68 results on '"Nitti, D."'
Search Results
2. Extent of lymph node dissection for adenocarcinoma of the stomach.
- Author
-
Mocellin S, McCulloch P, Kazi H, Gama-Rodrigues JJ, Yuan Y, and Nitti D
- Subjects
- Gastrectomy methods, Humans, Lymph Node Excision methods, Randomized Controlled Trials as Topic, Survival Rate, Adenocarcinoma surgery, Gastrectomy mortality, Lymph Node Excision mortality, Stomach Neoplasms surgery
- Abstract
Background: The impact of lymphadenectomy extent on the survival of patients with primary resectable gastric carcinoma is debated., Objectives: We aimed to systematically review and meta-analyze the evidence on the impact of the three main types of progressively more extended lymph node dissection (that is, D1, D2 and D3 lymphadenectomy) on the clinical outcome of patients with primary resectable carcinoma of the stomach. The primary objective was to assess the impact of lymphadenectomy extent on survival (overall survival [OS], disease specific survival [DSS] and disease free survival [DFS]). The secondary aim was to assess the impact of lymphadenectomy on post-operative mortality., Search Methods: We searched CENTRAL, MEDLINE and EMBASE until 2001, including references from relevant articles and conference proceedings. We also contacted known researchers in the field. For the updated review, CENTRAL, MEDLINE and EMBASE were searched from 2001 to February 2015., Selection Criteria: We considered randomized controlled trials (RCTs) comparing the three main types of lymph node dissection (i.e., D1, D2 and D3 lymphadenectomy) in patients with primary non-metastatic resectable carcinoma of the stomach., Data Collection and Analysis: Two authors independently extracted data from the included studies. Hazard ratios (HR) and relative risks (RR) along with their 95% confidence intervals (CI) were used to measure differences in survival and mortality rates between trial arms, respectively. Potential sources of between-study heterogeneity were investigated by means of subgroup and sensitivity analyses. The same two authors independently assessed the risk of bias of eligible studies according to the standards of the Cochrane Collaboration and the quality of the overall evidence based on the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria., Main Results: Eight RCTs (enrolling 2515 patients) met the inclusion criteria. Three RCTs (all performed in Asian countries) compared D3 with D2 lymphadenectomy: data suggested no significant difference in OS between these two types of lymph node dissection (HR 0.99, 95% CI 0.81 to 1.21), with no significant difference in postoperative mortality (RR 1.67, 95% CI 0.41 to 6.73). Data for DFS were available only from one trial and for no trial were DSS data available. Five RCTs (n = 3 European; n = 2 Asian) compared D2 to D1 lymphadenectomy: OS (n = 5; HR 0.91, 95% CI 0.71 to 1.17) and DFS (n=3; HR 0.95, 95% CI 0.84 to 1.07) findings suggested no significant difference between these two types of lymph node dissection. In contrast, D2 lymphadenectomy was associated with a significantly better DSS compared to D1 lymphadenectomy (HR 0.81, 95% CI 0.71 to 0.92), the quality of the body of evidence being moderate; however, D2 lymphadenectomy was also associated with a higher postoperative mortality rate (RR 2.02, 95% CI 1.34 to 3.04)., Authors' Conclusions: D2 lymphadenectomy can improve DSS in patients with resectable carcinoma of the stomach, although the increased incidence of postoperative mortality reduces its therapeutic benefit.
- Published
- 2015
- Full Text
- View/download PDF
3. Genetic variation and gastric cancer risk: a field synopsis and meta-analysis.
- Author
-
Mocellin S, Verdi D, Pooley KA, and Nitti D
- Subjects
- Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Neoplasm Proteins metabolism, Risk Factors, Stomach Neoplasms metabolism, Genetic Variation, Neoplasm Proteins genetics, Polymorphism, Genetic, Stomach Neoplasms genetics
- Abstract
Background: Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available., Methods: We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and Helicobacter pylori infection status (positive vs negative)., Results: Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analyses on 156 variants involving 101 genes. We identified 11 variants significantly associated with disease risk and assessed to have a high level of summary evidence: MUC1 rs2070803 at 1q22 (diffuse carcinoma subgroup), MTX1 rs2075570 at 1q22 (diffuse), PSCA rs2294008 at 8q24.2 (non-cardia), PRKAA1 rs13361707 5p13 (non-cardia), PLCE1 rs2274223 10q23 (cardia), TGFBR2 rs3087465 3p22 (Asian), PKLR rs3762272 1q22 (diffuse), PSCA rs2976392 (intestinal), GSTP1 rs1695 11q13 (Asian), CASP8 rs3834129 2q33 (mixed) and TNF rs1799724 6p21.3 (mixed), with the first nine variants characterised by a low FPRP. We also identified polymorphisms with lower quality significant associations (n=110)., Conclusions: We have identified several high-quality biomarkers of gastric cancer susceptibility. These data will form the backbone of an annually updated online resource that will be integral to the study of gastric carcinoma genetics and may inform future screening programmes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
- Published
- 2015
- Full Text
- View/download PDF
4. Lymphadenectomy extent and survival of patients with gastric carcinoma: a systematic review and meta-analysis of time-to-event data from randomized trials.
- Author
-
Mocellin S and Nitti D
- Subjects
- Adenocarcinoma mortality, Humans, Lymphatic Metastasis, Randomized Controlled Trials as Topic, Stomach Neoplasms mortality, Adenocarcinoma pathology, Adenocarcinoma surgery, Lymph Node Excision methods, Stomach Neoplasms pathology, Stomach Neoplasms surgery
- Abstract
Background: The extent of lymph node dissection in patients with resectable non-metastatic primary carcinoma of the stomach is still a controversial matter of debate, with special regard to its effect on survival., Materials and Methods: We conducted a systematic review and meta-analysis of time-to-event data from randomized controlled trials (RCTs) comparing the three main types of lymphadenectomy (D1, D2, and D3) for gastric cancer. Hazard ratio (HR) was considered the effect measure for both overall (OS), disease-specific (DSS) and disease-free survival (DFS). The quality of the available evidence was assessed using the GRADE system., Results: Eight RCTs enrolling 2515 patients were eligible. The meta-analysis of four RCTs (n=1599) showed a significant impact of D2 versus D1 lymphadenectomy on DSS (summary HR=0.807, CI: 0.705-0.924, P=0.002), the corresponding number-to-treat being equal to ten. This effect remained clinically valuable even after adjustment for postoperative mortality. However, the quality of evidence was graded as moderate due to inconsistency issues. When OS and DFS were considered, the meta-analysis of respectively five (n=1653) and three RCTs (n=1332) found no significant difference between D2 and D1 lymph node dissection (summary HR=0.911, CI: 0.708-1.172, P=0.471, and summary HR=0.946, CI: 0.840-1.066, P=0.366, respectively). However, at subgroup analysis D2 type resulted superior to D1 type lymphadenectomy in terms of OS considering the two RCTs carried out in Eastern countries (summary HR=0.627, CI: 0.396-0.994, P=0.047). As regards the D3 vs D2 comparison, the meta-analysis of the three available RCTs (n=862) showed no significant impact of more extended lymphadenectomy on OS (summary HR=0.990, CI: 0.814-1.205, P=0.924)., Conclusions: Our findings support the superiority of D2 versus D1 lymphadenectomy in terms of survival benefit. However, this advantage is mainly limited to DSS, the level of evidence is moderate, and the interaction with other factors affecting patient survival (such as complementary medical therapy) remains to be elucidated., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
5. HER2 status in gastroesophageal cancer: a tissue microarray study of 1040 cases.
- Author
-
Cappellesso R, Fassan M, Hanspeter E, Bornschein J, d'Amore ES, Cuorvo LV, Mazzoleni G, Barbareschi M, Pizzi M, Guzzardo V, Malfertheiner P, Micev M, Guido M, Giacomelli L, Tsukanov VV, Zagonel V, Nitti D, and Rugge M
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Female, Gene Amplification, Humans, Immunohistochemistry methods, In Situ Hybridization methods, Male, Middle Aged, Receptor, ErbB-2 genetics, Stomach Neoplasms pathology, Tissue Array Analysis methods, Biomarkers, Tumor analysis, Esophageal Neoplasms metabolism, Receptor, ErbB-2 metabolism, Stomach Neoplasms genetics
- Abstract
Among patients with gastric cancer (GC) and gastroesophageal cancer (G-EC), HER2 amplification identifies those who may benefit from trastuzumab. HER2 status assessment, however, is influenced by preanalytic, analytic, and postanalytic variables. In a series of 5426 microarray cancer tissue cores obtained from 1040 GC/G-ECs (824 GC, 216 G-EC) and 720 synchronous nodal metastases, we evaluated both the performances of 2 different immunohistochemistry (IHC) protocols and the HER2 status intratumor variability. The prevalence of HER2 amplification and protein overexpression were assessed by chromogenic in situ hybridization and by 2 IHC protocols (CB11 and 4B5). HER2 was amplified in 114 (11%) of 1040 cases; in 6 (5.3%) of 114 cases, gene amplification only involved nodal metastasis. HER2 amplification prevailed in intestinal-type (P = .001) and low-grade (P < .001) tumors, showing no correlation with patients' age/sex, tumor location, stage, and Ming histotype. Overall, 12.5% and 13.7% of cases IHC scored 2+/3+ using the CB11-IHC and the 4B5-IHC protocol, respectively. HER2 amplification was not associated with protein overexpression (score 0/1+) in 11.4% and 6.2% of cases using the CB11-IHC and the 4B5-IHC protocol, respectively. The 4B5-IHC protocol proved more sensitive than CB11-IHC (93.9% versus 88.6%) and just as specific (96.1% versus 96.9%). Tested by chromogenic in situ hybridization, intratumor HER2 status was "substantially" consistent in different tissue cores obtained from the same case (κ = 0.78). Similar results were obtained for HER2 protein expression (CB11-IHC, κ = 0.78, and 4B5-IHC, κ = 0.83). Immunohistochemistry testing, however, fails in identifying about 10% of HER2-amplified cancers, potentially excluding these patients from anti-HER2 therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
6. Gastric cancer and synchronous hepatic metastases: is it possible to recognize candidates to R0 resection?
- Author
-
Tiberio GA, Baiocchi GL, Morgagni P, Marrelli D, Marchet A, Cipollari C, Graziosi L, Ministrini S, Vittimberga G, Donini A, Nitti D, Roviello F, Coniglio A, and de Manzoni G
- Subjects
- Aged, Chemotherapy, Adjuvant, Female, Gastrectomy, Hepatectomy, Humans, Liver Neoplasms secondary, Liver Neoplasms therapy, Male, Neoplasms, Multiple Primary secondary, Neoplasms, Multiple Primary therapy, Palliative Care, Prognosis, Retrospective Studies, Stomach Neoplasms pathology, Survival Analysis, Liver Neoplasms surgery, Neoplasms, Multiple Primary surgery, Stomach Neoplasms surgery
- Abstract
Purpose: Management of patients with synchronous hepatic metastases as the sole metastatic site at diagnosis of gastric cancer is debated. We studied a cohort of patients admitted to surgical units, investigating prognostic factors of clinical relevance and the results of various therapeutic strategies., Methods: Retrospective multicentre chart review. We evaluated how survival from surgery was influenced by patient-related, gastric cancer-related, metastasis-related and treatment-related candidate prognostic factors., Results: Forty-four patients received palliative surgery without resection, 98 palliative gastrectomy (in 16 cases associated with R+ hepatectomy), whereas 53 patients received both curative gastrectomy and hepatic resection(s) (R0). Adjuvant chemotherapy was administered to 44 patients. Therapeutic approach was selected on the basis of extension of disease, patient's general conditions and surgeon's attitude. Surgical mortality was 4.6 % and morbidity was 17.4 %. Survival was independently influenced by the factor T of the gastric primary (p = 0.036) and by the degree of hepatic involvement (p = 0.010). T > 2 and H3 liver involvement were associated with worse prognosis with cumulative effect (p = 0.002). Therapeutic approach to the metastases (p = 0.009) and adjuvant chemotherapy (p < 0.001) displayed independent impact upon survival, with benefit for those receiving aggressive multimodal treatment. The 1-, 3-, and 5-year survival rates were 50.4, 14.0, and 9.3 %, respectively, for patients submitted to curative surgery, 16, 8.5, and 4.3 % after palliative gastrectomy, and 6.8, 2.3, and 0 % after palliative surgery without resection., Conclusions: Our data suggest some clinical criteria that may facilitate selection of candidates to curative surgery, which offers the best survival chances, especially when associated with adjuvant chemotherapy.
