Atsushi Takise

Histopathologic prognostic factors in adenocarcinomas of the peripheral lung less than 2 CM in diameter

The histologic prognostic factors of pulmonary adenocarcinomas of the lung less than 2 cm in diameter were analyzed in 75 patients who had undergone surgical resection. The pathologic stage, lymph node involvement, and pleural involvement were found to be the major determinants of prognosis (P < 0.01). In addition, other single factors, such as tumor differentiation (P < 0.01), vascular invasion (P < 0.01), the degree of collagenization in the fibrotic focus (P < 0.01), the standard deviation (SD) of nuclear areas (P < 0.05), and mitotic index (P < 0.05) correlated significantly with prognosis by the log‐rank test on the Kaplan‐Meier survival curves of these factors. Patients with dense infiltration of “T‐zone histiocytes” survived significantly longer than those with less infiltration (P < 0.05). Coxs proportional hazard general linear model analysis showed the importance of factors, such as lymph node or pleural involvement and the SD of nuclear area, when the pathologic stage was excluded, and of the mitotic index when all four factors were excluded to emphasize the cellular characteristics. It is possible to predict the postoperative prognosis of patients with small pulmonary adenocarcinoma more precisely by combination of the above histopathologic factors.

Impact of preexisting pulmonary fibrosis detected on chest radiograph and CT on the development of gefitinib-related interstitial lung disease.

Objectives:Although preexisting pulmonary fibrosis (PF) on chest radiograph is known to be a risk factor of gefitinib-related interstitial lung disease (ILD), the significance of PF detected by chest computed tomography (CT) on the development of gefitinib-related ILD has not been investigated sufficiently. Methods:We reviewed 182 nonsmall cell lung cancer patients treated with gefitinib between July 2002 and March 2003. Chest radiographs and CT were taken in all patients periodically and reviewed by radiologists. PF was defined as ground-glass attenuation, consolidation, or reticular shadow without segmental distribution. Gefitinib-related ILD was defined as the acute respiratory failure developed during the course of gefitinib administration and lack of evidence for other cause of respiratory failure. Expected risk factors for gefitinib-related ILD were evaluated in multivariate analysis. Results:There were 15 patients with PF. Nine PF were detected on both chest radiograph and chest CT, and 6 on only chest CT. Twelve patients (6.6%) developed ILD during the course of gefitinib monotherapy and 4 died of it. Univariate and multivariate analyses showed that PF detected on chest radiograph was found to be the only significant risk factor for developing ILD (32.2, P < 0.001). Preexisting fibrosis diagnosed on chest CT but not apparent on chest radiograph was not significantly correlated with ILD. Conclusion:Gefitinib should not be given to patients with PF apparent on chest radiograph. Patients with PF on chest CT but not detected on chest radiograph could be treated carefully with gefitinib, but a risk-benefit analysis should be considered.

CYFRA 21 -1: An Indicator of Survival and Therapeutic Effect in Lung Cancer

CYFRA 21-1 is a new tumor marker using two different monoclonal antibodies which recognize the divergent epitope on the N- or C-terminal region of domain 2 of cytokeratin 19 fragment, respectively. In this study, we investigated the relationship between levels of CYFRA 21-1 and survival duration, as well as the efficacy of chemotherapy associated with changes in CYFRA 21-1. Serum samples were obtained from 87 patients with nonoperable lung cancer (35 cases with squamous-cell carcinoma, 33 with adenocarcinoma, 3 with large-cell carcinoma, and 16 with small-cell carcinoma). The cutoff point was set at 3.5 ng/ml. In a CYFRA 21-1 assay, significantly more patients with squamous-cell carcinoma and adenocarcinoma were positive compared to patients with small-cell and large-cell carcinomas (p = 0.0017). Following chemotherapy, blood levels of CYFRA 21-1 decreased significantly in responders versus nonresponders (p = 0.0246). A significant correlation was noted between survival periods and pretreatment levels of CYFRA 21-1 (p = 0.0036). The present study suggests that CYFRA 21-1 might be useful as a possible indicator of survival and therapeutic effect for lung cancer.

Barium sulphate aspiration

Correspondence to: Dr Kyoichi Kaira k-kaira@maebashi.jrc.or.jp An asymptomatic 70-year-old man had a barium swallow to screen for gastric cancer. During the examination, the patient aspirated high-density barium contrast medium (200% weight/volume) into his lungs. After 1 h, the patient developed fever, so doctors gave him faropenem 600 mg orally. Chest radiographs showed massive barium sulphate depositions in both lower lobes, middle lobe, and lingula (figure). 48 h later, he became dyspnoeic with worsening hypoxaemia (PaO2 57·2 mm Hg, PaCO2 32·1 mm Hg, breathing room air), and was transferred to our hospital. We treated him with intravenous meropenem 1 g/day and clindamycin 1200 mg/day, physical therapy with postural drainage, and oxygen. He recovered, and was discharged 7 days later. Aspiration of large amounts of barium sulphate is a rare incident during radiographic contrast procedures. In spite of the inert character of barium sulphate, the aspiration of highdensity barium is potentially life-threatening. Barium sulphate aspiration

Phase II study of weekly docetaxel and cisplatin in patients with non-small cell lung cancer.

