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Interact Cardiovasc Thorac Surg. 2016 May; 22(5): 537–545.
Published online 2016 February 10. doi:  10.1093/icvts/ivw004
PMCID: PMC4892148

Outcomes of minimally invasive lung transplantation in a single centre: the routine approach for the future or do we still need clamshell incision?

Abstract

OBJECTIVES

Minimally invasive lung transplantation (MILT) via bilateral anterior thoracotomies has emerged as a novel surgical strategy with potential patient benefits when compared with transverse thoracosternotomy (clamshell incision, CS). The aim of this study is to compare MILT with CS by focusing on operative characteristics, postoperative organ function and support and mid-term clinical outcomes at Harefield Hospital.

METHODS

It was a retrospective observational study evaluating all bilateral sequential lung transplants between April 2010 and November 2013.

RESULTS

CS was performed in 124 patients and MILT in 70 patients. Skin-to-skin surgical time was less in the MILT group [285 (265, 339) min] compared with CS [380 (306, 565) min] and MILT-cardiopulmonary bypass [426 (360, 478) min]. Ischaemic time was significantly longer (502 ± 116 vs 395 ± 145 min) in the MILT group compared with CS (P < 0.01). Early postoperative physiological variables were similar between groups. Patients in the MILT group required less blood [2 (0, 4) vs 3 (1, 5) units, P = 0.16] and platelet transfusion [0 (0, 1) vs 1 (0, 2) units, P < 0.01]. The median duration of mechanical ventilation was shorter (26 vs 44 h, P < 0.01) and intensive therapy unit stay was 2 days shorter (5 vs 7) in the MILT group. While overall survival was similar, fraction of expired volume in 1 s (FEV1) and forced vital capacity (FVC) were consistently higher in the MILT group compared with CS during mid-term follow-up after transplantation. Specifically, FEV1 and FVC were, respectively, 86 ± 21 and 88 ± 18% predicted in the MILT group compared with 74 ± 21 and 74 ± 19% predicted in the CS group (P < 0.01) at the 6-month follow-up.

CONCLUSIONS

MILT was successfully introduced at our centre as a novel operative strategy. Despite longer ischaemic times and a more complex operation and management, MILT appears to offer early postoperative and mid-term clinical benefits compared with our traditional approach of clamshell operations. These observations warrant larger definite studies to further evaluate the impact of MILT on physiological, clinical and patient-reported outcomes.

Keywords: Lung transplantation, Minimally invasive, Cardiopulmonary bypass

INTRODUCTION

Transplantation is currently the only accepted treatment for end-stage pulmonary failure. Depending on their conditions, patients are listed for single, double or heart–lung transplantation [13]. Currently, bilateral lung transplantation comprises the majority of lung transplants, whereby the two lungs are implanted sequentially traditionally through a transverse thoracosternotomy (clamshell incision, CS) [46]. Although the benefits and problems associated with the use of cardiopulmonary bypass (CPB) in this operation have been debated, CPB is used routinely in many centres including ours until recently [79]. It has been suggested that the CS approach may contribute to postoperative complications by inducing surgical inflammation, postoperative pain with respiratory compromise and potential for impaired wound healing. To overcome these difficulties, a minimally invasive lung transplantation (MILT) approach, which avoids both the clamshell incision and the routine use of CPB, has been advocated recently [1014]. Although these centres have achieved good clinical and cosmetic results when compared with historical data, there is limited information comparing the minimally invasive approach and the clamshell method in a simultaneous fashion. Furthermore, the impact of MILT on perioperative inflammation and functional recovery remains largely unknown. Finally, it remains unknown if the postulated benefits of MILT relate to the surgical incision or avoidance of CPB.

Our transplant programme has uniquely encompassed both CS and MILT approaches for the last few years. This situation provides a special opportunity to scientifically evaluate these different surgical approaches at a single institution whereby the same perioperative medical management is applied to the two patient populations.

