Ann Thorac Surg 2005;80:1115-1117
© 2005 The Society of Thoracic Surgeons
Case report
Hyperbaric Oxygen Treatment of Hemorrhagic Radiation-Induced Gastritis After Esophagectomy
Kemp H. Kernstine, MD, PhD
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,
J. Eric Greensmith, MD, PhD,
Frederick C. Johlin, MD,
Gerry F. Funk, MD,
Daniel T. De Armond, MD,
Timothy L. Van Natta, MD,
Daniel J. Berg, MD
Departments of Surgery, Anesthesia, Internal Medicine, Otolaryngology, and Medical Oncology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Accepted for publication February 23, 2004.
* Address reprint requests to Dr Kernstine, Division of Cardiothoracic Surgery, Department of Surgery, The University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Room 1616-B JCP, Iowa City, IA52242-1009; (Email: kemp-kernstine{at}uiowa.edu).
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Abstract
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My colleagues and I present 2 cases of hemorrhagic postesophagectomy gastritis after chemoradiotherapy for esophageal cancer. On the basis of the location of the gastritis (lesser curve and midstomach) and the classic radiation injury appearance, radiation damage was believed to be the cause. In both patients, hyperbaric oxygen therapy rapidly arrested bleeding. This is the first description in which hyperbaric oxygen therapy was used to treat hemorrhagic postesophagectomy gastritis.
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Introduction
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Multicenter neoadjuvant esophageal cancer trials have reported conflicting survival results. An improved pathologic response in a small cohort patients treated with the novel regimen of paclitaxel, carboplatin, continuous fluorouracil, and concurrent radiation therapy (PCFR) has recently been reported [1]. My colleagues and I report a life-threatening bleeding complication of this regimen and its successful management with hyperbaric oxygen (HBO) therapy.
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Case Reports
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Patient 1
A 68-year-old man experienced hemorrhagic gastritis 4 to 5 weeks after an uncomplicated nontubed stomach transhiatal esophagectomy for a 2.5-cm distal esophageal T3 N0 adenocarcinoma. Before the operation, the patient received PCFR with 45 Gy of radiation. Four weeks after discharge, he presented with weakness, a hematocrit of 24%, and stools with occult blood. Upper gastrointestinal endoscopy showed bleeding radiation gastritis (Fig 1). There were no ulcers or bile staining, and the gastric conduit pH was 7 to 8. Biopsy samples were Helicobacter pylori negative. He had no bleeding history, and the coagulation profile was normal. Abdominal ultrasound was negative for splenic vein thrombosis and portal hypertension, and hepatic transaminases, bilirubin, and albumin were normal.
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Fig 1. Bleeding gastritis found in patient 1. Telangiectasias and edematous friable gastric mucosa were consistent with radiation injury [12]. The damage appeared in the midportion of the gastric conduit, an area within the radiation portal. The antrum and the anastomosis appeared healthy; thus, conduit stasis and hypoperfusion were less likely.
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Over several weeks we performed a variety of maneuvers to arrest the bleeding. Oral nutrition was stopped and parenteral nutrition started. We treated him with sequential attempts of propranolol, nitroglycerin paste, and an intravenous proton pump inhibitor while monitoring 24-hour gastric pH, cholestyramine, and oral 
-aminocaproic acid [2]; a combination of topical thrombin, Gelfoam (Pharmacia, Peapack, NJ), and sucralfate; and endoscopic laser therapy.
After 11 weeks and numerous maneuvers, the patient bled a total of 60 U of blood. He refused gastrectomy. Prompted by successful treatment of radiation-injured tissues, we treated the patient with HBO. Within 3 days his hematocrit stabilized, and the melena resolved. Repeat endoscopy 2 weeks later demonstrated almost complete resolution of bleeding and gastritis (Fig 2). The patient received 30 HBO treatments that consisted of 3 continuous-cycle sessions of 30 minutes of 100% oxygen and 10 minutes of room air at 45 feet of seawater (35.28 pounds per square inch) by using an oxygen administration facial hood while in a Perry Multiplace (Perry BaroMedical, Riviera Beach, FL). Each session lasted 2.5 hours. Now, 23 months later, there has been no further bleeding, dysphagia, or evidence of recurrence.
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Fig 2. Endoscopic view of the gastric conduit after 2 weeks of hyperbaric therapy in patient 1. Telangiectasias, friability, and active bleeding have resolved. Edema is still present.
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Patient 2
A 57-year-old man with a 5-cm T3 N1 distal esophageal adenocarcinoma and fine-needle aspiration–positive multiple nodal station periesophageal lymph nodes also experienced postesophagectomy gastric conduit bleeding 7 weeks after operation. Fluorodeoxyglucose positron emission tomography (PET) was suggestive of widely metastatic disease. Without confirmatory biopsy, the cancer was considered stage IV and treated with definitive PCFR with 64 Gy of radiation.
Repeat PET scan and endoscopy demonstrated only residual activity at the primary disease site. The patient was referred for possible resection. Because we doubted his original PET-based stage, a right-sided 3-hole 2-field esophagectomy was performed 10 weeks after the completion of his chemoradiation. No viable tumor was found in the surgical specimen or any of the 20 lymph nodes.
