Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

BACKGROUND: Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. METHODS: Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. RESULTS: On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. CONCLUSION: The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs.

Surgical and non-surgical management of repeat pulmonary metastasis from sarcoma following first pulmonary metastasectomy.

PURPOSE: Although repeat pulmonary metastasectomy for sarcoma is not uncommon and associated with a favorable survival in select patients, there is a paucity of data on the demographics and tumor characteristics of patients with repeat pulmonary metastasis following complete resection of pulmonary metastases from osteogenic or soft tissue sarcoma. METHODS: A retrospective chart review was performed to identify patients with isolated repeat pulmonary metastasis after complete resection of pulmonary metastases from sarcoma at Kyoto University Hospital between January 1990 and December 2014. Isolated pulmonary metastasis was defined as limited to presumable pulmonary metastasis according to the follow-up radiologic workup. RESULTS: Thirty-five patients were identified to have repeat pulmonary metastasis. Thirty patients underwent attempted repeat pulmonary metastasectomy (including 21 undergoing documented complete resection and 7 undergoing documented incomplete or aborted resections). Five patients received non-surgical management. The median follow-up period was 16 months (range 1-234) from repeat pulmonary metastasis. The five-year overall survival of the whole patient cohort and those undergoing repeat pulmonary metastasectomy were 37.6 and 41.1 %, respectively, from repeat pulmonary metastasis. CONCLUSIONS: A majority of patients with repeat pulmonary metastasis from sarcoma undergo repeat metastasectomy, which is associated with favorable survival outcomes. However, a greater accumulation of data on non-surgically managed patients is needed as such information is currently limited available.

Pleuroparenchymal fibroelastosis and non-specific interstitial pneumonia: frequent pulmonary sequelae of haematopoietic stem cell transplantation.

AIMS: Pulmonary sequelae, reported as chronic graft-versus-host disease (cGVHD), of haematopoietic stem cell transplantation (HSCT) include constrictive bronchiolitis obliterans (CBO), lymphocytic bronchiolitis (LB), and veno-occlusive disease (VOD); recently, pleuroparenchymal fibroelastosis (PPFE) has also been described in bone marrow transplant recipients. The histological features of pulmonary HSCT sequelae have not been described systematically. The aim of the study was to review and identify the histological features of PPFE after bone marrow transplant. METHODS AND RESULTS: A retrospective review of 20 patients who underwent lung transplantation for pulmonary disease following HSCT between 2004 and 2013 was conducted. The patient age at transplantation ranged from 8 years to 57 years (median, 27.5 years). Fifteen patients had cGVHD in other organs (skin, nine; liver, six; salivary gland, six). Lung transplantation was performed at a median of 4.6 years (range, 1.2-14.8 years) post-HSCT. Histologically, all cases had CBO, with concurrent LB in 10, and VOD in three. PPFE was identified in 15 cases (75%), with subpleural (15), paraseptal (11) and centrilobular (13) distributions; and non-specific interstitial pneumonia (NSIP) was identified in 15 cases (75%), with fibrotic (nine) and cellular (six) patterns. PPFE was distributed in all lobes, with a predominance in the upper lobe. NSIP was mostly focal, with two cases having diffuse involvement. CONCLUSIONS: PPFE and NSIP were frequently seen in HSCT patients. Possible causes may include reactions to drugs or radiation, or cGVHD.

Impact of the cardiac arrest mode on cardiac death donor lungs.

