Hybrid treatment of thoracoabdominal aortic aneurysm: case series and review of the literature Hibridni tretman aneurizmi torakoabdominalne aorte: serija bolesnika i pregled literature

Background/Aim. Open thoracoabdominal aortic aneurysm (ThAAAs) repair is a challenging mission. Total endovascular approach is performed at selected institutions in developing countries, however these are not generalizable. Hybrid procedures offer an alternative approach. The aim of this study was to present our results of the ThAAA hybrid treatment and a literature review. Methods. This is a retrospective study of all patients that underwent the hybrid ThAAA repair at our institution between January 2011 and January 2018. Hybrid ThAAA repair was done as a twostaged procedure – open visceral debranching followed by stent-graft placement (TEVAR). The following data from eligible studies were extracted and analyzed: first author, publication year, patient sample, 30-day/in-hospital mortality, permanent paraplegia rate, presence of endoleaks and graft patency after the follow-up period, overall survival and mean follow-up period. Results. Seven patients underwent the hybrid ThAAA repair at our institution. Neither intraoperative death nor technical failure due to TEVAR was observed. Mean follow-up rate after discharge was 51.71 months [95% confidence interval (CI): 14.67–88.74 months]. At the time of the follow-up, all bypasses were patent and no prosthesis migration was documented. After one year, a case of type Ib endoleak was identified and treated successfully. Twenty-five studies were eligible for the literature review. Primary technical success was 91.69% (95% CI: 85.34–97.24%). Mean percentage of permanent paraplegia was 5.27% (95% CI: 3.55–7.01%). Visceral graft patency during the mean follow-up of 27.54 months (95% CI: 17.41–37.66 months) was 94.5% (95% CI: 92.5–96.5%). Mean pooled percentage rate of overall endoleaks during the follow-up period was 16.72% (95% CI: 11.15–22.29%). Analysis revealed 15.32% (95% CI: 11.04–19.61%) of 30day/in-hospital mortality and 65.98% (95% CI: 58.15– 73.81%) of overall survival after the follow-up period. Conclusion. Although thought as less invasive, the hybrid ThAAA repair is still associated with a considerable morbidity and mortality.


Introduction
Surgical repair of thoracoabdominal aortic aneurysms (ThAAAs) is a challenging both for a patient and a surgeon.The results of high volume centers are excellent, where the cumulative 30-day mortality is even less then 10% in selected series 1,2 .Overall mortality was shown to be 10% according to the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2010 3 .Total endovascular approach is available at the selected institutions.This approach is associated with better outcomes, lower rates of mortality, morbidity and spinal cord ischemia [4][5][6] .Unfortunately, these are not generalizable due to the anatomic restrictions, problems with access to devices and need for custom fabrication as well as their costs.
Hybrid procedures are an alternative approach to the ThAAA management.Because it is a combination of standardized open techniques and off-the-shelf endografts, this is applicable to a wide range of patient anatomy.This approach offers the potential advantage of being less invasive since they avoid the extensive two cavity exposure, aortic crossclamping and mechanical circulatory support that comprise open ThAAA repair.
In this paper we present our results of the hybrid procedures for a complex thoracoabdominal aortic aneurysm in seven patients with the ThAAA and a review of the literature.

Patient population
This is a retrospective study of all patients that underwent the hybrid ThAAA repair at our institution between January 2011 and January 2018.A total of seven consecutive patients were identified.The study was approved by the Ethics Committee of our institution and was conducted according to the principles of the Declaration of Helsinki.
At our institution, there is a clear protocol for the ThA-AA treatment (Figure 1).Patients aged ≥ 75 years, with a severe coronary artery (three vessel/left main) or severe valvular disease, congestive heart failure, chronic obstructive pulmonary disease (Gold class III and IV), chronic kidney disease (stage IV and V), prior left chest surgery, prior open ThAAA/ThAA repair and no connective tissue disease undergo staged hybrid ThAAA repair.There were a total of 174 elective patients with the ThAAA admitted to our institution in period between January 2011 and January 2018.By using this algorithm, 111 patients were treated with open repair, 7, as previously said, with the hybrid approach and 56 patients were rejected due to a high risk of both strategies.
Baseline characteristics of patients are shown in Table 1.The specific pathologies were as follows: five degenerative ThAAA (three type III and two type V) and two chronic post-dissected ThAAA (both type I).All patients underwent a thorough preoperative assessment which included a computed tomography (CT) scan to evaluate the extent of the aortic pathology and to select the endoprosthesis size (Figure 2) and transthoracic echocardiography.Technically, a successful placement of the stent-graft was defined as a successful deployment of the graft without mortality, endoleaks and conversion to open surgery or graft occlusion within the first 24 hours.CT scan was done in all patients before discharge (Figure 3).Follow-up CT scans were performed immediately after the intervention, as well as after the first and sixth month, and after that on a year basis.

