Clinical and socioeconomic determinants of survival in biliary tract adenocarcinomas

BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival outcomes.Currently,there is limited data investigating the significance of socioeconomic status,race/ethnicity,and environmental factors in biliary tract cancer survival.Data from the Surveillance,Epidemiology,and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to 2016.Socioe-conomic data included smoking,poverty level,education,adjusted household income,and percentage of foreign-born persons and urban population.Survival was calculated with Cox proportional hazards models for death in the 5-year period following diagnosis.RESULTS Our study included 15883 gallbladder,11466 intrahepatic biliary,12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma cases.When analyzing county-specific demographics,patients from counties with higher incomes were associated with higher survival rates[hazard ratio(HR)=0.97,P<0.05].Similarly,counties with a higher percentage of patients with a college level education and counties with a higher urban population had higher 5-year survival rates(HR=0.96,P=0.002 and HR=0.97,P=0.004,respectively).CONCLUSION Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.

Endoscopic submucosal dissection vs endoscopic mucosal resection for early gastric cancer: A meta-analysis

AIM: To compare endoscopic submucosal dissection(ESD) and endoscopic mucosal resection(EMR) for early gastric cancer(EGC).METHODS: Computerized bibliographic search was performed on PubMed/Medline, Embase, Google Schol-ar and Cochrane library databases. Quality of each included study was assessed according to current Co-chrane guidelines. Primary endpoints were en bloc re-section rate and histologically complete resection rate. Secondary endpoints were length of procedure, post-treatment bleeding, post-procedural perforation and re-currence rate. Comparisons between the two treatment groups across all the included studies were performed by using Mantel-Haenszel test for fixed-effects mod-els(in case of low heterogeneity) or DerSimonian and Laird test for random-effects models(in case of high heterogeneity).RESULTS: Ten retrospective studies(8 full text and 2 abstracts) were included in the meta-analysis. Overall data on 4328 lesions, 1916 in the ESD and 2412 in the EMR group were pooled and analyzed. The mean operation time was longer for ESD than for EMR(stan-dardized mean difference 1.73, 95%CI: 0.52-2.95, P =0.005) and the "en bloc " and histological complete re-section rates were significantly higher in the ESD group [OR = 9.69(95%CI: 7.74-12.13), P < 0.001 and OR = 5.66,(95%CI: 2.92-10.96), P < 0.001, respectively]. As a consequence of its greater radicality, ESD provided lower recurrence rate [OR = 0.09,(95%CI: 0.05-0.17), P < 0.001]. Among complications, perforation rate was significantly higher after ESD [OR = 4.67,(95%CI, 2.77-7.87), P < 0.001] whereas the bleeding incidences did not differ between the two techniques [OR = 1.49(0.6-3.71), P = 0.39].CONCLUSION: In the endoscopic therapy of EGC, ESD showed a superior efficacy but higher complication rate with respect to EMR.

Therapeutic application of stem cells in gastroenterology:An up-date

Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells has expanded enormously and holds therapeutic promises for many patients suffering from currently disabling diseases. This paper focuses on the possible use of stem cells in the two main clinical settings in gastro-enterology, i.e., hepatic and intestinal diseases, which have a strong impact on public health worldwide. Despite encouraging results obtained in both regenerative medicine and immunemediated conditions,further studies are needed to fully understand the biology of stem cellsand carefully assess their put ativeonco- genicproperties.Moreover,there searchonstemcellsarousesferventethical,socialandpoliticaldebate.TheItalianSocietyofGastroenterologysponsoredaworkshoponstemcellsheldinVeronaduringtheⅩⅥCongressoftheFederationofItalianSocietiesofDigestiveDiseases(March 6-9,2010).Here,we report on the issues discussed,including liver and intestinal diseases that may benefit from stemcell therapy,the biology of hepatic and intestinal tissue repair,and stem cell usage inclinical trials.

