Treatment of Popliteal Artery Aneurysms by Means of Cryopreserved Homograft Luca Mezzetto,1 Lorenzo Scorsone,1 Rosario Pacca,1 Giovanni Puppini,2 Simone Perandini,2 and Gian Franco Veraldi,1 Verona, Italy
Background: Autologous saphenous vein is considered the gold standard conduit in the femoralepopliteal revascularization for popliteal artery aneurysms (PAAs). In several cases, it may be absent or unsuitable for length or diameter and so it may be considered unfit for a conduit. In such patients, a synthetic graft or the endovascular correction can be useful, but results are controversial. In this retrospective case series, we have analyzed the safety and efficacy of the cryopreserved homograft (CHg) as a conduit in the PAA revascularization. Methods: In the period between January 2005 and December 2013, 54 PAAs have been treated with an arterial CHg. Indications to surgery were asymptomatic aneurysm with >25-mm diameter in 30 cases (55.6%), ischemic symptoms in 20 (37%), and compressive symptoms in 4 (7.4%). An urgent treatment was performed in 8 cases (14.8%) for severe ischemic symptoms. All cases have been operated by the same vascular team: a posterior surgical approach was preferred whenever possible (33 cases, 61.1%). All patients received a clinical and radiologic follow-up, and all data were collected in a specific database. A >10-mm diameter increase of the conduit was considered significant for an aneurysmatic degeneration. Results: The primary outcomes were complications and reoperation rate, limb salvage, and primary and secondary patency. Secondary outcome was the incidence of aneurysmatic degeneration of the CHg. Mean diameter of the homografts was 6.3 mm (range, 4e8 mm). In the 30-day postoperative period, 7 PAAs (13%) developed a complication: 3 wound infections, 3 graft thrombosis, and 1 anastomotic bleeding. Six cases needed a reoperation: 2 surgical revascularizations, 2 wound debridement, and 1 anastomotic hemostasis; 1 major amputation was necessary for graft failure after the revascularization. Mean follow-up was 34.8 months (range, 1e96). Five cases (9.3%) developed a graft complication with 4 reoperations necessary (7.4%): 2 grafts required a percutaneous transluminal angioplasty for a perigraft stenosis and 2 underwent a femorodistal bypass in CHg for severe ischemic symptoms after CHg occlusion. Another one CHg occlusion was treated conservatively because it was clinically asymptomatic. Primary patency was 96.3%, 93.9%, and 88.3% at 12, 36, and 60 months, respectively; secondary patency was 98.1% at 12, 36, and 60 months. Freedom from amputation resulted in 98.1%. No aneurysmatic degeneration was observed. Univariate and multivariate analysis showed urgent surgery to be independent risk factors for complications, reoperations, and CHg occlusion (P < 0.05). Conclusions: In this retrospective study, the use of CHg showed to be safe and effective in the surgery of PAAs, either in the short or in the long-term follow-up. Urgent surgery can be considered predictive of graft failure. In our experience, CHg can be considered a good alternative conduit to the autologous saphenous vein.
1 Department of Vascular and Endovascular Surgery, Azienda Ospedaliera Universitaria Integrata di Verona, Polo Chirurgico ‘‘P. Confortini’’, Verona, Italy. 2
Unit of Interventional Radiology, Azienda Ospedaliera Universitaria Integrata di Verona, Polo Chirurgico ‘‘P. Confortini’’, Verona, Italy. of
Correspondence to: Gian Franco Veraldi, MD, Department Vascular and Endovascular Surgery, Azienda Ospedaliera
1090
Universitaria Integrata di Verona, Italy; E-mail: gianfranco.veraldi@ ospedaleuniverona.it Ann Vasc Surg 2015; 29: 1090–1096 http://dx.doi.org/10.1016/j.avsg.2015.02.007 Ó 2015 Elsevier Inc. All rights reserved. Manuscript received: November 2, 2014; manuscript accepted: February 26, 2015; published online: May 19, 2015.
Vol. 29, No. 6, August 2015
INTRODUCTION Popliteal artery aneurysm (PAA) represents a rare but potentially limb-treating condition. Treatment may be challenging especially in case of large or symptomatic aneurysms. The most common procedure is ligation followed by autologous bypass using a great saphenous vein (GSV) conduit with medial or posterior approach. Indication of this procedure is strictly related to the availability of a suitable autologous saphenous vein, whereas the use of a synthetic graft remains controversial. Since the 90s, the development of the endovascular repair has obtained fair results in selected cases; however, further evidence and follow-up data are still required. Cryopreserved homograft (CHg) conduit may be considered a valid alternative to the autologous vein although there is a substantial lack of data in the literature: different authors report varying results with a significant risk of thrombosis and aneurysmatic degeneration. The purposes of this study were to report our single-center experience and to evaluate early and long-term results of the CHg bypass in the treatment of PAAs, both in the elective and in the urgent setting.
