A. Rostello

Genetic Polymorphisms of Vitamin D Pathway Predict Antiviral Treatment Outcome in Slow Responder Naïve Patients with Chronic Hepatitis C

Vitamin D serum levels seem to influence antiviral response in chronic hepatitis C. Vitamin D pathway is controlled by genes presenting functional single nucleotide polymorphisms (SNPs). Data regarding the association between these polymorphisms and the rate of sustained viral response (SVR) following antiviral treatment in chronic hepatitis C virus (HCV) infection are largely incomplete. Aim of this study was to evaluate if the carriage of different SNPs of these genes could influence the rate of SVR in patients treated with interferon plus ribavirin. Two hundred and six HCV positive patients treated with PEG-interferon plus ribavirin were retrospectively evaluated. Polymorphic loci rs7041 G>T and rs4588 C>A of the vitamin D transporter GC-globulin, rs10741657 G>A of the vitamin D 25 hydroxylase CYP2R1 and rs10877012 G>T of vitamin D 1-hydroxylase CYP27B1 were genotyped. A genetic model named VDPFA (vitamin D Pathway Functional Alleles) was constructed considering for each patient the sum (from 0 to 8), derived from every functional allele carried, associated with the achievement of SVR. Three groups were identified: those carrying ≤4 VDPFA (N=108), those carrying 5-6 VDPFA (N=78) and those carrying ≥7 VDPFA (N=20). Significant associations were found between the rates of SVR and the VDPFA value both in all (61/108, 53/78, 17/20, p=0.009) and in 1/4-5 HCV genotypes (17/56, 23/43, 6/8, p=0.003). Moreover in patients who don’t achieve rapid viral response (RVR) SVR and VDPFA were found to be in stronger associations in all (12/55, 17/39, 7/9, p<0.001) and in 1/4-5 HCV genotypes (4/41, 12/31, 5/6, p=0.001). VDPFA value ≥7 could aid to select, among RVR negative difficult to treat 1/4-5 HCV genotypes, those achieving SVR. These observations could permit to extend the indication to adopt dual antiviral therapy beyond RVR positivity rule without reducing the chances of SVR.

NMR and MRCP After Secretin Infusion in a Long-Term Comparison Study of Pancreogastro- vs. Pancreojejuno-Duodenopancreatectomy

Context After pylorus-preserving pancreaticoduodenectomy the anastomosis of pancreatic remnant may be done with the stomach (pancreogastric, PGA) or the jejunum (pancreojejunum, PJA). Recently, we have found that, in the long-term, PGA is associated with a more severe impairment of the residual pancreatic function. No data are available on the RNM ability to demonstrate an impairment of the residual pancreatic secretion or morphological changes after surgery. Methods Patients who 6 years ago entered a controlled short term comparison of PGA and PJA were studied by RNM and MRCP after secretin infusion (quantification of residual pancreatic volume, pancreatic duct diameter immediately proximal to the anastomosis, qualitative impairment of secretion), and tests of exocrine (fecal elastase-1, fecal fat balance) function. Two radiologists, blinded to the results of functional parameters, independently scored the residual pancreatic volume, duct diameter and secretin-stimulated secretion. Mean±SEM are shown. The Student’s t test was used. Results We studied 34 patients (16 PGA, 18 PJA; age 56.6±2.7 vs . 57.5±2.5 years; time from surgery 81±5 vs . 80±3 months). PGA was associated with a more severe impairment of steatorrhea than PJA (26.6±4.1 vs . 18.2±3.6 g/day; reference range: 0-7; P<0.01) and of fecal elastase-1 (70.2±25.5 vs . 121.4±6.7 µg/g; P<0.001). RNM showed in PGA a more marked dilatation of the pancreatic duct (diameter 4.63±0.91 vs . 2.50±0.18 mm, P<0.05) and non significant tendency to a smaller residual pancreas (26.3±3.0 vs . 35.9±4.1 mL; P=0.069). There is a power correlation between residual pancreas and steatorrhea. After secretin infusion, the secretion was consistently considered by two different radiologists to be more frequently impaired in PGA (42%) than in PJA (18%; P=0.05, Fisher test). Conclusion The pancreo-gastric anastomosis is associated, in the long run, with more severe morphological and functional impairment of exocrine function than the pancreo-jejunal one. Normal 0 false false false EN-GB X-NONE X-NONE

OC.11.6: IN PATIENTS WITH PANCREO-DUODENAL RESECTION, PANCREO-GASTRO ANASTOMOSIS PRODUCES A MORE SEVERE PANCREATIC DERANGEMENT THAN PANCREO-JEJUNAL ANASTOMOSIS. RESULTS OF A LONG TERM RANDOMISED STUDY

tissue acquisition (EUS-FNTA) utilizing a 19-gauge needle to obtain tissue samples for histological diagnosis and Ki-67 expression in patients with suspected PETs. Material and methods: 25 consecutive patients (mean age 54±15 yrs; M/F 11/14) with suspicious of PETs on previously performed imaging studies who, between August 2009–September 2010, underwent attempted EUS-FNTA using a 19G needle. The collected specimens were placed directly in formalin for histological examination. Results: All patients had a single lesion localized in the pancreatic head in 5, in the uncinate process in 2, in the isthmus in 4, in the body in 5, in the tail in 6, and at the body-tail junction in 3. In 18 patients EUS-FNTA was performed using the conventional linear echoendoscope, while in the other 7 patients the newly developed forward viewing echoendoscope was used. The mean size of the biopsied lesions was 15.6±7.3 mm (range 7-100mm). Overall, EUS-FNTA could be performed in all patients without complications. A mean of 2.7±0.5 passes per patient were performed. Tissue samples for histological examination were retrieved in 23 out of the 25 patients (92%) and were sufficient to make a diagnosis of NETs in all these patients. Ki-67 determination could be performed in 21 of the 23 patients (91.3%) with available tissue from EUS-FNTA. In the 6 patients who underwent surgery, preand post-surgical Ki-67 values were concordant in 4, while in 2 patients upgrading of the Ki-67 in the post-surgical specimen occurred. Conclusions: In patients with suspected PETs, retrieval of tissue specimens with EUS-FNTA using a 19G needle is safe and feasible, with a high diagnostic accuracy even in those with small lesions localized in difficult segment of the pancreas to be sampled. Determination of Ki-67 on tissue samples acquired through this technique can be of help in guiding further management decision.

Diet, Polyps, and Cancer Where is the Truth?

Colorectal cancer (CRC) is among the leading causes of cancer-related mortality in Western countries. As for most other cancers, it is likely that CRC represents an interaction between genetic and environmental factors. Since genetic factors are a cause in only a minority of cases, environmental factors, particularly diet, are probably prevalent. Many studies have shown that an increase in meat consumption produces a clear increase in CRC. However, the difference is mostly in the extreme classes of meat intake (i.e. between people who eat a large amount of meat every day and those who hardly ever eat red meat). Moreover, the difference in risk is only 12-17% for an increase of 100 g/day in meat intake, probably not enough in itself to warrant large-scale campaigns to reduce meat intake. Similar conclusions can be drawn from the relationship between an increase in fruit, fiber, or milk intake and a decrease in CRC. However, all the suggested changes move towards a healthier diet, which also has positive effects on other highly prevalent disorders (cardiovascular, degenerative, and neoplastic). Sound dietary advice should therefore be offered even in the absence of formal evidence-based proof.