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C Vindigni

Publications and source records attributed to C Vindigni.

At least 19 recordsLinked to original sources

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.

Cadherins↗

Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study.

BACKGROUND: Few studies have analysed the association between alcohol intake and Hodgkin's lymphoma (HL) or multiple myeloma (MM) risks. MATERIALS AND METHODS: A multicentre population-based case-control study of 363 HL, 270 MM cases, and 1771 controls offered the opportunity to evaluate the relationship between alcohol and HL/MM risks. Unconditional logistic regression was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs), associated with alcohol intake (servings per week, grams per day of ethanol intake) or duration of exposure (year). RESULTS: For HL, considering nonsmokers only, ever drinkers had a significantly decreased risk than never drinkers (OR=0.46). Significantly lower risks in all levels of total alcohol intake were also detected, considering servings per week (OR for one to four servings per week=0.51, 95% CI 0.32-0.82; OR for five to nine servings per week=0.39, 95% CI 0.21-0.73; OR for 10-19 servings per week=0.26, 95% CI 0.12-0.54; OR for >or=20 servings per week=0.34, 95% CI 0.15-0.79) and grams per day of ethanol intake (OR for 0.1-9.0 g/day=0.45, 95% CI 0.27-0.74; OR for 9.1-17.9 g/day=0.52, 95% CI 0.30-0.90; OR for 18.0-31.7 g/day=0.27, 95% CI 0.13-0.57; OR for >31.7 g/day=0.35, 95% CI 0.15-0.79). In the analysis for ever-smoking HL cases and controls, ever drinkers had the same risk as never drinkers. For MM, ever drinkers had a non-significantly decreased risk than non-drinkers (OR=0.74), and ORs in almost all consumption levels were not significant (OR for 0.1-9.0 g/day=0.93; OR for 9.1-17.9 g/day=0.82; OR for 18.0-31.7 g/day=0.47; 95% CI 0.28-0.81; OR for >31.7 g/day=0.68). For HL and MM, the beverage type did not affect the risk significantly, and no consistent dose-response relationships were found, considering intensity or duration of alcohol consumption. CONCLUSIONS: Our study indicates a protective effect of alcohol consumption for nonsmoking HL cases.

Adult↗

Increased phospholipase activity in Helicobacter pylori strains isolated from patients with gastric carcinoma.

PURPOSE: Phospholipase activity, one of Helicobacter pylori pathogenicity factors, has not been investigated enough, so far, although it may induce a remarkable damage to the gastric mucosa. In the present work, we have compared the whole phospholipase activity of H. pylori strains isolated from patients with gastric carcinoma with that of strains isolated from dyspeptic patients without gastric carcinoma. METHODS: We measured the phospholipase activity of one distinct H. pylori colony isolated from each of 10 patients with gastric carcinoma and 10 controls, dyspeptic patients without endoscopic and histological signs of gastric carcinoma. We also determined the phospholipase activity of 20 additional strains isolated from different areas of neoplastic and non-neoplastic tissue of two patients with gastric carcinoma, the cagA and vacA positive G27 and 328 wild strains and their respective vacA and cagA negative isogenic mutants. The whole phospholipase activity of strains was determined by measuring the release of (14)C-labeled palmitic acid from the radioactive l-3-phosphatidylcholine, 1,2-di[1-(14)C]palmiloyl substrate; results were expressed in pmol of palmitic acid per mg of protein. RESULTS: H. pylori strains isolated from patients with gastric carcinoma had levels of phospholipase activity significantly higher than those of strains isolated from controls (99.37 [S.D. 40.45] versus 34.46 [S.D. 16.46], P<0.001). In patients with gastric carcinoma, the mean phospholipase activity of strains isolated from neoplastic tissue was similar to that of strains isolated from non-neoplastic tissues (123.02 [S.D. 44.36] and 115.77 [S.D. 81.48], respectively. Interruption of cagA gene caused a ca. 20% reduction of phospholipase activity (36.38 versus 45.22 of the wild strain); that of vacA caused no reduction of phospholipase activity (26.53 and 25.37 of the wild strain). CONCLUSIONS: The infection by H. pylori strains that produce high levels of phospholipase may increase the risk of developing gastric carcinoma. We hypothesise that indirect products of phospholipase activity, such as prostaglandins, leukotrienes and lysophospholipids, may mediate carcinogenesis.

