Divergent changes in survival for histological types of non-small-cell lung cancer in the southeastern area of The Netherlands since 1975

We studied the incidence and survival rates for the histological subtypes of non-small-cell lung cancer, using data from the Eindhoven Cancer Registry over the period 1975-94. The proportions with adenocarcinoma and large-cell undifferentiated carcinoma increased from 11% to 21% and from 11% to 15%, respectively, while those with squamous cell carcinoma decreased from 78% to 62%. The increase in the proportion with adenocarcinoma was only found among men. Although the overall prognosis for patients with non-small-cell lung cancer has remained unchanged, there have been divergent changes between morphological subtypes. Relative 1- and 5-year survival rates for squamous cell carcinoma have improved slightly from 48% to 51% and from 14% to 16%, respectively, because of an increase in the proportion with localized tumours, while relative 1- and 5-year survival rates for adenocarcinoma have decreased from 59% to 45% and from 28% to 18%, respectively, because of a decrease in localized tumours. The proportion with localized tumours and the relative 1-year survival for large-cell undifferentiated carcinoma (about 18% and 30% respectively) were markedly lower. The divergent trends could partly be explained by changes in the histological classification of tumours, but changes in patterns of risk and biological behaviour of adenocarcinoma cannot be excluded.     

Pelvic exenteration in gynecologic oncology: Experience at the Mount Sinai Center, 1975-1992

Thirty-nine patients underwent pelvic exenteration for gynecologic malignancies at The Mount Sinai Medical Center between 1975 and 1992. Surgical techniques, morbidity, survival, and other variables for patients so treated in two periods, 1975-1984 and 1985-1992, were compared. The primary cancer included squamous cell carcinoma of the cervix, 27; adenocarcinoma of the cervix, 1; squamous cell carcinoma of the vagina, 4; adenocarcinoma of the endometrium, 4; squamous cell carcinoma of the vulva, 2; and adenocarcinoma of the rectum, 1. Median survival was 23.1 months, with a median follow-up of 18 months. Survival was significantly related to status of the lymph nodes (p 0.0004) and surgical margins (p 0.0038). There were two postoperative mortalities, one due to pulmonary embolus and another to myocardial infarction. The ability in the second period analyzed, 1985-1992, to integrate a continent urinary reservoir and supralevator exenteration without colostomy yet not induce increased morbidity or decreased survival, has not been previously reported.     

Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer

This study was performed to clarify the different effects of each mutant exon of p53 as indicators of a poor prognosis in patients with non-small cell lung cancer (NSCLC). Tumor tissues of 204 patients with NSCLC were analysed; 96 tumors were stage I, 22 stage II, and 86 stage III. DNA was extracted from frozen specimens and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to investigate mutations of p53 from exon 5 to exon 8. Seventy-five patients with NSCLC (36.8%) had mutations in p53 which included 72 cases of missense mutations and three cases of non-missense mutations. The overall survival rate of patients with mutant p53 adenocarcinomas was strikingly worse than that of patients whose tumors had wild-type p53 (35.7% vs 53.8%; P=0.041), but no significant difference in survival was found in the patients with NSCLC and squamous cell carcinoma. Mutations in exon 5 of p53 occurred in 33 cases (16.2%), mutation in exon 6 was detected in only one case (0.5%), mutations in exon 7 in 20 cases (9.8%), and mutations in exon 8 in 18 cases (8.8%). The overall survival rate of patients with mutations in exon 7 was worse than that of patients with wild-type p53 in NSCLCs and adenocarcinomas (42.9% vs 56.0%; P=0.025 and 33.3% vs 53.8%; P=0.048, respectively), whereas the overall survival of patients with mutations in exon 5 was almost the same as that of patients with wild-type p53. In addition, the overall survival rate of patients with mutations in exon 8 was strikingly worse than that of patients with wild-type p53 in NSCLCs, adenocarcinomas and squamous cell carcinomas (22.9% vs 56.0%; P<0.001, 19.0% vs 53.8%; P=0.004 and 33.3% vs 62.5%; P=0.042, respectively). Multivariate analysis with the Cox regression model of patients with NSCLC, adenocarcinoma and squamous cell carcinoma indicated that mutations in exon 8 were best correlated with the overall survival rate, followed by lymph node status (P<0.001, P=0.015 and P=0.006, respectively), and mutations in exon 7 of NSCLC were also revealed to have good correlation, followed by lymph node status and mutations in exon 8 (P=0.031). Mutation of p53 was a poor prognostic factor for adenocarcinoma as described previously. Moreover, mutations in exon 8 were more useful indicators of prognosis not only for adenocarcinoma but also for NSCLC. Worse overall survival of the patients with mutations in exon 8 of p53 was suggested to be associated with codon 273 mutations as well as mutations between codon 280 and 285 included into the H2 alpha helix corresponding to residues 278-286. These results suggested that abnormal conformation of H2 alpha helix might play an important role not only in the loss of normal function but also in the acquisition of tumorigenesis. Investigation of mutations in exon 8, especially codon 273 mutation and mutant H2 alpha helix was considered to be a clinically useful approach for determining the prognosis of patients with NSCLC.     

