Pancreatic and hepatobiliary cancers: adjuvant therapy and management of inoperable disease.
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Biliary Tract Neoplasms↗
Biomedical subjects
B Glimelius
Publications and source records attributed to B Glimelius.
Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence.
PURPOSE: To quantify the risk of second cancers among long-term survivors of Hodgkin's disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences. PATIENTS AND METHODS: We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994. RESULTS: A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40. 2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale. CONCLUSION: Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.
Adolescent↗
Immunohistochemically detected thymidylate synthase in colorectal cancer: an independent prognostic factor of survival.
Intratumoral thymidylate synthase (TS) expression and M(r) 53,000 phosphoprotein (p53) overexpression were studied immunohistochemically in sections from stored paraffin-embedded primary colorectal cancers in 70 patients who had undergone surgery during the years 1987-1990. These cancers were classified according to Dukes' stage A-D, using monoclonal antibodies TS 106 and DO-7. In patients with Dukes' stage A-C tumors, univariate analyses showed that there was a significant correlation (P = 0.048) between disease-free survival and TS expression and between TS expression and time to death with colorectal cancer (P = 0.038). In patients with Dukes' stage A-D tumors, overall survival was correlated to TS expression (P = 0.015), Dukes' stage (P < 0.001), and level of tumor differentiation (P = 0.044) but not to p53 overexpression. Patients with low intratumoral TS expression survived significantly longer than patients with high expression. Cox multivariate analysis showed that Dukes' stage (P < 0.001) and TS expression (P = 0.043) could independently serve as prognostic factors for time to death with colorectal cancer in patients with Dukes' stage A-D tumors.
Adult↗
Molecular changes in second primary lung and breast cancers after therapy for Hodgkin's disease.
The risk of lung and breast cancer is significantly increased after therapy for Hodgkin's disease (HD), but there are few data that describe the molecular profiles of these tumors. We investigated the genetic abnormalities in second primary lung (n = 19) and breast cancers (n = 19) that follow therapy for HD ("post-HD cancers") and compared these with changes observed in corresponding tumor types (57 lung and 20 breast cancers) arising in the general population ("sporadic cancers"). DNA obtained from archival tissues was examined using PCR-based analyses for loss of heterozygosity and microsatellite alterations (MAs) at several chromosomal regions, TP53 and K-ras gene mutations, and frameshift mutations at minisatellite sequences at the coding regions of several genes (TGF-betaRII, IGFIIR, BAX, hMSH6, and hMSH3). The occurrence of loss of heterozygosity at all chromosomal regions taken together and frequencies at most individual areas were similar for the post-HD and sporadic cancers for both lung and breast sites. The overall frequency of MAs in the post-HD tumors was substantially greater (lung, 2.4-fold, P = 0.004; breast, 4.2-fold, P = 0.16) than that in the respective sporadic cancers. No differences in the pattern of TP53 and K-ras mutations were detected between post-HD and sporadic cancers. No mutations were detected at the minisatellite sequences examined. MAs, which reflect widespread genomic instability, occur at greatly increased frequency in post-HD lung and breast cancers. Although the mechanisms underlying the development of increased MAs are unknown, they have been associated with immunosuppression and radiation exposure. Future research should address the role that MAs, as well as other influences, may play in the development of neoplasias that occur after therapy for HD.
Adenocarcinoma↗
Is history of squamous-cell skin cancer a marker of poor prognosis in patients with cancer?
BACKGROUND: Nonmelanoma skin cancer is associated with increased occurrence of subsequent cancer and death from cancer, but it is not known whether a history of skin cancer is associated with poor prognosis after a second diagnosis of cancer. OBJECTIVE: To determine whether history of squamous-cell skin cancer is a marker of poor prognosis in patients with cancer. DESIGN: Population-based cohort study. SETTING: Sweden, 1958 to 1996. PATIENTS: All patients in the Swedish Cancer Registry with or without a first diagnosis of squamous-cell skin cancer and a subsequent or first diagnosis of non-Hodgkin lymphoma (including chronic lymphocytic leukemia) or cancer of the colon, breast, prostate, or lung. MEASUREMENTS: Relative risk (RR) for death determined by using Cox proportional hazards regression analysis. RESULTS: Patients with a history of squamous-cell skin cancer had a significantly greater risk for death than those with no such history after receiving a diagnosis of non-Hodgkin lymphoma (RR, 1.33), colon cancer (RR, 1.24), breast cancer (RR, 1.19), or prostate cancer (RR, 1.17). Patients with lung cancer and a history of squamous-cell skin cancer who survived for 1 year after diagnosis of lung cancer also had an increased risk for death (RR, 1.29). CONCLUSION: Patients with a registered history of squamous-cell skin cancer have a poor prognosis after diagnosis of subsequent cancer and warrant careful medical attention.
