Serotonin transporter and G protein beta 3 subunit gene polymorphisms in Greeks with irritable bowel syndrome.

BACKGROUND: Polymorphisms in the serotonin transporter (SERT) and G protein ß3 subunit (GNB3) genes might contribute to the pathophysiology of irritable bowel syndrome (IBS). Association studies of SERT and GNB3 polymorphisms and IBS have shown diverse results among different populations, which might be due to subject composition differences. AIMS: The aim of the study was to assess the potential association between SERT and GNB3 polymorphisms and IBS in Greeks. METHODS: A total of 124 patients with IBS diagnosed according to the Rome III criteria and 238 healthy individuals were included in the study. SERT and GNB3 gene polymorphisms were genotyped using polymerase chain reaction-based methods. RESULTS: It was shown that the frequencies of the SS genotype and S allele of the serotonin transporter polymorphism were significantly associated with IBS (P = 0.0314 and P = 0.019, respectively). TT genotype and T allele frequencies of G protein ß3 subunit showed also significant difference between the IBS patients and healthy controls IBS (P = 0.0163 and P = 0.0001, respectively). None of the clinical symptoms analyzed was significantly associated with the polymorphisms tested. CONCLUSIONS: The results suggest that SERT and GNB3 gene polymorphisms might be associated with irritable bowel syndrome predisposition in Greeks.

Epithelial cell turnover, p53 and bcl-2 protein expression during oncogenesis of early and advanced gastric cancer in a Western population.

OBJECTIVES: To investigate epithelial cell turnover alterations, and p53, bcl-2 protein expression during development of early and advanced gastric cancer in a Western population. METHODS: We investigated cell apoptosis and proliferation rates, p53 and bcl-2 protein expression in 17 early and 34 advanced gastric carcinomas and in the adjacent non-dysplastic mucosa. Cell proliferation, p53 and bcl-2 expression were detected immunohistochemically using MIB-1, anti-p53 and anti-bcl-2 monoclonal antibodies. Apoptosis was measured by TUNEL. The rate of the positive stained cells (labelling index) was count using image analysis technique. RESULTS: No difference was observed of either apoptotic (10 vs. 11) or proliferation (35 vs. 25) index between early and advanced cancers. However, the apoptotic index was significantly higher in intestinal type advanced tumors. While both apoptotic and proliferation indices were significantly higher in tumors than in the adjacent mucosa, no difference was observed of either apoptotic (2 vs. 2) or proliferation (8 vs. 13) index between the tissues adjacent to early and advanced tumors. p53 protein expression was significantly higher in advanced cancers (7 vs. 5, p=0.001) and in the non-dysplastic tissue adjacent to advanced tumors (3.5 vs. 2, p=0.001). bcl-2 labelling index was significantly higher in the mucosa adjacent to advanced carcinomas (15 vs. 5, p=0.016) but this difference did not reach significance in the tumors (20 vs. 15, p=0.37). CONCLUSIONS: Our data indicate similar cell turnover during tumorigenesis of early and advanced cancer. p53 and bcl-2 protein accumulation is more intense in gastric mucosa adjacent to advanced tumors and p53 immunoreactivity peaks in advanced carcinomas.

Comparison of T- and Z-score in identifying risk factors of osteoporosis in inflammatory bowel disease patients.

OBJECTIVE: Most studies have shown contradictory results regarding predictive factors of osteoporosis in inflammatory bowel disease (IBD). Since in these studies either T- or Z-scores has been used, our aim was to compare T- and Z-score in identifying risk factors of osteoporosis in IBD patients. MATERIALS AND METHODS: Bone density was measured by dual X-ray absorptiometry (DXA) at L2-L4 of the spine and femoral neck in 122 patients. Twenty-two clinical parameters were recorded prior to DXA and evaluated by univariate and multivariate analysis. RESULTS: On multivariate analysis, cumulative steroid dose was a predictive factor of femoral neck T-score (p<0.001) and Z-score (p=0.001). Age was a predictive factor of femoral neck T-score (p<0.001). BMI was a predictive factor of femoral neck Z-score (p=0.03). None of the other 19 variables tested had any predictive value for bone density. Age >or=55 years was a risk factor of low femoral neck T-score (OR 5.08, 95% CI 1.90-13.57, p=0.001), as was cumulative dose of prednisolone >or=5 g (OR 3.41, 95% CI 1.50-7.73, p=0.004). CONCLUSIONS: There is a discordance of results depending on whether T- or Z-scores are used in analysis. Among 22 parameters, cumulative steroid dose and age proved to be the most important factors.