Thoracic lymphangiomatosis

The prognostic value of p53 protein in tumor extracts as measured by ELISA was studied retrospectively in 228 non-small cell lung cancer (NSCLC) patients. The assay measures both wild-type and mutated p53. The specimens on which this study was performed have been used earlier to analyze the prognostic impact of components of the plasminogen activation system, which enabled an analysis of relationships between these components and p53 protein. The median of the p53 protein values in the 228 patients was 0.10 (range, 0-0.70) ng/mg protein. Survival analysis comparing patients with p53 levels below versus above the median showed no significant difference (P = 0.67). When analyzing the histological types, adenocarcinoma (n = 106), squamous cell carcinoma (n = 84), and large cell carcinoma of the lung (n = 38) separately, similarly, no significant differences in survival between patients having low versus high tumor p53 levels were found. When comparing levels of p53 protein in the three histological types, a significant difference (P < 0.0001) was found, with adenocarcinomas having the lowest levels. There was a weak positive correlation (r = 0.22) between p53 protein and plasminogen activator inhibitor type 1 (PAI-1). Multivariate analysis proved no impact of p53 on survival; tumor size, PAI-1, and lymph node involvement were the only variables with significant influence on survival. These data indicate that p53 protein quantitated with a sandwich ELISA in tumor extracts from NSCLC has no prognostic value, but the observed statistically significant difference of p53 protein content between histological subgroups may be related to differences in etiology and biology in different NSCLC subtypes. In addition, the weak association found between p53 protein and the independent prognostic marker PAI-1 could suggest yet undefined interactions in lung cancer.     

Angiotensin-1-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and their association with the metabolic syndrome and electrocardiographic coronary artery disease in Pima Indians

Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in those patients with histological evidence of "risk" features--lymph node metastases, lymphatic vascular tumour permeation and clinically undetected parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy. One hundred and eight patients (45.2%) had various poor prognostic histological features and received adjuvant chemotherapy--70 had cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk factors present in each group were identical. These patients have now been followed up for periods ranging from 8 to 14 years. All recurrences, except one, occurred within 23 months of surgery; in the remaining this occurred 8 years later. This suggests that very close long-term follow-up is needed. Recurrences were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The 10-year survival in patients without risk factors was 97.2%. In those patients with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year survivals in patients with positive nodes were similar--66.7% in the MMC group and 71.4% in the PVB group. The 10-year survival in patients with squamous cell carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU) group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%) (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those with adenocarcinoma, the PVB regime.     

