Radiation therapy among atomic bomb survivors, Hiroshima and Nagasaki

Occupational asthma is the most common occupational lung disease in the world. Occupational asthma comprises approximately 25-50% of occupational lung diseases and is responsible for up to 15% of all asthma cases. Either immunologic or nonimmunologic causes may be responsible for occupational asthma. There are approximately 250 compounds known to cause occupational asthma. Common examples include flour, animal dander, isocyanates, and latex. The diagnosis of occupational asthma depends on an accurate history of asthma and documentation that the asthma is caused by workplace exposure. Peak flow measurements are commonly used to provide data to define this relationship. Spirometry and bronchial provocation testing are also helpful. The key management tool in occupational asthma is avoidance of the causative agent. Avoidance is more important than treatment with medications. Occupational asthma can have major socioeconomic impacts on an individual, and the diagnostic work-up and management needs to be performed with this in mind.     

Chronic diffuse interstitial fibrosis of the lung in uranium miners

Many uranium miners have been disabled by and died of pulmonary fibrosis that was not recognized as an occupational disease. A review of animal studies, complications from whole body irradiation, pulmonary function, and mortality studies of uranium miners led us to suspect radiation-induced chronic diffuse interstitial fibrosis in miners who had inhaled excessive radon progeny. A selected group of uranium miners (22) with severe respiratory disease (but no rounded nodules in chest films) were studied. Lung tissue from five disclosed severe diffuse interstitial fibrosis, with "honeycomb lung" in all. Some also had small anthrasilicotic nodules and birefringent crystals. Although quartz crystals probably contributed, we concluded that the predominant injurious agent in these cases was alpha particles from radon progeny. This disease, after a long latent period, usually results in pulmonary hypertension, shortness of breath, and death by cardiopulmonary failure.     

Benign tumors of the digestive tract among atomic bomb survivors, 1961-1970 Hiroshima

The occurrence of benign tumors and diverticular of the digestive tract was investigated in an autopsy study of a fixed population of 100,000 samples in Hiroshima and Nagasaki. There were 664 benign tumors and 40 diveritcula. Polyps were the most frequent tumor, were found more often in older people, occurred as single pedunculated well-differentiated adenomatous tumors, and most were less than 5 mm in greatest dimension. Larger polyps tended to have more atypism, but none showed definite premalignant change. No transition from benign to malignant polyps was seen. Polyps were found most frequently in the large intestine and in a large number (21%) and, when cancer of the large intestine was present, benign polyps were also found. Far more polyps are found when special intensive search is made for them. Comparison of the occurrence of benign polyps in different geographic areas must be adjusted for age and method of search as well as for other features such as histological type, dysplasia, etc. There was no evidence that the occurrence of benign tumors or diveritcula was related to prior exposure to ionizing radiation.     

The risk of non-melanoma skin cancer incidence in the Japanese atomic bomb survivors

The latest Japanese atomic bomb survivor non-melanoma skin cancer incidence dataset is analysed and indicates substantial curvilinearity in the dose-response curve, consistent with a possible dose threshold of about 1 Sv, or with a dose-response in which the excess relative risk is proportional to the fourth power of dose, with a turning-over in the dose-response at high doses (> 3 Sv). The time distribution of the radiation-induced excess risk is best described by a model in which the relative excess risk is proportional to a product of powers of time since exposure and attained age. The fits of generalized relative risk models with exponential functions of time and age at exposure (and in particular of attained age) to adjust the relative risk are less satisfactory, as also are the fits of other models in which products of powers of time since exposure, age at exposure and attained age adjust the excess absolute risk. Sensitivity analyses indicate the importance of likely adjustments to the Hiroshima neutron doses for the optimal model parameters, particularly if values of the neutron relative biological effectiveness (RBE) of more than 5 are assumed. If adjustments recently proposed are made to the Hiroshima neutron doses, then using the optimal model (in which excess risk is proportional to the fourth power of dose) the best estimate of the neutron RBE is 1.3 (95% CI < 07.1). However, uncertainties in skin dose estimates for the atomic bomb survivors means that the findings with respect to the neutron RBE and the non-linearity in the dose-response curve should be treated with caution.     

