Effect of preoperative chemotherapy on the histopathological classification of gastric cancer.

BACKGROUND: In the era of individualized gastric cancer (GC) treatment, accurate determination of histological subtype becomes increasingly relevant. As yet, it is unclear whether preoperative chemotherapy may affect the histological subtype. The aim of this study was to assess concordance in histological subtype between pretreatment biopsies and surgical resection specimens before and after the introduction of perioperative treatment. METHODS: Histological subtype was centrally determined in paired GC biopsies and surgical resection specimens of patients treated with either surgery alone (SA) in the Dutch D1/D2 study or with preoperative chemotherapy (CT) in the CRITICS trial. The histological subtype as determined in the resection specimen was considered the gold standard. Concordance rates and sensitivity and specificity of intestinal, diffuse, mixed, and "other" subtypes of GC were analyzed. RESULTS: In total, 105 and 515 pairs of GC biopsies and resection specimens of patients treated in the SA and CT cohorts, respectively, were included. Overall concordance in the histological subtype was 72% in the SA and 74% in the CT cohort and substantially higher in the diffuse subtype (83% and 86%) compared to the intestinal (70% and 74%), mixed (21% and 33%) and "other" subtypes (54% and 54%). In the SA cohort, sensitivities and specificities were 0.88 and 0.71 in the intestinal, 0.67 and 0.93 in the diffuse, 0.20 and 0.98 in the mixed, and 0.50 and 0.93 in the "other" subtypes, respectively. CONCLUSION: Our results suggest that accurate determination of histological subtype on gastric cancer biopsies is suboptimal but that the impact of preoperative chemotherapy on histological subtype is negligible.

Parental sun-protective regimens and prevalence of common melanocytic naevi among 7-year-old children in Sweden: changes over a 5-year period.

BACKGROUND: Common melanocytic naevi and cutaneous malignant melanoma share a common risk profile, influenced by ultraviolet radiation exposure. A high density of common melanocytic naevi correlates with an increased lifetime risk of developing cutaneous malignant melanoma. Effective strategies for sun protection, starting in early childhood, are considered of great importance to reduce the steadily rising melanoma trend. OBJECTIVES: To investigate the 5-year changes in sun tanning habits, sun-protective regimens and density of common melanocytic naevi between two age-standardized populations of children. METHODS: Population-based cross-sectional study performed among 7-year-old children in southern Sweden in 2002 and 2007. The parents answered a questionnaire and all children were examined by the same, trained research nurse. RESULTS: In total, 1190 children were enrolled: 681 in 2002 and 509 in 2007. The results showed that sun-protective regimens, such as use of sunscreen (+29%), clothing (+30%), staying in the shade (+123%) or indoors (+136%) during peak sun hours, had all increased significantly (P<0·0001). Travelling to sunny seaside holiday resorts abroad before the age of 2years had almost doubled (P<0·0001). The adjusted mean number of naevi per square metre body surface was significantly (P<0·0001) lower in 2007: 6·6 [95% confidence interval (CI) 5·6-7·6], compared with 11·0 (95% CI 10·0-12·0) in 2002. CONCLUSIONS: This study demonstrates increased self-reported parental actions for sun protection of young Swedish children in recent years; in consistency, lower numbers of common melanocytic naevi were observed. Results support the use of common melanocytic naevi as an objective measure of sun exposure in children.

Trends in cancer risks among Swedish agricultural workers.

