Effect of oral anticoagulants on the outcome of faecal immunochemical test.

BACKGROUND: We aimed to evaluate whether oral anticoagulants (OACs) alter faecal immunochemical test (FIT) performance in average-risk colorectal cancer (CRC) screening. METHODS: Individuals aged 50-69 years were invited to receive one FIT sample (cutoff 75 ng ml(-1)) between November 2008 and June 2011. RESULTS: Faecal immunochemical test was positive in 9.3% (21 out of 224) of users of OAC and 6.2% (365 out of 5821) of non-users (P-trend=0.07). The positive predictive value (PPV) for advanced neoplasia (AN) in non-users was 50.4% vs 47.6% in users (odds ratio, 0.70; 95% CI, 0.3-1.8; P=0.5). The PPV for AN in OAC more antiplatelets (aspirin or clopidogrel) was 75% (odds ratio, 2; 95% CI, 0.4-10.8; P=0.4). CONCLUSIONS: Oral anticoagulant did not significantly modify the PPV for AN in this population-based colorectal screening program. The detection rate of advanced adenoma was higher in the combination OAC more antiplatelets.

Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection.

BACKGROUND: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. AIM: To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. METHODS: Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. RESULTS: Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. CONCLUSION: A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

Long-term follow-up of 1,000 patients cured of Helicobacter pylori infection following an episode of peptic ulcer bleeding.

OBJECTIVES: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients. METHODS: Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up. RESULTS: Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up. CONCLUSION: Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

Whipple's disease in Spain: a clinical review of 91 patients diagnosed between 1947 and 2001.

BACKGROUND: To determine the epidemiological, clinical, diagnostic and therapeutic characteristics of Whipple s disease in Spain. PATIENTS AND METHOD: Cases of Whipple s disease reported in the Spanish literature between 1947 and 2001 which meet histological or PCR criteria are reviewed. RESULTS: 91 cases were included, 87.5% of which were male. The maximum incidence was between 40 and 60 years of age (68%). There was no family clustering or susceptibility by profession or surroundings. The most common symptoms and signs were: weight loss (80%), diarrhoea (63%), adenopathies (35%), skin problems (32%), abdominal pain (27%), fever (23%), joint problems (20%) and neurological problems (16%). Arthralgias, diarrhoea and fever were noted prior to diagnosis in 58, 18 and 13% of patients, respectively. Diagnosis was histological in all cases except two, which were diagnosed by PCR. Intestinal biopsy was positive in 94%. Adenopathic biopsies (mesenteric or peripheral) were suggestive in 13% of cases, and treatment was effective in 89%. There were nine relapses, four of which were neurological, although all occurred before the introduction of cotrimoxazole. CONCLUSIONS: Whipple s disease is not uncommon, although it requires a high degree of suspicion to be diagnosed in the absence of digestive symptoms. The most common and most sensitive diagnostic method is duodenal biopsy. PCR is beginning to be introduced to confirm the diagnosis and as a therapeutic control. Initial antibiotic treatment with drugs that cross the blood-brain barrier, such as cotrimoxazole and ceftriaxone, is key to achieving a cure and avoiding relapses.

Pyogenic versus amoebic liver abscesses. A comparative clinical study in a series of 58 patients.

