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Biomedical subjects

Gianfranco Delle Fave

Publications and source records attributed to Gianfranco Delle Fave.

At least 19 recordsLinked to original sources
PubMed2006

Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis.

BACKGROUND: Malabsorption of thyroxine has been described in patients treated with drugs that modify an acidic environment. We determined whether there is an increased need for thyroxine in patients with euthyroid multinodular goiter and impaired secretion of gastric acid. METHODS: We assessed the dose of thyroxine required to obtain a low level of thyrotropin (0.05 to 0.20 mU per liter) in 248 patients with multinodular goiter. Of these 248 patients, 53 also had Helicobacter pylori-related gastritis and 60 had atrophic gastritis of the body of the stomach (31 with evidence of H. pylori infection and 29 without such evidence). The reference group comprised 135 patients with multinodular goiter and no gastric disorders. In addition, variation in the level of serum thyrotropin was prospectively studied in 11 patients treated with thyroxine before and after H. pylori infection and both before and during treatment with omeprazole in 10 patients treated with thyroxine who had gastroesophageal reflux. RESULTS: The daily requirement of thyroxine was higher (by 22 to 34 percent) in patients with H. pylori-related gastritis, atrophic gastritis, or both conditions than in the reference group. In prospective studies, the occurrence of H. pylori infection in the 11 patients treated with thyroxine led to an increase in the level of serum thyrotropin (P=0.002), an effect that was nearly reversed on eradication of H. pylori infection. In a similar way, omeprazole treatment was associated with an increase in the level of serum thyrotropin in all 10 patients treated with thyroxine, an effect that was reversed by an increase in the thyroxine dose by 37 percent. CONCLUSIONS: Patients with impaired acid secretion require an increased dose of thyroxine, suggesting that normal gastric acid secretion is necessary for effective absorption of oral thyroxine.

Adult↗
PubMed2005

Is colonoscopy sufficient for colorectal cancer surveillance in all HNPCC patients?

A 34-year-old male with hereditary non-polyposis colon cancer with a mutation in hMSH2 line is reported. Despite regular colonoscopic follow-up, he developed cecal cancer involving the extraluminal area. Due to sub-occlusive symptoms, the patient was submitted to further colonoscopy, however with no clear evidence of neoplasia. Thin slice multiplanar reconstruction computed tomography CT scan performed thereafter revealed a transmural mass 2.5 cm in size localized near the cecal valve. Discussion is made on the reliability of colonoscopic examinations as well as the need for further investigations in the follow-up of patients at very high risk of right-sided colon cancer, such as male hMSH2 carrier affected by hereditary non-polyposis colon cancer.

Adult↗
PubMed2005

Possible contribution of artificial neural networks and linear discriminant analysis in recognition of patients with suspected atrophic body gastritis.

AIM: To investigate whether ANNs and LDA could recognize patients with ABG in a database, containing only clinical and biochemical variables, of a pool of patients with and without ABG, by selecting the most predictive variables and by reducing input data to the minimum. METHODS: Data was collected from 350 consecutive outpatients (263 with ABG, 87 with non-atrophic gastritis and/or celiac disease [controls]). Structured questionnaires with 22 items (anagraphic, anamnestic, clinical, and biochemical data) were filled out for each patient. All patients underwent gastroscopy with biopsies. ANNs and LDA were applied to recognize patients with ABG. Experiment 1: random selection on 37 variables, experiment 2: optimization process on 30 variables, experiment 3: input data reduction on 8 variables, experiment 4: use of only clinical input data on 5 variables, and experiment 5: use of only serological variables. RESULTS: In experiment 1, overall accuracies of ANNs and LDA were 96.6% and 94.6%, respectively, for predicting patients with ABG. In experiment 2, ANNs and LDA reached an overall accuracy of 98.8% and 96.8%, respectively. In experiment 3, overall accuracy of ANNs was 98.4%. In experiment 4, overall accuracies of ANNs and LDA were, respectively, 91.3% and 88.6%. In experiment 5, overall accuracies of ANNs and LDA were, respectively, 97.7% and 94.5%. CONCLUSION: This preliminary study suggests that advanced statistical methods, not only ANNs, but also LDA, may contribute to better address bioptic sampling during gastroscopy in a subset of patients in whom ABG may be suspected on the basis of aspecific gastrointestinal symptoms or non-digestive disorders.

Adult↗
PubMed2005

Peanut-like 1 (septin 5) gene expression in normal and neoplastic human endocrine pancreas.

