Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a life-threatening complication of lung cancer operation for patients with IPF, and no effective prophylaxis has ever been reported. In ...this study, we investigate the effect of perioperative treatment with an anti-IPF agent on reduction of the risk of developing AE-IPF.
A consecutive series of 50 lung cancer patients with IPF who underwent operations at our institution from October 2006 to October 2014 was retrospectively investigated. Since September 2009, pirfenidone was orally administered to patients from 4 weeks before operation to 4 weeks after operation. Thirty-one patients received the perioperative pirfenidone treatment (PPT), and their clinical outcome was retrospectively compared with that of 19 patients who did not receive PPT.
No differences were found in age, smoking history, sex, vital capacity, KL-6, procedure, or risk score (10.5 ± 2.2 versus 11.2 ± 1.5) between the PPT and non-PPT groups. The incidence of AE-IPF for the PPT/non-PPT groups was 0.0%/10.5% within 30 postoperative days (p = 0.07) and 3.2%/21.1% within 90 postoperative days (p = 0.04), respectively. Logistic regression analysis showed a significant association between PPT and the incidence of AE-IPF within 30 (p = 0.045) and 90 (p = 0.04) postoperative days.
A prophylactic effect of PPT for postoperative AE-IPF in patients with lung cancer was suggested. Further confirmatory prospective studies should be considered for PPT.
Video-assisted thoracoscopic wedge resection of multiple small, non-visible, and nonpalpable pulmonary nodules is a clinical challenge. We propose an ultra-minimally invasive technique for ...localization of pulmonary nodules using the electromagnetic navigation bronchoscope (ENB)-guided transbronchial indocyanine green (ICG) injection and intraoperative fluorescence detection with a near-infrared (NIR) fluorescence thoracoscope.
Fluorescence properties of ICG topically injected into the lung parenchyma were determined using a resected porcine lung. The combination of ENB-guided ICG injection and NIR fluorescence detection was tested using a live porcine model. An electromagnetic sensor integrated flexible bronchoscope was geometrically registered to the three-dimensional chest computed tomographic image data by way of a real-time electromagnetic tracking system. The ICG mixed with iopamidol was injected into the pulmonary nodules by ENB guidance; ICG fluorescence was visualized by a near-infrared (NIR) thoracoscope.
The ICG existing under 24-mm depth of inflated lung was detectable by the NIR fluorescence thoracoscope. The size of the fluorescence spot made by 0.1 mL of ICG was 10.4 ± 2.2 mm. An ICG or iopamidol spot remained at the injected point of the lung for more than 6 hours in vivo. The ICG fluorescence spot injected into the pulmonary nodule with ENB guidance was identified at the pulmonary nodule with the NIR thoracoscope.
The ENB-guided transbronchial ICG injection and intraoperative NIR thoracoscopic detection is a feasible method to localize multiple pulmonary nodules.
Endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration allows for sampling of mediastinal lymph nodes. The external diameter, rigidity, and angulation of the convex probe EBUS ...renders limited accessibility. This study compares the accessibility and transbronchial needle aspiration capability of the prototype thin convex probe EBUS against the convex probe EBUS in human ex vivo lungs rejected for transplant.
The prototype thin convex probe EBUS (BF-Y0055; Olympus, Tokyo, Japan) with a thinner tip (5.9 mm), greater upward angle (170 degrees), and decreased forward oblique direction of view (20 degrees) was compared with the current convex probe EBUS (6.9-mm tip, 120 degrees, and 35 degrees, respectively). Accessibility and transbronchial needle aspiration capability was assessed in ex vivo human lungs declined for lung transplant. The distance of maximum reach and sustainable endoscopic limit were measured. Transbronchial needle aspiration capability was assessed using the prototype 25G aspiration needle in segmental lymph nodes.
In all evaluated lungs (n = 5), the thin convex probe EBUS demonstrated greater reach and a higher success rate, averaging 22.1 mm greater maximum reach and 10.3 mm further endoscopic visibility range than convex probe EBUS, and could assess selectively almost all segmental bronchi (98% right, 91% left), demonstrating nearly twice the accessibility as the convex probe EBUS (48% right, 47% left). The prototype successfully enabled cytologic assessment of subsegmental lymph nodes with adequate quality using the dedicated 25G aspiration needle.
Thin convex probe EBUS has greater accessibility to peripheral airways in human lungs and is capable of sampling segmental lymph nodes using the aspiration needle. That will allow for more precise assessment of N1 nodes and, possibly, intrapulmonary lesions normally inaccessible to the conventional convex probe EBUS.
