Investigation of the appropriate viscosity of fibrinogen in repairing pleural defects using ventilation and anchoring in an ex vivo pig model.

OBJECTIVE: Our previous study revealed that the viscosity of fibrinogen could influence the effectiveness of ventilation and anchoring (V/A) methods for controlling air leakages. Here, we examined the association between the viscosity of fibrinogen and effectiveness using an ex vivo pig model. METHODS: The fibrin glue used in this study was BOLHEAL® (KM Biologics Co., Ltd., Kumamoto, Japan). We prepared three types of fibrinogen with different viscosities (higher and lower than normal), including one without additives. Using an ex vivo pig model, a pleural defect was made, and the defect was repaired using three different viscosities of fibrinogen through the V/A method. We measured the rupture pressure at the repair site (N = 10) and histologically evaluated the depth of fibrin infiltration into the lung parenchyma at the repair sites. RESULTS: The median rupture pressure was 51.5 (40-73) cmH2O in Group 1 (lower viscosity), 47.0 (47-88) cmH2O in Group 2 (no change in viscosity), and 35.5 (25-61) cmH2O in Group 3 (higher viscosity). There was no statistically significant difference between Groups 1 and 2 (p = 0.819), but the rupture pressure was significantly higher in Group 2 than in Group 3 (p = 0.0136). Histological evaluation revealed deep infiltration of fibrin into the lung parenchyma in Groups 1 and 2, but no such infiltration was observed in the higher-viscosity group. CONCLUSIONS: The results of this experiment suggested that the V/A method using fibrin glue containing low-viscosity fibrinogen was more effective in controlling air leakage due to pleural defects.

Impact of Operation on Disease Progression and Survival of Patients With Pleural Mesothelioma.

BACKGROUND: The effects of surgery on the survival of patients with pleural mesothelioma remain poorly understood. We compared the therapeutic outcomes of patients receiving neoadjuvant chemotherapy, followed by surgery or refusing surgery, for pleural mesothelioma. METHODS: This retrospective study included consecutive patients who were eligible for curative-intent surgery after 3 cycles of neoadjuvant chemotherapy with platinum plus pemetrexed at our hospital during January 2011 to December 2021. Patients were divided into 2 groups. The surgery group comprised patients who underwent curative-intent surgery for pleural mesothelioma. The refusal-of-surgery group comprised patients who were medically eligible for surgery but refused to consent to surgery. Overall survival and progression-free survival were calculated using the Kaplan-Meier method with the generalized Wilcoxon test. RESULTS: Of the 296 eligible patients for the study, 272 underwent surgery and 24 refused surgery. During the surgery, 204 patients (75.0%), 43 (15.8%), and 25 (9.2%) underwent pleurectomy/decortication, extrapleural pneumonectomy, and exploratory thoracotomy, respectively. The median follow-up length was 28.4 months. The median overall survival periods were 40.7 months (95% CI, 32.2-45.6 months) for surgery and 23.6 months (95% CI, 15.2-43.0 months) for refusal of surgery (P = .03). The median progression-free survival periods were 20.2 months (95% CI, 17.0-22.5 months) for surgery and 12.9 months (95% CI, 8.3-16.8 months) for refusal of surgery (P < .001). CONCLUSIONS: Overall survival and progression-free survival were significantly better in surgery than in refusal of surgery. Surgery may improve the survival outcomes of patients with pleural mesothelioma.

Association between comorbidities and survival in patients with metastatic urothelial carcinoma treated with pembrolizumab.

BACKGROUND: This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. METHODS: From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. RESULTS: After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8 months) and a shorter OS (median, 12.4 vs. 18.8 months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. CONCLUSIONS: High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.

Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Presurgical immune-oncology/tyrosine kinase inhibitor combination therapy for renal cell carcinoma with a vena cava tumor thrombus: a single-institution case series.

