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Outcomes of various transplant procedures (single, sparing, inverted) in living-donor lobar lung transplantation
Date et al
Transplantation
Outcomes of various transplant procedures (single, sparing, inverted) in living-donor lobar lung transplantation Hiroshi Date, MD,a Akihiro Aoyama, MD,a Kyoko Hijiya, MD,a Hideki Motoyama, MD,a Tomohiro Handa, MD,b Hideyuki Kinoshita, MD,c Shiro Baba, MD,d Toshiyuki Mizota, MD,e Kenji Minakata, MD,f and Toyofumi F. Chen-Yoshikawa, MDa ABSTRACT Objectives: In standard living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted. Because of the difficulty encountered in finding 2 donors with ideal size matching, various transplant procedures have been developed in our institution. The purpose of this retrospective study was to compare outcomes of nonstandard LDLLT with standard LDLLT.
Results: Twenty-nine patients (44.6%) received nonstandard LDLLT, including 12 single-lobe transplants, 7 native upper lobe sparing transplants, 6 right-left inverted transplants, 2 sparing þ inverted transplants, and 2 others. Thirty-six patients (57.4%) received standard LDLLT. Three- and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P ¼ .712). Conclusions: Various transplant procedures such as single, sparing and inverted transplants are valuable options when 2 donors with ideal size matching are not available for LDLLT. (J Thorac Cardiovasc Surg 2016;-:1-8)
Lung transplantation has been performed successfully worldwide in patients with end-stage lung disease, and more than 50,000 lung transplants have been reported.1 Living-donor lobar lung transplantation (LDLLT) had
From the Departments of aThoracic Surgery, bRespiratory Medicine, cCardiovascular Medicine, dPediatrics, eAnesthesia, and fCardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Read at the 96th Annual Meeting of The American Association for Thoracic Surgery, Baltimore, May 14-18, 2016. Received for publication May 27, 2016; revisions received Sept 5, 2016; accepted for publication Oct 11, 2016. Address for reprints: Hiroshi Date, MD, Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan (E-mail: [email protected]). 0022-5223/$36.00 Copyright Ó 2016 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2016.10.017
Survivals comparing nonstandard versus standard living-donor lobar lung transplantation. Central Message We successfully developed various transplant procedures (single, sparing, inverted) to deal with size mismatch in living-donor lobar lung transplantation.
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Methods: Between June 2008 and January 2016, we performed 65 LDLLTs for critically ill patients. Functional size matching was performed by estimating graft forced vital capacity based on the donor’s measured forced vital capacity and the number of pulmonary segments implanted. For anatomical size matching, 3dimensional computed tomography volumetry was performed. In cases of oversize mismatch, single-lobe transplant or downsizing transplant was performed. In cases of undersize mismatch, native upper lobe sparing transplant or rightleft inverted transplant was performed. In right-left inverted transplants, the donor’s right lower lobe was inverted and implanted into the recipient’s left chest cavity.
Perspective Living-donor lobar lung transplantation is indicated for patients who are unlikely to survive the long wait for cadaveric lungs. It is difficult, however, to find 2 donors with ideal size matching. In the setting of size mismatch, our newly developed various transplant procedures (single, sparing, inverted) can be applied to critically ill patients who will die otherwise. The outcome was excellent.
been the only realistic option for most patients in Japan until 2010, when the Japanese organ transplant law was amended so that the family of the brain-dead donors could make the decision for organ donation.2,3 The revision of the law significantly increased the number of organ donations from brain-dead donors4; however, the average waiting time is still more than 800 days, resulting in many deaths of patients on the waiting list. LDLLT often remains the only realistic option for very ill patients, particularly children.
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Abbreviations and Acronyms CLT ¼ cadaveric lung transplantation ECMO ¼ extracorporeal membrane oxygenation FVC ¼ forced vital capacity LDLLT ¼ living-donor lobar lung transplantation 3D-CT ¼ 3-dimensional computed tomography
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In a standard LDLLT, the right and left lower lobes from 2 healthy donors are implanted in the recipient in place of whole right and left lungs5-7; however, finding 2 healthy blood typecompatible donors with ideal size matching is very difficult. An adult lower lobe may be too large for small children. The use of oversized grafts could cause high airway resistance, atelectasis, and hemodynamic instability by the time of chest closure.8 To overcome these problems, we have used several techniques, including single-lobe transplantation with or without contralateral pneumonectomy,9,10 delayed chest closure,11 downsizing the graft,12 and middle lobe transplantation. Conversely, it often is inevitable that small grafts may be implanted, particularly in adult male recipients. Excessively small grafts may cause high pulmonary artery pressure and result in lung edema.13 We have developed lobar-sparing transplantation14 and right-to-left inverted transplantation protocols15 for undersize grafts. Long-term outcomes of these nonstandard LDLLT have not been reported at the present time. The purpose of this retrospective study was to compare outcomes of nonstandard LDLLT patients with those of standard LDLLT patients in our institution. PATIENTS AND METHODS Recipient and Donor Selection Patients being considered for LDLLT should be younger than 65 years old and must meet the criteria for conventional cadaveric lung transplantation (CLT). The policy of our program has been to limit LDLLT to critically ill patients with progressive lung disease who are unlikely to survive the long wait for cadaveric lungs. Our acceptance criteria for living-donors included blood typecompatible immediate family members between 20 and 60 years old. Potential donors had to be competent; willing to donate free of coercion; medically and psychosocially suitable; fully informed of the risks and benefits as a donor; and fully informed of the risks, benefits, and alternative treatments available to the recipient. Each case was carefully reviewed and approved by the institutional Lung Transplant Evaluation Committee.
Size Matching For ‘‘functional size matching,’’ we used graft forced vital capacity (FVC).16 We previously proposed a formula to estimate the graft FVC based on the donor’s measured FVC and the number of pulmonary segments implanted.2 Given that the right lower lobe consists of 5 segments, the left lower lobe 4 segments and the both lungs 19 segments, total FVC of the 2 grafts was estimated. When the total FVC of the 2 grafts was more than 45% of the predicted FVC of the recipient (calculated from a knowledge of height, age, and sex), we accepted the size disparity.
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The ratio should be more than 50% for patients with pulmonary hypertension.17 The FVC size matching was used mainly to evaluate undersized grafts. For ‘‘anatomical size matching,’’ 3-dimensional computed tomography (3D-CT) volumetry was performed both for the donor and the recipient.12,18 CT images were obtained with a multidetector CT scanner during a single respiratory pause at the end of maximum inspiratory effort. Contiguous 0.5-mm slices, reconstructed with a standard lung reconstruction algorithm, were used for volumetric analysis and the entire CT image was exported to a workstation (AZE Virtual Place Lexus; AZE Co, Ltd, Tokyo, Japan) for 3D-CT volumetry. Via automated segmentation, the volumes of each lung and the graft lobes were calculated automatically. The upper and lower thresholds of anatomical size matching have not been determined at the present time. We have accepted a wide range of volume ratios between the donor’s lower lobe graft and the corresponding recipient’s chest cavity.18 The 3D-CT size matching mainly was used to evaluate oversized grafts. The volume ratio upper threshold appeared to be in the vicinity of 200% based on 3D-CT size matching.
Standard LDLLT In standard LDLLT, the right and left lower lobes from 2 healthy donors were implanted under cardiopulmonary support in the recipient in place of whole right and left lungs. We have used extracorporeal membrane oxygenation (ECMO) instead of conventional cardiopulmonary bypass in most LDLLT procedures since 2012. Activated clotting time was maintained between 180 and 200 seconds.
Strategies for Oversized Grafts For small children, an adult lower lobe may be too large. We have used several compensatory techniques, including single-lobe transplantation with or without contralateral pneumonectomy,9,10 delayed chest closure,9 downsizing the graft,12 and middle-lobe transplantation. Single LDLLT also was indicated when only one living-donor was found in the family.
Strategies for Undersized Grafts For large adults, 2 lower lobe grafts may be too small. We have developed 2 transplant procedures, native upper lobe sparing LDLLT14 and right-left inverted LDLLT.15 Native upper lobesparing LDLLT is indicated when the total graft FVC was less than 60% of the recipient’s predicted FVC. The recipient lung should not be infected and the interlobar fissure should be well developed. Ideally, the native upper lobes would be less impaired than the lower lobes as seen on high-resolution CT or would be better perfused on perfusion scintigraphy. The surgical procedure of native upper lobesparing transplant was similar to that of standard LDLLT except that the pulmonary vein was anastomosed to the lower pulmonary vein, the pulmonary artery to the interlobar artery, and the bronchus distally to the second carina (Video 1). In right-left inverted LDLLT, the donor right lower lobe (5 segments) is inverted and implanted into the recipient’s left chest cavity instead of the donor left lower lobe (4 segments). It is indicated when total graft FVC was less than 60% of the recipient’s predicted FVC or when donor’s left lower lobectomy would be technically difficult as the result of interlobar pulmonary artery anatomy.19 The technical details have been described previously.15 At the time of left pneumonectomy in the recipient, upper and lower bronchi are stapled separately. After the right lower lobe graft is rotated from its anatomic position to 180 about its superior-inferior axis, the graft is placed in the recipient’s left chest cavity. The bronchus is anastomosed to the recipient’s left upper bronchus and the left lower bronchial stamp is left closed. The pulmonary artery anastomosis is performed behind the bronchus. The donor pulmonary vein typically is anastomosed to the recipient’s left upper pulmonary vein or occasionally to the recipient’s left appendage (Video 2).
