Oxygen radical formation does not have an impact in the treatment of severe acute experimental pancreatitis using free cellular hemoglobin

AIM： Microcirculatory dysfunction and free oxygen radicals are important factors in the pathogenesis of severe acute pancreatitis. Additional oxygen delivery might enhance lipid peroxidation but may also improve pancreatic microcirculation. This study assesses the effect of free cellular bovine hemoglobin on the formation of oxygen radicals and microcirculation in a rodent model of severe acute pancreatitis. METHODS： Fifteen minutes after induction of acute pancreatitis Wistar rats received either 0.8 mL bovine hemoglobin （HBOC-200）, hydroxyethyl starch （HES） or 2.4 mL of normal saline to ensure normovolemic substitution. After 6 h of examination the pancreas was excised and rapidly processed for indirect measurement of lipid peroxidation products malondialdehyde （MDA） and reduced glutathione （GSH） in pancreatic tissue. RESULTS： The single application of HBOC-200 improved pancreatic microcirculation and reduced histopathological tissue damage significantly. Tissue concentration of MDA did not differ between the groups. Also no differences in GSH levels were detected.CONCLUSION： Though the single application of HBOC-200 and HES improve pancreatic microcirculation, no differences in lipid peroxidation products were detected. The beneficial effect of additional oxygen supply （HBOC-200） does not lead to enhanced lipid peroxidation.

Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy

AIM： To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS： Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three （41%） of the 106 patients were staged as pT1/2, 63 （59%） as pT3/4, 51 （48%） as pNo, and 55 （52%） as pN1. The study population included 59 （56%） patients exhibiting G1/2, and 47 （44%） patients with G3 tumors. Patients received no adjuvant chemoor radiation therapy and were followed up for a median of 12 （range： 3.5 to 139） mo.RESULTS： Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as ＂tumor free＂ by conventional histopathology in 73 （69%） out of the 106 patients. Twenty-nine （57%） of 51 patients staged histopathologically as pNo had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free （relative risk 2.92, P = 0.005） and overall （relative risk 2.49, P = 0.009） survival. CONCLUSION： The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports stratification of patients with may help to improve risk pancreatic cancer.

Obesity research: Status quo and future outlooks

Obesity is a multifactorial disease showing a pandemic increase within the last decades in developing, and developed countries. It is associated with several severe comorbidities such as type Ⅱ diabetes, hypertension, sleep apnea, non-alcoholic steatosis hepatis and cancer. Due to the increasing number of overweight individuals worldwide, research in the field of obesity has become more vital than ever. Currently, great efforts are spend to understand this complex disease from a biological, psychological and sociological angle. Further insights of obesity research come from bariatric surgery that provides new information regarding hormonal changes during weight loss. The initiation of programs for obesity treatment, both interventional and pharmaceutical, are being pursued with the fullest intensity. Currently, bariatric surgery is the most effective therapy for weight loss and resolution of comorbidities in morbid obese patients. Reasons for weight loss and remission of comorbidities following Roux-en-Y-Gastric Bypass,Sleeve Gastrectomy, and other bariatric procedures are therefore under intense investigation. In this review, however, we will focus on obesity treatment, highlighting new insights and future trends of gut hormone research, the relation of obesity and cancer development via the obesity induced chronic state of inflammation, and new potential concepts of interventional and conservative obesity treatment.

Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients

AIM: To verify and expand the known spectrum of serine protease inhibitor Kazal type 1 (SPINK1) gene mutations in chronic pancreatitis. METHODS: DNA extracted from 172 chronic pancreatitis patients was assayed for SPINK1 gene mutations by PCR and DNA sequencing. A control cohort of 90 unrelated healthy individuals was analysed by the same methods for presence of common populational polymorphisms, and frequency of five-loci haplotypes was calculated. Linkages of gene aberrations in single SPINK1 gene copies were analysed by long-distance PCR followed by allele-specifi c PCR and DNA sequencing. RESULTS: The most frequent SPINK1 gene mutation N34S was found at a frequency of 6%. Furthermore, we detected the heterozygous intervening sequence (IVS) 3 + 2 T > C mutated gene in 2 German patients and 1 Macedonian chronic pancreatitis patient. In all three SPINK1 gene copies an additional rare base substitution was found: 5’untranslated region (UTR)-215 G > A. Poly-morphism analysis revealed that all three affected genes carried the same fi ve-loci haplotype. DNA sequencing of another chronic pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any mutations in these 3 pa-tients.CONCLUSION: We found in 3 (2%) of 172 chronic pancreatitis patients an IVS3 + 2 T > C SPINK1 gene mutation and a base substitution 5’UTR-215 G > A inthe same gene copy. Most probably the 5’UTR-215 G >A represents a rare polymorphism and not a mutationas previously concluded. Haplotype analysis suggests acommon origin of the IVS3 + 2 T > C mutation in thesepatients.