Prospective screening for myocarditis in cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) improve clinical outcomes in various cancers, but sometimes induce autoimmune adverse effects, including myocarditis, which is the most serious complication. There are many reports on ICI-induced myocarditis; however, only a few prospective surveillance reports exist. Therefore, we developed a prospective screening protocol and performed monitoring clinically suspected myocarditis in every patient treated with ICIs. METHODS: We prospectively enrolled 126 consecutive patients treated with ICIs in this cohort. Outcomes of patients were determined and analyzed between April 2017 and May 2020. We evaluated vital signs, biomarkers, electrocardiograms, chest radiographs, and echocardiographs before and at 7 ±â€¯3, 14 ±â€¯3, 21 ±â€¯3, and 60 ±â€¯7 days after ICI initiation. RESULTS: Eighteen (14.3 %) presented troponin I elevation and 13 of them presented signs of clinically suspected myocarditis (10.3 %). Among the 13 patients, ICI was discontinued in four cases (3.2 %) without fatal events. Myocarditis appeared at an early stage of ICI treatment, regardless of severity (median, 44 days). CONCLUSIONS: We observed the frequency of patients with myocarditis or myocardial damage through a prospective screening program in the real world. Although the frequency was higher than expected, most cases were mild and ICI treatment could be continued under careful observation.

Effectiveness of Polyglycolic Acid Sheet Covering and Platelet-Rich Plasma after Video-Assisted Thoracic Surgery for Spontaneous Pneumothorax.

Background Video-assisted thoracic surgery (VATS) is widely used for the treatment of spontaneous pneumothorax, and the recurrence rate is high. The goal of the study was to examine the use of polyglycolic acid (PGA) sheets, together with platelet-rich plasma (PRP) from autologous blood for the prevention of postoperative recurrence of spontaneous pneumothorax. Materials and Methods We performed a retrospective study of 65 patients who underwent VATS for spontaneous pneumothorax from March 2008 to November 2011. The patients were divided into groups: without reinforcement (Group A, n = 33) and with reinforcement of the visceral pleura around the staple lines with the PGA sheet and PRP (Group B, n = 32). The postoperative follow-up period was 18 months. Results Chest tubes were used for 3.4 and 3.1 days in Groups A and B, respectively, with no significant difference between the groups. However, the recurrence rate (18.2%; 6 cases) in Group A was significantly higher than that in Group B (p = 0.02). The recurrence rates in patients younger than 25 years in Group A and Group B were 26.1 and 0.0%, respectively (p = 0.03). In Group A, the mean age with recurrence (18.3 years old) was significantly lower than the mean age without recurrence (p = 0.03). Conclusion These results suggest that the use of PGA sheets and PRP might be effective for the prevention of postoperative recurrence of spontaneous pneumothorax.

Surgical strategy for non-small cell lung cancer in octogenarians.

BACKGROUND AND OBJECTIVES: This study was conducted to determine the optimal surgical strategy for octogenarians with non-small cell lung cancer. METHODS: An observational study of 73 patients aged 80 years and over who underwent surgery for non-small cell lung cancer. Postoperative survival, mortality and morbidity were analysed. RESULTS: The age of the patients ranged from 80 to 89 with a mean of 83. Cancer types included adenocarcinoma (n = 46), squamous cell carcinoma (n = 22) and large cell carcinoma (n = 5). Lobectomy was performed in 47 patients and limited surgery in 26. The 5-year survival rate was 57.4% in pathological stage I, 88.9% in stage II and 18.2% in stage III, respectively. The 5-year survival rate of patients with stage I disease treated by limited resection (58.8%) was similar to that of patients treated by lobectomy (54.9%). Limited resection for stage IA showed slightly better survival than lobectomy (69.4% vs 48.2%, P = 0.10), however, lobectomy was superior to limited resection for stage IB (63.2% vs 16.7%, P = 0.07). Postoperative complications occurred in 27 patients (37%) and nine patients (12%) had multiple complications. There were three postoperative deaths (4.1%). CONCLUSION: The early detection of the disease, hopefully in stage IA enables surgical treatment by limited resection of patients aged 80 years and over. A favourable prognosis as well as low morbidity can be anticipated in such cases.