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VIDEO 1. Bilateral native upper lobesparing LDLLT. A 21-year-old man became bed-bound as the result of severe idiopathic pulmonary arterial hypertension. His lung donors were his father and his mother. Bilateral native upper lobesparing LDLLT was indicated because the ratio of calculated graft FVC to predicted FVC of the recipient was only 40%. Supported by extracorporeal membrane oxygenation, the right middle and lower lobectomy was performed followed by implantation of the right lower lobe graft. Then, the left lower lobectomy was performed followed by implantation of the left lower graft. LDLTT, Living-donor lobar lung transplantation; FVC, forced vital capacity. Video available at: http://www.jtcvs.org.
Study Design
VIDEO 2. Right-left inverted single LDLLT. A 43-year-old woman was about to be intubated as the result of end-stage idiopathic interstitial pneumonia. Her husband was the only eligible donor for LDLLT. His right lower lobe was estimated to provide 44.6% of the recipient’s predicted forced vital capacity, which would provide the borderline function required for LDLLT. Because her left lung was more damaged than her right lung, transplanting the right lower lobe graft into the left thorax and sparing the better native right lung was considered the only treatment option. Supported by extracorporeal membrane oxygenation, left pneumonectomy was performed and upper and lower bronchi were stapled separately. After we rotated the right lower lobe graft from its anatomic position to 180 about its superior-inferior axis, the graft was placed in the recipient’s left chest cavity. The bronchus was anastomosed to the recipient’s left upper bronchus. The pulmonary artery anastomosis was performed behind the bronchus. The donor pulmonary vein was anastomosed to the recipient’s left appendage. LDLTT, Living-donor lobar lung transplantation. Video available at: http://www.jtcvs.org.
This study was a retrospective study of 65 consecutive patients who underwent LDLLT at Kyoto University Hospital between June 2008 and January 2016. These patients were stratified by type of transplant procedure: nonstandard LDLLT and standard LDLLT. Data collected included pre- and perioperative variables and survival. All data were analyzed retrospectively as of April 2016. The study protocol was approved by the institutional review board of Kyoto University Hospital. No funding was used. All values are given as mean standard deviation. Bivariate comparison of continuous variables was performed with Student t test. The data of 3 groups were evaluated with the Fisher least significant difference. Associations between categorical variables were tested by the Pearson c2 test. Observed survival data were reported as Kaplan-Meier estimates; the log rank test was used to explore the significance of the difference between the 2 groups. Differences were considered significant at a probability value of less than .05. The statistical software used for the analysis was Excel Statistics 2010 (Social Survey Research Information Co, Ltd, Tokyo, Japan).
implanted. One adult female patient received right-left inverted single LDLLT from her husband. Bilateral nonstandard LDLLT was performed in 17 patients. Native upper lobesparing LDLLT was performed in 7 patients. Bilateral upper lobes were spared in 3 patients, right upper lobe in 2 patients, right upper lobe and left superior segment in 1 patient, and left upper lobe in 1 patient, respectively. Right-left inverted LDLLT was performed in 6 patients. In 2 patients, the right upper lobe was spared followed by right-left inverted LDLLT. One small child received bilateral middle lobe LDLLT with right-left inverted technique. In one child receiving bilateral LDLLT, the right graft was downsized by right S6 segmentectomy before implantation.
RESULTS Transplant Procedures LDLLT transplant procedures are summarized in Table 1. Among 65 patients, 29 patients (44.6%) received nonstandard LDLLT and 36 patients (55.4%) received standard LDLLT. Single LDLLT was performed in 12 patients. Two small children received right single-lobe transplantation with simultaneous left pneumonectomy to provide more space for the oversized graft. One of the 2 children had severe funnel chest, and right S6 segmentectomy of the graft was performed at the back table and the basal segmental graft was
TABLE 1. Summary of LDLLT procedures Single LDLLT Downsizing by right S6 segmentectomy Simultaneous left pneumonectomy Right to left inverted single LDLLT Bilateral nonstandard LDLLT Lobar sparing Right-to-left inverted Sparing þ inverted Middle lobe þ inverted Dowinsizing by right S6 segmentectomy Standard LDLLT
12 1 2 1 17 7 6 2 1 1 36
LDLLT, Living-donor lobar lung transplantation.
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Pretransplant Characteristics of the Recipients and Donors Pretransplant patient characteristics are summarized in Table 2. The average age was younger in the nonstandard group than in the standard LDLLT group (29.2 19.8 years vs 41.1 18.4 years, P ¼ .0151). This is because 10 of the 12 patients receiving single LDLLT were children. For the same reason, the average height was shorter in the nonstandard LDLLT group. Diagnosis distribution was similar between the 2 groups. The most frequent indication was interstitial lung disease (n ¼ 27), including idiopathic pulmonary fibrosis (n ¼ 23), interstitial pneumonia associated with dermatomyositis (n ¼ 2), interstitial pneumonia associated with scleroderma, and chronic hypersensitivity pneumonia (n ¼ 1). Pulmonary complications after hematopoietic stem cell transplantation was the second most frequent indication (n ¼ 25). Diagnoses for hematopoietic stem cell transplantation included hematological malignancies (n ¼ 19), aplastic anemia (n ¼ 3), primary macroglobulinemia (n ¼ 1), severe combined immunodeficiency (n ¼ 1), and Chediac-Higashi syndrome (n ¼ 1). Preoperative condition was equally poor in both groups. Half of the LDLLT patients had a body mass index less than 17 kg/m,2 and less than half of the patients were able to walk. Seven patients (10.8%) were on a ventilator as long as 7 months preoperatively. Donor characteristics are summarized in Table 3. There were 45 donors in the nonstandard LDLLT group and 72 donors in the standard LDLLT group. Among the total 117 donors, 24 were mothers of the recipients, 23 were TABLE 2. Pretransplant patient characteristics
Characteristic Age, y <17 Sex Male Female Height, cm Weight, kg BMI, kg/m2 Diagnosis Interstitial lung disease Pulmonary complications after HSCT Pulmonary hypertension Others Pretransplant condition Ambulatory Ventilator dependent
Nonstandard LDLLT, n ¼ 29
Standard LDLLT, n ¼ 36
29.2 19.8 12 (41.4%)
41.1 18.4 6 (16.7%)
16 (55.2%) 13 (44.8%) 143.8 26.0 37.9 19.6 16.8 4.4
15 (41.7%) 21 (58.3%) 155.9 12.1 43.5 11.3 17.7 3.5
10 (34.5%) 11 (37.9%)
17 (47.2%) 14 (38.9%)
4 (13.8%) 4 (13.8%)
2 (5.6%) 3 (8.3%)
11 (37.9%) 5 (17.2%)
17 (47.2%) 2 (5.6%)
P value .0151 .0269 .28
.0154 .156 .355 .757
.452 .131
LDLLT, Living-donor lobar lung transplantation; BMI, body mass index; HSCT, hematopoietic stem cell transplantation.
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TABLE 3. Pretransplant living-donor characteristics
Age, y Sex Male Female Height, cm Donated lobe Right lower lobe Left lower lobe Middle lobe
Nonstandard LDLLT, n ¼ 45
Standard LDLLT, n ¼ 72
40.2 10.7
40.3 12.2
21 (46.7%) 24 (53.3%) 164.9 7.8
41 (56.9%) 31 (43.1%) 165.9 8.0
35 8 2
36 36 0
P value .982 .279
.5 .0008
LDLLT, Living-donor lobar lung transplantation.
sons, 15 were fathers, 14 were brothers, 13 were daughters, 10 were sisters, 8 were husbands, 7 were wives, 1 was a grandfather, 1 was an uncle, and 1 was an aunt. Age, sex, and height were similar between the nonstandard LDLLT group and the standard LDLLT group. Right lower lobes were more often donated in the nonstandard group due to single LDLLT and right-left inverted LDLLT. Size Matching FVC size matching and 3D-CT size matching are summarized in Table 4 and depicted in Figure 1. Two cases, a middle lobe transplant and a downsizing transplant, were excluded from the size matching analysis. Procedures were divided into the following 3 groups: single LDLLT (n ¼ 12), sparing and/or inverted LDLLT (n ¼ 15), and standard LDLLT (n ¼ 36). Regarding FVC size matching, the estimated graft FVC ratio was significantly lower in the sparing and/or inverted LDLLT group than in the standard LDLLT group (53.4 9.1% vs 67.6 16.5%, P ¼ .0034). Regarding 3D-CT size matching, the volume ratio was defined as the ratio between the total graft volume to the total volume of the recipient chest cavities in bilateral LDLLT. In single LDLLT, it was defined as the ratio between the volume of the single lobe to the volume of the corresponding ipsilateral chest cavity. The volume ratio was significantly greater in the single LDLLT group than in the standard LDLLT group (199.7 74.0% vs 119.5 51.5%, P <.0001). The volume ratio was significantly lower in the sparing and/or inverted LDLLT group than in the standard LDLLT group (84.3 43.4% vs 119.5 51.5%, P ¼ .0455). Perioperative and Early Posttransplant Outcomes Implantation time and ischemic time were similar between the 2 groups (Table 5). The PaO2/fraction of inspired oxygen ratio was significantly lower in the nonstandard LDLLT group than in the standard LDLLT group immediately after reperfusion (402 128 vs 473 191, P ¼ .0077). The frequency of tracheostomy, ECMO
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TABLE 4. Size matching Type
Single LDLLT, n ¼ 12
Sparing and/or inverted LDLLT, n ¼ 15
Standard LDLLT, n ¼ 36
FVC size matching, % (range) 3D-CT size matching, % (range)
61.8 15.0 (41.2-90.4) 199.7 74.0 (80.4-395)
53.4 9.1 (40.0-105) 84.3 43.4 (28-174.9)
67.6 16.5 (47.4-109.4) 119.5 51.5 (46.3-248)
LDLLT, Living-donor lobar lung transplantation; FVC, forced vital capacity; 3D-CT, three-dimensional computed tomography.