Measurement of lung expansion with computed tomography and comparison with quantitative histology

The total and regional lung volumes were estimated from computed tomography (CT), and the pleural pressure gradient was determined by using the milliliters of gas per gram of tissue estimated from the X-ray attenuation values and the pressure-volume curve of the lung. The data show that CT accurately estimated the volume of the resected lobe but overestimated its weight by 24 +/- 19%. The volume of gas per gram of tissue was less in the gravity-dependent regions due to a pleural pressure gradient of 0.24 +/- 0.08 cmH2O/cm of descent in the thorax. The proportion of tissue to air obtained with CT was similar to that obtained by quantitative histology. We conclude that the CT scan can be used to estimate total and regional lung volumes and that measurements of the proportions of tissue and air within the thorax by CT can be used in conjunction with quantitative histology to evaluate lung structure.     

Comparison of breast cancer incidence in the Massachusetts tuberculosis fluoroscopy cohort and in the Japanese atomic bomb survivors

Breast cancer has occurred in excess among women exposed briefly to atomic bomb radiation and among those exposed repeatedly over many years to medical radiation for tuberculosis (TB). The excess relative risk of breast cancer incidence in the Japanese atomic bomb survivors, however, is significantly higher (two-sided P = 0.04) than that in the Massachusetts TB fluoroscopy patients. The best estimate of the ratio between the excess relative risk coefficients for the Japanese and Massachusetts cohorts is 2.11 (95% CI 1.05, 4.95). However, this higher relative excess risk is attributable to the lower baseline risk of breast cancer among Japanese women compared with the Massachusetts women, and the excess absolute breast cancer risks in the two data sets are statistically indistinguishable (two-sided P = 0.32). The best estimate of the ratio between the excess absolute risk coefficients among Japanese and Massachusetts women is 0.73 (95% CI 0.41, 1.44). After childhood exposures, an early onset of radiation-induced breast cancer was seen among Japanese atomic bomb survivors but not among the Massachusetts women. There are some indications (two-sided P = 0.04) of differences in the patterns of risk over time since exposure between these groups exposed in childhood. However, in general there are no marked differences between the Massachusetts and Japanese data sets in the age and time distribution of risk of radiation-induced breast cancer. These data provide little evidence for a reduction of breast cancer risk after fractionated irradiation.     

Risk of second primary cancer in two-year survivors of small cell lung cancer]

A total of 498 patients with small cell lung cancer received chemotherapy with or without chest irradiation at Osaka Prefectural Habikino Hospital from October 1977 through December 1991. Sixty-one who survived for more than two years were evaluated to determine the incidence and anatomic patterns of redevelopment of small cell lung cancer and development of second primary cancers. The numbers of expected cancers were estimated by cumulating person years of observation from 2 years after the start of treatment for small cell lung cancer to the date of death. Second primary cancers were observed in seven patients (four cases of non-small cell lung cancer, two of gastric cancer, and one of prostate cancer). The risk of a second primary cancer was 3.2 times greater than in the general population (95% Cl: 1.3-6.6). the relations between occurrence of a second primary cancer and family history of cancer, smoking history, smoking cessation after treatment of small cell lung cancer, and thoracic irradiation were studied. Occurrence of a second primary cancer correlated with family history (relative risk 7.5, 95% Cl: 1.5-22) and smoking cessation (relative risk 3.2, 95% Cl: 1.2-6.9). Long-term survivors were more likely to have a second primary cancer than a relapse of small cell lung cancer. Therefore, long-term survivors should be closely monitored for second primary cancers. Meta-analyses of studies done at several institutions may provide more detailed information on the occurrence of second primary cancers after small cell lung cancer.     

