[Carcinoma of the colon in Iceland 1955-1989. A study on pathology.].

OBJECTIVE: The objective of this study was to investigate various pathological parameters of colon carcinoma in Iceland in the 35 year time period from 1955-1989, and changes in these parameters during the study period. MATERIAL AND METHODS: Information on all patients diagnosed with colon carcinoma in the study period was obtained from the Icelandic Cancer Registry. All pathology reports and autopsy reports were checked. All pathology samples were reviewed and the tumours reevaluated, reclassified, tumour location determined, the tumours graded and Dukes staged and age standardized incidence was calculated according to revised diagnosis. Cancers in polyps are included in the study. The study period was separated into seven five year periods and changes in pathological parameters investigated according to time periods. RESULTS: After reevaluation of the tumours 1205 fulfilled the criteria for the diagnosis of colon carcinoma, 572 in men and 633 in women. The incidence increased in the study period for men from 8.2 to 21.5/105 and for women from 7.9 to 15.8/105. The pathological parameters were determined for 1109 tumours. Adenocarcinoma NOS was the most common diagnosis or 90.1% of the tumours and mucinous carcinomas came second. Most of the tumours were located in the sigmoid colon (38.6%), 19.1% in the coecum and 14.5% in the ascending colon. No significant observed changes occurred in tumour location in the study period. The mucinous histological type and signet ring tumour type were more common in the right colon. In Dukes staging of the tumours 9.1% were in stage A, 32.1% in stage B, 24.6% in stage C and 22.7% in stage D, whereas 11.5% proved indeterminate. A minimal trend to increase in Dukes A tumours was observed in the latter half of the study period, overall no significant changes in Dukes classification could be pinpointed in the time period. Most of the tumours were of intermediate tumour grade or 70.1%, but 16.5% were well differentiated and 13.4% were poorly differentiated. A much higher percentage of poorly differentiated tumours were present in the right colon in comparison to the left colon. A poorer differentiation of the tumours went hand in hand with worse Dukes stage of tumours. CONCLUSIONS: We conclude that: 1. the incidence of colon carcinoma has much increased during the study period for both sexes, 2. observed changes in studied pathological parameters over the study period were minimal. Of interest is the minimal change in Dukes stages of colon cancer in the study period.

Dietary cod liver oil decreases arachidonic acid in rat gastric mucosa and increases stress-induced gastric erosions.

The purpose of this study was to examine the influence of long-term feeding of dietary fat rich in either n-3 or n-6 fatty acids on the availability of arachidonic acid (20:4n-6) in major phospholipids of gastric mucosa in rats. Three groups of male Wistar rats were fed either a standard diet, a cod liver oil-enriched diet (10% by weight), or a corn oil-enriched diet (10% by weight) for 8 mon. Dietary cod liver oil significantly reduced the level of 20:4n-6 in phosphatidylcholine (PC) and in phosphatidylethanolamine (PE) of gastric mucosa. The loss of 20:4n-6 was compensated for by eicosapentaenoic acid (20:5n-3) in PC, whereas the decrease in 20:4n-6 in PE corresponded to the increase in three n-3 fatty acids: 20:5n-3, docosapentaenoic acid (22:5n-3), and docosahexaenoic acid (22:6n-3). The level of 20:5n-3 was higher than the level of 22:6n-3 both in PC and PE of mucosa in rats fed cod liver oil. Diets supplemented with corn oil increased the level of 18:2n-6 but decreased the monoene fatty acids 16:1 and 18:1n-7 in PC but not in PE of gastric mucosa. The 20:4n-6 levels of both PC and PE were markedly reduced by dietary cod liver oil, to about one-third of control levels. Similar changes were also observed in the stomach wall. Gastric erosions were observed in all rats exposed to restriction stress, but this form of stress induced twice the number of erosions in rats fed fish oil compared to control rats or rats fed corn oil. We conclude that a diet rich in fish oil altered the balance between n-6 and n-3 fatty acids in major gastric mucosal phospholipids, markedly reduced the availability of 20:4n-6, and increased the incidence of gastric erosions induced by restriction or emotional stress.

Gastric cancer in Iceland. What is the current status? Survival of 193 patients operated on for cure, 1980-1995.

