Mortality, cancer, and comorbidities associated with chronic pancreatitis: a Danish nationwide matched-cohort study.

BACKGROUND & AIMS: We aimed to assess the risk of death, cancer, and comorbidities among patients with alcoholic and nonalcoholic chronic pancreatitis (CP). METHODS: We performed a nationwide retrospective cohort study, collecting data from Danish registries from 1995 through 2010. We evaluated the prevalences and incidences of death, cancers, and comorbidities among subjects with CP (cases) compared with age- and sex-matched individuals (controls). In total, 11,972 cases (71,814 person-years) and 119,720 controls (917,436 person-years) were included in the analysis. Hazard ratios (HR) were estimated by Cox proportional hazards regression. RESULTS: Forty-six percent of the cases died during the follow-up period, compared with 13.0% of controls (mean age, 63.7 vs 72.1 y; P < .0001), corresponding to a HR of 5.0 for CP (95% confidence interval [CI], 4.8-5.2). Cancer was a frequent cause of death among cases (10.2%) and controls (3.3%). Cancer (particularly pancreatic cancer) was a frequent cause of death among cases; the HR was 6.9 (95% CI, 7.5-11.8). Alcoholic CP did not produce a higher risk for cancer or death than nonalcoholic CP. Cerebrovascular disease (HR, 1.3; 95% CI, 1.2-1.4), chronic pulmonary disease (HR, 1.9; 95% CI, 1.8-2.1), ulcer disease (HR, 3.6; 95% CI, 3.3-3.9), diabetes (HR, 5.2; 95% CI, 5.0-5.6), and chronic renal disease (HR, 1.7; 95% CI, 1.5-1.9) occurred more frequently among patients with CP, but myocardial infarction did not (HR, 0.9; 95% CI, 0.8-1.0). CONCLUSIONS: Based on a Danish nationwide cohort study, individuals with CP are at higher risk for death from cancer (particularly pancreatic cancer) and have a higher incidence of comorbidities than people without CP.

The risk of fractures among patients with cirrhosis or chronic pancreatitis.

BACKGROUND & AIMS: Cirrhosis and chronic pancreatitis (CP) are accompanied by inflammation and malnutrition. Both conditions can have negative effects on bone metabolism and promote fractures. We evaluated the risk of fractures among patients with CP or cirrhosis and determined the effect of fat malabsorption on fracture risk among patients with CP. METHODS: We performed a retrospective cohort study using the Danish National Patient Register to identify patients diagnosed with CP or cirrhosis. We analyzed data collected from January 1, 1995, to December 31, 2010, on 20,769 patients (35.5% women with cirrhosis and 11,972 patients (33.5% women) with CP. Each patient was compared with 10 age- and sex-matched controls. We also assessed the risk of fractures among patients with CP who received pancreatic enzyme substitution (PES) for fat malabsorption. RESULTS: During the study period, bone fractures occurred in 3954 patients with cirrhosis and 2594 patients with CP. The adjusted hazard ratio (HR) for any fracture was 2.4 in patients with cirrhosis (95% confidence interval [CI], 2.2-2.5) and 1.7 in patients with CP (95% CI, 1.6-1.8). The relative risk of low-trauma fractures was highest among individuals younger than 50 years old. Alcohol as an etiology was associated with an increased risk of fracture compared with patients with nonalcoholic cirrhosis (HR, 2.4 vs 1.5; P < .0001) and CP (HR, 2.0 vs 1.5; P < .0001). Patients with CP receiving PES for fat malabsorption had a lower risk of fractures than other CP patients (HR, 0.8; 95% CI, 0.7-0.9). However, increasing the duration of treatment with PES was associated with an increased risk of fracture. CONCLUSIONS: Patients, especially younger patients, with cirrhosis or CP have an increased risk of fractures of all types.

The effect of cholecalciferol and calcitriol on biochemical bone markers in HIV type 1-infected males: results of a clinical trial.

