Comparison of sensitivity of lung nodule detection between radiologists and technologists on low-dose CT lung cancer screening images.

OBJECTIVES: The objective of this study was to compare the sensitivity of detection of lung nodules on low-dose screening CT images between radiologists and technologists. METHODS: 11 radiologists and 10 technologists read the low-dose screening CT images of 78 subjects. On images with a slice thickness of 5 mm, there were 60 lung nodules that were ≥5 mm in diameter: 26 nodules with pure ground-glass opacity (GGO), 7 nodules with mixed ground-glass opacity (GGO with a solid component) and 27 solid nodules. On images with a slice thickness of 2 mm, 69 lung nodules were ≥5 mm in diameter: 35 pure GGOs, 7 mixed GGOs and 27 solid nodules. The 21 observers read screening CT images of 5-mm slice thickness at first; then, 6 months later, they read screening CT images of 2-mm slice thickness from the 78 subjects. RESULTS: The differences in the mean sensitivities of detection of the pure GGOs, mixed GGOs and solid nodules between radiologists and technologists were not statistically significant, except for the case of solid nodules; the p-values of the differences for pure GGOs, mixed GGOs and solid nodules on the CT images with 5-mm slice thickness were 0.095, 0.461 and 0.005, respectively, and the corresponding p-values on CT images of 2-mm slice thickness were 0.971, 0.722 and 0.0037, respectively. CONCLUSION: Well-trained technologists may contribute to the detection of pure and mixed GGOs ≥5 mm in diameter on low-dose screening CT images.

Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer.

Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.

Efficacy of droperidol in the prevention of cisplatin-induced delayed emesis: a double-blind, randomised parallel study.

We conducted a prospective, randomized, double-blind, parallel study comparing the antiemetic activity and tolerability of treatment with droperidol (2.5 mg d.i.v. twice daily for 5 days) and placebo, both combined with granisetron (3 mg d.i.v. on the first day) and dexamethasone (16 mg d.i.v. on the first day, 8 mg d.i.v. on days 2, 3, and 4 mg d.i.v. on days 4, 5). A total of 180 lung cancer patients receiving high-dose cisplatin (80 mg/m(2))-containing chemotherapy were enrolled in the study, and 171 of them were capable of being evaluated. The clinical characteristics of the patients in the two treatment arms were well balanced. Complete protection from nausea and vomiting was recorded in the acute phase in 97% of patients who treated with droperidol versus 98% of patients who given the placebo (P=0.920), and in 42% versus 38% in the delayed phase (P=0.615). The multiple logistic regression analysis showed that a history of motion sickness was a significant risk factor for cisplatin-induced delayed emesis (odds ratio [OR]=5.98; 95% CI=2.15 to 16.7, P=0.0006). Droperidol-containing treatment was well tolerated by most patients, however, the incidence of sleepiness in the droperidol group was higher than in the placebo group (69% versus 30%, P<0.0001). In conclusion, our data did not support the hypothesis that addition of droperidol to granisetron and dexamethasone reduces the delayed emesis induced by high-dose cisplatin.

A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients.

BACKGROUND: To evaluate the efficacy and safety of treatments for advanced non-small-cell lung cancer in elderly patients aged 75 years or older, we conducted a phase II study of cisplatin and docetaxel administered in three consecutive weekly infusions. PATIENTS AND METHODS: The eligibility criteria for the study included the presence of chemotherapy-naive advanced non-small-cell lung cancer, age > or =75 years, Eastern Cooperative Oncology Group performance status of 0 or 1, a measurable lesion, adequate organ functions and signed informed consent. The chemotherapy regimen consisted of cisplatin (25 mg/m(2)) and docetaxel (20 mg/m(2)) on days 1, 8 and 15 every 4 weeks. RESULTS: Between February 2000 and March 2002, 34 elderly patients with non-small-cell lung cancer were enrolled in the study and 33 patients were treated. Two complete responses and 15 partial responses were obtained for an objective response rate of 52% in 33 treated patients. The median survival period was 15.8 months, and the 1-year survival rate was 64%. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%), neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. CONCLUSION: Cisplatin and docetaxel administered in three consecutive weekly infusions was safe and effective for the treatment of elderly patients with chemotherapy-naive non-small-cell lung cancer.

Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507.

Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.

Triplet chemotherapy with vinorelbine, gemcitabine, and cisplatin for advanced non-small cell lung cancer: a phase II study.

