Biomedical subjects
Publications and source records attributed to N Takigawa.
Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0-4.9).
The anatomy of the lateral ulnar collateral ligament (LUCL) of the elbow was investigated in 26 fresh frozen cadavers. Two types of insertion of the LUCL were originally described but we found another type which is characterized by a broad single expansion along with a thin membranous fibre. Strain on the LUCL was measured in situ during extension and flexion with the forearm in supination, pronation and neutral. Strain in the proximal fibres started to occur at around 32 degrees flexion and peaked at between 50 degrees and 60 degrees flexion. Strains measured in the distal fibres were smaller in magnitude. Forearm rotation had little effect on strain during extension to flexion. Based on these results, we conclude that the LUCL functions in unison with the annular ligament.
Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age or=3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66-91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.
A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg x m(-2) was given first and followed by CPT-11 at a dose of 50 mg x m(-2). Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32-63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities.
PURPOSE: Breast-conserving surgery and postoperative radiotherapy have played important roles in the treatment of early breast cancer. Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has recently been reported to be one of the complications of adjuvant radiotherapy. The purpose of this study was to determine the incidence of and risk factors for BOOP syndrome in breast cancer patients. METHODS AND MATERIALS: Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conserving surgery. The criteria used for the diagnosis of BOOP syndrome were as follows: 1) radiation therapy to the breast within 12 months, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lung infiltrates outside the radiation port, and 4) no evidence of a specific cause. RESULTS: BOOP syndrome developed in 4 (2.5%) patients, who had fever and nonproductive cough, with patchy infiltrative shadows on chest roentgenograms which emerged between 5 and 6 months after radiotherapy. The symptoms and pulmonary infiltrates were rapidly improved by treatment with prednisone (40 mg/day), which was tapered over 2- to 5-month periods. However, BOOP syndrome relapsed in all cases during the tapering period or after withdrawal of prednisone. The eosinophil and neutrophil counts were increased and the ratios of CD4+ to CD8+ lymphocytes were elevated in bronchoalveolar lavage fluid in all four cases. There were no differences in proportions of patients by age, irradiated breast site, use of tamoxifen and/or chemotherapy, or radiation dose between those with and without BOOP syndrome. CONCLUSIONS: BOOP syndrome is considered an intractable form of lung toxicity after radiotherapy to the breast. An immunologic reaction mediated by eosinophils, neutrophils, and lymphocytes may be responsible for the development of this syndrome. Methods of prevention of BOOP syndrome should be established.
PURPOSE: A phase II study of nedaplatin and vindesine was conducted to evaluate their efficacy and safety for treatment of relapsed or refractory non-small-cell lung cancer (NSCLC). METHODS: Between August 1996 and September 1998, 48 patients who had previously received chemotherapy, thoracic radiotherapy, and/or surgery were enrolled in the study. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 to 2 and an age between 20 and 79 years. Treatment consisted of nedaplatin (80 mg/m2, day 1) and vindesine (3 mg/m2, days 1 and 8) every 3 to 4 weeks. RESULTS: Of 48 patients, 7 (14.6%) exhibited an objective response. Four (50%) of eight chemotherapy-naive patients had a partial response. However, of the 40 patients who had received prior chemotherapy, a partial response was observed in only 3 (7.5%). At a median follow-up time of 85.1 weeks, the median survival time was 43.6 weeks (95% confidence interval 34.4-52.7) for patients who had received chemotherapy, with a survival rate of 40% at 1 year. Grade 3 or 4 neutropenia occurred in 43 of 48 patients (90%), and neutropenic fever was observed in 3 of the 43 patients, one of whom died of sepsis. Pharmacokinetic and pharmacodynamic analyses of platinum were performed in 43 patients during the first cycle of chemotherapy. Percent reduction in absolute neutrophil count was correlated not only with the area under the plasma ultrafilterable platinum concentration versus time curve (r = 0.41, P = 0.007) but also with the duration of ultrafilterable platinum concentration above 1 microg/ml (r = 0.41, P = 0.007). Patients with progressive disease exhibited a shorter duration of ultrafilterable platinum concentration over 1 microg/ml (P = 0.046) than those with other responses. CONCLUSION: A combination of nedaplatin and vindesine was unsatisfactory as second-line chemotherapy for NSCLC, although the combination was well tolerated. The duration of ultrafilterable platinum concentration above 1 microg/ml was an important pharmacokinetic parameter for predicting both chemotherapy-induced neutropenia and treatment outcome.