METHODS Clinical data of 54 consecutive PAAs treated by means of a CHg bypass at the Department of Vascular and Endovascular Surgery of Verona, Italy, between January 2005 and December 2013 were retrospectively reviewed. Primary outcomes were complications and reoperation rate, limb salvage, and primary and secondary patency. Secondary outcome was the incidence of aneurysmatic degeneration of the CHg. Recommended standards were followed for indications, complications, and patency rates. Acute and chronic ischemias were defined according to the Rutherford classification. Indication for the surgery procedure included: acute leg ischemia with salvageable limb (class I and II), critical chronic limb ischemia (class IV, V, and VI), signs of distal embolization, compressive symptoms (i.e., leg edema, popliteal vein thrombosis, numbness, and pain), or asymptomatic PAAs with diameter >25 mm. Infective complications were classified as grade I, grade II, and grade III if the subcutaneous tissue, the muscle plane, and the vascular plane were involved, respectively. Bleeding complications were considered as major if a surgical reoperation was necessary (i.e., for
Popliteal artery aneurysm by means of cryopreserved homograft 1091
hemodynamic instability or compressive symptoms) and as minor if a conservative management was indicated. All the procedures were conducted by the same vascular team. All CHgs were obtained by the same Tissue Bank Foundation of Treviso, Italy, located approximately 150 km east from our institution. A cryopreserved GSV or iliac artery was used according to the anatomic criteria of the patient and the tissue availability of the bank. Grafts were usually delivered in a few hours. All the grafts were sent defrosted and ready for the implantation. The CHg did not need to be matched to patients by ABO and Rh compatibility, and no immunosuppressive agents were used. If PAA extended above the Hunter canal or in case of acute leg ischemia, a medial approach was chosen; in all other cases, a posterior was preferred. Moderate acute ischemia (class IIa) with tibial vessels occlusion was considered an indication for preoperative locoregional thrombolysis with our standard protocol (urokinase 200,000 UI bolus followed by 100,000 UI/hr, maximum 48 hr). Cases with severe acute ischemia (IIb) with tibial vessels occlusion were managed with immediate surgical thrombectomy and graft implantation. All patients underwent clinical and instrumental evaluation including duplex ultrasound at 30 days, 6 months, 12 months, and then, once a year. A straight follow-up or a second-level radiologic investigation with computed tomography angiography (CTA) or magnetic resonance angiography (MRA) was performed in case of any complication. Indication for reoperation included: extensive local infection (Grade IIeIII), major bleeding, graft occlusion with acute limb ischemia, and significative anastomotic or intragraft stenosis (>70% or peak systolic velocity ratio >2). Aneurysmatic degeneration was defined as an increase of the transversal diameter of the graft exceeding 10 mm during the follow-up. Primary graft patency was defined as a patent graft that did not require any reoperation to restore flow after occlusion. Secondary patency was defined as a patent graft that required a new surgical procedure after occlusion in addition to all cases of primary patency. Statistical analysis was conducted by using SPSS 20 software (SPS Inc, Chicago, IL). Cumulative graft patency was assessed by the KaplaneMeier method. Risk factors for complications, reoperations, and graft failure were estimated with univariate and multivariate analysis, chi-squared test, and binary logistic regression. ManneWhitney test was used as a nonparametric test. A P value < 0.05 was considered of statistical significance.
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RESULTS A total of 54 PAAs in 49 patients were treated (5 bilaterally). Of these, 18 had a concomitant abdominal aortic aneurysm. All but one (97.9%) were men, whereas 8.1% had a previous infrainguinal revascularization. Demographic data are summarized in Table I. A preoperative second-level radiologic investigation (CTA or MRA) was obtained in all cases. The average maximum popliteal diameter was 33 mm (range, 15e54 mm); the mean length was 43 mm (range, 21e94 mm). At the time of diagnosis, 30 PAAs were asymptomatic, 4 presented compressive symptoms, and 20 presented ischemic symptoms (Table II). Fortysix (85.6%) PAAs were treated with elective surgery and 8 were treated in an urgent setting for severe ischemic symptoms (critical ischemia, class IV-V-VI or acute ischemia, Class IeII). A posterior surgical approach was preferred in 33 cases. Mean operative time was longer for urgent procedures (230 min; range, 145e350 min) than in the elective ones (195 min; range, 115e300 min), although not statistically significant (P > 0.05). Associated procedures were necessary in 10 cases (18.5%), all in the urgent procedures: 3 PAAs required an intraoperative thrombectomy of tibial vessels and 7 required a preoperative fibrinolysis. At least one patent tibial vessel was obtained before the beginning of the graft implantation. In all cases, the morphologic characteristics of the CHg were considered satisfactory for the conduit (Table III). Mean preoperative CHg diameter was 6.3 mm (range, 4e8 mm). Mean hospital stay was 7 days (range, 4e12 days). Early results (within 30 days from the operation) showed 7 complications (13%): 1 major bleeding requiring surgical hemostasis, 3 local infections (1 grade II infection treated conservatively and 2 grade III infections treated with surgical debridement and muscular coverage), and 3 early graft occlusions that required urgent revascularization for acute ischemic symptoms (thrombectomy and reanastomosis). One major amputation was necessary for immediate graft failure after revascularization. Mean follow-up was 34.8 months (range, 1e96). Five cases (9.3%) developed graft complications. Four reoperations were necessary (7.4%): in 2 cases, the graft required balloon angioplasty (percutaneous transluminal angioplasty) for a perigraft stenosis, and in other 2 cases, a femorodistal bypass for severe ischemic symptoms after CHg occlusion was required. One CHg occlusion was treated conservatively because it was asymptomatic.
Annals of Vascular Surgery
Table I. Demographic data and risk factors of 49 patients with 54 PAAs Demographics
No
%
No. of PAA (no. of patients) Gender Male/female Mean age, years (range) Cardiac diseasea Diabetes mellitus Arterial hypertension Renal insufficiencyb Current smoke Previous ipsilateral revascularization Mean PAA diameter, mm (range) Mean PAA length, mm (range)
54 (49)
d
48/1 72 (40e91) 20 18 33 9 21 4 33 (15e54) 43 (21e94)
98/2 40.8 36.7 67.3 18.3 42.8 8.1 d d
a History of cardiac ischemia or moderate and/or severe cardiac dyspnea. b Serum creatinine >1.5 mg/dL.
Table II. Clinical assessment of PAA presentation Clinical assessment
No
%
Elective/urgent Asymptomatic Ischemic symptomsa Class I Class II Class III Class IV-V-VI or acute ischemia (class IeII) Compressive symptoms
46/8 30 20 7 3 2 8
85.2/14.8 55.6 37.0 13.0 5.6 3.7 14.8
a
4
7.4
From Rutherford Classification.