Herein, we present our initial experience with MILT at Harefield Hospital. The principle aim of the study is to review our experience with the MILT approach by reporting the first such surgical strategy in the UK. Secondly, we have compared our MILT experience with our more traditional CS strategy in terms of operative characteristics, early postoperative function and mid-term outcomes. To further evaluate the potential role of extracorporeal circulation, we also contrasted operations performed with or without the aid of CPB.

MATERIALS AND METHODS

Patients

We reviewed 194 patients undergoing bilateral sequential single-lung transplantation (LTx) at our centre from April 2010 to November 2013 utilizing a prospectively collected database. Single-lung transplants were excluded. Data were collected using the electronic database record (IntelliSpace Critical Care and Anaesthesia, Electronic Patient Record) and the clinical notes.

One hundred and twenty-four (63.9%) bilateral lung transplants were performed using the traditional clamshell approach, with the majority n = 105 utilizing CPB according to the routine practice of three to four surgeons. In the same time frame, 70 transplants were performed (36.1%) using the minimally invasive approach that included all patients from the beginning of the programme. The use of CPB was reported in 22 patients in the minimally invasive group.

Surgical approaches

The minimally invasive surgical method was described in detail before [12]. Surgery is performed on the right side first. A skin incision (10–12 cm) is made above the fifth intercostal space. In female patients, the incisions are placed under the breast to achieve an optimal cosmetic result. An anterolateral thoracotomy is performed in the fourth intercostal space, internally extending posteriorly to allow for easy access without fracturing ribs. Care is taken to avoid damage to the internal mammary artery. If necessary, the surgical field is illuminated with a flexible light source to facilitate dissection and pneumonectomy. Following identification of the phrenic nerve, the pulmonary artery is circumnavigated and occluded. At this point, single-lung ventilation with nitric oxide is commenced as a right heart protective measure. During the commencing phase of the operation, right heart function, gas exchange and lung mechanics are assessed continuously and a decision is made whether to commence CPB on the stability of the patient.

Next, the pulmonary veins are prepared and freed of the pericardium, the pericardium is opened anteriorly and cranially to the right atrium, and the right main pulmonary artery is prepared between the superior caval vein and the aorta and circumnavigated. Commencing venous preparation, the pericardium is opened cranially and the pulmonary artery is prepared between the aorta and the superior caval vein and circumnavigated. A small incision is made above the second intercostal space and a clamp is passed into the thorax and the PA is clamped between the aorta and the superior caval vein. The veins are ligated and the lung is excised. Following pneumonectomy, careful haemostasis is performed; the graft is prepared and implanted via the standard technique beginning with the anastomosis of the bronchus followed by the pulmonary artery and the left atrial cuff. After reperfusion and slow hand ventilation, full ventilation is commenced and the procedure repeated on the contralateral side.

The clamshell incision is performed according to routine practice and is well established. It is the preferred surgical option of most transplant surgeons who routinely use CPB for the procedure and are not experienced in MILT.

Perioperative management

Prior to routine introduction of MILT, several education sessions took place between the principal surgeon and anaesthetist/intensivist involved with the transplant programme. Beyond the routine perioperative strategies applied to CS operations, MILT requires the more aggressive use of inhaled and intravenous pulmonary vasodilators and inotropes/vasoconstrictors prior to clamping the right pulmonary artery, lung isolation generally using a left-sided Bronco-Cath (Mallinckrodt, Athlone, Ireland) double-lumen endobronchial tube, single-lung ventilation to avoid systemic hypoxia and excessive hypercapnia and careful monitoring of pulmonary haemodynamics and right ventricle performance. Particular attention is placed on management of pulmonary artery clamping, adequacy of single-lung ventilation, de-airing, reperfusion and post-reperfusion shunt management. The use of CPB is triggered by haemodynamic instability, excessive pulmonary hypertension following clamping, high-grade arrhythmias or insufficiency of gas exchange.

In both CS and MILT approaches, coagulation management included avoidance of haemodilution, use of antifibrinolytics, routine guidance by thrombo-elastography results and coagulation screen.

Study design

Patient groups

The primary comparison is between the two mainstream practices, i.e. CS operations and those performed with the MILT approach. The secondary aim was to address the important issue of CPB by comparing the operations that concluded without the use of CPB with those requiring bypass.

