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Background Osimertinib is associated with a relatively high frequency of drug-induced interstitial lung disease (D-ILD), and transient asymptomatic pulmonary opacities (TAPO) have been reported to occur during osimertinib administration. The frequency of TAPO during first-line treatment and the pros and cons of osimertinib continuation is unknown. Methods This was a multicenter, retrospective study. The purpose of this study was to research the frequency of TAPO and to evaluate osimertinib continuation in first-line therapy. We also evaluated progression-free survival (PFS) including subgroup analysis. Results From August 2018 to December 2020, 133 patients were enrolled into the study. The median observation period was 23.2 months (0.3–48.3 months). Thirty patients (22.6%) experienced D-ILD events, including 16 patients (12.1%) with CTCAE grade 1, five patients (3.8%) with grade 2, and nine patients (6.7%) with grade 3 and above D-ILD. Among the patients with grade 1 D-ILD, 11 cases (8.3%) of TAPO were observed, and all patients succeeded in osimertinib continuation. The TAPO images were characterized by localized patchy opacities (73%). The median PFS was 22.6 months (95% confidence interval [CI]: 17.8–28.7 months). Patients with TAPO had a significantly longer PFS than patients with non-TAPO D-ILD in the multivariate analysis. Conclusions This study showed that grade 1 D-ILD might include TAPO and that patients with TAPO might have good PFS. We need to consider the possibility of osimertinib continuation when lung opacities appear.

BackgroundEosinophilic polyangiitisgranulomatosa (EGPA) is a vasculitis syndrome that affects small and medium-sized blood vessels throughout the body. The mainstay of treatment is steroids, but there are no standardized doses or durations for steroids in combination with mepolizumab. MethodsWe investigated the efficacy, steroid administration, and course of steroid reduction in five patients who were diagnosed with EGPA and treated with mepolizumab for 1 year. Five patients who were diagnosed with EGPA using the American College of Rheumatology criteria and treated with mepolizumab for 1 year were included in our study from 2018–2020.ResultsEosinophil levels as well as the Birmingham Vasculitis Activity Score (BVAS), remission rate, annual relapse rate, and steroid dosage were observed at 1 year after mepolizumab treatment. Fifty-two weeks after mepolizumab treatment, eosinophils, BVAS, and the steroid dosage showed a trend toward improvement in four out of five patients. In the one patient who received no dose reduction, there was no exacerbation of bronchial asthma that had previously occurred during the follow-up period. Although neurological symptoms often remain even in remission, all patients with neurological symptoms at diagnosis improved. There were no cases of relapse in this study, including two anti-neutrophil cytoplasmic antibody-positive cases. ConclusionsManagement that includes early administration of mepolizumab may improve patients’ quality of life by alleviating lingering neurological symptoms that are caused by EGPA.

Purpose Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors >4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC. Patients and methods Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m2, on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit. Results Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4-83.7). Two-year RFS was 56.8% (95% CI, 29.7-76.9). Conclusion The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.

A 65-year-old woman visited our hospital complaining of dyspnea several days before admission. A chest X-ray showed massive right-sided pleural effusion, which was not observed 1 month previously. Although the patient had never been diagnosed with cirrhosis at regular visits, the patient was diagnosed with primary biliary cholangitis at admission. Hepatic hydrothorax was suspected because pleural effusion was transudative. A diaphragmatic fistula was confirmed and closed by thoracoscopy. Pleural effusion did not reappear after this procedure. Existence of a diaphragmatic defect should be confirmed under direct vision if pleural effusion accumulates acutely or becomes beyond control.

Pulmonary lymphangioleiomyomatosis accounts for the majority of cadaveric lung transplantation cases. Post-transplantation management is continuingly necessary not only to prevent the progression of LAM but also to address complications. A woman with lymphangioleiomyomatosis underwent cadaveric lung transplantation. She developed post-operative native lung hyperinflation and hemoptysis with cavity shadow in the native lung on computed tomography. Isolated Aspergillus from her sputum and positive Aspergillus galactomannan antigen in the blood led to a diagnosis of aspergillosis. Despite the reduction of hemoptysis by antifungal medication, she developed fatal hemoptysis. An autopsy showed an Aspergillus fungal mass in the bronchus in the native lung whilst the lung graft was free from lymphangioleiomyomatosis lesions. Endobronchial aspergilloma was suggested to be a cause of hemoptysis. This fatal clinical course suggested that hemoptysis due to endobronchial aspergilloma in the native lung should have been considered native lung pneumonectomy as a further intervention.

