EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : Pancreas transplantation, Pancreatectomy, Simultaneous pancreas and kidney transplant, Y-graft anastomosis

Mycotic pseudoaneurysms are an infectious arteritis that can lead to destruction of the arterial wall and are associated with high morbidity and mortality from arterial rupture, hemorrhage, or fulminant sepsis. Prompt diagnosis and intervention are critical for a successful patient outcome. Mycotic pseudo-aneurysms are a rare but life-threatening complication after pancreas transplant. Most pseudoaneurysms occur at the site of arterial anastomosis, but these can also result from a biopsy, surgical damage, graft pancreatitis, and bacteremia.¹ Common causative organisms in pancreas transplant patients are Candida species and Gram-negative enteric bacteria.² The standard of care for mycotic pseudoaneurysms has traditionally entailed open surgical repair of the pseudoaneurysm and graft pancreatectomy.³ In recent years, there have been case reports of endovascular management of mycotic pseudoa-neurysms in pancreas transplant recipients.^1-6 In this case study, we describe a staged endovascular and surgical approach to safely manage a large mycotic pseudoaneurysm in a recipient of a simultaneous pancreas and kidney transplant.

A 53-year-old male patient with insulin-dependent type 2 diabetes mellitus and end-stage renal disease underwent a simultaneous pancreas and kidney transplant. He was on hemodialysis for 6 months prior to transplant. His past medical history included hypertension and stroke. The donor was a 33-year-old woman with brain death secondary to anoxia from a drug overdose, with a terminal creatinine of 0.4 mg/dL. Baseline donor blood and urine culture results were negative. Induction immunosup-pression was solumedrol and rabbit anti-thymocyte globulin. The pancreas allograft arterial Y graft was anastomosed to the right common iliac artery (CIA), and the allograft portal vein was anastomosed to the recipient inferior vena cava. Enteric pancreatic exocrine drainage was achieved with a duodenoenterostomy to the recipient ileum. The kidney was anastomosed to the left external iliac vessels, and a standard Lich-Gregoir ureteroneocystostomy was performed. Both organs showed immediate graft function, and the patient was discharged home on postoperative day 14. Maintenance immunosuppression was prednisone, mycophenolate mofetil, and tacrolimus.

The patient reported dizziness and falls at home on postoperative day 46. He was admitted for treatment of orthostatic hypotension and received transfusion of 2 units of packed red blood cells for refractory anemia (hemoglobin 7.3 mg/dL). He was discharged after resolution of symptoms post-transfusion. He presented to the emergency department the following night with fever and rigors. The laboratory test results were notable for hemoglobin of 9.1 mg/dL and leukopenia. Pan-cultures were performed, and broad-spectrum antibiotics were initiated. Ultrasonography of the transplant pancreas demonstrated a pseudoaneurysm. Urgent magnetic resonance angiography was perfor-med and confirmed the presence of a large (6.3 cm × 5.1 cm × 5 cm), bilobed pseudoaneurysm arising from the right CIA, below the patent arterial Y graft of the transplant pancreas. Magnetic resonance angiography reconstructions and subsequent angiogram (Figure 1A) suggested a complete disruption of approximately 2.5 cm of the CIA wall. We proceeded with endovascular stent placement to occlude the pseudoaneurysm, as there was a high risk of rupture. We knew that the stent placement would concurrently sacrifice the pancreas allograft arterial inflow and necessitate transplant pancreatectomy (Figure 1B). After endovascular stent placement, we proceeded with laparotomy for transplant pancreatectomy. Vascular surgery was included in operative planning for potential lower extremity revascularization, with regard to the potential need to ligate the CIA, EIA, and hypogastric arteries.

Intraoperatively, the transplant duodenum was identified, and gastrointestinal anastomosis staplers were used to divide a short segment of the recipient ileum containing the duodenoenterostomy. The transplant pancreas portal vein and arterial Y graft were identified and divided with endovascular staple loads. The body and tail of the transplant pancreas were mobilized with a combination of blunt and sharp dissection until the pseudoaneurysm cavity was entered. The CIA wall had been eroded by the infection, and a long segment of the covered stent was exposed within the pseudoaneurysm (Figure 1C). Proximal vascular control was obtained on the right CIA at the aortic bifurcation. Distal vascular control was obtained by isolation of the EIA and hypogastric arteries. Extensive debridement was required to safely ligate the CIA, EIA, and hypogastric arteries. During this debridement, the endovascular stent was found to have only a few millimeters of purchase on the proximal and distal CIA. Bowel continuity was restored with an enteroenterostomy, the abdomen was extensively irrigated, surgical drains were placed in the operative bed, and the abdomen was closed. The operative field was then re-prepped for a femorofemoral bypass with an 8-mm ringed polytetrafluoroethylene graft and lower extremity 4-compartment fasciotomies.

