Filter cigarette smoking and lung cancer risk; a hospital-based case--control study in Japan.

Recent changes in the histology of lung cancer, namely a relative increase of adenocarcinoma compared to squamous cell carcinoma, might be due to a temporal shift from nonfilter to filter cigarettes. To investigate the association between type of cigarette and lung cancer by histological type, we conducted a case-control study in Japan, comprising 356 histologically confirmed lung cancer cases and 162 controls of male current smokers, who provided complete smoking histories. Overall, logistic regression analysis after controlling for age and prefecture revealed decreased risk, as shown by adjusted odds ratios, for both squamous cell carcinoma and adenocarcinoma among lifelong filter-exclusive smokers as compared to nonfilter or mixed smokers. This decrease was greater for squamous cell carcinoma than for adenocarcinoma. Among men under 54 years, filter-exclusive smokers displayed increased risk of adenocarcinoma, but decreased risk of squamous cell carcinoma. The recent shift in histology from squamous cell carcinoma to adenocarcinoma, particularly among younger smokers, might be due to changes in cigarette type. However, among subjects aged 65 years or more, no differences in histological type appeared related to type of cigarette smoked, implying that other factors are associated with increases in adenocarcinoma among older Japanese population.

Videothoracoscopic surgery for thoracic neurogenic tumors: a 7-year experience.

While videothoracoscopic surgery has rapidly become accepted as an effective method of performing minimally invasive surgery, the advantages and feasibility of using this surgical technique for the treatment of neurogenic tumors of the thorax are not yet well defined. Between August 1992 and May 1999, 15 solitary thoracic neurogenic tumors were surgically excised using videothoracoscopic surgery in our hospital. The patients comprised six women and nine men, with a mean age of 38.1 years. The mean tumor size was 3.5 cm, with a range of 1.5-6.5 cm and included 12 schwannomas, 2 ganglioneuromas, and 1 neurofibroma. Among the 15 patients, 4 were treated using videothoracoscopic surgery plus minithoracotomy. The only complication associated with videothoracoscopic surgery was hoarseness which developed in one patient. Our experience indicates that videothoracoscopic surgery is a useful alternative to facilitate the excision of small thoracic neurogenic tumors.

Population-based mapping of pulmonary adenoma susceptibility 1 locus.

Pulmonary adenoma susceptibility 1 (Pas1), the major locus affecting inherited predisposition to lung tumor development in mice, maps near the Kras2 gene. We previously reported a significant association between a KRAS2/RsaI polymorphism and the risk and prognosis of lung adenocarcinoma (ADCA) in the Italian population. In the present case-control study, we examined 269 lung ADCA patients, 121 squamous cell lung carcinoma patients, and 632 healthy individuals (general population controls) in the Japanese population with genetic markers spanning approximately 1200 kb in the KRAS2 region. Allele-specific oligonucleotide hybridization revealed the same KRAS2/RsaI polymorphism associated with risk and prognosis as in Italian lung ADCA patients; the polymorphism was significantly associated with clinical stage (P < 0.001) and survival rate (log rank = 0.0014), confirming the mapping of PAS1 and pointing to the role of this locus in human lung cancer.

Endobronchial metastasis from renal cell carcinoma: report of a case.

A case of endobronchial metastasis from renal cell carcinoma developing 5 years after a right nephrectomy in a 63-year-old man is reported. Bronchoscopic examination performed after the patient presented with hemoptysis showed a polypoid tumor obstructing the entrance to the left upper bronchus. A snare was introduced through a bronchofiberscope to remove the endobronchial tumor, following which his atelectasis improved remarkably and his hemoptysis resolved. No side effects were observed. Electrosurgical snaring proved useful as palliative treatment to relieve bronchial obstruction due to an endobronchial metastasis in this patient.

Prognostic implication of human papillomavirus infection in squamous cell carcinoma of the lung.

