Long-term results with azathioprine therapy in patients with corticosteroid-dependent Crohn's disease: open-label prospective study.

BACKGROUND: A substantial number of patients with Crohn's disease (CD) become dependent on steroids after induction therapy. Treatment with azathioprine (AZA) may be beneficial in such patients. The present open-label study evaluated the long-term safety and efficacy of AZA in steroid-dependent CD patients. METHODS: Adult patients with steroid-dependent CD were enrolled for AZA therapy over a 7-year period. The average dose of AZA was 2.0-3.0 mg/kg per day, adjusted according to clinical response and occurrence of adverse effects. Steroid therapy was tapered off according to a predefined schedule. Long-term outcome and adverse reactions were evaluated. RESULTS: Sixty-nine patients were prospectively included. Steroid-free remission was achieved in 68-81% of patients, partial response in 14.5-27.3% and failure to respond to AZA in 4-15.9% over the initial 48 months. However, the rate of wean from steroid therapy decreased to 53-60% while the rate of failure increased from 6.7% to 17.6% after this period. A breakthrough of symptoms during continuous AZA therapy was common, particularly after 48 months on AZA. The mean leukocyte count at the end of 12 months of therapy was significantly lower in patients who achieved complete response on AZA than in the non-responders (5197 +/- 1250 cells/mm(3) vs 8340 +/- 1310 cells/mm(3), respectively; P < 0.01). Azathioprine was relatively well-tolerated and the incidence of serious adverse effects was small. CONCLUSIONS: Azathioprine was relatively safe and moderately effective for long-term maintenance of steroid-free clinical remission in corticosteroid-dependent CD patients. Patients were more successfully weaned from prednisone treatment, and clinical remission was more often maintained during the first 48 months of AZA therapy. A significant decrease in the white blood cell count at the end of 12 months on AZA was the single factor associated with weaning from steroid dependence.

Oral refeeding in patients with mild acute pancreatitis: prevalence and risk factors of relapsing abdominal pain.

BACKGROUND AND AIM: In acute pancreatitis (AP), oral refeeding may stimulate pancreatic secretion, increasing the inflammation of the glandular tissue causing relapse of abdominal pain or even exacerbation of the disease. This study aimed to assess the prevalence and risk factors of abdominal pain relapse over oral refeeding in patients convalescing with AP as well as the impact of pain recurrence on the hospital stay. METHODS: Inclusion criteria were AP confirmed by biochemical and/or radiological data in the absence of severe disease or extensive necrosis. The same diet was offered to all patients during oral refeeding. Demographic, clinical, biochemical and radiological data were prospectively recorded and analyzed. RESULTS: A total of 130 patients were included. During the oral refeeding period, 32 (24.6%) patients had pain relapse, which was more common on days 1 (68.8%) and 2 (28.1%). Pain relapse was related to higher serum levels of lipase on the day before refeeding, higher serum levels of C-reactive protein on the fourth day, and presence of peripancreatic fluid collections (P < 0.01). Pain relapse significantly increased total hospital stay (P < 0.01). CONCLUSIONS: In patients with mild AP, pain relapse during oral refeeding was relatively high (24.6%), particularly on the first or second day. Their risk appeared be associated with more intense or persistent pancreatic inflammation on the day before refeeding, and presence of peripancreatic fluid collections. Pain relapse increased hospital stay, and likely overall costs on disease treatment.

Hereditary hemochromatosis: population screening based on phenotype in Brazilian blood donors.

GOALS: A population of blood donors was screened for hereditary hemochromatosis (HH) based on the phenotype strategy in accordance with the European consensus. STUDY: Nonfasting serum samples were obtained from 1,050 donors. Transferrin saturation (TS) was measured using a threshold of 45%. Donors with a TS > or = 45% were retested in a fasting sample. If TS was elevated, the participants were tested for iron overload by ferritin measurement followed by genetic testing. All donors underwent clinical and laboratory workup for expression of the disease. RESULTS: A total of 775 (74.6%) of the donors were men, 749 (72.1%) white, and had a mean age of 30 years (range, 8-60 years). Mean +/- SD TS was 25.9% +/- 13.1% (range, 2.1%-85.8%), and there were 58 (5.6%) donors with a TS > or = 45%. Fifty-four subjects had a repeat TS in a fasting serum sample with a mean +/- SD TS of 32.1% +/-16.1% (range, 15.4%-63.0%), and 12 donors had a TS > or = 45%. Ten complied with genetic testing and ferritin measurement. The study found four donors with HH-related mutations (C282Y and/or H63D); therefore, a gene allele frequency of 0.4%. Only the C282Y homozygote had diagnostic criteria for HH, defining a disease frequency of 0.1%. None of the donors who were mutations carriers had clinical or laboratory manifestations of organic injury. CONCLUSION: We conclude that this is a feasible screening strategy that, by timely diagnosing HH, allows patients not only to benefit from effective treatment but also to have disease progression halted.

