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Address for reprints: Daisuke Nakajima, MD, PhD, Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
The preset study evaluated the outcome of living-donor segmental lung transplantation for pediatric patients.
Methods
Between August 2009 and May 2021, we performed living-donor segmental lung transplantation in 6 critically ill pediatric patients, including 1 patient on a ventilator alone and another patient on a ventilator and extracorporeal membrane oxygenation (ECMO). There were 4 male and 2 female patients, with a median age of 7 years (range, 4-15 years) and a median height of 112.7 cm (range, 95-125.2 cm). The diagnoses included complications of allogeneic hematopoietic stem cell transplantation (n = 4) and pulmonary fibrosis (n = 2). All patients received bilateral lung transplantation under cardiopulmonary bypass. A basal segment and a lower lobe were implanted in 3 patients, and a basal segment and an S6 segment were implanted in the other 3 patients. In 2 patients, the right S6 segmental graft was horizontally rotated 180° and implanted as the left lung.
Results
Among the 9 segmental grafts implanted, 7 functioned well after reperfusion. Two rotated S6 segmental grafts became congestive, with 1 requiring graft extraction and the other venous repair, which was successful. There was 1 hospital death (14 days) due to sepsis and 1 late death (9 years) due to leukoencephalopathy. The remaining 4 patients are currently alive at 9 months, 10 months, 1.3 years, and 1.9 years.
Conclusions
Living-donor segmental lung transplantation was a technically difficult but feasible procedure with acceptable outcomes for small pediatric patients with chest cavities that were too small for adult lower lobe implantation.
Novel living-donor lung transplantation using basal and/or S6 segmental grafts overcame the issue of graft size mismatch for small pediatric patients, showing favorable posttransplant outcomes.
Various living-donor lobar lung transplant procedures have been employed to deal with graft size mismatch, such as native upper lobe-sparing transplant and/or right-to-left inverted transplant for undersized grafts and single-lobe transplant for oversized grafts. We successfully developed a segmental lung transplant technique for use when an adult lower lobe was too big for a pediatric patient.
See Commentary on page 2202.
The revision of the Japanese organ transplant law allowed families to give their consent to allow organ donation, which has gradually increased the number of organ donations from brain-dead donors.
However, the lung transplant candidates who have been newly registered in the Japan Organ Transplantation Network has nearly doubled in recent years, which has resulted in a severe donor organ shortage. Therefore, the average waiting time for brain-dead donor lungs still exceeds 800 days in Japan, which indicates that many patients on the waiting list die without having the opportunity to undergo lung transplantation.
Since living-donor lobar lung transplantation (LDLLT) was introduced in Japan in 1998 to address the issue of brain-dead donor organ shortage, it has become a viable life-saving option for patients with severe respiratory disorders, especially pediatric patients, and LDLLT currently accounts for 30% of all lung transplants in Japan.
In standard LDLLT, the right and left lower lobes from 2 healthy donors are implanted into a single recipient in place of the whole right and left lungs.
However, there are some concerns about graft size mismatch due to the use of a small or large lobar grafts in LDLLT patients. Therefore, various LDLLT procedures have been employed to deal with graft size mismatch. For example, native upper lobe-sparing transplant and/or right-to-left inverted transplant are performed as strategies for managing undersized grafts, whereas single-lobe transplant with or without contralateral pneumonectomy is performed to manage oversized grafts.
We recently developed a novel technique for living-donor segmental lung transplantation (LDSLT) for pediatric patients with extremely small chest cavities to receive adult lower lobar grafts. We herein report the short- and medium-term outcomes of 6 cases of LDSLT using basal and S6 segmental lung grafts.
Methods
Recipient and Living-Donor Selection
Among 33 pediatric patients (aged 15 years or younger) who underwent living-donor lung transplantation at Kyoto University Hospital between August 2009 and May 2021, 6 LDSLT recipients were included in this study. All data were analyzed retrospectively as of February 2022. Each transplant case was carefully reviewed and approved by the Lung Transplant Evaluation Committee at Kyoto University Hospital. This study was approved by the institutional review board of Kyoto University Hospital on May 25, 2021 (R2389), and written informed consent was obtained from all participants.