The Swedish Cancer-Environment Register was used to study time-related trends in relative risks (RRs) of cancer between 1961 and 1979 in a cohort of 254,417 Swedish men who were employed in agriculture in 1960. The reference cohort consisted of 1,725,845 Swedish men who were gainfully employed in economic activities other than agriculture or forestry in 1960. Altogether 24,763 cancers were observed in the study cohort and 146,900 in the reference cohort, giving an estimated RR for the entire study period of 0.82 (95% confidence interval: 0.81-0.83). The RR for all sites combined increased from 0.80 in 1961-73 to 0.84 in 1974-79 (P less than .01). The RR also increased over time for primary liver cancer (P less than .01), prostate cancer (P less than .01), cancer of other genital organs (P less than .01), cancer of urinary organs (P less than .01), lip cancer (P less than .05), and cancer of the nose and nasal cavities (P less than .05). For most of these sites the RR remained lower than unity. For prostate cancer, however, the RR was unity at the end of the study period. A decrease in the RR over time was observed for skin carcinomas of the trunk and limbs (P less than .05) and malignant tumors of the nervous system (P less than .05). For 27 of the 48 analyzed tumor sites the RR for the entire period 1961-79 was significantly lower than unity. The lowest RRs were seen for cancer of the pleura (0.25), cancer of the larynx (0.35), lung cancer (0.36), cancer of the hypopharynx (0.36), cancer of the floor of mouth (0.40), primary liver cancer (0.44), and cancer of the kidney pelvis (0.49). RRs significantly higher than unity were found for cancer of the lip (1.92), malignant melanoma, and carcinoma of the skin in the head and neck region (1.39 and 1.15, respectively), multiple myeloma (1.20), and cancer of the stomach (1.07).

Soft tissue sarcoma risk in Swedish agricultural and forestry workers.

The risk of soft tissue sarcoma following possible exposure to phenoxy acid herbicides was studied in 354,620 Swedish men, who were employed in agriculture or forestry according to a national census in 1960. This cohort was further divided into six subcohorts, on assumed exposure to phenoxy acid herbicides. The most commonly used phenoxy acid in Sweden was (4-chloro-2-methylphenoxy)acetic acid (CAS: 94-74-6). The reference cohort encompassed 1,725,845 Swedish men employed in other industries. All persons were followed up in the cancer-environment register during the period 1961-79. A total of 331 cases of soft tissue sarcomas was observed in the study cohort and there were 1,508 cases in the reference group [relative risk (RR), 0.9; 95% confidence interval, 0.8-1.0]. No subcohort of agricultural or forestry workers showed any significantly increased RR, nor was there any significant difference in RR between the subcohorts. Despite the greatly increased use of phenoxy acid herbicides from 1947 to 1970, no time-related increase in the RR of soft tissue sarcoma was found in the total cohort or in any of the subcohorts.

Cancer risk after iodine-131 therapy for hyperthyroidism.

Cancer incidence was studied in 10,552 patients (mean age, 57 years) who received 131I therapy (mean dose, 506 MBq) for hyperthyroidism between 1950 and 1975. Follow-up on these patients was continued for an average of 15 years. Record linkage with the Swedish Cancer Register for the period 1958-1985 identified 1543 cancers occurring 1 year or more after 131I treatment, and the standardized incidence ratio (SIR) was 1.06 (95% confidence interval = 1.01-1.11). Significantly increased SIRs were observed for cancers of the lung (SIR = 1.32; n = 105) and kidney (SIR = 1.39; n = 66). Among 10-year survivors, significantly elevated risks were seen for cancers of the stomach (SIR = 1.33; n = 58), kidney (SIR = 1.51; n = 37), and brain (SIR = 1.63; n = 30). Only the risk for stomach cancer, however, increased over time (P less than .05) and with increasing activity administered (P = not significant). The risk for malignant lymphoma was significantly below expectation (SIR = 0.53; n = 11). Overall cancer risk did not increase with administered 131I dose or with time since exposure. The absence of any increase in leukemia adds further support to the view that a radiation dose delivered gradually over time is less carcinogenic than the same total dose received over a short time. Only for stomach cancer was a possible radiogenic excess suggested.

Thyroid cancer after diagnostic doses of iodine-131: a retrospective cohort study.

