Journal of Vascular Surgery
Volume 33, Issue 4 , Pages 868-873, April 2001

Primary aortoduodenal fistula in a patient with a history of intravesical therapy for bladder cancer with bacillus Calmette-Guérin: Review of primary aortoduodenal fistula without abdominal aortic aneurysm☆☆☆★

Lebanon, NH

From the Sections of Vascular Surgery,a Internal Medicine,b and Pathology,c Dartmouth-Hitchcock Medical Center

Received 25 April 2000; accepted 22 September 2000.

Article Outline

 

Primary aortoenteric fistula (PAEF) is defined as a communication between the native aorta and any portion of the gastrointestinal tract. PAEF differs from secondary aortoenteric fistula (SAEF), which occurs when a pathologic communication develops between a previously placed vascular graft and a portion of the gastrointestinal tract. PAEF is a rare condition, and since its first description in 1817, fewer than 230 cases have been reported worldwide.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 Although most of these cases involved an abdominal aortic aneurysm (AAA), some involved an aorta without an aneurysm. This case report describes a patient who had a primary aortoduodenal fistula (PADF) and no evidence of an AAA. Possible etiologic mechanisms are discussed, and the literature on cases of PADF without AAA is reviewed.

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Case report 

The patient was a 74-year-old man who came to our emergency department (ED) with gastrointestinal hemorrhage. While at home, hours before his arrival at the ED, he experienced weakness, diaphoresis, dyspnea, and light-headedness. On arrival at the ED, he passed two large, maroon stools. He reported feeling lightheaded and fatigued, but denied any abdominal pain, nausea, vomiting, diarrhea, fevers, chills, night sweats, or recent travel.

His medical history was significant for coronary artery disease. He underwent coronary artery bypass grafting 11 years earlier. He had a history of hypertension and previously asymptomatic diverticulosis. He had no documented history of tuberculosis (TB). One year earlier, he was diagnosed as having transitional carcinoma of the bladder and underwent a course of intravesical bacillus Calmette-Guérin (BCG) instillation with isoniazide (INH) prophylaxis. Shortly after his second course of therapy, he was admitted to the hospital with confusion, chills, high fevers, pancytopenia, and transaminitis. The results of a skin test were negative for TB. At the time, noncaseating granulomatous inflammation was revealed by means of a bone marrow biopsy. Acid fast stain (AFB) was negative. An INH hypersensitivity reaction against a primary BCG infection was empirically diagnosed and was treated supportively. The patient eventually recovered his cell counts, and he was discharged from the hospital.

On physical examination, he appeared ill. His supine blood pressure was 150/70 mm Hg, and his supine heart rate was 66 bpm. His upright vital signs were: blood pressure, 125/70 mm Hg; heart rate, 102 bpm. His respiratory rate was 22, and his temperature was 36.5°C.

His skin was pale and clammy. Sclera were anicteric, and mucous membranes were dry. Carotid pulses were full without bruits. Normal breath sounds bilaterally were revealed by means of chest auscultation. Regular S1 and S2 with no murmurs, rubs, or gallops were revealed by means of heart auscultation. The abdomen was mildly obese, soft, and non-tender, with no pulsatile mass.

No masses and a maroon, strongly guiac-positive stool in the vault was revealed by means of a rectal examination. Distal pulses were diminished.

Laboratory evaluation results included a hematocrit level of 30.6%, a white blood cell count of 6600, and a platelet count of 169,000. These values were disclosed by means of laboratory studies: sodium, 140 mmol/L; potassium, 4.0 meq/L; chloride, 105 mmol/L; bicarbonate, 26 mmol/L; blood urea nitrogen, 21 mg/dL; and creatinine, 1.0 mg/dL.

Nasogastric tube aspirate was strongly heme-positive.

The patient was admitted to the intensive care unit with a diagnosis of an upper gastrointestinal hemorrhage. On arrival, his blood pressure dropped to 70/40 mm Hg, he passed frank blood per his rectum, and vomited blood around his nasogastric tube. At this point, his hematocrit level was 20%.

