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The sentinel node is the first lymph node to receive lymphatic drainage from a tumour and is usually the first site of metastases. Today, the sentinel node is used for tumour staging. Here, we focus on its immunological role and investigate lymphocytic function in sentinel nodes, identified intraoperatively by peritumoural dye injection, from 15 patients with colon cancer. Tumour infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and peripheral blood leukocytes were studied by flow cytometry, proliferation assays and interferon-gamma secretion after activation with autologous tumour homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the proliferation assays, lymphocytes from sentinel nodes proliferated dose dependently and secreted interferon-gamma upon stimulation with tumour homogenate. The responses were of varying magnitude and tended to be weaker in metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched source of tumour reactive lymphocytes, and may be useful in future trials of adoptive immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Lymphatic mapping and sentinel node biopsy entails better staging in malignant melanoma and breast cancer and we used this technique in patients with colon cancer to possibly improve detection of lymphatic spread. Methods: Thirty patients with invasive adenocarcinomas were investigated. The tumour status in identified sentinel node(s) was compared with the status in all other harvested regional nodes for each patient. Patients were followed at regular visits for more than 30 months. Results: Sentinel nodes were identified in all cases, either per-operatively (28 cases) or at dissection of the formalin-fixed specimen (2 cases). The sentinel nodes were diagnostic for the entire lymphatic field in 28 patients and the false negative rate was 2/12. In four cases, the sentinel nodes were the only metastatic nodes. After at minimum 30 months, three patients had died of colon cancer metastases. Conclusion: This method improved the identification of patients with lymph-node metastases, especially those with only few metastatic nodes. Patients dying from metastatic disease had lymph-node metastases at diagnosis. [Copyright &y& Elsevier]

There is an increased influx of activated eosinophils to the intestinal mucosa in active ulcerative colitis, and an increased release of eosinophil-derived proteins, such as ECP, has also been observed. These findings indicate that eosinophils may contribute to tissue damage and intestinal inflammation in this disease. The relative importance of different chemotactic factors and the impact of steroid treatment on their effect in active ulcerative colitis are not known. We measured the eosinophil chemotactic activity in perfusion fluids from 11 patients with ulcerative colitis before and after steroid treatment and from 7 control patients. The effect of neutralizing antibodies to IL-5 and -8, RANTES, eotaxin, MCP-3, TNF-alpha, GM-CSF was investigated. The chemotactic activity was higher in perfusion fluids from patients than from controls (P = 0.0043). Anti-IL-5 (P = 0.005) and -TNF-alpha (P = 0.017) inhibited the activity in perfusion fluids obtained before treatment. Steroid treatment prevented the effect of all antibodies but had no significant effect on the chemotactic activity. The chemotactic activity correlated with the levels of eosinophil granule proteins in the perfusion fluids. In conclusion, in ulcerative colitis, eosinophils are attracted to the intestinal tissue by chemotactic factors, of which IL-5 and TNF-alpha may be the most prominent steroid-sensitive ones. The steroid-insensitive chemotactic activities remain unidentified. [ABSTRACT FROM AUTHOR]

Background: Basic fibroblast growth factor (bFGF) promotes angiogenesis and several other biologic processes, including proliferation of mesenchymal cells and tumor progression. We investigated whether bFGF could be detected in the intraluminal secretion of the small intestine, sigmoid colon, and rectum in healthy individuals and in patients with ulcerative colitis. Methods: We used endoscopic perfusion techniques to obtain samples from well-defined intestinal segments. The perfusion fluid concentrations of bFGF, biochemical markers of inflammation, myeloperoxidase (MPO), interleukin-6 (IL-6), and permeability (albumin) were determined with immunochemical methods. Results: In the perfusion fluids the albumin concentration, which reflects passive diffusion, was less than 1% of the plasma concentration, whereas the intestinal concentration of bFGF was similar to that in plasma. Among healthy subjects the concentration of bFGF was eightfold higher in the jejunum and twofold higher in the rectum than in the sigmoid colon. The perfusion fluid from colorectal segments in patients with ulcerative colitis had a significantly higher mean concentration of bFGF than that from healthy individuals; an almost 10-fold difference was found in rectal segments. There were strong correlations between the concentration of bFGF and the concentrations of MPO and IL-6. Conclusions: The high concentrations of bFGF in the intestinal perfusion fluid reflect either a local synthesis or an active secretion of bFGF within the mucosa. The bFGF concentration differs in intestinal anatomic location and increases significantly in patients with ulcerative colitis in close relationship with biochemical markers of inflammation and permeability. [ABSTRACT FROM AUTHOR]