The recipient and donor characteristics are shown in Table 1. The LDSLT recipients were 4 boys and 2 girls with a median age of 7 years (range, 4-15 years) and a median height of 112.7 cm (range, 95-125.2 cm). Living-donor lung transplant candidates were basically limited to critically ill patients who would not survive the long waiting time for brain-dead donor lungs: 5 patients were hospitalized at the time of transplantation, 1 patient required mechanical respiratory support, and another patient required both mechanical ventilation and extracorporeal membrane oxygenation (ECMO) support immediately before transplantation. The primary indications for LDSLT included pulmonary complications after allogeneic hematopoietic stem cell transplantation (n = 4) and pulmonary fibrosis (n = 2).
Table 1Recipient and donor characteristics
Case
Recipient
Right donor
Left donor
Age, gender
Disease
Height (cm)
Age, relation
Height (cm)
Age, relation
Height (cm)
1
15 y, M
HSCT
121
42 y, Father
173
45 y, Mother
155
2
11 y, M
HSCT
125.2
46 y, Mother
164
Same as the right
3
7 y, F
HSCT
115
43 y, Father
171.6
42 y, Mother
165.4
4
4 y, M
IP
95
53 y, Grandmother
156
34 y, Father
166.7
5
6 y, M
IP
98.8
33 y, Mother
157.7
31 y, Father
170.4
6
7 y, F
HSCT
110.3
41 y, Mother
154.8
42 y, Father
172.2
M, Male; HSCT, pulmonary complications after hematopoietic stem cell transplantation; F, female; IP, interstitial pneumonia.
The eligibility criteria for living donation in Kyoto University Hospital are summarized as follows: the living donor should be between ages 20 and 60 years, the ABO blood type should be compatible with that of the recipient, donor candidates should be relatives within the third-degree or a spouse, arterial oxygen tension should be ≥80 Torr on room air, and the forced vital capacity (FVC) and forced expiratory volume in 1 second should be ≥85% of the predicted values. In this study, the donors were 5 fathers, 5 mothers, and 1 grandmother with a median age of 42 years (range, 31-53 years) and a median height of 165.4 cm (range, 154.8-173 cm).
Size Matching Between the Living-Donor Graft and Recipient
For functional size matching, the graft FVC was estimated based on the measured donor FVC and the number of resected pulmonary segments, using Date's previously reported formula.
A calculated graft FVC >45% (ideally 50%) of the recipient FVC predicted from the height, age, and gender was considered to be acceptable for size-matching the graft to the recipient. Size-matching data are presented in Table 2. In this study, a median FVC size matching was preoperatively 123.9% (range, 47.9%-161.2%).
For anatomical size matching, 3-dimensional computed tomography (3D-CT) volumetry was performed for both the donor and recipient to measure the donor lung volume and recipient chest cavity volume, respectively, as reported previously.
In the present study, a median CT volumetric size matching of the right lung graft to the recipient hemithorax was preoperatively 190.5% (range, 122.9%-381.7%), whereas the left lung graft was 161.1% (range, 95.4%-315.0%). The upper limit of the graft volume was considered to be 200% of the recipient hemithoracic volume, based on our experience.
In case 2, a mother was the only eligible donor for living-donor transplantation, and thus single-lobe transplant or split segmental transplant was preoperatively scheduled because the graft volume of the right lower lobe from his mother was 465.7% of the recipient right chest cavity volume. Downsizing the living-donor graft by segmentectomy was planned before retrieval in 3 cases (cases 3, 4, and 5), where the volume of the donor lower lobes was more than 200% of the recipient hemithoracic volume.