We conducted a phase II trial of triplet chemotherapy consisting of vinorelbine, gemcitabine, and cisplatin in patients with advanced non-small cell lung cancer to assess its efficacy and toxicity. Thirty-three patients with chemotherapy-naïve stage IIIB disease (n=8), stage IV disease (n=23), or recurrence after surgical resection (n=2) were given intravenous infusions of vinorelbine 25 mg m(-2), gemcitabine 1000 mg m(-2), and cisplatin 40 mg m(-2) on days 1 and 8 at 3-week intervals. There were 16 partial responses, and the objective response rate was 48% (95% confidence interval: 31-66%). The median survival time was 13.5 months (95% confidence interval: 10.6-16.4 months), and the one-year survival rate was 61%. Grade 4 haematologic toxicity consisted of neutropenia in 72% of patients, and febrile neutropenia occurred in 42% of the patients. There was one toxic death, and it was attributed to neutropenic fever and haemoptysis. Autopsy revealed diffuse pulmonary haemorrhage secondary to bacterial abscesses and vasculitis in both lungs. The common nonhaematologic toxicities included grade 2-3 nausea (39%) and vomiting (18%). Triplet chemotherapy containing vinorelbine, gemcitabine, and cisplatin is effective in the treatment of chemo-näive patients with advanced non-small cell lung cancer, but produces unacceptable frequent febrile neutropenia.

Serum levels of KL-6 are useful biomarkers for severe radiation pneumonitis.

The antigen KL-6, a mucin-like high-molecular-weight glycoprotein, is expressed on type-2 pneumocytes and bronchiolar epithelial cells. Serum levels of KL-6 have been shown to correlate well with the activities of several different kinds of interstitial pneumonia. The purpose of this study was to assess the usefulness of monitoring serum KL-6 levels in patients who had received thoracic radiotherapy (TRT). In particular, the usefulness of such a protocol for the early diagnosis of severe radiation pneumonitis (RP) and the evaluation of its progress and severity was examined. Serum KL-6 levels were retrospectively monitored in 16 patients with lung cancer who had received TRT with or without chemotherapy. Eight of these patients had developed severe RP and eight had developed localized (within the irradiated field) RP. Serum KL-6 levels were measured using a modified sandwich-type enzyme-linked immunosorbent assay. In patients who developed severe RP, serum KL-6 levels showed a consistent tendency to increase after the clinical diagnosis of RP. In four patients, serum KL-6 levels even began to rise before a clinical diagnosis of severe RP had been made. In the patients with localized RP, on the other hand, the serum levels did not show any tendency to increase during or after TRT. Moreover, patients whose serum KL-6 levels rose more than 1.5 times higher than their pre-treatment serum KL-6 level, had a large chance of developing severe RP that was unresponsive to steroid hormones and resulted in death. Serum KL-6 levels, therefore, should be useful indicators for the early diagnosis of severe RP and for estimating its progress and severity in patients treated with TRT.

Improved superoxide-generating ability by interferon gamma due to splicing pattern change of transcripts in neutrophils from patients with a splice site mutation in CYBB gene.

Chronic granulomatous disease (CGD) is an inherited disorder of host defense against microbial infections caused by defective activity of the phagocyte NADPH oxidase. Based on an increase of neutrophil superoxide-generating ability in response to interferon gamma (IFN-gamma) in a single patient with CGD, multicentered group studies demonstrated a beneficial effect of prophylactic IFN-gamma. However, no apparent increase of the phagocyte superoxide generation was found in patients enrolled in these studies. The present report offers an additional kindred in whom an IFN-gamma-dependent increase in neutrophil superoxide production was observed in 3 affected patients. The defect in the CYBB gene for gp91-phox was identified as an otherwise silent mutation adjacent to the third intron of the CYBB gene that alters messenger RNA splicing. By molecular analysis, significant differences were found in the splicing pattern of CYBB gene transcripts in patient neutrophils between 1 and 25 days after administration of IFN-gamma. Furthermore, a complete transcript containing the missing exons could be detected in all specimens after the treatment. The changes in the splicing pattern of the transcripts and the prolonged effect on superoxide-generating ability of patient neutrophils indicate that IFN-gamma induced a partial correction of the abnormal splicing of CYBB gene transcripts in myeloid progenitor cells.

Phase I studies of cisplatin and docetaxel administered by three consecutive weekly infusions for advanced non-small cell lung cancer in elderly and non-elderly patients.