Donor characteristics

To explore if donor factors impacted on surgical outcomes between MILT and CS patients, donor demographic parameters, cause of death, current clinical status, laboratory investigations, and past social and medical history were analysed. The information about donor smoking habits and estimate of pack-year consumption were obtained from the general practitioner or donor's next of kin.

Operative data and results

We have analysed patient demographics, total ischaemic times and duration of operations. We have also evaluated the requirement for postoperative revision and extracorporeal support.

Early postoperative lung function

Postoperative lung function and gas exchange was monitored sequentially during the first 72 h. Oxygenation was evaluated by the P/F ratios that consider the ratio of arterial PO2 and the inspired fraction of O2. The presence of primary graft dysfunction was graded in accordance with international society for heart and lung transplantation (ISHLT) gas exchange (P/F ratios) and chest radiograph criteria [15, 16], and the duration of mechanical ventilation (MV) was documented. Perioperative inflammatory response was assessed by monitoring cardiopulmonary resuscitation (CRP) levels, leucocytosis and requirement for vasoactive support. In addition, perioperative transfusion requirement was recorded and intensive care unit (ICU) and hospital length of stay and perioperative (30-day) and mid-term survival were compared between CS and MILT recipients.

Recipient lung function

All patients undergo routine spirometry tests with the first spirometry after transplantation being conducted when the patient's physical condition allows for performing the test. Forced vital capacity (FVC) and fraction of expired volume in 1 s (FEV1) in the first test after transplantation followed by those at 3, 6 and 12 months were compared among the groups. The results of the tests performed at the closest date to measurement time points were compared if spirometry had not been done exactly 3, 6 or 12 months after transplantation. The number of days between transplantation and the first test was compared as well. In addition, we also report the latest lung function available in these patients.

Acute rejection

Trans-bronchial biopsies were performed when clinically indicated. Acute rejection (AR) was graded based on ISHLT Lung Rejection Study Group recommendations [17]. The percentage of patients who developed at least one episode of AR grade 1–3 among the groups was compared.

Statistical analysis

The distribution of quantitative data was checked using the Kolmogorov–Smirnov test. Normally distributed data are presented as mean ± standard deviation (x¯±SD). Abnormally distributed data exhibiting non-normal distribution are presented as a median, lower quartile, upper quartile. Qualitative data are presented as a percentage of the whole analysed group. Analysis of variance or variance on ranks was used to compare experimental groups with appropriate post hoc tests. Qualitative data were compared using Fisher's exact test. Value of P < 0.05 was considered statistically significant. The analysis was performed using the Sigmaplot version 12.0., Statistical software package (Systat Software, Inc., 2011–2012).

RESULTS

Patient groups and recipient and donor demographics

The age of the patients [45 (28, 54) vs 47 (30, 57) years for CS and MILT, respectively], female-to-male ratio (46 vs 59%), and waiting list duration was similar between the overall CS and MILT groups. Cystic fibrosis (38 vs 37%), emphysema (26 vs 23%) and primary pulmonary hypertension (3 vs 4%) were equally represented between clamshell and MILT. Pulmonary fibrosis represented 11% of MILT operations compared with 4% in CS. Both groups included patients who required intensive care support prior to the transplant operation (7% each for CS and MILT, respectively) and those who had preoperative extracorporeal support (6% in each group). Four (3%) lungs were accepted for transplantation in the CS group after ex vivo lung reconditioning, while this figure was 3 (4%) for MILT. As part of an active programme utilizing the Transmedics Organ Care System (OCS) for lung preservation, three OCS lungs were included in both patient groups [18, 19]. Further demographic data are included in Table Table1,1, focusing on the subgroups with and without CPB. It appears that the majority of patients (71%) of the CS group were subjected to elective and routine CPB, whereas this only represented 7% in the MILT operations, generally those who were already on preoperative mechanical support, which continued during the surgical procedure. There were 16 unplanned conversions to CPB in the MILT group and 14 in the CS population. Haemodynamic instability (n = 10) upon clamping the pulmonary artery or following reperfusion of the lung allograft, insufficient gas exchange during one-lung ventilation (n = 12) and surgical issues (n = 8) were the main factors in the decision-making to convert a planned off-pump transplant to urgent CPB.

