Carboplatin plus Weekly Paclitaxel Combined with Bevacizumab as First-line Treatment for Non-small Cell Lung Cancer.

AIM: We aimed to evaluate the efficacy and safety of carboplatin plus weekly paclitaxel with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV or postoperative recurrent NSCLC (n=33) were treated with carboplatin (area under the curve of 6) on day 1; paclitaxel (80 mg/m2) on days 1, 8, and 15; and bevacizumab (15 mg/kg) on day 1 repeated every 4 weeks, for four to six cycles; followed by maintenance bevacizumab (15 mg/kg) every 3 weeks. RESULTS: The overall response rate was 76%. The median progression-free survival and overall survival were 8.4 months and 22.2 months, respectively. Grade 3-4 toxicities included neutropenia in 55% of patients, anemia in 18%, febrile neutropenia in 12%, and anorexia in 9%. No treatment-related deaths were observed. CONCLUSION: Carboplatin plus weekly paclitaxel with bevacizumab was effective and well tolerated by patients with advanced NSCLC.

[Clinicians' opinions on receiving the advance directives of terminal-stage patients vary according to the age of respondents].

AIM AND METHODS: We distributed 282 questionnaires to doctors to ascertain their opinions on obtaining the advance directives regarding the end-of-life treatment of patients at the terminal stage. We received 136 (48%) responses. RESULTS: A total of 62% of the respondents stated a desire for patients to indicate their advance directives "if at all possible". Only 36% stated that the need for advance directives "depended on the circumstances". A total of 80% of doctors aged under 40 wished patients to provide advanced directives "if at all possible", while 59% of doctors over 61 wanted advanced directives "depending on the circumstances" (p=0.008). A large number of doctors stated a desire for patients to indicate their preference in writing, particularly directives regarding the "use of a ventilator to prolong life" (76%) or the "use of artificial nourishment through a gastric fistula etc. as part of a proactive approach to sustaining life" (67%). Regarding the optimal timing of this declaration, 59% chose "at the first diagnosis of a terminal illness", and 47% chose "at the diagnosis of a chronic illness", regardless of whether it could become terminal. Of those respondents under 40, 32% believed that doctors should strictly follow the patients' advance directives, while only 11% of doctors over 61 years old believed the same. There was a statistically significant relationship between aging and dealing with advance directives of patients in the terminal stages of illness (p=0.002). CONCLUSION: These results suggest that doctors under 40 years of age should focus on how to correctly interpret the wishes of the patients expressed in the directives, while doctors over 61 should concentrate on the importance of the clinical application of advance directives, and how to balance the need to make qualified medical decisions on treatment in compliance with the wishes of end-stage terminal patients.

[A retrospective study of carboplatin and weekly paclitaxel combination chemotherapy for elderly patients with advanced non-small cell lung cancer].

OBJECTIVE: To perform a retrospective analysis of carboplatin (CBDCA) and weekly paclitaxel (PTX) combination chemotherapy for elderly patients with unresectable non-small cell lung cancer (NSCLC) in order to evaluate both treatment efficacy and toxicity. SUBJECTS: 48 patients aged more than 70 years with non-resectable NSCLC who received CBDCA+weekly PTX from January 2001 to March 2008. RESULTS: The median age of the patients (32 male, 16 female) was 74 years. Patients received 1-6 courses of this chemotherapy (median 4 courses). The overall response rate, time to progression, median survival time and 1-year survival rate was 51%, 183 days, 411 days and 52%, respectively. With regard to toxicity, grade 3-4 neutropenia was observed in 38% of patients and anemia in 25% of the patients, and 29% of the patients had grade 2 and above periferal nerve disorder. CONCLUSION: This regimen showed a good response and was safe for elderly patients with advanced NSCLC, but a high incidence of neuropathy was observed.

Incidence and survival of childhood cancer cases diagnosed between 1998 and 2000 in Hiroshima City, Japan.