Antigens, Bacterial↗

Acute abdomen due to small bowel anisakiasis.

The popularity in Western countries of dishes based on raw fish has led to an increased incidence of anisakiasis, a human parasitic disease caused by the ingestion of live anisakid larvae. The entire digestive tract may be involved, but the stomach and the small intestine are the most frequently affected sites. We report a case of acute abdomen due to Anisakis simplex infection that caused small bowel obstruction.

Abdomen, Acute↗

Delayed infection, late tonsillectomy or adenoidectomy and adult leukaemia: a case-control study.

In a population-based case-control study among adults in Italy, of 261 lymphoid and 313 myeloid leukaemias and 1718 controls, a later age at adenoidectomy and tonsillectomy (after age 10 years) increased considerably the risk of lymphocytic (but not myeloid) leukaemia (odds ratio 4.2, 95% confidence interval 1.1-16.2). We propose that late infection is a proliferative stimulus for B-cells.

Adenoidectomy↗

Experimental internal anal sphincter replacement with demucosated colonic plication.

BACKGROUND: Selective re-creation of a new internal anal sphincter could be indicated when the natural one is irreversibly damaged or excised. METHODS: In this preliminary experimental work, surgical techniques of internal anal sphincter replacement in pigs were investigated. After preoperative anorectal manometry, surgical procedure was done in two phases: abdominal, mobilization of the colon-rectum to the pelvic floor; and perianal, dissection of the anal canal from the external anal sphincter through the intersphincteric space. The fully mobilized anorectal segment, including the internal anal sphincter, was pulled down through the anus and resected. The distal colonic stump was then demucosated and two types of plications of the demucosated segment were accomplished, each type in three animals. The plicated segment was then returned into the anal canal, inside the external sphincter. Short-term follow-up with clinical and manometric evaluations was performed and, subsequently, histological analysis of the plicated segment, after the animals were sacrificed. RESULTS: None of the animals became incontinent. Anal manometry identified a high-pressure zone and relaxation reflex in the new anal canal. Histologic studies showed hypertrophy of smooth muscle layers without degenerative changes. CONCLUSION: This study indicates that a plication of colonic smooth muscle wall can re-create a high-pressure zone in the anal canal after the internal anal sphincter has been excised.

Anal Canal↗

[Expression of p27 and proliferative (MIB-1), mitotic (MI) and apoptotic indices in early-phase (EGF) gastric carcinoma. Results of a study by the Italian Gastric Cancer Research Group (IRGGC)].

AIMS: Since the Japanese Society for Gastroenterology and Endoscopy (JSGE) introduced the definition of Early Gastric Cancer (EGC), much more and deeper studies were done, which demonstrated that EGC was a more complex phase of the neoplastic disease with different morphologic characteristics, tightly linked to the prognosis. We evaluated the clinical impact of some prognostic factors, known being important in the advanced lesions, in a series of EGC patients with special reference to the clinicomorphological features. METHODS AND RESULTS: We analysed the mitotic (MI) and apoptotic (AI) indices and the immunohistochemical expression of p27 and MIB-1 in 83 EGC cases consecutively recruited in the hospitals of Forlì, Verona, Siena and Milan (IRGGC) in the period 1994-95. The classifications of JSGE, Lauren and Kodama were used to define the macroscopic, microscopic and growth pattern types, respectively. Decreased p27 expression correlated with the macroscopic escavated lesions and diffused mixed histotypes; the increase of MIB-1 detection with tumour size larger than 2 cm, but lesser than 4 cm; MI with intestinal histologic types and AI with mucosal and penetrating lesions, according to Kodama. Statistical analysis showed significative correlations among MIB-1, MI and AI, but not with p27 and the other variables. All these factors did not influence the prognosis of our patients. CONCLUSIONS: In our series, p27, MIB-1, MI, and AI did not add any useful clinical. So, in EGC patients the morphological features have still the most important role in influencing the prognosis and treatment of patients.