BACKGROUND: Non-small cell lung cancer (NSCLC) is resistant to chemotherapy and prognosis of advanced NSCLC patients is considered to be dependent on various prognostic factors. METHODS: We analyzed prognostic factors in patients with advanced NSCLC who had been enrolled in clinical trials conducted by the Okayama Lung Cancer Study Group between 1978 and 1992 using two kinds of multivariate analysis, Cox's multivariate analysis and recursive partitioning and amalgamation (RPA) analysis. RESULTS: The first analysis was performed on 261 patients using 28 variables. Performance status (PS), clinical stage, liver metastasis or serum albumin level was an independent prognostic factor by Cox's analysis. In the second analysis performed on 128 patients having data on neuron specific enolase (NSE), NSE was the most important prognostic factor. Using the RPA method, three subgroups with significantly different survival potentials were defined. Among them, patients with normal serum NSE levels and good PS were found to obtain a markedly favorable prognosis [median survival time (MST) 22.1 months, 3-year survival rate 42.9%], whereas the survival of patients with elevated serum NSE levels and bone metastasis was extremely short (MST 4.7 months, 3-year survival rate 0%). CONCLUSIONS: These results indicate that analysis of prognostic factors including serum levels of NSE is useful for predicting the survival of patients with advanced NSCLC.
We describe two cases of atypical carcinoid of the thymus. One was an 82-year-old woman with complaints of nonproductive cough and back pain, and the other a 64-year-old woman with no symptoms. Computed tomography scans of the chest in both cases revealed a large mass in the anterior mediastinum. Multiple metastases to bone and liver were also noted in the former case. Histological examination of their tumors revealed that the tumor cells were arranged in a nested, trabecular, or pseudorosette pattern, with increased numbers of mitoses, nuclear pleomorphism, and presence of necrosis. In addition, immunohistochemically, the cells stained for neuron-specific enolase, synaptophysin and chromogranin A. Combination chemotherapy consisting of carboplatin and etoposide was performed as initial chemotherapy in the former case and as adjuvant therapy in the latter. The former patient achieved a short-term partial response. It is important to differentiate atypical carcinoid from other thymic tumors, since such tumors including thymoma have a much better prognosis than does atypical carcinoid.
To evaluate the nature and scope of treatment for non-small cell lung cancer (NSCLC) in the elderly, we retrospectively analyzed the cases of 166 patients (aged 75 years or more) who had been treated at our hospital between 1986 and 1997. In addition, we assessed the effectiveness and feasibility of combination chemotherapy consisting of ifosfamide and vindesine for 21 elderly patients. As their initial treatment, 20 patients (12%) received surgery; 65 (39%), curative chest radiotherapy; 30 (18%), chemotherapy; and 51 (31%), best supportive care. With combination chemotherapy consisting of ifosfamide (1.6 g/m2 on hospital days 1 through 3) and vindesine (2.5 mg/m2 on days 1 and 8), the response rate was 48% and the median survival time was 13.9 months (95% confidence interval: 5.6-22.2). Grade 3 or 4 leukopenia and neutropenia developed in 76% and 86% of the patients, respectively. However, other toxicities were generally mild, and no treatment-related deaths were observed. The combination of ifosfamide with vindesine may be effective for selected elderly NSCLC patients, and warrants further clinical study.
Patients with cancer receive an explanation of their disease and the recommended treatment when they are asked to give informed consent (IC). In the course of this process patients suffer severe distress, including anxiety and depression, but physicians tend to underestimate it. The goal of this study was to reveal the magnitude of such stress and any changes to this during the IC process by means of the Hospital Anxiety and Depression (HAD) scale, a self-assessment scale. Of 171 in-patients newly diagnosed with lung cancer, 119 were assessable for serial HAD scale scores on admission, immediately after the IC process, and at 1 and again at 2 weeks after the IC. Both anxiety and depression scores increased significantly immediately after IC. Female patients had significantly higher anxiety and depression scores than males at 1 week after the IC. The patients with poor performance status demonstrated high anxiety scores on admission and immediately after the IC, and substantial depression persisted longer in these patients. The prevalence of high scores of more than 11 (judged as adjustment disorder or more severe state) immediately after the IC was 50% for anxiety and 31% for depression. The prevalence decreased significantly within 1 or 2 weeks, but 41% and 14% of the patients still showed high anxiety and depression scores, respectively. Physicians should be aware of these facts and pay special attention to their patients' psychological distress in routine clinical practice.
The clinicopathologic characteristics of atypical adenomatous hyperplasia (AAH) remain unclear. A total of 137 patients underwent resection for adenocarcinoma of the lung at our institution. Examination of resected lung tissue showed that in addition to adenocarcinoma AAH was present in 26 cases and was not present in 111 cases. All nonsmokers with AAH (n = 13) had earlier-stage disease (stage IA, IB, IIA, and IIB) and no history of respiratory disease. Among patients with stage IA disease, the relapse-free and overall survival curves for those with AAH (n = 14) tended to be better than for those without AAH (n = 40), but the difference was not statistically significant (P = 0.056 and 0.087, respectively). Concurrent presence of AAH may be a favorable prognostic indicator in patients with stage IA adenocarcinoma.