Drinking plain water is associated with decreased risk of depression and anxiety in adults:Results from a large cross-sectional study

AIM To investigate the relation between plain water drinking and risk of depression and anxiety among a large sample of Iranian adults.METHODS A total of 3327 Iranian general adults were included in this cross-sectional study. Validated Iranian version of the Hospital Anxiety and Depression Scale was used to assess anxiety and depression. Water consumption was assessed by asking about the number of glasses of water that consumed daily. Water consumption was categorized into < 2, 2-5, and ≥ 5 glasses of water/d.RESULTS In the crude model, the lowest level of water drinking(< 2 glasses/d) compared with reference group(≥ 5 glasses/d) doubled the risk of depression and anxiety(P < 0.0001). After adjusting potential confounders, this inverse link remained significant for depression(OR: 1.79; 95%CI: 1.32, 2.42; P < 0.0001), but not for anxiety(OR: 1.49; 95%CI: 0.98, 2.25; P = 0.109). In stratified analyses by sex, after controlling for potential confounders, water drinking < 2 glasses/d was associated with 73% and 54% increment in the risk of depression in men and women, respectively(P < 0.05), whilst no significant association was observed for anxiety either in men or in women.CONCLUSION We found inverse associations between plain water consumption and depression. Also, these findings showed a tended risky association, but not statistically significant, between lower levels of water consumption and anxiety. These findings warrant evaluation in prospective and clinical trials studies to establish the plausible role of water in mental health status.

Current and future antiviral drug therapies of hepatitis B chronic infection

Despite significant improvement in the management of chronic hepatitis B virus(HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon(IFN)-α and monotherapy with five nucleos(t)ide analogues(NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection.

Efficacy and safety of thalidomide in patients with hepatocellular carcinoma

AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment. METHODS: From July 2002 to July 2004, patients with HCC who received thalidomide treatment, were enrolled. We extracted relevant data from the patients’ medical records, including history and type of hepatitis, comorbidity, serum α-fetoprotein (α-FP) level, volumetric changes in tumor, length of survival, and the dose, duration, side effects of thalidomide treatment. The tumor response was evaluated. On the basis of these data, the patients were divided into two groups: those with either partial response or stable disease (PR + SD group) and those with progressive disease (PD group). RESULTS: Two of 42 (5%) patients had a partial tumor response after treatment with thalidomide, 200 mg/d, and 9 (21%) had stable disease. Patients in the PR + SD group all had cirrhosis. Comparing patients with and without cirrhosis, the former were more likely to respond to thalidomide therapy (PR + SD: 100% vs PD: 64.5%, P = 0.041 < 0.05). Thalidomide was significantly more likely to be effective in tumors smaller than 5 cm (PR + SD: 63.6% vs PD: 25.8%, P = 0.034 < 0.05). Compared with patients with progressive disease (PD), patients in the PR + SD group had a higher total dose of thalidomide (13 669.4 ± 8446.0 mg vs 22 022.7 ± 11 461.4 mg, P = 0.023 < 0.05) and a longer survival (181.0 ± 107.1 d vs 304.4 ± 167.1 d, P = 0.047 < 0.05). Patients with comorbid disease had a significantly greater incidence of adverse reactions than those without (93.8% vs 60.0%, P = 0.021 < 0.05). The average number of adverse reactions in each person with a comorbid condition was twice as high as in those without other diseases (2.2 ± 1.3 vs 1.1 ± 1.2; P = 0.022 < 0.05). CONCLUSION: Thalidomide therapy is most likely to beeffective in patients with early stage small HCC, espe- cially in those with other underlying diseases. A low dose (200 mg/d) of thalidomide is recommended to continue the treatment long enough to make it more effective.

Role of soluble triggering receptor expressed on myeloid cells in inflammatory bowel disease

AIM： To investigate the probable role of soluble triggering receptor expressed on myeloid cells-1 （sTREM-1） in the pathogenesis of inflammatory bowel disease （IBD）.METHODS： Fifty-eight patients were enrolled; nineteen healthy volunteers served as controls; 8 patients were diagnosed with Crohn＇s disease, and 31 with ulcerative colitis, Clinical and endoscopic activity indexes of patients with Crohn＇s disease and ulcerative colitis respectively were estimated, Upon admission blood was sampled; sTREM-1 and TNFα were measured by an immunoassay and malondialdehyde （IDA） by the thiobarbitourate assay, after passage through an HPLC system,RESULTS： Median ± SE of TNFα of controls, patients with Crohn＇s disease and patients with ulcerative colitis were 6.02 ± 3.94, 7.98 ± 5.08 （P = NS vs controls）, and 8.45 ± 4.15 ng/L （P = 0.018 vs controls） respectively. Respective values of sTREM-1 were 53.31 ± 32.93, 735.10 ± 197.17 （P = 0.008 vs controls） and 435.82 ± 279.71 ng/L （P = 0.049 vs controls）, sTREM-1 was positively correlated with Crohn＇s disease activity index and clinical and endoscopic activity indexes of ulcerative colitis （P = 0.002, 0.001 and 0.009, respectively）, sTREM-1 of patients with ulcerative colitis was positively correlated with TNFα （P = 0.001）.CONCLUSION： sTREM-1 seems to behave as a novel mediator in IBD in correlation with the degree of the intlammatory reaction of the intestinal mucosa.