Peanut-like 1 (PNUTL1) is a septin gene which is expressed at high levels in human brain. There it plays a role in the process of membrane fusion during exocytosis by interacting with syntaxin and synaptophysin. As the secretory apparatus of pancreatic islet cells closely resembles that of neurons, we decided to study the expression of PNUTL1 in the human endocrine pancreas, both in normal islets and in pancreatic endocrine tumors (PETs). Normal pancreatic tissue, purified islets, 11 PETs and two cell lines were used to evaluate the presence of PNUTL1 by RT-PCR and Western blot. The expression of the PNUTL1 protein was also evaluated by immunohistochemistry on normal pancreas, additional 26 PETs, eight pancreatic adenocarcinomas, one mixed endocrine-exocrine pancreatic neoplasm, a specimen of solid papillary pseudomucinous tumor, an adult islet cell hyperplasia and a case of neonatal nesidioblastosis. In addition, a tissue array (LandMark High Density Cancer Tissue MicroArray) comprising 280 various tumor and matched normal specimens was utilized. In PETs, the expression of pancreatic hormones, chromogranin-A, synaptophysin and Ki-67 were also evaluated. In the normal pancreas PNUTL1 expression is almost exclusively confined to the islet cells, weak expression was occasionally seen in some acinar cells, while immunoreactivity was completely absent in the ductal epithelia. PNUTL1 expression is maintained at similar high levels in hyperplastic and neoplastic islet cells, but this did not correlate with any of the clinicopathological data nor with proliferation status in PETs. Weak immunoreactivity was also noted in a proportion of exocrine neoplasms. Our findings describe for the first time the high expression levels of PNUTL1 in human pancreatic endocrine cells that suggests a similar role of this protein in islet cells to that demonstrated in neuronal tissues, and warrants further functional studies of this protein.

Adult↗
PubMed2005

Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis.

AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. METHODS: A total of 140 atrophic body gastritis patients, diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori (H pylori) antibodies. Gastritis was assessed according to Sydney System. RESULTS: Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r = 0.2216, P = 0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations. CONCLUSION: The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.

Adult↗
PubMed2005

Endocrine tumours of the stomach.

Gastric endocrine tumours (gastric carcinoids) usually grow from enterochromaffin-like (ECL) cells. Three types of tumour may be distinguished on the basis of the background gastric pathology: type I, which develops in atrophic body gastritis (ABG); type II, which is associated with multiple endocrine neoplasia and Zollinger-Ellison syndrome; and the sporadic type III, which is not associated with any background pathology. This classification plays a major role in determining the optimal approach to these diseases. In fact, type I carcinoids can be considered to be benign lesions, with exceptional risk of metastases. Type II, in contrast, may be associated with distant metastases, which are also common in type III carcinoids. The therapeutic approach is based mainly on endoscopic excision and somatostatin analogues in types I and II, or on surgical resection in type III. Both types I and II grow under the stimulus of hypergastrinaemia through a well-described sequence. However, gastrin is sufficient to cause ECL cell hyperplasia and dysplasia, but not transformation, which is due to menin defects in MEN-I patients, or to other unknown alterations in ABG. Several other candidates--including Bcl2, p53 and MMP9--have been linked with carcinoid initiation and progression. The biology of type III tumours which are not associated with hypergastrinaemia is still poorly understood.

Biopsy, Needle↗
PubMed2005

Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization.

Since gastro-entero-pancreatic endocrine tumors are rare and heterogeneous diseases, their prognosis and long-term survival are not well known. This study aimed at identifying prognostic factors and assessing long-term survival in gastro-entero-pancreatic endocrine tumors. A total of 156 patients enrolled. Prognostic factors were determined by univariate/multivariate analysis; survival rates were assessed by the Kaplan-Meier method. The tumors were non-functioning in 59.6% of patients, and originated from the pancreas in 42.9%. At diagnosis, 64.3% of patients had metastases. The tumors were well differentiated in 89.6% of patients. Ki67 was >2% in 39.6% of patients. Primary tumor size was >3 cm in 49.6% of cases studied. For the univariate analysis, the negative prognostic factors were: pancreatic origin (rate ratio 4.64, P = 0.0002), poorly differentiated tumor (rate ratio 7.70, P = 0.0001), primary tumor size >3 cm (rate ratio 4.26, P = 0.0009), presence of distant metastases (liver: rate ratio 5.88, P = 0.01; distant extra-hepatic: rate ratio 13.41, P = 0.0008). The pancreatic site, the poor degree of differentiation and the distant metastases were confirmed as negative prognostic factors at multivariate analysis. Overall 5-year survival rate was 77.5%. Survival rates differed according to: primary tumor site (62% for pancreatic vs 89.9% for gastrointestinal tract, P = 0.0001) and size (65.7% for >3 cm vs 88.8% for < or = 3 cm, P = 0.0003), degree of differentiation (22% for poor vs 86.8% for good, P < 0.0001), Ki67 (53.5% for > 2% vs 90.1% for < or = 2%, P = 0.003), metastases (96.1, 77, 73.3 and 50.1% for absent, local, liver and distant extra-hepatic metastases respectively), age at diagnosis (85.3% for < or = 50 years vs 70.3% for > 50 years, P = 0.03). Although 64.3% of gastro-entero-pancreatic endocrine tumors present metastases at diagnosis, the 5-year survival rate is 77.5%. Pancreatic site, a poor degree of tumor cell differentiation and distant extra-hepatic metastases are the major negative prognostic factors.

