Long-term results of combined ESWL and ERCP treatment of chronic calcific pancreatitis

Objective: Extracorporeal shock wave lithotripsy (ESWL) combined with endotherapy (ET) is the standard treatment for pancreatic duct stones (PDS) in chronic pancreatitis (CP). Our aim was to report the short- and long-term results of ESWL and ET.

Material and methods: Consecutively treated 83 patients with symptomatic PDS using ESWL and ET. Success was defined (i) technically: PDS fragmentation and clearance obtained and (ii) clinically: improvement/resolution of pain. To get information on quality of life, we conducted a phone survey whereby we contacted 64 (89%) patients. The long-term results are presented in those patients with ≥2 years follow-up.

Results: Treated PDS with median size of 10 (5–25) mm were located in the head, body, or the tail of the pancreas in 78, 4, and 1 patients, respectively. The primary results were that technical success was achieved in 69 patients (83%) and clinical success in 66 patients (80%). Fourteen patients had technical failure, but eight of them became free of pain. Thus, clinical success can be considered to have been achieved in 74 of 83 patients (89%). In patients with persistent pseudocyst (PC) at the time of ESWL (n?=?19), the PC disappeared in a year in 14 patients (74%). The long-term results were obtained from 61 (73%) ESWL- and ET-treated patients. The median follow-up for them was 53 months (range: 24–124) and 57 patients (93%) became pain-free or had less pain.

Conclusions: For patients with CP and PDS ESWL combined with ET is an effective and safe treatment giving favorable long-term results.     

Diminished IFN-gamma response to diabetes-associated autoantigens in children at diagnosis and during follow up of type 1 diabetes

BACKGROUND: Imbalance of T-helper (Th)1- and Th2-like cytokines has been associated with type 1 diabetes. We therefore studied the immune deviation in antigen-specific T cells from diagnosis onwards in type 1 diabetic children. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 15 children after 4 days, 3 months and 18 months of being diagnosed with type 1 diabetes, from 15 healthy children matched by age and gender to the type 1 diabetic children and from 14 children with and 35 children without HLA-risk genes. Secretion of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was detected by ELISPOT after stimulation with glutamic acid decarboxylase (GAD(65), protein and aa 247-279), recombinant tyrosinphosphatase (IA-2), insulin, ovalbumin and phytohaemagglutinin (PHA). RESULTS: Secretion of IFN-gamma in PBMC stimulated with GAD(65) (p < 0.05), the GAD(65)-peptide (p < 0.01), IA-2 (p < 0.01), and insulin (p < 0.01) was lower in diabetic children at diagnosis than in healthy children. Stimulation of PBMC with GAD(65) and IA-2 decreased the secretion of IFN-gamma in children with HLA-risk genotype. Spontaneous and antigen-induced IFN-gamma secretion increased significantly after diagnosis of the disease, but did not exceed the levels observed in healthy children. Fasting C-peptide levels at diagnosis correlated with insulin-induced IFN-gamma (R = 0.52; p = 0.05) and negatively with spontaneous IL-4 secretion (R = -0.62; p < 0.05). CONCLUSION: A diminished IFN-gamma secretion and the association of fasting C-peptide levels with cytokine response in children with type 1 diabetes suggest that factors related to beta-cell function in type 1 diabetes may modify T-cell function. Thus, the T-cell responses detected at or after diagnosis may not reflect the pathogenic process leading to type 1 diabetes.     