Table III. Comparison between arterial and venous homografts
Graft type
No. of cases
Graft stenosis/ occlusion
Aneurysmatic degeneration
Arterial homograft Venous homograft Total
49 5 54
6 2 8
d d d
Primary patency was 96.3%, 93.9%, and 88.3% at 12, 36, and 60 months, respectively. Secondary patency was 98.1% at 12, 36, and 60 months (Figs. 1 and 2). Freedom from amputation resulted in 98.1% (Fig. 3). Univariate and multivariate analyses show that urgent surgery for severe ischemic symptoms is a statistically significant independent risk factor for early complications (P ¼ 0.004, odds ratio, 14.3;
Vol. 29, No. 6, August 2015
Popliteal artery aneurysm by means of cryopreserved homograft 1093
Fig. 1. Primary patency (96.3%, 93.9%, and 88.3% at 12, 24, and 60 months, respectively).
Fig. 3. Freedom from major amputation.
Fig. 2. Secondary patency (98.1% at 12, 24, and 60 months).
Fig. 4. Freedom from 30-day complication (elective versus urgent surgery).
95% confidence interval, 2.3e87.9), reoperations (P ¼ 0.03, odds ratio, 11.9; 95% confidence interval, 1.2e111.7), and graft failure (P ¼ 0.03, odds ratio, 0.08; 95% confidence interval, 0.09e0.78; Figs. 4e6). Mean increase of transversal graft diameter was 4.1 mm (range, 0e8 mm), and no significative aneurysmatic graft degeneration was observed.
unavailable or unfit superficial veins. In such cases, a synthetic bypass (either made of polytetrafluorethylene or Dacron) is an interesting opportunity. This option suffers from suboptimal results, especially in cases of poor runoff or in cases where a distal revascularization is required. Ravn et al.2 confirmed fair results by using a GSV conduit with a lesser risk of amputation compared with the use of prosthetic grafts in a study of 717 legs followed up to 18 years. The endovascular approach continues to be exciting. Since 1994, after the experience of Marin et al., different authors reported series of PAAs treated by this minimally invasive approach.3e5 Pulli et al. published a recent multicenter analysis comparing 178 open surgery cases versus 134 endovascular procedures. They concluded that both
DISCUSSION The bypass procedure using the GSV conduit is considered the reference technique in the treatment of PAAs. Huang et al.1 analyzed 358 PAAs treated with different conduits and concluded that GSV had the best results at 10 years of follow-up. However, it is common experience to find patients with
1094 Mezzetto et al.
Fig. 5. Freedom from 30-day reoperation (elective versus urgent surgery).
Fig. 6. Primary patency (elective versus urgent surgery).
treatments are feasible and safe, providing satisfactory early and long-term results as long as a careful selection of patients in term of clinical and anatomic characteristics has been previously carried out.6 Despite the good outcomes of the previously mentioned cases series, different reviews concluded that, with the exception of high-risk patients, it is difficult to justify a routine endovascular treatment in PAAs.7,8 CHg has been proposed as an alternative solution in patients requiring a peripheral revascularization lacking proper superficial veins. Theoretically, it would represent an optimal compromise between an autologous and a synthetic material, with favorable results especially in the case of local infectious complications. Practically, for many years, the use of such an option has been discussed, highlighting different critical aspects and uncertain results that
Annals of Vascular Surgery
lead to limited indications. In particular, this conduit has been reported to be prone to early thrombosis and late aneurysmatic degeneration. In 1993, Walker et al.9 concluded that CHg offered better results than a synthetic conduit, but its use should be deferred until improved preparation techniques could provide a more durable conduit. Similarly, Harris et al.10 obtained similar unexciting results. More recently, in the 15-year long experience of Randon et al., the analysis of 108 CHg bypasses showed satisfactory results; the study deemed an improved graft and patient selection, a stricter graft surveillance and an immunologic matching mandatory to improve outcomes.11 Part of the cited authors obtained their results in selective cases, especially while dealing with the management of a previous graft infection, which represents one of the most challenging complication in the vascular practice.12e15 No data are available about the routine use of the CHg conduit in the elective or urgent surgery of PAA. In an early period of our experience, we used the CHg conduit in selected patients only, and in particular, in those with absent or unfit saphenous vein. During follow-up, as we were witnessing very satisfactory mid-term results, we extended the indications to all patients with PAA. All our patients were operated by the same vascular team that learned, during the years, what we consider the best intraoperative management of the CHg conduit. The conduit was managed with great care, avoiding direct clamping, traction, or leaving redundant segments during the revascularization. We consider these few rules of paramount importance to reduce the risk of CHg failure. The analysis of early follow-up (within 30 days from the operation) showed an incidence of 13% (7 of 54) of complications, of which 6 cases (11.1%) required a reoperation. Wound infection was documented in 5% of cases but no graft complications occurred in these patients, confirming the good resistance of the material. Three early graft occlusions were observed and required a prompt reoperation for acute ischemic symptoms. In all cases, a thrombectomy and a new anastomosis was required. Both cases presented with severe ischemic symptoms and one was subsequently amputated for early graft occlusion. During long-term follow-up, 3 grafts occluded. Two patients required a reoperation for acute ischemic symptoms and one was treated conservatively. All had a favorable evolution with limb preservation.
