Donor Lobar Lung Transplantation Research Articles

Detection of Restored Lung by Novel Radiologic Parameter in Living Lobar Lung Transplant Donors

Purpose Postoperative compensatory lung growth (CLG) after lung resection has been established in animal models. However, detecting CLG in clinical patients is limited. Our purpose was to determine CLG by evaluating preoperative and postoperative “estimated lung weight (ELW)” in living lobar lung transplant donors. Methods and Materials A total of 18 consecutive patients who underwent a right or left lower lobectomy as a living donor for lung transplantation from 2008 to 2010 were selected. The 18 patients were evaluated by spirometry, CT volumetry, and mean CT numbers (Hounsfield Units) both before and one year after surgery. “ELW” was calculated by multiplying lung volume (ml) and estimated mean lung density (g/ml): density = (mean CT number + 1000) / 1000. All parameters were evaluated by “%postoperative values”: actual postoperative values / predicted post operative values (%); predicted values were based on the number of resected segments. [figure 1] Results The predicted postoperative values of spirometry underestimated the actual values and the differences were significant (forced vital capacity, p<0.001, forced expiratory volume in 1 second, p<0.001 and diffusing capacity for carbon monoxide, p=0.002). The cohort had significantly larger % postoperative lung volumes (152±31.5%, p<0.001) and “ELW” (126±15.2%) than the predicted values on the surgical side. Conclusions Restored lung function, volume and quantity after major lung resection in living lobar lung transplant donors was revealed by the novel radiologic parameter. Major lung resection may trigger CLG on the surgical side that can be clinically evaluated by the “ELW.”

Lobar Lung Transplantation – Is It Comparable to Standard Lung Transplantation?

Purpose Lobar lung transplantation (LLT) is a therapeutic option mainly for urgent small recipients. Only series with limited numbers have been reported. This approach is technically more demanding than standard LuTX or simple downsizing by wedge resections. In our center this approach was liberally applied and we report the largest series of deceased donor LLT so far. Methods and Materials We performed an analysis of our prospective lung transplant database from 1/2001 to 10/2012 and compared the clinical outcome of LLT recipients to those receiving standard donor organs or downsizing by simple peripheral wedge resection. Results 779 LuTX (group 1) were performed either in standard technique (n=542) or with downsizing by wedge resections (n=237). 132 LuTXwere performed in lobar technique (group 2). In group 2 there were significantly more females (57,6% vs. 45,4%; p=0,011). Patients in group 2 were significantly younger (median 36,5 vs. 51,6 years, p Conclusions Patients receiving LLT represent a different patient group than those receiving standard LuTX. The observed outcome is in contrast to previous publications inferior to standard LuTX recipients, which is explained by the different indication spectrum and a higher rate of patients invasively bridged to transplantation. Nevertheless LLT remains a valid and important option in the management of urgent small recipients.

Live related donor lobar lung transplantation recipients surviving well over a decade: still an option in times of advanced donor management

As waiting lists for lung transplantation are ever increasing, the number of organ donors is not able to keep pace with it. Living donor lobar lung transplantation is a source of organs which could be lifesaving in end-stage lung disease patients who cannot wait for cadaveric organs due to deteriorating lung function and clinical condition. Two young women with end stage cystic fibrosis received lobes from their relatives and an altruistic friend. They are surviving for more than 12 and 14 years with good lung functions.

Cadaveric donor lobar lung transplantation for patients on extracorporeal membrane oxygenation as bridge-to-transplant

The total number of lung transplants reported to the International Society of Heart and Lung Transplantation registry continues to increase steadily. In the US, the lung transplant volume has increased from 1172 in 2004 to 1822 in 2011 since lung allocation score system was implemented in 2005 while the overall 1-year survival after transplantation has not changed significantly. One of the most common reasons why lung offers are declined is size-mismatch. Size-reduced lung transplantation including non-anatomical lung volume reduction and lobar lung transplantation is an advanced surgical technique to alleviate donor organ shortage. Living-related donor lung transplantation almost disappeared in the US, but alternatively, we perform lobar transplantation using cadaveric donor lungs. With recent advances in extracorporeal membrane oxygenation (ECMO) technology and surgical experience, ECMO has been used before, during and after lung transplant surgery successfully.

