Peptic esophageal perforation in Zollinger-Ellison syndrome: a case report of a rare and severe complication

Introduction

Zollinger-Ellison syndrome (ZES), first described by Zollinger and Ellison nearly 80 years ago, is a rare disorder caused by gastrin-secreting neuroendocrine tumors, typically found in the pancreas or duodenum (1). The resulting hypergastrinemia causes severe peptic ulcer disease, with complications including gastric-duodenal perforations and, more rarely, esophageal peptic perforations. Although resection can normalize gastrin levels, delayed diagnosis and surgery often result in significant complications (2). Esophageal perforation may occur despite proton pump inhibitor (PPI) therapy, especially in cases of suboptimal dosage or poor compliance. This condition is challenging to manage and is associated with high morbidity and mortality (3). Its rarity often leads to delayed recognition, and patients frequently present in a critically ill state with sepsis and mediastinal or pleural contamination. Management is further complicated by the fragility of the esophageal tissue, which is often chronically inflamed due to severe esophagitis, making primary repair unsuitable and increasing the need to consider alternative treatment options (4,5).

We describe a case of peptic esophageal perforation in a 51-year-old woman with ZES from a known prepyloric gastrinoma. We present this article in accordance with the CARE reporting checklist (available at https://aoe.amegroups.com/article/view/10.21037/aoe-25-20/rc) (6).

Case presentation

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The requirement for institutional review board approval and informed consent for publication of this case report, accompanying images and the videos was waived in accordance with the policy on “Use And Disclosure Of Patient Information for Case Studies Guidelines” (Policy No. DHARE.800.20.048; effective December 11, 2023) that applies to Dignity Health Arizona Research Enterprise and its Direct Affiliates and Subsidiaries.

A 51-year-old Caucasian woman presented to an outside hospital with nausea and vomiting, intractable abdominal pain, and melena. Her history was notable for hypertension and prior surgical repair of a perforated duodenal ulcer eight months earlier, during which a prepyloric mass was biopsied and diagnosed as a gastrinoma. She was started on pantoprazole 80 mg twice daily, with positron emission tomography/computed tomography (PET/CT) planned for staging, which was delayed due to insurance issues. The patient had a 10-pack-year smoking history, denied alcohol consumption, and had a body mass index of 20.6 kg/m².

Three days prior to presentation, a gallium-68 DOTATATE PET/CT scan revealed activity along the lesser curvature of the stomach and in lymph nodes within the porta hepatis.

Upon admission, laboratory results showed a hemoglobin of 5.6 g/dL and a white blood cell count of 12.9×10⁹/L. Abdominal CT was performed, revealing duodenal thickening and extraluminal air around the esophagus on the lower chest cuts. However, the latter finding was initially missed by the radiologist and only identified on later review. Consequently, management in the emergency department focused on the anemia and duodenal thickening. High-dose intravenous PPIs (80 mg twice daily) were initiated, and an upper endoscopy was performed. The endoscopy identified a bleeding duodenal ulcer (Forrest class Ib), which was treated with epinephrine injection and cautery. Additionally, Los Angeles grade D esophagitis was noted, without evidence of bleeding. A CT performed the next day showed a right hydropneumothorax, prompting chest tube placement. Due to clinical deterioration, the patient was transferred to our institution for a higher level of care.

On arrival, she was tachycardic, hypotensive (blood pressure: 90/55 mmHg), and hypoxic (SpO₂: 85% on room air). Laboratory studies revealed a hemoglobin of 7.2 g/dL and an elevated white blood cell count of 15.4×10⁹/L. Esophagram and CT confirmed a distal esophageal perforation with contrast extravasation into the right chest (Figure 1A,1B), and therefore, surgery was planned.

Figure 1 Diagnostic imaging of the esophageal perforation. (A) Esophagram demonstrating contrast extravasation from the distal esophagus. (B) Computed tomography scan showing oral contrast extravasation from the distal esophagus.