We present two cases of intrapulmonary lymph node. The patients were a 44-year-old woman and a 71-year-old man each with a small peripheral nodule in the lung. On computed tomography (CT) scans, both nodules were spiculated. Since histological diagnosis could not be obtained by bronchoscopic examination or CT-guided needle biopsy, they underwent video-assisted thoracoscopic surgery. Histological examination of the resected material revealed that both nodules were composed of lymph node. Intrapulmonary lymph node has until recently been assigned no clinical significance; however, differential diagnosis of this lesion from lung cancers and other metastatic tumors is now clinically important.
Anti-p53 antibodies in sera are known to be products of the host immune response to mutated p53 protein, and are present in some patients with various types of cancer. In this study, we measured serum anti-p53 antibody levels in 52 patients with lung cancer and 63 normal volunteers to determine the relationship between anti-p53 antibody level and clinical features of lung cancer patients. Anti-p53 antibody level was measured by an enzyme-linked immunosorbent assay and expressed as an anti-p53 antibody index, defined as the ratio of absorption of serum sample to that of p53-positive serum. The median anti-p53 antibody index was 6.6 for lung cancer patients, and higher than that in normal volunteers (1.7) (P = 0.0000). For lung cancer patients, significant differences in index levels were found by histology (4.3, n = 25, adenocarcinoma vs 8.7, n = 18, squamous cell carcinoma vs 64.8, n = 2, large-cell carcinoma vs 9.8, n = 7, small-cell carcinoma; P = 0.0109). High anti-p53 antibody index levels were observed for both large-cell carcinoma and small-cell carcinoma. When the cut-off level was set at 7.2, determined using the twice 95% specificity level for normal volunteers, the sensitivities of anti-p53 antibodies were 46.1% for all lung cancers, 28.0% for adenocarcinoma, 55.6% for squamous cell carcinoma, 100% for large-cell carcinoma and 71.4% for small-cell carcinoma. However, there were no significant differences in index level by gender, age, smoking index, presence of previous or concomitant cancer or disease stage. Multivariate analysis using a logistic regression model demonstrated that histological type of tumour was a dominant factor associated with elevation of anti-p53 antibody index level (P = 0.0184). These findings suggest that serum anti-p53 antibody index level might be independent of tumour burden and the presence of previous or concomitant cancer in our series of lung cancer patients, but is clearly strongly correlated with tumour histological type.
PURPOSE: To determine the risk factors contributing to development of radiation pneumonitis (RP) in patients with lung cancer who undergo radiation therapy to the thorax. METHODS AND MATERIALS: Development and severity of RP were retrospectively analyzed for 89 patients with lung cancer who underwent radiation therapy with or without chemotherapy at the National Shikoku Cancer Center Hospital between 1991 and 1995. The severity of RP was determined using a modified grading scale based on that of the Radiation Therapy Oncology Group and the European Organization for the Research and Treatment of Cancer. RESULTS: Fifty-two (58%) patients developed RP: 34 patients with Grade 1, 5 with Grade 2, 8 with Grade 3, and 5 with Grade 5 RP. Severe RP tended to develop earlier than less severe RP, but not to a significant extent (p = 0.151). On logistic regression analysis including both patient condition and treatment factors, development of Grade 1 or more severe RP was most frequently observed for Stage I-II disease (p = 0.011). The use of chemotherapy, large daily radiation dose, and once-daily fractionation (vs. twice-daily fractionation) were possibly related to the development of RP (p = 0.057, p = 0.069, and p = 0.092, respectively). For the group of 48 patients who underwent chemoradiation therapy, the use of large daily radiation dose was a significant risk factor for RP (p = 0.014). In addition, the use of once-daily fractionation was a marginally significant risk factor (p = 0.052). Among chemotherapy drugs administered, cisplatin was a favorable factor (p = 0.011), while adriamycin was a risk factor (p = 0.061). CONCLUSIONS: In radiation therapy for lung cancer, administration of a large daily dose should be avoided in order to prevent RP, particularly when radiation therapy is combined with chemotherapy.
