Predicting pathological highly invasive lung cancer from preoperative [18F]FDG PET/CT with multiple machine learning models.

PURPOSE: The efficacy of sublobar resection of primary lung cancer have been proven in recent years. However, sublobar resection for highly invasive lung cancer increases local recurrence. We developed and validated multiple machine learning models predicting pathological invasiveness of lung cancer based on preoperative [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) radiomic features. METHODS: Overall, 873 patients who underwent lobectomy or segmentectomy for primary lung cancer were enrolled. Radiomics features were extracted from preoperative PET/CT images with the PyRadiomics package. Seven machine learning models and an ensemble of all models (ENS) were evaluated after 100 iterations. In addition, the probability of highly invasive lung cancer was calculated in a nested cross-validation to assess the calibration plot and clinical usefulness and to compare to consolidation tumour ratio (CTR) on CT images, one of the generally used diagnostic criteria. RESULTS: In the training set, when PET and CT features were combined, all models achieved an area under the curve (AUC) of ≥ 0.880. In the test set, ENS showed the highest mean AUC of 0.880 and smallest standard deviation of 0.0165, and when the cutoff was 0.5, accuracy of 0.804, F1 of 0.851, precision of 0.821, and recall of 0.885. In the nested cross-validation, the AUC of 0.882 (95% CI: 0.860-0.905) showed a high discriminative ability, and the calibration plot indicated consistency with a Brier score of 0.131. A decision curve analysis showed that the ENS was valid with a threshold probability ranging from 3 to 98%. Accuracy showed an improvement of more than 8% over the CTR. CONCLUSION: The machine learning model based on preoperative [18F]FDG PET/CT images was able to predict pathological highly invasive lung cancer with high discriminative ability and stability. The calibration plot showed good consistency, suggesting its usefulness in quantitative risk assessment.

Thrombus formation at the stump of the pulmonary vein after lobectomy: a prospective multi-institutional study.

PURPOSE: Recent reports suggest that postoperative cerebral infarction following lung cancer surgery is caused by thrombus formation at the stump of the pulmonary vein and that the risk is highest after left upper lobectomy (LUL). Thrombosis at the stump of the pulmonary vein and the incidence of cerebral infarction was investigated prospectively in patients who underwent lobectomy for lung cancer. METHODS: Lung cancer patients undergoing planned pulmonary lobectomy were enrolled. The endpoint was to confirm if there is a higher incidence of thrombus formation (primary) and a higher incidence of cerebral infarction (secondary) in patients undergoing LUL. We planned to accrue 600 patients. An interim analysis was scheduled for just after the data center received the final clinical review form of the 300th patient. RESULTS: The interim analysis revealed a significant difference in the primary endpoint. In the final analysis, thrombus was identified in 16 of 88 LUL patients (20.5%), and in 4 of 247 patients who underwent other types of lobectomy (1.6%) (p < 0.05). Cerebral infarction was identified in 1 of the LUL patients (1.3%) and in 9 of the other patients (3.6%) (p = 0.318). CONCLUSIONS: Thrombus frequently forms at the stump of the left superior pulmonary vein after LUL. However, our study did not identify a relationship between thrombosis and cerebral infarction.

[The Basic Research of Antigen-antibody Reaction in Lung Transplantation].

Lung transplantation has become popular in Japan, showing better survival rate than other countries. However, the results are still not satisfactory compared with other solid organ transplantation. One of the reasons for this might be that knowledge on donor-specific antibodies or antibody-related rejection, which has been attracting attention these days, is less than that of kidney or liver transplantation. Our laboratory has continued basic research in this field using rodent lung transplantation model. We have previously shown that type V collagen is associated in chronic rejection as an autoimmune, and that oral administration of type V collagen induces tolerance. The murine chronic rejection model of the minor antigen mismatch was developed, and involvement of the humoral immunity and role of the complement activation were shown. We are now studying the effects of immune checkpoint molecules, which play a central role in the field of cancer therapy, on rejection after lung transplantation. We are also working to verify the effects of anti-complement drugs and molecular targeted drugs in the future treatment on rejection.

