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Pulmonary artery pseudoaneurysms (PAPs) are rare but can cause massive hemoptysis if they rupture. Infectious PAPs are often treated by surgery or transcatheter embolization and are rarely treated conservatively with antibiotics. We herein report a case of PAP treated conservatively in a 21-year-old woman with lung abscess. Except for one massive hemoptysis early in the course, the patient responded well to the empirical therapy with ampicillin/sulbactam and systemic hemostatic agents. After six weeks of antibiotics, the pseudoaneurysm disappeared. Conservative therapy with careful observation can be considered in small infectious PAPs when there is a good clinical response to initial conservative therapy.

A 74-year-old man was transferred to our hospital following loss of consciousness and a 1-month history of anorexia. He underwent lung lobectomy 3 years before the current presentation because of lung carcinoma (T2N1M0). He was initially treated with antibiotics for aspiration pneumonia and his

Criteria for discontinuation of nivolumab

Kaplan-Meier curves for overall survival (A) and progressionfree survival (B) for all patients according tumor type (epithelioid and non-epithelioid subtypes)

We herein report a 48-year-old man with a history of chronic atrial fibrillation (AF) and repeated hemoptysis after radiofrequency ablation. Contrast tomography showed soft tissue thickening of the left hilar region and left pulmonary vein stenosis. We performed bronchial artery embolization, but the hemoptysis did not disappear, and AF was not controlled. We performed left lung lobectomy and maze procedures since we considered surgical removal necessary as radical treatment. After the surgery, hemoptysis and atrial fibrillation did not recur. Refractory hemoptysis after catheter ablation is rare, but occasionally occurs in patients with severe pulmonary vein stenosis.

Background and purpose Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab. Materials and methods We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis. Results Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab. Conclusion CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5

This study aimed to evaluate the correlation and agreement between end-tidal COWe analyzed the correlation and the agreement between EtCOA total of 100 samples were included that comprised 67 men (67%). The mean age of the subjects was 77 ± 13 years. Chronic obstructive pulmonary disease (COPD) (43%) was the most common disease. There was a high correlation between EtCOEtCO

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for the treatment of EGFR mutation positive advanced nonsmall cell lung cancer (NSCLC); however, acquired resistance is known to develop during these treatments. Among these mechanisms, histological transformation is seldom encountered. Although platinum based chemotherapy has been reported to be effective in the treatment of patients with small cell lung cancer transformation, there is a lack of information on the treatment of patients with squamous cell carcinoma (SQ) transformation.An 80-year-old nonsmoking woman was referred to our hospital because of an abnormal shadow on her chest radiograph. Diagnostic bronchoscopy was performed and pathological examination revealed adenocarcinoma. Mutation analysis of the EGFR gene revealed deletion of E746-A750 in exon 19. She refused both surgical treatment and radiation therapy, and preferred periodic radiologic follow-up. Unfortunately, approximately a year and a half after the initial diagnosis, the primary lesion enlarged, and many pleural nodules were newly detected (clinically T4N2M1a, stage IVA).Based on EGFR mutation analysis, a reduced dose of daily erlotinib was prescribed, which achieved a partial response and 34 months of progression-free survival (PFS). A repeated biopsy with an endobronchial cryoprobe was performed on the enlarged primary lesion. Pathological examination revealed SQ harboring an identical EGFR mutation with a secondary EGFR T790M mutation. Osimertinib 80 mg once a day was started as second line therapy, which resulted in 8 months of PFS and 15 months of survival.The literature review and our report suggest that osimertinib is a promising treatment for NSCLC regardless of histology if T790M is present as an acquired mutation.

