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1.
G Chir ; 33(5): 194-8, 2012 May.
Article in English | MEDLINE | ID: mdl-22709459

ABSTRACT

PURPOSE: Anastomotic strictures occur in 3-30% of colorectal anastomosis and one of the main causes may be a reaction to the presence of the metal staples used for suturing. The aim of this study was to evaluate the efficacy of a compression anastomosis ring using the memory shaped device in initial, i.e. nickel-titanium alloy (NiTi) for the prevention of colorectal anastomotic strictures. PATIENTS AND METHODS: A compression anastomosis ring device (NiTi CAR 27™) was used to perform compression anastomosis in 20 patients underwent left hemicolectomy and anterior resection of the rectum for carcinoma. An endoscopic check of the anastomosis was carried out at one month and at six months after surgery. RESULTS: In 2 patients (10%) a dehiscence of the anastomosis occurred on the fifth and the eighth postoperative day. No anastomotic strictures were observed in any of the other 18 patients at six months follow-up after surgery. CONCLUSION: Our preliminary results suggest that the use of a compression anastomosis ring might well be a valid method of preventing anastomotic strictures in colorectal surgery. Further studies involving a larger number of patients are needed in order to confirm these preliminary results.


Subject(s)
Anastomosis, Surgical , Colon , Colectomy , Colon/surgery , Constriction, Pathologic , Humans , Rectum/surgery
2.
Endocr Relat Cancer ; 18(6): 669-85, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21903858

ABSTRACT

BRAF(V600E) is the most common mutation found in papillary thyroid carcinoma (PTC). Tissue inhibitor of metalloproteinases (TIMP-1) and nuclear factor (NF)-κB have been shown to play an important role in thyroid cancer. In particular, TIMP-1 binds its receptor CD63 on cell surface membrane and activates Akt signaling pathway, which is eventually responsible for its anti-apoptotic activity. The aim of our study was to evaluate whether interplay among these three factors exists and exerts a functional role in PTCs. To this purpose, 56 PTC specimens were analyzed for BRAF(V600E) mutation, TIMP-1 expression, and NF-κB activation. We found that BRAF(V600E) mutation occurs selectively in PTC nodules and is associated with hyperactivation of NF-κB and upregulation of both TIMP-1 and its receptor CD63. To assess the functional relationship among these factors, we first silenced BRAF gene in BCPAP cells, harboring BRAF(V600E) mutation. We found that silencing causes a marked decrease in TIMP-1 expression and NF-κB binding activity, as well as decreased invasiveness. After treatment with specific inhibitors of MAPK pathway, we found that only sorafenib was able to increase IκB-α and reduce both TIMP-1 expression and Akt phosphorylation in BCPAP cells, indicating that BRAF(V600E) activates NF-κB and this pathway is MEK-independent. Taken together, our findings demonstrate that BRAF(V600E) causes upregulation of TIMP-1 via NF-κB. TIMP-1 binds then its surface receptor CD63, leading eventually to Akt activation, which in turn confers antiapoptotic behavior and promotion of cell invasion. The recognition of this functional trilogy provides insight on how BRAF(V600E) determines cancer initiation, progression, and invasiveness in PTC, also identifying new therapeutic targets for the treatment of highly aggressive forms.


Subject(s)
Cell Transformation, Neoplastic/genetics , NF-kappa B/metabolism , Proto-Oncogene Proteins B-raf/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Tissue Inhibitor of Metalloproteinase-1/genetics , Adult , Amino Acid Substitution/physiology , Carcinoma , Carcinoma, Papillary , Cell Transformation, Neoplastic/pathology , Disease Progression , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks/physiology , Glutamic Acid/genetics , Humans , Male , Middle Aged , Mutation, Missense/physiology , Neoplasm Invasiveness , Proto-Oncogene Proteins B-raf/physiology , Signal Transduction/genetics , Signal Transduction/physiology , Thyroid Cancer, Papillary , Thyroid Neoplasms/pathology , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tumor Cells, Cultured , Up-Regulation/genetics , Valine/genetics
3.
Minerva Chir ; 65(6): 627-33, 2010 Dec.
Article in Italian | MEDLINE | ID: mdl-21224797

