Faecal calprotectin and lactoferrin values during irradiation of prostate cancer correlate with chronic radiation proctitis: Results of a prospective study

Objective. Acute proctitis and chronic radiation proctitis are relevant complications of pelvic radiation. The purpose of this study was to investigate two markers of gut inflammation during and after irradiation for prostate cancer to evaluate a correlation between acute and chronic proctitis. Material and methods. Two patient groups were analysed. In group 1, stool samples from 20 patients were collected before therapy, every week during therapy, at the end of therapy, and 13 and 27 months after therapy. Group 2 comprised 47 patients who had undergone irradiation 40 months earlier. Toxicity was determined by common toxicity criteria (CTC) and the LENT soma scale. Calprotectin and lactoferrin values were determined by ELISA. Results. In group 1, acute values for both faecal markers were significantly correlated with chronic proctitis symptoms and all patients with chronic toxicity had acute proctitis symptoms with elevated faecal values. In group 2, where stool samples were solely collected 40 months after irradiation, the Pearson square test showed both a significant correlation between calprotectin and lactoferrin values and toxicity after 40 months. Conclusions. Within a group of 19 patients followed for two years after irradiation for prostate cancer, and 47 patients tested 40 months after irradiation, increased faecal values of calprotectin and lactoferrin were significantly correlated with the occurrence of chronic proctitis. This observation should be confirmed in an expanded study.     

Recent trends in survival of adult patients with acute leukemia: overall improvements,but persistent and partly increasing disparity in survival of patients from minority groups

The survival of younger patients with acute leukemia has improved in the early 21^st century, but it is unknown whether people of all ethnic and racial backgrounds have benefited equally. Using cancer registry data from the Surveillance, Epidemiology and End Results Program, we assessed trends in 5-year relative survival for patients aged 15 years or more with acute lymphoblastic leukemia and acute myeloblastic leukemia divided by racial and ethnic group, including non-Hispanic whites, African-Americans, Hispanics, and Asian-Pacific Islanders in the 1990s and the early 21^st century. Modeled period analysis was used to obtain the most up-to-date estimates of survival. Overall, the 5-year survival increased from 31.6% in 1997-2002 to 39.0% in 2003-2008 for patients with acute lymphoblastic leukemia and from 15.5% in 1991-1996 to 22.5% in 2003-2008 for those with acute myeloblastic leukemia. Nevertheless, among patients with acute lymphoblastic leukemia, age-adjusted 5-year relative survival rates remained lower for African-Americans and Hispanics than for non-Hispanic whites. Among patients with acute myeloblastic leukemia, the increase in survival was greatest (from 32.6% in 1991-1996 to 47.1% in 2003-2008) for younger patients (15-54 years), and was more pronounced for non-Hispanic whites (+16.4% units) than for other patients (+10.8% units). Increases in survival are observed in all ethnic or racial groups. Nevertheless, among patients with acute leukemias, disparities in survival persist between non-Hispanic white people and people of other ethnic or racial groups. Disparities are increasing in younger patients with acute myeloblastic leukemia. Improvements in access to treatment, especially for minority patients, may improve outcomes.     

Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: Epidemiological changes in Germany

AIM:To study the epidemiologic changes of gastroenteropancreatic neuroendocrine tumors(GEP-NET)in Germany,we analyzed two time periods 1976-1988 and1998-2006.METHODS:We evaluated epidemiological data of GEP-NET from the former East German National Cancer Registry(DDR Krebsregister,1976-1988)and its successor,the Joint Cancer Registry(GKR,1998-2006),which was founded after German reunification.Due to a particularly substantial database the epidemiological data from the federal states of Mecklenburg-Western Pomerania,Saxony,Brandenburg and Thuringia,covering a population of more than 10.8 million people,were analyzed.Survival probabilities were calculated using life table analysis.In addition,GEP-NET patients were evaluated for one or more second(non-GEP-NET)primary malignancies.RESULTS:A total of 2821 GEP neuroendocrine neoplasms were identified in the two registries.The overall incidence increased significantly between 1976 and2006 from 0.31(per 100.000 inhabitants per year)to2.27 for men and from 0.57 to 2.38 for women.In the later period studied(2004-2006),the small intestine was the most common site.Neuroendocrine(NE)neoplasms of the small intestine showed the largest absolute increase in incidence,while rectal NE neoplasms exhibited the greatest relative increase.Only the incidence of appendiceal NET in women showed little change between 1976 and 2006.Overall survival of patients varied for sex,tumor site and the two periods studied but improved significantly over time.Interestingly,about 20%of the GEP-NET patients developed one or more second malignancies.Their most common location was the gastrointestinal tract.GEP-NET patients without second malignancies fared better than those with one or more of them.CONCLUSION:The number of detected GEP-NET increased about 5-fold in Germany between 1976 and2006.At the same time,their anatomic distribution changed,and the survival of GEP-NET patients improved significantly.Second malignancies are common and influence the overall survival of GEP-NET patients.Thus,GEP-NET     