Met-RANTES ameliorates fibrous airway obliteration and decreases ERK expression in a murine model of bronchiolitis obliterans.

OBJECTIVES: Bronchiolitis obliterans (BO) is the main cause of late mortality among long-term survivors of lung transplantation. Chemokine-chemokine receptor (CCR) interaction and subsequent recruitment of infiltrating cells to the graft are early events in the development of chronic rejection of transplanted lungs. The present study investigated whether blockade of chemokine receptors CCR1 and CCR5 with Met-regulated-on-activation, normal T cells expressed and secreted (RANTES), an amino-terminal modified derivative of RANTES/CCL5, affects the development of BO in murine model and we sought to determine the expression of RANTES/CCL5 and their relationship with extracellular signal-regulated kinase (ERK). MATERIALS AND METHODS: BALB/c mouse tracheas were heterotopically transplanted into C57Black6 recipients and treated for 21 days with either Met-RANTES at 20 microg/day or vehicle. Animals were killed at 21 days after transplantation for histologic examination of ERK expression. RESULTS: RANTES/CCL5 was highly expressed in allografts compare to isografts. Met-RANTES treatment ameliorated fibrous airway obliteration in a mouse model of BO and decreased ERK expression. CONCLUSION: Blockade of chemokine receptors by Met-RANTES ameliorated airway obliteration and decreased ERK expression. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and ERK may be a new molecular target for chronic rejection.

Comprehensive diagnostic bronchoscopy of central type early stage lung cancer.

Due to advances in interventional bronchoscopy, curative treatment has become possible for central type lung cancer if it is detected in the early stage. However, expertise is required to diagnose the extent of tumor invasion and the depth of tumor involvement by conventional white light bronchoscopy alone, but judgement is still subjective. The development of autofluorescence bronchoscopy (AFB) and endobronchial ultrasonography (EBUS) has had a large impact on diagnostic bronchoscopy in the past decade and have been employed especially for the diagnosis of central type tumors. Objective evaluation by a comprehensive approach using AFB, EBUS and optical coherence tomography (OCT) enables selection of the optimal therapeutic strategy for central type early lung cancer (CELC).

Early detection of bronchial lesions using newly developed videoendoscopy-based autofluorescence bronchoscopy.

The combination of white light and autofluorescence bronchoscopy has been reported to show better sensitivity in detecting dysplasia and cancer of the bronchus than white light alone. However, fiberoptic bronchoscopy has been replaced by videoendoscopy at most leading facilities for over a decade. To avoid interruption of the videoendoscopy examination to perform fiberscopy-based autofluorescence examination as well as enhancing the sensitivity of intraepithelial lesions, autofluorescence diagnosis system integrated into a videoendoscope (SAFE 3000, Pentax, Tokyo) was created. A total of 154 consecutive patients were studied using this system, containing 83 known or suspected lung cancer cases, 46 of the cases with abnormal sputum cytology findings, 10 follow up cases following lung cancer operations, and 15 heavy smokers with respiratory symptoms. Abnormal findings were recognized by white light and/or SAFE 3000 at 166 sites and biopsies were taken to evaluate the relationship between endoscopic findings and pathology results. The sensitivity of the system for CIS+dysplasia was 65% in white light and 90% in SAFE. This videoendoscopy-based autofluorescence system had significantly higher sensitivity for intraepithelial lesions than white light videoendoscopy alone.

Optical coherence tomography in the diagnosis of bronchial lesions.

