Prevalence and characteristics of Epstein-Barr virus-associated gastric carcinomas in Portugal.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract and is the third leading cause of cancer death worldwide. Epstein-Barr virus (EBV) has been associated with approximately 10% of the total cases of gastric carcinomas. No previous study has analyzed the prevalence of EBV infection in gastric cancer of the Portuguese population. METHODS: In the present study, we have analyzed 82 gastric carcinoma cases and 33 healthy individuals (control group) from Coimbra region for the presence of EBV by polymerase chain reaction (PCR) and by in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs). The status of H. pylori infection was assessed by serology and by PCR. RESULTS: EBV was detected by PCR in 90.2% of stomach cancer cases, whereas EBERs were detected in 11%. In our series, EBV-associated gastric carcinoma (EBVaGC) were significantly associated with gender and the majority of them presented lymph node metastasis. These cases were generally graded in more advanced pTNM stages and, non-surprisingly, showed worse survival. H. pylori infection was detected in 62.2% of the gastric cancers and 64.7% of these patients were CagA+. On the other hand, the H. pylori prevalence was higher in the EBV-negative gastric carcinomas (64.4%) than in those carcinoma cases with EBV+ (44.4%). CONCLUSIONS: The present study shows that prevalence of EBVaGC among Portuguese population is in accordance with the worldwide prevalence. EBV infection seems to be associated to poorer prognostic and no relation to H. pylori infection has been found. Conversely, the presence of H. pylori seems to have a favourable impact on patient's survival. Our results emphasize that geographic variation can contribute with new epidemiological data on the association of EBV with gastric cancer.

Capsule endoscopy in inflammatory bowel disease type unclassified and indeterminate colitis serologically negative.

BACKGROUND: The value of capsule endoscopy in the setting of inflammatory bowel disease type unclassified (IBDU) and indeterminate colitis (IC) remains obscure. The aim was to evaluate the clinical impact of capsule endoscopy on IBDU/IC patients with negative serology. METHODS: Eighteen patients with long-standing IBDU (n = 14) and IC (n = 4) were enrolled to undergo a capsule endoscopy and then followed prospectively. Lesions considered diagnostic of Crohn's disease (CD) were 4 or more erosions/ulcers and/or a stricture. The median follow-up time after capsule endoscopy was 32 ± 11 months (23-54 months). RESULTS: Total enteroscopy was possible in all patients. In 2 patients the examination was normal (Group 1). In 9 patients subtle findings were observed (Group 2): focal villi denudation (n = 1) and fewer than 4 erosions/ulcers (n = 8). In 7 patients, 4 or more erosions/ulcers were detected (Group 3), leading to a diagnosis of CD. However, their treatment was not reassessed on the basis of the capsule findings. Until now, a definitive diagnosis has been achieved in 2 additional patients: 1 from Group 1 (ulcerative colitis) and another patient from Group 2 (CD), who began infliximab infusions. Nine patients remained indeterminate at follow-up. CONCLUSIONS: Although capsule endoscopy enabled the diagnosis of CD in 7 patients, in none of them was the clinical management changed. Moreover, a change in therapy due to a diagnosis of CD was made for only 1 patient, who presented nonspecific findings. Our results suggest that capsule findings are not helpful in the work-up of these patients.

The effect of metoclopramide in capsule enteroscopy.

Clinical utility of prokinetics in capsule endoscopy (CE) is not clearly established. The objective of this prospective, randomized, single-blind, controlled trial was to determine if metoclopramide is useful in CE by increasing the rate of complete enteroscopy. Ninety-five patients referred for CE were randomized to no metoclopramide (group B, n = 48) or 10 mg metoclopramide (group A, n = 47). Complete enteroscopy was possible in 38 patients of group A (80.9%) and 37 of group B (77.1%) (P = 0.422) with two cases of gastric retention in group B (4.2%; P = 0.253). Median gastric transit time was 26 min (1-211) in group A and 28 min (4-200) in group B (P = 0.511). Mean small bowel transit time, calculated after excluding 20 patients with incomplete enteroscopy, was similar in both groups (221.2 +/- 89 min vs. 256 +/- 82.2 min; P = 0.083). There were also no differences in the total number of findings (group A 4.5 +/- 4.7; group B 4.7 +/- 3.7, P = 0.815). Administration of 10 mg metoclopramide orally 15 min before capsule ingestion did not significantly increase the rate of total enteroscopies and had no effect on transit times. It also did not modify CE diagnostic yield.