Table 1:
Preoperative and surgical characteristics of patients undergoing bilateral single sequential lung transplantation

Lung transplant donors of the MILT and CS groups had comparable demographics and baseline characteristics, except for a trend towards higher number of pack-years among smokers in the MILT group: 19 (10, 29) pack-years in the MILT group vs 10 (5, 20) pack-years in the CS group (P = 0.09). As presented in Table Table2,2, there were no statistically significant differences in donor cause of death, percentage of donation after cardiac death (DCD) (P = 0.26), abnormal chest X ray [chest X ray (CXR), P = 0.97], bronchoscopy (P = 0.40), duration of donor MV(P = 0.13) and last preretrieval PaO2/FiO2 ratio (P = 0.15). Also, a subgroup analysis of patients who underwent lung transplantation using CPB or the off-pump technique did not reveal any statistically significant differences in terms of donor characteristics.

Table 2:
Donor characteristics and lung procurement

Operative characteristics

Overall skin-to-skin time of surgery was shorter in the MILT group [320 (274, 381) vs 374 (300, 495) (P < 0.01)], whereas ischaemic time was significantly longer (502 ± 116 vs 395 ± 145) in MILT (P < 0.01). When extracorporeal circulation was required in the MILT group, the duration of CPB was similar to that of the CS group (Table (Table1).1). However, duration of surgery was approximately an hour longer in the MILT-CPB group. The requirement for surgical revision tended to be lower in the MILT group (4%) and higher in the MILT-CPB group (46%) (Table (Table11).

Early postoperative function

Gas exchange calculated as P/F ratios was similar between the CS and MILT groups on arrival to intensive care [34 (23, 42) vs 31 (19, 45)] and up to 72 h (data not shown). The fraction of patients extubated either in theatre or less than 24 h was 34% for MILT and 32% for CS (P = 0.62) (Table (Table3)3) . Overall, the duration of invasive MV was significantly less [26 (16, 252) vs 44 (20, 405) h, (P < 0.01] in the MILT group. In addition, there was also a tendency for reduced severe primary graft dysfunction in the MILT group compared with the two other groups. For instance, Grade 3 primary graft dysfunction at 72 h after surgery was 0 in the MILT group, and 11 and 14% in the CS and MILT-CPB groups (P = 0.31 and 0.27), respectively.

Table 3:
Postoperative gas exchange as assessed by P/F ratios

For the main group analysis, there were no statistically significant differences in requirement for extracorporeal mechanical support (11 vs 13%), rate of tracheostomy (40 vs 31%) or intensive therapy unit (ITU) readmissions (12 vs 10%) for CS and MILT, respectively. However, ITU length of stay was 2 days shorter [5 (3, 17) vs 7 (4, 24) days; P = 0.03] in the MILT group than in the CS group. Total hospital stay was nearly a week shorter [26 (19, 48) days vs 32 (22, 52) days] in MILT than CS groups but this did not achieve statistical significance (P = 0.10).

The results of the subgroup analysis for postoperative and ICU outcomes are presented in Table Table4,4, showing significant intergroup differences for most variables and demonstrating that outcomes were significantly better in patients who were not subjected to CPB in both surgical approaches.

Table 4:
Summary of postoperative ITU and hospital stay outcomes of patients undergoing bilateral single-lung transplantation

Inflammatory response

Both CS and MILT were associated with a strong inflammatory response with up to a 3-fold increase in white cell count and 10- to 20-fold increase in CRP, which lasted over several days. There was no statistical difference in either baseline values or during the early postoperative days among groups either for main or subgroup analysis.

Nearly all patients received some form of haemodynamic support. The most common vasoactive agent was noradrenaline both intraoperatively and during early ICU stay. The median noradrenaline requirement in CS operations was 237 (89, 450) μg/kg for the first 72 h compared with 212 (92, 359) μg/kg for MILT (P = 0.35). Subgroup analysis showed a trend for less noradrenaline use in MILT off-pump operation but this did not reach statistical significance.