Bronchial anastomotic complication occurred in 2 of 46 anastomoses (4.3%) in the nonstandard group and it occurred in 3 of 72 anastomoses (4.2%) in the standard group (P ¼ .966). None of them were fatal. Survival At the time of final data analysis on April 30 2016, the mean time from nonstandard LDLLT to final analysis for the 29 recipients was 33 months (range 3- 96 months). The mean time from standard LDLLT to final analysis for the 36 recipients was 39 months (range 7-94 months). Survival curves are shown in Figure 2. Three- and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P ¼ .712). In the nonstandard LDLLT
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support, and the duration of mechanical ventilation required were similar between the 2 groups. Thirty-day mortality occurred in only 1 patient (3.5%) after nonstandard LDLLT. An 11-year-old boy who received right basal segmental transplantation died of sepsis on day 14. Hospital mortality was encountered in 3 patients (10.3%) after nonstandard LDLLT and 1 patient (2.8%) after standard LDLLT. A 14-year-old girl with pulmonary hypertension received left single-lobe transplantation as a retransplant and died of graft failure on day 108. A 9year-old boy with congenital proteinosis received bilateral middle lobe transplantation and died of graft failure with persistent pulmonary hypertension on day 112. A 64-yearold man with idiopathic pulmonary fibrosis received standard LDLLT and died of aspiration pneumonia on day 98.
FIGURE 1. A, FVC size matching. The estimated graft FVC ratio was significantly lower in the sparing and/or inverted LDLLT group than in the standard LDLLT group (53.4 9.1% vs 67.6 16.5%, P ¼ .0034). B, 3D-CT size matching. The volume ratio was significantly greater in the single LDLLT group than in the standard LDLLT group (199.7 74.0% vs 119.5 51.5%, P<.0001). The volume ratio was significantly lower in the sparing and/or inverted LDLLT group than in the standard LDLLT group (84.3 43.4% vs 119.5 51.5%, P ¼ .0455). FVC, Forced vital capacity; 3D-CT, three-dimensional computed tomography.
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TABLE 5. Perioperative and early posttransplant outcome
Implantation time, min Ischemic time, min PaO2/FiO2 immediately after reperfusion Tracheostomy Yes Use of ECMO support Yes Duration of mechanical ventilation, d 30-d mortality Hospital mortality Bronchial anastomotic complication
Nonstandard LDLLT, n ¼ 29
Standard LDLLT, n ¼ 36
P value
60 12 130 41 402 128
60 13 142 41 473 191
.431 .066 .0077
24 (57.1%)
17 (45.9%)
3 (10.3%) 17.1 17.7
3 (8.3%) 14.9 24.3
.711
1 (3.5%) 3 (10.3%) 2/46 (4.3%)
0 (0%) 1 (2.8%) 3/72 (4.2%)
.262 .207 .996
.488 .781
LDLLT, Living-donor lobar lung transplantation; FiO2, fraction of inspired oxygen; ECMO, extracorporeal membrane oxygenation.
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group, a 61-year-old man with idiopathic pulmonary fibrosis died of bronchiolitis obliterans syndrome 40 months after receiving right upper lobe sparing LDLLT. Donor Outcomes We encountered minor surgical morbidities such as prolonged air leak, wound infection, and pleural effusion after donor lobectomy. All living-donors returned, however, to their previous life styles without restriction. DISCUSSION The shortage of cadaveric lung donors remains an important unsolved problem in Japan. Aggressive use of marginal donors results in a high utilization ratio (>60%) of the lungs
FIGURE 2. Actuarial survival after nonstandard LDLLT (n ¼ 29) compared with that after standard LDLLT (n ¼ 36). Three- and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P ¼ .712). LDLLT, Living-donor lobar lung transplantation.
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of brain-dead donors; however, the mortality rate for patients on the waiting list for CLT is still about 40%. LDLLT is often the only realistic option for very ill patients. During the study period, we performed 65 LDLLTs and 62 CLTs in our institution. We recently reported that LDLLT provided similar survival to CLT even for very ill patients.20 The methods of evaluation of size matching and managing size disparity in LDLLT are very important. Because only lobes are implanted into the recipient, a wide range of size mismatch is often encountered in LDLLT. In CLT, efforts are made to find size-matched cadaveric donor lungs for the recipient. In Japan, size matching in CLT is accomplished by the use of predicted vital capacity comparisons between donors and recipients. Other size-matching strategies have been described, including height, total lung capacity, chest roentgenogram dimensions, and inframammary circumference. In contrast, precise evaluation of size matching is possible preoperatively in LDLLT because pulmonary function test and 3D-CT volumetry can be performed not only for the recipient but also for the livingdonors, which is practically impossible for most of the cadaveric donors. We accept only immediate family members (relatives within third degree or a spouse) as livingdonors and their ABO blood type must be compatible with that of the recipient. With these donor selection criteria, finding 2 suitable living donors is difficult. For small pediatric recipients, finding size matched cadaveric donors is extremely difficult in Japan. Only 4 children younger than 10 years have received CLT in whole country at the present moment.4 LDLLT is often the only realistic option for children, but adult lobes are too large to fit into the small chest cavity of the pediatric recipient when the 3D-CT volume ratio exceeds 200%. One of the solutions is single-lobe transplantation with or without contralateral pneumonectomy. We previously reported on an 8-year-old girl receiving right single-lobe transplantation who received simultaneous left pneumonectomy.10 She is alive and doing well more than 7 years after the transplantation. One of the children in the current study, an 11-yearold boy, had severe funnel chest and his mother’s right lower lobe was 395% bigger than his right chest cavity by 3D-CT volumetric evaluation. Right S6 segmentectomy of the graft was performed at the back table and the basal segmental graft was implanted followed by left pneumonectomy. Even with these efforts, the chest could not be closed because of the severe size mismatch, and the patient died of sepsis on day 14. A lobe that is small for the body but large for the chest cavity should not be used. We reported on 14 critically ill patients who had undergone single LDLLT using a single donor at 3 lung transplant centers in Japan.21 Three- and five-year survival rates were 70% and 56%, respectively. The result was acceptable but not as good as bilateral LDLLT. We concluded that single LDLLT is an acceptable option for sick patients when
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only one suitable living-donor is available but bilateral LDLLT is a better option if 2 living-donors are found. Another strategy for an oversize graft is to use the middle lobe instead of the lower lobe as a graft. Although Oto and colleagues22 reported successful middle lobe transplantation, we lost our patient receiving bilateral middle lobe transplantation due to graft failure with persistent pulmonary hypertension. Two lobes may be too small for the adult recipient. Previously, we did not accept patients when the FVC graft ratio was less than 45%.2,3 To solve this problem, we developed 2 procedures, lobar-sparing LDLLT14 and right-left inverted LDLLT.15 Lobar-sparing LDDLT is technically straightforward if the interlobar fissure is well developed. Using a canine lung transplantation model, Sugimoto and colleagues23 demonstrated the technical feasibility of sparing native upper lobes. We previously reported 5 cases receiving lobarsparing LDLLT,14 and the current study included 9 cases (2 cases combined with right-left inverted LDLLT). Candidates should not have infectious lung disease. Diagnoses included idiopathic pulmonary fibrosis (n ¼ 4), idiopathic pulmonary arterial hypertension (n ¼ 2), bronchiolitis obliterans (n ¼ 1), chronic hypersensitivity pneumonia (n ¼ 1), and interstitial pneumonia associated scleroderma (n ¼ 1). Under normal physiology, it is well known that the lower lobe functions better than the upper lobe due to diaphragm motion. It was for this reason that we always spared the diseased native upper lobe and implanted normal lower lobe graft. Scintigraphy demonstrated a limited perfusion to the spared lobes at 1 year,14 particularly in patients with pulmonary hypertension. We believe that the spared upper lobes provided an adequate chest cavity for the small lower lobe grafts and functioned as a reservoir in the early postoperative period. Late complications attributed to the spared lobes were airway stenosis after Aspergillus infection in one patient and late onset of native lobe pneumothorax in 2 patients. All these complications were manageable. Right-left inverted LDLLT was developed based on the fact that the right lower lobe (5 segments) is generally larger than the left lower lobe (4 segments). When we planned to use this technique for the first time, we used 3D models produced by a 3D printer.15 This allowed us to simulate the positional relationship of hilar structures and to determine the anastomotic sites for the bronchus, pulmonary artery, and pulmonary vein preoperatively. When the right lower lobe graft was inverted and placed in the left chest cavity, the interlobar pulmonary artery was positioned behind the bronchus. The donor bronchus was anastomosed to the recipient’s left upper bronchus, leaving left lower bronchial stamp closed, and allowing us to perform pulmonary artery anastomosis behind the bronchus. We previously reported 3 cases receiving right-left inverted LDLLT15 and the current study included 8 cases (2 cases combined with lobar sparing