OBJECTIVE: The incidence of gastric cancer has been decreasing in the last decades. Nevertheless, gastric cancer is still a substantial health problem in Iceland. The aim of this study was to analyze the survival of patients with gastric cancer operated on for cure. MATERIAL AND METHODS: We reviewed all medical files for above-mentioned patients, operated on at the National University Hospital in Reykjavik and the Quarter District Hospital of Akureyri during 1980-1995. The study was divided into three periods: 1980-1985, 1986-1990 and 1991-1995. The five-year survival for each study period and for the whole group was evaluated. RESULTS: The study group included 193 patients between the ages of 21-96 (median 71). The five-year survival for the whole group was 28% (26% 1980-1985, 22% 1986-1990, 35% 1991-1995). Despite longer survival during the last period, it was not statistically significant (p = 0.16). The major survival factor of gastric cancer was the stage of the disease at diagnosis. A greater number of patients were at stage IA during 1991-1995. The complication rate was rather high or 31% and the hospital mortality was 6.7%. CONCLUSION: The survival of patients with gastric cancer operated on for cure was low in Iceland but comparable to that in other countries. During the last years, the survival has been rising, and fortunately, more were diagnosed at a lower stage of the disease. These operations have a considerable risk and the hospital mortality was substantial.

Low back pain, smoking and employment during pregnancy and after delivery - a 3-month follow-up study.

Low back pain (LBP.), smoking and employment was studied among 111 consecutive women admitted to a maternity ward over a 6-week period, 40 were primiparas and 71 multiparas. LBP was defined as any pain in the low back, irrespective of the specific cause of the pain. Two specially constructed questionnaires were utilised. The first was a, 14-item questionnaire which all participants answered before leaving the maternity ward. It included questions on employment and smoking and self-rating Visual Analogue Scales used for rating LBP. LBP was rated during the pregnancy and 3 days after delivery. The second questionnaire was used in a 90-day follow-up interview. The mean age of participants was 28 years. The prevalence of LBP during pregnancy was 58.5% among the 111 participants. Of the 111, 75% continued to have LBP postpartum and at the 90-day post-delivery follow-up, 54% of those with LBP during pregnancy were still experiencing LBP. Previous births and birth weight were not found to correlate positively with LBP. LBP during pregnancy did not affect the length of employment during pregnancy. Smokers had LBP more frequently during pregnancy and also after (P <0.002). It is concluded that smoking does seem to contribute to LBP during and after pregnancy. Birth weight does not affect LBP and LBP does not affect the length of employment during pregnancy.

Pregnancies of women with epilepsy: a population-based study in Iceland.

PURPOSE: Women with epilepsy who become pregnant are commonly considered to be at high risk for complications during pregnancy or delivery. The offspring are also considered to have increased risk of perinatal mortality, congenital malformations, and maturational delay. Because few of these studies are population based, potential bias exists because of selection. METHODS: We performed a historical population-based cohort study in Iceland to determine the prevalence of epilepsy among pregnant women, to identify pregnancy and delivery complications in women with epilepsy, and to determine the outcome of their pregnancies as compared with that in the general population of Iceland. We identified all women with active epilepsy who gave birth during a 19-year period in Iceland. RESULTS: In this population, 3.3 in 1,000 pregnancies involve mothers with active epilepsy. The frequency of adverse events (AE) during pregnancy in the women with epilepsy is similar to that observed among all live births in the population, but cesarean section was performed twice as frequently as in the general population. Perinatal mortality rate and mean birth weight are not significantly different in the offspring of women with epilepsy as compared with rest of the population. The risk of major congenital malformations (MGM) is increased 2.7-fold over that expected when a mother is treated with antiepileptic drugs (AEDs) during a pregnancy. CONCLUSIONS: Our study indicates that the rate of complications of pregnancy in mothers with active epilepsy is low and similar to that of the general population with epilepsy. Use of AEDs by the mother during pregnancy significantly increases the risk of MGM in the offspring.

Mapping loss of heterozygosity at chromosome 13q: loss at 13q12-q13 is associated with breast tumour progression and poor prognosis.

