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Introduction Binaural beats are an auditory phenomenon when two sounds with a certain frequency difference are transmitted simultaneously to each ear, one perceives a beat with a frequency exactly equal to that frequency difference. Previous studies have shown that binaural beats synchronize neural oscillations and induce related brain states and behaviors. One previous study showed that listening to binaural beats at 1 Hz during naps increased the duration of slow-wave sleep. However, the effect of binaural beats in the slow frequency range (< 1 Hz) on sleep is poorly understood. Methods We hypothesized that 0.25 Hz-binaural beats could synchronize slow neural oscillations and thus enhance slow-wave sleep by shortening its latency and lengthening its duration. Twelve healthy subjects (six females, 25.3 ± 2.6 years) were included in this study. The experiment consisted of four 90-minute afternoon naps, including a sham condition (no acoustic stimulation) and three binaural-beat conditions (0 Hz, 0.25 Hz, 1 Hz) with a 250 Hz carrier tone. Participants were not informed of these conditions. Auditory stimuli were delivered through headphones and continued throughout the 90-minute nap. Results The results showed that the binaural-beat condition at 0.25 Hz had shorter latencies for both N2 and N3 than the sham stimulus condition. Conclusion This study suggests that binaural beats at slow frequencies, such as 0.25 Hz, may induce slow-wave sleep faster in healthy individuals. Support (if any) KYOCERA Corporation, Japan, AMED (Grants No. JP21zf0127005), and World Premier International Research Center Initiative (WPI), MEXT, Japan.

Pembrolizumab, either as a type of monotherapy or in combination with cytotoxic anticancer agents, is effective in the treatment of advanced non-small cell lung cancer (NSCLC). However, the development of cancer cachexia may adversely affect anticancer drug therapy. The present study investigated the effect of cancer cachexia on clinical outcomes in patients with advanced NSCLC who received first-line pembrolizumab. The data of patients with advanced NSCLC receiving first-line monotherapy or combination therapy with pembrolizumab were retrospectively analyzed. The primary endpoint was time to treatment failure (TTF), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). Clinical outcome was compared between patients with and without cancer cachexia. A total of 53 patients were analyzed. Among all patients, median TTF and OS were significantly shorter in patients with cancer cachexia than in those without [TTF: 5.8 vs. 10 months; hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.07-4.24; P=0.016; OS: 12.1 months vs. not reached; HR: 5.85; 95% CI: 2.0-17.1; P=0.001]. In addition, TTF in the pembrolizumab monotherapy group was significantly shorter in patients with cancer cachexia than in those without, but no significant difference was detected in patients receiving pembrolizumab combination therapy. The incidence of AEs did not significantly differ between patients with and without cancer cachexia, except with regard to hypothyroidism. In conclusion, although cancer cachexia is prognostic of a poor outcome in patients with advanced NSCLC who receive first-line pembrolizumab, cancer cachexia might not affect therapeutic efficacy in combination therapy with pembrolizumab and cytotoxic anticancer agents.

Although co-administration of cisplatin (CDDP) and vinorelbine (VNR) has been established as a standard of care adjuvant chemotherapy for non-small cell lung cancer (NSCLC), there is a lack of clinical data on its safety and efficacy in Japanese patients receiving split-dose administration of CDDP. The present study analyzed patients who received CDDP + VNR with split-dose administration of CDDP after undergoing complete resection of NSCLC. Patients received four courses of CDDP (40 mg/m(2)) and VNR (25 mg/m(2)) on days 1 and 8, every 3 weeks. There were 27 male and 13 female patients; the mean age was 65 years (range 38-78 years), the postoperative disease staging distribution was IIA/IIB/IIIA: 14/8/18 patients, and histological distribution was adenocarcinoma/squamous cell carcinoma/others: 24/12/4 patients, respectively. Of the 40 patients, 28 (70%) completed the four courses of treatment. The mean total dose administered was 279 mg/m(2) CDDP (87.2%) and 172 mg/m(2) VNR (86%). The major adverse events included Grade (G) 3 or higher neutropenia (80%), G3 phlebitis (5%) and vomiting (2.5%). There was no G2 or higher serum creatinine level elevation, G3 or higher anorexia and nausea, or any treatment-related deaths. The overall completion rate of four courses was 70 and 62.5% for patients aged 70 years and older, whereas the overall percentage of patients that could complete three or more courses was 85 and 87.5% for patients aged 70 years and older. The relapse-free survival rate was 60% at 3 years and 57.5% at 5 years. Overall survival rate was 80% at 3 years and 60% at 5 years. The present study demonstrated the sufficient tolerability, safety and efficacy of combined CDDP + VNR adjuvant chemotherapy with split-dose administration of CDDP, with a low risk of gastrointestinal toxicities or nephrotoxicity.

