Rectal cancer treatment and outcome in the elderly: an audit based on the Swedish rectal cancer registry 1995–2004

<p>Abstract</p> <p>Background</p> <p>Limited information is available regarding the effect of age on choice of surgical and oncological treatment for rectal cancer. The objective of this study was to assess the influence of age on treatment and outcome of rectal cancer.</p> <p>Methods</p> <p>We utilized data in the Swedish Rectal Cancer Registry (SRCR) from patients treated for rectal cancer in Sweden in 1995–2004.</p> <p>Results</p> <p>A total of 15,104 patients with rectal cancer were identified, 42.4% of whom were 75 years or older. Patients ≥75 years were less likely to have distant metastases than younger patients (14.8% vs. 17.8%, <it>P </it>< 0.001), and underwent abdominal tumor resection less frequently (68.5% vs. 84.4%, <it>P </it>< 0.001). Of 11,725 patients with abdominal tumor resection (anterior resection [AR], abdominoperineal excision [APE], and Hartmann's procedure [HA]), 37.4% were ≥75 years. Curative surgery was registered for 85.0% of patients ≥ 75 years and for 83.9% of patients < 75 years, <it>P </it>= 0.11. Choice of abdominal operation differed significantly between the two age groups for both curative and non-curative surgery, The frequency of APE was similar in both age groups (29.5% vs. 28.6%), but patients ≥75 years were more likely to have HA (16.9% vs. 4.9%) and less likely to have preoperative radiotherapy (34.3vs. 67.2%, <it>P </it>< 0.001). The relative survival rate at five years for all patients treated with curative intent was 73% (70–75%) for patients ≥75 years and 78% (77–79%) for patients < 75 years of age. Local recurrence rate was 9% (8–11%) for older and 8% (7–9%) for younger patients.</p> <p>Conclusion</p> <p>Treatment of rectal cancer is influenced by patient's age. Future studies should include younger and older patients alike to reveal whether or not age-related differences are purposive. Local recurrence following surgery for low tumors and quality of life aspects deserve particular attention.</p

What if cancer survival in Britain were the same as in Europe: how many deaths are avoidable?

OBJECTIVE: To estimate the number of deaths among cancer patients diagnosed in Great Britain that would be avoidable within 5 years of diagnosis if the mean (or highest) survival in Europe for patients diagnosed during 1985-1989, 1990-1994 and 1995-1999 were achieved. DESIGN: Five-year relative survival for cancers in Great Britain compared with that from other countries in the EUROCARE-2, -3 and -4 studies. Calculation of excess deaths (those more than expected from mortality in the general population) that would be avoidable among cancer patients in Britain if relative survival were the same as in Europe. SETTING: Great Britain (England, Wales, Scotland) and 13 other European countries. SUBJECTS: 2.8 million adults diagnosed in Britain with 1 of 39 cancers during 1985-1989 (followed up to 1994), 1990-1994 (followed up to 1999) and 1995-1999 (followed up to 2003). MAIN OUTCOME MEASURE: Annual number of avoidable deaths within 5 years of diagnosis. Percentage of the excess (cancer-related) deaths among cancer patients that would be avoidable. RESULTS: Compared with the mean European 5-year relative survival, the largest numbers of avoidable deaths for patients diagnosed during 1985-1989 were for cancers of the breast (about 18% of the excess mortality from this cancer, 7541 deaths), prostate (14%, 4285), colon (9%, 4090), stomach (8%, 3483) and lung (2%, 3548). For 1990-1994, the largest numbers of avoidable deaths were for cancers of the prostate (20%, 7335), breast (15%, 6165), colon (9%, 4376), stomach (9%, 3672), lung (2%, 3735) and kidney (22%, 2644). For 1995-1999, most of the avoidable deaths were for cancers of the prostate (17%, 5758), breast (15%, 5475), lung (3%, 4923), colon (10%, 4295), stomach (9%, 3137) and kidney (21%, 2686).Overall, some 6600-7500 premature deaths would have been avoided each year among cancer patients diagnosed in Britain during 1985-1999 if the mean survival in Europe had been achieved. This represents 6-7% of cancer-related mortality. Compared with the highest European survival, avoidable premature mortality among cancer patients fell from about 12 800 deaths a year (12.2% of cancer-related mortality) to about 11 400 deaths a year (10.6%) over the same period.A large component of the avoidable mortality is due to prostate cancer: excluding this cancer from comparison with the European mean survival reduces the annual number of avoidable deaths by 1000-1500, and the percentage of excess mortality by up to 1%. Compared with the highest survival, the annual number of avoidable deaths would be 1500-2000 fewer, and 1-2% lower as a percentage of excess mortality, but the overall trend in avoidable premature mortality among cancer patients would be similar, falling from 11.4% (1985-1989) to 10.3% (1990-1994) and 9.7% for those diagnosed during 1995-1999.For several cancers, survival in Britain was slightly higher than the mean survival in Europe; this represented some 110-180 premature deaths avoided each year during the period 1985-2003. CONCLUSIONS: Avoidable premature mortality among cancer patients diagnosed in Britain during 1985-1999 has represented 6-7% of cancer-related mortality compared with the mean survival in Europe. Compared with the highest levels of survival in Europe, the reduction from 12.2% to 10.6% of cancer-related mortality reflects small but steady progress over the period 1985-2003

