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Abstract We aimed to compare the prognostic impacts of adenocarcinoma subtypes, programmed death-ligand I (PD-L1), and CD155 expression on patients with resected pathological stage (p-stage) I lung adenocarcinoma. In total, 353 patients with completely resected p-stage I lung adenocarcinomas were retrospectively reviewed. The expression levels of PD-L1 and CD155 in tumour cells from each adenocarcinoma subtype were evaluated using several clinicopathological and histological features, such as the presence of a micropapillary pattern. A total of 52 patients (14.7%) had PD-L1-positive tumours, whereas 128 patients (36.3%) had CD155-positive tumours, with a tumour proportion score of 5% for both PD-L1 and CD155 expression. Compared with patients with other adenocarcinoma subtypes, those with solid-predominant adenocarcinomas were significantly more positive for PD-L1 and CD155. Multivariate analysis showed that PD-L1 expression status was significantly associated with progression-free survival and overall survival, whereas CD155 expression and the presence of a micropapillary pattern were not significantly associated with either parameter. Patients with PD-L1-positive tumours had poorer prognoses than those with CD155-positive tumours. Moreover, PD-L1 and CD155 were significantly expressed in solid-predominant adenocarcinomas. The results of this study suggest that immune checkpoint inhibitors can be used as adjuvants in the treatment of patients with p-stage I adenocarcinoma.

Pulmonary enteric adenocarcinoma (PEAC) is a rare lung adenocarcinoma with morphological features similar to those of primary and metastatic colorectal adenocarcinoma. To date, only a few studies have reported the therapeutic effects of chemoradiotherapy on PEAC. This report describes the case of a 28-year-old woman with pregnancy-related PEAC who presented with left shoulder pain. A superior sulcus tumor was identified in the left thoracic cavity, and the biopsy indicated more than 50% intestinal differentiation components. Moreover, immunohistochemical staining revealed positive CDX2 and CK7 expression. Positron emission tomography-computed tomography, upper endoscopy, colonoscopy, and small intestinal capsule endoscopy revealed no gastrointestinal malignancies. The patient was diagnosed with locally advanced PEAC (clinical stage T4N0M0; stage IIIA). Therefore, the patient was treated with preoperative chemoradiotherapy and underwent gross total resection during surgery. Pathological evaluation of the specimen revealed no residual tumor, indicating that the chemoradiotherapy for PEAC was highly effective. One subsequent brain metastasis was also resected, and the patient has not experienced recurrence in 28 months since this resection and continues to be monitored regularly. This is the first pathologically confirmed report of the use of chemoradiotherapy (carboplatin [CBDCA] and paclitaxel [PTX]) for PEAC and its clinical efficacy. Unlike previous reports, the efficacy of this treatment is attributed to the use of PTX in preoperative chemotherapy and the p21− status of the patient, which may have increased sensitivity to chemoradiation therapy. Therefore, chemoradiotherapy (CBDCA + PTX) may be a viable treatment option for advanced intestinal lung adenocarcinoma.

Background No consensus exists regarding surgical intervention for rheumatoid nodule–related pneumothorax. Clinical policy decisions rely on individual clinicians' experience and are usually intractable.

Abstract We investigated the effect of preoperative therapy for non-small cell lung cancer on programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), poliovirus receptor (CD155), and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) expression and prognosis with the cases of 28 patients received preoperative concurrent chemo-radiotherapy (cCRT) and 27 received preoperative drug therapy. The post-treatment PD-L1 expression was higher in cCRT group than in the drug therapy (50.0% vs 5.0%, p = 0.000), whereas that of CD155 did not significantly differ (40.0% vs 60.0%, p = 0.131). The PD-1 expression was not significantly different between the cCRT and drug therapy groups (51.1% vs 42.9%, p = 0.076), while the TIGIT was significantly higher in the cCRT group (41.5% vs 34.0%, p = 0.008). The patients who received cCRT resulted in elevated PD-L1and TIGIT values had a worse prognosis (p = 0.008). The PD-L1 and TIGIT expression after cCRT was significantly higher than after drug treatment. The cCRT population with high expression of both had a significantly poorer prognosis, indicating elevation of PD-L1 and TIGIT after cCRT as a negative prognostic factor. Combination therapy with anti-PD-L1 and anti-TIGIT antibodies after cCRT may contribute to an improved prognosis.

