The race for mainstream gastrointestinal endoscopy: frontrunners.

In recent years, gastrointestinal endoscopy has evolved and branched out from a primary naked-eye diagnostic technique to a multitude of sophisticated investigative and therapeutic procedures. While many of the new endoscopic techniques are currently too complex or expensive to make it to mainstream clinical practice, others are already bringing major progress to the management of digestive diseases. In this review we will discuss a selected group of the emerging techniques and technologies used to increase the diagnostic yield in the colon and small intestine, including Third Eye® Retroscopes®, colon capsule endoscopy, spiral enteroscopy and confocal laser endomicroscopy. We will also discuss over-the-scope clip devices, a relatively simple and inexpensive tool potentially capable of noninvasive closing intestinal perforations and allowing the removal of infiltrating tumors.

Anti-TNF's for postoperative recurrence in Crohn's disease: the if's and how's.

Recurrence of Crohn's disease (CD) is extremely frequent after surgery and its prevention remains a fundamental problem in the medical management of these patients. As of today, none of the medications traditionally used to treat the spontaneous disease (i.e. mesalamine, steroids, immunosuppressives and antibiotics) has shown a clear benefit. Recent data, coming from our center and from a small RCT do indicate that infliximab is extremely effective in preventing this complication in the large majority of patients. While additional, larger studies may be desirable, the strength and consistency of the available data suggest that future trials may merely confirm these observations. A number of issues however remain to be solved and include the long term strategy in patients treated for years with infliximab, whether treating early endoscopic lesions may be as effective as preventing them and whether immunosuppressives should be used together with infliximab. A thorough understanding of the mechanisms by which infliximab appears so effective in the postoperative setting may provide us with essential information regarding patients' management and, ultimately, highlight the molecular mechanisms at the very basis of Crohn's disease.

Infliximab in Crohn's disease: a look at the (not so distant) future.

Although infliximab has brought about a major advance in the treatment of Crohn's disease (CD), several questions remain unanswered. In particular, there is no consensus regarding the best timing to use it in the ideal therapeutic algorithm. Another controversial issue is whether this medication should be given or not for life once proven effective in the individual patient. Therapy with infliximab has also been associated to the development of intestinal strictures in CD: hence, some authors have discouraged its use in their presence. Finally, given its powerful antiinflammatory action, infliximab could in theory be effective in preventing postsurgical recurrence of CD, an as yet almost inescapable consequence of "curative" surgery. This review will focus on and discuss the relevant recent literature related to these issues with special regard to the efficacy and safety of infliximab in the presence of intestinal strictures and the potential role of this medication in preventing recurrence after surgery.

Role of biologics and other therapies in stricturing Crohn's disease: what have we learnt so far?

BACKGROUND: Therapy of strictures, one of the most common complications of Crohn's disease (CD), remains a challenging task in gastroenterology. While infliximab is widely recognized as being very effective in active CD, it has been reported to cause strictures in some patients. As a consequence, essentially by inference, many clinicians have chosen not to use it in the presence of strictures. AIMS: To find evidence in the available data that infliximab does not cause strictures and that there is no rational basis to avoid its a priori use when a stricture is already present. In addition, to review what is currently known on the general management of strictures in CD. METHODS: Discussion of the data that led to the hypothesis of a causal association between infliximab and strictures. Review of the mechanisms and the risk factors for stricture development in CD; of the different types of CD-related strictures; of the available means to distinguish them, and of the literature related to the efficacy and safety of infliximab as well as other biologics and other therapies in different stricturing scenarios. RESULTS AND CONCLUSIONS: Although larger controlled studies are due in the near future, current evidence indicates that infliximab does not cause strictures in CD. The drug appears safe and effective in the presence of an inflammatory stenosis while being predictably ineffective, but not harmful, in the presence of fibrosis. Different stricturing scenarios in CD must be clearly distinguished for proper management of this complication.

"Cervia II Working Group Report 2006": guidelines on diagnosis and treatment of Helicobacter pylori infection in Italy.

