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Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0–4.9).British Journal of Cancer (2006) 95, 1142–1144. doi:10.1038/sj.bjc.6603422 www.bjcancer.com Published online 10 October 2006 [ABSTRACT FROM AUTHOR]

We investigated the clinical characteristics of refractory asthma associated with the effectiveness of bronchial thermoplasty (BT). We retrospectively evaluated data from 10 patients who underwent BT between June 2016 and December 2017 at Okayama Medical Center. The following were measured before and 6 months post-BT: forced expiratory volume in 1.0 s (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) level, blood eosinophil counts (Eosi), Asthma Quality of Life Questionnaire (AQLQ) score, and preventive medication use. At baseline, the mean post-bronchodilator FEV1 was 80.9% of the predicted value (range 45.6-115.7%). All patients were being treated with moderate- or high-dose inhaled corticosteroids and long-acting β2 agonists. The AQLQ improved from 4.26±1.67 at baseline to 5.59±0.94 at 6 months post-BT (p<0.05). The %FEV1, FeNO, IgE, and Eosi did not change significantly between baseline and 6 months post-BT. No severe complications were reported. BT was effective for non-allergic and non-eosinophilic in 3 patients, and allergic or eosinophilic in 4 patients. Their AQLQ improved by > 0.5 points post-BT. For both allergic and eosinophilic asthmatics following mepolizumab, BT was not useful. BT was effective for non-allergic and non-eosinophilic or allergic asthmatics, but insufficient for both allergic and eosinophilic following mepolizumab., Competing Interests: No potential conflict of interest relevant to this article was reported.

Bronchial thermoplasty is a novel procedure for patients with severe asthma showing a stable lung function. We herein report two cases with a deteriorating lung function. The lung function tended to improve in one case, while the other case discontinued mepolizumab medication after the procedure. Treatment was performed safely under general anesthesia in both cases. The use of bronchial thermoplasty may therefore be useful for the treatment of patients with a deteriorating lung function.

Mucosa-associated lymphoid tissue lymphoma is a common type of primary pulmonary carcinoma, but the presence of polypoid nodules is extremely rare. We herein report two cases with multiple nodules in the trachea. One case involved polypoid nodules and airway stenosis mimicking asthma; the other case had concurrent nontuberculous mycobacterial infection. The diagnosis of both cases was confirmed by bronchoscopy. The two cases were sensitive to radiotherapy and chemotherapy, respectively.

Aim: Assessment of the efficacy of docetaxel plus carboplatin vs. paclitaxel plus carboplatin in Japanese patients with advanced non-small cell lung cancer (NSCLC)., Patients and Methods: Chemotherapy-naïve patients were randomly assigned at a ratio of 2 to 1 to receive six cycles of either docetaxel (60 mg/m(2)) plus carboplatin [area under the curve (AUC)=6 mg/ml min] or paclitaxel (200 mg/m(2)) plus carboplatin (same dose), on day 1 every 21 days. The primary end-point was progression-free survival (PFS)., Results: A total of 90 patients were enrolled. Overall response rate, median PFS and median survival time in the docetaxel-plus-carboplatin group and the paclitaxel-plus-carboplatin group were 23% vs. 33%, 4.8 months vs. 5.1 months, and 17.6 months vs. 15.6 months, respectively. The docetaxel-plus-carboplatin group had a higher incidence of grade 3 or 4 neutropenia (88% vs. 60%)., Conclusion: Both regimens were similarly effective in Japanese patients with advanced NSCLC.

A 29-year-old man developed a persistent dry cough. Chest high-resolution computed tomography (HRCT) revealed centrilobular ultrafine granular shadows scattered in all lung fields. A lung biopsy with video-assisted thoracoscopic surgery revealed findings compatible with pulmonary tumor thrombotic microangiopathy (PTTM). However, the primary tumor was not identified. Combination chemotherapy with S-1 and cisplatin decreased his cough and improved the chest HRCT findings. The illness, however, gradually became difficult to control. He eventually developed pulmonary hypertension and died. Typically, an antemortem diagnosis of PTTM cannot be made. In this case, the diagnosis of PTTM and combination chemotherapy improved the chest HRCT findings, respiratory symptoms, and prognosis.