ABSTRACT

AIM: Intra- and postoperative bleeding represents an extremely serious and frequent complication of hepatic surgery. The aim of this study was to evaluate the effectiveness of TachoSil® to improve hemostasis in radiofrequency assisted minor hepatic resection. METHODS: Between July 2008 and June 2010, 31 patients underwent radiofrequency assisted minor hepatic resection. At the end of the liver resection a sponge of TachoSil® was applied on the liver. RESULTS: The mean intraoperative bleeding from the liver was 56.1 mL (range 0-300 mL). No patients received intra- and postoperative blood transfusion. Surgical drains were removed between the first and the sixth-eight postoperative day. CONCLUSION: According to the authors Tacho-sil® is helpful to improve hemostasis and biliary leakage in patients undergoing radiofrequency assisted minor hepatic resection.


Subject(s)
Catheter Ablation , Fibrinogen , Hemostatic Techniques , Hepatectomy/methods , Liver Diseases/surgery , Surgical Sponges , Thrombin , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Drug Combinations , Female , Humans , Male , Middle Aged
4.
Aliment Pharmacol Ther ; 28(1): 62-75, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18373636

ABSTRACT

BACKGROUND: A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately. AIM: To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC. METHODS: We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model. RESULTS: One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among treated patients, albumin, bilirubin and performance status were the only independent variables significantly associated with survival. Mortality was independently predicted by bilirubin, alpha-fetoprotein and portal vein thrombosis in untreated patients. CLIP achieved the best discriminative capacity in the entire HCC cohort and in the advanced untreatable cases, while BCLC was the ablest in predicting survival in treated patients. CONCLUSIONS: Overall predictive ability of BCLC, CLIP and GRETCH staging systems was not satisfactory, and was not uniform for treated patients and untreated patients. None of the scoring systems provided confident prediction of survival in individual patients.


Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Cirrhosis/mortality , Liver Neoplasms/pathology , Neoplasm Staging/methods , Aged , Carcinoma, Hepatocellular/mortality , Diagnostic Imaging/instrumentation , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging/standards , Prognosis , Sensitivity and Specificity , Survival Rate/trends
5.
Dig Liver Dis ; 40(8): 684-9, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18294940

ABSTRACT

BACKGROUND: Neoplastic seeding of hepatocellular carcinoma may arise after radiofrequency ablation. AIMS: In order to clarify the real risk of seeding, we observed a prospective cohort of patients undergoing radiofrequency ablation. METHODS: Ninety-three (22.9%) out of 406 consecutive patients with hepatocellular carcinoma superimposed to cirrhosis diagnosed at our Liver Unit (2000-2005) were selected for radiofrequency ablation according to the Barcelona 2000 EASL guidelines. Seventy-one patients were treated by a percutaneous approach and 22 at laparotomy. After radiofrequency ablation ultrasound scan was repeated every 3 months and spiral-computed tomography every 6 months. RESULTS: Overall 145 sessions were performed in 93 patients: 113 (77.9%) by a percutaneous approach and 32 (22.1%) at laparotomy. The median follow-up was 23 months (range 1-60). Only 1 of the 71 patients (1.4%; 95% C.I. 0.25-7.56) treated percutaneously and none of the 22 (0%; 95% C.I. 0-14.8) treated at laparotomy showed neoplastic seeding. CONCLUSION: In our experience the risk of seeding of hepatocellular carcinoma after radiofrequency ablation was small (1.1% per patient, 95% C.I. 0.19-5.84; 0.7% per procedure, 95% C.I. 0.12-3.80). A stringent selection of patients for radiofrequency ablation and retraction of the needle with a hot tip may have been instrumental in obtaining this low frequency.