BACKGROUND: Donation after cardiac death (DCD) organs could alleviate the shortage of donor lungs. This study aimed to assess the influence on lung injuries of the way in which cardiac arrest was induced and to investigate the mechanisms leading to any differences. MATERIALS AND METHODS: Male rats were allocated into three groups as follows: sham (no warm ischemia), ventricular fibrillation (VF), and asphyxia group. Cardiac arrest was induced by either VF by way of a fibrillator or asphyxia caused by withdrawal of ventilation, which reflected uncontrolled and controlled DCD situations, respectively. The impact on lung flushing after 60 min of warm ischemia time was evaluated (n = 5, in each group). The physiological functions of the lungs in an isolated lung perfusion circuit were also evaluated with warm ischemia time prolonged to 150 min (n = 8, in each group). Messenger RNA expression levels of surfactant proteins (SPs) and inflammatory cytokines, pathologic findings, and high-energy phosphates of the lung tissues were investigated. RESULTS: In the asphyxia group, flushing and physiological functions in the isolated lung perfusion circuit were the most severely affected. Reverse transcription-polymerase chain reaction and pathologic findings revealed depletion of surfactant protein (SP)-C in lung tissues of the asphyxia group after reperfusion. The VF group was characteristic with elevated pulmonary vascular resistance. CONCLUSIONS: Lung injuries were mainly attributed to alveolar wall damage and depletion of SP in the asphyxia group, and perivascular area prominent edema in the VF group. DCD donor lungs were affected differently by the way in which cardiac arrest was induced.

Gefitinib treatment in patients with postoperative recurrent non-small-cell lung cancer harboring epidermal growth factor receptor gene mutations.

BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib is an effective treatment for recurrent or advanced lung cancer harboring EGFR gene mutations, and has improved progression-free survival in several clinical trials. However, the effect of gefitinib treatment for recurrent lung cancers with EGFR gene mutations after complete resection and the influence of the timing of such treatment have not been fully elucidated in a practical setting. METHODS: We investigated 64 patients (median age: 68 years; men: 22; women: 42; adenocarcinoma: 61; adenosquamous cell carcinoma: 2; combined large cell neuroendocrine carcinoma: 1) with recurrent lung cancer after complete resection who received gefitinib for the recurrent lesions and in whom the tumors had EGFR gene mutations. Progression-free survival, response rate, and safety were analyzed. RESULTS: Complete response and partial response were achieved in 2 patients and in 42 patients, respectively (objective response rate: 69 %). Stable disease was obtained in 16 patients, the disease control rate was 94 %, and median progression-free survival was 16 months. The timing of gefitinib treatment (first line, second line, or later) and the type of EGFR gene mutation present did not influence progression-free survival. However, a smaller number of recurrent sites at the start of gefitinib treatment was linked to better progression-free survival. Hematologic and nonhematologic toxicities were generally mild, but 1 patient experienced interstitial lung disease. CONCLUSIONS: Our results suggest that gefitinib treatment for recurrent lung cancer with gene EGFR mutations is a useful option in a practical setting, irrespective of the timing of such treatment and the type of EGFR gene mutation present.

Preoperative Hypercapnia as a Predictor of Hypotension During Anesthetic Induction in Lung Transplant Recipients.

OBJECTIVE: To determine the incidence and predisposing factors of hypotension during anesthetic induction in lung transplant recipients. DESIGN: Retrospective study. SETTING: University hospital. PARTICIPANTS: Patients who underwent lung transplantation between 2008 and 2013 (n = 68). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors analyzed the mean arterial pressure (MAP) from administration of anesthetic drugs to 10 minutes after endotracheal intubation (ie, the anesthetic induction) among participants who underwent lung transplantation. Patients were considered to have clinically significant hypotension (CSH) when the following criteria were fulfilled: An MAP decrease of>40% from baseline and MAP of<60 mmHg. Overall, 41.2% of patients experienced CSH during the induction of anesthesia. The preoperative partial pressure of carbon dioxide (PaCO2) was significantly higher in patients who experienced CSH during anesthetic induction than in those who did not (p = 0.005). Preoperative PaCO2 predicted the development of CSH during anesthetic induction (area under the curve = 0.702; p = 0.002), with an optimal cut-off point of 55 mmHg determined by maximizing the Youden index. The incidences of CSH during anesthetic induction for patients with (PaCO2 ≥ 55) and without (PaCO2<55) preoperative hypercapnia were 75.0% (95% confidence interval [CI] [53.8-89.2]) and 30.8% (95% CI 26.4-37.3), respectively. After adjustment for known predicting factors, the odds ratio for the relationship between preoperative hypercapnia and CSH during anesthetic induction was 12.54 (95% CI 3.10-66.66). CONCLUSIONS: Hypotension during anesthetic induction is common in lung transplant recipients, and is independently predicted by preoperative hypercapnia.