Two Case Reports of Successful Withdrawal of Mycofenolate Mofetil After Living Donor Lobar Lung Transplantation

BackgroundLung transplantation cases have immunosuppression maintainedusing a calcineurin inhibitor, anti-metabolites, and steroid. Case ReportWe report 2 clinical cases inwhich anti-metabolites (mycophenolate mofetil) were successfully withdrawn after livingdonor lobar lung transplantation by monitoring immune function using the ImmuKnow®assay. In the first case, a 43-year-old woman underwent living donor lobar lungtransplantation for pulmonary alveolar proteinosis. Two healthy relatives donated alower lobe each. Immunosuppression was maintained using tacrolimus, mycophenolatemofetil, and steroid. Six months posttransplantation, she developed invasivepulmonary aspergillosis. During anti-fungal treatment, we withdrew mycophenolate mofetiland tacrolimus trough levels were kept around 8 ng/mL. Despite the resultinglow-level immunosuppression, the ImmuKnow assay showed immune function to bein the moderate range with tacrolimus and steroid alone, encouraging us tomaintain this strategy to avoid recurrence of invasive pulmonary aspergillosis. In thesecond case, a 24-year-old man underwent living donor lobar lung transplantation forcystic fibrosis. Two healthy relatives donated a lower lobe each. Immunosuppressionwas maintained using tacrolimus, mycophenolate mofetil, and steroid. Five monthsposttransplantation, he developed persistent Pseudomonas aeruginosa pneumonia derivedfrom the paranasal sinuses. Under ImmuKnow assay monitoring, mycophenolate mofetilwas withdrawn, but immune function was maintained within the moderate range usingtacrolimus and steroid alone. DiscussionRespiratory function in both cases was maintained; nofindings of bronchiolitis obliterans syndrome were noted during this period. To the bestof our knowledge, no reports have described successful anti-metabolite withdrawal inlung transplantation with ImmuKnow monitoring. Immune evaluation by ImmuKnowcould offer a useful method to monitor and control immune status, particularly amongrecipients susceptible to infection, revealing that moderate immune function could bemaintained using tacrolimus and steroid in living donor lobar lung transplantation.

142 Fifteen-Year Experience of Living Donor Lobar Lung Transplant: Update on the Outcomes and Pulmonary Function of Recipients

142 Fifteen-Year Experience of Living Donor Lobar Lung Transplant: Update on the Outcomes and Pulmonary Function of Recipients

Are three patients better than one?

Lung transplantation represents the only effective strategy for treatment of end stage respiratory failure. Nevertheless its clinical application remains quite limited and a significant discrepancy between the number of LTx performed and its real need still remains evident [1]. Therefore patients wait for LTx for a long period with a high mortality rate while on the waiting list. For this reason we wrote a review with a provocative title in which we wondered if LTx was a clinical reality or should be conversely considered an experimental procedure [2]. In the recent period, we are witnessing epochal changes at different levels in the field of lung transplantation. On the side of donor management, application of particular ventilatory strategies may be effective in increasing the rate of lung suitability [3]. After the initial experience published by Steen [4], very recently an important article from the Toronto Lung Transplant Program showed how initially rejected or sub-optimal grafts can be successfully transplanted after the recovery of a normal pulmonary function, obtained by ex-vivo lung perfusion [5]. ECMO and interventional lung assist devices have been introduced in the clinical armamentarium for the management of lung transplant recipients suffering from severe deterioration of pulmonary function. As it happens for heart and kidney recipients, novel technological advances of the devices nowadays available allow their applications as a bridge to transplant also for LTx. These technologies not only increase the life expectancy of patients in the waiting list but also avoid the necessity of mechanical ventilation and lead these patients to LTx in better conditions even without the need of an intensive care unit stay [6–8]. Waiting time for LTx is highly dependent from somatic characteristics of recipients and very small patients may wait for a suitable graft for a longer period. For these patients, living lobar lung transplant may be one of the possible strategies to overcome this issue. Chen et al. describe excellent results regarding pulmonary function on living lobar lung transplant donors. This is an important message but a word of caution is mandatory. In comparison with other solid transplant performed using living donor graft (e.g. kidney), living lobar lung transplant is a highly demanding procedure performed on ‘healthy’ patients (the donor). In fact, the procedure Correspondence Massimo Boffini, Cardiac Surgery Department, San Giovanni Battista Hospital, University of Turin, Corso Bramante 88, Turin 18100, Italy. Tel.: +39 011 6335511; fax: +39 011 6336130; e-mail: massimo.boffini@unito.it