Apoptosis↗

Smoking and hematolymphopoietic malignancies.

OBJECTIVE: Tobacco use is the most prominent cause of respiratory cancers. Little is known, however, about the influence of smoking on hematolymphopoietic malignancies. To evaluate this relation, a population-based case-control study was carried out in 12 areas of Italy. METHODS: Detailed interviews on tobacco smoking habits were administered to 1450 non-Hodgkin's lymphoma (NHL), 365 Hodgkin's disease (HD), 270 multiple myeloma (MM), and 649 leukemia (LEU) patients occurring from 1990 to 1993, and 1779 population controls. RESULTS: We found a slightly increased risk for NHL in smokers (odds ratio 1.2, 95% confidence interval 1.0-1.4 for ever smokers), but a consistent positive association was shown only for follicular NHL. In this subtype, a significant excess risk was observed for ever versus never smokers, after adjustment for gender, age, geographic residence, education, and respondent (OR = 1.8, 95%, CI 1.3-2.7), with a positive exposure-response gradient for smoking duration (p < 0.01). The risk for follicular NHL was significantly elevated only among women, with ever smokers showing OR = 2.3 (CI 1.4-3.8), while for men we found OR = 1.3 (CI 0.69-2.3). No major differences were shown according to age. Female subjects also showed significant positive exposure-response trends for duration. CONCLUSION: Cigarette smoking could be a risk factor for follicular NHL among women. For HD, MM, or LEU, no clear association was observed.

Adult↗

Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.

Loss of the cell adhesion molecule E-cadherin has been observed in a variety of human carcinomas, and germline E-cadherin mutations have been found in several familial cases of diffuse gastric cancer. We sought to determine the prevalence and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We performed comprehensive sequencing of the coding region, loss of heterozygosity (LOH) analysis, and immunohistochemical protein expression determination on 40 sporadic gastric adenocarcinomas. In total, 7 of 25 diffuse-type cancers harbored genetic alterations in the E-cadherin gene. Novel mutations predicted to significantly compromise protein function were found within 4 of these cancers, 2 of which harbored alterations resulting in biallelic inactivation of the gene product. Three diffuse cancers failed to amplify Exon 8 of E-cadherin, suggesting the presence of a homozygous abnormality. Notably, one germline E-cadherin mutation was also identified within these "sporadic" diffuse cancers. Significant gene mutations were not found in the 14 intestinal-type or histologically mixed cancer. Immunohistochemistry revealed aberrant or negative protein expression in seven diffuse-type tumors, four of which correlated with the genetic alterations. Both diffuse and intestinal-type tumors exhibited low rates of LOH, suggesting that allelic loss at the locus is not a common mechanism for E-cadherin inactivation during gastric tumorigenesis. Our observations suggest that inactivation of the E-cadherin gene occurs only in a subset of diffuse-type gastric cancers, as the majority of cases did not contain genetic alterations or identifiable protein abnormalities. Germline E-cadherin alterations, although rare, may underlie some diffuse gastric cancer cases that have important biologic and practical implications

Adenocarcinoma↗

A multicenter case-control study in Italy on hematolymphopoietic neoplasms and occupation.

We conducted a population-based, case-control study on hematolymphopoietic malignancies in 12 areas in Italy to investigate associations between different hematolymphopoietic malignancies and exposure to solvents and pesticides. We collected all incident cases 20-74 years of age from 12 areas, with a combined population of approximately 7 million residents. The control group was formed by a random sample of the study population. Data presented in this paper refer to 2,737 interviewed cases of 3,357 eligible cases and to 1,779 of 2,391 eligible controls. We analyzed risks associated with occupation using job-title information to evaluate disease pattern according to job category. An earlier publication presented results for women; here, we report the findings for men and discuss the overall patterns in both genders. The most consistent overall finding was an approximate doubling in relative risk for all four types of malignancies among male managers and related occupations. Several additional occupations were associated with elevated risk of one or more malignancies among men. These included cooks, waiters, and bartenders, and building caretakers and cleaners, for non-Hodgkin's lymphoma; textile workers and machinery fitters for Hodgkin's lymphoma; metal processors, material handlers, rubber workers, and painters for leukemia; and hairdressers, metal processors, tailors, electrical workers, and plumbers for multiple myeloma. The finding of increased risk of non-Hodgkin's lymphoma among both male and female cooks, waiters, and bartenders has not been previously reported; nor has the elevated risk of leukemia among material handlers. Among people engaged in agriculture, those employed as tractor drivers and as "orchard, vineyard, and related tree and shrub workers" appeared to be at increased risk for hematolymphopoietic malignancies.

