Akihiro Aoyama

Living-donor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patients †

OBJECTIVES Living-donor lobar lung transplantation (LDLLT) has been performed as a life-saving procedure for critically ill patients who are unlikely to survive the long wait for cadaveric lungs. The purpose of this study was to compare the preoperative condition and outcome of LDLLT patients with those of conventional cadaveric lung transplantation (CLT) patients. METHODS A new lung transplant programme was established in 2008 at Kyoto University. Between June 2008 and January 2014, we performed 79 lung transplants, including 42 LDLLTs (10 single, 32 bilateral) and 37 CLTs (22 single, 15 bilateral). Data collected included pre- and perioperative variables and mid-term survival. All data were analysed retrospectively as of January 2014. RESULTS The majority of patients were female (57.1%) in the LDLLT group and male (64.9%) in the CLT group. The average age was similar (36.6 ± 20.7 vs 39.7 ± 12.6 years, P = 0.42) between the two groups. Preoperatively, interstitial lung disease was more common in LDLLT patients than in CLT patients (47.6 vs 24.3%, P = 0.048); prior haematopoietic stem cell transplantation was performed more often in LDLLT patients than in CLT patients (33.3 vs 13.5%, P = 0.040) and there were more steroid-dependent LDLLT patients than CLT patients (64.3 vs 29.7%, P = 0.0022). Based on preoperative criteria of lower body mass index (17.2 ± 4.0 vs 19.3 ± 3.3 kg/m(2), P = 0.013), less ambulatory ability (42.9 vs 86.5%, P = 0.0001) and more ventilator dependence (11.9 vs 2.7%, P = 0.12), LDLLT patients were more debilitated than CLT patients. LDLLT patients required longer postoperative mechanical ventilation than CLT patients (15.6 ± 16.2 vs 8.5 ± 8.1 days, P = 0.025). However, 1- and 3-year survival rates were similar between the two groups (89.7 and 86.1% vs 88.3 and 83.1%, P = 0.55). All living donors returned to their previous lifestyles without restriction. CONCLUSIONS Although LDLLT patients were in a worse preoperative condition than CLT patients, LDLLT patients demonstrated survival rates similar to CLT patients. LDLLT is a viable option for patients too ill to survive a long waiting time for cadaveric donors.

Outcome of living-donor lobar lung transplantation using a single donor

OBJECTIVE Living-donor lobar lung transplantation usually requires 2 healthy donors who donate either a right or a left lower lobe; however, finding 2 healthy donors is difficult. Several case reports have been published on successful living-donor lobar lung transplantation using a single donor; however, little is known about its outcome. METHODS We retrospectively investigated 14 critically ill patients who had undergone single living-donor lobar lung transplantation at 3 lung transplant centers in Japan. There were 10 female and 4 male patients, including 10 children and 4 adults. Size matching was assessed by estimated graft forced vital capacity and 3-dimensional computed tomography volumetry. The diagnoses included complications of allogeneic hematopoietic stem cell transplantation (n = 6), pulmonary hypertension (n = 4), and others (n = 4). RESULTS At a mean follow-up of 45 months (range, 2-128), the 3- and 5-year survival rate was 70% and 56%, respectively. There were 4 early deaths, for a hospital mortality of 29%, with 1 additional death at 40 months. The main cause of early death was primary graft dysfunction, most likely related to size mismatching. The survival among these 14 patients was significantly worse than the survival in a group of 78 patients undergoing bilateral living-donor lobar lung transplantation during the same period (P = .044). CONCLUSIONS Single living-donor lobar lung transplantation provides acceptable results for sick patients who would die soon otherwise. However, bilateral living-donor lobar lung transplantation appears to be a better option if 2 living donors are found.