Outcomes and pulmonary function in living lobar lung transplant donors

Successful living-donor lobar lung transplantation (LDLLT) largely depends on donor outcome; however, there are few studies that have assessed outcomes of LDLLT donors, particularly pulmonary function. We investigated the outcomes and pulmonary function after donor lobectomy in LDLLT donors. Retrospective evaluation of consecutive 33 LDLLT donors was performed. Preoperative characteristics and perioperative and postoperative variables were investigated. Evaluation of pulmonary function 3, 6 and 12 months after donor lobectomy was performed prospectively. All donors were well alive after donor lobectomies. Morbidity was found in five donors (15%). Postoperative complications consisted of re-accumulation of pleural effusion requiring readmission in three donors and prolonged air leakage in two donors. Sacrifice of pulmonary arteries was performed in 20 donors (61%) with 1.4 ± 0.6 branches. Forced vital capacity was 77.8 ± 6.1%, 84.8 ± 6.0% and 89.4 ± 6.6% of the preoperative value 3, 6 and 12 months after donor lobectomy, respectively. Forced expiratory volume in 1 s was 80.5 ± 7.8%, 85.6 ± 8.9% and 89.3 ± 8.7% of the preoperative value 3, 6, and 12 months postoperatively. Living-donor lobectomy was performed with low morbidity. Pulmonary function even after lobectomy was better preserved than expected.

Postoperative pleural effusion in living lobar lung transplant donors

In living-donor lobar lung transplantation, the importance of donor safety should be emphasized because of the necessity of placing two donors at risk for each recipient. Approximately 3% of donors were reportedly readmitted to hospitals owing to complications after the donor surgery. Herein, we report two cases of living lobar lung transplant donors who exhibited accumulation of pleural effusion after discharge and were readmitted for treatment. The mechanism of this complication was not clearly elucidated, but surgeons should not ignore the possibility of pleural effusion necessitating readmission in living-donor lobar lung transplant donors.

Balloon angioplasty for pulmonary artery stenosis after lung transplantation

We report here a successful case of balloon angioplasty for a stenosis of the pulmonary artery after lung transplantation. A 49-year-old patient with end stage diffuse bronchiectasis with sinusitis underwent bilateral living donor lobar lung transplantation. After treatment of postoperative right pneumothorax, a perfusion lung scan revealed deficient perfusion in the left lung. Pulmonary angiography showed a severe stenosis in the left pulmonary artery just distal to the anastomosis. Percutaneous balloon angioplasty improved both pulmonary perfusion and respiratory function.

Complicações relacionadas à lobectomia em doadores de transplante pulmonar intervivos

To evaluate post-operative complications in living lobar lung transplant donors. Between September of 1999 and May of 2005, lobectomies were performed in 32 healthy lung transplant donors for 16 recipients. The medical charts of these donors were retrospectively analyzed in order to determine the incidence of postoperative complications and alterations in pulmonary function after lobectomy. Twenty-two donors (68.75%) presented no complications. Among the 10 donors presenting complications, the most frequently observed complication was pleural effusion, which occurred in 5 donors (15.6% of the sample). Red blood cell transfusion was necessary in 3 donors (9.3%), and 2 donors underwent a second surgical procedure due to hemothorax. One donor presented pneumothorax after chest tube removal, and one developed respiratory infection. There were two intra-operative complications (6.25%): one donor required bronchoplasty of the middle lobe; and another required lingular resection. No intra-operative mortality was observed. Post-operative pulmonary function tests demonstrated an average reduction of 20% in forced expiratory volume in one second (p < 000.1) compared to pre-operative values. Lobectomy in living lung transplant donors presents high risk of post-operative complications and irreversible impairment of pulmonary function. Careful pre-operative evaluation is necessary in order to reduce the incidence of complications in living lobar lung transplant donors.

