Genetic Variants in the Manganese Superoxide Dismutase 2 Gene and in the Catalase Gene are not Associated With Alcoholic Chronic Pancreatitis.

AIMS: Oxidative stress may contribute to the development of chronic pancreatitis (CP). The enzymes manganese superoxide dismutase 2 (MnSOD, SOD2) and catalase (CAT) counteract free radical activity within the mitochondria and the cytosol. Moreover, CAT activity contributes to the transformation of ethanol to acetaldehyde, a toxic intermediate product of ethanol metabolism, which has been associated with pancreatic damage. Common functional polymorphisms have been described in the MnSOD gene [rs4880, NM_000636.3:c.47 T > C, alanine (ALA) to valine (Val)] and in the CAT promoter region [rs1001179, NG_013339.1:g.4760 C > T]. We investigated whether these polymorphisms are associated with alcoholic CP. METHODS: We genotyped 470 patients with alcoholic CP for these MnSOD and CAT polymorphisms. We also analysed these variants in 357 healthy control subjects, and in an additional control group of 113 individuals with non-alcoholic CP. We used the age at onset of CP as marker of disease severity and investigated whether different genotypes are associated with different ages at onset. In patients with alcoholic CP, we investigated whether an interaction exists between smoking behaviour and genotypes by comparing genotype distributions in smokers and non-smokers. RESULTS: We did not observe significant differences of genotype frequencies between patient groups and controls. In patient groups, we did not find significant differences in the ages at onset between different genotypes. We did not observe an interaction between these polymorphisms. We did not find an association of these variants with smoking behaviour. CONCLUSIONS: The investigated MnSOD and CAT polymorphisms do not predispose to the development of alcoholic CP. SHORT SUMMARY: Patients with alcoholic pancreatitis and controls were genotyped for polymorphisms in oxidative stress genes. There were no significant differences of genotype frequencies between patients and controls, and no association with the age at onset of disease was observed. The polymorphisms are not associated with the development of alcoholic pancreatitis.

Non-Invasive Assessment of Inflammation and Treatment Response in Patients with Crohn's Disease and Ulcerative Colitis using Contrast-Enhanced Ultrasonography Quantification.

BACKGROUND AND AIM: Novel biological therapies in Crohn's disease (CD) or Ulcerative colitis (UC) require a proper follow-up for the assessment of bowel inflammation. While endoscopy is the standard method, the imaging techniques using contrast, particularly contrast enhanced ultrasonography (CEUS), are better tolerated by the patients and can be used more frequently. Our aim was to find the usefulness of dynamic CEUS quantification as compared to endoscopy in the assessment of disease activity and in the follow-up under therapy of the patients suffering from either CD or UC. METHOD: We have prospectively evaluated 67 patients with UC and 46 with CD, diagnosed by ileo-colonoscopy and biopsy, comparing the endoscopic scores with clinical scores, C reactive protein (CRP), intestinal wall thickness, layer scores after CEUS and TIC parameters (using SonoLiver® software - Imax, RT, TTP, mTT and AUC). For 25 patients with UC and 13 with CD we performed comparisons of the parameters before and after 3 months of treatment and correlated them with the changes in the endoscopic scores. RESULTS: For UC, time-intensity curves (TIC) volume parameters (AUC) correlated better with endoscopy (ρ=0.64) than the clinical score (ρ =0.62). Other parameters such as CRP and thickness showed significant but less strong correlation, while TIC flow parameters (RT, TTP and mTT) did not show a significant correlation. Results were similar for CD (ρ=0.64 for Imax vs ρ=0.58 for CDAI). The best predictor for endoscopic improvement in both UC and CD was ln(AUC), with a Wilcoxon Z score of 3.76 and 2.61, respectively. There was also a good correlation between the difference of its values and the difference in endoscopic scores before and after the treatment (rho is 0.68 in UC and 0.73 in CD).

Bleeding Dieulafoy's-like lesions of the gut identified by capsule endoscopy.

Dieulafoy's-like lesions (DLs-like) represent a cause of obscure gastrointestinal bleeding, enteroscopy being the main diagnostic and therapeutic procedure. Frequently, more than one enteroscopy is needed to identify the bleeding vessel. In our practice, video capsule endoscopy (VCE) identified and guided therapy in four cases of DLs-like; three of them were localized on the small bowel. We report, for the first time, a diagnosis of colonic DL-like performed by colon capsule endoscopy. Two patients presented with severe cardiovascular disorders, being hemodynamically unstable during VCE examination. Based on the VCE findings, only one invasive therapeutic procedure per patient was necessary to achieve hemostasis. VCE and enteroscopy may be regarded as complementary procedures in patients with gut DLs-like.

Survival and quality of life of cholangiocarcinoma patients: a prospective study over a 4 year period.