LDLLT). The bronchial anastomosis and the stump of the left lower bronchus healed nicely in all cases. In 1 case, nonsymptomatic mild stenosis in the left pulmonary artery was detected by postoperative enhanced CT scan. Because the LDLLT recipients were very sick at the time of transplantation, meticulous postoperative management was mandatory. Oxygenation immediately after reperfusion was significantly worse in the nonstandard LDLLT group than in the standard LDLLT group because of the residual diseased lung in single LDLLT and spared upper lobes in lobar sparing LDLLT; however, use of ECMO support and the duration of mechanical ventilation required were similar between the 2 groups. Although hospital death occurred in 3 patients in the nonstandard group, they were extremely difficult cases; right basal segmental transplantation with left pneumonectomy, right single LDLLT as a retransplantation, and bilateral middle lobe transplantation. All patients who received lobar sparing LDLLT and/or right-left inverted LDLLT were discharged from the hospital without supplemental inhaled oxygen. Twenty-nine of 65 LDLLTs (44.6%) were performed as nonstandard LDLLT. Most of those patients would not have been accepted if the aforementioned new techniques were not used. Figure 1 clearly shows the greater degree of size disparity in nonstandard LDLLT; however, the survival rates of 89.1% and 76.6% at 3 and 5 years, respectively, after nonstandard LDLLT were similar to survival rates after standard LDLLT. These excellent long-term survival rates were most encouraging. Limitations of the present study included it being a nonrandomized, retrospective study and the relatively small number of transplant procedures. CONCLUSION Various transplant procedures such as single, sparing and inverted transplants are valuable options when 2 donors with ideal size matching are not found in LDLLT. Conflict of Interest Statement Authors have nothing to disclose with regard to commercial support. References 1. Yusen RD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Goldfarb SB, et al. The registry of the International Society for Heart Lung Transplantation: thirty-second official adult lung and heart-lung transplantation report—2015; focus theme: early graft failure. J Heart Lung Transplant. 2015;34:1264-77. 2. Date H, Aoe M, Nagahiro I, Sano Y, Andou A, Matsubara H, et al. Living-donor lobar lung transplantation for various lung diseases. J Thorac Cardiovasc Surg. 2003;126:476-81. 3. Date H, Aoe M, Sano Y, Nagahiro I, Miyaji K, Goto K, et al. Improved survival after living-donor lobar lung transplantation. J Thorac Cardiovasc Surg. 2004; 128:933-40. 4. Sato M, Okada Y, Minami M, Shiraishi T, Nagayasu T, Yoshino I, et al. Registry of the Japanese Society of Lung and Heart-Lung Transplantation: official Japanese lung transplant report, 2014. Gen Thorac Cardiovasc Surg. 2014;62:594-601. 5. Starnes VA, Bowdish ME, Woo MS, Barbers RG, Schenkel FA, Horn MV, et al. A decade of living lobar lung transplantation. Recipient outcomes. J Thorac Cardiovasc Surg. 2004;127:114-22.
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6. Cohen RG, Barr ML, Schenkel FA, DeMeester TR, Wells WJ, Starnes VA. Living-related donor lobectomy for bilateral lobar transplantation in patients with cystic fibrosis. Ann Thorac Surg. 1994;57:1423-7; discussion 1428. 7. Barr ML, Baker CJ, Schenkel FA, Bowdish ME, Bremner RM, Cohen RG, et al. Living donor lung transplantation: selection, technique, and outcome. Transplant Proc. 2001;33:3527-32. 8. Oto T, Date H, Ueda K, Hayama M, Nagahiro I, Aoe M, et al. Experimental study of oversized grafts in a canine living-donor lobar lung transplantation model. J Heart Lung Transplant. 2001;20:1325-30. 9. Shoji T, Bando T, Fujinaga T, Date H. Living-donor single-lobe lung transplant in a 6-year-old girl after 7-month mechanical ventilator support. J Thorac Cardiovasc Surg. 2010;139:e112-3. 10. Sonobe M, Bando T, Kusuki S, Fujinaga T, Shoji T, Chen F, et al. Living-donor single-lobe lung transplantation and simultaneous contralateral pneumonectomy in a child. J Heart Lung Transplant. 2011;30:471-4. 11. Chen F, Matsukawa S, Ishii H, Ikeda T, Shoji T, Fujinaga T, et al. Delayed chest closure assessed by transesophageal echocardiogram in single-lobe lung transplantation. Ann Thorac Surg. 2011;92:2254-7. 12. Chen F, Fujinaga T, Shoji T, Yamada T, Nakajima D, Sakamoto J, et al. Perioperative assessment of oversized lobar graft downsizing in living-donor lobar lung transplantation using three-dimensional computed tomographic volumetry. Transplant Int. 2010;23:e41-4. 13. Fujita T, Date H, Ueda K, Nagahiro I, Aoe M, Andou A, et al. Experimental study on size matching in a canine living-donor lobar lung transplant model. J Thorac Cardiovasc Surg. 2002;123:104-9. 14. Aoyama A, Chen F, Minakata K, Yamazaki K, Yamada T, Sato M, et al. Sparing native upper lobes in living-donor lobar lung transplantation: five cases from a single center. Am J Transplant. 2015;15:3202-7. 15. Chen F, Miyamoto E, Takemoto M, Minakata K, Yamada T, Sato M, et al. Right and left inverted lobar lung transplantation. Am J Transplant. 2015; 15:1716-21.
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16. Date H, Aoe M, Nagahiro I, Sano Y, Matsubara H, Goto K, et al. How to predict forced vital capacity after living-donor lobar-lung transplantation. J Heart Lung Transplant. 2004;23:547-51. 17. Date H, Kusano KF, Matsubara H, Ogawa A, Fujio H, Miyaji K, et al. Livingdonor lobar lung transplantation for pulmonary arterial hypertension after failure of epoprostenol therapy. J Am Coll Cardiol. 2007;50:523-7. 18. Chen F, Kubo T, Yamada T, Sato M, Aoyama A, Bando T, et al. Adaptation over a wide range of donor graft lung size discrepancies in living-donor lobar lung transplantation. Am J Transplant. 2013;13:1336-42. 19. Chen F, Fujinaga T, Shoji T, Kubo T, Sonobe M, Sato M, et al. Short-term outcome in living donors for lung transplantation: the role of preoperative computer tomographic evaluations of fissures and vascular anatomy. Transplant Int. 2012;25:732-8. 20. Date H, Sato M, Aoyama A, Yamada T, Mizota T, Kinoshita H, et al. Livingdonor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patientsy. Eur J Cardiothorac Surg. 2015;47:967-73; discussion 972-3. 21. Date H, Shiraishi T, Sugimoto S, Shoji T, Chen F, Hiratsuka M, et al. Outcome of living-donor lobar lung transplantation using a single donor. J Thorac Cardiovasc Surg. 2012;144:710-5. 22. Oto T, Miyoshi K, Sugimoto S, Yamane M. Living related donor middle lobe lung transplant in a pediatric patient. J Thorac Cardiovasc Surg. 2015;149:e42-4. 23. Sugimoto S, Date H, Sugimoto R, Aoe M, Sano Y. Bilateral native lung-sparing lobar transplantation in a canine model. J Thorac Cardiovasc Surg. 2006;132: 1213-8.
Key Words: living-donor lobar lung transplantation, single lobe transplant, native upper lobe–sparing transplant, rightleft inverted transplant, oversized graft, undersized graft, size matching
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Outcomes of various transplant procedures (single, sparing, inverted) in livingdonor lobar lung transplantation Hiroshi Date, MD, Akihiro Aoyama, MD, Kyoko Hijiya, MD, Hideki Motoyama, MD, Tomohiro Handa, MD, Hideyuki Kinoshita, MD, Shiro Baba, MD, Toshiyuki Mizota, MD, Kenji Minakata, MD, and Toyofumi F. Chen-Yoshikawa, MD, Kyoto, Japan We successfully developed various transplant procedures (single, sparing, inverted) to deal with size mismatch in living-donor lobar lung transplantation.