Long-term Improvement in Pulmonary Function After Living Donor Lobar Lung Transplantation

As an alternative to cadaveric transplantation, living donor lobar lung transplantation (LDLLT) has been applied in critical patients with end-stage pulmonary disease because of the mismatch between the supply and demand of lungs for transplantation. However, it is unclear whether two pulmonary lobes can provide adequate long-term pulmonary function and satisfactory clinical outcome in recipients. Between October 1998 and September 2004, 28 females and 3 males, including 5 children, underwent LDLLT at Okayama University Hospital. Their mean age was 31.8 years, and the mean observation period was 53.8 months. One patient who underwent single-lung transplantation and another who died peri-operatively were excluded from further analyses. The most common indication for transplantation was pulmonary arterial hypertension (32.3%). The overall survival rate was 93.6%. Seven recipients (22.6%) developed bronchiolitis obliterans syndrome after LDLLT. The mean percent predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) improved between 12 and 24 months after transplantation (71.8 +/- 12.9% and 65.8 +/- 17.2% at 12 months vs 77.4 +/- 16.6% and 72.8 +/- 14.6% at 24 months; p < 0.005 and p < 0.05, respectively). The actual recipient FVC ultimately reached 123.0% of the estimated graft FVC of two donor lobes (calculated based on the donor FVC and number of segments implanted) at 36 months after LDLLT. Although LDLLT may be associated with the limitation of size mismatch, it holds promise for providing well-functioning pulmonary lobar grafts to critically ill patients with poor life expectancy.

Medical and Psychologic Outcome of Living Lobar Lung Transplant Donors

Living donor lobar lung transplantation is a viable therapy for carefully selected patients with end-stage pulmonary disease. Its success is largely dependent upon donor outcome, including both physical and emotional factors. To date, there has been little focus on psychosocial outcomes of lobar lung donors. Retrospective evaluation of 15 of 20 living lobar lung transplant donors was performed. Donors underwent evaluation of pulmonary function after recovery from donor lobectomy. Participants completed two self-report questionnaires, the SF-36 Health Survey (SF-36) and the Beck Depression Inventory (BDI), as well as an open-ended psychiatric interview. After lobar donation, mean forced expiratory volume in 1 second (FEV(1)) decreased by 21 +/- 2%, forced vital capacity (FVC) decreased by 16 +/- 3%, total lung capacity (TLC) decreased by 15 +/- 3%, and single-breath diffusing capacity (DLCO) decreased by 14 +/- 4%. All subjects scored higher than the national average on both the physical and mental health components of the SF-36. The BDI scores showed no evidence of clinical depression. However, the subjective interviews elicited two common complaints: (1) a decline in exercise performance, not accounted for by resting lung function measurements; and (2) a dissatisfaction with the degree of acknowledgment of their donation. Living lobar lung transplant donors enjoy generally satisfactory physical and emotional health. Donors report positive feelings about donation, but wish to be recognized and valued by the transplant team and by the recipient. Despite preservation of lung function within the normal range, some donors also experience a subjective decline in exercise tolerance. Long-term medical and psychologic follow-up appears warranted to monitor symptoms of exercise impairment and to enhance the donor experience.