Trends in cervical cancer incidence in the district of Florence

The trend in cervical cancer incidence in the District of Florence from 1975 to 1989 was investigated. Tuscany Cancer Registry data were available since 1985. Incidence data from 1975 to 1985 were obtained through a retrospective survey of all the Departments of Pathology and Gynaecology in the district. Cytological screening for cervical cancer has been available in the district since 1973, and since 1980 active invitation of residents aged 25 to 59 years has been in use. A significant trend in decreasing incidence was evident for the overall population (P = 0.003) and for 40-49 (P = 0.028), 50-59 (P < 0.001) and 60-69 (P = 0.002) year age groups, whereas no significant trend was observed for the age group 30-39 years. An association between attendance to screening and reduced incidence was evident, in that a greater reduction was evident for those cohorts (ages 50-59 and 60-69) who had a higher compliance to screening 10-15 years before. If the decrease in cervical cancer incidence was spontaneous, a parallel decrease of CIN3, which is commonly assumed to be the precursor of invasive carcinoma, would be expected. On the contrary, the detection rate of CIN3 at first Pap test showed a significant increase in the study period. All these findings suggest that the observed reduction in cervical cancer incidence was mostly due to the effect of screening, and stress the need for optimising the coverage of the invited population.     

Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992

BACKGROUND: Little is known about the cause of inflammatory breast carcinoma (IBC), the most aggressive form of breast cancer. To the authors' knowledge, no studies have investigated whether IBC risk factors are different from those for breast carcinoma overall, and there has been only one report of IBC incidence and survival patterns. METHODS: The authors used data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for the period 1975-1992 to calculate age-adjusted incidence and survival rates for 913 white and 121 African American women with IBC involving dermal invasion of lymphatic ducts and 166,375 white and 13,674 African American women with other types of breast carcinoma (non-IBC). RESULTS: Between 1975-1977 and 1990-1992, IBC incidence doubled, increasing among whites from 0.3 to 0.7 cases per 100,000 person-years and among African Americans from 0.6 to 1.1 cases. However, rates for African Americans varied due to the small numbers of IBC cases. The twofold increase in IBC incidence was higher than that observed for non-IBC during the same period (27% for African Americans and 25% for whites). IBC patients were significantly younger at diagnosis than non-IBC patients; and among both IBC and non-IBC patients, African Americans were younger than whites. Overall survival was significantly worse for IBC patients than for non-IBC patients and for African Americans than for whites. Among whites, 3-year survival improved more for IBC patients than for non-IBC patients between 1975-1979 and 1988-1992, increasing from 32% to 42% for IBC patients (P=0.0001) and from 80% to 85% for non-IBC patients (P=0.0001). CONCLUSIONS: The disparities observed in incidence trends and age at diagnosis, particularly according to race, highlight the need for further investigation of the differences between IBC and non-IBC incidence.     

NDPK/nm23 expression and its correlation with lymph node metastasis in human lung cancer

Using labelled streptavidin-biotin (LSAB) method, we examined the expression of nucleoside diphosphate kinase(NDPK), the product of metastasis suppressor gene nm23, in human lung cancer. Of 88 patients tested, 48 (54.5%) showed positive staining. The positive staining rate was higher in adenocarcinoma (28/42, 66.7%) than in squamous cell carcinoma (20/46, 43.5%; P < 0.05). Higher incidence of positive staining was also found in squamous cell carcinoma without hilar or mediastinal lymph node metastasis (16/27, 59.3%) than in that with hilar or mediastinal lymph node involvement (4/19, 21.1%; P < 0.05). NDPK/nm23 was equally expressed in adenocarcinoma irrespective of lymph node status. In both cell types of carcinoma, expression of NDPK/nm23 was not correlated with tumor cell differentiation, nor was it correlated with the P-TNM staging. Our results suggest that NDPK/nm23 may play different roles in the pathogenesis and metastasis of human pulmonary squamous cell carcinoma and adenocarcinoma. Its expression levels are inversely correlated with lymph node metastasis in squamous cell carcinoma.     

Relationship between nm23-H1 expression and lymph node metastasis and prognosis in cervical cancer

