Marja-Leena Kylänpää

Endoscopic treatment of pancreatic pseudocysts

BackgroundThis study aimed to assess the effectiveness of therapeutic endoscopy in the treatment of pancreatic pseudocysts, and to define factors limiting endoscopic therapy.MethodsThe results of therapeutic endoscopy were evaluated for 170 patients with pancreatic pseudocysts treated at the Department of Surgery, Helsinki University Central Hospital, during the 6-year period from 1998 to 2003.ResultsThe therapeutic endoscopy success rate was 86.1%, with 23 (13.9%) patients requiring operative treatment because therapeutic endoscopy was unsuccessful or technically impossible. There was little morbidity and no procedure-related mortality. The majority of the 38 complications, which arose from 380 procedures, could be treated conservatively.ConclusionsEndoscopic methods are safe and effective for the treatment of pancreatic pseudocysts. The indications for surgery include inaccessible pancreatic duct, location, or content of the pseudocyst rendering the problem not amenable to endoscopic therapy, as well as complications of the endoscopic treatment.

Primary Sphincter Repair: Are the Results of the Operation Good Enough?

PURPOSE: This study was designed to evaluate the clinical outcome of primary anal sphincter repair caused by obstetric tears and to analyze possible risk factors associated with sphincter rupture during vaginal delivery. METHODS: A total of 52 females with a third-degree or fourth-degree perineal laceration during vaginal delivery were examined. The symptoms of anal incontinence were obtained by a standard questionnaire. In addition to a clinical examination, endoanal ultrasound, anal manometry, and pudendal nerve terminal motor latency examinations were performed. A control group consisted of 51 primiparous females with no clinically detectable perineal laceration after vaginal delivery. RESULTS: After primary sphincter repair, 31 females (61 percent) had symptoms of anal incontinence. Fecal incontinence occurred in 10 females (20 percent). According to Hardcastle and Parks’ and Jorge and Wexner’s classifications, the study group had more severe symptoms of anal incontinence than the control group (P < 0.001 in both classification groups). In endoanal ultrasound examination, a persistent defect of the external anal sphincter was found in 39 females (75 percent) in the rupture group compared with 10 females (20 percent) in the control group (P < 0.001). Anal sphincter pressures were significantly lower in the rupture group than in the control group. An abnormal presentation was the only risk factor for anal sphincter rupture during vaginal delivery. CONCLUSIONS: After primary sphincter repair, persistent external anal sphincter defect and symptoms of anal incontinence are common in females who have had a primary sphincter repair after vaginal delivery. The means of improving the results of primary repair should be studied further.

The endoscopic management of pancreatic fistulas.

BackgroundInterest in the use of therapeutic endoscopy for the treatment of pancreatic diseases has been on the increase for several years. Our aim was to assess the efficacy of endoscopic retrograde cholangiopancreaticography (ERCP) in the treatment of pancreatic fistulas.MethodsWe evaluated the results of therapeutic ERCP in 50 patients with pancreatic fistula treated at the Helsinki University Central Hospital from 1998 to 2003.ResultsThe success rate of fistula closure after therapeutic ERCP was 82%. Five patients required operative treatment when ERCP was unsuccessful. There was little morbidity and no procedure-related mortality. Four patients died because severe illnesses made them unfit for any further procedures.ConclusionERCP is a safe and effective modality and should be considered as first-line therapy in the management of pancreatic fistula.

Mutations N34S and P55S of the SPINK1 gene in patients with chronic pancreatitis or pancreatic cancer and in healthy subjects: A report from Finland

Objective Mutations in the Kazal type 1 serine protease inhibitor (SPINK1) gene have recently been associated with chronic pancreatitis (CP), an established risk factor for pancreatic cancer. The aim of this study was to investigate the frequency of the SPINK1 gene mutations (N34S and P55S) in patients with CP, or pancreatic cancer, and in healthy subjects in Finland. Material and methods The N34S and P55S mutations were determined by PCR amplification followed by solid-phase minisequencing in 116 patients with CP and in 188 with pancreatic cancer. In patients with CP, alcohol was the aetiological factor in 87 (75%), pancreas divisum in 4 (3%), gallstones in 5 (5%) and 20 patients (17%) had an idiopathic disease; 459 healthy individuals were enrolled as controls. Results The frequency of the N34S mutation was significantly higher in patients with CP (14/116, 12%) than in controls (12/459, 2.6%) (p<0.0001). There was no difference in the frequency of the P55S mutation between patients with CP (1/116, 0.9%) and controls (6/459, 1.3%). The N34S mutation was present in 9 (10%) out of 87 patients with alcoholic CP, and in 5 (25%) patients with idiopathic CP. No SPINK1 mutations were found in patients with CP caused by anatomical variations or gallstones. Among the 188 patients with a pancreatic malignant tumour, the N34S mutation was present in 7 cases (3.7%). The frequency of the N34S mutation in healthy controls in this study was significantly higher than earlier reported in other countries (p=0.03). Conclusions The SPINK1 N34S mutation was significantly associated with an increased risk of CP. The association of the N34S mutation with alcoholic CP was marginally stronger than in earlier studies, whereas in the Finnish population in general, this mutation was significantly more frequent than reported elsewhere.

Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutations in Patients With Acute Pancreatitis

Objectives: Mutations in the secretory trypsin inhibitor (SPINK1) gene have been found to be associated with hereditary and chronic pancreatitis. There are no previous reports on SPINK1 mutations in patients with acute pancreatitis (AP). Methods: The study population consists of 371 patients with AP, of which 207 patients had mild and 164 had a severe form of the disease. The etiologies of AP were identified. Four hundred fifty-nine blood donors served as controls. SPINK1 N34S and P55S mutations were detected by minisequencing and confirmed by direct sequencing. Results: The N34S mutation was found in 29 (7.8%) of the patients and in 12 (2.6%) of the controls (P < 0.0001, Fisher exact test). There was no difference in the frequency of the P55SS mutation between the groups. A majority of the patients (n = 229; 61.7%) had alcohol-induced AP. The frequency of the N34S mutation was higher in the subgroups of severe AP (15/164; 9.1%) and alcohol-induced AP (21/229; 9.2%), but the differences were not statistically significant. No differences in age at admission and number of attacks of AP were observed between the groups. Conclusion: SPINK1 N34S mutation enhances the susceptibility of AP.

Monocyte anergy is present in patients with severe acute pancreatitis and is significantly alleviated by granulocyte-macrophage colony-stimulating factor and interferon-gamma in vitro.

Objectives: Severe acute pancreatitis (AP) is frequently associated with immune suppression, which increases the risk of infections, organ failure, and death. Our aims were to measure monocyte function (ie, HLA-DR expression and tumor necrosis factor-α [TNF-α] production as markers of immune suppression) in patients with severe AP and to determine whether treatment of blood samples with granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interferon-γ (IFN-γ) corrected the functional defects of monocytes in vitro. Methods: The study consisted of 28 patients with severe AP who were treated at intensive care unit and in whom the proportion of HLA-DR-positive monocytes in the circulation was less than 70%, and 28 matched control subjects who were selected from healthy laboratory personnel. HLA-DR density was determined by whole blood flow cytometry. Monocyte TNF-α production in response to bacterial lipopolysaccharides (LPSs) was studied in a whole blood assay. Aliquots of blood were supplemented with IFN-γ (all 28 patients), GM-CSF (the last 24 patients), or both (the last 12 patients). Results: The median proportion of HLA-DR-positive monocytes was 45% in patients (range, 18%-73%) and was 98% in controls (range, 86%-100%; P < 0.001). TNF-α levels in response to LPSs were lower in patients (545 pg/mL; range, 84-1990 pg/mL) than in controls (1415 pg/mL; range, 660-5490 pg/mL; P < 0.001). The proportion of HLA-DR-positive cells correlated positively with TNF-α levels (r = 0.56; P < 0.01). Both GM-CSF and IFN-γ increased HLA-DR expression of monocytes in patients (98%; range, 74%-100% for GM-CSF; 99%; range, 86%-100% for IFN-γ; both P < 0.001). The combination restored monocyte HLA-DR expression (99%; range, 96%-100%; P = 0.002). Compared with basal levels, GM-CSF increased TNF-α production of monocytes both in blood samples from patients (median, 1320 pg/mL; range, 35-8015 pg/mL) and controls (median, 3450 pg/mL; range, 1040-9835 pg/mL; both P < 0.001). IFN-γ increased TNF-α production by monocytes in patients (683 pg/mL; range, 186-2705 pg/mL; P < 0.05) but not in controls (1658 pg/mL; range, 765-4755 pg/mL; P = 0.31). With the combination of GM-CSF and IFN-γ, the TNF-α levels of monocytes in patients (3185 pg/mL; range, 545-8280 pg/mL) and in controls (2800 pg/mL; range, 1080-6860 pg/mL) were comparable. Conclusions: The proportion of HLA-DR-positive monocytes correlates with TNF-α production, and they both reflect the degree of immune suppression. The low proportion of HLA-DR-positive monocytes in AP can be reversed in vitro by GM-CSF and/or IFN-γ. The GM-CSF and IFN-γ treatments also increase LPS-induced TNF-α production. By the combination of GM-CSF and IFN-γ, but not by either agent alone, LPS-induced TNF-α production of monocytes was equally high in patients and in controls.