A 65-year-old man had suffered from systemic erythema from November 2008 and had noticed gradually progressing weakness in the upper and lower limbs. He received medical treatment in another hospital but his symptoms did not improve. He was admitted to our hospital for treatment of diabetes in June 2009, and his chest X-ray images and CT scans showed a mass shadow in the right upper lobe with hilar and mediastinal lymphadenopathy. We performed bronchoscopy, and diagnosed small cell lung cancer (T2N2M1, stage IV). However, he had hand grip weakness and continuing upper and lower limb muscle weakness, and therefore electromyography was performed, which showed the presence of waxing in the right leg. Subsequently, a diagnosis of Lambert-Eaton myasthenic syndrome was made. As he also showed ataxia of the left lower extremity, we also diagnosed paraneoplastic cerebellar degeneration. We gave the patient chemotherapy consisting of carboplatin and etoposide which resulted in the disappearance of his waxing, and his grip strength and erythema immediately improved with regression of the tumor after 1 course of chemotherapy. We report a case of small cell lung cancer associated with Lambert-Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration and erythema which presented as paraneoplastic syndrome, which improved with chemotherapy.

Purpose: To demonstrate the efficacy of docetaxel and cisplatin (DP) chemotherapy with concurrent thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC)., Patients and Methods: Patients age 75 years or younger with LA-NSCLC, stratified by performance status, stage, and institution, were randomly assigned to two arms consisting of DP (docetaxel 40 mg/m(2) and cisplatin 40 mg/m(2) on days 1, 8, 29, and 36) or mitomycin, vindesine, and cisplatin (MVP) chemotherapy with concurrent TRT., Results: Between July 2000 and July 2005, 200 patients were allocated into either the DP or MVP arm. The survival time at 2 years, a primary end point, was favorable to the DP arm (P = .059 by a stratified log-rank test as a planned analysis and P = .044 by an early-period, weighted log-rank as an unplanned analysis). There was a trend toward improved response rate, 2-year survival rate, median progression-free time, and median survival in the DP arm (78.8%, 60.3%,13.4 months, and 26.8 months, respectively) compared with the MVP arm (70.3%, 48.1%, 10.5 months, and 23.7 months, respectively), which was not statistically significant (P > .05). Grade 3 febrile neutropenia occurred more often in the MVP arm than in the DP arm (39% v 22%, respectively; P = .012), and grade 3 to 4 radiation esophagitis was likely to be more common in the DP arm than in the MVP arm (14% v 6%, P = .056)., Conclusion: DP chemotherapy combined with concurrent TRT is an alternative to MVP chemotherapy for patients with LA-NSCLC.

Background: Data comparing the incidence and pattern of interstitial lung disease (ILD) in non-small cell lung cancer patients receiving treatment with gefitinib versus erlotinib, both of which are epidermal growth factor receptor tyrosine kinase inhibitors, are scarce. We investigated the incidence of ILD in Japanese patients treated with gefitinib or erlotinib., Methods: We reviewed the clinical records of 209 patients treated with erlotinib in 2008 (cohort A) and 330 treated with gefitinib between 2000 and 2003 (cohort B). Toxicity within the first month of treatment was investigated., Results: The patients in cohort A had fewer known risk factors for ILD (e.g., poor performance status and prior pulmonary fibrosis). ILD was detected in two patients (1.0%) from cohort A and eight patients (2.4%) from cohort B during the first month of treatment. The events were graded as follows: one patient each in grades 1 and 2 (cohort A), and one, one, and six patients in grades 3, 4, and 5, respectively (cohort B). Multivariate analysis revealed that poor performance status and prior pulmonary fibrosis were significantly correlated with the occurrence of ILD, but the type of epidermal growth factor receptor tyrosine kinase inhibitor administered was not., Conclusion: There was a somewhat lower incidence of ILD with erlotinib therapy than with gefitinib therapy, despite no statistically significant difference. Patient selection based on awareness by Japanese physicians of the risk factors for ILD, rather than the type of agent, may explain the difference in ILD incidence between the two treatments.