Given her previous laparotomy, a right-sided video-assisted thoracoscopic approach was chosen. The procedure was performed by an experienced foregut surgeon of more than 20 years. After lung decortication and mediastinal exposure, a 7-mm perforation was identified in the distal esophagus (Video 1). The perforation had developed in an area of chronic inflammation and was characterized by thick, fibrotic edges. Intraoperative endoscopy confirmed the perforation about 1 cm proximal to the EGJ, surrounded by severe esophagitis. Primary repair was deemed unsafe due to fibrotic edges and a chronic inflammatory state. Therefore, a 19-Fr silicone T-tube was placed inside the perforation and secured with absorbable sutures (Video 2). A 19-Fr Blake drain was placed alongside the esophagus, and two chest tubes were placed in the pleural space. A nasogastric tube was advanced endoscopically into the distal stomach.

Postoperatively, the patient received intravenous broad-spectrum antibiotics and high-dose intravenous PPI therapy, resulting in gradual improvement of her septic condition. Serum gastrin levels were markedly elevated, exceeding 2,000 pg/mL (normal <100 pg/mL). The hepatobiliary team was then consulted. On POD 4, the patient underwent distal gastrectomy, locoregional lymphadenectomy with Billroth II reconstruction, and jejunal feeding tube placement. Pathological examination revealed a 1.5-cm, well-differentiated grade 2 gastrinoma with 4 of 18 positive lymph nodes (T2N1). After surgery, the serum gastrin level decreased to <10 pg/mL. A postoperative swallow study performed on POD 10 from thoracoscopic surgery showed no esophageal extravasation and a mild distal esophageal stricture.

The patient was discharged on POD 18 on a clear liquid diet while maintaining the T-tube, with a plan to reassess her 2 weeks later. However, twelve days after discharge, she returned with difficulty managing secretions. Endoscopy revealed severe distal esophageal stenosis without residual perforation or visible T-tube. Therefore, the T-tube was removed, and an esophageal stent was placed. Recurrent stent migration led to a switch to serial endoscopic dilations. At 11-month follow-up, the patient remains in good clinical condition, continues to undergo periodic dilations, and is able to tolerate oral intake. The feeding tube has been removed. The case report timeline is shown in Figure 2.

Figure 2 Timeline summarizing the patient’s diagnostic workup, surgical interventions, and postoperative course. Created in https://BioRender.com. CT, computed tomography; T, time; POD, postoperative day.

Discussion

ZES results from gastrin-secreting tumors (gastrinomas) that lead to hypergastrinemia, severe peptic ulcers, reflux, and chronic diarrhea. Around 80% of gastrinomas are sporadic, whereas 20% to 30% are associated with multiple endocrine neoplasia type 1 (MEN-1), an autosomal dominant condition characterized by endocrine tumors or hyperplasia affecting multiple endocrine glands (7). Our patient was not evaluated for MEN-1 during the current admission but was referred to her hometown hospital for appropriate workup as determined by her oncology and gastroenterology providers. Unfortunately, the results are not available to us.

Early detection and surgery in non-metastatic cases yield a 15-year survival of over 80%, but 25% to 50% of patients present with metastatic disease and have a worse prognosis (8,9). Timely treatment is essential not only to improve oncological outcomes but also to prevent complications such as duodenal bleeding/perforation and peptic esophageal stricture/perforation, which carry high morbidity (10-12). Earlier resection of our patient’s tumor at the time of diagnosis more than eight months prior might have prevented this complication. Somatostatin analogues could also have contributed to disease control (13); however, detailed information regarding her prior oncological management is unavailable, and her lack of insurance may have limited access to these therapies.

Although PPIs have significantly reduced the incidence of reflux-related complications, their effectiveness is highly dependent on adequate dosing and patient adherence. In rare instances, severe complications such as erosive esophagitis, strictures, and even perforation have been reported despite maximal PPI therapy (14,15). In this context, newer agents like vonoprazan, a potassium-competitive acid blocker, may offer superior acid suppression. However, vonoprazan had not been used in our patient, and current evidence supporting its efficacy in patients with a gastrinoma is still limited (16,17). One possible reason for the development of the perforation in our case is that, despite being prescribed pantoprazole 40 mg twice daily, the patient may have been a non-responder or may not have been taking the medication as prescribed, potentially due to her insurance issues.

Although the patient presented with vomiting, Boerhaave syndrome was excluded as a possible diagnosis given the chronically inflamed and fibrotic nature of the perforation margins, which are uncommon in an acute, spontaneous tear.