Urgent capsule endoscopy is useful in severe obscure-overt gastrointestinal bleeding.

AIM: With capsule endoscopy (CE) it is possible to examine the entire small bowel. The present study assessed the diagnostic yield of CE in severe obscure-overt gastrointestinal bleeding (OOGIB). METHODS: During a 3-year period, 15 capsule examinations (4.5% of all CE in a single institution) were carried out in 15 patients (11 men; mean age 69.9 +/- 20.1 years) with severe ongoing bleeding, defined as persistent melena and/or hematochezia, with hemodynamic instability and the need for significant red blood cell transfusion. CE was carried out after non-diagnostic standard upper and lower endoscopy. The mean time from admission until CE was 4.1 +/- 4.4 days (0-15 days). RESULTS: CE revealed active bleeding in seven patients and signs of recent bleeding in four. Etiology of bleeding was correctly diagnosed in 11 patients (73.3%) (portal hypertension enteropathy, three patients; subepithelial ulcerated lesion, two patients; angiodysplasia, two patients; jejunal ulcer with visible vessel, one patient; multiple small bowel ulcers, one patient; jejunal tumor, one patient; jejunal mucosa irregularity with adherent clot, one patient). One patient (6.7%) had active bleeding but no visible lesion. As a consequence of the capsule findings, specific therapeutic measures were undertaken in 11 patients (73.3%) with five managed conservatively, four endoscopically and two surgically. Two patients experienced bleeding recurrence. One of them, with a probable small bowel tumor, refused any other interventions. CONCLUSIONS: CE is useful in patients with severe OOGIB by providing positive findings in the majority of patients, with subsequent impact on therapeutic procedures.

Small bowel pseudomelanosis and oral iron therapy.

Small bowel pseudomelanosis is a rarely reported clinical entity characterized by brown pigmentation of small bowel mucosa. The authors describe two cases, both with iron deficiency anemia, one of an 81-year-old female patient submitted for capsule endoscopy that revealed a brown pigmentation of all small bowel mucosa and another of an 81-year-old male whose retrograde double-balloon enteroscopy revealed a diffuse brown pattern of small bowel mucosa. Ileal biopsies confirmed intense iron deposition in the macrophages of the lamina propria. Both patients were on oral iron therapy and the second one had a previous double-balloon enteroscopy, 2 years earlier, which revealed only ileal angiodysplasias. These two cases demonstrate the importance of two new endoscopic methods for diagnosis of small bowel pseudomelanosis, the rarity of such an entity and its close relation with oral iron therapy.

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization.

BACKGROUND AND AIMS: Aberrant crypt foci (ACF) are preneoplastic lesions in animal models of colorectal cancer. The aim of the study is to investigate if ACF are involved in human colorectal carcinogenic process and if they can be helpful in predicting the presence of a colorectal neoplasia. METHODS: The study included, between 2003 and 2005, 182 patients, 62 with adenoma, 55 with colorectal carcinoma, 53 without colorectal lesions, and 12 with nonneoplastic mucosal polyps. The number of rectal ACF was determined by colonoscopy. Proliferation and apoptosis indexes were evaluated by immunohistochemistry in rectal ACF, in normal rectal mucosa, and in carcinomatous tissue. RESULTS: The mean number of rectal ACF in patients with rectal neoplasia was 12.64, significantly higher than in patients with neoplastic lesions elsewhere in the colon (p=0.01). The apoptosis index in ACF of patients with colorectal carcinoma or adenoma aged 50 years or older was significantly lower than in younger patients (1.3% vs 2.7%, p=0.01) and, in patients with carcinoma, lower than in normal mucosa (1.1% vs 2.1%, p=0.002). The proliferation index was significantly higher in ACF of patients with colorectal neoplasia aged less than 50 years than in normal mucosa (10.9% vs 7.7%, p=0.02). The apoptosis index in ACF foci of patients with carcinoma (1.1%) was significantly lower than in patients without lesions (2.2%) and than in normal mucosa (2%). The mean number of ACF is significantly higher in patients with polyps larger than 1 cm (11.28 vs 6.27, p=0.02). CONCLUSION: Aberrant crypt foci probably precede the appearance of neoplasia and may be helpful in predicting the presence of a colorectal neoplastic lesion.