Segmental Graft Preparation
The surgical LDSLT procedures are summarized in Table 2. In 3 cases (cases 1, 2, and 6), the donor lower lobe was downsized ex vivo by segmentectomy on a back table via direct visual inspection of the size discrepancy between the donor lung graft and the recipient chest cavity. Following flushes of the donor lower lobe by cold organ preservation solution on a back table, the segmental graft arteries, veins, and bronchus were identified and divided, and then the lower lobe was split into the S6 and basal segments using staples.
In the other 3 cases (cases 3, 4, and 5), segmentectomy was preoperatively scheduled and performed in vivo in donors. The pulmonary arteries and veins of the S6 and basal segments were dissected, and the dominant vessels of the nongraft segment were clamped after inflation of the donor lower lobe. Following the intravenous administration of indocyanine green, the graft segment was gradually stained green and the intersegmental plane between the S6 and basal segments was clearly observed by near-infrared thoracoscopy.
The intersegmental plane was completely divided in vivo using electrocautery before retrieval of the lung graft, and the divided intersegmental planes were then covered with fibrin glue and an absorbable piece of polyglycolic acid felt to prevent air leakage.
Graft Implantation
LDSLT recipients underwent bilateral lung transplantation using segmental lung grafts under conventional cardiopulmonary bypass (CPB). Double-lumen endotracheal tube could not be used for small pediatric patients, and we thus chose CPB support to completely stop ventilation during transplant procedure. A basal segment and lower lobe were implanted in 3 cases (cases 1, 3, and 6) (Figure 1, A), and a basal segment and an S6 segment were implanted in the other 3 cases (cases 2, 4, and 5) (Figure 1, B) (Video 1).
Figure 1Living-donor segmental lung transplantation, using a basal segment and a lower lobe (A) or using a basal segment and an S6 segment (B).
The implant technique of the basal segment was similar to that of the lower lobe graft in conventional LDLLT: the graft bronchus was anastomosed to the recipient's main stem bronchus, the pulmonary vein (PV) to the recipient's upper PV or left atrium, and the pulmonary artery (PA) to the recipient's main PA. The basal segments were vertically rotated 90° after implantation, so the anastomoses were carefully created in order not to become twisted in the vessels and bronchus.
In 2 cases, the right S6 segmental graft was horizontally rotated 180° and implanted into the recipient left chest cavity (cases 2 and 4) (Figure 1, B): the graft bronchus was connected to the recipient's main stem bronchus, the PV to the recipient's upper PV, and the PA to the recipient's main PA. The left S6 segment was implanted into the recipient's left chest cavity in 1 case (case 5): the graft bronchus was attached to the recipient's left upper bronchus, the PV to the recipient's lower PV, and the PA to the recipient's main PA (Video 1).
The median graft implanting time was 67 minutes (range, 36-80 minutes), and the median graft ischemic time was 164 minutes (range, 95-301 minutes). Oversized grafts were downsized by additional large wedge resection after implantation in 2 patients (cases 3 and 5) (Figure 2). After finishing the transplant procedure, the chest was temporarily closed using expanded polytetrafluoroethylene sheets without rib approximation due to the oversized nature of the grafts in 5 patients (Video 1), except for case 1. Delayed chest closure was performed on postoperative day (POD) 2 in 2 patients (cases 3 and 6), POD 6 in 1 patient (case 4), and POD 11 in 1 patient (case 5). The chest could not be closed in 1 patient who died of sepsis on POD 14 (case 2).
Figure 2A, In case 3, a right basal segment with a computed tomography (CT) volumetric size match of 272.0% was implanted as a right lung, and a left lower lobe with a CT volumetric size match of 315.0% was implanted as a left lung. B, The oversized grafts were downsized by additional large wedge resection after implantation.
