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Biomedical subjects

F M Vecchio

Publications and source records attributed to F M Vecchio.

At least 19 recordsLinked to original sources

High accuracy and cost-effectiveness of a biopsy-avoiding endoscopic approach in diagnosing coeliac disease.

BACKGROUND: The 'immersion' technique during upper endoscopy allows the visualization of duodenal villi and the detection of total villous atrophy. AIM: To evaluate the accuracy of the immersion technique in detecting total villous atrophy in suspected coeliac patients. The accuracy in diagnosing coeliac disease and the potential cost-sparing of a biopsy-avoiding approach, based on selection of individuals with coeliac disease-related antibodies and on endoscopic detection of absence of villi, were also analysed. METHODS: The immersion technique was performed in 79 patients with positive antibodies and in 105 controls. Duodenal villi were evaluated as present or absent. As reference, results were compared with histology. Diagnostic approaches, including endoscopy with or without biopsy, were designed to investigate patients with coeliac disease-related antibodies and total villous atrophy. A cost-minimization analysis was performed. RESULTS: All patients with positive antibodies had coeliac disease. The sensitivity, specificity, positive and negative predictive values of endoscopy to detect total villous atrophy was always 100%. The sensitivity, specificity, positive and negative predictive values of biopsy-avoiding or biopsy-including strategies in diagnosing coeliac disease when villi were absent was always 100%. The biopsy-avoiding strategy was cost-sparing. CONCLUSIONS: Upper endoscopy is highly accurate in detecting total villous atrophy coeliac patients. A biopsy-avoiding approach is both accurate and cost-sparing to diagnose coeliac disease in subjects with marked duodenal villous atrophy.

Adolescent↗

Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid.

AIMS: The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel. METHODS AND RESULTS: One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies. CONCLUSION: An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.

Biomarkers, Tumor↗

Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma.

BACKGROUND: There is a lack of data in the literature concerning the identification of potential prognostic factors in ampullary adenocarcinoma. AIMS: To examine the prognostic significance of Bax, Bcl-2, and p53 protein expression and the apoptotic index in a large cohort of uniformly treated patients with radically resected ampullary cancer. METHODS: All patients with a pathological diagnosis of ampullary cancer and radical resection were evaluated. Expression analysis for p53, Bax, and Bcl-2 was performed by immunohistochemistry. Apoptotic cells were identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Thirty nine tumour specimens from patients with radically resected ampullary adenocarcinoma were studied. A positive significant correlation between Bax and p53 expression was found by rank correlation matrix (p < 0.001). A trend towards a positive correlation was found between the apoptotic index and p53 expression (p = 0.059). By univariate analysis, overall survival was influenced by Bax expression, p53 expression, and TUNEL staining (p = 0.001, p = 0.01, and p = 0.03, respectively). Bcl-2 expression did not influence overall survival in these patients (p = 0.55). By multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was Bax expression (p = 0.020). CONCLUSIONS: These results provide evidence that apoptosis may be an important prognostic factor in patients with radically resected ampullary cancer. This study is the first to assess the clinical usefulness of Bax expression in radically resected ampullary cancer.

Adenocarcinoma↗

A human umbilical cord stem cell rescue therapy in a murine model of toxic liver injury.

BACKGROUND: Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver. AIMS: In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice. METHODS: We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment. RESULTS: Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process. CONCLUSIONS: We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.

Animals↗

Mesorectal microfoci adversely affect the prognosis of patients with rectal cancer.

