To evaluate the clinical effectiveness of FCSEMS in managing upper gastrointestinal AL after oncologic surgery.

METHODS

A retrospective cohort study was conducted at a tertiary care hospital. From December 2013 to December 2023, all consecutive patients who developed AL after upper gastrointestinal oncologic surgery and were treated with FCSEMS were included in the study. We analyzed clinical data, leakage characteristics, FCSEMS technical and clinical success, stent-related complications, and mortality.

RESULTS

A total of 70 patients (80% male, median age 65.5 years) were included. Surgery was performed due to esophageal (25.7%), esophagogastric junction (47.1%), and gastric (27.1%) cancers. Neoadjuvant treatment was administered in 68.6% patients; Ivor-Lewis esophagectomy (30%), McKeown esophagectomy (22.9%), and total gastrectomy (42.9%) were the most common surgeries. Intensive care unit admission occurred in 48.6%, and external drainage in 88.6%. Leakage size was < 20 mm in 80%; neoadjuvant therapy was associated with larger leaks (P = 0.029). Stent migration occurred in 31 cases. The average number of FCSEMS per patient was 1.5 (1-4); neoadjuvant therapy was associated with a higher number of stents (P = 0.011). Technical success was achieved in 95.7% of cases, with clinical success in 57 (81.4%) patients.

CONCLUSION

FCSEMS offer effective management of AL in the upper gastrointestinal tract. Specifically for oncological AL, their placement should be considered due to their high technical and clinical success rates.

Key Words: Anastomotic leakage; Oncologic surgery; Endoscopic management; Fully covered self-expandable metallic stents; Clinical success

Core Tip: Anastomotic leakage following upper gastrointestinal oncologic surgery is a life-threatening condition, for which optimal treatment is still not standardized. Fully covered self-expandable metallic stents are a validated endoscopic option with which our center has long-term experience. We retrospectively reviewed all patients treated with this modality (n = 70), from 2013 to 2023, and our findings demonstrate its effectiveness in the management of anastomotic leaks in oncological patients.

INTRODUCTION

Anastomotic leakage (AL) occurrence following upper gastrointestinal surgery is one of the most feared and severe complications. In fact, AL is associated with a significant health burden with elevated postoperative morbimortality reported[1]. Despite significant advances in surgical techniques and perioperative standardized protocols implementation, its incidence remains about 11.4% for esophagectomy[2] and 9% for gastrectomy[3].

In the oncological setting, AL poses an even greater threat, as patients are frequently frail, and postoperative complications can adversely affect their prognosis[4,5].

Although universally recognized as a life-threatening condition, consensus on the best therapeutic approach is still lacking. With the emergence of multiple endoscopic options, surgical intervention as the preferred therapeutic modality has been progressively replaced by less invasive ones.

Currently available endoscopic therapies, such as fully covered self-expandable metallic stents (FCSEMS), endoscopic vacuum therapy (EVT), endoscopic suture, tissue sealants, and cardiac septal occluders have all shown favorable results[6].

Esophageal stents enable defect sealing, thus contributing to sepsis control and mucosal healing, while also allowing early oral intake. Metallic stents seem to achieve superior outcomes to plastic[7], and their use is already recommended by the European Society of Gastrointestinal Endoscopy[8]. However, data on stent effectiveness, particularly in the oncological setting, are still limited, and prospective data comparing it to other endoscopic techniques are also lacking.

As more AL endoscopic treatment options arise, detailed knowledge regarding each modality’s outcomes is needed, in order to clarify their relative efficacy.

This retrospective analysis contributes to this knowledge, by evaluating the use of FCSEMS for upper gastrointestinal AL treatment in a tertiary oncological care center.

MATERIALS AND METHODS

Patients

A retrospective observational study was conducted in a tertiary care hospital. All consecutive patients were included who developed an AL following oncological upper gastrointestinal surgery between December 2013 and December 2023, and who were treated with FCSEMS.

