Mitsumasa Kawago

Histoculture drug response assay for gefitinib in non-small-cell lung cancer

ObjectiveThere are many predictive factors for gefitinib sensitivity, including epidermal growth factor receptor (EGFR) gene mutation, EGFR copy number, and k-ras mutation. To investigate all of them is too expensive. We evaluated the chemosensitivity for gefitinib in non-small-cell lung cancer (NSCLC) using a histoculture drug response assay (HDRA).MethodsSurgically resected fresh tumor specimens from 22 patients with NSCLC were used. There were 13 male and 9 female patients, ranging in age from 49 to 84 (average 70) years old. Sixteen patients (73%) were smokers. Sixteen adenocarcinomas, four squamous cell carcinomas, and two other histological types were included. Small pieces of viable cancer tissue were placed on the collagen gel and then cultured for 7 days in the presence of gefitinib.ResultsThe HDRA was successful in all specimens. A dose-response relation was observed between inhibition rates and gefitinib concentration (p = 0.016). The inhibition rate at 20 μg/ml (IR20) in adenocarcinoma without smoking (39.2% ± 35.1%, n = 6) was higher than that with smoking (2.2% ± 5.0%, n = 10, P = 0.001) and that of nonadenocarcinoma (16.9% ± 23.6%, n = 6, P = 0.09). Gene mutation analysis was performed in two of three adenocarcinomas without smoking, which showed especially high IR20 values, and sensitizing mutations were observed in these specimens. A cutoff inhibition rate of approximately 40%–50% appeared to be suitable for a concentration of 20 μg/ml.ConclusionHDRA appears to be applicable for evaluating sensitivity to gefitinib in NSCLC. It provides a convenient method for predicting the response to gefitinib in patients with NSCLC whose fresh tumor specimens are available.

Epidermal Growth Factor Receptor Mutations Are Associated with Docetaxel Sensitivity in Lung Cancer

Introduction: A recent large randomized controlled trial revealed that patients with lung cancer with epidermal growth factor receptor (EGFR) mutations had better prognoses when treated with the EGFR-tyrosine kinase inhibitor, gefitinib, than with cytotoxic chemotherapeutic agents. Lung cancer with EGFR mutations is highly sensitive to EGFR-tyrosine kinase inhibitors. The previous trial implied that EGFR mutations might be predictive of the response to cytotoxic chemotherapy. Methods: Forty-six tumor tissue specimens (32 adenocarcinomas and 14 nonadenocarcinomas) were obtained from patients with lung cancer who underwent surgical resection. EGFR mutations were detected using polymerase chain reaction-invader assay. A histoculture drug response assay was used as an in vitro drug sensitivity test. The inhibition rates of cisplatin, docetaxel (DOC), vinorelbine, and gemcitabine were measured. Results: Sensitizing EGFR mutations were detected in samples from 14 patients, all with adenocarcinomas. The inhibition rate of cisplatin in tumors with EGFR mutations (group M) was 34.8 ± 15.5%, which was significantly lower (p = 0.0153) than in wild-type tumors (group W; 46.6 ± 14.0%). The inhibition rate of DOC in group M (18.8 ± 13.4%) was also significantly lower (p = 0.0051) than in group W (35.4 ± 19.1%). There were no significant differences in inhibition rates of gemcitabine and vinorelbine between groups M and W. Inhibition rates of DOC were significantly lower in group M (p = 0.0256) than in group W (32.6 ± 18.4) in samples from patients with adenocarcinoma. Conclusion: The histoculture drug response assay indicated that lung cancers with EGFR mutations were less sensitive to DOC than EGFR wild-type tumors.

Primary Clear-Cell Sarcoma in the Mediastinum

We report a case of primary clear-cell sarcoma (CCS) in the mediastinum. In October 2011, a 63-year-old man was admitted to our hospital for surgical resection. The tumor was completely excised by video-assisted thoracoscopic surgery. The tumor was well encapsulated and did not invade the pleura. Histological examination led to a final diagnosis of primary CCS in the mediastinum. The patient remains alive without evidence of recurrence at 15 months after surgery.

Removal of an endobronchial foreign body using an ultrathin flexible bronchoscope and a novel suction system.