On the subtropical island of Okinawa, squamous cell carcinoma (SCC), particularly the well-differentiated form, is the most frequent type of lung cancer, while this form is relatively rare on the Japanese mainland and in other countries. Furthermore, in Okinawa, in 1993, 80% of SCC cases of the lung were found to be infected with human papillomavirus (HPV). We studied the prognosis of SCC of the lung with HPV infection (n = 25) and compared it with non-HPV-infected SCC (n = 16). Using the Kaplan-Meier method (Wilcoxon analysis), the prognosis of HPV-infected cases was found to be better than that of the non-infected cases. In the virus-infected cases, apoptosis and infiltration of a large number of Langerhans cells were demonstrated. In addition to these findings, the virus-infected tumors were demonstrated to be histologically well-differentiated, perhaps contributing to the favorable prognosis. However, among the virus-infected cases, the type 16 virus-infected cases showed a poorer prognosis, compared to those infected with other HPV types. p53 gene mutation was also examined, and was considered to be an unfavorable prognostic factor, as reported elsewhere. However, in Okinawa, HPV-positive cases with p53 mutations showed a slightly better prognosis than did non-viral infected cases with p53 mutations. The TNM staging system was also useful for categorizing the virus-infected cases. The prognosis of stage III (A and B) cases was poor. All of our present cases received surgical treatment. Chemotherapy and radiation therapy were not performed. Such treatment, however, might be effective, because virus-infected uterine cervical carcinomas have been routinely treated with chemotherapy and radiation. Furthermore, if the immunological basis of increased Langerhans cell infiltration in HPV-infected cases is elucidated, a clinical trial with immunotherapy may be favorable for the clinical outcome.

Risk modification in lung cancer by a dietary intake of preserved foods and soyfoods: findings from a case-control study in Okinawa, Japan.

To disclose the association of dietary intake of preserved foods and soyfoods with lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan, from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched population controls, provided the following major findings. (1) The more the miso soup intake, the higher the risk (test for trend: P = 0.001 for males; P = 0.043 for females). (2) Frequent intake of pickles (excluding salted fish) tended to be linked with an elevated risk in males. The adjusted odds ratio (OR) for once or twice per week or more, relative to less than once a month was 1.88 (95% confidence interval (CI): 1.26-2.81). (3) Frequent intake of soybeans was associated with a decreased risk in men (OR: 0.63, 95% CI: 0.40-0.98 for once or twice per week or more, relative to less than once a month). (4) Daily consumers of tofu were at a decreased risk, particularly for squamous cell carcinoma; the OR (95% CI) being 0.55 (0.34-0.89) in males and 0.14 (0.02-0.89) in females. These findings suggested deleterious effects of preserved foods and protective ones of soyfoods rich in isoflavones.

Lung cancer incidence rates by histologic type in high- and low-risk areas; a population-based study in Osaka, Okinawa, and Saku Nagano, Japan.

We investigated lung cancer incidence by histologic type using the data from population-based cancer registries in high-risk (Osaka and Okinawa) and low-risk (Saku Nagano) areas. Since the proportion of cases with histologic types identified was not sufficiently high, sex- and age-specific incidence rates by histologic type were estimated assuming that the distribution of histologic types was the same across the same sex and age groups regardless of reporting status. Compared to Saku in Nagano Prefecture, the cumulative risk of lung cancer incidence rates in Osaka and Okinawa were 1.3 and 1.5 times higher for males and 1.3 and 1.2 times higher for females, respectively. When divided by histologic type, male adenocarcinoma and small cell carcinoma were 1.6-2.1 times higher in Osaka and Okinawa, while squamous cell carcinoma was 1.6 times higher only in Okinawa compared to Saku Nagano. In females, squamous cell carcinoma and small cell carcinoma were 2.5-3.3 times higher in Osaka and Okinawa compared to Saku Nagano, while adenocarcinoma was almost equal in the 3 areas. These results indicate that the pattern of incidence of lung cancer by histologic type may differ between high- and low- risk areas.

hOGG1 Ser326Cys polymorphism and lung cancer susceptibility.