Abstract Aims With the rapidly increasing ageing population, heart failure is an urgent challenge, particularly in developed countries. The study aimed to investigate the main aetiologies of chronic heart failure in a super‐aged society. Methods and results The KUNIUMI registry chronic cohort is a community‐based, prospective, observational study of chronic heart failure in Awaji Island, Japan. Inhabitants of this island aged ≥65 years accounted for 36.3% of the population. In the present study, data from patients with symptomatic heart failure were extracted from the registry. A total of 1646 patients were enrolled from March 2019 to March 2021, accounting for ~1.3% of the inhabitants of Awaji Island. We analysed 852 patients with symptomatic heart failure. The mean age was high (78.7 ± 11.1 years), with 357 patients (41.9%) being female. The proportion of women increased significantly with advancing age and constituted more than half of the patients aged 85 years and older (P 75 years. Patients with atrial functional mitral regurgitation had a higher prevalence of atrial fibrillation (especially long‐standing persistent atrial fibrillation) and a larger left atrial volume index when compared with patients with other types of mitral regurgitation (P

Abstract Aims Acute decompensated heart failure (ADHF) is a frequent cause of hospitalization for patients with heart disease, and ADHF patients are at high risk of heart failure (HF) re‐hospitalization. Residual congestion at discharge is also a strong predictor of poor outcomes and re‐hospitalization for ADHF patients. However, the impact of residual congestion at discharge on worsening renal function (WRF) in both high‐aged and older patients remains uncertain because previous studies of WRF in ADHF patients were conducted for older patients. We therefore designed and conducted a retrospective, population‐based study using the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) Registry to investigate the association of residual congestion at discharge with WRF in ADHF patients according to age. Methods and results We studied 966 hospitalized ADHF patients with a mean age of 80.2 ± 11.4 years from among 1971 listed in the KUNIUMI Registry. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level during the hospital stay compared with the value on admission. The primary endpoint was defined as cardiovascular death or HF re‐hospitalization after discharge over a mean follow‐up period of 2.0 ± 0.1 years. The primary endpoint was recorded for 369 patients (38.2%). As expected, patients with both WRF and residual congestion at discharge had significantly less favourable outcomes compared with those without one of them, and patients without either of these two characteristics had the most favourable outcomes, whereas those with residual congestion and with WRF had the least favourable outcomes. Moreover, WRF was significantly associated with worse outcomes for high‐aged patients ≥80 years old, but not for those

Abstract Background Middle lobe torsion is a rare complication of right upper lobectomy. Middle lobe torsion can be critical; thus, various preventive measures are used. Case presentation A 77-year-old man underwent thoracoscopic right upper lobectomy with partial middle resection and S6 segmentectomy for right upper lobe lung cancer located at the confluence of the three lobes and lower lobe lung cancer. Inversion of the middle lobe was observed during lung expansion before chest closure. A bridging structure with an absorptive sheet and fibrin glue was placed in the basal section of the middle lobe under lung expansion to prevent torsion. On postoperative day 1, the patient was tachycardic and was found to have decreased lung field permeability. The patient underwent emergency surgery for suspected middle lobe torsion. Dislocation of the bridging structure between the basal segments of the middle lobe was confirmed, and the middle lobe was deviated cephalad. In addition, pulmonary congestion in S4 due to pressure stenosis of V4 caused by the deviation of the middle lobe was observed, and middle lobe resection was performed. The postoperative course was uneventful. Conclusions This case suggested that the reinforcement method with an absorptive sheet and fibrin glue lacked sufficient strength to prevent middle lobe torsion. Stronger fixation should be considered if the middle lobe rotation is thought to be sufficiently strong when the lung is reinflated before chest closure.

