Differences in Adherence Barriers to Inhaled Medicines between Japanese Patients with Chronic Obstructive Pulmonary Disease and Asthma Evaluated using the "Adherence Starts with Knowledge 20" (ASK-20) Questionnaire.

Objective This multicenter, cross-sectional, non-interventional trial aimed to investigate adherence barriers to inhaled medicines when compared with oral medicines in Japanese patients with chronic obstructive pulmonary disease (COPD) and asthma. Methods The self-reporting "Adherence Starts with Knowledge 20" (ASK-20) questionnaire was administered for adherence barriers of inhaled and oral medicines to outpatients with regular clinic attendance. Results Patients with COPD and asthma reported different adherence barriers to inhaled medicines. Independent adherence barriers [odds ratio (95% confidence interval)] to inhaled medicines relative to those for oral medicines among patients with COPD and asthma were those related to item Q8 [ "I know if I am reaching my health goals"; 2.49 (1.39-4.47); p=0.0022] and item Q2 [ "I run out of my medicine because I do not get refills on time"; 2.69 (1.26-5.75); p=0.0127], respectively. Among patients with poor adherence to only inhaled medicines, those with COPD and asthma recognized item Q3 [ "consuming alcohol and taking medicines"; 6.63 (1.27-34.7); p<0.05] and item Q1 [ "forget to take medicines only sometimes"; 4.29 (1.83-10.0); p<0.05], respectively, were recognized as independent adherence barriers to inhaled medicines. The total ASK-20 scores and total barrier counts in patients with poor adherence to inhaled medicines were significantly higher than in those without poor adherence among patients with asthma (p=0.0057) but not those with COPD (p>0.05). Conclusion These results will aid in personalizing education on adherence to inhaled medicines among patients with COPD and asthma.

Rechallenge treatment with a platinum-based regimen in patients with sensitive relapsed small-cell lung cancer.

Among patients with relapsed small-cell lung cancer (SCLC), those who relapse > 90 days after first-line chemotherapy are classified sensitive relapse. Rechallenge with a first-line platinum-based regimen has been used in sensitive relapsed SCLC patients, but its importance is not known. We evaluated the outcome of rechallenge with platinum-based chemotherapy for sensitive relapse patients. We reviewed consecutive patients with sensitive relapsed SCLC who received second-line chemotherapy between January 1999 and December 2016. We evaluated the treatment outcomes of platinum-based rechallenge and non-rechallenge regimens for second-line chemotherapy in sensitive relapse patients. Of 245 patients, 81 sensitive relapse patients received second-line chemotherapy. Sixty-seven patients (82.7%) were treated with rechallenging platinum-based regimens ("rechallenge group") and 14 patients (17.3%) were treated with other regimens ("non-rechallenge group") as second-line chemotherapy. Median progression-free survival (PFS) was 5.1 months in the rechallenge group and 3.5 months in the non-rechallenge group, and median survival time was 10.8 and 8.2 months, respectively. There were no significant differences in PFS or overall survival (OS) between the two groups. Sub-analyses of patients who received chemotherapy alone as first-line treatment showed that the rechallenge group had longer PFS than that of the non-rechallenge group (median 5.4 vs. 3.6 months, p = 0.0038), and the rechallenge group had a tendency to have longer OS than non-rechallenge group. These data suggest that rechallenge treatment with a platinum-based regimen could be second-line chemotherapy in patients with sensitive relapsed SCLC, especially those treated with chemotherapy alone as first-line therapy.

Sarcomatoid Type Primary Pericardial Mesothelioma with a Long-term Survival after the Onset of Cardiac Tamponade.

Primary pericardial malignant mesothelioma is a very rare clinical entity and its prognosis is very poor. We herein report a 67-year-old man who presented with pericardial mesothelioma that was diagnosed 21 months after the onset of cardiac tamponade as the initial manifestation. Despite undergoing pericardiocentesis and surgical pericardial fenestration at the onset of cardiac tamponade, we were unable to make a conclusive diagnosis of mesothelioma based on the cytological and histological findings. This unusual case had a relatively long progression-free period without treatment before the appearance of pleural tumors that showed the histological features of malignant sarcomatoid mesothelioma.

Ulcerative colitis in a patient with non-small-cell lung cancer receiving bevacizumab.

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, is anticipated to prolong survival with inhibition of angiogenesis in patients with non-small-cell lung cancer. Rare life-threatening adverse events affecting the digestive tract have been reported, such as gastrointestinal hemorrhage and bowel perforation. A 62-year-old Japanese woman who was diagnosed as having stage IIIB (cT4N2M0) lung adenocarcinoma received chemotherapy with bevacizumab, pemetrexed and carboplatin every 3 weeks for four cycles, which resulted in a partial response, and then continued with maintenance bevacizumab monotherapy. Fourteen days after completion of the seventh cycle of bevacizumab maintenance therapy, the patient developed sudden abdominal pain with more than 10 episodes of hematochezia per day. On the basis of colonoscopic and pathological findings, ulcerative colitis (UC) with severe pancolitis was diagnosed. This case was unresponsive to medical treatment and required subtotal colectomy for management of the ulcerative colitis. This is the first reported case of ulcerative colitis occurring during bevacizumab therapy. The anti-angiogenesis activity of bevacizumab may have been involved in the development and exacerbation of UC in this patient.