OBJECTIVE: To investigate the expression of nm23-H1 in cervical carcinoma and its significance. METHODS: Expression of nm23-H1 was examined by immunohistochemical method in 39 cases of adenocarcinoma and 39 cases of squamous cell carcinoma of the uterine cervix. The relationship between expression of nm23-H1 and clinic-pathologic factors and prognosis was analyzed by chi-square test. RESULTS: Positive staining rate of nm23-H1 was 44.6% in adenocarcinoma and 39.2% in squamous cell Carcinoma. The positive staining rate of nm23-H1 in stage I and II adenocarcinoma was 61.1% and 28.6% respectively (P = 0.044); in patients with recurrence nm23-H1 positive rate was lower than that in patients without recurrence (21.5% vs 56%, P = 0.39); in patients with lymph node negative, nm23-H1 positive staining was more than that in patients with lymph node positive (52% vs 28.6%), however, this difference was not statistically significant (P = 0.162). None of 14 cases of lymph node metastasis was strong positive stainig, whereas 7 of 25 without lymph node metastasis were demonstrated to have strong positive staining (P = 0.031). The 5-year survival rate in negative staining group was lower than that in the positive staining group (52.5% vs 82.4%, P = 0.042). In squamous cell carcinoma there was no statistically significant relationship between nm23-H1 expression and clinic-pathologic factors and prognosis. CONCLUSIONS: nm23-H1 expression was associated with biologic behavior in cervical adenocarcinoma.     

Histopathologic changes seen in esophagectomy specimens from the high-risk region of Linxian, China: potential clues to an etiologic exposure?

Esophageal cancer is one of the most fatal cancers worldwide and is characterized by great variation in rates among different populations. Linxian, a county in Henan Province, located in north-central China, has one of the highest rates of esophageal squamous cell carcinoma in the world. Most squamous cell carcinomas in low-risk populations are attributable to alcohol and tobacco consumption, but the causative agents in high-risk populations are less clear. The prevention and treatment of esophageal cancer in high-risk regions, such as Linxian, are limited by our inability to identify these agent(s). During a preliminary histological review, the authors noticed characteristic findings in the arteries, nerves, and lymph nodes of esophagectomy specimens from Linxian and wondered whether these findings might offer clues to the cause of squamous cell carcinoma (eg, polycyclic aromatic hydrocarbon exposure) in the Linxian population. The purpose of this study was to report these previously undescribed histopathologic changes and to compare their presence and severity with those found in esophageal squamous cell carcinomas and adenocarcinomas from a lower-risk population in the United States. Forty esophagectomies were reviewed, including 13 squamous cell carcinomas from Linxian and 21 squamous cell carcinomas and six adenocarcinomas from the United States. The presence and severity of arteriosclerosis and myxoid degeneration of nerves and the presence of anthracosis in periesophageal lymph nodes were recorded. The prevalence and severity of these findings in the three groups of esophagectomies were compared. The esophageal squamous cell carcinomas from Linxian, China, had a higher prevalence of arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes than the squamous cell carcinomas from the United States (Wilcoxon test, P < .04 for all comparisons). There were also significant differences in the prevalence of arteriosclerotic vessels and anthracotic lymph nodes between the esophageal squamous cell carcinomas from Linxian and the adenocarcinomas from the United States. Arteriosclerosis and the myxoid degeneration were significantly more severe in the esophageal squamous cell carcinomas from Linxian than in the esophageal squamous cell carcinomas or adenocarcinomas from the United States (Mantel trend test, P < .006 for all comparisons). Arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes can be seen in association with esophageal squamous cell carcinomas from the high-risk region of Linxian, China. These changes appear to be more prevalent and severe than those seen in association with esophageal squamous cell carcinomas or adenocarcinomas from a low-risk population in the United States. These characteristic changes may be causatively significant and may represent histological evidence of high-level environmental exposure to polycyclic aromatic hydrocarbons.     

Use of polymerase chain reaction with L1 consensus primer for detection of HPV16 and HPV18 in cervical cancer tissues

Biopsy materials of cervical carcinoma including 20 cervical adenocarcinomas and 20 squamous cell carcinomas were collected. A rapid method for determining HPV type was developed, based on DdeI restriction enzymes analysis within the L1 region of HPV, amplified by PCR using consensus primers. The results indicated that HPV type 16 was detected more often in squamous cell carcinomas than in adenocarcinomas (80% vs 15%, P < 0.001), conversely, HPV type 18 was detected significantly more often in adenocarcinoma tissues (45% vs 5%, P < 0.001). These differences may reflect the presence of different virus receptors in cancer cells with different morphologic potential, or, they may indicate that the specific HPV infection actually plays a direct role in the process of carcinogenesis.     