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Acute limb ischemia due to PAA is a challenging complication, with a 20e60% incidence of limb loss and up to 12% of mortality reported in the literature.16e20 The analysis of our results confirmed that urgent surgery for severe ischemic symptoms (critical ischemia, class IV-V-VI or acute ischemia, class IeII) is an independent factor risk for early complication, reoperation, and graft failure. Poor runoff is probably the cause of the failed graft in our group, and it is likely independent from the nature of conduit. Aneurysmatic degeneration of the CHg conduit has been described; however, the real incidence rate is unknown. Bisdas et al.21 reported only 1 case of aneurysmatic degeneration in 110 aortic revascularizations with CHg (1.7%). Other cases series reported similar rates.22 Kieffer et al. described 2 possible causes for graft degeneration, a mechanical one and an immune-mediated one,23e25 but the real mechanism remains unknown.26,27 No data are available regarding this particular complication in PAA revascularization. In our case series, we did not observe any aneurysmatic degeneration, even in the longterm follow-up, so that, we strengthened the belief that the correct preoperative and intraoperative management of the graft may reduce the risk of graft-related complications. In our experience, the CHg was frosted, stored, and defrosted by a single tissue bank, following its own protocols and arrived ready to use within a few hours. We consider this aspect as fundamental to preserve the integrity of the material. It has been shown experimentally that cryopreservation protects against both early and late arterial allograft dilatation.28,29 Our study suffers from a few limitations. In the first place, it is a retrospective single-center analysis with a relatively small cohort of patients and a limited number of complications, so that it does not allow for a significant subgroup analysis. In the second place, the study design lacks direct comparison to a control group treated with the GSV. A prospective randomized work is necessary to clarify the role of CHg before routine use in PAA surgical treatment.
CONCLUSIONS Up to date, there is a substantial lack of studies in the literature regarding the routine use of the CHg conduit in PAAs surgery. In this retrospective single-center study, it was shown to be safe and effective, besides having
Popliteal artery aneurysm by means of cryopreserved homograft 1095
appealing results both in the early and in the longterm follow-up. In particular, no aneurysmatic degeneration was observed. This study also contributes to current knowledge by defining urgent surgery for severe ischemic symptoms predictive for early complications, reoperations, and graft failure. Exceptional care in the preoperative and intraoperative management of the CHg may reduce the risk of the graft-related complications. In our experience, arterial CHg can be considered an attractive alternative conduit to the autologous saphenous vein. REFERENCES 1. Huang Y, Gloviczki P, Noel AA, et al. Early complications and long-term outcome after open surgical treatment of popliteal artery aneurysms: is exclusion with saphenous vein bypass still the gold standard? J Vasc Surg 2007;45: 706e13. 2. Ravn H, Wanhainen A, Bj€ orck M, Swedvasc. Surgical technique and long-term results after popliteal artery aneurysm repair: results from 717 legs. Swedish Vascular Registry. J Vasc Surg 2007;46:236e43. 3. Garg K, Rockman CB, Kim BJ, et al. Outcome of endovascular repair of popliteal artery aneurysm using the Viabahn endoprosthesis. J Vasc Surg 2012;55:1647e53. 4. Marin ML, Veith FJ, Panetta TF, et al. Transfemoral endoluminal stented graft repair of a popliteal artery aneurysm. J Vasc Surg 1994;19:754e7. 5. Midy D, Berard X, Ferdani M, et al. A retrospective multicenter study of endovascular treatment of popliteal artery aneurysm. J Vasc Surg 2010;51:850e6. 6. Pulli R, Dorigo W, Castelli P, et al. A multicentric experience with open surgical repair and endovascular exclusion of popliteal artery aneurysms. Eur J Vasc Endovasc Surg 2013;45:357e63. 7. Lovegrove RE, Javid M, Magee TR, et al. Endovascular and open approaches to non-thrombosed popliteal aneurysm repair: a meta-analysis. Eur J Vasc Endovasc Surg 2008;36: 96e100. 8. Ying H, Gloviczki P. Popliteal artery aneurysms: rationale, technique, and results of endovascular treatment. Perspect Vasc Surg Endovasc Ther 2008;20:201e13. 9. Walker PJ, Mitchell RS, McFadden PM, et al. Early experience with cryopreserved saphenous vein allografts as a conduit for complex limb-salvage procedures. J Vasc Surg 1993;18:561e8. 10. Harris RW, Schneider PA, Andros G, et al. Allograft vein bypass: is it an acceptable alternative for infrapopliteal revascularization? J Vasc Surg 1993;18:553e9. 11. Randon C, Jacobs B, De Ryck F, et al. Fifteen years of infrapopliteal arterial reconstructions with cryopreserved venous allografts for limb salvage. J Vasc Surg 2010;51: 869e77. 12. Diener H, Hellwinklel O, Carpenter S, et al. Homografts and extra-anatomical reconstructions for infected vascular grafts. J Cardiovasc Surg (Torino) 2014;55(2 Suppl 1): 217e23. 13. Bı´r o G, Szeberin Z, Nemes A, et al. Cryopreserved homograft and autologous deep vein replacement for infrarenal aorto and iliaco-femoral graft infection: early and late results. J Cardiovasc Surg (Torino) 2011;52:169e76.
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14. Brown KE, Heyer K, Rodriguez H, et al. Arterial reconstruction with cryopreserved human allografts in the setting of infection: a single-center experience with midterm followup. J Vasc Surg 2009;49:660e6. 15. McCready RA, Bryant MA, Fehrenbacher JW, et al. Longterm results with cryopreserved arterial allografts (CPAs) in the treatment of graft or primary arterial infections. J Surg Res 2011;168:e149e53. 16. Mahmood A, Salaman R, Sintler M, et al. Surgery of popliteal artery aneurysms: a 12-year experience. J Vasc Surg 2003;37:586e93. 17. Robinson WP 3rd, Belkin M. Acute limb ischemia due to popliteal artery aneurysm: a continuing surgical challenge. Semin Vasc Surg 2009;22:17e24. 18. Pulli R, Dorigo W, Troisi N, et al. Surgical management of popliteal artery aneurysms: which factors affect outcomes? J Vasc Surg 2006;43:481e7. 19. Martelli E, Ippoliti A, Ventoruzzo G, et al. Popliteal artery aneurysms. Factors associated with thromboembolism and graft failure. Int Angiol 2004;23:54e65. 20. Kropman RH, Schrijver AM, Kelder JC, et al. Clinical outcome of acute leg ischaemia due to thrombosed popliteal artery aneurysm: systematic review of 895 cases. Eur J Vasc Endovasc Surg 2010;39:452e7. 21. Bisdas T, Bredt M, Pichlmaier M, et al. Eight-year experience with cryopreserved arterial homografts for the in situ
Annals of Vascular Surgery
22.