Virtual-assisted lung mapping: outcome of 100 consecutive cases in a single institute

OBJECTIVES We developed virtual-assisted lung mapping (VAL-MAP), a bronchoscopic multispot dye-marking technique using three dimensional (3D) virtual imaging, for precise thoracoscopic sublobar lung resection with safe surgical margins. We herein review the results of 100 consecutive cases of VAL-MAP in our institute to identify types of tumours or resections that benefit from VAL-MAP. METHODS Markings were bronchoscopically made within 2 days preoperatively using virtual 3D images. Post-VAL-MAP computer tomography (CT) scans localizing the actual markings were reconstructed into 3D images for intraoperative navigation. All data on patients, markings and outcomes were prospectively collected, and the contribution of VAL-MAP to the operation was graded by the surgeon. RESULTS Resections of 156 lung lesions in 100 consecutive patients were planned from July 2012 to March 2014. The lesion diameter was 8.3 ± 4.9 (range, 2-24) mm. The total number of actually conducted markings was 380 (3.83 ± 1.07 markings/patient). Eighty-four lesions were resected by 71 wedge resections using 158 markings (2.1 ± 0.1/resection; range, 1-3). Seventy lesions were resected by 63 segmentectomies using 224 markings (3.6 ± 0.1/resection; range, 2-6). Markings were identifiable on post-VAL-MAP CT mostly as ground-glass opacities (87.7%) and/or bronchial dilatation (56.1%). During the operation, 357 of 380 markings (93.9%) were visible on the pleural surface and significantly associated with marking visibility on CT. Multiple markings that were complementary to one another appeared to have contributed to the high rate of successful resection (99.3%) with satisfactory resection margins. The contribution of VAL-MAP to the operation as graded by surgeons demonstrated that VAL-MAP is most effective during wedge resection or complex segmentectomy for hardly palpable, small tumours, while VAL-MAP still plays an important role in simple segmentectomy or resection of palpable tumours by providing higher confidence levels to surgeons during the operation. Minor pneumothoraces were found on post-VAL-MAP CT images in 4 patients without symptoms or a need for treatment. CONCLUSIONS The present study further demonstrated the efficacy and safety of VAL-MAP. VAL-MAP is likely to benefit a broader range of patients than are conventional marking techniques by assisting with both accurate tumour identification and precise determination of resection lines.

Protective effect of plasmin in marginal donor lungs in an ex vivo lung perfusion model

BACKGROUND Donor lung thrombi are considered an important etiology for primary graft dysfunction in lung transplantation. We hypothesized that thrombolysis before lung transplantation could alleviate ischemia-reperfusion injury. This study was designed to evaluate the effect of the fibrinolytic agent plasmin on lungs damaged by thrombi in an ex vivo lung perfusion (EVLP) system. METHODS Rats were divided into control, non-plasmin, and plasmin groups (n = 7 each). In the control and plasmin groups, cardiac arrest was induced by withdrawal of mechanical ventilation without heparinization. Ventilation was restarted 150 minutes after cardiac arrest. The lungs were flushed, and the heart and lungs were excised en bloc. The lungs were perfused in the EVLP system for 60 minutes, and plasmin or placebo was administered upon EVLP initiation. RESULTS Fibrin/fibrinogen degradation products in the perfusate were significantly higher in the plasmin group than in the control and non-control groups (p < 0.001 for both). Plasmin administration significantly decreased pulmonary vascular resistance (plasmin vs non-plasmin, p = 0.011) and inhibited the exacerbation of dynamic compliance (plasmin vs non-plasmin, p = 0.003). Lung weight gain was less in the plasmin group than in the non-plasmin group (p = 0.04). CONCLUSIONS Our results confirmed that plasmin administration in an EVLP model dissolved thrombi in the lungs, resulting in reconditioning of the lungs as assessed by various physiologic parameters.

Mediastinal infectious complication after endobronchial ultrasound-guided transbronchial needle aspiration

We report here a mediastinal infectious complication after endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) that was successfully treated using intravenous antibiotic therapy. EBUS-TBNA was performed for a 59-year old man with mediastinal adenopathy 8 years after left pneumonectomy for squamous cell carcinoma of the lung. A single-needle pass produced an adequate cytology and histology sample, and the lesion was diagnosed as small-cell lung cancer. The procedure itself was uneventful, but the patient developed a nightly fever after the biopsy. Finally, he was readmitted, and intravenous antibiotic therapy was required for 4 weeks to treat a mediastinal infection after EBUS-TBNA before chemotherapy for small-cell lung cancer.

