Surgery for pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma.

BACKGROUND: There has been little information on the actual diagnosis of pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma (TCC) and short- and long- outcomes of pulmonary resection for these patients. METHODS: In the present study, the data of 37 consecutive patients with a history of TCC who underwent pulmonary resection for solitary pulmonary lesions were reviewed, and the clinical factors and short- and long-term outcomes were analyzed. RESULTS: The study population included 35 male patients, and 2 female patients. The mean age was 72.5 years. Twenty patients (80%) were smokers and showed a high incidence of chronic obstructive pulmonary disease. Pulmonary lesions and primary TCC were detected simultaneously in 5 patients and metachronously in 32 patients. The median interval between treatment for primary TCC and the detection of pulmonary lesion was 43 months. The mean tumor diameter was 23 mm. The types of resection included lobectomy (n = 19), segmentectomy (n = 8), and partial resection (n = 10). Twelve of 37 patients (32%) developed postoperative complications. The pathological diagnoses included primary lung cancer (n = 28), pulmonary metastasis from TCC (n = 7), and others (n = 2). The 5-year overall survival rate for all patients was 72%. The 5-year overall survival rate of patients with primary lung cancer was 74%, while that of patients with pulmonary metastasis from TCC was 57%. CONCLUSIONS: Surgery can be proactively considered for treating pulmonary lesions in patients with a previous history of TCC, as it provides favorable long-term outcomes.

Integrated cardiothoracic team approach for complex lung transplantation procedures in Japan-current status and future direction.

The first lung transplant procedure in the world was performed in 1983, while in Japan that was first accomplished in 1998. Over the following 25 years, lung transplantation has become a viable treatment option for Japanese patients with a variety of end-stage lung diseases. Seventy cadaveric-donor lung (41 single, 29 bilateral), 11 bilateral living-donor lobar lung, and three heart-lung transplants have been performed with use of an integrated cardiothoracic team approach at medical facilities associated with Osaka University. Extremely advanced clinical and surgical skill sets are required to complete a lung transplant procedure, including surgical knowledge and techniques, as well as management of cardiovascular surgery, especially in regard to mechanical circulatory support (MCS), vascular anastomosis in difficult cases, and concomitant cardiac surgery. We have found that a collaborative effort by general thoracic and cardiac surgeons is an important key for success with lung transplantation. Complex lung transplant surgery and management in Japan are performed by use of an integrated cardiothoracic team approach, which has led to a synergistic impact on successful lung transplantation cases by capitalizing greatly on the experiences, techniques, and expertise of cardiac and thoracic experts. The present review is focused on the role of cardiac surgeons from the viewpoint of our experience with these cases.

[A Case of Advanced Gastric Cancer with Preoperative Liver Metastasis and Postoperative Adrenal Metastasis, That Obtained Long-Term Recurrence-Free Survival after Resection and Chemotherapy].

The case was a 70-year-old man of highly advanced gastric cancer with 2 liver metastases(S3, S8)and pancreatic invasion. Three courses of S-1 plus L-OHP(SOX therapy)were performed, and total gastrectomy and combined resection of the spleen and body and tail of the pancreas and partial resection of the liver S3 and S8 were performed after reduction of primary tumor and liver metastasis. S-1 therapy was continued for 1 year as postoperative adjuvant chemotherapy. Left adrenal metastasis was detected by CT, 1 year and 6 months after the operation. PET-CT revealed no other areas suspected of recurrence, so left adrenalectomy was performed through the retroperitoneal space. Radical resection was not achieved because adhesions and scarring from the previous surgery were severe. Paclitaxel plus Ramucirumab was started and after 10 courses, the disappearance of the tumor shadow was observed on enhanced CT, and PET-CT. Three years and 3 months after the initial surgery and 1 year and 8 months after resection of adrenal metastasis, the patient is alive without recurrence.

Utility of the surgical Apgar score for predicting the short- and long-term outcomes in non-small-cell lung cancer patients who undergo surgery.