Intraoperative red blood cell transfusion requirement was 3 U (1, 5) in the CS and 2 U (0, 4) in the MILT patients (P = 0.16). Intraoperative use of fresh frozen plasma and platelet transfusions were significantly less in the MILT group (P < 0.01 for both transfusions). Similar data were obtained for the ICU stay with CS associated with higher platelet and fresh frozen plasma preparations. Table Table55 summarizes transfusion requirements in the subgroups showing less blood product use in off-CPB subgroups.

Table 5:
Perioperative usage of blood products considering the intraoperative period and the next 72 h

Lung function tests

The first lung function test following transplantation was performed at 26 (17, 48) days for the MILT and 31 (21, 48) for the CS operations. Both FEV1 and forced vital capacity (FVC) have been higher [66 (54, 75) and 60 (50, 71)% predicted, respectively] in the MILT patients when compared with CS [53 (44, 63) and 49 (41, 59), P < 0.01]. FEV1 values increased over the course of the first-year follow-up period in all patient groups. As demonstrated in Fig. Fig.1A,1A, these values remained significantly higher in the MILT group compared with the CS group at all time points. Similar observations were made regarding FVC with statistically significant differences observed throughout the first year after transplantation (Fig. (Fig.11B).

Figure 1:
Lung function tests in recipients of bilateral sequential lung transplantation grouped according to the surgical technique and the use of CPB. (A) FEV1 (% predicted); (B) FVC (% predicted). FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; ...

Rejection episodes

The percentage of patients who developed a histopathologically proven episode of AR grade 1–4 is given in Table Table6.6. There were no statistically significant differences between the two main groups in terms of development and grade of AR. Similarly, we could not identify any significant differences among subgroups of patients operated on using CPB and with the off-pump technique.

Table 6:
Acute rejection episodes in patients undergoing bilateral lung transplantation according to surgical strategies

Survival

The perioperative (30-day) survival rate was 96 and 93% in the CS and MILT groups, respectively. Notably, all patients operated on without CPB survived the perioperative period. The Kaplan–Meier survival analysis over the 3-year follow-up period is presented in Fig. Fig.2.2. Regarding main group comparison, the CS and MILT groups were associated with similar early and midterm survival (Log rank, P = 0.83; Breslow, P = 0.61; Tarone-Ware, P = 0.70; Fig. Fig.2A).2A). To explore the potential impact of CPB on survival, we have explored a subgroup analysis including this variable. As depicted in Fig. Fig.2B,2B, there is a clear trend for better survival in the off-CPB groups (especially during the first year following transplantation). Pairwise comparison reveals statistically significant difference between the MILT off-CPB and CS-CPB groups (Log rank, P = 0.04; Breslow, P = 0.01; Tarone-Ware, P = 0.02) but there was no difference between the MILT off-CPB and CS off-CPB groups. In addition, patients requiring CPB in the MILT group appeared to have worse survival than the CS bypass patients (Log rank, P = 0.048; Breslow, P = 0.04; Tarone-Ware, P = 0.04).

Figure 2:
Kaplan–Meier survival curves for the patients who underwent bilateral sequential lung transplantation through the CS versus bilateral mini-thoracotomy (MILT) (A). There is no statistically significant difference in cumulative survival between ...

DISCUSSION

This study represents the first UK experience with MILT and significantly expands currently limited worldwide experience by providing exciting new information on the clinical and physiological impact of this novel surgical strategy.

By taking unique advantage of the presence of simultaneous surgical strategies at a single large-volume lung transplant centre, thereby reducing confounding factors related to historical controls and ever-changing perioperative management, our investigation provides important insights into crucial postoperative aspects of lung transplantation. While we anticipated more complex surgery, we hypothesized that MILT will reduce the surgical inflammatory response and will provide better functional recovery. In addition, we hypothesized that the minimally invasive approach allows safe conversion to CPB if clinical need for this arises during the operation. Our data clearly indicate some early postoperative benefits of MILT and demonstrate for the first time superior lung function recovery in the mid-term following lung transplantation.