Adolescent↗
PubMed2004

Rapid and sustained relief from the symptoms of carcinoid syndrome: results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide.

This 6-month, open, non-controlled, multicenter, dose-titration study evaluated the efficacy and safety of 28-day prolonged-release (PR) lanreotide in the treatment of carcinoid syndrome. Eligible patients had a carcinoid tumor with > or =3 stools/day and/or > or =1 moderate/severe flushing episodes/day. Six treatments of 28-day PR lanreotide were administered by deep subcutaneous injection. The dose for the first two injections was 90 mg. Subsequent doses could be titrated (60, 90, 120 mg) according to symptom response. Seventy-one patients were treated. Flushing decreased from a mean of 3.0 at baseline to 2.3 on day 1, and 2.0 on day 2, with a daily mean of 2.1 for the first week post-treatment (p < 0.05). Diarrhea decreased from a mean of 5.0 at baseline to 4.3 on day 1 (p < 0.05), and 4.5 on day 2, with a daily mean of 4.4 for the first week post-treatment (p < 0.001). Symptom frequency decreased further after the second and third injections, and reached a plateau after the fourth injection. By month 6, flushing and diarrhea had significantly decreased from baseline by a mean of 1.3 and 1.1 episodes/day, respectively (both p < or = 0.001); 65% of patients with flushing as the target symptom and 18% of diarrhea-target patients achieved > or =50% reduction from baseline. Median urinary 5-hydroxyindoleacetic acid and chromogranin A levels decreased by 24 and 38%, respectively. Treatment was well tolerated. 28-day PR lanreotide was effective in reducing the symptoms and biochemical markers associated with carcinoid syndrome.

Adult↗
PubMed2004

Expression of the proto-oncogene c-KIT in normal and tumor tissues from colorectal carcinoma patients.

BACKGROUND AND AIMS: The proto-oncogene c-KIT encodes a tyrosine kinase receptor essential during embryonic development and postnatal life. Although deregulated expression of c-KIT has been reported, its role in colorectal carcinoma remains controversial: some authors have described a correlation between c-KIT expression and colorectal cancer (CRC), while others have failed to detect the receptor in the majority of neoplasia examined. To address this question, we designed a prospective study to analyze the expression of c-KIT in normal and neoplastic colonic mucosa of the same patient. PATIENTS AND METHODS: We analyzed the tissues of 20 patients undergoing surgical resection for colorectal carcinoma by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry, whose results were correlated with histopathological parameters. RESULTS: Most patients (90%) showed c-KIT expression in normal tissue both at RNA and protein level, while in neoplastic tissue it was observed in 30% of patients at RNA level and in 10% at protein level. By immunohistochemistry the localization of c-KIT protein in the normal colon was restricted to interstitial cells scattered in the stroma, whereas the non-neoplastic epithelium was always negative. The mucinous carcinomas were all c-KIT negative, whereas the only case in which c-KIT was displayed in the neoplastic epithelium was a G3 adenocarcinoma. CONCLUSION: Most colorectal carcinomas do not express c-KIT. We suggest that c-KIT expression is rarely present in this neoplasia; thus, the use of receptor inhibitors should be conducted in selected sub-groups of colon carcinoma patients, subsequent to the clear demonstration of c-KIT overexpression in the neoplastic cells.

Aged↗
PubMed2004

Can patient characteristics predict the outcome of endoscopic evaluation of iron deficiency anemia: a multiple logistic regression analysis.