BACKGROUND AND AIMS: Cholangiocarcinomas (CCAs) are tumors with a poor prognosis and a lower quality of life (QoL). The aim of this study was to evaluate the survival rate and quality of life in CCA patients. METHOD: We prospectively enrolled 133 patients diagnosed with CCA in the 3rd Medical Clinic, Cluj Napoca, over a 4-year period (2005-2009). The QoL was evaluated by means of a QoL questionnaire (EORTC QLQ-C30). RESULTS: The mean age of the patients was 65 +/- 10.6 years: 55% were males. 71% of the patients had hilar tumor (Klatskin), 23% distal and 6% intrahepatic CCA (IH). Only 11.3% of the patients were eligible to receive curative treatment. The 1-year overall survival was 22.3 +/- 4.4% and the 2-year survival was 3.4 +/- 2.1%. The patients receiving metallic stents had better survival than those receiving plastic stents (40.4% vs 12.5% at 1 year, 9.1% vs 5.0% at 2 years, respectively). The 1-year survival was significantly improved for patients who underwent surgery plus adjuvant chemotherapy. The post-therapy QoL demonstrated a less improvement in Klatskin tumor patients than in patients with other types of tumors. Endoscopic palliative therapy allowed a faster community reintegration, but with variable evolution. CONCLUSIONS: The highest 2-year survival rate was 5.5%. Slightly longer survival was recorded when chemotherapy was added and also after endoscopic placement of metallic stents. Endoscopic biliary decompression improved the QoL faster than surgery.

B-mode and contrast enhanced ultrasound guided biopsy of portal vein thrombosis. Value in the diagnosis of occult hepatocellular carcinoma in liver cirrhosis.

AIM: The ultrasonographic (US) detection of hepatocellular carcinoma (HCC) in patients with liver cirrhosis is based on the visualization of focal lesions. However, in some cases HCC cannot be clearly identified at US, the only sign being a portal vein thrombosis (PVT). Contrast enhanced ultrasound (CEUS) is an excellent method to characterise focal lesions and portal thrombosis in patients with liver cirrhosis. The aim of the study was to assess the value of US and CEUS -guided PVT core biopsy in the diagnosis of an occult HCC in patients with cirrhosis. MATERIAL AND METHODS: Twenty patients with cirrhosis, PVT and no focal lesion on high-resolution US were studied. In 17 cases the thrombus was interpreted as malignant at US. All patients had normal coagulation parameters. The biopsies of an intrahepatic PVT were performed using an 18G Bard needle coupled on "Biopty Gun".US and CEUS guidance was used in16 respectively 4 patients. In 10 cases with a very inhomogeneous hepatic echostructure near the PVT (coarse echo pattern) a liver biopsy from that area was performed. RESULTS: Adequate histological specimens were obtained in all cases, requiring 1 to 2 passes (mean 1.5 per patient). Only 1 patient had severe pain. No major complications were detected. The overall sensitivity of core biopsy in the diagnosis of malignant PVT was 94.4 % (17/18). The sensitivities of US and CEUS guided PVT biopsy were 92.8% (13/14) and 100% (4/4) respectively. In 6 of 10 cases with coarse echo pattern the same type of HCC was found in the surrounding parenchyma. No false positive results were noted. CONCLUSIONS: US-guided core biopsy of PVT is a safe and useful technique in the diagnosis of occult HCC in cirrhosis and should be performed in all cases with PVT with malignant US features and no evidence of focal lesions. The "coarse echo pattern" found in the vicinity of a malignant thrombus is frequently the expression of an inapparent, occult HCC. CEUS guided PVT biopsy is a new, promising method with excellent results in establishing the nature of a portal thrombus.

Quantitative analysis of tissue perfusion using contrast-enhanced transabdominal ultrasound (CEUS) in the evaluation of the severity of acute pancreatitis.

INTRODUCTION: contrast enhanced ultrasound provides information on the vascularization of the pancreatic parenchyma, detecting areas of inflammation, necrosis, as well as the residual parenchyma in acute pancreatitis. The AIM of our study was to assess the role of contrast enhanced ultrasound in appreciating the severity of acute pancreatitis by quantitative analysis of the degree of vascularization and the areas of pancreatic parenchymal necrosis. MATERIAL AND METHODS: The study was prospective (December 2008 - April 2010) and included 25 patients with acute pancreatitis. CEUS examination was performed with a Logiq 7 ultrasound machine, using the afferent software for the quantitative analysis of the acoustic signal. RESULTS: The analysis of the average value of the maximum acoustic signal intensity (max I) after contrast injection, and of the mean time to signal enhancement appearance (mT): a) superior mesenteric artery: max I 19.37 +/- 8.53 dB, mT 15.85 +/- 4.6 sec; b) inflammation area: max I 14.76 +/- 6.7 dB, mT 15.15 +/- 3.6 sec; c) necrosis area: max I 8.89 +/- 9.91 dB, mT 22.17 +/- 7.9 sec; d) structural ill-defined hypoechoic area: max I 12.03 +/- 5.4 dB, mT 21.67 +/- 4.47 sec. The comparison of pancreatic necrosis area measured with contrast enhanced ultrasound and CT revealed a 62.5% concordance. CONCLUSIONS: Our study attests the usefulness of CEUS in quantifying the necrosis area in acute pancreatitis, with similar results to those obtained by CT.