PURPOSE: Mesorectal involvement is a common feature in rectal tumors. Neoplastic foci can be identified at pathologic examination of the mesorectum, but their incidence and prognostic significance remain to be defined. METHODS: A series of 77 patients with extraperitoneal rectal cancer, resected with total mesorectal excision, entered the study. After fixation, the excised specimens were submitted to serial transverse sections and staining. Direct tumor infiltration, lymph node involvement, and neoplastic microfoci in the mesorectum were investigated. Patients with mesorectal foci were compared with those without deposits with regard to clinical and pathologic parameters; different patterns of foci (endovasal, endolymphatic, perineural, isolated) were also considered. Univariate and multivariate analyses were used to evaluate the impact on survival rate. RESULTS: Neoplastic mesorectal involvement was found in 64 patients (83.1 percent). Direct tumor infiltration was detected in 66.2 percent, node involvement in 28.6 percent, microscopic foci in 44.2 percent of cases (endovasal in 11.7 percent, endolymphatic in 15.7 percent, perineural in 26 percent, isolated in 14.3 percent). In 7 cases (10.9 percent) microfoci alone (without any kind of other mesorectal involvement) were detected. Deposits were found in 18.8 percent of TNM Stage I tumors, in 46.9 percent of Stage II and in 59.3 percent of Stage III cancers. Similar incidence was found in patients treated with integrated therapies and surgery alone (43.3 vs. 44.7 percent, P = not significant). Poorer median (44.5 vs. 57 months, P = 0.04) five-year overall survival rate (43.4 vs. 63.3 percent, P = 0.016) and disease-free survival rate (43.3 vs. 57.7 percent, P = 0.048) were observed in patients with microscopic foci compared with those without deposits. Tumor configuration was found to be a independent prognostic factor for both overall and disease-free survival rates; furthermore, endolymphatic, perineural, and isolated foci significantly affected overall survival rate, while TNM staging affected disease-free survival rate. CONCLUSIONS: The incidence of neoplastic foci in the mesorectum is high, even in early staged tumors and despite aggressive preoperative treatment. They seem to affect prognosis. Such features should, therefore, be considered when local excision of the tumor is planned. Presence of mesorectal foci should modify conventional staging of the rectal tumor.

Adult↗

Role of Helicobacter pylori CagA+ infection in determining oxidative DNA damage in gastric mucosa.

BACKGROUND: Although Helicobacter pylori is a risk factor for gastric cancer, the role of the bacterium in the development of this malignancy is not defined precisely. Reactive oxygen species (ROS) could play an important role in carcinogenesis by inducing DNA damage. The aims of the present study were: 1) to assess the production of ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury, in gastric mucosa, according to H. pylori status and cytotoxic associated gene product A (CagA); 2) to determine the relationship between ROS generation and amount of 8-OHdG. METHODS: Gastric biopsy specimens were obtained from 60 consecutive patients. ROS generation was measured by luminol enhanced chemiluminescence. 8-OHdG detection was performed by an immunoperoxidase method, using a specific anti 8-OHdG monoclonal antibody. RESULTS: 40/60 patients (67%) were H. pylori-positive. ROS generation was significantly higher in patients positive for H. pylori infection as compared to negative. 8-OHdG detection was performed in 30 patients in which CagA presence was also investigated. High expression of 8-OHdG was detected in 14/20 (70%) H. pylori-positive patients (13 CagA+ and 1 CagA-) and in 2/10 (20%) H. pylori-negative patients. A significant correlation was found between ROS production and 8-OHdG content. CONCLUSION: H. pylori infection by a CagA+ strain is associated with the highest production of ROS to which a severe oxidative DNA damage corresponds. This sequence of events could support the hypothesis that the oxygen-free radicals-mediated damage due to H. pylori cytotoxic strains could be a driving force that leads from chronic gastritis to gastric carcinoma.

8-Hydroxy-2'-Deoxyguanosine↗

Non-alcoholic steatohepatitis induced by carbamazepine and variegate porphyria.

A 42-year-old woman presented with acute bullous skin lesions and angio-oedema that had developed 3 months after initiation of treatment with carbamazepine for epilepsy. Chromatographic analysis of urinary porphyrins was compatible with variegate porphyria. This was manifested initially by neurological symptoms that were mistaken for epilepsy and later by cutaneous symptoms also. Histological findings excluded hepatic porphyria, but revealed severe fatty changes thought to be caused by idiosyncratic metabolism of carbamazepine. While the porphyrinogenicity of carbamazepine is well known, the presence of variegate porphyria has not been reported. The toxic hepatic effects of the drug on hepatic cytochrome P-450, which is involved in haem metabolism, could have aggravated the pre-existent porphyria, provoking the onset of skin lesions.

Adult↗

Hepatocellular carcinoma complicating liver cirrhosis in type IIIa glycogen storage disease.

Type III glycogen storage disease (GSD III) is an autosomal recessive disorder characterized by the accumulation of abnormal glycogen in the liver and, in most patients, in the muscle. Although liver fibrosis is a well-known consequence of GSD III, until now only eight cases of liver cirrhosis and two cases of hepatocellular carcinoma have been described in patients affected by this disease. In this case report, the authors describe the clinical history of a patient affected by GSD III who developed severe liver disease during her adult life, progressing from fibrosis to cirrhosis and finally to hepatocellular carcinoma. Until now, the hepatic involvement in GSD III has been considered by most authors as mild and almost always self-limiting. This report, together with the previously published cases, clearly indicates that severe and progressive liver disease may complicate this metabolic disorder. These observations advise a careful hepatologic follow-up of patients affected by GSD III.

