Phase I/II study of nedaplatin and nab-paclitaxel for patients with previously untreated advanced squamous cell lung cancer: Kanto Respiratory Disease Study Group (KRSG) 1302.

BACKGROUND: Nedaplatin and nab-paclitaxel are each efficacious in the treatment of squamous cell lung cancer. PATIENTS AND METHODS: Eligibility criteria were: no prior chemotherapy, advanced squamous cell lung cancer; performance status 0-1, age > 20 years but < 75 years, and adequate hematologic, hepatic and renal function. Patients received escalating doses of nab-paclitaxel under a fixed dose of nedaplatin (100 mg/m2, day 1) every 3 weeks in phase I. The initial nab-paclitaxel dose was 100 mg/m2 on days 1 and 8 (level 1), and the next dose was 100 mg/m2 on days 1, 8, and 15 (level 2). In phase II, patients received the recommended doses. The primary endpoint was tumor response rate. RESULTS: In phase I, three patients at level 1 experienced no dose-limiting toxicities (DLTs) and two patients at level 2 experienced DLTs. Level 1 was thus determined as the recommended dose. Twenty-three patients were enrolled in phase II. The 3 patients in level 1 and 23 patients in phase II were included together for analyses. Three of these 26 patients were excluded from response analysis due to pneumonia and patient refusal. Response rate was 91.3% (95% confidence interval, 72.0-98.9%). Toxicities observed during all cycles were tolerable. CONCLUSIONS: The recommended dose for this combination was nedaplatin at 100 mg/m2 on day 1 and nab-paclitaxel at 100 mg/m2 on days 1 and 8 every 3 weeks. The combination of nedaplatin and nab-paclitaxel appears safe and efficacious in patients with untreated advanced squamous cell lung cancer.

Loop-Mediated Isothermal Amplification as Point-of-Care Testing for EGFR-Mutated Lung Adenocarcinoma.

Liquid biopsy has been adapted as a diagnostic test for EGFR mutations in patients with advanced or metastatic non-small cell lung cancer (NSCLC). Loop-mediated isothermal amplification (LAMP) has been widely used for the rapid detection of pathogens through DNA amplification. This study investigated the efficacy of an EGFR-LAMP assay using plasma samples of patients with resected NSCLC tumors. The EGFR status was investigated using both LAMP and next-generation sequencing (NGS) assays in cases that met the following criteria: (1) pulmonary adenocarcinoma with EGFR mutation detected by the Therascreen EGFR PCR Kit and (2) preoperative plasma samples contained enough DNA for the LAMP and NGS experiments. Among 51 specimens from patients with EGFR-mutated tumors or metastatic lymph nodes, the LAMP assay detected 1 EGFR mutation that was also detected in the NGS assay. However, a plasma sample that demonstrated EGFR wild type in the LAMP assay showed an EGFR mutant status in NGS. The detection rates (1.9% in LAMP and 3.9% in NGS) were very low in both assays, demonstrating a similar performance in detecting EGFR mutations in NSCLC tumors; therefore, it could be a more suitable test for the advanced stage, not the early stage. Notably, the LAMP assay was more time-saving, cost-effective, and straightforward. However, further investigation is required to develop a more sensitive assay.

