ABSTRACT
Various surgical approaches address complex heart disease with arch anomalies. Bilateral pulmonary artery banding (bPAB) is a strategy for critically ill patients with complex arch anomalies. Some reports argued the potential effect of bPAB on the growth of the left ventricular outflow tract (LVOT) during inter-stage after bPAB. This study aimed to analyze the LVOT growth for biventricular repair candidates with arch anomaly and systemic ventricular outflow tract (SVOT) for univentricular repair candidates with arch anomaly. This retrospective study analyzed 17 patients undergoing initial bPAB followed by arch repair. The Z-scores of LVOT and SVOT were compared between pre-bPAB and pre-arch repair. Patient characteristics, transthoracic echocardiogram data, and PAB circumferences were reviewed. The diameter of the minimum LVOT for biventricular repair (BVR) candidates, the pulmonary valve (neo-aortic valve, neo-AoV) and the pulmonary trunk (the neo-ascending aorta, neo-AAo) for univentricular repair (UVR) candidates, and the degree of aortic or neo-aortic insufficiency in each candidate was statistically analyzed. 17 patients were divided into the UVR candidates (group U) with 9 patients and the BVR candidates (group B) with 8 patients. In group B, the median value of the Z-score of the minimum LVOT increased from -3.2 (range: - 4.1 ~ - 1.0) at pre-PAB to -2.8 (range: - 3.6 ~ - 0.3) at pre-arch repair with a significant difference (p = 0.012). In group U, the median value of the Z-score of the neo-AoV increased from 0.5 (range: - 1.0 ~ 1.7) at pre-bPAB to 1.2 (range: 0.2 ~ 1.9) at pre-arch repair with a significant difference (p < 0.01). The median value of the Z-score of the neo-AAo was also increased from 3.1 (range: 1.5 ~ 4.6) to 4.3 (range: 3.1 ~ 5.9) with a significant difference (p = 0.028). The growth of the LVOT for BVR candidates and SVOT for UVR candidates during the inter-stage between bPAB and arch repair was observed. These results suggest the potential advantage of bPAB in surgical strategies. Further research is needed to validate these findings and refine surgical approaches.
ABSTRACT
OBJECTIVES: The aim of this study is to analyze long-term results of the total aortic arch replacement with the frozen elephant trunk technique for primary chronic type B aortic dissection. METHODS: Among 322 patients who had the frozen elephant trunk technique, 43 (13.4%) patients (median age, 64.0 years) with primary chronic type B aortic dissection were analyzed. The patients underwent surgery at a median of 27.0 months after the onset of aortic dissection. The false lumen was patent in 30 (69.8%) patients preoperatively. RESULTS: Two patients suffered paraplegia and another died of cerebral infarction. Complete thrombosis of the peri-stent false lumen was achieved in 36 (83.7%) patients. Overall survival, freedom from aortic events, and freedom from aortic reintervention were 83.5%, 37.2%, and 42.2% at 5 years, respectively. Survival rates of the patients with or without aortic events were 75.0% and 95.8% at 5 years (Log-rank, p = 0.22). Late aortic events occurred in 19 (44.2%) patients including distal stent graft-induced new entry, type Ib endoleak, and false lumen dilation. The ratio of the stent graft diameter to the preoperative short axis diameter of the true lumen (hazard ratio, 1.90; 95% confidence interval, 1.01-3.59), and the maximal diameter of a postdissection aneurysm (1.07; 1.01-1.12) were the significant multivariate risk predictors of late aortic events. CONCLUSIONS: Late aortic events occurr fairly frequently, and new strategies need to be explored to enhance the effectiveness of this procedure in the future.