Aggressive volume resuscitation was initiated with crystalloid and packed red blood cells. Blood in the stomach, an adherent clot in the third portion of the duodenum, and no other lesions were revealed by means of an esophagogastroduodenoscopy (EGD; Fig 1).

The results of an abdominal computed tomography (CT) scan were consistent with an aortoduodenal fistula and moderate compression of the third portion of the duodenum (Fig 2, A ).
  • View full-size image.
  • Fig. 2. 

    A, Abdominal computed tomography scan revealing what appeared to be 5-cm infrarenal abdominal aortic aneurysm with contrast penetrating the thrombus. This was later interpreted as contrast extravasation into the duodenum. B, A representative slice of comparison abdominal computed tomography scan from 1 year before presentation revealing no evidence of abdominal aortic aneurysm.

No evidence of an aneurysm of the abdominal aorta was found on an abdominal CT scan taken a year earlier (Fig 2, B).

The patient was taken to the operating room. On arrival, he experienced projectile bloody emesis, his systolic blood pressure dropped to 50 mm Hg, and his hematocrit level was 12%. During a laparotomy, he was found to have no intraperitoneal or retroperitoneal hematoma. There was edema in the retroperitoneal tissues, and the third portion of the duodenum was intimately associated with a nonaneurysmal infrarenal aorta.

The supraceliac aorta was clamped, and the infrarenal aorta was opened. There was a small punched-out opening in the wall of the lateral infrarenal aorta that directly communicated with the duodenum. Posterior to the aortoduodenal fistula and in communication with the aorta, there was a small cavity with fresh thrombus. The aortic wall surrounding the fistula was excised and sent for pathological and microbiological evaluation.

Direct reconstruction of the aorta was performed with a Dacron prosthesis that was presoaked in 60 mg/mL of rifampin. An omental flap was created and positioned over the graft. The duodenal defect was closed primarily.

The patient's postoperative course was complicated by respiratory insufficiency, an enterococcal urinary tract infection, and candidal sepsis. He was treated with a regimen of 2 weeks of intravenous cefotetan and 6 weeks of amphotericin B.

Many leukocytes but no organisms were shown by means of an aortic tissue Gram stain. The results of Gram and AFB stains were negative. The results of bacterial cultures were negative. The AFB culture was not sent.

Caseating granulomatous inflammation was revealed by means of a pathological evaluation of the aortic wall.

The patient was discharged on the 21st postoperative day. Antimycobacterial therapy was not initiated postoperatively because of the patient's mental status changes, previous adverse effects from INH, and his family's strong desire to avoid any further adverse drug reactions. Ten months later, the patient came to our hospital with pain and a pulsatile mass in the left thigh. Intraoperatively, he was found to have a pseudoaneurysm of the left superficial femoral artery. The pseudoaneurysm was repaired with a vein graft, and the patient had an uneventful recovery. No evidence of graft infection was shown by means of an abdominal CT scan. A culture of the pseudoaneurysm sample grew colonies that were Mycobacterium positive by means of a DNA probe. Ethambutol and rifampin therapy was initiated shortly after the patient's discharge. At 6 months' follow-up, the patient had no further symptoms.

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Discussion 

PAEFs are very rare. In one of the largest single institutional case series from the Netherlands, eight patients with a PAEF were treated in a 16-year period. This represents 0.18% of all patients coming to that institution with gastrointestinal hemorrhage.2 A recent review of 69 cases of PAEF revealed a 3-to-1 man-to-woman ratio and a mean age at presentation of 61 years (range, 23-91 years).3 Although PAEF can affect any part of the gastrointestinal tract, the duodenum, mostly its third and fourth portion, was involved in 82% of the cases. PADF is commonly associated with AAA, and the lack of this association is extremely rare.2, 3

