cagA positive and negative Helicobacter pylori strains are simultaneously present in the stomach of most patients with non-ulcer dyspepsia: relevance to histological damage

^a Institute of Internal Medicine, University of Siena, Siena, Italy, ^b Institute of Pathology, University of Siena, ^c IRIS, Siena, ^d Institute of Surgical Clinics, University of Siena, ^e Institute of Internal Medicine, University of Bologna, Bologna, Italy

Correspondence to: Dr N Figura, Institute of Internal Medicine, University of Siena, Policlinico Le Scotte, viale Bracci, I-53100 Siena, Italy.

Accepted for publication 6 February 1998

Background/Aims—Infection with Helicobacter pylori strains harbouring the cagA gene (cagA+) is associated with an increased risk of developing peptic ulcer and gastric cancer. The aim of this study was to assess whether H pylori isolates with different cagA status were present in patients with non-ulcer dyspepsia, and whether a variable cagA status is relevant to histological gastric mucosal damage and glandular cell proliferation.
Methods—Well separated H pylori colonies (between 2 and 25) from primary plates, per gastric area, for each of 19 patients with non-ulcer dyspepsia were examined for cagA by hybridisation. Western blotting was used to examine both representative colonies for CagA expression and the patients' sera for antibody response to CagA. Glandular gastric cell proliferation was assessed immunohistochemically.
Results—Of the 747 colonies examined, 45.3% were cagA+. All colonies from four patients were cagA+, and all colonies from two patients were cagA−. In 13 patients (68%) both cagA+ and cagA− colonies were found. CagA expression of isolates corresponded to their cagA status. H pylori strains with different CagA molecular masses were present in three patients. Results based on all 19 patients studied showed that the prevalence of cagA+ colonies in areas with mucosal atrophy associated or not with intestinal metaplasia (67.9%) was significantly higher than in normal mucosa (44.7%) and mucosa from patients with chronic gastritis (44.0%) (p< 0.001). High levels of cell proliferation were associated with histological atrophy with or without intestinal metaplasia, but not with the possession of cagA by organisms colonising the same mucosal sites.
Conclusions—Most patients with non-ulcer dyspepsia are infected by both cagA+ and cagA− H pylori colonies. The cagA status of infecting organisms may play a role in the development of atrophy and intestinal metaplasia.
(GUT 1998;:772-778)

Keywords: gastritis; Helicobacter pylori infection;  cagA;  mucosal atrophy;  cell proliferation

     

Thrombosis and survival in essential thrombocythemia: A regional study of 1,144 patients

To identify prognostic factors affecting thrombosis‐free survival (TFS) and overall survival (OS), we report the experience of a Regional cooperative group in a real‐life cohort of 1,144 patients with essential thrombocythemia (ET) diagnosed from January 1979 to December 2010. There were 107 thrombotic events (9.4%) during follow‐up [60 (5.3%) arterial and 47 (4.1%) venous thromboses]. At univariate analysis, risk factors for a shorter TFS were: age >60 years (P < 0.0054, 95% CI 1.18–2.6), previous thrombosis (P < 0.0001, 95% CI 1.58–4.52) and the presence of at least one cardiovascular risk factor (P = 0.036, 95% CI 1.15–3.13). Patients with a previous thrombosis occurred ≥24 months before ET diagnosis had a shorter TFS compared to patients with a previous thrombosis occurred <24 months (P = 0.0029, 95% CI 1.5–6.1); furthermore, patients with previous thrombosis occurred <24 months did not show a shorter TFS compared with patients without previous thrombosis (P = 0.303, 95% CI 0.64–3.21). At multivariate analysis for TFS, only the occurrence of a previous thrombosis maintained its prognostic impact (P = 0.0004, 95% CI 1.48–3.79, RR 2.36). The 10‐year OS was 89.9% (95% CI 87.3–92.5): at multivariate analysis for OS, age >60 years (P < 0.0001), anemia (P < 0.0001), male gender (P = 0.0019), previous thromboses (P = 0.0344), and white blood cell >15 × 10⁹/l (P = 0.0370) were independent risk factors. Previous thrombotic events in ET patients are crucial for TFS but their importance seems related not to the occurrence per se but mainly to the interval between the event and the diagnosis. Am. J. Hematol. 89:542–546, 2014. © 2014 Wiley Periodicals, Inc.     