Background: Previous malignant melanoma studies regarding prognostic factors have often selected their patients from hospitals. Unfortunately, most of these studies have had small numbers of patients, consisted of short-term data sets, omitted important factors, did not optimize histopathologic classification, had too short or inadequate follow-up, and did not test their predictive models.Purpose: Our study goals were to identify independent clinical and histopathologic determinants of survival in malignant melanoma, to analyze changes in prognostic value over follow-up time, and, finally to construct a prognostic index.Methods: A random sample from the Swedish Cancer Registry of the records of 498 (246 men and 252 women) patients defined by gender, five 5-year time periods of diagnosis from 1960 through 1984, and five anatomic sites formed the cohort on whom data were analyzed by univariate analyses. Multivariate analyses were based on data on 476 patients with complete information about all variables. All patients in the cohort had complete follow-up through December 31, 1989. Clinical information was abstracted and recorded as: date of diagnosis, stage at diagnosis, sex, age, anatomic site of primary tumor, date of death, and cause of death. Histopathologic slides were re-examined and classified with regard to histogenetic type, level of invasion, tumor thickness, ulceration, vascular invasion, regression, lymphocytic reaction, pre-existing nevus, and cell type.Results: All variables, except pre-existing nevus and cell type, were significant predictors of survival. In the multivariate analyses including all variables, women still had a significant, 33% lower relative hazard than men. The prognosis was poor in the youngest age group. Patients with external ear, scalp-neck, and trunk-located melanoma had increasing relative hazard when all variables were included. Regional metastases and tumor thickness remained independent prognostic factors. No significant association between histogenetic type or level of invasion persisted. Patients whose tumors showed ulceration or vascular invasion had lower relative hazard when all variables were included. Level of invasion, tumor thickness, ulceration, and vascular invasion were significantly associated with the prognosis during both short- and long-term follow-up. The patients were subgrouped according to percentage fractions of their score on the prognostic index. Survival curves for these groups of patients were well separated, thus identifying patients with a low or high risk of death from malignant melanoma.Conclusion: The present population-based study identifies independent clinical and histopathologic predictors of survival in cutaneous malignant melanoma and emphasizes the role of histopathologic characteristics such as tumor thickness, ulceration, and vascular invasion besides anatomic site. [ABSTRACT FROM AUTHOR]

We compared measurements of temporal trends in cancer survival either based on observed survival or relative survival. Survival rates for cutaneous malignant melanoma diagnosed in Sweden 1960-1982 were used as an example. In a proportional hazards model based on observed survival, the hazard ratio for patients diagnosed during the period 1975-1979 was 0.56 (95% confidence limits 0.49-0.64) in men and 0.45 (0.38-0.53) in women when the period 1960-1964 was the reference. When relative survival was the outcome measure, during the same period, the hazard ratio decreased to 0.47 (0.39-0.56) in men and 0.36 (0.29-0.44) in women. Thus, the effect of period of diagnosis was larger when the analysis was based on relative survival rates. The reasons for the differences between these two alternative measurements are explained in the article and advantages/disadvantages of the two approaches are discussed. [ABSTRACT FROM AUTHOR]

Objectives: This study examined invasive colorectal cancer incidence-rates in Sweden from 1959 through 1993 (n = 134,643 cases).Methods: Age-standardized rates were calculated using the Swedish population in 1970 as a reference.Results: In right-sided colon cancer (ascending and transverse colon including right and left flexures), male age-standardized rates rose from 8.0 to 15.0 (1.8 percent annually, 95 percent confidence interval [CI] = 1.3-2.4) and female rates increased from 9.1 to 14.4 (1.5 percent annually, CI = 1.0-2.0). For left-sided colon cancer (descending and sigmoid colon), the rates have been stable recently. For rectal cancer, the rates among men rose from 18.8 to 23.0 and among women from 10.7 to 14.7. For both men and women, the relative risk (RR) of right-sided colon cancer had been increasing in successive generations, until leveling-off in those born after 1930. The RR of left-sided colon cancer had been almost constant for cohorts born before 1930 but steadily decreasing in later-born cohorts. The RR of rectal cancer was slightly increasing in successive cohorts.Conclusions: Changes in lifestyle or carcinogenic exposures during early life probably explain Swedish colorectal cancer incidence-trends better than improved diagnostic activities. [ABSTRACT FROM AUTHOR]

This study investigates the incidence trends of urinary bladder cancer in Sweden from 1960 through 1993 (a total of 46,211 cases). Age-standardized incidence rates increased among men from 14.6 per 10(5) in 1960 to 33.5 in 1993 and among women from 4.8 to 8.8, corresponding to an average annual increase of 2.4 percent (95 percent confidence interval [CI]) = 2.0-2.7 percent) and 1.1 percent (CI = 0.9-1.4 percent), respectively. The largest increase occurred in the oldest age-groups. The proportion of patients with transitional cell carcinoma increased in men from 66.0 percent in 1960-64 to 93.6 percent in 1990-93 and in women from 61.0 percent to 89.4 percent. The proportion of patients with papillomas decreased, whereas those with adenocarcinoma and squamous cell carcinoma were stable. Regression modeling (based on the period 1960-89) showed a strong linear effect due to either period and/or cohort. Among men, additional non-linear effects by both period and cohort were obtained. The cohort effects were more important. Cohort data on having smoked daily showed considerable similarities with the estimated cohort-effects. Our findings suggest that the increase of tobacco smoking in successive generations can explain the increase in incidence rates of bladder cancer in Sweden, whereas improved diagnostic activities and registration are less likely to explain fully the changes in incidence rates. [ABSTRACT FROM AUTHOR]