Highly Neutralizing COVID-19 Convalescent Plasmas Potently Block SARS-CoV-2 Replication and Pneumonia in Syrian Hamsters.

Despite various attempts to treat severe acute respiratory syndrome coronavirus 2 (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 plasmas, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in a significant reduction of viral titers in lungs by up to 32-fold compared to the viral titers in hamsters receiving control nonneutralizing 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 more 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 microcomputerized 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 to 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.

Correlation of toxicities and efficacies of pemetrexed with clinical factors and single-nucleotide polymorphisms: a prospective observational study.

BACKGROUND: Pemetrexed is an efficacious multi-targeted antifolate with acceptable toxicity for non-squamous non-small cell lung cancer (non-Sq NSCLC) and malignant pleural mesothelioma. Vitamin B12 and folic acid as premedication can reduce the frequency of severe toxicities of pemetrexed chemotherapy. However, adverse effects are frequent in clinical settings. In this study, we aimed to identify the clinical factors and single-nucleotide polymorphisms (SNPs) associated with the toxicity and efficacy of pemetrexed chemotherapy. METHODS: This observational study was conducted from October 2012 to December 2019; we evaluated the toxicities and efficacies of pemetrexed chemotherapy using multivariate logistic or Cox regression analysis. In total, 106 patients received pemetrexed chemotherapy. SNPs were analyzed for four patients with malignant pleural mesothelioma and 67 with non-Sq NSCLC. RESULTS: The median progression-free survival (PFS) and overall survival of 63 patients with non-Sq NSCLC, excluding four in the adjuvant setting, were 6.8 and 33.3 months, respectively. Per propensity-score-adjusted multivariate Cox analyses, favorable factors for PFS were folic acid level ≥ 9.3 ng/mL before premedication, platinum combination, bevacizumab combination, vitamin B12 level < 1136 pg/mL before chemotherapy, A/A + A/G of BHMT (742 G > A), and A/A + A/C of DHFR (680 C > A). Favorable prognostic factors included good performance status, low smoking index, body mass index ≥ 20.66 kg/m2, folic acid level ≥ 5.55 ng/mL before premedication, higher retinol-binding protein before chemotherapy, and A/G of MTRR (66 A > G). Among the 71 patients who were analyzed for SNPs, the frequencies of hematologic toxicities and non-hematologic toxicities in Grades 3-4 were 38% and 36.6%, respectively. Per propensity-score-adjusted multivariate logistic analyses, risk factors for Grades 3-4 hematologic toxicities were vitamin B12 level < 486 pg/mL before premedication, leucocyte count < 6120 /µL before chemotherapy, folic acid level < 15.8 ng/mL before chemotherapy, status with a reduced dose of chemotherapy, and C/T + T/T of MTHFR (677 C > T). Risk factors for Grades 2-4 non-hematologic toxicities were homocysteine levels ≥ 11.8 nmol/mL before premedication, transthyretin level < 21.5 mg/dL before chemotherapy, C/C + T/T of MTHFR (677 C > T), and A/A + G/G of SLC19A1 [IVS2 (4935) G > A]. CONCLUSION: The information on metabolites and SNPs of the folate and methionine cycle will help predict the toxicities and efficacies of pemetrexed. TRIAL REGISTRATION: This trial was retrospectively registered with the University hospital Medical Information Network (UMIN000009366) on November 20, 2012.

Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations.

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.

Multicenter, placebo-controlled, double-blind, randomized study of fosnetupitant in combination with palonosetron for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.

BACKGROUND: The current randomized, double-blind, phase 2 study assessed the efficacy and safety profile of a single intravenous administration of fosnetupitant, a neurokinin 1 receptor antagonist prodrug, for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving cisplatin-based chemotherapy. METHODS: Patients scheduled to receive cisplatin (at a dose of ≥70 mg/m2 )-based regimens were randomly assigned to receive fosnetupitant at a dose of 81 mg or 235 mg or placebo in combination with palonosetron at a dose of 0.75 mg and dexamethasone. The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase (0-120 hours). The overall CR rate was compared between each dose of fosnetupitant and the placebo group adjusting for the stratification factors of sex and age class (age <55 years vs age ≥55 years). Safety was assessed, with special attention given to events that potentially were suggestive of infusion site reactions. RESULTS: A total of 594 patients were randomized. Of these, 194 patients, 195 patients, and 195 patients, respectively, in the placebo and fosnetupitant 81-mg and 235-mg dose groups were evaluable for efficacy. The overall CR rate was 54.7% for the placebo group, 63.8% for the fosnetupitant 81-mg dose group (adjusted difference, 9.1%; 95% CI, -0.4% to 18.6% [P = .061]), and 76.8% for the fosnetupitant 235-mg dose group (adjusted difference, 22.0%; 97.5% CI, 11.7% to 32.3% [P < .001]). Safety profiles were comparable between the 3 groups. The incidence of infusion site reactions related to fosnetupitant was ≤1% in each dose group. CONCLUSIONS: Fosnetupitant at a dose of 235 mg provided superior prevention of chemotherapy-induced nausea and vomiting among patients receiving cisplatin-based chemotherapy compared with the control group, and with a satisfactory safety profile.

