A Randomized Phase 2 Study of 5-Aminolevulinic Acid Hydrochloride and Sodium Ferrous Citrate for the Prevention of Nephrotoxicity Induced by Cisplatin-Based Chemotherapy of Lung Cancer.

INTRODUCTION: Cisplatin-based chemotherapy was established in the 1980s, and it has been improved by the development of a short hydration protocol in lung cancer therapy. However, cisplatin-based chemotherapy is still associated with renal toxicity. Because 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) is known to be a mitochondrial activator and a heme oxygenase-1 (HO-1) inducer, 5-ALA with SFC is speculated to mitigate cisplatin-induced renal inflammation. METHODS: We investigated the effects of oral administration of 5-ALA with SFC for preventing cisplatin-based nephrotoxicity in patients with lung cancer and evaluated its benefits for patients who received cisplatin-based chemotherapy. The primary endpoint was the significance of the difference between the serum creatinine (sCr) levels of the patients administered 5-ALA with SFC and those given placebo after course 1 of chemotherapy. The difference in the estimated glomerular filtration rate (eGFR) between the two groups was also evaluated as the secondary endpoint. RESULTS: The double-blind, randomized two-arm studies were conducted at 15 medical facilities in Japan; 54 male and 20 female patients with lung cancer who received cisplatin-based chemotherapy between the ages of 42 and 75 years were included in the study. The compliance rate was greater than 94% in the primary assessment and subsequent drug administration periods. All enrolled patients completed the four cycles of cisplatin-based chemotherapy with short hydration. The average level of sCr on day 22 of course 1 was 0.707 mg/dL in the group treated with 5-ALA and SFC and 0.735 mg/dL in the placebo group, respectively, and the sCr in the test group was significantly lower than that in the placebo group (p = 0.038). In addition, the eGFR was significantly higher in the SPP-003 group than in the placebo group up to day 1 of course 3 (84.66 and 75.68 mL/min/1.73 m2, respectively, p = 0.02) and kept better even after the last administration of the study drug (82.37 and 73.49 mL/min/1.73 m2, respectively, p = 0.013). CONCLUSIONS: The oral administration of 5-ALA with SFC is beneficial to patients undergoing cisplatin-based chemotherapy for lung cancer with short hydration.

A stealth antigen SPESP1, which is epigenetically silenced in tumors, is a suitable target for cancer immunotherapy.

Recent studies have revealed that tumor cells decrease their immunogenicity by epigenetically repressing the expression of highly immunogenic antigens to survive in immunocompetent hosts. We hypothesized that these epigenetically hidden "stealth" antigens should be favorable targets for cancer immunotherapy due to their high immunogenicity. To identify these stealth antigens, we treated human lung cell line A549 with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5Aza) and its prodrug guadecitabine for 3 d in vitro and screened it using cDNA microarray analysis. We found that the gene encoding sperm equatorial segment protein 1 (SPESP1) was re-expressed in cell lines including solid tumors and leukemias treated with 5Aza, although SPESP1 was not detected in untreated tumor cell lines. Using normal human tissue cDNA panels, we demonstrated that SPESP1 was not detected in normal human tissue except for testis and placenta. Moreover, we found using immunohistochemistry SPESP1 re-expression in xenografts in BALB/c-nu/nu mice that received 5Aza treatment. To assess the antigenicity of SPESP1, we stimulated human CD4+ T-cells with a SPESP1-derived peptide designed using a computer algorithm. After repetitive stimulation, SPESP1-specific helper T-cells were obtained; these cells produced interferon-γ against HLA-matched tumor cell lines treated with 5Aza. We also detected SPESP1 expression in freshly collected tumor cells derived from patients with acute myeloid leukemia or lung cancer. In conclusion, SPESP1 can be classified as a stealth antigen, a molecule encoded by a gene that is epigenetically silenced in tumor cells but serves as a highly immunogenic antigen suitable for cancer immunotherapy.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for clinical microbiology in 2014: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2014. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January 2014 and April 2015 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1534 strains (335 Staphylococcus aureus, 264 Streptococcus pneumoniae, 29 Streptococcus pyogenes, 281 Haemophilus influenzae, 164 Moraxella catarrhalis, 207 Klebsiella pneumoniae, and 254 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 43.6%, and those of penicillin-susceptible S. pneumoniae was 100%. Among H. influenzae, 8.2% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 49.1% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 9.2% and 0.4%, respectively.

Highly sensitive detection of ALK resistance mutations in plasma using droplet digital PCR.

