Sampling error and observer variation in the interpretation of esophageal biopsies

Esophageal autopsy specimens from 11 subjects were used to determine observer variation and sampling error in assessing alterations attributed to gastroesophageal reflux. Inter- and intraobserver variation exceeded 20% even when the diagnosis was limited to a normal and abnormal reading. Marked differences in basal cell thickness but not in papillary height occurred when specimens were obtained from different levels of the lower esophagus. The differences were less marked in specimens obtained from the same level. Based on these data the reliability of basal cell thickness and papillary height as an index of gastroesophageal reflux appears limited.     

Gastric cancer survival in Sweden. Lack of improvement in 19 years.

A total of 34,549 patients constituting 87.0% of all patients with gastric cancer diagnosed in Sweden in 1960-1978 and reported to the National Cancer Registry were included in a complete follow-up over a period of 1-20 years. The poor outcome in this disease was again established in this unselected material. Thus, the 5-year relative survival rate (with 95% confidence limits) was 12.7% (12.1-13.2%) among the men and 14.1% (13.4-14.9%) among the women, without any long-term difference between the sexes. The annual hazard rates in male and female patients were still 11.0% (8.3-13.7%) and 9.0% (7.1-10.9%), respectively, after 5 years and did not approach zero until 10 years after the diagnosis. Men older than 75 showed a slightly higher mortality during the first year, but there were seemingly no relationships of tumor-biological or clinical significance between age at diagnosis and long-term relative survival. The overall prognosis remained unchanged during the 19 years of the study, whereas the incidence was reduced by about 40% in the whole Swedish population.     

Natural history of cervical neoplasia: consistent results obtained by an identification technique

Swedish population-based incidence and mortality rates for cancer of the uterine cervix, both in situ and invasive, during the period 1958 to 1981 were determined by means of a dynamic model. This new approach describes without any preconceptions the development of the disease as a sequential process over the stages cancer in situ, invasive cancer before and after diagnosis, and death. The strong disturbance of the steady-state situation that occurred after the introduction of cytological mass screening in the early 1960s permitted the use of a computerized identification technique. The whole natural history of cervical cancer could thus be identified and described consistently, with the mutual compatibility between statistical data, structure, parameters, and the states and flows between the states. The estimated age-specific incidence of cancer in situ increased rapidly to a maximum of 650 per 10(5) woman-years at the age of 30 years, after which it declined, and that of invasive cancer to a maximum of 55 per 10(5) at the age of 43. The natural history of cervical neoplasia did not differ appreciably between eight successive 5-year birth cohorts. The proportion of cases of new cancer in situ that progressed to invasive cancer was 12.2%, with a mean duration of the in situ stage in these cases of 13.3 years. The preclinical phase of the invasive stage (without screening) lasted on average about 4 years.     

Rat gastric secretion "in vitro": interaction between histamine and various antisecretagogues acting by different mechanisms

The interaction between histamine and various antisecretagogues acting by different mechanisms has been investigated in the isolated fundus from the rat stomach. Histamine evoked a concentration-dependent stimulatory effect which was competitively antagonized by the H2-receptor antagonist, ranitidine and non competitively by the H+/K+-ATPase inhibitor, omeprazole. The histamine induced secretion was highly resistant to the action of the calcium entry blocker verapamil, somatostatin and KSCN, but some inhibition was obtained with the calmodulin antagonist, trifluoperazine. Removal of calcium ions from the bathing media (both mucosal and serosal) greatly enhanced histamine-induced gastric secretion. The results suggest that the relationship between receptor stimulation and the intracellular events leading to acid secretion is far from being elucidated.     

Symptomatic cimetidine treatment of duodenal and prepyloric ulcers

In a randomized trial, 75 patients with an endoscopically confirmed and symptomatic duodenal (N=50) or prepyloric (N=25) ulcer were allocated to cimetidine treatment (1 g/day) either regularly for four weeks (standard treatment group) or regularly for a minimum of one week and thereafter only until the symptoms were controlled (symptomatic treatment group). The four-week healing frequencies in the standard and symptomatic treatment groups were 72 and 67%, respectively. The difference ±95% confidence limits was 5±21%. Prospective recording of pain revealed that the two treatment regimens were about equally effective in relieving symptoms during weeks 2–4. Patients with unhealed ulcers reported pain during the day and night significantly more often than those with healed ulcers. In the symptomatic treatment group the average patient saved 11 days of cimetidine medication during weeks 2–4. We believe that disappearance of symptoms might be a valuable means of deciding when treatment for peptic ulcers can be discontinued. Provided its efficacy and safety can be further confirmed, symptomatic treatment might become a practical and possibly a money-saving mode of ulcer management, which should also be applicable to the ulcer regimens of tomorrow.     