Quality of life and survival survey of cancer cachexia in advanced non-small cell lung cancer patients-Japan nutrition and QOL survey in patients with advanced non-small cell lung cancer study.

PURPOSE: Although cancer cachexia is mainly characterized by persistent loss of body weight (BW), usually in response to a malignancy, the pathophysiology of cachexia remains unresolved. To elucidate the relationship between the loss of BW and other related clinical factors, we conducted a nationwide, multi-institutional, prospective, observational study in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Treatment-naïve stage IV NSCLC patients with an Eastern Cooperative Oncology Group performance status (PS) of 0-2 were eligible. BW, handgrip strength (HGS), quality of life (QOL), Karnofsky Performance Scale (KPS), biochemical parameters, and survival were evaluated at baseline and every 4 weeks for 1 year. The relationship between BW loss and other factors was examined by linear regression analysis. Estimated survival curves were drawn by the Kaplan-Meier method and applied by the log-rank test. Clinical factors associated with cancer cachexia were identified through principal component analysis. The generalized estimating equation approach was used to analyze the deterioration of QOL resulting from the progression of cachexia. RESULTS: A total of 406 patients were analyzed. BW loss was significantly associated with worsening of QOL, HGS, KPS, and biochemical parameters. The incidence of BW loss was observed throughout the study period. Overall survival was significantly shorter in patients as BW loss progressed. BW loss, decrease in HGS, anorexia, and fatigue were identified as core factors of cachexia that contributed to the deterioration of QOL. CONCLUSION: BW loss most likely deteriorated QOL and shortened survival in patients with advanced NSCLC and should be closely monitored.

[Additional external radiotherapy to multiple metastases originating from thymic neuroendocrine tumor following peptide receptor radionuclide therapy: a case report].

We describe the case of a 60-year-old man suffering from an advanced thymic neuroendocrine tumor with left supraclavicular lymph node and multiple bone metastases. The patient initially underwent systemic therapy with somatostatin analogues. Thereafter, peptide receptor radionuclide therapy (PRRT) was considered because the lesions had remained stable despite the pharmacological therapy. PRRT was performed 10 months after the initial treatment in a European hospital. Eighteen months after the treatment, cranial nerve palsy arising from skull base metastases and Horner's syndrome induced by left supraclavicular lymph node metastases became exacerbated. Therefore, a course of external radiotherapy was performed with palliative intent in our hospital. During the radiotherapy planning, the biodistribution of 111In-octreotide was examined to determine whether the absorbed dose of the previous PRRT was acceptable. As a result, external radiotherapy was performed, and an acute radiation reaction was observed; the severity of the reaction was typical of reactions to neck radio-therapy. The treatment course of the present case was considered to be instructive because PRRT cannot be performed in Japan at present.

[Usefulness of thoracoscopy under local anesthesia in the diagnosis of tuberculous pleurisy occurring during infliximab administration: a case report].

We report the case of a 71-year-old man with rheumatoid arthritis. Infliximab administration was started as treatment for rheumatoid arthritis in January 2009. As he showed a positive result for the tuberculin test, he was treated with isoniazid for 9 months. He was subsequently referred to our department in October 2011 with a right-sided pleural effusion. When thoracoscopy was performed under local anesthesia, white and red protruding lesions of various sizes were observed in the pleural cavity. A biopsy revealed fibrous granulation tissue, and tissue culture and all sensitivity tests were positive for Mycobacterium tuberculosis. Therefore, thoracoscopy is useful for not only diagnosis but also determining whether resistant tuberculosis is present.

Clinical usefulness of end-tidal CO2 measured using a portable capnometer in patients with respiratory disease.