Development of synchronous bilateral lung cancers after esophagectomy for esophageal cancer: report of a case

It is well known that squamous cell carcinoma of the esophagus can be associated with carcinoma of other organs. We report herein the rare case of a 60-year-old man who developed synchronous bilateral lung cancers after undergoing esophagectomy for esophageal cancer. Staged bilateral lobectomy was successfully performed to minimize respiratory complications 3 years after his esophagectomy. This case report serves to demonstrate that aggressive and careful surgical approach with adequate followup offers the chance of long-term survival for patients with multiple primary cancers.     

Genetic analysis of second primary lung cancers in patients surviving small cell lung cancer

We performed genetic analysis on 12 second primary non-small cell lung cancers in patients surviving small cell lung cancer to assess the potential contribution of smoking to the development of these tumors. Mutations of TP53 were found in three (25%) tumors, KRAS2 in three (25%) tumors, and CDKN2 in two (18%) tumors. Four (50%) mutations (one each in TP53 and CDKN2 and two in KRAS2) were G:C to T:A transversions on the coding strand, a mutation accounting for approximately one-third of mutations in smoking-related tumors but uncommonly found in lung cancers not associated with smoking. The genetic changes in these second lung cancers are more representative of smoking-associated malignancies than lung cancers arising in patients occupationally exposed to irradiation and atomic bomb survivors.     

Tumour development, histology and grade of breast cancers: prognosis and progression

A case of giant cell tumor localized in the proximal end of the right tibia, initially treated by simple curettage is described. After 11 years there was local recurrence, confirmed anatomopathologically, observed during wide resection and reconstruction by arthroplasty plus homoplastic grafting. After a few months there were metastatic lesions in the left parietooccipital and right retroorbitary area. Biopsy of the parietooccipital lesion showed giant cells in a sarcomatous stroma. The patient died after several attempts at chemotherapy. Even if only sporadic cases have been described of late recurrences and of extrapulmonary metastases for giant cell tumors, the case presented here is exceptionally rare. The factors that influence recurrence of these tumors and their ability to metastasize is discussed.     

152Eu depth profiles in granite and concrete cores exposed to the Hiroshima atomic bomb

Two granite and two concrete core samples were obtained within 500 m from the hypocenter of the Hiroshima atomic bomb, and the depth profile of 152Eu was measured to evaluate the incident neutron spectrum. The granite cores were obtained from a pillar of the Motoyasu Bridge located 101 m from the hypocenter and from a granite rock in the Shirakami Shrine (379 m); the concrete cores were obtained from a gate in the Gokoku Shrine (398 m) and from a pillar top of the Hiroshima bank (250 m). The profiles of the specific activities of the cores were measured to a depth of 40 cm from the surface using low background germanium (Ge) spectrometers. According to the measured depth profiles, relaxation lengths of incident neutrons were derived as 13.6 cm for Motoyasu Bridge pillar (granite), 12.2 cm for Shirakami Shrine core (granite), and 9.6 cm for concrete cores of Gokoku Shrine and Hiroshima Bank. In addition, a comparison of the granite cores in Hiroshima showed good agreement with Nagasaki data. Present results indicates that the depth profile of 152Eu reflects incident neutrons not so high but in the epithermal region.     

Color Doppler ultrasound pulsatile flow signals of thoracic lesions: comparison of lung cancers and benign lesions