Internal pancreatic fistulas: proposal of a management algorithm based on a case series analysis.

BACKGROUND AND AIMS: Internal pancreatic fistulas (IPF) are an uncommon but well-recognized complication of chronic pancreatitis (CP) that are associated with significant morbidity and mortality. Because of their low incidence, management is still controversial. The aims of this study are to report the 8-year experience with IPF management in a Brazil University-affiliated hospital and to propose a management algorithm. STUDY: A centralized diagnostic index was used to retrospectively identify all patients with IPF admitted to a teaching hospital from 1995 to 2003. The patient's medical records were reviewed for clinical features, diagnostic work-up, treatment strategies, response to therapy, and the length of hospital stay. All patients underwent contrast-enhanced computed tomography of the abdomen and endoscopic retrograde cholangiopancreatography, to guide the therapeutic modality to be offered. Conservative therapy included withholding of oral feedings in conjunction with total parenteral nutrition, octreotide subcutaneously, and multiple paracentesis or thoracentesis. Interventional therapy was either endoscopic or surgical. RESULTS: IPF was identified in 11 (7.3%) of 150 patients with CP. They ranged in age from 24 to 47 years (mean 36.1), with a male to female ratio of 10:1. All patients had underlying alcoholic CP. The presentation was pancreatic ascites in 9 patients and pleural effusion in 2 cases. Five patients were undergoing the conservative treatment, all presenting main pancreatic duct (MPD) dilatation; endoscopic placement of transpapillary pancreatic duct stent was performed in 4 patients who presented partial MPD stricture or disruption; surgical therapy was performed in 2 patients exhibiting complete MPD obstruction or disruption. Stents were removed 3 to 6 weeks after initial placement. IPF resolved in 10 of 11 patients (90.9%) within 6 weeks. The resolution of IPF was faster (13 +/- 5 vs. 25 +/- 13 days, P < 0.01) and the length of hospital stay was significantly shorter (17.2 +/- 5.6 vs. 31.2 +/- 4.4 days, P < 0.01) in patients subject to interventional treatment compared with those treated conservatively. There was 1 death due to sepsis in a patient managed conservatively; no death was recorded in the interventional therapy group. There was no recurrence of IPF at a mean follow-up of 38 months. CONCLUSIONS: Our results suggest that interventional therapy should be considered the best approach for the management of IPF in patients presenting MPD disruption or obstruction. Conservative therapy must be reserved for those showing MPD dilatation without ductal disruption or stricture. Early interventional therapy reduced hospital stay and convalescence, which likely resulted in lower healthcare overall costs.

Prevalence and pathogenesis of duodenal ulcer in chronic alcoholic pancreatitis.

BACKGROUND: The prevalence of duodenal ulcer (DU) has been considered high in patients with chronic pancreatitis; however, its pathogenesis is unclear. We hypothesized that Helicobacter pylori infection plays the major pathogenetic role. STUDY: One hundred seven cases (97 men, 10 women) of chronic alcoholic pancreatitis (CAP) were prospectively investigated from 1997 to 2001. One hundred thirty-seven DU patients and 59 nonulcer dyspepsia patients formed the two control groups. Pancreatic function was evaluated by determination of fecal fat excretion and fasting blood glucose concentration. Upper gastrointestinal endoscopy was performed in all patients, and gastric mucosal biopsies were taken for assessment of H. pylori infection with a modified Giemsa stain and rapid urease test. RESULTS: Fifteen (14%) of the 107 patients with CAP had active DU. There was a trend toward an association between the presence of diabetes mellitus and/or steatorrhea and the occurrence of DU in patients with CAP (p = 0.06). The rate of H. pylori infection was significantly higher in patients with CAP and DU than in those with only CAP (86.7% vs. 54.3%, p = 0.02) but the rate similar to that in patients with simple DU (75.2%). Trends toward higher prevalence of H. pylori infection in CAP with DU were noticed when they were compared with the nonulcer dyspepsia group (86.7% vs. 66.1%). There was no significant difference in prevalence of H. pylori between CAP patients without DU and dyspeptic patients (54.3% vs. 66.1%). CONCLUSIONS: These data demonstrate that the prevalence of DU in CAP is relatively high. H. pylori infection seems to play the major pathogenetic role in DU associated with CAP.