Biomedical subjects

Gabriella Nesi

Publications and source records attributed to Gabriella Nesi.

At least 19 recordsLinked to original sources

PubMed2007

CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study.

Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992-1998, provided life-style and dietary information and a blood sample (360,000; mean follow-up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually-matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels <22 microg/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti-H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4-fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2-5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3-12.6); on the other hand, a ten-fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% CI 3.0-40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites.

Adenocarcinoma↗

PubMed2006

Well-differentiated endocrine tumor of the distal common bile duct: a case study and literature review.

Primary carcinoid tumors of the extrahepatic biliary tree are exceedingly rare, accounting for 0.2-2% of all digestive carcinoids. The authors in this study describe a case of biliary duct primary well-differentiated endocrine tumor in a 30-year-old man with symptoms of biliary obstruction and watery diarrhoea. Abdominal ultrasound showed a 2-cm solid lesion in the head of the pancreas, compressing the distal common bile duct. A computed tomography scan confirmed these findings, revealing the hypervascular pattern of the tumor. Gastrointestinal hormonal screening demonstrated an increase in plasma serotonin. The patient underwent standard pylorus-preserving pancreatoduodenectomy. Pathological examination showed a neuroendocrine tumor of the distal common bile duct measuring 1.8 cm in greatest dimension. The tumor cells were immunopositive for neuron-specific enolase (NSE), chromogranin A, synaptophysin, serotonin, and cytokeratin. Stains for gastrin and somatostatin were negative. Seven years later, the patient is well, with no evidence of disease. Given the site of these tumors and the difficulty in differentiating them from periampullary lesions, decisions as to the appropriate surgical approach may be problematic. After an exhaustive review of the literature, the authors conclude that pancreatoduodenectomy is the treatment of choice.

Adult↗

PubMed2006

Meat intake and risk of stomach and esophageal adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC).

BACKGROUND: Dietary factors are thought to have an important role in gastric and esophageal carcinogenesis, but evidence from cohort studies for such a role is lacking. We examined the risks of gastric cancer and esophageal adenocarcinoma associated with meat consumption within the European Prospective Investigation Into Cancer and Nutrition (EPIC) cohort. METHODS: A total of 521,457 men and women aged 35-70 years in 10 European countries participated in the EPIC cohort. Dietary and lifestyle information was collected at recruitment. Cox proportional hazard models were used to examine associations between meat intake and risks of cardia and gastric non-cardia cancers and esophageal adenocarcinoma. Data from a calibration substudy were used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. In a nested case-control study, we examined interactions between Helicobacter pylori infection status (i.e., plasma H. pylori antibodies) and meat intakes. All statistical tests were two-sided. RESULTS: During a mean follow-up of 6.5 years, 330 gastric adenocarcinoma and 65 esophageal adenocarcinomas were diagnosed. Gastric non-cardia cancer risk was statistically significantly associated with intakes of total meat (calibrated HR per 100-g/day increase = 3.52; 95% CI = 1.96 to 6.34), red meat (calibrated HR per 50-g/day increase = 1.73; 95% CI = 1.03 to 2.88), and processed meat (calibrated HR per 50-g/day increase = 2.45; 95% CI = 1.43 to 4.21). The association between the risk of gastric non-cardia cancer and total meat intake was especially large in H. pylori-infected subjects (odds ratio per 100-g/day increase = 5.32; 95% CI = 2.10 to 13.4). Intakes of total, red, or processed meat were not associated with the risk of gastric cardia cancer. A positive but non-statistically significant association was observed between esophageal adenocarcinoma cancer risk and total and processed meat intake in the calibrated model. In this study population, the absolute risk of development of gastric adenocarcinoma within 10 years for a study subject aged 60 years was 0.26% for the lowest quartile of total meat intake and 0.33% for the highest quartile of total meat intake. CONCLUSION: Total, red, and processed meat intakes were associated with an increased risk of gastric non-cardia cancer, especially in H. pylori antibody-positive subjects, but not with cardia gastric cancer.

Adenocarcinoma↗

PubMed2006

Cancer progression after anterograde radical prostatectomy for pathologic Gleason score 8 to 10 and influence of concomitant variables.