- Published
- 2015
- Full Text
- View/download PDF
7. Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer.
- Author
-
Bajetta E, Floriani I, Di Bartolomeo M, Labianca R, Falcone A, Di Costanzo F, Comella G, Amadori D, Pinto C, Carlomagno C, Nitti D, Daniele B, Mini E, Poli D, Santoro A, Mosconi S, Casaretti R, Boni C, Pinotti G, Bidoli P, Landi L, Rosati G, Ravaioli A, Cantore M, Di Fabio F, Aitini E, and Marchet A
- Subjects
- Camptothecin administration & dosage, Chemotherapy, Adjuvant, Cisplatin administration & dosage, Combined Modality Therapy, Docetaxel, Fluorouracil administration & dosage, Humans, Leucovorin administration & dosage, Stomach Neoplasms surgery, Taxoids administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Camptothecin analogs & derivatives, Stomach Neoplasms drug therapy
- Abstract
Background: Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer., Patients and Methods: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm)., Results: From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively., Conclusions: A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01640782., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2014
- Full Text
- View/download PDF
8. Follow-up after gastrectomy for cancer: an appraisal of the Italian research group for gastric cancer.
- Author
-
Baiocchi GL, Marrelli D, Verlato G, Morgagni P, Giacopuzzi S, Coniglio A, Marchet A, Rosa F, Capponi MG, Di Leo A, Saragoni L, Ansaloni L, Pacelli F, Nitti D, D'Ugo D, Roviello F, Tiberio GA, Giulini SM, and De Manzoni G
- Subjects
- Adult, Aged, Aged, 80 and over, Endoscopy, Gastrointestinal, Female, Fluorodeoxyglucose F18, Follow-Up Studies, Humans, Italy, Liver Neoplasms secondary, Lung Neoplasms secondary, Lymphatic Metastasis, Male, Middle Aged, Peritoneal Neoplasms secondary, Physical Examination, Positron-Emission Tomography, Radiopharmaceuticals, Retrospective Studies, Stomach, Survival Rate, Time Factors, Tomography, X-Ray Computed, Ultrasonography, Gastrectomy, Liver Neoplasms diagnosis, Lung Neoplasms diagnosis, Lymph Node Excision, Neoplasm Recurrence, Local diagnosis, Peritoneal Neoplasms diagnosis, Stomach Neoplasms surgery
- Abstract
Background: The Italian Research Group for Gastric Cancer supports the practice of follow-up after radical surgery for gastric cancer., Methods: This multicenter, retrospective study (1998-2009) included patients with T1-4N0-3M0 gastric cancer who had undergone D2 gastrectomy and lymphadenectomy, with at least 15 lymph nodes examined, and who had developed recurrent disease. Timing and site of recurrence were correlated to the actual scheduled follow-up timing and modalities., Results: From eight centers, 814 patients with recurrent cancer and over 1,754 (46.4 %) patients undergoing gastrectomy were investigated (median follow-up 31 months). The most frequent sites of recurrence were local/regional lymph nodes (35.4 %), liver (24.3 %), peritoneum (30.3 %), lung (10.4 %) and intraluminal (7.5 %). Ninety-four percent of the recurrences were diagnosed within 2 years and 98 % within 3 years. Thoracoabdominal computed tomography (CT) scan and (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18-FDG-PET) detected more than 90 % of recurrences, abdominal ultrasound detected 70 % and tumor markers detected 40 %, while <10 % were identified by physical examination, chest X-ray, and upper gastrointestinal endoscopy. Twenty-six percent of patients with recurrence were treated, but only 3.2 % were treated with potentially radical intent., Conclusion: Oncological follow-up after radical surgery for gastric cancer should be focused in the first 3 years, and based mainly on thoracoabdominal CT scan and 18-FDG-PET.
- Published
- 2014
- Full Text
- View/download PDF
9. The SIC-GIRCG 2013 Consensus Conference on Gastric Cancer.
- Author
-
De Manzoni G, Baiocchi GL, Framarini M, De Giuli M, D'Ugo D, Marchet A, Nitti D, Marrelli D, Morgagni P, Rinnovati A, Rosati R, Roviello F, Allieta R, Berti S, Bracale U, Capelli P, Cavicchi A, Di Martino N, Donini A, Filippini A, Francioni G, Frascio M, Garofalo A, Giulini SM, Grassi GB, Innocenti P, Martino A, Mazzocconi G, Mazzola L, Montemurro S, Palasciano N, Pantuso G, Pernthaler H, Petri R, Piazza D, Sacco R, Sgroi G, Staudacher C, Testa M, Vallicelli C, Vettoretto N, Zingaretti C, Capussotti L, Morino M, and Verdecchia GM
- Subjects
- Delphi Technique, Endosonography, Female, Humans, Italy, Lymph Node Excision, Male, Neoplasm Staging, Societies, Medical, Stomach Neoplasms diagnosis, Stomach Neoplasms pathology, Stomach Neoplasms surgery, Stomach Neoplasms therapy
- Abstract
The topic chosen by the Board of the Italian Society of Surgery for the 2013 annual Consensus Conference was gastric cancer. With this purpose, under the direction of 2 chairmen, 36 experts nominated by the Regional Societies of Surgery and by the Italian Research Group for Gastric Cancer (GIRCG) participated in an experts consensus exercise, preceded by a questionnaire and mainly held by telematic vote, in accordance with the rules of the Delphi method. The results of this Consensus Conference, presented to the 115th National Congress of the Italian Society of Surgery, and approved in plenary session, are reported in the present paper.
- Published
- 2014
- Full Text
- View/download PDF
10. The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis.
- Author
-
Fassan M, Pizzi M, Realdon S, Balistreri M, Guzzardo V, Zagonel V, Castoro C, Mastracci L, Farinati F, Nitti D, Zaninotto G, and Rugge M
- Subjects
- Adenocarcinoma metabolism, Adenocarcinoma pathology, Aged, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Cell Dedifferentiation genetics, Cell Line, Tumor, Esophageal Neoplasms metabolism, Esophageal Neoplasms pathology, Gene Expression Regulation, Neoplastic, Humans, Male, MicroRNAs metabolism, Receptor, ErbB-2 metabolism, Retrospective Studies, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Adenocarcinoma genetics, Esophageal Neoplasms genetics, MicroRNAs genetics, Receptor, ErbB-2 genetics, Stomach Neoplasms genetics
- Abstract
A subset of gastric (intestinal-type) and esophageal (Barrett) adenocarcinoma features HER2 protein overexpression. Consistent evidence demonstrates that microRNAs have a major role in HER2 (dys)regulation. MiR-125a-5p and miR125b expressions were tested in the spectrum of lesions in the gastroesophageal carcinogenic cascade, also correlating miR-125a-5p/125b levels with HER2 status. MiR-125a-5p and miR-125b expression (quantitative reverse transcriptase polymerase chain reaction [qRT-PCR]) and HER2 status (immunohistochemistry [IHC] and chromogenic in situ hybridization [CISH]) were assessed in a series of 90 biopsy samples spanning the whole histologic spectrum of gastric and esophageal carcinogenesis. To support the obtained results, the qRT-PCR levels of microRNAs and their expression (in situ hybridization) were tested in an adjunctive series of gastric and esophageal adenocarcinoma, including (IHC/CISH validated) HER2-negative and HER2-positive cases. Both miR-125a-5p and miR-125b levels were significantly down-regulated throughout the gastric and esophageal carcinogenic cascade. HER2 status (IHC and CISH) correlated inversely with miR-125 expression (qRT-PCR and in situ hybridization). Dysregulation of miR-125a-5p/125b and HER2 is an early event in the gastric (intestinal-type) and esophageal (Barrett) oncogenesis. In both oncogenetic cascades, miR-125 expression correlates inversely with HER2 status. MiR-125a-5p/125b can be considered among the therapeutic targets in HER2-positive esophageal and gastric adenocarcinoma., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
11. Precancerous lesions in the stomach: from biology to clinical patient management.
- Author
-
Rugge M, Capelle LG, Cappellesso R, Nitti D, and Kuipers EJ
- Subjects
- Gastritis, Atrophic epidemiology, Gastritis, Atrophic pathology, Gastritis, Atrophic therapy, Helicobacter Infections epidemiology, Helicobacter Infections pathology, Helicobacter Infections therapy, Helicobacter pylori pathogenicity, Humans, Precancerous Conditions epidemiology, Precancerous Conditions therapy, Stomach Neoplasms epidemiology, Stomach Neoplasms therapy, Precancerous Conditions pathology, Stomach Neoplasms pathology
- Abstract
Gastric cancer is the final step in a multi-stage cascade triggered by long-standing inflammatory conditions (particularly Helicobacter pylori infection) resulting in atrophic gastritis and intestinal metaplasia: these lesions represent the cancerization field in which (intestinal-type) gastric cancer develops. Intraepithelial neoplasia is consistently recognized as the phenotypic bridge between atrophic/metaplastic lesions and invasive cancer. This paper addresses the epidemiology, pathology, molecular profiling, and clinical management of advanced precancerous gastric lesions., (Copyright © 2013. Published by Elsevier Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
12. Multivisceral resection for locally advanced gastric cancer: an Italian multicenter observational study.
- Author
-
Pacelli F, Cusumano G, Rosa F, Marrelli D, Dicosmo M, Cipollari C, Marchet A, Scaringi S, Rausei S, di Leo A, Roviello F, de Manzoni G, Nitti D, Tonelli F, and Doglietto GB
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma pathology, Aged, Female, Gastrectomy, Humans, Italy epidemiology, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Staging, Observation, Postoperative Complications epidemiology, Prognosis, Proportional Hazards Models, Stomach Neoplasms mortality, Stomach Neoplasms pathology, Survival Rate, Treatment Outcome, Adenocarcinoma surgery, Stomach Neoplasms surgery
- Abstract
Importance: The role of multivisceral resection, in the setting of locally advanced gastric cancer, is still debated. Previous studies have reported a higher risk for perioperative morbidity and mortality, with limited objective benefit in terms of survival. Conversely, recent studies have shown the feasibility of enlarged resections and the potential advantage of extended resection for clinical stage T4b gastric adenocarcinoma with good long-term results., Objective: To analyze the role of multivisceral resection for locally advanced gastric cancer with particular attention to the brief and long-term results and to the prognostic value of clinical and pathologic factors., Design: Prospective multicenter study using data from between January 1, 1995, and December 31, 2008., Settings: Seven Italian surgery centers., Patients: A total of 2208 patients underwent curative resections for gastric carcinoma at the centers. Among them, 206 patients presented with a clinical T4b carcinoma. One hundred twelve underwent a combined resection of the adjacent organs with a gastrectomy owing to suspicion or direct invasion of these organs by the gastric cancer., Main Outcomes and Measures: Clinical and pathologic variables were prospectively collected and the feasibility and efficacy of multivisceral resection for locally advanced clinical T4b gastric cancer were assessed., Results: Postoperative mortality and complication rates of patients who underwent a gastrectomy with a combined resection of the involved organs were 3.6% and 33.9%, respectively. Pathologic factors revealed that the nodal involvement was present in about 89.3% of patients and the mean (SD) number of pathologic lymph nodes was 14.8 (16.6). The overall 5-year survival rate was 27.2%. The completeness of resection and lymph node invasion represent independent prognostic parameters at multivariate analysis., Conclusions and Relevance: Our study indicates that patients undergoing extended resections experience acceptable postoperative morbidity and mortality rates, and an en bloc multivisceral resection should be performed in patients when a complete resection can be realistically obtained and when lymph node metastasis is not evident.