Color Doppler ultrasound (US) was performed in 153 patients (including 102 with lung cancer and 51 with benign lesions) to assess pulsatile flow signals in thoracic lesions. The values of resistive index (RI) and pulsatility index (PI) of color Doppler US pulsatile flow signals in lung cancers and benign lesions were measured, analyzed, and compared. In the enrolled 153 patients with thoracic lesions, 61 lung cancers and 34 benign lesions had detectable color Doppler US pulsatile flow signals, and lung cancers had lower RI and PI values than benign lesions (RI: 0.70+/-0.03 vs. 0.79+/-0.04, p < 0.05; PI: 1.61+/-0.15 vs. 2.44+/-0.25, p < 0.005). However, overlapping RI and PI values in lung cancers and benign lesions somewhat limited color Doppler US pulsatile flow signals to differentiate lung cancers from benign lesions. Further analysis of RI and PI values in subgroups of lung cancers [squamous cell carcinoma (SCC, n = 34), adenocarcinoma (AC, n = 18), and small-cell lung cancer (SCLC, n = 6)] and benign lesions [cavitary benign lesions (CBL, n = 8), and noncavitary benign lesions (NCBL, n = 26)] revealed that all different cell types of lung cancers (SCC, AC, and SCLC), indeed, had lower RI and PI values than NCBL (for RI, all p < 0.01; for PI, all p< or =0.001). Moreover, the mean RI and PI values showed a significant incremental decrease from NCBL (mean RI, PI = 0.88, 2.94) toward SCC and AC (for SCC, mean RI, PI = 0.71, 1.68; for AC, mean RI, PI = 0.68, 1.67) and, finally, to SCLC (mean RI, PI = 0.62, 1.05). In contrast, CBL had relatively lower RI and PI values than AC and SCLC (for CBL, mean RI, PI = 0.53, 0.80; both p > 0.05 for RI and PI), and even a significant difference from SCC (p < 0.05 for RI and PI). We conclude that color Doppler US pulsatile flow signal is somewhat limited to differentiate lung cancers from benign lesions, but provides a noninvasive in vivo model to assess the neovascularity intensity of lung cancers.     

Validity of self-reported cancers in a prospective cohort study in comparison with data from state cancer registries

The accuracy of self-reported cancer diagnoses in a prospective study was compared with population-based cancer registry data in four states. The study cohort included 65,582 men and women aged 39-96 years who were participants in the Cancer Prevention Study II Nutrition Survey, begun by the American Cancer Society in 1992. Estimates of sensitivity (the proportion of study participants with a registry-documented cancer who self-reported the cancer) ranged from 0.79 for an exact match of cancer site and year of diagnosis (+/- 1 year) to 0.93 for a match of any reported cancer. The sensitivity of exact matches varied considerably by cancer site and was highest for breast, prostate, and lung cancers (0.91, 0.90, and 0.90, respectively) and lowest for rectal cancer and melanoma (0.16 and 0.53, respectively). Sensitivity also varied slightly by the age, education, and smoking status of study participants. Estimates of sensitivity were virtually identical for each of the four states. The positive predictive value (the proportion of self-reported cancers that were confirmed by the registries) was 0.75 overall and also varied by cancer site. Unlike sensitivity, however, this proportion varied considerably by state. All self-reports of cancer that were not confirmed by the registries were further investigated by repeat questionnaires and acquisition of medical records. Low positive predictive values were due to underascertainment of true cancer cases by the registries, inaccurate reporting on the part of study participants, and problems with the algorithm used by the state to link the study population to the registry data. In conclusion, the ability of members of this cohort to report a past diagnosis of cancer accurately is quite high, especially for cancers of the breast, prostate, lung, and colon, or for the occurrence of any cancer.     

Variability in the detection of enlarged mediastinal lymph nodes in staging lung cancer: a comparison of contrast-enhanced and unenhanced CT