Comparative study of the loop-mediated isothermal amplification method and the QIAGEN therascreen PCR kit for the detection of EGFR mutations in non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are important biomarkers in the treatment of patients with advanced or metastatic diseases. The therascreen EGFR Rotor-Gene Q (RGQ) PCR Kit® (Qiagen, Inc.) is an approved diagnostic test for EGFR mutations in non-small cell lung cancer (NSCLC). This study aims to investigate the diagnostic capability of a loop-mediated isothermal amplification (LAMP) assay as an accurate, efficient, and cost-effective alternative to the therascreen assay. METHODS: EGFR mutations were investigated by LAMP and therascreen assays using tissue samples that were surgically resected or biopsied from 117 consecutive patients with NSCLC tumors. The EGFR status from the LAMP assay was compared with that of the therascreen assay. Next-generation sequencing (NGS) was performed to confirm EGFR status of tumors that did not match in both assays. To establish an optimal LAMP AUC value, receiver operating characteristics (ROC) curve analysis was performed within tumors with exon 19 deletion or L858R point mutation. RESULTS: Of the 117 tumors assayed, 45 tumors with EGFR mutations and 68 tumors with EGFR wild type were matched in both assays, four tumors having mismatched EGFR statuses. NGS further confirmed that two of the four discordant tumors had the same EGFR status that was determined by the LAMP assay. The AUC values were 0.973 (95% CI: 0.929-1.00) in exon 19 deletion, and 0.952 (95% CI: 0.885-1.00) in L858R point mutation. In exon 19 deletion, sensitivity, specificity, and accuracy were 89.3%, 98.9%, and 96.6%, respectively, and 94.7%, 95.9%, and 95.7%, respectively, in L858R using AUC value of 0.222. CONCLUSIONS: The LAMP assay compared favorably with the therascreen assay and has potential as an effective, simple, rapid, and low-cost diagnostic alternative. Based on these results, a liquid biopsy LAMP system should be developed for point-of-care testing of oncogenes in the near future.

Left upper lobectomy for cancer of the left lung with a rare mediastinal left basal pulmonary artery.

We report a rare case wherein a mediastinal left basal pulmonary artery was detected during surgery. Intraoperative findings revealed mediastinal left lingular and basal segments of the pulmonary artery (A4+5 + A8-10) just dorsal to the superior pulmonary vein. The mediastinal left basal pulmonary artery is classified by its branching type, (1) complete type-wherein the entire that all basal pulmonary artery flow lies between the superior pulmonary vein and the left upper bronchus, as in like this case, (2) incomplete type-wherein that a part of the left basal pulmonary artery segment is on the flow mediastinal side. It is important to understand this rare aberration for undergoing safe surgery.

A novel loop­mediated isothermal amplification method for efficient and robust detection of EGFR mutations.

The activation of somatic mutations conferring sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been widely used in the development of advanced or metastatic primary lung cancer therapy. Therefore, identification of EGFR mutations is essential. In the present study, a loop­mediated isothermal amplification (LAMP) method was used to identify EGFR mutations, and its efficiency was compared with the Therascreen quantitative PCR assay. Using LAMP and Therascreen to analyze surgically resected tissue samples from patients with pulmonary adenocarcinoma, EGFR mutations were observed in 32/59 tumor samples (LAMP) and 33/59 tumor samples (Therascreen). Notably, the LAMP assay identified one tumor as wild­type, which had previously been identified as a deletion mutation in exon 19 via the Therascreen assay (Case X). However, the direct sequencing to confirm the EGFR status of the Case X adhered to the results of the LAMP assay. Further experiments using Case X DNA identified this exon 19 deletion mutation using both methods. In addition, a novel deletion mutation in exon 19 of the EGFR was identified. Overall, the present study shows that the LAMP method may serve as a valuable alternative for the identification oncogene mutations.

Optimal sublobar resection for c-stage I non-small cell lung cancer: significance of margin distance to tumor size ratio and margin cytology (Supplementary analysis of KLSG-0801): complete republication.

BACKGROUND: Sublobar resection for lung cancer is associated with a higher risk of recurrence than that of lobectomy; we evaluated the factors considered to be predictors of recurrence. METHODS: By analyzing multicenter prospective studies of sublobar resection for patients with c-stage I non-small lung cancer who were unable to undergo lobectomy (KLSG-0801), we investigated the relationship between (1) tumor location (TL) and margin distance from the stump (MD), (2) the MD/tumor size (TS) ratio and prognosis, (3) and the margin cytology (MC) and prognosis. RESULTS: The correlation between TS and MD was statistically significant in cases of easily resectable regions defined by Lewis' classification (n = 18). However, there was no correlation in difficult-to-resect regions (n = 14). Among cases of recurrence, the MD/TS ratio was less than 1. The 3-year survival rate was 100% for patients with MD/TS > 1 (n = 12), 59.7% for patients with MD/TS ≤ 1 (n = 20) (p = 0.06), 88.1% in cases of negative MC (n = 18), and 20% in cases of positive MC (n = 5) (p = 0.001). CONCLUSION: Cases with positive MC had a significantly worse prognosis than those with negative MC. It may be difficult to secure an MD greater than the TS in a difficult-to-resect region according to Lewis' classification.