ABSTRACT
BACKGROUND/AIM: Lung adenocarcinoma and lung squamous cell carcinoma represent the most prevalent subtypes of non-small cell lung cancer eligible for surgery in the early stages. The emergence of immune checkpoint inhibitors as adjuvant therapy has shown promising potential in improving the postoperative prognosis of patients with lung cancer. Hence, a comprehensive understanding of the clinicopathological and molecular features of programmed cell death ligand-1 (PD-L1) expression in lung adenocarcinoma and squamous cell carcinoma is crucial. PATIENTS AND METHODS: In this retrospective study, we conducted a comparative analysis of clinicopathological features associated with the expression of PD-L1, stratifying patients who underwent surgical resection into two distinct groups: 289 patients with lung adenocarcinoma and 66 with lung squamous cell carcinoma. Furthermore, we investigated the associations between the expression of PD-L1 and genetic alterations in well-established oncogenic driver mutations. RESULTS: Among the cases, 52.9% exhibited negative PD-L1 expression, 32.9% had low PD-L1 expression, and 12.3% had high PD-L1 expression in adenocarcinoma, while the PD-L1 expression in squamous cell carcinoma showed a near-even distribution. Notably, male sex, smoking history, the presence of invasive pathological factors, and disease progression significantly influenced PD-L1 expression in adenocarcinoma, whereas none of these factors were associated with PD-L1 expression in squamous cell carcinoma. Additionally, the distribution of PD-L1 expression varied based on the type of specific driver gene mutation in adenocarcinoma. CONCLUSION: The present study revealed clinicopathological and molecular differences between lung adenocarcinoma and squamous cell carcinoma patients promoting the expression of PD-L1.
Subject(s)
Adenocarcinoma of Lung , B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Male , Adenocarcinoma , Adenocarcinoma of Lung/genetics , B7-H1 Antigen/genetics , Carcinoma, Squamous Cell/genetics , Lung Neoplasms/genetics , Retrospective StudiesABSTRACT
Designing novel catalysts is key to solving many energy and environmental challenges. Despite the promise that data science approaches, including machine learning (ML), can accelerate the development of catalysts, truly novel catalysts have rarely been discovered through ML approaches because of one of its most common limitations and criticisms-the assumed inability to extrapolate and identify extraordinary materials. Herein, we demonstrate an extrapolative ML approach to develop new multi-elemental reverse water-gas shift catalysts. Using 45 catalysts as the initial data points and performing 44 cycles of the closed loop discovery system (ML prediction + experiment), we experimentally tested a total of 300 catalysts and identified more than 100 catalysts with superior activity compared to those of the previously reported high-performance catalysts. The composition of the optimal catalyst discovered was Pt(3)/Rb(1)-Ba(1)-Mo(0.6)-Nb(0.2)/TiO2. Notably, niobium (Nb) was not included in the original dataset, and the catalyst composition identified was not predictable even by human experts.
ABSTRACT
Background: Chest wall malignant tumor (including primary and metastatic lesions) is rare, representing less than 5% of all thoracic malignancies. Local control of chest wall malignancies requires wide resection with tumor-free margins. These requirements increase the risk of thoracic cavity failure and subsequent pulmonary failure. The restoration strategy for chest wall defects comprises chest wall reconstruction and soft-tissue coverage. Various reconstruction methods have been used, but both evidence and guidelines for chest wall reconstruction remain lacking. The purposes of this study were to collate our institutional experience, evaluate the outcomes of full-thickness chest wall resection and reconstruction for patients with chest wall malignant tumor, and identify problems in current practice for chest wall reconstruction with a focus on local control, complications, pulmonary function and scoliosis. Methods: Participants comprised 30 patients with full-thickness chest wall malignant tumor who underwent chest wall resection and reconstruction between 1997 and 2021 in Mie University Hospital. All patients underwent chest wall resection of primary, recurrent or metastatic malignant tumors. A retrospective review was conducted for 32 operations. Results: Recurrence was observed after 5 operations. Total 5-year recurrence-free survival (RFS) rate was 79.3%. Diameter ≥5 cm was significantly associated with poor RFS. The postoperative complication rate was 18.8%. Flail chest was observed with resection of ≥3 ribs in anterior and lateral resections or with sternum resection without polyethylene methylmethacrylate reconstruction. Postoperative EFV1.0% did not show any significant decrease. Postoperative %VC decreased significantly with resection of ≥4 ribs or an area of >70 cm2. Postoperative scoliosis was observed in 8 of 28 patients. Posterior resection was associated with a high prevalence of scoliosis (88.9%). Conclusion: With chest wall reconstruction, risks of pulmonary impairment, flail chest and scoliosis were significantly increased. New strategies including indications for rigid reconstruction are needed to improve the outcomes of chest wall reconstruction.