23.
24.
25.
26.
27.
28.
29.
reconstruction of abdominal aortic infections. J Vasc Surg 2010;52:323e30. Uberruck T, Zanow J, Rauchfuss F, et al. Endovascular treatment of aneurysms after implantation of an aortic-femoral homograft bypass. Zentralbl Chir 2008;133:376e9. Kieffer E, Gomes D, Chiche L, et al. Allograft replacement for infrarenal aortic graft infection: early and late results in 179 patients. J Vasc Surg 2004;39:1009e17. Neves JP, Gulbenkian S, Ramos T, et al. Mechanisms underlying degeneration of cryopreserved vascular homografts. J Thorac Cardiovasc Surg 1997;113:1014e21. Schmitz-Rixen T, Megerman J, Colvin RB, et al. Immunosuppressive treatment of aortic allografts. J Vasc Surg 1988;7:82e92. Feingold B, Wearden PD, Morell VO, et al. Expression of A and B blood group antigens on cryopreserved homografts. Ann Thorac Surg 2009;87:211e4. Kadner A, Chen RH, Mitchell RN, et al. Hemograft crossmatching is unnecessary due to the absence of blood group antigens. Ann Thorac Surg 2001;71(5 Suppl):S349e52. Giglia JS, Ollerenshaw JD, Dawson PE, et al. Cryopreservation prevents arterial allograft dilation. Ann Vasc Surg 2002;16:762e7. Motomura N, Imakita M, Yutani C, et al. Histologic modification by cryopreservation in rat aortic allografts. Ann Thorac Surg 1995;60(2 Suppl):S168e71.
Background: Autologous saphenous vein is considered the gold standard conduit in the femoralepopliteal revascularization for popliteal artery aneurysms (PAAs). In several cases, it may be absent or unsuitable for length or diameter and so it may be considered unfit for a conduit. In such patients, a synthetic graft or the endovascular correction can be useful, but results are controversial. In this retrospective case series, we have analyzed the safety and efficacy of the cryopreserved homograft (CHg) as a conduit in the PAA revascularization. Methods: In the period between January 2005 and December 2013, 54 PAAs have been treated with an arterial CHg. Indications to surgery were asymptomatic aneurysm with >25-mm diameter in 30 cases (55.6%), ischemic symptoms in 20 (37%), and compressive symptoms in 4 (7.4%). An urgent treatment was performed in 8 cases (14.8%) for severe ischemic symptoms. All cases have been operated by the same vascular team: a posterior surgical approach was preferred whenever possible (33 cases, 61.1%). All patients received a clinical and radiologic follow-up, and all data were collected in a specific database. A >10-mm diameter increase of the conduit was considered significant for an aneurysmatic degeneration. Results: The primary outcomes were complications and reoperation rate, limb salvage, and primary and secondary patency. Secondary outcome was the incidence of aneurysmatic degeneration of the CHg. Mean diameter of the homografts was 6.3 mm (range, 4e8 mm). In the 30-day postoperative period, 7 PAAs (13%) developed a complication: 3 wound infections, 3 graft thrombosis, and 1 anastomotic bleeding. Six cases needed a reoperation: 2 surgical revascularizations, 2 wound debridement, and 1 anastomotic hemostasis; 1 major amputation was necessary for graft failure after the revascularization. Mean follow-up was 34.8 months (range, 1e96). Five cases (9.3%) developed a graft complication with 4 reoperations necessary (7.4%): 2 grafts required a percutaneous transluminal angioplasty for a perigraft stenosis and 2 underwent a femorodistal bypass in CHg for severe ischemic symptoms after CHg occlusion. Another one CHg occlusion was treated conservatively because it was clinically asymptomatic. Primary patency was 96.3%, 93.9%, and 88.3% at 12, 36, and 60 months, respectively; secondary patency was 98.1% at 12, 36, and 60 months. Freedom from amputation resulted in 98.1%. No aneurysmatic degeneration was observed. Univariate and multivariate analysis showed urgent surgery to be independent risk factors for complications, reoperations, and CHg occlusion (P < 0.05). Conclusions: In this retrospective study, the use of CHg showed to be safe and effective in the surgery of PAAs, either in the short or in the long-term follow-up. Urgent surgery can be considered predictive of graft failure. In our experience, CHg can be considered a good alternative conduit to the autologous saphenous vein.
1 Department of Vascular and Endovascular Surgery, Azienda Ospedaliera Universitaria Integrata di Verona, Polo Chirurgico ‘‘P. Confortini’’, Verona, Italy. 2
Unit of Interventional Radiology, Azienda Ospedaliera Universitaria Integrata di Verona, Polo Chirurgico ‘‘P. Confortini’’, Verona, Italy. of
Correspondence to: Gian Franco Veraldi, MD, Department Vascular and Endovascular Surgery, Azienda Ospedaliera
1090
Universitaria Integrata di Verona, Italy; E-mail: gianfranco.veraldi@ ospedaleuniverona.it Ann Vasc Surg 2015; 29: 1090–1096 http://dx.doi.org/10.1016/j.avsg.2015.02.007 Ó 2015 Elsevier Inc. All rights reserved. Manuscript received: November 2, 2014; manuscript accepted: February 26, 2015; published online: May 19, 2015.