Fine-needle aspiration diagnosis of synovial chondromatosis of the tibiofibular joint

We report a case of synovial chondromatosis of the tibiofibular joint in a 25-year-old woman that was diagnosed by fine-needle aspiration (FNA). The patient presented with pain in the left knee and a mass in the popliteal fossa. Synovial chondromatosis usually presents with joint symptoms and is often associated with intra-articular loose bodies, whereas presentation as a soft tissue mass is unusual and may raise the clinical suspicion of malignant neoplasm. The diagnosis is commonly confirmed by histopathologic examination of biopsy or excision of the specimen. To the best of our knowledge, this is the first case of synovial chondromatosis of a large joint successfully diagnosed by FNA. Two cases of synovial chondromatosis of the temporomandibular joint have been reported in which the diagnosis was suspected on the basis of FNA. In both these cases, the final diagnosis was established by histopathology of the excised specimens.     

Proinflammatory Cytokines,Adiponectin, and Increased Risk of Primary Cardiovascular Events in Diabetic Patients With or Without Renal Dysfunction: Results from the ESTHER study

OBJECTIVE

Inflammatory processes contribute to both diabetes and cardiovascular risk. We wanted to investigate whether circulating concentrations of proinflammatory immune mediators and adiponectin in diabetic patients are associated with incident cardiovascular events.

RESEARCH DESIGN AND METHODS

In 1,038 participants with diabetes of the population-based ESTHER study, of whom 326 showed signs of renal dysfunction, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association of increasing concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, macrophage migration inhibitory factor (MIF), adiponectin, and leptin with cardiovascular events (myocardial infarction, stroke, or fatal cardiovascular event) during a follow-up period of 8 years.

RESULTS

During follow-up, 161 subjects with diabetes experienced a primary cardiovascular event. Proinflammatory markers were not associated with a higher risk for primary cardiovascular events in the total study population after adjustment for multiple confounders. However, IL-6 and MIF were associated with cardiovascular events in subjects with renal dysfunction (HR for the comparison of top vs. bottom tertile 1.98 [95% CI 1.12–3.52], P [trend] = 0.10 for IL-6; 1.48 [0.87–2.51], P [trend] = 0.04 for MIF). Adiponectin levels were associated with cardiovascular events in the total population (1.48 [1.01–2.21], P [trend] = 0.03), and the association was even more pronounced in the subgroup with renal dysfunction (1.97 [1.08–3.57], P [trend] = 0.02).

CONCLUSIONS

In particular, the absence of an association between CRP and a U-shaped association of adiponectin levels with incident cardiovascular events show that associations between circulating immune mediators and cardiovascular risk differ between diabetic patients and subjects of the general population.Increased circulating concentrations of mostly proinflammatory immune mediators reflect inflammation-related processes that contribute to the development of type 2 diabetes and cardiovascular events. The proinflammatory cytokine interleukin-6 (IL-6) and the acute-phase protein C-reactive protein (CRP) are the most frequently investigated markers of subclinical inflammation in the context of cardiovascular risk (1–3). Both markers of subclinical inflammation were reported to predict cardiovascular events in a range of studies (1–3). However, these studies were mainly population based or consisted of individuals with a history of cardiovascular disease, whereas data for large populations of diabetic patients, who are characterized by an increased risk of myocardial infarction and stroke, are relatively rare (4–8). Thus, it is still unclear whether further immune activation in patients with type 2 diabetes, a proinflammatory state itself, additionally contributes to the increased cardiovascular risk of diabetic patients. A previous study indicated that circulating IL-6 and IL-18, but not CRP, are more strongly associated with incident cardiovascular events in individuals with high, compared with low, fasting glucose levels (9).In addition to reports linking proinflammatory immune mediators and cardiovascular risk, there are also numerous studies on adiponectin in this context. Adiponectin is an adipocyte-derived hormone with anti-inflammatory, insulin-sensitizing, and atheroprotective properties at least in rodents, but this is less clear in humans. In epidemiological studies conducted in the general population, there is usually no significant association or an inverse association between circulating adiponectin concentrations and cardiovascular events or mortality. However, increased adiponectin levels are often associated with increased cardiovascular risk in individuals with certain pre-existing conditions, including comorbidities that are prevalent in diabetic patients such as renal dysfunction and chronic heart failure (10,11). Data on the direction of the association between adiponectin and risk of cardiovascular events in cohorts of diabetic patients are still scarce.Our study in a large cohort of patients with diabetes had the following aims. First, we wanted to characterize the relationship between proinflammatory immune mediators (CRP, IL-6, IL-18, leptin, macrophage migration inhibitory factor [MIF]), adiponectin, and other cardiovascular risk factors. Second, we wanted to assess the risk for incident primary cardiovascular events with increasing proinflammatory immune mediators and adiponectin. Due to the link of kidney diseases to both immune activation and increased cardiovascular risk, the third aim was to explore these associations in diabetic patients with prevalent renal dysfunction at baseline.