Genetic alterations in squamous cell lung cancer associated with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are at higher risk of developing lung cancers including squamous cell lung carcinoma (SCC), which typically carries a poor prognosis. Although the molecular basis of cancer development subsequent to IPF has not been fully investigated, we recently reported two epigenetic phenotypes characterized by frequent and infrequent DNA hypermethylation in SCC, and an association of the infrequent hypermethylation phenotype with IPF-associated SCCs. Here, we conducted targeted exon sequencing in SCCs with and without IPF using the Human Lung Cancer Panel to investigate the genetic basis of IPF-associated SCC. SCCs with and without IPF displayed comparable numbers of total mutations (137 ± 22 vs 131 ± 27, P = .5), nonsynonymous mutations (72 ± 14 vs 69 ± 16, P = .5), indels (3.0 ± 3.5 vs 3.0 ± 3.9, P = 1) and synonymous mutations (62 ± 9.1 vs 60 ± 12, P = .5). Signature 1 was the predominant signature in SCCs with and without IPF. SETD2 and NFE2L2 mutations were significantly associated with IPF (44% vs 13%, P = .03 for SETD2; 38% vs 10%, P = .04 for NFE2L2). MYC amplification, assessed by copy number variant analysis, was also significantly associated with IPF (18.8% vs 0%, P = .04). Mutations in TP53 and CDKN2A were observed relatively frequently in SCCs with frequent hypermethylation (P = .02 for TP53 and P = .06 for CDKN2A). Survival analysis revealed that the SETD2 mutation was significantly associated with worse prognosis (P = .04). Collectively, we found frequent involvement of SETD2 and NFE2L2 mutations and MYC amplification in SCCs with IPF, and an association of a SETD2 mutation with poorer prognosis.

[Surgical Treatment of Metachronous Second Primary Lung Cancer].

Although the incidence of metachronous second primary lung cancer (MSPLC) after curative resection for primary lung cancer may be increasing, appropriate treatment and the outcome are unclear yet. We reviewed the literature and conducted a retrospective chart review of the patients who underwent surgery for MSPLC in our institute. We had 27 surgical cases for MSPLC during 2017 and 2018. The interval from the previous surgery was 59.4±35.2 months. Comparing to the patients who were underwent surgery for first primary lung cancer in the same period, the patients with MSPLC showed significantly older age and lower respiratory function. More than 90% of resected MSPLC were stage 0 orⅠand we selected limited surgery for more than 90% of the MSPLC patients. Maybe due to limited surgery, time for surgical procedure and postoperative complication were significantly less than first primary lung cancer cases. No death or recurrence were observed until one year after surgery for MSPLC. For performing feasible limited surgery to early-stage MSPLC cases, continuous computed tomography surveillance in the late phase after the first primary lung cancer surgery should be important.

A phase I study of loco-regional immunotherapy by transbronchial injection of α-galactosylceramide-pulsed antigen presenting cells in patients with lung cancer.

We conducted a phase I study of the trans-bronchial injection of α-galactosylceramide (αGalCer)-pulsed antigen presenting cells (APCs) to evaluate their safety, immune responses, and anti-tumor activities. Patients with advanced or recurrent non-small cell lung cancer (NSCLC) refractory to standard treatments were eligible. αGalCer-pulsed APCs were administered intratumorally or intranodally by bronchoscopy. Twenty-one patients were enrolled in this study. No severe adverse events related to the cell therapy were observed during this study in any patient. After αGalCer-pulsed APCs were administrated, increased iNKT cell numbers were observed in PBMCs from eight cases, and IFN-γ producing cells were increased in the peripheral blood of 10 cases. Regarding clinical responses, one case exhibited a partial response and eight were classified as stable disease. In the tumor microenvironment, IFN-γ expression was upregulated after treatment in partial response or stable disease cases and TGF-ß was upregulated in progressive disease cases.