OBJECTIVES: The surgical Apgar score (SAS) is a simple score that predicts postoperative complications based on 3 intraoperative valuables. The present study evaluated the association between the SAS and postoperative outcomes in non-small-cell lung cancer patients who underwent surgery. METHODS: A total of 585 patients who underwent lung resection were enrolled in the present study. We calculated the SAS of each patient and investigated its influence on the short- and long-term outcomes. RESULTS: Postoperative complications of any grade were detected in 164 cases (28%). The morbidity rate increased with decreasing SAS. When all the patients were divided into 2 groups (SAS <7 vs ≥7), postoperative complications were observed more frequently in the SAS <7 group than in the SAS ≥7 group (41% vs 25%, P < 0.001). In the multivariate analysis, the SAS was an independent risk factor for postoperative complications (odds ratio: 1.64 [1.03-2.61], P = 0.036). In terms of long-term outcomes, the 5-year disease-free survival (54.1% vs 73.2%, P < 0.001) and overall survival (73.8% vs 83.0%, P = 0.031) were significantly worse in the SAS <7 group than in the SAS ≥7 group. In a multivariate analysis, however, the SAS was not found to be an independent prognostic factor for either disease-free survival (hazard ratio: 1.39 [0.97-2.00], P = 0.075) or overall survival (hazard ratio: 0.90 [0.57-1.42], P = 0.642). CONCLUSIONS: The SAS reflected preoperative and intraoperative characteristics and was able to stratify the morbidity rate, suggesting it to be a useful predictor of short-term outcomes in non-small-cell lung cancer patients who undergo surgery.

Usefulness of positron-emission tomography for predicting the World Health Organization grade of thymic epithelial tumors.

BACKGROUND: It is often difficult to distinguish between thymoma and thymic carcinoma by preoperative radiological tests. While there have been some reports that the maximum standardized uptake value (SUVmax ) in positron emission tomography-computed tomography (PET-CT) is useful to this end, no large-scale analysis has been performed. We therefore analyzed the usefulness of the SUVmax and tumor size (TS) for differentiating thymic epithelial tumors. METHODS: From 2011 to 2019, 129 patients with thymic epithelial tumor who underwent PET-CT before surgical treatment were enrolled. The relevance of the SUVmax to the World Health Organization (WHO) histological type was assessed. To reduce the impact of the TS, the ratio of the SUVmax to the TS was also investigated. RESULTS: A total of 99 thymoma cases and 30 thymic carcinoma cases were enrolled into the study. The SUVmax and SUVmax /TS of thymic carcinoma were significantly higher than those of thymoma (SUVmax : 7.7 ± 3.4 vs. 3.3 ± 1.3, p < 0.01; SUVmax /TS: 1.5 ± 0.7 vs. 0.6 ± 0.4, p < 0.01). Focusing on the patients with a moderate SUVmax of ≤5 (84 thymoma and 4 thymic carcinoma), the SUVmax /TS values of thymic carcinoma were still significantly higher than those of thymoma (1.6 ± 0.8 vs. 0.6 ± 0.4, p < 0.01). CONCLUSIONS: PET-CT might provide significant information for differentiating images of thymoma and thymic carcinoma. We experienced several cases of thymic carcinoma with a moderate SUVmax of ≤5, and SUVmax /TS was considered a useful parameter for differentiating such cases.

Prognostic Impact of Number of Organ Invasions in Patients with Surgically Resected Thymoma.

PURPOSE: This study aimed to explore the clinical implications and prognostic value of the number of organ/structure invasions (NOI) in patients with thymoma after curative surgical resection. METHODS: We retrospectively analyzed 306 consecutive Japanese patients with thymoma who underwent curative surgical resection. Tumor invasions of pericardium, mediastinal pleura, phrenic nerve, lung, and venous structures were examined histopathologically. Cases were classified into four subgroups according to NOI: group 0, no tumor invasion; group 1, tumor invasion into single organ/structure; group 2, tumor invasion of two organs/structures; group 3, invasion of three or more organs/structures. Associations with NOI and several clinical characteristics and their prognostic significance were analyzed. RESULTS: Pleural invasion was found in 100 cases (32.7%), lung invasion in 48 cases (15.7%), pericardial invasion in 46 cases (15%), phrenic nerve invasion in 29 (9.5%), and venous invasion in 22 cases (7.2%). NOI was classed as group 0 in 201 cases (65.0%), group 1 in 42 cases (13.7%), group 2 in 20 cases (6.5%), and group 3 in 43 cases (14.1%). Cases with higher NOI showed significantly worse relapse-free survival (RFS) and overall survival (OS). Cox's proportional hazard model analysis also identified NOI as a prognostic factor affecting RFS and OS. CONCLUSIONS: Cases with higher NOI of thymoma after radical surgical resection showed significantly worse recurrence rates and survival.