Several chromosome regions exhibit loss of heterozygosity (LOH) in human breast carcinoma and are thought to harbour tumour suppressor genes (TSG). At chromosome 13q, two TSGs have been identified, RB1 at 13q14 and BRCA2 at 13q12-q13. In this study, 139 sporadic breast tumours were analysed with 18 polymorphic microsatellite markers for detailed mapping of LOH at chromosome 13q and evaluation of an association with known progression factors. LOH with at least one marker was observed in 71 (51%) of the tumours analysed. The deletion mapping indicated three LOH target regions, 13q12-q13, 13q14 and 13q31-q34. LOH at chromosome 13q12-q13 was associated with low progesterone receptor content, a high S phase fraction and aneuploidy. Multivariate analysis adjusting for lymph node involvement and S phase fraction showed that patients with tumours exhibiting LOH at 13q12-q13 have a 3-4-fold increased risk of recurrence and death compared with other patients. Our results suggest there are at least three separate LOH target regions at chromosome 13q and inactivation of one or more genes at chromosome 13q12-q13 results in poor prognosis for breast cancer patients.

Topoisomerase II alpha expression in normal, inflammatory, and neoplastic conditions of the gastric and colonic mucosa.

Topoisomerase II alpha (TP) excises and reconnects double-stranded super-coiled DNA during the replicative cell cycle. We studied the localization of TP and Ki-67 in inflammatory and neoplastic mucosal lesions of the stomach and of TP in similar conditions of the colon. TP expression was correlated with tumor stage, grade, and survival time in the colonic tumors to evaluate its potential utility as a predictive marker for clinical outcome. Forty-three sections of chronic gastritis, lesions indefinite for dysplasia, low- and high-grade dysplasia, and gastric adenocarcinomas were immunostained with antibody against TP and Ki-67. For the colon, 71 sections of normal mucosa, chronic colitis, hyperplastic polyps, adenomas, and carcinomas were examined; fresh tissue was analyzed by flow cytometry. Expression of TP in non-neoplastic gastric mucosa was maximal in neck/foveolar cells and focal in surface and deep gland cells. Increased surface and deep gland positivity was found in low-grade dysplasia and a diffuse distribution of positive cells in high-grade dysplasia and carcinoma. The Ki-67 staining pattern was similar. TP in non-neoplastic colon was restricted to the lower crypt zone; it was greatly expanded in the surface/upper crypt region in adenomas and was diffuse in carcinomas. Flow cytometric analysis revealed TP expression mainly in the S and G2/M phase, with higher labeling index in tumors. There was no correlation of TP with stage, grade, or survival times in the colonic tumors. Staining for TP and Ki-67 might help in the distinction of inflammatory and neoplastic lesions of the stomach and colon.

Racial variation in the O-acetylation phenotype of human colonic mucosa.

O-acetylated and non-O-acetylated sialoglycoproteins can be distinguished by the mPAS (mild periodic acid-Schiff) histochemical technique. Individual adults show one of three different patterns of staining of large intestinal mucosa: uniformly mPAS-positive, uniformly mPAS-negative, or mPAS-negative with scattered mPAS-positive crypts. To test our hypothesis that these variations are the result of a single autosomal gene (oat) polymorphism, we have studied the frequency of the three patterns of staining in a total of 435 adult colon specimens from six geographically separate populations: British, South African blacks, Icelanders, Japanese, Hong Kong Chinese, and Bahrainis. The distribution of the three types of staining fell into two groups. In Japanese and Chinese, uniformly mPAS-positive cases were much more frequent than uniformly mPAS-negative cases; this distribution differed significantly (chi 2, P < 0.001) from that in non-Sino-Japanese, where the uniformly mPAS-positive phenotype was much less frequently found than the uniformly mPAS-negative phenotype. In neither of the groups did the frequency of the three phenotypes differ significantly from that predicted for a single gene polymorphism by the Hardy-Weinberg law. The variation in staining patterns between populations is consistent with variation in frequency of a single polymorphic autosomal gene (oat) controlling O-acetylation of sialic acid, probably by an O-acetyl transferase enzyme. Loss of function mutation in the high acetylator gene (oata) in a colonic crypt stem cell in heterozygous individuals would account for the scattered discordant crypts. Gene frequencies for a variety of enzymes differ between the Sino-Japanese and non-Sino-Japanese races.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric carcinoma: correlation of diagnosis based on biopsies and resection specimens with reference to the Laurén classification.