Double-balloon enteroscopy and small bowel tumors: a South-European single-center experience.

Small bowel tumors are rare, accounting for 1-2% of all gastrointestinal neoplasms. We sought to determine the diagnostic and therapeutic impact of double-balloon enteroscopy (DBE) in patients with small bowel tumors. Between January 2005 and March 2008, 78 patients underwent 96 DBE. All nine patients (seven males; mean age 68 +/- 11.3 years) with small bowel tumors were retrospectively reviewed. Clinical presentation was: mid-gastrointestinal bleeding or iron-deficient anemia (55.6%); abdominal pain (22.2%); nausea/vomiting and abdominal distension (22.2%). Five patients had abnormal findings in previous capsule endoscopy and four in previous radiologic examinations. Route of insertion was exclusively oral and abnormal lesions were detected in all patients (jejunum 8; ileum 1). Biopsies were taken in seven patients and provided definitive histological diagnosis in all except one. There were no complications of DBE. Surgical resection took place in eight patients. Final histologic diagnosis were: primary carcinoma (33.3%), gastrointestinal stromal tumor (GIST) (33.3%), malignant lymphoma (22.2%), and carcinoid tumor (11.1%). Mean follow-up time was 15.4 +/- 12.7 months (range 2-34 months). Six patients were submitted to chemotherapy. Two patients died. Small bowel tumors are common in patients submitted to DBE. Given its safety and diagnostic capabilities, DBE should be considered the gold-standard method in the study of these neoplasms.

Primary leiomyoma of the liver: accurate preoperative diagnosis on liver biopsy.

Primary leiomyoma of the liver is an exceptionally rare tumour in non-immunocompromised patients. Preoperative diagnosis of the lesion is difficult as complete imaging of this type of lesion is scarcely defined and preoperative biopsy was not the practice in previously reported cases. We report a voluminous primary leiomyoma of the liver occurring in a healthy middle-aged woman where a preoperative diagnosis was accurately achieved on biopsy. Because of its size, surgery was undertaken for exclusion of malignancy. A 16-month uneventful follow-up has been completed. We discuss the advantage of a preoperative diagnosis and propose that an imaging-guided liver biopsy should be undertaken, provided malignancy features are absent. This could prevent liver surgery merely for diagnostic purposes. Finally, we report imaging features that have not been previously described, namely on magnetic resonance imaging, which may provide an insight about the nature of this particular lesion and, advantageously, contribute toward a non-invasive diagnosis.

In-hospital mortality in spontaneous bacterial peritonitis: a new predictive model.

INTRODUCTION AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhotics with ascites. Early identification of high-risk patients is crucial for prognostic improvement. Model for end-stage liver disease (MELD) relies on a few objective variables and predicts short-term survival. We aimed to determine the predictive value of MELD score, at admission, in the short-term mortality of SBP patients. METHODS: We conducted a retrospective study of 73 SBP episodes admitted in our department between January 2002 and April 2006. Diagnosis (neutrophil count in ascitic fluid >or=250/mm3) was established within 24 h and cefotaxime was immediately started. Data collected included age, sex, etiology of liver disease, severity of ascites and hepatic encephalopathy, serum creatinine, total bilirubin and albumin, prothrombin time with international normalized ratio, and ascitic fluid analysis. STATISTICS: Student's t-test, chi2 test, univariate analysis, logistic regression model, and receiver operating characteristic curves. RESULTS: In-hospital mortality rate was 37%. In multivariate analysis, MELD score (P<0.001), and advanced age (P<0.05) were independent predictors of mortality. Receiver operating characteristic curve for MELD score revealed an excellent discriminatory ability to predict death, with an area under curve of 0.84. Age increased the predictive ability of MELD score, represented by an increment of area under curve to 0.88. CONCLUSION: MELD score and older age were independent predictors of mortality. Age increased the discriminatory ability of MELD score to predict death. This new model may be useful for stratifying patients in future therapeutic trials, deserving further validation.