- Published
- 2013
- Full Text
- View/download PDF
13. Early HER2 dysregulation in gastric and oesophageal carcinogenesis.
- Author
-
Fassan M, Mastracci L, Grillo F, Zagonel V, Bruno S, Battaglia G, Pitto F, Nitti D, Celiento T, Zaninotto G, Fiocca R, and Rugge M
- Subjects
- Adenocarcinoma etiology, Adenocarcinoma genetics, Adenocarcinoma metabolism, Adenocarcinoma pathology, Barrett Esophagus complications, Barrett Esophagus genetics, Barrett Esophagus metabolism, Barrett Esophagus pathology, Carcinoma in Situ etiology, Carcinoma in Situ genetics, Carcinoma in Situ metabolism, Carcinoma in Situ pathology, Esophageal Neoplasms etiology, Esophageal Neoplasms pathology, Esophagus metabolism, Esophagus pathology, Gastric Mucosa metabolism, Gastric Mucosa pathology, Gene Amplification, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, In Situ Hybridization, Metaplasia, Stomach Neoplasms etiology, Stomach Neoplasms pathology, Esophageal Neoplasms genetics, Esophageal Neoplasms metabolism, Genes, erbB-2, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Stomach Neoplasms genetics, Stomach Neoplasms metabolism
- Abstract
Aims: To explore human epidermal growth factor receptor 2 (HER2) status in the histological phenotypes [metaplasia, intraepithelial neoplasia (IEN, i.e. dysplasia), and adenocarcinoma] involved in the morphogenesis of both intestinal-type gastric cancer (GC) and Barrett's adenocarcinoma (BAc)., Methods and Results: A consecutive series of 275 samples of stomach and oesophagus tissue (representing the whole spectrum of the phenotypic changes involved in gastric and Barrett's carcinogenesis) was studied. HER2 status was assessed by applying two immunohistochemistry (IHC) protocols, using the antibodies 4B5 and CB11. Dual-colour silver chromogenic in-situ hybridization (SISH) was also performed on the same tissue samples. In both oesophageal and gastric samples, the rate of HER2 overexpression rose significantly from low-grade to high-grade IEN to adenocarcinoma (P < 0.001), with the two IHC protocols showing consistent staining (consistency 95%; k = 0.78; P < 0.001). Intratumour heterogeneity was documented in both GC and BAc (using both IHC protocols). The rate of HER2 amplification (using SISH) increased significantly along with IEN dedifferentiation (P < 0.001). Neither native nor metaplastic mucosa samples (obtained from either stomach or oesophagus) ever showed HER2 amplification. There was excellent agreement between HER2 amplification and protein overexpression (both IHC protocols: SISH/4B5--consistency 97.8%, k = 0.89, P < 0.001; SISH/CB11-consistency 97.8%, k = 0.91, P < 0.001)., Conclusions: There is early involvement of HER2 dysregulation (amplification and protein overexpression) in both gastric (intestinal-type) and Barrett's oncogenesis., (© 2012 Blackwell Publishing Limited.)
- Published
- 2012
- Full Text
- View/download PDF
14. MINT31 methylation in gastric noninvasive neoplasia: potential role in the secondary prevention of gastric cancer.
- Author
-
Negrini M, Miotto E, Sabbioni S, Cardin R, Rugge M, Tieppo C, Piciocchi M, Maddalo G, Nitti D, and Farinati F
- Subjects
- Aged, DNA-Binding Proteins, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Invasiveness, RNA-Binding Proteins, Stomach Neoplasms pathology, Biomarkers, Tumor genetics, CpG Islands, DNA Methylation, Homeodomain Proteins genetics, Nuclear Proteins genetics, Secondary Prevention, Stomach Neoplasms prevention & control
- Abstract
Gastric cancer (GC) is still a leading cause of cancer-related death worldwide, and environmental, genetic, and epigenetic DNA changes are involved in the process of gastric carcinogenesis. The objective of this study was to establish the extent of DNA methylation at various CpG islands in GC and in precancerous changes [gastric noninvasive neoplasia (NIN)]. Eighty-one gastric samples were analyzed using methylation-specific PCR at several CpG islands. Thirty-eight samples were obtained at surgery [19 neoplastic (GC) and 19 nonneoplastic cancer-surrounding tissues (sGC)] and 43 at endoscopy (biopsies in 23 NIN patients and 20 controls). Hypermethylation of TPEF (a growth inhibitor), PTGER3 (a prostaglandin receptor isoform), and MINT31 (a promoter locus regulating calcium channels that is involved in p53 mutation) discriminated NIN and GC from normal mucosa, suggesting an early role as initiating events, whereas hypermethylation at ARGHAP20 developed with the progression from NIN to GC. MINT31 hypermethylation predicted persistence or worsening of NIN and cancer development. In conclusion, these data support a progressive accumulation of aberrant methylations in NIN and GC at various CpG islands with distinct time courses. With hypermethylation, the genes involved in regulating the balance between apoptosis and cell proliferation may become silenced and trigger gastric tumorigenesis. Hypermethylation of MINT31 predicted NIN persistence, as well as progression to higher grade or to GC, and might be used as a marker of GC risk.
- Published
- 2012
- Full Text
- View/download PDF
15. Lesions indefinite for intraepithelial neoplasia and OLGA staging for gastric atrophy.
- Author
-
Fassan M, Pizzi M, Farinati F, Nitti D, Zagonel V, Genta RM, and Rugge M
- Subjects
- Adult, Aged, Aged, 80 and over, Disease Progression, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Staging, Precancerous Conditions pathology, Retrospective Studies, Risk Factors, Carcinoma in Situ pathology, Gastritis, Atrophic pathology, Stomach pathology, Stomach Neoplasms pathology
- Abstract
Gastric intraepithelial neoplasia (IEN; formerly dysplasia) is an advanced precancerous lesion. Lesions indefinite for IEN mimic the IEN phenotype but lack some morphologic attributes of IEN. Indefinite for IEN lesions may arise in native foveolae (atypical foveolar hyperproliferation [aFH]) or intestinalized glands (hyperproliferative intestinal metaplasia [HIM]). The clinicopathologic outcome of such lesions is debated. We retrospectively studied the clinicopathologic behavior of 129 consecutive indefinite for IEN lesions (HIM, 98; aFH, 31; median follow-up, 31 months) and correlated outcome with the extent and topography of mucosal atrophy (assessed by OLGA staging) at the initial endoscopy/biopsy. At enrollment, aFH never coexisted with severe/extensive atrophy (all cases were in low-risk OLGA stages [0-II]), whereas HIM was associated with low- and high-risk OLGA stages (0-II, 73; III-IV, 25). At follow-up, IEN was never documented among cases enrolled as aFH, while follow-up endoscopy/biopsy documented 6 neoplastic intraepithelial lesions among 98 cases of HIM (6%, all had high-risk OLGA stages at initial biopsy). OLGA staging can stratify indefinite for IEN lesions into different risk classes, potentially contributing to decisions for a patient-specific follow-up strategy.
- Published
- 2012
- Full Text
- View/download PDF
16. Validation of the new AJCC TNM staging system for gastric cancer in a large cohort of patients (n = 2,155): focus on the T category.
- Author
-
Marchet A, Mocellin S, Ambrosi A, Morgagni P, Vittimberga G, Roviello F, Marrelli D, de Manzoni G, Minicozzi A, Coniglio A, Tiberio G, Pacelli F, Rosa F, and Nitti D
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Lymphatic Metastasis, Male, Middle Aged, Prognosis, Stomach Neoplasms classification, Stomach Neoplasms mortality, Survival Analysis, Neoplasm Staging methods, Stomach Neoplasms pathology
- Abstract
Background: The prognostic value of T subclassification in patients with gastric carcinoma has been just implemented in the new AJCC TNM staging system, which has reclassified T2a and T2b into T2 and T3 tumors, respectively. The aim of the present study was to validate the prognostic significance of the new T categorization within the frame of the latest TNM staging system., Methods: We retrospectively reviewed the records of 686 T2/T3 patients among 2155 subjects who underwent radical resection for gastric carcinoma at six Italian centers from 1988 through 2006., Results: Upon multivariate analysis, the new T categories, extent of lymph node dissection (D) and patient's age were retained by the survival model as independent prognostic factors. In particular, the death risk for patients with T3 tumors was higher than that of patients with T2 tumors (HR: 1.42, P = 0.005). Among the 686 patients previously classified as having T2 tumors, patients with T2 and T3 disease were 270 (39.4%) and 416 (60.6%), respectively. After a median follow-up of 55 months, the 5-year overall survival rates were 67.3% and 52.3% for patients with T2 and T3 tumors, respectively (P < 0.001). The survival advantage for the T2 as compared to T3 category was maintained even when N0 and N+ patients were separately considered (P = 0.0154 and P < 0.001, respectively)., Conclusions: Our data confirm the prognostic difference between the newly proposed T2 and T3 categories, which should be implemented in the routine clinical practice to improve risk stratification of patients with gastric cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
17. Gastric type I carcinoid: a pilot study with human G17DT immunogen vaccination.
- Author
-
Tieppo C, Betterle C, Basso D, Mescoli C, Rugge M, Martini C, Zorzetto V, Maddalo G, Cazzagon N, Nitti D, and Farinati F
- Subjects
- Aged, Carcinoid Tumor immunology, Female, Gastritis, Atrophic immunology, Gastritis, Atrophic prevention & control, Humans, Immunoenzyme Techniques, Male, Pilot Projects, Prognosis, Stomach Neoplasms immunology, Survival Rate, Tumor Microenvironment, Vaccination, Cancer Vaccines administration & dosage, Carcinoid Tumor prevention & control, Gastrins administration & dosage, Stomach Neoplasms prevention & control
- Abstract
Context: Gastric type I carcinoid is a rare neoplasm, deriving from enterochromaffin-like cells (ECL), mainly affecting women with autoimmune gastritis. The approach to treatment, either endoscopic, medical or surgical, is not well defined, particularly in multifocal tumours or carcinoids with rapid growth/frequent recurrence., Objective: To determine whether an anti-G17 vaccination might interfere on the natural history of gastric type I carcinoid., Setting: Padua teaching Hospital, outpatient clinic., Design and Patients: Three patients with type I gastric carcinoid in autoimmune gastritis were administered, after informed consent and ethic committee approval, with a vaccine against gastrin 17 (G17), a synthetic peptide that stimulates specific and high-affinity anti-G17 antibodies, and followed up endoscopically and clinically for a mean of 36 months., Main Outcome Measures: Gastric histology and specifically carcinoid growth/recurrence and trend in time in gastrin, G17, pepsinogens, chromogranin A and clinical parameters., Results: Following vaccination, carcinoid regression was observed in 2/3 patients and, in one of the patients, even the disappearance of ECL hyperplasia, with a reduced ECL cells stimulation, confirmed by a significant reduction in chromogranin A levels. Regression was observed in the two patients that showed a more clear local response to the vaccine. Increased autoantibody titre was observed, but no appearance of new autoimmune diseases., Conclusions: Anti-G17 vaccination induced regression of type I gastric carcinoid and could be considered for the treatment of this tumour, when endoscopic removal is not indicated.
- Published
- 2011
- Full Text
- View/download PDF
18. EUS for the staging of gastric cancer: a meta-analysis.
- Author
-
Mocellin S, Marchet A, and Nitti D
- Subjects
- False Negative Reactions, False Positive Reactions, Humans, Neoplasm Staging, Odds Ratio, Sensitivity and Specificity, Endosonography, Stomach Neoplasms diagnostic imaging, Stomach Neoplasms pathology
- Abstract
Background: The role of EUS in the locoregional staging of gastric carcinoma is undefined., Objective: We aimed to comprehensively review and quantitatively summarize the available evidence on the staging performance of EUS., Design: We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE databases for relevant studies published until July 2010., Setting: Formal meta-analysis of diagnostic accuracy parameters was performed by using a bivariate random-effects model., Patients: Fifty-four studies enrolling 5601 patients with gastric cancer undergoing disease staging with EUS were eligible for the meta-analysis., Main Outcome Measurements: EUS staging accuracy across eligible studies was measured by computing overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR)., Results: EUS can differentiate T1-2 from T3-4 gastric cancer with high accuracy, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.86 (95% CI, 0.81-0.90), 0.91 (95% CI, 0.89-0.93), 9.8 (95% CI, 7.5-12.8), 0.15 (95% CI, 0.11-0.21), and 65 (95% CI, 41-105), respectively. In contrast, the diagnostic performance of EUS for lymph node status is less reliable, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.69 (95% CI, 0.63-0.74), 0.84 (95% CI, 0.81-0.88), 4.4 (95% CI, 3.6-5.4), 0.37 (95% CI, 0.32-0.44), and 12 (95% CI, 9-16), respectively. Results regarding single T categories (including T1 substages) and Bayesian nomograms to calculate posttest probabilities for any target condition prevalence are also provided., Limitations: Statistical heterogeneity was generally high; unfortunately, subgroup analysis did not identify a consistent source of the heterogeneity., Conclusions: Our results support the use of EUS for the locoregional staging of gastric cancer, which can affect the therapeutic management of these patients. However, clinicians must be aware of the performance limits of this staging tool., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
19. Do perioperative blood transfusions influence prognosis of gastric cancer patients? Analysis of 927 patients and interactions with splenectomy.