A 62‐year‐old woman with rheumatoid arthritis and a history of receiving immunosuppressant therapy had a recurrence of lung adenocarcinoma with EGFR L858R mutation. Following 14 months of treatment with erlotinib, computed tomography (CT) findings revealed the presence of small diffuse nodules. Bronchoscopy was performed as metastasis was suspected; however, this was not detected on lung biopsy with forceps. Transbronchial lung cryobiopsy (TBLC) succeeded in detecting metastatic adenocarcinoma, and T790M and L858R gene mutations. Pathological examination revealed a cluster of tumor cells in the intralobular interstitial areas, which was consistent with the CT findings. This report provides important information regarding the role of TBLC in diagnosing metastatic cancer, such as diffuse small miliary nodules, and its genetic mutations., This case report shows that cryobiopsy enables the diagnosis of miliary nodules as adenocarcinoma and its genetic mutations, and is a less invasive procedure than surgical lung biopsy. Cryobiopsy may be used to investigate malignant tumors and their genetic mutation in miliary nodules which liquid biopsy is unable to detect.

Introduction The coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly all over the world. The Japanese government lifted the state of emergency, announced in April 2020, on May 25, but there are still sporadic clusters. Asymptomatic patients who can transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause some of these clusters. It is thus urgent to investigate the seroprevalence of antibodies against SARS-CoV-2 and their neutralizing activity. We conducted a cross-sectional study of >10,000 samples at hospitals in Hyogo Prefecture, Japan. Methods Between August 6 and October 1, 2020, we collected samples of residual blood from the patients who visited or were admitted to five hospitals and a foundation in Hyogo. We tested the samples for antibodies against SARS-CoV-2 by electrochemiluminescence immunoassay (ECLIA) and chemiluminescent enzyme immunoassay (CLEIA). Sera that were positive by ECLIA or CLEIA were analyzed by an immunochromatographic (IC) test and neutralizing activity assay. Results We tested 10,377 samples from patients aged between 0 and 99 years old; 27 cases (0.26%) were positive on the ECLIA, and 51 cases (0.49%) were positive on CLEIA. In the 14 cases that tested positive on both ECLIA and CLEIA, the positive rates on the IC test and for neutralizing activity were high (85% and 92%, respectively). In 50 cases (0.48%) that were positive by either ECLIA or CLEIA, the corresponding rates were low (20% and 6%, respectively). The positive rate of neutralizing antibody was 0.15%. Conclusions These results indicate that most Hyogo Prefecture residents still do not have antibodies and should avoid the risk of incurring a SARS-CoV-2 infection. Two or more antibody tests should be required for seroepidemiological studies of the antibody for SARS-CoV-2, and a neutralizing activity assay is also essential.

Immune checkpoint inhibitors (ICIs) are reportedly effective against many kinds of neoplasm, but may be responsible for several kinds of immune‐related adverse events (irAEs). Among these irAEs, the incidence of myelosuppression due to ICIs is relatively low. Corticosteroids are needed to control most cases of myelosuppression. Here, we report an 88‐year‐old woman with squamous cell lung cancer who was administered pembrolizumab. After five cycles of pembrolizumab, she developed severe pancytopenia. The pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long‐term antitumor efficacy. Key points Significant findings of the study There are several kinds of immune‐related adverse events. We encountered a case of pembrolizumab‐induced pancytopenia with squamous cell lung cancer. What this study adds Corticosteroids are needed to control most cases of myelosuppression induced by ICIs, but pancytopenia induced by pembrolizumab in our case improved without steroids., An 88‐year‐old woman with squamous cell lung cancer was administered pembrolizumab. After 5 cycles of pembrolizumab, she developed severe pancytopenia. Pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long‐term anti‐tumor efficacy.

The recommended daily dose of erlotinib was determined for patients with all types of non-small cell lung cancer (NSCLC). We determined the optimal dose (OD) in patients with NSCLC harboring only epidermal growth factor receptor (EGFR) sensitizing mutations. EGFR-tyrosine kinase inhibitor-naive patients with sensitizing mutations were eligible. Clinical OD was determined in a phase I/II study based on the continual re-assessment method (CRM) of both disease control and dose-limiting toxicity, defined as any toxicity of grade 2 (G2) or higher within 8 weeks. We also determined the pharmacologic OD via a pharmacokinetic (PK) study. Thirty-eight patients were enrolled. Clinical OD was 25 mg/day by the CRM. Median progression-free survival (mPFS) was 9.3 months. In receiver operating characteristic (ROC) analysis of mPFS, the trough concentration ( Cminss ) was ≥ 0.30 μg/mL. The area under the curve (AUC) and Cminss were predicted via population PK (PopPK) or a bootstrap of 100 iterations (PopPK100 ). TOX20 was defined as

