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Background Real-life long-term data on infliximab treatment in ulcerative colitis are limited. Aim To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined. Methods A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age 18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant. Results Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy. Conclusions Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.

Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited. Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined. Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant. Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy. Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy., Funding Agencies:Thorsten-Segerfalks Foundation 86026Olle Olsson Memory Foundation 86030Stig and Ragna Gorthons Foundation 2013-92 2014-149 2015-1259

BACKGROUND: Sentinel node biopsy has recently evolved as a means of staging the axilla in breast cancer with minimal surgical trauma. The aim of this prospective multicentre study was to identify factors that influenced the detection and false-negative rates during the learning phase. METHODS: Data on all 498 sentinel node biopsies performed between August 1997 and December 1999 in Sweden were collected. RESULTS: A sentinel node was found in 450 patients (90 per cent). Preoperative scintigraphy visualized 83 per cent of all sentinel nodes. The detection rate was higher with same-day injection of tracer than with injection the day before (96 versus 86 per cent; P < 0.01). Dye injected less than 5 min or more than 30 min before the start of the operation lowered the detection rate (less than 60 per cent versus more than 65 per cent; P = 0.02). The detection rate varied from 61 to 100 per cent between surgeons. The false-negative rate was 11 per cent. The presence of multiple tumour foci and a high S-phase fraction increased the risk of a false-negative sentinel node, whereas the number of operations performed by each surgeon was less important. CONCLUSION: Training of the individual surgeon influenced the detection rate, as did timing of tracer and dye injection. The false-negative rate seemed to be related to biological factors.

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.

Pigmentary changes during pregnancy and sex-specific differences in incidence patterns of cutaneous malignant melanoma (CMM) suggest that sex hormones may be involved in the development of CMM. We explored possible associations between childbearing and the risk of CMM in a case-control study "nested' in a nation-wide cohort. A total of 4,779 incident cases of CMM in women aged 24-65 were compared with 23,888 individually age-matched controls. Delayed childbearing was associated with an increased risk of CMM, corresponding to approximately 16% per 5 years. Parous women had a significantly lower risk of CMM compared with nulliparous women; in univariate analysis there was an 8% reduction in risk for each additional birth (odds ratio = 0.92; 95% confidence interval = 0.89-0.95). In multivariate analyses the risk of CMM was best explained by a model including both age at first birth and parity. Age at first birth was the most important variable. Time since most recent birth was unrelated to risk of CMM. These findings indicate that early childbearing and multiparity reduce the risk of CMM. Conceivable explanations are hormonal changes induced by childbearing, enhanced immunologic activity via exposure to fetal antigens during pregnancy, or long-lasting effects of pregnancy-associated hyperpigmentation. Our results need confirmation in studies with proper adjustment for confounding; less sun exposure in young mothers and high parity women may represent an alternative explanation but is unlikely to explain entirely the twofold difference in risk found between extreme categories of age at first birth and parity.

Survival rates were analysed in 29,055 patients with urinary bladder cancer diagnosed in Sweden from 1960 to 1986 and followed up until 1987. The 2-, 5- and 10-year relative survival rates were 79, 70 and 64% for men and 75, 68 and 63% for women, respectively. Patients with a history of bladder cancer for at least 15 years ran a negligible risk of dying from their disease. Prognosis was consistently better in younger than in older patients; below 50 years of age the 5-year relative survival rate was 90%, as compared with 60% in patients aged 70-79 years. Patients diagnosed between 1960 and 1964 had a 60% 5-year relative survival, as compared to 71% in those diagnosed between 1980 and 1984. Multivariate analyses further confirmed that age but not sex is an important prognostic factor in bladder cancer and, further, that a substantial improvement in survival rates took place during the 1960-1986 period. Compared with 1960-1964 the risk of dying of bladder cancer within 5 years in patients diagnosed between 1980 and 1984 was 51% lower in men [relative risk (RR) = 0.49; 95% confidence interval (C.I.) 0.42-0.57] and 44% lower in women (RR = 0.56; 95% C.I. 0.45-0.70).

The methods of somatic cell genetics and molecular hybridization were applied to a panel of mouse X rat hepatocyte hybrids segregating rat chromosomes to assign the rat genes coding for two serum proteins, albumin and alpha-fetoprotein (Alb and Afp). The molecular hybridization of DNAs from different hybrids with cloned DNA probes showed that all the hybrid clones possessing the rat Alb gene and expressing it also retained the rat Afp locus, which is not expressed in these hybrids. So the Alb and Afp genes are syntenic in the rat, as in the mouse. Furthermore, the cytogenetic analysis allowed the assignment of these two loci to rat chromosome 14., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

The methods of somatic cell genetics and molecular hybridization were applied to a panel of mouse X rat hepatocyte hybrids segregating rat chromosomes to assign the rat genes coding for two serum proteins, albumin and alpha-fetoprotein (Alb and Afp). The molecular hybridization of DNAs from different hybrids with cloned DNA probes showed that all the hybrid clones possessing the rat Alb gene and expressing it also retained the rat Afp locus, which is not expressed in these hybrids. So the Alb and Afp genes are syntenic in the rat, as in the mouse. Furthermore, the cytogenetic analysis allowed the assignment of these two loci to rat chromosome 14., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published