The incidence of thyroid cancer was evaluated in 35,074 patients examined for suspected thyroid disorders between 1951 and 1969 with an average of 1.92 megabecquerel [(MBq) 52 microCi] of 131I. The radiation dose to the thyroid gland was, on the average, approximately 0.5 Gy. The mean age at the time of examination was 44 years; 5% were under age 20. Patients were followed for an average of 20 years. Record linkage with the Swedish Cancer Register identified 50 thyroid cancers occurring 5 years or more after the initial 131I examination, in contrast to 39.4 expected based on general population rates [standardized incidence ratio (SIR) = 1.27, 95% confidence interval = 0.94-1.67]. Risk was highest among males (SIR = 2.70, n = 10), patients followed 5-9 years (SIR = 2.22, n = 23), and patients receiving more than 74 microCi or 2.74 MBq of 131I (SIR = 2.04, n = 17). However, these observations were confounded by the fact that patients examined for a suspected thyroid tumor received the highest 131I exposures and were at highest overall risk (SIR = 2.77, n = 34). Patients given 131I for reasons other than a suspected tumor were not at increased risk (SIR = 0.62, n = 16). Patients anticipated to be at highest risk, i.e., women (SIR = 1.12, n = 40) and those observed for 10 years or more (SIR = 0.93, n = 27), showed no evidence of a dose response. Overall, these data provide little proof that 131I is carcinogenic in humans and support the notion that the carcinogenic potential of internal 131I beta particles might be as low as four times less than external x rays or gamma rays.

Cancer risk in population examined with diagnostic doses of 131I.

Previously, we conducted a study of 35,074 patients receiving diagnostic doses of 131I for suspected thyroid disorders between 1951 and 1969. We reported that, between 1958 and 1984, the incidence of thyroid cancers in these patients was insignificantly greater than the incidence expected in the general population. This increase was attributed to the underlying condition that prompted the examination and not to the administration of 131I. The purpose of the present study was to analyze the total cancer risk in the same cohort of patients examined with diagnostic doses of 131I. To further evaluate the underlying risk of disease in these patients, we compared the incidence of all cancers with that expected in the general population. The average radiation dose was approximately 500 mGy to the thyroid and less than 10 mGy to other organs. In the 35,074 patients, 3,746 cancers occurred following the first 5 years after examination, and the resulting standardized incidence rate (SIR) was 1.01 (95% confidence interval = 0.98-1.04). SIRs were significantly increased for endocrine tumors other than thyroid cancer (1.93) and for lymphomas (1.24), leukemias (1.34), and nervous system tumors (1.19). The risk of leukemia was similar for chronic lymphocytic leukemia (CLL) (SIR = 1.30) and non-CLL (SIR = 1.34). SIR was significantly decreased for cancers of the female genital organs (0.86). The risk for cancer of all sites and types combined was highest 5-9 years after examination (SIR = 1.07) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I. Overall, the data exclude cancer risk increments greater than 5% (SIR = 1.05) with 95% confidence. The significant increase in the risk of non-CLL, a prominent radiogenic malignancy, however, warrants special attention. We are continuing our study to determine the possible factors involved in the significant increase in the risk of leukemia.

Multiple myeloma in Swedish agricultural workers.

Increased risk of multiple myeloma was found among farmers in studies reported in the literature. A retrospective cohort study of Swedish agricultural workers is now presented. All 254417 men aged 20-69 years at the time of the national census in 1960, who stated that they were working in agriculture, formed the study cohort. The reference cohort consisted of 1725845 men otherwise gainfully employed. The cohorts were followed from 1 Jan 1961 until 31 Dec 1979. The cases of multiple myeloma were identified in the Swedish cancer register by computerized record linkage. The 568 cases found in the study cohort resulted in an estimate of the relative risk of 1.20 (95% confidence interval 1.09-1.33).

An application of the Swedish Cancer-Environment Registry. Leukaemia among telephone operators at the telecommunications administration in Sweden.

The detection of 4 cases of leukaemia among telephone operators at the Telecommunications Administration in Gothenburg within a period of 6 years (1969-74) evoked disquiet among the employees. Following an inquiry to the National Board of Health and Welfare a retrospective study was undertaken with a view to examining whether this incidence was consistent with the risk for the country as a whole. The study was based on the newly established Cancer-Environment Registry for the period 1961-73 covering the entire country. This was the first occasion on which the Registry had been applied in an investigation of cancer risk for a specific occupational group. The analysis disclosed no higher risk of leukaemia among telephone operators in the Telecommunications Administration in Sweden than among the population as a whole.