Technical details
Hybrid ThAAA repair was done as a two-staged procedure, which consisted of the open visceral debranching and stent-graft placement.The first stage of visceral debranching was achieved in all cases from a transabdominal approach via midline laparotomy.Prosthetic retrograde bypass grafts (all Dacron prosthesis) were constructed from the common iliac arteries or a Dacron graft which was used for the reconstruction of infrarenal AAA.Visceral target vessels were ligated proximal to the revascularization to prevent endoleak after the endoprosthesis placement.Celiac artery was identified through omentum minus and its revascularisation was performed in all casses with a bypas to the common hepatic artery in order to preserve visceral circulation.The superior mesenteric artery (SMA) was identified in some cases through omental bursa and in other at the base of the transverse colon.First option through the omental bursa has an advantage of being proximal to the origin of the middle colic artery allowing ligation of the SMA just proximal to the graft.The left and right renal artery were identified as they emerge from the aorta with the right renal artery behind the inferior vena cava.The prosthetic bypass grafts were used as a variety of custom-branched graft configurations.The second stage of the hybrid repair consisting of the stent-graft placement was performed in a delayed fashion since we did not have a hybrid operating room.All patients remained hospitalized between the first and second stage.Through the transfemoral approach in all 7 cases, a diagnostic aortography was accomplished with a pigtail catheter.An endoprosthesis was selected in order to cover the entire lesion and was oversized by 10%-20% according to the diameter of landing zones.An overlapping between two stentgrafts or between the stent-grafts and the Dacron prosthesis was done according to the instruction for use protocol for each type of graft.The postoperative mean blood pressure was kept above 100 mmHg and cerebrospinal fluid (CSF) drainage was used for the first 72 hours, as per our institutional protocol for the SCI prevention.

Literature search strategy
All paper that were published about the hybrid ThAAA treatment until March 2018 were extensively searched.The following medical subject heading term search strategy for indentification of the eligible studies was used: "thoracic", "thoracoabdominal", "aortic aneurysm", "endovascular", "stent-graft", "visceral bypass graft", "visceral revascularization", "visceral debranching", "hybrid".The following electronic search engines were used: Google Scholar, Medline, Scopus and Cochrane Library.Furthermore, all retrieved articles were examined for a relevant case series.Hybrid repair should consist of two stages: open debranching followed by the endoprosthesis placement.Both staged and single procedures were analysed.The eligible study for this review should have: 1) a visceral bypass followed by the endoprosthesis placement; 2) at least one basic outcome criteria; 3) series of at least 15 patients.Exclusion criteria were: articles that were not in English, studies with the hybrid aortic arch debranching, case reports and papers with less than 15 patients.Some papers also reported patients with the combined visceral debranching and endovascular exclusion for different thoracoabdominal pathologies.These were also taken into account and analyzed as a part of a greater cohort of patients only if the data for them were separatly shown.The eligible studies for this review were independently assessed by two reviewers.Data that were extracted and analyzed were: first author, year of publication, patient sample, 30-day/in-hospital mortality, percentage of permanent paraplegia, presence of endoleaks and graft patency after the follow-up period, overall survival and the mean followup period.

Results
Three patients underwent a concomitant infrarenal AAA repair with the visceral debranching (Figure 4).In other four cases, the visceral debranching was done as a retrograde bypass graft from the common iliac arteries.In one case, the hybrid aortic arch repair was previously performed.Technical success was achieved in 6 (85.71%) cases.Neither intraoperative death nor technical failure due to TEVAR was observed intraoperatively.Six patients were extubated 24 hours after the surgery.One patient was re-intubated on postoperative day 4 (POD 4) and re-intervened because of the peptic ulcer perforation and kept ventilated for 6 days due to a respiratory failure secondary to pneumonia.In one case, there was an early AMS graft occlusion which required early re-intervention and new bypass creation.No postoperative transient or permanent SCI occurred.In all cases the CSF drainage was performed for 72 hours as per protocol.Follow-up rate was 100%.Mean follow-up rate after discharge was 51.71 months (95% CI: 14.67-88.74).Afer the followup period, all bypasses were patent and no case of a stentgraft migration was noted.After one year, a case of type Ib endoleak was documented in patient number 7. This complication was successfully treated by endovascular means later on.Table 2 shows the intra-and postoperative data.