BACKGROUND: The purpose of this study was to identify clinical and biochemical variables that predict the outcome of upper/lower endoscopy in outpatients with iron deficiency anemia and to determine which endoscopic procedure should be performed first. METHODS: Ninety-eight patients (74 women, 24 men; mean age 55 years) with iron deficiency anemia referred from the hematology department were interviewed and responded to a questionnaire that included clinical and biochemical variables, and underwent EGD (with biopsies) and colonoscopy. The endoscopic findings were recorded as presence/absence of GI cancer, upper/lower GI tract lesions and bleeding/non-bleeding-associated GI lesions. A multiple logistic regression analysis was applied to identify variables significantly related with the outcome of the investigations. Multiple analyses were performed so that a Bonferroni correction for multiple testing removed significance except where p<0.01. RESULTS: A likely cause of iron deficiency anemia was found in 86.7% of patients. The risk factors for GI malignancies were: male gender (OR 7.5: 95% CI[1.7, 31.9]; p<0.01), advanced age (OR 1.1/y: 95% CI[1, 1.2]; p<0.01), and lower mean corpuscular volume (OR 1.1/unit: 95% CI[1, 1.2]; p<0.002). The risk factors for bleeding-related diseases were the following: greater age (OR 1.1/y: 95% CI[1.1, 1.2]; p<0.001), absence of lower-GI tract symptoms (OR 4.7: 95% CI[1.3, 16.6]; p<0.05), and a positive fecal occult blood test (OR 4.1: 95% CI[1.2, 14.3]; p<0.05). The risk factors for non-bleeding-related GI tract diseases were the following: negative fecal occult blood test (OR 4.5: 95% CI[1.16, 20]; p<0.05) and higher Hb level (OR 1.4/unit: 95% CI[1.1, 1.8]; p<0.05). CONCLUSIONS: For non-hospitalized patients with iron deficiency anemia, colonoscopy should be the initial investigation in those greater than 50 years of age, particularly men, and those without upper-GI tract symptoms and with lower values for mean corpuscular volume and Hb. EGD should be performed first in younger patients, particularly those with a mild decrease in Hb and a negative fecal occult blood test.

Age Factors↗
PubMed2004

Training with a computer-based simulator achieves basic manual skills required for upper endoscopy: a randomized controlled trial.

BACKGROUND: Changes in medical practice have constrained the time available for education and the availability of patients for training. Computer-based simulators have been devised that can be used to achieve manual skills without patient contact. This study prospectively compared, in a clinical setting, the efficacy of a computer-based simulator for training in upper endoscopy. METHODS: Twenty-two fellows with no experience in endoscopy were randomly assigned to two groups: one group underwent 10 hours of preclinical training with a computer-based simulator, and the other did not. Each trainee performed upper endoscopy in 19 or 20 patients. Performance parameters evaluated included the following: esophageal intubation, procedure duration and completeness, and request for assistance. The performance of the trainees also was evaluated by the endoscopy instructor. RESULTS: A total of 420 upper endoscopies were performed; the computer pretrained group performed 212 and the non-pretrained group, 208. The pretrained group performed more complete procedures (87.8% vs. 70.0%; p < 0.0001), required less assistance (41.3% vs. 97.9%; p < 0.0001), and the instructor assessed performance as "positive" more often for this group (86.8% vs. 56.7%; p < 0.0001). The length of procedures was comparable for the two groups. CONCLUSIONS: The computer-based simulator is effective in providing novice trainees with the skills needed for identification of anatomical landmarks and basic endoscopic maneuvers, and in reducing the need for assistance by instructors.

Adult↗
PubMed2004

Role of noninvasive tests (C-urea breath test and stool antigen test) as additional tools in diagnosis of Helicobacter pylori infection in patients with atrophic body gastritis.

BACKGROUND: Detection of Helicobacter pylori infection in atrophic body gastritis (ABG) is difficult, as during progression of body atrophy, H. pylori disappears. AIM: To increase the diagnostic yield of detection of active H. pylori infection in atrophic body gastritis patients by using noninvasive tests such as (13)C-Urea Breath Test ((13)C-UBT) and H. pylori stool antigen test (HpSA) would be useful. PATIENTS: 27 consecutive patients with newly-diagnosed atrophic body gastritis (19F/7M, age 27-73 years). METHODS: Gastroscopy with biopsies (antrum n = 3, body n = 3) and histology according to updated Sydney system, H. pylori IgG serology, (13)C-UBT, and HpSA. RESULTS: All tests used in the diagnosis of H. pylori infection were in agreement in 9/27 atrophic body gastritis patients (33.3%), being all positive in four (14.8%) and all negative in five patients (18.5%). Ten of the 27 (37%) patients were Giemsa stain-positive and serology-positive (group I). Seventeen of the 27 (63%) patients were Giemsa stain-negative: 5/17 with positive serology (group II) and 12/17 with negative serology (group III). In group I, 5/10 (50%) were (13)C-UBT positive and 4/10 (40%) HpSA positive. In group II, two patients were (13)C-UBT positive, but all were HpSA negative. Also in group III, all patients were HpSA negative, but one had a positive (13)C-UBT. CONCLUSIONS: In atrophic body gastritis patients, neither (13)C-UBT nor HpSA per se add useful information regarding active H. pylori infection, but these noninvasive tests may be important in combination with histology and serology to define the H. pylori status in some atrophic body gastritis patients.