OBJECTIVE: To compare the clinical and epidemiological characteristics of patients with pyogenic liver abscess (PLA) and with amebic liver abscess (AHA) in order to determine the potential factors that may help improve diagnosis and treatment for this disease. MATERIAL AND METHOD: A retrospective study of clinical histories of 45 patients with PLA and 13 with ALA, diagnosed between 1985 and 2005 in Donostia Hospital in San Sebastián. RESULTS: Among the 45 patients with PLA (30 men and 15 women, with a mean age of 61 years and 11 months), more than a half were cholangitic (13 cases) or were of unknown origin (15 cases). In 10 patients, diabetes was considered to be a predisposing condition. Increased ESR (> 30), leukocytosis (> 12,000), fever and abdominal pain were observed in 95.5%, 86.7%, 82.8% and 68.9%, respectively. Twenty-five patients had single abscesses. Abscess and blood cultures were positive in 77.1% and 50% of cases, respectively (44.4% with polymicrobial infection). E. coli and S. milleri were the most commonly found germs. A percutaneous drainage was performed on 22 patients. Mean hospital stay was 27 days, and overall mortality, including that related to concomitant conditions, was 7 of 45 cases.Of the 13 cases of ALA (7 men and 6 women, with mean age of 42,9 years), 2 were locally acquired. Increased AF and GGTP (> 2N), fever, leukocytosis and ESR (> 30) were observed in 92.3, 77, 70 and 61.5% of cases, respectively. There were single abscesses in 10 patients and all except one were located in the right lobe. The serological test for E. histolytica (IFF > or = 1/256) was positive in 100% of cases. A percutaneous drainage was carried out on 6 patients. Mean hospital stay was 18 days and two patients died. CONCLUSIONS: In our series, the clinical parameters suggesting pyogenic origin were: age 50 or older, male gender, diabetes, moderately elevated bilirubin and transaminases. In amoebic cases the associated features were being aged 45 or younger, diarrhoea, and presence of a single abscess in the right lobe. Parasitism by E. histolytica must be considered in the differential diagnosis of liver abscesses, even with no epidemiological clinical history of travel and/or immigration.

[Porphyria cutanea tarda. An analysis of HFE gene mutations, hepatitis viruses, alcohol intake, and other risk factors in 54 patients from Guipúzcoa, Basque Country, Spain]. / Porfiria cutánea tarda: asociación con mutaciones HFE, hepatitis virales, alcohol y otros factores de riesgo en Guipúzcoa, País Vasco.

AIM: To study the frequency of HFE gene mutations (C282Y, H63D, S65C) in a group of 54 sporadic PCT patients and in a group of healthy controls (blood donors) from Guipúzcoa, Spain. We studied the association of PCT with HCV, HBV, alcohol abuse, and other established risk factors. METHODS: The analysis of mutations was made by PCR. Allelic and genotypic frequencies were compared. Probability was determined and a Chi-squared test was performed. RESULTS: No association was observed between C282Y mutation and PCT (5.76 vs. 5% in controls). A high H63D mutation frequency was observed in PCT (34.25%) but was not statistically significant (controls 29.31%) because of the high prevalence of this mutation in the Basque general population. The S65C mutation was lower in PCT than in controls. There is a similar presence for H63D heterozygosis in PCT (38.8 vs. 38.8%). HCV association was observed in 35.18% of patients with PCT. HBV infected 7.4% of patients. Heavy alcohol intake (> 60 g/day) was present in 55.55% of patients. No HIV-infected patients were detected. The study of other risk factors revealed only one of the five women with PCT taking estrogens. CONCLUSION: Our results found no relevant role for C282Y and H63D mutations. External factors such as HCV and alcohol could be determinant in the development of PCT in the Basque population.

Effects of long-term cyclo-oxygenase 2 selective and acid inhibition on Barrett's oesophagus.

BACKGROUND: There is an overexpression of cyclo-oxygenase 2 (COX-2) in Barrett's oesophagus (BO). AIM: To determine the long-term effect of a COX-2 inhibitor on cellular mechanisms involved in BO. METHODS: A randomized controlled trial was conducted in BO patients allocated to continue the usual proton pump inhibitor (PPI) alone treatment, or PPI combined with rofecoxib (25 mg/day) for 6 months. Cell proliferation index and COX-2 expression in BO glands was determined in biopsy specimens at baseline and after treatment. Cell apoptosis, cyclin D1, p53 and vascular endothelial growth factor (VEGF) expression was also explored in a subset of patients. Student-t test and the U-Mann-Whitney test were used for quantitative and ordinal variables. RESULTS: Of 62 patients, 58 completed the study. A higher proportion of patients on rofecoxib + PPI exhibited a decrease in COX-2 expression compared to those treated with PPI alone, but cell proliferation index was not affected. Unlike PPI alone, rofecoxib + PPI was associated with an increase in the apoptotic cell index, a decrease in p53 cell staining and VEGF expression in mucosal vessels. No effect on low-grade dysplasia or cyclin D1 was observed. CONCLUSIONS: The addition of rofecoxib to PPI therapy does not affect cell proliferation index in BO cells after 6 months of therapy, but does reduce COX-2 and VEGF expression and increases cell apoptosis.