Carcinoma, Hepatocellular↗

[Evaluation of the "N" factor in nonsmall cell lung cancer. Correlation between computerized tomography and pathologic anatomy].

PURPOSE: To evaluate the role of CT in identifying other morphological signs of metastatic lymph node involvement from non small cell bronchogenic carcinoma. This is done to improve N staging, a critical step in this disease. In fact, since diameter is the only criterion used to distinguish normal form abnormal lymph nodes, medistinal CT only has 80% diagnostic accuracy. MATERIAL AND METHODS: 137 patients with known or suspected lung cancer were examined with Helical CT during early and late arterial phases (2 min delay, 3 mm thickness, 5 mm interslice gap) to depict node characteristics. Mediastinal lymph nodes, located according to the American Thoracic Society mapping, were considered normal when they were not visible or, if visible, less than 1 cm in diameter and of homogeneous density; lymph nodes over 1 cm in diameter and homogeneous density were considered reactive. A lymph node was considered metastatic when, independent of size, the following signs were found: central hypodensity; hyperdense thin/thick rim, with nodules within; hyperdense strands or diffuse hyperdensity in perinodal adipose tissue. The tumor site was also considered. RESULTS: Seventy patients were excluded because they were inoperable. Sixty-five of the remaining 67 patients were operated on, 1 underwent mediastinoscopy and another one mediastinoscopy followed by surgery. Based on the above CT signs, 46 patients were staged as N0, 61 as N1 and 15 as N2. In 44/46 N0 patients there was agreement between anatomical and pathologic findings; 3 of the 44 patients had lymph nodes over 1 cm in diameter and with homogeneous density. Micrometastases to mediastinal lymph nodes (N2) were found at histology in 2/46 patients (CT false negatives). In the 6 N1 and the 15 N2 patients there was complete agreement between anatomical and pathologic findings; in particular, 9 N2 patients had lymph nodes less than 1 cm in diameter with signs of metastasis and 4 had lymph nodes over 1 cm in diameter with signs of metastasis and 2 had lymph nodes either over or less than 1 cm. In all N2 patients the tumor histotype and the mediastinal location were also considered relative to the lesion site. DISCUSSION: A closer correlation was found with node morphology and density than with size. Indeed, CT sensitivity, specificity and diagnostic accuracy were 97, 100 and 97%, respectively, for the former versus 52, 93 and 77% for the latter. Adenocarcinoma was the predominant histotype (70.5%) in N2 patients. Metastases to node region 4 were predominant in right upper lobe carcinomas while node region 5 was predominant in left upper lobe lesions. CONCLUSIONS: Other criteria can be associated with size to improve CT diagnostic accuracy in N staging. Technique optimization plays a major role particularly in the late, thin slice, examination phase.

Adenocarcinoma↗

Accurate lymph-node detection in colorectal specimens resected for cancer is of prognostic significance.

PURPOSE: Lymph-node involvement is the most important prognostic factor in colorectal cancers. Many staging systems adopted node status as a parameter of tumor classification. However, the number of identified and positive glands varies across articles, depending on specimen examination. There is a consistent risk of substaging tumors and undertreating patients. Aim of this study was to investigate the prognostic significance of different pathologic methods. METHODS: Eight hundred one patients who underwent curative resection of colorectal cancer entered the study and were divided into two groups. In Group 1 the specimen was "en bloc" fixed, and nodes were identified by sight and palpation. In Group 2 the mesentery of the excised specimen was dissected away from the bowel, stretched, and pinned to cork board. The mesenteric segment surrounding the origin of principal vessels was divided from the segment surrounding the colic vessels. All specimen segments were fixed, node identification being performed by sight and palpation. Examined and positive nodes were recorded, and metastatic rate and incidence was calculated in the two groups. Patients were classified with use of different staging systems. Survival rates were calculated, related to tumor stage, and compared statistically. Pathologic procedures were included in a multivariate analysis. RESULTS: A significantly higher number of detected and positive nodes and metastatic rate (37.5 vs. 30.2 percent; P < 0.05) were observed in Group 2; 45.2 percent of Group 2 and 25.3 percent of Group 1 cases had more than three positive nodes (P < 0.05). In Group 2 several patients shifted from earlier to more advanced stages compared with Group 1 cases. Five-year and ten-year survival rates were significantly higher (P = 0.04) in Group 2 (81.5 and 77.2 percent) than in Group 1 (76.7 and 61.5 percent), mostly in patients with TNM Stage N0. Survival analysis related to Astler and Coller's and Tang's classifications confirmed such features. Higher rates of local recurrences and distant metastases were found in Group 1, particularly if related to node status (P < 0.05). Multivariate analysis demonstrated the pathologic method is an independent prognostic factor. CONCLUSIONS: This study demonstrates the prognostic impact of specimen examination. Inaccurate methods could down-stage the tumor and exclude the patient from adjuvant therapies, with detrimental effects on the outcome of the case.