Value of reagent strips in the rapid diagnosis of spontaneous bacterial peritonitis.

BACKGROUND/AIMS: Spontaneous bacterial peritonitis is a severe complication in cirrhotic patients with ascites. Early antibiotics are essential to improve the prognosis. An ascites neutrophil count >250/mm3 is an indication for antibiotic therapy. However this procedure requires intensive labor and is not available in all hospitals on emergency setting. The aim of this study was to assess the utility of Human-Test Combina strips for the rapid diagnosis of spontaneous bacterial peritonitis. The interobserver variability in the result reading was also evaluated. METHODOLOGY: A prospective study of 109 consecutive ascitic fluid samples colected from 55 patients was carried out. The results of the reagent strips were compared with the neutrophil count by conventional optical microscopy. Interobserver agreement was tested in 37 cases. RESULTS: The prevalence of infection was 8.3%. Reagent strips had sensitivity, specificity, positive and negative predictive values of 78%, 88%, 37% and 98% for a cut-off level > or =2 and 67%, 98%, 75% and 97% for > or =3, respectively. Concordance between investigators was 100%. CONCLUSIONS: Reagent strips are a rapid, simple and easily available method for the diagnosis of spontaneous bacterial peritonitis. A positive result should be an indication to start antibiotics and a negative result can be useful to exclude the possibility of infection.

External validation of a classification for methylene blue magnification chromoendoscopy in premalignant gastric lesions.

BACKGROUND: Conventional endoscopy has low sensitivity, specificity, and interobserver agreement for the diagnosis of gastric atrophy, intestinal metaplasia, and dysplasia. Magnification chromoendoscopy (ME) may optimize the evaluation of premalignant gastric lesions. OBJECTIVE AND DESIGN: As part of a multicenter trial, we aimed at validating a previously proposed classification for gastric methylene blue ME at a different center. SETTING, PATIENTS, AND INTERVENTIONS: A sample of patients (n = 42) with previously diagnosed chronic atrophic gastritis with or without intestinal metaplasia underwent ME (Pentax EG-3430Z) with 1% methylene blue by 2 endoscopists. MAIN OUTCOME MEASUREMENTS: A simplified version of a previously published ME classification (group I, group II [further divided into subgroups IIE and IIF], and group III) was used for macroscopic lesions (n = 203) with Sydney-Houston and Vienna classifications being used for histologic analysis (n = 479 biopsy specimens). RESULTS AND LIMITATIONS: Excellent reproducibility (wK = 0.92 [95% CI, 0.88-0.96]) was observed for classification in groups and substantial reproducibility (wK = 0.78 [95% CI, 0.72-0.84]) was found for classification in subgroups. Global validity was 82% (range 78%-86%), showing no false negatives (sensitivity of 100% [1/1 biopsy]) and a very low rate of false positives (specificity 99% [297/299 biopsies]) for dysplasia detection. CONCLUSIONS: This classification for methylene blue ME was highly reproducible and valid for the diagnosis of premalignant gastric lesions when used in a center different from that involved in its conception. Despite requiring an unconventional endoscope and a longer procedure, these results could reinforce ME as a valuable technique in the surveillance of patients at risk for gastric cancer.

Effect of portal hypertension in the small bowel: an endoscopic approach.