Historically, our centre routinely utilized the clamshell surgical technique and elective CPB, based on surgical preference, clinical results and physiological considerations [9]. Our data seem to confirm that the clinical outcome of this approach at our centre is comparable if not superior to those reported by the ISHLT and other high-volume centres. Also, in the recent years, ex vivo lung perfusion and a transportable OCS have been increasingly utilized in our hospital [18, 19].

The minimally invasive approach represents multiple surgical and anaesthetic management challenges and so far represents the preferred surgical strategy of only one of our surgeons. Indeed, all MILT procedures during the study reporting period were done by this one surgeon. The individual surgeon contribution to the reported lung transplant programme, their elective and unplanned use of CPB and the surgeon-specific outcomes are reported in Supplementary Table S1.

The successful introduction of the MILT procedure suggests that the surgical approach provides acceptable exposure to critical surgical areas facilitating safe dissection of recipient and implantation of donor lungs. Interestingly, the total surgical time was less in MILT, suggesting that the surgical technique does not prolong the overall procedure duration and perhaps facilitates speed of chest closure due to less bleeding complications. Indeed, a significant fraction of MILT surgery was completed without the use of blood products. In those who required transfusion, the MILT group required significantly less plasma, platelet and specific haemostasis products. There was also a trend for less red blood cell usage both intraoperatively and in the ICU. However, in some patients, we encountered major vascular bleeding during the MILT surgery, which required conversion of the procedure to CPB. In this subset, the blood transfusion requirement was actually higher than that of the other groups.

In our experience, MILT has been successfully applied to a broad spectrum of patients, suggesting that MILT can be considered for most lung pathologies. However, severe pulmonary hypertension represents unique challenges for both off-pump bilateral sequential lung transplantation and MILT and we prefer elective bypass for transplantation for primary pulmonary hypertension.

While the CS group exhibited good postoperative lung function and clinical course in the ICU, there was a significant fraction of patients requiring extracorporeal support and surgical revision, and who developed postoperative complications requiring prolonged MV, slow weaning with tracheostomy, haemodynamic and renal support. While some of these complications were also present in MILT operations, the duration of MV and overall ICU stay were shorter. These differences are statistically highly significant and clinically relevant. Although the exact reasons for this remain unknown, donor and recipient factors appeared well balanced for these groups. Ischaemic time could be a potential factor; however, this was longer in the MILT group, mainly due to surgical preference to start these operations during daytime. We note an emerging international trend for this change of practice in lung transplantation, which is based on recent recognition that questions the risk of ischaemic time per se in survival. We therefore believe that the observed early outcome differences between our MILT and CS groups likely reflect the true effect of the surgical approach and perioperative management.

It is likely that the benefits of MILT could be explained by routine avoidance of CPB. Firstly, the benefits of MILT were generally lost where the operation had to be completed with use of CPB, although this latter patient population represents a higher-risk group. Secondly, the excellent results of the MILT off-CPB group seemed to be matched by a smaller group of CS patients in whom CPB was electively avoided as the new surgical preference of one surgeon. This analysis however may be complicated by selection bias.

In a pro–con debate, we have previously addressed the potential clinical aspects of CPB in lung transplantation [9]. In addition, we have also recently explored the clinical risks associated with CPB, per se, in our centre in a similar reporting period. In that study, intraoperative use of CPB was one of the predictors of 1-year mortality in univariate analysis [20]. Moreover, the on-pump technique also turned out to be a risk factor with borderline significance in the multivariate model. In addition, subgroup analysis of patients who underwent on-pump transplant revealed that unplanned intraoperative conversion to CPB had a significant negative influence on 1-year as well as overall cumulative survival compared with planned on-pump and off-pump procedures.

While the clinical and physiological benefits of MILT may suggest that the minimally invasive approach was associated with reduced surgical inflammation and pulmonary and systemic inflammatory response, our clinical laboratory parameters do not appear to support this notion. In our experience, both CS and MILT was associated with similar kinetics and magnitude of leucocytosis and CRP increase. This would suggest that either the inflammatory response is largely determined by lung ischaemia and reperfusion injury and/or the current technique of MILT approach contributes to the inflammatory response to the same degree as the clamshell incision. Future immunological studies aimed at leucocyte activation, cytokine release and balance of pro- and anti-inflammatory mediators will shed light on this important issue.