The preoperative blood and urine cultures and intraoperative cultures grew Pseudomonas aeruginosa. The patient completed a 6-week course of intravenous antibiotics followed by an additional 3 months of oral antibiotic therapy. He maintained excellent renal allograft function (creatinine 1.5 mg/dL) at 18 months after transplant.

Mycotic pseudoaneurysms are a rare vascular complication that can occur after pancreas transplant and have very high risk of morbidity and mortality. Risk factors for mycotic pseudoaneurysms in pancreas transplant recipients include perioperative infection, enteric anastomotic leak, and peripancreatic abscess.^1,6 Although mycotic pseudoaneurysms are more common with enteric exocrine drainage, these have also been seen after bladder exocrine drainage.⁶ The overall incidence of pseudoaneurysm in pancreas allografts has been reported to range from 0.3%6 to 0.8%2 in the modern era. However, recent studies suggest that noninfected pseudoaneurysms are often unrecognized in pancreas allografts, particularly in nonfunctioning allografts.⁷

Pseudoaneurysms can present a diagnostic challenge, as signs and symptoms are often subtle. Additionally, pseudoaneurysms frequently present years after graft failure or pancreatectomy, which may lead to delayed diagnosis^1,2,4,6,7-10 (Table 1). Prior case reports have documented the importance of a high index of clinical suspicion when faced with pancreas transplant recipients with fatigue, refractory anemia, allograft dysfunction, abdominal pain, a sentinel retroperitoneal bleed, or unexplained source of gastrointestinal bleeding.^1,6 Any of these clinical scenarios should prompt dedicated imaging surveillance to rule out the presence of a pseudoaneurysm. Delayed diagnosis can lead to pseudoaneurysm rupture, with hypotension and life-threatening hemorrhage associated with high morbidity and high mortality.² In retrospect, our patient had fatigue and refractory anemia for 7 weeks posttransplant, but these symptoms were attributed to postoperative deconditioning and medication side effects. Diagnostic imaging surveillance of his pancreas allograft mycotic pseudoaneurysm was delayed until he developed fever and rigors.

The size, location, and presence/absence of infection are all critical factors that affect clinical decisions regarding pseudoaneurysms. Endovascular approaches have been used as definitive therapy for noninfectious pseudoaneurysms in pancreas allografts, particularly those presenting years after transplant in a nonfunctioning pancreas allograft^1,4,11-15 (Table 1). In the studies cited in Table 1, for the 6 patients who presented with a noninfectious pseudoaneurysm in a functioning allograft, endovascular interventions were successful in graft salvage in 4 cases (75%) (Table 1). However, it is notable that coil embolization succeeded as a definitive therapy in only 2 of 9 patients (22%) when it was used as the initial treatment.^1,6-8,12-15 Green and colleagues performed coil embolization to treat a pseudoaneurysm of the pancreas graft superior mesenteric artery.¹² However, the patient required pancreatectomy after presenting with recurrent bleeding 2 weeks later.¹² Higgins and colleagues reported a simultaneous pancreas and kidney transplant recipient who presented with a massive gastrointestinal bleed and underwent coil embolization in 2 separate procedures, before ultimately dying during the third episode of bleeding.⁷ Likewise, endovascular stent placement was required after coil embolization failed to occlude pseudoaneurysms in the pancreatic arterial Y graft1 and EIA.¹⁵ Coil embolization is likely best used as a temporization procedure when faced with massive hemorrhage after pseudoaneurysm rupture.^13,14 Coil embolization achieved prompt arrest of bleeding after pseudoaneurysm rupture in 2 patients, allowing stabilization and resuscitation of the patients prior to graft pancreatectomy.^13,14

Endovascular interventions have been used to treated mycotic pseudoaneurysms in pancreas transplant recipients^1-6 (Table 2). Endovascular stent placement has proved to be a valuable primary intervention for mycotic pseudoaneurysms in pancreas allografts. Endovascular stents can improve the safety of surgical graft pancreatectomy and can reduce transfusion requirements.¹ However, endovascular stent placement into an infected site is associated with a high likelihood for persistent sepsis and recurrent pseudoaneurysm with the attendant risks for rupture, hemorrhage, and death.² Thus, transplant patients must be carefully monitored after endovascular interventions for recurrent mycotic pseudoaneurysms. In this case report, our patient presented with a large mycotic pseudoaneurysm with significant erosion of the arterial wall. We placed an endovascular stent as a bridge to definitive surgical intervention. Finally, there is no consensus for the duration of antibiotic therapy after mycotic pseudoaneurysm treatment. In transplant recipients, especially those who remain on immunosuppression, a prolonged course of several months of intravenous antibiotic therapy is typically coupled with serial imaging surveillance for evidence of recurrent pseudoaneurysm.²

Volume: 21 Issue: 2 February 2023

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