Motoko Tachihara,1 Tatsunori Kiriu,1 Akito Hata,2 Yukihisa Hatakeyama,3 Kyosuke Nakata,1 Tatsuya Nagano,1 Masatsugu Yamamoto,1 Kazuyuki Kobayashi,1 Hisashi Ohnishi,3 Nobuyuki Katakami,2 Yoshihiro Nishimura11Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan; 2Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Hyogo 650-0047, Japan; 3Department of Respiratory Medicine, Akashi Medical Center, Akashi, Hyogo 674-0063, JapanBackground: Nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) significantly improved overall survival in patients with metastatic pancreatic adenocarcinoma. Anti-tumor synergy between GEM and nab-PTX was recently demonstrated in a mouse model. We planned to assess the efficacy and safety of the combination of nab-PTX + GEM in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.Methods: Patients with advanced NSCLC with progressive disease after platinum-based chemotherapy, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and adequate kidney, liver and bone marrow function were eligible. Treatment consisted of nab-PTX (100 mg/m2) + GEM (1000 mg/m2) on days 1 and 8 of each 3-week cycle until progression disease or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS).Results: Of the 28 patients enrolled, all were evaluable for response and toxicity. The median age was 68 years (range 47–79), and 23 were male and 5 female. The histologic subtypes were: adenocarcinoma in 19 patients, and squamous cell carcinoma in 9 patients. Seventeen patients had ECOG PS 1 and 11 patients had PS 0. Twenty-four patients were second line and 4 patients were third line. The median number of cycles administered was 4 (range 1–10). The overall response rate was 17.9%. The disease control rate was 67.9%. The median progression-free survival was 3.1 months (95% confidence interval [CI] =1.6–4.1). Adverse events were generally tolerable except grade 3 interstitial pneumonia with in 4 patients (14.3%).Conclusion: The efficacy of nab-PTX in combination with GEM in advanced second or third-line NSCLC patients was limited and the frequent occurrence of interstitial pneumonia was unacceptable.Keywords: nab-paclitaxel, gemcitabine, non-small-cell lung cancer

A 78-year-old Japanese man who had undergone total prostatectomy for prostate cancer (pT3cN1M0, Gleason score 3 + 3) 20 years previously was referred to the Respiratory Medicine Department of our institution because of a 1-week history of chest pain and cough. Computed tomography showed multiple small nodules and mediastinal lymph node enlargement. Bronchoscopy revealed multiple soft polypoid masses and obstruction of the lingular segment. Prostate-specific antigen (PSA) concentrations had increased markedly from 0.48 ng/mL in 2014 to 741 ng/mL in 2018. The diagnosis of prostatic cancer metastases was confirmed by revealing the presence of PSA via immunohistological staining of a bronchoscopically obtained biopsy of one of the masses. The patient had not been attending scheduled follow-up visits for the past 4 years. Treatment with degarelix (a gonadotropin-releasing hormone) was started, and the PSA concentration decreased dramatically (29 ng/mL). Metastases from prostate cancer are rarely first diagnosed two decades after radical prostatectomy. This patient illustrates the importance of obtaining a complete medical history. Keywords: Bronchoscopy, Prostate cancer, Endobronchial metastases, Metastatic lung cancer, PSA