Adhesive small bowel obstruction: How long can patients tolerate conservative treatment?

AIM: To evaluate how long patients with small bowel obstruction caused by postoperative adhesions can tolerate conservative treatment.METHODS: The records of patients with small bowel obstruction due to postoperative adhesions were retrospectively reviewed. Data collected included the number of admissions, type of management for each admission,duration of conservative treatment, number of repeat laparotomies, and operative findings.RESULTS: One hundred fifty-five patients with this condition from January 1999 to December 2001, for a total of 293 admissions were enrolled in this study. Medical treatment alone was given in 220 admissions, and repeat laparotomy was performed in 73 admissions. The period of observation in patients managed medically ranged from 2 to 12 days (average: 6.9 days), while for those who underwent surgery,the range was 1 to 14 days (average 5.4 days). At surgery,adhesions were the only finding in 46 cases, while there were intestinal complications in 27, or 9.2 % of all 293admissions. Fever and leukocytosis greater than 15 000/mm3were prediction of intestinal complications.CONCLUSION: With closely monitoring, most patients with small bowel obstruction due to postoperative adhesions could tolerate supportive treatment and recover well averagely within 1 week, although some patients require more than 10 days of observation.

Endoscopic management of chronic radiation proctitis

Chronic radiation proctopathy occurs in 5%-20% of patients following pelvic radiotherapy. Although many cases resolve spontaneously,some lead to chronic symptoms including diarrhea,tenesmus,urgency and persistent rectal bleeding with iron deficiency anemia requiring blood transfusions. Treatments for chronic radiation proctitis remain unsatisfactory and the basis of evidence for various therapies is generally insuff icient. There are very few controlled or prospective trials,and comparisons between therapies are limited because of different evaluation methods. Medical treatments,including formalin,topical sucralfate,5-amino salicylic acid enemas,and short chain fatty acids have been used with limited success.Surgical management is associated with high morbidity and mortality. Endoscopic therapy using modalities such as the heater probe,neodymium:yttrium-aluminium-garnet laser,potassium titanyl phosphate laser and bipolar electrocoagulation has been reported to be of some benef it,but with frequent complications.Argon plasma coagulation is touted to be the preferred endoscopic therapy due to its eff icacy and safety profile.Newer methods of endoscopic ablation such as radiofrequency ablation and cryotherapy have been recently described which may afford broader areas of treatment per application,with lower rate of complications.This review will focus on endoscopic ablation therapies,including such newer modalities,for chronic radiation proctitis.

Effects of six months losartan administration on liver fibrosis in chronic hepatitis C patients: A pilot study

AIM： TO evaluate the safety and efficacy of chronic administration of Iosartan on hepatic fibrosis in chronic hepatitis C patients.METHODS： Fourteen patients with chronic hepatitis C non-responders （n = 10）, with contraindications （n = 2） or lack of compliance （n = 2） to interferon plus ribavirin therapy and liver fibrosis were enrolled. Liver and renal function test, clinical evaluation, and liver biopsies were performed at baseline and after Iosartan administration at a dose of 50 mg/d during the 6 mo. The control group composed of nine patients with the same inclusion criteria and paired liver biopsies （interval 6-14 mo）. Histological activity index （HAI） with fibrosis stage was assessed under blind conditions by means of Ishak＇s score. Subendothelial fibrosis was evaluated by digital image analyses.RESULTS： The changes in the fibrosis stage were significantly different between Iosartan group （decrease of 0.5±1.3） and controls （increase of 0.89±1.27; P〈0.03）. In the treated patients, a decrease in fibrosis stage was observed in 7/14 patients vs 1/9 control patients （P〈0.04）. A decrease in sub-endothelial fibrosis was observed in the Iosartan group. No differences were found in HAI after Iosartan administration. Acute and chronic decreases in systolic arterial pressures （P〈0.05） were observed after the Iosartan administration, without changes in mean arterial pressure or renal function.CONCLUSION： Chronic AT-Ⅱ type 1 receptor （AT1R） blockade may reduce liver fibrosis in patients with chronic hepatitis C.