Sphincter rupture and anal incontinence after first vaginal delivery

Background.  The aim of this prospective study was to establish the incidence of anal incontinence and sphincter defects after first vaginal delivery.

APCAP - activated protein C in acute pancreatitis: a double-blind randomized human pilot trial

IntroductionPrevious human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP.MethodsA prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (Days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means (DIM, 95% CIs) and regarding categorical variables with Fishers exact test. For all comparisons P < 0.05 was considered significant.ResultsNo serious bleeding was detected clinically or by CT scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found (difference in means (DIM) +2.3, 95% CI -0.7 to +5.3). Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside the hospital were detected.ConclusionsNo serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.Trial registrationClinicalTrials.gov NCT01017107.

Polymorphisms of the Tnf, Cd14, and Hspa1b Genes in Patients With Acute Alcohol-induced Pancreatitis

Objectives: Genotype assessment has been suggested to be a tool for predicting disease severity in acute pancreatitis (AP). To study this hypothesis, we performed genotype analysis of tumor necrosis factor (TNF) −308 A/G, CD14 −159C/T, and HSPA1B +1267 A/G polymorphisms. Methods: This is a case-control association study of 397 patients with AP (214 of whom had an alcohol-induced AP) and 300 controls. The control group comprised 218 subjects with detailed data of alcohol consumption, 70 of whom were heavy drinkers (daily alcohol intake >40 g), and 92 blood donors. The severity of AP was determined according to the Atlanta classification. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-assisted genotyping method. Results: Major allele frequency in TNF gene was 0.87 for patients with AP and 0.86 for controls. For CD14, the gene major allele frequency was 0.60 for patients and 0.63 for controls. For HSPA1B, the major allele frequencies were 0.52 for patients and 0.49 for controls, respectively. The allele frequencies did not differ significantly between AP patients with organ failure and those with mild disease, patients with alcohol-induced AP, or those with biliary AP. The patients with septic infectious complications (n = 47) had genotype distribution no different from those with mild, uncomplicated disease (n = 245). Conclusions: The TNF, CD14, and HSPA1B polymorphisms studied seem not to play a role in determining the severity of AP or the risk of alcohol-induced AP and thus do not serve as a tool for predicting disease severity.

Serum levels of mast cell tryptase, vascular endothelial growth factor, and basic fibroblast growth factor in patients with acute pancreatitis.

Purpose Mast cell tryptase, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) possibly play a role in the pathogenesis of acute pancreatitis (AP). The aim is to describe their serum levels in relation to severity of AP. Methods Seventy patients with AP were studied. Thirty-one had mild acute pancreatitis and 39 severe AP of whom 21 developed organ dysfunction. Serum concentration of tryptase was determined with fluoroimmunoassay (UniCAP), and VEGF and bFGF with ELISA at admission and on days 1, 2, and 7 post-hospitalization. Results The peak tryptase levels and tryptase levels at 2nd day after symptom onset, although mostly within normal range, were significantly higher in patients with organ dysfunction than in patients without organ dysfunction (6.6 &mgr;g/l (inter quartile range 4.8 to 12.6) versus 4.0 &mgr;g/l (2.7 to 6.2); P = 0.018 and 6.0 &mgr;g/l (4.4 to 7.6) versus 3.4 &mgr;g/l (2.3 to 4.8); P = 0.006, respectively). Median serum VEGF and bFGF concentrations increased during follow-up, were significantly higher on day 7 than on days 0, 1, and 2, but were not related to development of organ dysfunction. Conclusions Mast cell activation, as defined by serum tryptase levels, may play a role in the development of remote organ dysfunction in patients with AP. However, neither tryptase nor the factors VEGF and bFGF serve as predictors of organ dysfunction in clinical AP.