Endobronchial ultrasonography and guide sheath (EBUS-GS) technique has high diagnostic yield in lung nodules. Virtual bronchoscopic navigation (VBN) can lead bronchoscope to the target bronchi. The aim of this prospective study was to compare the diagnostic yield of two bronchoscopic procedures: bronchoscopy under EBUS-GS and VBN with or without x-ray fluoroscopy in small peripheral pulmonary lesions (PPLs, ≤30mm) with apparent CT-bronchus sign.31 patients with PPLs which had apparent CT-bronchus sign were randomly assigned to the X-ray or the non-X-ray groups (18 with and 13 without fluoroscopy) between September 1, 2012, and September 30, 2015. A bronchoscope was introduced into the target bronchus using the VBN system. Sites of specimen sampling were verified using EBUS-GS with or without fluoroscopy.The overall diagnostic yield was 83.3% in the X-ray and 69.2% in the non-X-ray group. The diagnostic yield of malignancy was 88.2% and 81.8%, respectively. The duration of the examination and time elapsed until the first EBUS visualization were similar in the X-ray and the non-X-ray group (9.0 (5.8-20.) min vs 11.0 (5.3-17.3) min, and 2.5 (1.3-14.2) min vs 4.1 (1.4-8.1) min, respectively). The fluoroscopy exposure time was 3.7 (2.9-10.56) min. The only adverse event was mild pneumothorax in a patient from the non-X-ray group, who had consequent TBB under fluoroscopy.There was a possibility that VBN-guided EBUS-transbronchial diagnosis without fluoroscopy might be equivalent to that under fluoroscopy. Further multi-center randomized study may be desired. (UMIN000008592).

Primary pleural synovial sarcoma is a malignant tumour and thought to be more aggressive than synovial sarcoma which occurs in extremities. Its treatment strategy has not been fully established because of its rarity. We report a primary pleural synovial sarcoma case which achieved a long-term survival with repeated surgery of recurrent pleural tumour. A 39-year-old man presented with a gradually enlarged tumour in the left hemithorax. The tumour was resected and diagnosed as primary pleural synovial sarcoma. The tumour was slowly growing and repeatedly recurrent in the left pleura. The surgical resections for the recurrent tumours were performed 6 years and 11 years after the initial surgery. Intriguingly, recurrent tumour which developed after second surgery exhibited temporally spontaneous regression. Our patient remains alive 12 years after the initial surgery. Repeated resection of metastatic lesion can achieve long survival in primary pleural synovial sarcoma.

The purpose is to examine the synergistic effect of pemetrexed (PEM) and amrubicin (AMR) on the proliferation of lung cancer cell lines. In vitro, dose-dependent synergistic effects of concurrent PEM and AMRol, which is an active metabolite of AMR were observed in A549 and H460 cells. In real-time RT-qPCR analysis and western blotting, expression of the target enzymes of PEM were suppressed in cells treated with amrubicinol alone. In vivo, AMR/PEM treatment also showed synergistic antitumor activity both in A549-bearing and H520-bearing mice. PEM and AMR work synergistically to inhibit the proliferation of several different lung cancer cell lines.

The present study describes a case of a 60-year-old Japanese man who was histologically diagnosed with lung adenocarcinoma harboring L858R mutation of epidermal growth factor receptor. He was successfully treated with gefitinib, but eventually developed leptomeningeal carcinomatosis. He underwent ventriculoperitoneal shunting for hydrocephalus and received erlotinib in place of gefitinib with concurrent whole brain radiotherapy; this resulted in dramatic improvement in his symptoms and performance status from four to one and he survived for as long as 13.6 months after the initiation of erlotinib therapy. This multidisciplinary approach may be particularly useful in terms of increasing survival and improving quality of life.

A 73-year-old Japanese man was histologically diagnosed with lung adenocarcinoma harboring an exon 19 deletion in the epidermal growth factor receptor. The patient was treated with gefitinib for 6 weeks until he developed substantially elevated hepatic enzyme levels that resulted in the discontinuation of gefitinib. Gefitinib was reintroduced with an intermittent treatment schedule after the transaminase levels normalized, but the patient's enzyme levels rose again, and the cancer progressed. Gefitinib was eventually replaced with erlotinib. There was stable disease for 7 weeks without any signs of liver toxicity. Thus, erlotinib may be a beneficial and well-tolerated treatment option for patients with gefitinib-related hepatotoxicity.