Nebulized Phosphodiesterase III Inhibitor During Warm Ischemia Attenuates Pulmonary Ischemia–Reperfusion Injury

BACKGROUND The control of warm ischemia-reperfusion injury is crucial in managing donors after cardiac death for lung transplantation. We focused on transalveolar administration as a drug-delivery route for such donors. Milrinone is a phosphodiesterase 3 inhibitor that inhibits the breakdown of cyclic adenosine monophosphate and selectively relaxes smooth muscle. We hypothesized that nebulized milrinone would mitigate warm ischemia-reperfusion injury of lung. METHODS This study was conducted with an isolated rat lung perfusion model. Lungs were excised, exposed to 55-minute ischemia at 37 degrees C, and reperfused for 60 minutes. During ischemia, nebulized milrinone (n = 6) or saline (n = 6) was inhaled. Lungs were continuously perfused without ischemia as a sham group (n = 6). Airway resistance, pulmonary vascular resistance, pulmonary compliance, weight gain and blood gas were measured. Adenine nucleotide levels and apoptosis were investigated in the reperfused lungs. RESULTS Milrinone nebulization decreased post-ischemic pulmonary vascular resistance (0.98 +/- 0.05 and 1.74 +/- 0.17 cm H(2)O/ml.min at 60 minutes of reperfusion in the milrinone and control groups, respectively [p < 0.01]). It did not alter cyclic adenosine monophosphate levels, but it did elevate adenosine triphosphate levels (9.87 +/- 0.38 and 6.91 +/- 0.45 in the milrinone and control groups, respectively [p < 0.01]) and suppressed apoptosis (3.83 +/- 0.91 and 46.17 +/- 3.39 of mean apoptotic cell numbers in the milrinone and control groups, respectively [p < 0.01]). CONCLUSIONS Milrinone nebulization decreased post-ischemic pulmonary vascular resistance, elevated adenosine triphosphate levels, and suppressed apoptosis. Nebulized milrinone has some protective effects against warm ischemia.

Thoracoscopic wedge lung resection using virtual-assisted lung mapping

Background Virtual-assisted lung mapping is a novel bronchoscopic preoperative lung marking technique using virtual images to conduct multiple concurrent lung markings with dye. This study analyzed the indications, mapping design, and outcomes of lung wedge resection using virtual-assisted lung mapping. Methods From August 2012 to October 2013, 35 patients with 59 lesions were planned to undergo thoracoscopic lung wedge resection aided by virtual-assisted lung mapping. The data related to virtual-assisted lung mapping were prospectively collected, with the exception of the mapping design which was retrospectively analyzed. Results Suspected primary lung cancer (21 lesions in 18 patients) and metastatic lung tumors (38 lesions in 17 patients) were treated by thoracoscopic lung wedge resection with the aid of virtual-assisted lung mapping; 50 wedge resections were conducted with 107 markings. Virtual-assisted lung mapping was most frequently designed to place 2 (n = 15 wedge resections) or 3 (n = 17) markings to both identify the tumor(s) and secure a sufficient resection margin. In 7 wedge resections, anatomical landmarks and/or imaginary auxiliary lines functioned as complementary parts of the lung map when bronchial anatomy did not allow for markings at ideal spots. The resection outcomes were satisfactory without clinically evident complications. Conclusion Multiple markings of virtual-assisted lung mapping not only enabled tumor identification, but also secured sufficient resection margins. Special techniques using anatomical landmarks and imaginary auxiliary lines were complementary to the lung map when bronchial anatomy did not allow for markings at ideal spots.