A review of the English-language literature from the latter half of this century revealed 19 patients who were documented as having a PADF but no AAA (Table). The average age of these patients was 53 years (range, 23-81 years). All patients had gastrointestinal bleeding. Twelve patients (63%) had associated abdominal pain. Most patients had antecedent “herald bleeds” that preceded the major hemorrhage by as many as 14 months (15 patients [83%]). The most common modality used in patient evaluation was EGD. However, EGD and other radiologic modalities were usually nondiagnostic (Table). Most patients were taken to the operating room (16 patients [84%]) without a diagnosis. In addition, the diagnosis was still missed intraoperatively in 16% of the patients. Aortic replacement with a prosthetic graft was performed in four patients (22%), and primary aortic closure was performed in seven patients (39%). Most of those patients who underwent surgery died either during or within 30 days of the operation (10 of 16 patients [63%]). The overall mortality rate of PADF was 67% (12 patients). The origins of PADF included trauma from a swallowed pin,4 pancreatic cancer,5 peptic ulcer disease,6, 7 giant cell arteritis,8 and radiation therapy for malignancy.9, 10, 11 Two patients had tuberculous arteritis,12, 13 and one patient had streptococcal arteritis.14 In nine patients (47%), the exact etiology was unknown.15, 16, 17, 18, 19, 20, 21, 22

Table. Comparison of presentation, diagnostic modalities, treatment, and outcomes of reported cases of aortoenteric fistulas
Patient (age [y], sex)PresentationAntecedent herald bleedEvaluationDiagnosisOperationPathologic conditionOutcomeReference
30, MHematemesisn/an/an/an/aSwallowed pinn/a4
55, FHematemesis/melena, ABD pain1 monthBaSLaparotomy1° aortotomy WhippleInvasion by pancreatic carcinomaDeath, POD15
71, FABD pain, hematemesis, HX of esophagectomyNoIVP, EGD, ABD CT, BaEAutopsyCompletion gastrectomy2-cm duodenal ulcer; candidal infiltrationDeath, POD36
49, FPostprandial ABD pain for 3 years, hematemesis1 weekBaSAutopsyNone2-cm duodenal ulcerDeath7
55, MHematemesis, ABD pain, melena1 monthEGD, ABD USAutopsyNoneAortic round/giant cell inflammation; elastic lamina disruptionDeath8
63, FHematemesis, melena, ABD pain, HX of recent ABD XRT for metastatic breast cancer24 hoursEGDLaparotomy1° aortotomy distal duodenectomyRadiation aortitisAlive9
24, MHematemesis, HX of ABD XRT for testicular cancerNon/aLaparotomy1° aortotomyn/aDeath, POD110
41, MHematochezia, s/p ABD XRT for testicular cancer3 hoursEGDLaparotomy1° aortotomyRadiation aortitisAlive11
75, MHematemesis, ABD pain, hematochezia, HX of tuberculosis3 daysBaS, EGDLaparotomyDacron graft repairCaseating granulomas; AFB positiveAlive12
63, MHematochezia, hematemesis, HX of TB2 daysEGDLaparotomyDacron graft repairGranulomatous inflammationAlive13
60, FABD pain, fever, hematemesisNoIVP, ABD US, ABD CTUS: contained aortic ruptureAortic resection, attempted reconstructionPseudoaneurysm suppurative inflammation, Streptococcus viridans positiveIntra-operative death14
75, MHematemesis, melena24 hoursBaS, EGDLaparotomy1° aortotomyNon-specific inflammationAlive15
56, MABD pain, melena, hematemesis14 monthsEGD, BaE, ABD US, angiography, RBC scanAutopsyNegative laparotomyChronic inflammationDeath16
59, MHematemesis, hematochezia, ABD pain4 weeksEGD (3 times)Laparotomy1° aortotomy (Dacron patch)Granulomatous inflammation; AFB negativeIntra-operative death17
71, MHematemesis30 hoursEGDLaparotomyDacron graft repairn/aDeath, POD2418
23, MHematemesis, melena7 monthsEGD, BaS, ABD US, angiographyAngiography: aortic contrast extravation1° aortotomyNo inflammationAlive19
81, FABD pain, fever, hematemesis, melena24 hoursEGDLaparotomy—Atherosclerotic changesIntra-operative death20
38, FABD pain, fever, hematemesis36 hoursBaSLaparotomyTeflon graft repairNo inflammationDeath, POD221
23, FHematochezia, ABD pain7 monthsAngiography, sigmoidoscopy, EGDLaparotomy (3 times)—n/aIntra-operative eath22