BACKGROUND: To determine the maximum tolerated dose and recommended dose of cisplatin and docetaxel administered by three consecutive weekly infusions in both non-elderly (< or =74 years) and elderly (> or =75 years) patients, we conducted two independent phase I studies for nonelderly and elderly patients with non-small cell lung cancer. METHODS: Between April 1998 and September 1999, 26 non-elderly (median, 54 years; range, 44-73 years) and 12 elderly (median, 76 years; range, 75-80 years) patients with non-small cell lung cancer were entered in these studies. The eligibility criteria of both cohorts were identical except for age. Chemotherapy consisted of cisplatin 25 mg/m2 and an escalated dose of docetaxel on days 1, 8 and 15 every 4 weeks. The initial dose of docetaxel was 20 mg/m2 and it was increased by 5 mg/m2 at each dose level. RESULTS: In the non-elderly and elderly cohorts, up to 45 or 25 mg/m2 of docetaxel, respectively, were administered. Dose-limiting toxicities were neutropenia, liver damage, pneumonia and omission of treatment on day 15 by leukopenia and refusal in the non-elderly cohort; pneumonia and omission of treatment on day 15 by refusal due to fatigue/asthenia or fever in the elderly cohort. We considered the recommended doses for phase II studies were cisplatin 25 mg/m2 and docetaxel 35 mg/m2 on days 1, 8 and 15 for non-elderly patients and cisplatin 25 mg/m2 and docetaxel 20 mg/m2 on days 1, 8 and 15 for elderly patients. Seven of 26 (27%) and seven of 12 (58%) patients achieved a partial response, median survival times were 8.7 and 7.2 months and 1 year survival rates were 27 and 27% in the non-elderly and elderly cohorts, respectively. CONCLUSIONS: Further evaluation of this combination chemotherapy is warranted for both nonelderly and elderly patients with non-small cell lung cancer but the dose of docetaxel should be lower for elderly than non-elderly patients.

Phase I and pharmacological study of paclitaxel given over 3 h with cisplatin for advanced non-small cell lung cancer.

BACKGROUND: To establish the toxicities and maximum tolerated dose of paclitaxel given over 3 h in combination with cisplatin, to determine the pharmacokinetic profiles of these two drugs and to observe their antitumor activity, we conducted a combination phase I study in non-small cell lung cancer. METHODS: Patients received paclitaxel doses of 150-210 mg/m2 given over 3 h and cisplatin doses of 60-80 mg/m2 as a 1 h infusion 2 h after the end of the paclitaxel infusion. RESULTS: A total of 25 patients with previously untreated non-small cell lung cancer were enrolled. Granulocytopenia was the most frequent hematological toxicity and the most prominent non-hematological toxicity was sensory dominant neuropathy. Two of six patients experienced dose limiting toxicities (leukopenia, infection and neuropathy) at a dose of paclitaxel 210 mg/m2 and cisplatin 60 mg/m2, which was considered the maximum tolerated dose. There were seven partial responses among 24 evaluable patients, for an overall response rate of 29%. The median survival time was 341 days and the 1 year survival rate was 45.8%. As the paclitaxel pharmacokinetic parameters in this study were consistent with those of our previous single agent study, we found no significant drug-drug interaction between the 3 h infusion paclitaxel and cisplatin. CONCLUSION: The recommended doses for further study are determined to be paclitaxel 180 mg/m2 and cisplatin 80 mg/m2. This is a well-tolerated and active regimen for non-small cell lung cancer. In view of the promising survival outcome, further evaluation in prospective randomized trials versus other regimens is warranted.

Clinicopathological characteristics of surgically resected lung cancer associated with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. It is important to clarify the clinical and pathological features of lung cancer with IPF in understanding the pathogenesis of lung cancer in IPF patients. We compared clinicopathological factors of lung cancer in patients with and without IPF. METHODS: A retrospective study was conducted in 711 surgically resected lung cancer patients. Medical records were compared of IPF and non-IPF patients. RESULTS: Of the 711 patients, 53 (7.5%) were IPF patients. Lung cancer in IPF patients was more frequent in elderly male smokers. Most lung cancers in IPF (79%) arose in peripheral areas involving fibrosis (P < 0.01). The incidence of squamous cell carcinoma in the IPF patients (46%) was significantly higher than that in non-IPF patients (22%) (P < 0.01). The incidence of multiple lung cancer in IPF cases (17%) was also significantly higher. CONCLUSIONS: These results suggest that IPF has the potential to develop into lung cancer, especially peripheral squamous cell carcinoma. Further molecular analyses are necessary to clarify the relationship between IPF and lung cancer.