Prognostic significance of the Ackerman classification and other histopathological characteristics in breast cancer. An analysis of 1,349 consecutive cases with complete follow-up over seven years

Survival rates during a follow-up period of more than seven years were analyzed in 1,349 women with breast cancer in relation to the histo-pathological classification of female breast cancer proposed by Ackerman and to other commonly used histo-pathological criteria, including the axillary node status. The information was collected prospectively during a case-control study. Major emphasis was placed on multivariate evaluation. In analyses based on the histo-pathological findings in the mastectomy specimen alone, the Ackerman grouping was found to be of prognostic value, but apart from nuclear polymorphism the other recorded characteristics (histo-pathological type, histological grading, lymphocyte infiltration, and sinus histiocytosis) did not give any prognostic information. When the axillary node status was included in the multivariate models, the presence of axillary metastases correlated well with the prognosis and the Ackerman classification provided no significant additional information. The results indicate that in cases where the histopathological axillary status is known, little additional prognostic information can be gained from traditional histo-pathological evaluation over and above this status. However, the Ackerman classification and the degree of nuclear polymorphism separate distinct prognostic groups with the same degree of difference in observed survival rates as one discriminated by the axillary node status.     

International renal-cell cancer study. V. Reproductive factors,gynecologic operations and exogenous hormones

The relationships between reproductive factors, exogenous hormones and renal-cell cancer were examined in an international, multicenter, population-based, case-control study undertaken in 1989-1991. Data from 5 centers situated in Australia, Denmark, Germany, Sweden and the United States included for analysis 608 women with renal-cell cancer and 766 female controls. A significant trend in risk (p = 0.002) was associated with number of births, with an 80% excess risk for 6 or more births [RR = 1.8, 95% confidence interval (CI) = 1.1 to 2.9] compared with one birth. A decreasing risk was seen for increasing age at first birth, although this was confounded by body-mass index and number of births. A suggestive reduction of risk was also seen for increasing age at menarche. Age at menopause was unrelated to risk of renal-cell cancer. An increased risk was observed for women having had both a hysterectomy and an oophorectomy. Use of oral contraceptives in non-smoking women reduced the risk of renal-cell cancer (RR = 0.5, 95% CI = 0.4 to 0.8); this reduction increased with longer duration of use. No association was observed for estrogen replacement therapy. Our results indicate that certain hormonal and reproductive variables may be related to risk of renal-cell cancer and deserve further investigation, both epidemiologically and experimentally. © 1995 Wiley-Liss, Inc.     

Testicular cancer incidence in eight northern European countries: secular and recent trends.

OBJECTIVE: Striking geographic variation and marked increasing secular trends characterize the incidence of testicular cancer. However, it is not known whether these patterns have attenuated in recent years and whether they are similar for seminomas and nonseminomas, the two main histologic groups of testicular cancer.METHOD: Cancer registry data, including 27,030 testicular cancer cases, were obtained from Denmark, Estonia, Finland, Latvia, Lithuania, Norway, Poland, and Sweden. Between 57 (Denmark) and 9 (Poland) years of registration were covered. Country-specific temporal trends were estimated, with focus on the last decade and seminomas and nonseminomas. Data from the Nordic countries were further analyzed using an age-period-cohort approach.RESULTS: Age-standardized incidence rates increased annually by 2.6% to 4.9% during the study period, with marginal differences between seminomas and nonseminomas. In the last decade, the increasing trend attenuated only in Denmark (annual change, -0.3%; 95% confidence interval, -1.5 to 0.9). In 1995, the highest and the lowest age-standardized incidence rates (per 10(5)) were 15.2 in Denmark and 2.1 in Lithuania. Incidence rates (i.e., for all cancers and for seminomas and nonseminomas, separately) depended chiefly on birth cohort rather than on calendar period of diagnosis (although both birth cohort and period determined the Danish incidence rates).CONCLUSIONS: Testicular cancer incidence is still increasing, with the exception of Denmark, and a large geographic difference exists. The increasing trend is mainly a birth cohort phenomenon also in recent cohorts. Temporal trends for seminomas and nonseminomas are similar, which suggests that they share important causal factors.