Posttransplant outcomes are summarized in Table 3. Among the 9 segmental lung grafts (6 basal and 3 S6 segments) implanted, 7 (6 basal and 1 S6 segments) functioned well after transplantation. Pulmonary congestion gradually progressed in 2 rotated S6 segmental grafts; 1 needed graft removal on POD 1 due to severe primary graft dysfunction (PGD) requiring ECMO support (case 2), and in the other case, the superior segmental vein was re-anastomosed after widening the recipient's venous stump to improve the venous drainage on POD 2, which gradually ameliorated pulmonary edema in the S6 segmental graft (case 4) (Figure 3). The other segmental graft-related complication was seen in case 4 as bilateral long-term persistent air leakage that repeatedly required pleurodesis by minocycline and an autologous blood patch. No bronchial anastomotic complications were encountered.
Table 3Outcomes of living-donor segmental lung transplantation
Figure 3In case 4, a right S6 segment was horizontally rotated 180° and implanted as a left lung. The rotated S6 segmental graft appeared to function well on postoperative day (POD) 1. However, the graft developed pulmonary congestion due to poor pulmonary venous drainage on POD 2, which was successfully treated by re-anastomosis of the superior segmental vein. The pulmonary edema gradually improved on chest radiograph.
There was 1 in-hospital mortality due to sepsis (case 2) on POD 14 and 1 late death at 9 years after LDSLT due to leukoencephalopathy (case 1). The other 4 patients are currently alive at 9 months, 10 months, 1.3 years, and 1.9 years after LDSLT (Figure 4). The median observation period for 5 patients except 1 in-hospital mortality case was 1.3 years, and chronic lung allograft dysfunction was not observed in any of the LDSLT recipients.
Figure 4Two patients died at 14 days and 9 years after living-donor segmental lung transplantation (LDSLT). However, the other 4 patients are currently alive at 9 months, 10 months, 1.3 years, and 1.9 years after LDSLT. The dashed lines are the lower and upper 95% CI limits.
Details of the in-hospital mortality (case 2) are as follows: an 11-year-old boy had an extremely small thoracic cage due to severe funnel chest. The estimated graft FVC of the right lower lobe from his mother was 47.9% of the recipient's predicted FVC, whereas the graft volume of the right lower lobe was 465.7% of the recipient right thoracic volume. Therefore, the patient required downsizing of the oversized graft by resection of the superior segment on a back table. The basal segmental graft was implanted as a right lung. However, the basal segmental graft was still oversized for the recipient's small chest cavity; the ratio of the basal segmental graft volume to the recipient right thoracic volume was still 341.6% even after graft size reduction. Following left pneumonectomy, the resected S6 segment was then rotated 180° horizontally and implanted as a left lung. The patient required ECMO support after transplantation, and the congestive S6 segmental graft was removed due to severe PGD on POD 1. The chest was unable to be closed because of the extreme graft size mismatch, and the patient ultimately died of sepsis on POD 14.
Donor Outcome
We performed lower lobectomy in 6 living donors, basal segmentectomy in 3 donors, and S6 segmentectomy in 2 donors. The residual basal or S6 segments expanded well, which preserved the lung volume in all donors who underwent segmentectomy. No postoperative complications such as prolonged air leakage and bleeding were observed in any of the 11 donors. All donors survived and returned to their previous lifestyles.
Discussion
When adult lower lobes are too big for a small pediatric patient, single-lobe transplantation is performed with or without contralateral pneumonectomy, downsizing, and/or delayed chest closure, as seen in case 2.
Therefore, bilateral living-donor lung transplantation, which has shown significantly better posttransplant outcomes than single-lobe transplantation, is certainly a better option when 2 living donors are available.
reported a successful case of pediatric lung transplantation using a middle lobe graft, but the middle lobe is useful as a graft only when it has a single branch of dominant arteries, veins, and bronchus. In the present study, we thus developed the novel technique of bilateral LDSLT for small pediatric patients using a basal segmental graft and/or an S6 segmental graft.