There have been few studies on cancer incidence and survival among children in Japan. Childhood cancer cases in Hiroshima City can be ascertained almost perfectly in terms of completeness and validity as both a population-based cancer registry and a tissue registry cover the whole area. We report here recent incidence and survival of childhood cancer in Hiroshima City. Subjects were cancer patients less than 15 years of age in Hiroshima City registered in the Hiroshima City Cancer Registry and/or the Hiroshima Prefecture Tumor Registry (tissue registry) between 1998 and 2000. Cancer incidence in Hiroshima City was calculated for 12 diagnostic groups according to the International Classification of Childhood Cancer, and compared with general incidence in Japan. Five-year survival was calculated by the Kaplan-Meier method. There were 63 children who had a cancer newly diagnosed during 1998-2000, with only one death-certificate-only case (1.6%). Age-standardized incidence rates (per million) were 144.3 for boys and 93.9 for girls. Leukemia was the most frequent (29%) among the 12 diagnostic groups. There were 13 cancer deaths during this period and five-year survival was 79% (95% Confidence Interval: 67%-87%). Childhood cancer incidence was slightly higher than that for all of Japan, but the relative distribution of patients by diagnostic group was compatible with the general pattern. Both of these observations might be due to the high quality of the tumor and tissue registries.

[Clinical investigation of weekly Carboplatin and Paclitaxel with concurrent radiation therapy for locally advanced non-small cell lung cancer].

PURPOSE: The aim of this study was to evaluate retrospectively chemotherapy of weekly carboplatin and paclitaxel with concurrent radiation therapy for patients with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Between January 2000 and March 2008, 38 patients were treated by chemotherapy with carboplatin and paclitaxel once a week, repeated for 6 weeks, with thoracic radiation therapy of 1 or 2 times a day on weekdays. After concurrent chemoradiotherapy, we planned consolidation chemotherapy of carboplatin(AUC 5-6)and weekly paclitaxel(70- 80 mg/m(2)) on day 1, 8 and 15, when possible. RESULTS: The enrolled patients were 31 men and 7 women, with the median age of 59 years (39-76 years), stage III A/III B: 10/28, Ad/Sq/AdSq/Un: 17/17/2/2. The response rate of this chemoradiotherapy was 78. 9%. The median survival time and time to progression were 24. 7 months and 8. 1 months, respectively. Grade 3 or 4 hematological toxicities during concomitant chemoradiotherapy were leukocytopenia(5. 2%)and neutropenia(5. 2%). Grade 3 or 4 non-hematological toxicities were esophagitis(2. 6%)and pneumonitis (5. 2%). There was a therapy-associated death by radiation pneumonitis. CONCLUSION: Carboplatin and paclitaxel with concurrent radiation therapy for a patient with stage III NSCLC showed a good response with relatively mild side effects. We reached the conclusion that concurrent chemoradiotherapy would be a useful choice for locally advanced non-small cell lung cancer on the practical clinic.

[A foreigner case of pulmonary tuberculosis with patient's and doctor's delay].

A 80-year-old man who came from Korea a few days previously, had a high fever and dyspnea. Chest radiography and computed tomography showed various shadow suggesting tumors, small nodules and reticular shadows with effusion. We made a clinical diagnosis of lung cancer with pneumonia. Finally, however, the culture of bronchial lavage fluid and transbronchial biopsy revealed tuberculosis. It was obvious that there were delaying factors such as the patient's social and economical situation as well as the diagnostic difficulty concerning the chest image findings. Whenever we find a abnormal shadow on chest images, we should consider mycobacterium infection in the differential diagnosis disease.

[Clinical study of 37 pneumonia patients in whom MRSA was identified from sputum].

When we studied the clinical aspects of 37 pneumonia patients with underlying respiratory disease in whom MRSA 1 + was identified from sputum, 43.2% of these 37 pneumonia cases were diagnosed as MRSA colonization. The whole clinical course of these pneumonia patients with MRSA colonization was average 39.5 days, on the other hand, the whole clinical course of MRSA pneumonia group was 55.3 days. We should consider that MRSA must be a cause of pneumonia, in only such cases as follows; (1) patients with unstable diabetes mellitus, or with long-term administration of steroid, (2) patients with infiltrative shadows appeared not only in the lower lobe but also the upper lobe in the chest x-ray films, (3) patients with remarkable decrease of PaO2 or patients who failed to recover within one month from MRSA isolation, (4) patients with nosocomial pneumonia or patients with poor performance status or poor prognosis, (5) patients with purulent sputum containing MRSA or other bacteria such as K. pneumoniae etc and patients who failed to respond to general antibacterial agents.