Expression of nucleolar protein p120 in human lung cancer: difference in histological types as a marker for proliferation

The function of proliferation-associated nucleolar protein p120 is unclear. A recent report that a yeast protein, NOP2, 67% homologous to human p120, is up-regulated during the onset of growth and influences the morphology of the nucleolus supports the notion that this protein could serve as a marker for proliferation in neoplastic cells. Lung cancer is characteristic in that different histological types show different biological features. We attempted to evaluate the levels of p120 expression in resected human lung cancer tissues of different histological types and the relation of p120 expression and cell proliferation using human lung cancer cell lines. When 37 frozen specimens of human lung cancer and normal lung were stained with a p120 monoclonal antibody, the nucleoli of cancer cells were positively stained, whereas a few macrophages in normal lung revealed only weak staining. The labeling index of p120 in squamous cell carcinoma (67.7 +/- 12.4%) was significantly higher than that in adenocarcinoma (35.3 +/- 12.6%) or in large cell carcinoma (30.1 +/- 17.3%; P < 0.01). In six human lung cancer cell lines and one normal lung fibroblast cell line cultured in vitro, there was a significant correlation between S-phase fraction and p120 mRNA (r = 0.851, P < 0.02)/p120 protein (r = 0.869, P < 0.01) or between doubling time and p120 protein (r = -0.928, P < 0.01). In the context of the reports that indicate higher [3H]thymidine incorporation and shorter doubling time in the squamous cell carcinoma, these results indicate that p120 can be a marker for proliferation in human lung cancer cells in vivo and in vitro, and that it has an important function in the cell cycle of tumor proliferation.     

Cathepsin-D expression in cervical carcinoma and its prognostic significance

An immunohistochemical study was made of cathepsin-D protein expression in each of the three main types of uterine cervical carcinoma (squamous carcinoma, adenosquamous carcinoma and adenocarcinoma) with particular reference to lymph node status and prognosis. Of the 61 cases, 54.1% showed cytoplasmic staining in more than 2.5% of tumour cells counted. Cathepsin-D expression was significantly higher in adenocarcinoma (mean -3.128) than in squamous carcinoma and adenosquamous carcinoma (mean -3.709, p = 0.047 using logit transformation). Cathepsin-D had no prognostic value in any of the three tumour types. No relationship was found between cathepsin-D staining and lymph node status and there was no advantage in adding cathepsin-D values to lymph node status. These results suggest that immunostaining for cathepsin-D protein expression is unlikely to be of use as a prognostic marker.     

A marked increase in the rate of diagnosed prostate cancer in the Netherlands during 1990-1996

OBJECTIVE: To study the variation of the number of histologically detected adenocarcinomas of the prostate in the Netherlands during the period 1990-1996. DESIGN: Retrospective. SETTING: National study. METHOD: Use was made of data from the National Automated Morbid-Anatomical Record Department (PALGA), Utrecht. The following data were established for each year of the study period: the total number of histological examinations of the prostate, the number of men involved (often several histological examinations of the prostate of the same man in the same year), how often adenocarcinoma was diagnosed by these examinations and how many men were involved, as well as the age of all carcinoma patients. These data were compared with those concerning variation and incidence of cancer of the prostate obtained from the Netherlands. Cancer Registration and the Central Statistics Office. RESULTS: In 7 years a total of 205,525 histological examinations of the prostate were performed in 179,298 men; the diagnosis 'adenocarcinoma of the prostate' was made 52,964 times in 44,182 men. The number of tissue examinations with the diagnosis 'carcinoma of the prostate' increased by 63% (from 5,596 to 9,146), the number of men in whom this diagnosis was made increased by 62% (from 4,710 to 7,614). The relative frequency of prostate carcinoma in relation to all examinations of the prostate increased in 6 years (1991-1996) from 22% to 28%. In that period, the (uncorrected) incidence increased by 50%, while mortality corrected for age remained the same. CONCLUSION: Of the marked increase of the number of detected cases of carcinoma of the prostate in the study period, only a small part could be attributed to demographic changes. Since autopsies have shown that there exists a large 'stock' of subclinical carcinomas, most of the growth can probably be explained by the more intensive diagnostics with prostate-specific antigen and transrectal ultrasonography.     

Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia

OBJECTIVE: To determine trends in the clinicopathology of vulvar squamous cell carcinoma over the past 2 decades, with particular reference to the possible effects of the increasing incidence of vulvar intraepithelial neoplasia (VIN) during this time. METHODS: Two cohorts of 56 and 57 women with squamous cell carcinoma of the vulva and separated by at least 2 decades were reviewed retrospectively. Pathologic specimens were analyzed concurrently. RESULTS: In the 1965-1974 cohort, only one of 56 patients was younger than 50 years of age at the time of presentation, whereas in the 1990-1994 cohort, 12 of 57 (21%) were younger than 50 years of age (P = .001). Ten of 13 women younger than 50 years of age, compared with 13 of 100 of women 50 years of age or older, had warty or basaloid VIN associated with their invasive carcinoma (P < .001). Cigarette smoking and multiple lower genital tract neoplasia were both significantly more common in women younger than 50 years of age (P < .001). CONCLUSION: Over the past 2 decades, a subset of women younger than 50 years of age with squamous cell carcinoma of the vulva has emerged. Most of these carcinomas appear to arise in a field of warty or basaloid VIN. This suggests that the increasing incidence of VIN seen in young women during the past 2 decades is being reflected now in VIN-associated squamous cell carcinoma of the vulva in younger women.     

Prognostic factors of cervical lymph node metastasis in head and neck squamous cell carcinoma

AIMS AND BACKGROUND: The metastatic spread of squamous cell carcinoma of the head and neck (SCCHN) to the cervical lymph nodes is a negative prognostic factor in terms of survival. We have used multivariate analysis to identify the possible prognostic significance of a number of clinical and pathological characteristics in relation to possible involvement of the cervical lymph nodes in a series of 396 patients. METHOD: 396 patients with SCCHN were studied. Variables regarding the patient, the carcinoma and histology were analysed by multivariate analysis using BMDP's PLR programme. RESULTS: Some variables appear to represent predisposing factors for tumor spread to the lymph nodes: tumor site (supraglottic larynx: P = 0.005; base of the tongue: P = 0.02; hypopharynx: P = 0.02), grading (P = 0.001), and a number of histological parameters (lower degree of histological differentiation: P = 0.001; vascular permeation: P = 0.04; perineural invasion: P < 0.05; prevalently plasmocytic infiltrate: P < 0.05). CONCLUSION: The identification of cases at risk for metastasis can be improved by the assessment of prognostic factors, with a consequent improvement in treatment strategies.     

Risk of esophageal and gastric adenocarcinomas in relation to use of calcium channel blockers, asthma drugs, and other medications that promote gastroesophageal reflux

Incidence of adenocarcinomas of the esophagus and gastric cardia has risen dramatically over the past 2 decades in the U. S., for reasons that are not yet clear. A number of common medications (e.g., calcium channel blockers, tricyclic antidepressants, and certain asthma medications) promote gastroesophageal reflux by relaxing the lower esophageal sphincter (LES). Reflux is thought to increase cancer risk by promoting cellular proliferation, and by exposing the esophageal epithelium to potentially genotoxic gastric and intestinal contents. Recent studies have suggested that calcium channel blockers may also increase cancer risk by inhibiting apoptosis. Using personal interview data from a multicenter, population-based case-control study conducted between 1993 and 1995 in three areas of the U. S., we evaluated whether the use of LES-relaxing drugs was associated with increased risk of adenocarcinomas of the esophagus and gastric cardia. Cases of esophageal adenocarcinoma (n = 293) and gastric cardia adenocarcinoma (n = 261) were compared with general population controls (n = 695). Information on additional case groups of esophageal squamous cell carcinoma (n = 221) and noncardia gastric cancer (n = 368) were also available for comparison. Overall, 27.4% of controls had used one or more of these drugs for at least 6 months, compared with 30.2% of esophageal adenocarcinoma and 23.8% of gastric cardia adenocarcinoma cases. The adjusted odds ratios (ORs) for ever use were 1.0 [95% confidence interval (CI) = 0.7-1.5] and 0.8 (95% CI = 0.5-1.1), respectively. There was little evidence of increasing risk with increasing duration of use of all LES-relaxing drugs together. We found an increased risk of esophageal adenocarcinoma among persons reporting use of asthma drugs containing theophylline (OR = 2.5; 95% CI = 1.1-5.6) or beta agonists (OR = 1.7; 95% CI = 0.8-3.8). Risks were higher among long-term users (>5 years) of these drugs (OR = 3.1; 95% CI = 0.9-10.3 and OR = 2.3; 95% CI = 0.8-7.0, respectively). In contrast, there was no evidence that the use of calcium channel blockers or other specific groups of drugs increased the risk of any of the cancers studied. These results provide reassuring evidence that the increases in incidence of adenocarcinomas of the esophagus and gastric cardia are not likely to be related to the use of LES-relaxing drugs as a group, or calcium channel blockers in particular, but they do suggest that persons treated for long-standing asthma may be at increased risk of esophageal adenocarcinoma.     