The Dynamic Processing of CD46 Intracellular Domains Provides a Molecular Rheostat for T Cell Activation

Adequate termination of an immune response is as important as the induction of an appropriate response. CD46, a regulator of complement activity, promotes T cell activation and differentiation towards a regulatory Tr1 phenotype. This Tr1 differentiation pathway is defective in patients with MS, asthma and rheumatoid arthritis, underlying its importance in controlling T cell function and the need to understand its regulatory mechanisms. CD46 has two cytoplasmic tails, Cyt1 and Cyt2, derived from alternative splicing, which are co-expressed in all nucleated human cells. The regulation of their expression and precise functions in regulating human T cell activation has not been fully elucidated.Here, we first report the novel role of CD46 in terminating T cell activation. Second, we demonstrate that its functions as an activator and inhibitor of T cell responses are mediated through the temporal processing of its cytoplasmic tails. Cyt1 processing is required to turn T cell activation on, while processing of Cyt2 switches T cell activation off, as demonstrated by proliferation, CD25 expression and cytokine secretion. Both tails require processing by Presenilin/γSecretase (P/γS) to exert these functions. This was confirmed by expressing wild-type Cyt1 and Cyt2 tails and uncleavable mutant tails in primary T cells. The role of CD46 tails was also demonstrated with T cells expressing CD19 ectodomain-CD46 C-Terminal Fragment (CTF) fusions, which allowed specific triggering of each tail individually.We conclude that CD46 acts as a molecular rheostat to control human T cell activation through the regulation of processing of its cytoplasmic tails

Survival of patients with metastatic breast cancer: twenty-year data from two SEER registries

BACKGROUND: Many researchers are interested to know if there are any improvements in recent treatment results for metastatic breast cancer in the community, especially for 10- or 15-year survival. METHODS: Between 1981 and 1985, 782 and 580 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries of the Surveillance, Epidemiology, and End Results (SEER) database. The lognormal statistical method to estimate survival was retrospectively validated since the 15-year cause-specific survival rates could be calculated using the standard life-table actuarial method. Estimated rates were compared to the actuarial data available in 2000. Between 1991 and 1995, further 752 and 632 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries. The data were analyzed to estimate the 15-year cause-specific survival rates before the year 2005. RESULTS: The 5-year period (1981–1985) was chosen, and patients were followed as a cohort for an additional 3 years. The estimated 15-year cause-specific survival rates were 7.1% (95% confidence interval, CI, 1.8–12.4) and 9.1% (95% CI, 3.8–14.4) by the lognormal model for the two registries of Connecticut and San Francisco-Oakland respectively. Since the SEER database provides follow-up information to the end of the year 2000, actuarial calculation can be performed to confirm (validate) the estimation. The Kaplan-Meier calculation for the 15-year cause-specific survival rates were 8.3% (95% CI, 5.8–10.8) and 7.0% (95% CI, 4.3–9.7) respectively. Using the 1991–1995 5-year period cohort and followed for an additional 3 years, the 15-year cause-specific survival rates were estimated to be 9.1% (95% CI, 3.8–14.4) and 14.7% (95% CI, 9.8–19.6) for the two registries of Connecticut and San Francisco-Oakland respectively. CONCLUSIONS: For the period 1981–1985, the 15-year cause-specific survival for the Connecticut and the San Francisco-Oakland registries were comparable. For the period 1991–1995, there was not much change in survival for the Connecticut registry patients, but there was an improvement in survival for the San Francisco-Oakland registry patients

Calcitriol modulates the CD46 pathway in T cells

The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)2D3 or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNc ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS

Bronchopulmonary dysplasia: clinical aspects and preventive and therapeutic strategies

Abstract Background Bronchopulmonary dysplasia (BPD) is the result of a complex process in which several prenatal and/or postnatal factors interfere with lower respiratory tract development, leading to a severe, lifelong disease. In this review, what is presently known regarding BPD pathogenesis, its impact on long-term pulmonary morbidity and mortality and the available preventive and therapeutic strategies are discussed. Main body Bronchopulmonary dysplasia is associated with persistent lung impairment later in life, significantly impacting health services because subjects with BPD have, in most cases, frequent respiratory diseases and reductions in quality of life and life expectancy. Prematurity per se is associated with an increased risk of long-term lung problems. However, in children with BPD, impairment of pulmonary structures and function is even greater, although the characterization of long-term outcomes of BPD is difficult because the adults presently available to study have received outdated treatment. Prenatal and postnatal preventive measures are extremely important to reduce the risk of BPD. Conclusion Bronchopulmonary dysplasia is a respiratory condition that presently occurs in preterm neonates and can lead to chronic respiratory problems. Although knowledge about BPD pathogenesis has significantly increased in recent years, not all of the mechanisms that lead to lung damage are completely understood, which explains why therapeutic approaches that are theoretically effective have been only partly satisfactory or useless and, in some cases, potentially negative. However, prevention of prematurity, systematic use of nonaggressive ventilator measures, avoiding supraphysiologic oxygen exposure and administration of surfactant, caffeine and vitamin A can significantly reduce the risk of BPD development. Cell therapy is the most fascinating new measure to address the lung damage due to BPD. It is desirable that ongoing studies yield positive results to definitively solve a major clinical, social and economic problem