Chronic hepatitis B therapy: available drugs and treatment guidelines.

There are currently several drugs approved for the treatment of chronic hepatitis B including recombinant interferons, such as interferon-α and its pegylated formulation, and the nucleos(t)ide analogues, such as lamivudine, adefovir, telbivudine, entecavir and tenofovir. Pegylated-interferon is an immune-modulatory agent that works mainly by enhancing the innate immune response while nucleos(t)ide analogues are oral drugs with direct inhibition of viral replication. Each agent has its own advantages and drawbacks. Pegylated-Interferon treatment has a finite duration without induction of drug resistance but only a limited number of patients achieve a sustained virological response to therapy. On the other hand, the care with nucleos(t)ide analogues requires a long-term treatment with a potential risk of induction of drug resistance, but higher rates of viral replication suppression are achieved. Nevertheless, second generation nucleos(t)ide analogues, such as Entecavir and Tenofovir, have both high genetic barrier to resistance and potent antiviral action. This review describes the mechanisms of antiviral activity and the efficacy of viral suppression of the different available drugs for chronic hepatitis B treatment, considering the recent clinical guidelines for an optimal management of chronic HBV infection.

[Diagnosis and treatment of Helicobacter pylori infection in pediatrics: recommendation for 2014 clinical practice]. / Diagnosi e terapia dell'infezione da Helicobacter pylori in pediatria: raccomandazioni per la pratica clinica del 2014.

Helicobacter pylori (H. pylori) infection is a large worldwide infection usually acquired during childhood, whose prevalence in pediatric population varies, with lower incidence rates in developed countries compared to developing countries (up to 10-15% and 70%, respectively). Diagnosis can be performed both with endoscopic-based methods and noninvasive diagnostic tests, such as urea breath test and fecal antigen. Current guidelines recommend endoscopic evaluation of the young patients, in order to determine the underlying cause of abdominal pain. Even in case of suspected functional pain, patient should not be investigated for infection, unless upper endoscopy is performed to rule out organic causes. Nowadays, in pediatric population, applications of noninvasive tests are limited to verifying eradication after therapy and to investigating the presence of infection in asymptomatic patients with first-degree relatives affected by gastric cancer. Since correlation between abdominal pain and H. pylori gastritis, in absence of peptic ulcer disease is still debated, "test and treat" strategy is not recommended in children. As for adults, treatment regimens are based on the combination of proton-pump inhibitor and two or more antibiotics, for 7-14 days, depending on resistance rates of geographic areas.

Gastrointestinal damage by non-steroidal anti-inflammatory drugs: updated clinical considerations.

Gastrointestinal (GI) damage by non-steroidal anti-inflammatory drugs (NSAIDs) is an important Public Health problem due to morbility and elevated mortality rate. The logic behind the development and sale of molecules which are selective cyclooxegnase-2 (COX-2) inhibitors called coxibs, is to limit the undesired effects of traditional NSAIDs, which should theoretically derive from the inhibition of COX-1. With respect to the emphasis of the initial trials, to now epidemiological studies, open-label studies, meta-analyses and reviews of the same data with longer follow-up, have produced opposite conclusions. Indeed, a recent series of meta-analyses has shown that the risks of GI events are similar for coxib and diclofenac, while they are significantly higher during the assumption of ibuprofen or naproxen. Moreover, the presumed lower gastrolesivity of coxibs is based on a highly simplified hypothesis, that the gastroprotective PGs derive from COX-1 and that the phlogistic processes are related to COX-2. Also in geriatric populations, though less tolerated than coxibs, diclofenac presents minor GI side effects when compared with naproxen and ibuprofen. In this context, in the case of moderate pain intensity, it is possible to use combinations with weak opioids, such as paracetamol-tramadol. Though intestinal damage by NSAIDs are a nosological entity of growing interest, to now no trial has been conducted with optimal criteria to demonstrate the superiority of coxibs over traditional NSAIDs. For this reason, chronic inflammation of the intestine still represents a contraindication to the administration of coxibs.