- Author
-
Pacelli F, Rosa F, Marrelli D, Pedrazzani C, Bossola M, Zoccali M, Marchet A, Di Cosmo M, Roata C, Graziosi L, Cavazzoni E, Covino M, D'Ugo D, Roviello F, Nitti D, and Doglietto GB
- Subjects
- Adenocarcinoma pathology, Aged, Female, Humans, Male, Prognosis, Retrospective Studies, Stomach Neoplasms pathology, Survival Rate, Adenocarcinoma surgery, Blood Transfusion, Perioperative Care, Splenectomy, Stomach Neoplasms surgery
- Abstract
Background: This study was to assess the influence of perioperative blood transfusions on the prognosis of patients undergoing a potentially curative resection for gastric cancer and to investigate the interaction between transfusions and splenectomy., Materials and Methods: Between January 1990 and December 2005, 927 patients from 6 Italian tertiary referral centers underwent curative resections for gastric cancer. Clinical and pathologic variables were prospectively collected. The influence of perioperative blood transfusions on survival were evaluated by univariate and multivariate analysis. Moreover, the influence of splenectomy both in transfused and nontransfused patients undergoing total gastrectomy was also evaluated., Results: The overall 5-year survival was 54.6%. The 5-year survival rate in transfused patients (n = 327) was 50.6% compared with 56.6% in nontransfused patients (n = 600) (P = .094). In the subgroup of patients who underwent total gastrectomy with spleen preservation (n = 209), 5-year survival rate was 46% and 51.4% in transfused and nontransfused patients, respectively (P = .418); those who underwent total gastrectomy with splenectomy (n = 199) presented a 5-year survival rate of 45% in transfused group compared with 39.1% in nontransfused patients (P = .571)., Conclusions: Our study indicates a slightly, but not significantly, negative effect of allogeneic blood transfusion on prognosis of gastric cancer patients. In the subgroup of patients who underwent total gastrectomy, splenectomy seems to invert this mild effect, with a positive influence on overall survival.
- Published
- 2011
- Full Text
- View/download PDF
20. A multicentric Western analysis of prognostic factors in advanced, node-negative gastric cancer patients.
- Author
-
Baiocchi GL, Tiberio GA, Minicozzi AM, Morgagni P, Marrelli D, Bruno L, Rosa F, Marchet A, Coniglio A, Saragoni L, Veltri M, Pacelli F, Roviello F, Nitti D, Giulini SM, and De Manzoni G
- Subjects
- Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Gastrectomy, Humans, Italy epidemiology, Lymph Node Excision, Lymphatic Metastasis pathology, Male, Middle Aged, Prognosis, Retrospective Studies, Stomach Neoplasms pathology, Lymph Nodes pathology, Stomach Neoplasms mortality
- Abstract
Background: The presence of lymph node metastasis is one of the most important prognostic factors in patients with gastric carcinoma. Node-negative patients have a better outcome, nevertheless a subgroup of them experience disease recurrence., Aim: To analyze the clinicopathological characteristics of lymph node-negative advanced gastric carcinoma patients submitted to gastrectomy and D2 lymphadenectomy with a retrieved number of nodes greater than 15, after an actual follow-up of almost 5 years, and to evaluate outcome indicators., Study Design: The records of 301 patients who underwent curative gastrectomy for gastric carcinoma and were adequately staged as N0 between 1992 and 2002 were retrospectively analyzed from the prospectively collected database of 7 centers participating to the Italian Research Group for Gastric Cancer., Results: Disease-specific and disease-free survival after 3, 5, and 10 years were 90.4%, 86.1%, 75.9%, and 72.1%, 57.3%, 57.3%, respectively. Mortality was 1.7%. The factors associated with a better disease-free survival at univariate analysis were age <60, T2 tumors, distal location, intestinal histotype, and number of retrieved nodes >25; depth of infiltration and histotype were the only 2 independent predictors of 5-year recurrence-free survival at multivariate analysis., Conclusion: These parameters must be considered to stratify node-negative gastric cancer patients for an adjuvant treatment and follow-up scheduling. Survival was similar to that previously reported by Eastern Centers. Lymphadenectomy is suggested to be effective, and retrieval of more than 25 nodes may be warranted.
- Published
- 2010
- Full Text
- View/download PDF
21. Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival.
- Author
-
Bertazza L, Mocellin S, Marchet A, Pilati P, Gabrieli J, Scalerta R, and Nitti D
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor blood, Biomarkers, Tumor genetics, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Humans, Inhibitor of Apoptosis Proteins, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Prognosis, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms genetics, Survivin, Transcription, Genetic, Microtubule-Associated Proteins blood, Microtubule-Associated Proteins genetics, Stomach Neoplasms blood, Stomach Neoplasms diagnosis
- Abstract
Background: The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma., Methods: Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5)., Results: Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome., Conclusions: Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients.
- Published
- 2009
- Full Text
- View/download PDF
22. Metachronous hepatic metastases from gastric carcinoma: a multicentric survey.
- Author
-
Tiberio GA, Coniglio A, Marchet A, Marrelli D, Giacopuzzi S, Baiocchi L, Roviello F, de Manzoni G, Nitti D, and Giulini SM
- Subjects
- Aged, Combined Modality Therapy, Female, Gastrectomy methods, Humans, Lymphatic Metastasis, Male, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local therapy, Neoplasm Staging, Patient Selection, Prognosis, Proportional Hazards Models, Retrospective Studies, Risk Factors, Stomach Neoplasms surgery, Survival Rate, Liver Neoplasms secondary, Liver Neoplasms therapy, Neoplasms, Second Primary pathology, Neoplasms, Second Primary therapy, Stomach Neoplasms pathology
- Abstract
Background: The treatment of hepatic metastases from gastric cancer is controversial, due to biologic aggressiveness of the disease., Objective: To survey the clinical approach to the subset of patients presenting with metachronous hepatic metastases as sole site of recurrence after curative resection of gastric cancer, focusing on the results achieved by different therapies and to investigate the prognostic factors of major clinical relevance., Methods: Retrospective multi-center chart review evaluating 73 patients, previously submitted to D >or= 2 gastrectomy for gastric cancer, who developed exclusive hepatic recurrence. Prognostic factors related to the patient, to the gastric malignancy and its treatment, and to the metastatic disease and its therapy were evaluated., Results: Forty-five patients received supportive care, 17 were submitted to chemotherapy, and 11 to hepatic resection. Survival was independently influenced by the variables T (p=0.019), N (p=0.05) and G (p=0.018) of the gastric primary and by the therapeutic approach to the metastases (p<0.005). In particular, T4 gastric cancer, presence of lymph-node metastases and G3 tumor displayed a negative prognostic value. Therapeutic approach to the metastases was the principal prognostic variable: 1, 2, and 3 years survival rates were 22.2%, 4.4% and 2.2%, respectively, for patients without specific treatment; 44.9%, 12.8% and 6.4% after chemotherapy (p=0.08) and 80.8%, 30.3% and 20.2% after surgical resection (p<0.001)., Conclusions: Our data suggest some clinical criteria that may facilitate selection of therapy for patients with hepatic recurrence after primary gastric cancer resection. The best survival rates are associated with surgical treatment, which should be chosen whenever possible.
- Published
- 2009
- Full Text
- View/download PDF
23. Prognostic value of subclassification of T2 tumours in patients with gastric cancer.
- Author
-
Nitti D, Marchet A, Mocellin S, Rossi GM, Ambrosi A, and Mencarelli R
- Subjects
- Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Lymphatic Metastasis, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Stomach Neoplasms mortality, Stomach Neoplasms classification
- Abstract
Background: This study was designed to evaluate the prognostic value of tumour stage T2 subcategorization (T2a and T2b) in patients with gastric carcinoma., Methods: Clinicopathological details of a prospective series of patients who had radical resection of gastric adenocarcinoma in a single institution were analysed. Univariable and multivariable survival analyses were performed with the log rank test and Cox's model respectively., Results: Of 373 evaluable patients, 49 (13.1 per cent) had a T2a and 143 (38.3 per cent) a T2b tumour. At a median follow-up of 35.5 months, the 5-year overall survival rate was 73 and 31.1 per cent for patients with T2a and T2b lesions respectively (P < 0.001). On multivariable analysis, T stage remained an independent prognostic factor. Compared with T1a, the mortality risk for patients with T1b (hazard ratio (HR) 1.00; P = 0.992) and T2a (HR 0.97; P = 0.916) tumours was similar; by contrast, the risk of death associated with T2b (HR 1.81; P = 0.031) and T3 (HR 1.89; P = 0.038) lesions was significantly greater than for T1a tumours., Conclusion: Subclassification of T2 tumours should be undertaken routinely in order to stratify patients with gastric cancer more accurately in terms of their mortality risk., ((c) 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)
- Published
- 2009
- Full Text
- View/download PDF
24. Indexes of surgical quality in gastric cancer surgery: experience of an Italian network.
- Author
-
Verlato G, Roviello F, Marchet A, Giacopuzzi S, Marrelli D, Nitti D, and de Manzoni G
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Intestinal Neoplasms mortality, Intestinal Neoplasms pathology, Italy epidemiology, Lymph Node Excision, Lymph Nodes pathology, Lymph Nodes surgery, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Staging, Postoperative Complications epidemiology, Prognosis, Risk Factors, Stomach Neoplasms mortality, Stomach Neoplasms pathology, Survival Rate, Young Adult, Gastrectomy, Intestinal Neoplasms surgery, Quality of Health Care, Stomach Neoplasms surgery
- Abstract
Background: Short-term results of gastric cancer surgery vary remarkably worldwide, and international surgical quality criteria are urgently needed. To contribute to defining these criteria, we reviewed short-term results of gastrectomy for gastric cancer in three centers of the Italian Research Group for Gastric Cancer, with an average of 24.7, 29.5, and 18 gastrectomies per year., Methods: Between 1988 and 2002, 1,032 patients underwent gastrectomy for gastric cancer in Verona, Siena, and Padua. D1, D2, and D3 lymphadenectomy were performed, respectively, in 228, 584, and 220 cases., Results: The median number of retrieved lymph nodes was 14 (interquartile range 9-18.75) after D1, 29 (21-38) after D2, and 46.5 (37-57) after D3. Fewer than 15 nodes were retrieved in 54.5%, 6.2%, and 1.4% of cases undergoing, respectively, D1, D2, and D3. Adjacent organ removal was rare during D1 (splenectomy: 6.1%, splenopancreasectomy: 1.8%), and quite common during D3 (11.4%, 11.4%). Forty patients (3.9%) died postoperatively. Neither postoperative morbidity nor mortality was significantly associated with extension of lymphadenectomy., Conclusion: We conclude that at least D2 lymphadenectomy is necessary to achieve adequate disease staging (>or=15 nodes retrieved). Spleen and pancreas tail are more frequently removed during D3, but this removal is not associated with higher postoperative morbidity or mortality.
- Published
- 2009
- Full Text
- View/download PDF
25. Resection line involvement after gastric cancer surgery: clinical outcome in nonsurgically retreated patients.
- Author
-
Morgagni P, Garcea D, Marrelli D, De Manzoni G, Natalini G, Kurihara H, Marchet A, Saragoni L, Scarpi E, Pedrazzani C, Di Leo A, De Santis F, Panizzo V, Nitti D, and Roviello F
- Subjects
- Adolescent, Adult, Aged, Cohort Studies, Humans, Italy, Lymph Node Excision, Middle Aged, Neoplasm Invasiveness, Neoplasm, Residual, Reoperation, Retrospective Studies, Stomach Neoplasms mortality, Survival Rate, Treatment Outcome, Young Adult, Gastrectomy, Stomach Neoplasms pathology, Stomach Neoplasms surgery
- Abstract
Purpose: Resection line infiltration (RLI) after surgical treatment represents an unfavorable prognostic factor in advanced gastric cancer. We performed a retrospective analysis of 89 patients with resection line involvement who did not undergo reoperation., Methods: On behalf of the Italian Research Group for Gastric Cancer, we present the characteristics and outcome of 89 patients who were submitted to surgical resection for gastric cancer from 1988 to 2001 and did not undergo reoperation because of disease extension or associated pathologies., Results: RLI was significantly higher in patients with T4 tumors and diffuse histological type. Anastomotic leakages were observed in 4.8% of infiltrated esophageal resection margins, whereas 1.9% of infiltrated duodenal resection lines showed duodenal fistulas. Five-year overall survival of patients with RLI was 29%. Prognosis was not affected by RLI in early forms (100% 5-year survival); however, 5-year survival in T2 and T3 stages was significantly lower with respect to the same stages without residual tumor. The influence of RLI on prognosis was confirmed in N0 as well as in N1 and N2 patients. RLI also was an independent prognostic at multivariate analysis (odds ratio = 1.5; 95% confidence interval, 1.08-2.08; P = 0.0144)., Conclusions: RLI significantly affects long-term survival of advanced gastric cancer. The impact on prognosis is independent of lymph node involvement. Patients in good general condition for whom radical surgery is possible should be considered for reoperation.