Recurrence of Helicobacter pylori infection after several eradication therapies: long-term follow-up of 1000 patients.

AIM: To study the incidence of Helicobacter pylori recurrence, its chronological aspects, and the variables that might influence it. METHODS: A total of 1000 patients in whom H. pylori had been eradicated were prospectively studied. Therapies were classified as low and high efficacy regimens. Four to eight weeks after completion of therapy, 13C-urea-breath-test was performed, and it was repeated yearly up to 5 years. In some patients, endoscopy with biopsies was also performed to confirm H. pylori eradication. RESULTS: A total of 1000 patients were included, giving 2744 patient-years of follow-up. Seventy-one H. pylori recurrences were observed (2.6% per patient-year). Probability of being H. pylori-negative at 1 year was 94.7%, and at 5 years 90.7%. In the multivariate analysis, low age (OR: 1.84; 95% CI: 1.04-3.26) and low efficacy therapies (OR: 2.5; 1.23-5.04) correlated with 1-year H. pylori recurrence. Differences were observed when Kaplan-Meier curves were compared depending on age and therapy regimen. CONCLUSION: Risk of posteradication H. pylori recurrence is higher during the first year, which suggests that most recurrences during this period are recrudescence and not true reinfections. H. pylori recurrence is more frequent in younger patients and in those treated with low efficacy therapies, but is exceptional if high efficacy therapies are used, in which case post-therapy eradication can be safely confirmed at 4 weeks with 13C-urea-breath-test.

MRI and endoscopic ultrasonography in the staging of gastric cancer.

OBJECTIVE: to determine the diagnostic precision of endoscopic ultrasounds (EUS) and magnetic resonance imaging (MRI) in the preoperative staging of gastric cancer. METHODS: a prospective, blind study was carried out in 17 patients diagnosed with gastric cancer (GC) using endoscopic biopsy from November 2002 to June 2003. Patients underwent preoperative MRI and EUS. The reference test used was pathology, and laparotomy for non-resectable cases. RESULTS: MRI (53%) was better than EUS in the assessment of gastric wall infiltration (35%). MRI (50%) was also superior to EUS (42%) for N staging. After pooling stages T1-T2 and T3-T4 together, results improved for both MRI (67 and 87.5%, respectively) and EUS (67 and 62.5%, respectively) (p < 0.05). N staging--lymph node invasion--results were correct in 50% for MRI as compared to EUS (42%). In classifying positive and negative lymph nodes EUS was superior to MRI (73 versus 54%). CONCLUSIONS: MRI was the best method in the assessment of gastric wall infiltration. EUS was superior to MRI for T1 staging, and in the assessment of lymph node infiltration.

The value of colonoscopy to assess rectal bleeding in patients referred from Primary Care Units.

OBJECTIVES: Rectal bleeding is very common in the general population. It is produced mainly because of benign disease originating in the anus and the rectum. Our aim was to evaluate the need for colonoscopy in patients presenting with rectal bleeding. PATIENTS AND METHODS: Patients referred from Primary Care Units and complaining of rectal bleeding were included prospectively in a three-month study. All patients underwent a careful medical history along with physical examination, laboratory tests, and colonoscopy. RESULTS: 126 patients with a mean age of 49.2 years (range: 19-80) were studied. Rectal digital examination was abnormal in 75 cases (59.5%). Severe disease was encountered in 22 patients (neoplasm, angiodysplasia, and inflammatory bowel disease); 10 patients had polyps, 6 had colorectal cancer, and 6 had inflammatory bowel disease. Out of 63 patients younger than 50 years, 5 had severe disease, all of them in the form of inflammatory bowel disease. CONCLUSIONS: A neoplasm of the rectum and colon in patients younger than 50 years is a rare event. A colonoscopy must be performed in this group of patients to rule out inflammatory bowel disease.

[Type III glycogen storage disease associated with hepatocellular carcinoma]. / Glucogenosis tipo III asociada a carcinoma hepatocelular.