To the Editor: Foreign body aspiration in children is a serious condition and a pediatric emergency. If the diagnosis is delayed, complications such as persistent pneumonia, recurrent attacks of bronchospasm, lung abscess, recurrent hemoptysis, and bronchiectasis may develop, necessitating surgical intervention.1 We report a case of a persistent pneumonia of 3 weeks duration in an infant from aspiration of peanuts that was successfully managed by using an ultrathin flexible bronchoscope and a handmade suction system and a balloon catheter. Three weeks before the admission, a healthy 8-monthold boy suffered with productive cough and fever and was diagnosed with acute bronchitis. Despite the medical treatment, his symptoms persisted. A chest computed tomography (CT) scan revealed findings suggestive of a foreign body in the left main bronchus and a left lower lobe pneumonia (Fig. 1A). Under general anesthesia, an ultrathin flexible bronchoscope, 2.2mm in diameter (BFN20; Olympus, Tokyo, Japan) was inserted into the endobronchial tree through the endotracheal tube, 4.5 Fr in diameter. There was a thick white discharge in the left main bronchus and a foreign body, which was a piece of peanut, was observed. The scope was too slim and had no suction port. We made a handmade suction system by placing a small cut over the proximal end of a conventional suction catheter and inserted the bronchoscope into the tubing (Fig. 1B). We attempted to aspirate the foreign body with this modified suction device. However, it resulted in fragmentation of the peanut emitting moderate amount of white discharge from the distal airways (Fig. 1C). A 5.2 Fr balloon angioplasty catheter was then passed by the side of the bronchoscope placing the balloon distal to the foreign body. The balloon was then inflated with air and used to push the foreign body in a retrograde manner (pull). This maneuver allowed the foreign body to be brought proximally without further fragmentation. A split portion of the peanut was easily removed using the suction. (Fig. 1D). Patient’s symptoms promptly resolved, and there was no further recurrence of his pneumonia. Foreign body aspiration is a common pediatric emergency. More than 80% of cases of foreign body aspiration occur during early childhood, with a peak incidence between the ages of 10 and 24 months.2 Only 17.2% of patients with proven foreign bodies did not have an eyewitness to the aspiration episode, and only 20% of foreign bodies are radiopaque. Most of the aspirated foreign bodies in the pediatric age group are food particles, especially nuts or seeds. The diagnosis of a pediatric airway foreign body is more difficult because the patients are unable to communicate and delay in the treatment is not uncommon.3 The bronchoscopic removal of a foreign body among infants is not without challenges as fragmentation or distal migration of the foreign body can occur.4,5 Traditionally, rigid bronchoscopy was the procedure of choice for the removal of foreign bodies in children.6 However, flexible bronchoscopy is increasingly being used for the indication.7,8 Flexible bronchoscope has many advantages compared with rigid bronchoscope. Most importantly, its small diameter and flexibility enable to reach foreign bodies located in distal airways, which are difficult to access with a rigid bronchoscope. Second, flexible bronchoscope may allow simultaneous retrieval of fluids, especially mucus or blood clots, without requiring separate suction catheter.8 When the diagnosis is delayed, such as in our case, and if the foreign body is nuts or seeds, fragmentation is likely with the use of rigid instruments. We always perform the flexible bronchoscopy first before giving consideration to the rigid scope. The weakness of the ultrathin flexible bronchoscope could be the lack of a suction port, as one in our case. Our handmade suction system appeared to be useful to overcome this weak point. Flexible bronchoscopy combined with our handmade suction system and balloon catheter might come handy in similar situations. Disclosure: There is no conflict of interest or other disclosures. LETTERS TO THE EDITOR

Preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen level predicts postoperative distant metastasis in patients with non-small-cell lung cancer.

OBJECTIVES To examine the relationship between preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (I-CTP) levels and postoperative distant metastasis in patients with non-small-cell lung cancer (NSCLC). METHODS We retrospectively reviewed 143 patients in whom preoperative serum I-CTP level was measured from January 2006 to March 2011, including 91 males and 52 females with an average age of 70.1 ± 8.2 years. Histological subtypes included adenocarcinoma (n = 95), squamous cell carcinoma (n = 34) and other (n = 14). Preoperative serum carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA) levels were also measured. Patients with abnormal renal function or preoperative bone fractures were excluded. RESULTS The mean preoperative serum I-CTP level was 4.1 ± 1.6 ng/ml, and the preoperative serum I-CTP level was elevated (>4.5 ng/ml) in 29 patients. Distant metastasis was detected in 21 patients during the 39 ± 18 (range 1-79) months of follow-up. The rate of distant metastasis was significantly higher in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (≤4.5 ng/ml) (P < 0.0001). The 5-year recurrence-free survival rate was lower in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (41.8 vs 92.9%; P < 0.0001). CONCLUSIONS An elevated preoperative serum I-CTP level predicts postoperative distant metastasis in patients with NSCLC.