OBJECTIVE: Because CT protocols for staging lung cancer vary and little information exists regarding the diagnostic importance of using i.v. contrast material, our intent was to evaluate intra- and interobserver agreement in the detection of enlarged mediastinal lymph nodes, comparing i.v. contrast-enhanced and unenhanced CT. SUBJECTS AND METHODS: Fifty patients with known or suspected bronchogenic carcinoma underwent unenhanced thoracic CT followed by contrast-enhanced CT. Three observers noted enlarged lymph nodes (> 10 mm in the short axis) and assigned the enlarged nodes to American Thoracic Society nodal station designations. Enlarged lymph nodes were grouped two ways: by assigning the exact number of enlarged lymph nodes found (zero, one, two, three, four or more), and by assigning whether at least one, or no, enlarged mediastinal lymph nodes were found at a station ("one or none"). Agreement levels were determined for inter- and intraobserver interpretations using weighted kappa statistics and the McNemar test. RESULTS: The number of enlarged lymph nodes with enhanced CT was 11% higher than on unenhanced studies (418 versus 377; p = .044). Numbers of enlarged lymph nodes were different for five stations; however, the numbers were small except for the right upper paratracheal station (2R) (contrast-enhanced, 68 enlarged lymph nodes; unenhanced, 44 enlarged lymph nodes; p = .014). With regard to all stations together, intraobserver agreement between contrast-enhanced and unenhanced studies was almost perfect (kappa range, .85-.94), and no difference was found for any observer in the proportion of patients with at least one enlarged lymph node. Interobserver agreement was substantial or almost perfect for the total number of enlarged lymph nodes. For specific stations, the lowest kappa value was .48 at 2R. One observer reported more patients with at least one enlarged lymph node with contrast enhancement at station 2R (p = .031). Greater agreement existed between two observers at station 2R with contrast enhancement versus no enhancement (kappa = .85 versus .48; p = .02). Conclusions matched, and calculations of estimated kappa values gave similar results for determination of the specific number of enlarged lymph nodes at a station and the "one or none" category. CONCLUSION: We found high agreement for intra- and interobserver interpretations for contrast-enhanced and unenhanced CT, although contrast-enhanced CT revealed more enlarged lymph nodes, especially at station 2R.     

Abuse characteristics among childhood sexual abuse survivors in therapy: a gender comparison

OBJECTIVE: The goal of this investigation was to examine similarities and differences in childhood sexual abuse (CSA) characteristics between men and women survivors in outpatient psychotherapy utilizing a substantial sample size of men, while examining an extensive range of abuse characteristics. METHOD: Abuse characteristics of 48 men from an outpatient treatment program for adult survivors of CSA in a university-based community mental health center were compared with those of 257 women from the same program. Data on abuse history were collected at admission or as soon thereafter as possible using a structured clinical interview with established reliability. RESULTS: Women were significantly more likely to have been sexually abused by a family member. Men were significantly more likely to report having oral sex performed upon them. Otherwise, no significant gender differences not attributable to anatomical differences (e.g., vaginal vs. anal intercourse) were found. CONCLUSIONS: The findings suggest that very few differences exist in the nature and extent of CSA reported by men and women. Thus CSA perpetrated on boys appears largely comparable in nature and extent to that committed against girls.     

Wound healing of scleral self-sealing incision: a comparison of ultrasound biomicroscopy and histology findings

PURPOSE: The goal of this study was to compare the morphologic findings of wound healing in scleral self-sealing incisions using ultrasound biomicroscopy and histology. METHODS: Using a slit-knife, we made a scleral self-sealing incision in the rabbit eye. At various time points postoperatively, ultrasound biomicroscopy was performed to evaluate wound healing; the eyes then were enucleated and studied histologically. We also performed ultrasound biomicroscopy at various time points postoperatively in patients who received a scleral self-sealing incision during cataract surgery. RESULTS: In rabbit eyes, on days 1 and 2 postoperatively, we detected the scleral wound; thereafter, detection became increasingly difficult. On day 7 postoperatively, the wound was undetectable. By light-microscopic observation, the scleral wound was open at 1 day postoperatively. On day 2 postoperatively, fibrovascular tissue barely extended into the wound; on day 5 postoperatively, connective tissue extended through the full thickness of the wound. On day 7 postoperatively, the connective tissue became dense and aligned with the lamella. In human eyes, using ultrasound biomicroscopy, the scleral incision was detectable until 5 days postoperatively, but undetectable at 7 days postoperatively. CONCLUSIONS: Ultrasound biomicroscopy demonstrates the stages of wound healing of scleral self-sealing incisions. We believe that careful observation is necessary for approximately 7 days following self-sealing incision cataract surgery.