Ole Thorlacius-Ussing

Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND A high consumption of fruit and vegetables is possibly associated with a decreased risk of colorectal cancer (CRC). However, the findings to date are inconsistent. OBJECTIVE We examined the relation between self-reported usual consumption of fruit and vegetables and the incidence of CRC. DESIGN In the European Prospective Investigation into Cancer and Nutrition (EPIC), 452,755 subjects (131,985 men and 320,770 women) completed a dietary questionnaire in 1992-2000 and were followed up for cancer incidence and mortality until 2006. A multivariate Cox proportional hazard model was used to estimate adjusted hazard ratios (HRs) and 95% CIs. RESULTS After an average follow-up of 8.8 y, 2,819 incident CRC cases were reported. Consumption of fruit and vegetables was inversely associated with CRC in a comparison of the highest with the lowest EPIC-wide quintile of consumption (HR: 0.86; 95% CI: 0.75, 1.00; P for trend = 0.04), particularly with colon cancer risk (HR: 0.76; 95% CI: 0.63, 0.91; P for trend < 0.01). Only after exclusion of the first 2 y of follow-up were these findings corroborated by calibrated continuous analyses for a 100-g increase in consumption: HRs of 0.95 (95% CI: 0.91, 1.00; P = 0.04) and 0.94 (95% CI: 0.89, 0.99; P = 0.02), respectively. The association between fruit and vegetable consumption and CRC risk was inverse in never and former smokers, but positive in current smokers. This modifying effect was found for fruit and vegetables combined and for vegetables alone (P for interaction < 0.01 for both). CONCLUSIONS These findings suggest that a high consumption of fruit and vegetables is associated with a reduced risk of CRC, especially of colon cancer. This effect may depend on smoking status.

Secular trends in incidence and 30-day case fatality of acute pancreatitis in North Jutland County, Denmark: A register-based study from 1981-2000

Background: The incidence rate of acute pancreatitis has been reported as having increased during recent decades in Western countries. Reported mortality lies around 10% and has improved during the past 20 years. The incidence rate and 30-day case fatality rate of acute pancreatitis in North Jutland County, Denmark were examined for the period 1981 to 2000. Methods: Data were collected from the Hospital Discharge Registry of North Jutland County for the period 1981-2000. Sex- and age-standardized incidence rates and 30-day case fatality rate of a first attack of acute pancreatitis were calculated. Data on endoscopic procedures were assessed for the period 1992 to 2000 and on certain drugs for 1991 to 1999. Results: The incidence rate of acute pancreatitis in women increased from 17.1 per 100,000 person-years in 1981 (95% confidence interval (CI), 12.6-23.2) to 37.8 per 100,000 person-years in 2000 (95% CI, 31.0-46.1). The corresponding increase in men was from 18 per 100,000 person-years in 1981 (95% CI, 13.3-24.2) to 27.1 per 100,000 person-years in 2000 (95% CI, 21.5-34.3). The incidence rate of acute pancreatitis increased with age in both sexes. The overall 30-day case fatality rate was 7.5% (95% CI, 6.5-8.7) increasing with age, adjusted odds ratio (OR) = 6.4 (95% CI, 3.5-11.6) and decreased with time, adjusted OR = 0.7 (95% CI, 0.4-1.0). Conclusion: The incidence of acute pancreatitis has increased, and in women surpassed that in men in 1999 and 2000. Short-term prognosis has improved.

Zinc in the Anterior Pituitary of Rat: A Histochemical and Analytical Work

Recent studies have suggested zinc to be a possible modulator of hormone secretion from the anterior pituitary. The three aims of the present study were: to estimate the total amount of zinc in the gland by instrumental analysis; to visualize the zinc at light and electron microscopical levels, and to estimate the amount of zinc that can be visualized by histochemical techniques. PIXE measurement showed the total amount of zinc to be 74 ng/mg dry weight in males and 100 ng/mg dry weight in females, which is a highly significant difference. Histochemically, the zinc was shown by a modified Timm method and the selenium method to be localized to the secretory granules, and to a smaller extent to the Golgi apparatus of the somatotrophs, corticotrophs and thyrotrophs. Chelation of tissue zinc by intravital dithizone treatment effectively blocked subsequent selenium and Timm staining in the secretory granules, and PIXE assays of the chelated metal (extracted into CCl4) showed it constituted less than 5% of the total zinc in the tissue. It is concluded from the study that zinc is present in the anterior pituitary of rats in rather high amounts and that loosely bound zinc, which is suggested to exert a biological effect by itself, can be located to the parts of the cells responsible for production, storing and release of hormones.