Risk factors in chronic pancreatitis.

Chronic pancreatitis is an inflammatory disease followed by structural alterations--inflammation, fibrosis and acinar atrophy--pain emergence, exocrine and endocrine pancreatic insufficiency, severe alteration of quality of life. The pathogenetic mechanisms characteristic to this disease are not thoroughly known, but the identification of some genetic and autoimmune factors in certain entities has elucidated several pathogenetic links. The etiologic risk factors for chronic pancreatitis may associate each other and may cause different evolutions to the disease. By tracing out the risk factors and their typical working mechanisms, further pathogenetic treatments may occur, taking place precociously and preventing the evolution of the disease towards exocrine and endocrine pancreatic insufficiency.

Investigation of the SPINK1 N34S mutation in Romanian patients with alcoholic chronic pancreatitis. A clinical analysis based on the criteria of the M-ANNHEIM classification.

BACKGROUND AND AIMS: The N34S mutation in the serine protease inhibitor Kazal type I (SPINK1) gene has been associated with chronic pancreatitis. Clinical data about the phenotypic expression of alcoholic chronic pancreatitis with the N34S variant are limited. The prevalence of the N34S mutation in patients with chronic pancreatitis and healthy individuals from Eastern Europe is unknown. METHODS: We studied Romanian patients with chronic pancreatitis and investigated the clinical presentation in patients with N34S mutation. The SPINK1 N34S variant was analysed in 94 chronic pancreatitis patients and 96 healthy controls by an allele specific PCR method and a restriction fragment length polymorphism method. A meta-analysis was conducted with previous N34S association studies. The clinical course of alcoholic pancreatitis was evaluated according to the severity criteria of the M-ANNHEIM classification system of chronic pancreatitis. RESULTS: A heterozygous N34S mutation was found in 1 of 96 healthy individuals (1%) and in 4 of 80 patients (5%) with alcoholic chronic pancreatitis. The meta-analysis confirmed the status of N34S as a risk factor for the development of alcoholic chronic pancreatitis (OR=5.3). However, the clinical course of the disease was similar in patients with and without N34S mutation. CONCLUSION: The N34S mutation is a weak risk factor for alcoholic chronic pancreatitis.

Contrast-enhanced ultrasound of the pancreas--a method beyond its potential or a new diagnostic standard?

Contrast-enhanced ultrasound is a relatively new technique, currently used for liver tumors diagnosis. Newer contrast agents are composed of stabilized micro-bubbles capable of traversing the capillary circulation. Lately, the method has also been used in the assessment of pancreatic disorders. Pulse inversion harmonic imaging allows the assessment of the hypervascularised masses as neuroendocrine tumors, of the hypoperfused masses as adenocarcinomas and of the necrotic areas in acute pancreatitis. Also, this imaging method allows a better assessment of the pancreatic tumor resectability and the identification of septa inside the cystic lesion. Contrast-enhanced ultrasound might represent a valuable additional imaging method to contrast CT for selected cases.

Risk factors in patients with chronic pancreatitis in Romania.

UNLABELLED: Chronic pancreatitis is due mostly to alcohol consumption in industrialized countries. However, beside alcohol consumption there are other known etiologic risk factors, some patients combining more of them. The aim of our study was to assess the different etiologic risk factors in patients with chronic pancreatitis in Romania. METHODS: There were 94 patients with chronic pancreatitis (CP) enrolled in this prospective study. The diagnosis of CP was established by typical findings on ultrasonography, computed tomography, endoscopic retrograde cholangiography. The visits included a careful history of alcohol use, smoking, drug use, a clinical examination and laboratory tests. The previous hospital records of each patient were reviewed. RESULTS: Out of the 94 patients, 80 had alcoholic chronic pancreatitis (ACP), 10 idiopathic pancreatitis (ICP), 2 patients had obstructive chronic pancreatitis due to pancreas divisum, 1 patient chronic pancreatitis due to hypertriglyceridemia and 1 patient posttraumatic chronic pancreatitis. The most frequent risk factors were alcohol consumption and smoking, the association of these two factors was found in 91% of patients with ACP and a large proportion of patients continued to smoke after diagnosis was established. CONCLUSION: Similar to other countries alcoholic chronic pancreatitis is the most frequent etiology, followed by the idiopathic one. Patients with ICP must be tested for gene mutations in the future. A small proportion of patients have other etiologies like pancreas divisum, which require specific treatment.

Contribution of ultrasound to the diagnosis of chronic pancreatitis and to evaluating its main complications.

Chronic pancreatitis is a disease with a potentially severe evolution due to the pain altering life quality and to the possibility of causing exocrine and endocrine pancreatic insufficiency. Ultrasound represents the main imaging technique to be used in this disease since the identification of pancreatic calcifications has diagnostic significance. Endoscopic ultrasound may sometimes identify parenchymal changes facilitating diagnosis in the early stages of chronic pancreatitis when transabdominal ultrasound and endoscopic retrograde cholangiopancreatography show normal situations or non-characteristic changes.