Inter-tumor heterogeneity of PD-L1 expression in non-small cell lung cancer.

BACKGROUND: The Dako PD-L1 immunohistochemistry (IHC) 22C3 pharmDx and the Dako 28-8 IHC pharmDx assays were approved by the US Food and Drug Administration, as a companion diagnostic test for pembrolizumab (Keytruda, Merk, Kenilworth, NJ, USA) and a complementary diagnostic test for nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY, USA) in non-small cell lung cancer (NSCLC), respectively. Increased PD-L1 expression levels can be associated with greater therapeutic efficacy of pembrolizumab relative to other anti-PD-1 agents. However, in treatment decision making, little is known about which tissue (primary or metastatic lesion) should be stained by 22C3 antibody. We investigated the relationship between PD-L1 expression in primary tumors and paired metastatic lymph nodes using the 22C3 assay, and evaluated the concordance between the 22C3 and 28-8 assays. METHODS: PD-L1 expression was evaluated in cells from primary tumors and paired metastatic lymph nodes using the 22C3 and 28-8 IHC assays. Total 35 patients with primary tumor and paired metastatic lymph node were enrolled into this study, and all samples were surgically resected, formalin-fixed, and paraffin-embedded NSCLC tissues. Tumor cells exhibiting complete or partial membrane staining, were considered as PD-L1 positive. On the basis of tumor proportion score (TPS), all samples were classified as no expression (TPS: <1%), low expression (TPS: 1-49%), or high expression (TPS: ≥50%). RESULTS: TPS distribution was markedly different between primary tumors and paired metastatic lymph nodes. In 22C3 IHC assay, TPS similar to that of metastatic lymph nodes was demonstrated in 10 primary tumors, and concordance rate between them was 28.6%. Concurrently, in 28-8 IHC assay, 11 primary tumors had TPS similar to that of metastatic lymph nodes, with a concordance rate of 31.4%. CONCLUSIONS: TPS concordance rates (for both 22C3 and 28-8 antibodies) between primary tumors and paired lymph nodes were low. Inter-tumor heterogeneity of PD-L1 expression is an important issue for clinical oncologists during treatment planning.

[Present Status and Future Issues of Multidisciplinary Treatment of Lung Cancer from the Viewpoint of a Respiratory Surgeon].

With the advent of molecular targeted therapeutic agents and immunity checkpoint inhibitors, lung cancer drug therapy has advanced. We cannot expect to improve the performance of surgical treatment without drug therapy. The problem of improving the performance of surgical treatment for lung cancer is:① the role of surgery in multidisciplinary treatment for c-stageⅢ N2 lung cancer, ② post-operative adjuvant therapy, ③ multidisciplinary treatment of post-operative recurrence, ④ salvage surgery, and ⑤ sublobar resection in high risk cases. We will describe each of these with reference to our own experiences and literature considerations.

A clinicopathological study of surgically resected lung cancer in patients with usual interstitial pneumonia.