[Surveillance Bronchoscopy after Lung Transplantation].

Acute cellular rejection( ACR) is one of the major complications of the acute phase after lung transplantation. In addition, ACR is considered to be a major cause of chronic lung allograft dysfunction (CLAD). Therefore, the diagnosis and treatment for ACR are major issues at transplantation facilities. Surveillance bronchoscopy( SB) is performed at many institutions as the golden standard for ACR diagnosis, and our hospital also implements long-term post-transplant monitoring of ACR as a preventive measure for CLAD. However, the suitability of SB may be questioned due to the risk of complications such as bleeding and pneumothorax. Here, we would like to report the results of SB in our department and discuss future diagnosis and treatment policy for ACR.

Prognostic impact of tumor volume in patients with complete resection of thymoma.

BACKGROUND: The impact of tumor volume on prognosis is unclear. We therefore investigated the correlation between tumor volume and prognosis in patients with complete resection of thymoma. METHODS: A total of 177 patients who underwent curative surgical resection for thymoma were retrospectively collected and reviewed. We performed a volumetric analysis of each case using the modified version of "Watchin GGO" and evaluated the relationship between tumor volume and recurrence. RESULTS: The median tumor size was 5.0 (range 0.5-15) cm, and the median tumor volume was 35.1 (range 0.265-881.0) cm3 . The Pearson product-moment correlation coefficient was 0.658, suggesting a moderately strong connection between tumor volume and tumor size. To determine the impact of tumor volume on tumor recurrence, receiver operating characteristic curves of the recurrence and tumor volume were calculated. The area under the curve was 0.65 (95% confidence interval [CI]: 0.51-0.80), and the optimal cutoff level of the tumor volume for recurrence was 82.6 cm3 , with a sensitivity and specificity of 0.64 (11/17) and 0.74 (119/160), respectively. Patients with tumors ≥82.6 cm3 had a significantly worse recurrence-free survival than those with smaller tumors (p = 0.0122, hazard ratio: 2.99), with 5-year recurrence rates of 74.9% (95% CI: 58.6%-86.3%) versus 88.9% (95% CI: 79.0%-94.4%). CONCLUSION: The volume of completely resectable thymoma may be a useful prognostic indicator.

Thymic Lymphoepithelial Carcinoma Associated with Epstein-Barr Virus: Experiences and Literature Review.

Thymic lymphoepithelial carcinoma (TLEC) is a primary thymic carcinoma that accounts for about 14% of all thymic epithelial tumors and is classified into 14 types. The histological morphology is similar to lymphoepithelioma, a type of undifferentiated nasopharyngeal carcinoma. It has been reported that squamous carcinoma accounts for approximately 80% of thymic carcinoma, followed by TLEC, which accounts for 6%. TLEC has been reported to be associated with Epstein-Barr virus (EBV), with EBV infection in TLEC tumor cells first noted by Lyvraz et al. in 1985. Tumors shown to be EBV-positive are classified as TLEC if lymphoplasmacytic infiltration is lacking. However, only about 50% of the cases are positive for EBV, which is lower compared to nasopharyngeal lymphoepithelioma. Instances of EBV infection in other types of thymic epithelial tumor have been reported at lower rates, which suggests that EBV infection may have an important influence on the carcinogenesis of TLEC, though the etiology is unknown. TLEC is a highly malignant tumor with poor prognosis, as affected patients have a median survival time of 22 months, according to 58 cases from the literature, while the 5-year survival rate is 34.4%. Presently, prognosis is not considered to be affected by the presence or absence of EBV positivity.