We conducted a phase II study to examine the efficacy and safety of weekly docetaxel and cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC). Forty chemotherapy-naïve patients (10 with stage IIIB and 30 with stage IV NSCLC) with an Eastern Cooperative Oncology Group performance status of 0–2 and adequate organ functions were enrolled. Chemotherapy consisted of cisplatin (80 mg/m2) on day 1, and docetaxel (35 mg/m2) on days 1, 8 and 15, delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. There were 18 partial responses, with an overall response rate of 45% (95% confidence interval 29.6–60.4%) in 40 treated patients. The median survival period was 19.9 months, median progression-free survival was 5.5 months and 1-year survival rate was 69.4%. Hematologic toxicities were mild and included grade 3 or 4 neutropenia in 37.5%. There were no severe infections or septic deaths. Non-hematologic toxicities were generally mild. Grade 3 or 4 transaminase elevations were observed in two patients. Grade 3 events included two cases each of vomiting, and one case each of hypokalemia, diarrhea and creatinine elevations. Weekly docetaxel and cisplatin is an effective and safe combination in the treatment of patients with advanced NSCLC.

Late-Onset Chylothorax After Blunt Chest Trauma at an Interval of 20 Years: Report of a Case

We herein report an extremely rare case of a patient chylothorax at an interval of 20 years after thoracic vertebrae fractures, who underwent a successful thoracoscopic thoracic duct ligation and pleurodesis. A 51-year-old man was referred to our hospital with shortness of breath on effort about 1 month after participating in archery. Twenty years previously, he was involved in a traffic accident. At that time, the patient sustained trauma to the spine and suffered a spinal injury, thus resulting in paralysis in the lower part of his body. A chest roentgenogram and computed tomogram revealed a large amount of bilateral pleural effusion. After thoracentesis was performed, a diagnosis of chylothorax was made and the patient was hospitalized. Conservative management by a low-fat diet proved to be unsuccessful. The patient did not request pleurodesis, because pleural adhesions might impair pulmonary function. As a result, we decided to perform surgery. On the right side, we performed video-assisted thoracoscopic surgery by clipping the thoracic duct and applying an absorbable sealing material. Thereafter, pleurodesis was performed and OK-432 was instilled. Thereafter, the pleural fluid flow was almost completely stopped. On the left side, pleurodesis was effective. The patient has since remained symptom free and has been followed up on an outpatient basis for 9 months after the 100th postoperative day. We assumed that the chylothorax in this case was related to the earlier traffic accident.

Spontaneous Expectoration of Primary Pulmonary Synovial Sarcoma

A-34-year-old Chinese man who had smoked about 20 cigarettes per day for the past 14 years presented with cough and hemoptysis that had persisted for 2 months. Chest radiography revealed mass shadow in the left lower field. A computed tomographic scan of the chest revealed the tumor in the left lower lobe, occupying left main bronchus lumen with polypoid endobronchial growth (Figure 1). Physical examination revealed wheezing in the left lung field. Routine laboratory investigations were within the normal limit. An abdominal–pelvic computed tomographic scan, bone scan, and Ga-67 citrate scintigraph were performed, and there was no evidence of diseases other than this lung mass. Bronchoscopy was performed, revealing a smooth, well-demarcated polypoid mass (Figure 2). The biopsy specimens only revealed necrotic tissue. Twelve days after the bronchoscopy, the patient expectorated a polypoid mass tissue with concurrent hemoptysis (Figure 3). Thoracotomy was performed for resection of the mass and lobectomy of the left lower lobe, and the patient was uneventful after the surgical resection. Macroscopically, a polypoid tumor arose from the left lower lobe, protruding into the left lower bronchus to the left primary bronchus. Microscopically, this tumor was suggestive of synovial sarcoma (Figure 4). Immunohistochemically, tumor cells were positive for vimentin and focally positive for pancytokeratin, recognized by AE1/AE3, cytokeratin 7, and

Intense accumulation of gallium-67 citrate in pancreatic endocrine tumor

We report intense accumulation of gallium-67 (Ga-67) citrate in a pancreatic endocrine tumor. A 69-year-old woman was admitted because of cough, fever, and weight loss. An abdominal enhanced computed tomography (CT) scan revealed a large tumor located between the liver and pancreas as well as swollen paraaortic lymph nodes. Whole-body scintigraphy with Ga-67 revealed intense accumulation in the upper abdomen corresponding to the mass, as well as in the midabdomen and the mediastinal lesion. Percutaneous needle biopsy was performed, and the diagnosis was adenocarcinoma of the pancreas. The patients condition deteriorated, and she died 2 months after admission. The pathological examination at autopsy revealed a pancreatic endocrine tumor. No report has described findings of Ga-67 citrate scintigraphy of pancreatic endocrine tumors. Pancreatic endocrine tumor should be included in a differential diagnosis when such scintigraphic findings are encountered.

A phase II study of combined chemoradiotherapy for limited disease-small-cell lung cancer.

A study to evaluate the efficacy of cisplatin, doxorubicin, and etoposide chemotherapy with combined radiotherapy was undertaken in 26 patients with limited disease-small-cell lung cancer. Patients were treated with cisplatin (80 mg/m2) intravenously (i.v.) on day 1, doxorubicin (30 mg/m2) i.v. on day 1, and etoposide (80 mg/m2) i.v. on days 1, 3, and 5, every 4 weeks for four cycles. Thoracic irradiation of 40 Gy in 20 fractions was delivered during 4 weeks to the primary site starting on day 8 of the second cycle of chemotherapy. The objective response rate was 100%. A complete response was observed in 10 patients (38%). The median survival time was 23 months, and the 3-year survival rate was 42%. Seven patients (27%) continued to survive at least 8 years and remain free from disease. Grade III/IV leukopenia was observed in 25 patients (96%). Grade III/IV thrombocytopenia developed in 19 patients (73%). Grade III/IV esophagitis was not seen. Interstitial pneumonitis occurred in two patients. This regimen is effective and has acceptable toxicity for use in the treatment of limited disease-small-cell lung cancer.

A phase II study of carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.