Background: Although current guidelines recommend administering adjuvant immunotherapy following resection of advanced primary renal cell carcinoma (RCC), the clinical benefit of presurgical immunotherapy for patients with RCC remains uncertain. Case Description: We conducted a retrospective analysis of five patients diagnosed with RCC who developed inferior vena cava (IVC) tumor thrombus and were treated with radical nephrectomy following combined immunotherapy with a tyrosine kinase inhibitor. The median follow-up after nephrectomy was 23 months (range, 19-30 months). In all cases, the size of the IVC tumor thrombus decreased, and three of the cases demonstrated a decrease in the tumor thrombus level. Surgical margins were negative in all cases, and none of the patients experienced any major intraoperative complications. However, adhesions were encountered at the operative sites during surgery in all cases. One patient required a lymphatic intervention due to abdominal lymphatic leakage (Clavien IIIa) within 90 days after operation. Our case series demonstrated a median progression-free survival (PFS) of 11 months [95% confidence interval (CI)]: 5.5-22.5 months). No patient died during the follow-up period. Conclusions: Presurgical therapy combined with immunotherapy and tyrosine kinase inhibitors warrants consideration. Nevertheless, surgeons should be mindful of the difficulties that may arise beyond the clinical stage.

Prognosis prediction of patients with malignant pleural mesothelioma using conditional variational autoencoder on 3D PET images and clinical data.

BACKGROUND: Deep learning (DL) has been widely used for diagnosis and prognosis prediction of numerous frequently occurring diseases. Generally, DL models require large datasets to perform accurate and reliable prognosis prediction and avoid overlearning. However, prognosis prediction of rare diseases is still limited owing to the small number of cases, resulting in small datasets. PURPOSE: This paper proposes a multimodal DL method to predict the prognosis of patients with malignant pleural mesothelioma (MPM) with a small number of 3D positron emission tomography-computed tomography (PET/CT) images and clinical data. METHODS: A 3D convolutional conditional variational autoencoder (3D-CCVAE), which adds a 3D-convolutional layer and conditional VAE to process 3D images, was used for dimensionality reduction of PET images. We developed a two-step model that performs dimensionality reduction using the 3D-CCVAE, which is resistant to overlearning. In the first step, clinical data were input to condition the model and perform dimensionality reduction of PET images, resulting in more efficient dimension reduction. In the second step, a subset of the dimensionally reduced features and clinical data were combined to predict 1-year survival of patients using the random forest classifier. To demonstrate the usefulness of the 3D-CCVAE, we created a model without the conditional mechanism (3D-CVAE), one without the variational mechanism (3D-CCAE), and one without an autoencoder (without AE), and compared their prediction results. We used PET images and clinical data of 520 patients with histologically proven MPM. The data were randomly split in a 2:1 ratio (train : test) and three-fold cross-validation was performed. The models were trained on the training set and evaluated based on the test set results. The area under the receiver operating characteristic curve (AUC) for all models was calculated using their 1-year survival predictions, and the results were compared. RESULTS: We obtained AUC values of 0.76 (95% confidence interval [CI], 0.72-0.80) for the 3D-CCVAE model, 0.72 (95% CI, 0.68-0.77) for the 3D-CVAE model, 0.70 (95% CI, 0.66-0.75) for the 3D-CCAE model, and 0.69 (95% CI 0.65-0.74) for the without AE model. The 3D-CCVAE model performed better than the other models (3D-CVAE, p = 0.039; 3D-CCAE, p = 0.0032; and without AE, p = 0.0011). CONCLUSIONS: This study demonstrates the usefulness of the 3D-CCVAE in multimodal DL models learned using a small number of datasets. Additionally, it shows that dimensionality reduction via AE can be used to learn a DL model without increasing the overlearning risk. Moreover, the VAE mechanism can overcome the uncertainty of the model parameters that commonly occurs for small datasets, thereby eliminating the risk of overlearning. Additionally, more efficient dimensionality reduction of PET images can be performed by providing clinical data as conditions and ignoring clinical data-related features.