Study ObjectivesPulse rate variability (PRV) derived from peripheral blood flow has been reported as a surrogate parameter for heart rate variability (HRV). However, there are currently no studies reporting systematic comparisons of PRV with HRV in a normal sleep state. Whether PRV can provide similar information regarding sleep stages remains unclear. Peripheral blood flow may also be modulated differently across sleep stages. Thus, we aimed to investigate blood flow dynamics and compare PRV with HRV across sleep stages to see if blood flow can provide further information about sleep stages.MethodsWe performed electrocardiography and simultaneously measured blood flow from the right index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 ± 3.4 years) during one night of sleep. Time-domain, frequency-domain, and non-linear indices of PRV/HRV, and time- and frequencydomain blood flow parameters were calculated.ResultsFinger-PRV results showed similar patterns to HRV results for most parameters. Finger-blood flow parameters in the time and frequency domains also showed information about the different sleep stages. Further, both finger- and ear-blood flow results showed 0.2–0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation (of respiration) within this frequency band.ConclusionsThese results suggest that PRV can provide as much information as HRV for different sleep stages. Furthermore, the results show that blood flow + PRV could be more advantageous than HRV alone in the assessment of the sleep state and related autonomic nervous activity.Statement of SignificanceThe research provides comprehensive information on peripheral blood flow (BF) activity across sleep stages for the first time, as the major novelty of our work. The second contribution is a systematic study comparing BF-derived pulse rate variability (PRV) with heart rate variability across sleep stages in a normal sleep state. We believe that our work makes a significant contribution to the literature because it provides comprehensive information on the potential of BF+PRV as a new biomarker for assessing the sleep state. Further, this study contributes to developing a more convenient method of assessing the sleep state in the clinical and home/work setting.

Due to the increasing complexity of cancer chemotherapy and its associated supportive care, the role of clinical pharmacists in cancer chemotherapy is becoming increasingly more important. The present study evaluated the clinical interventions of a single pharmacist on the adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy. A single-center, retrospective study was conducted at the 614-bed, tertiary care Gifu University Hospital. Hospitalized patients with thoracic cancer who received cancer chemotherapy in the respiratory medicine ward between April 2013 and May 2014 were enrolled. One of the two clinical pharmacists in charge was based in the respiratory medicine ward and implemented pharmaceutical care for the patients, including management of adverse events. Patient data were recorded in the electronic medical chart and retrospectively analyzed. A total of 445 patients with thoracic cancer received cancer chemotherapy in the respiratory medicine ward. A total of 152 interventions (101 patients) were performed by the clinical pharmacist prior to the administration of cancer chemotherapy, half of which comprised the addition of drugs to prevent adverse events. A total of 190 patients (39.4%) experienced grade ≥2 non-hematological or grade ≥3 hematological adverse events associated with cancer chemotherapy, and 223 medical interventions for relief of adverse events lowered the incidence of grade ≥2 non-hematological or grade ≥3 hematological adverse events to 17.8%. Of these, 45.3 and 7.5% of medical interventions for non-hematological and hematological adverse events, respectively, were implemented based on the pharmacist's recommendations. These findings revealed the marked contribution of a single clinical pharmacist in the respiratory medicine ward to the prevention and relief of adverse events in hospitalized patients with thoracic cancer receiving cancer chemotherapy.