Despite various attempts to treat SARS-CoV-2-infected patients with COVID-19-convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly-neutralizing COVID-19-convalescent plasma (hn-plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn-plasmas, which were in the best 1% of 340 neutralizing-activity-determined convalescent plasma samples, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in significant reduction of viral titers in lungs by up to 32-fold as compared to the viral titers in hamsters receiving control non-neutralizing plasma, while with two moderately neutralizing plasmas (mn-plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn-plasmas also reduced viral titers in lungs than those from the two mn-plasmas. The severity of lung lesions seen in hamsters receiving hn-plasmas was minimal to moderate as assessed using micro-computerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19-convalescent-plasmas variably contained antibodies against SARS-CoV-2 components including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent-neutralizing-activity-confirmed COVID-19-convalescent plasmas would be efficacious in treating patients with COVID-19. Importance Convalescent plasmas obtained from patients, who recovered from a specific infection, have been used as agents to treat other patients infected with the very pathogen. To treat using convalescent plasmas, despite that more than 10 randomized-controlled-clinical-trials have been conducted and more than 100 studies are currently ongoing, the effects of convalescent plasma against COVID-19 remained uncertain. On the other hand, certain COVID-19 vaccines have been shown to reduce the clinical COVID-19 onset by 94-95%, for which the elicited SARS-CoV-2-neutralizing antibodies are apparently directly responsible. Here, we demonstrate that highly-neutralizing-effect-confirmed convalescent plasmas significantly reduce the viral titers in the lung of SARS-CoV-2-infected Syrian hamsters and block the development of virally-induced lung lesions. The present data provide a proof-of-concept that the presence of highly-neutralizing antibody in COVID-19-convalescent plasmas is directly responsible for the reduction of viral replication and support the use of highly-neutralizing antibody-containing plasmas in COVID-19 therapy with convalescent plasmas.

A 66-year-old man with a history of non-small cell lung cancer treated with nivolumab underwent contrast-enhanced CT and FDG PET/CT. No recurrence was demonstrated; however, soft-tissue thickening that showed delayed contrast enhancement and FDG uptake was detected around an abdominal aortic aneurysm. After discontinuation of nivolumab, the periaortic lesion disappeared within 2 months, indicating nivolumab-induced periaortitis. Immune checkpoint inhibitors such as nivolumab can cause vasculitis and periaortitis, a potentially fatal condition, as immune-related adverse events. The underlying aortic aneurysm may have contributed to genesis of periaortitis. FDG PET/CT can be useful for detecting periaortitis and excluding other forms of vasculitis.

Chylothorax is the accumulation of lipid pleural effusion. Few reports have described chylothorax caused by gastric cancer. A 45-year-old woman presented with progressive lymphedema and bilateral chylothorax. Although repetitive thoracentesis was performed to relieve her dyspnea, swelling of her axillary lymph nodes became significant. Positron emission tomography/computed tomography demonstrated the accumulation of 18F-fluorodeoxyglucose in these nodes, and a lymph node biopsy showed signet ring cell carcinoma. The primary site was a 0-IIc type lesion in the gastric body that was only detected by upper gastrointestinal endoscopy. The patient was diagnosed with advanced gastric cancer 3.5 months after presentation for chylothorax.