Monocytes in systematic inflammatory response syndrome:Differences between sepsis and acute pancreatitis

AIM: To unravel the differences between systematic in- flammatory response syndrome (SIRS) of acute pancre- atitis compared to the same syndrome in sepsis. METHODS: Twenty-five patients were enrolled, 12 with sepsis and 13 acute pancreatitis. After diagnosis 20 ml blood was sampled. Half were assayed for isolation of monocytes and 10 ml was centrifuged for serum test of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6). Half of monocytes were incubated in the presence of patients’ serum and supernatants were collected. The other half was treated for estimation of optical photom- etry under caspase-3 inhibition. TNFα and IL-6 were es- timated by an enzyme immunoassay. RESULTS: median ± SE of serum IL-6 in septic patients and acute pancreatitis patients was 192.30 ± 35.40 ng/L and 21.00 ± 16.05 ng/L, respectively (P < 0.01). Re- spective values of caspase-3 were 0.94 ± 0.17 pmol/min 104 cells and 0.34 ± 0.09 pmol/min 104 cells (P < 0.05). IL-6 of monocyte supernatants of patients with sepsis was significantly increased after addition of patients’ serum, while that of patients with acute pancreatitis did not show significant difference. CONCLUSION: The data have shown that monocyte activity is different between acute pancreatitis and sepsis. This phenomenon might be explained as a different pathway to the pro-inflammatory cytokines release or could be a novel anti-inflammatory response in acute pancreatitis.

Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis

AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry. RESULTS: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased. No signs of cell death were observed in the pacemaker region. CONCLUSION: These results are consistent with the hypothesis that a lack of Kit expression may lead to impaired functioning of ICC. Total gastrectomy proves to be curative.

Neurological disorders and inflammatory bowel diseases

Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease(IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.

Noninvasive molecular analysis of Helicobacter pylori : Is it time for tailored first-line therapy?

The main problem of Helicobacter pylori(H. pylori) infection management is linked to antibiotic resistances. This phenomenon has grown in the last decade, inducing a dramatic decline in conventional regimen effectiveness. The causes of resistance are point mutations in bacterial DNA, which interfere with antibiotic mechanism of action, especially clarithromycin and levofloxacin. Therefore, international guidelines have recently discouraged their use in areas with a relevant resistance percentage, suggesting first-line schedules with expected high eradication rates, i.e., bismuth containing or non-bismuth quadruple therapies. These regimens require the daily assumption of a large number of tablets. Consequently, a complete adherence is expected only in subjects who may be motivated by the presence of major disorders. However, an incomplete adherence to antibiotic therapies may lead to resistance onset, since sub-inhibitory concentrations could stimulate the selection of resistant mutants. Of note, a recent meta-analysis suggests that susceptibility tests may be more useful for the choice of first than second-line or rescue treatment. Additionally, susceptibility guided therapy has been demonstrated to be highly effective and superior to empiric treatments by both meta-analyses and recent clinical studies. Conventional susceptibility test is represented by culture and antibiogram. However, the method is not available everywhere mainly for methodology-related factors and fails to detect hetero-resistances. Polymerase chain reaction(PCR)-based, culture-free techniques on gastric biopsy samples are accurate in finding even minimal traces of genotypic resistant strains and hetero-resistant status by the identification of specific point mutations. The need for an invasive endoscopic procedure has been the most important limit to their spread. A further step has, moreover, been the detection of point mutations in bacterial DNA fecal samples. Few studies on clarithromycin susceptibility have shown an overall high sensitivity and specificity when compared with culture or PCR on gastric biopsies. On these bases, two commercial tests are now available although they have shown some controversial findings. A novel PCR method showed a full concordance between tissue and stool results in a preliminary experience. In conclusion, despite poor validation, there is increasing evidence of a potential availability of noninvasive investigations able to detect H. pylori resistances to antibiotics. These kinds of analysis are currently at a very early phase of development and caution should be paid about their clinical application. Only further studies aimed to evaluate their sensitivity and specificity will afford novel data for solid considerations. Nevertheless, noninvasive molecular tests may improve patient compliance, time/cost of infection management and therapeutic outcome. Moreover, the potential risk of a future increase of resistance to quadruple regimens as a consequence of their use on large scale and incomplete patient adherence could be avoided.