- Published
- 2008
- Full Text
- View/download PDF
26. Oxidative DNA damage in gastric cancer: CagA status and OGG1 gene polymorphism.
- Author
-
Farinati F, Cardin R, Bortolami M, Nitti D, Basso D, de Bernard M, Cassaro M, Sergio A, and Rugge M
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine, Adult, Aged, Antigens, Bacterial genetics, Atrophy genetics, Atrophy metabolism, Bacterial Proteins genetics, Deoxyguanosine metabolism, Electrophoresis, Gel, Two-Dimensional, Female, Gastritis, Atrophic metabolism, Helicobacter pylori isolation & purification, Humans, Male, Metaplasia genetics, Metaplasia metabolism, Middle Aged, Nucleic Acid Amplification Techniques, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Predictive Value of Tests, Prospective Studies, Stomach Neoplasms genetics, Stomach Neoplasms microbiology, Urease metabolism, Antigens, Bacterial metabolism, Bacterial Proteins metabolism, Biomarkers, Tumor metabolism, DNA Damage, DNA Glycosylases genetics, Deoxyguanosine analogs & derivatives, Intestines pathology, Oxidative Stress, Polymorphism, Genetic, Stomach Neoplasms metabolism
- Abstract
Oxidative DNA damage is thought to play an important part in the pathogenesis of H. pylori-induced mucosal damage. 8-OHdG is a sensitive marker of DNA oxidation and is repaired by a polymorphic glycosylase (OGG1) more effectively than by OGG1-Cys(326). The aims of this study were to ascertain the respective roles of H. pylori, cagA status and OGG1 polymorphism in determining 8-OHdG levels in benign and premalignant stomach diseases and in gastric cancer (GC). The study involved 50 GC patients (for whom both neoplastic tissue and surrounding mucosa were available), 35 with intestinal metaplasia and atrophy (IMA) and 43 controls. H. pylori and cagA status were determined by histology and polymerase chain reaction for urease and cagA. 8-OHdG was assayed using HPLC with an electrochemical detector (HPLC-ED). The OGG1 1245C-->G transversion was identified using RFLP analyses. 8-OHdG levels were significantly higher in GC, with no differences in relation to H. pylori or cagA status. OGG1 polymorphism was documented in 34% of GC (15 Ser/Cys, 2 Cys/Cys). OGG1 1245C-->G polymorphism was detected in 54% of IMA patients, but only 16% of controls (p = 0.0004) and coincided with significantly higher 8-OHdG levels. In the multivariate analysis, 8-OHdG levels were predicted by histotype and OGG1 status. OGG1 1245C-->G polymorphism was common in both GC and IMA, but very rare in controls, and correlated more closely with 8-OHdG levels than do H. pylori infection or cagA status., ((c) 2008 Wiley-Liss, Inc.)
- Published
- 2008
- Full Text
- View/download PDF
27. Recent advances in conventional and molecular prognostic factors for gastric carcinoma.
- Author
-
Nitti D, Mocellin S, Marchet A, Pilati P, and Lise M
- Subjects
- Apoptosis, Cell Cycle, Disease Progression, Gene Expression, Genes, p53, Humans, Neoplasm Staging, Prognosis, Stomach Neoplasms genetics, Stomach Neoplasms physiopathology, Vascular Endothelial Growth Factor A, Stomach Neoplasms surgery
- Abstract
Despite radical surgery, the prognosis of patients who have gastric carcinoma remains unsatisfactory because of the intrinsic but unpredictable aggressiveness of this malignancy. During the past decade an ever-growing list of molecular prognostic factors has been proposed based on the discovery of the mechanisms underlying gastric cancer aggressiveness. Studies performed in larger and more homogeneous series of patients and adequate statistical analysis are warranted before any of the candidate biomarkers can be implemented in the routine clinical setting for the identification of patients at higher risk and thus for the selection of candidates for adjuvant or more aggressive therapies.
- Published
- 2008
- Full Text
- View/download PDF
28. Helicobacter pylori, inflammation, oxidative damage and gastric cancer: a morphological, biological and molecular pathway.
- Author
-
Farinati F, Cardin R, Cassaro M, Bortolami M, Nitti D, Tieppo C, Zaninotto G, and Rugge M
- Subjects
- Animals, DNA Damage physiology, Gastritis genetics, Helicobacter Infections pathology, Humans, Stomach Neoplasms genetics, Gastritis complications, Helicobacter Infections complications, Helicobacter pylori, Oxidative Stress physiology, Signal Transduction genetics, Stomach Neoplasms etiology, Stomach Neoplasms pathology
- Abstract
Gastric carcinogenesis is a complex, multistep and multifactorial event, characterized by progressive cyto-histological dedifferentiation, in which the role of Helicobacter pylori infection has been established. Among the pathways relevant to gastric carcinogenesis and correlated with H. pylori infection, it has been demonstrated that the production of reactive oxygen species, with damage to the DNA, may be quite important. Oxidative damage, alone and/or in combination with exogenous and endogenous factors, induces several molecular changes. The assumption is that, in precancerous lesions, these molecular changes belong to the same biological spectrum as their invasive counterpart. The molecular profile of these preneoplastic lesions is heterogeneous, however, and there are still no molecular markers enabling the distinction between atypical hyperplastic lesions and low-grade noninvasive neoplasia (NiN) or between high-grade NiN and early invasive neoplasia. Indeed, within the spectrum of morphological changes characterizing this multistep evolution, dysplasia (NiN) is the lesion coming closest to the development of invasive adenocarcinoma. Several of the genetic and epigenetic alterations reported in gastric precancerous lesions affect DNA repair system genes, tumor suppressor genes, oncogenes, cell cycle regulators, growth factors, and adhesion molecules. Although we await reliable molecular markers, it is best to monitor patients harboring NiN closely with endoscopy and extensive bioptic sampling, and to eradicate any H. pylori to prevent the accumulation of oxidative DNA damage and its consequent progression. The growing body of evidence of the regression of precancerous changes and the high prevalence of superficial gastric carcinoma demonstrated in long-term follow-up studies on NiN make this approach mandatory.
- Published
- 2008
- Full Text
- View/download PDF
29. The prognostic value of N-ratio in patients with gastric cancer: validation in a large, multicenter series.
- Author
-
Marchet A, Mocellin S, Ambrosi A, de Manzoni G, Di Leo A, Marrelli D, Roviello F, Morgagni P, Saragoni L, Natalini G, De Santis F, Baiocchi L, Coniglio A, and Nitti D
- Subjects
- Adenocarcinoma mortality, Aged, Aged, 80 and over, Analysis of Variance, Female, Gastrectomy methods, Humans, Immunohistochemistry, Lymph Node Excision statistics & numerical data, Lymphatic Metastasis, Male, Middle Aged, Multicenter Studies as Topic, Multivariate Analysis, Predictive Value of Tests, Probability, Prognosis, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Sensitivity and Specificity, Stomach Neoplasms mortality, Survival Analysis, Adenocarcinoma secondary, Adenocarcinoma surgery, Lymph Nodes pathology, Neoplasm Staging methods, Stomach Neoplasms pathology, Stomach Neoplasms surgery
- Abstract
Aims: The proportion between metastatic and examined lymph nodes (N-ratio) has been proposed as an independent prognostic factor in patients with gastric cancer. In the present work we validated the reliability of N-ratio in a large, multicenter series., Patients and Methods: We retrospectively reviewed the data of 1853 patients who underwent radical resection for gastric carcinoma. Survival of patients with >15 (Group-1, n=1421) and those with < or =15 (Group-2, n=432) lymph nodes examined was separately analyzed in order to evaluate the influence of lymph node dissection on disease staging. N-ratio categories (N-ratio 0, 0%; N-ratio 1, 1-9%; N-ratio 2, 10-25%; N-ratio 3, >25%) were determined by the best cut-off approach., Results: At multivariate analysis, N-ratio (but not TNM N-category) was retained as an independent prognostic factor both in Group-1 and Group-2 (HR for N-ratio 1, N-ratio 2 and N-ratio 3=1.67, 2.96 and 6.59, and 1.56, 2.68 and 4.28, respectively). After a median follow-up of 45.5 months, the 5-year overall survival rates of TNM N0, N1 and N2 patients were significantly different in Group-1 vs Group-2. This was not the case when adopting the N-ratio classification, suggesting that a low number of excised lymph nodes can lead to patients being understaged using the N-category, but not N-ratio. Moreover, N-ratio identified subsets of patients with significantly different survival rates within TNM N1 and N2 categories in both groups., Conclusions: N-ratio is a simple and reproducible prognostic tool that can stratify patients with gastric cancer, including those cases with limited lymph node dissection. These data support the rationale to propose the implementation of N-ratio into the current TNM staging system.
- Published
- 2008
- Full Text
- View/download PDF
30. Indefinite for non-invasive neoplasia lesions in gastric intestinal metaplasia: the immunophenotype.
- Author
-
Cassaro M, Rugge M, Tieppo C, Giacomelli L, Velo D, Nitti D, and Farinati F
- Subjects
- Adult, Aged, Aged, 80 and over, CDX2 Transcription Factor, Caspase 3 metabolism, Female, Gastric Mucosa metabolism, Gastric Mucosa microbiology, Gastritis metabolism, Gastritis microbiology, Gastritis pathology, Helicobacter Infections complications, Helicobacter pylori, Homeodomain Proteins metabolism, Humans, Immunoenzyme Techniques, Immunophenotyping, Male, Metaplasia metabolism, Metaplasia microbiology, Middle Aged, Neoplasm Proteins metabolism, Observer Variation, Precancerous Conditions microbiology, Precancerous Conditions pathology, Retrospective Studies, Stomach Neoplasms microbiology, Stomach Neoplasms pathology, Telomerase metabolism, Ubiquitin-Protein Ligases metabolism, Biomarkers, Tumor metabolism, Gastric Mucosa pathology, Precancerous Conditions metabolism, Stomach Neoplasms metabolism
- Abstract
Background: In the Padova International Classification, gastric precancerous lesions are labelled as "indefinite for non-invasive neoplasia" (Indef-NiN) cytohistological alterations mimicking non-invasive neoplasia (NiN), but lacking all the attributes required for a definite NiN categorisation., Aim: To apply a panel of immunohistochemical (IHC) markers of cell proliferation (Mib1), intestinal differentiation (Cdx2), apoptosis (pro-caspase 3) and cell immortalisation (hTERT) to compare the IHC profiles of a series of precancerous lesions arising in gastric intestinalised (ie, IM-positive) glands., Materials and Methods: By applying the histological criteria consistently provided by both the Padova Classification and the World Health Organization International Agency, 112 consecutive cases were considered: intestinal metaplasia (IM; n = 54), Indef-NiN in IM-positive gastric glands (n = 28) and low-grade (LG) NiN (n = 30). In each histological category, the expression of the marker was separately scored in superficial, proliferative and coil compartments., Results: In all glandular compartments, Mib1, Cdx2, hTERT and pro-caspase 3 were consistently more expressed in LG-NiN than in either IM or Indef-NiN lesions (analysis of variance: p<0.001). Significant ORs (calculated by ordinal logistic regression analysis for each glandular compartment) associated IM, Indef-NiN and LG-NiN with the expression of the considered markers., Conclusions: A consistent overexpression (unrestricted to the proliferative zone) of IHC markers of cell proliferation, intestinal differentiation, decreased apoptosis and cell immortalisation differentiates LG-NiN from both (simple) IM and Indef-NiN (arising in IM). An increased proliferative activity in the proliferative zone discriminates Indef-NiN lesions (ie, hyperproliferative IM) from IM. Such divergent IHC profiles may provide a rationale for scheduling follow-up protocols more properly tailored on the patient's risk for cancer.