The role of NSAIDs in colon cancer prevention.

Experiments in animals and population-based studies have shown the efficacy of nonsteroidal antiinflammatory drugs in colorectal cancer prevention. COX-2 is overexpressed in dysplastic and neoplastic epithelium. COX-2 is a key-enzyme in several tumorigenic pathways, such as promotion of tumor angiogenesis. Non-selective inhibition of COX enzyme demonstrates a protective effect as well, suggesting that more than one mechanism takes place in neoplastic transformation. Blockade of COX enzyme by NSAIDs down-regulates its metabolic product prostaglandin E2. Inhibition of PGE2 seems to have a negative effect in cancer occurrence. Induction of apoptosis is another mechanism that explains the protective effect of NSAIDs. The recently discovered PPARdelta factor, is also overexpressed in neoplastic tissue, and may be a mediator through which COX-2 exerts its oncogenic effect.

The Bcl-2/Bax system and apoptosis in ulcerative colitis.

BACKGROUND/AIMS: Ulcerative colitis (UC) constitutes a chronic inflammatory process of the colon of unknown etiology. Current data support a pivotal role of apoptosis in the evolution of pathogenesis of UC. We performed a prospective study in order to determine the role of Bcl-2, Bax and Bcl-x in the apoptotic pathway in UC. METHODOLOGY: We included 23 patients with UC and 11 controls. Histological severity of the disease was assessed according to the Sidney classification system. Patients in the UC group were divided in 2 groups according to histological severity of the disease. The TUNEL method was used for the in situ evaluation of apoptosis. Immunohistochemical staining was used for the detection of Bax, Bcl-2, Bcl-x. For the assessment of cellular proliferation we used the monoclonal antibody Ki67. Appropriate statistical methods were applied. RESULTS: Overall 77 specimens were assessed; 57 from UC patients and 20 from controls. Bcl-2, Bax and Bcl-x were upregulated in the group of patients with UC compared to controls. Nevertheless, Bax in epithelial cells and Bcl-x in lymphocytes were downregulated in patients with moderate/severe disease (p = 0.029 and 0.04 respectively). A weak correlation between epithelial apoptosis and Bcl-x expression in lymphocytes (r = 0.31, p = 0.02) was found. An even weaker correlation was also noticed between the epithelial component apoptosis and Bax in lymphocytes (r = 0.02, p = 0.07). CONCLUSIONS: Bcl-2/Bax system does not appear to be involved in the induction of apoptosis in UC. Activation of intraepithelial lymphocytes may be associated with epithelial apoptosis or simply represent epiphenomena related to the inflammatory process.

Small bowel capsule endoscopy for the investigation of obscure gastrointestinal bleeding: When we should do it and what should we expect.

Obscure gastrointestinal bleeding is defined as bleeding of unknown origin that persists or recurs (i.e. recurrent or persistent iron deficiency anemia, fecal occult blood test positivity or visible bleeding) after a negative initial workout that necessarily includes gastroscopy and colonoscopy. In clinical practice, small bowel capsule endoscopy is recommended as a third stage examination in these patients, since it is a simple, safe, non-invasive and reliable test. To date there are three available small bowel capsule systems that have gained FDA approval and their diagnostic yield has shown to be superior to other diagnostic modalities for the investigation of the small bowel in patients with obscure gastrointestinal bleeding. The test should be performed as close to the bleeding episode as possible and the administration of a purgative bowel preparation before the administration of capsule endoscopy is recommended by the European Society of Gastrointestinal Endoscopy (ESGE). Issues that still remain to be solved are the definition of bleeding lesions and what really represents a positive finding, as well as the question of whether the outcome of patients with obscure gastrointestinal bleeding is altered after the test, i.e. to better define subgroups of patients that will mostly benefit from capsule endoscopy. In the future small bowel capsule endoscopy might be able to get guided, while tissue samples might be available as well. (Acta gastro-enterol. belg., 2016, 79, 355-362).

The puzzle of somatostatin: action, receptors, analogues and therapy.

The scientific search for the revelation of the multiple physiological aspects of somatostatin has already begun. Investigators have managed to clarify many pathophysiological processes that have been influenced or regulated by somatostatin. The focus of future research seems to be the therapeutic application of this accumulated knowledge. The aim of this study is to collect the available information on the action, receptors and use of somatostatin analogues in human tissues. For this reason findings were based on Internet search and complete studies with abstracts written in English. A special mention on the influence of somatostatin on the immune system and inflammatory bowel disease is also included.