Helicobacter pylori infection and respiratory diseases: actual data and directions for future studies.

Helicobacter pylori (H. pylori) has been conclusively related to several gastroduodenal diseases. The possible role of the bacterium in the development of extragastric manifestations has been investigated in the past few years. To identify all publications on the association between H. pylori and respiratory diseases, a MEDLINE search of all studies published in English from 1965 to 2013 was conducted. All data are based on case-control studies. Controversial findings of H. pylori seroprevalence have been obtained in patients with bronchial asthma, lung cancer, pulmonary tuberculosis, sarcoidosis, cystic fibrosis, chronic bronchitis and bronchiectasis. At present, on epidemiological bases, there is no definite evidence of a causal relationship between H. pylori infection and respiratory diseases. There is a low consideration of confounding factors as poorer socioeconomic status and tobacco use. The activation of pro-inflammatory cytokines by H. pylori might be a possible pathogenetic mechanism. However, there are no convincing data about the influence of H. pylori on the inflammatory changes of the bronchoepithelium so far. Further studies are needed on the impact of H. pylori eradication, on the prevention, development and natural history of these disorders.

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.

GastroPanel® test for non-invasive diagnosis of atrophic gastritis in patients with dyspepsia.

AIM: Atrophic gastritis (AG), first step in the cascade leading to gastric adenocarcinoma, is related to Helicobacter pylori (H. pylori) infection. Currently, the gold standard for the diagnosis of AG is esophagogastroduodenoscopy (EGD) with histological examination of the biopsy specimens. However, since the latter are taken in random order and the distribution of AG is often patchy, histology is only representative of mucosal status. Considering this limitation, a test named GastroPanel®, that measures the blood concentrations of pepsinogen I and II, gastrin-17 and H. pylori antibodies, has been developed as a potential non-invasive biopsy. Aim of this study has been to assess the accuracy of GastroPanel® in patients with AG. METHODS: Forty-seven dyspeptic patients (24 males, mean age 52.2±9.3 years), in follow-up for antral or diffuse AG, were enrolled. All underwent at least two EGDs with random biopsies and blood collection for GastroPanel® parameters examination. RESULTS: Of the 47 patients, 16 (34.1%) had histological diagnosis of antral and 31 (65.9%) multifocal AG; 17 (36.2%) patients had mild and 30 (63.8%) had moderate-severe AG. H. pylori was detected in 39 (82.9%) and intestinal metaplasia was found in all patients. GastroPanel® showed 82.9% sensitivity for the diagnosis of AG and 53.8% for the diagnosis of H. pylori infection. The prediction of advanced atrophy was not sufficiently accurate, neither in patients with antral nor in those with multifocal AG. CONCLUSION: GastroPanel® can be useful for detecting patients with AG. However, it does not reflect the severity of atrophy.

Inflammatory bowel diseases and primary sclerosing cholangitis: hepatic and pancreatic side effects due to azathioprine.

BACKGROUND AND OBJECTIVES: In up to 80% of cases primary sclerosing cholangitis (PSC) is associated with inflammatory bowel diseases (IBD). The efficacy of azathioprine (AZA), in the maintenance of remission of IBD has been suggested by several studies. However, AZA tends to exter varied well-known toxicity. Since the rate of hepato-pancreatic side-effects in patients with IBD and PSC is still unclear, we investigated this issue. MATERIALS AND METHODS: Consecutive subjects who underwent Outpatient Clinic admission for both IBD and PSC were included. Both conditions were diagnosed according to International Guidelines. RESULTS: Data of 43 patients were elaborated. Twelve of them underwent therapy with AZA. Five (41.7%) presented hepatic (n=4) or pancreatic toxicity. Eighty percent of the patients with hepato-pancreatic reactions versus 28.6% of those without (p < 0.001) were males, with 60% affected by ulcerative colitis and 40% by Crohn's disease versus 57% and 43%, respectively. Forty percent of patients with reactions versus 43% of those without needed an operation for IBD, and the same percentage underwent orthotopic liver transplantation, with a 100% versus 66.7% (p < 0.001) need of second transplantation. Colonic neoplasia (20%) was detected only in the former group while cholangiocarcinoma (28.6%) only in the latter. CONCLUSIONS: The occurrence of hepato-pancreatic reactions from AZA in our caseload is higher (41.7%) compared to that reported in literature (4%). Therefore, the presence of PSC, in association to IBD, may strongly affect AZA tolerability compared to presence of IBD only.  