Gastroparesis after living-donor lobar lung transplantation: report of five cases.

Gastroparesis is a challenging gastrointestinal complication of deceased-donor lung transplantation and heart-lung transplantation, but it has not been reported after living-donor lobar lung transplantation (LDLLT). To better understand this complication after LDLLT, we reviewed our institutional experiences. Among the 32 patients who survived for at least 3 months after LDLLT, five (16 %) developed symptomatic gastroparesis. All five patients had undergone bilateral LDLLT, and gastroparesis was diagnosed within 2 months after transplantation. Neither adult patients who received single lobar LDLLT nor pediatric patients who received either bilateral or single lobar LDLLT developed gastroparesis. Although gastroparesis-related symptoms improved after medical treatment in three patients, two patients died of complications related to gastroparesis. We conclude that gastroparesis can occur after LDLLT and may cause grave complications unless carefully managed.

Clinical application of ET-Kyoto solution for lung transplantation.

Because of the severe donor shortage in Japan, even after the revision of the Organ Transplant Law in 2010, the frequency of recovery of extended criteria lungs has increased in Japan. We developed a new lung preservation solution, "ET-Kyoto solution," to enhance lung preservation, to minimize primary graft dysfunction (PGD) and to improve the post-transplant outcomes. In this study, we retrospectively analyzed our results of lung transplantation using the ET-Kyoto solution. From 2002 to 2012, 26 patients underwent transplantation of lungs preserved with ET-Kyoto solution from brain-dead donors. We retrospectively reviewed the post-transplant pulmonary function and long-term survival. The graft performance was assessed by the PGD grading system. The mean graft ischemic time was 483.8 ± 19.0 min. The oxygenation capacity after reperfusion and recovery of respiratory function were both acceptable despite the long ischemic time. The survival rate at 5 years after transplantation was 85.1 %. Lungs preserved by ET-Kyoto solution had satisfactory postoperative lung function, despite the long preservation time, with excellent long-term survival. The results were acceptable for the use of grafts with a long ischemic time.

The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation.

PURPOSE: We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. METHODS: Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. RESULTS: The incidence of oxygen desaturation (SpO2 < 90 %) during anesthetic induction and severe respiratory acidosis (pH < 7.2) after anesthetic induction were 21.1 and 26.3 %, respectively. Reduced dynamic compliance (Cdyn) during mechanical ventilation was significantly associated with oxygen desaturation during anesthetic induction (p = 0.01), as well as severe respiratory acidosis after anesthetic induction (p = 0.01). The preoperative partial pressure of carbon dioxide in arterial blood (PaCO2; r = -0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. CONCLUSIONS: Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn.

Update on ischemia-reperfusion injury in lung transplantation.

PURPOSE OF REVIEW: Primary graft failure, which represents one of the most frequent causes of early mortality, is mostly caused by ischemia-reperfusion injury (IRI). IRI may also induce rejection, which is the principal cause of mortality after transplantation. It is essential to understand the mechanism of pulmonary IRI for improving the outcomes of lung transplantation, and therefore we reviewed the state of the art concerning pulmonary IRI in lung transplantation. RECENT FINDINGS: Numerous strategies have been conducted to reduce IRI after lung transplantation both from the experimental and clinical aspects. The greatest efforts have been done in the method of lung preservation and reperfusion. Recently, ex-vivo lung perfusion system was developed and has been clinically introduced. Furthermore, more experimental studies to understand the pathophysiology of IRI and to alleviate lung IRI have been performed worldwide, and various new treatment modalities including inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, subzero preservation, and mesenchymal stromal cell therapy are going to be applied to the clinical practice. SUMMARY: IRI, whose pathophysiology remains incompletely understood, is one of the most critical phenomena in lung transplantation, and therefore more studies to control pulmonary IRI are required for improving the outcomes of lung transplantation.