OBJECTIVES: To evaluate the outcome in patients with clinically localized prostate cancer and pathologic Gleason score 8 to 10 disease treated by anterograde radical prostatectomy, either alone for node-negative disease or with early hormonal therapy for node-positive disease, and to characterize the prognostic significance of other pathologic variables. METHODS: A total of 729 patients underwent radical prostatectomy for clinically localized prostate cancer between 1989 and 2003. We identified 116 patients (15.9%) with specimen Gleason score 8 or greater. The mean follow-up was 48 months (range 6 to 145). RESULTS: The 5-year biochemical-free survival rate for those with pT2, pT3a, and pT3b diseases was 100%, 65.1%, and 10.5%, respectively (P < or =0.05). The 5-year biochemical-free survival rate for those with specimen Gleason score 8 and 9 was 72.1% and 38.2%, respectively (P < or =0.05). The incidence of positive surgical margins was 14.6% and led to a high pT3a specimen-confined detection rate. The preoperative prostate-specific antigen level, primary Gleason pattern, and surgical margin status had no statistically significant impact on biochemical recurrence-free survival. The multivariate Cox model showed seminal vesicle invasion to be the only independent prognostic factor. The 3 and 5-year progression-free survival rate of the 45 node-positive patients was 72.6% and 60.5%, respectively. CONCLUSIONS: Our findings emphasize the need for early diagnosis, which can make this disease curable by radical prostatectomy alone, and show that poorly differentiated prostate cancer that has invaded the capsule can be cured by surgery. Biochemical recurrence represented a common event in pT3b and Gleason score 9 disease, suggesting a possible role for early adjuvant treatment.

Aged↗

PubMed2006

Multiplex polymerase chain reaction for microsatellite analysis of urine sediment cells: a rapid and inexpensive method for diagnosing and monitoring superficial transitional bladder cell carcinoma.

PURPOSE: Several urinary markers have been recently introduced in clinical practice for improving the noninvasive diagnosis of transitional cell carcinoma. Although microsatellite analysis must be considered the best method in terms of results, its cost and method time are unacceptable for daily use. We validated a more rapid and inexpensive method of determination using rapid DNA extraction and automatic multiplex polymerase chain reaction amplification. MATERIALS AND METHODS: A total of 120 patients who presented consecutively to a urological office, including 73 with transitional cell carcinoma and 43 who served as controls, were selected for study. Microsatellite analysis was performed in the blood/urine pair using 3 multiplex polymerase chain reactions per patient. Urine sediment inflammatory cells were assessed by urine dipstick test. Ten microsatellite loci were investigated. Numerical data collected during electrophoresis of the amplified segment in an ABI Prism 310 Genetic Analyzer were used to calculate the cutoff for allelic imbalance. Method sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: A total of 66 patients had microsatellite analysis alterations in urine sediment, of whom 59 had transitional cell carcinoma, while 7 had other urological diseases. Test sensitivity and specificity were 80.8% and 85.1%, respectively. Statistical analysis did not indicate any significant influence of inflammatory status on microsatellite analysis diagnostic performance. In the control group the allelic imbalance on chromosome 9 was significantly lower than on other chromosomes (p = 0.0143). This could confirm that chromosome 9 has a specific role in transitional cell carcinoma. The multiplex microsatellite analysis method was low cost and not time-consuming. CONCLUSIONS: Multiplex microsatellite analysis is a noninvasive, rapid, inexpensive and reproducible method for screening for and monitoring superficial transitional cell carcinoma. It should be considered an alternative method to urinary cytology and it should also be considered in the presence of urine sediment inflammatory cells.

Carcinoma, Transitional Cell↗

PubMed2006

Pancreatectomy in multiple endocrine neoplasia type 1-related gastrinomas and pancreatic endocrine neoplasias.

OBJECTIVE: The aim of this study was to evaluate the results of pancreatic resection in pancreatic endocrine neoplasias (PENs) in patients affected by multiple endocrine neoplasia type 1 (MEN1) syndrome. BACKGROUND: Since these tumors often show an indolent course, the role of diagnostic procedures and type of surgical approach are controversial. Experience with new diagnostic approaches and more aggressive surgery is still limited. METHODS: Sixteen MEN1 patients were referred to our Surgical Unit (1992-2003) and were operated on for the indications of hypergastrinism, hypoglycemia, and/or pancreatic endocrine neoplasias larger than 1 cm. Zollinger-Ellison syndrome (ZES) was present in 13 patients, 2 of whom experienced a recurrence after previous surgery. Preoperative tumor localization was carried out using ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), somatostatin receptor scintigraphy (SSRS), or selective arterial secretin injection (SASI). Rapid intraoperative gastrin measurement (IGM) was carried out in 8 patients, and 1 patient also underwent an intraoperative secretin provocative test. RESULTS: Either pancreatoduodenectomy (PD) or total pancreatectomy (TP) or distal pancreatectomy was performed. There was no postoperative mortality; 37% complications included pancreatic (27%) and biliary (6%) fistulas, abdominal collection (6%), and acute pancreatitis (6%). EUS and SSRS were the most sensitive preoperative imaging techniques. At follow-up, 10 of 13 hypergastrinemic patients (77%) are currently eugastrinemic with negative secretin provocative test, while 3 are showing a recurrence of the disease. All patients affected by insulinoma were cured. CONCLUSIONS: MEN1 tumors should be considered surgically curable diseases. IGM may be of value in the assessment of surgical cure. Our experience suggests that PD is superior to less radical surgical approaches in providing cure with limited morbidity in MEN1 gastrinomas and pancreatic neoplasias.