Molecular Nodal Staging Using miRNA Expression in Lung Cancer Patients by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

BACKGROUND: The limited negative predictive value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has often been discussed. OBJECTIVE: The aim of this study was to identify a highly sensitive molecular biomarker for lymph node staging by EBUS-TBNA. METHODS: Five microRNAs (miRNAs) (miR-200a, miR-200b, miR-200c, miR-141, and let-7e) were selected as biomarker candidates for the detection of nodal metastasis in a miRNA expression analysis. After having established a cutoff level of expression for each marker to differentiate malignant from benign lymph nodes among surgically dissected lymph nodes, the cutoff level was applied to snap-frozen EBUS-TBNA samples. Archived formalin-fixed paraffin- embedded (FFPE) samples rebiopsied by EBUS-TBNA after induction chemoradiotherapy were also analyzed. RESULTS: The expression of all candidate miRNAs was significantly higher in metastatic lymph nodes than in benign ones (p < 0.05) among the surgical samples. miR-200c showed the highest diagnostic yield, with a sensitivity of 95.4% and a specificity of 100%. When the cutoff value for miR-200c was applied to the snap-frozen EBUS-TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.4, 81.8, 95.0, 90.0, and 94.0%, respectively. For restaging FFPE EBUS- TBNA samples, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 60.0, 80.0, 100, and 84.6%, respectively. Among the restaged samples, 4 malignant lymph nodes were false negative by EBUS-TBNA, but they were accurately identified by miR-200c. CONCLUSIONS: miR-200c can be used as a highly sensitive molecular staging biomarker that will enhance nodal staging of lung cancer.

Concordant pattern of radiologic, morphologic, and genomic changes during compensatory lung growth.

BACKGROUND: Although compensatory lung growth (CLG) after lung resection has been reported in various mammalian species, it has generally been thought that the lung cannot regenerate in adult humans. We recently developed a method for evaluating lung weight using a radiologic analysis and demonstrated that the lung was heavier than expected in adult humans after pulmonary resection. In this study, we serially evaluated the morphologic, radiologic, and genomic status during CLG in pneumonectomized mice. METHODS: The serial changes in morphology and gene expression of the remnant right lung after left pneumonectomy were examined in adult male mice. The alveolar density was determined by the mean linear intercept, and the weight was estimated using the Hounsfield value and volumetric data from micro-computed tomography. The parameters were obtained on days 3, 7, and 30 after left pneumonectomy or thoracotomy only (sham control). RESULTS: After left pneumonectomy, the right lung became significantly progressively larger in volume and weight on postoperative days 3, 7, and 30 in comparison to the sham controls (P < 0.01). The estimated weight also significantly increased in association with the real volume on postoperative days 3, 7, and 30 (P < 0.01). The cardiac lobe markedly increased in size. During the observation period, the alveolar density was always lower in the pneumonectomized mice than in controls. A microarray analysis revealed that multiple genes related to proliferation (but not specific alveolar development) were initially upregulated until postoperative day 7 and then returned to normal after 1 mo. The morphologic and genomic changes were more evident in the cardiac lobe than in the upper lobe during the observation period. CONCLUSIONS: The morphologic, radiologic, and genomic changes during CLG were related to each other in pneumonectomized mice. The present study revealed an association between the radiologically estimated weight and other parameters, indicating a marked CLG reaction of the cardiac lobe.

Mini grasping basket forceps for endobronchial foreign body removal in pediatric patients.