Type III glycogen storage disease is a hereditary disorder with autosomal recessive transmission. It is characterized by accumulation of abnormal glycogen in the liver and, in 80% of patients, in muscle. The liver can also show fibrosis and sometimes cirrhosis. Until 2000, 9 cases of cirrhosis had been published, 3 of which showed associated hepatocarcinoma. We present the case of a 31-year-old woman, diagnosed in childhood with type III glycogen storage disease, who 30 years after onset developed a hepatocellular carcinoma with portal thrombosis in the context of advanced cirrhosis. This is the first case to be reported in the Spanish literature of type III glycogen storage disease associated with hepatocellular carcinoma.

Lewis, secretor, and ABO phenotypes, and sulfomucin expression in gastric intestinal metaplasia.

The closely interrelated Lewis, secretor, and ABO phenotypes have long been linked to the risk of peptic ulcers and gastric cancer and may modulate the interaction between Helicobacter pylori and the gastric surface epithelium. We explored the association between the expression of sulfomucins in gastric intestinal metaplasia, a known marker of preneoplastic progression, and the expression of Lewis, secretor, and ABO phenotypes, in 523 subjects from Nariño, Colombia, and 856 subjects from northern Spain. In both study populations, Lewis (a+/b-) and nonsecretor phenotypes showed a significant positive association with the expression of sulfomucins (odds ratios, 2.4 and 2.6, respectively).

Expression of type 1 blood group precursor in human gastric carcinoma.

The surface epithelium of normal gastric mucosa from patients with gastric adenocarcinoma expressed the type 1 blood group precursor only in Lewis (Le) non-secretor individuals, Le a+b- (se/se, Le/-) and Le a-b- (se/se, le/le). In secretors, the superficial mucosa was negative. Deep areas of the mucosa showed no type 1 precursor regardless of secretor status. Expression of type 1 precursor was anomalously found in neoplastic cells in 14 of 16 Le a-b+ (secretors) patients and in 4 of 5 Le a-b- (secretors) patients. The 1 Le a-b- non-secretor carcinoma expressed type 1 precursor strongly. 6 of 8 Le a+b- non-secretor carcinomas showed positivity for the monoclonal antibody K-21. Thus the type 1 precursor reacted with the non-neoplastic gastric surface of non-secretors but not with those of secretors, and also with most gastric adenocarcinoma regardless of secretor status and Lewis phenotype.

Blood-group phenotypes, sulfomucins, and Helicobacter pylori in Barrett's esophagus.

Barrett's esophagus, morphologically analogous to gastric intestinal metaplasia, often precedes the development of esophageal adenocarcinoma. In the stomach, expression of sulfomucins and aberrant Lewis(a) (Le[a]) antigen is an excellent predictor of premalignant progression, and Helicobacter pylori infection is a crucial determinant for the development of atrophy, metaplasia, and adenocarcinoma. In the esophagus, the significance of sulfomucin expression is controversial, the aberrant expression of Le(a) has not been explored, and the role of H pylori in the evolution of preneoplastic conditions is unknown. We investigated in 155 patients referred for endoscopy the association of Barrett's esophagus with expression of sulfomucins, Lewis, secretor, and ABO phenotypes, and H pylori infection. We report a subtype of intestinal metaplasia, present in all patients with esophageal adenocarcinoma, similar to gastric intestinal metaplasia of colonic type (type III or incomplete), that expresses sulfomucins and aberrant Le(a) in goblet and columnar cells. Lewis(a+b-), nonsecretor and blood group A phenotypes, were all positively associated with esophageal adenocarcinoma, suggesting a genetic susceptibility. H pylori infection was detected in 75% of patients with esophageal adenocarcinoma.

Influence of Helicobacter pylori infection and eradication on blood lipids and fibrinogen.