Adult↗

PubMed2006

The Vienna classification applied to colorectal adenomas.

BACKGROUND AND AIM: In 1999, a group of Western and Asian pathologists gathered in Vienna reached consensus regarding the classification of gastrointestinal epithelial neoplasia. In this study, that classification is applied to colorectal adenomas. METHODS: Colorectal adenomas from 1552 patients were histologically classified according to the categories listed in Vienna: category 3, low-grade dysplasia; 4.1, high-grade dysplasia; 4.2, carcinoma in situ; 4.3, suspicious of intramucosal carcinoma; 5.1, intramucosal carcinoma; and 5.2, submucosal carcinoma. The criteria used to diagnose these lesions are described in detail. Adenomas with dysplasia (categories 3 and 4.1) or with carcinoma (categories 4.2, 4.3, 5.1 and 5.2) were analyzed separately. On basis of their configuration, adenomas were classified into tubular, tubulovillous, villous, serrated, microtubular and combined phenotypes (i.e. other than tubulovillous). RESULTS: The highest percentage of adenomas with carcinoma was found amongst villous adenomas (29.6%), followed by combined adenomas (27.8%). Villous adenoma with carcinoma was the most frequent neoplasia at all ages; combined adenomas with carcinoma were more frequent among younger patients. In elderly patients (> or = 60 years of age) the highest percentage of adenomas with carcinoma was recorded in villous adenomas (28.1%), followed by serrated adenomas (19.2%). Villous adenomas and combined adenomas with carcinoma were more frequent in males. CONCLUSION: The Vienna classification of colorectal adenomas seems to be influenced by parameters inherent to the patient such as age and sex and by the histological phenotype of the adenoma. With the recent improvement in medical technology it is possible to laser-microdissect a defined group of neoplastic glands (such as with carcinoma in situ or with intramucosal carcinoma) for specific molecular analysis. This modern technology will permit in future the translation of histological structures into molecular terms.

Adenoma↗

PubMed2006

Enterogenous cyst of the testis.

Enterogenous cyst is a rare congenital lesion generally located in the mediastinum or the abdominal cavity. We reported the first case of testicular enterogenous cyst in a 55-year-old white male presented with testicular pain and a gradually enlarging left scrotal mass with a 2-week duration.

Cysts↗

PubMed2006

Intravesical gemcitabine in BCG-refractory T1G3 transitional cell carcinoma of the bladder: a pilot study.

OBJECTIVE: The aim of this pilot study is to analyze the safety and short-term efficacy of gemcitabine (GEM) as salvage intravesical therapy in a very selected population of bacille Calmette-Guérin (BCG)-resistant T1G3 patients. METHODS: 9 recurrent BCG-refractory pT1G3 patients, unsuitable for radical treatment, were treated with GEM, and compared with 10 pT1G3 patients previously treated with at least two courses of transurethral resection plus BGC, with further conservative endovesical BCG administration. RESULTS: Both intravesical administrations of GEM and BCG were generally well tolerated: no severe adverse events were reported. Of the 9 patients treated with GEM, 3 were recurrence-free after 13, 17 and 21 months and 7 kept an intact bladder, with an overall survival rate of 9 of 9. Among 10 patients treated with BCG instillation, 1 was recurrence-free after 27 months and 6 kept their bladders, with a survival rate of 8 of 10. CONCLUSIONS: Our experience confirms the high risk of tumor recurrence and progression of BCG-refractory pT1G3 transitional cell carcinoma. In this case, further BCG courses seem to be unsuitable, resulting in a high risk of tumor progression and mortality. The use of GEM in BCG-refractory pT1G3 patients has to be considered experimental until multicentric randomized studies with adequate follow-up are able to confirm the preliminary results of this pilot study.