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Outcomes of various transplant procedures (single, sparing, inverted) in living-donor lobar lung transplantation Hiroshi Date, MD,a Akihiro Aoyama, MD,a Kyoko Hijiya, MD,a Hideki Motoyama, MD,a Tomohiro Handa, MD,b Hideyuki Kinoshita, MD,c Shiro Baba, MD,d Toshiyuki Mizota, MD,e Kenji Minakata, MD,f and Toyofumi F. Chen-Yoshikawa, MDa ABSTRACT Objectives: In standard living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted. Because of the difficulty encountered in finding 2 donors with ideal size matching, various transplant procedures have been developed in our institution. The purpose of this retrospective study was to compare outcomes of nonstandard LDLLT with standard LDLLT.
Results: Twenty-nine patients (44.6%) received nonstandard LDLLT, including 12 single-lobe transplants, 7 native upper lobe sparing transplants, 6 right-left inverted transplants, 2 sparing þ inverted transplants, and 2 others. Thirty-six patients (57.4%) received standard LDLLT. Three- and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P ¼ .712). Conclusions: Various transplant procedures such as single, sparing and inverted transplants are valuable options when 2 donors with ideal size matching are not available for LDLLT. (J Thorac Cardiovasc Surg 2016;-:1-8)
Lung transplantation has been performed successfully worldwide in patients with end-stage lung disease, and more than 50,000 lung transplants have been reported.1 Living-donor lobar lung transplantation (LDLLT) had
From the Departments of aThoracic Surgery, bRespiratory Medicine, cCardiovascular Medicine, dPediatrics, eAnesthesia, and fCardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Read at the 96th Annual Meeting of The American Association for Thoracic Surgery, Baltimore, May 14-18, 2016. Received for publication May 27, 2016; revisions received Sept 5, 2016; accepted for publication Oct 11, 2016. Address for reprints: Hiroshi Date, MD, Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan (E-mail: [email protected]). 0022-5223/$36.00 Copyright Ó 2016 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2016.10.017
Survivals comparing nonstandard versus standard living-donor lobar lung transplantation. Central Message We successfully developed various transplant procedures (single, sparing, inverted) to deal with size mismatch in living-donor lobar lung transplantation.
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Methods: Between June 2008 and January 2016, we performed 65 LDLLTs for critically ill patients. Functional size matching was performed by estimating graft forced vital capacity based on the donor’s measured forced vital capacity and the number of pulmonary segments implanted. For anatomical size matching, 3dimensional computed tomography volumetry was performed. In cases of oversize mismatch, single-lobe transplant or downsizing transplant was performed. In cases of undersize mismatch, native upper lobe sparing transplant or rightleft inverted transplant was performed. In right-left inverted transplants, the donor’s right lower lobe was inverted and implanted into the recipient’s left chest cavity.
Perspective Living-donor lobar lung transplantation is indicated for patients who are unlikely to survive the long wait for cadaveric lungs. It is difficult, however, to find 2 donors with ideal size matching. In the setting of size mismatch, our newly developed various transplant procedures (single, sparing, inverted) can be applied to critically ill patients who will die otherwise. The outcome was excellent.
been the only realistic option for most patients in Japan until 2010, when the Japanese organ transplant law was amended so that the family of the brain-dead donors could make the decision for organ donation.2,3 The revision of the law significantly increased the number of organ donations from brain-dead donors4; however, the average waiting time is still more than 800 days, resulting in many deaths of patients on the waiting list. LDLLT often remains the only realistic option for very ill patients, particularly children.
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Abbreviations and Acronyms CLT ¼ cadaveric lung transplantation ECMO ¼ extracorporeal membrane oxygenation FVC ¼ forced vital capacity LDLLT ¼ living-donor lobar lung transplantation 3D-CT ¼ 3-dimensional computed tomography
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In a standard LDLLT, the right and left lower lobes from 2 healthy donors are implanted in the recipient in place of whole right and left lungs5-7; however, finding 2 healthy blood typecompatible donors with ideal size matching is very difficult. An adult lower lobe may be too large for small children. The use of oversized grafts could cause high airway resistance, atelectasis, and hemodynamic instability by the time of chest closure.8 To overcome these problems, we have used several techniques, including single-lobe transplantation with or without contralateral pneumonectomy,9,10 delayed chest closure,11 downsizing the graft,12 and middle lobe transplantation. Conversely, it often is inevitable that small grafts may be implanted, particularly in adult male recipients. Excessively small grafts may cause high pulmonary artery pressure and result in lung edema.13 We have developed lobar-sparing transplantation14 and right-to-left inverted transplantation protocols15 for undersize grafts. Long-term outcomes of these nonstandard LDLLT have not been reported at the present time. The purpose of this retrospective study was to compare outcomes of nonstandard LDLLT patients with those of standard LDLLT patients in our institution. PATIENTS AND METHODS Recipient and Donor Selection Patients being considered for LDLLT should be younger than 65 years old and must meet the criteria for conventional cadaveric lung transplantation (CLT). The policy of our program has been to limit LDLLT to critically ill patients with progressive lung disease who are unlikely to survive the long wait for cadaveric lungs. Our acceptance criteria for living-donors included blood typecompatible immediate family members between 20 and 60 years old. Potential donors had to be competent; willing to donate free of coercion; medically and psychosocially suitable; fully informed of the risks and benefits as a donor; and fully informed of the risks, benefits, and alternative treatments available to the recipient. Each case was carefully reviewed and approved by the institutional Lung Transplant Evaluation Committee.
Size Matching For ‘‘functional size matching,’’ we used graft forced vital capacity (FVC).16 We previously proposed a formula to estimate the graft FVC based on the donor’s measured FVC and the number of pulmonary segments implanted.2 Given that the right lower lobe consists of 5 segments, the left lower lobe 4 segments and the both lungs 19 segments, total FVC of the 2 grafts was estimated. When the total FVC of the 2 grafts was more than 45% of the predicted FVC of the recipient (calculated from a knowledge of height, age, and sex), we accepted the size disparity.
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The ratio should be more than 50% for patients with pulmonary hypertension.17 The FVC size matching was used mainly to evaluate undersized grafts. For ‘‘anatomical size matching,’’ 3-dimensional computed tomography (3D-CT) volumetry was performed both for the donor and the recipient.12,18 CT images were obtained with a multidetector CT scanner during a single respiratory pause at the end of maximum inspiratory effort. Contiguous 0.5-mm slices, reconstructed with a standard lung reconstruction algorithm, were used for volumetric analysis and the entire CT image was exported to a workstation (AZE Virtual Place Lexus; AZE Co, Ltd, Tokyo, Japan) for 3D-CT volumetry. Via automated segmentation, the volumes of each lung and the graft lobes were calculated automatically. The upper and lower thresholds of anatomical size matching have not been determined at the present time. We have accepted a wide range of volume ratios between the donor’s lower lobe graft and the corresponding recipient’s chest cavity.18 The 3D-CT size matching mainly was used to evaluate oversized grafts. The volume ratio upper threshold appeared to be in the vicinity of 200% based on 3D-CT size matching.
Standard LDLLT In standard LDLLT, the right and left lower lobes from 2 healthy donors were implanted under cardiopulmonary support in the recipient in place of whole right and left lungs. We have used extracorporeal membrane oxygenation (ECMO) instead of conventional cardiopulmonary bypass in most LDLLT procedures since 2012. Activated clotting time was maintained between 180 and 200 seconds.
Strategies for Oversized Grafts For small children, an adult lower lobe may be too large. We have used several compensatory techniques, including single-lobe transplantation with or without contralateral pneumonectomy,9,10 delayed chest closure,9 downsizing the graft,12 and middle-lobe transplantation. Single LDLLT also was indicated when only one living-donor was found in the family.
Strategies for Undersized Grafts For large adults, 2 lower lobe grafts may be too small. We have developed 2 transplant procedures, native upper lobe sparing LDLLT14 and right-left inverted LDLLT.15 Native upper lobesparing LDLLT is indicated when the total graft FVC was less than 60% of the recipient’s predicted FVC. The recipient lung should not be infected and the interlobar fissure should be well developed. Ideally, the native upper lobes would be less impaired than the lower lobes as seen on high-resolution CT or would be better perfused on perfusion scintigraphy. The surgical procedure of native upper lobesparing transplant was similar to that of standard LDLLT except that the pulmonary vein was anastomosed to the lower pulmonary vein, the pulmonary artery to the interlobar artery, and the bronchus distally to the second carina (Video 1). In right-left inverted LDLLT, the donor right lower lobe (5 segments) is inverted and implanted into the recipient’s left chest cavity instead of the donor left lower lobe (4 segments). It is indicated when total graft FVC was less than 60% of the recipient’s predicted FVC or when donor’s left lower lobectomy would be technically difficult as the result of interlobar pulmonary artery anatomy.19 The technical details have been described previously.15 At the time of left pneumonectomy in the recipient, upper and lower bronchi are stapled separately. After the right lower lobe graft is rotated from its anatomic position to 180 about its superior-inferior axis, the graft is placed in the recipient’s left chest cavity. The bronchus is anastomosed to the recipient’s left upper bronchus and the left lower bronchial stamp is left closed. The pulmonary artery anastomosis is performed behind the bronchus. The donor pulmonary vein typically is anastomosed to the recipient’s left upper pulmonary vein or occasionally to the recipient’s left appendage (Video 2).