Purpose: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with poor prognosis. Patients with MPM who do not respond to standard first-line chemotherapy have limited treatment options. We evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, for the treatment of advanced or metastatic MPM. Patients and Methods: Japanese patients with unresectable, advanced, or metastatic MPM resistant or intolerant to ≤2 regimens of chemotherapy and ≥1 measurable lesion(s) were enrolled. Patients received nivolumab 240 mg intravenously every 2 weeks until progressive disease or unacceptable toxicity. The primary endpoint was objective response rate by central assessment according to the Modified Response Evaluation Criteria in Solid Tumors. Adverse events (AEs) and treatment-related AEs (TRAEs) were evaluated. Results: Thirty-four patients were enrolled between July 2016 and October 2016. Median follow-up was 16.8 (range: 1.8–20.2) months. Ten (29%, 95% confidence interval, 16.8–46.2) patients showed a centrally assessed objective response. The objective response rates were 26% (7/27), 67% (2/3), and 25% (1/4) patients for epithelioid, sarcomatoid, and biphasic histologic subtypes, respectively. Median duration of response was 11.1 months with a 68% disease control rate. Median overall survival and progression-free survival were 17.3 and 6.1 months, respectively. The objective response rate was 40% with programmed death-ligand 1 expression ≥1% and 8% with Conclusions: Nivolumab met the primary endpoint as second- or third-line treatment for patients with MPM and showed promising efficacy with manageable toxicity. See related commentary by Mansfield and Zauderer, p. 5438

Despite various attempts to treat SARS-CoV-2-infected patients with COVID-19-convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly-neutralizing COVID-19-convalescent plasma (hn-plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn-plasmas, which were in the best 1% of 340 neutralizing-activity-determined convalescent plasma samples, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in significant reduction of viral titers in lungs by up to 32-fold as compared to the viral titers in hamsters receiving control non-neutralizing plasma, while with two moderately neutralizing plasmas (mn-plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn-plasmas also reduced viral titers in lungs than those from the two mn-plasmas. The severity of lung lesions seen in hamsters receiving hn-plasmas was minimal to moderate as assessed using micro-computerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19-convalescent-plasmas variably contained antibodies against SARS-CoV-2 components including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent-neutralizing-activity-confirmed COVID-19-convalescent plasmas would be efficacious in treating patients with COVID-19.ImportanceConvalescent plasmas obtained from patients, who recovered from a specific infection, have been used as agents to treat other patients infected with the very pathogen. To treat using convalescent plasmas, despite that more than 10 randomized-controlled-clinical-trials have been conducted and more than 100 studies are currently ongoing, the effects of convalescent plasma against COVID-19 remained uncertain. On the other hand, certain COVID-19 vaccines have been shown to reduce the clinical COVID-19 onset by 94-95%, for which the elicited SARS-CoV-2-neutralizing antibodies are apparently directly responsible. Here, we demonstrate that highly-neutralizing-effect-confirmed convalescent plasmas significantly reduce the viral titers in the lung of SARS-CoV-2-infected Syrian hamsters and block the development of virally-induced lung lesions. The present data provide a proof-of-concept that the presence of highly-neutralizing antibody in COVID-19-convalescent plasmas is directly responsible for the reduction of viral replication and support the use of highly-neutralizing antibody-containing plasmas in COVID-19 therapy with convalescent plasmas.

This paper provides an overview of perioperative treatment for non-small cell lung cancer (NSCLC), including the current widespread use of cytotoxic anticancer agents, promising molecular targeted agents, and immuno-checkpoint inhibitors. Multiple clinical trials have confirmed that postoperative chemotherapy with cytotoxic anticancer agents should be given for stage IIB to III (according to the 8th edition of the TNM classification for NSCLC) if possible, and preoperative treatment also is recommended for patients with N2 or higher stage. However, advances in concurrent chemoradiotherapy are expected to change the significance of neoadjuvant therapy. Perioperative treatment with molecular targeted agents appears to extend disease-free survival, but there is currently no evidence that it can extend overall survival. Perioperative treatment with immune checkpoint inhibitors requires further evidence but is likely to be effective. Although perioperative treatment of NSCLC could be costly it continues to evolve in hopes of a cure.