[A case of systemic amyloidosis treated by chemotherapy with autologous peripheral blood stem cell transplantation].

A 67-year-old woman was admitted to our hospital because of breathlessness. Systemic amyloidosis had been diagnosed 5 years previously. Her chest X-ray film showed multiple nodules in both lung fields. Chest computed tomography (CT) revealed some of the nodules had calcifications. Bronchoscopy demonstrated amyloid deposits in the bronchial walls. The serum titer of anti-SS-A antibody was high. Results of both the Schirmer Test and the Rose-Bengal Test were positive. The final diagnosis was systemic amyloidosis with Sjögren's syndrome. She was treated by chemotherapy using high dose melphalan with autologous peripheral blood stem cell transplantation (PBSCT). It was obvious that her chest X-ray film findings and bronchoscopic findings had improved 9 months after high dose chemotherapy with PBSCT. The disappearance of M protein and improvement of thirst, a symptom of Sjögren's syndrome, were also observed.

[A case of natural killer cell lymphoma with high adenosine deaminase level in pleural effusion].

A 61-year-old man was admitted to our hospital with cough, breathlessness, anorexia and chest pain. Chest radiograph showed right pleural effusion and also a chest CT scan showed right pleural effusion with thickening of the right visceral pleura, pericardial effusion and a liver tumor. The pleural effusion was slightly bloody and exudative. The adenosine deaminase (ADA) level in the pleural effusion was elevated. Because the cytological examintion of the pleural effusion showed no malignancy, we diagnosed pleuritis tuberculosa. The serum-soluble interleukin-2 receptor level was also elevated. His general condition worsened in spite of the chemotherapy with antibiotics and antituberculous drugs. We finally diagnosed the case as natural killer (NK) cell lymphoma from CT-guided needle biopsy just before death, and necropsy. In this case, the high level of ADA in the pleural effusion suggested lymphoma.

Polymorphism of the MUC1 mucin gene is associated with susceptibility to lung adenocarcinoma and poor prognosis.

MUC1 is a highly glycosylated glycoprotein that is often overexpressed in adenocarcinomas. MUC1 has molecular diversity because of a variable number of tandem repeats (from 25-125 repeats) in the extracellular domain of its core protein. MUC1 plays an important role in facilitating invasion and metastasis of malignant cells, and it also inhibits anti-cancer immune activity against malignant cells. We hypothesize that MUC1 allele length polymorphism (variable number of tandem repeats) is associated with development of lung adenocarcinoma. We evaluated MUC1 gene polymorphism using Southern blot analysis of peripheral blood from patients with non-small cell lung cancer (n=56), patients with benign respiratory disease (n=52), and healthy volunteers (n=52). We found that large MUC1 allele length was significantly associated with lung adenocarcinoma but not with squamous cell carcinoma of the lung. Adenocarcinoma patients with a homozygous large MUC1 genotype had a worse prognosis than patients with a heterozygous (large + small) MUC1 genotype or a homozygous small MUC1 genotype. These results suggest that the large MUC1 allele is associated with susceptibility to lung adenocarcinoma and poor prognosis.

[Differences in the way of thinking about health and infectious diseases between the elderly and medical staff].

The majority of our inpatients and outpatients are senior citizens. They are in marked contrast to the majority of current medical workers who are far younger than their patients. We investigated the problems which may arise due to this age gap using a questionnaire asking about viewpoints on "health" and "infectious diseases among the elderly" Interest in general health was lower among medical workers than common citizens. Lifestyles which the public may consider to be good for health are more specific and cover a wider range than those of medical professionals. Medical staff thought home care is important for infectious diseases among the elderly. They were concerned with the appearance of resistant bacilli and considered that the type of treatment should vary in accordance with the patient's age and stamina, whereas the elderly citizens cared more strongly about the treatments result. Medical workers should understand that the general citizens have a different way of thinking about health and infectious diseases from their own.

[Case of pulmonary carcinosarcoma and a summary of 17 cases reported in Japan].