- Published
- 2007
- Full Text
- View/download PDF
31. The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients.
- Author
-
Marchet A, Mocellin S, Ambrosi A, Morgagni P, Garcea D, Marrelli D, Roviello F, de Manzoni G, Minicozzi A, Natalini G, De Santis F, Baiocchi L, Coniglio A, and Nitti D
- Subjects
- Aged, Female, Humans, Italy, Male, Multivariate Analysis, Proportional Hazards Models, Retrospective Studies, Stomach Neoplasms surgery, Lymph Node Excision methods, Lymphatic Metastasis, Neoplasm Staging methods, Stomach Neoplasms mortality, Stomach Neoplasms pathology
- Abstract
Purpose: To investigate whether the ratio between metastatic and examined lymph nodes (N ratio) is a better prognostic factor as compared with traditional staging systems in patients with gastric cancer regardless of the extension of lymph node dissection., Patients & Methods: We retrospectively reviewed the data of 1853 patients who underwent radical resection for gastric carcinoma at 6 Italian centers. Patients with >15 (group 1, n = 1421) and those with
25%) were determined by the best cut-off approach., Results: After a median follow-up of 45.5 months (range, 4-182 months), the 5-year overall survival of N0, N1, and N2 patients of group 1 versus group 2 was 83.4% versus 74.2% (P = 0.0026), 54.3% versus 44.3% (P = 0.018), and 32.7% versus 14.7% (P = 0.004), respectively, suggesting that a low number of excised lymph nodes can lead to the understaging of patients. N ratio identified subsets of patients with significantly different survival rates within N1 and N2 stages in both groups. At multivariate analysis, the N ratio (but not N stage) was retained as an independent prognostic factor both in group 1 and group 2 (HR for N ratio 1, N ratio 2, and N ratio 3 = 1.67, 2.96, and 6.59, and 1.56, 2.68, and 4.28, respectively). In our series, the implementation of N ratio led to the identification of subgroups of patients prognostically more homogeneous than those classified by the TNM system., Conclusion: N ratio is a simple and reproducible prognostic tool that can stratify patients with gastric cancer also in case of limited lymph node dissection. These data may represent the rational for improving the prognostic power of current UICC TNM staging system and ultimately the selection of patients who may most benefit from adjuvant treatments. - Published
- 2007
- Full Text
- View/download PDF
32. Gene expression profile of primary gastric cancer: towards the prediction of lymph node status.
- Author
-
Marchet A, Mocellin S, Belluco C, Ambrosi A, DeMarchi F, Mammano E, Digito M, Leon A, D'Arrigo A, Lise M, and Nitti D
- Subjects
- Biomarkers, Tumor metabolism, Gene Expression Regulation, Neoplastic, Humans, Lymphatic Metastasis, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Neoplasm genetics, RNA, Neoplasm metabolism, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, Biomarkers, Tumor genetics, Gene Expression Profiling, Genetic Testing statistics & numerical data, Lymph Nodes pathology, Stomach Neoplasms diagnosis
- Abstract
Background: The identification of gastric tumors associated with a higher risk of lymph node metastasis could help surgeons select patients who may benefit from extended lymph node dissection. The aim of this study was to screen the genome in the search of primary gastric cancer gene expression profiles that might predict lymph node status., Methods: The gene expression profile was evaluated in frozen tumor samples obtained from 32 patients with primary gastric adenocarcinomas. The array consisted of a duplicated spot panel of 5,541 human genes. To classify node-positive (N+) and node-negative (N-) cases, a logistic regression model was fitted optimizing the Akaike Information Criteria after a stepwise gene selection. The accuracy was evaluated by means of leave-one-out cross validation., Results: All patients underwent radical gastrectomy and extended lymphadenectomy. Of all the cases, 21 were N+ and 11 demonstrated no lymph node involvement (N-). After quality filtering, the analysis of variance selected a set of 136 genes potentially correlated with nodal involvement (P value <.05). Of these 136 genes, 5 were differentially expressed (adjusted P value <.05). After a stepwise gene selection, only three genes (Bik, aurora kinase B, eIF5A2) were retained in the logistic model, which could correctly predict lymph node status in 30 of 32 cases., Conclusions: If our findings were confirmed, the identified gene pattern might be used to tailor the extent of lymph node dissection on a single patient basis.
- Published
- 2007
- Full Text
- View/download PDF
33. Epidermal growth factor receptor (EGFR): mutational and protein expression analysis in gastric cancer.
- Author
-
Mammano E, Belluco C, Sciro M, Mencarelli R, Agostini M, Michelotto M, Marchet A, and Nitti D
- Subjects
- Adenocarcinoma metabolism, Adenocarcinoma pathology, Adult, Aged, Aged, 80 and over, DNA Mutational Analysis, Female, Humans, Immunoenzyme Techniques, Male, Middle Aged, Polymerase Chain Reaction, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Adenocarcinoma genetics, ErbB Receptors genetics, ErbB Receptors metabolism, Mutation genetics, Stomach Neoplasms genetics
- Abstract
Background: Since specific epidermal growth factor receptor (EGFR) somatic mutations have been demonstrated to influence the response to anti-EGFR therapy in non-small cell lung cancer, EGFR gene mutational analysis of different types of neoplasm is under investigation., Patients and Methods: EGFR protein expression and gene mutations in exons 18, 19 and 21 were investigated in 49 gastric adenocarcinomas., Results: no specific EGFR gene mutations were detected, while EGFR positive staining was detected in 6% of the cases., Conclusion: Our findings indicate that in gastric adenocarcinoma, specific EGFR gene mutations are very rare or absent and the rate of EGFR protein expression is low.
- Published
- 2006
34. Does resection line involvement affect prognosis in early gastric cancer patients? An Italian multicentric study.
- Author
-
Morgagni P, Garcea D, Marrelli D, de Manzoni G, Natalini G, Kurihara H, Marchet A, Vittimberga G, Saragoni L, Roviello F, Di Leo A, De Santis F, Panizza V, and Nitti D
- Subjects
- Adult, Duodenum pathology, Duodenum surgery, Female, Humans, Lymph Node Excision, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Staging, Neoplasm, Residual mortality, Postoperative Complications mortality, Stomach pathology, Stomach Neoplasms mortality, Stomach Neoplasms pathology, Survival Rate, Gastrectomy methods, Neoplasm, Residual pathology, Postoperative Complications pathology, Stomach Neoplasms surgery
- Abstract
Background: Resection line involvement has been indicated as an important prognostic factor for gastric cancer. Its late detection renders the choice of treatment difficult for surgeons., Materials and Methods: We describe the multicenter experience of a group of 11 patients with early gastric carcinoma (EGC) and positive resection confirmed at histological examination who did not undergo surgical retreatment for reasons of associated disease, surgical considerations on duodenal stump, or patient refusal., Results: The gastric margin was involved in 4 patients, and 7 patients had duodenal resection line involvement. No surgical complications or postoperative deaths were observed. Five and 8-year survival was 100% and 86%, respectively. The only patient who relapsed did not have lymph node involvement and died from liver metastases, without local recurrence., Conclusions: It is sometimes difficult to accurately define the resection line in gastric cancer surgery, especially in the early stages of disease, but because of the strongly negative prognostic value of an infiltrated margin, frozen sections are recommended if neoplastic invasion is suspected and a new resection is always recommended if possible. Nevertheless, the good prognosis of resected EGC patients with resection line involvement must be considered before submitting patients with associated diseases to radical surgical retreatment.
- Published
- 2006
- Full Text
- View/download PDF
35. Randomized phase III trials of adjuvant FAMTX or FEMTX compared with surgery alone in resected gastric cancer. A combined analysis of the EORTC GI Group and the ICCG.
- Author
-
Nitti D, Wils J, Dos Santos JG, Fountzilas G, Conte PF, Sava C, Tres A, Coombes RC, Crivellari D, Marchet A, Sanchez E, Bliss JM, Homewood J, Couvreur ML, Hall E, Baron B, Woods E, Emson M, Van Cutsem E, and Lise M
- Subjects
- Adenocarcinoma surgery, Adult, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Chemotherapy, Adjuvant, Clinical Trials, Phase III as Topic, Combined Modality Therapy, Disease-Free Survival, Doxorubicin administration & dosage, Epirubicin administration & dosage, Female, Fluorouracil administration & dosage, Humans, Male, Methotrexate administration & dosage, Middle Aged, Randomized Controlled Trials as Topic, Stomach Neoplasms surgery, Survival Analysis, Adenocarcinoma drug therapy, Stomach Neoplasms drug therapy
- Abstract
Background: In patients who underwent radical resection for gastric cancer, we investigate the relative efficacy of combined 5-fluorouracil+adriamycin or epirubicin and methotrexate with leucovorin rescue (FAMTX or FEMTX) compared with a control arm., Patients and Methods: This report is a prospective combined analysis of two randomized clinical trials conducted on patients who underwent radical resection for histologically proven adenocarcinoma of the stomach or esophago-gastric junction. Three hundred and ninety-seven untreated patients, 206 from 23 European Organization for Research and Treatment of Cancer (EORTC) institutions and 191 from 16 International Collaborative Cancer Group (ICCG) institutions, were randomized. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and the treatments were compared for these end-points by means of the log-rank test, retrospectively stratified by trial., Results: In a planned combined analysis of the two trials, no significant differences were found between the treatment and control arms for either DFS (hazards ratio: 0.98, P=0.87) or OS (hazards ratio: 0.98, P=0.86). The 5-year OS was 43% in the treatment arm and 44% in the control arm and the 5-year DFS was 41% and 42%, respectively., Conclusion: Neither FAMTX nor FEMTX can be advocated as adjuvant treatment in patients who undergo resection for gastric cancer.
- Published
- 2006
- Full Text
- View/download PDF
36. Non-invasive neoplasia of the stomach.
- Author
-
Rugge M, Nitti D, Farinati F, di Mario F, and Genta RM
- Subjects
- Disease Progression, Genes, Tumor Suppressor, Genomic Instability, Humans, Long-Term Care methods, Precancerous Conditions genetics, Stomach Neoplasms genetics, Terminology as Topic, Precancerous Conditions pathology, Stomach Neoplasms pathology
- Abstract
Invasive gastric cancer is the final step of a cascade of genomic and phenotypic changes, which have been defined as multistep oncogenesis. This process includes a continuum of progressively dedifferentiated phenotypes, which may result in a biologically new (i.e., nuepsilonomega = neo) cell characterized by autonomous, potentially metastatic, growth (i.e., pilambdaalphazetaomega = plasia). The clinico-pathological characterization of the advanced gastric precancerous lesions has important implications for both primary and secondary cancer prevention. The WHO agency has recently redefined dysplasia as intraepithelial [i.e., non-invasive neoplasia (NiN)]; such a proposal is consistent with the biological profile of dysplasia, which shares with invasive cancer some significant molecular attributes. Long-term follow-up studies have demonstrated that, in the natural history of gastric cancer, NiN precedes invasive adenocarcinoma. In this review, the morphological features of gastric NiN are described, also illustrating differences and similarities between the current and the previously adopted histological diagnostic criteria. The molecular profile of NiN is summarized and the spectrum of the options in the clinical management of gastric NiN are reported.
- Published
- 2005
- Full Text
- View/download PDF
37. Extended lymphadenectomy (D2) in patients with early gastric cancer.
- Author
-
Nitti D, Marchet A, Mammano E, Ambrosi A, Belluco C, Mencarelli R, Maino M, Marconato G, Farinati F, and Lise M
- Subjects
- Adenocarcinoma secondary, Age Factors, Aged, Cause of Death, Female, Follow-Up Studies, Gastrectomy, Humans, Lymphatic Metastasis pathology, Male, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Postoperative Complications, Prospective Studies, Retrospective Studies, Survival Rate, Treatment Outcome, Adenocarcinoma surgery, Lymph Node Excision, Stomach Neoplasms surgery
- Abstract
Aims: To investigate the survival benefit of extended lymphadenectomy (D2) in EGC patients in one European Institution., Methods: A review was made of our prospective gastric database from January 1980 to December 2001. Of 527 patients with primary gastric adenocarcinoma, 119 with EGC underwent potentially curative resection (R0) with D2 lymphadenectomy., Results: There were two post-operative deaths. Of the 117 evaluable cases, 96 were classified as N0 and 21 as N+, with metastases in the perigastric lymph nodes (level 1) in 13, and beyond this site (level 2) in eight. Five-year survival was 85.9 and 83.0% in N0 and N+ patients, respectively. During a median follow-up of 90 months, five of the eight patients with level 2 metastases died of recurrent disease and three were alive. The estimated survival benefit for 119 patients with EGC was 2.5% (3/119 cases)., Conclusions: In patients with EGC, metastases to level 2 are rare. Our results indicate that D2 lymphadenectomy has a limited survival benefit and that in these cases a less extensive lymphadenectomy (D1) could be performed.