Background: The Japan-Multinational Trial Organization (JMTO) lung cancer (LC) 0003 was a prospective randomized phase III trial investigating advanced non-small cell lung cancer comparing paclitaxel (P) plus carboplatin (C) versus vinorelbine (V), gemcitabine (G) followed by docetaxel (D). This trial was conducted with Southwest Oncology Group (SWOG) 0003 using a common arm of PC. An analysis of SWOG 0003 samples showed that low osteopontin (OPN) plasma levels were highly prognostic for a better outcome. We performed an independent investigation to validate these results using samples from Japanese patients enrolled in the JMTO LC 0004, a correlative study associated with JMTO LC 0003., Methods: A total of 20 ml of blood was collected before treatment from patients enrolled in JMTO LC 0003. Serum concentrations of OPN and basic fibroblast growth factor (bFGF) were measured by enzyme-linked immunosorbent assay. Effects of OPN and bFGF levels on tumor response, progression-free survival (PFS), and overall survival (OS) were examined., Results: Seventy-one samples were obtained, including 32 specimens from the PC arm and 39 from the VGD arm. There were no significant relationships between either OPN or bFGF levels with patient characteristics. In an analysis of clinical outcome, low OPN levels correlated with better OS and progression-free survival (hazard ratio [HR] = 0.57; 95% confidence interval [CI], 0.33-0.97; p = 0.037, HR = 0.42; 95% CI, 0.25-0.70; p = 0.001, respectively) and high bFGF levels correlated with better OS (HR = 0.53; 95% CI, 0.31-0.90; p = 0.018)., Conclusion: Consistent with the findings from SWOG 0003, low OPN serum levels were significantly associated with a favorable prognosis in the JMTO LC 0004. Additionally, high bFGF levels were associated with improved survival.

A 63-year-old man visited our department due to dry cough in September 2005. Chest radiography showed an infiltrative shadow extending from the bilateral hila to the peripheral areas. Chest CT scanning revealed a crazy-paving appearance. Bronchoalveolar lavage and transbronchial lung biopsy confirmed alveolar proteinosis. In addition, based on the absence of an underlying disease and a high titer of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody, a diagnosis of autoimmune alveolar proteinosis was made. His course was observed on an outpatient basis because of mild symptoms, but dyspnea on exertion gradually increased. In July 2007, GM-CSF inhalation therapy was initiated in another hospital, but no improvement was observed. In November of the same year, he underwent whole-lung lavage for one lung followed by that for the other at our department. The symptoms rapidly improved after the lavage but were aggravated again after 6 months. In May 2008, whole-lung lavage was performed again. There have been no reports of adults with autoimmune alveolar proteinosis who did not respond to GM-CSF inhalation therapy and who underwent whole-lung lavage twice. GM-CSF inhalation therapy for autoimmune alveolar proteinosis is a pathogenesis-based epoch-making therapy, but the response rate is about 60%. In patients with treatment-resistant autoimmune alveolar proteinosis showing repeated aggravation of symptoms, whole-lung lavage under general anesthesia is a reliable therapeutic method.

A 55-year-old woman had a history of left mastectomy due to early breast cancer in 1998. She had been suffering from dyspnea on effort and dry cough since August in 2007, and visited our hospital 6 months later because the symptoms had been becoming worse. She was hypoxic and her chest radiograph showed bilateral diffuse shadows, so she was hospitalized. The specimen of transbronchial lung biopsy showed undifferentiated adenocarcinoma cells in lymphatics identified by lymphatic endothelium antibody D2-40 stain, so we diagnosed carcinomatous lymphangiosis. It also revealed the cells staining positive for Cytokeratin 7, negative for Cytokeratin 20, and positive for both estrogen receptor and progesterone receptor. These features were identical to the immunohistological findings of the specimen from the previously resected breast cancer. Chemotherapy with docetaxel was effective and improved her respiratory condition and the chest radiograph. The immunohistological findings are useful for diagnosis and selection of cancer therapy. We cannot find any case reports of recurrence with carcinomatous lymphangiosis over 10 years after resection of breast cancer in Japan. We must keep in mind that some cancers relapse after a long disease-free interval.

