Benefit of supplements in functional dyspepsia after treatment of Helicobacter pylori.

AIM: Functional dyspepsia, though benign, leads to deterioration of the quality of life and high costs for healthcare systems. The optimal therapy for functional dyspepsia is still to be defined because of its multifactorial pathogenesis. In an open multicentric study of patients with functional dyspepsia, we prospectively evaluated the benefit of treatment with a food supplement composed of sodium alginate, carbonate calcium, pineapple, papaya, ginger, α-galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy). METHODS: Ninety-one consecutive patients were included, suffering from functional dyspepsia, who had been previously submitted to therapy to eradicate the infection from Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test (UBT). The primary goal was to establish the percentage of patients who continued to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT, differentiating between patients who were treated (N.=55) with Perdiges and those who were not (N.=36). Our secondary goal was to document the differences within the 2 groups in terms of symptoms perceived between the start and end of the observation period. The wellness reported, during or in absence of treatment with Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale) completed before the start of the treatment and after 30 days. RESULTS: All the patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The VAS scale of those who took Perdiges improved on average by 1.78 points versus a worsening of 0.08 points of those who did not take it (P<0.0001). Furthermore, while among those who took Perdiges there was a statistically significant improvement (P<0.0001) in the VAS scale, between the baseline and the end of treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who did not take it. CONCLUSION: Perdiges is significantly effective in the period following treatment to eradicate the infection from H. pylori in patients with functional dyspepsia. This allows to reduce the need to use antisecretive drugs. Further randomised studies, with wide ranging case histories, must assess its long-term efficacy.

Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation.

The extracellular matrix polysaccharide hyaluronan (HA) exerts size-dependent effects on leukocyte behavior. Low-molecular weight HA is abundant at sites of active tissue catabolism and promotes inflammation via effects on Toll-like receptor signaling. Conversely, high-molecular weight HA is prevalent in uninjured tissues and is anti-inflammatory. We propose that the ability of high-molecular weight but not low-molecular weight HA to cross-link CD44 functions as a novel form of pattern recognition that recognizes intact tissues and communicates "tissue integrity signals" that promote resolution of local immune responses.

Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development.

The growth factor family of neurotrophins has major roles both inside and outside the nervous system. Here, we report a detailed histological analysis of key phenotypes generated by the ablation of the Kinase D interacting substrate of 220 kDa/Ankyrin repeat-rich membrane spanning (Kidins220/ARMS) protein, a membrane-anchored scaffold for the neurotrophin receptors Trk and p75(NTR). Kidins220 is important for heart development, as shown by the severe defects in the outflow tract and ventricle wall formation displayed by the Kidins220 mutant mice. Kidins220 is also important for peripheral nervous system development, as the loss of Kidins220 in vivo caused extensive apoptosis of DRGs and other sensory ganglia. Moreover, the neuronal-specific deletion of this protein leads to early postnatal death, showing that Kidins220 also has a critical function in the postnatal brain.

Clinical identification and long-term surveillance of 22 hereditary non-polyposis colon cancer Italian families.

OBJECTIVE: To assess the efficacy of a hereditary non-polyposis colon cancer (HNPCC) identification and surveillance policy. METHODS: Familial clustering of colorectal cancer (CRC) and extracolonic cancers (ECs) was investigated in 1520 consecutive CRC patients and relatives. HNPCC was identified by Amsterdam criteria, and individuals at risk were offered biennial colonoscopy and other examinations, starting from age 25 years. RESULTS: Twenty-two HNPCC families were identified. The CRC prevalence was 27.8% (121/435), decreasing from 59.4% in the first generation to 24.4% and 8% in the second and third generation, respectively. Twenty-nine patients had multiple CRC and 34 patients (in 12 families) had ECs.A total of 199/331 at-risk individuals accepted surveillance. The mean follow-up was 48+/-32 months. CRCs were detected at first surveillance in four out of 199 surveilled individuals (2%); in two surveilled individuals (1%), three CRCs developed during follow-up. The overall CRC incidence was 7/199 (3.5%) in surveilled individuals and 5/132 (3.7%) in unsurveilled individuals. CRCs were less advanced in surveilled than in unsurveilled patients. Eleven individuals had 22 adenomas (one with high-grade dysplasia). Three individuals had adenomas at first surveillance; two of them and eight more individuals during surveillance. Seven surveilled individuals and six unsurveilled individuals, all belonging to families with a history of EC, had EC during the study period. All patients with CRC detected by surveillance are alive. One of the unsurveilled patients who had CRC died 18 months after the diagnosis. CONCLUSIONS: Data confirm the importance of the family history collected in each patient with CRC for identification of HNPCC and support the efficacy of repeated colonoscopies for early diagnosis and prevention of CRC in at-risk members. Reasons for surveillance failure could be an accelerated progression of small adenomas and a lesion missing at colonoscopy. Longer follow-up is required to assess the efficacy of surveillance for EC.