Seven weeks after operation, he complained of weakness. His hematocrit was 25%, and a stool occult blood test was positive. Esophagogastroscopy demonstrated radiation injury; HBO was initiated, and bleeding was arrested within 3 days. Now, 18 months later, the patient has had no further bleeding or dysphagia. Two months ago the patient presented with an isolated brain metastasis, for which he received radiation therapy. Further chemotherapy was administered.
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Comment
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These 2 cases represent an alarming complication of induction chemoradiotherapy: uncontrollable persistent bleeding in the gastric conduit 1 to 2 months after esophagectomy. For patient 1, we reviewed our induction protocol, compared his treatment with that of other protocol patients, and discussed the case with other esophageal cancer programs and have found no reported bleeding complications with standard induction therapy.
Induction therapy with PCFR has a high reported response rate, with nearly 50% of patients having a pathologic complete response (CR) [1]. CR patients are more likely to be cured by the multimodality approach. The PCFR CR is more than twice the response seen in other induction protocols. We have not seen postesophagectomy radiation-induced hemorrhagic gastritis in our subsequent patients.
Bleeding gastritis has occurred from radiotherapy and may be potentiated by the administration of concurrent fluorouracil [3]. The prevalence of subclinical hemorrhagic gastritis may be more frequent than realized, because asymptomatic postesophagectomy gastric conduit ulcers are present in more than 5% of patients [4]. In contrast, these 2 patients had sufficiently bled to warrant investigation.
Normal tissues in proximity to a targeted neoplasm may develop a ballooning degeneration with ischemia and cell death that is dose dependent, resulting in sloughing and bleeding [3, 5]. HBO serves as a stimulus to develop neovascularity in tissues rendered hypoxic as a result of late-onset radiation damage [6]. It is effective in radiation-damaged vagina [7], bladder [8], bowel and rectum [9], and head and neck osteoradionecrosis [10]. After 10 or more treatments, neovascularity becomes apparent, growing in from the wound edges [6]. After 20 to 30 HBO exposures, angiogenesis becomes complete. Successful HBO therapy outcome in our 2 patients, particularly given the lack of response to the other aggressive maneuvers, strongly suggests a role for HBO in treating this vexing complication of neoadjuvant therapy.
There have been 3 prior case reports of successful postesophagectomy bleeding gastric conduit treatment. In one report [11], gastrectomy was performed. Oral -aminocaproic acid [2] and argon beam coagulation [12] were successful in 2 patients. These were not options or did not stop the bleeding in our patients.
There is no evidence that providing HBO to cancer patients will result in cancer recurrence or poorer survival. Patient 1 is nearly 2 years from the date of his esophagectomy for stage II disease and has had no evidence of recurrence; patient 2 had stage IV disease, which recurred in the brain.
Postesophagectomy gastric conduit bleeding is a rare complication. In our 2 cases, it appeared to be due to preoperative radiotherapy, possibly accentuated by concurrent chemotherapy. Other causes, such as venous congestion, ischemia, stasis, and H pylori infection, seem unlikely. HBO seems to be a safe and effective alternative treatment for this complication.
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References
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- Meluch AA, Hainsworth JD, Gray JR, et al. Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancerpreliminary results of a Minnie Pearl Cancer Research Network phase II trial. Cancer J Sci Am 1999;5:84-91.[Medline]
- Grover N, Johnson A. Aminocaproic acid used to control upper gastrointestinal bleeding in radiation gastritis Dig Dis Sci 1997;42:982-984.[Medline]
- Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation Int J Radiat Oncol Biol Phys 1991;21:109-122.[Medline]
- Uchida Y, Tomonari K, Murakami S, Hadama T, Shibata O, Shirabe J. Occurrence of peptic ulcer in the gastric tube used for esophageal replacement in adults Jpn J Surg 1987;17:190-194.[Medline]
- Marx R. Radiation injury to tissueIn: Kindall EP, Whelan HT, editors. Hyperbaric medicine practice. 2nd ed. Flagstaff, AZ: Best Publishing; 1999. pp. 665-723.
- Marx RE, Johnson RP. Studies in the radiobiology of osteoradionecrosis and their clinical significance Oral Surg Oral Med Oral Pathol 1987;64:379-390.[Medline]
- Williams Jr JA, Clarke D, Dennis WA, et al. The treatment of pelvic soft tissue radiation necrosis with hyperbaric oxygen Am J Obstet Gynecol 1992;167:412-416.[Medline]
- Bevers RF, Bakker DJ, Kurth KH. Hyperbaric oxygen treatment in haemorrhagic radiation cystitis Lancet 1995;346:803-805.[Medline]
- Woo TC, Joseph D, Oxer H. Hyperbaric oxygen treatment for radiation proctitis Int J Radiat Oncol Biol Phys 1997;38:619-622.[Medline]
- Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosisa randomized prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc 1985;111:49-54.[Abstract]
- Yeung YP, Ho CM, Wong KH, et al. Surgical treatment of recalcitrant radiation-induced gastric erosions Head Neck 2000;22:303-306.[Medline]
- Morrow JB, Dumont JA, Vargo II JJ. Radiation-induced hemorrhagic carditis treated with argon plasma coagulator Gastrointest Endosc 2000;51:498-499.[Medline]
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Abstract
Introduction