Background Carboplatin (CBDCA) is known to exhibit a high emetic risk among moderate-emetic risk anticancer drugs, and the dose of CBDCA varies in different therapies. In concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC), the weekly administration of CBDCA (area under the curve (AUC) 2 mg/ml/min) and paclitaxel (PTX: 40 mg/m2) is frequently applied as standard therapy. However, the optimal antiemetic measures in the use of such low-dose CBDCA remain unclear. In this study, we retrospectively assessed the antiemetic effect of a single-dose of a first-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone in the weekly CBDCA+PTX therapy in CCRT. Patients and methods The subjects were patients with NSCLC who were administered weekly CBDCA+PTX therapy in CCRT between January 2011 and December 2016 at our Department. As an antiemetic measure, a first-generation 5-HT3RA, azasetron (10 mg, orally) or granisetron (3 mg, intravenously), and dexamethasone (9.9 mg, intravenously) were administered on day 1. The patients were evaluated for the following efficacy end-points for the first cycle: Complete response (CR; defined as no vomiting or retching episodes with no rescue medication) in the acute phase (0-24 hours), delayed phase (>24-120 hours), and overall phase (0-120 hours). Other efficacy endpoints evaluated were no vomiting or retching, and no nausea in all phases. Results The subjects we assessed in this study were 46 patients who were administered weekly CBDCA+PTX therapy in CCRT. For the overall, acute, and delayed phases, the complete response rates were 89.1%, 100%, and 89.1%, respectively. The rate of no nausea in the overall, acute, and delayed phases was 78.3%, 100%, and 78.3%, respectively. The rate of no vomiting in the overall, acute, and delayed phases was 95.7%, 100%, and 95.7%, respectively. Conclusion A single dose of a first-generation 5-HT3RA and dexamethasone had a favorable suppressive effect on nausea and vomiting in weekly CBDCA+PTX therapy for NSCLC.

Antibodies targeting the receptor programmed death 1 on T cells have been approved for the treatment of lung cancer. Immune checkpoint inhibitors (ICIs) induce various immune-related adverse events. Life-threatening hematotoxicity can be provoked by ICI therapy. Although ICI-related endocrinopathy and interstitial lung disease have been well documented, hematotoxicity requiring intensive treatment is relatively rare. We describe a case of nivolumab induced thrombocytopenia after transient mild fever. A 77-year-old man with non-small cell lung cancer was administered nivolumab (240 mg/body, every 2 weeks) as second line therapy. On the day 2 after the first nivolumab infusion, he had a fever and his C-reactive protein level was elevated. Thoracic computed tomography revealed no interstitial lung disease or pneumonia. The fever resolved on day 9 and was not seen thereafter. On day 15 after the first nivolumab infusion, severe thrombocytopenia suddenly emerged. A bone marrow examination revealed no dysplasia or invasion. Based on the presence of high platelet-associated IgG titer, normal bone marrow plasticity and a lack of effectiveness of platelet infusion, we diagnosed nivolumab-induced immune thrombocytopenia. Daily administration of 60 mg of prednisolone restored the patient's platelet count and platelet-associated IgG. We also found that there was significant shrinkage of the primary lesion and that stable disease was achieved. One must be aware of this relatively rare side effect and the unusual clinical findings that could be associated with immunoreaction. Keywords: Immune checkpoint inhibitors, Nivolumab, Thrombocytopenia, Lung cancer, Immune-related adverse events, Platelet-associated IgG