A case of eosinophilic cystitis coexisting of superficial bladder cancer, mimicking muscle-invasive cancer.

Introduction: Here, we present a rare case of eosinophilic cystitis coexisting with bladder cancer, which appeared to be an invasive carcinoma on imaging. Case presentation: A 46-year-old man presented with urinary urgency. Computed tomography revealed an irregular and thickly enhanced bladder wall, which seemed to be invasive bladder cancer. Cystoscopy revealed a raspberry-like mass lesion on the entire bladder circumference. Pathological diagnosis after transurethral resection was pathological T1 urothelial carcinoma. After a thorough discussion of treatment options, the patient elected to receive intravesical Bacillus Calmette-Guérin. Three months after Bacillus Calmette-Guérin administration, no residual disease was confirmed by transurethral biopsy, and no recurrence was observed over 2 years. As peripheral eosinophilia and submucosa eosinophil infiltration were identified, the patient was diagnosed with coexisting eosinophilic cystitis and urothelial carcinoma. Conclusion: Clinicians should consider the possibility of eosinophilic cystitis with superficial bladder cancer coexistence in patients who present with an irregular and thick bladder wall.

Prognostic role of preoperative fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography with an image-based harmonization technique: A multicenter retrospective study.

Objectives: Despite the prognostic impacts of preoperative fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography examination, fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography-based prognosis prediction has not been used clinically because of the disparity in data between institutions. By applying an image-based harmonized approach, we evaluated the prognostic roles of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters in clinical stage I non-small cell lung cancer. Methods: We retrospectively examined 495 patients with clinical stage I non-small cell lung cancer who underwent fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography examinations before pulmonary resection between 2013 and 2014 at 4 institutions. Three different harmonization techniques were applied, and an image-based harmonization, which showed the best-fit results, was used in the further analyses to evaluate the prognostic roles of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters. Results: Cutoff values of image-based harmonized fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters, maximum standardized uptake, metabolic tumor volume, and total lesion glycolysis were determined using receiver operating characteristic curves that distinguish pathologic high invasiveness of tumors. Among these parameters, only the maximum standardized uptake was an independent prognostic factor in recurrence-free and overall survivals in univariate and multivariate analyses. High image-based maximum standardized uptake value was associated with squamous histology or lung adenocarcinomas with higher pathologic grades. In subgroup analyses defined by ground-glass opacity status and histology or by clinical stages, the prognostic impact of image-based maximum standardized uptake value was always the highest compared with other fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters. Conclusions: The image-based fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography harmonization was the best fit, and the image-based maximum standardized uptake was the most important prognostic marker in all patients and in subgroups defined by ground-glass opacity status and histology in surgically resected clinical stage I non-small cell lung cancers.

Efficacy and safety of nivolumab with ipilimumab for recurrent malignant pleural mesothelioma after primary surgical intervention.

BACKGROUND: Treatment of recurrent malignant pleural mesothelioma (MPM) remains challenging. Our study examined the efficacy, tolerability, and safety of nivolumab with ipilimumab treatment for recurrent MPM after primary curative-intent surgery. METHODS: Treatment comprised 360 mg nivolumab every 3 weeks and 1 mg/kg of ipilimumab every 6 weeks, both administered intravenously. Both were discontinued for progressive disease or serious adverse events (AEs). Additional post-treatment data were evaluated, including objective response rate (ORR), disease control rate (DCR), post-treatment survival, progression-free survival (PFS), and AEs. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Survival analysis was estimated using a Kaplan-Meier plot. Feasibility analysis was performed using the National Cancer Institute Common Terminology Criteria for AEs version 5.0. RESULTS: Forty-one patients received nivolumab with ipilimumab for recurrent MPM after primary curative-intent surgery (median follow-up, 10.4 months; median treatment, 5.1 months). Overall, 18 patients exhibited partial response, 13 exhibited stable disease, and 10 had documented progressive disease. ORR and DCR were 43.9 and 75.6%, respectively. The 12-month post-treatment survival rate and PFS rate were 74.2 and 40.0%, respectively (median survival, not calculated; median PFS, 7.3 months). Further, 47 AEs were reported in 29 patients (70.7%), including grade 3-4 AEs in 14 patients (34.1%). Grade 4 hepatobiliary disorders were observed in 2 patients and grade 4 neutropenia was observed in 1. CONCLUSION: Nivolumab with ipilimumab treatment in patients with recurrent MPM after primary surgical treatment may be clinically efficacious, although serious AEs may be frequently observed.