BACKGROUND: The clinicopathological characteristics of lung cancer with concomitant usual interstitial pneumonia (UIP) are insufficiently understood. This study aimed to elucidate a characteristic pathological feature of lung cancer that develops in patients with UIP, with a focus on the location of its onset. METHODS: We reviewed surgically obtained specimens, including 547 tumors from 526 patients who underwent lobectomy for lung cancer. Surveyed patients were classified into three groups: patients with UIP (UIP group), patients with lung pathology other than UIP (non-UIP group), and patients without any associated lung pathology (normal group). The histology as well as the lobe and location of the onset of lung cancer were compared among these groups. The peripheral location was subdivided into subpleural, inner and tumor involved centrally secondary to extension. RESULTS: The UIP group comprised 82 patients (male, 71 [87%]; mean age, 71 years; smoking rate, 94%), the non-UIP group comprised 334 patients (male, 267 [80%]; mean age, 69 years; smoking rate, 81%), and the normal group comprised 110 patients (male, 33 [30%]; mean age, 63; smoking rate, 29%). No statistical differences were noted in sex, mean age, or smoking index between the UIP and non-UIP groups. Compared with the non-UIP group, the frequency of squamous cell carcinoma (63% vs. 32%), lower lobe origin (76% vs. 32%), and subpleural location (24% vs. 5%) were significantly higher in the UIP group. CONCLUSIONS: Lung cancers in patients with UIP show a predilection for the subpleural region, where UIP is also thought to originate.

Multicenter prospective study of sublobar resection for c-stage I non-small cell lung cancer patients unable to undergo lobectomy (KLSG-0801): complete republication.

BACKGROUND: Local therapy for stage I non-small cell lung cancer (NSCLC) is divided into surgical and radiation treatment, and given to patients unable to tolerate a lobectomy. A prospective phase II study of cases that received stereotactic body radio therapy (SBRT) (JCOG0403) revealed an overall 3-year survival rate (3-YSR) of 76.0 %, 3-year relapse free survival rate (3-YRFS) of 69.0 %, and rate of morbidity of grade 3 or greater of 9 %. However, few prospective multicenter studies have reported regarding surgery for high-risk stage I NSCLC patients. METHODS: We investigated this issue in the setting of a prospective multicenter observational study. Thirty-two high-risk NSCLC patients (30 males, 2 females; median age 74 years, 61-85 years) were analyzed. RESULTS: Two (6.3 %) showed morbidity of grade 3 or greater, though there were no postoperative deaths. The margin local control rate was 97.0 % (surgical margin recurrence, 1) and local recurrence control rate was 75.0 % (ipsilateral thorax recurrence, 8), while the 3-YSR and 3-YRFS was 79.0 and 75.9 %, respectively. CONCLUSION: A sublobar pulmonary resection for patients unable to tolerate a lobectomy with stage I NSCLC was shown to be safe and provided results comparable with those of SBRT.

Acute ischaemic lung injury due to pulmonary vascular obstruction.

AIMS: We have encountered cases of a distinctive myxomatous alveolar wall thickening around pulmonary infarctions, and have termed it 'acute ischaemic lung injury' (AILI). In this study we determined if pulmonary infarction is the only cause of AILI and have elucidated its histological features. METHODS AND RESULTS: We examined 2941 cases that underwent lobectomy, surgical lung biopsies for nodular lesions or autopsies between 1994 and 2014. Cases were divided into pulmonary infarction and non-infarction groups. The histological features of AILI sought were lobule-based alveolar wall thickening (myxomatous or fibrous) with epithelial metaplasia and negligible inflammation. In order to characterize AILI further, we performed immunohistochemical staining using several antibodies. Thirty-four of 69 cases in the infarction group (mean age 57.1 years, 30 males) had AILI, whereas only one (but with vascular obstruction) of the remaining 2872 in the non-infraction group had AILI. AILI was located around infarctions. Separation of the epithelial and endothelial basement membranes of the alveolar wall was observed in 75% of cases. CONCLUSIONS: AILI is associated almost exclusively with lung infarction, caused presumably by vascular obstruction. We consider AILI to represent a distinct lung lesion other than pulmonary haemorrhage and infarction.

Asbestos exposure increases the incidence of histologically confirmed usual interstitial pneumonia.