ABSTRACT
INTRODUCTION: Due to its many technical advantages, the scope of robot-assisted thoracic surgery (RATS) is expanding to include extended pulmonary resection. Among such procedures, right bilobectomy is one with a high risk of inducing development of a bronchial stump fistula. MATERIALS AND SURGICAL TECHNIQUE: The pericardial fat pad case involved a 71-year-old man with a 31-mm adenocarcinoma in the right lung that had progressed to the intermediate bronchus. During lower bilobectomy, to confirm the tumor margin, an L-shaped stapler was used with stapling only at the oral side, and the bronchus was cut using a scalpel blade grasped with robot forceps. After confirming a negative stump, the pericardial fat was collected at the pedicle and sewn onto the stump. The intercostal muscle (ICM) flap case involved a 61-year-old man with a 16-mm nodule shadow in the lower lobe of his lung and swollen #11i and 7 lymph nodes. Intraoperatively, the #7 lymph node was diagnosed as non-small-cell lung cancer by frozen sections, and lower bilobectomy was performed. The bronchus was divided using a stapler with a green cartridge, and the ICM flap was harvested by changing the direction of the camera to a look-up view and positioning the camera at the 5th intercostal site. His numeric rating score (NRS) at 30 and 90 days post-surgery was 2 and 0, respectively. DISCUSSION: Our RATS technique was useful for harvesting the ICM flap. More cases should be accumulated to extend the surgical indication for RATS.
Subject(s)
Bronchial Fistula , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Robotic Surgical Procedures , Robotics , Humans , Lung Neoplasms/surgery , Carcinoma, Non-Small-Cell Lung/surgery , Bronchi/surgery , Bronchial Fistula/etiology , Bronchial Fistula/surgery , Pneumonectomy/methodsABSTRACT
PURPOSE: To explore what extent of ablative margin depicted by computed tomography (CT) immediately after radiofrequency (RF) ablation is required to reduce local tumor progression (LTP) for colorectal cancer (CRC) lung metastases. MATERIALS AND METHODS: This retrospective study was undertaken as a supplementary analysis of a previous prospective trial. Seventy patients (49 men and 21 women; mean age ± standard deviation, 64.9 years ± 10.6 years) underwent RF ablation for CRC lung metastases, and 95 tumors that were treated in the trial and followed up with CT at least 12 months after RF ablation were evaluated. The mean tumor size was 1.0 cm ± 0.5 cm. The ablative margin was estimated as the shortest distance between the outer edge of the tumor and the surrounding ground-glass opacity on CT obtained immediately after RF ablation. The impact of the ablative margin on LTP was evaluated using logistic regression analysis. Multivariate logistic regression analysis was also performed to identify the risk factors for LTP. The result was validated with multivariate logistic regression applying a bootstrap method (1,000 times resampling). RESULTS: The mean ablative margin was 2.7 mm ± 1.3 (range, 0.4-7.3 mm). LTP developed in 6 tumors (6%, 6/95) 6-19 months after RF ablation. The LTP rate was significantly higher when the margin was less than 2 mm (P = .023). A margin of <2 mm was also found to be a significant factor for LTP (P = .048) on multivariate analysis and validated using the bootstrap method (P = .025). CONCLUSIONS: An ablative margin of at least 2 mm is important to reduce LTP after RF ablation for CRC lung metastases.
Subject(s)
Colorectal Neoplasms , Lung Neoplasms , Radiofrequency Ablation , Female , Humans , Male , Colorectal Neoplasms/pathology , Disease Progression , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Lung Neoplasms/surgery , Radiofrequency Ablation/adverse effects , Retrospective Studies , Treatment Outcome , Middle Aged , AgedABSTRACT
Radiation-induced lung damage (RILD) is a critical problem in lung cancer radiotherapy, and it is difficult to predict its severity. Although no biomarkers for RILD have been established, tenascin C (TNC) is an extracellular matrix glycoprotein involved in the remodeling of damaged tissues and has been implicated in inflammation and fibrosis. We report the unique case of a 36-year-old man with adenocarcinoma of the lung, Union for International Cancer Control stage IIIB, who was treated with radiotherapy before lung surgery. The surgical specimen showed histopathological expression of TNC in the region where radiation pneumonitis was observed radiographically. Serum TNC levels were elevated after radiotherapy. In this case, TNC is suggested to be implicated in RILD and may be a potential candidate as a biomarker for the onset and severity of the condition.