We examined the impact of pretreatment neutrophil count on survival in patients with advanced non-small-cell lung cancer (NSCLC). A total of 388 chemo-naïve patients with stage IIIB or IV NSCLC from a randomised controlled trial were evaluated. The effects of pretreatment peripheral blood neutrophil, lymphocyte and monocyte counts and neutrophil-lymphocyte ratio on survival were examined using the proportional hazards regression model to estimate hazard ratios after adjustment for covariates. The optimal cut-off value was determined by proportional hazards regression analysis with the minimum P-value approach and shrinkage procedure. After adjustment for prognostic factors, the pretreatment elevated neutrophil count was statistically significantly associated with short overall (P=0.0008) and progression-free survival (P=0.024), whereas no association was found between prognosis and lymphocyte or monocyte count. The cut-off value selected for neutrophil count was 4500 mm(-3) (corrected hazard ratio, 1.67; 95% confidence interval (CI), 1.09-2.54). The median survival time was 19.3 months (95%CI, 16.5-21.4) for the low-neutrophil group (4500 mm(-3), n=204) and was 10.2 months (95%CI, 8.0-12.3) for the high-neutrophil group (4500 mm(-3), n=184). We confirmed that pretreatment elevated neutrophil count is an independent prognostic factor in patients with advanced NSCLC receiving modern chemotherapy. Neutrophil count is easily measured at low cost, and it may be a useful indicator of patient prognosis.

A 47-year-old woman suddenly developed abdominal pain and visited the emergency room of our hospital. Chest and abdominal CT scan revealed free air in the abdominal cavity and a bulky pulmonary tumor in the right middle lobe. The perforated sigmoid colon was removed in an emergency operation. Histological examination of the resected tissue revealed undifferentiated carcinoma, but the histological differentiation could not be determined. We used immunohistochemical staining to distinguish primary non-small cell lung cancer from colon cancer; the resected tumor was positive for TTF-1 and CK7, but negative for CK20. Therefore, by using immunohistochemical staining we could diagnose the tumor of the large intestine as metastasis from non-small cell lung cancer. After the operation, systemic chemotherapy with carboplatin and docetaxel was repeated, but the lung tumor did not regress and the patient died. Autopsy examination confirmed the histology of the lung tumor as pleomorphic carcinoma. Morphological characteristics and the immunohistochemical staining pattern of the pulmonary tumor were consistent with that of the colon tumor. In Japan, this is the first report in which the initial manifestation of lung cancer was perforation of the large intestine due to metastasis.

Purpose: The aim of this study was to evaluate the diagnostic capacity of F-18 fluorodeoxyglucose dual-time-point (DTP) positron emission tomography (PET)/computed tomography (CT) for intrathoracic lymph node (LN) metastases in patients with nonsmall cell lung cancer (NSCLC)., Materials and Methods: Thirty-four patients had DTP PET/CT, with 60 minutes and 2-hour scans (n=19, NSCLC; n=15, benign pulmonary disease). LN diagnoses were confirmed by surgery or clinical follow-up (n=14, metastatic LNs; n=45, nonmetastatic LNs; n=39, inflammatory LNs)., Results: The maximum standardized uptake value (SUVmax) in the metastatic group was significantly higher than those in the nonmetastatic and inflammatory groups on both early- and delayed-phase imaging (each P<0.0001). The retention index (RI) of SUVmax (RI-SUVmax) in the metastatic group was significantly higher than in the nonmetastatic (P=0.0008) and inflammatory groups (P=0.0074). No significant difference was found between SUVmax values of the nonmetastatic and inflammatory groups on early- (P=0.6461) or delayed-phase (P=0.6913), or between RI-SUVmax values of the nonmetastatic and inflammatory groups (P=0.5717). For early-phase SUVmax, the cut-off value for highest accuracy with metastatic LNs was 3.61, yielding a sensitivity of 86.67% and a specificity of 88.00%. For delayed-phase SUVmax, the cut-off value was 4.00, yielding a sensitivity of 91.6% and specificity of 92.9%. For RI-SUVmax, the cut-off value was 20.91%, yielding a sensitivity of 73.6% and specificity of 75.9%., Conclusions: DTP PET/CT with a semiquantitative technique may improve diagnostic capacity for nodal staging of NSCLC.