Adjuvants, Immunologic↗

PubMed2006

Prognostic value of static cytometry in transitional cell carcinoma of the bladder: recurrence rate and survival in a group of patients at 10 years follow-up.

Many studies have indicated that nuclear DNA content evaluation can be used to predict biological behavior of transitional cell carcinoma (TCC) of the bladder. Some authors also indicated that static cytometry is more useful in DNA content analysis than flow cytometry. The aim of the present study was to evaluate the prognostic significance of DNA ploidy in TCC of the bladder, performed by using static cytometry with an image analyzer, and monitoring patients at 10 years follow-up. Thirty-one consecutive patients underwent transurethral or open surgery for bladder tumors, and neoplastic tissue samples taken from each patient were imprinted on glass slides and sent for histopathological and DNA content evaluation. DNA ploidy evaluation was performed using a CAS 200 image analyzer. Nuclear DNA content evaluation was compared to patient follow-up on recurrence, progression or survival performed 10 years after surgery. Pathological evaluation demonstrated the presence of superficial TCC in 23 patients, while 8 had an invasive bladder tumor. Twenty-nine tumor samples were adequate for DNA content measurement, with 13 showing diploid DNA content and 16 with aneuploid DNA content. At 10 years follow-up, all patients with aneuploid DNA content demonstrated a lower survival time (p=0.049) and higher recurrence rate (p=0.0346). A log-rank test demonstrated that stage, grade and nuclear DNA content are the most useful prognostic parameters for predicting the biological behavior of TCC of the bladder. These results confirm that static cytometry is a good and reliable method to evaluate DNA tumor content and considered a useful prognostic parameter for predicting recurrence rate, disease progression or survival in patients affected by bladder tumors.

Adult↗

PubMed2006

Prognostic role of the tumor-associated tissue inflammatory reaction in transitional bladder cell carcinoma.

Many authors have indicated that the presence of an inflammatory response within the tumor may predict not only recurrence and progression but also survival in several tumors, including transitional cell carcinoma (TCC) of the urinary bladder. Several studies have been performed with a mean follow-up period that is often too limited for predicting patient outcome. The aim of the present study was to define the influence of inflammatory cell infiltrate on recurrence, progression and survival in TCC of the bladder over a long follow-up period. Between January and December 1995, 410 consecutive patients, who had undergone transurethral or open surgery for bladder tumors at the same urologic center, were selected for the study. All cases were reviewed to assess histotype, stage and grade of the tumor and presence or absence of tumor-associated inflammatory reaction. To better evaluate the prognostic role of each single factor in TCC, a follow-up of 10 years after surgery was performed. Pathologic evaluation showed superficial TCC in 312 patients, while 98 had an invasive bladder tumor. Three among 410 bladder tumors were squamous cell carcinomas. Out of 407 TCCs, 119 (29.23%) presented inflammation within the tumor or the lamina propria. At 10 years follow-up, a statistically significant association was shown between the presence of inflammation within the tumor or lamina propria and the number of recurrences (p<0.0001). Moreover, the absence of inflammatory infiltrate in the tumor established the relative risk of suffering more than one recurrence at 2.287 (95% CI 1.180-3.346). The Mann-Whitney test confirmed a statistically significant difference between superficial bladder tumors with inflammation and those without (26.3 vs 11.5 months, p<0.001). In terms of survival rate, a statistically significant difference was reported between carcinomas with and without inflammation (p=0.0261). On multivariate analysis, the presence of inflammation within the tumor was found to be an independent predictor of survival in patients with TCC of the bladder (p=0.027). Survival analysis by means of the Kaplan-Meier curves showed a statistically significant difference between patients with tumor-associated inflammatory reaction and those without (p=0.0098). These results confirm that the presence of inflammatory reaction has a good prognostic value in transitional bladder cell carcinoma. However, to better define its prognostic significance, the characterization of inflammatory cells in tumor-associated tissue reaction must be accomplished.

Adult↗

PubMed2006

p16(INK4a) expression in urinary bladder carcinoma.