- Published
- 2005
- Full Text
- View/download PDF
38. Ratio between metastatic and examined lymph nodes is an independent prognostic factor after D2 resection for gastric cancer: analysis of a large European monoinstitutional experience.
- Author
-
Nitti D, Marchet A, Olivieri M, Ambrosi A, Mencarelli R, Belluco C, and Lise M
- Subjects
- Adult, Aged, Databases, Factual, Female, Humans, Lymph Node Excision, Male, Middle Aged, Multivariate Analysis, Prognosis, Retrospective Studies, Survival Analysis, Adenocarcinoma pathology, Adenocarcinoma surgery, Lymphatic Metastasis, Neoplasm Staging methods, Stomach Neoplasms pathology, Stomach Neoplasms surgery
- Abstract
Background: In view of the lack of consensus on the level and number of lymph nodes to be examined for accurate staging of patients with gastric cancer, our aim was to evaluate the prognostic significance of lymph node status in a large European monoinstitutional experience., Methods: A review was made of our prospective database from 1980 to 2000, when 314 of 445 patients operated for gastric adenocarcinoma underwent radical resection (R0) with D2 lymphadenectomy. Survival was determined by the Kaplan-Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression., Results: In 277 evaluable patients, 5-year survival was 57% (median follow-up, 48 months; range, 2-251). A total of 7668 lymph nodes were examined (median, 27; range, 11-62). The 5-year survivals according to the metastatic/examined lymph nodes ratio (N ratio) were 14%, 50%, 61%, and 82% in the group of patients with N ratio >25%, 11%-25%, 1%-10%, and 0%, respectively (P <.0001). At multivariate analysis, the N ratio was the best single independent prognostic factor (P =.000)., Conclusions: After R0 resection for gastric cancer, the N ratio is a potent prognostic factor. It should therefore be considered in the clinical decision making process.
- Published
- 2003
- Full Text
- View/download PDF
39. Hyperthermic intraperitoneal intraoperative chemotherapy for peritoneal carcinomatosis arising from gastric adenocarcinoma.
- Author
-
Rossi CR, Pilati P, Mocellin S, Foletto M, Ori C, Innocente F, Nitti D, and Lise M
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin administration & dosage, Female, Humans, Male, Middle Aged, Mitomycin administration & dosage, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms secondary, Peritoneal Neoplasms surgery, Survival Analysis, Treatment Outcome, Adenocarcinoma secondary, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Hyperthermia, Induced, Infusions, Parenteral methods, Peritoneal Neoplasms therapy, Stomach Neoplasms pathology
- Abstract
Background: Patients with peritoneal carcinomatosis from gastric carcinoma have a dismal prognosis. Hyperthermic intraperitoneal intraoperative chemotherapy (HIIC) has been proposed to treat residual disease after cytoreductive surgery., Patients and Methods: From January 1998 through July 2002, 13 patients with peritoneal carcinomatosis from gastric cancer underwent complete cytoreductive surgery followed by HIIC. Chemo-hyperthermia was performed using mitomicin C (3.3 mg/m2) and cisplatin (25 mg m2) for 90 minutes, at a mean intraperitoneal temperature of 41.7 degrees C., Results: No postoperative death was observed. Moderate locoregional toxicity (ileus) was observed in eight cases (42%), while two patients (10%) experienced mild systemic toxicity (myelosuppression or fever). Postoperative complication rate was 26% (pleural effusion, n = 4; septicemia = 1). Median overall survival was 15 months, and the median local progression free survival was 10 months., Conclusions: Cytoreductive surgery followed by HIIC resulted a feasible procedure, the overall morbidity rate being acceptable. Although the study was conducted in a subset of patients with peritoneal carcinomatosis from gastric cancer (resectable disease), survival results are encouraging.
- Published
- 2003
40. Lymphadenectomy in patients with gastric cancer. A critical review.
- Author
-
Nitti D, Marchet A, Olivieri M, Ambrosi A, Mencarelli R, Farinati F, Belluco C, and Lise M
- Subjects
- Adult, Aged, Analysis of Variance, Female, Gastrectomy, Humans, Italy, Lymph Nodes surgery, Lymphatic Metastasis diagnosis, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Prognosis, Risk Factors, Adenocarcinoma secondary, Adenocarcinoma surgery, Lymph Node Excision, Lymph Nodes pathology, Stomach Neoplasms pathology, Stomach Neoplasms surgery
- Abstract
Background: Surgical resection is still the main treatment for patients with gastric cancer. However, while surgical procedures for the treatment of the primary tumor have been standardized, there has been no worldwide consensus as yet on the extent of lymphadenectomy. The aim of the present study was therefore to evaluate the outcome following extended lymphadenectomy, and the prognostic significance of lymph node status, in a group of patients who underwent radical resection for gastric cancer., Methods: Among 445 consecutive patients operated on for gastric adenocarcinoma between 1980 and 2000 at Clinica Chirurgica II of the Padua University, 314 underwent radical resection (R0). A D2 lymphadenectomy was performed in 293/314 cases (93.3%), and a D1 in 21/314 (6.7%). The rate of postoperative morbidity was 22% (69/314 patients), and the postoperative mortality (within 30 days of surgery), 4.1% (13/314 patients). Survival was determined using the Kaplan Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression., Results: Of 301 valuable patients, a total of 7991 lymph nodes were examined (mean, 27.18; range, 9-62) and the total number of metastatic lymph nodes was 1343 (mean, 4.5; range, 1-47). After a median follow-up of 49 months (range, 2-251), the overall 5-year survival was 57%. At multivariate analysis of all 301 patients, factors retained were depth of invasion (P < 0.001), age (P = 0.027), number of lymph node metastasis (P = 0.029), and metastatic/examined lymph node ratio (P < 0.0001)., Conclusions: D2 dissection can be performed without incurring high mortality and morbidity rates. At least 15 lymph nodes must be removed to achieve an accurate disease staging. As confirmed at multivariate analysis, a metastatic/examined lymph node ratio greater than 25% is an independent negative prognostic factor.
- Published
- 2003
41. Low level of p27(Kip1) protein expression in gastric adenocarcinoma is associated with disease progression and poor outcome.
- Author
-
Nitti D, Belluco C, Mammano E, Marchet A, Ambrosi A, Mencarelli R, Segato P, and Lise M
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma surgery, Adult, Aged, Aged, 80 and over, Cyclin-Dependent Kinase Inhibitor p27, Disease Progression, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Invasiveness, Prognosis, Stomach Neoplasms pathology, Stomach Neoplasms surgery, Survival Analysis, Treatment Outcome, Adenocarcinoma metabolism, Cell Cycle Proteins biosynthesis, Stomach Neoplasms metabolism, Tumor Suppressor Proteins biosynthesis
- Abstract
Background and Objectives: Low tumor expression of the p27(Kip1) protein, which is involved in cell cycle control and apoptosis, is considered a negative prognostic factor in different types of cancer. The aim of this study was to evaluate the clinical and pathological significance of low p27(Kip1) protein expression in patients who had undergone resection for gastric adenocarcinoma., Methods: p27(Kip1) protein was studied by immunohistochemistry in formalin-fixed tumor sections from 95 patients who underwent resection for gastric adenocarcinoma between 1991 and 1996. Based on the median value of protein expression, p27(Kip1) protein expression was classified as low or high., Results: Low p27(Kip1) protein expression was significantly associated with tumor de-differentiation, increased penetration through the gastric wall, lymph node metastasis, and advanced tumor stage. In the group of 84 patients who underwent curative surgery, 5-year survival was 74% in cases with high p27(Kip1) protein expression and 38% in those with low p27(Kip1) protein expression (P < 0.001). At multivariate analysis, low p27(Kip1) protein expression was an independent negative prognostic factor for survival (RR = 3.671; P = 0.004)., Conclusions: In gastric adenocarcinoma, low p27(Kip1) protein expression is associated with poorly differentiated and advanced tumors and is a negative prognostic factor of potential clinical value., (Copyright 2002 Wiley-Liss. Inc.)
- Published
- 2002
- Full Text
- View/download PDF
42. Gastric non-Hodgkin's lymphoma: analysis of 252 patients from a multicenter study.
- Author
-
Salvagno L, Sorarù M, Busetto M, Puccetti C, Sava C, Endrizzi L, Giusto M, Aversa S, Chiarion Sileni V, Polico R, Bianco A, Rupolo M, Nitti D, Doglioni C, and Lise M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Lymphoma, Non-Hodgkin pathology, Male, Middle Aged, Neoplasm Staging, Prognosis, Retrospective Studies, Risk Factors, Stomach Neoplasms pathology, Survival Analysis, Treatment Outcome, Lymphoma, Non-Hodgkin diagnosis, Lymphoma, Non-Hodgkin therapy, Stomach Neoplasms diagnosis, Stomach Neoplasms therapy
- Abstract
Aims and Background: The stomach is the most common site of primary extranodal non-Hodgkin's lymphoma (NHL) and no agreement has been reached so far on the best therapeutic approach. The main objects of this study were to report the long-term results and to evaluate the importance of some possible prognostic factors in a large series of patients. NHL was considered primary gastric if the main symptoms at presentation were those of gastric disease., Methods and Study Design: We analyzed 252 consecutive patients treated between 1980 and 1993 in five hospitals in north-east Italy. According to the Working Formulation, 98 patients had low grade lymphoma, 59 intermediate grade (D to F), 81 G or high grade and 14 were not classified. The patients were divided into two groups: one including patients with limited disease (localized to the stomach or perigastric lymph nodes: 165 patients) and one including those with advanced disease (87 patients). The treatment consisted of surgery, chemotherapy, radiotherapy or combinations of these. Sixteen patients received only supportive therapy., Results: The five-year overall survival was 65.4%: 80.3% for patients with limited disease and 36.7% for those with advanced disease (P < 0.0001). Among the limited disease patients the five-year survival was 84.4% for those treated with gastrectomy alone and 88.7% for those who received also adjuvant chemotherapy (P = 0.11). However, while chemotherapy did not improve survival in low grade NHL, it seemed to produce a better survival in the intermediate and high grade groups (P = 0.06). Twelve patients were treated with primary chemotherapy and the five-year survival was 71.2%. In multivariate regression analysis the most important variable for overall survival was surgery for the whole group of 252 patients (P < 0.0001), while it was age for the group with limited disease (P = 0.0008)., Conclusions: Surgery alone can be curative for most patients with gastric lymphoma limited to the stomach or to the perigastric lymph nodes; surgery followed by chemotherapy seems to produce better results than surgery alone in intermediate and high grade lymphomas. Also a non-surgical approach with first-line chemotherapy is associated with a high rate of complete remissions and five-year survival. In advanced disease the five-year survival is similar to that of nodal NHL.
- Published
- 1999
43. Augmented membrane type 1 matrix metalloproteinase (MT1-MMP):MMP-2 messenger RNA ratio in gastric carcinomas with poor prognosis.