Outcome of laparoscopic colorectal resection.

BACKGROUND: The aim of this study was to assess the feasibility and safety of laparoscopic surgery for colorectal diseases. METHODS: A retrospective review was undertaken of all patients undergoing a laparoscopic colorectal procedure (LCP) for large bowel disease. All operations were performed by a single experienced team. Patients were divided chronologically into three consecutive groups (G1, G2, and G3). Data collection included the incidence and cause of both "proper" and "mandatory" conversions to laparotomy, the incidence and type of early and late postoperative complications, incidence of operative mortality, and the length of hospital stay. The incidences of conversion to laparotomy and of early and late postoperative complications were also determined as related to diagnosis, type of LCP attempted, and chronological group. RESULTS: Between January 1996 and December 2001, a total of 108 patients (49 men and 59 women) with a mean age of 65.1 years underwent an LCP for colorectal disease. Proper conversion to open surgery was necessary in five patients (4.6%), whereas a mandatory conversion was needed in 10 with patients advanced cancer (9.2%). The overall morbidity rate was 11.9%. There were no anastomotic leaks. In two patients (1.85%) developed a complication requiring reoperation. Postoperative mortality was nil. Mean postoperative hospital stay was 7.2 days. The rates of conversion and of early and late complications decreased through the three chronological periods. No trocar site recurrences were observed in the cancer patients. CONCLUSION: Laparoscopic colorectal surgery performed in experienced centers is safe; the observed morbidity and mortality rates are low and acceptable and compare favorably to those observed after standard open surgery.

Prevalence of the E1317Q variant of the APC gene in Italian patients with colorectal adenomas.

Loss of APC is an initial, rate-limiting event in inherited and sporadic colorectal tumorigenesis. Rare germline APC mutations have been identified in patients with multiple colorectal adenomas. Recently, the E1317Q APC variant has been associated with a predisposition to the development of multiple colorectal adenomas. In this study, the prevalence of the E1317Q variant was examined in 182 patients with single or multiple colorectal adenomas, and in 235 controls. In all, E1317Q was identified in two of 182 patients with adenomatous polyps (1.1%) and in two of 235 controls (0.8%) (p = 0.59). The risk of harboring adenoma(s) among subjects bearing the E1317Q variant was 1.29 (95% CI 0.09-18.0). No difference in the prevalence of E1317Q between cases with single (2.0%) or multiple colorectal adenomas (0.7%) and controls (0.8%) was found. None of the subjects with a family history of colorectal cancer carried the E1317Q variant. In conclusion, our results confirm that only a very small fraction of colorectal adenomas may be associated with the presence of E1317Q.

Hepatitis B and C virus infection in Crohn's disease.

Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-alpha (IFN-alpha) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00-2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04-11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61-3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37-3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37-3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06-1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-alpha for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD.

Treatment with interferon-alpha2b of naive non-cirrhotic patients with chronic hepatitis C according to viraemia and genotype. Results of a randomized multicentre study. The North West Italian Hepatological Group.