Data collection

The variables analyzed included demographic data, tumor characteristics and treatment, leakage diagnostic details, timing of stent placement, duration of stent therapy, clinical and AL evolution, number of stents per patient, adverse events, technical and clinical success, need for additional/rescue therapy and overall mortality.

Endoscopic procedures

At our center, all stents were placed by experienced gastroenterologists, either in the endoscopy suite or in the intensive care unit (ICU), under deep sedation. Following diagnosis, all patients were kept nil-by-mouth and started antibiotics, as per protocol. When appropriate, external drainage of associated collections was also performed.

In the vast majority of patients, FCSEMS was the first-line endoscopic treatment. However, patients treated with FCSEMS only after the failure of another endoscopic modality were also included.

The clinical practice at our center is that surgical revision for AL is only performed after failure of endoscopic therapy. EVT for the esophagus only became available at our institution in 2019; therefore, it was only an option in the last 5 years of the study period. Due to the high burden of procedures that EVT places on the endoscopy unit, EVT was reserved as the first-line option for patients with AL associated infected cavities. Clips were only used as first-line option for AL smaller than 10 mm.

After leakage evaluation and multidisciplinary discussion, FCSEMS were placed over a guidewire, under direct endoscopic guidance, most frequently without fluoroscopy due to limited availability for urgent procedures. All stents were fully covered self-expanding metal stents, had a 23 mm body diameter and a length ranging from 100 mm to 150 mm. Proximal stent fixation using through-the-scope (TTS) clips (1 or 2) was performed at the endoscopist’s discretion, but not routinely.

Contraindications for FCSEMS placement: The presence of an AL related collection without external drainage; less than a 2 cm margin from the proximal margin of the leak to the upper esophageal sphincter.

A same-day chest radiograph was routinely performed to document correct stent positioning and exclude procedure-related complications. Liquid diet was started 6-12 hours after correct stent placement assessed by X-ray.

If the patient had a favorable clinical evolution, endoscopic revision with stent removal was typically performed at 6-8 weeks, under deep sedation, in the fluoroscopy room, for endoscopic and radiological evaluation (using iodine contrast instillation in the previous defect area) after stent removal. In the absence of a complete closure of the defect, a new stent was placed.

In any patient showing clinical decline, urgent endoscopy (usually preceded by a computed tomography [CT] scan) was performed to reassess stent placement and rule out adverse events.

Definitions

Technical success was defined as correct positioning of the FCSEMS after its deployment, resulting in AL effective sealing. This was determined by endoscopic findings and confirmed by same day radiography.

Clinical success was defined as complete closure of the defect, which was determined by endoscopy and/or radiological imaging with oral contrast after stent removal, or by a sustained asymptomatic evolution when the stent was left in place.

Partial clinical success was considered when, after stent removal, endoscopy revealed AL improvement without achieving complete closure, therefore requiring additional endoscopic therapy.

Therapeutic failure was defined as AL persistence after one or more stent placements.

Statistical analyses

Statistical analyses were performed using SPSS statistics software version 25 (IBM Corp., Armonk, NY, United States). For descriptive analysis, continuous variables are expressed as the mean ± SD and qualitative variables as n (%). For comparison of variables, the χ² test or Fisher’s exact test for categorical variables and Student’s t-test for continuous variables were employed. P < 0.05 was considered statistically significant.

Ethical considerations

All patients provided written informed consent for all the endoscopic procedures. The study was reviewed and approved by the Institutional Review Board of Instituto Português de Oncologia de Lisboa Francisco Gentil (Approval No. UIC/1781).

RESULTS

From December 2013 to December 2023, 70 patients with AL following upper gastrointestinal oncologic surgery were managed with FCSEMS at our center.

Fifty-six patients (80%) were male, with a median age at diagnosis of 65.5 (range 39.0-87.0) years. Patients’ clinical characteristics are summarized in Table 1.

Table 1 Clinical characteristics.