AIMS: We hypothesized that asbestos exposure increases the incidence of macroscopically visible and histologically confirmed usual interstitial pneumonia (histological UIP). METHODS AND RESULTS: We retrospectively examined 1718 cases (1202 males; mean age 66.7 years) who underwent lobectomy for resection of pleuropulmonary tumours. Objective markers for asbestos exposure included: the presence of malignant pleural mesothelioma, the presence of pleural plaques (PPs) and asbestos bodies in the histological specimen. Risk factors for histological UIP were examined. Two separate groups were studied: 183 with asbestos exposure, and 239 with histological UIP. The 183 cases with asbestos exposure had higher rates of positive occupational history and histological UIP (31%) than the remaining 1535. Among the asbestos-exposed group, small numbers of asbestos bodies were found in histological specimens of 21 cases of histological UIP. PPs and asbestos bodies were more frequent in the 239 patients with histological UIP than in the remaining 1479 UIP-negative patients. Multivariate analysis showed that asbestos exposure, especially positivity for asbestos bodies, that does not meet the current criteria for asbestosis increases the risk of histological UIP (P < 0.0001). CONCLUSIONS: Asbestos exposure causes asbestosis and increases the incidence of histological UIP.

Multiple, thin-walled cysts are one of the HRCT features of airspace enlargement with fibrosis.

PURPOSE: Airspace enlargement with fibrosis (AEF) has been identified pathologically as a smoking related change. We sought to identify the HRCT findings of AEF and search for distinguishing features from honeycombing. MATERIALS AND METHODS: 50 patients (47 males; mean age 69) were evaluated. All had undergone lobectomy for lung cancer and had confirmed AEF and/or usual interstitial pneumonia (UIP) by pathological evaluation. HRCT findings were first evaluated preresection for resected lobes, and then correlated with the subsequent pathological findings in the resection specimens. Three groups were devised: one with AEF alone to determine the HRCT findings of AEF, a second with AEF and UIP and third with UIP alone. HRCT features of AEF and honeycombing were compared. RESULTS: There were 11 patients (10 male; mean age 69) with AEF alone, 24 patients (22 male; mean age 69) with AEF and UIP, and 15 patients (15 male; mean age 68) with UIP alone. The HRCT on the AEF alone showed subpleural (but not abutting the pleura) multiple thin-walled cysts (MTWCs) in 7 and reticular opacities in 3. The HRCT in AEF and UIP showed MTWCs in 10, reticular opacities in 17; and honeycombing in 5. Among these 35 patients with the pathological finding of AEF (with or without UIP), 17 showed MTWCs. The maximum cyst wall thickness of MTWCs (mean 0.81 mm) was significantly thinner than that of honeycombing (mean 1.56 mm). MTWCs did not locate in lung base and was distant from the pleura. HRCT findings correlated with gross findings on both cysts and honeycombing. No MTWCs were seen in the 15 patients with UIP, 8 of 15 had honeycombing on CT. CONCLUSIONS: We confirmed that HRCT features of AEF were MTWCs and/or reticular opacities. MTWCs might be distinguished from those of honeycomb change. While we prefer the term MTWCs, these sorts of changes have probably been confused with/interpreted as honeycombing and/or empysema in the past.

Airspace enlargement with fibrosis shows characteristic histology and immunohistology different from usual interstitial pneumonia, nonspecific interstitial pneumonia and centrilobular emphysema.

The histologic characteristics of air space enlargement with fibrosis (AEF) are compared with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and centrilobular emphysema (CLE) to determine similarities and differences. Lung specimens from 39 patients were studied; 9 with AEF, 13 with UIP and 5 with CLE identified in lobectomy specimens for cancer and 12 NSIP cases identified on surgical lung biopsies. We determined the characteristics of cystic structures (i.e. abnormal airspace), degree of inflammation and severity of pneumocyte injury semi-quantitatively. In AEF, the wall thickness of the cystic lesions (0.8 mm) was thinner than in UIP (2.1 mm) and thicker than in CLE (0.07 mm). The degree of inflammation and granulation tissue were milder in AEF than in UIP and NSIP and CLE showed milder inflammatory cells than AEF. As for pneumocyte injury, AEF had fewer erosions (0.1/case) and fewer ubiquitin-positive pneumocytes than UIP (4.8 cells/slide) and NSIP (9.8 cells/slide). Our data suggested that the histological characteristics of AEF differed significantly from UIP, NSIP and CLE.