Vol. 29, No. 6, August 2015
INTRODUCTION Popliteal artery aneurysm (PAA) represents a rare but potentially limb-treating condition. Treatment may be challenging especially in case of large or symptomatic aneurysms. The most common procedure is ligation followed by autologous bypass using a great saphenous vein (GSV) conduit with medial or posterior approach. Indication of this procedure is strictly related to the availability of a suitable autologous saphenous vein, whereas the use of a synthetic graft remains controversial. Since the 90s, the development of the endovascular repair has obtained fair results in selected cases; however, further evidence and follow-up data are still required. Cryopreserved homograft (CHg) conduit may be considered a valid alternative to the autologous vein although there is a substantial lack of data in the literature: different authors report varying results with a significant risk of thrombosis and aneurysmatic degeneration. The purposes of this study were to report our single-center experience and to evaluate early and long-term results of the CHg bypass in the treatment of PAAs, both in the elective and in the urgent setting.
METHODS Clinical data of 54 consecutive PAAs treated by means of a CHg bypass at the Department of Vascular and Endovascular Surgery of Verona, Italy, between January 2005 and December 2013 were retrospectively reviewed. Primary outcomes were complications and reoperation rate, limb salvage, and primary and secondary patency. Secondary outcome was the incidence of aneurysmatic degeneration of the CHg. Recommended standards were followed for indications, complications, and patency rates. Acute and chronic ischemias were defined according to the Rutherford classification. Indication for the surgery procedure included: acute leg ischemia with salvageable limb (class I and II), critical chronic limb ischemia (class IV, V, and VI), signs of distal embolization, compressive symptoms (i.e., leg edema, popliteal vein thrombosis, numbness, and pain), or asymptomatic PAAs with diameter >25 mm. Infective complications were classified as grade I, grade II, and grade III if the subcutaneous tissue, the muscle plane, and the vascular plane were involved, respectively. Bleeding complications were considered as major if a surgical reoperation was necessary (i.e., for
Popliteal artery aneurysm by means of cryopreserved homograft 1091
hemodynamic instability or compressive symptoms) and as minor if a conservative management was indicated. All the procedures were conducted by the same vascular team. All CHgs were obtained by the same Tissue Bank Foundation of Treviso, Italy, located approximately 150 km east from our institution. A cryopreserved GSV or iliac artery was used according to the anatomic criteria of the patient and the tissue availability of the bank. Grafts were usually delivered in a few hours. All the grafts were sent defrosted and ready for the implantation. The CHg did not need to be matched to patients by ABO and Rh compatibility, and no immunosuppressive agents were used. If PAA extended above the Hunter canal or in case of acute leg ischemia, a medial approach was chosen; in all other cases, a posterior was preferred. Moderate acute ischemia (class IIa) with tibial vessels occlusion was considered an indication for preoperative locoregional thrombolysis with our standard protocol (urokinase 200,000 UI bolus followed by 100,000 UI/hr, maximum 48 hr). Cases with severe acute ischemia (IIb) with tibial vessels occlusion were managed with immediate surgical thrombectomy and graft implantation. All patients underwent clinical and instrumental evaluation including duplex ultrasound at 30 days, 6 months, 12 months, and then, once a year. A straight follow-up or a second-level radiologic investigation with computed tomography angiography (CTA) or magnetic resonance angiography (MRA) was performed in case of any complication. Indication for reoperation included: extensive local infection (Grade IIeIII), major bleeding, graft occlusion with acute limb ischemia, and significative anastomotic or intragraft stenosis (>70% or peak systolic velocity ratio >2). Aneurysmatic degeneration was defined as an increase of the transversal diameter of the graft exceeding 10 mm during the follow-up. Primary graft patency was defined as a patent graft that did not require any reoperation to restore flow after occlusion. Secondary patency was defined as a patent graft that required a new surgical procedure after occlusion in addition to all cases of primary patency. Statistical analysis was conducted by using SPSS 20 software (SPS Inc, Chicago, IL). Cumulative graft patency was assessed by the KaplaneMeier method. Risk factors for complications, reoperations, and graft failure were estimated with univariate and multivariate analysis, chi-squared test, and binary logistic regression. ManneWhitney test was used as a nonparametric test. A P value < 0.05 was considered of statistical significance.
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RESULTS A total of 54 PAAs in 49 patients were treated (5 bilaterally). Of these, 18 had a concomitant abdominal aortic aneurysm. All but one (97.9%) were men, whereas 8.1% had a previous infrainguinal revascularization. Demographic data are summarized in Table I. A preoperative second-level radiologic investigation (CTA or MRA) was obtained in all cases. The average maximum popliteal diameter was 33 mm (range, 15e54 mm); the mean length was 43 mm (range, 21e94 mm). At the time of diagnosis, 30 PAAs were asymptomatic, 4 presented compressive symptoms, and 20 presented ischemic symptoms (Table II). Fortysix (85.6%) PAAs were treated with elective surgery and 8 were treated in an urgent setting for severe ischemic symptoms (critical ischemia, class IV-V-VI or acute ischemia, Class IeII). A posterior surgical approach was preferred in 33 cases. Mean operative time was longer for urgent procedures (230 min; range, 145e350 min) than in the elective ones (195 min; range, 115e300 min), although not statistically significant (P > 0.05). Associated procedures were necessary in 10 cases (18.5%), all in the urgent procedures: 3 PAAs required an intraoperative thrombectomy of tibial vessels and 7 required a preoperative fibrinolysis. At least one patent tibial vessel was obtained before the beginning of the graft implantation. In all cases, the morphologic characteristics of the CHg were considered satisfactory for the conduit (Table III). Mean preoperative CHg diameter was 6.3 mm (range, 4e8 mm). Mean hospital stay was 7 days (range, 4e12 days). Early results (within 30 days from the operation) showed 7 complications (13%): 1 major bleeding requiring surgical hemostasis, 3 local infections (1 grade II infection treated conservatively and 2 grade III infections treated with surgical debridement and muscular coverage), and 3 early graft occlusions that required urgent revascularization for acute ischemic symptoms (thrombectomy and reanastomosis). One major amputation was necessary for immediate graft failure after revascularization. Mean follow-up was 34.8 months (range, 1e96). Five cases (9.3%) developed graft complications. Four reoperations were necessary (7.4%): in 2 cases, the graft required balloon angioplasty (percutaneous transluminal angioplasty) for a perigraft stenosis, and in other 2 cases, a femorodistal bypass for severe ischemic symptoms after CHg occlusion was required. One CHg occlusion was treated conservatively because it was asymptomatic.