The human homologue of the yeast OGG1 gene, hOGG1, has been cloned, and its genetic structure has been determined. Several polymorphisms in the hOGG1 gene were detected in the Japanese populations, and among them, the Ser-Cys polymorphism at codon 326 has been shown to have a functional difference in complementation of mutant Escherichia coli that is defective in the repair of 8-hydroxyguanine. Activity in the repair of 8-hydroxyguanine is greater in hOGG1-Ser326 protein than in hOGG1(326) protein. Because many environmental carcinogens produce 8-hydroxyguanine residue and mismatching to this modified base potentially causes oncogenic mutations, the capacity to repair these lesions can be involved in cancer susceptibility in human beings. We, therefore, examined allele distributions of the Ser326Cys polymorphism in a case-control study of male lung cancer in Okinawa. The analyses based on 241 cases and 197 hospital controls disclosed the following findings. (a) Those with the Cys/Cys genotype were at an increased risk of squamous cell carcinoma and nonadenocarcinoma compared to those with the Ser/Cys and those with the Ser/Ser genotypes combined. The odds ratios adjusted for age and smoking history were 3.01 (95% confidence interval, 1.33-6.83) and 2.18 (95% confidence interval, 1.05-4.54), respectively. (b) The odds ratios for other histological subtypes of lung cancer or those in total were not significant. Those for Cys/Cys or Ser/Cys genotype against Ser/Ser did not reach statistical significance in any cell type. (c) The distributions of this polymorphism varied for different populations (Chinese, Japanese, Micronesians, Melanesians, Hungarians, and Australian Caucasians), with much less prevalence of Cys allele in the latter three populations. Although our sample size was limited, these results indicate that the Ser326Cys variant may be related to squamous cell lung cancer susceptibility. The Cys/Cys genotype appears to be more susceptible to squamous cell carcinoma, although the risk is less than that previously reported to be associated with the CYP1A1 gene. Further studies are needed to assess the importance of the interpopulation variation to cancer susceptibility.

Genetics and lung carcinoma in Okinawa Prefecture, Japan.

BACKGROUND: Although the incidence of all cancers in Okinawa is the lowest in Japan, that of lung cancer is high. This study was performed to clarify the underlying mechanism of this tendency. MATERIALS AND METHODS: Family histories of the lung cancer patients in Okinawa, p53 mutation, microsatellite alterations, and titers of serum anti-p53 antibodies were examined. RESULTS: The number of patients who had relatives with some malignancies in relatives was low in Okinawa, but lung cancer was frequently observed in their relatives. Overexpression of p53 protein was frequently observed in squamous cell carcinoma (SCC) than in adenocarcinoma (AD), and in smokers than in non-smokers. Anti-p53 antibodies were detected in 17.4%. The incidence of loss of heterozygosity at D3S643 and at IFNA were higher in SCC than in AD. CONCLUSIONS: Lung cancer was frequently observed in relatives of lung cancer patients. Pulmonary SCC had different genetic alterations compared with pulmonary AD in Okinawa.

Association of Ile462Val (Exon 7) polymorphism of cytochrome P450 IA1 with lung cancer in the Asian population: further evidence from a case-control study in Okinawa.

Okinawa, a group of islands that lie between the East China Sea and the Pacific Ocean, 2000 km south of the Japanese main islands, has a different profile of diseases, ethnicities, and cultures than does the rest of Japan. We examined an Ile462Val polymorphism (CYP1A1*2 allele) of cytochrome P450 IA1 in a hospital-based case-control study of lung cancer patients (247 cases and 185 controls) in Okinawa to ascertain the association of this variant with lung cancer. In addition, the distribution of this genotype was studied in populations from different areas of Japan, including Tokyo (n = 69) and Iwate (northern part of Japan; n = 81), as well as in a Chinese group from the Jiangsu province (n = 39) and in an Australian Caucasian group (n = 146). Genotype frequency in controls was not significantly different from area to area in Japan. In Okinawa, however, the genotype encoding Val/Val was associated with a significantly higher risk of lung cancer (odds ratio = 3.32, P = 0.013), especially of squamous cell carcinoma and small cell carcinoma (odds ratio = 4.85 and 9.35, respectively). The Val-encoding allele was less frequent in the Chinese population and was rare in Australian Caucasians. Thus, this study gives support to the value of the cytochrome P450 IA1 Ile462Val polymorphism as a practical high-risk marker of lung cancer in populations, especially those in southeast Asia, in which this variant is more common.

[Clinical efficacy of sulbactam/ampicillin in comparison with cefotiam in the treatment of elderly patients with pneumonia].