[Clinical analysis of mycobacteriosis patients with pneumothorax].

BACKGROUND: Secondary pneumothorax caused by mycobacteriosis is rare. The frequency of incidence of pneumothorax in tuberculosis patients is reported to be only 1.5%, and that in nontuberculous mycobacteriosis patients may be very low. It is important to detect mycobacteriosis at an earlier stage in patients hospitalized for pneumothorax, in general wards so that nosocomial infections such as tuberculosis can be prevented. OBJECTIVE: Chart review of mycobacteriosis patients with secondary pneumothorax admitted to the isolation ward, and that of the mycobacteriosis patients with pneumothorax admitted in the general wards of our hospital. METHODS: We reviewed records of 555 mycobacteriosis patients admitted to the isolation ward of our hospital from January 2006 to December 2008. We analyzed the reasons for admission and cause, treatment, and outcome of pneumothorax. RESULTS: Of the 555 mycobacteriosis patients, 11 (2.0%) had complications of pneumothorax. Among these 11 patients, 9 had tuberculosis, and 2 had nontuberculous mycobacteriosis. Of the 11, 5 were discharged, but 6 (54.5%) died during hospitalization, while among the remaining 544 mycobacteriosis patients without pneumothorax, 49 (9%) died during hospitalization. The hospital death rate of mycobacteriosis patients with pneumothorax was significantly higher than that of mycobacteriosis patients without pneumothorax (p < 0.0001). Among the 9 tuberculosis patients, 4 in whom pneumothorax was caused by rupturing of bullae showed improvement except one patient, but 5 in whom pneumothorax was caused by tuberculosis died. Excluding the 555 patients admitted to the isolation ward, 388 pneumothorax patients were admitted to the general ward during the same period, among which 3 (0.8%) had mycobacteriosis. CONCLUSION: Tuberculosis-induced pneumothorax has a poor prognosis because the occurrence of tuberculosis impairs the mechanism of recovery from pneumothorax.

Survival after surgery for pathologic stage IA non-small cell lung cancer associated with idiopathic pulmonary fibrosis.

BACKGROUND: Many problems exist in regard to the treatment of lung cancer patients with idiopathic pulmonary fibrosis (IPF), but few reported studies have investigated the long-term prognosis after pulmonary resection in such patients. The purpose of the present study was to determine the postoperative survival of patients with pathologic stage IA non-small cell lung cancer (NSCLC) and IPF. METHODS: We retrospectively reviewed 350 patients with pathologic stage IA NSCLC who underwent pulmonary resections at our institution between September 1994 and December 2007. We analyzed and compared 28 of these patients, who had simultaneous lung cancer and IPF, with the remaining 322 lung cancer patients without IPF. RESULTS: The 5-year survival rates were 54.2% in pathologic stage IA lung cancer patients with IPF and 88.3% in those without IPF (p < 0.0001). Univariate analyses showed that age, sex, Brinkman Index, limited resection, operation time, adenocarcinoma, and IPF were significant prognostic factors for survival (p < 0.10). By multivariate analysis, however, only IPF was a significant prognostic factor for survival (p = 0.007). Propensity score-matching analysis confirmed that only IPF was significant prognostic factor (p = 0.043). CONCLUSIONS: The 5-year survival rate of patients with pathologic stage IA NSCLC and IPF is 54.2%. IPF has independent, adverse effects on survival of pathologic stage IA NSCLC patients treated with pulmonary resection.

Isolation of Candida species is an important clue for suspecting gastrointestinal tract perforation as a cause of empyema.