Different aspects in functional dyspepsia.

Functional dyspepsia is still a puzzling medical problem. The causes are unknown, the pathogenetic mechanisms are uncertain, the management is controversial and medications are many times insufficient. The research so far has given conflicting results at all levels of investigation. This study represents an effort to collect all available data concerning the most disputed issues of functional dyspepsia. Topics regarding Helicobacter pylori eradication, pathophysiology, endoscopic and histologic correlations with symptomatology, the placebo effect and management options are presented following an evidence-based approach. Many articles, published in recent years, are discussed in order to obtain an overall insight of this peculiar symptom complex, named functional dyspepsia.

Systemic absorption of 5-aminosalicylic acid in patients with inactive ulcerative colitis treated with olsalazine and mesalazine.

OBJECTIVE: To compare the systemic load of 5-aminosalicylic acid (5-ASA) as a basis for potential long-term toxicity during treatment in usual dosage with olsalazine (Dipentum) and one controlled-release mesalazine preparation (Salofalk) in patients with inactive ulcerative colitis. DESIGN: Open, randomized, crossover study. TREATMENT SCHEDULE: Olsalazine 500 mg twice daily for 7 days and mesalazine 500 mg thrice daily for 7 days consecutively. PATIENTS: Fifteen patients (12 males/3 females) aged between 18-70 years with ulcerative colitis in endoscopically confirmed remission for at least one month. METHODS: A morning predose plasma sample and a 24-h urine collection on days 6 and 7 of each course were obtained from all patients for quantitative determination of 5-ASA and acetyl-5-ASA (Ac-5-ASA) concentrations. High performance liquid chromatography was used and all analyses were performed blindly on coded samples. RESULTS: Treatment with mesalazine compared with olsalazine gave significantly higher levels of 5-ASA and Ac-5-ASA in plasma and urine. Maximum values and ranges of all variables were higher in the mesalazine group than in the olsalazine group. It is noteworthy that there was clear discriminance in the range of urine 5-ASA and Ac-5-ASA concentrations after mesalazine and olsalazine treatment. CONCLUSION: 1. The mesalazine preparation used, in comparison with olsalazine given in usual dosages, causes significantly higher levels of 5-ASA and Ac-5-ASA in plasma and urine in patients with inactive ulcerative colitis. 2. The lower systemic load of 5-ASA may reduce the potential risk of adverse events and in particular of nephrotoxicity.

p53 protein accumulation and colonic adenoma recurrence.

OBJECTIVES: The prognostic value of p53 protein accumulation in colonic adenomas is still controversial. The aim of the present study was to determine whether the evaluation of p53 protein accumulation in newly diagnosed colonic adenomas could predict the development of metachronous adenomas. DESIGN/METHODS: Fifty-five patients who underwent prior endoscopic polypectomy for colonic adenomas were colonoscopically re-evaluated at 24-38 months after index colonoscopy. In cases with more than one adenoma, the one with the greatest diameter and the most serious histology was taken into account. p53 protein expression was immunohistochemically examined using specific monoclonal antibody. RESULTS: p53 protein was detected in 41.8% of the 55 index adenomas. Recurrent adenomas were present in 21 patients (38.2%). Metachronous adenomas were present in 56.5% of patients with p53-positive index adenomas and in 25% of those with p53-negative index adenomas (odds ratio 3.90, P = 0.018). Among patients with 1 or 2 index adenomas, metachronous adenomas were found in 50% of those with p53-positive index adenomas and in 22.6% of those with p53-negative index adenomas (odds ratio 3.43, P= 0.042). Multivariate stepwise logistic regression analysis revealed that number of index adenomas per patient (1 or 2 versus > 2) and p53 expression (positive versus negative) in index adenomas contain independent prognostic information for adenoma recurrence (chi2 = 8.2, P= 0.004 and chi2 = 4.08, P = 0.04 respectively). Patients aged < 60 years developed recurrent adenomas relatively more frequently if they had a p53-positive index adenoma (P= 0.068). In the subgroup of patients aged < 60 years with 1 or 2 index adenomas, the recurrence of adenomas was more frequent in those with a p53-positive index adenoma but the difference did not reach statistical significance (P= 0.13). CONCLUSIONS: Our data suggest that p53 expression in index adenomas is associated with recurrent colonic adenomas.