OBJECTIVE: To establish whether tailoring the dosage of interferon (IFN)-alpha2b in non-cirrhotic naive patients with chronic hepatitis C according to hepatitis C virus (HCV) genotype and viraemic level improves the rate of sustained response (normal alanine aminotransferase values and HCV-RNA negativity 6 months after the end of therapy). PATIENTS: A total of 538 consecutively collected HCV-positive patients with non-cirrhotic chronic hepatitis who had not been previously treated. METHODS: Quantitative viraemia and genotype were determined in each patient by a core laboratory. The patients were randomized to: Group 1, 86 patients with genotype non-1 and viraemia < 1,000,000 HCV genome equivalents/ml (GenEq/ml) treated with 3 Million Units (MU) IFN three times weekly (t.i.w.) for 1 year; Group 2, 42 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 3 MU IFN t.i.w. for 1 year; Group 3, 46 patients with genotype 1 and viraemia < 1,000,000 GenEq/ ml treated with 5 MU IFN t.i.w. for 1 year; Group 4, 85 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 5, 88 patients with genotype non-1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN t.i.w. for 1 year; Group 6, 94 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 3 MU IFN t.i.w. for 1 year; Group 7, 97 patients with genotype 1 and viraemia > 1,000,000 GenEq/ml treated with 5 MU IFN daily for 2 months followed by 5 MU t.i.w. for a further 10 months. RESULTS: According to an intention-to-treat analysis, a sustained virological response (negative HCV-RNA by polymerase chain reaction 6 months after the end of therapy) was observed in 42% of Group 1 patients, in 21% of Group 2 patients versus 24% of Group 3 patients [P = not significant (NS)], in 28% of Group 4 patients versus 35% of Group 5 patients (P = NS), and in 8.5% of Group 6 patients versus 12% of Group 7 patients (P = NS). CONCLUSIONS: Even though a trend towards a therapeutic improvement is observed, the adoption of more aggressive IFN protocols, such as induction therapy, does not appear to significantly improve the rate of sustained response in patients with chronic hepatitis C associated with HCV genotype 1 and highly viraemic levels compared with standard therapy. Moreover, patients with only one unfavourable predictive factor (genotype 1 or high viraemia) do not gain major therapeutic benefits when treated with high doses of IFN.

Idiopathic myenteric ganglionitis underlying intractable vomiting in a young adult.

Inflammatory infiltration of intestinal myenteric plexuses (i.e. myenteric ganglionitis), along with severe intestinal motor abnormalities, may accompany paraneoplastic syndromes, neurological disorders and gastrointestinal infections, although rare cases can be idiopathic. In this report, we describe the case of a patient who presented with chronic intractable vomiting and weight loss associated with idiopathic myenteric ganglionitis mainly involving the stomach. Tissue analysis showed that the inflammatory infiltrate comprised T lymphocytes (CD4+ and CD8+), and peptide immunolabelling revealed a marked decrease of substance P/tachykinin immunoreactive staining in nerve fibres and myenteric neurones. Following systemic steroid therapy, the patient's symptoms dramatically improved, and after one year of follow-up his general condition remains satisfactory. The possible mechanisms leading to symptom generation and gastric dysmotility in the context of an idiopathic myenteric ganglionitis are discussed.

Enteroscopic identification of an adenocarcinoma of the small bowel in a patient with previously unrecognized hereditary nonpolyposis colorectal cancer syndrome.

Tumors of the small bowel are uncommon and seldom suspected on a clinical basis. Together with the relative inaccessibility of the small bowel to endoscopic investigation, the rarity of these tumors undoubtedly delays their diagnosis. The case reported is of a patient with an adenocarcinoma of the jejunum presenting as gastrointestinal bleeding of obscure origin. Diagnosis was by push enteroscopy, after several years of unsuccessful radiological and upper and lower endoscopic evaluation. The patient's family fulfilled the Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome, which was previously unrecognized. This report emphasizes the value of push enteroscopy and the limits of radiography of the small bowel when investigating patients with obscure GI bleeding. It also underlines the importance of a careful evaluation of the pedigree (concerning history of colorectal and extracolonic cancer) of all patients, including those who present with adenocarcinoma of the small bowel; it is similarly important to consider the possibility of small bowel cancer in members of families with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.

Dysplastic changes in gastric fundic gland polyps of patients with familial adenomatous polyposis.