Subject(s)
Extracellular Matrix , Tenascin , Adult , Biomarkers/metabolism , Extracellular Matrix/metabolism , Glycoproteins , Humans , Inflammation , Lung , Male , Tenascin/metabolismABSTRACT
Breast cancer is the most common cancer in women worldwide, and lung metastasis is one of the most frequent distant metastases. When breast cancer metastasizes to the lung, group 2 innate lymphoid cells (ILC2s) are thought to promote tumor growth via the activation of myeloid-derived suppressor cells (MDSCs), which are known to negatively regulate anticancer immune responses. However, it remains to be elucidated exactly how this ILC2-MDSC interaction is involved in tumor growth during metastases formation. Using a 4T1/LM4 breast cancer mouse model, we found that ILC2s were activated in both the micro- and macrometastatic regions, suggesting sustained activation throughout the metastatic cascades via IL-33/ST2 signaling. Consistent with IL-13 secretion from activated ILC2s, the frequencies of polymorphonuclear (PMN)- and monocytic (M)-MDSCs were also significantly elevated during the progression from micro- to macrometastatic cancer. However, the effects of ILC2-induced MDSC functionality on the microenvironment differed in a metastatic-stage-specific manner. Our findings indicate that ILC2s may induce the immunosuppressive functions of MDSCs during the later stages of metastasis. Concomitantly, ILC2 may instigate extracellular matrix remodeling by PMN-MDSC activation during the early stages of metastasis. These metastatic-stage-specific changes may contribute to metastatic tumor growth in the microenvironment of breast cancer lung metastasis.
ABSTRACT
A 52-year-old woman with a past history of anterior myocardial infarction 15 years previously was found to have a pedunculated mobile thrombus with a narrow stalk originating from the left ventricle, and a huge laminated mural thrombus. Surgical extraction of the two organized thrombi was successfully performed with transmitral approach using a novel, flexible, self-retained, and reusable leaflet retractor, which was originally developed for exposure of the subvalvular apparatus during mitral valve repair. Excellent access, exposure, and visualization of the left ventricle were achieved by this heart valve retractor and an endoscope for removal of a huge mural thrombus.
ABSTRACT
BACKGROUND: A better understanding of the tumor immune microenvironment (TIME) will facilitate the development of prognostic biomarkers and more effective therapeutic strategies in patients with lung cancer. However, little has been reported on the comprehensive evaluation of complex interactions among cancer cells, immune cells, and local immunosuppressive elements in the TIME. METHODS: Whole-exome sequencing and RNA sequencing were carried out on 113 lung cancers. We performed single sample gene set enrichment analysis on TIME-related gene sets to develop a new scoring system (TIME score), consisting of T-score (tumor proliferation), I-score (antitumor immunity) and S-score (immunosuppression). Lung cancers were classified according to a combination of high or low T-score, I-score, and S-scores (eight groups; G1-8). Clinical and genomic features, and immune landscape were investigated among eight groups. The external data sets of 990 lung cancers from The Cancer Genome Atlas and 76 melanomas treated with immune checkpoint inhibitors (ICI) were utilized to evaluate TIME scoring and explore prognostic and predictive accuracy. RESULTS: The representative histological type including adenocarcinoma and squamous cell carcinoma, and driver mutations such as epidermal growth factor receptor and TP53 mutations were different according to the T-score. The numbers of somatic mutations and predicted neoantigens were higher in Thi (G5-8) than Tlo (G1-4) tumors. Immune selection pressure against neoantigen expression occurred only in Thi and was dampened in Thi/Ilo (G5-6), possibly due to a reduced number of T cells with a high proportion of tumor specific but exhausted cells. Thi/Ilo/Shi (G5) displayed the lowest immune responses by additional immune suppressive mechanisms. The T-score, I-score and S-scores were independent prognostic factors, with survival curves well separated into eight groups with G5 displaying the worst overall survival, while the opposite group Tlo/Ihi/Slo (G4) had the best prognosis. Several oncogenic signaling pathways influenced on T-score and I-scores but not S-score, and PI3K pathway alteration correlated with poor prognosis in accordance with higher T-score and lower I-score. Moreover, the TIME score predicted the efficacy of ICI in patients with melanoma. CONCLUSION: The TIME score capturing complex interactions among tumor proliferation, antitumor immunity and immunosuppression could be useful for prognostic predictions or selection of treatment strategies in patients with lung cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Lung Neoplasms/genetics , Phosphatidylinositol 3-Kinases , Prognosis , Tumor MicroenvironmentABSTRACT
Osler's disease is an autosomal dominant disorder characterized by epistaxis, telangiectases, and arteriovenous malformations of the internal organs. Herein, we report the first published case of dissecting thoracoabdominal aortic aneurysm repair in a 66-year-old woman with hereditary hemorrhagic telangiectasia associated with ACVRL1 gene mutations. We maintained the activated clotting time around 400 seconds during cardiopulmonary bypass to avoid lethal hemorrhage from telangiectases or arteriovenous malformations. The Adamkiewicz artery could not be identified on imaging studies preoperatively. Therefore, we used the snake technique for intercostal revascularization, which was effective in preventing paraplegia.