Proper management of Helicobacter pylori infection in clinical practice--when supported by evidence-based data--is expected to produce substantial cost-efficacy advantages. This consideration has prompted the Cervia Working Group to organise a meeting of experts to update the National Guidelines on the diagnosis and treatment of H. pylori infection in Italy. Recommendations in the new European Guidelines were considered in the National setting, here in the light of factors such as the incidence of gastric cancer and gastric lymphoma, the accessibility to different diagnostic tools, the prevalence of bacterial resistance against antibiotics, and the availability of different drugs. The main revisions in respect to the previous guidelines include H. pylori eradication in non-ulcer dyspepsia patients and in non-steroidal, anti-inflammatory drug users, as well as in patients with idiopathic thrombocytopenic purpura and iron deficiency anaemia. The stool antigen test is now accepted as a valid test for confirmation of H. pylori eradication following therapy. New therapeutic approaches have been recommended for both first- (sequential therapy) and second-line (levofloxacin-based) treatment in our country.

Cavernous transformation of the portal vein associated to multiorgan developmental abnormalities.

Initial diagnosis of cavernous transformation of the portal vein (portal cavernoma) is rarely made in adults. Its main clinical manifestation is upper gastrointestinal hemorrhage due to variceal bleeding. More rarely, diagnosis is made from obstructive jaundice. In children, this condition is frequently associated to prehepatic portal hypertension and congenital anomalies, the most frequent of which are atrial septal defects or malformations of the biliary tract or of the inferior vena cava. We describe here a case of a 23-year-old female presenting with massive hematemesis due to the presence of esophageal and small intestinal varices. She had a cavernous transformation of the portal vein with prehepatic portal hypertension associated with heretofore unreported malformations such as right pulmonary hypoplasia, cardiac dextroposition, and right renal ectopia. A unifying hypothesis (e.g. an intrauterine vascular insult) to explain the pathogenesis of these defects seems unlikely. Appropriate tests failed to identify specific functional abnormalities in these organs. Although she bled more than once, the combination of sclerotherapy and beta-blockers has been, thus far, able to control the major clinical consequences of this disease.

Gastric mucosa as an additional extrahepatic localization of hepatitis C virus: viral detection in gastric low-grade lymphoma associated with autoimmune disease and in chronic gastritis.

The hepatitis C virus (HCV) has been linked to B-cell lymphoproliferation and autoimmunity, and has been localized in several tissues. The clinical observation of an HCV-infected patient with Sjögren's syndrome (SS) and Helicobacter pylori (HP) positive gastric low-grade B-cell non-Hodgkin's lymphoma (NHL), which did not regress after HP eradication, led us to investigate the possible localization of HVC in the gastric microenvironment. HCV genome and antigens were searched in gastric biopsy specimens from the previously mentioned case, as well as from 9 additional HCV-infected patients (8 with chronic gastritis and 1 with gastric low-grade B-cell NHL). HCV-specific polymerase chain reaction (PCR) and immunohistochemistry procedures were used. The gastric B-cell NHL from the patient with SS was characterized by molecular analyses of B-cell clonality. HCV RNA was detected in both the gastric low-grade B-cell NHL and in 3 out of 6 gastric samples from the remaining cases. HCV antigens were detected in the residual glandular cells within the gastric B-cell NHL lesions, in glandular cells from 2 of the 3 additional gastric lesions that were HCV positive by PCR, and in 1 additional chronic gastritis sample in which HCV-RNA studies could not be performed. By molecular analyses, of immunoglobulin genes, the B-cell NHL from the patient with SS was confirmed to be a primary gastric lymphoma, subjected to ongoing antigenic stimulation and showing a significant similarity with rheumatoid factor (RF) and anti-HCV- antibody sequences. Our results show that HCV can localize in the gastric mucosa.

Colorectal cancer screening in Italy: feasibility and cost-effectiveness in a model area.