BACKGROUND: On-target resistance mechanisms found in one-third of patients receiving anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are secondary ALK mutations in ALK-rearranged non-small cell lung cancer (NSCLC). There are large variations in the resistant mutations, unlike the epithelial growth factor receptor (EGFR) T790 M seen with the use of EGFR-TKIs. Liquid biopsy approaches using cell-free DNA (cfDNA) are used for screening and monitoring of mutations in NSCLC. However, feasible protocol for the simultaneous detection of multiple secondary ALK mutations using droplet digital PCR (ddPCR) has not been developed. An efficient strategy using cfDNA in cancer diagnostics, the development of more accurate and cost-effective tools to identify informative multiple secondary ALK mutations is clinically required. METHODS: To establish a feasible assay to monitor ALK-TKI resistance mutations, we first evaluated the feasibility of ddPCR-based screening for cfDNA mutation detection of 10 distinct secondary ALK mutations. Positive samples were then re-analyzed using mutation-specific probes to track the growth of mutation clones with a high sensitivity. RESULTS: Blood samples from seven ALK-positive patients were analyzed using the ddPCR protocol. Secondary G1202R ALK mutations were identified in 2 of 7 patients by the screening assay. Using the mutation-specific probes, monitoring the resistant clone during the clinical course of the disease was well demonstrated in each of the patients. CONCLUSION: The protocol for ddPCR-based liquid biopsy has a feasibility for the screening of secondary ALK-TKI resistance mutations and offers a tool for a cost-effective monitoring of progression in NSCLC.

Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report.

BACKGROUND: Immune checkpoint blockade is developed as standard treatment for non-small cell lung cancer. However immune-related adverse events (irAE) have still unknown complications. Here, we report a patient with lung squamous cell carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab. CASE PRESENTATION: A 75-year-old Japanese man with lung squamous cell carcinoma was administered nivolumab as second-line treatment. Two months after treatment with nivolumab, he presented acute paralysis in the bilateral lower limbs, sensory loss. Spinal magnetic resonance imaging showed T2 hyperintense lesions between C5-6 and Th12-L1. He was diagnosed with neuromyelitis optica spectrum disorder (NMOSD) by anti-aquaporin-4 antibody-positive in the serum and other examinations. After treatment, steroid reactivity was poor. CONCLUSION: This is the first patient who developed anti-AQP4 antibody-positive NMOSD as a nivolumab-induced irAE. Clinicians should be aware of this kind of potential neurological complication by using immune check point inhibitor and start the treatment of this irAE as soon as possible.

Observation of Zn-photoprotoporphyrin red Autofluorescence in human bronchial cancer using color-fluorescence endoscopy.

BACKGROUND: We observed red autofluorescence emanating from bronchial cancer lesions using a sensitive color-fluorescence endoscopy system. We investigated to clarify the origin of the red autofluorescence. METHODS: The wavelengths of the red autofluorescence emanating from lesions were measured in eight patients using a spectrum analyzer and compared based on pathologic findings. Red autofluorescence at 617.3, 617.4, 619.0, and 617.1 nm was emitted by normal bronchus, inflamed tissue, tissue exhibiting mild dysplasia, and malignant lesions, respectively. Protoporphyrin, uroporphyrin, and coproporphyrin, the major porphyrin derivatives in human blood, were purchased to determine which porphyrin derivative is the source of red fluorescence when acquired de novo. We synthesized photoporphyrin, Zn-protoporphyrin and Zn-photoprotoporphyrin from protoporphyrin. RESULTS: Coproporphyrin and uroporphyrin emitted only weak fluorescence. Fluorescence was emitted by our synthesized Zn-photoprotoporphyrin at 625.5 nm and by photoprotoporphyrin at 664.0 nm. CONCLUSIONS: From these results, we conclude that Zn-photoprotoporphyrin was the source of the red autofluorescence observed in bronchial lesions. Zn-protoporphyrin is converted to Zn-photoprotoporphyrin by radiation with excitation light. Our results suggest that red autofluorescence emanating from Zn-photoprotoporphyrin in human tissues could interfere with photodynamic diagnosis using porphyrin derivatives such as Photofrin® and Lazerphyrin® with a sensitive endoscopy system, because color cameras cannot differentiate Zn-photoprotoporphyrin red fluorescence from that of other porphyrin derivatives.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2012: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, Japanese association for infectious diseases and Japanese society for Clinical Microbiology in 2012. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January and December in 2012 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standard Institutes. Susceptibility testing was evaluated in 1236 strains (232 Staphylococcus aureus, 225 Streptococcus pneumoniae, 16 Streptococcus pyogenes, 231 Haemophilus influenzae, 147 Moraxella catarrhalis, 167 Klebsiella pneumoniae and 218 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 51.3%, and those of penicillin-intermediate S. pneumoniae was 0.4%. Among H. influenzae, 5.6% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 37.2% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.2% and 3.2%, respectively. Continuous national surveillance is important to determine the actual situation of the resistance shown by bacterial respiratory pathogens to antimicrobial agents.

[Persistent Chemotherapy-Induced Hiccups Successfully Treated with Pregabalin].

A 62-year-old male was diagnosed with large cell lung cancer(c-Stage IV)based on pathological examination of an anterior chest tumor. He received chemotherapy with cisplatin, pemetrexed, and bevacizumab. He suffered from persistent hiccups from day 2 of the first course of chemotherapy. He was unsuccessfully treated with chlorpromazine, shakuyakukanzoto, and gabapentin. Therefore, we administered pregabalin to him, and his hiccups subsided immediately. To prevent hiccups, he subsequently took pregabalin along with his chemotherapy regimen, and was able to receive 4 courses of chemotherapy without persistent hiccups. Pregabalin is a possible therapeutic option for treating persistent chemotherapy-induced hiccups.

Evaluation of a Quantitative Serological Assay for Diagnosing Chronic Pulmonary Aspergillosis.

The purpose of this study was to evaluate the clinical utility of a quantitative Aspergillus IgG assay for diagnosing chronic pulmonary aspergillosis. We examined Aspergillus-specific IgG levels in patients who met the following criteria: (i) chronic (duration of >3 months) pulmonary or systemic symptoms, (ii) radiological evidence of a progressive (over months or years) pulmonary lesion with surrounding inflammation, and (iii) no major discernible immunocompromising factors. Anti-Aspergillus IgG serum levels were retrospectively analyzed according to defined classifications. Mean Aspergillus IgG levels were significantly higher in the proven group than those in the possible and control groups (P < 0.01). Receiver operating characteristic curve analysis revealed that the Aspergillus IgG cutoff value for diagnosing proven cases was 50 mg of antigen-specific antibodies/liter (area under the curve, 0.94; sensitivity, 0.98; specificity, 0.84). The sensitivity and specificity for diagnosing proven cases using this cutoff were 0.77 and 0.78, respectively. The positive rates of Aspergillus IgG in the proven and possible groups were 97.9% and 39.2%, respectively, whereas that of the control group was 6.6%. The quantitative Aspergillus IgG assay offers reliable sensitivity and specificity for diagnosing chronic pulmonary aspergillosis and may be an alternative to the conventional precipitin test.

Open-label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron.

The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1-3 in combination with palonosetron (PALO), a second-generation 5-HT3 receptor antagonist, for chemotherapy-induced nausea and vomiting (CINV) in non-anthracycline and cyclophosphamide (AC) moderately-emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi-center, randomized, open-label, non-inferiority design. Patients who received non-AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2-3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non-inferiority margin was set at -15% (study treatment group - control group). From April 2011 to March 2013, 305 patients who received non-AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non-inferior to PALO plus DEX days 1-3 (difference, 2.5%; 95% confidence interval [CI]: -7.8%-12.8%; P-value for non-inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti-emetic DEX administration on days 2-3 may be eliminated when used in combination with PALO in patients receiving non-AC MEC.

Photodynamic diagnosis of pleural malignant lesions with a combination of 5-aminolevulinic acid and intrinsic fluorescence observation systems.

BACKGROUND: We have developed a new diagnostic method using the photosensitizer 5-aminolevulinic acid (5ALA) for diagnosing intrathoracic malignant lesions. When ingested exogenously, 5ALA is metabolized to a heme precursor, protoporphyrin IX, which stays in malignant cells and emits red to pink luminescence of about 630 nm. METHODS: We enrolled 40 patients who underwent respiratory surgery and consented to participate in this study. Twenty-eight patients had primary lung cancer, 8 metastatic lung tumors, 2 malignant pleural tumors, and 2 benign tumors. Localization of malignant lesions was attempted by observing such lesions with an autofluorescence imaging system and by comparing the color tone of the autofluorescence between malignant lesions and normal tissues after oral administration of 5ALA. Malignant lesions on the pleural surface emitted pink autofluorescence in contrast to the green autofluorescence of the surrounding normal tissues. RESULTS: When 28 patients with primary lung cancer were examined according to the degree of pleural infiltration (pl), red fluorescence was confirmed in 10 of 10 patients (100%) with p11-p13 and 5 of 18 patients (27.7%) with p10. The latter 5 patients had been diagnosed with PL1 preoperatively or intraoperatively. CONCLUSION: This system achieved accurate localization of malignant lesions, suggesting that it may also be applicable to photodynamic therapy.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents. Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S. pneumoniae were 1.1% and 0.0%, respectively. Among H. influenzae, 17.6% of them were found to be ß-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be ß-lactamase-non-producing ABPC-resistant and 11.0% to be ß-lactamase-producing ABPC-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 2.9% and 0.6%, respectively. Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

Ratios of peripheral-to-central airway lumen area and percentage wall area as predictors of severity of chronic obstructive pulmonary disease.

OBJECTIVE: The purpose of this study was to assess the ability of the ratios of peripheral-to-central airway lumen area (hereafter referred to as LA) and percentage wall area (hereafter referred to as %WA) to predict the severity of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SUBJECTS AND METHODS: We examined 32 patients (27 men and five women; mean age ± SD, 70.0 ± 6.8 years; seven GOLD stage 0 [at risk for COPD], 19 GOLD stage 1-2 [mild to moderate airflow limitation], and six GOLD stage 3-4 [severe to very severe airflow limitation]) using inspiratory CT. Mean LA and %WA were measured for the first (main bronchi), third, and fifth generations of five bronchi in each lobe and the ratios of peripheral to central airways were calculated (third to first, fifth to first, and fifth to third) and statistically compared. RESULTS: The fifth-generation LA, LA fifth to first, and LA fifth to third significantly decreased and fifth %WA, %WA fifth to first, and %WA fifth to third also increased with progression of GOLD stage (p < 0.05), but central measurements, including first and third generations, did not. There were significant differences between GOLD 0 and GOLD 1-2 for %WA fifth to third and LA fifth to third and between GOLD 0 and GOLD 3-4 for all six parameters (p < 0.05); %WA fifth to third had the best cutoff value of 1.02 (sensitivity, 92%; specificity, 86%) for diagnosis of COPD (GOLD 1-4). The %WA fifth to first of 1.51 (sensitivity, 83%; specificity, 89%) was best for diagnosis of GOLD 3-4. CONCLUSION: Ratios of peripheral-to-central airway LA and %WA show improved correlation with COPD severity.

Real-World Efficacy of Ensitrelvir in Hospitalized Patients With COVID-19 in Japan: A Retrospective Observational Study.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) pandemic necessitates continuously evaluating antiviral treatments, especially for high-risk groups, including older individuals. This study aimed to compare the efficacy of three antiviral drugs, including remdesivir, molnupiravir, and ensitrelvir, in hospitalized patients as measured by our own institution's antigen test, focusing on outcomes, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen levels, hospitalization duration, and fever resolution. METHODS: This retrospective observational study was conducted at Yoshida Hospital, Asahikawa City, Japan, enrolling 154 patients who received antiviral treatment upon COVID-19 diagnosis from July 1, 2022, to September 15, 2023. The diagnosis was confirmed by proprietary antigen tests or loop-mediated isothermal amplification assays. Patients who received treatment outside the hospital or with consistently negative antigen results were excluded. Drug administration was determined by attending physicians, considering oral administration challenges and renal dysfunction. The data were statistically analyzed using an unpaired two-tailed Student's t-test and one-way analysis of variance complemented by the Tukey post-hoc test for detailed group comparisons. RESULTS: No significant differences were observed in the initial antigen levels among the treatment groups. By day 10, the ensitrelvir group showed lower antigen levels than the other groups, but not significantly. The ensitrelvir group had a higher antigen-negative conversion rate and a significantly shorter hospital stay than the molnupiravir group. However, no significant differences were noted in the fever resolution time among the groups. CONCLUSION: This study suggests the potential benefits of ensitrelvir in reducing antigen levels and hospitalization duration. However, the overall efficacy of the antiviral agents for symptomatic relief appears similar. These findings underscore the need for further research to optimize COVID-19 management by considering personalized treatment approaches and long-term outcomes.

Complications associated with endobronchial ultrasound-guided transbronchial needle aspiration: a nationwide survey by the Japan Society for Respiratory Endoscopy.