Objectives Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) represent the first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Afatinib is a second-generation EGFR-TKI with excellent therapeutic effects. However, severe diarrhea and skin disorders are observed at high frequencies, often leading to treatment interruption because of low quality of life (QOL). The relationship between individual variations and the onset of these side effects remains to be elucidated. This study aimed to reveal the association among these side effects, pharmacokinetics, and related genetic polymorphisms. Materials and methods In total, 33 patients were recruited between July 2014 and June 2017. Afatinib plasma concentrations were measured at day 9 when the concentrations reached a steady state (early phase) and when the prescription dose was stable for more than 1 month (stable phase). We analyzed single nucleotide polymorphisms in the genes ATP-binding cassette sub-family B member 1 (ABCB1), ABCG2, and flavin-containing monooxygenase 3. Results The incidences of both diarrhea and acneiform eruption were greater than 80%. Afatinib plasma concentration and the severity of diarrhea in the early phase were correlated. Pharmacokinetics-related genetic polymorphisms influenced the severity of diarrhea. Particularly, the afatinib plasma concentration was higher and diarrhea was more severe in patients carrying the A allele of ABCG2 C421A. Onset of side effects, genetic polymorphisms, and diarrhea in the maintenance phase or acneiform eruption in the early or maintenance phases were not correlated. The severity of diarrhea is influenced by drug plasma concentrations in the early phase and genetic polymorphisms related to afatinib pharmacokinetics. Conclusion Particular genetic polymorphisms can be screened before afatinib administration and the dose adapted to individual patients can be controlled, leading to reduced side effects, improved QOL, and better patient compliance to maintain the therapeutic effects.

The G-CSF is used as a therapeutic drug of the febrile neutropenia in lung cancer chemotherapy, however, there were few reports that showed the effects of combination effects of G-CSF and anticancer drugs against lung cancer. In the present study, we investigated the effects of G-CSF and the combination effects of G-CSF and cisplatin on lung cancer growth. We investigated the effect of G-CSF against the LL-2 and KLN-205 cells by MTT assay and tried to detect the G-CSF receptor by RT-PCR. Next, to analyze the G-CSF effects in vivo, we transplanted the LL-2 into C57BL/6 mice, intraperitoneally administered G-CSF (30 micro/kg/day) with or without cisplatin (5 mg/kg), measured the tumor size and analyzed pathologically by HE and immunostaining. In vitro analyses, G-CSF showed no effects in LL-2 and KLN-205 cells, and RT-PCR revealed no G-CSF receptor mRNA. In vivo analyses, G-CSF alone did not significantly suppress tumor growth. However, concurrent G-CSF administration with cisplatin significantly enhanced the tumor suppressing effect of cisplatin in early stage of tumor growth. The analysis data of vWF immunostaining indicated that the neovascularization in the peripheral region of the tumors was more enhanced in G-CSF treatment mice. ELISA assay revealed that G-CSF did not influence the serum concentration of TNF-alpha and IL-12 in tumor-bearing mice. This study suggests that concurrent (combination) administration of cisplatin with G-CSF is a safe and effective method for enhancing anticancer effects and reducing chemotherapeutic agent-induced myelosuppression.

Background Endobronchial ultrasonography (EBUS) facilitates a lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of the ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether the IBS technique can be used in lung tissue diagnoses. Methods Thirty-five consecutive patients who underwent surgery for lung cancer were prospectively enrolled. Surgical specimens of the lung and the tumor tissue were obtained, and the IBS values were measured within 48 h after surgery. Histologic images of lung and tumor tissues were compared with IBS values, and the relative interstitial area according to results of Masson’s trichrome staining were determined by using an imaging processor. Results The IBS values in tumor tissue were significantly lower than those in normal lung tissue (–50.9 ± 2.6 dB and –47.6 ± 2.6 dB, respectively; P P r = 0.53 and r = 0.67; P Conclusions Qualitative diagnosis of lung tumors was possible, with a sensitivity of 84% and a specificity of 85%, using the ultrasound IBS technique.