Endoscopic ultrasound in the 2013 preoperative evaluation of gastric cancer.

The capacity of endoscopic ultrasound (EUS) to distinguish the different wall layers of the gastrointestinal (GI) tract and the possibility to obtain samples of suspicious lesions or lymph nodes by means of EUS-guided fine-needle aspiration (EUS-FNA), make EUS an ideal staging modality for GI cancers. After an endoscopic and histological diagnosis of gastric cancer (GC), an accurate preoperative evaluation is essential to choose the correct management decision, because for this malignancy various and radically different stage-oriented therapies can be performed. Even if EUS is inserted in the last guidelines for the management of GC as an essential pretherapeutic staging modality, in the literature the reported accuracy, the imaging features and the performances of the technique are variable. In this review, we synthesize the current status and the imaging findings of EUS when describing and staging GC, with a particular attention to the early GC that represents till today a diagnostic and therapeutic challenge. Currently, the EUS study is mandatory for the preoperative staging, to assess with a good accuracy the tumor depth of wall invasion, the presence of suspicious lymph-nodes and of ascites (predictive of peritoneal involvement). The main limitations for a correct EUS staging remain some features of the lesion or its localization, so more attention should be paid when these characteristics are present.

Liver steatosis in celiac disease: the open door.

Non-alcoholic fatty liver disease (NAFLD) is a common disease of unknown origin characterized by histological features similar to alcoholic-like liver injury but in the absence of significant alcohol intake. Non-alcoholic fatty liver disease refers to a spectrum of diseases of the liver ranging from simple steatosis (i.e., fatty infiltration of the liver) to nonalcoholic steatohepatitis (i.e., steatosis with inflammation and hepatocyte necrosis) to cirrhosis. Non-alcoholic fatty liver disease is frequently associated with disorders such as insulin resistance, obesity, type 2 diabetes mellitus, hyperlipidemia and protein-calorie malnutrition. However, in a subgroup of NAFLD patients, the true relevant cause remains undetermined. Celiac disease (CD) is a common immune-mediated disorder and develops in genetically susceptible subjects after the ingestion of gluten proteins. Celiac disease has been found in about 10% of patients with unexplained abnormal liver tests, and in about 3.5% of patients with NAFLD as the only manifestation of the disease. The frequency of subclinical or silent presentations in older children and adults highlights the importance of CD screening in patients with unexplained chronic abnormal liver function tests and NAFLD without any specific etiology. The pathogenesis of liver steatosis in CD is uncertain. The aims of this review are to describe the possible mechanisms involved in the occurrence and progression of liver steatosis in CD patients.

[Skin ulcer pain]. / Il dolore da ulcera cutanea.