Gastric carcinomas in 382 patients were studied histologically and the results from the preoperative endoscopic biopsies were compared with those from the resected specimens. Using the Laurén classification an overall histological diagnostic agreement between the two specimens was reached in 317 cases, or 83%. The highest diagnostic agreement, 87%, was for intestinal carcinomas. For diffuse carcinomas the diagnostic agreement was 75%. The disagreement in intestinal carcinomas was mainly due to foci of undifferentiated cells and/or signet-ring cells predominating in the biopsy. The disagreement in diffuse carcinomas was mainly because glandular structures were present at the surface in some of the cases and therefore led to an erroneous diagnosis of intestinal carcinoma. In conclusion, the intestinal type of gastric carcinoma can in most cases be diagnosed correctly from an endoscopic biopsy, whereas the diagnosis of a diffuse carcinoma is less accurate until the resected specimen is available for histological study.

Gastric cancer in Iceland: a retrospective study of resected gastric specimens in a high-risk country during 30 years (1960-1989).

The world-wide incidence of gastric cancer is decreasing, especially in high-risk populations such as the Icelanders. We examined retrospectively 1,040 specimens of resected gastric cancers from a 30-year period, 1960-1989. The decrease in incidence in both sexes involved mainly the largest histological group, the intestinal-type tumours. In males there was also a decrease in diffuse tumours but in females these remained relatively unchanged. Tumours of the antrum and the corpus decreased in both sexes. In males there was a significant increase in tumours of the cardia and most of these were of the intestinal type. In females there was a minor increase in tumours of the cardia, all of which were of the intestinal type. An increase in incidence of tumours of the cardia concomitant with a decrease in incidence of tumours in other parts of the stomach suggests a difference in aetiological factors. The death risk for patients with tumours of the cardia was 59% higher than that for those with tumours in other parts. The death risk following gastric resection was not significantly different when patients with intestinal-type tumours and diffuse tumours were compared.

The prevalence of hypertrophic cardiomyopathy in men: an echocardiographic population screening study with a review of death records.

The purpose of this study was to estimate the prevalence of hypertrophic cardiomyopathy (HCM) in 3607 men from the Reykjavik study of 1979-81. Of these, 452 men had an abnormal (group A) and 3155 a normal electrocardiogram. An echocardiographic control group of 128 men was selected from cohorts with a normal electrocardiogram (group B). Until 1987, 189 deaths had occurred, 59 from group A and 130 from cohorts with a normal ECG including 4 from group B. To identify subjects with HCM, survivors of groups A and B were examined by echocardiography and by review of all autopsy data and death certificates. HCM was found in 14 subjects from group A but none in group B. Two additional cases were found at autopsy in cohorts with a normal ECG. The prevalence of HCM in men with an abnormal and normal ECG was 3.6% and 0.8%, respectively. The overall prevalence was calculated to be 1.1% with a 95% confidence interval of 0.3-3.2%. Men with HCM reported more symptoms than others in groups A and B (P < 0.05-0.001). 25% were without symptoms. Asymptomatic ventricular arrhythmias were detected by Holter monitoring in 45% of men with HCM. The total annual mortality was 1.6% compared with 0.5% in the group with a normal ECG (P < 0.001).

Tumours in Iceland. 16. Malignant tumours of the stomach. Histological classification and description of epidemiological changes in a high-risk population during 30 years.

Iceland is one of the high-risk countries for stomach cancer. During the period 1955-84 the incidence declined from 76 to 28 per 10(5) p.a. for males and from 30 to 12 for females. Tissue material from the primary site in 978 males and 448 females was available for histological typing. By the WHO classification tubular carcinoma was most frequent in both sexes, 66% in males and 63% in females, and signet-ring carcinoma second, 13% in males and 16% in females. By the Laurén classification in males 78.1% were intestinal and 16.5% diffuse carcinomas, and in females 73.1% were intestinal and 20.7% diffuse carcinomas. The decline in stomach cancer in Icelanders has mostly affected the intestinal type of tumour (Laurén) and the tubular type of tumour (WHO). Diffuse type tumours (Laurén) have declined slightly. This supports the theory that intestinal carcinomas are more influenced by environmental and especially dietary factors, and that diffuse carcinomas are more influenced by other as yet unknown factors. For epidemiological studies both histological classifications have their value, the WHO especially in that it is based on standard histopathological criteria and the Laurén especially in that it only includes two tumour types. The WHO classification can roughly be transcribed to the Laurén classification as tubular, mucinous and papillary carcinomas fall into the group of intestinal tumours, and signet-ring and more than half of undifferentiated carcinomas into the group of diffuse tumours.