Cancer risks among male farmers in Sweden.

We have conducted a cohort study of cancer risks among 140,208 Swedish farmers in order to compare their cancer risks with those of the general male population. Since there were no individual data regarding exposure to agricultural chemicals and acquiring such data was not realistic, we obtained crude and hypothetical estimates for exposure by dividing the data into time periods, year-of-birth cohorts and geographical areas. The cohort was followed-up in the Cancer Environment Register from 1 January 1971 either until death or until 31 December 1987. The relative risk was computed as the ratio of the observed and expected number of cases (SIR = standardized incidence ratio). A total of 15,040 cases were observed vs 18,918 expected, resulting in a statistically significant decreased SIR of 0.80 (95% confidence interval: 0.78-0.81). The SIR was significantly decreased for several cancer sites, and the lowest value was found for tongue, lung, oesophagus, liver and urinary organs, which is in agreement with other studies on cancer risks among farmers. Other major cancer sites with decreased SIRs were the colon, rectum, pancreas and kidney. Lip cancer and multiple myeloma showed statistically significant increased risks. SIRs for stomach cancer, prostate cancer, skin carcinoma, malignant melanoma, tumours in connective tissue or muscle, malignant lymphomas and leukaemia were all close to unity, which is not consistent with several other studies that have shown increased risks for these sites. For malignant lymphomas the SIR increased over time, though not significantly, and was highest among younger farmers. The SIR for non-Hodgkin lymphoma was lowest in the northernmost region. This gives some support to the hypothesis that there is an association between non-Hodgkin lymphoma and exposure to pesticides and other agricultural chemicals. It is of note that the SIR for multiple myeloma was significantly increased in those parts of Sweden where the use of pesticides has been less frequent and in lower amounts.

Prediction of cancer mortality in the Nordic countries in 2005: effects of various interventions.

Rough estimates of the effect in 2005 of various preventive measures aimed at reducing cancer mortality in the Nordic countries were made using the American software CAN*TROL. The effect was measured as the percentage reduction in cancer mortality in 2005. The calculations were performed for changes in the smoking, dietary and sunbathing habits of the population (primary prevention), earlier diagnosis (secondary prevention) and improvements in survival resulting from better treatment (tertiary prevention). The calculations incorporate many assumptions, some of them more firmly based than others, such as uniformity of incidence trend in all the Nordic countries and also concerning the causality of various relations. For lack of evaluated Nordic data, we have used American figures concerning stage distributions and stage-specific relative survival rates. These assumptions should be borne in mind when drawing conclusions from the results obtained. The results show that there is a potential of up to several tens of percent for reducing total cancer mortality by the year 2005.

Cancer risk in offspring of male pesticide applicators in agriculture in Sweden.

AIMS: To explore cancer risk from date of birth until 1994 in children, born 1958 or later, of Swedish male pesticide applicators. METHODS: Records of male pesticide applicators licensed 1965-76 were linked to the Multigeneration Register. The records of their offspring were then linked to the Swedish Cancer Registry and the Cause of Death Register. RESULTS: In total 51 cases of cancer were observed, which is significantly lower than the expected 73.0 (standardised incidence ratio (SIR) 0.70, 95% CI 0.52 to 0.92). Tumours of the nervous system was most common, amounting to 20 cases, 39% of all cancer cases (SIR 1.01, 95% CI 0.62 to 1.56). A statistically significant reduced risk for leukaemia was found (SIR 0.43, 95% CI 0.19 to 0.86). For non-Hodgkin's lymphoma, three cases were observed and 4.8 expected (SIR 0.63, 95% CI 0.13 to 1.83). For Hodgkin's disease, five cases were observed versus 3.7 expected (SIR 1.36, 95% CI 0.44 to 3.17). Two cases of testicular cancer were observed and 1.7 expected (SIR 1.19, 95% CI 0.13 to 4.28). CONCLUSIONS: None of the a priori hypotheses of increased risk of tumours of the nervous system, kidney cancer, leukaemia, lymphoma, soft tissue sarcoma, and testicular cancer in children of male pesticide applicators could be confirmed.