Risk factors of treatment-related death in chemotherapy and thoracic radiotherapy for lung cancer.

We retrospectively analysed the incidence and risk factors of treatment-related death in the treatment of chemotherapy- and thoracic radiotherapy-naïve patients with lung cancer. Between July 1992 and December 1997, 1799 patients were diagnosed as having lung cancer in our hospital and 926 patients received chemotherapy and/or thoracic radiotherapy. 25 patients (2.7%) died from toxicity of the treatment, 10 from pneumonia, 7 from radiation pneumonitis, 6 from sepsis, 1 from perforation of the small intestine and 1 for an unknown reason. 18 patients (2.3%) died from chemotherapy-related toxicity. The incidence of treatment-related death (TRD) from chemotherapy was highly correlated with the performance status (PS), PS 0: 0.7%, PS 1: 2.2%, PS 2: 4.0%, PS 3: 7.7% and PS 4: 25% (P=0.004). 7 patients (1.6%) died from pneumonitis after thoracic radiotherapy. Multivariate analyses demonstrated that poor PS (relative risk (RR): 1.95, 95% confidence interval (CI): 1.05-3.65, P=0.034) and chemotherapy using the cisplatin+vindesine+mitomycin C regimen (RR: 9.36, 95% CI: 1.29-68.0, P=0.027) are associated with treatment-related death from chemotherapy. Pulmonary fibrosis identified on a plain chest X-ray film (RR: 165.7, 95% CI: 8.79-3122, P<0.001), the combination of cisplatin+irinotecan (RR: 120.5, 95% CI: 2.90-4993, P=0.012), advanced age (RR: 1.17, 95% CI: 1.002-1.37, P=0.047), and elevated lactate dehydrogenase (LDH) (RR: 10.4, 95% CI: 1.20-90.2, P=0.033) were also associated with treatment-related death from thoracic radiotherapy. The administration of mitomycin C in addition to cisplatin-based regimens for patients with lung cancer should be carefully considered.

Secretion of hCG/beta-hCG by squamous cell carcinoma of the lung in a 31-year-old female smoker.

We describe a rare case of pulmonary squamous cell carcinoma secreting human chorionic gonadotropin (hCG) and its beta-subunit (beta-hCG) in a young female smoker. A 31-year-old mother of one child had been suffering from dysfunctional uterine bleeding for about 1 year. Pelvic examinations and abdominal ultrasonography yielded no abnormal findings and no signs of pregnancy. She developed a pain in the right chest and a huge (12x10 cm) squamous cell carcinoma was diagnosed in the right lower lobe. The serum hCG and beta-hCG levels were high: hCG 5611 mlU/ml (normal upper limit 0.7 mIU/ml), beta-hCG 12 238 mIU/ml (normal upper limit 0.5 mIU/ml). The patient underwent right lower lobectomy and systematic lymph node dissection. Microscopic study showed a poorly differentiated squamous cell carcinoma. The pathological stage was T2N0M0, stage IB. Immunohistochemical staining of the tumor was strongly positive for hCG. The serum hCG level returned to normal 1 month after the operation, while an additional 2 months were necessary for the beta-hCG level to normalize. Dysfunctional uterine bleeding disappeared and the patient is doing well, with no signs of recurrence, 9 months after the resection.

Significance of serum pro-gastrin-releasing peptide as a predictor of relapse of small cell lung cancer: comparative evaluation with neuron-specific enolase and carcinoembryonic antigen.

Neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) have been reported to be useful markers for staging, monitoring treatment, and predicting relapse in patients with small cell lung cancer (SCLC). Recently, pro-gastrin-releasing peptide (Pro-GRP) became available as a sensitive, specific, and reliable tumor marker for patients with SCLC. The aim of this study is to determine the most useful tumor marker to detect the relapse of SCLC. Furthermore, we analyzed the relationship between tumor markers at relapse and survival from relapse or response to salvage chemotherapy. Medical records were reviewed to obtain serum levels of Pro-GRP, NSE, and CEA before and after the initial chemotherapy, and at relapse. Consecutive 66 patients with SCLC, with an objective response and confirmed relapse treated at the National Cancer Center Hospital East, were analyzed in this study. The percentages of patients whose tumor marker level were elevated before treatment, decreased after the treatment, and increased again at relapse were 67% (95% CI, 55-78) for Pro-GRP, 20% (10-29) for NSE, and 38% (26-50) for CEA. Multivariate analysis indicated that poor performance status before initial treatment and elevated serum levels of lactate dehydrogenase at relapse were poor prognostic factors for patients with recurrent SCLC (P<0.005). None of the serum levels of Pro-GRP, NSE, and CEA at relapse was a significant prognostic factor and associated with an objective response to salvage chemotherapy. The present study demonstrated that serum levels of Pro-GRP reflect the disease course of patients with SCLC most accurately.