Chronic or acute pain related to skin ulcers or their management (medication, debridement) is a typical case of mixed pain, both neuropathic and nociceptive. It represents a disabling clinical condition that deteriorates the patient's quality of life. The pharmaceutical therapy must be based on both, intensity and the type of pain. Although NSAIDs, Non Steroidal Anti-Inflammatory Drugs are notoriously effective on nociceptive pain, do not give great results on neuropathic and mixed pain. Also the consumption of NSAIDs is affected by a series of side effects that may involve several organs. In case of neuropathic pain, the benefit deriving from the use of a single active principle is relative. This sets the rational grounds for the use of combined drugs. The paracetamol/tramadol combination represents an innovative solution in the treatment of both the neuropathic and nociceptive components of the pain, since both active principles have a different action mechanism, multiple targets and different pharmacokinetics. It is very interesting, from the clinical point of view, that tramadol is a pure antagonist, not selective, of µ, δ, and κ receptors and carries out and important inhibition action of serotonin and norepinephrine reuptake. This double mechanism, opioid and non-opioid, explains its analgesic efficacy also on neuropathic pain. Besides, since its opioid action is rather weak, it does not induce the severe side effects typical of traditional opioids. The benefit of such combination comes from their complementary pharmacokinetic profile, since the first has a quick action insurgence, while tramadol has a more prolonged effect. Therefore, this combination allows to obtain a quick and long lasting effect with a high tolerability profile also when treating skin ulcer pain.

Role of endoscopy in the management of gastroenteropancreatic neuroendocrine tumours.

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) represent in clinical practice a diagnostic dilemma because they are often very small, located deeply within the retroperitoneum or in an extramucosal site in the gastrointestinal (GI) tract and, lastly, because they may be multi-sited. Modern digestive endoscopy offers a myriad of techniques, useful for localization, diagnosis and treatment (therapeutic endoscopy). The available tools include upper digestive endoscopy (esophagogastroduodenoscopy, endoscopic retrograde cholangiopancreatography), lower digestive endoscopy (ileo-colonoscopy), enteroscopy (push-type, intra-operative, capsule, double or single balloon), for examining the small intestine, diagnostic and interventional echo-endoscopy (EUS), with radial, linear and miniprobe equipment. This narrative review offers scientific support to affirm that endoscopy and EUS give imaging and diagnostic possibilities that are unbeatable in the localization of GEP-NETs both of the GI tract and the pancreas. Endoscopy is useful for localization, bioptic diagnosis and curative resection of small neuroendocrine lesions of the stomach, duodenum, colon-rectum and more recently of the jejuno-ileum. EUS associated with dedicated instruments, particularly high frequency miniprobes, is a valuable procedure in locoregional staging of lesions of the GI wall and can supply information which has a clinical impact on therapeutic options and prognostic value. EUS is still today the sole technique in a certain number of cases which provides a definitive diagnosis of pancreatic insulinoma and to detect and follow subcentimetric lesions of the pancreas in patients with MEN-1 syndrome. It should be used in all those cases where results from radiographic imaging or nuclear medicine techniques show negative or dubious.

Molecular findings on Helicobacter pylori: update for clinicians.

Helicobacter pylori (H. pylori) is a gram-negative bacterium which is responsible for a wide range of disorders of the stomach, from chronic gastritis to peptic ulcers to gastric cancer which, however, occurs in a lower percentage of subjects. The difference in the clinical course of infection seems to be correlated both to the typical pathogenicity of the bacterium and to factors related to the host. The reasons underlying these observations include differences in bacterial pathogenicity as well as in host susceptibility. Numerous studies published in the last year have provided new insights into H. pylori virulence factors, their interaction with the host and the relative consequences in the pathogenesis. In this review, we have set ourselves the target of summarising the latest progress made in understanding the molecular aspects of H. pylori infection of notable importance for the physician.

Complications of endoscopic ultrasonography.

Since its development in the 1980s, endoscopic ultrasonography (EUS) has undergone a great deal of technological modifications. EUS has become an important tool in the evaluation of patients with various clinical disorders and is increasingly being utilized in many centers. EUS has been evolving over the years; EUS-guided fine needle aspiration (FNA) for cytological and/or histological diagnosis has become standard practice and a wide array of interventional and therapeutic procedures are performed under EUS guidance for diseases which otherwise would have needed surgery, with its associated morbidities. EUS shares the risks and complications of other endoscopic procedures. This article addresses the specific adverse effects and risks associated with EUS, EUS-FNA and interventional EUS, namely perforation, bleeding, pancreatitis and infection. Measures to help minimizing these risks will also be discussed.