BACKGROUND: An association between Helicobacter pylori infection and heart disease has been suggested. A potential mechanism may be inflammation-induced atherogenic changes of lipoproteins, but epidemiological studies have provided conflicting results. METHODS: In a prospective multicentre study, 830 patients submitted for endoscopy and H. pylori testing were evaluated. Of the 686 H. pylori-positive patients, 487 received and 199 did not receive eradication treatment. Serum lipids and plasma fibrinogen were measured at baseline in all patients and 3 months later in those initially positive for H. pylori. RESULTS: H. pylori had no influence on baseline lipid or fibrinogen levels. Increases in high-density lipoprotein cholesterol were observed in 368 patients who received eradication treatment and in 193 untreated patients: 0.06 mmol/L (P=0.000) and 0.07 mmol/L (P=0.009), respectively. Similar minor increases in total cholesterol and triglycerides occurred in both groups. Lipid changes were related to symptom relief and a reduction in smoking. Eradication therapy was associated with a minor decrease in plasma fibrinogen irrespective of the resolution of infection. CONCLUSIONS: H. pylori has no influence on blood lipids or fibrinogen. Both the eradication of infection and symptomatic treatment without eradication are associated with minor lipid changes related to symptom relief and lifestyle modifications. Thus, the inflammatory changes associated with H. pylori are unlikely to affect lipoprotein or fibrinogen metabolism.

Expression of type 1 and type 2 blood group-related antigens in normal and neoplastic gastric mucosa.

The distribution of the blood group-related antigens type 1 (Lewis(a) [Le(a)], Lewis(b) [Le(b)]) and type 2 (H type 2, Y) has been examined in histologically normal and malignant mucosa of 40 surgical specimens of patients with adenocarcinoma of the stomach, with the use of a panel of monoclonal antibodies. Patients' Lewis phenotype and secretor status are correlated to the authors' findings. The surface epithelium of normal pyloric and fundic mucosa expressed the Lewis isoantigen (Le(a) in Le[a+b-] phenotype and Le(b) in Le[a-b+] phenotype), whereas the deep areas of this mucosa no showed the Le(a), Le(b) antigens and expressed the Y and H type 2 antigens whatever the secretor status of patients. Nineteen of 24 patients with Le(a-b+) phenotype showed anomalous expression of Lea antigen in neoplastic cells. In three of them, this alteration was found in tumor adjacent mucosa. No expression of Le(a) or Le(b) antigens was found in tumors or normal mucosa from Le(a-b-) phenotype patients.

[Esophageal amyloidosis secondary to rheumatoid arthritis simulating achalasia]. / Amiloidosis esofágica secundaria a artritis reumatoide que simula acalasia.

The involvement of the esophagus in amyloidosis secondary to rheumatoid arthritis is rare. The case of a female patient with rheumatoid arthritis and secondary esophageal amyloidosis (type AA) with a radiologic and endoscopic clinical picture compatible with achalasia is presented. In the manometry carried out after two cardiomyotomies, abundant non propulsant tertiary waves were seen, as were two primary waves, intraesophageal pressure higher than that of the gastric fundus and lower hypertensive esophageal sphincter which was completely relaxed on one occasion, resulting in a manometric pattern which was different to that of the other two cases published with the same disease. Endoscopic cardiomyotomies and dilatations were performed. The patient died after 2 years due to post dilatation esophageal perforation. The manometric findings are compared with those of the two previous similar cases with emphasis being made in that the anarchic arrangement of the amyloid in the esophagus produces different unforeseen and uncharacteristic motility patterns. The authors only found in the literature two cases of esophageal amyloidosis secondary to rheumatoid arthritis simulating achalasia.

[Alcoholism, polyneuropathy, and liver disease. A prospective electrophysiologic study]. / Alcoholismo, polineuropatía y enfermedad hepática. Estudio prospectivo electrofisiológico.

A prospective clinical and electrophysiologic study was performed in 50 alcoholic patients in order to assess the incidence and clinical manifestations of alcoholic polyneuropathy, the value of the electrophysiologic parameters studied, and the influence of liver disease on the appearance of neuropathy. The proposed criteria for polyneuropathy were fulfilled by 24% of the patients. Abolition of the Achillean reflexes was the most frequent clinical finding, while reduced amplitude of muscular potential was the most sensitive electrophysiologic parameter. There were no differences in alcohol consumption, frequency of liver disease, and degree of alteration of liver function in cirrhotics between patients with and without polyneuropathy.