Periostin secreted by activated fibroblasts in idiopathic pulmonary fibrosis promotes tumorigenesis of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) patients with idiopathic pulmonary fibrosis (IPF) show poor prognosis. Periostin is an extracellular matrix protein highly expressed in the lung tissues of IPF. This study aimed to investigate the possibility that periostin secreted by fibroblasts derived from IPF lung might affect proliferation of NSCLC cells. Periostin was more highly expressed and secreted by fibroblasts from diseased human lung with IPF (DIPF) than by normal human lung fibroblasts (NHLF). Cocultivation of NSCLC cells with conditioned media (CM) from DIPF increased proliferation of NSCLC cells through pErk signaling, with this proliferation attenuated by periostin-neutralizing antibodies. Knockdown of integrin ß3, a subunit of the periostin receptor, in NSCLC cells suppressed proliferation of NSCLC cells promoted by recombinant human periostin and CM of DIPF. On in vivo examination, DIPF promoted tumor progression more than NHLF, and knockdown of integrin ß3 in NSCLC cells suppressed tumor progression promoted by DIPF. Fibroblasts derived from surgical specimens from IPF patients also increased secretion of periostin compared to those from non-IPF patients. Periostin secreted from IPF-activated fibroblasts plays critical roles in the proliferation of NSCLC cells. The present study provides a solid basis for considering periostin-targeted therapy for NSCLC patients with IPF.

Preoperative evaluation and indications for pulmonary metastasectomy.

Pulmonary metastasectomy (PM) is an established treatment that can provide improved long-term survival for patients with metastatic tumor(s) in the lung. In the current era, where treatment options other than PM such as stereotactic body radiation therapy (SBRT), immunotherapy, and molecular-targeted therapy are available, thoracic surgeons should review the approach to the preoperative evaluation and the indications. Preoperative evaluation consists of history and physical examinations, physiological tests, and radiological examinations. Radiological examinations serve to identify the differential diagnosis of the pulmonary nodules, evaluate their precise number, location, and features, and search for extra thoracic metastases. The indication of PM should be considered from both physiological and oncological points of view. The general criteria for PM are as follows; (I) the patient has a good general condition, (II) the primary malignancy is controlled, (III) there is no other extrapulmonary metastases, and (IV) the pulmonary lesion(s) are thought to be completely resectable. In addition to the general eligibility criteria of PM, prognostic factors of each tumor type should be considered when deciding the indication for PM. When patients have multiple poor prognostic factors and/or a short disease-free interval (DFI), thoracic surgeons should not hesitate to observe the patient for a certain period before deciding on the indication for PM. A multidisciplinary discussion is needed in order to decide the indication for PM.

Current status of inhaled nitric oxide therapy for lung transplantation in Japan: a nationwide survey.

OBJECTIVES: Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation. METHODS: Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan. RESULTS: During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged < 18 years. CONCLUSIONS: Inhaled NO therapy was performed in almost all patients who underwent lung transplantation in Japan and showed reasonable efficacy. Therefore, public health insurance coverage for inhaled NO therapy during lung transplantation is recommended.

Hepatocyte growth factor ameliorates methylglyoxal-induced peritoneal inflammation and fibrosis in mouse model.