Adult↗
Tobacco smoking as a risk factor in anal carcinoma: an antiestrogenic mechanism?
BACKGROUND: Human papillomavirus-associated anogenital carcinogenesis depends on poorly defined cofactors. Smoking was recently suggested to increase the risk of anal cancer more in premenopausal women than in postmenopausal women. Thus, we used our population-based anal cancer case-control study in Denmark and Sweden to test this hypothesis. METHODS: Our study included 417 patients (324 women and 93 men) who were diagnosed with anal cancer (84% invasive cancer) from 1991 through 1994; it also included five patients diagnosed in 1995. Two control groups were used: 1) 554 population control subjects (349 women and 205 men) and 2) 534 patients with rectal adenocarcinoma (343 women and 191 men). Odds ratios (ORs), calculated from logistic regression analyses, were used as measures of relative risk. All P values are two-sided. RESULTS: Compared with the risk for lifelong nonsmokers, the risk of anal cancer was high among premenopausal women who currently smoked tobacco (multivariate OR = 5.6; 95% confidence interval [CI] = 2.4-12.7) and increased linearly by 6.7% per pack-year smoked (one pack-year is equivalent to one pack of cigarettes smoked per day for 1 year) (P for trend <.001). Smoking was not statistically significantly associated with anal cancer risk in postmenopausal women or men. Women whose menstrual periods started late were at high risk (multivariate OR = 3.6; 95% CI = 1.8-7.3, for > or = 17 years of age versus < or = 12 years of age; P for trend <.001), and body mass index (weight in kg/[height in m]2) was inversely associated with risk among women (P<.001). CONCLUSIONS: Because the risk of anal cancer associated with smoking was restricted to premenopausal women and because higher risk was associated with late menarche and lean body composition, female sex hormones may be a factor in anal cancer development in women. Since the anal mucosa is an estrogen-sensitive area, we hypothesize an antiestrogenic mechanism of action for smoking in anal carcinogenesis.
Adult↗
Sunlight and non-Hodgkin's lymphoma: a population-based cohort study in Sweden.
Indirect evidence, notably ecological comparisons and an association with skin cancer, links non-Hodgkin's lymphoma (NHL) with exposure to sunlight. We conducted a population-based, nationwide cohort study with exposure to outdoor work inferred from job titles reported in the population and housing censuses in 1960 and/or 1970 and by classifying each individual's work and home addresses according to latitude. Follow-up for cancer incidence was accomplished through record linkages with the virtually complete Swedish Cancer Registry. The cohort included all Swedish residents who were recorded as gainfully employed in both censuses. Altogether 4,171,175 individuals contributing 69,639,237 person-years accrued through 1989 were included in the analyses. We identified 10,381 cases of NHL, 4,018 cases of chronic lymphocytic leukemia (CLL), 11,398 cases of malignant melanoma (MM) and 11,913 cases of squamous cell skin cancer (SCC). We calculated age-adjusted relative risks for NHL, CLL, MM and SCC in strata based on estimated residential and occupational sunlight exposure. Interaction effects were considered for pesticide and solvent exposure. NHL, MM and SCC, but not CLL, were positively associated with increasingly southerly residential latitude, with stronger associations seen for skin cancer compared to NHL. Occupational sun exposure was not associated with the risk of developing any of the studied cancers. Pesticides and solvents also were not related to an increased risk of NHL, nor did these exposures enhance effects of residential or occupational sunlight exposure. Our results provide some support for an association of sunlight exposure with NHL incidence based on the associations seen using geographic latitude of residence as a proxy for exposure. Although type of occupation may be an imperfect index of the biologically relevant ultraviolet (UV) light dose, our data on individual exposure are not consistent with an important role of sunlight in the etiology of NHL.