OBJECTIVE: To evaluate the feasibility and cost-effectiveness of screening programmes for colorectal cancer in Italy. DESIGN; We compared five types of programmes: annual faecal occult blood testing, sigmoidoscopy (every 5 years), faecal occult blood testing plus sigmoidoscopy (every 1 and 5 years), colonoscopy (every 10 years) (all in the age group 55-69 years, last examination at 70 years) and 'filter' colonoscopy. The latter had to be performed in persons at 50 years of age and repeated every 10 years until the age of 70. Costs for the tests and colon cancer care were paid by the Regional Health Office to the hospitals performing the procedures/treatments. SETTING: Data were applied to a small model area in northern Italy (Gemona, 80,000 inhabitants) with well-known demographic (age distribution) and epidemiological (colon cancer incidence) features. RESULTS: All-inclusive 10-year costs per screenee and per death prevented (in US dollars) were: 965 and 77,200 for faecal occult blood testing; 436 and 15,500 for sigmoidoscopy; 1521 and 35,000 for sigmoidoscopy plus faecal occult blood testing; 510 and 15,100 for colonoscopy; 510 and 14,000 for 'filter' colonoscopy. With 'filter' colonoscopy the programme required 870 colonoscopies per year, while with colonoscopy 13,700 colonoscopies were needed at time zero. CONCLUSIONS: In Italy, screening programmes based on sigmoidoscopy/colonoscopy are more cost effective than those based on faecal occult blood testing. 'Filter' colonoscopy at age 50 appears superior to the other types of endoscopy-based screening programmes because it utilizes, at any point in time, a much smaller fraction of available resources.

Intestinal leiomyosarcoma and gastroparesis associated with von Recklinghausen's disease.

The rare association between intestinal leiomyosarcoma, von Recklinghausen's disease (type-1 neurofibromatosis) and gastroparesis is described. A 20-year-old male, diagnosed 12 years earlier as having pelvic von Recklinghausen's disease, presented with nausea and vomiting. A gastric scintigraphy demonstrated an extremely slow gastric emptying time in the absence of obvious causes for gastroparesis. A small ileal leiomyosarcoma was later found and removed by surgery. The latter was followed by a marked improvement in the clinical condition of the patient.

Characterization of prelymphomatous stages of B cell lymphoproliferation in Sjögren's syndrome.

OBJECTIVE: To determine whether the prelymphomatous stages of B cell lymphoproliferation in Sjögren's syndrome (SS) may be better characterized by the integration of clinical, pathologic, and molecular data, the latter focusing on the expansion, persistence, and dissemination of clonal B cells in the course of the disease. METHODS: Multiple tissue lesions (synchronous from different tissues and metachronous from the same tissue) were evaluated in biopsy specimens obtained from 6 consecutive patients with SS who had an associated lymphoproliferative disorder. Fully benign gastric lesions were evaluated in tissue from an additional 11 patients with SS who had no associated lymphoproliferative disorder. Multiple and complementary molecular analyses of B cell clonality were used: Southern blot, polymerase chain reaction, single-strand conformation polymorphism, DNA sequencing, and hybridization with clonospecific oligoprobes. All the patients were then strictly followed up for the appearance of lymphoma. RESULTS: Different scenarios of SS-associated B cell lymphoproliferation were identified: 1) the ongoing expansion of the same dominant clone, localized or disseminated, in tissue from 2 patients, 1 of whom later developed an overt B cell lymphoma; 2) different dominant clones in different synchronous or metachronous tissues from the remaining 4 patients with an associated lymphoproliferative disorder; and 3) small oligoclonal expansions in 7 of the 11 benign gastric lymphoid infiltrates. CONCLUSION: Prelymphomatous B cell lymphoproliferation in SS was better characterized following integration of the findings. The different types of B cell clonal expansion (oligoclonal or monoclonal, smaller or larger in size, fluctuating or established, localized or disseminated) may imply a different risk of lymphoma progression. An accurate clinical, histopathologic, and molecular characterization may therefore be crucial in future studies aimed at clarifying the pathobiology of SS-associated lymphoproliferation.

Gastric B-cell clonal expansion and Helicobacter pylori infection in patients with autoimmune diseases and with dyspepsia. A follow-up study.