Computed tomography screening for lung carcinoma in Japan.

BACKGROUND: In Japan, lung carcinoma is the leading cause of cancer-related deaths. Adenocarcinoma accounts for roughly half of all lung carcinomas. Earlier detection of lung carcinoma is expected to reduce mortality rates. Computed tomography (CT) provides higher contrast resolution and greater visualization of chest compartments that are difficult to view with chest radiography, such as the mediastinum. CT further permits the detection of minute peripheral nodules. At present, several institutions and research groups are evaluating the utility of low dose spiral CT for lung carcinoma screening. METHODS: From September 1993 to December 1998, 1669 individuals underwent a biannual screening program for lung carcinoma. The program included posteroanterior radiograph, sputum cytology, and low dose spiral CT at a for-profit organization: The Anti-Lung Cancer Association (ALCA). A total of 9993 examinations were carried out. The low dose spiral CT parameters used were 120 kvP, 50 mA, 10-mm collimation, and 2:1 pitch. RESULTS: Peripheral lung carcinoma was detected in 31 of 9993 examinations (0.3%). Of the 31 cases, 24 tumors (77%) were detected by low dose spiral CT but were not visible on standard chest radiography. Twenty-two of the 24 tumors were Stage IA (T1N0M0, according to staging system revised in 1997). CONCLUSIONS: Low dose spiral CT shows promise for lung carcinoma screening. The effectiveness of the technique for the detection of minute lung lesions remains to be established. Routine use of the technique will require resolution of several issues. These issues include the establishment of CT diagnostic criteria, the development of a diagnostic support system, the establishment of methods for definite diagnosis, and assessments of efficacy.

Detection failures in spiral CT screening for lung cancer: analysis of CT findings.

PURPOSE: To clarify the computed tomographic (CT) findings and the progression of minute lung cancers that were missed at initial spiral CT screening but were later detected. MATERIALS AND METHODS: The findings from seven patients with lung cancer that was missed at the initial spiral CT screening were reviewed. Retrospective CT findings, time to detection, cell type, and pathologic stage were evaluated. RESULTS: Minute lung cancers missed at early spiral CT included a nodule among the shadows of old tuberculosis (n = 2), a faint nodule with high attenuation in the center of the nodule (n = 1), an increase in attenuation just adjacent to an axial peripheral pulmonary vessel (n = 1) and adjacent to a craniocaudal peripheral pulmonary vessel (n = 1), and a minute faint nodule (n = 2). The time to detection ranged from 6 to 18 months. At pathologic examination, six cancers were stage I, and one was stage II. CONCLUSION: Minute nodules of lung cancer that are near the threshold of detectability may be missed at spiral CT screening. It is important to examine noncalcified nodules with thin-section CT even when lesions from prior disease, such as those from old tuberculosis, exist and to evaluate the shadows of pulmonary vessels carefully. A follow-up examination is highly recommended.

Effect of nebulized morphine in cancer patients with dyspnea: a pilot study.

BACKGROUND: It is known that opioids may decrease subjective dyspnea. The recent finding that opioid binding sites are present in the peripheral bronchus supports the possibility of a local action of opioids. However, the clinical benefit of nebulized morphine is controversial. The purpose of this study was to confirm the feasibility of nebulized morphine and to evaluate its clinical benefits. PATIENTS AND METHODS: Fifteen cancer patients with dyspnea in the Thoracic Oncology Division and Palliative Care Unit in the National Cancer Center Hospital East were given 20 mg of morphine hydrochloride dissolved in 5 ml of normal saline through an ultranebulizer. The subjective effects were evaluated using a visual analog scale (VAS) immediately before and 60 min after inhalation. Respiratory rate (RR), hemoglobin oxygen saturation (SpO2) and blood pressure also were measured twice at these two time points. A questionnaire about adverse reactions was included. RESULTS: No major adverse reactions such as respiratory depression, sleepiness, nausea or vomiting were observed. VAS was significantly decreased after nebulization (p = 0.005) without any significant change in RR or SpO2. In eight of 15 patients, dyspnea was improved as measured by a decrease in VAS of more than 10%. This correlated with the desire of the patients to continue its use. CONCLUSION: Our preliminary data confirmed the feasibility of nebulized morphine and suggested its possible clinical benefit for dyspneic patients. A randomized controlled study is warranted to exclude a placebo effect and to compare the clinical benefits of nebulized morphine with those of other methods of treatment.