Abstract Background The artery of Adamkiewicz (AKA) provides the major blood supply to the lower two-thirds of the spinal cord. As the AKA typically arises from a left posterior intercostal artery at the levels between 9 and 12th thoracic vertebrae, injury of the AKA during thoracic surgery such as resection of a lower paravertebral tumor may cause serious neurological complications. Robot-assisted thoracic surgery (RATS) has several advantages over video-assisted thoracic surgery including three-dimensional and high-definition view with high image magnification and reduced restriction in movement of surgical instruments. Here, we present a case of a left paravertebral ganglioneuroma originating from the sympathetic trunk. Whereas both tumor-feeding arteries and the AKA arose from the 9th intercostal artery, complete tumor resection with preserving the AKA was achieved by RATS. Case presentation A 15-year-old girl admitted for surgery for a posterior mediastinal tumor. Chest computed tomography showed a well-circumscribed 8.0 cm tumor adjacent to 8–11th thoracic vertebrae and the descending aorta. Contrast-enhanced CT and angiography revealed that the AKA arose from the left 9th intercostal artery that ran between the tumor and the vertebrae and that tumor-feeding arteries also arose from the same intercostal artery. RATS was performed with the left intercostal approach using the da Vinci Xi system (Intuitive Surgical, Mountain View, CA). The tumor originating from the sympathetic trunk was completely resected with preserving the sympathetic trunk and the AKA. Postoperative course was uneventful without any adverse event, such as neurological complications. The final pathological diagnosis of the tumor was ganglioneuroma. Conclusions RATS is a useful surgical approach for removal of a mediastinal tumor with preserving surrounding organs or tissues, such as the AKA.

Abstract Background Salvage surgery following definitive radiotherapy or systemic treatment has become a feasible treatment option in selected patients with advanced initially unresectable non-small cell lung cancer. Recent clinical trials of neoadjuvant treatment have showed that surgery following immuno-chemotherapy is safely performed. Here, we present the first case of salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced lung large cell carcinoma. Case presentation A 44-year male was admitted to our hospital for salvage surgery. Ten months prior to this administration, he had been diagnosed with unresectable large cell carcinoma with malignant pericardial effusion (clinical stage IVA/T3N2M1A; no driver-gene alteration) originating from the right upper lobe (RUL). Due to rapid intrabronchial tumor growth causing severe dyspnea, emergency bronchial stenting in the right main bronchus using an expandable metallic stent had been performed. Thereafter, he had received immuno-chemotherapy with concurrent definitive radiotherapy. Despite dramatic radiographic response, he had suffered from persistent and refractory Pseudomonas aeruginosa lung infection associated with bronchial stent placement. As pericardial effusion had disappeared and no distant metastasis had developed, he was diagnosed with a potentially curable disease and was referred to our hospital. An extended sleeve resection was successfully performed, and pathological sections revealed that pathologic complete response was achieved with immuno-chemo-radiotherapy. The patient received no subsequent treatment, and is alive without tumor recurrence at 8 months after surgery. Conclusions Salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced non-small cell lung cancer may be feasible in selected patients, and may be considered as a treatment option to control local disease.

Abstract Background Post-esophagectomy bronchopleural fistulas can be life-threatening in patients who are exhausted, for example, by surgical stress and pleural infection; therefore, establishment of a reliable surgical procedure is extremely important. We here report a novel procedure entailing muscle flap closure for bronchopleural fistula. Case presentation A 64-year-old man developed a right bronchopleural fistula after esophagectomy. Because he was exhausted by surgical stress and malnourished, we considered reliable surgical closure of the fistula essential. Intraoperatively, it was found to connect with the membranous portion of the right main bronchus. We decided to close the fistula with a pedicled fourth and fifth intercostal muscle flap. After separating the intercostal muscles near the angle of the rib, we passed a muscle flap between the azygos vein and bronchus and sutured it securely to the fistula. The postoperative course was uneventful, and there was no thoracic infection. Postoperative bronchoscopy confirmed the muscle flap had securely closed the fistula. Conclusions The route and suturing technique of the intercostal muscle flap to a fistula are important, especially in exhausted patients.