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VIDEO 1. Bilateral native upper lobesparing LDLLT. A 21-year-old man became bed-bound as the result of severe idiopathic pulmonary arterial hypertension. His lung donors were his father and his mother. Bilateral native upper lobesparing LDLLT was indicated because the ratio of calculated graft FVC to predicted FVC of the recipient was only 40%. Supported by extracorporeal membrane oxygenation, the right middle and lower lobectomy was performed followed by implantation of the right lower lobe graft. Then, the left lower lobectomy was performed followed by implantation of the left lower graft. LDLTT, Living-donor lobar lung transplantation; FVC, forced vital capacity. Video available at: http://www.jtcvs.org.
Study Design
VIDEO 2. Right-left inverted single LDLLT. A 43-year-old woman was about to be intubated as the result of end-stage idiopathic interstitial pneumonia. Her husband was the only eligible donor for LDLLT. His right lower lobe was estimated to provide 44.6% of the recipient’s predicted forced vital capacity, which would provide the borderline function required for LDLLT. Because her left lung was more damaged than her right lung, transplanting the right lower lobe graft into the left thorax and sparing the better native right lung was considered the only treatment option. Supported by extracorporeal membrane oxygenation, left pneumonectomy was performed and upper and lower bronchi were stapled separately. After we rotated the right lower lobe graft from its anatomic position to 180 about its superior-inferior axis, the graft was placed in the recipient’s left chest cavity. The bronchus was anastomosed to the recipient’s left upper bronchus. The pulmonary artery anastomosis was performed behind the bronchus. The donor pulmonary vein was anastomosed to the recipient’s left appendage. LDLTT, Living-donor lobar lung transplantation. Video available at: http://www.jtcvs.org.
This study was a retrospective study of 65 consecutive patients who underwent LDLLT at Kyoto University Hospital between June 2008 and January 2016. These patients were stratified by type of transplant procedure: nonstandard LDLLT and standard LDLLT. Data collected included pre- and perioperative variables and survival. All data were analyzed retrospectively as of April 2016. The study protocol was approved by the institutional review board of Kyoto University Hospital. No funding was used. All values are given as mean standard deviation. Bivariate comparison of continuous variables was performed with Student t test. The data of 3 groups were evaluated with the Fisher least significant difference. Associations between categorical variables were tested by the Pearson c2 test. Observed survival data were reported as Kaplan-Meier estimates; the log rank test was used to explore the significance of the difference between the 2 groups. Differences were considered significant at a probability value of less than .05. The statistical software used for the analysis was Excel Statistics 2010 (Social Survey Research Information Co, Ltd, Tokyo, Japan).
implanted. One adult female patient received right-left inverted single LDLLT from her husband. Bilateral nonstandard LDLLT was performed in 17 patients. Native upper lobesparing LDLLT was performed in 7 patients. Bilateral upper lobes were spared in 3 patients, right upper lobe in 2 patients, right upper lobe and left superior segment in 1 patient, and left upper lobe in 1 patient, respectively. Right-left inverted LDLLT was performed in 6 patients. In 2 patients, the right upper lobe was spared followed by right-left inverted LDLLT. One small child received bilateral middle lobe LDLLT with right-left inverted technique. In one child receiving bilateral LDLLT, the right graft was downsized by right S6 segmentectomy before implantation.
RESULTS Transplant Procedures LDLLT transplant procedures are summarized in Table 1. Among 65 patients, 29 patients (44.6%) received nonstandard LDLLT and 36 patients (55.4%) received standard LDLLT. Single LDLLT was performed in 12 patients. Two small children received right single-lobe transplantation with simultaneous left pneumonectomy to provide more space for the oversized graft. One of the 2 children had severe funnel chest, and right S6 segmentectomy of the graft was performed at the back table and the basal segmental graft was
TABLE 1. Summary of LDLLT procedures Single LDLLT Downsizing by right S6 segmentectomy Simultaneous left pneumonectomy Right to left inverted single LDLLT Bilateral nonstandard LDLLT Lobar sparing Right-to-left inverted Sparing þ inverted Middle lobe þ inverted Dowinsizing by right S6 segmentectomy Standard LDLLT
12 1 2 1 17 7 6 2 1 1 36
LDLLT, Living-donor lobar lung transplantation.
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Pretransplant Characteristics of the Recipients and Donors Pretransplant patient characteristics are summarized in Table 2. The average age was younger in the nonstandard group than in the standard LDLLT group (29.2 19.8 years vs 41.1 18.4 years, P ¼ .0151). This is because 10 of the 12 patients receiving single LDLLT were children. For the same reason, the average height was shorter in the nonstandard LDLLT group. Diagnosis distribution was similar between the 2 groups. The most frequent indication was interstitial lung disease (n ¼ 27), including idiopathic pulmonary fibrosis (n ¼ 23), interstitial pneumonia associated with dermatomyositis (n ¼ 2), interstitial pneumonia associated with scleroderma, and chronic hypersensitivity pneumonia (n ¼ 1). Pulmonary complications after hematopoietic stem cell transplantation was the second most frequent indication (n ¼ 25). Diagnoses for hematopoietic stem cell transplantation included hematological malignancies (n ¼ 19), aplastic anemia (n ¼ 3), primary macroglobulinemia (n ¼ 1), severe combined immunodeficiency (n ¼ 1), and Chediac-Higashi syndrome (n ¼ 1). Preoperative condition was equally poor in both groups. Half of the LDLLT patients had a body mass index less than 17 kg/m,2 and less than half of the patients were able to walk. Seven patients (10.8%) were on a ventilator as long as 7 months preoperatively. Donor characteristics are summarized in Table 3. There were 45 donors in the nonstandard LDLLT group and 72 donors in the standard LDLLT group. Among the total 117 donors, 24 were mothers of the recipients, 23 were TABLE 2. Pretransplant patient characteristics
Characteristic Age, y <17 Sex Male Female Height, cm Weight, kg BMI, kg/m2 Diagnosis Interstitial lung disease Pulmonary complications after HSCT Pulmonary hypertension Others Pretransplant condition Ambulatory Ventilator dependent
Nonstandard LDLLT, n ¼ 29
Standard LDLLT, n ¼ 36
29.2 19.8 12 (41.4%)
41.1 18.4 6 (16.7%)
16 (55.2%) 13 (44.8%) 143.8 26.0 37.9 19.6 16.8 4.4
15 (41.7%) 21 (58.3%) 155.9 12.1 43.5 11.3 17.7 3.5
10 (34.5%) 11 (37.9%)
17 (47.2%) 14 (38.9%)
4 (13.8%) 4 (13.8%)
2 (5.6%) 3 (8.3%)
11 (37.9%) 5 (17.2%)
17 (47.2%) 2 (5.6%)
P value .0151 .0269 .28
.0154 .156 .355 .757
.452 .131
LDLLT, Living-donor lobar lung transplantation; BMI, body mass index; HSCT, hematopoietic stem cell transplantation.
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TABLE 3. Pretransplant living-donor characteristics
Age, y Sex Male Female Height, cm Donated lobe Right lower lobe Left lower lobe Middle lobe
Nonstandard LDLLT, n ¼ 45
Standard LDLLT, n ¼ 72
40.2 10.7
40.3 12.2
21 (46.7%) 24 (53.3%) 164.9 7.8
41 (56.9%) 31 (43.1%) 165.9 8.0
35 8 2
36 36 0
P value .982 .279
.5 .0008
LDLLT, Living-donor lobar lung transplantation.
sons, 15 were fathers, 14 were brothers, 13 were daughters, 10 were sisters, 8 were husbands, 7 were wives, 1 was a grandfather, 1 was an uncle, and 1 was an aunt. Age, sex, and height were similar between the nonstandard LDLLT group and the standard LDLLT group. Right lower lobes were more often donated in the nonstandard group due to single LDLLT and right-left inverted LDLLT. Size Matching FVC size matching and 3D-CT size matching are summarized in Table 4 and depicted in Figure 1. Two cases, a middle lobe transplant and a downsizing transplant, were excluded from the size matching analysis. Procedures were divided into the following 3 groups: single LDLLT (n ¼ 12), sparing and/or inverted LDLLT (n ¼ 15), and standard LDLLT (n ¼ 36). Regarding FVC size matching, the estimated graft FVC ratio was significantly lower in the sparing and/or inverted LDLLT group than in the standard LDLLT group (53.4 9.1% vs 67.6 16.5%, P ¼ .0034). Regarding 3D-CT size matching, the volume ratio was defined as the ratio between the total graft volume to the total volume of the recipient chest cavities in bilateral LDLLT. In single LDLLT, it was defined as the ratio between the volume of the single lobe to the volume of the corresponding ipsilateral chest cavity. The volume ratio was significantly greater in the single LDLLT group than in the standard LDLLT group (199.7 74.0% vs 119.5 51.5%, P <.0001). The volume ratio was significantly lower in the sparing and/or inverted LDLLT group than in the standard LDLLT group (84.3 43.4% vs 119.5 51.5%, P ¼ .0455). Perioperative and Early Posttransplant Outcomes Implantation time and ischemic time were similar between the 2 groups (Table 5). The PaO2/fraction of inspired oxygen ratio was significantly lower in the nonstandard LDLLT group than in the standard LDLLT group immediately after reperfusion (402 128 vs 473 191, P ¼ .0077). The frequency of tracheostomy, ECMO
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TABLE 4. Size matching Type
Single LDLLT, n ¼ 12
Sparing and/or inverted LDLLT, n ¼ 15
Standard LDLLT, n ¼ 36
FVC size matching, % (range) 3D-CT size matching, % (range)
61.8 15.0 (41.2-90.4) 199.7 74.0 (80.4-395)
53.4 9.1 (40.0-105) 84.3 43.4 (28-174.9)
67.6 16.5 (47.4-109.4) 119.5 51.5 (46.3-248)
LDLLT, Living-donor lobar lung transplantation; FVC, forced vital capacity; 3D-CT, three-dimensional computed tomography.