Annals of Vascular Surgery
Table I. Demographic data and risk factors of 49 patients with 54 PAAs Demographics
No
%
No. of PAA (no. of patients) Gender Male/female Mean age, years (range) Cardiac diseasea Diabetes mellitus Arterial hypertension Renal insufficiencyb Current smoke Previous ipsilateral revascularization Mean PAA diameter, mm (range) Mean PAA length, mm (range)
54 (49)
d
48/1 72 (40e91) 20 18 33 9 21 4 33 (15e54) 43 (21e94)
98/2 40.8 36.7 67.3 18.3 42.8 8.1 d d
a History of cardiac ischemia or moderate and/or severe cardiac dyspnea. b Serum creatinine >1.5 mg/dL.
Table II. Clinical assessment of PAA presentation Clinical assessment
No
%
Elective/urgent Asymptomatic Ischemic symptomsa Class I Class II Class III Class IV-V-VI or acute ischemia (class IeII) Compressive symptoms
46/8 30 20 7 3 2 8
85.2/14.8 55.6 37.0 13.0 5.6 3.7 14.8
a
4
7.4
From Rutherford Classification.
Table III. Comparison between arterial and venous homografts
Graft type
No. of cases
Graft stenosis/ occlusion
Aneurysmatic degeneration
Arterial homograft Venous homograft Total
49 5 54
6 2 8
d d d
Primary patency was 96.3%, 93.9%, and 88.3% at 12, 36, and 60 months, respectively. Secondary patency was 98.1% at 12, 36, and 60 months (Figs. 1 and 2). Freedom from amputation resulted in 98.1% (Fig. 3). Univariate and multivariate analyses show that urgent surgery for severe ischemic symptoms is a statistically significant independent risk factor for early complications (P ¼ 0.004, odds ratio, 14.3;
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Fig. 1. Primary patency (96.3%, 93.9%, and 88.3% at 12, 24, and 60 months, respectively).
Fig. 3. Freedom from major amputation.
Fig. 2. Secondary patency (98.1% at 12, 24, and 60 months).
Fig. 4. Freedom from 30-day complication (elective versus urgent surgery).
95% confidence interval, 2.3e87.9), reoperations (P ¼ 0.03, odds ratio, 11.9; 95% confidence interval, 1.2e111.7), and graft failure (P ¼ 0.03, odds ratio, 0.08; 95% confidence interval, 0.09e0.78; Figs. 4e6). Mean increase of transversal graft diameter was 4.1 mm (range, 0e8 mm), and no significative aneurysmatic graft degeneration was observed.
unavailable or unfit superficial veins. In such cases, a synthetic bypass (either made of polytetrafluorethylene or Dacron) is an interesting opportunity. This option suffers from suboptimal results, especially in cases of poor runoff or in cases where a distal revascularization is required. Ravn et al.2 confirmed fair results by using a GSV conduit with a lesser risk of amputation compared with the use of prosthetic grafts in a study of 717 legs followed up to 18 years. The endovascular approach continues to be exciting. Since 1994, after the experience of Marin et al., different authors reported series of PAAs treated by this minimally invasive approach.3e5 Pulli et al. published a recent multicenter analysis comparing 178 open surgery cases versus 134 endovascular procedures. They concluded that both
DISCUSSION The bypass procedure using the GSV conduit is considered the reference technique in the treatment of PAAs. Huang et al.1 analyzed 358 PAAs treated with different conduits and concluded that GSV had the best results at 10 years of follow-up. However, it is common experience to find patients with
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Fig. 5. Freedom from 30-day reoperation (elective versus urgent surgery).
Fig. 6. Primary patency (elective versus urgent surgery).
treatments are feasible and safe, providing satisfactory early and long-term results as long as a careful selection of patients in term of clinical and anatomic characteristics has been previously carried out.6 Despite the good outcomes of the previously mentioned cases series, different reviews concluded that, with the exception of high-risk patients, it is difficult to justify a routine endovascular treatment in PAAs.7,8 CHg has been proposed as an alternative solution in patients requiring a peripheral revascularization lacking proper superficial veins. Theoretically, it would represent an optimal compromise between an autologous and a synthetic material, with favorable results especially in the case of local infectious complications. Practically, for many years, the use of such an option has been discussed, highlighting different critical aspects and uncertain results that
Annals of Vascular Surgery
lead to limited indications. In particular, this conduit has been reported to be prone to early thrombosis and late aneurysmatic degeneration. In 1993, Walker et al.9 concluded that CHg offered better results than a synthetic conduit, but its use should be deferred until improved preparation techniques could provide a more durable conduit. Similarly, Harris et al.10 obtained similar unexciting results. More recently, in the 15-year long experience of Randon et al., the analysis of 108 CHg bypasses showed satisfactory results; the study deemed an improved graft and patient selection, a stricter graft surveillance and an immunologic matching mandatory to improve outcomes.11 Part of the cited authors obtained their results in selective cases, especially while dealing with the management of a previous graft infection, which represents one of the most challenging complication in the vascular practice.12e15 No data are available about the routine use of the CHg conduit in the elective or urgent surgery of PAA. In an early period of our experience, we used the CHg conduit in selected patients only, and in particular, in those with absent or unfit saphenous vein. During follow-up, as we were witnessing very satisfactory mid-term results, we extended the indications to all patients with PAA. All our patients were operated by the same vascular team that learned, during the years, what we consider the best intraoperative management of the CHg conduit. The conduit was managed with great care, avoiding direct clamping, traction, or leaving redundant segments during the revascularization. We consider these few rules of paramount importance to reduce the risk of CHg failure. The analysis of early follow-up (within 30 days from the operation) showed an incidence of 13% (7 of 54) of complications, of which 6 cases (11.1%) required a reoperation. Wound infection was documented in 5% of cases but no graft complications occurred in these patients, confirming the good resistance of the material. Three early graft occlusions were observed and required a prompt reoperation for acute ischemic symptoms. In all cases, a thrombectomy and a new anastomosis was required. Both cases presented with severe ischemic symptoms and one was subsequently amputated for early graft occlusion. During long-term follow-up, 3 grafts occluded. Two patients required a reoperation for acute ischemic symptoms and one was treated conservatively. All had a favorable evolution with limb preservation.