To the best of our knowledge, only a few cases of peptic esophageal perforation in patients with ZES have been reported, making this case a valuable addition to the limited existing literature (4,5,15,18). Reported cases have been treated with stent placement/diversion associated with drainage, or gastroesophageal resection. Uniquely, our case describes the successful management of such a perforation using T-tube drainage. A primary repair was considered unsafe due to the presence of chronically inflamed and fibrotic margins of the perforation as well as marked inflammation in the surrounding tissue. Goldstein and Thompson (18) reported a case of esophageal perforation with similar characteristics, treated with thoracotomy tube placement and nasogastric intubation; however, the patient died shortly after surgery due to complications.

In the context of an already septic patient, T-tube placement was selected as the safer option. The T-tube provided reliable control of the leak, allowing effective drainage, thereby reducing the risk of further contamination and facilitating gradual healing. Additionally, the anatomical location of the perforation (i.e., approximately 1 cm proximal to the EGJ) posed a particular challenge. This region is known to be a high-risk site for stent migration (19). Attempting stent placement in this setting could have led to displacement and thus to uncontrolled leakage and further clinical deterioration (our thought process in this regard was unfortunately proved correct, as stents placed at later dates promptly migrated). The T-tube approach was favored not only for its technical feasibility but also for its ability to mitigate the risks associated with both primary repair failure and stent migration in a critically ill patient.

T-tube control of a fistula has been reported as an effective treatment for esophageal perforation, particularly in delayed presentations (20,21). In these situations, inflammation results in friable or fibrotic tissue at the perforation site, making primary repair unfeasible and the T-tube placement a suitable option. Although the etiology of inflammation in our case was different, the local tissue characteristics and clinical context closely mirrored those reported in the literature where T-tube placement was successfully employed.

The postoperative swallow study performed on day 10 showed no opacification of the T-tube. This finding may be explained either by obstruction of the tube or by healing of the defect. The latter is further supported by the complete closure of the perforation and the absence of the T-tube in the esophagus at the time of readmission endoscopy (POD 30), suggesting that closure may have already occurred at the time of the swallow study. In either case, we believe the T-tube fulfilled its intended role, as the leak was now absent, fulfilling a primary priority in this septic patient.

In general, T-tube drainage should be considered a salvage option. Primary repair is preferred but requires healthy margins to be successful. Stenting is another viable alternative; however, it carries significant risks, including worsening reflux and migration, particularly when the perforation is near the EGJ and acid secretion is uncontrolled. These conditions applied to our case, particularly as a definitive treatment plan for the underlying gastrinoma had not yet been established at the time of perforation management. Therefore, given its potential complications, and the critical need for a reliable leak control, stent placement was considered a high-risk option.

Our patient subsequently developed esophageal stenosis, necessitating periodic endoscopic dilations. Notably, a mild stricture was already apparent on the preoperative esophagram, possibly due to severe inflammation secondary to esophagitis. The progression of the stricture after the tumor resection likely reflected the combined healing process of both the perforation and the underlying severe esophagitis. Similarly, Ito et al. (5) described a case of esophageal perforation in a patient with ZES and severe esophagitis who developed a stricture following primary repair, which eventually required esophageal resection. It is possible that the use of a covered self-expanding stent instead of T-tube placement during the initial management would have prevented the risk of stricture formation.

Although covered stent placement is an established treatment option for esophageal perforation (22,23), it is not without limitations. A major concern is stent placement near the EGJ, where a stent may fail to achieve adequate mucosal apposition due to its tubular design, resulting in compromised sealing of the perforation and an increased risk of migration (24,25). In our case, the risk of incomplete or failed leak containment was a critical factor during the acute phase and strongly influenced the decision to choose T-tube drainage over stenting. Notably, a covered stent was later used to manage the post-healing stricture. We anticipated that the stricture would minimize the risk of stent migration; however, displacement occurred shortly after placement. This also confirmed our initial concerns regarding persistent leakage risk with the use of stent therapy. While adjunctive fixation techniques such as clips or suturing are valid options, they were not employed in this case (26).

Interestingly, Shaik et al. (4) reported the case of a 67-year-old man who presented with an esophageal perforation 38 cm from the incisors, and was later diagnosed with ZES. He was treated with stent placement and robotic posterior mediastinal drainage and discharged without major complications. This case highlights the evidence that covered stents can be a viable treatment option for esophageal perforation when the anatomical conditions are favorable and the risk of migration is deemed low by the surgical team.