Combined idiopathic pulmonary fibrosis with pulmonary emphysema (CPFE) is a syndrome with a characteristic presentation of upper lobe emphysema and lower lobe fibrosis. Dyspnea on exertion (DOE) is a major symptom of CPFE. We report a patient with DOE due to CPFE who was successfully treated with acupuncture.Case report.A 72-year-old Japanese man with a 4-year history of DOE was diagnosed with CPFE 2 years previously in another hospital. He received standard Western medicine treatment, which included bronchodilators. However, his DOE did not improve. Consequently, he visited our hospital for acupuncture treatment and received acupuncture treatment once a week for 1 year.After 10 weeks of acupuncture treatment, the results of the 6-minute walk test (6-minute walking distance, 379 m; lowest oxygen saturation, 86%; modified Borg dyspnea scale score: 2 units) were better than those at baseline (352 m, 84%, 4 units, respectively). These values were sustained at both 30 weeks (470 m, 88%, 1 unit) and 60 weeks (473 m, 85%, 2 units). Serum interstitial biomarkers, Krebs von den Lungen and surfactant protein-D, decreased after commencement of acupuncture therapy.A patient with CPFE showed improvements in dyspnea scores, exercise tolerance, and serum biomarkers during a 1-year course of acupuncture treatment. Use of acupuncture might be an effective adjunct therapy in relieving DOE due to CPFE. A large, well-designed cohort study that includes patients with CPFE treated with acupuncture should be conducted.

Carboplatin (CBDCA) is known to exhibit a high emetic risk among moderate-emetic risk anticancer drugs, and the dose of CBDCA varies in different therapies. In concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC), the weekly administration of CBDCA (area under the curve (AUC) 2 mg/ml/min) and paclitaxel (PTX: 40 mg/mThe subjects were patients with NSCLC who were administered weekly CBDCA+PTX therapy in CCRT between January 2011 and December 2016 at our Department. As an antiemetic measure, a first-generation 5-HTThe subjects we assessed in this study were 46 patients who were administered weekly CBDCA+PTX therapy in CCRT. For the overall, acute, and delayed phases, the complete response rates were 89.1%, 100%, and 89.1%, respectively. The rate of no nausea in the overall, acute, and delayed phases was 78.3%, 100%, and 78.3%, respectively. The rate of no vomiting in the overall, acute, and delayed phases was 95.7%, 100%, and 95.7%, respectively.A single dose of a first-generation 5-HT

A 78-year-old man presented with urinary retention and difficulty walking. Both legs showed muscle weakness, and he was experiencing lower body hypoesthesia. T2-weighted magnetic resonance imaging revealed lesions with high signal intensity and enhancement in the spinal cord and cerebrum. A cerebrospinal fluid specimen showed inflammatory changes, but negative cytology findings. Chest computed tomography revealed a tumor measuring 40 mm in diameter, and a lung biopsy revealed the presence of squamous cell carcinoma. We diagnosed the patient with paraneoplastic neurological syndrome related to lung cancer. The patient was treated with steroid pulse therapy and chemotherapy, which relieved the symptoms and enabled the patient to achieve an independent gait.

Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.

We report a case of gefitinib-induced bilateral upper urinary tract bleeding in an 82-year-old woman administered the drug daily for advanced non-small cell adenocarcinoma of the lung (T4N3M0). Hematuria is an uncommon adverse effect of gefitinib, and in most cases, the bleeding site is unknown. On the 44th day of oral gefitinib administration, the patient noted asymptomatic macroscopic bloody urine. Cystoscopy revealed bleeding from the bilateral ureteric orifices without hemorrhagic inflammation of the bladder. One week later, she was admitted complaining of severe abdominal pain, and her condition was found to be complicated by liver damage and renal dysfunction. We stopped gefitinib administration and started hydration and diuresis. Renal function and urine output soon recovered, and at the request of the patient, we restarted gefitinib, administering it every other day, which was sufficient to maintain antitumor activity and stabilize the disease. On the 41 st day after restarting gefitinib, hematuria and proteinuria reappeared. We therefore stopped the gefitinib, and the patient was followed with supportive care. The patient's autopsy findings denied organic urologic diseases. Instead, the reproducibility of the hematuria from the upper urinary system strongly suggests an unexpected gefitinib-related adverse effect.