BACKGROUND AND AIM: The effects of portal hypertension in the small bowel are largely unknown. The aim of the study was to prospectively assess portal hypertension manifestations in the small bowel. METHODS: We compared, by performing enteroscopy with capsule endoscopy, the endoscopic findings of 36 patients with portal hypertension, 25 cirrhotic and 11 non-cirrhotic, with 30 controls. RESULTS: Varices, defined as distended, tortuous, or saccular veins, and areas of mucosa with a reticulate pattern were significantly more frequent in patients with PTH. These two findings were detected in 26 of the 66 patients (39%), 25 from the group with PTH (69%) and one from the control group (3%) (P < 0.0001). Among the 25 patients with PTH exhibiting these patterns, 17 were cirrhotic and 8 were non-cirrhotic (P = 0.551). The presence of these endoscopic changes was not related to age, gender, presence of cirrhosis, esophageal or gastric varices, portal hypertensive gastropathy, portal hypertensive colopathy, prior esophageal endoscopic treatment, current administration of beta-blockers, or Child-Pugh Class C. More patients with these endoscopic patterns had a previous history of acute digestive bleeding (72% vs. 36%) (P = 0.05). Active bleeding was found in two patients (5.5%). CONCLUSIONS: The presence of varices or areas of mucosa with a reticulate pattern are manifestations of portal hypertension in the small bowel, found in both cirrhotic and non-cirrhotic patients. The clinical implications of these findings, as regards digestive bleeding, are uncertain, although we documented acute bleeding from the small bowel in two patients (5.5%).

[A thousand total colonoscopies: what is the relationship between distal and proximal findings?]. / Mil colonoscopias totais: que relação entre os achados distais e proximais?

BACKGROUND: Flexible sigmoidoscopy is indicated for colorectal cancer screening. The decision about who needs total colonoscopy based on distal findings is still controversial because of the uncertainty of the associations between distal and proximal findings. AIM: The purpose of the study was to characterize distal findings in patients with total colonoscopy, to investigate its importance as markers of advanced proximal lesions and to evaluate the usefulness of a clinical Predictive Index, already published in the literature, in the identification of these lesions. METHODS: Retrospective analysis of the patients submitted to total colonoscopy between January 2006 and February 2007, with selection of 1000 consecutive cases with reference to polyps. We analysed demographic data, indication for the exam and morphological and histological characteristics of the polyps. Advanced lesion was defined as any adenoma larger than 10 mm or any polyp with villous characteristics, high grade dysplasia or cancer. The Predictive Index was obtained through the assignment of points to 3 categories: sex, age and distal findings, which result in 3 groups: low, intermediate and high risk. RESULTS: The mean age of patients was 64,69 years and 65,1% were male. Distal and proximal polyps were identified in 829 (82,9%) and 369 (36,9%) patients, respectively. Advanced distal lesion was found in 342 patients (34,2%) and advanced proximal lesion in 98 (9,8%). 587 patients (58,7%) were in the high risk group. In the group of patients with advanced proximal lesion, a third presented low and intermediate risk, 52% had no distal polyps, 88,7% had less than three distal polyps and 71,4% had no advanced distal lesion. Sensitivity values for these four categories ranged between 11,2% and 66,6%. CONCLUSION: If the decision to perform total colonoscopy is based on distal colonic findings or on the Predictive Index, the ability to identify advanced proximal lesion is markedly reduced, endangering the aim of a screening program.

Fulminant hepatic failure: a Portuguese experience.

BACKGROUND: Fulminant hepatic failure (FHF) is a rare condition. Several series have been reported either by individual centres or in multicentre studies but, to our knowledge, this is the first report from a Portuguese population and might be a good example of FHF cases in a SouthWestern European population. AIMS: To present the experience in FHF of a Portuguese Hepatogastroenterological Intensive Care Unit. MATERIALS AND METHODS: Retrospective study of 61 cases of FHF consecutively admitted between February 1992 and October 2006. Definition and classification of FHF were those suggested by Trey and Davidson (1970) and O'Grady et al. (1993), respectively. Criteria and contraindications for hepatic transplantation (HT) were those proposed by Bernuau et al. (1991) and Muñoz (1993), respectively. RESULTS: Fifty-seven per cent of patients were women and median age was 37 years (range: 8-73). Most common cause of FHF was indeterminate (26%) followed by viral (23%) and drug-induced (23%), with 51% of cases with a hyperacute evolution. Global HT rate was 54% with criteria for HT present in 87% of the patients resulting in an applicability rate of 62%. Overall survival was 69% and transplant-free survival was 15%; transplanted patients had survival rates of 70 and 68% at 6 and 12 months, respectively. CONCLUSIONS: Drug-induced and viral agents were responsible for almost half of FHF cases with a clear predominance of hyperacute presentation. The HT rate was 54% and the applicability rate was 62%. The overall 1 year survival of 69% might reflect the adequacy of the HT criteria used.