Lastly, it is worth noting that the esophageal perforation in our patient may have been caused or exacerbated by the upper endoscopy performed to treat the bleeding duodenal ulcer, particularly given that the perforation was not identified during the procedure. However, the pre-endoscopy CT had already demonstrated extraluminal air around the esophagus, which was not recognized at the time but only on subsequent review of the images. Moreover, while esophageal perforation is a rare but recognized complication of endoscopy, particularly in the presence of severe esophagitis (27), the intraoperative findings in this case suggest a more chronic and progressive process. The esophageal wall at the site of perforation, as noted during surgery, was thickened and fibrotic, consistent with longstanding inflammation rather than acute trauma. These findings suggest that the perforation likely developed spontaneously, secondary to the hypersecretory state. Although the contribution of endoscopic instrumentation cannot be definitively ruled out, the overall clinical, radiologic, endoscopic, and intraoperative evidence points more to a chronic, progressive process that likely preceded the endoscopy and was overlooked during the initial examination.

This study has several limitations. As it describes a single patient, the findings cannot be generalized to the broader population. Case reports are inherently limited in their evidentiary strength and primarily serve to generate various options to manage a problem rather than defensively promote a particular treatment plan. Moreover, the observer’s subjectivity might bias the quality and interpretation of the observation.

Conclusions

This case highlights a rare but life-threatening complication of ZES, peptic esophageal perforation, which was successfully managed through a combination of interventions, including washout, T-tube drainage, and definitive treatment of the underlying gastrinoma. In the context of chronic inflammation and the high-risk anatomical location near the EGJ, creating a controlled fistula with T-tube drainage offered a safe and effective alternative to primary repair or stenting. As the first reported case of T-tube placement for an esophageal perforation in a patient with ZES, it adds to the limited literature and may inform future management in similarly high-risk patients.

Acknowledgments

We would like to thank Kristine Nally for her editorial assistance. Our abstract was accepted for presentation at Digestive Disease Week 2025, San Diego, California, taking place between the 3^rd and 6^th of May, 2025.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://aoe.amegroups.com/article/view/10.21037/aoe-25-20/rc