BACKGROUND: Fundic gland polyps are the most common gastric lesion in patients with familial adenomatous polyposis and are traditionally considered a condition with no malignancy potential. However, some reports have recently questioned this view. AIMS: To prospectively evaluate their prevalence and the associated dysplastic/malignant changes in a series of affected patients. PATIENTS AND METHODS: Thirty-seven affected patients were carefully investigated by upper endoscopy over a three-year period. Multiple (at least 10) complete excisions of any representative polyp of the body-fundus were performed and a thorough pathological search for microscopic adenomatous/dysplastic changes carried out. RESULTS: Of 37 patients, 19 (51.3%) showed gastric fundic gland polyposis and 18 of them gave consent for polypectomies. Overall, 425 endoscopic polypectomies were performed, with a mean of 23.6 +/- 14.6 per patient. At pathology, all excised polyps of the body-fundus were found to be fundic glandular. Microscopic adenomatous changes within such polyps were identified in 8 (44.4%) patients. All the adenomatous foci revealed mild dysplasia with no case of severe atypia or carcinoma. Patients with microadenomas showed a significantly higher total number of gastric polyps compared with those without microadenomas (p < 0.03). No other differences between the two groups were observed. Two further patients presented microadenomas in apparently normal antral mucosa and one also showed a 6 mm antral adenoma with mild dysplasia. Finally, the search for Helicobacter pylori was always negative. CONCLUSIONS: Patients with familial adenomatous polyposis and gastric fundic gland polyps have a high prevalence of microscopic adenomatous foci within such lesions; nevertheless, these foci seem not to be associated with signs of severe atypia or carcinoma. Moreover, microadenomas are ubiquitous throughout the stomach, as well as in the rest of the gut, and their natural history is still undefined. Thus, their malignancy potential remains uncertain. More extensive follow-up is warranted to better investigate the long-term biological behaviour of these lesions but, at present, our data do not support the need for a change in the usual intervals of upper endoscopy surveillance in familial polyposis patients with or without gastric fundic glands polyps.

Monoethyl glycine xylidide (MEGX) test evaluation in primary biliary cirrhosis: comparison with Mayo score.

OBJECTIVE: To evaluate the clinical and prognostic value of the monoethyl glycine xylidide (MEGX) test in patients with primary biliary cirrhosis (PBC) in comparison with the Mayo score (Mayo). DESIGN: A prospective study. METHODS: MEGX determinations at enrolment were compared to the Mayo score as well as to conventional clinical and laboratory parameters in 92 patients with PBC. RESULTS: The MEGX test yielded higher basal values in long-term survivors compared to patients that were transplanted or died during the follow up; patients belonging to the last two groups displayed significantly higher Mayo scores at baseline. Although values for prothrombin time, serum albumin, alkaline phosphatase, cholesterol, cholinesterase, and gamma-glutamyltranspeptidase were significantly different in survivors compared to either transplanted or dead patients at univariate analysis, the multivariate analysis demonstrated an independent prognostic value for the MEGX and the Mayo score solely. The best discrimination between probability of death or survival was achieved with a cutoff value of 25 ng/ml for the MEGX test and of 6 for the Mayo score. When plotting both MEGX test and Mayo score, the point distribution displayed a bimodal trend, and the wide range of values given by the MEGX test was observed to supply a more precise assessment of liver reservoir and a better discrimination of progressive changes in liver function; the limited range of the Mayo score for values below 6 could only identify gross deteriorations. CONCLUSION: Our data show that the asymptomatic progressive functional deterioration occurring during the natural history of PBC can be monitored by the MEGX test because it appears to be able to identify abnormalities prior to the onset of alterations in conventional laboratory and/or clinical parameters which are likely to affect the Mayo score.

High prevalence of adenomas and microadenomas of the duodenal papilla and periampullary region in patients with familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) are traditionally considered to be at high risk for duodenal-papillary and periampullary adenomas and cancer. AIM: To evaluate prospectively the prevalence, histology and clinical significance of ampullary and periampullary macroscopic and microscopic lesions in our population of affected patients. SETTING: Three gastroenterological departments of northern Italian hospitals. PATIENT AND METHODS: Twenty-five affected patients were carefully investigated over a 24-month period by end-viewing and side-viewing upper panendoscopy. Biopsies were performed on representative macroscopic lesions and randomly on normal-appearing papillary and periampullary mucosa. RESULTS: Seven patients had macroscopic adenomas of the duodenal papilla, three of the periampullary region and five at both sites (cumulative prevalence 40%). An additional six patients had macroadenomas in the rest of the duodenum (overall prevalence 64%). Microscopic adenomas were identified in nine and two patients in the papilla and periampullary region, respectively, and in three at both sites (overall prevalence 44%). Thus, a total of 17 (68%) patients presented macro- or microadenomas at these locations. The prevalence rose to 72%, when a further patient with macroadenomas in the rest of the duodenum only was included. Malignancy was not encountered and severe dysplasia was observed only in a macroadenoma of the second duodenal portion. A higher frequency of macroadenomas in the papilla and periampullary region was significantly correlated with the presence and number of such lesions in the rest of the duodenum (P = 0.04). No other significant association was detected either between micro- or macroadenomas at different sites or with the demographic, clinical and pathological features. CONCLUSION: This study confirms that the duodenal papilla and periampullary region are sites with high prevalence of macro- and microscopic adenomas in patients with FAP. However, our data do not seem to support a higher frequency and malignancy potential of such lesions as compared to polyps in the rest of the duodenum. Nevertheless, these findings warrant a periodic, careful examination of the duodenum with either end-viewing or side-viewing endoscopy, the need for random biopsies of the papilla and periampullary region and the removal of any larger or rapidly growing lesions detected.