Risk of acute pancreatitis in users of azathioprine: a population-based case–control study

OBJECTIVE:Azathioprine has been linked to subsequent acute pancreatitis in several case reports and small case series. We examined the risk for acute pancreatitis in users of azathioprine in North Jutland County, Denmark, with about 490,000 inhabitants.METHODS:We identified patients with incident cases of acute pancreatitis from the Hospital Discharge Registry of the county from 1991–2000, and selected 10 controls per case, matched by age and sex, from the Central Personal Registry using incidence density sampling technique. All prescriptions of azathioprine within 90 days before admission were likewise collected from the population-based North Jutland Prescription Database. Data on potential confounders were extracted from registries. We used conditional logistic regression to adjust for confounding.RESULTS:A total of 1,388 patients and 13,836 controls were included in the study. We found that 1,317 persons in the entire population redeemed a total of 15,811 prescriptions of azathioprine in the county. The incidence rate for acute pancreatitis among all users of azathioprine was one per 659 treatment year. The crude OR of having redeemed prescriptions for azathioprine within 90 days before admission for acute pancreatitis was 7.5 (95% CI = 2.6–21.6). After adjustment for gallstone disease, alcohol-related diseases, inflammatory bowel disease, and use of glucocorticoids, the OR increased to 8.4 (95% CI = 2.4–29.4). The population-attributable risk, which measures the proportion of all cases of pancreatitis that are attributable to the use of azathioprine in our study population, was 0.4%.CONCLUSIONS:There was a substantially increased relative risk of acute pancreatitis in users of azathioprine.

Plasma Vitamins B2, B6, and B12, and Related Genetic Variants as Predictors of Colorectal Cancer Risk

Background: B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive. Methods: We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, including 1,365 incident colorectal cancer cases and 2,319 controls matched for study center, age, and sex. We measured the sum of B2 species riboflavin and flavin mononucleotide, and the sum of B6 species pyridoxal 5′-phosphate, pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as well as vitamin B12 in plasma samples collected at baseline. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for colorectal cancer were estimated using conditional logistic regression, adjusted for smoking, education, physical activity, body mass index, alcohol consumption, and intakes of fiber and red and processed meat. Results: The relative risks comparing highest to lowest quintile were 0.71 [95% confidence interval (95% CI), 0.56-0.91; Ptrend = 0.02] for vitamin B2, 0.68 (95% CI, 0.53-0.87; Ptrend <0.001) for vitamin B6, and 1.02 (95% CI, 0.80-1.29; Ptrend = 0.19) for vitamin B12. The associations for vitamin B6 were stronger in males who consumed ≥30 g alcohol/day. The polymorphisms were not associated with colorectal cancer. Conclusions: Higher plasma concentrations of vitamins B2 and B6 are associated with a lower colorectal cancer risk. Impact: This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(10); 2549–61. ©2010 AACR.

The Clinical Value of Procalcitonin in Early Assessment of Acute Pancreatitis

OBJECTIVES:Early assessment of the severity and the etiology is crucial in the management of acute pancreatitis. To determine the value of procalcitonin (PCT) as a prognostic marker and as an indicator of biliary etiology in the early phase of acute pancreatitis.METHODS:In a prospective study, 75 consecutive patients were included (severe pancreatitis in 12 patients, biliary etiology in 42 cases). The value of PCT as a prognostic marker was compared to C-reactive protein (CRP), hematocrit (HCT), acute physiology and chronic health evaluation (APACHE) II score, and Ranson score. The value of PCT as an indicator of biliary etiology was compared to alanine aminotransferase (ALT) and alkaline phosphatase (AP). The area under the receiver operating characteristic curve (AUC) was applied as a measure of the overall accuracy of the single markers and multiple scoring systems.RESULTS:The most accurate prediction of severe disease was provided by the APACHE II score on the day of admission (AUC: APACHE II, 0.78; CRP, 0.73; HCT, 0.73; and PCT, 0.61), and by CRP after 48 h (AUC: CRP, 0.94; Ranson score, 0.81; PCT, 0.71; APACHE II score, 0.69; and HCT, 0.46). ALT was the most accurate indicator of biliary pancreatitis (AUC: ALT, 0.83; AP, 0.81; and PCT, 0.68).CONCLUSIONS:PCT is of limited additional value for early assessment of severity and etiology in acute pancreatitis. CRP is found to be a reliable prognostic marker with a delay of 48 h, while ALT is validated as the best indicator of biliary etiology.

Biologic treatment or immunomodulation is not associated with postoperative anastomotic complications in abdominal surgery for Crohn's disease

Abstract Objectives. There are concerns that biologic treatments or immunomodulation may negatively influence anastomotic healing. This study investigates the relationship between these treatments and anastomotic complications after surgery for Crohns disease. Patients and methods. Retrospective study on 417 operations for Crohns disease performed at four Danish hospitals in 2000–2007. Thirty-two patients were preoperatively treated with biologics and 166 were on immunomodulation. In total, 154 were treated with corticosteroids of which 66 had prednisolone 20 mg or more. Results. Anastomotic complications occurred at 13% of the operations. There were no difference in patients on biologic treatment (9% vs. 12% (p = 0.581)) or in patients on immunomodulation (10% vs. 14% (p = 0.263)). Patients on 20 mg prednisolone or more had more anastomotic complications (20% vs. 11% (p = 0.04)). Anastomotic complications were more frequent after a colo-colic anastomosis than after an entero-enteric or entero-colic (33% vs. 12% (p = 0.013)). Patients with anastomotic complications were older (40 years vs. 35 years (p = 0.014)), had longer disease duration (7.5 years vs. 4 years (p = 0.04)), longer operation time (155 min vs. 115 min (p = 0.018)) and more operative bleeding (200 ml vs. 130 ml (p = 0.029)). Multivariate analysis revealed preoperative treatment with prednisolone 20 mg or more, operation time and a colo-colic anastomosis as negative predictors of anastomotic complications. Conclusions. Preoperative biologic treatment or immunomodulation had no influence on anastomotic complications. The study confirms previous findings of corticosteroids and a colo-colic anastomosis as negative predictors and also that surgical complexity, as expressed by bleeding and operation time, may contribute to anastomotic complications.