Subject(s)
Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/therapy , Catheter Ablation/adverse effects , Liver Cirrhosis/complications , Liver Neoplasms/complications , Liver Neoplasms/therapy , Neoplasm Seeding , Aged , Carcinoma, Hepatocellular/pathology , Catheter Ablation/methods , Clinical Protocols , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Prospective Studies , Treatment Outcome
6.
Ann Oncol ; 18 Suppl 6: vi136-40, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17591808

ABSTRACT

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that are believed to originate from a neoplastic transformation of the intestinal pacemaker cells (interstitial cells of Cajal) normally found in the bowel wall or their precursors. Although the microscopic features have been known for a long time, the defining characteristic of GIST is the presence of the cell-surface antigen CD117 (KIT), which is demonstrated by immunohistochemistry. KIT, which is a growth factor transmembrane receptor, is the product of the proto-oncogene c-kit (chromosome 4). Surgical removal remains the only curative treatment for patients with GISTs. Tumor size, mitotic index, anatomic location, tumor rupture and disease-free interval are the classic characteristics used to predict the clinical course of patients who undergo complete gross resection. Most GISTs express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. Imatinib mesylate is a rationally designed, molecularly specific oral anticancer agent that selectively inhibits several protein tyrosine kinases central to the pathogenesis of human cancer and which has demonstrated remarkable clinical efficacy in patients with chronic myeloid leukemia and malignant GISTs. More recently Sunitinib, a new KIT/PDGFRA kinase inhibitor, has been tested in patients with GIST resistant to imatinib, with promising results.


Subject(s)
Gastrointestinal Stromal Tumors/chemistry , Gastrointestinal Stromal Tumors/pathology , Drug Resistance, Neoplasm/genetics , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/drug therapy , Humans , Proto-Oncogene Mas
7.
Ann Oncol ; 17 Suppl 7: vii137-41, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16760277

ABSTRACT

BACKGROUND: Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. PATIENTS AND METHODS: The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of 33 SG tumor patients and in a consecutive series of 66 sporadic CRC patients. RESULTS: Hypermethylation was observed in 9% of the LSCC cases, in all cases of SG cancer and in 21% of the CRC cases. No significant association was observed between p16 hypermethylation and clinicopathological variables in all the tissue samples analyzed. Moreover at univariate analysis p16 mutations were not independently related at disease relapse and death in LSCC and CRC. CONCLUSIONS: The results of this study suggest that the lack of p16 function could happen in advanced stage of SG tumors.


Subject(s)
Colorectal Neoplasms/genetics , DNA Methylation , Genes, p16 , Head and Neck Neoplasms/genetics , Carcinoma, Squamous Cell/genetics , Colorectal Neoplasms/pathology , Head and Neck Neoplasms/pathology , Humans , Neoplasm Staging , Promoter Regions, Genetic
8.
Minerva Gastroenterol Dietol ; 51(2): 171-8, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15990706

ABSTRACT

AIM: Radio-frequency thermal ablation (RFTA) may prolong the survival of patients with small hepatocellular carcinoma (HCC) associated with cirrhosis. The aim of this study was to evaluate efficacy and safety of RFTA. METHODS: We performed the Kaplan-Meier analysis to estimate the survival rate in 69 consecutive patients with HCC (mean age 66+/-6.5 years; 44/25 male/female; 56 Child-Pugh class A and 13 Child-Pugh class B) treated by RFTA. A single lesion was observed in 60/69 (87%), two lesions in 8/69 (11.6 %), and 3 lesions in 1/69 (1.4 %) of patients. The tumor size was = or <3 cm in 60/69 (87%). RESULTS: Twenty-two patients died during follow-up. Overall survival rates were 81%, 66%, and 46% at 1-, 2-, and 3-years, respectively. Cancer-free survival rates were 64% at 1 year, 30% at 2 years and 25% at 3 years. The 3-years rate of appearance of separate new lesions and local recurrence were 27.5% (19/69) and 26 % (18/69). CONCLUSIONS: Our study shows that patients with HCC and compensated cirrhosis may benefit from RFTA treatment, especially for tumors = or <3 cm. Nevertheless, the high rate of recurrence (both local and distant) points out the palliative role of this therapy.