Clinical efficacy and safety of pareteral sulbactam/ampicillin (SBT/ABPC) was compared with cefotiam (CTM) in a randomized clinical trial of pneumonia in the elderly at 13 National Hospitals of Kyushu island. 37 patients received SBT/ABPC 3 g i.v., b.i.d., and 31 patients received CTM 1 g i.v., b.i.d. for 7 to 14 days. 1. 68 patients (37 for SBT/ABPC and 31 for CTM) were evaluated for safety. No statistical differences were noted in the patients' backgrounds of either group. 2. The clinical efficacy of SBT/ABPC was 96.3% (26/27 cases) while CTM was 75.2% (17/23 cases). This was found to be statistically significant (Fisher's exact test: p < 0.05). 3. 100% of evaluated cases (10 for SBT/ABPC and 4 for CTM) showed bacterial elimination. 4. No side effects were observed in the study. 5. Abnormal laboratory findings were noted in 10.8% (4/37 cases) for SBT/ABPC and 3.2% (1/31 cases) for CTM. The major adverse events were mild elevation of GOT, GPT and A1-P for SBT/ABPC, and mild platelets overproduction for CTM. No statistical differences were noted in both groups. These results are consistent with SBT/ABPC as a highly effective antibiotic in the treatment of elderly patients with pneumonia.

Smoking habits, local brand cigarettes and lung cancer risk in Okinawa, Japan.

To disclose the association between smoking habits and lung cancer in Okinawa, Japan, we analyzed the data from a case-control study conducted from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched population controls, provided the following major findings. (a) The odds ratios (ORs) for current smokers relative to nonsmokers were much greater for squamous cell carcinoma than for adenocarcinoma. The OR was 9.82 for squamous cell carcinoma and 2.18 for adenocarcinoma in males, 28.2 and 1.14, correspondingly, in females. (b) Males who quit smoking for 20 years or more demonstrated no elevated lung cancer risk. (c) Among male current smokers, the more the number of cigarettes smoked per day, the higher the lung cancer risk for both cell types, but particularly for squamous cell carcinoma. In contrast, deep smoke inhalation significantly increased the risk for adenocarcinoma in particular. (d) Okinawan brand cigarettes were more strongly associated with the risk, compared with other brand ones. This finding might partly explain the higher frequency of lung cancer in males with the relatively lower smoking rate in Okinawa.

Human papillomavirus DNA in squamous cell carcinoma of the lung.

AIM: To compare the incidence of squamous cell carcinoma (SCC) of the lung in Okinawa with that in Niigata on the mainland. METHODS: All patients presenting with SCC of the lung in Okinawa and Niigata in 1993 were included in the study. Diagnoses were confirmed by conventional histological examination of paraffin wax sections. Human papillomavirus (HPV) was detected by non-isotopic in situ hybridisation (NISH) and polymerase chain reaction (PCR) amplification with primers specific for the E6 and E7 regions of the HPV genome. PCR products were analysed by Southern and dot blotting. RESULTS: The incidence of well differentiated SCC of the lung was high in patients from Okinawa compared with moderately and poorly differentiated types, and compared with the incidence of SCC in patients from Niigata. This is despite similar patterns of age, sex (predominatly male), and smoking habit. More patients from Okinawa, however, were positive for HPV DNA by PCR (79%) and NISH (53%). Many patients haboured HPV types 6, 16, and 18. Only 30% of patients from Niigata were positive for HPV DNA by PCR and 20% by NISH. These patients all harboured one HPV type only. CONCLUSION: Surprisingly large numbers of patients from Okinawa were positive for HPV DNA. The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation.

[Clinical evaluation on causes of death in patients with active pulmonary tuberculosis].