Introduction We examined the long-term efficacy and safety of nivolumab, a human monoclonal antibody that inhibits interactions between the programmed cell death protein-1 receptor and its ligands (programmed death-ligand 1 and programmed death-ligand 2), in Japanese patients with malignant pleural mesothelioma (MPM). Methods Japanese patients with previously treated MPM (one or two regimens) were enrolled in a single-arm, phase 2 study and received nivolumab intravenously 240 mg every 2 weeks until progressive disease or unacceptable toxicity. The primary end point was the centrally assessed objective response rate. Other end points included overall survival (OS), progression-free survival (PFS), treatment-related adverse events, and patient-reported outcomes (Lung Cancer Symptom Scale for mesothelioma and EuroQOL visual analog scale). Patient enrollment started on June 16, 2016. Here, we report 3-year follow-up data (cutoff date: November 12, 2019). Results Thirty-four patients were enrolled. The centrally assessed objective response rate was previously reported (29.4%). The 2- and 3-year OS rates were 35.3% and 23.5%, respectively, and the corresponding PFS rates were 17.0% and 12.7%. Median OS and PFS were 17.3 and 5.9 months, respectively. Eight patients were alive at 3 years of follow-up. Nivolumab was well tolerated and no new safety signals were found. The patient-reported outcomes were maintained without marked deteriorations during the study. Conclusions Our results reveal clinically relevant long-term efficacy and safety of nivolumab for the treatment of MPM.

Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe bronchial asthma. Some studies have shown the clinical efficacy of this intervention, but its cost-effectiveness is unclear. The aim of this study was to evaluate the cost-effectiveness of BT. We collected data from the medical records of 16 Japanese patients who were treated with BT between February 2015 and April 2017, and compared asthma-related medical expenses between the year preceding and the year following BT. Four patients were Global Initiative for Asthma (GINA) treatment step 4, and 12 were step 5. In 8 patients who had a successful response to BT, the annual asthma-related medical expenses decreased because of a reduction in hospitalization and emergency outpatient visits due to asthma attacks, and termination of the use of biologics. Most patients in the non-responder group had increased asthma-related medical costs postoperatively. The main reason for the increase in medical costs was the add-on treatment of biologics. BT was cost-effective in the responder group. If its effects continue for more than 10 years, BT will be a cost-effective treatment. Medical costs will be reduced if those who respond to BT can be identified prior to commencement of treatment.

Background Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than the first-generation EGFR-TKIs used for first-line treatment, its efficacy with respect to long-term patient survival remains unclear even upon the administration of a complete sequence of EGFR-TKI therapy. Moreover, limited information is available regarding genetic diagnostic approaches after the treatment of EGFR-TKI–naïve patients. This study investigated the clinical characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistant to EGFR-TKIs, as well as the advantages of rebiopsy and liquid biopsy for these patients. Methods The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs, except for osimertinib, single-plexus cobas version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy. Results From April 2016 through May 2019, 113 patients were found to harbor EGFR mutations. Sixty patients were treated with EGFR-TKIs, among whom 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue biopsies and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, had a new lesion, and were administered gefitinib as first-line therapy, they were suspected to harbor the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with coexisting original mutations, brain metastases, tumor enlargement by ≥12 mm, or metastases at minor sites. Conclusion Among patients with positive factors associated with the T790M mutation, repeated tissue or liquid biopsies are useful to maximize the detection rate of the T790M substitution. Furthermore, these biopsies need to be repeated numerous times in order to reduce “detection overlook” among such patients.

Quantitative CT assessment of patients with pulmonary emphysema is used to measure pulmonary function. The present study evaluated whether the quantitative CT value can accurately estimate the risk of radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) in patients with and without emphysema. A total of 80 patients with stage I NSCLC receiving SBRT at a dose of 50 or 60 Gy in five fractions at our hospital between November 2003 and October 2015 were included in the analysis. A total of 33 (41%) patients were diagnosed with emphysema on CT examination. Dosimetric parameters, quantitative CT percentage value of low attenuation area (LAA%) in the whole lung, and average whole lung CT density values were used to examine the risk of RP. Among the 80 patients, 26 (33%) and 3 (4%) experienced Grade 1 and Grade 2 RP, respectively, during the median observation period of 18.8 (1.8-106.8) months. The RP rate for patients with a LAA% (25% (P=0.037). The RP rate in subjects with an average HU value of >-790 HU was significantly higher compared with that of patients with ≤-790 HU (P=0.036). Age (hazard ratio [HR]=2.46; P=0.03) and average HU (HR=3.39; P=0.02) were significantly associated with RP, whereas mean lung dose was not identified to be significant in multivariate analysis. The quantitative CT value was associated with RP after SBRT.