Phase I study of cisplatin and docetaxel plus mitomycin C in patients with metastatic non-small cell lung cancer.

BACKGROUND: Docetaxel, cisplatin and mitomycin C are some of the active drugs used in the treatment of patients with metastatic non-small cell lung cancer (NSCLC). The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose of the three drugs in combination for such patients. METHODS: Chemotherapy-native patients with metastatic NSCLC were enrolled in this study. The doses of docetaxel and cisplatin were fixed at 60 and 80 mg/m2, respectively. It was planned to increase the dose of mitomycin C from 4 to 6 and 8 mg/m2. All drugs were administered on day 1 and repeated every 3-4 weeks. RESULTS: All six patients received 60 mg/m2 of docetaxel and 80 mg/m2 of cisplatin, three of them with 4 mg/m2 of mitomycin C (level 1) and the other three with 6 mg/m2 of mitomycin C (level 2). Two of the three level 2 patients experienced dose-limiting toxicities (DLTs) in first cycle: febrile neutropenia and grade 3 hyponatremia. Based on these data, the MTD was concluded to be 60 mg/m2 for docetaxel, 80 mg/m2 for cisplatin and 6 mg/m2 for mitomycin C. Evaluation of the data from all of the cycles, however, showed that four of the six patients experienced DLTs. CONCLUSIONS: The addition of mitomycin C to docetaxel and cisplatin resulted in relatively high toxicities. It was impossible to use a high enough dose of mitomycin C to improve the survival of NSCLC patients. We therefore concluded that further evaluation of this combination is unwarranted.

Computer-aided diagnosis for pulmonary nodules based on helical CT images.

In this paper, we present a computer-assisted automatic diagnostic system for lung cancer that detects nodule candidates at an early stage from helical CT images of the thorax. Our diagnostic system consists of analytical and diagnostic procedures. In the analytical procedure, first we extract the lung and the pulmonary blood vessel regions using the fuzzy clustering algorithm, then we analyze the features of these regions using image-processing techniques. In the diagnostic procedure, we define diagnostic rules utilizing the extracted features which support the determination of the candidate nodule locations. We show the effectiveness of our system by giving the results from its application to image data for mass screening of 450 patients.

Clinicopathologic characteristics of patients with nonsmall cell lung carcinoma with elevated serum progastrin-releasing peptide levels.

BACKGROUND: Progastrin-releasing peptide (proGRP) is a specific tumor marker in patients with small cell lung carcinoma (SCLC). It has been reported that serum proGRP levels rarely are elevated in patients with nonsmall cell lung carcinoma (NSCLC); the reported frequency is <3%. The purpose of this study was to examine the clinicopathologic features of NSCLC patients with high serum proGRP levels. METHODS: The authors measured serum proGRP levels with a TND-4 kit, a newly developed enzyme-linked immunoadsorbent assay, in 544 NSCLC and 206 SCLC patients. Pathologic features were examined using conventional hematoxylin and eosin staining and histochemical and immunohistochemical staining using polyclonal antibodies to proGRP, chromogranin A, calcitonin, and monoclonal antibody to the neural cell adhesion molecule (NCC-Lu-243). RESULTS: The serum proGRP levels were elevated in 140 SCLC patients (68.0%) and in 23 NSCLC patients (4.2%). Seven of these 23 NSCLC patients had serum proGRP levels > or = 100 pg/mL. They included two patients with renal dysfunction, one patient diagnosed cytologically with adenocarcinoma without undergoing precise pathologic examination, two patients diagnosed histologically with squamous cell carcinoma with foci of small cell elements, and two patients diagnosed with large cell neuroendocrine carcinoma and poorly differentiated adenocarcinoma, respectively, which showed neuroendocrine differentiation on immunohistologic analysis. The remaining 16 NSCLC patients had serum proGRP levels < 70 pg/mL. CONCLUSIONS: Nearly all NSCLC patients had serum proGRP levels < 100 pg/mL. However, if an NSCLC patient presents with a proGRP level > or = 100 pg/mL, the clinicopathologic features must be examined with regard to the small cell component, neuroendocrine differentiation, and renal dysfunction.