Age Factors↗
Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses.
High-risk types of human papillomaviruses (hrHPVs) may be a necessary cause in cervical cancer and in some subtype of anal, vulvar, and penile cancers. Large studies aimed at characterizing hrHPV-associated and non-hrHPV-associated subtypes of anal carcinomas are, however, lacking. We searched for human papillomavirus type 16 and 13 other hrHPVs in tumor tissue by PCR and performed a systematic histological evaluation of specimens from 386 patients with anal cancer (86% invasive; 302 women and 84 men). Cancers in women and homosexual men were more often hrHPV positive (P < 0.01) and located in the anal canal (P < or = 0.01) than were cancers in heterosexual men. In both women and men, anal canal cancers contained hrHPV clearly more often than did perianal skin cancers, and increasing hrHPV positivity was seen with higher localization in the anal canal. Indeed, 95 and 83% of cancers involving the anal canal in women and men, respectively, were hrHPV positive versus 80 and 28% of perianal skin cancers (P-trend < 0.001). Basaloid feature, adjacent anal intraepithelial neoplasia, poor or absent keratinization, and a predominance of small or medium neoplastic cells were all strongly positively associated with hrHPV status. Like cancer of the uterine cervix, the development of cancer of the anal canal may require infection with hrHPV, whereas a dual etiology of perianal skin cancers bears parallels to vulvar and penile cancers.
Age Factors↗
Stereotactic irradiation of skull base meningiomas with high energy protons.
Nineteen patients with inextirpable skull base meningioma with involvement of neurovascular structures were given irradiation with a 180 MeV proton beam at the The Svedberg Laboratory, Uppsala, Sweden. The patients were treated seated in a fixed position with a stereotactic approach. Titanium-markers to the outer table served for identification and verification of the target positioning for dose planning and irradiation. The patients were given a total dose of 24 Gy in four consecutive daily 6 Gy fractions. All patients have been followed for at least 36 months. So far no meningiomas have progressed after treatment. Two patients have developed corticosteroid responsive oedema in the target area 6 moths after treatment. Late, but not serious, symptoms of side effects have been observed in one patient.
Adult↗
The Swedish version of the patient-generated subjective global assessment of nutritional status: gastrointestinal vs urological cancers.
PURPOSE: To translate and evaluate the Patient-Generated Subjective Global Assessment (PG-SGA) a method for the assessment of nutritional status. METHOD: Eighty-seven patients with gastrointestinal and urological tumours completed four sections and the remaining sections were independently completed by a doctor and a dietician. Patients were classified as SGA A (well nourished), SGA B (moderately/suspected of being malnourished) or SGA C (severely malnourished). RESULTS: Interobserver agreement was complete in 90% of the cases. More patients with gastrointestinal cancers than with urological cancers were classified as SGA B and C. Mean levels of S-albumin and P-prealbumin differed between the SGA-classes. Multivariate logistic regression analyses showed independent contributions to the overall classification by weight loss in the last 6 months, level of food intake, problems with eating, physical activity and muscle wastage. Survival was significantly higher in SGA A than in SGA B+C, P < 0.001. CONCLUSION: The PG-SGA is useful for the assessment of nutritional status. Patients had no problems in answering the questions. The PG-SGA also carried prognostic information.
Adult↗
Predicting delayed anxiety and depression in patients with gastrointestinal cancer.