Functional and anatomical size matching between an oversized graft and a small recipient is very important. In the current case 2, the functional graft size-matching to the recipient was 47.9%, whereas the CT volumetric size-matching of the right basal segment to the recipient hemithorax was 341.6%. The patient eventually developed severe PGD and required ECMO support until he died on POD 14. We previously reported that patients who received a lobar graft with an FVC <60% and CT volume >170% developed severe PGD requiring ECMO support after transplantation.
In the present study, most implanted grafts <200% of the recipient hemithorax functioned well after transplantation, although the oversized graft >250% of the recipient hemithorax needed downsizing by additional large wedge resection after implantation. Considering these findings, the reasonable upper limit of the graft volume in bilateral LDSLT is still considered to be 200% of the recipient hemithoracic volume. Although the volume of donor lower lobe was under 200% in the cases 1 and 6, we were not able to implant the whole lower lobe unexpectedly perhaps because of the recipient abnormal chest shape. Therefore, we needed to downsize the donor lower lobe on a back table in these cases. In addition, delayed chest closure seems to be almost mandatory and large wedge resection may be required in bilateral LDSLT.
In this study, conventional CPB was employed for intraoperative mechanical circulatory support during LDSLT procedure. However, several potential benefits of intraoperative ECMO support in pediatric lung transplantation have recently been reported, in comparison to CPB.
A comparison of cardiopulmonary bypass versus extracorporeal membrane oxygenation: does intraoperative circulatory support strategy affect outcomes in pediatric lung transplantation?.
This suggests that a reasonable alternative to CPB in pediatric lung transplantation can be the use of ECMO support.
The surgical technique of implanting segmental grafts in LDSLT is more complicated in comparison to that of lobar grafts in standard LDLLT. The basal segment will be rotated 90° vertically after implantation, so the vessels and bronchus of the donor segmental graft should be carefully anastomosed to those of the recipient. In the current study, all the basal segmental grafts functioned well after implantation. However, 2 rotated S6 segmental grafts developed pulmonary edema, perhaps because of poor venous drainage. In case 2, the donor right lower lobe was split into the S6 segment and the basal segment using linear stapling devices on the back table. The stapling line appeared to be too close to the intersegmental vein, resulting in irreversible graft congestion. Regarding the development of intersegmental plane, indocyanine green-oriented division by electrocautery in vivo is preferable, although meticulous air sealing is required. Division of the intersegmental plane using electrocautery could fully expand the residual adjacent segments in donors and the segmental grafts in recipients to obtain maximum pulmonary function. On the other hand, dividing the intersegmental plane by stapling devices could not only inhibit the full expansion of the lung grafts but also cause deformation of the segmental grafts, which might increase a risk of graft rotation and congestion immediately after implantation. In case 4, a good venous return was ascertained by transesophageal echocardiography immediately after reperfusion in the initial surgery. Congestion was not observed in the segmental grafts when we temporarily closed the chest with polytetrafluoroethylene sheets. The rotated S6 segmental graft probably became moved or rotated after temporary chest closure, which might have caused pulmonary venous kinking with impaired venous drainage. Given that the rotated S6 segment may be easily moved or further rotated after chest closure and that the superior segmental vessels are very small, vascular anastomosis should be meticulously performed during implantation of the rotated S6 segmental graft. When graft congestion is suspected, reoperation should be performed as soon as possible before the graft damage becomes irreversible. We successfully repaired venous anastomosis in case 4. When the left S6 segment was implanted into the recipient left chest cavity without horizontal rotation in case 5, the graft bronchus was anastomosed to the recipient left upper lobe bronchus. This bronchial elongation procedure provided better alignment of pulmonary vasculatures for subsequent anastomoses. We left the recipient left lower bronchial stump closed. There was obvious concern regarding whether a bronchial fistula would develop in the immunosuppressed patient. The recipient left bronchus should be carefully dissected to maintain the bronchial artery circulation, whereas the bronchial stump should be left as short as possible and reinforced with a pericardial fat pad.