Outcomes of endoscopic sinus surgery in adult lung transplant patients with cystic fibrosis

European Archives of Oto-Rhino-Laryngology - Cystic Fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. Due to its pathological mechanism, chronic rhino sinusitis...     

CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions

Background

Obstructive jaundice is frequently associated with false CA19-9 elevation in benign conditions. The diagnostic accuracy of this tumor marker was evaluated in the present longitudinal study.

Methods

In 128 patients admitted for obstructive jaundice (87 with pancreato-biliary malignancy and 41 benign disease) serum CA19-9 was measured. Statistical analysis of marker levels obtained before and after endoscopic biliary drainage was performed in 60 patients.

Results

Elevated CA19-9 levels (>37 U/mL) were found in 61% of benign cases and 86% of malignancies. After biliary drainage, decrease of serum CA19-9 was observed in 19 of 38 malignant cases and in almost all benign cases (Wilcoxon matched pairs test: P = .207 and P <.001, respectively). Receiver operating characteristic (ROC) analysis identified a cut-off value of 90 U/mL to be associated with improved diagnostic accuracy after biliary drainage (sensitivity 61%, specificity 95%).

Conclusions

In the presence of successfully drained obstructive jaundice, CA19-9 serum levels that remain unchanged or measure more than 90 U/mL are strongly indicative of a malignant cause of obstruction. However, the real clinical utility of this marker remains controversial.     

Clinical utility of CEA, CA 19-9, and CA 72-4 in the follow-up of patients with resectable gastric cancer

BACKGROUND: The aim of this longitudinal study was to evaluate the effectiveness of the serum tumor markers CEA, CA 19-9, and CA 72-4 in the early diagnosis of recurrence of gastric cancer. METHODS: One hundred and thirty-three patients who had undergone potentially curative surgery were considered. Serum samples were obtained preoperatively, 1 week after surgery, and at every follow-up examination. Mean follow-up time for the entire patient population was 41 +/- 33 months, and 71 +/- 27 months for patients classified as disease-free. RESULTS: Preoperative positivity was 16% for CEA, 35% for CA 19-9, and 20% for CA 72-4. Recurrence of disease was found in 75 patients (56%). Marker sensitivity in recurrent cases was 44% for CEA, 56% for CA 19-9, and 51% for CA 72-4; the combined use of the three markers increased sensitivity to 87%, which reached 100% in patients with positive preoperative levels. Marker specificity, evaluated in 58 disease-free patients, was 79% for CEA, 74% for CA 19-9, and 97% for CA 72-4. CONCLUSIONS: The combined assay of CEA, CA 19-9, and CA 72-4 may be useful for early diagnosis of recurrence of gastric cancer; however, only CA 72-4 positivity should be considered a specific predictor of tumor recurrence.     

Hereditary diffuse gastric cancer and E-cadherin: description of the first germline mutation in an Italian family.

AIMS: Germline mutation of the E-cadherin gene (CDH1) accounts for the Hereditary Diffuse Gastric Cancer (HDGC) syndrome. Fourteen pedigrees with Diffuse Gastric Cancer that fulfilled the International Gastric Cancer Linkage Consortium (IGCLC) criteria were selected and screened for CDH1 germline mutations. METHODS: The entire coding region of the CDH1 gene and all intron-exon boundaries were analyzed by direct sequencing in the 14 families fulfilling the IGCLC criteria. E-cadherin immunohistochemical expression was evaluated on tumour as well as normal formalin-fixed paraffin embedded tissues. RESULTS: A novel germline missense mutation was found. It was a single C-->T substitution in exon 8, resulting in a transition of CCG-->CTG (C1118T; Pro373Leu) demonstrated in the proband and her brother. At immunohistochemical analysis, the staining intensity was reduced and considered weakly positive (15%). CONCLUSIONS: The first CDH1 germline mutation of an Italian family is herein reported. The present missense mutation has never been described so far.     