Lung cancer immunotherapy is an effective treatment option; however, it can be hampered by adverse events, including pancreatitis, associated with excessive immune activation. Here, we report the case of a 70‐year‐old patient who presented with recurrent lung squamous carcinoma and was started with pembrolizumab treatment (200 mg every three weeks). The patient developed pembrolizumab‐induced pancreatitis. After 14 months of pembrolizumab treatment, positron emission tomography–computed tomography showed a tumour‐shaped, highly integrated lesion at the pancreatic head and significantly elevated tumour markers, including carbohydrate antigen 19‐9 (149.3 U/mL), s‐pancreas antigen‐1 (44.7 U/mL), and duke pancreatic monoclonal antigen type 2 (412 U/mL). Pembrolizumab‐induced immune‐related pancreatitis was effectively treated with prednisolone 90 mg (1 mg/kg/day). Four months later, normal levels of the three specific tumour markers were detected, with improved pancreatic enzymes and radiographic findings. To our knowledge, this is the first reported case of immune‐related pancreatitis with elevated pancreatic cancer‐specific markers., We report a case of pembrolizumab‐induced immune‐related pancreatitis with the elevation of pancreatic tumour markers in a patient with squamous cell lung cancer.

Introduction In the phase III JCOG0301 trial, chemoradiotherapy (CRT) with daily low-dose carboplatin showed significant benefits in elderly patients with locally advanced non–small-cell lung cancer (NSCLC) compared with radiotherapy (RT) alone. However, the long-term patterns and cumulative incidences of toxicity associated with CRT and RT in elderly patients are not well elucidated. We report long-term survival data and late toxicities after a minimum follow-up of 6.4 years. Patients and Methods Eligible patients were older than 70 years and had unresectable stage III NSCLC. They were randomly assigned to RT or CRT. Prognosis and adverse events data were collected beyond those in the initial report. Late toxicities were defined as occurring more than 90 days after RT initiation. Results From September 2003 to May 2010, 200 patients (RT arm, n = 100; CRT arm, n = 100) were enrolled. Consistent with the initial report, the CRT arm had better overall survival than the RT arm (hazard ratio, 0.743; 95% confidence interval, 0.552-0.998; 1-sided P = .0239). The proportion of Grade 3/4 late toxicities were 7.4% (heart 2.1%, lung 5.3%) in the RT arm (n = 94) and 7.5% (esophagus 1.1%, lung 6.5%) in the CRT arm (n = 93). No additional cases of late toxicity (Grade 3/4) and treatment-related death have been seen since the initial report that was published. Conclusion Long-term follow-up confirmed the survival benefits of CRT for elderly patients with locally advanced NSCLC. There was no observed increase in late toxicity with CRT compared with RT alone.

Background The British Thoracic Society guidelines for diagnostic flexible bronchoscopy (FB) in adults recommend that intravenous sedation should be offered to patients undergoing bronchoscopy. However, it is difficult to determine the adequate depth of sedation for each patient because of inter-individual variability. Methods This prospective, open-label, single-arm study was conducted in patients undergoing routine bronchus examination with FB. All patients underwent FB under local anesthesia and conscious sedation, with initial administration of 0.03 mg/kg midazolam. The sedation level during FB was objectively assessed using the Ramsay sedation score (RSS). Two hours after the procedure, patients completed a questionnaire about its efficacy and adverse effects using a visual analog scale (VAS). Receiver operating characteristic (ROC) curve analyses were performed to determine the optimal RSS that could improve the subjective efficacy indicated by the VAS. Results This study enrolled 110 consecutive patients between September 2008 and February 2012. The median total amount of midazolam administered was 1.65 mg per patient. In an analysis of ROC curves between RSS and VAS, the area under the ROC curve for an RSS of 4 against the others was 0.66 (95% CI: 0.54 to 0.77, p = 0.014). The area under the ROC curve was not shown to be statistically significant for RSSs other than 4. Conclusions The optimal depth of conscious sedation during FB for conventional examination was achieved at an RSS of 4. The patients’ subjective evaluations indicated that a deep level of conscious sedation does not seem necessary for FB.