Adult↗

Cell proliferation, cell death, E-cadherin, metalloproteinase expression and angiogenesis in gastric cancer precursors and early cancer of the intestinal type.

The aim of this study was to analyse the morphological, kinetic and molecular characteristics of low-grade (LGD) and high-grade dysplasias (HDG) in comparison with intestinal metaplasia type III (IM III) and normal mucosa (NM) as well as with early gastric cancer of the intestinal type (EGC). Based on this it was verified whether these categories are distinct, progressive proliferative steps from IM III to LGD, HGD and EGC, according to Correa's sequence of events. The morphology, mitotic index (MI), and the apoptotic index (AI) were assessed. The E-cadherin expression (E-Cad), matrix-metalloproteinase activity (MMP2), and the number of microvessels (NV) were also evaluated. Among the categories, MI increases from NM to IM III and LGD, and from LGD to HGD and EGC, while AI continues to increase also from HGD to EGC. E-cad decreases from NM to EGC, although not significantly from LGD to HGD; MMP2 is significantly more expressed only in EGC. Three groups are obtained by means of cluster analysis. The first group includes all the NMs and IM IIIs, all except 1 LGD, about half of HGDs, and 1 EGC. E-Cad is highly expressed, MMP2 and angiogenesis are low, the proliferative activity is low and mitoses are partly balanced by apoptoses. The second group includes some EGCs and HGDs and is characterised by a very high proliferative activity and cell death; there is an initial loss of cell adhesion, an increase of MMP2 and NV. The third group includes the majority of EGCs, but also 1 HGD: it has intermediate MI and AI, the lowest expression of E-Cad, the highest expression of MMP2 and the most numerous microvessels. These results underscore the necessity of evaluating each case individually within the same singular category of Correa's sequence. The use of kinetic and molecular parameters in addition to the morphological analysis may give important information on the behaviour of the various lesions.

Cadherins↗

Vitamin E serum levels and gastric cancer: results from a cohort of patients in Tuscany, Italy.

Alpha-tocopherol has been reported to play an important role against oxidative damage and in the inhibition of cell transforming and mutagenesis. We analysed vitamin E serum levels in 51 cases of patients affected by gastric cancer at different stages of the disease, and in 49 age-matched controls. All patients had normal values of alpha-tocopherol. However, when patients have been grouped according to histotype of gastric lesions, a significant vitamin E increase has been found in diffuse gastric cancer histotype compared to the intestinal histotype. Our results suggest that a correlation between vitamin E serum levels and gastric cancer histotype should be considered.

Aged↗

Delayed infection, family size and malignant lymphomas.

BACKGROUND: The annual incidence of non-Hodgkin's lymphomas (NHL) is increasing by 3%-4% in different parts of the developed world. Excesses of NHL have been observed in populations exposed to immunosuppressants and to HIV, but these causes do not explain the increasing trends. It is suggested that delayed infection could explain NHL trends, through an impairment of the Th1/Th2 lymphocyte patterns. METHODS: In a population-based study on 1388 patients with NHL, 354 with Hodgkin's disease (HD) and 1718 healthy controls, the age of first occurrence of bacterial and viral diseases was investigated. Clinical records were perused in one centre to check the anamnestic data. FINDINGS: The age of occurrence of bacterial and viral diseases was significantly higher among NHL patients than in the controls. The association between later age at first bacterial or viral disease was limited to small families (OR= 1.95; 95% confidence intervals 1.26, 3.00, for age 4-8 at first infection; OR=1.91; 1.19, 3.06, for age 9+, compared with less than 4). The association was more obvious for bacterial diseases (possibly for the lower degree of misclassification). High grade lymphomas showed the strongest association. The later age of occurrence of bacterial or viral diseases in NHL patients is consistent with a higher incidence of lymphomas observed in higher social groups. No clear association was found between HD and age at first bacterial or viral diseases. INTERPRETATION: It is proposed that delayed infection could explain the increasing NHL trends, through an impairment of the Th1/Th2 lymphocyte patterns. The model of delayed infection has been proposed also to explain increasing prevalence rates of asthma.