The patient was a 69-year-old man who complained of dyspnea and severe general fatigue. Chest CT showed a large tumor (6 x 5 cm) in the left S3 together with left pleural effusion. Despite pleurodesis and chemotherapy, he died 1.5 months after admission. At autopsy, a final diagnosis of pulmonary carcinosarcoma was obtained. We have summarized 17 cases of pulmonary carcinosarcoma reported in Japan. All patients were men, and had an average age of 68 years. The majority of the patients were heavy smokers. Death was reported in 70% of cases, the median survival period being 5 months, whereas the patients reported as living had operable cases of T2 tumor without distant metastatic lesions.

Noninvasive positive pressure ventilation in treatment of non-COPD related acute respiratory failure cases.

We used Noninvasive Positive Pressure Ventilation (NPPV) in nine patients with acute respiratory failure (ARF), not related to chronic obstructive pulmonary disease (COPD). After separating the nine patients into a hypercapnic group (five patients) and a non-hypercapnic group (four patients), we investigated its effectiveness in physiological improvement and avoiding intubation. Dyspnea, physiological findings and ABG improved rapidly in both groups without serious adverse effects. The intubation avoidance rate was 66.7% (6 of 9) in total, and 80% in the hypercapnic group and 50% in the non-hypercapnic group. The ratio of PaO2 to FiO2 (P/F ratio) increased during NPPV in most cases where intubation could be avoided. It is worthwhile to use NPPV as a bridging therapy between O2 therapy and invasive ventilation in patients with non-COPD related ARF, regardless of the existence of hypercapnia. Careful monitoring of the P/F ratio and complications is needed to make an appropriate decision whether avoiding intubation will be possible or not.

Legionella micdadei pneumonia diagnosed by culture isolation and DNA-dNA hybridization from bronchial lavage fluid.

An 80-year-old man was admitted because of dyspnea on effort. We suspected an acute exacerbation of chronic heart failure and idiopathic interstitial pneumonia caused by right-sided pneumonia. A nodular shadow in right upper lobe spread and consolidated into the airspace, and it failed to improve despite administration of meropenem trihydrate, vancomycin hydrochloride and clindamycin. A definitive diagnosis of Legionella micdadei pneumonia was made on the basis of this organism being isolated in culture from bronchial lavage fluid and subsequent identification of Legionella micdadei using DNA-DNA hybridization. The airspace consolidation gradually improved following treatment with intravenous erythromycin and minocycline hydrochloride.

[A case of primary pulmonary leiomyosarcoma with history of pneumonia 5 years before].

A 35-year-old woman with past history of pneumonia in the right lung field 5 years before was admitted to our hospital because of fever and cough. Chest radiographs showed a pulmonary tumor with atelectasis of the right lower lung. Chest CT also revealed a round clear-edged tumor at the right S6 with atelectasis of the right lower lung lobe. Bronchoscopic findings showed a yellowish endobronchial tumor in the right truncus intermedius, which proved to be leiomyosarcoma. We could not find any other malignant lesion, and therefore, on a diagnosis of primary pulmonary leiomyosarcoma, right middle and lower lobectomy was performed with lymph node excision. Retrospective examination of the chest radiographs revealed not only that the original region of the leiomyosarcoma seemed to be near the site of the earlier pneumonia, but also that the atelectasis-like findings 2 years before were similar to the findings on this admission. It was reported that, if an operation could not be performed at an early stage, the prognosis might be poor. In the follow-up of the abnormal chest radiographic findings, the clinic physician should observe the symptoms from the same viewpoint as hospital doctors. It is important to keep an active relationship between clinic and hospital. We might have reached our final diagnosis earlier if we had been more active in seeking an examination for abnormal chest radiographic findings, without attaching too much importance to the patient's age.

Cigarette smoking-induced acute eosinophilic pneumonia showing tolerance in broncho-alveolar lavage findings.

A 19-year-old man was admitted due to acute respiratory failure. He had started cigarette smoking (CS) about three weeks prior to onset. Multiple nodular shadows and patchy infiltrations were found on chest computed tomography. His respiratory state improved promptly by intravenous methylprednisolone. He resumed CS soon after discharge without any symptoms. We suspected CS-induced acute eosinophilic pneumonia and performed broncho-alveolar lavage (BAL) about one month after onset. The proportion of eosinophils in BAL fluid was 72%. A second BAL was performed about 18 months after onset and BAL fluid included no eosinophils, despite the fact that he had continued CS.