Development of aspergilloma is common in cases with a fungus ball-like shadow in cavities due to old tuberculosis. Some reports have shown that blood clots tend to appear as a fungus ball-like shadow. A 71-year-old man with a history of pulmonary tuberculosis presented with a fungus ball-like shadow in an old cavity and hemoptysis. There was no evidence of aspergillus infection on various examinations. We confirmed a blood clot and aneurysm of an artery under direct vision by bronchoscopy. A lateral thoracic artery aneurysm was detected by angiography. Transcatheter arterial embolization was performed. After treatment, the artery aneurysm disappeared.

Bronchoscopy is a procedure for diagnosis and treatment decision-making in patients with lung disease, especially those with acute respiratory failure. However, the optimal bronchoscopic method for patients with acute respiratory failure is not known. Therefore, in the real world, we sometimes hesitate to perform bronchoscopy in such patients because of safety and have experienced treating patients without bronchoscopy. To address this problem, we evaluated the usefulness and safety of Jackson mask ventilation, a novel noninvasive method of bronchoscopy performed under mask ventilation using the Jackson Rees circuit, in patients with acute respiratory failure.We retrospectively reviewed patients with acute respiratory failure who underwent bronchoscopy at our institution between January 2015 and May 2018. We compared patients who received Jackson mask ventilation (Jackson group) and those who received conventional oxygen administration (conventional group). Mean percutaneous oxygen saturation (SpO2) and mean oxygen flow rate were compared between the groups by the Wilcoxon signed-rank test. We excluded patients who were intubated and those without acute respiratory failure who received Jackson mask ventilation preventively.Of 1262 patients who underwent bronchoscopy, 12 were classified into the Jackson group and 13 into the conventional group. Proper oxygenation was maintained in the Jackson group, with SpO2 increasing after Jackson mask ventilation (89.4% to 96.8%, P = .03). Mean SpO2 was significantly higher in the Jackson group than in the conventional group (96.8% vs 95.2%, P = .03). Mean oxygen flow rate was significantly lower in the Jackson group (4.0 L/min vs 7.9 L/min, P

Anti-tumor necrosis factor α (anti-TNFα) agents increase the risk of tuberculosis (TB), but cases are rarely fatal. This report concerns a patient who was undergoing treatment with infliximab and presented with acute respiratory distress syndrome due to miliary TB without a miliary shadow. The findings of a pathological autopsy revealed innumerable granulomas in the organs, and the miliary nodules in the lung consisted of more unstructured granulomas. Anti-TNFα agents are unusual in the presentation of TB. It is important, particularly for patients receiving anti-TNFα agents, to constantly consider the possibility of TB and to prepare for appropriate management.

This case report describes the re-administration of abatacept to successfully reduce the articularsymptoms of a patient with rheumatoid arthritisduring the intensive phase of anti-tuberculous therapy. A 75-year-old man developed active pulmonary tuberculosis during the administration of abatacept for rheumatoid arthritis. The patient experienced a paradoxical reaction and exacerbation of rheumatoid arthritis that caused us to discontinue the abatacept. Later re-administration of abatacept along with anti-tuberculosis treatment led to well-controlled rheumatoid arthritis without exacerbation of the tuberculosis. This case shows that re-administration of abatacept may be much safer than TNF inhibitor to treat patients who are infected with mycobacteria during thetreatment of immunological diseases such asrheumatoid arthritiswith biological agents.