Subject(s)
Carcinoma, Hepatocellular/therapy , Catheter Ablation , Hyperthermia, Induced , Liver Cirrhosis/complications , Liver Neoplasms/therapy , Aged , Cancer Care Facilities , Carcinoma, Hepatocellular/etiology , Catheter Ablation/adverse effects , Catheter Ablation/methods , Disease-Free Survival , Female , Humans , Hyperthermia, Induced/adverse effects , Italy , Liver Neoplasms/etiology , Male , Middle Aged , Prospective Studies , Survival Analysis , Treatment Outcome
9.
Ann Oncol ; 16 Suppl 4: iv50-55, 2005 May.
Article in English | MEDLINE | ID: mdl-15923430

ABSTRACT

BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% (68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% (74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13. CONCLUSION: Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.


Subject(s)
Adenocarcinoma/genetics , Colorectal Neoplasms/genetics , Mutation , Proto-Oncogene Proteins/genetics , Tumor Suppressor Protein p53/genetics , ras Proteins/genetics , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Disease Progression , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Levamisole/administration & dosage , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prospective Studies , Proto-Oncogene Proteins p21(ras)
10.
Ann Oncol ; 13(9): 1438-46, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12196370

ABSTRACT

BACKGROUND: K-ras mutations, one of the earliest events observed in colorectal carcinogenesis, are mostly found in codons 12 and 13, and less frequently in codon 61, all three of which are estimated to be critical for the biological activity of the protein. Nevertheless the prognostic significance of such mutations remains controversial. Our purpose was to assess whether any or specific K-ras mutations in primary colorectal cancer had prognostic significance and were linked to clinico-pathological parameters. PATIENTS AND METHODS: Paired tumor and normal tissue samples from a consecutive series of 160 untreated patients (median of follow up 71 months), undergoing resective surgery for primary colorectal carcinoma, were prospectively studied for K-ras mutations by PCR/single strand conformation polymorphism sequencing. RESULTS: Seventy-four of the 160 (46%) primary colorectal carcinomas presented mutations in K-ras: 54% in codon 12, 42% in codon 13 (particularly G-->A transition) and 4% in both. Codon 12 K-ras mutations were associated with mucinous histotype (P <0.01), while codon 13 K-ras mutations were associated with advanced Dukes' stage (P <0.05), lymph-node metastasis (P <0.05) and high S-phase fraction (P <0.05). Multivariate analysis showed that codon 13 K-ras mutations, but not any mutation, were independently related to risk of relapse or death. CONCLUSIONS: Our results suggest that codon 12 K-ras mutations may have a role in the mucinous differentiation pathway, while codon 13 mutations have biological relevance in terms of colorectal cancer clinical outcome.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA, Neoplasm/analysis , Genes, ras/genetics , Mutation , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Aged , Analysis of Variance , Biopsy, Needle , Codon , Colorectal Neoplasms/surgery , Culture Techniques , Female , Flow Cytometry , Genetic Markers , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Polymerase Chain Reaction/methods , Predictive Value of Tests , Probability , Prognosis , Proportional Hazards Models , Prospective Studies , Sensitivity and Specificity
11.
Eur Rev Med Pharmacol Sci ; 6(2-3): 55-9, 2002.
Article in English | MEDLINE | ID: mdl-12708611

ABSTRACT

States of hyperinsulinemia with insulin resistance are frequently associated with proliferative tissue abnormalities, via stimulation of DNA synthesis and cell proliferation through the IGF-1 receptor. Such elements of metabolic syndrome (hyperinsulinemia/insulin-resistance, obesity, type 2 diabetes mellitus, hypertension, dyslipidemia) are explored in a population of 125 women (n. 50 with histologically confirmed diagnosis of breast cancer, Group A; n. 50 with benign breast pathology, Group B; n. 25 with no breast pathology, Group C, controls), affering to a Center for the prevention of breast cancer, in order to investigate for an eventual relationship between these pathologies. The prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia, was higher in group of women affected by breast cancer vs. benign breast pathology and controls. This finding is in agreement with the hypothesis of the interrelationship of hyperinsulinism/insulin resistance with the growth-related abnormalities of breast cancer.


Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/metabolism , Adult , Blood Pressure , Body Composition/physiology , Body Mass Index , Breast Neoplasms/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Hypertension/complications , Hypertension/epidemiology , Lipids/blood , Middle Aged , Risk Assessment
12.
Lung Cancer ; 34 Suppl 4: S31-5, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11742700

ABSTRACT

To evaluate the efficacy and toxicity of weekly docetaxel (D) as II line treatment in non-small cell lung cancer (NSCLC), in November 1999, we started a phase II study on advanced (stages IIIB-IV) NSCLC patients pre-treated with at least one platinum-based chemotherapy regimen with or without radiotherapy. The schedule consisted of D 40 mg/m(2), weekly for 6 weeks, followed by a rest period of 2 weeks, for three cycles or until progression. Eligibility criteria were: histopathologic diagnosis of NSCLC; age

Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Paclitaxel/analogs & derivatives , Paclitaxel/therapeutic use , Taxoids , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Docetaxel , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Quality of Life
13.
Clin Pharmacokinet ; 40(6): 473-83, 2001.
Article in English | MEDLINE | ID: mdl-11475470

ABSTRACT

OBJECTIVE: To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease. PATIENTS AND PARTICIPANTS: 58 consecutive patients (19 women and 39 men), aged 16 to 64 years (mean age 38 years), with a diagnosis of ulcerative colitis (29 patients) or Crohn's disease (29 patients). METHODS: Patients were treated with oral doses of cyclosporin microemulsion ranging from 200 to 400 mg daily. Blood samples were collected after 7 days of treatment; blood was drawn at 0, 0.5, 1, 2, 3, 5, 7 and 12 hours after the morning dose. In 23 patients out of 29 with ulcerative colitis and 23 out of 29 with Crohn's disease, these profiles were repeated immediately before hospital discharge, which took place an average of 18 days after admission. Blood specimens were assayed for cyclosporin immunoreactivity on the day of blood withdrawal by a radioimmunoassay technique. MAIN OUTCOME MEASURES AND RESULTS: In the range of doses employed, the average peak plasma drug concentration (Cmax) and area under the concentration-time curve to 12 hours tended to increase linearly with the dose (from 782.35 to 1,607.98 microg/L and from 3,612 to 7,221 microg x h/L for doses of 200 mg and 400 mg, respectively), whereas the time to Cmax (tmax) and elimination half-life (t 1/2beta) ranged between 78 and 95.2 min and 85.5 and 162 min, respectively, and did not appear to change with the dose. After dose-normalisation by transformation of data into percentage increase over baseline (trough) concentration for each patient, single kinetic parameters for the whole study population (n = 58) could be calculated (Cmax 620% vs baseline. tmax 86.5 min, t 1/2 115 min). Comparison between patients with Crohn's disease and ulcerative colitis showed that the latter had higher Cmax values (702% compared with 543% vs baseline, p < 0.05) whereas tmax and t 1/2beta values overlapped. CONCLUSIONS: The pharmacokinetic parameters of cyclosporin microemulsion in patients with inflammatory bowel disease are broadly similar to those previously measured in healthy volunteers and in other disorders requiring cyclosporin treatment.


Subject(s)
Cyclosporine/pharmacokinetics , Immunosuppressive Agents/pharmacokinetics , Inflammatory Bowel Diseases/metabolism , Adolescent , Adult , Analysis of Variance , Area Under Curve , Colitis, Ulcerative/blood , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Crohn Disease/blood , Crohn Disease/drug therapy , Crohn Disease/metabolism , Cyclosporine/blood , Cyclosporine/therapeutic use , Dose-Response Relationship, Drug , Emulsions , Female , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/blood , Inflammatory Bowel Diseases/drug therapy , Male , Middle Aged
14.
Cancer ; 92(2): 294-302, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11466682