Effectiveness of pembrolizumab in trial-ineligible patients with metastatic urothelial carcinoma.

BACKGROUND: The KEYNOTE-045 trial showed that pembrolizumab therapy improved the survival of patients with advanced urothelial carcinoma (UC). However, its effectiveness in trial-ineligible patients remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective study to evaluate the effectiveness of pembrolizumab in patients with metastatic UC who were trial-ineligible. The data of 164 consecutive patients with platinum-treated metastatic UC who received pembrolizumab as second-line therapy were analyzed. Trial eligibility was assessed using the KEYNOTE-045 criteria. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Overall survival (OS) and progression-free survival (PFS) were examined using the IPTW-adjusted Kaplan-Meier method. IPTW-adjusted restricted mean survival times (RMSTs) were compared between ineligible and eligible patients. RESULTS: Seventy-five patients (45.7%) were classified as ineligible based on the KEYNOTE-045 criteria. Baseline hemoglobin concentration of less than 9.0 g/dL was the most common reason for trial protocol violation (N = 23 [14.0%]). An IPTW-adjusted logistic regression model showed that the trial-eligibility was not significantly associated with objective response (OR: 0.65, 95% CI: 0.32 to 1.29, P = 0.22). Ineligible patients had similar RMST for PFS (difference: 3.8 months, 95% CI: -1.6 to 9.3, P = 0.17) and RMST for OS (difference: 1.4 months, 95% CI: -5.4 to 8.2, P = 0.93) compared with eligible patients. CONCLUSIONS: This study suggests that the effectiveness of pembrolizumab may be retained in ineligible patients with platinum-treated metastatic UC. Expanding trial eligibility criteria for these patients may be beneficial.

Vertebral osteomyelitis secondary to infective endocarditis detected by repeated magnetic resonance imaging: a case report.

Background: Patients with infective endocarditis (IE) experience various symptoms, a major one being back pain, which is occasionally caused by concomitant vertebral osteomyelitis (VO). Magnetic resonance imaging (MRI) is generally used to detect VO; however, the sensitivity of detection using MRI is very low in the early stages of VO. Case summary: A 60-year-old man visited our hospital with complaints of fever and persistent back pain over the past 7 days. A holosystolic heart murmur was auscultated, and an echocardiography revealed a vegetation on the posterior mitral leaflet. Blood cultures were positive for Streptococcus sanguinis. He was diagnosed with IE and treated with antimicrobials. A lumbar spine MRI on Day 1 showed no clear signs of vertebral infection, but the back pain continued and gradually worsened. Magnetic resonance imaging retest on Day 8 showed high signal intensity within the lumbar vertebral bodies and the disk on T2-weighted sequences, indicating VO. Intravenous antimicrobial therapy was extended, followed by oral antimicrobials, and a corset was put on to protect the lumbar spine to prevent bone degradation. Discussion: For persistent back pain in IE patients, repeat MRIs at regular intervals of time can detect possible vertebral infection even if signs of vertebral infection were absent on the initial MRI.

Long-term outcomes and risk factors of residual thoracic spaces after pleurectomy/decortication for mesothelioma.