BACKGROUND: Appropriate device selection is crucial for endobronchial foreign body removal using a bronchoscope. In pediatric patients, bronchoscopy requires the use of a thin device due to the narrow access to the airway, limiting the range of useful endobronchial devices. We herein review our experience in endobronchial foreign body removal with a focus on the type of bronchoscope and the instruments used in comparison with the literature, and investigate the utility of mini grasping basket forceps (FG-55D, Olympus® ; and Zero Tip™ , Airway Retrieval Basket, Boston Scientific). METHODS: Between April 2008 and April 2016, foreign bodies were removed from the airway of 12 pediatric patients by bronchoscopy. These cases are reviewed in this study. The clinical presentation, location and characteristics of the foreign bodies, and the type of bronchoscope and instruments used were analyzed. RESULTS: A consecutive series of 12 pediatric patients was retrospectively reviewed, and the therapeutic characteristics investigated. Nuts were the most frequently observed foreign body. Seven of the 12 pediatric patients required an ultrathin bronchoscope (diameter, 2.8 mm) for foreign body removal. Only one patient required a rigid scope in addition to flexible bronchoscopy. The most frequently used instrument was a mini grasping basket forceps (n = 7; 58%), which was used with a 1.2 mm instrument channel (n = 4; 33%). CONCLUSIONS: The use of a mini grasping basket forceps in combination with an ultrathin flexible bronchoscope was useful for removing smooth, soft materials such as a nuts or beans in pediatric cases.

Does segmentectomy really preserve the pulmonary function better than lobectomy for patients with early-stage lung cancer?

PURPOSE: Recently, segmentectomy has been considered as an alternative to lobectomy in early peripheral non-small lung cancer (NSCLC); however, controversy has remained regarding the long-term functional advantage after segmentectomy. The aim of this study was to analyze the postoperative lung function after segmentectomy and lobectomy for non-small cell lung cancer. METHODS: Patients with p-T1aN0M0 NSCLC who had undergone segmentectomy (n = 37) or lobectomy (n = 33) were retrospectively analyzed. The ratios of postoperative to preoperative forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were defined as the recovery rates. The radiological lung volume and weight were evaluated before and more than 6 months after surgery, and the postoperative values were compared with the predicted values that were calculated from the preoperative values, subtracting the resected lobes or segments. RESULTS: The clinical characteristics, including the preoperative lung function showed no significant differences between the groups. No statistical differences were recognized in the trend lines for recovery ratios of FVC and FEV1.0 (P = 0.96 and P = 0.33). The recovery ratios for radiologic lung volume and weight showed no significant differences (P = 0.46 and P = 0.22). The postoperative lung volume and weight were almost the same as the predicted values after segmentectomy, whereas those after lobectomy were significantly higher than the predicted values. CONCLUSIONS: No functional advantage for segmentectomy was observed during long-term follow-up, possibly due to compensatory lung growth after lobectomy.

A phase II trial evaluating the efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection: West Japan Oncology Group 6711 L (PEOPLE Study).

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. Pirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer. METHODS: Pirfenidone was orally administered to IPF patients who were candidates for lung cancer surgery; pirfenidone was dosed at 600 mg/day for the first 2 weeks, followed by 1200 mg/day. Surgery was performed after at least 2 weeks of 1200-mg/day administration. The primary endpoint was non-AE-IPF rate during postoperative days 0-30, compared to the null value of 80 %, and the secondary endpoint was safety. Radiologic and pathologic diagnoses of IPF and AE-IPF were confirmed by an independent review committee. RESULTS: From June 2012 to January 2014, 43 cases were enrolled, and 39 were eligible (full analysis set [FAS]). Both pirfenidone treatment and surgery were performed in 36 patients (per protocol set [PPS]). AE-IPF did not occur in 37/39 patients (94.9 % [95 % confidential interval: 82.7-99.4 %, p = 0.01]) in the FAS, and in 38/39 patients (97.2 % [95 % confidential interval: 85.5-99.9 %, p = 0.004] in the PPS. A grade 5 adverse event (death) occurred in 1 patient, after AE-IPF; no other grade 3-5 adverse events were observed. CONCLUSIONS: Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients. TRIAL REGISTRATION: This clinical trial was registered with the University Hospital Medical Information Network (UMIN) on April 16th, 2012 (REGISTRATION NUMBER: UMIN000007774 ).