Adult↗

Haematopoietic cancer and medical history: a multicentre case control study.

BACKGROUND: Viruses (such as Epstein-Barr virus) and pathological conditions (mainly involving immunosuppression) have been shown to increase the risk of haematolymphopoietic malignancies. Other associations (diabetes, tonsillectomy, autoimmune diseases) have been inconsistently reported. METHODS: The association between different haematolymphopoietic malignancies (lymphomas, myelomas and leukaemias) and the previous medical history has been studied in a population-based case-control investigation conducted in Italy, based on face to face interviews to 2669 cases and 1718 population controls (refusal rates 10% and 19%, respectively). Controls were a random sample of the general population. RESULTS: Previous findings were confirmed concerning the association between non-Hodgkin's lymphoma (NHL) and lupus erythematosus (odds ratio, OR=8.4; 95% CI 1. 6, 45), tuberculosis (OR=1.6; 1.05, 2.5) and hepatitis (1.8; 1.4, 2. 3). An association was found also between NHL and maternal (OR=2.8; 1.1, 6.9) or paternal tuberculosis (OR=1.7; 0.7, 3.9). Odds ratios of 4.0 (1.4, 11.8) and 4.4 (1.1, 6.6) were detected for the association between NHL and Hodgkin's disease, respectively, and previous infectious mononucleosis, but recall bias cannot be ruled out. No association was found with diabetes, tonsillectomy and adenoidectomy. An association with malaria at young age and "low grade" lymphatic malignancies is suggested. One interesting finding was the observation of four cases of poliomyelitis among NHL patients, one among Hodgkin's disease and one among myeloid leukaemia patients, compared with none among the controls (Fisher's exact test for NHL and Hodgkin's disease, p= 0.03, one tail). CONCLUSIONS: Some of these findings are confirmatory of previous evidence. Other observations, such as the putative role of the polio virus and of malaria are new. A unifying theory on the mechanisms by which previous medical history may increase the risk of haematolymphopoietic malignancies is still lacking.

Adult↗

Occupational, environmental, and life-style factors associated with the risk of hematolymphopoietic malignancies in women.

BACKGROUND: The etiology of lymphomas, leukemias, and multiple myeloma is still largely unknown. The known risk factors (ionizing radiation, solvent exposure, pesticide exposure, immunosuppression) explain only a small proportion of the cases that occur. METHODS: We conducted a multicenter population-based case-control study on hematolymphopoietic malignancies in Italy and interviewed 2,011 women (1,183 cases and 828 controls). RESULTS: There was a suggestion of a positive association between smoking and the risk of non-Hodgkin's lymphoma + chronic lymphocytic leukemia. A slight increased risk of leukemias was observed among women using permanent hair dye. Housewives were at increased risk for leukemia and multiple myeloma. The risk of non-Hodgkin's lymphomas + chronic lymphocytic leukemia, leukemias, multiple myeloma, and Hodgkin's disease increased among women employed as hairdressers and textile workers. Teachers were at increased risk for non-Hodgkin's lymphomas + chronic lymphocytic leukemia, leukemias, and Hodgkin's disease. CONCLUSIONS: These results confirm previous associations and may provide additional clues to some determinants of hematolymphopoietic malignancies in women.

Adult↗

P53 accumulation is a prognostic factor in intestinal-type gastric carcinoma but not in the diffuse type.

BACKGROUND: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer. METHODS: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis. RESULTS: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression. CONCLUSIONS: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.

Adult↗