Immunosuppressive disorders and risk of anal squamous cell carcinoma: A nationwide cohort study in Denmark, 1978–2005

Compromised immune function may increase the risk of anal squamous cell carcinoma (SCC). We examined the risk of anal SCC in patients with HIV infection and other chronic disorders associated with immunosuppression. A population‐based cohort study was conducted using the Danish National Patient Registry and the Danish Cancer Registry (DCR). We identified all patients with a first‐time hospital contact or procedure for HIV infection, solid organ transplantation or autoimmune disease or a first‐time record of haematologic malignancy in the DCR, 1978–2005, and followed these for a subsequent anal SCC, starting follow‐up 1 year after diagnosis of the index disease. Standardised incidence ratios (SIRs) were computed as the ratio of observed to expected numbers of anal SCCs, based on national age‐, sex‐ and period‐specific rates. Among 4,488 patients with HIV, we observed 21 anal SCCs with 0.3 expected (SIR: 81.1 (95% confidence interval (CI): 51.6–121.9)). Risk of anal SCC was markedly increased among 5,113 solid organ recipients (SIR: 14.4 (CI: 7.0–26.4)) and 30,165 patients with haematologic malignancies (SIR: 2.3 (CI: 1.1–4.2)) but only moderately increased among 242,114 patients with autoimmune diseases (SIR: 1.3 (CI: 1.0–1.6)). SIRs varied according to type of autoimmune disease and were high in patients with Crohns disease (SIR: 3.1 (CI: 1.2–6.4)), psoriasis (SIR: 3.1 (CI: 1.8–5.1)), polyarteritis nodosa (SIR: 8.8 (CI: 1.5–29.0)) and Wegeners granulomatosis (SIR: 12.4 (CI: 2.1–40.8)). In conclusion, we found HIV infection, solid organ transplantation, haematologic malignancies and a range of specific autoimmune diseases strongly associated with increased risk of anal SCC.

Coagulation and Fibrinolysis during Laparoscopic Cholecystectomy

Laparoscopic surgery appears to be less traumatic to the patient than open surgery, but its influence upon coagulation and fibrinolysis is incompletely elucidated. Our aim was to measure markers of coagulation and fibrinolysis before, during. and after laparoscopic cholecystectomy (LC). Blood samples drawn on admission, on four occasions during operation as well as 2 hours after operation and on the first postoperative day in 50 patients undergoing elective LC were analyzed for prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), D-dimer (DD), fibrin degradation products (FbDP), tissue-type plasminogen activator (tPA) activity and antigen, and plasminogen activator inhibitor (PAI) activity and antigen. F1+2, SF, DD, and FbDP levels increased significantly after LC. Differences between pre- and postoperative PAI and tPA levels were not significant apart from a transient increase in tPA antigen levels. tPA activity was significantly increased during operation.

Distribution of dietary mercury in a dog. Quantitation and localization of total mercury in organs and central nervous system

An Alsatian dog which had been fed fish contaminated with methyl mercury for 7 years was examined after its death at the age of 12, 4 years after the exposure to methyl mercury had ceased. Two dogs of the same age and breed served as controls. In the exposed dog, mercury was found in all of the organs examined; the highest concentrations were found in the kidneys, and the lowest in the gastrointestinal tract and skeletal muscles. In the central nervous system (CNS) the mercury was fairly uniformly distributed, with 93% in the inorganic state, whereas the skeletal muscles contained approximately 30% inorganic mercury. This demonstrates time-dependent demethylation and suggests a variation in the rate from one type of tissue to another. At the time of death, the mercury level in the dog was still falling. In the control dogs, detectable amounts (0.01 mg kg-1) of mercury were only found in the kidney and liver. The distribution of mercury was determined by a histochemical method (autometallography) for locating mercury in tissue sections. Sections from autometallography of the central nervous system showed large deposits of mercury in all areas of the cerebral hemispheres, the brainstem and the spinal cord, including nerve cells, astrocytes, microglial cells and vessel walls. The granular layer of the cerebellar hemispheres was especially loaded, while only a few granules were present in the Purkinje cells. In the leptomeninges the vessels and the macrophages were heavily encrusted. High amounts of histochemically demonstrable mercury were observed in the liver, thyroid gland and kidney. In the control dogs, all the organs examined were practically devoid of deposits.