Abstract Background Balloon aortic valvuloplasty (BAV) offers an alternative to conventional aortic valve replacement in elderly and frail patients with severe aortic stenosis (AS) for whom there are no other effective options. We aimed to investigate the mid-term effect of BAV on mitral regurgitation (MR) in patients with severe AS. Methods Our analysis was based on the data from 83 patients with severe AS (mean age, 86 ± 5 years; female, 68) treated using BAV. Echocardiography was performed before the procedure and at 1 and 3 months after. MR was quantified by measuring the MR jet area, with more-than-moderate MR being clinically significant. Results Forty patients were classified in this group (MR group). Significant reduction of MR was observed in the MR group at 1 month and 3 months after procedure, with no improvement in patients in the non-MR group. At 3 months, 15 of the 40 patients in the MR group still had significant MR, with the change at 1 month in the left ventricular end-systolic dimension (OR: 1.36; 95% CI: 1.05–1.76; P = 0.022) and MR jet area (OR: 1.95; 95% CI: 1.16–3.29; P = 0.012) being predictive of persisting significant MR at 3 months after BAV. The prevalence of New York Heart Association functional class III or IV decreased at 1 and 3 months after BAV in both groups. Conclusions BAV provides a useful therapeutic strategy for elderly patients with severe AS who are not candidates for surgical or transcatheter aortic valve replacement, especially in those with significant MR.

Background Although patients with a cancer history have a 2 to 3 times higher risk for acute coronary syndrome (ACS), the morphological characteristics of ACS culprit plaque in those patients and their relations with clinical outcomes remain unknown. Methods and Results This retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent optical coherence tomography‐guided emergent percutaneous coronary intervention. Patients were categorized into those without a cancer history, those with a cancer history, and those currently receiving cancer treatment. ACS culprit lesions were classified as plaque rupture, plaque erosion, or calcified nodule using optical coherence tomography. Plaque erosion frequency was significantly higher in culprit lesions of patients with current cancer and patients with cancer history than in those of patients without cancer history (56.3% versus 61.7% versus 36.5%). Calcified nodule incidence was significantly higher in patients without cancer history than in patients with current cancer and patients without cancer history (patients with current cancer: 12.4% versus patients without cancer history: 25.5% versus patients without cancer history: 12.6%, P

This article presents a continuous cascade model of volatility formulated as a stochastic differential equation. Two independent Brownian motions are introduced as random sources triggering the volatility cascade: one multiplicatively combines with volatility; the other does so additively. Assuming that the latter acts perturbatively on the system, the model parameters are estimated by the application to an actual stock price time series. Numerical calculation of the Fokker–Planck equation derived from the stochastic differential equation is conducted using the estimated values of parameters. The results reproduce the probability density function of the empirical volatility, the multifractality of the time series, and other empirical facts.

Abstract Background Malignant pleural mesothelioma (MPM) is an uncommon malignant tumor, and its synchronous occurrence with primary lung cancer is extremely rare. Here, we report the first surgical case of synchronous MPM and contralateral lung adenocarcinoma. Extrapleural pneumonectomy (EPP) combined with surgery for contralateral lung cancer may not be tolerated, and a lung-sparing procedure including pleurectomy/decortication (P/D) can be an alternative to achieve complete resection. Case presentation A 69-year-old male with right MPM and lung adenocarcinoma in the left upper lobe presented. Two lesions were judged to be synchronous MPM and lung cancer that were both potentially resectable clinical stage I diseases, and complete resection of both tumors was successfully achieved with right P/D following left upper division segmentectomy. Conclusions P/D, not EPP, is a less invasive surgical procedure for MPM with curative intent and can be performed in combination with contralateral lung resection.