Successful Sub-zero Non-freezing Preservation of Rat Lungs at 2°C Utilizing a New Supercooling Technology

BACKGROUND A lower temperature, namely below 0 degrees C, has been thought to be desirable for organ preservation because of the lower rate of metabolism; however, its benefits are still poorly understood. Supercooling is a non-freezing state of liquid below the freezing point, and the new development of a refrigerator for supercooling has now made it possible to preserve organs at sub-zero temperatures in a non-frozen state without cryoprotectants. METHODS Rat lungs were ventilated and perfused for 60 minutes in the 3 groups (n = 7 each): (1) the fresh group, in which the lungs were reperfused immediately after harvesting; (2) the 4 degrees C group, in which the lungs were stored after harvesting in ET-Kyoto solution at 4 degrees C for 17 hours before reperfusion; and (3) the supercooling group, in which lungs were preserved in ET-Kyoto solution at -2 degrees C for 17 hours. RESULTS Ischemia-reperfusion injury was significantly attenuated in the supercooling group, with a decrease in the pulmonary artery pressure (p < 0.02) and weight gain (p < 0.001), and an increase in the tidal volume (p = 0.001) and arterial oxygen tension (p < 0.001) compared with the 4 degrees C group. In the supercooling group, most of these indicators were equivalent to the fresh lung, with less damage to the endothelial cells of the pulmonary arteries and higher levels of adenosine triphosphate than in the 4 degrees C group. CONCLUSIONS Lungs stored using this new supercooling method of lung preservation showed better organ function than conventional storage at 4 degrees C.

Postoperative pulmonary function and complications in living-donor lobectomy

BACKGROUND Successful living-donor lobar lung transplantation largely depends on the donors outcome. Because surgical skills and peri-operative management have evolved over time, this study evaluated the recent outcomes of donor lobectomies. METHODS Between 2008 and 2014, 48 consecutive living-donor lobar lung transplantations with 85 donor lobectomies were performed at Kyoto University. All donors were prospectively followed up regularly until 1 year after surgery. RESULTS Right and left lower lobectomies were performed in 49 and 36 donors, respectively. Pulmonary arterial branches were sacrificed at equal frequency in both lobectomies, whereas pulmonary arterioplasty was only performed in left lower lobectomy (n = 9). All donors were discharged after the lobectomies, and none died during follow-up. Post-operative complications occurred in 24 donors (28%) overall, without a significant difference between donor sides. Intraoperative complications were found in 2 donors. Early and late post-operative complications were noted in 17 and 6 donors, respectively. Pneumothorax, pleuritis, and pleural effusion were the most frequent. Post-operative pulmonary function sequentially recovered more than expected and was not significantly affected by the sacrifice of pulmonary arterial branches during lobectomy. By contrast, pulmonary function at 1 year after donor lobectomy in the donors who had peri-operative complications was significantly lower than that in the donors who did not, although even post-operative pulmonary function in the donors with peri-operative complications still recovered more than expected. CONCLUSIONS Living-donor lobectomies have been safely performed in recent decades with low morbidities and without mortality.

Predictive factors of myasthenic crisis after extended thymectomy for patients with myasthenia gravis

OBJECTIVES Postoperative myasthenic crisis (POMC) is one of the serious complications after extended thymectomy for patients with myasthenia gravis (MG). This study aims to clarify the risk factors of POMC occurrence. METHODS The clinical data of 55 MG patients (25 male, 30 female; median age, 51 years) who underwent extended thymectomy at Kyoto University from 2000 to 2013 were retrospectively reviewed. Surgical outcomes and pre- and perioperative predictive factors of POMC were analysed. RESULTS The preoperative Myasthenia Gravis Foundation of America stage was I, II, III and IV in 24, 22, 8 and 1 patients, respectively. Ten patients (18.2%) developed POMC; 6 required prolonged intubation over 24 h and 4 required reventilatory support. All patients were weaned after 5.6 (2-26) days of ventilator support, and were discharged. Univariate analysis revealed a correlation with a high preoperative anti-acetylcholine receptor antibody titre (P = 0.009), history of myasthenic crisis (MC) (P = 0.0004) and unstable MG after preoperative medical therapy (P = 0.003). Multivariate logistic regression analysis showed history of MC (odds ratio, 11.84; 95% confidential interval, 1.05-372; P = 0.045) and unstable MG (odds ratio, 29.45; 95% confidential interval, 2.00-1063; P = 0.013) independently predicted POMC. The surgical response rate was not significantly different between the two groups (66.7% with POMC, 85.4% without POMC; P = 0.334). CONCLUSIONS POMC occurred more frequently in unstable MG before surgery or in patients with a history of MC. Adequate preoperative medical therapy and perioperative care should be provided to these patients.