Tumours in Iceland. 13. Malignant tumours of the testis. A histological classification, epidemiological considerations and survival.

Data from 76 patients with malignant tumours of the testis registered with the Icelandic Cancer Registry during the period 1955-1984 were analyzed and classified histologically according to the WHO criteria. In 55 patients the tumours were of one histological type (72% of total). In the order of frequency, seminoma was diagnosed in 35 (46%), embryonal carcinoma in 14 (18%) and teratoma in 6 patients (8%). Twenty patients had tumours of more than one histological type (26%), i.e. a combination of embryonal carcinoma and teratoma (teratocarcinoma) in nine (12%) and combined tumours (seminoma component with other tumours) in seven (9%). Two patients had choriocarcinomas and three had yolk sac (endodermal sinus) tumours, both of them in combination with other neoplasms. Embryonal rhabdomyosarcoma was the only malignant non-germ cell tumour diagnosed. The age-adjusted incidence of malignant testis tumours increased by 48% from 1.6 per 100,000 per annum in 1955-1964 to 3.1 per 100,000 in 1975-1984. The increase affected both seminoma and non-seminomatous tumours (NSGCT). There has been an improvement in survival with time. Sixteen deaths were related to testis tumours and all occurred within four years of diagnosis. The incidence of testicular tumours in Iceland is intermediate between "high risk" and "low risk" countries.

Tumors in Iceland. 12. Malignant tumours of the corpus of the uterus. A histological classification, epidemiological considerations and survival.

All malignant tumours of the corpus of the uterus diagnosed in Iceland during 1955-1984 and available for review were typed histologically, using both the WHO Classification and the more recent classifications proposed by the International Society of Gynecological Pathologists. Of a total of 391 tumours 53 were excluded for various reasons. Of the 338 remaining tumours 309 were carcinomas, 17 sarcomas, 10 mixed Müllerian tumors and 2 choriocarcinomas. The adenocarcinomas were by far the most common of the carcinomas, comprising 93%. The incidence of carcinomas is similar to that found in the other Nordic Countries. A considerable increase in the incidence of adenocarcinomas was observed during the survey period and this was largely due to a steady steep rise in incidence of the best differentiated or Grade I tumours. This might be looked at as supportive evidence for the etiological role of estrogen replacement therapy which has been in constantly increasing use during the latter two decades of the study period. The mean age at diagnosis increased during the survey period. Generally, survival of patients did not clearly improve during the period but, however, increased considerably for the better differentiated tumours. Finally, we give our evaluation of the two systems of classification used in the study.

Carcinoid tumors of the appendix in children younger than 16 years. A retrospective clinical and pathologic study.

Eighteen cases of appendiceal carcinoid in children aged 4 to 15 years, 14 of them girls, are reviewed. Most (73%) of the tumors were located in the distal third of the appendix. Tumor size, measured in histologic sections, ranged from 0.1 to 1.2 cm. In three cases the tumor had invaded the mesoappendix. No metastases were found. Standard appendectomy was performed in all cases as the only surgical procedure. The preoperative clinical diagnosis in 15 cases was acute appendicitis, which was histologically confirmed in 53%. At follow-up 2.2 to 29.3 years postoperatively (mean 16.4 years), all the patients were alive and without suspected or verified recurrence of carcinoid.

Incidence and relation to parity of pregnancy-induced hypertension in Iceland.