Normothermic ex vivo lung perfusion in clinical lung transplantation.

BACKGROUND: More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP. METHODS: In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital. RESULTS: During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP. CONCLUSIONS: Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).

Identification of subsets of patients with favorable prognosis after recurrence in completely resected non-small cell lung cancer.

BACKGROUND: This retrospective study aimed to determine prognostic factors associated with postrecurrence survival of completely resected non-small cell cancer patients with postoperative recurrence. METHODS: Characteristics, treatment modality, and postrecurrence survival of 234 patients (157 males and 77 females, mean age at recurrence: 68.7 years, 152 adenocarcinomas and 82 non-adenocarcinomas), who underwent complete resection for non-small cell lung cancer between 2003 and 2009 at our hospital and experienced recurrence, were analyzed for prognostic factors. Cox proportional hazard model was applied for multivariate analysis. RESULTS: Among 234 patients, the median survival time after the diagnosis of recurrence was 21 months, and the 5-year postrecurrence survival rate was 19.9 %. Eastern Cooperative Oncology Group Performance Status (ECOG PS) (hazard ratio [HR]: ECOG PS-0/PS-1/PS-2 = 1/3.313/7.622), time to recurrence after surgery (HR: >2 years/1-2 years/<1 year = 1/1.881/2.185), and number of initial recurrent organs (HR: 1 organ/2 organs/3 or more organs = 1/1.896/2.818) were independent prognostic factors. Patients who received resection or stereotactic irradiation for limited number of brain metastases or solitary extracranial metastasis, and those who received mediastinal radiation or chemoradiation for recurrence at regional lymph nodes and/or resected stump had better survival (median survival time after recurrence: 34, 64, and 25 months, respectively). CONCLUSIONS: Poor ECOG PS, shorter time from initial surgery to recurrence, and increasing number of initial recurrent regions are associated with poor prognosis after recurrence. When the number of recurrent lesions is limited, intensive local treatment with curative intent should be applied for achieving long-term postrecurrence survival.

Redo living-donor lobar lung transplantation for bronchiolitis obliterans associated with antibody-mediated rejection.

Living-donor lobar lung transplantation (LDLLT) is an established therapy for patients with end-stage lung disease, but living-donor lobar lung retransplantation (re-LDLLT) is rarely reported. We previously reported a case of unilateral antibody-mediated rejection after LDLLT in the presence of newly formed donor-specific antibodies against a right-lobe donor. The same patient developed contralateral bronchiolitis obliterans, resulting in bilateral bronchiolitis obliterans, but re-LDLLT was successful. Pathological findings of the explanted lungs were consistent with the clinical course of the patient. One year after re-LDLLT, the patient is doing well without any anti-human leukocyte antigen antibodies. Four lobes from four different donors were transplanted in this patient. The first two lobes were rejected eventually, but the two lobes implanted later presented no signs of rejection at least for 1 year after the transplant. Herein, we report this rare case and compare the clinical course and pathological findings.

Prognostic factors for patients in postoperative brain metastases from surgically resected non-small cell lung cancer.