Variable	n (%)
Sex
Male	56 (80.0)
Female	14 (20.0)
Age (median, range)	65.5 (39.0-87.0)
Tumor location
Esophageal	18 (25.7)
Esophagogastric junction	33 (47.1)
Gastric	19 (27.1)
Histology
Adenocarcinoma	51 (72.9)
Squamous cell carcinoma	15 (21.4)
High grade dysplasia	2 (2.9)
GIST	2 (2.9)
Neoadjuvant treatment
None	22 (31.4)
Chemotherapy	13 (18.6)
Chemoradiotherapy	35 (50.0)
Surgery
Esophagectomy	37 (52.9)
McKeown	16 (22.9)
Ivor Lewis	21 (30)
Gastrectomy	31 (44.3)
Total	30 (42.9)
Atypical	1 (1.4)
Merendino surgery	2 (2.9)

GIST: Gastrointestinal stromal tumor.

In all patients, surgery was performed due to upper gastrointestinal cancer, namely esophageal (25.7%), esophagogastric junction (47.1%), and gastric (27.1%). The most frequently performed surgeries were Ivor-Lewis esophagectomy (30%), McKeown esophagectomy (22.9%), and total gastrectomy (42.9%) but atypical gastrectomy (1.4%) and jejunal interposition after distal esophagectomy and partial gastrectomy (Merendino; 2.9%) were also reported. These surgeries followed neoadjuvant treatment in 68.6% of patients. The most frequent tumor histology was adenocarcinoma (72.9%).

Before diagnostic endoscopy, 57.1% patients underwent imaging: CT (51.4%) or contrast esophagogram (5.7%). In all cases, AL diagnosis was established by endoscopy, which was performed at a median of 6.5 (1-85) days after surgery. FCSEMS was the initial treatment in almost all patients (95.7%). In the remaining 3 cases, EVT or over-the-scope clip (OTSC) were first attempted and failed and FCSEMS was placed subsequently. Considering only the patients primarily treated with FCSEMS, the mean interval between diagnosis and stent placement was 0.75 ± 1.3 (0-5) days.

Table 2 summarizes AL characteristics and stent therapy details.

Table 2 Fully covered self-expandable metallic stents treatment.

Variable	n (%)
Defect size (mm)
< 10	44 (62.9)
10-20	12 (17.1)
> 20	14 (20)
Location (cm)
< 25	25 (35.7)
25-30	15 (21.4)
> 30	30 (42.9)
CRP at diagnosis	312.1 ± 116.4
Predicted probability of stent success (9)
< 50% (score < 130)	6 (8.5)
50%-70% (score 111-170)	39 (55.7)
> 70% (score > 170)	25 (35.7)
Stents/patient
1	46 (65.7)
2	19 (27.1)
3	1 (1.4)
4	4 (5.7)

CRP: C-reactive protein.

The defect size was lower than 20 mm in the majority of patients (80%) and its location was the proximal esophagus (< 25 cm from incisors) in 35.7% of cases, the mid esophagus (25-30 cm from incisors) in 21.4% and the distal esophagus (> 30 cm from incisors) in 42.9%. These data, along with the C-reactive protein (CRP) levels at diagnosis, allowed us to calculate the predicted probability of success with stent therapy[9]: Only 6 patients showed a low chance of stent clinical success (score < 130).

TTS clips were used for stent fixation in 20% of cases.

A total of 106 FCSEMS were placed, with an average number of 1.5 (1-4) FCSEMS per patient. The median stent dwell time was 48.0 (9-115) days.

Due to the common occurrence of AL associated clinical complications, such as pleural effusion (42.4%), abscess (16.7%), empyema (18.2%) or pneumothorax (27.3%)—some of them causing single or multiple organ failure—34 (48.6%) patients required ICU admission. At least one external drainage thoracic tube was placed in the vast majority of patients (88.6%)—this decision was made on a case-by-case basis.

A total of 40 stent related adverse events were observed, corresponding to 36 (51.4%) patients, and only two were considered severe.