Bronchial anastomotic complication occurred in 2 of 46 anastomoses (4.3%) in the nonstandard group and it occurred in 3 of 72 anastomoses (4.2%) in the standard group (P ¼ .966). None of them were fatal. Survival At the time of final data analysis on April 30 2016, the mean time from nonstandard LDLLT to final analysis for the 29 recipients was 33 months (range 3- 96 months). The mean time from standard LDLLT to final analysis for the 36 recipients was 39 months (range 7-94 months). Survival curves are shown in Figure 2. Three- and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P ¼ .712). In the nonstandard LDLLT
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support, and the duration of mechanical ventilation required were similar between the 2 groups. Thirty-day mortality occurred in only 1 patient (3.5%) after nonstandard LDLLT. An 11-year-old boy who received right basal segmental transplantation died of sepsis on day 14. Hospital mortality was encountered in 3 patients (10.3%) after nonstandard LDLLT and 1 patient (2.8%) after standard LDLLT. A 14-year-old girl with pulmonary hypertension received left single-lobe transplantation as a retransplant and died of graft failure on day 108. A 9year-old boy with congenital proteinosis received bilateral middle lobe transplantation and died of graft failure with persistent pulmonary hypertension on day 112. A 64-yearold man with idiopathic pulmonary fibrosis received standard LDLLT and died of aspiration pneumonia on day 98.
FIGURE 1. A, FVC size matching. The estimated graft FVC ratio was significantly lower in the sparing and/or inverted LDLLT group than in the standard LDLLT group (53.4 9.1% vs 67.6 16.5%, P ¼ .0034). B, 3D-CT size matching. The volume ratio was significantly greater in the single LDLLT group than in the standard LDLLT group (199.7 74.0% vs 119.5 51.5%, P<.0001). The volume ratio was significantly lower in the sparing and/or inverted LDLLT group than in the standard LDLLT group (84.3 43.4% vs 119.5 51.5%, P ¼ .0455). FVC, Forced vital capacity; 3D-CT, three-dimensional computed tomography.
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TABLE 5. Perioperative and early posttransplant outcome
Implantation time, min Ischemic time, min PaO2/FiO2 immediately after reperfusion Tracheostomy Yes Use of ECMO support Yes Duration of mechanical ventilation, d 30-d mortality Hospital mortality Bronchial anastomotic complication
Nonstandard LDLLT, n ¼ 29
Standard LDLLT, n ¼ 36
P value
60 12 130 41 402 128
60 13 142 41 473 191
.431 .066 .0077
24 (57.1%)
17 (45.9%)
3 (10.3%) 17.1 17.7
3 (8.3%) 14.9 24.3
.711
1 (3.5%) 3 (10.3%) 2/46 (4.3%)
0 (0%) 1 (2.8%) 3/72 (4.2%)
.262 .207 .996
.488 .781
LDLLT, Living-donor lobar lung transplantation; FiO2, fraction of inspired oxygen; ECMO, extracorporeal membrane oxygenation.
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group, a 61-year-old man with idiopathic pulmonary fibrosis died of bronchiolitis obliterans syndrome 40 months after receiving right upper lobe sparing LDLLT. Donor Outcomes We encountered minor surgical morbidities such as prolonged air leak, wound infection, and pleural effusion after donor lobectomy. All living-donors returned, however, to their previous life styles without restriction. DISCUSSION The shortage of cadaveric lung donors remains an important unsolved problem in Japan. Aggressive use of marginal donors results in a high utilization ratio (>60%) of the lungs
FIGURE 2. Actuarial survival after nonstandard LDLLT (n ¼ 29) compared with that after standard LDLLT (n ¼ 36). Three- and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P ¼ .712). LDLLT, Living-donor lobar lung transplantation.
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of brain-dead donors; however, the mortality rate for patients on the waiting list for CLT is still about 40%. LDLLT is often the only realistic option for very ill patients. During the study period, we performed 65 LDLLTs and 62 CLTs in our institution. We recently reported that LDLLT provided similar survival to CLT even for very ill patients.20 The methods of evaluation of size matching and managing size disparity in LDLLT are very important. Because only lobes are implanted into the recipient, a wide range of size mismatch is often encountered in LDLLT. In CLT, efforts are made to find size-matched cadaveric donor lungs for the recipient. In Japan, size matching in CLT is accomplished by the use of predicted vital capacity comparisons between donors and recipients. Other size-matching strategies have been described, including height, total lung capacity, chest roentgenogram dimensions, and inframammary circumference. In contrast, precise evaluation of size matching is possible preoperatively in LDLLT because pulmonary function test and 3D-CT volumetry can be performed not only for the recipient but also for the livingdonors, which is practically impossible for most of the cadaveric donors. We accept only immediate family members (relatives within third degree or a spouse) as livingdonors and their ABO blood type must be compatible with that of the recipient. With these donor selection criteria, finding 2 suitable living donors is difficult. For small pediatric recipients, finding size matched cadaveric donors is extremely difficult in Japan. Only 4 children younger than 10 years have received CLT in whole country at the present moment.4 LDLLT is often the only realistic option for children, but adult lobes are too large to fit into the small chest cavity of the pediatric recipient when the 3D-CT volume ratio exceeds 200%. One of the solutions is single-lobe transplantation with or without contralateral pneumonectomy. We previously reported on an 8-year-old girl receiving right single-lobe transplantation who received simultaneous left pneumonectomy.10 She is alive and doing well more than 7 years after the transplantation. One of the children in the current study, an 11-yearold boy, had severe funnel chest and his mother’s right lower lobe was 395% bigger than his right chest cavity by 3D-CT volumetric evaluation. Right S6 segmentectomy of the graft was performed at the back table and the basal segmental graft was implanted followed by left pneumonectomy. Even with these efforts, the chest could not be closed because of the severe size mismatch, and the patient died of sepsis on day 14. A lobe that is small for the body but large for the chest cavity should not be used. We reported on 14 critically ill patients who had undergone single LDLLT using a single donor at 3 lung transplant centers in Japan.21 Three- and five-year survival rates were 70% and 56%, respectively. The result was acceptable but not as good as bilateral LDLLT. We concluded that single LDLLT is an acceptable option for sick patients when
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only one suitable living-donor is available but bilateral LDLLT is a better option if 2 living-donors are found. Another strategy for an oversize graft is to use the middle lobe instead of the lower lobe as a graft. Although Oto and colleagues22 reported successful middle lobe transplantation, we lost our patient receiving bilateral middle lobe transplantation due to graft failure with persistent pulmonary hypertension. Two lobes may be too small for the adult recipient. Previously, we did not accept patients when the FVC graft ratio was less than 45%.2,3 To solve this problem, we developed 2 procedures, lobar-sparing LDLLT14 and right-left inverted LDLLT.15 Lobar-sparing LDDLT is technically straightforward if the interlobar fissure is well developed. Using a canine lung transplantation model, Sugimoto and colleagues23 demonstrated the technical feasibility of sparing native upper lobes. We previously reported 5 cases receiving lobarsparing LDLLT,14 and the current study included 9 cases (2 cases combined with right-left inverted LDLLT). Candidates should not have infectious lung disease. Diagnoses included idiopathic pulmonary fibrosis (n ¼ 4), idiopathic pulmonary arterial hypertension (n ¼ 2), bronchiolitis obliterans (n ¼ 1), chronic hypersensitivity pneumonia (n ¼ 1), and interstitial pneumonia associated scleroderma (n ¼ 1). Under normal physiology, it is well known that the lower lobe functions better than the upper lobe due to diaphragm motion. It was for this reason that we always spared the diseased native upper lobe and implanted normal lower lobe graft. Scintigraphy demonstrated a limited perfusion to the spared lobes at 1 year,14 particularly in patients with pulmonary hypertension. We believe that the spared upper lobes provided an adequate chest cavity for the small lower lobe grafts and functioned as a reservoir in the early postoperative period. Late complications attributed to the spared lobes were airway stenosis after Aspergillus infection in one patient and late onset of native lobe pneumothorax in 2 patients. All these complications were manageable. Right-left inverted LDLLT was developed based on the fact that the right lower lobe (5 segments) is generally larger than the left lower lobe (4 segments). When we planned to use this technique for the first time, we used 3D models produced by a 3D printer.15 This allowed us to simulate the positional relationship of hilar structures and to determine the anastomotic sites for the bronchus, pulmonary artery, and pulmonary vein preoperatively. When the right lower lobe graft was inverted and placed in the left chest cavity, the interlobar pulmonary artery was positioned behind the bronchus. The donor bronchus was anastomosed to the recipient’s left upper bronchus, leaving left lower bronchial stamp closed, and allowing us to perform pulmonary artery anastomosis behind the bronchus. We previously reported 3 cases receiving right-left inverted LDLLT15 and the current study included 8 cases (2 cases combined with lobar sparing