BACKGROUND: Peritoneal dialysis (PD) is essential for patients with end-stage renal disease. Peritoneal fibrosis (PF) is a complex inflammatory, fibrogenic process. No effective treatments are available to prevent these processes. Hepatocyte growth factor (HGF) possesses anti-inflammatory and anti-fibrotic properties. The aim of this study was to analyze whether HGF suppresses MGO-induced peritoneal inflammation and fibrosis in a mouse model. METHODS: PF was induced by intraperitoneal (IP) injections of MGO for 14 days. C57/BL/6 mice were divided into three groups: Sham group (only vehicle); Sham + MGO group (PF induced by MGO); and HGF + MGO group (PF mice treated with recombinant human-HGF). PF was assessed from tissue samples by Masson's trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry and quantitative real-time PCR. RESULTS: MGO-injected mice showed significant thickening of the submesothelial compact zone with PF. Treatment with HGF significantly reduced PM thickness and suppressed the expression of collagen I and III and α-SMA. Expression of profibrotic and proinflammatory cytokines (TGF-ß, TNF-α, IL-1ß) was reduced by HGF treatment. The number of macrophages, and M1 and M2 macrophage-related markers, such as CD86, CD206, and CD163, was reduced in HGF + MGO mice. CONCLUSION: HGF attenuates MGO-induced PF in mice. Furthermore, HGF treatment reduces myofibroblast and macrophage infiltration, and attenuates the upregulated expression of proinflammatory and profibrotic genes in peritoneal tissues. HGF might be an effective approach to prevent the development of PF in patients undergoing PD.

Risk factors for non-cancer death after surgery in patients with stage I non-small-cell lung cancer.

OBJECTIVES: With improvements in the outcome of treatment for non-small-cell lung cancer (NSCLC), other diseases may account for a high death rate after surgery in patients with stage I NSCLC. In the present study, we analysed the associations between the clinical factors and non-cancer death after surgery in these patients. METHODS: The records of 514 patients with stage I NSCLC who underwent surgery were retrospectively reviewed; a proportional hazards model for the subdistribution of a competing risk was conducted to define the risk factors for non-cancer death. RESULTS: The mean patient age was 67 years. A total of 367 patients (71%) underwent bilobectomy or lobectomy while 147 (29%) underwent sublobar resection. The pathological stage was IA in 386 (75%) and IB in 128 (25%) patients. Three patients (0.6%) died within 90 days after surgery, and 108 (21%) experienced postoperative complications. Until the time of writing this report, 83 patients had died during the follow-up. The cause of death was primary lung cancer in 38 (46%) patients and other diseases in 45 (54%) patients, including non-cancer causes in 29 patients, such as pneumonia, cardiac death and cerebral stroke. According to a multivariable competing risk analysis for non-cancer death age (≥70 years), sex (male), body mass index (BMI <18.5), postoperative complications and % forced expiratory volume in 1 s (<80) were identified as risk factors for postoperative non-cancer death. CONCLUSIONS: Advanced age (≥70 years), male sex, low BMI (<18.5), postoperative complications and low preoperative % forced expiratory volume in 1 s (<80) were found to be the risk factors for postoperative non-cancer death after surgery in patients with stage I NSCLC.

Importance of the preoperative prognostic nutritional index score as a predictor of chronic lung allograft dysfunction after lung transplantation: a Japanese single-institution study.

PURPOSES: Numerous indicators have been discussed as predictive markers for the incidence of chronic allograft dysfunction (CLAD) after lung transplantation (LTX). The aim of this study was to evaluate whether or not the preoperative prognostic nutrition index (PNI) correlated with the development of CLAD. METHOD: This study is a single-center and retrospective cohort study. Forty-six patients underwent cadaveric lung transplantation between 2000 and 2016 at our institution. The primary endpoint of this study was the CLAD-free survival of the patients. RESULT: CLAD was diagnosed in 11 patients (23%) during the follow-up period. Potential risk factors included recipient factors, donor factors, number of HLA mismatches, operation-related factors, and preoperative blood test results, including the preoperative PNI. The patients with a higher PNI showed a longer CLAD-free survival after LTX than those with lower values according to univariate and multivariate analyses (p = 0.01, 0.04, respectively). The 5-year CLAD-free survival rates in the higher-PNI patients and lower-PNI patients were 94% and 62%, respectively. CONCLUSION: We found that a lower preoperative PNI of the recipient was significantly associated with a higher incidence rate of CLAD. The preoperative PNI may, therefore, be useful as a predictor of the development of CLAD.

Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis.

PURPOSE: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). METHODS: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. RESULTS: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P < 0.01). However, Kaplan-Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m2 vs. 1 year post-transplant, 15.6 ± 2.5 kg/m2; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01). CONCLUSIONS: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

A case of latent heterozygous Fabry disease in a female living kidney donor candidate.