Background: Gefitinib is effective in patients with lung adenocarcinoma. Smoking status also affects the responsiveness to gefitinib, but it has not been fully evaluated whether a sex difference exists in the influence of smoking on the efficacy of gefitinib in patients with lung adenocarcinoma., Methods: We reviewed the clinical records of 260 Japanese patients with lung adenocarcinoma who received gefitinib therapy (250 mg/day), and whose smoking status was known. Tumour response and survival were evaluated and stratified by smoking status and gender., Results: Among the 260 patients, 157 were male (60%). Median pack-years was 40 (range 8-160) and 23 (range 1-74) in male and female smokers, respectively. Objective response was observed in 62 (23.8%) of the 260 patients, and 1-year overall survival and progression-free survival were 45.1 and 24.3%, respectively. Multivariate analysis revealed that smoking status (pack-years) was an independent predictive factor for response to gefitinib [odds ratio (OR) = 0.971, 95% confidence interval (CI) = 0.947-0.995; P = 0.0159] in male patients, but not in female patients (OR = 0.999, 95%CI = 0.957-1.042). Additionally, pack-years significantly influenced the overall survival in males (hazard ratio = 1.010; 95%CI = 1.002-1018, P = 0.0169), while differential survival of females was not significantly predicted by this factor (P = 0.7639)., Conclusions: In male patients with lung adenocarcinoma, cumulative smoking significantly affected response and survival following gefitinib treatment, while in female patients, responsiveness to gefitinib was independent of smoking status. These results suggest that the influence of smoking habit on responsiveness to gefitinib is gender specific.

Cases of septic pulmonary embolism (SPE) diagnosed clinically by CT after dental extraction rarely include verification of bacteria from the local infection site. We report the case of a 70-year-old man without background disease suffering severe pyothrax after dental extraction. We detected two species of oral bacteria from his pleural effusion. Treatment was so difficult that it required surgical debridement by video assisted thoracoscopic surgery (VATS), even after the appropriate administration of antibiotics. According to the American Heart Association (AHA) prophylaxis guidelines for preventing infective endocarditis indicate that it is uncommon to prescribe antibiotics to patients without background disease after dental extraction. No appropriate Japanese guidelines exist considering the prevention of SPE causing severe pyothorax as in our case. The hematogenous spread of bacteria such as SPE caused by sepsis after tooth extraction thus requires more attended careful consideration in clinical practice if patients are to be properly protected against potentially serious complications.

Purpose: We conducted a phase I/II study of triplet chemotherapy consisting of cisplatin (CDDP), docetaxel (DCT) and gemcitabine (GEM) in patients with advanced non-small-cell lung cancer (NSCLC)., Methods: Fifty-three untreated patients with stage IIIB or IV NSCLC were enrolled. All drugs were given on days 1 and 8. The doses of CDDP and DCT were fixed at 40 mg/m(2) and 30 mg/m(2), respectively. In the phase I portion, a dose escalation study of GEM with starting dose of 400 mg/m(2) was conducted and primary objective in the phase II portion was response rate., Results: The maximally tolerated dose (MTD) and recommended dose (RD) of GEM were determined as 800 mg/m(2) because grade 3 non-hematological toxicity (liver damage, diarrhea, and fatigue) developed in three of nine patients evaluated at that dose level. In pharmacokinetic analysis, C (max) and AUC of dFdC and dFdU were increased along with the dose escalation of GEM. However, no relationship between pharmacokinetic parameters and toxicity or response was observed. Objective response rate was 34% and median survival time was 11.7 months. Though major toxicity was myelosuppression, there were no life-threatening toxicities., Conclusion: These results indicate that this triplet chemotherapy is feasible and effective in patients with advanced NSCLC.