[Detection of MRSA with antimicrobial susceptibility by using chemiluminescent assay].

Chemiluminescent assay can give the result of the detection of MRSA about 13 hours more rapidly than conventional broth microdilution method. In order to apply chemiluminescent assay to detection of MRSA, we compared MIC and antimicrobial susceptibility to MPIPC in using chemiluminescent assay with these in using broth microdilution method. In MSSA, rate of concordance of MIC and antimicrobial susceptibility to MPIPC obtained by both methods was 87%, but all MICs come to be agreed by modifying the concentration of bacterial liquid. In MRSA, all MICs and susceptibility to MPIPC are agreed in both methods. Although we have used chemiluminescent assay to detect MRSA for one year, no trouble has been reported by clinical side. The chemiluminescent assay is evaluated to be good in detecting MRSA.

[A case of severe pneumoconiosis with synchronous triple lung cancer].

A 70-year-old man who had worked in a stonepit for about fifty years was admitted to our hospital for detailed examination of the signs of pneumoconiosis (3/3, q) and a nodular shadow in the right upper lung field. Under a clinical diagnosis of lung cancer complicated with pneumoconiosis, right upper lobectomy with a right S6 resection was performed. Pathological examination revealed moderately differentiated adenocarcinoma of the right S2, well-differentiated adenocarcinoma of the right S6, and a squamous cell carcinoma of the right S1 which was not detected by chest CT. In addition to the difficulty of diagnosing lung cancer in a patient with severe pneumoconiosis, treatment for lung cancer may be limited by the poor pulmonary function that results from pneumoconiosis. Although the labor administration's decision that lung cancer patients with concomitant pneumoconiosis deserve compensation can be evaluated as a good one, the study of the relationship between pneumoconiosis and lung cancer needs further study through follow-up examination of pneumoconiosis cases.

[Evaluation of the Rapid Lumi 'Eiken' using chemiluminescent assay for rapid antimicrobial susceptibility testing].

One hundred ninety eight clinical isolates, including Enterobacteriaceae (70 strains), Pseudomonas aeruginosa (20 strains), Acinetobacter baumannii (10 strains), staphylococci (50 strains), enterococci (20 strains), Streptococcus pneumoniae (15 strains) and Haemophilus influenzae (13 strains) were tested for their antimicrobial susceptibilities by using the Rapid Lumi 'Eiken' (RL). As a reference method, broth microdilution method according to the National Committee for Clinical Laboratory Standards was used. Then, each MIC obtained by both of these methods was compared. In order to improve the discrepancy between MICs obtained by both methods, modification of the RL method was studied. All MICs using the RL method were obtained with an incubation period of 4 hours. The essential agreement (to within one twofold dilution) between MICs obtained by both methods was 82%. The false susceptible in the RL method test results (very major error) and the false resistant in the RL tests (major error) were 0.9% and 2.3%, respectively. The agreement of interpretive category (that is, when the categories obtained by both methods are in perfect agreement) was 89%. Proteus spp. and A. baumannii showed low essential agreements, 59% and 46% respectively. The differences were resulted from the RL method's MICs being higher than the reference method. In order to improve the difference between both methods, the RL method's procedure was modified in the inoculum size (10(6) CFU/mL to 10(5) CFU/mL), the menadione concentration (5 mg/L to 25 mg/L) and the interpretive criteria for Enterobacteriaceae and A. baumannii. As the results of the modification, the essential agreement in Proteus spp. and A. baumannii increased to 82% and 81%, respectively, and there was no significant change in the other species of Enterobacteriaceae. In the case of the modified RL method to Enterobacteriaceae and A. baumannii, the essential agreement, the very major error, the major error and the agreement of interpretive category of all 198 strains were 87%, 1.4%, 1.5% and 90%, respectively. In conclusion, with only 4-hour incubation period, the RL method based on chemiluminescent assay gave reliable susceptibility testing among the most clinically important bacteria. Although several tests showed low essential agreement, it was possible to improve by use of the modified RL method. The Rapid Lumi 'Eiken' will provide useful information for choosing the most effective antibiotic for primary treatment to bacterial infections.