The aim of this study was to examine the possibility of predicting anxiety and depression 6 months after a cancer diagnosis on the basis of measures of anxiety, depression, coping and subjective distress associated with the diagnosis and to explore the possibility of identifying individual patients with high levels of delayed anxiety and depression associated with the diagnosis. A consecutive series of 159 patients with gastrointestinal cancer were interviewed in connection with the diagnosis, 3 months (non-cured patients only) and 6 months later. The interviews utilized structured questionnaires assessing anxiety and depression [Hospital Anxiety and Depression (HAD) scale], coping [Mental Adjustment to Cancer (MAC) scale] and subjective distress [Impact of Event (IES) scale]. Patient anxiety and depression close to the diagnosis were found to explain approximately 35% of the variance in anxiety and depression that was found 6 months later. The addition of coping and subjective distress measures did little to improve that prediction. A model using (standardized) cut-off scores of moderate to high anxiety, depression (HAD) and intrusive thoughts (IES subscale) close to the diagnosis to identify patients at risk for delayed anxiety and depression achieved a sensitivity of 75% and a specificity of 98%. Levels of anxiety and depression at diagnosis predicted a similar status 6 months later. The results also indicated that the HAD scale in combination with the IES intrusion subscale may be used as a tool for detecting patients at risk of delayed anxiety and depression.
Adaptation, Psychological↗
Microsatellite instability in sporadic colorectal cancer is not an independent prognostic factor.
Hereditary non-polyposis colorectal cancer (HNPCC) is linked to an inherited defect in the DNA mismatch repair system. DNA from HNPCC tumours shows microsatellite instability (MSI). It has been reported that HNPCC patients have a better prognosis than patients with sporadic colorectal cancer. We examined whether the presence of MSI in a series of unselected colorectal tumours carries prognostic information. In a series of 181 unselected colorectal tumours, 22 tumours (12%) showed MSI. Survival analysis at 5-10 years follow-up showed no statistically significant difference in prognosis between MSI-positive and -negative tumours. Our results suggest that the MSI phenotype as such is not an independent prognostic factor.
Aged↗
Changing strategy for rectal cancer is associated with improved outcome.
BACKGROUND: In 1980, surgery for rectal cancer at the Department of Surgery, Uppsala University Hospital was concentrated to a colorectal unit and a more systematic use of adjuvant radiotherapy began. In 1985, total mesorectal excision was introduced. The aim of this study was to determine whether these changes had an impact on the overall treatment outcome. METHODS: Some 423 consecutive patients with rectal cancer had surgery between 1974 and 1995 and were followed up until 1 January 1998. Outcome analysis was made according to the following predefined intervals of diagnosis: 1974-1979, 1980-1984 and 1985-1995. RESULTS: The overall local recurrence rate was 47 per cent in the first interval, and 13 and 11 per cent during the second and third respectively (P < 0.001). In the third interval, of 119 patients who received preoperative irradiation and underwent radical resection, only three (3 per cent) had locally recurrent rectal cancer. There was improved cancer-specific survival between the first and the last intervals of the study (P = 0.03). CONCLUSION: These data are consistent with the interpretation that the results of treatment can be improved by concentration of surgery to a colorectal team.
Adult↗
Intensified primary cancer care: a randomized study of home care nurse contacts.
Newly diagnosed cancer patients (n=527) were randomised to intensified primary care or a control group. Intensified primary care comprised routines to improve general practitioners' and home care nurses' possibilities to support and monitor patients, i.e. increased information from specialist care, education and supervision in cancer care. The aims of this paper are to evaluate the effects of intensified primary care on cancer patients' home care nurse contacts, and to study if patients' use of home care services 6 months after diagnosis can be predicted. The intervention resulted in a marked increase of follow-up contacts. About 90% of intensified primary care patients reported such contacts, compared to 26% of control patients. The results indicate that standard care does not routinely include follow-up contacts, not even for the oldest (80+ years) or those with advanced disease. Only 27% and 36% of these groups of control patients reported follow-ups. Logistic regression analysis identified intensified primary care as the strongest predictor for reporting a continuing contact 6 months after diagnosis. Intensified primary care patients were 14 times more likely than controls to report a such contact. The strongest predictor of a continuing contact in the intensified primary care group was high age. Patients with advanced disease were more likely than patients with non-advanced disease to report a continuing contact, and living in a rural district was positively associated with reporting a contact. A majority of the patients (70%) assessed the time for the first contact as the 'right time' and estimated that the nurse gave expected support to a very large or large extent (67%). The results suggest that routines like those implemented through intensified primary care may be an effective strategy to increase the accessibility and continuity of care, especially for elderly people and for patients with a need for long-term contacts.