Subject(s)
Aortic Aneurysm, Thoracic , Arteriovenous Malformations , Telangiectasia, Hereditary Hemorrhagic , Telangiectasis , Activin Receptors, Type II , Aged , Animals , Aortic Aneurysm, Thoracic/complications , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/surgery , Arteriovenous Malformations/complications , Female , Humans , Snakes , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasia, Hereditary Hemorrhagic/surgery , Telangiectasis/complicationsABSTRACT
BACKGROUND: Aortic valve neocuspidization (AVNeo) has emerged as a promising aortic valve procedure, and is expected to have a larger effective orifice area (EOA) than commercially available bioprostheses. It is, however, unclear which indices could facilitate left ventricular (LV) reverse remodeling after AVNeo. The aim of this study is to verify the impact of global left ventricular afterload on the LV reverse remodeling following AVNeo. METHODS: Data-available consecutive 38 patients (median age, 77; interquartile range, 72.8-82.0) undergoing AVNeo for severe aortic stenosis were enrolled in this study. Preoperative and the last follow-up echocardiographic data were retrospectively analyzed including the valvuloarterial impedance (Zva), a marker of global LV afterload. Reduction in LV geometry index (LVGI) and relative wall thickness (RWT) were used as an indicator for LV reverse remodeling. RESULTS: The Zva reduced in 24 patients (63.2%) during the follow-up period (median, 12 months). Reduction in Zva significantly correlated to improvement of LV geometry (LVGI (r = 0.400, p = 0.013) and RWT (r = 0.627, p < 0.001)), whereas increase in EOA index did not significantly correlate to LVGI (r = 0.009, p = 0.957), or RWT (r = 0.105, p = 0.529)). The reduction in Zva was the multivariate predictor of LV reverse remodeling. CONCLUSIONS: Low global LV afterload led to significant LV reverse remodeling even after AVNeo, which could achieve better valve performance than the conventional bioprostheses.
Subject(s)
Aortic Valve Stenosis , Aortic Valve , Aged , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Electric Impedance , Humans , Retrospective Studies , Ventricular RemodelingABSTRACT
BACKGROUND: Multiple exostoses generally develop in the first decade of life. They most frequently arise from the distal femur, proximal tibia, fibula, and proximal humerus. Costal exostoses are rare, contributing to 1%-2% of all exostoses in hereditary multiple exostoses (HME). They are usually asymptomatic, but a few cases have resulted in severe thoracic injuries. Pneumothorax caused by costal exostoses is rare, with only 13 previously reported cases. We report a new case of pneumothorax caused by costal exostoses. CASE SUMMARY: A 17-year-old male with HME underwent surgery for removal of exostoses around his right knee. Four months following the operation, he felt chest pain when he was playing the trumpet; however, he did not stop playing for a week. He was referred to our hospital with a chief complaint of chest pain. The computed tomography (CT) scan revealed right pneumothorax and multiple exostoses in his right ribs. The CT scan also revealed visceral pleura thickness and damaged lung tissues facing the exostosis of the seventh rib. We diagnosed that exostosis of the seventh rib induced pneumothorax. Costal exostosis resection was performed by video-assisted thoracoscopic surgery (VATS) 2 wk after the onset. The patient's postoperative course was uneventful, and there was no recurrence of pneumothorax for 2 years. CONCLUSION: Costal exostoses causing thoracic injuries should be resected regardless of age. VATS must be considered in cases with apparently benign and relatively small exostoses or HME.