Toxicity and efficacy of pemetrexed monotherapy in advanced non-small-cell lung cancer patients with impaired renal function treated between May 2009 and May 2012 at Gifu University Hospital were retrospectively analyzed. A total of 10 and 17 patients had a creatinine clearance rate (Ccr) of45 mL/min and ≥45 mL/min, respectively. The median age was higher in the Ccr45 mL/min group (78.9 years) than in the ≥45 mL/min group (65.2 years). The rate of neutropenia above Grade 3 was 30% in the Ccr45 mL/min group and 6% in the ≥45 mL/min group. Therefore, reducing the dose of pemetrexed should be considered in patients with impaired renal function. Non-hematologic toxicities were not correlated with the renal function. There was no treatment-related death, and most of the toxicities were mild and tolerable. Stable disease was observed in 6 patients (60%) in the Ccr45 mL/min group, and in 12 patients (70%) in the Ccr≥45 mL/min group, although some patients in both groups showed neither complete nor partial responses. The disease control rate and median progression-free survival time were 60% and 2.8 months in the Ccr45 mL/min group, and 70% and 2.9 months in the Ccr≥45 mL/min group, respectively. Thus, in this analysis, treatment with pemetrexed resulted in clinically equivalent efficacy in advanced non-small-cell lung cancer patients regardless of the state of renal function.

Endobronchial ultrasonography (EBUS) facilitates a lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of the ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether the IBS technique can be used in lung tissue diagnoses.Thirty-five consecutive patients who underwent surgery for lung cancer were prospectively enrolled. Surgical specimens of the lung and the tumor tissue were obtained, and the IBS values were measured within 48 h after surgery. Histologic images of lung and tumor tissues were compared with IBS values, and the relative interstitial area according to results of Masson's trichrome staining were determined by using an imaging processor.The IBS values in tumor tissue were significantly lower than those in normal lung tissue (-50.9 ± 2.6 dB and -47.6 ± 2.6 dB, respectively; P .001). The IBS values of adenocarcinomas associated with a good 5-year survival rate were higher than those of non-adenocarcinomas (-48.1 ± 1.6 dB and -52.6 ± 1.4 dB; P .001). There were significant correlations between the IBS values and the relative interstitial area or micro air area in tumor (r = 0.53 and r = 0.67; P .01). After combining normal lung tissue and adenocarcinomas with a good prognosis, the sensitivity and specificity for establishing the presence of lung tumors were 84% and 85%.Qualitative diagnosis of lung tumors was possible, with a sensitivity of 84% and a specificity of 85%, using the ultrasound IBS technique.

The acute antiemetic effect was compared between oral azasetron and intravenous granisetron based on the 5-hydroxytryptamine(3) (5-HT(3)) receptor occupancy theory.Receptor occupancy was estimated from reported data on plasma concentrations and affinity constants to 5-HT(3) receptor. A randomized non-inferiority study comparing acute antiemetic effects between oral azasetron and intravenous granisetron was performed in 105 patients receiving the first course of carboplatin-based chemotherapy for lung cancer.Azasetron exhibited the highest 5-HT(3) receptor occupancy among various first-generation 5-HT(3) antagonists. The complete response to oral azasetron was shown to be non-inferior to that of intravenous granisetron, in which the risk difference was 0.0004 (95% confidence interval: -0.0519-0.0527). The lower limit of the confidence intervals did not exceed the negative non-inferiority margin (-0.1). The complete response during the overall period was not different (68% versus 67%).Oral azasetron was found to be non-inferior to intravenous granisetron in the acute antiemetic effect against moderately emetogenic chemotherapy.

Air embolism in the arterial system is a very rare but potentially fatal complication of percutaneous transthoracic needle biopsy or marking. We report a case of a patient with interstitial pneumonia associated with Sjogren syndrome, who presented with systemic arterial air embolism as a complication of computed tomography-guided marking of the lung. The air inflow route was depicted clearly on computed tomography from the peripheral pulmonary vein that crossed the needle pathway to the left atrium.

Objective: When treating lung cancer, pneumocystic pneumonia is a life-threatening complication seen during chemotherapy. Polymerase chain reaction is used to detect its cause, Pneumocystis jirovecii, but polymerase chain reaction positives without pneumocystic pneumonia are sometimes seen. The purpose of this study was to assess the frequency of pneumocystic pneumonia during cancer treatment. Methods: Fifty induced sputum specimens and 4 bronchoalveolar lavage specimens collected from 50 patients with acute respiratory symptoms during anticancer therapy were retrospectively studied after classifying the patients into lung cancer (n ¼ 29) and solid tumor (n ¼ 21) groups. All of the patients in both groups had an interstitial shadow suspected of being pneumocystic pneumonia, and all had polymerase chain reaction tests. Results: Eleven of the 54 specimens were polymerase chain reaction positive, and 1 patient was clinically diagnosed with pneumocystic pneumonia. The incidence of polymerase chain reaction positivity in the lung cancer group was significantly higher than in the solid tumor group (31 vs. 5%; P ¼ 0.03), and the incidence of subclinical pneumocystic pneumonia (29 vs. 5%; P ¼ 0.059) also tended to be higher in that group. There were no significant biochemical differences between the two groups, irrespective of the polymerase chain reaction results. Among polymerase chain reaction-positive patients in the lung cancer group, the cumulative dose of corticosteroid administration tended to be higher than among the polymerase chain reaction-negative patients (P ¼ 0.09). Following the polymerase chain reaction tests, nearly all polymerase chain reaction-positive patients without pneumocystic pneumonia received antipneumocystic agents, and none developed pneumocystic pneumonia. Conclusions: Our findings suggest polymerase chain reaction positivity for P. jirovecii will be detected in a fraction of lung cancer patients. Although it is difficult to predict the need for administration of pneumocystic pneumonia treatment to subclinical pneumocystic pneumonia based on polymerase chain reaction and biochemical results, polymerase chain reactionpositive patients should be followed-up with antipneumocystic agents to ensure they are not at an early stage of pneumocystic pneumonia.

We report a rare case of sarcoidosis-lymphoma syndrome with vertebral bone destruction. A 63-year-old woman was previously diagnosed as sarcoidosis by supraclavicular lymph node biopsy, and came to our hospital complaining of back pain. Both serum angiotensin-converting enzyme and lysozyme level had been continuously elevated. Magnetic resonance imaging revealed lumbar vertebral bone destruction. Histopathologic examination of lumbar vertebral tumor obtained by CT-guided biopsy revealed non-caseating epithelioid granuloma with CD 68 (+), AE1/AE3 (-), and no malignant cells. She was admitted to our hospital again for dyspnea and pancytopenia. We diagnosed active sarcoidosis and administered oral 30mg prednisolone daily. One month later, prednisolone became ineffective. Flow cytometry of tumor cells obtained from the gastric ulcer floor showed CD 5 (+), CD 20 (+), K chain monoclonality and we diagnosed B-cell non Hodgkin's lymphoma. She was treated by eight cycles of CHOP plus rituximab chemotherapy and achieved complete response. FDG uptake of the entire body decreased, whereas MRI revealed residual mass in the vertebrae. Sarcoidosis had been diagnosed for two and half years before lymphoma developed. Bone destruction is very rare and sarcoidosis is rarely the cause. This is quite an unusual case presenting histologically proved epithelioid granuloma and vertebral destruction in sarcoidosis-lymphoma syndrome.