Poorer survival of nulliparous women with endometrial carcinoma

BACKGROUND: Several epidemiologic studies have shown an inverse relationship between parity and the incidence of endometrial carcinoma. A prognostic influence of reproductive factors has been reported for carcinomas of the breast and uterine cervix; but no such independent influence has been reported for endometrial carcinoma, to the authors' knowledge. Therefore, the authors investigated the prognostic importance of parity in an unselected group of patients. METHODS: Clinical and histopathologic data on all 316 patients treated for endometrial carcinoma during the period 1981-1990 in Hordaland County, Norway, were related to cause specific death in univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression model) analyses. The median follow-up for the survivors was 9 years (range, 4-16 years). No patients were lost due to insufficient follow-up information. RESULTS: Nulliparous women had a poorer 5-year survival rate compared with patients who had had 1 or more deliveries (57% vs. 81%, P = 0.0001), and they were significantly older and had more advanced disease at the time of primary surgery than the parous women. After adjustment for traditional risk factors, a hazard ratio of 2.81 (95% confidence interval, 1.55-5.06) was found for nulliparous versus parous women. International Federation of Gynecology and Obstetrics stage, curative treatment, and tumor differentiation grade were also identified as independent prognostic factors, whereas age and menopausal status had prognostic significance in the univariate analysis only. CONCLUSIONS: The decreased survival among nulliparous women reported herein may reflect biologic differences between parous and nulliparous endometrial carcinoma patients. It may also be due in part to a greater delay in diagnosing the women in the nulliparous group.     

Trends in incidence rates of adenocarcinoma of the oesophagus and gastric cardia in New Zealand, 1978-1992

BACKGROUND: Increasing incidence rates for adenocarcinomas of the oesophagus and gastric cardia have been reported from the United States, Denmark, United Kingdom, Switzerland, and Sweden. This paper reports on the incidence of adenocarcinomas of the oesophagus and gastric cardia in New Zealand in the Maori (Polynesian), and non-Maori (predominantly European) populations. METHODS: Incidence data from the National Cancer Registry for 1978 through 1992 were used to compute age-adjusted rates by sex, ethnic group, anatomic subsite, morphology, 14 area health districts, and for three periods: 1978-1982, 1983-1987 and 1988-1992. Statistical tests for significance of trends and differences in frequencies were employed. RESULTS: Incidence rates for adenocarcinoma of the oesophagus are increasing in non-Maori men and women, but at a lesser rate than that reported for the US. The rate of 2.3 per 100000 population (1988-1992) for non-Maori men is similar to the rate for US white men of 2.5 (1988-1990). Rates for adenocarcinoma of the gastric cardia in non-Maori men declined from 2.5 in 1983-1987 to 1.9 in 1988-1992, and were stable at 0.4 in non-Maori women. However, rates for cases with unspecified anatomic subsite fluctuated over the 15-year period and probably caused a deflation in rates in the most recent 5-year period. CONCLUSIONS: The incidence patterns of adenocarcinomas of the oesophagus and gastric cardia in New Zealand should be monitored over the next decade for confirmation of the trends observed here. There is need to review the quality of the data in the New Zealand registry.