Genes and gastric cancer.

Gastric cancer remains quite a common malignancy and counts among the most important causes of cancer-related death worldwide. Although the pathogenesis is multifactorial, familial aggregation in a significant proportion of cases suggests the importance of genetic predisposition. The association between the E-cadherin/CDH1 gene germline mutations and the development of diffuse gastric cancer was the first evidence for a molecular basis of gastric cancer in predisposed families and led many authorities in the world to produce guidelines regarding the management of such families members. The recent advances in genetics resulted in the discovery of numerous genetic events occurring during the course of gastric carcinogenesis (activation of oncogenes, silencing of tumor suppressor genes, mutations in DNA-repairing genes) and contributed to a better understanding in pathogenesis. Many genetic changes described have been found to affect tumor's biological behavior. In this article the authors attempt a review of all the molecular alterations in gastric cancer described in the literature and their impact on the management of patients with an inherited predisposition to gastric cancer. The promising role of gene therapy in the treatment of gastric cancer in the near future is also commented on.

A family of five first degree relatives affected by Lynch II syndrome.

Hereditary non-polyposis colorectal cancer (Lynch syndromes) has been reported in the international literature over the last decade. We now present a case of a family with Lynch II syndrome, in which five first-degree relatives were affected by colorectal cancer; in addition, the two female patients had ovarian or breast cancer.

Predictors of the early development of advanced metachronous colon adenomas.

BACKGROUND/AIMS: In order to reduce the number of colonoscopies performed for the surveillance of patients after polypectomy, suitable predictors of adenomas recurrence are needed. The aim of this study was to find predictors of the early development of metachronous adenomas and specifically of advanced ones. MATERIALS AND METHODS: Forty-four patients underwent total colonoscopy 24-26 months after initial endoscopic polypectomy. All polyps were endoscopically removed and an adenoma was considered as advanced if the diameter was > 1 cm and/or villous component and/or severe dysplasia were present. RESULTS: Metachronous adenomas were detected in 16 (36.4% patients. Five (11.4%) of them had advanced metachronous adenomas. Early recurrence of adenomas was significantly correlated with the total number of indices adenomas (p = 0.027). On the contrary, the presence of metachronous adenomas was not related to any of the patients' characteristics nor to the site and the histology of the indices adenomas. The development of advanced metachronous adenomas during the same period was significantly correlated with patients' age, as it was observed only in patients aged > or = 60 years (5/21 or 23.8%) and in none of the patients aged < 60 years (Odds ratio: 15.7, p = 0.02). Logistic regression analysis revealed that patient's age was the only significant predictor of the early development of advanced metachronous adenomas (beta = 0.40, p = 0.02) and that the number of the indices adenomas was the only significant predictor for the recurrence of all adenomas (beta = 1.59, p = 0.02). CONCLUSIONS: 1. Only patients aged > or = 60 years seem to develop advanced metachronous adenomas two years after polypectomy and 2. The likelihood for developing metachronous adenomas during the same period is related to the number of indices adenomas.

Seasonal variation in exacerbations of ulcerative colitis.

BACKGROUND/AIMS: The aim of this study was to determine whether there is seasonal variability in exacerbations of ulcerative colitis. METHODOLOGY: The timing of ulcerative colitis relapses was retrospectively studied in a group of consecutive patients with quiescent ulcerative colitis. Ninety-four patients were followed-up at least every three months for a mean of 29.3 (range: 12-67) months. RESULTS: In total, 248 relapses of ulcerative colitis were observed with a mean number of 2.6 (range: 0-9) per patient. The timing of the relapses was characterized by a clear monthly and seasonal pattern (p < 0.001). In particular, the occurrence of relapses peaked during October and November (observed/expected (O/E): 30/20 in both months) and showed three troughs: during July and August, during December, and during February (O/E: 13/21, 7/21, 8/20, and 15/21, respectively). Moreover, the relapse rate was high during autumn and spring (O/E: 84/62 and 72/61, respectively) and low during summer and winter (O/E: 45/61 and 47/64, respectively). CONCLUSIONS: These data support the premise that there is seasonal variability in terms of relapses in ulcerative colitis patients and suggest that the role of seasonal triggering factors must be further investigated.

Endoscopic sedation in Greece: results from a nationwide survey for the Hellenic Foundation of gastroenterology and nutrition.