OBJECTIVES: The residual thoracic spaces (RTS) after pleurectomy/decortication (P/D) remain unexplored to date. Hence, this study aims to examine the details and risk factors of RTS during the 3 post-P/D months. METHODS: We retrospectively examined patients who underwent neoadjuvant chemotherapy, followed by P/D for malignant pleural mesothelioma from September 2012 to December 2020. The RTS group included cases of residual thoracic cavity unaccompanied by pleural effusion on 3 postoperative months computed tomography. We determined risk factors for RTS using univariable and multivariable analyses. RESULTS: Of 170 patients examined, 58 (34.1%) were in the RTS group and 112 (65.9%) in the non-RTS group. In the RTS group, 43 patients recovered from RTS during the follow-up period; 4 patients developed chronic fistular empyema, while 2 required fenestration and 2 were thoracoscopic debridement. Besides, 11 patients exhibited RTS continuously. The univariable analysis revealed that compared with the non-RTS group, the RTS group reported a significantly longer postoperative air leak (>7 days; P < 0.01) and right P/D (P = 0.04). The multivariable analysis demonstrated that longer postoperative air leak (>7 days) remained a risk factor for RTS (odds ratio 2.5, 95% confidence interval: 1.3-4.9, P < 0.01). CONCLUSIONS: RTS was a postoperative event that frequently observed in patients undergoing P/D. Overall, the current study findings suggest longer postoperative air leak (>7 days) as a significant risk factor for RTS.

Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling.

Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulate in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbates inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuates inflammation and pathological vascular remodeling. Single-cell RNA sequencing reveals that beige adipocytes abundantly express neuregulin 4 (Nrg4) which critically regulate alternative macrophage activation. Importantly, significant beiging is observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induces the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitates alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrates the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.

Proposal for a new local recurrence score in patients with recurrent malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is associated with high rates of local recurrence (LR) up to 75%. Second line treatment should be applied tailored to relapse pattern. We aimed to establish a new score for LR pattern with prognostic impact in this observational study of retrospective nature. Methods: MPM patients with LR after surgery, verified by serial imaging during follow-up visits or biopsy were included in a retrospective analysis using a new local recurrence score (LRS). We divided the thoracic cavity into six sections and calculated the LRS according to the tumor burden. We assessed the impact on survival after recurrence using cox regression model. Results: From 2001 until 2017, 128 consecutive MPM patients with LR who underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy (EPP, n=61) or by (extended) pleurectomy/decortication [(E)PD, n=67], were included in the present analysis; 104 patients received second line therapy. Patients with chest wall (CW) recurrence had the shortest survival after recurrence (9 vs. 16 months, P=0.05) as well as patients with affected lymph nodes (LN) (9 vs. 17 months, P=0.02). In subgroup analysis, the (E)PD group had a significantly higher LRS (P≤0.001) despite a longer survival time after recurrence of 12.4 months (IQR, 6.45-20.32) compared to 9.3 months (IQR, 2.93-17.40, EPP group) (P=0.04). Patients with LRS ≤4 had a longer survival undergoing radiotherapy or local surgery for second line treatment whereas patients with LRS >4 only if they underwent chemotherapy. Conclusions: LRS might be a useful prognostic tool in MPM patients with LR after multimodality therapy to guide second line treatment allocation.

Incidence and Risk Factors of Chest Wall Metastasis at Biopsy Sites in Patients with Malignant Pleural Mesothelioma.

To investigate the incidence and risk factors of chest wall metastasis (CWM) at biopsy sites in patients with malignant pleural mesothelioma (MPM). This retrospective cohort study was conducted in 262 consecutive MPM patients who underwent multimodal treatment in which including neoadjuvant chemotherapy (NAC) and curative-intent surgery, from August 2009 to March 2021. CWM was evaluated radiologically (r-CWM) and pathologically (p-CWM). We also investigated the risk factors of p-CWM and the consistency between r-CWM and p-CWM. Of 262 patients, 25 patients were excluded from analysis due to missing data or impossibility of evaluation. Of the eligible 237 patients, pleural biopsy was performed via video-assisted thoracoscopic surgery in 197 (83.1%) and medical thoracoscopy in 40 (16.9%). Pleurodesis was performed after pleural biopsy in 74 patients (31.2%). All patients received NAC followed by curative-intent surgery. Radiological examination showed r-CWM in 43 patients (18.1%), while pathological examination showed p-CWM in 135 patients (57.0%). The incidence of p-CWM was significantly higher in the patients who received pleurodesis after pleural biopsy (77.0% vs. 47.9%, <0.001). Multivariate logistic regression analysis for p-CWM revealed that pleurodesis is an independent risk factor of p-CWM (adjusted hazard ratio, 3.46; 95% confidence interval, 1.84−6.52, <0.001). CWM at the biopsy site was pathologically proven in more than half of the patients (57.0%) who received NAC followed by curative-intent surgery, which was higher than the numbers diagnosed by radiological examinations (p-CWM: 57.0% vs. r-CWM: 18.1%). Pleurodesis after pleural biopsy is an independent risk factor of p-CWM.

Association between thoracic epidural block and major complications after pleurectomy/decortication for malignant pleural mesothelioma under general anesthesia.

INTRODUCTION: A curative-intent surgical procedure, pleurectomy/decortication, for malignant pleural mesothelioma is accompanied by a high incidence of major postoperative complications. Although epidural block, which suppresses nociception during and after surgery, reportedly has both benefits and disadvantages in terms of outcomes after thoracic surgery for other diseases, the effects of epidural block on major complications after pleurectomy/decortication have not been evaluated. The aim of this study was to evaluate the association between epidural block and major postoperative complications following pleurectomy/decortication. METHODS: In a single-institutional observational study, consecutive adult patients undergoing pleurectomy/decortication under general anesthesia were enrolled from March 2019 to December 2021. Multivariable logistic regression analysis was performed to determine the association between perioperative variables and major complications. Next, patients were divided into two groups: general anesthesia with and without epidural block. Incidences of major postoperative complications, defined as Clavien-Dindo grades≥III, were compared between groups. RESULTS: In all patients enrolled with American Society of Anesthesiologists (ASA) physical status II or III (n=99), general anesthesia without epidural block was identified as a sole risk factor for major complications among perioperative variables. The incidence of major complications was 32.3% (95% CI 19.1% to 49.2%) in patients with epidural block (n=34), which was significantly lower than 63.1% (95% CI 50.9% to 73.8%) in patients without epidural block (n=65). In sensitivity analysis in patients with ASA physical status II alone, the same results were obtained. CONCLUSION: Epidural block is likely associated with reduction of the incidence of major complications after pleurectomy/decortication for malignant pleural mesothelioma under general anesthesia.

An Unusual Case of Left Ventricular Outflow Tract Obstruction after Aortic Valve Replacement.

Surgical valve replacement improves the symptoms and prognosis of patients with valvular heart diseases. Aortic regurgitation elicits volume overload that causes enlargement of the left ventricle (LV), while the LV size often shrinks to near normal after aortic valve replacement (AVR), which is referred to as "reverse remodeling". We experienced a case in which LV outflow tract (LVOT) obstruction became apparent after AVR, resulting in worsening of heart failure. A 65-year-old man who had undergone surgical AVR for aortic valve regurgitation 15 months previously exhibited dyspnea on effort accompanied with severe LVOT obstruction. With double pressure catheters, we directly recorded an augmented pressure gradient in the LVOT and rapid relief of the obstruction by intravenous administration of the anti-arrhythmic drug cibenzoline. Since the considerable LV hypertrophy had been indicated by an electrocardiogram and echocardiography before AVR, we suspected that dilation of the LV chamber due to aortic valve regurgitation could have masked the subclinical LVOT obstruction, which became clinically evident after LV size reduction due to reverse remodeling after AVR.

Circulating tumor cell methylation profiles reveal the classification and evolution of non-small cell lung cancer.

Background: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) could improve pathological diagnosis and the selection of treatments for non-small cell lung cancer (NSCLC). Previous studies have shown that deoxyribonucleic acid (DNA) methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. Methods: We first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We then performed whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. Results: The bioinformatics analysis revealed a NSCLC-specific DNA methylation marker panel, which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on the CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between the CTCs and their primary tumors, and found very high similarities between the CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. However, the CTCs also displayed some characteristics that differed to those of primary tumor tissues, which suggest that CTCs acquire some unique characteristics after migrating from the primary tumor; these characteristics may partly explain the ability of tumor cells to evade immune surveillance. Conclusions: Our findings provide insights into the potential use of CTCs in the pathological classification of NSCLC patients. Our findings also show how CTC primary tumor inheritance and CTC evolution affect metastasis and immune escape.

Control of air leakage during pleurectomy/decortication by the ventilation and anchoring method.

OBJECTIVES: We previously established a novel method of lung repair called the ventilation and anchoring (V/A) method. We evaluated the usefulness of the V/A method for controlling air leakage during pleurectomy/decortication (P/D). METHODS: For this study, we enrolled patients with malignant pleural mesothelioma (MPM) who planned to receive P/D. Our lung repair method involves (1) suturing lung parenchyma for an apparent injured lesion and (2) coating the lung parenchyma with fibrin glue (FG) using the V/A method. The tidal volume (TV) was measured under pressure-controlled ventilation in the ipsilateral-affected lung 10 times at the following four points: after thoracotomy, at completion of visceral pleurectomy, after suturing lung parenchyma, and 5 min after coating with FG. The primary endpoint was the mean TV (mTV) change, and the secondary endpoints were the duration of air leakage and incidence of pleurodesis. RESULTS: Between April 2014 and April 2016, 25 patients of the 29 consecutive patients enrolled were eligible. The mTV significantly decreased after completion of visceral pleurectomy but significantly increased after repair of the lung parenchyma, especially after coating with FG. The median duration of postoperative air leakage was 4 days (range: 2-19 days). Postoperative air leakage > 7 days was observed in 11 (44%) patients. Of these 11 patients, 6 received pleurodesis; however, no further revision was needed. CONCLUSIONS: Significant increases in TV were observed after coating with FG via the V/A method during P/D. Coating with FG using the V/A method can contribute to a reduction in air leakage during P/D.

Japanese Current Status of Curative-Intent Surgery for Malignant Pleural Mesothelioma.

BACKGROUND: Few reports about surgical outcomes in malignant pleural mesothelioma (MPM) have been based on reliable nationwide databases. Here, we analyzed the incidence, surgical outcome, and operative risk factors using Japanese nationwide database. METHODS: Characteristics and perioperative data from 622 patients who underwent curative-intent surgery for MPM between January 2014 and December 2017 were recorded from National Clinical Database of Japan. We analyzed the incidence, surgical outcomes, and risk factors for surgical complications after 2 surgical procedures (extrapleural pneumonectomy [EPP] and pleurectomy/decortication [P/D]). RESULTS: During 4 years, EPP was performed in 279 patients and P/D in 343. EPP was more frequently performed in institutions less experienced in MPM, while P/D was more frequently performed in institutions well experienced in MPM (P < .001), especially in high-volume centers with more than 10 cases during this period. P/D was more frequently performed, especially in high-volume centers. The morbidity rates were 45.2% in EPP and 35.9% in P/D. Heart failure and pneumonia were most frequent in EPP, while prolonged air leakage was most frequent in P/D. Thirty-day and in-hospital mortality rates were 1.1% and 3.2% (EPP) and 1.2% and 3.2% (P/D), respectively. Regression analyses revealed that higher age (>65 years) was associated with operative complications in EPP (odds ratio, 3.56 [95% confidence interval, 1.26-8.56]), whereas no risk factor was observed in P/D. CONCLUSIONS: In Japanese nationwide annual database, P/D was more frequently performed, especially in high-volume centers. Morbidity was higher in EPP than P/D; however, the mortality rates were quite low in Japan regardless surgical procedures.