PURPOSE: Optical coherence tomography (OCT) can obtain high-resolution, cross-sectional microscopic images of tissue, potentially enabling optical biopsy to substitute for conventional excisional biopsy. We sought to investigate the capability of OCT to image the microstructure of normal and abnormal bronchial tissue. EQUIPMENT: The OCT system was produced by Light Lab Imaging (Boston, U.S.A.) and Pentax. (Tokyo, Japan). Preliminary examination: the OCT system was used to image-resected lung specimens from patients who had given written informed consent for this study. We inserted the OCT catheter via the working channel of the bronchoscope to evaluate the bronchial lumen. The catheter delivers a radial OCT beam and scans circumferentially to generate a transluminal image. We collected OCT images of normal bronchus, primary tumors and alveoli. All images were saved and labeled according to the patient and type of tissue imaged for later correlation with histologic studies. Clinical examination: five other patients, all of whom had given written informed consent, were examined with the OCT system under local anesthesia. The OCT catheter was inserted into the working channel of the bronchoscope for evaluation of the bronchial lumen. We collected OCT images of the normal bronchus and tumors in vivo. RESULTS: (1) Normal bronchus: the bronchial mucosal and submucosal layers appear homogeneous in OCT images. The submucosal layer is relatively reflective due to the presence of an extracellular matrix. A membrane can be seen between the submucosal and the smooth muscle layer, and areas of cartilage show high levels of scattering. (2) Alveoli: OCT images show the uniform appearance of the bronchial wall and the structure of air-containing alveoli. (3) Central type lung cancers: in preliminary and clinical examinations, the tumors showed unevenly distributed high backscattering areas and resultant loss of the normal layer structure. CONCLUSIONS: This study was the first report of the endobronchial OCT for lung cancer in clinical practice. Layers of the bronchial wall were distinctly observed in the normal bronchus on the OCT images, as opposed to bronchial tumors which lacked a layered structure. The ability of OCT to identify abnormal areas may well revise present methods for early diagnosis endoscopically.

Present strategy of lung cancer screening and surgical management.

Previous lung cancer screening trials in the United States (US) employing chest X ray and sputum cytology did not demonstrate reductions in lung cancer mortality. However, recent case control studies in Japan demonstrated a decrease in lung cancer mortality in the computed tomography (CT) screened group. Lung cancer screening using chest CT detected more cancers at an earlier stage than chest X ray. Before CT screening is widely performed, lung cancer mortality reduction should be proved in a scientific manner. The problem of a much higher false positive rate of this method should be solved. The subtypes of adenocarcinoma; bronchioloalveolar carcinoma (BAC) tends to show specific CT findings called ground glass opacity (GGO) and a favorable prognosis can be expected. BAC is usually invisible by chest X ray and detected only by CT. Recent studies have shown the proportion of GGO is strongly related to biological malignancy of small adenocarcinoma. Based on this fact, thoracic surgeons wish to identify the possibility of limited resection for minimally invasive cancers. Lung cancer researchers are interested in evaluating the nature of small adenocarcinoma as well as the carcinogenic process. A comprehensive understanding of screening-detected cancers including the CT images, pathology and genetic analysis is necessary for optimum management of such nodules.

Cytokine responsiveness in cultured human small airway epithelial cells in relation to lung transplantation.

BACKGROUND: We report a new method for collecting and establishing small airway epithelial cells (SAEC). This method enables the evaluation of the cytokine responsiveness of SAEC, which is still unknown. In this study we evaluated intercellular adhesion molecule-1 (ICAM-1) expression on SAEC stimulated with several inflammatory cytokines and compared it with that on large airway epithelial cells (LAEC). MATERIALS AND METHODS: LAEC and SAEC were treated with IFN-gamma, TNF-alpha, IL-1beta, or their combination. ICAM-1 expression under various conditions was quantified by flow cytometry. Furthermore, immunocytochemical staining was performed to determine intranuclear displacement of signal transducer and activator transcription 1 (Stat1) during ICAM-1 expression by various cytokine stimulations. RESULTS: 1) ICAM-1 expression on both LAEC and SAEC was significantly increased by IFN-gamma stimulation alone and synergistically enhanced by IFN-gamma plus TNF-alpha or IL-1beta stimulation, 2) intranuclear displacement of Stat1 in SAEC by the stimulation with IFN-gamma plus TNF-alpha or IL-1beta was recognized earlier in comparison with that by IFN-gamma stimulation alone. CONCLUSION: The previously unknown peripheral cytokine responsiveness and its mechanisms of SAEC were revealed by this study, which contributes to the understanding of chronic lung allograft rejection recognized around small airways.