Lung carcinoma is often associated with interstitial lung disease (ILD), and the prognosis of lung cancer accompanied by ILD is unfavorable. In this study, cases of patients with primary lung cancer ...with or without ILD were reviewed to analyze surgical outcome, with special interest in the conformity of clinical and pathologic stages, pathologic findings of pleural invasion, malignant pleurisy first detected at the time of thoracotomy, and survival.
Retrospective chart review was performed for 1,264 primary lung cancer patients who underwent surgery from 2004 to 2015. Concomitant ILD was diagnosed by pathological examination or preoperative chest computed tomography findings.
ILD was found in 104 patients (8.2%) with primary lung cancer. Conformity of clinical and pathological stages in the ILD-positive patients was poor, with a lower kappa value than that for the 1,160 ILD-negative patients (0.34 versus 0.51). The ILD group had significantly higher incidences of pleural invasion and unexpected malignant pleurisy than did the non-ILD group (for pleural invasion, 49.0% versus 24.5%, p < 0.0001; for malignant pleurisy, 7.69% versus 1.47%, p < 0.0001). The 5-year overall survival rates of the ILD group showed significantly lower than those of the non-ILD group (45.2% versus 70.1%; p = 0.0014) after propensity score matching.
In lung cancer, the concomitant existence of ILD is a risk factor for pleural invasion. Concomitant ILD might cause underestimation of clinical staging, increase the chance of unexpected malignant pleurisy during surgery, and shorten survival time.
Abstract Context There is controversy around the association between depressive symptoms and age in adult cancer patients. Objectives The aim of this study was to evaluate the following hypotheses: ...1) cancer patients' depressive symptoms decrease with age, and 2) in individuals aged 65 years or older, depressive symptoms increase because of the effect of somatic symptoms. Methods We retrospectively analyzed a database of 356 cancer patients who were consecutively recruited in a previous multicenter cross-sectional study. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9), and correlations with age and other factors were assessed by hierarchical multivariate regression analysis. Age was entered as the dependent variable in the first step, patient characteristics and cancer-related variables were entered in the second step, and somatic symptoms were entered in the last step. We analyzed this model for both the total sample and the subpopulation aged 65 years or older. Results In the total sample, the PHQ-9 score was significantly associated with lower age, fatigue, and shortness of breath (adjusted R2 14.2%). In the subpopulation aged 65 years or older, no factor was associated with the PHQ-9 score (adjusted R2 7.3%). Conclusion The finding that depressive symptoms in cancer patients decreased with age was concordant with our first hypothesis, but the second hypothesis was not supported. Younger cancer patients were vulnerable to depressive symptoms and should be monitored carefully. Further studies using more representative samples are needed to examine in detail the association between depressive symptoms and age in older cancer patients.
Abstract 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.
Localization of small, nonvisible and nonpalpable nodules is challenging during video-assisted thoracoscopic surgery. We evaluated the feasibility of using a new ultrasound thoracoscope to localize ...nodules in resected ex vivo human lungs.
The tumor was localized and measured in its greatest dimension with a prototype ultrasound thoracoscope (XLTF-UC180; Olympus Corporation, Tokyo, Japan) at different frequencies (5.0 to 12.0 MHz) and different lung specimen states (deflated, semiinflated). Measured tumor size and depth from lung surface were compared and correlated to the true diameter and depth from lung surface acquired from pathologic morphology.
Ex vivo evaluation was performed on 16 solid nodules and nine part solid ground-glass nodules. All tumors were successfully localized in the deflated lung specimens (average size, 13.7 ± 5.2 mm). The tumor boundaries were best evaluated with an ultrasound frequency of 10 MHz. Solid nodules were more easily visualized than ground-glass nodules. Part solid ground-glass nodules were not easily detected in the semiinflated specimen owing to peritumoral air surrounding the tumor. Tumor boundaries were also difficult to identify in deeply situated tumors and in lungs with underlying disease. A strong positive correlation existed between the ultrasound measurement and true measurement of tumor size (R
= 0.89, p < 0.001).
The ultrasound thoracoscope can be used to localize nodules in resected human lungs. The clarity of the tumor boundaries is influenced by the tumor type and depth and the underlying pulmonary disease. Complete lung deflation and the use of 10 MHz ultrasound frequency optimize the visualization of target tumors.