Previous reports on the anterolateral thoracotomy and MILT procedures suggested good functional recovery of lung function following transplantation compared with historical controls [11, 21]. These reports only covered the very first lung function tests after the procedure. Our study clearly demonstrates that this recovery is consistently better with the MILT approach than the CS incision in the mid-term follow-up. In our study lung function improved steadily over the first year after transplantation with the CS reaching ~80% predicted FEV1 and FVC after 6 months. Our data confirm the previous reports by the Vienna group regarding superior lung function at the first measurement time point following lung transplantation. Importantly, our novel data also suggest that MILT provides consistently superior lung function during the first year after transplantation that may extend to a longer mid-term follow-up. At this stage, we cannot be certain that this improved functional recovery is related to the surgical incision or avoidance of CPB. The bilateral thoracotomies may have a favourable impact on chest wall and lung mechanics in early postoperative periods. Furthermore, such lung function benefits may relate to reduced ventilation requirements in the MILT group. Our independent studies lend some support to this notion as we find strong correlations between early ventilation strategies and requirement for high inflation pressures and evolution of lung function (unpublished observations).

By limiting surgical inflammation, MILT may also have impact on early rejection and infection episodes. Indeed, AR is a common complication after lung transplantation and is reported in 35% of cases within the first year after the procedure. It also has an adverse influence on long-term survival after lung transplantation [3, 22]. In our study, we did not observe any significant difference in the prevalence of AR episodes among analysed groups. The overall incidence of AR in our series is relatively low. This could be related to the fact that we do not perform routine surveillance biopsies, which may result in underestimation of the prevalence of AR, especially in case of clinically silent minimal rejection. However, the same rules were applied to all patient groups and, thus, the potential error should be equally distributed among the groups, minimizing the bias.

There is only relatively limited information available regarding the influence of intraoperative variables such as surgical technique and CPB on rejection episodes. de Boer et al. [23] reported improvement in 1-year survival in patients transplanted due to emphysema using CPB compared with the off-pump group. They suggested that it could be related partially to immunosuppressive action of CPB. However, in the same study, they showed no difference in the number of rejection episodes between the groups. Burdett et al. [8] showed no difference in histopathologically proven AR 30 days after single-lung transplantation with or without CPB. No intraoperative factor was identified as an independent predictor of AR by Mangi et al. as well [24]. Thus, our study seems to suggest that the MILT strategy may not be able to beneficially impact on occurrences of AR after lung transplantation.

Our study has important limitations. Firstly, it is a retrospective analysis and not a prospective randomized trial. The two main surgical groups, i.e. MILT and CS are uncontrolled and significantly different in many important variables including operating surgeon and especially the use of elective CPB and CPB conversion. As a consequence, the differences could be related to the unbalanced use of CPB rather than the surgical incision. Indeed, our preliminary subgroup analysis indicates no significant differences in survival between the MILT off-pump and CS off-pump groups. Secondly, as in most single-centre studies in lung transplantation the patient numbers are relatively small, no definite conclusions can be made for many important parameters. In addition, our study is focusing on clinical and physiological responses rather than mechanistic investigations into primary graft dysfunction and recovery. Nevertheless, it represents one of the largest experiences with the minimally invasive approach demonstrating significant clinical benefits for the first time in the UK lung transplant population. We believe that, based on the current study and previous reports, a definite large-scale multicentre study is warranted to evaluate the exact place of the minimally invasive strategy in lung transplantation. The current investigation may provide important information into the exact design and meaningful endpoints of such a trial and evidence for the wider implementation of the MILT approach.

Funding

This study was supported by an institutional award from the RBHT Respiratory Biomedical Research Unit funded by the NIHR.

Conflict of interest: none declared.

Supplementary Material

Supplementary Data:

ACKNOWLEDGEMENTS

We are thankful for the help of our transplant coordinators and fellows for their valuable help.

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