The most common complication was stent migration, occurring in 31 (30.1%) cases: 14 of these occurred within the first 24 hours after stent placement. Stent migration required stent endoscopic repositioning and TTS clip fixation, or stent removal followed by placement of another stent.

Additionally, 6 patients developed esophageal stenosis, all managed by endoscopic dilation. One of these patients also required biodegradable stent placement due to stenosis persistence.

Concerning hemorrhage, there were 3 occurrences: One episode of self-limited bleeding episode that required no specific therapy; 2 severe bleeding episodes due to aortoesophageal fistula development. Both of these were managed with thoracic endovascular aortic repair, but the procedure was only successful in one of the patients, the other one resulting in a fatal outcome.

No other stent-related complications were observed.

Outcomes and follow-up

Technical success was achieved in 103 (95.7%) stent placements. In the 3 remaining cases, FCSEMS failed to achieve immediate AL sealing due to distal migration and inability to achieve stent repositioning. A second FSCEMS was successfully placed in all 3 cases.

Clinical success was observed in 57 (81.4%) patients: From these, in 38 cases defect closure was documented by endoscopy after stent removal; in 19 patients the stent was left in place due to disease progression, but no AL related clinical decline occurred, which was consistent with effective closure.

In 2 other patients, despite not achieving complete clinical success, revision endoscopy revealed AL improvement. Therefore, a complementary endoscopic therapy was employed (OTSC), ultimately achieving complete defect closure.

In 11 patients (15.7%), no significant improvement was seen after FCSEMS therapy. These patients underwent alternative therapies: Surgical revision (6 patients), EVT (4 patients); in one patient with a poor oncological prognosis, a jejunostomy was performed for nutritional support, without further attempts at AL closure.

Representative endoscopic images of an anastomotic leak, stent placement and complete defect closure are shown in Figure 1.

Figure 1 Endoscopic image. A: Endoscopic image of an anastomotic leakage in an esophageal anastomosis (arrow); B: Endoscopic image after stent placement; C: Endoscopic image after stent removal with no defect.

There were no leak recurrences in the patients considered as clinical successes during the follow-up period, defined as the time from the first FCSEMS placement to the last patient contact. The mean follow-up period was 701.4 ± 775.8 days.

At the end of follow-up, the overall mortality rate was 68.6%, with 48 deaths to report: Only one death was related to stent therapy (aortoesophageal fistula); 17 were attributed to leak associated complications; 27 were considered leak unrelated, as they were attributable either to oncologic disease progression or to complications related to preexisting comorbidities; and 3 were due to unknown causes.

Regarding outcome prediction, no statistically significant associations were found between clinical success and patient sex (P = 0.219), age (P = 0.792), tumor type (P = 0.878), tumor histology (P = 0.661), neoadjuvant treatment (P = 0.472), type of surgery (P = 0.888), the predicted probability of success (P = 0.967) or time since diagnosis to stent placement (P = 0.462). Furthermore, no association could be found between TTS prophylactic placement and stent migration (P = 0.253).

However, neoadjuvant treatment was significantly associated with larger defects (AL > 20 mm; P = 0.029) and higher number of stents requirement (P = 0.011).

In the multivariate analysis, no statistically significant associations were observed, likely due to the limited sample size.

DISCUSSION

AL remains one of the most challenging complications following upper gastrointestinal surgery, for which the optimal therapeutic approach is not yet determined. As endoscopic alternatives emerge, the ideal method for each patient is still under debate and, currently, this choice is mostly determined by local expertise and devices availability.

Endoscopic stenting has been used in our center for over a decade. In our cohort, therapy with FCSEMS achieved a high technical success rate and a clinical success rate of 81.4%—a favorable outcome that is consistent with previously published data (65%-86%)[10,11]. In 54% of the patients, AL closure was endoscopically and radiologically confirmed after stent removal and in the 19 patients in whom stent removal was not attempted due to disease progression there was no clinical evidence of leak persistence, although we cannot exclude overestimation of the clinical success.