ABSTRACT

BACKGROUND: The prognostic value of DNA ploidy, S-phase fraction (SPF) and K-ras-2 mutations in gastric carcinoma (GC) has not yet been clearly defined. The aim of this study was to clarify the association between biomolecular variables, tumor characteristics, and clinical outcome in GC patients. METHODS: Resected specimens from a consecutive series of 69 patients with GC who underwent potentially curative surgery were studied prospectively. DNA ploidy and SPF were assessed by flow cytometry on multiple frozen tumor samples, whereas K-ras-2 mutations were detected by polymerase chain reaction followed by single-strand conformation polymorphism. All the patients involved in this study were followed up for a mean of 95 months. RESULTS: DNA aneuploidy was present in 72% of the cases (50 of 69), whereas 10% of these (5 out of 50) showed multiclonality. Mutations of K-ras-2 were detected in 8% of the tumors (5 of 63). Both DNA ploidy and SPF were associated with TNM stage (American Joint Committee on Cancer [AJCC] staging system) and node status. Moreover, DNA aneuploidy was significantly related to high SPF. K-ras-2 mutations were not associated with clinicopathologic variables or flow cytometric indicators. At univariate analysis, advanced TNM stage, node involvement, diffuse histotype, depth of invasion, DNA aneuploidy, and high SPF proved to be significantly related to quicker tumor relapse and to shorter overall patient survival. With multivariate analysis, DNA aneuploidy, high SPF, and depth of invasion were related to risk of tumor relapse and patient death, whereas diffuse histotype was independently related to patient risk of tumor relapse. CONCLUSIONS: DNA ploidy and SPF, when associated with clinicopathologic staging, might be useful for the identification of GC patients who have different risks for death or relapse of disease.


Subject(s)
Aneuploidy , Carcinoma/genetics , DNA, Neoplasm/analysis , Genes, ras/genetics , S Phase , Stomach Neoplasms/genetics , Adult , Aged , Biomarkers, Tumor , Carcinoma/pathology , Carcinoma/surgery , Female , Flow Cytometry , Gastrectomy , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Factors , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Survival Analysis
15.
Clin Cancer Res ; 6(1): 178-84, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10656448

ABSTRACT

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aspartic Acid Endopeptidases/analysis , Cysteine Endopeptidases/metabolism , Ploidies , Serine Endopeptidases/analysis , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Adenocarcinoma/enzymology , Adenocarcinoma/mortality , Adult , Aged , Biomarkers, Tumor/analysis , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Predictive Value of Tests , Probability , Prognosis , S Phase , Stomach Neoplasms/enzymology , Stomach Neoplasms/mortality , Survival Analysis , Time Factors
16.
Anticancer Res ; 20(6C): 4841-51, 2000.
Article in English | MEDLINE | ID: mdl-11205230

ABSTRACT

This review focuses on the functional role and structural features of the genes involved in common hereditary cancers. Most of these tumors are sporadic and the genetic alterations responsible for their genesis take place over several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family history that includes at least three generation pedigrees, an appropriate cancer risk assessment and an effective genetic counseling). At present, the most useful methods of risk assessment are those performed on the following genes: BRCA1 and BRCA2 especially for hereditary breast and ovarian cancer, hMLH1 and hMSH2 for hereditary non polyposis colorectal cancer, APC for familial adenomatous polyposis, ret for medullary thyroid carcinoma, p53 for the Li-Fraumeni syndrome, p16 for melanoma and RB1 for retinoblastoma. In conclusion, the development of new diagnostic tests will permit a more accurate assessment of risk in individuals who have not so far shown any sign or symptom of the disease.


Subject(s)
Genetic Predisposition to Disease , Models, Genetic , Neoplasms/genetics , Animals , Biomarkers, Tumor/genetics , Female , Genes, Tumor Suppressor , Humans , Male , Pedigree , Risk Assessment
17.
Minerva Chir ; 54(4): 239-44, 1999 Apr.
Article in Italian | MEDLINE | ID: mdl-10380522