M, Male; F, female; ABD, abdominal; HX, history; XRT, x-ray therapy; s/p, status post; TB, tuberculosis; n/a, not applicable; BaS, barium swallow; EGD, esophagogastroduodenoscopy; CT, computed tomography; BaE, barium enema; US, ultrasound; RBC, red blood cell; AFB, acid fast stain; PODx, preoperative diagnosis.

The patient presented in this report had a classic presentation of a primary PADF. The diagnosis was made by means of the combination of EGD and CT. Although the initial interpretation of the CT scan invoked the presence of an infrarenal AAA, this was neither substantiated at laparotomy nor supported by the subsequent review of the patient's earlier CT scan. The infrarenal aorta was of normal caliber, and, with the exception of the presence of edema around the fistula and a small collection of adjacent retroperitoneal thrombus, there were no other specific findings. Because of the concern for the presence of an occult infectious process and recent favorable experience with rifampin-bonded grafts,23 the aorta was replaced with a rifampin-soaked prosthetic graft. The patient recovered well, despite a prolonged hospitalization. The pathologic evaluation of the aortic wall surrounding the PADF was notable for the presence of caseating granulomas. This finding is of particular interest because of the patient's past treatment with intravesicular BCG and a previous episode of systemic primary BCG infection. Despite the negative results of an AFB stain, the patient's bone marrow contained evidence of granulomatous inflammation.

BCG is the attenuated strain of the bovine tuberculous bacterium and consists of living and dead bacilli, as well as subcellular debris. It has been used with success both as a vaccine against TB and as immunoadjuvant therapy for a number of cancers.24 Although most patients tolerate BCG well, major complications, including life-threatening sepsis, have been reported.24, 25 BCG is notoriously difficult to identify in tissue samples.24 Intravesical BCG injections in the treatment of bladder cancer have been associated with mycotic aneurysms of the infrarenal aorta26, 27 and femoral artery.28 These patients had BCG therapy 6 to 18 months before their initial examination, and most of these patients had associated collections that yielded positive mycobacterial stains and cultures.

Although we were not able to definitively identify BCG as an etiologic agent of PADF in our patient, it likely played a critical role. Our patient's immunosupression, lack of a history of TB, an episode of what appeared to be primary BCG infection with bone marrow granulomas, a primary aortoduodenal fistula without a degenerative AAA, and evidence of caseating granulomas in the aortic wall point to BCG as a likely culprit.

Furthermore, a subsequent pseudoaneurysm of the left superficial femoral artery, positive for mycobacteria, confirms our suspicion of a disseminated BCG infection. The duration of postoperative antimycobacterial therapy is controversial. However, life-long therapy is preferred by most experts after in situ aortic reconstruction.29

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Conclusion 

PADF without an AAA is a very rare entity, and only 19 cases have been reported in the modern English-language literature. This syndrome has a high mortality rate, and in almost half the patients, it has no obvious etiology. A high index of suspicion and prompt laparotomy are essential for a favorable outcome. This is the first report of two arterial perforations resulting from a BCG infection.

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References 

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☆ Competition on interest: nil.

☆☆ J Vasc Surg 2001;33:868-73.

★ Reprint requests: Richard J. Powell, MD, Section of Vascular Surgery, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756 (e-mail: Richard.Powell@Hitchcock.org ).

PII: S0741-5214(01)51947-3

doi:10.1067/mva.2001.112327

Journal of Vascular Surgery
Volume 33, Issue 4 , Pages 868-873, April 2001

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