BACKGROUND: With the recent widespread use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there have been occasional reports on complications associated with its use. Previous reviews on EBUS-TBNA have been limited to studies by skilled operators, thus the results may not always be applicable to recent clinical practice. To assess the safety of EBUS-TBNA for the staging and diagnosis of lung cancer in Japan, a nationwide survey on its current usage status and complications associated with its use was conducted by the Japan Society for Respiratory Endoscopy (JSRE). METHODS: A questionnaire about EBUS-TBNA performed between January 2011 and June 2012 was mailed to 520 JSRE-accredited facilities. RESULTS: Responses were obtained from 455 facilities (87.5%). During the study period, EBUS-TBNA was performed in 7,345 cases in 210 facilities (46.2%) using a convex probe ultrasound bronchoscope, for 6,836 mediastinal and hilar lesions and 275 lung parenchymal lesions. Ninety complications occurred in 32 facilities. The complication rate was 1.23% (95% confidence interval, 0.97%-1.48%), with hemorrhage being the most frequent complication (50 cases, 0.68%). Infectious complications developed in 14 cases (0.19%) (Mediastinitis, 7; pneumonia, 4; pericarditis, 1; cyst infection, 1; and sepsis, 1). Pneumothorax developed in 2 cases (0.03%), one of which required tube drainage. Regarding the outcome of the cases with complications, prolonged hospitalization was observed in 14 cases, life-threatening conditions in 4, and death in 1 (severe cerebral infarction) (mortality rate, 0.01%). Breakage of the ultrasound bronchoscope occurred in 98 cases (1.33%) in 67 facilities (31.9%), and that of the puncture needle in 15 cases (0.20%) in 8 facilities (3.8%). CONCLUSIONS: Although the complication rate associated with EBUS-TBNA was found to be low, severe complications, including infectious complications, were observed, and the incidence of device breakage was high. Since the use of EBUS-TBNA is rapidly expanding in Japan, an educational program for its safe performance should be immediately established.

Bronchoscopic practice in Japan: a survey by the Japan Society for Respiratory Endoscopy in 2010.

BACKGROUND AND OBJECTIVE: To ensure the safety of bronchoscopic practice, the Japan Society for Respiratory Endoscopy conducted a national survey to investigate the current state of procedure for this technique. METHODS: A questionnaire survey about procedures carried out during the whole of the year 2010 was mailed to 538 facilities accredited by the society. RESULTS: Responses were obtained from 511 facilities (95.0%). Rigid bronchoscopes were used in only 18.5% of the facilities, while mobile/thin bronchoscopes were used in ≥ 50%, and fluoroscopy systems were used in 99.8%. Biopsies were performed after discontinuation of therapy in patients receiving antiplatelet drugs and anticoagulants in 96.7% and 97.4% of the facilities, respectively. Atropine was administered for premedication in 67.5% of the facilities, a decrease from previous surveys. Intravenous sedation was given in 36.1% of the facilities. In 21.9% of these, the procedure was conducted in the outpatient clinic for ≥ 70% of patients. A bronchoscope was orally inserted in ≥ 70% of patients in 95.7% of the facilities. Intravenous access was maintained during the examination in 92.5% of the facilities, oxygen saturation was monitored during examinations in 99.0%, oxygen was administered in 97.6% and resuscitation equipment was available in 96%. In 98.6% of the facilities, bronchoscopes were disinfected using an automatic washing machine, with glutaraldehyde used in 42.2%. CONCLUSIONS: Japan-specific characteristics of bronchoscopic practice were identified. Whether procedures used in Japan meet international guidelines with respect to safety should be monitored continuously. In addition, a Japanese evidence-based consensus is needed.

[An elderly patient with large cell neuroendocrine carcinoma(LCNEC)for whom chemotherapy with irinotecan and split-dose cisplatin(CDDP)proved very effective].

Large cell neuroendocrine carcinoma(LCNEC)is a rare malignant disease with a poor and the clinical outcome. Although no standard chemotherapy regimen has been developed, LCNEC should be treated in a manner similar to that used for small cell lung cancer because of their similar chemosensitivity and aggressive characteristics, even though LCNEC is classified as non-small cell lung cancer. A 78-year-old man was admitted with the complaint of convulsions on the left side of his body. A chest computed tomographic(CT)scan on admission demonstrated a 4 cm mass in a left lung S9. Brain magnetic resonance imaging(MRI)revealed enhanced tumors in the left occipital lobe. The brain tumor was surgically resected and histological findings were diagnosed as LCNEC. After induction of 4 courses with irinotecan and split-dose cisplatin chemotherapy, a partial response was obtained. After 4 courses, the tumor size was increased, and the chemotherapy was changed to amrubicin. The patient is alive and with no relapse.