Endoscopic appearance of esophageal hematomas

INTRODUCTIONEsophageal hematomas develop from the dissectionof the mucosa from the muscular layers of theesophageal wall and represent an uncommoncondition affecting all ages.Although the mostcommon cause of esophageal hematomas isiatrogenic mechanical injury-induced by prolongednasogastric intubation,difficult or forcefulendoscopic intubation,or the result of

Viral hepatitis prevalence in patients with active and latent tuberculosis

AIM: To assess the prevalence of hepatitis B virus(HBV) and hepatitis C virus(HCV) infection and association with drug induced liver injury(DILI) in patients undergoing anti-tuberculosis(TB) therapy.METHODS: Four hundred and twenty nine patients with newly diagnosed TB- either active disease or latent infection- who were due to commence antiTB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus(HIV) infections- hepatitis B core antigen(HBc Ag), hepatitis B surface antigen(HBs Ag), hepatitis B e antigen, Ig G and Ig M antibody to HBc Ag(anti-HBc), HCV Ig G antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of antiTB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher's exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant.RESULTS: Of the 429 patients, 270(62.9%) had active TB disease and 159(37.1%) had latent TB infection. 61(14.2%) patients had isolated anti-HBc positivity, 11(2.6%) were also HBs Ag positive and 7(1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis(HBs Ag or HCV antibody positive; P = 0.023). Similarly the proportion of HBs Ag positive patients were significantly greater in the active vs latent TB infection group(10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three(5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25(9.5%) patients without; P = 0.04.CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV.

Novel oral-targeted therapies for mucosal healing in ulcerative colitis

Ulcerative colitis(UC), a chronic, relapsing, remitting disease of the colon and rectum, is characterized by inflammatory ulceration of the mucosa. Current UC therapy relies on controlling acute episodes and preventing relapse. To predict modifications in the natural course of UC, mucosal healing(MH) has emerged as a major treatment goal. Endoscopic evaluation is considered the gold standard for assessing MH, which can be achieved by conventional drugs and biologics in many, but not all, patients. Consequently, interest is focusing on the development of new substances for UC therapy, and new oral agents are in the pipeline. This review will focus on the ability of newly developed oral drugs to induce and maintain MH in UC patients.

Usefulness of duodenal biopsy during routine upper gastrointestinal endoscopy for diagnosis of celiac disease

AIM： To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical practice. METHODS： A 15 year-trend （1990 to 2004） in duodenal biopsy performed when undertaking upper gastrointestinal endoscopy was studied. We analysed the prevalence of celiac disease in the overall group, and in the subgroups with anaemia and/or chronic diarrhoea. RESULTS： Duodenal biopsy was performed in 1033 of 13 678 upper gastrointestinal endoscopies （7.6%）; an increase in the use of such was observed over the study period （1.9% in 1990-1994, 5% in 1995-1999 and 12.8% in 2000-2004）. Celiac disease was diagnosed in 22 patients （2.2%）, this being more frequent in women than in men （3% and 1% respectively）. Fourteen out of 514 （2.7%） patients with anaemia, 12 out of 141 （8.5%） with chronic diarrhoea and 8 out of 42 （19%） with anaemia plus chronic diarrhoea had celiac disease. A classical clinical presentation was observed in 55% of the cases, 23% of the patients had associated dermatitis herpetiformis and 64% presented anaemia; 9% were diagnosed by familial screening and 5% by cryptogenetic hypertransaminasaemia. CONCLUSION： Duodenal biopsy undertaken during routine upper gastrointestinal endoscopy in adults, has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of celiac disease in high risk groups such as those with anaemia and/or chronic diarrhoea.

Functional brain imaging of gastrointestinal sensation in health and disease

It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitive- exert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested, mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear, mainly due to a lack of non-invasive methods to study the （neurobiological） mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly, has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective ＆ cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut （brain- gut axis） will be briefly outlined, including brain imaging evidence in healthy volunteers. Second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail. Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.

Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up

AIM: To assess the evolution of duodenal lymphocytosis(DL), a condition characterized by increased intraepithelial lymphocytes(IELs), over 2 years of follow-up.METHODS: Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease(CD) were included. Evaluation of IELs infiltrate in duodenal biopsy sampleswas carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: Ig G and Ig A anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance i m a g i n g w e r e p e r f o r m e d w h e n n e c e s s a r y. R i s k factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR.RESULTS: Eighty-five patients(16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15-25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed Ig G anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity(GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn's disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack of diagnostic evidence. At multivariate analysis, the evolution towards CD was associated with an IELs infiltrate > 25(OR = 1640.4) or 15-25(OR = 16.95), human leukocyte antigen(HLA) DQ2/8(OR = 140.85) or DQA1*0501(OR = 15.36), diarrhea(OR = 5.56) and weakness(OR = 11.57). GS was associated with IELs 15-25(OR = 28.59), autoimmune thyroiditis(OR = 87.63), folate deficiency(OR = 48.53) and diarrhea(OR = 54.87).CONCLUSION: DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS.