[en] Irinotecan, when combined with cisplatin, is an effective treatment for advanced non-small cell lung cancer (NSCLC). This constitutes a rationale for conducting a phase I study of chemoradiotherapy including this combination for locally advanced NSCLC. Patients with locally advanced NSCLC and a performance status of 0 or 1 were eligible. The protocol consisted of escalating doses of irinotecan on days 1 and 15, and daily low-dose cisplatin (6 mg/m² daily for a total dose of 120 mg/m²) combined with concurrent hyperfractionated accelerated thoracic irradiation (1.5 Gy twice daily for a total dose of 60 Gy). The maximum tolerable dose was 50 mg/m² of irinotecan, and the dose-limiting toxicity was esophagitis. Tumor response was observed in 50% of cases, and the median survival time of the 12 patients enrolled was 10.1 months, including two patients with 5-year disease-free survival. A pharmacokinetics study demonstrated an accumulation of total platinum, but not of free platinum, during the 26-day treatment period. The recommended dose for phase II studies was determined. (author)

[en] A 77 year-old man with bronchogenic epidermoid carcinoma in the left hilum received a course of radiotherapy, after completion of chemotherapy with Cisplatin and Vindesine. Primary lesion and the mediastinum were irradiated up to 70 Gy. Subsequently, he developed serious radiation pneumonitis bilaterally, and died of acute respiratory failure. High dose and wide field irradiation, irradiation to the mediastinum, concomitant chemotherapy and withdrawal of steroids were supposed to be important factors to cause such a serious bilateral pneumonitis. In this case, the most unique point was that the right lung, contralateral to the irradiated lung was affected more seriously than the irradiated lung. It was surmised that due to tumor invasion severely narrowed bronchi and pulmonary arteries in the left lung might have played a role in suppressing effect on the progress of pneumonitis in the left side. We could find no similar case in the literature. (author)

[en] Long-acting bronchodilators are recommended as a first-line treatment for chronic obstructive pulmonary disease (COPD), although their effects for postoperative lung cancer patients with COPD are still not well known. A prospective randomized trial was used to examine the efficacy of bronchodilators on postoperative pulmonary function and quality of life (QOL). Twenty lung cancer patients with COPD who had lobectomies were randomized. A control group (n=10) did not receive bronchodilators. An experimental group (n=10) received tiotropium and salmeterol. Patients were divided into two COPD grades: stage I COPD and stage II-III COPD. Results for pulmonary function, 6-minute walking test, and the St. George's Respiratory Questionnaire (SGRQ) were compared. Diaphragmatic motion on dynamic magnetic resonance imaging was also analyzed. The patient demographics were similar in the two groups. Except for pulmonary function results at 2 weeks, no other parameters were significantly different. However, in stage II-III COPD, forced expiratory volume in 1 second, forced vital capacity, inspiratory capacity, the total score of the SGRQ, and diaphragmatic motion in the experimental group (n=5) were significantly better than those in the control group (n=4) at various time points (all P<0.05). The daily inhalation of bronchodilators was effective for maintaining the respiratory function and QOL in lung cancer patients with moderate to severe COPD. (author)

[en] The objective of this study was to examine the effects of dose-volume factors on the development of radiation pneumonitis in patients with non-small-cell lung cancer who received twice-daily radiotherapy concurrently with carboplatin and paclitaxel chemotherapy. Radiotherapy consisted of twice-daily fractionation of 1.2 Gy, to a total dose of 60 Gy. Weekly carboplatin and paclitaxel were used as a concurrent chemotherapy. Effects of radiotherapy parameters on the development of radiation pneumonitis were retrospectively analyzed. Fourteen of 37 patients developed Grade 2 or worse (≥G2) radiation pneumonitis. Grade 2 or worse radiation pneumonitis occurred in all 5 patients with V5 >40%, all 4 patients with V10 >35%, all 4 patients with V13 >32%, 9 of 14 patients with V20 >24% and 8 of 11 patients with V30 >22%, whereas 9 of 32 patients with V5 <40%, 10 of 33 patients with V10 <35%, 10 of 33 patients with V13 <32%, 5 of 23 patients with V20 <24% and 6 of 26 patients with V30 <22%, with respective P values of 0.0045, 0.015, 0.015, 0.015 and 0.008. Eight of 11 patients with a mean lung dose of >14 Gy developed ≥G2 radiation pneumonitis in contrast to 6 of 26 patients with a mean lung dose of <14 Gy (P=0.008). Several cut-off values in the V_dose and the mean lung dose differentiating probabilities of developing ≥G2 radiation pneumonitis were identified in this combination therapy. (author)

[en] Dilatation of the bronchial arteries is a well-recognized feature in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of the current study was to use computed tomography (CT) to assess the relationship between dilated bronchial arteries and the extent of thrombi, and to evaluate the predictive value of the former for surgical outcome. Fifty-nine patients with CTEPH and 16 with pulmonary arterial hypertension (PAH) were retrospectively evaluated. The total cross-sectional area of bronchial arteries was measured by CT and its relationship with the central extent of thrombi or surgical outcome was assessed. The total area of the bronchial arteries in CTEPH patients was significantly larger than that in PAH patients (median [range], 6.9 [1.7-29.5] mm² vs 3.2 [0.8-9.4] mm²), with the total area of bronchial arteries correlating with the central extent of thrombi. In patients who had undergone pulmonary thromboendarterectomy (PTE) (n=22), the change in PaO₂ after surgery had a tendency to correlate with the total area of the bronchial arteries. The total cross-sectional area of the bronchial arteries correlated with the extent of central disease in patients with CTEPH, and it might predict gas exchange improvement after PTE. (author)

[en] The development of computerized tomography (CT) has made CT fluoroscopy possible with real-time CT images. However examination are expected to have high medical and occupational exposures. Then, exposures to patients and operating and assisting physicians during the CT fluoroscopy-guided lung biopsy were estimated. And changes in the examination conditions to lower the dose were made. Patient exposure was measured using an anthropomorphic phantom by simulation of clinical examination conditions. The surface dose to the physician was measured during actual clinical examinations. The average effective dose for the patient was 34±22 mSv. The highest surface dose amounted to 1.9 Gy, although this was in a very narrow field. Patient doses could be reduced by a factor of 2.5-3 by changing examination methods while still retaining diagnostic quality. The highest dose to the operating physician was 10 mGy which was recorded on the back of the hand and the average effective dose was estimated as 5.99 μSv per 1-minute examination. Doses were reduced by about a factor of 50 by lowering the tube voltage from 120 kV to 80 kV and using a supplementary tool. The doses for assisting physicians were not significant. The exposure for physicians and patients was much affected by lowering the tube voltage used for fluoroscopy. Using a supplementary tool was effective for reducing the dose for physicians. (author)

[en] There are no peculiar clinical conditions in the diagnosis of thrombosis, and the role that the diagnostic imaging play is a great. Particularly, contrast Enhanced CT is low invasive diagnostics, and the thrombus in the pulmonary artery can be detected as a low density without the contrast effect. Moreover, because describing the change of concentration in lung field and the decline in lung blood vessel shadow is also possible, it is indispensable to diagnose of thrombosis. As the image diagnosis support, it is hoped to classify the pulmonary artery and vein that relate to the thrombosis, and to analyze the lung blood vessel quantitatively. In this report, the effectiveness of the method is shown by analyzing the structure by using the extracted pulmonary artery through semi-automated method, measuring the vessel diameter, and comparing it with a normal example. (author)

[en] The addition of bevacizumab to cytotoxic agents prolongs survival in patients with nonsquamous non-small cell lung cancer (NSCLC). To date, there is no evidence to suggest that treatment with a cytotoxic agent plus bevacizumab is more effective than a cytotoxic agent alone for nonsquamous NSCLC in elderly patients. We conducted a feasibility study of pemetrexed plus bevacizumab as a first-line treatment for advanced or recurrent nonsquamous NSCLC in elderly patients. Major eligibility and exclusion criteria included: chemotherapy-naive status; non-fitness for bolus combination chemotherapy; stage III/IV or relapsed nonsquamous NSCLC; age ≥70; performance status 0–1; absence of brain metastasis; and no history of hemoptysis and thoracic irradiation. Pemetrexed (500 mg/m"2) and bevacizumab (15 mg/kg) were administered intravenously on day 1, and repeated every 3 weeks thereafter. The primary endpoint was safety, and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the percentage of patients who completed ≥3 cycles. From October 2010 to April 2012, a total of 12 patients were enrolled. No dose-limiting toxicity or treatment-related deaths were observed. Three patients achieved PR, and the ORR was 25 %. The median PFS and OS were 5.4 months (95 % CI 1.1–8.8 months) and 13.6 months (95 % CI 5.3–15.6 months), respectively. Seven of 12 patients (58 %) received ≥3 cycles. Pemetrexed plus bevacizumab in the treatment of elderly patients with nonsquamous NSCLC was well tolerated and shows promise as first-line treatment

[en] Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and is a predictive immunomarker of the response to S-1 NAC and patient prognosis

[en] Purpose: To evaluate whether dual-time point scanning with integrated fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography and computed tomography (PET/CT) is useful for evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT. Materials and methods: PET/CT data and pathological findings of 560 nodal stations in 129 patients with pathologically proven non-small cell lung cancer diagnosed as operable by contrast-enhanced CT were reviewed retrospectively. Standardized uptake values (SUVs) on early scans (SUVe) 1 h, and on delayed scans (SUVd) 2 h after FDG injection of each nodal station were measured. Retention index (RI) (%) was calculated by subtracting SUVe from SUVd and dividing by SUVe. Logistic regression analysis was performed with seven kinds of models, consisting of (1) SUVe, (2) SUVd, (3) RI, (4) SUVe and SUVd, (5) SUVe and RI, (6) SUVd and RI, and (7) SUVe, SUVd and RI. The seven derived models were compared by receiver-operating characteristic (ROC) analysis. k-Fold cross-validation was performed with k values of 5 and 10. p < 0.05 was considered statistically significant. Results: Model (1) including the term of SUVe showed the largest area under the ROC curve among the seven models. The cut-off probability of metastasis of 3.5% with SUVe of 2.5 revealed a sensitivity of 78% and a specificity of 81% on ROC analysis, and approximately 60% and 80% on k-fold cross-validation. Conclusion: Single scanning of PET/CT is sufficiently useful for evaluating mediastinal and hilar nodes for metastasis.