Adult↗
PubMed2004

Beta3-adrenoceptors: relaxant function and mRNA detection in smooth muscle cells isolated from the human colon.

Functional involvement of beta3-adrenoceptors in controlling human gastrointestinal motility has not been unequivocally assessed yet. The direct myogenic contribution of these receptors was examined, by in vitro functional studies and analysis of mRNA expression, on smooth muscle cells separately isolated from taenia coli and circular muscle layers of the human colon. Isoproterenol, a nonselective beta-adrenoceptor agonist, relaxed, in a concentration-dependent manner, both human taenia coli and circular colonic smooth muscle cells, although displaying a higher intrinsic activity (65.3 +/- 2.3 vs. 55.2 +/- 1.4% maximal relaxation) and potency (pEC50: 7.41 +/- 0.07 vs. 6.32 +/- 0.08) were greater on taenia coli than circular cells. In the presence of the beta1-antagonist CGP20712A and of the beta2-antagonist ICI 118,551, a 25-30% decrease in isoproterenol intrinsic activity was observed on both cell types and on taenia coli, the nonselective beta1/beta2-antagonist propranolol produced a rightward shift of the isoproterenol concentration-response curve with mean estimated pKB values (8.12 +/- 0.27 at 0.1 microM and 6.45 +/- 0.13 at 1 microM) lower than that expected for both beta1- and beta2-adrenoceptors. CGP12177A and SR 58611A, two beta3-adrenoceptor agonists, presented an intrinsic activity comparable to that of isoproterenol in the presence of beta1- and beta2-antagonists, the former being more potent on taenia coli than on circular smooth muscle cells. Beta3-adrenoceptor mRNA was detected by reverse transcription PCR on both cell types. These results strongly suggest a direct functional role of beta3-adrenoceptors in the human colon.

Adrenergic beta-Agonists↗
PubMed2004

Gastric neuroendocrine tumors.

Gastric carcinoids are rare neuroendocrine tumors, usually classified as type I, if associated with atrophic body gastritis; type II, if associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I, and type III, in the absence of any gastric pathology (sporadic tumors). The pathological features, as well as the prognosis of the tumor and the patient's survival strictly depend on this classification. The correct management of the patient with gastric carcinoid can only be proposed when the tumor has been classified by an accurate pathological and clinical evaluation of the patient. While the therapeutic approach in types I and II is based on a conservative strategy, including endoscopic resection, an adequate follow-up program, and the possible use of somatostatin analogues, an aggressive surgical approach is required in type III.

Enterochromaffin Cells↗
PubMed2004

Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid diseases.

Juvenile patients affected with autoimmune thyroid disorders showed a 14-21% prevalence of parietal cell antibodies (PCA) reacting against the H+/K+-ATPase of the gastric parietal cells. PCA are the principal immunological markers of atrophic body gastritis (ABG).ABG is characterized by loss of oxyntic glands, achlorhydria, and hypergastrinemia. The aim of this study was to determine whether PCA positivity could be associated with biochemical and histological manifestations of gastric autoimmunity in juvenile patients with autoimmune thyroid disease (AITD). We studied 129 children (96 females and 33 males) with chronic lymphocytic thyroiditis (n = 115) or Graves' disease (n = 14). Mean age at diagnosis of AITD was 9.7 +/- 3.3 yr, and mean age at sampling was 12.3 +/- 3.7 yr. We determined PCA and Helicobacter pylori antibodies, gastrin, and pepsinogen I plasma levels. Gastroscopy with multiple biopsies was carried out in a subgroup of patients with PCA positivity. We found that 30% of children had detectable PCA. Hypergastrinemia was found in 45% of the PCA-positive children (range, 40-675 pg/ml) vs. 12% of PCA-negative children (range, 35-65 pg/ml; P < 0.001). Eighteen patients with PCA positivity underwent gastroscopy; eight of these children had normogastrinemia, which showed no signs of ABG, and 10 children had hypergastrinemia, of whom five had mild to severe ABG. Our study shows that autoimmune gastritis is an early event in juvenile AITD with detectable PCA. Gastrin plasma level is a reliable marker of gastric atrophy.

Adolescent↗