HIV-1-infected patients have an increased risk of osteoporosis and fractures. The main objective of this study was to evaluate the bone metabolism in HIV-1-infected patients exposed to calcitriol and cholecalciferol. We also investigated the relationship between T cells and bone markers. We conducted a placebo-controlled randomized study running for 16 weeks including 61 HIV-1-infected males, of whom 51 completed the protocol. Nineteen participants were randomized to daily treatment with (A) 0.5-1.0 µg calcitriol and 1,200 IU (30 µg) cholecalciferol, 17 participants to (B) 1,200 IU cholecalciferol, and 15 participants to (C) placebo. At baseline and after 16 weeks, we determined collagen type 1 trimeric cross-linked peptide (CTx), procollagen type 1 N-terminal peptide (P1NP), parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. We determined naive CD4(+) and CD8(+), activated CD4(+) and CD8(+), and regulatory CD4(+)CD25(+)CD127(low) T lymphocytes. Baseline levels of P1NP and CTx correlated (coefficient 0.5, p<0.001) with each other but not with PTH, 25OHD, or 1,25(OH)2D. In patients receiving calcitriol and cholecalciferol, the mean levels of P1NP (p<0.001) and CTx (p= 0.002) declined significantly compared to our placebo group. Based on changes in P1NP and CTx, we estimated that net bone formation occurred more frequently in group A compared to groups B and C. PTH correlated inversely with naive CD4(+) and CD8(+) cells. Otherwise, no relationships between bone markers and T lymphocytes were demonstrated. Supplementation with calcitriol and cholecalciferol induced biochemical indications of bone formation in HIV-1 patients.

Changes in 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D are associated with maturation of regulatory T lymphocytes in patients with chronic pancreatitis: a randomized controlled trial.

OBJECTIVES: We studied the impact of changes in 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) on regulatory T lymphocytes (Tregs) in patients with chronic pancreatitis (CP) and fat malabsorption in a prospective clinical trial. METHODS: The patients were randomized to 1 of 3 treatments during 10 weeks: weekly UV-B in a tanning bed (group A), 1520-IU/d vitamin D supplement (group B), or placebo (group C). A placebo tanning bed was used in groups B and C. We determined the levels of CD4 Tregs (CD3(+)CD4(+)CD25(+)CD127(low)FoxP3(+)) and CD8(+) Tregs (CD3(+)CD8(+)CD25(+)CD127(low)FoxP3(+)), together with 25OHD and 1,25(OH)2D. For baseline comparisons, we included 8 healthy individuals. Of the 30 included patients, 27 (group A, 7 patients; group B, 9 patients; and group C, 11 patients) completed the protocol. RESULTS: The baseline levels of CD4(+) Tregs relative to total CD4(+) count were higher in 22 patients with CP compared with healthy controls (2.8% vs 1.9%, P < 0.05) and were comparable for CD8+ Tregs (0.13% vs 0.05%, P = 0.3). Increases in levels of CD4(+) Tregs correlated to changes in 1,25(OH)(2)D (2% per 100 pmol/L, P = 0.002) and 25OHD (3% per 100 nmol/L, P = 0.01). CONCLUSIONS: Patients with CP have elevated relative levels of CD4(+) Tregs. Increases in 25OHD and 1,25(OH)(2)D were both related with increases in levels of Tregs.

Changes in serum 25-hydroxyvitamin D and cholecalciferol after one whole-body exposure in a commercial tanning bed: a randomized study.

We wanted to evaluate the cutaneous synthesis of 25OHD and cholecalciferol after one whole-body exposure to ultraviolet radiation type B (UVB) in a randomized setup. Healthy volunteers were randomized to one whole-body exposure in a commercial tanning bed with UVB emission (UVB/UVA ratio 1.8-2.0%) or an identical placebo tanning bed without UVB. The output in the 280-320 nm range was 450 µW/cm². Blood samples were analyzed for 25OHD and cholecalciferol at baseline and during 7 days after treatment. We included 20 volunteers, 11 to UVB and 9 to placebo treatment. During the first 6 h, no significant differences in 25OHD between the groups were found. At the end of the study, we found a mean increase of 25OHD in the UVB group of 4.5 nmol/l (SD 7 nmol/l) compared to a decline of -1.2 nmol/l (SD 7 nmol/l) in the placebo group (p = 0.1). A linear mixed model yielded an increase of 25OHD in the UVB group of 1.0 nmol/l per 24 h (p < 0.01). For cholecalciferol, we found a near significant increase of 1 pmol/l per hour in the UVB group compared to the placebo group during the first 6 h (p = 0.052). One tanning bed session had significant, but modest impact on the level of 25OHD during 7 days after exposure to UVB.