BACKGROUND: Empyema due to Candida species is a rare entity, and the significance of isolation of Candida species from the pleural effusion is not fully understood. OBJECTIVE: To elucidate the clinical features of Candida empyema. METHODS: We retrospectively reviewed the cases of 128 patients with culture-positive empyema. RESULTS: These 128 patients included 7 whose cause of empyema was esophago- or gastropleural fistula. Empyema was due to Candida species in 5 of the 7 patients. Primary diseases of these 5 patients were spontaneous esophageal rupture in 3 patients, esophageal rupture due to lung cancer invasion in 1 patient, and gastric ulcer perforation in 1 patient. None of these 5 patients had esophageal candidiasis. Among the 121 other patients with empyema not due to esophago- or gastropleural fistula, no patient had empyema due to Candida. CONCLUSION: We believe that the empyema in these 5 patients was caused by normal commensal Candida species entering the pleural cavity when the fistula between the gastrointestinal tract and pleural cavity was formed. Isolation of Candida species can be an important clue for suspecting gastrointestinal tract perforation as a cause of empyema.

Spontaneous hemorrhage of a thymic cyst in an adult: report of a case.

Mediastinal cysts account for about 19% of all mediastinal masses, and thymic cysts represent only about 1.5% of anterior mediastinal masses. Thymic cysts do not usually cause symptoms and are often found incidentally on routine chest radiography. We report the case of a thymic cyst that hemorrhaged into the mediastinum and the right pleural cavity, causing chest pain. The patient, a 55-year-old man, underwent emergency surgical resection and recovered uneventfully.

Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin.

Aprepitant is a new neurokinin-1 (NK(1) ) receptor antagonist developed as a treatment for chemotherapy-induced nausea and vomiting (CINV). To evaluate the efficacy and safety of aprepitant used in combination with standard therapy (granisetron and dexamethasone), we conducted a multicenter, phase II, placebo-controlled, double-blind, randomized study in Japanese cancer patients who received cancer chemotherapy including cisplatin (≥70mg/m(2) ). Aprepitant was administered for 5days. A total of 453 patients were enrolled. In the three study groups, (i) standard therapy, (ii) aprepitant 40/25mg (40mg on day 1 and 25mg on days 2-5) and (iii) aprepitant 125/80mg (125mg on day 1 and 80mg on days 2-5), the percentage of patients with complete response (no emesis and no rescue therapy) was 50.3% (75/149 subjects), 66.4% (95/143 subjects) and 70.5% (103/146 subjects), respectively. This shows that efficacy was significantly higher in the aprepitant 40/25mg and 125/80mg groups than in the standard therapy group (χ(2) test [closed testing procedure]: P=0.0053 and P=0.0004, respectively) and highest in the aprepitant 125/80mg group. The delayed phase efficacy (days 2-5) was similar to the overall phase efficacy (days 1-5), indicating that aprepitant is effective in the delayed phase when standard therapy is not very effective. In terms of safety, aprepitant was generally well tolerated in Japanese cancer patients. (ClinicalTrials.gov number, NCT00212602.)

[A surgical case of extramedullary plasmacytoma in the left main bronchus].

A 69-year-old woman complaining of cough and wheezing of 2-months duration was admitted for diagnosis and treatment. She had been treated for bronchial asthma. Chest computed tomography showed an endobronchial tumor in the left main bronchus. Bronchoscopic biopsy yielded a diagnosis of plasmacytoma. We confirmed the absence of M-protein in the serum and urine, bone lesions in bone scintigraphy, and other organ dysfunction. In addition bone marrow biopsy and revealed normal findings. We diagnosed extramedullary plasmacytoma in the left main bronchus. We performed a sleeve resection of the left main bronchus including the tumor and reconstructed the bronchus with primary end-to-end anastomoses. We achieved complete excision and were able to maintain lung function. One year after the operation, the patient remains well, with no evidence of recurrence, or conversion to multiple myeloma. When a patient complains of wheezing, a bronchial tumor should always be considered.