BACKGROUND: It is not clear whether gastric B-cell clonal expansion, a possible precursor of mucosa-associated lymphatic tissue (MALT) lymphoma, is exclusively linked to Helicobacter pylori infection and virulence. METHODS: In this study we followed up, for up to 33 months, 16 VDJ polymerase chain reaction-positive patients (4 with dyspepsia, 9 with Sjögren's syndrome, and 3 with other autoimmune diseases). Of these, 12 were H. pylori-positive. In addition, in H. pylori-positive patients we tested whether the serum anti-cag-A (a potential marker of virulence) was preferentially associated with B-cell clonality. RESULTS: In all but one patient clonality appeared temporally unrelated to H. pylori infection. The prevalence of anti-cagA was not higher in H. pylori/VDJ-positive patients than in controls. CONCLUSIONS: These data indicate that, in addition to H. pylori, gastric B-cell clonality may be sustained by other agents/mechanisms. Anti-cag-A does not appear to be involved in the pathogenesis of clonality.

Widespread clonal B-cell disorder in Sjögren's syndrome predisposing to Helicobacter pylori-related gastric lymphoma.

Helicobacter pylori has been identified as a critical antigenic stimulus to the development of gastric lymphoma, but additional factors should be required for such evolution. This topic is now of major importance to clarify the pathobiology of gastric lymphomagenesis. Peculiar autoimmune diseases, such as Sjögren's syndrome, are well known to predispose to B-cell lymphomas. We report on a patient with Sjögren's syndrome and a widespread B-cell lymphoproliferative disorder. A pathological picture of low-grade lymphoma was observed in the stomach, concomitantly with H. pylori infection. However, the B-cell disorder was definitely nonmalignant in the other tissues involved, i.e., the parotid gland and lymph nodes, which are the characteristic targets of Sjögren's syndrome-associated lymphoproliferation. After H. pylori eradication, a dramatic regression of gastric lymphoma into chronic gastritis was observed, but no amelioration occurred in the parotid and nodal involvement. Multiple molecular analyses showed the expansion of the same B-cell clone in synchronous and metachronous lymph node, parotid, and gastric lesions before and after H. pylori eradication. Thus, H. pylori played a crucial role in the local boosting of B-cell lymphoproliferation, but the underlying B-cell disorder was that associated with the autoimmune disease and was nonmalignant. The comprehensive clinical, pathological, and molecular approach allowed us to then distinguish the role of peculiar individual predisposing factors and of local infection in the pathobiology of mucosa-associated lymphoid tissue-associated lymphoproliferation.

B-cell clonality and infection with Helicobacter pylori: implications for development of gastric lymphoma.

BACKGROUND: Although Helicobacter pylori has been implicated in the pathogenesis of gastric mucosa associated lymphoid tissue (MALT) and MALT lymphoma, it is not known how it may trigger these lesions and whether there is an identifiable pre-neoplastic stage. AIMS: To investigate the relation between MALT, H pylori infection, and B-cell clonality (a potential marker of pre-neoplastic lesions). PATIENTS: 141 subjects with simple dyspepsia. METHODS: Gastric biopsy specimens from all patients were examined for MALT and H pylori. Of these, 25 consecutive MALT positive specimens were scored for features of MALT lymphoma and VDJ clonality studied by polymerase chain reaction. RESULTS: Overall, prevalence was 62% for H pylori and 46% for MALT. VDJ clonality was frequent in the sub-group studied (nine of 25), mostly associated with lymphoid follicles (eight of nine or 89%), and with a high scoring for MALT lymphoma. VDJ clonality was equally frequent in patients with and without H pylori (seven of 20 and two of five or 35% and 40% respectively). CONCLUSIONS: B-cell clonality is unexpectedly common in subjects with simple dyspepsia and MALT raising clinical management questions. These findings also suggest that the cascade MALT formation--B-cell clonality--MALT lymphoma may not be uniquely associated with H pylori infection.

B cell clonality in gastric lymphoid tissues of patients with Sjögren's syndrome.