Deficiency of 25-hydroxyvitamin D in male HIV-positive patients: a descriptive cross-sectional study.

The aim of this descriptive cross-sectional study was to describe the prevalence of hypovitaminosis D in a cohort of HIV-seropositive males. Blood samples were collected in November and December 2004 and analyzed in the hospital laboratory. The concentration of 25-hydroxyvitamin D (25(OH)D) was defined as excellent when >75 nmol/l, normal when >50 nmol/l, insufficient when <50 nmol/l, deficient when <25 nmol/l and severely deficient when <12.5 nmol/l. Patient information was extracted from the medical records. A total of 115 males, median age 44 y (range 19-63 y), were included in the study. The median 25(OH)D concentration was 43.0 nmol/l (range 8-163 nmol/l) and the 25(OH)D level was excellent in 13%, normal in 27%, insufficient in 36%, deficient in 20%, and severely deficient in 4% of the cases. Vitamin D level was not associated with age, y with HIV infection, highly active antiretroviral therapy (HAART) or CD4 count. Compared to patients not in treatment, patients on HAART (n = 71) had higher levels of total alkaline phosphatase (median 83.0 vs 75.5 U/l; p = 0.031) and lower, though not significantly, total body mineral density (1.055 vs 1.107 g/cm(2); p = 0.077). This study confirms that the prevalence of hypovitaminosis is high among HIV-infected patients.

A descriptive cross-sectional study of the prevalence of 25-hydroxyvitamin D deficiency and association with bone markers in a hospitalized population.

Patients with gastrointestinal disease may be in particular risk of hypovitaminosis D because of reduced intestinal uptake or metabolism in the liver. The aim of the present study was to evaluate the prevalence of vitamin D deficiency in several groups of patients with various gastroenterologic diseases compared with patients without any chronic disease. We tested the hypothesis that persons with a gastrointestinal disease are at higher risk of hypovitaminosis D than persons with no chronic disease and whether this group needs special attention regarding their nutrition. We included patients admitted to our department of gastroenterology. The concentration of 25-hydroxyvitamin D (25(OH)D2+D3) was defined as insufficient when less than 50 nmol/L, deficient when less than 25 nmol/L, and severely deficient when less than 12.5 nmol/L. We included 146 patients with a mean age of 55 years (range, 16-93 years). 25(OH)D was sufficient in 47%, insufficient in 29%, deficient in 12%, and severely deficient in 11% of the population. Participants without chronic disease had a significantly higher mean level of 25(OH)D (57 nmol/L) compared to participants with cirrhosis (15 nmol/L, P = .002) and alcoholism (31 nmol/L, P = .003). A linear relationship between 25(OH)D and alkaline phosphatase could be demonstrated (Spearman rho, -0.299; P < .001). Participants with severe 25(OH)D deficiency had higher levels of total alkaline phosphatase (149.5 vs 76 U/L, P = .001) and parathyroid hormone (5.1 vs 2.8 pmol/L; P = .001). We recommend measuring the level of 25(OH)D and parathyroid hormone in patients with chronic diseases, especially alcoholism and cirrhosis.

[The use of adalimumab in severe fistulising Crohn's disease]. / Behandling af svaer aktiv morbus Crohn med adalimumab.

So far infliximab is the only approved anti-TNF-alpha antibody for patients with Crohn's disease. Development of antibodies to infliximab may result in allergic reactions or reduced effect. We report three patients who received adalimumab, which induced longstanding remission in all three patients.

Pharmacological approach to acute pancreatitis.

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-alpha) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.

[Cholecystic fistula with atypical symptoms]. / Fistel fra galdeblaeren til colon.

We report a patient with spontaneous cholecystocolonis fistula secondary to cholelithiasis. A 93 year-old woman was admitted because of weight loss, diarrhoea and upper abdominal pain. Ultrasound examination revealed air in the biliary tract and cholescientigraphy revealed a fistula between the gallbladder and right colon. Using endoscopic retrograde cholangiopancreatography a calculus was extracted from the bile duct and the symptoms disappeared.