ABSTRACT
PURPOSE: Here, we investigated the oncological outcomes of lung metastasectomy and/or radiofrequency ablation (RFA) of 92 patients with soft tissue sarcoma (STS) at nine institutions. METHODS: The study cohort included 65 men and 27 women with a mean age of 59 years at the time of metastasis. The mean follow-up duration was 51 months. All patients underwent metastasectomy and/or RFA for lung metastasis. RESULTS: The mean maximum size of the initial lung metastasis was 14.6 mm. At the initial evaluation, 41 patients had a single metastasis, whereas 51 patients had multiple metastases. The mean number of metastasectomies and/or RFA was 2 per patient. A total of 70 patients underwent lung metastasectomy, whereas the other 13 underwent lung RFA. The remaining nine patients underwent both RFA and metastasectomy. The 5-year post-metastatic survival rate was 52%. The patients who underwent complete treatment for the initial metastasis had better post-metastatic survival rates than those who underwent incomplete treatment. A univariate analysis of all possible prognostic factors for complete treatment confirmed the predictive value of disease-free interval, metastasis at initial presentation, distribution, tumor size, and number of lung metastases. Of the 92 patients, 74 underwent complete treatment for initial metastasis; in these patients, univariate and multivariate analyses showed that a smaller tumor size and single-lung metastasis were prognostic factors for superior post-metastatic survival. The patients with a smaller (<11.5 mm) single metastasis had better post-metastasis survival. The 5-year post-metastatic survival rates were 89.9% for patients with a smaller (<11.5 mm) single metastasis versus 22.7% for patients with larger (>11.5 mm) and multiple metastases. DISCUSSION: We propose that complete treatment for lung metastasis in patients with STS may improve post-metastatic survival rates. Furthermore, tumor number and size are important variables for clinical decision-making.
ABSTRACT
BACKGROUND: Endobronchial metastasis is a very rare type of recurrence after lung cancer surgery. Surgical intervention may be difficult to perform due to the postoperative reduction in the activities of daily living (ADL) and the invasiveness associated with redo surgery. In such cases, endobronchial brachytherapy (EBBT) plays an important role not only as a palliative treatment, but also as a definitive treatment with curative intent. CASE PRESENTATION: Three men (64, 69, and 74 years old) underwent combination therapy of external beam radiation therapy (EBRT) and EBBT for endobronchial metastasis after lobectomy of stage I-II non-small cell lung cancer (NSCLC): 2 cases of squamous cell carcinoma and 1 of adenocarcinoma. We used a special source-centralizing applicator for EBBT to avoid eccentric distribution of the radiation dose. Follow-up was considered to start from the end of brachytherapy. None of our patients experienced severe adverse events, and none needed extensive outpatient treatment. Local control was achieved in all cases by a bronchoscopic evaluation. All patients were alive after 31, 38, and 92 months of follow-up, respectively. In the adenocarcinoma patient, two metastases to the lung were discovered 3 years after EBBT, and the patient underwent partial wedge resection. CONCLUSIONS: EBBT may be a promising treatment with curative intent for endobronchial metastasis after surgery of NSCLC.
Subject(s)
Brachytherapy , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Activities of Daily Living , Carcinoma, Non-Small-Cell Lung/radiotherapy , Humans , Lung Neoplasms/radiotherapy , Male , Neoplasm Recurrence, Local , Prognosis , Radiotherapy DosageABSTRACT
Endothelial cells adapt their functions as a consequence of sensing extracellular substrate stiffness; these alterations allow them to maintain their vascular structure and function. Substrate stiffness-mediated yes-associated protein 1 (YAP) activation plays an important role in mechano-transduction and pro-angiogenic phenotype of endothelial cells, and Delta-like ligand 4 (Dll4)-Notch1 signaling is closely related to angiogenesis; however, the impact of substrate stiffness-mediated interrelation of these pathways on endothelial cell functions remains elusive. We confirmed that endothelial cells on softer substrates not only elongate cellular aspects but also attenuate YAP activation compared to cells on stiffer substrates. Endothelial cells on softer substrates also upregulate the vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 mRNA expression that is enhanced by VEGF stimulation. We determined that endothelial cells on softer substrates increased Dll4 expression, but not Notch1 expression, via YAP signaling. Moreover, endothelial cells on soft substrates induced not only VEGFRs upregulation but also suppression of pro-inflammatory interleukin-6 and plasminogen activator inhibitor-1 mRNA expression and the facilitation of anti-coagulant thrombomodulin and pro-coagulant tissue factor mRNA expression. Our results suggest that endothelial cells activate the YAP-Dll4-Notch signaling pathway in response to substrate stiffness and dictate cellular function.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Calcium-Binding Proteins/metabolism , Endothelial Cells/metabolism , Receptor, Notch1/metabolism , Transcription Factors/metabolism , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Neovascularization, Pathologic/metabolism , Neovascularization, Physiologic/physiology , YAP-Signaling ProteinsABSTRACT