Carbon dioxide insufflation versus air insufflation during endoscopic retrograde cholangiopancreatography under general anesthesia.

AIM: The aim of this paper was to evaluate the effect of carbon dioxide (CO2) vs. air insufflation on post-endoscopic retrograde cholangiopancreatography (ERCP) abdominal pain and distension. In addition, we investigated the changes in the partial pressure of end-tidal CO2 (PetCO2) and the partial pressure of arterial CO2 (PaCO2). METHODS: From October 2009 to January 2010, all patients admitted to our centre for ERCP were screened for enrollment; the patients recruited were randomised to CO2 or air insufflation. The patients were asked to rate their abdominal pain intensity and distension using a 100-mm Visual Analogue Scale (VAS) before, in the recovery room and at 1, 3, 6 and 24 hours after the ERCP. All anesthesiological and endoscopic details and complications were evaluated. RESULTS: We included 76 patients, 39 in the Air group and 37 in the CO2 group. The groups were similar for age, gender, indications and duration of the procedure. Post-procedure mean values of pain (in the recovery room and at 1, 3 and 6 hours) and distension (at recovery room, and at 1 and 3 hours) according to the VAS were significantly reduced in the CO2 group as compared to the Air group. At baseline, the PetCO2 values were similar between the two groups while, during the ERCP, they increased significantly in CO2 group as compared to the Air group; these values were reduced by simply increasing the ventilation. CONCLUSION: CO2 insufflation during ERCP significantly reduces post-procedural abdominal pain and distension. Increased PetCO2 and PaCO2 values remained within acceptable or readily controllable ranges.

Short- and long-term outcomes of self-expanding metal stent placement as a bridge to surgery for acute left-sided colorectal cancer obstruction.

AIM: The aim of this study was to evaluate the short- and long-term outcomes of self-expanding metal stent (SEMS) insertion as a bridge to surgery (BTS) in patients presenting with acute left-sided colorectal cancer obstruction (LCCO). METHODS: All patients with acute LCCO who underwent endoscopic SEMS placement as a BTS between January 2005 and December 2010 were reviewed and included in the study. RESULTS: Thirty-six patients (19M and 17F; mean age 68.5) were included. The most frequent location was the sigmoid colon (47.2%). Technical success was achieved in 91.6% and clinical success in 88.9%. Technical failure was related to the location of the stricture at the rectosigmoid junction (P=0.03). There were four SEMS-related complications: one fecal obstruction, one haemorrhage treated with APC and two silent perforations which were noted during surgical resection. The mean time between SEMS insertion and surgical treatment was 19 days (range 6-80 days) and the most frequent intervention was a left hemicolectomy (46.9%). No intraoperative mortality and morbidity, or postoperative mortality were observed. The postoperative morbidity rate was 18.8% (two wound infections, one deep venous thrombosis, one case of pneumonia and one anastomotic dehiscence). Finally, after discharge from hospital, a total of 29 patients (90%) were stoma free. At the end of the follow-up period, 24 patients are still alive and the mean survival rate was 37.3±18 months (range 9-72). CONCLUSION: In our experience, SEMS placement as a BTS is a safe and effective strategy for the treatment of patients with acute LCCO.

Efficacy and tolerability of a novel galactomannan-based formulation for symptomatic treatment of gastroesophageal reflux disease: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Proton Pump Inhibitors (PPIs) and traditional antacids are the common standard set of therapy for the management of gastroesophageal reflux disease (GERD) symptoms. The aim of the current study was to evaluate efficacy and safety of a novel galactomannan-based liquid formulation in reducing typical GERD symptoms in patients not taking PPIs. PATIENTS AND METHODS: This was a single-center, randomized, double-blind, placebo-controlled study. Sixty patients met the eligibility criteria and were treated either with the investigational product (RefluG™) or placebo, one sachet three times per day for 14 consecutive days. Symptom intensity/frequency and quality of life were assessed over the course of the study by Reflux Disease Questionnaire (RDQ) and GERD-Health related Quality of life (HRQL) Questionnaire, respectively. The primary endpoint was to determine the number of subjects with at least 30% symptoms reduction from baseline to day 14 compared to placebo. RESULTS: RefluG™ was statistically superior to placebo (p <0.001) as 100% of subjects experienced at least 30% symptoms reduction at the end of the study while none achieved a 30% reduction in the placebo group. For all domains both after 7 and 14 days of treatment, significant improvement in HRQL was seen in the active group in comparison to placebo. Tolerability and safety were good and comparable between groups. CONCLUSIONS: The investigational product was safe and effective as mono-therapy in providing early resolution of troublesome GERD symptoms as well as for improving quality of life.