Serum CD44 standard and CD44 variant 6 levels were measured in 45 non-small cell lung cancer (NSCLC) patients and 33 patients with benign lung disease by enzyme-linked immunosorbent assay (ELISA). Expression of CD44 variant 6 in trans-bronchial biopsy specimens from the NSCLC patients was studied by an immunoperoxidase method. CD44 standard and CD44 variant 6 levels in NSCLC patients were not significantly different from those in benign lung disease patients. However, serum CD44 variant 6 level in squamous cell carcinoma patients (226.8 +/- 152.7 ng/ml) was significantly higher than in patients with benign lung disease (154.8 +/- 46.4 ng/ml) (P = 0.011). Neither the serum level of CD44 standard nor that of CD44 variant 6 was correlated with disease Stage and metastasis. CD44 variant 6 expression was most frequently observed in squamous cell carcinoma (P = 0.00058); 15 (79%) of 19 squamous cell carcinoma cases were positive, as were five (22%) of 23 adenocarcinoma cases and two (67%) of three large cell carcinoma cases. Serum CD44 variant 6 levels were 217.1 +/- 143.1 and 156.1 +/- 48.8 ng/ml in patients with and without positive expression of CD44 variant 6, respectively (P = 0.020). Serum CD44 standard and CD44 variant 6 levels are not useful indicators of tumor burden and metastasis in patients with NSCLC. CD44 variant 6 expression might be associated with histological features of NSCLC.
Serum hepatocyte growth factor/scatter factor (HGF/SF) levels were measured in 25 patients with small cell lung cancer (SCLC), 16 patients with benign lung diseases and 15 healthy subjects with an enzyme-linked immunosorbent assay. The patients with SCLC did not have bacterial or interstitial pneumonia. Patients with benign lung diseases included eight with bacterial pneumonia, three with interstitial pneumonia, and five with benign lung tumor. Serum HGF/SF levels were significantly higher in patients with SCLC (mean +/- S.D.: 0.40 +/- 0.17 ng/ml) than in healthy subjects (0.26 +/- 0.093 ng/ml) (P = 0.0083). Patients with bacterial pneumonia had significantly higher serum HGF/SF (0.52 +/- 0.19 ng/ml) than did those with benign lung tumors (0.27 +/- 0.058 ng/ml) and healthy subjects (P = 0.013 and P = 0.0019, respectively). By clinical stage of SCLC, HGF/SF levels were 0.34 +/- 0.12 and 0.47 +/- 0.20 ng/ml in patients with limited disease and extensive disease, respectively; this difference was not significant (P = 0.080). Although serum HGF/SF levels were increased in patients with SCLC, this increase might not have been related to tumor burden.
Serum p53 protein levels were measured in 36 patients with small cell lung cancer (SCLC) and 35 patients with benign lung diseases in order to evaluate the relationship of these levels to clinicopathological features of SCLC. Serum levels of p53 protein were measured by an enzyme-linked immunosorbent assay, p53 protein level was 23.92 +/- 6.78 pg/ml in patients with SCLC, and similar to that (17.47 +/- 2.86 pg/ml) in patients with benign lung diseases. By the clinical stage of SCLC, the mean level of p53 protein was 16.68 +/- 4.62 pg/ml in 21 patients with limited disease, and lower than that in 15 patients with extensive disease (34.05 +/- 14.84 pg/ml) (P = 0.23). The levels of p53 protein were not correlated with age, smoking index, or presence of cancer history for patients with SCLC. However, immunohistochemical examination disclosed a mild correlation between the expression of p53 protein by SCLC tumor and p53 protein serum level (r = 0.45, P = 0.02). Two patients with SCLC had an elevated serum level of p53 protein (> 2 S.D. above the mean for benign lung diseases). However, measurement of p53 protein serum level was not found to be clinically useful for detection of SCLC.
A case-control study of leukemia and diagnostic X-ray exposure was conducted by a multi-institution co-operative study group. The subjects were 134 patients with acute myelogenous leukemia, 57 with chronic myelogenous leukemia, 56 with acute lymphocytic leukemia and 50 with myelodysplasia syndrome, who were between 15 and 79 years old, and diagnosed at one of 27 hospitals between September 1993 and August 1995. The controls were 479 first-visit patients seen at eight of these 27 hospitals. History of diagnostic X-ray tests between 1982 and 1991 was determined by an anonymous self-administered questionnaire. The total relative dose of radiation exposure was calculated by summing the products of given weights and frequencies of each test. The relative risk was 0.83 (95% confidence interval (C.I.), 0.58-1.19) for relative dose of 10-30 (equivalent to 4-11 times of UGI series), 0.76 (0.48-1.20) for relative dose of 30 or more (more than 12 times of UGI series), when compared with relative dose of 0-10 (0-3 times of UGI series). Analysis according to type of leukemia revealed that only acute myelogenous leukemia had an estimated relative risk above unity (1.08, 95% C.I. 0.69-1.69, for relative dose 10-30). This study did not support the hypothesis that diagnostic X-ray tests increases leukemia risk.