Pediatric living donor lobar lung transplantation

Living donor lobar lung transplantation (LDLLT) was developed in order to mitigate the growing competition for deceased donor (DD) lungs and resultant increase in waiting list mortality. Because each of the two donor lobes serves as an entire lung for the recipient, donors who are taller than the recipient are preferred. Therefore LDLLT is particularly well suited for pediatric recipients for whom adults serve as donors. Although long-term outcomes after LDLLT reported by the Organ Procurement and Transplantation Network (OPTN) are worse compared with DD recipients, overall pediatric outcomes as well as single center reports from the most experienced programs are more promising. Particularly encouraging are the findings that bronchiolitis obliterans (OB) is less frequent or less severe in LDLLT recipients in comparison to DD recipients. Moreover, outcomes may be improved by careful selection of donors to ensure adequately sized donor lobes and minimization of infectious risks. Although no donor deaths have been reported, there is a moderate risk of significant short-term complications. Long-term follow-up has not been reported. The use of LDLLT has decreased in recent years, and the recent change by the OPTN to an urgency/benefit allocation system for DD lungs in patients 12 yr and older may further reduce the demand. Nonetheless, we anticipate that LDLLT will continue to be utilized in select circumstances, particularly in children under 12 where access to DD organs remains challenging.

Living donor lobar grafts improve pediatric lung retransplantation survival

Lung retransplantation is a controversial practice due to increased morbidity and mortality and the scarcity of available donor organs. Living donor lobar lung transplantation increases the number of available donor organs and facilitates a more organized procedure than traditional cadaveric donation for this complex reoperation. The purpose of this study was to evaluate our experience with pediatric lung retransplantation and to compare the outcomes of living donor lobar lung transplantation with cadaveric donation. Retrospective review of a prospectively collected database identified 39 children who underwent lung retransplantation from 1991 to 2004. Retransplantation was performed with living donor lobar lung transplantation in 13 patients and cadaveric donation in 26 patients. Short- and long-term outcomes were compared between the 2 groups. Perioperative mortality was 1/13 (7.7%) in the patients who had living donor lobar lung transplantation versus 11/26 (42.3%) in the cadaveric donation group (P = .03). Five-year survival for living donor lobar lung transplantation and cadaveric donation was 40.4% and 29.7%, respectively (P = .27). Both groups had a significant improvement in their forced expiratory volume in 1 second 6 months after retransplantation (P < .001). Multivariate analysis identified the use of cadaveric donation (relative risk = 6.16, P = .001) and early graft dysfunction (relative risk = 6.19, P = .001) as the major independent predictors of decreased survival following retransplantation. Living donor lobar lung transplantation reduces perioperative mortality and is an independent predictor of improved survival following pediatric lung retransplantation. This strategy offers significant benefit for this high-risk group and preserves the limited supply of donor lungs for other children at risk of dying while waiting for lung transplantation.

Peripheral Lung Volume Reduction Improved Early Graft Function in Severe Size Mismatched Living Donor Lobar Lung Transplantation

Background Lung transplantation from adults to infants or small children is still challenging because of concerns related to size disparity. Peripheral lung volume reduction for size disparity in cadaveric donor lung transplantation has been widely performed; however, little is known about the efficacy and the functional outcomes of downsizing the implanted lobes for severe size disparity in living donor lobar lung transplantation. Methods Thirteen size-mismatched (donor/recipient lung volume ratio >2.82) bilateral living donor lobar lung transplants were performed with (reduction group, n = 6) or without (no-reduction group, n = 7) peripheral lung volume reduction. Results On spontaneous respiration, PaO 2 in the reduction group was significantly higher than that in the no-reduction group ( P < .01) and PaCO 2 in the reduction group was significantly lower than that in the no-reduction group ( P < .001). Pulmonary vascular resistance in the reduction group remained significantly lower than that in the no-reduction group throughout the assessment periods after chest closure ( P < .05). Peak airway pressure in the no-reduction group increased significantly at the time of chest closure ( P < .001) and remained significantly higher than that in the reduction group throughout the assessment period on mechanical ventilation ( P < .01). The percentage of weight reduced from implanted grafts significantly correlated with donor/recipient lung volume ratio ( r = 0.82, P < .05). Conclusions Peripheral lung volume reduction is useful to improve early graft function in severe size mismatched experimental living donor lobar lung transplantation. The technique might allow for further flexibility in donor size and for increasing the donor pool for small recipients.