OBJECTIVE: To determine the prevalence of mucosa associated lymphoid tissue (MALT) in the stomach and of a possible antigen driven proliferation, in patients with Sjögren's syndrome (SS). METHODS: Twenty one patients with primary SS and 80 dyspeptic controls underwent upper endoscopy. Lymphoid tissue and Helicobacter pylori were assessed by histopathological analysis. Epstein-Barr virus (EBV) or human herpes virus-6 (HHV-6) genome were studied by polymerase chain reaction (PCR) DNA amplification. Two PCR VDJ procedures were used to detect immunoglobulin heavy chain (IgH) gene rearrangement. RESULTS: Organised MALT was found in 33.3% of the patients, compared with 21.5% of the controls (NS). H pylori infection was seen in 71% of patients and 63% of controls. Genomic EBV or HHV-6 was found in a minor portion of SS gastric tissues. B cell expansion was detected in nine of the 21 patients. Infectious agents in the stomach might have contributed to B cell clonality only in 55.5% of the cases. No strict relationship was found between lymphoid follicles and clonality. CONCLUSION: Lymphoid accumulation in the gastric mucosa is common in Sjögren's syndrome, but full evidence for an antigen driven B cell expansion could not be demonstrated. Only a portion of those with clonal B cell expansion had evidence of an infectious agent. Other unknown infectious agents or factors related to the underlying disease (autoantigen) and its tissue environment may have a further role as possible causes of B clonal expansion in the gastric mucosa.

Helicobacter pylori, gastric MALT and B-cell clonality.

MALT, or mucosa associated lymphoid tissue, is normally not present in gastric tissue. Its presence is often associated with persistent antigenic stimulation. MALT is a precursor of gastric MALT lymphoma, a low-grade lymphoma whose incidence recently appears to have increased. Although much epidemiologic and clinical evidence has linked both MALT and MALT lymphoma to Helicobacter pylori infection, it is not known whether other agents and or mechanisms may also play a role and whether there is a clearly defined pre-neoplastic lesion. In particular, the clinical significance of B-cell clonality remains unknown. In a recent study we attempted to define the role of H. pylori and MALT in the genesis of B-cell clonality in a northern Italian patient population referred to us for simple dyspepsia. The results show that B-cell clonality is unexpectedly frequent in these patients regardless of the presence of H. pylori infection. These observations raise the possibility that agents and mechanisms other than H. pylori may be involved in the genesis of MALT lymphoma. Indeed, other studies conducted by our group in patients with Sjögren's syndrome indicate that genetic/immunologic factors and possibly viruses may play a role. The high prevalence of B-cell clonality in an otherwise healthy population suggests either that most of these patients are at risk of developing MALT lymphoma (in which case this condition at the moment may be greatly underdiagnosed) or that B-cell clonality is a very early step in the development of neoplasia, which requires several other factors and which will occur only in a restricted fraction of these patients. Careful follow-up studies will provide an answer to this question.

The hepatocellular uptake of free fatty acids is selectively preserved during starvation.

BACKGROUND/AIMS: The liver loses protein during fasting. This study sought to determine if hepatic protein loss during fasting selectively preserves functions important to survival such as uptake of fatty acids, which are major energy substrates in that condition. METHODS: Initial [3H]oleate uptake and efflux rates in hepatocytes from starved (for 48 hours) and fed male rats were measured in media containing 250 mumol/L albumin at oleate/albumin ratios of 0.2:1-2:1. Uptake rates of sulfobromophthalein, taurocholate, and glucose were also determined. RESULTS: Initial oleate uptake rate was saturable with respect to unbound oleate concentration. Maximum initial velocity expressed per cell number did not differ between fasted and fed animals, but measured cell volume and estimated surface area were decreased in starved vs. fed hepatocytes (921 +/- 21 vs. 1623 +/- 58 microns2, respectively; P < 0.001). Consequently, when expressed per surface area, maximum initial velocity was greater in starved cells (17 +/- 3 vs. 10 +/- 2 [pmol.min-1.micron2] x 10(-7); P < 0.02). Expressed similarly, oleate efflux was also greater from starved hepatocytes and was inhibited by an antibody to plasma membrane fatty acid binding protein (FABPpm). FABPpm concentration per unit area of plasma membrane also increased in starved hepatocytes (P < 0.05). By contrast, uptake rates of sulfobromophthalein, taurocholate, and glucose by starved hepatocytes were decreased when expressed per cell number and unchanged per unit area. CONCLUSIONS: During fasting, the hepatocellular uptake mechanism for oleate is selectively preserved compared with those for sulfobromophthalein, taurocholate, or glucose.