BACKGROUND AND STUDY AIMS: Recent surveys regarding practices in sedation during endoscopic procedures are limited, particularly in Greece where they are nonexistent. This survey was designed to provide national data on sedation practices in Greece. METHODS: A 27-item survey regarding practices of endoscopy and sedation was mailed nationwide to 502 members of the Hellenic Society of Gastroenterology. RESULTS: A total of 201 questionnaires were returned (40%). Survey respondents performed an average of 48 oesophagogastroduodenoscopies (EGD) and 35 colonoscopies per month. 50 of the respondents, who perform endoscopic retrograde cholangiopancreatography (ERCP), conducted an average of 10 ERCP per month. 15 of the respondents, who perform endoscopic ultrasound (EUS), conducted an average of 6 EUS per month. Respondents administered sedation intravenously in 64% of EGD, 78% of colonoscopies, 100% of ERCP and 100% of EUS. 125 of the respondents (62.1%) reported the use of synergistic sedation (benzodiazepines plus opioids), 71 of the respondents (35.3%) reported the use of benzodiazepines alone and 68 of the respondents (33.8%) reported the use of propofol based sedation in selected cases (more than one response was permitted). In most cases, propofol administration was directed by an anaesthesiologist. The majority of the respondents monitored vital signs and pulse oximetry (90% and 96%, respectively). CONCLUSION: The use of sedation and physiologic monitoring in Greece is now standard practice during endoscopy. Benzodiazepines, either alone or combined with an opioid, are used by the majority of endoscopists, while propofol is used in selected cases, mainly in the presence of an anaesthesiologist.

Intestinal decontamination improves liver haemodynamics in patients with alcohol-related decompensated cirrhosis.

BACKGROUND: Endotoxaemia is commonly seen in cirrhotic patients with ascites and this may be associated with increased portal pressure. AIM: To investigate the effect of intestinal decontamination on liver haemodynamics in alcohol-related cirrhotic patients with ascites. METHODS: We included 30 patients. At day 0, systemic and splanchnic circulation endotoxin levels were determined and HVPG measurement performed. Patients received rifaximin (1200 mg/day) for 28 days. At day 29, systemic and splanchnic circulation endotoxin levels were determined and HVPG measurement performed again. RESULTS: Median (range) plasma endotoxin levels decreased significantly after rifaximin administration both in systemic [1.45(0-3.1) vs. 0.7(0-2.7), P < 0.0001] and splanchnic circulation [1.8(0-3.4) vs. 0.8(0-2.1), P < 0.0001]. Meanwhile, the difference seen in endotoxin levels between the splanchnic and systemic circulation at day 0 (P = 0.001) was not noted at day 29 (P = 0.137). HVPG measurement was possible in 28 patients. Median (range) HVPG values were 18 mmHg (12.7-26.3) on day 0 vs. 14.7 mmHg (7-20) on day 29 (P < 0.0001). HVPG decreased after rifaximin in 23, remained stable in two and increased in three patients. CONCLUSION: Hepatic venous pressure gradient values decreased significantly after intestinal decontamination with rifaximin in patients with alcohol-related decompensated cirrhosis and this might have been achieved through significant reduction of plasma endotoxin levels.

Clinical trial: The effect of somatostatin vs. octreotide in preventing post-endoscopic increase in hepatic venous pressure gradient in cirrhotics with bleeding varices.

BACKGROUND: Hepatic venous pressure gradient (HVPG) increases significantly after endoscopic therapy in patients with bleeding oesophageal varices, which may precipitate further haemorrhage. Whether vasoactive drugs can suppress these changes remains unknown. AIM: To investigate the efficacy of somatostatin when compared with octreotide in preventing the post-endoscopic increase in HVPG during acute bleeding and whether the changes affect outcome. METHODS: Thirty-three cirrhotics with bleeding varices were randomized to receive somatostatin (n = 17) or octreotide (n = 16) under double-blind conditions, soon after their admission. HVPG measurements were performed before and immediately after endoscopic treatment. RESULTS: In the somatostatin group, postendotherapy HVPG values did not change significantly when compared with pre-treatment values (18.9 vs. 17.2, P = 0.092). Conversely, in the octreotide group, HVPG increased significantly after endoscopy (18.2 vs. 20.8, P = 0.003). The probability of 6-week survival without treatment failure was significantly higher in the somatostatin group (P = 0.024). Post-endoscopic HVPG value was independently associated with 6-week failure. CONCLUSIONS: Somatostatin, but not octreotide, effectively prevents the post-endoscopic increase in HVPG, which may be associated with low probability of treatment failure.