Deaths and complications associated with respiratory endoscopy: a survey by the Japan Society for Respiratory Endoscopy in 2010.

BACKGROUND AND OBJECTIVE: In order to survey the current status of the use and complications associated with respiratory endoscopy, the Japan Society for Respiratory Endoscopy conducted a nationwide postal questionnaire survey. METHODS: The survey was mailed to all 538 facilities certified by the society. The subjects were patients who underwent respiratory endoscopy in 2010. The numbers of procedures, and associated complications and deaths were investigated according to lesion and procedure using a specific inventory. RESULTS: The inventory was completed by 483 facilities (89.8%). The total number of diagnostic flexible bronchoscopy procedures performed was 103 978, and four patients died (0.004%). The complication rate according to lesion ranged from 0.51% to 2.06%, with the highest rate being observed in patients with diffuse lesions. The complication rate according to procedure ranged from 0.17% to 1.93%, with the highest rate being observed in patients who underwent forceps biopsy. The complication rate after forceps biopsy of solitary peripheral pulmonary lesions was 1.79% (haemorrhage: 0.73%, pneumothorax: 0.63%), and that after endobronchial ultrasound-guided transbronchial needle aspiration of hilar and/or mediastinal lymph node lesions was 0.46%. Therapeutic bronchoscopy was performed in 3020 patients; one patient (0.03%) died due to haemorrhage induced by insertion of an expandable metallic stent. The complication rate according to procedure was highest for foreign body removal (2.2%). Medical pleuroscopy was performed in 1563 patients. The highest complication rate was for biopsy without electrocautery (1.86%). A total of 228 facilities (47.2%) experienced breakage of bronchoscopes and/or devices. CONCLUSIONS: Respiratory endoscopy was performed safely, but education regarding complications caused by new techniques is necessary.

Nationwide surveillance of bacterial respiratory pathogens conducted by the Surveillance Committee of Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Clinical Microbiology in 2009: general view of the pathogens' antibacterial susceptibility.

For the purpose of nationwide surveillance of antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, the Japanese Society of Chemotherapy (JSC) started a survey in 2006. From 2009, JSC continued the survey in collaboration with the Japanese Association for Infectious Diseases and the Japanese Society for Clinical Microbiology. The fourth-year survey was conducted during the period from January and April 2009 by the three societies. A total of 684 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 635 strains (130 Staphylococcus aureus, 127 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 123 Haemophilus influenzae, 70 Moraxella catarrhalis, 78 Klebsiella pneumoniae, and 103 Pseudomonas aeruginosa). A maximum of 45 antibacterial agents including 26 ß-lactams (four penicillins, three penicillins in combination with ß-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), four aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). Incidence of methicillin-resistant S. aureus (MRSA) was as high as 58.5 %, and that of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) was 6.3 % and 0.0 %, respectively. Among H. influenzae, 21.1 % of them were found to be ß-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 18.7 % to be ß-lactamase-non-producing ABPC-resistant (BLNAR), and 5.7 % to be ß-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5 %) of ß-lactamase-producing strains has been suspected in Moraxella catarrhalis isolates. Four (3.2 %) extended-spectrum ß-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5 %) of P. aeruginosa were found to be metallo-ß-lactamase-producing strains, including three (1.9 %) suspected multi-drug resistant strains showing resistance against imipenem, amikacin, and ciprofloxacin. Continuous national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

Phase II study of irinotecan plus S-1 combination for previously untreated advanced non-small cell lung cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0601.

OBJECTIVE: Platinum-free regimens can represent an alternative for advanced non-small cell lung cancer (NSCLC) if similar efficacy is provided with better tolerability. This study evaluated the efficacy and safety of combined irinotecan and S-1 for chemotherapy-naïve advanced NSCLC. METHODS: Chemotherapy consisted of 4-week cycles of intravenous irinotecan (100 mg/m(2), days 1 and 15) and oral S-1 (80 mg/m(2), days 1-14). The primary endpoint was response rate, while secondary endpoints were overall survival, progression-free survival (PFS), and safety. RESULTS: A total of 112 cycles was administered to 40 patients (median 3 cycles; range 1-6 cycles). Twelve patients showed partial response and 17 patients had stable disease, representing a response rate of 30% and a disease control rate of 72.5%. Median survival time and median PFS were 16.1 and 4.8 months, respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common nonhematological toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055). CONCLUSION: The combination of irinotecan and S-1 offers good efficacy and tolerability for previously untreated advanced NSCLC.