Adult↗
Potential gains using high-energy protons for therapy of malignant tumours.
High-energy protons have physical properties that virtually always will result in geometrically better dose distributions than can be achieved using photons or electrons. The clinical gains in terms of the probability of higher tumour control and/or the reduced probability of normal tissue complications are, however, not completely known. Comparative model dose planning studies using real patients offer the possibility of estimating the potential gains using a new technique. Several recently completed model studies, including clinically relevant endpoints, indicate that protons may have advantages, even when compared with the conventional treatment that is likely to be introduced at the most advanced hospitals world-wide within the next decade. These advantages can be seen not only in well-demarcated targets close to risk organs, but also when irradiating extended irregular tissue volumes at risk of containing tumour cells.
Humans↗
Perioperative radiotherapy in rectal cancer.
Local failure of rectal cancer is one of the principal causes of morbidity and mortality. In order to lower unacceptably high local failure rates, pre- or postoperative radiotherapy has been extensively investigated. The collected information from all controlled trials reported so far shows that the proportion of local recurrences is reduced to less than half when radiotherapy up to moderately high doses is given preoperatively. This reduction is smaller after postoperative radiotherapy, even if higher doses are used. In addition, there is a positive influence on survival from preoperative radiotherapy. Improved survival has also been seen in trials using postoperative radiotherapy, but only when combined with chemotherapy. With proper radiation techniques, sufficiently high doses can be given preoperatively with little, if any, increase in postoperative mortality and morbidity. Furthermore, late toxicity can be anticipated to be low provided the technique is optimal. The beneficial effects noted so far have been achieved in trials where 'standard' surgery has been used, followed by a local recurrence rate of more than 20% (average 29%, range 23-46%) of the patients. It is, however, possible that the reduction in local failure rates is proportionally even greater added to 'optimal' surgery, although the absolute number of failures prevented is lower.
Clinical Trials as Topic↗
Epstein-Barr virus distribution in Hodgkin's disease in an unselected Swedish population.
All patients with Hodgkin's disease (HD) (n = 117) identified in the Uppsala/Orebro region of Sweden between 1985 and 1988 were examined for the presence of Epstein-Barr virus (EBV) in the Hodgkin and Reed-Sternberg (HRS) cells. EBV was detected with LMP-1 immunostaining and in situ hybridization for EBERs. Overall, 32 (27%) tumours were EBV-positive but there were significant differences in EBV-positivity between histopathological subgroups (p = 0.03). In MC, 8/21 (38%) were positive, in NS 20/67 (23%), LD 3/3, LP 1/5, and in unclassified 0/1. Patients with EBV-positive tumours were significantly older, mean 52 vs. 42 years (p = 0.02), and were likely to have significantly more B-symptoms or advanced stage disease. Patients with EBV-positive tumours tended to have a poorer survival rate (p = 0.11). The proportion of EBV-positive tumours, and especially the proportion of EBV-positive MC, was lower than previously reported. This could be explained by selection of patients from previous studies, or by differences in EBV-positivity in different geographical or ethnic populations of HD.
Adolescent↗
Comparison of cell survival models for mixed LET radiation.
PURPOSE: Biophysical models for predicting survival for mixed LET radiations have been investigated by comparisons with experimental results from heavy ion irradiations. The aim was to choose a model for further theoretical studies on the effects of a variable RBE for protons. METHODS AND MATERIALS: Predicted survival curves by the Katz track-structure model, the linear quadratic model, LQ model, by Kellerer and Rossi and the lesion additivity model of Lam were compared to experimental survival curves for V79 cells that were irradiated with a mixture of nitrogen ions with an LET of either 78 or 165 keV/microm and 60Co gamma-rays. RESULTS: Results showed that all three models could predict survival within the uncertainty of the measurements for the different mixed radiation schedules used in this study. CONCLUSION: The choice of model could be made on other grounds, such as the type of model parameters and the availability of biological data for these parameters. Also, the possibility of including dose-rate effects and repair functions should be considered. For the purpose of carrying out theoretical studies on the effects of a variable RBE for protons, the LQ model was preferred.
Animals↗