Adult↗

Antipyrine clearance in chronic and neoplastic liver diseases: a study of 518 patients.

Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve of the liver. It is well known that metabolism of this drug is impaired in subjects with acute hepatitis or cirrhosis, but conflicting data have been reported regarding patients with chronic postinfectious hepatitis or liver cancer. We studied conventional liver-function parameters and antipyrine metabolism (antipyrine per o.s. 18 mg/kg) in 518 subjects. One hundred and one patients had liver metastases (various primaries). Based on the number and size of lesions, the hepatic involvement was considered minimal in 47 and massive in 54 (groups B1 and B2, respectively). One hundred and two had chronic active hepatitis (CAH); 51 patients with histological evidence of fibrosis/early cirrhosis and 51 patients were without histological evidence of fibrosis/early cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control group was composed of 103 subjects with healthy livers (group A). Antipyrine clearance (AP Cl) in CAH patients with fibrosis (0.246 +/- 0.98 mL/min per kg) was similar to that observed in patients with cirrhosis (0.223 +/- 0.148 mL/min per kg), and both values were significantly lower than that found in CAH patients without fibrosis (0.406 +/- 0.159 mL/min per kg, P < 0.01). Antipyrine clearance in patients with liver metastases (0.426 +/- 0.174 mL/min per kg) was similar to that of the healthy group (0.489 +/- 0.210 mL/min per kg). Cirrhotics and cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of impairment. Antipyrine clearance was positively correlated with serum albumin (r2 = 0.10, P = 0.01) and prothrombin time (r2 = 0.129, P < 0.01) in all groups, except those with liver metastases. In patients with CAH, the presence of fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of impairment in groups with liver metastases suggests that the functional hepatic reserve is maintained even in the presence of massive neoplastic invasion.

Adolescent↗

Epithelial-cell apoptosis and proliferation in Helicobacter pylori-related chronic gastritis.

BACKGROUND: Several studies have shown that Helicobacter pylori infection is associated with enhanced gastric epithelial-cell proliferation, which is thought to be involved in its apparent carcinogenicity. This hyperproliferation is believed to be related to the inflammatory effects of the bacterium. The role of Helicobacter pylori in gastric epithelial apoptosis, however, is less clear. AIM: We attempted to identify the effect of Helicobacter pylori infection on apoptosis in the gastric epithelium and its possible relation to epithelial-cell proliferation and mucosal inflammation. PATIENTS AND METHODS: We studied cell proliferation (via bromodeoxyuridine labelling), apoptosis (using in situ TdT-mediated dUTP-biotin nick end labelling of DNA strand breaks) and mononuclear and polymorphonuclear cell infiltrates (computer-assisted image analysis) in gastric antral biopsies obtained from 37 gastritis patients (20 Helicobacter pylori-positive, 17 Helicobacter pylori-negative). RESULTS: Helicobacter pylori-positives displayed significantly enhanced proliferation within the gastric epithelium that was positively correlated with both acute and chronic inflammatory-cell densities. Apoptotic indexes were similar in both groups and showed no correlation with any of the parameters under consideration. CONCLUSIONS: Enhanced epithelial cell proliferation and an altered distribution of cycling cells within the gastric glands are a common feature of chronic superficial gastritis caused by Helicobacter pylori. In vivo immunohistochemically detected apoptosis of gastric epithelial cells does not seem to be affected by Helicobacter pylori infection. Further study is needed to clarify the effect of this infection on programmed cell death within gastric glands.

Adult↗

Cholestatic hepatitis due to ticlopidine: clinical and histological recovery after drug withdrawal. Case report and review of the literature.

A 72-year-old housewife presented with clinical and laboratory signs of acute cholestatic hepatitis. Symptoms had appeared 6 months after she was started on ticlopidine 250 mg/day. Infectious aetiologies were excluded by serology and there was no history of alcohol abuse or use of other drugs. Clinical findings were confirmed by liver biopsy. The drug was discontinued and symptoms gradually subsided. A second biopsy obtained during this phase documented complete resolution of the hepatic damage. A review of the literature shows that the late onset of hepatic toxicity in this case is unique and this is the first report to include histological documentation during the acute phase and after recovery.