Background We evaluated the importance of high‐density lipoprotein (HDL) functionality for target‐lesion revascularization in patients treated with coronary stents using a rapid cell‐free assay system to evaluate the functional capacity of HDL to accept additional cholesterol (cholesterol‐uptake capacity; CUC). Methods and Results From an optical coherence tomography (OCT) registry of patients treated with coronary stents, 207 patients were enrolled and their HDL was functionally evaluated by measuring the CUC. Follow‐up OCT was performed (median duration, 24.5 months after stenting) to evaluate the presence of neoatherosclerosis. Clinical follow‐up was performed to assess target‐lesion revascularization for a median duration of 42.3 months after stent implantation. Neoatherosclerosis was identified in 37 patients (17.9%). Multivariate logistic regression analysis revealed that a decreased CUC was independently associated with neoatherosclerosis (odds ratio, 0.799; P

Circulating tumor cell (CTC) is a potentially useful surrogate of micro-metastasis, but detection of rare tumor cells contaminated in a vast majority of normal hematologic cells remains technical challenges. To achieve effective detection of a variety of CTCs, we have developed a novel microfluidic system (CTC-chip) in which any antibody to capture CTCs is easily conjugated. In previous studies, we employed an antibody (clone E-1) against podoplanin that was strongly expressed on mesothelioma cells. The CTC-chip coated by the E-1 antibody (E1-chip) provided a modest sensitivity in detection of CTCs in malignant pleural mesothelioma (MPM). Here, to achieve a higher sensitivity, we employed a novel anti-podoplanin antibody (clone NZ-1.2). In an experimental model, MPM cells with high podoplanin expression were effectively captured with the CTC-chip coated by the NZ-1.2 antibody (NZ1.2-chip). Next, we evaluated CTCs in the peripheral blood sampled from 22 MPM patients using the NZ1.2-chip and the E1-chip. One or more CTCs were detected in 15 patients (68.2%) with the NZ1.2-chip, whereas only in 10 patients (45.5%) with the E1-chip. Of noted, in most (92.3%, 12/13) patients with epithelioid MPM subtype, CTCs were positive with the NZ1.2-chip. The CTC-count detected with the NZ1.2-chip was significantly higher than that with the E1-chip (p = 0.034). The clinical implications of CTCs detected with the NZ1.2-chip will be examined in a future study.

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) may achieve long-term survival in selected cases with advanced non-small cell lung cancer harboring activating mutations in the EGFR gene, but a cured case has not been reported yet. Here, we present the first case of EGFR-mutated lung adenocarcinoma cured with an EGFR-TKI, as the 75-year-old Japanese man has achieved complete response with gefitinib treatment and has survived without tumor 10 years after termination of gefitinib treatment.

Background. Treatment of tracheostenosis after tracheostomy in pediatric patients is often difficult. Mucopolysaccharidosis is a lysosomal storage disease that may induce obstruction of the airways. Case Presentation. A 16-year-old male patient underwent long-term follow-up after postnatal diagnosis of type II mucopolysaccharidosis. At 11 years of age, tracheostomy was performed for mucopolysaccharidosis-induced laryngeal stenosis. One week prior to presentation, he was admitted to another hospital on an emergency basis for major dyspnea. He was diagnosed with tracheostenosis caused by granulation. The patient was then referred to our institution. The peripheral view of his airway was difficult because of mucopolysaccharidosis-induced tracheomalacia. For airway management, a mediastinal tracheostoma was created with extracorporeal membrane oxygenation. To maintain the blood flow, the skin incision for the mediastinal tracheal hole was sharply cut without an electrotome. The postoperative course was uneventful, and the patient was weaned from the ventilator on postoperative day 19. He was discharged 1.5 months postoperatively. Although he was referred to another institution because of respiratory failure caused by his primary disease 6 months postoperatively, his airway management remained successful for 1.5 years postoperatively. Conclusion. Mediastinal tracheostomy was useful for treatment of tracheostenosis caused by granulation tissue formation after a tracheostomy.