Evolution of a Lung-Sparing Strategy with Sleeve Lobectomy and Induction Therapy for Non-small Cell Lung Cancer: 20-Year Experience at a Single Institution.

BACKGROUND: To elucidate the evolution of a lung-sparing strategy with sleeve lobectomy (SL) and induction therapy for non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 205 patients with NSCLC who underwent pneumonectomy (PN, n = 54) or SL (n = 151) from 1994 to 2013. The study period was divided into four 5-year periods, and surgical trends were analyzed, focusing on the PN:SL ratio. RESULTS: PN was associated with a significantly advanced pathological stage, a larger tumor size and less pulmonary function compared with SL. The PN group had higher 30-day (3.7 vs. 0 %, p = 0.018) and 90-day (13.0 vs. 1.3 %, p = 0.0003) mortality than the SL group. The overall 5-year survival rate was significantly higher with SL (71.5 %) versus PN (42.8 %, p = 0.011) for patients with pN0-1. The ratio of PN among total surgeries decreased significantly over the four periods (1994-1998, 1999-2003, 2004-2008, and 2009-2013) from 5.63 % to 3.17, 1.40, and 1.38 %, respectively (p < 0.0001); in contrast, the PN:SL ratio increased significantly from 1.64 to 2.50, 3.71, and 5.44, respectively (p = 0.041). During the last period, when we introduced induction therapy, 38 of 651 who received surgery underwent induction therapy. The PN:SL ratios of those who did and did not undergo induction therapy were 15 (PN: 1, SL: 15) and 4.25 (PN: 8, SL: 34), respectively. CONCLUSIONS: A lung-sparing strategy with SL for NSCLC can decrease the PN rate to less than 2 % with less mortality. Induction therapy may facilitate SL and increase the PN:SL ratio.

Risk factors predictive of atrial fibrillation after lung cancer surgery.

Postoperative atrial fibrillation (POAF), the most frequent arrhythmia after pulmonary resection, is a cause of both morbidity and mortality. Being able to predict the risk of POAF before surgery would help us evaluate the surgical risk and plan prophylaxis. We investigated the reported preoperative risk factors associated with the incidence of POAF and found that the recommended predictive factors were quite variable. Therefore, we evaluated the previously reported preoperative risk factors for POAF using our institutional data. We discuss our findings in this short review. Male gender, resected lung volume, brain natriuretic peptide (BNP), and left ventricular early transmitral velocity/mitral annular early diastolic velocity (E/e') calculated by echocardiography were suggested as independent predictors for POAF, but the predictive values of each individual parameter were not high. The lack of definitive predictors for POAF warrants further investigations by gathering the reported knowledge, to establish an effective preoperative examination strategy.

Is left upper lobectomy for lung cancer a risk factor for cerebral infarction?

PURPOSE: Cerebral infarction is a rare complication of lung resection that can result in severe sequelae. Our aim was to investigate the characteristics of patients who suffer from cerebral infarction after surgery for lung cancer. METHODS: We retrospectively reviewed all patients who underwent resection of at least a single lobe for lung cancer at our institution between January 2008 and October 2013. We compared the patients who presented with cerebral infarction with those patients who did not within 30 days of surgery. RESULTS: A total of 562 patients underwent surgery, with five males and one female subsequently experiencing cerebral infarction. Five patients underwent left upper lobectomy and one underwent left lower lobectomy. Patient age, sex, body mass index, smoking index, and operative time were not significantly different between the six patients with postoperative cerebral infarction and the other 556 patients; only the type of operative procedure was significantly different (p < 0.001). Contrast-enhanced computed tomography revealed thrombosis in the stump of the left superior pulmonary vein in patients with postoperative cerebral infarction. CONCLUSIONS: Cerebral infarction occurs at a high frequency in patients who undergo left upper lobectomy for lung cancer. Thrombosis in the left superior pulmonary-vein stump might cause cerebral infarction.

[The History and Development of Experimental Rodent Models of Chronic Lung Allograft Dysfunction after Lung Transplantation].