Some of our patients’ clinical and leak related features may have contributed to this successful outcome. In fact, most of the patients (80%) had a leak smaller than < 20 mm and in 91.4% of cases the predicted probability of success was higher than 50% (based on 4 clinical predictors: Etiology of the leak, location of the leak, baseline CRP level, and size of the leak)[9,12].

Another factor to consider is the short delay between AL diagnosis and FCSEMS placement, with a mean of 0.75 ± 1.3 days. Considering our center substantial experience with upper gastrointestinal surgery, our team developed a high clinical suspicion for AL occurrence, aiming at an early intervention. In fact, early stent placement has been shown to improve outcomes by limiting infectious complications and promoting healing[13].

Although previous studies have shown that neoadjuvant treatment does not seem to increase AL incidence[14], in our series it was significantly associated with larger defects (P = 0.029) and with a higher number of stents needed per patient (P = 0.011). However, there was no difference in clinical success of AL stenting between patients with or without previous neoadjuvant treatment. As such, neoadjuvant treatment interference with AL remains to be clarified.

In our series there was no significant correlation between the type of surgery/anastomosis location and the success of the FCSEMS endoscopic therapy, but our small numbers limit the analysis.

Regarding adverse events, stent migration was, as expected, the most frequent one, occurring in 30.1% of patients. The exclusive use of FCSEMS in our center may have contributed to this number. However, we did not find any clinical or endoscopic factors associated with its occurrence, nor did stent migration seem to influence overall clinical success. Additionally, no difference in migration rate was observed between stents fixated with TTS clips and those without.

Recently, stent fixation methods other than TTS clips have been described such as OTSC clip[15] and endoscopic suture[16]. Their use has been associated with lower migration rates so hopefully in the future these promising devices may contribute to reduce stent adverse events and consequently decline the number of additional endoscopic procedures. The cost-effectiveness of these different approaches remains to be evaluated.

There were only two severe adverse events reported, both consisting of bleeding due to aortoesophageal fistula, one of which resulted in a patient’s death. This a well described complication of SEMS and, although its exact incidence is unknown, some series report it in up to 10% of cases, with the main risk factors including repeated dilations, previous radiotherapy, proximal stricture location, and inappropriate stent choice[17]. Our incidence was much lower, but the high mortality of this complication was confirmed.

The overall mortality reported in this cohort should be interpreted in the context of a specialized oncologic center, the inherently high-risk nature of the surgeries performed, and the advanced age of the patients.

Our study had some limitations. First, its retrospective and single-center nature could lead to bias. As a standard protocol for AL management is lacking, several stent related decisions - such as choosing FCSEMS as the first line therapy, stent fixation, stent dwell time and the need for further intervention (e.g., repeat stenting vs alternative endoscopic therapy)—were mostly guided by the endoscopist’s clinical judgment and preference. Finally, endoscopies were performed by multiple operators, which may have contributed to even more variability.

Nonetheless, our 10 years of experience in treating AL in oncological patients yields valuable knowledge and the study reflects clinical practice at our institution, where surgical revision for AL is only performed after failure of endoscopic therapy. During the first 5 years of the study period, EVT was unavailable as an alternative to FCSEMS and latter it was mainly used as first line therapy only for AL with associated infected cavities.

As alternative endoscopic techniques became more widely available, particularly EVT, research comparing its effectiveness with FSCEMS is evolving[18]. In the future, we hope that robust, prospective, randomized controlled studies will definitively provide evidence on the optimal therapeutic management of these patients. Until then, our findings support the use of FCSEMS as a successful first line treatment option, especially for patients with defects under 20 mm.

CONCLUSION

While the ideal endoscopic method for AL closure has not yet been established, our long-term experience managing oncological patients with FCSEMS reveals high technical and clinical success rates. Our results support this as a safe and effective endoscopic therapy and are in agreement with current guideline recommendations.