BACKGROUND: Postoperative recurrence in non-small cell lung cancer (NSCLC) reduces the life expectancy of patients. In this retrospective study, we investigated the prognostic factors in patients with postoperative brain metastases from surgical resected non-small cell lung cancer (NSCLC). METHODS: We conducted a retrospective chart review of patients who had undergone resection for NSCLC between April 2004 and February 2009 and found 65 had experienced postoperative brain metastases by March 2010. We reviewed these patients for clinicopathological information, treatments and responses to treatment, and overall survival. RESULTS: The 5-year survival rate after the diagnosis of brain metastases was 15.4 %. Significantly favorable prognostic factors for patients after a diagnosis of brain metastases included female gender, adenocarcinoma, a small number (1-3) of brain metastases, no extracranial metastasis at the diagnosis of brain metastases, radiation treatment (whole-brain radiation and/or stereotactic irradiation), and local treatment [stereotactic irradiation and/or surgical operation (craniotomy)]. Furthermore, in patients with only brain metastases as the postoperative initial recurrence, the favorable positive prognostic factors included a small number (1-3) of brain metastases, adjuvant chemotherapy, chemotherapy (including adjuvant and other chemotherapy and excluding epidermal growth factor receptor-tyrosine kinase inhibitors), and local treatment. CONCLUSIONS: Our study found that the foregoing clinical characteristics in postoperative brain metastases and the administration of treatment contributed to patient life expectancy.

Postoperative respiratory management in living donor lobar lung transplantation.

BACKGROUND: We evaluated postoperative respiratory management of living donor lobar lung transplantation (LDLLT). METHODS: Perioperative variables were reviewed in 21 patients who underwent LDLLT at our institution. Recipients were kept intubated for at least two d after LDLLT to maintain optimal expansion of the implanted lobes. Subsequently, if weaning from artificial ventilation could be tolerated, extubation was considered with the assistance of non-invasive ventilation (NIV). If this could not be tolerated, early tracheostomy was considered. RESULTS: All 21 recipients were weaned from artificial ventilation. Twelve patients underwent tracheotomy 4.4 ± 1.8 d after LDLLT and were weaned from artificial ventilation 24.3 ± 17.0 d after LDLLT. Eleven patients were extubated 3.6 ± 1.7 d after LDLLT with NIV, but two of them were reintubated, and finally weaned from artificial ventilation via tracheostomy. Excluding these two patients, NIV was required for 3.8 ± 3.9 d after extubation. The early postoperative course was significantly eventful in patients with tracheostomies, and artificial ventilation, ventilatory support, and intensive care unit stays were longer. Twenty patients (95%) showed survival at 24.4 ± 13.4 months of follow-up. CONCLUSIONS: Postoperative respiratory management with NIV and early tracheostomy were useful after LDLLT.

Incidence and pattern of hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation.

PURPOSE: Living-donor lobar lung transplantation (LDLLT) has been successfully performed in Japan. In LDLLT, the recipient usually receives one lower lobe from each of two donors; however, finding two ABO-matched donors is often difficult. Solid organ transplants from donors with minor ABO-mismatches can be complicated by hemolysis. We investigated the incidence of de novo anti-ABO antibody production and hemolysis in patients receiving LDLLT across minor ABO-mismatches. METHODS: We evaluated 23 patients who underwent LDLLT between June 2008 and December 2011, including 11 patients who underwent minor ABO-mismatched transplantation. We measured the anti-A/B antibody serum titers, hemoglobin concentrations and indirect bilirubin levels. RESULTS: None of the patients showed any clinical signs of hemolytic anemia (mean follow-up period; 16 months). Two of the 11 patients (18 %) receiving minor ABO-mismatched LDLLTs showed a small amount of de novo anti-B antibodies for a transient period. These patients showed gradual progression of anemia, and weak de novo anti-A/B antibodies were detected with column agglutination technology. The patients received only 2 U of washed type O red blood cells; thereafter, the hemolytic anemia did not develop further in either case. CONCLUSION: LDLLT across minor ABO-mismatches results in the transient appearance of weak de novo anti-A/B antibodies with a low incidence; thus, this procedure can be a safe treatment.

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.

Short-term outcome in living donors for lung transplantation: the role of preoperative computer tomographic evaluations of fissures and vascular anatomy.