Correlation between chronic gastritis of the gastric stump,Helicobacter pylori infections and iron deficiency after gastrectomy for gastric cancer

Atrophic chronic gastritis and Helicobacter pylori infection are considered possible causes of iron deficiency anemia, and sideropenic anemia is also frequent after subtotal gastrectomy. In this study, thirty-three patients who underwent subtotal gastrectomy for primary adenocarcinoma of stomach were follow-up for at least 3 years, and included in this analysis. The presence of atrophic gastritis and H. pylori infection were detected by biopsy sampling and endoscopy every year after surgery. The iron status was evaluated by the assay of serum ferritin, serum iron and hemoglobin level. Statistical analysis revealed that atrophic gastritis was associated with lower iron serum levels, and gastric stump H. pylori infection was related to lower serum ferritin levels; on the contrary, no correlation of these factors with sex, age, malabsorption symptoms and stage of tumor was found. Atrophic chronic gastritis and Helicobacter pylori infection seem to play an important role as possible causes of post gastrectomy anaemia.     

Nonocclusive intestinal ischemia in patients with acute aortic dissection

BACKGROUND: In aortic dissection, visceral complications that result from aortic branch compromise have been described extensively, whereas intestinal ischemia not associated with the false lumen anatomy has rarely been discussed. The aim of this report is to identify clinical factors that may contribute to the development of this form of acute mesenteric ischemia, to profile the patients at greatest risk, and to review diagnostic and treatment methods that emerged from our experience. METHODS: With a computerized database, we identified 371 patients who underwent treatment in our institution with a diagnosis of aortic dissection between July 15, 1985, and January 10, 2001. Mesenteric ischemia was present in 73 patients (19%). In 36 patients (9%), bowel ischemia was not associated with a false lumen anatomy or an extension of the dissection process. From a general analysis of the determinants of mesenteric ischemia in aortic dissection, we investigated, with univariate and multivariate analysis, the specific characteristics of these patients with nonocclusive ischemia. A retrospective analysis of the oxygen metabolic profile of patients who underwent operation also was performed. RESULTS: The mortality rate in patients with nonocclusive mesenteric ischemia was 86%; sepsis and multiple organ failure were the causes of death in all nonsurvivors. Surgical treatment was beneficial only in the early phases of the disease. The results of the multivariate analysis showed the multifactorial origin of nonocclusive mesenteric ischemia; cerebral ischemia, thrombosis of the false lumen, severe coagulation disorders, chronic obstructive pulmonary disease, aortic calcinosis, prolonged hypotension, chronic renal insufficiency, and low cardiac output were independent predictors of the condition. In patients who underwent operation, the significant risk factors were severe coagulation disorders, postoperative cerebral ischemia, maximal oxygen extraction rate of more than 0.40, aortic calcinosis, chronic obstructive pulmonary disease, thrombosis of the false lumen, inotropic support, and chronic renal insufficiency. An oxygen extraction rate of more than 0.4 at 6 hours after operation was found to be an index of intestinal damage sufficient to initiate an evaluation for visceral ischemia. Significant differences with occlusive ischemia also were evidenced with this study. CONCLUSION: In aortic dissection, nonocclusive mesenteric ischemia shows some unique clinical and individual predisposing factors. Most instrumental investigations are of poor diagnostic value, and prognosis is poor, especially when mesenteric gangrene had already taken place. Prevention can be exercised only with a heightening of our awareness of this condition and with timely correction of metabolic disturbances. In suspected cases, an aggressive surgical attitude may represent the only means for reducing mortality.