Clinical enteroscopy.

We prospectively evaluated the diagnostic yield of push enteroscopy using either the Olympus SIF 10-LY fiberscope or the SIF-100 video enteroscope in 120 patients suspected of having small-bowel pathology. Insertion beyond the ligament of Treitz, checked by fluoroscopy, ranged from 30 to 150 cm (median 100). The source of bleeding was identified in 25 (41%) of 61 patients referred for gastrointestinal bleeding of obscure origin; vascular malformations were the most common finding, followed by neoplasias. Of 16 patients with inherited polyposis syndromes, multiple distal duodenal or jejunal hamartomas were diagnosed in five of six with Peutz-Jeghers syndrome and multiple duodenal or jejunal adenomas in six of 10 with familial adenomatous polyposis. Overall, isolated vascular malformations were successfully cauterized in three patients, and polypectomy was performed in 12 patients. Endoscopic and histological alterations, in both duodenum and jejunum, were found in 16 of 43 patients with diarrhea and/or malabsorption of unclear origin. The remaining 27 had normal duodenal and jejunal mucosal appearances; six had abnormal histological findings only in the jejunum and one both in the duodenum and in the jejunum. If we take jejunal histology as diagnostic, the sensitivity of duodenal histology was 74% and the specificity was 100%. We conclude that push enteroscopy provides useful diagnostic information and has therapeutic capabilities in patients with small-bowel pathology.

Clinical aspects and management of hereditary non-polyposis colorectal cancer (HNPCC).

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomical dominant trasmitted disease phenotypically defined according to the "Amsterdam criteria" as follows: at least 3 affected relatives, one of whom first degree relative of other two, at least two successive generations affected. Important cardinal features are: 1) prevalent proximal location of cancers (above splenic flexure); 2) multiple synchronous or methachronous large bowel cancers; 3) early age of onset (<50 years); 4) presence of extracolonic cancers (endometrium, stomach, urinary tract, skin). The treatment is essentially surgical and total colectomy with ileo-rectum anastomosis is already proposed as standard procedure with annual endoscopic examination of retained rectum. The screening of individuals at risk, so determined by the analysis of pedigree or the results of molecular tests, must be performed every 1-2 years by colonoscopy starting around the age of 25 years. In this review are described and analysed the spectrum of the disease with particular attention to the frequency and characteristics of extracolonic cancers. Moreover, the guidelines of the surveillance and screening are reported following the data of the literature and as proposed by the International Collaborative Group (ICG-HNPCC).

Minute and small early gastric cancers in a Western population: a clinicopathologic study.

Early endoscopic diagnosis improves the prognosis of patients with gastric cancer, as shown by the finding that 5-year survival rates exceeding 90% are observed in Japanese patients with early gastric cancer. It has been hypothesized that tumor size may have prognostic significance; therefore, a distinction between minute, small, and large early gastric cancers has been proposed. The aim of this study was to determine the prevalence of minute and small early gastric cancers in Western countries and to compare their clinicopathologic features with those of large early gastric cancers. Of 465 Italian patients with gastric cancer who were studied, 20.5% had an early gastric cancer, and 34.7% of these were minute or small. Tumor size is correlated with intramural spreading and metastasis to perigastric lymph nodes. Nodal involvement occurs more frequently in the diffuse than in the intestinal type of early gastric cancer. Long-term survival rate is not correlated with tumor size, intramural spreading, or nodal metastasis. The minute and small early gastric cancers of Italian patients are indistinguishable from those occurring in Japanese patients. These lesions are more common than previously thought and should be carefully searched for by endoscopists. The correlation of tumor size with intramural invasion and perigastric lymph node metastasis suggests that minute and small early gastric cancers are precursors of large early gastric cancers. Although the distinction between minute, small, and large early gastric cancers is of low prognostic value, the distinction might be useful for selecting different therapeutic approaches.