Chronic lung allograft dysfunction (CLAD) is a critical impediment to the long-term survival after lung transplantation. A rat orthotopic lung transplantation model was developed in the early 1970s, and using this model, our laboratory has shown that the immunopathogenesis of CLAD involves both allogeneic immunity and autoimmunity. However, further investigation of CLAD is limited by the scarcity of transgenic and knockout strains. The model most widely used to study CLAD, the mouse model of heterotopic tracheal transplantation, has some incomplete pathophysiologic features of CLAD, which limits the utility of this model. Unlike other solid organ transplants, vascularized and aerated murine lung transplantation has only recently been developed. We have also reported that minor, but not major, histocompatibility antigens mismatch induced the development of CLAD in murine orthotopic lung transplants and that CLAD development was interleukin-17-dependent. This mini-review underscores the history and development of rodent models of CLAD after lung transplant, including the findings from our previous studies. In addition, the future direction of rodent models is also discussed.

Elastography for Predicting and Localizing Nodal Metastases during Endobronchial Ultrasound.

BACKGROUND: Elastography is a relatively new technology that can generate images reflective of tissue stiffness (elasticity). Neoplastic tissue is usually stiffer than normal structures. OBJECTIVES: The aim of this study was to evaluate the feasibility and utility of elastography when combined with convex-probe endobronchial ultrasound (CP-EBUS) for predicting and localizing metastatic lymph nodes during endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA). METHODS: Consecutive results of endobronchial elastography of lymph nodes performed using EBUS- TBNA were prospectively collected and retrospectively analyzed. Elastography images were acquired as JPEG images and also recorded as video clips. Stiff area ratios [(stiff areas as blue pixels) / (lymph node areas as region of interest pixels)] for each lymph node determined by elastography were collated with the results of pathological diagnosis. We also performed elastography of surgically resected lymph nodes and compared image findings with pathological sections. RESULTS: We evaluated 49 lymph nodes in 21 patients by CP-EBUS. There were 16 metastatic nodes (10 lung cancer metastases and 6 metastases from extrathoracic malignancies). Mean stiff area ratios were significantly greater for metastatic lymph nodes (0.478) than for benign nodes (0.216; p = 0.0002). Using a cutoff value of 0.311 for stiff area ratios, the sensitivity and specificity for predicting metastatic disease were 0.81 and 0.85, respectively. The stiff area was histologically compatible with metastatic distribution in surgically resected lymph nodes. CONCLUSIONS: Endobronchial elastography is feasible for lymph nodes when combined with CP-EBUS. Stiff area ratios are useful for predicting metastatic lymph nodes, which may be an efficient guide for TBNA.

Long-term outcomes of surgery for thymic carcinoma: experience of 25 cases at a single institution.

BACKGROUND: Thymic carcinoma, a relatively rare entity, often presents as locally advanced disease, and sometimes as distant metastatic disease. The treatment strategy, long-term surgical outcomes and clinical prognostic factors have yet to be fully elucidated. METHODS: Clinical charts of 25 patients who underwent surgery for thymic carcinoma at our institution from 1991 to 2014 were retrospectively reviewed. RESULTS: The Masaoka stage was stage I in three patients (12%), II in eight (32%), III in four (16%), IVa in four (16%), and IVb in six (24%). Histologic subtypes were squamous cell carcinoma in 12 patients, well-differentiated neuroendocrine carcinoma in 5, undifferentiated carcinoma in 3, adenocarcinoma in 1, and others in 4. Three patients had paraneoplastic syndrome including myasthenia gravis, multiple endocrine neoplasia type 1 (MEN1), and Cushing syndrome. Neoadjuvant chemotherapy was administered to five patients (20%). Complete resection was achieved in 17 patients (68%). There were no perioperative deaths. Twelve patients received postoperative therapy. The 5- and 10-year overall survival rates were 76.2 and 63.5%, respectively. The 5- and 10-year survival rates of patients with Masaoka stage I-III were 88.9 and 74.1%, respectively, whereas the 5-year survival rate of stage IV was 50.0%. The 5- and 10-year survival rates of 17 patients who underwent complete resection were 88.9 and 71.1%, respectively. Of the 17 patients with complete resection, 3 patients experienced recurrence including lung and supraclavicular lymph node. CONCLUSION: Even for this highly malignant disease, surgery could contribute to favorable long-term outcomes in the setting of multimodality therapy.

Recurrent pneumothorax associated with bronchial atresia: report of a case.

We herein report a case of recurrent pneumothorax associated with congenital bronchial atresia. A 26-year-old male presented with chest pain. Chest roentgenograms showed left pneumothorax, a left apical bulla and an area of hyperlucency in the left upper lung field, and chest computed tomography revealed a discontinuation of the left superior bronchus. Additionally, both ventilation and perfusion scintigraphy showed a defect in the left superior segment. A thoracoscopy-assisted left superior segmentectomy was performed, and a pathological examination indicated left superior segmental bronchial atresia, which might have predisposed the peripheral lung to emphysematous conditions. No relapse was observed 6 months after the operation. Although this entity is rare, congenital bronchial atresia should be considered in the differential diagnosis when a patient has suffered from a recurrent spontaneous pneumothorax.

Experience with perioperative pirfenidone for lung cancer surgery in patients with idiopathic pulmonary fibrosis.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse lung disease associated with an increased risk of lung cancer. Patients with IPF sometimes develop a life-threatening acute exacerbation of IPF (AE-IPF) after lung cancer surgery. In this retrospective study, pirfenidone, an antifibrotic agent, was perioperatively administered to IPF patients with lung cancer with the aim of preventing postoperative AE-IPF, and the feasibility and clinical outcomes were investigated. METHODS: Twelve IPF patients with concomitant lung cancer who received perioperative pirfenidone treatment (PPT) for lung cancer surgery were retrospectively investigated. Sixteen IPF patients undergoing lung cancer surgery without PPT were analyzed as historical controls. RESULTS: Compared to the controls, the PPT patients had a more severely impaired preoperative pulmonary function and a larger number of limited pulmonary resections. There was a significant preoperative decrease in the serum KL-6 levels of the PPT patients. No severe pirfenidone-related complications or IPF-related events occurred in the PPT patients, while six control patients developed AE-IPF (P = 0.0167). A quantitative histopathological evaluation of resected lung specimens found that tissue changes associated with IPF were significantly fewer in the PPT patients (P = 0.021). CONCLUSIONS: PPT is a feasible perioperative treatment for IPF patients with lung cancer. Its effectiveness in preventing postoperative AE-IPF thus warrants prospective verification.

Spirometric and radiological evaluation of the remnant lung long after major pulmonary resection: can compensatory phenomena be recognized in clinical cases?

PURPOSES: The purpose of this study was to investigate the compensatory phenomena after lung resection in clinical cases by evaluating the spirometric and radiological parameters. METHODS: Forty patients undergoing lobectomy for stage IA lung cancer were divided into the following groups: (A) patients with <10 (n = 20) and (B) patients with ≥10 resected subsegments (n = 20). Comparisons were made of the predicted and observed postoperative values of spirometry and radiological parameters, such as lung volumetry and the "estimated lung weight". Predicted values were based on the number of resected subsegments. The postoperative time to re-evaluation was at least 1 year for both groups. RESULTS: The predicted postoperative values of spirometry underestimated the actual values, and the differences were more significant in group B (forced vital capacity, p = 0.006, forced expiratory volume in 1 s, p = 0.011). Focusing on the remnant lungs on the surgical side, group B had significantly larger % postoperative lung volumes (161 ± 6.0 %) and % estimated lung weight (124 ± 5.4 %) than did group A (114 ± 3.8%, p < 0.0001; 89.5 ± 4.4%, p < 0.0001, respectively). CONCLUSIONS: Major lung resection in clinical cases causes a compensatory restoration of the pulmonary function and tissue.