Hepatitis C virus infection and lichen planus: a systematic review with meta-analysis.

OBJECTIVE: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease worldwide but its morbidity is also due to a variety of extra-hepatic manifestations including mixed cryoglubulinemia, non-Hodgkin lymphoma, diabetes, porphyria cutanea tarda and lichen planus. The aims of this study were to conduct a systematic review and a meta-analysis on the prevalence of HCV in lichen planus patients and on the prevalence of lichen planus in chronic HCV infection. MATERIALS AND METHOD: Bibliographic searches were conducted in several electronic databases. Pooled data were analysed by calculating odds ratios, using a random effects model. RESULTS AND CONCLUSIONS: Thirty-three studies comparing the seroprevalence of HCV in lichen planus patients and six reporting the prevalence of lichen planus in patients with HCV infection were included in the meta-analysis. The summary estimate showed that LP patients have significantly higher risk (odds ratio 4.85; 95% confidence interval 3.58-6.56) than controls of being HCV seropositive. A similar odds ratio of having lichen planus was found among HCV patients (4.47; 95% confidence interval 1.84-10.86). Sub-analyses indicated that variability of HCV/lichen planus association seemed only partially depending on geographic effect.

Helicobacter pylori infection and diabetes.

The bacterium Helicobacter pylori (H. pylori), prime causal agent of gastroduodenal diseases, has been involved in various aspects of several extragastric manifestations. Although currently available data do not provide proof of its role in most of them, a potential relationship cannot be ruled out. In the present review, the consistency of a role of H. pylori infection in the pathogenesis of diabetes mellitus (DM) as well as in the gastric abnormalities of diabetics is analyzed and critically discussed. Several controversies emerge from the epidemiological data. The clinical consequence of H. pylori infection in terms of metabolic control seems to be low. Regarding interventional studies, the bacterial eradication rate is significantly lower in DM patients than in controls. The difference in the eradication rate observed between adults and children affected by diabetes could be due to the fact that the latter have no history of repeated infectious diseases and antibiotic treatments, with minor antibiotic-resistant H. pylori strain selection. Finally, a higher H. pylori re-infection rate in DM patients than in general population has been shown.

Potential link between Helicobacter pylori and ischemic heart disease: does the bacterium elicit thrombosis?

Over the past fifteen years, numerous observations have linked Helicobacter pylori (H. pylori) infection to ischemic heart disease (IHD). Despite the controversial literature data, it has been postulated that if a role is plausible, it will be in the early events of the acute coronary syndrome. According to this model, we focused on the potential pathogenic mechanisms relating H. pylori to IHD like platelet aggregation and thrombosis. To identify all publications in this field, a MEDLINE search of studies published in English from 1965 to 2009 was conducted. Although very few investigations were found, these showed data of paramount importance. In particular, it has been demonstrated that some strains of H. pylori bind von Willebrand factor and interact with glycoprotein Ib to induce platelet aggregation in humans. In experiments from animal models, such infection promoted the formation of platelet aggregates by both a marked increase in the flux of rolling leukocytes and the appearance of platelet and leukocyte-platelet aggregates in gastric venules. This aggregate formation was abrogated by antibodies against specific adhesion molecules (L- and P-selectin). The future challenge is to gain more knowledge in this field and to translate these information into clinical practice.