INTRODUCTION: This study aimed to evaluate the correlation and agreement between end-tidal CO2 (EtCO2 ) measured with the novel portable capnometer (CapnoEye®) and partial pressure of arterial carbon dioxide (PaCO2 ) levels in patients with respiratory diseases and to compare the efficacy of EtCO2 and PvCO2 in predicting PaCO2 levels. METHODS: We analyzed the correlation and the agreement between EtCO2 and PaCO2 and between PvCO2 and PaCO2 using Pearson's moment correlation coefficient in patients with type 1 and type 2 respiratory failure and both groups overall. RESULTS: A 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 EtCO2 and PaCO2 (r = 0.88; p < 0.0001). Sixty-six PvCO2 samples were obtained, and there was a high correlation between PvCO2 and PaCO2 (r = 0.81; p < 0.0001). Regarding type 2 respiratory failure, there was a high correlation between EtCO2 and PaCO2 (r = 0.81). The Bland-Altman analysis between PaCO2 and EtCO2 revealed a bias of 5.7 mmHg, with limits of agreement ranging from -5.1 mmHg to 16.5 mmHg. In contrast, the analysis between PaCO2 and PvCO2 revealed a bias of -6.8 mmHg, and the limits of agreement ranged from -22.13 mmHg to 8.53 mmHg. CONCLUSION: EtCO2 measured by CapnoEye® was significantly correlated to PaCO2 levels in patients with respiratory diseases. Moreover, CapnoEye® may be more useful for predicting hypercapnia conditions in which respiratory diseases are compared with measure PvCO2 .

The pharmacokinetics and long-term therapeutic effects of gefitinib in patients with lung adenocarcinoma harboring the epidermal growth factor receptor(EGFR)mutation.

INTRODUCTION: The relationship between the pharmacokinetics and long-term antitumor activity of gefitinib in patients with epidermal growth factor receptor(EGFR)mutation-positive lung adenocarcinoma has not yet been clarified in clinical practice. The present study assessed the correlation between the pharmacokinetics and long-term therapeutic effects of gefitinib in patients with lung adenocarcinoma harboring the EGFR-activating mutation. METHODS: Fifteen patients with lung adenocarcinoma harboring the EGFR mutation were administered 250 mg of gefitinib daily. Blood samples were collected prior to the first administration of gefitinib and after 1, 4, 6, 8, and 24 h. Plasma concentrations of gefitinib were measured via liquid chromatography mass spectrometry, and the peak plasma concentration(Cmax)and area under the plasma concentration time curve from 0 to 24 h(AUC 0-24)of gefitinib were determined. The correlations between these pharmacokinetic variables and the objective responses, including progression-free survival(PFS)and overall survival(OS), were retrospectively analyzed. RESULTS: The Cmax of gefitinib in patients with a partial response(PR)was significantly lower than that of patients with stable disease(SD)(median Cmax: 278 vs 588 ng/mL, p<0.05 ). However, the Cmax of gefitinib did not correlate with longer PFS. Conversely, a significant negative correlation was found between the AUC 0-24 of gefitinib and longer survival(r=-0.545, p<0.05 ). CONCLUSIONS: It may be possible that a high concentration of gefitinib is not necessary to achieve long-term therapeutic effects in patients with lung adenocarcinoma harboring the EGFR mutation.

[Efficacy of combination therapy with EGFR-TKI and cytotoxic drug in lung adenocarcinoma already treated with EGFR-TKI].

UNLABELLED: OBJECITVE: To assess the efficacy of combination therapy with EGFR-TKI and a cytotoxic drug in lung adenocarcinoma already being treated with EGFR-TKI. METHODS: Eight patients with adenocarcinoma who were treated with combination therapy of EGFR-TKI and a cytotoxic drug between April 2008 and December 2010 were retrospectively evaluated for response rate, disease-control rate, progression-free survival(PFS), time-to-treatment-failure(TTF)and overall survival(OS). RESULTS: Among the 7 patients with tumor samples available, EGFR-mutations were detected in six.The median number of prior therapy regimens received by the patients was 5.All the patients had been treated before with both gefitinib and erlotinib.Among 8 patients, six showed stable disease, including three patients intolerant because of severe hematological toxicities, and 2 with progressive disease.The disease-control rate was 75%, and median TTF, PFS, and OS were 42 days, 84 days, and 495 days, respectively. CONCLUSION: Combination therapy with EGFR-TKI and a cytotoxic drug after the failure of EGFR-TKI may be a useful therapeutic option for selected patients.