Living Donor Lobar Lung Transplantation: Current Status and Future Directions

Living lobar lung transplantation was developed as a procedure for adult and pediatric patients considered too ill to await cadaveric transplantation. One hundred thirty-eight living lobar transplants have been performed in 133 patients at our institution between January 1993 and September 2004. Actuarial 1-, 3-, and 5-year survival are similar to ISHLT registry data. There has been no donor mortality, and morbidity has been relatively low. Long-term postoperative pulmonary function studies demonstrate the relatively smaller-sized lobes can provide similar pulmonary function and exercise capacity to bilateral cadaveric lung transplants. Living lobar lung transplantation should be considered a viable option in patients with end-stage lung disease deemed unable to await a cadaveric organ and in those patients in which further deterioration would make cadaveric transplantation inappropriate.

Living donor lobar lung transplantation improves survival following lung re-transplantation in children

Lung re-transplantation is an accepted but controversial practice due to the scarcity of available donor organs. Living donor lobar lung transplantation (LDLLT) increases the number of available donor organs while preserving the supply of traditional cadaveric donor lungs (CDL) for children on the waiting list. The purpose of this study was to compare the short and long-term survival of LDLLT and CDL following lung re-transplantation in children.

An overview of paediatric lung transplantation.

Paediatric lung transplantation is indicated in selected children with end-stage lung disease that is not amenable to conventional medical or surgical therapy. The indications and complications differ from adult lung transplant patients. Due to the long waiting times for suitable cadaveric lungs, other types of lung transplantation, such as living donor lobar and split-lung procedures, have been utilised in paediatric patients. Unlike adult candidates, cystic fibrosis and primary pulmonary hypertension are the primary indications. Most recipients are in the adolescent age group. Complications that occur with greater frequency in paediatric lung recipients include somatic growth and graft function, post-transplant lymphoproliferative disease and medical non-adherence. While long-term outcome remains similar between adult and paediatric lung transplant recipients, there is a lower risk of bronchiolitis obliterans in very young recipients and in those who receive living donor lobar lung transplantation. Research into these clinical problems is hampered by the fact that only a small number of paediatric transplants are performed at each centre. Hence, improvement in outcome for these children will be dependent on developing methods to produce better tolerance, understanding the mechanisms/treatment of bronchiolitis obliterans and multi-centre studies that focus on the problems that primarily affect the paediatric lung transplant recipient.

Single center comparison of pediatric living donor lobar and cadaveric lung transplant

Living donor lobar transplant (LDLT) has been used to address the ongoing shortage of cadaveric lungs and unpredictable course of end-stage lung disease. Because LDLT involves putting two healthy patients at risk, we compared outcomes between cadaveric lung transplant and LDLT. From July 1994 to May 2002, 38 LDLTs were performed at this center. A cohort of cadaveric recipients, also transplanted here during that era, matched by age at transplant, sex and underlying disease was selected to serve as a controls. LDLT recipients were less stable at the time of transplant: more patients (12/38) in the LDLT cohort were mechanically ventilated compared to 2/38 in the controls. The average ischemic times were significantly shorter in the LDLT patients (1:32) compared to controls (4:46). One and 3 year survival for the LDLT recipients was 60 % and 48% compared to 89% and 58% for the control cohort. The difference in Kaplan-Meier survival curves was statistically significant (P=0.03). There was no difference in the incidence of acute rejection between the LDLT and control cohorts. Post-transplant FEV1 and FVC were not significantly different. However, freedom from bronchiolitis obliterans syndrome (BOS) at 1 and 3 years was 92% and 85% compared to 75% and 53% in the cadaveric cohort (P=0.03). Not surprisingly, the causes of death in the LDLT population reflected this difference. Only 2/24 (8%) of deaths in the LDLT cohort were due to BOS compared to 8/18 (45%) of deaths in the control cohort. In contrast, 11/24 (46%) of deaths in the LDLT cohort were related to infection compared to 2/18 (11%) in the control population. Based on this comparison, we conclude that LDLT can be performed successfully in pediatric patients. Although the decreased incidence of BOS makes us optimistic about the long-term survival of LDLT recipients, efforts focusing on minimizing infectious complications are necessary to improve overall survival.