A 52-year-old woman had been found to have hematuria at her annual checkup 5 years in a row. She hoped to donate her kidney to her husband, so we performed a percutaneous kidney biopsy at our department. It was difficult for us to detect apparent abnormalities under a light microscopic examination, and she was determined to meet the eligibility criteria for living kidney transplantation. However, the sample for electron microscopy was not evaluated before kidney donation. She subsequently underwent living kidney transplantation as a donor. A 1-h biopsy revealed swelling and obvious vacuolation of the glomerular podocytes, which were characteristic of Fabry disease. Her medical history and examinations were reviewed. No findings or episodes were observed. Pre-donation electronmicroscopy revealed numerous zebra bodies in the podocytes. A definite diagnosis of heterozygous Fabry disease was made based on the GLA gene mutation despite the normal range of leukocyte α-Gal A activity. Based on the pathological deposition of GL-3, chaperone therapy was initiated to suppress the progression of organ damage. In this case, we could not confirm a diagnosis of Fabry disease despite performing a renal biopsy prior to kidney donation. Kidney donor candidates may sometimes have factors that cannot be assumed based on medical or family history. Thus, it is important to perform a renal biopsy before kidney donation when necessary, and to always conduct a detailed evaluation including electron microscopy.

Surgical management of thymic epithelial tumors.

Resection is the mainstay of treatment for thymic epithelial tumors (TETs), with complete removal of the tumor and involved organs being the ultimate aim. The choice of surgical approach plays a major role in defining treatment success, and the optimal choice of method should thus provide an adequate surgical view to achieve complete tumor resection. While median sternotomy is considered the gold standard for access to the mediastinum, several minimally invasive approaches to thymectomy have been described, including video-assisted robotic-assisted thymectomy, although the oncological outcomes of that procedure remain unclear. A multimodal approach incorporating chemotherapy or chemoradiotherapy followed by extended surgery may improve resectability and outcomes for patients with advanced TETs. Surgical debulking is also reportedly acceptable for invasive thymoma because of its potential for achieving favorable outcomes. Re-resection is an acceptable option for patients with recurrent thymoma after initial resection, and repeat resection for recurrent pleural dissemination seems effective. Here, the literature on current clinical practices in the surgical management and treatment of TETs is reviewed.

Usefulness of a preoperative inflammatory marker as a predictor of asymptomatic acute rejection after lung transplantation: a Japanese single-institution study.

BACKGROUND: Surveillance bronchoscopy (SB) is performed as routine follow-up after lung transplantation (LTx), primarily for the early detection of clinically asymptomatic acute rejection (AR). To identify appropriate candidates for SB over a long period, we explored risk factors of asymptomatic AR after LTx. METHOD: This study is a single-center and retrospective cohort study. Forty-five patients underwent cadaveric LTx between 2000 and 2016 in our institution. All enrolled patients had at least three months of follow-up. SB is scheduled at 1, 2, 3, 6, and 12 months after LTx routinely and annually thereafter until 5 years after LTx. A histological assessment for AR was performed according to the International Society for Heart and Lung Transplantation (ISHLT) criteria. The analysis of potential risk factors for AR was performed using a chi-square test and logistic regression analysis. RESULTS: The median period of follow-up after LTx for the entire cohort was 64 months. Asymptomatic AR (grade A1-A3) was detected in 22 patients, 14 of whom showed severe AR (worse than grade A2). The percentage of patients with AR was 5-24% at each time point, and 15% of patients still showed severe AR (A2 and A3) at 24 months after LTx. Potential risk factors included recipient factors (diagnosis, age, gender, BMI), donor factors (age, gender, smoking history, cause of brain death), HLA mismatch, operation-related factors, neutrophil-to-leucocyte ratio (NLR), platelet-to-leucocyte ratio (PLR), and other scores. Patients with a higher NLR showed a higher incidence of AR after LTx than others during follow-up (P=0.01). CONCLUSIONS: An increased perioperative NLR was significantly associated with a higher odds ratio of AR during follow-up. Patients with a high NLR seem to be good candidates for long-term SB.