T790M mutation positive squamous cell carcinoma transformation from EGFR-mutated lung adenocarcinoma after low dose erlotinib: A case report and literature review.

RATIONALE: 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. PATIENT CONCERNS AND DIAGNOSIS: 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). INTERVENTIONS AND OUTCOMES: 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. LESSON: 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.

Infectious Pulmonary Artery Pseudoaneurysm That Resolved with Conservative Treatment.

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.

Endobronchial hamartoma resected via bronchoscopy using high-frequency electrosurgical snare-Preoperative strategies using virtual bronchoscopy.

Pulmonary hamartomas are common benign lung tumors; however, endobronchial hamartomas are relatively rare. We report a case of asymptomatic endobronchial hamartoma in a 51-year-old man. Chest computed tomography revealed a 10-mm protrusion in the right main bronchus. Preoperative virtual bronchoscopy (VBS) was performed; subsequently, minimally invasive bronchoscopic resection was safely performed under local anesthesia. The use of VBS is a useful treatment strategy and follow-up modality.

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

An early intensive intervention for inducing inactive asthma in adults--a one-year follow-up observation study.

BACKGROUND: Treatment strategy that reduces dependence on long-term medication for chronic asthma is preferable. The purpose of the study is to investigate the efficacy of an early intensive intervention for inducing inactive asthma in adults and identify factors that affect the efficacy. METHODS: A prospective study was conducted on subjects who had asthma for two years or less. An intensive intervention consisting of systemic corticosteroid treatment for two weeks followed by inhaled corticosteroid for further 16 weeks with concomitant administration of bronchodilator(s) was administrated on 109 subjects. As a control group, 33 subjects were treated according to the current asthma treatment guidelines for 18 weeks. The primary outcome of the intervention was assessed with symptomatology and use of medication during 12 months after the cessation of treatment period. RESULTS: At one year after the intervention, significantly more patients in the intensive intervention group (41%) than in the control group (24%) had no respiratory symptoms and were medication-free or had experienced minor upper respiratory symptoms (inactive asthma) (P = 0.01). The intensive intervention maintained a significant factor associated with one-year inactive asthma (adjusted odds ratio: 3.61, 95% confidence interval: 1.20-10.84; P = 0.02). Infection as onset cause, asthma duration and pre-treatment %FEV(1.0) were also identified independently associated with inactive asthma. As the limitation, the study was not randomized trial. CONCLUSIONS: Intensive therapy in the early stage is very likely to contribute to increasing one-year asthma inactivity, which may reduce patients' dependence on long-term management by medical treatment.

[Survival-related clinical factors of patients with advanced non-small cell lung cancer after 2000].

PURPOSE: To find new survival-related clinical factors in patients with non-small cell lung cancer (NSCLC) after 2000. PATIENTS AND METHOD: Two hundred one patients were registered with primary NSCLC from years 2000 to 2005. One hundred eighty-six patients were pathologically diagnosed with NSCLC (all patients in the group). These patients were reviewed after wards in order to find any new survival-related clinical factors. RESULTS: One hundred forty-nine patients had adenocarcinoma. Median age was 68 years old, and median performance status (PS) was 1. Fifty-nine patients were treated with gefitinib, which is an epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitor (TKI). In initial treatment, 22 patients were given gefitinib, and 37 patients after secondary treatment. Sixteen patients were managed with the best supportive care, and 12 patients were not allowed to know their precise treatment. These 28 patients were excluded from the all patients group i. e., the treated patients group. In multivariate analysis of this group, the PS, the treatment by gefitinib, the number of metastasized organs, and the serum total bilirubin were independent survival-related clinical factors. The median survival time without use of gefitinib was 46 weeks, and the survival times in first-line or more than first-line were 40 or 105 weeks, respectively (p = 0. 01). CONCLUSION: In addition to PS, the number of metastasized organs, and serum total bilirubin, treatment by gefitinib was considered to be one of the survival-related clinical factors in unselected patients with NSCLC.

[A case of lung cancer complicated with active non-tuberculous mycobacterium (NTM) infection successfully treated with anti-cancer agents and anti-NTM agents].