Successful living-donor lobar lung transplantation (LDLLT) largely depends on donor outcome. We reviewed our experiences with LDLLT and focused on preoperative computed tomographic evaluations of donors. Twenty-five LDLLTs were performed in Kyoto University. As a routine preoperative assessment, high-resolution chest computed tomography (CT), and three-dimensional (3D)-CT angiography were performed. Preoperative evaluations, surgical procedures, and early postoperative outcomes were reviewed in 43 consecutive LDLLT donors. All donors were discharged home after the donor lobectomies. Severely incomplete fissures were intraoperatively identified in two donors, whose interlobar fissures were mostly not identified by high resolution CT preoperatively. Preoperative 3D-CT angiography was effective for the identification of the branches of the pulmonary artery and vein. Pulmonary arterioplasties were performed with auto pericardial patches in three left donors. The bilateral donors had to be exchanged because of an anomaly of the pulmonary veins in one donor. Small pulmonary arterial branches to the remaining lobes were to be sacrificed in 23 donors (53%). Early postoperative complications were ascertained in seven donors, and five of them presented air leak-related complications. Living donor lobectomies were safely performed with low morbidities in our institution. Preoperative computer tomographic evaluations might be useful in donor lobectomies.

Therapeutic effect of surfactant inhalation during warm ischemia in an isolated rat lung perfusion model.

Warm ischemia-reperfusion injury related to donation after cardiac death donors is a crucial and inevitable issue. As surfactant function is known to deteriorate during warm ischemia, we hypothesized that surfactant inhalation during warm ischemia would mitigate warm ischemia-reperfusion injury. We used an isolated rat lung perfusion model. The rats were divided into three groups: sham, control, and surfactant. In the control and surfactant groups, cardiac arrest was induced by ventricular fibrillation. Ventilation was restarted 110 min later; subsequently, the lungs were flushed, and heart and lung block was recovered. In the surfactant group, a natural bovine surfactant Surfacten(®) was inhaled for 3 min at the end of warm ischemia. Then, the lungs were reperfused for 80 min. Surfactant inhalation significantly improved graft functions, effectively increased lung tissue ATP levels, and significantly decreased mRNA levels of IL-6 and IL-6/IL-10 ratio at the end of reperfusion. Histologically, lungs in the surfactant group showed fewer signs of interstitial edema and hemorrhage, and significantly less neutrophilic infiltration than those in the control group. Our results indicated that surfactant inhalation in the last phase of warm ischemia maintained lung tissue energy levels and prevented cytokine production, resulting in the alleviation of warm ischemia-reperfusion injury.

Hyperfractionated irradiation with 3 cycles of induction chemotherapy in stage IIIA-N2 lung cancer.

BACKGROUND: The purpose of the present study was to improve the prognosis of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). To achieve that goal, we performed induction chemoradiotherapy followed by surgery. METHODS: The criteria for this phase II study were ≤75-year-old patients with pathologically diagnosed stage IIIA-N2 NSCLC who had performance statuses of 0 or 1 with good organ function. Three cycles of chemotherapy with paclitaxel and carboplatin were carried out, with concurrent hyperfractionated irradiation (42 Gy). After re-evaluation, pulmonary resections were considered unless patients showed progressive disease. The primary endpoint was overall survival (OS), and the secondary endpoints were disease-free survival (DFS) and absence of toxicity. RESULTS: All 22 patients enrolled in this study completed the induction chemoradiotherapy without any severe complications. In these 22 patients, the 2- and 5-year OS were 81 and 47%, respectively. There were no therapy-related deaths. Surgery was subsequently performed in 19 patients (86%). Pathological complete responses were seen in 6 patients (27%), while node downstaging was obtained in 10 patients (45%). In the 19 patients who underwent surgery, the 2- and 5-year OS rates were 83 and 62%, respectively, and the 2-year DFS rate was 63%. All 6 patients with pathological complete responses survived without disease. Patients with residual multiple-station N2 showed worse OS and DFS rates than did those with downstaged and single-station N2 (P=0.026 and P<0.0001, respectively). CONCLUSIONS: This trimodal therapy was effective and well tolerated, and it is an acceptable therapeutic option for patients with locally advanced stage IIIA-N2 NSCLC. Patients without persistent multiple-station N2 showed promising survival.