Aside from these issues, the LDSLT procedure was considered technically feasible, with a median graft implantation time of 67 minutes (range, 36-80 minutes), which was comparable to that of standard LDLLT (average, 60 minutes).
recently reported 3 cases of bilateral LDSLT using a split lower lobe from a single adult living donor. This technique needed only 1 living donor, whereas our newly developed LDSLT procedure required 2 living donors. However, implantation of 2 lung grafts obtained from different donors may be of great benefit to the recipient because the contralateral unaffected lung graft may work as a reservoir if chronic lung allograft dysfunction occurs unilaterally.
The present study was associated with some limitations, including its small number of transplant procedures, the absence of a standard LDLLT control group, and a relatively short-term follow-up. Despite the small sample size in this preliminary study, it includes the largest experience of living-donor lung transplantation describing the utility of segmental lung grafts for small pediatric patients with severe respiratory disorders.
Conclusions
LDSLT had the potential to overcome the extensive graft size mismatch in small pediatric recipients, showing favorable short- and medium-term outcomes (Figure 5). Further accumulation of data is needed to compare the posttransplant outcomes, including morbidity and mortality, between novel LDSLT and standard LDLLT. Longer follow-up is also required to elucidate how segmental grafts will function as small pediatric patients grow in height and weight.
Figure 5Living-donor segmental lung transplantation for pediatric patients.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Living-donor segmental lung transplantation with grafts of the right basal segment and left S6 segment. The implant technique of the basal segment was similar to that of the lower lobe in conventional living-donor lobar lung transplantation. The video shows implantation of the left S6 segmental lung graft in case 5. The bronchus was anastomosed to the recipient's left upper bronchus with running 5-0 polydioxanone (PDS) sutures for the membranous portion and interrupted 5-0 PDS sutures for the cartilaginous portion. The pulmonary vein of the graft was anastomosed to the inferior pulmonary vein of the recipient with running 6-0 Prolene sutures. The pulmonary artery was reconstructed by direct end-to-end anastomosis with running 7-0 Prolene sutures. Temporary chest closure without rib approximation was performed using expanded polytetrafluoroethylene sheets. Video available at: https://www.jtcvs.org/article/S0022-5223(22)00828-5/fulltext.
Living-donor segmental lung transplantation with grafts of the right basal segment and left S6 segment. The implant technique of the basal segment was similar to that of the lower lobe in conventional living-donor lobar lung transplantation. The video shows implantation of the left S6 segmental lung graft in case 5. The bronchus was anastomosed to the recipient's left upper bronchus with running 5-0 polydioxanone (PDS) sutures for the membranous portion and interrupted 5-0 PDS sutures for the cartilaginous portion. The pulmonary vein of the graft was anastomosed to the inferior pulmonary vein of the recipient with running 6-0 Prolene sutures. The pulmonary artery was reconstructed by direct end-to-end anastomosis with running 7-0 Prolene sutures. Temporary chest closure without rib approximation was performed using expanded polytetrafluoroethylene sheets. Video available at: https://www.jtcvs.org/article/S0022-5223(22)00828-5/fulltext.
References
Sato M.
Okada Y.
Oto T.
Minami M.
Shiraishi T.
Nagayasu T.
et al.
Registry of the Japanese Society of Lung and Heart–Lung Transplantation: official Japanese lung transplantation report, 2014.
A comparison of cardiopulmonary bypass versus extracorporeal membrane oxygenation: does intraoperative circulatory support strategy affect outcomes in pediatric lung transplantation?.
“Tailor-made” is a common expression used in fashion to state that clothing has been made specifically for someone and thus fits very well. Likewise, appropriate donor-to-recipient size matching in lung transplantation is important, as the rigid chest cavity is less flexible to accommodate an oversized pulmonary graft, especially in patients with fibrotic lung disease. Finding an adequate lung donor for small recipients is even more challenging, as pediatric cadaveric donors are very scarce.
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