A 55-year-old man with pulmonary Mycobacterium avium complex (MAC) disease was referred to our hospital with dyspnea on exertion and general fatigue. Chest computed tomography (CT) revealed a nodular shadow with pleural indentation in the left S(1+2), left pleural effusion, and a thick-walled cavitary lesion due to pulmonary MAC disease in the right S1. A biopsy specimen of the nodule in the left S(1+2) revealed adenocarcinoma, which various examinations confirmed to be stage IV lung adenocarcinoma (T2aN0M1a) complicated with active pulmonary MAC disease. Anti-non-tuberculous mycobacteriosis (NTM) chemotherapy consisting of rifampicin, ethambutol, clarithromycin and streptomycin was administered to treat the pulmonary MAC disease, and the lung cancer was then treated with 4 courses of carboplatin/pemetrexed. This improved the patient's pulmonary MAC disease, and the lung cancer went into partial remission without severe adverse effects. Although a more detailed analysis of the drug interaction is required, we concluded that a combination of anti-NTM and carboplatin/pemetrexed chemotherapy was safe and effective.

[A case of chylothorax in which thoracoscopy under local anesthesia and thoracic duct scintigraphy were useful to locate the leakage site].

BACKGROUND: Detailed investigation of the cause of chylothorax and its treatment should be performed by thoracoscopy under general anesthesia, but if this is difficult due to multiple complications it is possible to perform a detailed investigation by combining thoracoscopy under local anesthesia and thoracic duct scintigraphy. CASE PRESENTATION: A 74-year-old woman presented with exertional dyspnea. Chest X-ray films showed right pleural effusion, and thoracocentesis yielded a milky white pleural effusion, meeting the criteria of chylothorax, after excluding conditions such as malignant lymphoma, amyloidosis and trauma. Since the patient's medical history included pacemaker insertion, dialysis and diabetes, thoracoscopy was performed under local anesthesia rather than general anesthesia, to investigate the cause in detail. The pleural cavity was visualized, but no obvious tumor or other cause was present in the parietal pleura. There was partial adhesion of the lower lobe and chest wall, and the leakage of a milky white pleural effusion from this site was confirmed. We then performed thoracic duct scintigraphy, which revealed an area of enhancement corresponding to the leakage site near the right pulmonary hilum. CONCLUSION: We describe a case in which thoracoscopy under local anesthesia and thoracic duct scintigraphy were useful for determining the leakage site in chylothorax.

[Results of questionnaire on decision-making to treat advanced non-small cell lung cancer based on American and European practical guidelines].

During 2009, practical routine guidelines for advanced non-small cell lung cancer used in Europe or USA were updated because the clinical benefits of molecular target agents were confirmed through several pivotal clinical trials. These molecular target agents appeared in guidelines which became available in Japan by the end of 2009. We made a questionnaire for decision-making to treat advanced non-small cell lung cancer based on these practical guidelines. Oncologists of lung cancer working in the Shinjuku area of Tokyo in Japan were eligible. Between March 15th and April 9th in 2010, 28 oncologists from 12 departments in 7 hospitals completed this questionnaire. Most of them made the global standard decision-making according to the new guidelines, including new proposals such as usage of epidermal growth factor receptor-tyrosine kinase inhibitors. There were 3 differences from the guidelines. 1)Platinum doublets were selected even in 2nd- or 3rd-line treatment because of the expected tumor shrinkage. 2)Single cytotoxic agents were selected even for 3rd-line treatment. The tendency of a backward shift in decision-making was observed. 3)There were few selections of regimens including bevacizumab because of medical systems such as DPC(Diagnosis Procedure Combination)that is Japanese DRG(Diagnosis-Related Group)/PPS(Prospective Payment System).

[A case of acute exacerbation of interstitial pneumonia complicated with dermatomyositis during treatment for lung cancer, and literature review].

A 72-year-old man was referred to our hospital with complaints of cough, facial rash, proximal muscle pain and weakness. Chest computed tomography (CT) revealed a nodule in the right S6, interstitial pneumonia in bilateral lower lobes and mediastinal lymph node swelling. A biopsy specimen of the nodule revealed non-small cell lung carcinoma. Gottron's sign was noted on his hands, and elevated skeletal muscle enzymes were recognized. Based on clinical and histopathological examinations, the patient was given a diagnosis of dermatomyositis. He was treated with chemotherapy (carboplatin/paclitaxel) for lung cancer and his dermatomyositis was treated with steroids (1 mg/kg of prednisolone) for prolonged muscle pain and cough. Although both therapies were successful, he died of respiratory failure due to acute exacerbation of interstitial pneumonia. In the present case, we found that decreasing tumor size might be related to the activity level of skin and muscle symptoms, not interstitial pneumonia. A combination of 3 diseases is thought to be very rare, and we discussed the intercorrelation among lung cancer, dermatomyositis and interstitial pneumonia with a review of the literature.