Discussion
Since the first introduction of this hybrid procedure at our instution 32 , we have successfully treated patients with this approach because they were in a high risk for open ThAAA repair.Visceral debranching can be accomplished via a standard median laparotomy, without entering the chest cavity, and without the aortic cross-clamping or mechanical circulatory support.That is why the hybrid repair is "lessinvasive" than the open ThAAA repair and results in less physiological derangement.The real-world data on the other side, show mixed results (Table 3), leaving ambiguity of the exact role of hybrid repairs  .
This literature review was performed with a purpose to explore contemporary results and concerns of the technique.In order to avoid the bias of the small sample, we excluded case reports and small case series.When analyzing the morbidity and mortality rates, a significant heterogeneity was found, with the mean pooled rate of 14.58% for 30-day mortality and 5.27% for an irreversible spinal cord injury (SCI).Similar results were presented in the Society for Vascular Surgery (SVS) meeting in 2012 from the North American Complex Abdominal Aortic Debranching (NACAAD).Their data for 30-day mortality was 16% and for SCI 14%, which was associated with the extent of the aortic disease and aneurysm rupture 36 .Better results in our material might be explained by a low number of patients and careful selection.Available open repair option provides unbiased selection while most patients in our group had the chronic obstructive pulmonary disease (COPD) and obesity as a risk factor with the average age lower than reported.
Substantial mortality associated with this hybrid approach could be explained by the fact that a majority of these patients are elderly and with major comorbidities that cannot withstand this kind of reconstruction.This highlights the importance of patient selection.In our sample of patients, the mean age was 70.57years, they were mainly obese (71.42%) and all of them had the American Society of Anesthesiologists (ASA) score ≥ 3.In examining the specifics of the patients, as seen from the literature  , it appears that they tend to be in a higher risk. It sems that hybrid repair can offer some advantage in high-risk patients, but it is certainly not the low-risk approach.Also, even more important is that it demonstrates that there are limits of how far the hybrid technique can be pushed.In the end, in the population of patients with the extremely high-risk, a non-operative approach may be actually the best option.
What is even more interesting point is that this technique was adopted by centers with little previous experience in treating patients with the ThAAA.A few large-volume centers both in the USA and Europe display the constant evidence of better results demonstrating how extensive experience in the treatment of this pathology, learning curve and an organized perioperative background are required for the best management.
There is no significant amount of data which demonstrates weather the endoprosthesis placement for the exclusion of the ThAAA should be done concomitantly or in a delayed fashion 8 .Those who are oponents of staged approach say that this leaves a patient to a potential rupture, although there are little data to support this approach 9 .This approach is associated with longer hospital stay at the Intensive Care Units (ICU) and higher morbidity rate 38 .On the other side, the delayed approach has one major advantage.It allows the patients to recover from debranching surgery, before exposing them to the placement of the aortic endoprosthesis.This has the larger influence on the kidney function, as it allows them to recover from ischemia due to debranching surgery before exposing them to the contrast during the second, endovascular part of the hybrid repair that also has nephrotoxic effect.That is why this double-staged procedure should be mainstay of treatment for the patients who require the extensive ThAAA reconstruction, with single-staged reserved only to those who are at high-risk of aneurysm rupture.
Another concerns are the endograft complications, and on the other side, visceral graft patency.Our patient sample revealed 100% of the visceral graft patency during the mean follow-up of 51.71 months.One (14.28%) patient had an endoleak type Ib treated with additional endograft in the distal landing zone.The literature review data revealed the visceral graft patency of 94.5% during the mean follow-up of 27.54 months, whereas 16.72% had an endoleak.Kuratani et al. 18 , with the longest follow-up period (88.5 months, n = 86), reported two intraporcedural deaths, one patient died because of a visceral graft occlusion and bowel necrosis and the other because of a graft infection.
Due to financial and technical reasons we do not perform branched or fenestrated procedures in our country.Inaccessibility of these treatment options brings non-selectivity, but on the other hand, our institution has extensive experience with the open repair [37][38][39][40][41] as an option in treatment of this complex pathology.For unfit patients, the hybrid repair is the only viable option.We think that a thorough case selection and a choice of the right procedure are two most important things.In large-volume centers or those with suitable expertise, visceral hybrid repair is an alternative treatment strategy for the high-risk population of patients with the limited open and fully endovascular therapeutic alternatives.
Our study has several limitations.Firstly, this was a retrospective study with prospectively collected data in a single center where a patient accrual required nearly seven years.Secondly, our study was performed on a small number of patients.Thirdly, there was an absence of a control group.The main strength of this study is detailed clinical information, especially in the literature review which provides enough statistical power to make valid conclusions.

Conclusion
Although thought as less invasive, hybrid ThAAA repair is still associated with a considerable morbidity and mortality rate since it is frequently performed in fragile patients.Despite the improvements in the branched and fenestrated procedures, hybrid approach may continue to have a role in the hostile anatomy of those patients or when advanced stent grafts are not available.That is why this should be reserved for the largevolume centers with enough experience that can determine a patient suitability and offer all treatment options with high standards of perioperative care.