Background: Pemetrexed (PEM) is an efficacious multi-targeted antifolate with acceptable toxicities for non-squamous non-small cell lung cancer (non-Sq NSCLC). However, in the clinical setting, PEM has more severe adverse effects than those reported. The aim of this study was to identify the factors for the toxicities of PEM-containing chemotherapy in non-Sq NSCLC patients in the clinical setting. Patients and Methods: We retrospectively evaluated the factors related to PEM toxicities in chemotherapy-naive patients with non-Sq NSCLC from September 2009 to July 2013 at our hospital. Logistic regression model was used in the univariate and multivariate analyses. Results: In total, 104 patients were analyzed. Grades 3 to 5 hematologic toxicities were frequent and included neutropenia (42%), febrile neutropenia (7%), anemia (18%), thrombocytopenia (17%), and disseminated intravascular coagulation (2%). On multivariate analyses, the predictors were poor performance status (PS) [odds ratio (OR): 4.89, 95% confidence interval (CI): 1.22 - 19.4] and low body mass index (OR: 1.44, 95% CI: 1.05 - 1.98) for febrile neutropenia; concomitant chronic infectious disease (OR: 6.63, 95% CI: 1.59 - 27.5) and bevacizumab use (OR: 3.57, 95% CI: 1.36 - 9.32) for neutropenia; poor PS (OR: 3.02, 95% CI: 1.33 - 6.85) for thrombocytopenia; and low serum albumin level (OR: 0.22, 95% CI: 0.08 - 0.63) for non-hematologic toxicities. Conclusions: In addition to the previously reported predictors of PEM toxicities, the presence of concomitant chronic infectious disease was associated with hematologic toxicities. Patient groups who are not sufficiently evaluated in clinical trials should be carefully monitored for the development of more toxicities than expected.

Among patients with non-small cell lung cancer (NSCLC), best supportive care (BSC) is well-known to improve patient’s quality of life and prolong survival. This study aimed to clarify (1) the decision-making factors of BSC alone and (2) the prognostic factors after selection of no further anticancer therapies. We retrospectively reviewed the clinical data of patients with NSCLC between November 2004 and February 2014, who received BSC as only therapy and BSC after completion of anticancer therapies. One hundred eighteen patients received BSC alone. Among 860 patients treated with anticancer therapies, 236 were selected as control group, 160 of whom received BSC after anticancer therapy. The significant reasons for receiving BSC alone were: comorbidities of dementia, poor Eastern Cooperative Oncology Group performance status (ECOG-PS), patients’ wishes, pulmonary comorbidities, wild type epidermal growth factor receptor (EGFR), relevant social background and psychiatric comorbidities. Poor prognostic factors at the start of BSC were poor ECOG-PS, presence of disseminated intravascular coagulation (DIC), and history of anticancer therapy. NSCLC patients with comorbidities, wild type EGFR, and relevant social background factors tended to receive BSC alone. Post-cancer therapy NSCLC patients and those with DIC and declining ECOG-PS have a shorter survival period from the start of BSC.

Pleuroscopy under local anesthesia is performed by physicians in case with unexplained pleural effusion. There are limits to the bending angle and image resolution of conventional fiberscopes. Olympus Corporation and 4 Japanese institutions, including our hospital, developed a new pleuroscope for use under local anesthesia. Compared to the conventional pleuroscope (LTF-260; Olympus, Japan), the new pleuroscope (LTF-Y0032; Olympus, Japan) comes with an improved bending angle from 160 degrees to 180 degrees, and the internal diameter from 2.8mm to 3.0mm. The quality of images has also been improved. We evaluated the new pleuroscope clinically. The study population comprised 30 patients with pleural effusion of unknown etiology at our hospital, who underwent pleuroscopy using the new pleuroscope from December 2016 to January 2019. The patients included 21 men and 9 women (median age, 76 years) with 18 right and 12 left pleural effusions. In the final diagnosis, there were 17 cases of malignant disease (10 cases of pleural metastasis of lung cancer, 4 cases of malignant pleural mesothelioma, 3 cases of malignant lymphoma), and 13 cases of benign disease (4 cases of pyothorax, 4 cases of nonspecific pleurisy, 2 cases of tuberculous pleurisy, 2 cases of asbestos-related pleurisy and 1 case of IgG4-related disease). In one case of mesothelioma, the lesion was confined to a part of the pleura that cannot be observed with conventional pleuroscope, but it could be visualized by bending the new pleuroscope by 180 degrees. The new pleuroscope has an improved bending angle, image quality and channel inner diameter. The improved bending angle is likely to minimize the blind spot, improving the diagnostic rate.