LDLLT). The bronchial anastomosis and the stump of the left lower bronchus healed nicely in all cases. In 1 case, nonsymptomatic mild stenosis in the left pulmonary artery was detected by postoperative enhanced CT scan. Because the LDLLT recipients were very sick at the time of transplantation, meticulous postoperative management was mandatory. Oxygenation immediately after reperfusion was significantly worse in the nonstandard LDLLT group than in the standard LDLLT group because of the residual diseased lung in single LDLLT and spared upper lobes in lobar sparing LDLLT; however, use of ECMO support and the duration of mechanical ventilation required were similar between the 2 groups. Although hospital death occurred in 3 patients in the nonstandard group, they were extremely difficult cases; right basal segmental transplantation with left pneumonectomy, right single LDLLT as a retransplantation, and bilateral middle lobe transplantation. All patients who received lobar sparing LDLLT and/or right-left inverted LDLLT were discharged from the hospital without supplemental inhaled oxygen. Twenty-nine of 65 LDLLTs (44.6%) were performed as nonstandard LDLLT. Most of those patients would not have been accepted if the aforementioned new techniques were not used. Figure 1 clearly shows the greater degree of size disparity in nonstandard LDLLT; however, the survival rates of 89.1% and 76.6% at 3 and 5 years, respectively, after nonstandard LDLLT were similar to survival rates after standard LDLLT. These excellent long-term survival rates were most encouraging. Limitations of the present study included it being a nonrandomized, retrospective study and the relatively small number of transplant procedures. CONCLUSION Various transplant procedures such as single, sparing and inverted transplants are valuable options when 2 donors with ideal size matching are not found in LDLLT. Conflict of Interest Statement Authors have nothing to disclose with regard to commercial support. References 1. Yusen RD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Goldfarb SB, et al. The registry of the International Society for Heart Lung Transplantation: thirty-second official adult lung and heart-lung transplantation report—2015; focus theme: early graft failure. J Heart Lung Transplant. 2015;34:1264-77. 2. Date H, Aoe M, Nagahiro I, Sano Y, Andou A, Matsubara H, et al. Living-donor lobar lung transplantation for various lung diseases. J Thorac Cardiovasc Surg. 2003;126:476-81. 3. Date H, Aoe M, Sano Y, Nagahiro I, Miyaji K, Goto K, et al. Improved survival after living-donor lobar lung transplantation. J Thorac Cardiovasc Surg. 2004; 128:933-40. 4. Sato M, Okada Y, Minami M, Shiraishi T, Nagayasu T, Yoshino I, et al. Registry of the Japanese Society of Lung and Heart-Lung Transplantation: official Japanese lung transplant report, 2014. Gen Thorac Cardiovasc Surg. 2014;62:594-601. 5. Starnes VA, Bowdish ME, Woo MS, Barbers RG, Schenkel FA, Horn MV, et al. A decade of living lobar lung transplantation. Recipient outcomes. J Thorac Cardiovasc Surg. 2004;127:114-22.
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6. Cohen RG, Barr ML, Schenkel FA, DeMeester TR, Wells WJ, Starnes VA. Living-related donor lobectomy for bilateral lobar transplantation in patients with cystic fibrosis. Ann Thorac Surg. 1994;57:1423-7; discussion 1428. 7. Barr ML, Baker CJ, Schenkel FA, Bowdish ME, Bremner RM, Cohen RG, et al. Living donor lung transplantation: selection, technique, and outcome. Transplant Proc. 2001;33:3527-32. 8. Oto T, Date H, Ueda K, Hayama M, Nagahiro I, Aoe M, et al. Experimental study of oversized grafts in a canine living-donor lobar lung transplantation model. J Heart Lung Transplant. 2001;20:1325-30. 9. Shoji T, Bando T, Fujinaga T, Date H. Living-donor single-lobe lung transplant in a 6-year-old girl after 7-month mechanical ventilator support. J Thorac Cardiovasc Surg. 2010;139:e112-3. 10. Sonobe M, Bando T, Kusuki S, Fujinaga T, Shoji T, Chen F, et al. Living-donor single-lobe lung transplantation and simultaneous contralateral pneumonectomy in a child. J Heart Lung Transplant. 2011;30:471-4. 11. Chen F, Matsukawa S, Ishii H, Ikeda T, Shoji T, Fujinaga T, et al. Delayed chest closure assessed by transesophageal echocardiogram in single-lobe lung transplantation. Ann Thorac Surg. 2011;92:2254-7. 12. Chen F, Fujinaga T, Shoji T, Yamada T, Nakajima D, Sakamoto J, et al. Perioperative assessment of oversized lobar graft downsizing in living-donor lobar lung transplantation using three-dimensional computed tomographic volumetry. Transplant Int. 2010;23:e41-4. 13. Fujita T, Date H, Ueda K, Nagahiro I, Aoe M, Andou A, et al. Experimental study on size matching in a canine living-donor lobar lung transplant model. J Thorac Cardiovasc Surg. 2002;123:104-9. 14. Aoyama A, Chen F, Minakata K, Yamazaki K, Yamada T, Sato M, et al. Sparing native upper lobes in living-donor lobar lung transplantation: five cases from a single center. Am J Transplant. 2015;15:3202-7. 15. Chen F, Miyamoto E, Takemoto M, Minakata K, Yamada T, Sato M, et al. Right and left inverted lobar lung transplantation. Am J Transplant. 2015; 15:1716-21.
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16. Date H, Aoe M, Nagahiro I, Sano Y, Matsubara H, Goto K, et al. How to predict forced vital capacity after living-donor lobar-lung transplantation. J Heart Lung Transplant. 2004;23:547-51. 17. Date H, Kusano KF, Matsubara H, Ogawa A, Fujio H, Miyaji K, et al. Livingdonor lobar lung transplantation for pulmonary arterial hypertension after failure of epoprostenol therapy. J Am Coll Cardiol. 2007;50:523-7. 18. Chen F, Kubo T, Yamada T, Sato M, Aoyama A, Bando T, et al. Adaptation over a wide range of donor graft lung size discrepancies in living-donor lobar lung transplantation. Am J Transplant. 2013;13:1336-42. 19. Chen F, Fujinaga T, Shoji T, Kubo T, Sonobe M, Sato M, et al. Short-term outcome in living donors for lung transplantation: the role of preoperative computer tomographic evaluations of fissures and vascular anatomy. Transplant Int. 2012;25:732-8. 20. Date H, Sato M, Aoyama A, Yamada T, Mizota T, Kinoshita H, et al. Livingdonor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patientsy. Eur J Cardiothorac Surg. 2015;47:967-73; discussion 972-3. 21. Date H, Shiraishi T, Sugimoto S, Shoji T, Chen F, Hiratsuka M, et al. Outcome of living-donor lobar lung transplantation using a single donor. J Thorac Cardiovasc Surg. 2012;144:710-5. 22. Oto T, Miyoshi K, Sugimoto S, Yamane M. Living related donor middle lobe lung transplant in a pediatric patient. J Thorac Cardiovasc Surg. 2015;149:e42-4. 23. Sugimoto S, Date H, Sugimoto R, Aoe M, Sano Y. Bilateral native lung-sparing lobar transplantation in a canine model. J Thorac Cardiovasc Surg. 2006;132: 1213-8.
Key Words: living-donor lobar lung transplantation, single lobe transplant, native upper lobe–sparing transplant, rightleft inverted transplant, oversized graft, undersized graft, size matching
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Outcomes of various transplant procedures (single, sparing, inverted) in livingdonor lobar lung transplantation Hiroshi Date, MD, Akihiro Aoyama, MD, Kyoko Hijiya, MD, Hideki Motoyama, MD, Tomohiro Handa, MD, Hideyuki Kinoshita, MD, Shiro Baba, MD, Toshiyuki Mizota, MD, Kenji Minakata, MD, and Toyofumi F. Chen-Yoshikawa, MD, Kyoto, Japan We successfully developed various transplant procedures (single, sparing, inverted) to deal with size mismatch in living-donor lobar lung transplantation.
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The Journal of Thoracic and Cardiovascular Surgery c Volume -, Number -