Purpose: The aim of this trial was to investigate the efficacy and safety of cisplatin (P) and irinotecan (I) (PI) alternating with doxorubicin (A), cyclophosphamide (C) and etoposide (E) (ACE) in patients with extensive-disease small-cell lung cancer (ED-SCLC)., Patients and Methods: Patients with previously untreated ED-SCLC were enrolled in this trial. In the first, third and fifth cycles, PI (P: 60 mg/m(2) on day 1; I: 60 mg/m(2)/day on days 1, 8 and 15) was administered, whereas ACE (A: 50 mg/m(2) on day 1; C: 750 mg/m(2) on day 1; E 80 mg/m(2)/day on days 1-3) was given in the second, fourth and sixth cycles. Each cycle was repeated every 4 weeks. At the end of six cycles, patients who had obtained a complete response were given prophylactic cranial irradiation., Results: In total, 28 patients were enrolled, of whom 27 were assessable for efficacy and safety. Objective responses, including 4 (15%) complete responses, were observed in 25 patients (93%). Median survival time was 12.9 months. The principal toxicity was myelosuppression; grade 4 neutropenia and thrombocytopenia were observed in 89 and 4%, respectively. Febrile neutropenia occurred in 30% of patients. Diarrhea was mild (grade 3-4; 4%). All toxicities were reversible and there were no treatment-related deaths. The mean percentage of the delivered doses, relative to the projected doses, of PI and ACE were 84.6 and 91.1%, respectively., Conclusions: These results indicate the PI-ACE regimen to have promising activity against ED-SCLC with moderate toxicities.

Unlabelled: Risk factors for the development of interstitial lung disease in patients with non-small cell lung cancer receiving gefitinib and the prognostic factors after interstitial lung disease development have not been established. The aim of this study was to retrospectively identify and evaluate these possible factors., Patients and Methods: We reviewed the clinical records and radiographs of 365 consecutive patients with non-small cell lung cancer who received gefitinib in West Japan between 2000 and 2003., Results: In total, 330 patients were eligible for interstitial lung disease evaluation, and 15 patients (4.5%) were finally confirmed to have developed interstitial lung disease by blinded expert review. Multivariate analysis revealed that preexisting pulmonary fibrosis, poor performance status, and prior thoracic irradiation were independent risk factors for interstitial lung disease, with odds ratios of 21.0 (95% confidence interval, 5.12-86.3, P < 0.0001), 9.70 (2.27-41.4, P = 0.001), and 4.33 (1.27-14.8, P = 0.019), respectively. Among the 15 patients who developed interstitial lung disease, eight have died of the condition. Short interval from the initiation of gefitinib treatment to the onset of interstitial lung disease, acute interstitial pneumonia pattern, and the presence of pre-existing pulmonary fibrosis were associated with poor prognosis., Discussion: Our results suggest the importance of patient selection for gefitinib treatment based on interstitial lung disease risk factors in the Japanese population identified.

We evaluated the safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer (NSCLC). We retrospectively compared toxicity, response and survival outcomes for gefitinib in patients aged 75 years or older (elderly group) with the same outcomes in patients aged younger than 75 years. In total, 350 patients were eligible for this analysis, of whom 92 were in the elderly group and 258 in the non-elderly group. In the elderly group, adverse events were generally mild to moderate and grade 3-4 adverse events were observed in 8 (9%) patients. The objective response rate (17 vs. 21% for elderly vs. non-elderly, respectively) and median survival time (7.6 vs. 9.3 months) were also similar in the two groups. Multivariate analysis revealed elderly patients with lower Brinkman index tended to be more sensitive to gefitinib (odds ratio: 4.57, 95% confidence interval: 0.91-22.72, p = 0.0642). In this study, treatment with gefitinib appeared to be as safe and effective in elderly patients (aged 75 or older) with NSCLC as in non-elderly patients.

NSIP associated with primary lung cancer has been rarely reported. In the present report, three cases of histologically proven non-specific interstitial pneumonia (NSIP) associated with primary lung cancer are described. Importantly, in our 3 cases, interstitial pneumonia which is histologically proven to be NSIP was observed diffusely in both lungs. NSIP in these 3 cases responded to steroid therapy. However, 2 patients died from primary lung cancer and 1 patient died from progression of the interstitial pneumonia. Although the association between lung cancer and NSIP has been rarely documented, this combination was considered to be one of the paraneoplastic phenomena. The possible association between primary lung cancer and NSIP is discussed.