ABSTRACT

BACKGROUND AND AIMS: The increasingly frequent use of mammography for the early diagnosis of breast cancer and the consequent identification of mammary lesions at a preclinical stage raises the fundamental problem of the differential diagnosis between non-suspected non-palpable lesions (NPL) which can therefore be monitored over time and suspected NPL or definite carcinoma requiring histological confirmation and surgical biopsy. The diagnostic accuracy of mammography alone is not sufficiently high to differentiate benign lesions from malignant or strongly suspected ones. The use of surgical biopsy in the event of suspected NPL could be significantly reduced by the use of stereotaxic cytology which would improve the diagnostic accuracy of mammography. METHODS: The study refers to 72 suspected NPL undergoing surgical biopsy after having performed stereotaxic cytology on a sample taken with a dedicated mammographic device (Mammotest-TRC). RESULTS: The rate of inadequate samples for correct cytological evaluation was 16.1%. Of the 72 NPL undergoing surgical biopsy, 40 (55.5%) were found to be carcinomas and 32 (44.5%) were benign lesions. The sensitivities of mammography alone and cytology alone in identifying infraclinical breast carcinoma were respectively 0.85 and 0.95. If the results of the two methods were evaluated together, the level of sensitivity was 0.98. CONCLUSIONS: The use of stereotaxic cytology enables a marked improvement to be achieved in the diagnostic accuracy of mammography for the identification of suspected NPL to undergo surgical biopsy, notably reducing the cost of biopsy (number of benign lesions for each carcinoma diagnosed) and consequent discomfort for patients.


Subject(s)
Breast Diseases/diagnosis , Palpation , Aged , Biopsy , Breast Neoplasms/diagnosis , Carcinoma/diagnosis , Cytodiagnosis/methods , Cytodiagnosis/statistics & numerical data , Diagnosis, Differential , Female , Humans , Mammography , Middle Aged
18.
Br J Rheumatol ; 37(2): 208-10, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9569078

ABSTRACT

The occurrence and clinical value of anticardiolipin antibodies (aCL) were studied in 33 patients with giant cell arteritis (GCA) and in seven patients with polymyalgia rheumatica (PMR), at onset and during follow-up. aCL were present in 19/40 (47.5%) GCA/PMR cases, most of them of the IgG isotype, whereas all controls (21 subjects) were aCL negative. The presence of aCL was not associated with inflammatory parameters or clinical signs of arteritis; however, they disappeared in a significant percentage (56%) of patients during steroid therapy. No correlation was found between ischaemic events and aCL, suggesting that they are not important for the development of vascular complications in GCA/PMR patients. Moreover, a retrospective evaluation of our data showed a correlation between aCL positivity and anaemia, whose significance remains to be elucidated.


Subject(s)
Antibodies, Anticardiolipin/analysis , Giant Cell Arteritis/immunology , Polymyalgia Rheumatica/immunology , Adult , Aged , Aged, 80 and over , Female , Humans , Immunoglobulin G/analysis , Immunoglobulin Isotypes/analysis , Male , Middle Aged
19.
Br J Rheumatol ; 36(1): 124-5, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9117152

ABSTRACT

The actiopathogenesis of leucocytoclastic vasculitis is still unknown, but recently hepatitis C virus (HCV) has been suggested as trigger of autoimmunity. We report a case of a 26-yr-old patient with purpura due to leucocytoclastic vasculitis associated with hepatitis C virus infection. Laboratory findings showed AST, ALT, gamma GT within normal limits, positive antibodies to HCV (IIF and Riba II) and polymerase chain reaction for HCV RNA. Anti-nuclear antibodies, IgG and IgM anti-cardiolipin antibodies, anti-platelet antibodies and anti-neutrophil cytoplasmic antibodies with perinuclear pattern were also present. A skin biopsy specimen of a purpuric lesion showed leucocytoclastic vasculitis with small vessel thrombosis and perivascular deposition of IgM and fibrinogen on immunofluorescence study. This case shows a role of HCV in leucocytoclastic vasculitis; it is possible that this HCV can induce autoimmunity independently of cryoglobulins and liver involvement.


Subject(s)
Antibodies, Viral/blood , Hepacivirus/immunology , Hepatitis C/immunology , Vasculitis, Leukocytoclastic, Cutaneous/etiology , Vasculitis, Leukocytoclastic, Cutaneous/virology , Adult , Autoantibodies/blood , Cryoglobulinemia/complications , Cryoglobulinemia/immunology , Female , Hepatitis C/complications , Humans , Immunoglobulin G/blood
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