Background: Bronchial artery (BA) embolization (BAE) is recommended as a minimally invasive therapy for hemoptysis, though some patients recover after only conservative treatment. Objectives: The purpose of our study was to assess the characteristics of BAs using multidetector row computed tomography (MDCT) and identify BAs requiring BAE without BA angiography (BAG). Methods: We retrospectively studied 41 patients and classified the visualized BAs into groups based on their BAE and bleeding statuses. Patients presenting with massive hemoptysis requiring emergency BAE were excluded. Patients presenting with persistent hemoptysis that was resistant to conservative treatment received BAE. Radiologists measured BA diameters at the ostium, bronchial bifurcation and pulmonary hilum, and also evaluated the degree of vascularization. Results: MDCT enabled visualization of 102 ostia and 96 traceable BAs. Among the participating patients, 13 had at least one ectopic origin. We obtained a good correlation between BAG and MDCT diameters (r = 0.709, p < 0.001). The diameters of BAs responsible for bleeding and receiving BAE were apparently larger in each measured segment than those that were not (p < 0.05). Moreover, the diameters of arteries receiving BAE remained largely unchanged from the origin to the hilum and through the mediastinum. BAs with low MDCT scores were significantly less likely to required BAE than those with high scores (p = 0.004), and in multiple logistic regression analysis, ostium diameter and bleeding status were independent predictive factors for BAE. Conclusions: Evaluation of BAs on MDCT could be useful for identifying the anatomical characteristics of bleeding-related BAs and determining whether BAE is indicated or whether conservative treatment is sufficient.

The purpose of this study was to assess the effect on bone mineral density (BMD) of systemic corticosteroid (SCS) intermittently administered for rescue from asthmatic exacerbation. Through digital image processing and calculation of four other indices, BMD was compared in groups of asthmatic patients receiving inhaled corticosteroid (ICS) alone or ICS plus intermittent SCS. We defined SCS as intermittent administration of the equivalent of 1 mg/day prednisolone in the management of asthma exacerbations during the previous 1 year. Serum NTX, a bone resorption marker, was significantly higher (p = 0.02) in the SCS group than the ICS group. SCS had no effect on BMD, although the frequency of patients at "high-risk" for osteoporosis according to the Female Osteoporosis Self-assessment Tool for Asia (FOSTA) tended to be higher in the SCS group (35%) than in the ICS (28%) or control (10%) group. Because patients in the ICS group already had impaired respiratory function due to repeated asthma exacerbations, it was difficult to determine whether it was asthma itself or SCS that is the risk factor for osteoporosis. In addition, the response of biochemical markers of bone turnover to intermittent SCS remains unclear and likely differs from that elicited by high-dose, short-term, or continuous SCS. That said, relatively low-dose intermittent administration of SCS raised levels of bone resorption markers, which likely reflects altered bone metabolism. Taken together, these findings suggest that, without consideration of its effects on bone, SCS administration should be avoided.

A 65-year-old man was admitted to our hospital complaining of diplopia, dysarthria, difficulty in walking and progressive dysesthesia that developed in his left hand and leg. Brain MRI revealed high signal intensity regions on T2-weighted and FLAIR images of the hippocampus and the corpus amygdaloideum. After admission, the patient's neurological symptoms progressed to delirium and dementia with hallucinations. When he eventually developed severe respiratory failure requiring ventilatory support, brain MRI revealed new high signal intensity regions on T2-weighted images of the medulla oblongata and pons. Chest CT scans showed a mass under the aortic arch, and based on subsequent histopathological examination of a transesophageal endoscopic ultrasonography-guided fine needle aspiration biopsy of the tumor, a diagnosis of small cell lung cancer was made. In addition, anti-Hu antibody was found in the patient's serum, leading to a diagnosis of paraneoplastic encephalomyelitis/sensory neuropathy. One course of chemotherapy (carboplatin + etoposide) was administered; however, the protocol was not completed because the patient developed severe pneumonia. Given that neurological symptoms usually precede a diagnosis of malignancy in paraneoplastic neurological syndromes, it is important that these are considered carefully, as they may contribute to early diagnosis and treatment. Here we report a rare case of severe central hypoventilation in paraneoplastic encephalomyelitis/sensory neuropathy.