Aged↗

Local excision and external beam radiotherapy in early rectal cancer.

PURPOSE: To assess the local control and survival of local excision and postoperative radiation in patients with early stage rectal cancer. METHODS AND MATERIALS: From 1980 to 1992, 21 patients with clinical stage T1-2NxM0 adenocarcinoma of the middle and lower rectum were treated with transanal excision and postoperative external beam radiotherapy (44.6 Gy). The pathologic T stages were: 9 T1 (43%) and 12 T2 (57%). One patient had unassessable resection margins. The median follow-up was 54 months (range: 18-128 months). RESULTS: The actuarial local recurrence-free survival at 5 years was 85.2%, and the overall survival at 5 years was 80.6%. One patient developed a local recurrence and distant metastases at 22 months, and two patients had local recurrence at 11 and 15 months, respectively; both had abdomino-perineal resection (APR) and one remained free of disease 16 months after APR. The incidence of Grade 3 diarrhea was 5%. Sphincter function was good to excellent in the 18 patients with local control. No patients developed clinical evidence of pelvic lymph node recurrence. CONCLUSION: These results are similar to other published series and suggest that this approach is feasible in selected patients with T1-2NxM0 rectal cancer and results in good long-term control of the disease.

Adenocarcinoma↗

Prevention and treatment of low-grade B-cell primary gastric lymphoma by anti-H. pylori therapy.

Mucosa-associated lymphoid tissue (MALT) showing a follicular structure can develop in the gastric mucosa as a response to Helicobacter pylori infection. We emphasize the importance of anti-H. pylori antibiotic therapy in the elimination of acquired MALT. Of the 200 patients studied, acquired MALT was found in 70 of the 151 H. pylori-positive patients, whereas it was present in only five of the 49 H. pylori-negative patients. Thirty-eight H. pylori-positive and MALT-positive patients were treated with antibiotic therapy and reevaluated after 6 months: 21 patients were H. pylori negative/MALT negative, 12 were H. pylori positive/MALT positive, four were H. pylori negative/MALT positive, one was H. pylori positive/MALT negative. In the control group (n = 20), H. pylori and acquired MALT were still present at follow-up. One patient with histological and immunohistochemical evidence of low-grade B-cell gastric MALT lymphoma underwent antibiotic treatment and was reexamined after 8, 12, and 24 weeks: histological examination of biopsy samples showed regression of the MALT lymphoma in tandem with the disappearance of H. pylori colonization. Our data confirm the correlation between H. pylori infection and acquired MALT, as documented by the ability of antibiotic therapy to induce the disappearance of acquired MALT and regression of MALT lymphoma. Considering the potential evolution of MALT into low-grade B-cell MALT lymphoma, H. pylori eradication should play a role in the prevention of this tumor.

Adolescent↗

DNA ploidy pattern in human chronic liver diseases and hepatic nodular lesions. Flow cytometric analysis on echo-guided needle liver biopsy.

BACKGROUND: Significantly elevated fractions of diploid hepatocytes and reduction in the polyploid populations have been reported in human and experimentally induced hepatocellular carcinomas (HCC). This study was conducted to determine how these changes are related to conditions that often precede HCC, such as chronic hepatitis, cirrhosis, and premalignant focal nodules in cirrhotic livers. METHODS: Ultrasound-guided needle biopsy specimens of the liver were obtained from patients with chronic hepatitis, cirrhosis, or ultrasonographically diagnosed nodules within cirrhotic livers; biopsy specimens also were taken from patients without hepatic disease. DNA flow cytometry was performed on isolated nuclei to determine the percentages of diploid, tetraploid, and octaploid hepatocytes; the S-phase fraction for each diploid peak and the diploid/polyploid (tetraploid + octaploid) ratio also were calculated. Part of each specimen was reserved for evaluation of hepatocyte binuclearity. RESULTS: Chronically hepatitic (18 patients) and cirrhotic (18 patients) livers showed significantly increased diploid/polyploid ratios, with respect to normal livers, that were significantly correlated with decreases in hepatocyte binuclearity. This trend was even more marked in euploid nodules (4 premalignant and 5 malignant), in which the S-phase fractions were significantly higher than those of normal liver; aneuploidy was found in 6 of 11 malignant and 2 of 6 premalignant nodules.

Aged↗