Associations of microalbuminuria and blood pressure with carotid, aortic and femoral atheromatous plaques in elderly Finns

AIMS: To evaluate the possible associations of microalbuminuria (MA) and blood pressure (BP) with the ultrasonographic manifestations of carotid, aortic and femoral atherosclerosis in 65-year-old Finns. METHODS: Ultrasonographic measurements were performed on 54 diabetic subjects, 97 subjects with impaired glucose tolerance (IGT) and 57 normoglycemic subjects (NGT). Urinary albumin and creatinine concentrations were measured from an early morning spot urine sample, and the urinary albumin-to-creatinine ratio (ACR) of > or = 2.5 mg/mmol in men and > or = 3.5 mg/mmol in women was used as a measure of MA. Hypertension was defined as either a systolic BP of > or = 160 mmHg or a diastolic BP of > or = 95 mmHg or being on antihypertensive medication. RESULTS: Eighteen subjects were microalbuminuric and 176 subjects normoalbuminuric. MA was associated with diabetes mellitus and high systolic and diastolic BP. The subjects were divided into two groups according to the median total number of carotid, aortic and femoral plaques: > or = 9 versus 0-8 plaques. A high number of plaques were associated with hypertension, male gender, smoking and MA. When the study subjects were stratified according to hypertension, it turned out that MA was associated with a high number of plaques in hypertensive, but not in nonhypertensive subjects. According to the results of logistic regression analysis with a high number of plaques as the dependent variable, the unadjusted OR for smoking was 6.0 (95% CI 2.4-15.3) in hypertensive subjects. Microalbuminuria was of borderline statistical significance (OR 4.5, 95% CI 0.9-22.9). After adjustment for systolic blood pressure and fasting glucose concentration, the OR for microalbuminuria was reduced to 3.3 (95% CI 0.6-18.4).     

Echocardiographic Imaging of Right Ventricular Outflow Obstruction During Chemotherapy of Mediastinal Lymphoma

Transthoracic echocardiography is a versatile method for imaging cardiac complications caused by mediastinal tumors. Especially, the response to therapeutic measures can be assessed promptly. We present echocardiographic imaging of the regression of right ventricular outflow tract obstruction by chemotherapy.     

Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur

Mantle cell lymphoma (MCL) is a heterogenic non-Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early - based on the median observation time of 4 years - results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation (ASCT), with more than 60% event-free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6·5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event-free survival of 7·4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index (MIPI) and Ki-67-expression were the only independent prognostic factors. Subdivided by the MIPI-Biological Index (MIPI + Ki-67, MIPI-B), more than 70% of patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the patients with high MIPI-B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk-adapted treatment strategy for MCL. The study was registered at www.isrctn.org as ISRCTN 87866680.     

LRP5 in premature adrenarche and in metabolic characteristics of prepubertal children

Objective  Premature adrenarche (PA) is associated with unfavourable metabolic characteristics. We hypothesized that genetic variation in low density lipoprotein (LDL) receptor-related protein 5 (LRP5), which is involved in Wnt signalling in the adrenal cortex and in cholesterol metabolism, plays a role in the pathogenesis of PA.
Design and patients  We performed a cross-sectional association study in 73 Finnish children with PA and 97 age- and gender-matched healthy controls.
Measurements  LRP5 genotypes were determined by direct sequencing. Single-marker associations with clinical-metabolic characteristics, including adrenocortical function, glucose tolerance and lipid profile, were examined with age and gender as covariates.
Results  Nineteen single nucleotide polymorphisms (SNPs) in LRP5 were found in the 170 children. No significant differences in the genotype distributions were observed between the PA and control groups. SNPs A1330V and N740N were associated with higher serum dehydroepiandrosterone sulphate (DHEAS) levels in the control subjects (A/A vs. A/a; mean 0·8 vs. 1·4 µmol/l, P  = 0·01). They were also associated with higher plasma levels of total (4·2 vs. 4·7 mmol/l, P  = 0·02) and LDL cholesterol (2·4 vs. 2·9 mmol/l, P  = 0·02) in the control group, as was SNP V1119V ( P  = 0·04 and P  = 0·03, respectively). SNPs F549F and V1119V were associated with higher systolic blood pressure ( P  = 0·04 and P  = 0·02, respectively). There were no differences in the parameters of glucose metabolism between the genotype groups.
Conclusions  Genetic variation in LRP5 did not predispose to PA but was associated with metabolic characteristics, especially lipid profile, in healthy prepubertal children.