BACKGROUND: Premeditated induction chemotherapy followed by surgical resection is accepted as safe and effective. Studies on salvage surgery in patients with incompletely cured lung cancer are lacking. This study aimed to demonstrate the safety and efficacy of salvage surgery. METHODS: We conducted a retrospective multi-institutional cohort study on patients who underwent salvage surgery for advanced (stage III and IV) non-small cell lung cancer (NSCLC) between January 2005 and December 2016 at the 14 hospitals of the Chubu Lung Cancer Surgery Study Group. A total of 37 patients were assigned to the salvage surgery group; a lobectomy with mediastinal lymph node dissection was performed. The survival benefit was assessed using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: Although postoperative complications were observed in 11 patients (29.7%), surgery-related death occurred in only one patient (mortality rate: 2.7%) resulting from respiratory failure caused by interstitial pneumonia exacerbation. Postoperative recurrence was observed in 22 patients (61.1%), the incidence of brain metastasis being high (nine patients: 40.9%). The five-year survival rate from the first day of treatment was 60%. The survival of the postoperative pathological stage (s'-stage) I group was significantly better (five-year survival rate: 80.9%) than that of the other groups (p < 0.05). S'-stage was the most significant factor (p < 0.01) associated with long-term survival. CONCLUSIONS: Salvage surgery is a feasible therapeutic modality for advanced lung cancer. Downstaging to s'-stage I with previous treatment was most important for survival. Complete resection (R0) should be the goal because surgical procedures were tolerated despite intense treatment.
Subject(s)
Lung Neoplasms/surgery , Salvage Therapy/methods , Adult , Aged , Cohort Studies , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Survival Analysis , Treatment OutcomeABSTRACT
OBJECTIVES: The prognostic impact of surgical intervention for recurrent or residual non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement after tyrosine-kinase inhibitor (TKI) treatment remains unclear. We aimed to describe the characteristics and outcomes of patients undergoing salvage surgery in this setting. METHODS: We retrospectively collected and analyzed nationwide Japanese data on perioperative and postoperative outcomes of patients who underwent salvage surgery after EGFR or ALK-TKI during 2010-2015. The primary endpoint was a 3-year overall survival (OS) rate and secondary endpoints were the rate of adverse events, perioperative mortality rate, 3-year recurrence-free survival (RFS) rate, and median survival time after salvage lung resection. Univariate and multivariate analyses were performed to identify independent prognostic factors of OS and RFS. RESULTS: Thirty-six patients were included (EGFR-TKI: 33, ALK-TKI: 3). The 3-year OS and RFS after the surgery were 75.1 % (95 % confidence interval [CI] 55.9-86.9 %) and 22.2 % (95 % CI 8.6-39.7 %), respectively. Of clinicopathological factors, the progression of disease while on TKI and preoperative carcinoembryonic antigen (CEA) levels (≥5 ng/mL) were shown to be worse independent prognosticators of OS (hazard ratio [HR] 9.38, 95 % CI 1.57-55.88, P = .014; HR 4.84, 95 % CI 1.62-14.46, P = .005, respectively). Older age at initial treatment (≥70 years) and advanced pathological T stage (T2-T4) were the worse prognosticators for RFS (HR 12.58, 95 % CI 2.51-62.97, P = .002; HR 3.06, 95 % CI 1.04-9.03, P = .043, respectively). Grade 3 adverse events occurred in 5.6 % (2/36) patients, but no deaths were reported within 90 days after surgery. CONCLUSION: Our study showed that salvage surgery after TKI treatment was safe and feasible and may contribute to prolonged OS time by reducing the local tumor burden.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/surgery , Mutation , Protein Kinase Inhibitors/adverse effects , Retrospective StudiesABSTRACT
An urgent surgery was performed for a 28-year-old man who sustained a traumatic descending thoracic aortic injury in an automobile collision. Severe respiratory failure was encountered during surgery, which did not allow for single-lung ventilation for adequate exposure of the descending aorta. We used venopulmonary artery extracorporeal lung assist by main pulmonary artery cannulation with concurrent distal aortic perfusion using a single centrifugal pump. Cannulating the easily accessible main pulmonary artery for venopulmonary artery extracorporeal lung assist is a safe and feasible technique in patients complicated with profound respiratory failure undergoing aortic surgery via left thoracotomy.