The most common genetic damage in urothelial carcinoma is partial loss of chromosome 9. The area around 9p21 where the CDKN2A/ARF gene is located is one of the major sites for deletion. This gene encodes for p16 protein which impedes the cell cycle. Specific binding of the p16 product to the cyclin-dependent protein kinases cdk4 or cdk6 inhibits the catalytic activity of the cyclin D-cdk complex, and consequently arrests the cell cycle at the G1/G2 phase. This study aims to immunohistochemically assess p16 expression in urothelial carcinoma in order to evaluate the correlation of this biological marker with tumour stage and/or grade. We studied specimens of transurethral resection (TURB) from 17 cases of non-invasive papillary urothelial carcinoma and from 22 cases of invasive urothelial carcinoma of the bladder. We observed strong p16 immunoreactivity in 11 cases (28.2%), while 28 cases (71.8%) did not show p16 staining. The expression of p16 was statistically associated with disease stage (p = 0.026, according to the chi-square test), but not with either tumour grade or disease progression. These observations call for further studies to focus the importance of p16 expression in bladder cancer development and/or progression. Additional data may provide insight into treatment guided by molecular changes.

Aged↗

PubMed2005

GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high-risk italian population.

Glutathione S-Transferases (GSTs) are a family of phase II enzymes involved in the detoxification of potential carcinogens and provided of a strong antioxidant function by neutralizing electrophiles and free radicals. The GSTM1 and GSTT1 isoenzymes exhibit deletion polymorphisms, resulting in a lack of activity, and the null genotypes have been associated with increased cancer risk at several sites, including the stomach, although with contrasting results. We carried out a case-control study to evaluate whether these polymorphisms modulate the risk of developing gastric cancer (GC). Genotypes for GSTM1 and GSTT1 were obtained from a series of 175 histologically confirmed GC patients and a large series of 546 healthy controls randomly sampled from the general population of Tuscany, an area at high GC risk. No difference in the frequency of GSTM1 null genotype was observed between cases and controls, whereas the GSTT1 null genotype was more frequent among cases (p = 0.04). Multivariate single-gene analyses adjusted for possible confounders showed that the GSTT1 null genotype, but not the GSTM1 null genotype, was associated with an increased GC risk. Combined-genotype analyses showed a significantly increased GC risk only for the double null (GSTM1-GSTT1) genotype (OR = 2.27; 95% CI: 1.14-4.53). A statistically significant positive interaction between the 2 null genotypes was observed (p = 0.02). Our findings suggest that only subjects lacking both GSTM1 and GSTT1 activity are at increased GC risk. This study provides further support to the hypothesis that the risk of developing GC is influenced by inter-individual variation in both carcinogen detoxification and antioxidant capacity. (c) 2005 Wiley-Liss, Inc.

Aged↗

PubMed2005

Annuloaortic ectasia and giant cell arteritis.

BACKGROUND: Thoracic aortic aneurysm, aortic dissection and aortic valve regurgitation have been widely described in patients with Horton disease, also known as giant cell arteritis. We present our midterm experience with patients with these features. METHODS: A total of 386 cases of ascending aorta and aortic valve replacement performed for thoracic aortic aneurysm and aortic insufficiency between 1998 and 2004 were reviewed. Among them 10 cases of histopathologically confirmed GAA were identified. Patients were predominantly female (90%); the mean age was 74.5 +/- 4.6 years. RESULTS: Eight patients (80%) showed typical annuloaortic ectasia, leading to significant aortic valve regurgitation. These subjects underwent a Bentall operation. Two patients whose sinuses seemed undilated and macroscopically normal had separate valve graft replacement at first operation and underwent reoperation due to dilatation of the native sinuses. Eight patients had partial aortic arch replacement (hemiarch), and 1 underwent total arch replacement. Six-year survival was 0.9 +/- 0.09; freedom from reoperation at 6 years was 0.77 +/- 0.13. CONCLUSIONS: Annuloaortic ectasia is a common finding in giant cell arteritis. In patients with Horton disease, the aortic root should always be replaced regardless of macroscopic findings.

Aged↗

PubMed2005

Immunohistochemistry in the differential diagnosis between primary and secondary intestinal adenocarcinoma of the urinary bladder.