A retrospective study was made to determine the incidence of pregnancy-induced hypertension (PIH, pre-eclampsia) in Iceland. One-fourth of all births in Iceland in 1985 were selected from the national birth registry files by random number allocation, a total of 904 women. Maternity records were found in 97.9% of the cases. The criteria used to define PIH were met in 17.4% of the women. There were 146 (16.5%) with mild PIH (blood pressure of greater than or equal to 140/90 mmHg with or without proteinuria after the 20th gestational week). Eight (0.9%) had severe PIH (blood pressure of greater than or equal to 160/110 mmHg with or without proteinuria after the 20th gestational week). Primigravid women formed one-third of the group and of these 20.9% had PIH compared with 15.4% of the parous women. The incidence in parous women was higher than usually reported.

Bronchopulmonary carcinoids in Iceland 1955-1984. A retrospective clinical and histopathologic study.

Twenty-two cases of bronchopulmonary carcinoid tumor diagnosed in Iceland in the 30-year period 1955-1984 were analyzed. Carcinoid comprised 2% of all primary lung tumors registered in that period. The crude incidence was 0.36 cases/100,000 population/year. The patients' mean age was 48 years and 68% were female. The most common presenting symptom was recurrent pneumonia; only three patients had hemoptysis. One patient had carcinoid syndrome. Two of the 22 tumors were peripheral. Tumor size was 0.8-9 cm, mean 2.8 cm. Of the resectable bronchial tumors, 80% had invaded the pulmonary parenchyma and 18% had metastasized to lymph nodes. Four carcinoid tumors were atypical and showed more malignant behavior. One of them was originally diagnosed as oat-cell carcinoma. Sixteen patients with resectable carcinoid tumor were alive 3 1/2 to 29 years after removal of the tumor.

Arachidonic acid level of non-esterified fatty acids and phospholipids in serum and heart muscle of patients with fatal myocardial infarction.

The relationship between non-esterified fatty acids (NEFA) in serum and heart muscle was examined in 15 patients who died of myocardial infarction (MI) and seven people who died suddenly in accidents. There was no correlation between NEFA levels of serum and non-infarcted cardiac muscle in patients with fatal MI. No significant difference was encountered in cardiac NEFA content between patients with fatal MI and people who died in accidents. The phospholipid (PL) content was significantly lower in patients with fatal MI than observed in people who died in accidents. The arachidonic acid (20:4 (n-6)) concentration of serum NEFA was significantly lower in patients with fatal MI compared to normal subjects. The cardiac NEFA and PL in patients with fatal MI contained significantly lower percentage levels of arachidonic acid compared to people who died in accidents. The results indicate that the death of the MI patients was not accompanied by elevated cardiac NEFA levels.

Coronary atherosclerosis and myocardial infarction in nonagenarians: a retrospective autopsy study.

Autopsy records of two groups of persons, aged 90 years and older and 70 years and younger, were analysed for coronary atherosclerosis and myocardial infarction. In each group were 74 males and 140 females who died during 1951-1980. In nonagenarians, moderate and severe degrees of coronary atherosclerosis were more frequent, but myocardial infarction both new and old was less frequent when compared with those aged 70 and younger. The sex difference in the degree of coronary stenosis within each age group was small but the frequency of myocardial infarction was less in females in both age groups.

Carcinoma of the lung in Iceland: 1931-1974.

During the period 1931-1974, 464 cases of primary lung cancer were diagnosed in Iceland. Only 34 cases were recorded from 1931-1954, but during the next two decades 156 cases and 274 cases were reported, a total of 430 cases which are analyzed in this paper. There is a preponderance of small cell anaplastic carcinoma 33.4% in this series. Epidermoid or squamous cell carcinoma was found in only 24.7% of cases and large cell anaplastic carcinoma in 15.4%. During the period 1955-1974, 143 major surgical procedures were performed for lung cancer in this country, 68 exploratory thoracotomies and 75 resections. Of the resections 58.7% were pneumonectomies. There were 3 surgical deaths in the resected series, for a mortality of 4%. Pneumonectomy carried a mortality of 6.8%, but lobectomies or segmental resections carried no mortality. In the resected series the absolute 5-year survival rate is 29.3%. Patients with epidermoid lesions have the most favorable prognosis. There is a definite correlation between tobacco consumption or cigarette smoking in Iceland and the rising incidence of lung carcinoma.