A Swedish cancer-environment register available for research.

The National Board of Health and Welfare and the National Central Bureau of Statistics in Sweden have jointly established a register containing, in addition to the data of the Swedish Cancer Register, information on occupation, economic activity, place of domicile, etc, from the 1960 population census. In the autumn of 1978 this Register was made available for interested scientists in all countries. It can be used for epidemiologic studies on the relationship that occupation, place of domicile, and similar factors may bear to the incidence of different types of cancer. The project was designated the Cancer-Environment Register. The present paper contains a synopsis of this register.

Cancer among farmers. A review.

During the performance of routine tasks farmers may come in contact with a variety of substances, including pesticides, solvents, oils and fuels, dusts, paints, welding fumes, zoonotic viruses, microbes, and fungi. Because some of these substances are known or suspected carcinogens, the epidemiologic literature regarding cancer risks concerning farmers has been reviewed. Farmers had consistent deficits for cancers of the colon, rectum, liver, and nose. The deficits for cancer of the lung and bladder were particularly striking, presumably due to less frequent use of tobacco among farmers than among people in many other occupational groups. Malignancies frequently showing excesses among farmers included Hodgkin's disease, leukemia, non-Hodgkin's lymphoma, multiple myeloma, and cancers of the lip, stomach, prostate, skin (nonmelanotic), brain, and connective tissues. The etiologic factors that may contribute to these excesses in the agricultural environment have not been identified. Detailed, analytic epidemiologic studies that incorporate environmental and biochemical monitoring are needed to clarify these associations.

Risk of cancer of the breast after legal abortion during first trimester: a Swedish register study.

An increase in induced abortions in Sweden has been accompanied by an increase in the incidence of breast cancer of about 40% in women aged 20-44. To assess whether the apparent risk is real the risk of breast cancer was investigated in practically all Swedish women with a history of a legal abortion in the first trimester before the age of 30 during 1966-74 (n = 49,000). The cohort was followed up in the Swedish cancer register to identify cases of breast cancer diagnosed more than five years after the abortion until the end of 1984. The number of observed cases of breast cancer was 65 compared with an expected number of 84.5, estimated from the contemporary Swedish population with due consideration to age, giving a relative risk of 0.8 (95% confidence interval 0.58 to 0.99). Contrary to most earlier reports, this study did not indicate any overall increased risk of breast cancer after an induced abortion in the first trimester in young women.

Counselling and communication in hospital dentistry.

Many of the people who are members of hospital dental teams are highly motivated, caring individuals. Unfortunately, though, they are not given the kind of training or support that is necessary to enable them to perform their tasks most effectively. This study was initiated at a hospital dental clinic where burdensome cutbacks and reorganization had been keenly felt by the personnel. A counselling group was formed under the leadership of a professional counsellor, and in the course of the year there were seven meetings, each of which lasted 1.5-2 hours. The open way in which counselling was designed presented opportunities for the six group members to influence the topics of each meeting, something all of them preferred to more structured sessions. Different stress factors in the environment were discussed. The group members concluded that the counselling programme had increased their self-esteem and facilitated effective communication between the group and patients by giving them all the opportunity to discuss barriers and confusing clinical situations. Counselling had also facilitated interpersonal relationships between the team members by revealing hierarchical difficulties. Apart from the clear humanitarian need for counselling there is a good economic argument. Effective staff support is not a luxury, nor is it a waste of time. Adequate time for counselling must be provided, simply.

[Low cancer risk among female agricultural workers]. / Låg cancerrisk bland kvinnliga lantbrukare.

In a cohort study of cancer incidence, 50,682 women registered in the 1970 Swedish census as engaged in agriculture were followed up in the national Cancer- Environment Register from 1971 to 1987. Instead of the expected incidence of 5,273 cases, a total of only 4,474 cases were found, yielding a significantly reduced standardised incidence ratio (SIR) of 0.85. Thus, site specific SIRs were also significantly reduced for cancer of the breast (0.83), cervix uteri (0.40), lung (0.46), urinary tract (0.57), and several other sites.