Distinguishing between primary adenocarcinomas and secondary colonic adenocarcinomas of the urinary bladder is often difficult because they appear morphologically similar but invariably require different treatment strategies. The aim of the study was to define the utility of a limited immunohistochemical panel consisting of CDX-2, cytokeratins 7 (CK7) and 20 (CK20), and carcinoembryonic antigen (CEA) in differentiating primary from secondary bladder adenocarcinomas. Formalin-fixed, paraffin-embedded tissues from 8 primary bladder adenocarcinomas and 23 colorectal adenocarcinomas involving the bladder were included in the study. Statistical analysis was performed using the Fisher exact test. The majority (87.5%) of primary bladder adenocarcinomas were CDX-2 negative, and only one case of primary bladder adenocarcinoma was positive, while CDX-2 was strongly expressed in the nucleus of all cases of secondary (colonic) bladder tumor (P < 0.0005). Five cases (62.5%) of primary bladder adenocarcinoma and one case (4.3%) of secondary bladder tumor showed positive staining for CK7 (P = 0.002), whereas CK20 showed positive staining in five cases (62.5%) of primary bladder adenocarcinoma and in all the secondary bladder tumors (P = 0.012). All 23 secondary bladder tumors and 7 primary bladder adenocarcinomas (87.5%) expressed CEA (P = 0.25). These data demonstrate that a restricted immunohistochemical panel consisting of CDX-2, CK7, CK20, and CEA may be of use in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin.

Adenocarcinoma↗

PubMed2005

Carcinoma of the breast metastatic to the ureter seven years later.

We present a case of ureteral metastasis from a primary breast cancer where the disease recurred with an episode of renal colic 7 years after diagnosis. A surgical operation was performed to remove the terminal ureter and the perimeatal area of the urinary bladder. Urological and radiological outcome was satisfactory after a 2-year follow up.

Breast Neoplasms↗

PubMed2005

Qualitative and quantitative analysis of angiogenetic factors in transitional cell bladder carcinoma: relationship with clinical course at 10 years follow-up.

Many authors have shown that tumor hypoxia exerts its own influence on malignant progression by inducing angiogenetic factors and new blood vessels inside and around the tumor. This event usually suggests a poor prognosis and/or aggressive tumor behavior. The objective of the present study is to compare molecular analysis of angiogenetic factors with microvessel density (MVD) in bladder carcinoma. Twenty-nine consecutive patients underwent transurethral or open surgery for bladder tumors. Neoplastic tissue samples, normal-appearing bladder mucosa and blood samples were taken from each patient. All the tissues underwent mRNA extraction and Northern blot analysis, marked with specific probes for inducible nitric oxide sinthase (iNOS), cyclo-oxygenase-2 (cox-2), vascular endothelial growth factor (VEGF) and were evaluated by gel-electrophoresis. Microvessel density, a quantitative analysis for neoangiogenesis, was also evaluated by using CD31 immunohistochemical assay and compared with both molecular analysis and patient follow-up. Two follow-up for recurrence and/or progression were performed at 74 months and 10 years from surgery respectively. Pathological evaluation demonstrated the presence of superficial transitional cell carcinoma (sTCC) in 15 patients, while 14 had an invasive bladder tumor (iBT). At both 74 months and 10 years follow-up, all patients with lower MVD had a shorter survival time. No significant results were obtained by comparing disease progression or survival rate with VEGF, iNOS and COX-2 levels. A proportional increase of VEGF expression and MVD compared with poor prognosis was the expected outcome of our study. These results were disregarded at both the 1st and the 2nd follow-up. A strong association between MVD>20 and survival rate was noted both in sTCC (p=0.024) and iBT (p>0.001) patients. These results confirm that MVD could be considered a good prognostic factor. The angiogenetic cytokines overexpression found in control tissue samples of sTCC could have clinical significance, either as a macroscopically unidentified diffuse carcinogenetic process or the presence of a systemic immune-response against tumor cells.

Aged↗

PubMed2004

p53 and DPC4 alterations in the bile of patients with pancreatic carcinoma.

INTRODUCTION: Pancreatic cancer is still predominantly diagnosed in advanced stages, and 85%-90% of patients are not eligible for surgery at diagnosis. This is mainly due to the great difficulty in detecting the tumour at an early stage and presently no satisfactory results have been obtained to overcome this problem. Studies on molecular genetic profile of pancreatic cancer may represent an important approach. This study was focused on the mutations of p53 and DPC4 detectable in the bile of patients with histologically proven pancreatic cancers. MATERIALS AND PATIENTS: We analysed specimens of bile collected through percutaneous transhepatic biliary catheters, placed to treat malignant biliary obstruction in 25 patients with pancreatic adenocarcinoma. A percentage of mutation was obtained of 43 % for the microsatellite D17S945 (p53), 54% and 50 % for D18S46 and D18S474 (DPC4), respectively. The percentage of amplification was 67%, 93,6%, and 80%. CONCLUSION: We consider the results encouraging enough to decide to enlarge the number of patients examined. The aim is to determine if a test for DPC4 and p53 mutations is eligible for introduction in clinical routine use. More sets of samples are required to satisfactorily answer this question.

Adenocarcinoma↗