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Acute limb ischemia due to PAA is a challenging complication, with a 20e60% incidence of limb loss and up to 12% of mortality reported in the literature.16e20 The analysis of our results confirmed that urgent surgery for severe ischemic symptoms (critical ischemia, class IV-V-VI or acute ischemia, class IeII) is an independent factor risk for early complication, reoperation, and graft failure. Poor runoff is probably the cause of the failed graft in our group, and it is likely independent from the nature of conduit. Aneurysmatic degeneration of the CHg conduit has been described; however, the real incidence rate is unknown. Bisdas et al.21 reported only 1 case of aneurysmatic degeneration in 110 aortic revascularizations with CHg (1.7%). Other cases series reported similar rates.22 Kieffer et al. described 2 possible causes for graft degeneration, a mechanical one and an immune-mediated one,23e25 but the real mechanism remains unknown.26,27 No data are available regarding this particular complication in PAA revascularization. In our case series, we did not observe any aneurysmatic degeneration, even in the longterm follow-up, so that, we strengthened the belief that the correct preoperative and intraoperative management of the graft may reduce the risk of graft-related complications. In our experience, the CHg was frosted, stored, and defrosted by a single tissue bank, following its own protocols and arrived ready to use within a few hours. We consider this aspect as fundamental to preserve the integrity of the material. It has been shown experimentally that cryopreservation protects against both early and late arterial allograft dilatation.28,29 Our study suffers from a few limitations. In the first place, it is a retrospective single-center analysis with a relatively small cohort of patients and a limited number of complications, so that it does not allow for a significant subgroup analysis. In the second place, the study design lacks direct comparison to a control group treated with the GSV. A prospective randomized work is necessary to clarify the role of CHg before routine use in PAA surgical treatment.
CONCLUSIONS Up to date, there is a substantial lack of studies in the literature regarding the routine use of the CHg conduit in PAAs surgery. In this retrospective single-center study, it was shown to be safe and effective, besides having
Popliteal artery aneurysm by means of cryopreserved homograft 1095
appealing results both in the early and in the longterm follow-up. In particular, no aneurysmatic degeneration was observed. This study also contributes to current knowledge by defining urgent surgery for severe ischemic symptoms predictive for early complications, reoperations, and graft failure. Exceptional care in the preoperative and intraoperative management of the CHg may reduce the risk of the graft-related complications. In our experience, arterial CHg can be considered an attractive alternative conduit to the autologous saphenous vein. REFERENCES 1. Huang Y, Gloviczki P, Noel AA, et al. Early complications and long-term outcome after open surgical treatment of popliteal artery aneurysms: is exclusion with saphenous vein bypass still the gold standard? J Vasc Surg 2007;45: 706e13. 2. Ravn H, Wanhainen A, Bj€ orck M, Swedvasc. Surgical technique and long-term results after popliteal artery aneurysm repair: results from 717 legs. Swedish Vascular Registry. J Vasc Surg 2007;46:236e43. 3. Garg K, Rockman CB, Kim BJ, et al. Outcome of endovascular repair of popliteal artery aneurysm using the Viabahn endoprosthesis. J Vasc Surg 2012;55:1647e53. 4. Marin ML, Veith FJ, Panetta TF, et al. Transfemoral endoluminal stented graft repair of a popliteal artery aneurysm. J Vasc Surg 1994;19:754e7. 5. Midy D, Berard X, Ferdani M, et al. A retrospective multicenter study of endovascular treatment of popliteal artery aneurysm. J Vasc Surg 2010;51:850e6. 6. Pulli R, Dorigo W, Castelli P, et al. A multicentric experience with open surgical repair and endovascular exclusion of popliteal artery aneurysms. Eur J Vasc Endovasc Surg 2013;45:357e63. 7. Lovegrove RE, Javid M, Magee TR, et al. Endovascular and open approaches to non-thrombosed popliteal aneurysm repair: a meta-analysis. Eur J Vasc Endovasc Surg 2008;36: 96e100. 8. Ying H, Gloviczki P. Popliteal artery aneurysms: rationale, technique, and results of endovascular treatment. Perspect Vasc Surg Endovasc Ther 2008;20:201e13. 9. Walker PJ, Mitchell RS, McFadden PM, et al. Early experience with cryopreserved saphenous vein allografts as a conduit for complex limb-salvage procedures. J Vasc Surg 1993;18:561e8. 10. Harris RW, Schneider PA, Andros G, et al. Allograft vein bypass: is it an acceptable alternative for infrapopliteal revascularization? J Vasc Surg 1993;18:553e9. 11. Randon C, Jacobs B, De Ryck F, et al. Fifteen years of infrapopliteal arterial reconstructions with cryopreserved venous allografts for limb salvage. J Vasc Surg 2010;51: 869e77. 12. Diener H, Hellwinklel O, Carpenter S, et al. Homografts and extra-anatomical reconstructions for infected vascular grafts. J Cardiovasc Surg (Torino) 2014;55(2 Suppl 1): 217e23. 13. Bı´r o G, Szeberin Z, Nemes A, et al. Cryopreserved homograft and autologous deep vein replacement for infrarenal aorto and iliaco-femoral graft infection: early and late results. J Cardiovasc Surg (Torino) 2011;52:169e76.
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