Objective It is controversial whether lung regeneration contributes to compensatory lung growth after pulmonary resection in mature individuals. The objectives of this study were to clarify the ...molecular mechanisms that regulate the process of compensatory lung growth and investigate the influence of transplantation of lung cells enriched in alveolar type II cells on compensatory lung growth. Methods Serial changes of morphology and gene expression were examined in the remnant right lung after pneumonectomy in adult male Wistar rats. One day after surgery, animals received endotracheal transplants of rat lung cells enriched in alveolar type II cells at a dose of 2.5 × 106 cells. Serial morphologic changes were examined in comparison with pneumonectomy alone. Engraftment of lung cells was validated with a sex-mismatch model. Results The alveolar density with mean linear intercept was always lower in pneumonectomized rats than in sham surgical controls for 6 months after surgery. Microarray analysis revealed that multiple genes related to proliferation (but not specific alveolar development) were initially up-regulated and then returned to normal after 1 month. In the pneumonectomized rats with transplantation, the alveolar density was equivalent to that in the sham controls. Engraftment of the transplanted cells from male donors in the alveoli of female recipients was proven by detection of Y-chromosome positive cells and quantified by real-time polymerase chain reaction for the Sry gene. This occurred in pneumonectomized rats but not in sham controls. Conclusions We postulate that lung cell transplantation stimulates lung regeneration in the remnant lung after pneumonectomy in mature rats.
Surgical treatment of small cell lung cancer (SCLC) is limited to stage I disease. Therefore, accurate lymph node staging is mandatory in SCLC patients. The purpose of this study was to evaluate the ...utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the evaluation of mediastinal and hilar lymph node metastasis in patients with SCLC.
Forty patients with untreated SCLC who underwent EBUS-TBNA for lymph node staging between November 2002 and September 2008 were retrospectively analyzed. The convex probe endobronchial ultrasonography was used for EBUS-TBNA. Lymph nodes assessed by the convex probe endobronchial ultrasonography were aspirated until EBUS-TBNA revealed malignant cells by rapid on-site cytology.
Endobronchial ultrasound-guided transbronchial needle aspiration was successfully performed in all patients, and revealed lymph node status as follows: N0, 13 cases; N1, 5 cases; and N2, 22 cases. Among the 13 N0 cases, 9 patients underwent surgery, whereas 4 patients did not undergo surgical intervention because of enlargement of subaortic or paraaortic lymph nodes (stations 5 and 6) that precluded EBUS-TBNA assessment (n = 3) or poor performance status (n = 1). Pathologic examination of dissected nodes confirmed an N0 diagnosis in 8 patients, whereas 1 patient had hilar lymph node metastasis (N1). The sensitivity, specificity, and diagnostic accuracy rate of EBUS-TBNA were 96.4%, 100%, and 97.2%, respectively. The overall 5-year survival rate for the 9 patients who underwent surgery was 77.8%.
Endobronchial ultrasound-guided transbronchial needle aspiration has a high diagnostic yield for the evaluation of mediastinal and hilar lymph node metastasis in SCLC and has a high impact on patient management.
This retrospective study investigated long-term graft patency and outcomes for malignant diseases with invasion of the superior vena cava (SVC).
From October 1995 to November 2008, 20 patients ...underwent combined surgical resection of malignant tumors and the SVC with vascular reconstruction using a ringed polytetrafluoroethylene graft (8 to 12 mm) Sigmoid-curved spatulation of the graft end at the right auricle was performed to obtain a wide orifice left graft. Anticoagulation therapy was routinely administered for 3 to 6 months. Postoperative graft patency was verified at 2 to 4 weeks, 3 months, and after 12 months. Indications were lung cancer in 9 patients, thymic tumors in 8, germ cell tumors in 2, and thyroid cancer in 1.
Procedures were single graft replacement in 9 patients, bilateral grafts in 10, and bilateral SVC grafts and 1 pulmonary artery graft in 1. All grafts were patent over a short-term period, but 1 limb of the bilateral grafts became occluded in 2 patients who received bilateral grafts during long-term follow-up. Bronchial dehiscence after lung cancer resection caused 1 in-hospital death. Mean follow-up was 44.7 months. Median survival was 22.1 months. Overall survival was 66.4% and 41.5% at 1 and 5 years, respectively. Survival for lung cancer was significantly worse at 5 years (62.5%) than thymic tumor (18.8%, p = 0.04).
Prosthetic reconstruction of the SVC for anterior mediastinal tumors and lung cancer is feasible. Reconstruction of the SVC using a single left graft to avoid total cross-clamping of the SVC is effective.
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