Seventy one patients with active pulmonary tuberculosis who died during the past 5 years (1989 to 1993) were evaluated on their causes of death. Twenty two patients (31%) died directly of tuberculosis, and among them, 18 patients (81%) of 22 patients who died of tuberculosis) had very advanced tuberculosis. The majority of them (64%) were old age over 70 years and were bedridden due mostly to cerebrovascular injuries. The serum level of albumin was low in all 17 patients in whom it was measured. Establishment of diagnosis of tuberculosis was delayed over one month after the onset of symptoms in 59% of patients who died of severe disease. Sixty one percent (11/18) of patients died within the first month after the initiation of chemotherapy and about 90% (16/18) died within 3 months. Two patients died from massive hemoptysis and other patients died of either respiratory failure or tuberculosis meningitis. From these observations it was found that very advanced tuberculosis was the major cause of death in patients who died of tuberculosis and that the advanced disease was chiefly caused by the delay on the establishment of diagnosis, and it was most important to detect tuberculosis as early as possible, with regular check up of chest X-ray and frequent examination for AFB (acid-fast bacilli) for tuberculosis suspected patients. On the other hand, the majority of patients (49/71) died of complicating medical problem unrelated to tuberculosis. Seventeen patients died from malignancy (seven lung cancer, four lymphoma, two laryngeal cancer, etc). Ten deaths were the result of bacterial superinfection. Other patients died from respiratory failure due to COPD, arteiosclerotic heart disease, or cerebrovascular injuries, etc. Two patients of old age died of hepatic failure possibly caused by adverse reaction of TB chemotherapy. It was found that diseases unrelated to tuberculosis were the cause of death in approximately 70% of patients with active tuberculosis, and it should be emphasized to detect early and to treat these diseases, in particular malignancy. And it is also imperative that the chemotherapy for TB must be instituted very carefully with frequent monitoring of liver function in patients with old age.

Tea consumption and lung cancer risk: a case-control study in Okinawa, Japan.

To disclose the relationship between tea consumption and lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched controls, provided the following major findings. (a) The greater the intake of Okinawa tea (a partially fermented tea), the smaller the risk, particularly in women. For females, the odds ratios (and 95% confidence intervals) for those who consumed 1-4, 5-9, and 10 cups or more of Okinawan tea every day, relative to non-daily tea drinkers, were 0.77 (0.28-2.13), 0.77 (0.26-2.25) and 0.38 (0.12-1.18), respectively (trend: P = 0.032). The corresponding odds ratios for males were 0.85 (0.45-1.55), 0.85 (0.45-1.56) and 0.57 (0.31-1.06) (trend: P = 0.053). (b) The risk reduction by Okinawan tea consumption was detected mainly in squamous cell carcinoma. Daily tea consumption significantly decreased the risk of squamous cell carcinoma in males and females, the odds ratios being 0.50 (95% confidence interval 0.27-0.93) and 0.08 (0.01-0.68), respectively. These findings suggest a protective effect of tea consumption against lung cancer in humans.

[Hilar type squamous cell carcinoma confined within the bronchial wall with hilar lymph node metastasis: a case report].

A 60-year-old male patient visited our hospital for evaluation of positive sputum cytology. A chest X-ray film revealed no abnormal shadows. Bronchofiberscopy showed a protruding lesion at the spur between left B8 and B9. Histological findings indicated squamous cell carcinoma. Left lower lobectomy with hilar and mediastinal lymph node dissection was performed. The tumor did not infiltrate beyond the bronchial cartilage on postoperative histologic examination. However, hilar lymph node (#12 l) metastasis was identified. Surgical resection with lymph node dissection is mandatory even in the hilar type lung cancer confined within the bronchial wall.

[Double blind controlled study of ubenimex (Bestatin) against squamous cell lung cancer--a multicenter cooperative study].

To investigate effects of the combination of ubenimex, chemotherapy, and radiotherapy against unresectable advanced squamous cell carcinoma of the lung, a placebo controlled double-blind study was performed. Of 365 registered cases, there were 258 cases in the complete radiation group in which the treatment as specified in the protocol (irradiation of 40 Gy or more to the thorax subsequent to chemotherapy) was conducted; the 50% survival time was 449 days and 363 days in the ubenimex group and the placebo group, respectively. A significant (p = 0.0473) prolongation of the survival time was noted in the ubenimex group, and the response rate was 60.9% and 50.0% (p = 0.087). From these results it was confirmed that ubenimex, when used in combination with chemotherapy and radiotherapy, not only enhances the tumor-reducing effect but also prolongs the survival time.

Ectopic intrapulmonary thyroid.

An 83-year-old woman underwent resection of a pulmonary tumor. Histologic examination of the tumor demonstrated thyroid follicles without evidence of malignancy or teratomatous elements. Developmental anomaly may account for the ectopic intrapulmonary thyroid, which, to our knowledge, has not been reported in the literature.