Significance of programmed cell death-ligand 1 expression and its association with survival in patients with small cell lung cancer.

BACKGROUND: Programmed cell death 1 receptor-ligand interaction is a major pathway often hijacked by tumors to suppress immune control. The aim of this retrospective study was to investigate the prevalence and prognostic roles of programmed cell death -ligand 1 (PD-L1) expression in small cell lung cancer (SCLC). METHODS: The expression of PD-L1 was evaluated by immunohistochemical analysis in 102 specimens of SCLC. Tumors with staining in over 5% of tumor cells were scored as positive for PD-L1 expression. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Expression of PD-L1 in tumor cells was observed in 71.6% (73 of 102) of SCLCs, and was significantly correlated with a limited disease (LD) stage. SCLC patients with PD-L1-positive tumors showed significantly longer overall survival (OS) than those with PD-L1-negative (median OS, 16.3 versus 7.3 months; p < 0.001, respectively). Multivariate analyses demonstrated that a good performance status, LD stage, and expression of PD-L1 were significantly predictive of better OS, independently of other factors. We found no relevance between PD-L1 expression and progression-free survival for first-line treatment in LD- and extensive disease-SCLC patients. CONCLUSIONS: In patients with SCLC, expression of PD-L1 is positively correlated with a LD stage, and is independently predictive of a favorable outcome.

Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy.

BACKGROUND: [¹8F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. METHODS: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. RESULTS: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio=2.34; 95% confidence interval, 1.18-4.64; P=0.015] and OS (hazard ratio=2.80; 95% confidence interval, 1.12-6.96; P=0.003), whereas SUVmean and SUVmax had no significant association with PFS (P=0.693 and P=0.322, respectively) or OS (P=0.587 and P=0.214, respectively). CONCLUSIONS: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

[A case of pulmonary multicentric Castleman disease which appeared as a very large lesion].

A 31-year-old man visited our hospital with a persistent cough. Computed tomography (CT) scans of his chest showed a very large mass and multiple nodular lesions in the right lung field, mediastinal and hilar lymph node enlargement and splenomegaly. Laboratory analysis showed polyclonal hyperimmunoglobulinemia and increased levels of serum C-reactive protein (14.05 mg/dl) and interleukin-6 (44.2 pg/ml). The pathological findings of lung specimens obtained using video-assisted thoracoscopy revealed hyperplasia of the lymphoid follicles with germinal centers, plasma cell infiltration which stained positively with either anti-kappa chain or anti-lambda chain antibodies, and fibrosis in the alveolar septum. We made a diagnosis of multicentric Castleman disease based on high levels of serum IL-6, multiple lymph node enlargement and splenomegaly, although this case had histological findings in common not only with Castleman disease but also with inflammatory myofibroblastic tumor. His abnormal chest radiography findings and laboratory data significantly improved 6 months after his first visit, without any treatment. Multicentric Castleman disease showing a very large mass is extremely rare.

Prognostic value of SUVmax measurements obtained by FDG-PET in patients with non-small cell lung cancer receiving chemotherapy.

[(18)F]Fluorodeoxyglucose (FDG) uptake has been shown to correlate well with tumor proliferation rates. In patients with non-small cell lung cancer (NSCLC) receiving chemotherapy, we analyzed the relationships between the maximum standardized uptake value (SUVmax) obtained by FDG positron emission tomography (FDG-PET) and other clinical factors, and examined whether or not SUVmax could predict progression-free survival (PFS) and/or overall survival (OS). This retrospective study involved 62 consecutive NSCLC patients (35 male and 27 female: median age, 65 years). All patients underwent FDG-PET examination before treatment. As the first-line treatment, the patients received chemotherapy with (n=15) or without (n=47) radiotherapy. Survival curves were obtained by the Kaplan-Meier method, and differences in survival between subgroups were analyzed by the log-rank test and the Cox proportional hazards model. Significant correlations were observed between SUVmax and gender (P=0.006), histology (P<0.001), smoking status (P=0.049), stage (P=0.015), and treatment modality (P=0.008), but not other factors, including age (P=0.402) and performance status (P=0.421). The median SUVmax was 5.1 (25-75th percentile: 3.45-7.0) in patients with adenocarcinoma and 8.3 (25-75th percentile: 6.9-9.9) in those with other types of NSCLC. Adenocarcinomas showed significantly lower SUVmax than the other tumor types (P<0.001). Cox analysis adjusting for possible confounding factors, including gender, smoking status, histology and stage, demonstrated that the hazard ratios increased as the SUVmax increased in terms of both PFS (P=0.008) and OS (P=0.045), indicating that SUVmax predicts outcome independently of other clinical factors, such as histology and stage. Our findings indicate that FDG-PET examination can provide information useful for prognostication in NSCLC.