Peer Review File: Available at https://aoe.amegroups.com/article/view/10.21037/aoe-25-20/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoe.amegroups.com/article/view/10.21037/aoe-25-20/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The requirement for institutional review board approval and informed consent for publication of this case report, accompanying images and the videos was waived in accordance with the policy on “Use And Disclosure Of Patient Information for Case Studies Guidelines” (Policy No. DHARE.800.20.048; effective December 11, 2023) that applies to Dignity Health Arizona Research Enterprise and its Direct Affiliates and Subsidiaries.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg 1955;142:709-23; discussion, 724-8.
2. Rossi RE, Elvevi A, Citterio D, et al. Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World J Gastroenterol 2021;27:5890-907. [Crossref] [PubMed]
3. Shehata Z, Alasmar M, Altarawni M, et al. Spontaneous compared with iatrogenic esophageal perforation: A comparison between etiologies. Surgery 2025;186:109572. [Crossref] [PubMed]
4. Shaik MR, Shaik NA, Kunarathnam V, et al. Esophageal Perforation Unveiling the Diagnosis of Zollinger-Ellison Syndrome. J Community Hosp Intern Med Perspect 2023;13:77-81. [Crossref] [PubMed]
5. Ito S, Ogawa R, Komura M, et al. Severe esophageal stricture after perforation and necrotizing esophagitis: unusual presentation of a duodenal gastrinoma. J Surg Case Rep 2023;2023:rjad679. [Crossref] [PubMed]
6. Gagnier JJ, Kienle G, Altman DG, et al. The CARE guidelines: consensus-based clinical case reporting guideline development. BMJ Case Rep 2013;2013:bcr2013201554. [Crossref] [PubMed]
7. Metz DC, Cadiot G, Poitras P, et al. Diagnosis of Zollinger-Ellison syndrome in the era of PPIs, faulty gastrin assays, sensitive imaging and limited access to acid secretory testing. Int J Endocr Oncol 2017;4:167-85. [Crossref] [PubMed]
8. Mendelson AH, Donowitz M. Catching the Zebra: Clinical Pearls and Pitfalls for the Successful Diagnosis of Zollinger-Ellison Syndrome. Dig Dis Sci 2017;62:2258-65. [Crossref] [PubMed]
9. Weber HC, Venzon DJ, Lin JT, et al. Determinants of metastatic rate and survival in patients with Zollinger-Ellison syndrome: a prospective long-term study. Gastroenterology 1995;108:1637-49. [Crossref] [PubMed]
10. Bondeson AG, Bondeson L, Thompson NW. Stricture and perforation of the esophagus: overlooked threats in the Zollinger-Ellison syndrome. World J Surg 1990;14:361-3; discussion 363-4. [Crossref] [PubMed]
11. Nirula R. Esophageal perforation. Surg Clin North Am 2014;94:35-41. [Crossref] [PubMed]
12. Roy PK, Venzon DJ, Shojamanesh H, et al. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine (Baltimore) 2000;79:379-411. [Crossref] [PubMed]
13. Guarnotta V, Martini C, Davì MV, et al. The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the treatment of the gastrinoma? Endocrine 2018;60:15-27. [Crossref] [PubMed]
14. Chen QN, Bai BQ, Xu Y, et al. Sporadic gastrinoma with refractory benign esophageal stricture: A case report. World J Clin Cases 2024;12:1284-9. [Crossref] [PubMed]
15. Ng T, Maziak DE, Shamji FM. Esophageal perforation: a rare complication of Zollinger-Ellison syndrome. Ann Thorac Surg 2001;72:592-3. [Crossref] [PubMed]
16. Imagawa N, Sato T, Tanaka K, et al. A case of severe esophagoduodenal ulcers associating zollinger-ellison syndrome successfully treated by vonoprazan fumarate, a novel potassium-competitive acid blocker. Endosc Forum Dig Dis 2015;31:135-40.
17. Patel A, Laine L, Moayyedi P, et al. AGA Clinical Practice Update on Integrating Potassium-Competitive Acid Blockers Into Clinical Practice: Expert Review. Gastroenterology 2024;167:1228-38. [Crossref] [PubMed]
18. Goldstein LA, Thompson WR. Esophageal perforations: a 15 year experience. Am J Surg 1982;143:495-503. [Crossref] [PubMed]
19. Chou IT, Yu FJ, Shih HY, et al. Risk factors of stent migration in esophageal cancer patients who underwent fully-covered self-expanding metal stents for malignant dysphagia or tracheoesophageal fistula. J Formos Med Assoc 2025;124:432-8. [Crossref] [PubMed]
20. Do YW, Lee CY, Lee S, et al. Successful Management of Delayed Esophageal Rupture with T-Tube Drainage Using Video-Assisted Thoracoscopic Surgery. Korean J Thorac Cardiovasc Surg 2016;49:478-80. [Crossref] [PubMed]
21. Nakabayashi T, Kudo M, Hirasawa T, et al. Successful late management of esophageal perforation with T-tube drainage. Case Rep Gastroenterol 2008;2:67-70. [Crossref] [PubMed]
22. Fairbairn K, Worrell SG. Esophageal Perforation: Is Surgery Still Necessary? Thorac Surg Clin 2023;33:117-23. [Crossref] [PubMed]
23. Gray KE, Sarode A, Jiang B, et al. Surgical Repair vs Stent for Esophageal Perforation: A Multi-institutional Database Analysis. Ann Thorac Surg 2023;115:1378-84. [Crossref] [PubMed]
24. Freeman RK, Van Woerkom JM, Vyverberg A, et al. Esophageal stent placement for the treatment of spontaneous esophageal perforations. Ann Thorac Surg 2009;88:194-8. [Crossref] [PubMed]
25. Khaitan PG, Famiglietti A, Watson TJ. The Etiology, Diagnosis, and Management of Esophageal Perforation. J Gastrointest Surg 2022;26:2606-15. [Crossref] [PubMed]
26. Park KH, Lew D, Samaan J, et al. Comparison of no stent fixation, endoscopic suturing, and a novel over-the-scope clip for stent fixation in preventing migration of fully covered self-expanding metal stents: a retrospective comparative study (with video). Gastrointest Endosc 2022;96:771-9. [Crossref] [PubMed]
27. Bhatia NL, Collins JM, Nguyen CC, et al. Esophageal perforation as a complication of esophagogastroduodenoscopy. J Hosp Med 2008;3:256-62. [Crossref] [PubMed]