- Author
-
Caenazzo C, Onisto M, Sartor L, Scalerta R, Giraldo A, Nitti D, and Garbisa S
- Subjects
- Biopsy, Female, Gelatinases metabolism, Humans, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinases, Membrane-Associated, Metalloendopeptidases metabolism, Prognosis, Reproducibility of Results, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Tissue Inhibitor of Metalloproteinase-2 biosynthesis, Urokinase-Type Plasminogen Activator biosynthesis, Gelatinases biosynthesis, Metalloendopeptidases biosynthesis, Stomach Neoplasms enzymology
- Abstract
The activation of zymogen and the amount of proteinase and its inhibition are important in determining the eventual activity of matrix-degrading enzymes involved in tumor aggressiveness. To evaluate a gene complement leading to matrix metalloproteinase 2 (MMP-2; Mr 72,000 gelatinase) activity, membrane type 1 MMP (MT1-MMP), urokinase-type plasminogen activator, MMP-2, and tissue inhibitor of metalloproteinase 2 transcriptional levels were measured in gastric carcinoma biopsies. Comparative tumor:normal tissue reverse transcription-PCR in a cohort of 25 patients revealed up to a 10-fold difference in the expression of MT1-MMP, a metalloproteinase that has been proposed as a membrane receptor activator of MMP-2; a 1-unit increment resulted in a 30% risk to survival. A 20% risk also resulted from a 1-unit increment in the MT1-MMP: MMP-2 ratio, which showed differences of up to 15-fold. Instead, the expression of urokinase-type plasminogen activator, which trips off a cascade ending in the activation of MMP-2, as well as the expression of MMP-2 itself and its inhibitor, tissue inhibitor of metalloproteinase 2, lacked correlation with patient follow-up. Zymography revealed MMP-2 activities that were often in conflict with the transcription results and also with follow-up. The results suggest the evaluation of MT1-MMP and/or MT1-MMP:MMP-2 transcription as a new preoperative molecular-level prognostic factor for gastric carcinoma.
- Published
- 1998
44. [Complementary treatment to surgery of gastric carcinoma: role of adjuvant and neoadjuvant chemotherapy].
- Author
-
Lise M, Nitti D, Marchet A, Tripodi M, Pilati P, and Pasetto L
- Subjects
- Chemotherapy, Adjuvant, Humans, Stomach Neoplasms drug therapy, Stomach Neoplasms surgery
- Abstract
Although there has been a decline in the incidence of gastric cancer worldwide, its mortality rate is still high. In the West, attempts with adjuvant chemotherapy to improve survival have been disappointing. The promising results reported with the FAM (5-FU, Adriamycin, Mitomycin C) regimen in patients with advanced disease, have not been confirmed in an adjuvant setting. Randomized trials on adjuvant chemotherapy in Japan have shown a positive outcome in treated patients only when subgroups with advanced disease are considered. As results with adjuvant chemo-immunotherapy were better than those with chemotherapy alone, immunostimulators have been widely utilized in clinical trials conducted in Japan in recent years. However, chemo-immunotherapy may be more effective in patients with minimal residual disease, due to the combined action of a lower stage at diagnosis and to a diffuse application of standard wide lymphadenectomy. Inadequate lymphadenectomy, like that performed in many western studies, may compromised radicality in patients with "curable" disease and the concept of "minimal residual disease" must therefore be considered in future trials on adjuvant chemotherapy. Future trends for new therapeutic combinations (FAMTX, EAP, 5-FU/Cisplatin, PELF, etc) tested in phase II and III clinical trials are also discussed. Whatever the type of approach used, the high incidence of intra-abdominal recurrences indicates that an improvement in the prognosis of patients with advanced diseases will only come with the development of additional treatment modalities such as neoadjuvant or intraperitoneal chemotherapy.
- Published
- 1997
45. Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric carcinogenesis.
- Author
-
Farinati F, Herszényi L, Plebani M, Carraro P, De Paoli M, Cardin R, Roveroni G, Rugge M, Nitti D, Grigioni WF, D'Errico A, and Naccarato R
- Subjects
- Adult, Aged, Aged, 80 and over, Cathepsin L, Cysteine Endopeptidases, Female, Gastritis, Atrophic metabolism, Humans, Immunohistochemistry, Male, Middle Aged, Cathepsin B analysis, Cathepsins analysis, Endopeptidases, Plasminogen Activator Inhibitor 1 analysis, Stomach Neoplasms metabolism, Urokinase-Type Plasminogen Activator analysis
- Abstract
Background: Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL)], the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) play an important part in cancer invasion. No data are available on the relationship between these proteases and gastric precancerous changes., Aims: To determine CATB, CATL, UPA, PAI-1 in chronic atrophic gastritis, intestinal metaplasia and gastric epithelial dysplasia, as precancerous changes, and to compare these data with those obtained in gastric cancer., Patients: Endoscopic biopsies were obtained from 12 patients with gastric cancer (cancerous tissue), 33 patients with chronic atrophic gastritis (all with intestinal metaplasia and 12 with dysplasia) and from 47 control subjects, for a total of 92 patients., Methods: Antigen concentrations were measured using ELISA methods. Immunohistochemistry was performed using monoclonal anti-CATB and anti-PAI-1 antibodies., Results: CATB, CATL, UPA and PAI-1 were significantly higher in chronic atrophic gastritis than in controls (CATB: P < 0.001; CATL: P < 0.005; UPA: P < 0.000001; PAI-1: P < 0.005). The same was observed for cancer. CATB and UPA were significantly higher in chronic atrophic gastritis, with versus without dysplasia (P < 0.05). Dysplastic epithelia showed strong immunoreactivity to PAI-1 and CATB., Conclusions: Our study demonstrates that cathepsins, UPA and PAI-1 may have a role not only in the process of cancer invasion, but also in the progression of precancerous changes into cancer.
- Published
- 1996
- Full Text
- View/download PDF
46. Prognostic factors in resectable gastric cancer: results of EORTC study no. 40813 on FAM adjuvant chemotherapy.
- Author
-
Lise M, Nitti D, Marchet A, Sahmoud T, Duez N, Fornasiero A, dos Santos JG, Labianca R, Lasser P, and Gignoux M
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma pathology, Chemotherapy, Adjuvant, Doxorubicin administration & dosage, Fluorouracil administration & dosage, Humans, Mitomycin administration & dosage, Neoplasm Staging, Prognosis, Stomach Neoplasms mortality, Stomach Neoplasms pathology, Survival Rate, Adenocarcinoma drug therapy, Adenocarcinoma surgery, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Stomach Neoplasms drug therapy, Stomach Neoplasms surgery
- Abstract
Background: The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment., Methods: In a randomized clinical trial on adjuvant FAM2 chemotherapy, quality of surgery was evaluated by comparing surgical and pathology data. Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients, tumor, and therapy., Results: Of 314 patients randomized from 28 European institutions, 159 comprised the control and 155 the FAM2 group. After a median follow-up of 80 months, no statistically significant difference was found between survivals. However, for recurrence time, treated patients had a significant advantage over controls (p = 0.02). At univariate analysis, statistically significant differences in survival and time to progression emerged for T, N, disease stage and "adequacy" of surgery. The multivariate analysis retained preoperative Hb level, T, N, and "adequacy" of surgery for time of survival; and T, N, "adequacy" of surgery and adjuvant chemotherapy for recurrence time., Conclusions: Disease stage is the most important prognostic factor. "Adequate" surgery has an important effect. Adjuvant FAM2 delayed time of recurrence, but did not influence overall survival.
- Published
- 1995
- Full Text
- View/download PDF
47. Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer.
- Author
-
Lise M, Nitti D, Marchet A, Sahmoud T, Buyse M, Duez N, Fiorentino M, Dos Santos JG, Labianca R, and Rougier P
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma mortality, Adenocarcinoma surgery, Chemotherapy, Adjuvant, Combined Modality Therapy, Disease-Free Survival, Doxorubicin administration & dosage, Europe, Female, Fluorouracil administration & dosage, Humans, Male, Mitomycin administration & dosage, Proportional Hazards Models, Stomach Neoplasms mortality, Stomach Neoplasms surgery, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Stomach Neoplasms drug therapy
- Abstract
Purpose: In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval., Patients and Methods: Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis., Results: Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068)., Conclusion: FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.
- Published
- 1995
- Full Text
- View/download PDF
48. Cysteine and serine proteases in gastric cancer.
- Author
-
Plebani M, Herszènyi L, Cardin R, Roveroni G, Carraro P, Paoli MD, Rugge M, Grigioni WF, Nitti D, and Naccarato R
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma pathology, Adenocarcinoma secondary, Adult, Aged, Aged, 80 and over, Cathepsin B analysis, Cathepsin L, Cathepsins analysis, Enzyme-Linked Immunosorbent Assay, Female, Gastric Mucosa chemistry, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, Middle Aged, Plasminogen Activator Inhibitor 1 analysis, Prognosis, Stomach Neoplasms mortality, Stomach Neoplasms pathology, Survival Analysis, Urokinase-Type Plasminogen Activator analysis, Adenocarcinoma chemistry, Cysteine Endopeptidases analysis, Endopeptidases, Serine Endopeptidases analysis, Stomach Neoplasms chemistry
- Abstract
Background: Cysteine proteases (cathepsin B [CATB] and cathepsin L [CATL]), the serine protease urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) are thought to play an important part in cancer invasion and metastasis. The aims of this study were to measure CATB, CATL, UPA, and PAI-1 in gastric cancer (GC) and normal mucosa distant from the tumor (NORM); to evaluate whether tissue levels are related to tumor stage, grade, or histotype; to assess their prognostic relevance; and to examine UPA and PAI-1 expression immunohistochemically., Methods: Gastric cancer and NORM samples were obtained from 25 patients with gastric cancer patients undergoing surgery (17 males, 8 females; mean age, 62 years; range, 31-84 years). Antigen concentrations were measured using the enzyme-linked immunosorbent assay method. Immunohistochemistry was performed using monoclonal UPA and PAI-1 antibodies., Results: Significantly higher antigen levels were found: (1) in GC vs. NORM (CATB, CATL, UPA, PAI-1) tissues; (2) in GC with versus without metastasis (CATB, CATL, UPA); (3) in poorly or moderately versus well differentiated GC; and (4) in diffuse versus intestinal-type GC (CATB, CATL). Urokinase-type plasminogen activator, PAI-1 and CATB levels had a significant prognostic impact. Cancer and stromal cells, showed immunoreactivity to anti-UPA and anti-PAI-1 antibodies., Conclusions: These results confirm the important role of CATB, CATL, UPA and PAI-1 in gastric cancer progression. Higher levels are detected in GC with metastases, poorer differentiation, and diffuse histotype, thus identifying patients with a worse prognosis.
- Published
- 1995
- Full Text
- View/download PDF
49. Pathology and ploidy in the prognosis of gastric cancer with no extranodal metastasis.
- Author
-
Rugge M, Sonego F, Panozzo M, Baffa R, Rubio J Jr, Farinati F, Nitti D, Ninfo V, and Ming SC
- Subjects
- Aged, Female, Flow Cytometry, Humans, Male, Middle Aged, Neoplasm Staging, Ploidies, Prognosis, Stomach Neoplasms genetics, Survival Rate, DNA, Neoplasm analysis, Stomach Neoplasms mortality, Stomach Neoplasms pathology
- Abstract
Background: The prognostic relevance of morphology in advanced gastric cancer is well known. Data on tumor cell DNA content are still inadequate and contradictory., Methods: Morphologic parameters and DNA ploidy were evaluated in 76 gastric cancer patients with no extranodal metastases (Stage I, 10 cases; Stage II, 20 cases; and Stage III, 46 cases), using formalin-fixed paraffin-embedded tissue. All cases were followed for at least 6 years after surgery or until death., Results: Among the potential prognostic factors analyzed by Mantel-Cox and generalized Wilcoxon statistics, male sex (P = 0.02), cardiac location of neoplasia (P = 0.02), deeper infiltration of the gastric wall (P = 0.001), vascular neoplastic invasion (P = 0.006), metastatic lymph nodes (P = 0.001), pathologic stage (P = 0.0001), and aneuploidy (P = 0.01) were significantly associated with lower survival rate. Testing of all of the above-mentioned variables by the Cox stepwise multiple regression model disclosed that factors independently associated with survival were stage (P = 0.0001), ploidy (P = 0.0006), and vascular carcinomatous invasion (P = 0.01)., Conclusions: In gastric cancer with no extranodal metastases, DNA ploidy was found to be the most significant prognostic parameter after pathologic stage.
- Published
- 1994
- Full Text
- View/download PDF
50. Adjuvant treatment for gastric cancer.
- Author
-
Lise M, Nitti D, Marchet A, and Fornasiero A
- Subjects
- Combined Modality Therapy, Humans, Stomach Neoplasms drug therapy, Stomach Neoplasms surgery, Antineoplastic Agents therapeutic use, Chemotherapy, Adjuvant, Stomach Neoplasms therapy
- Abstract
In spite of progress made in surgical techniques and intensive care, only a slight improvement in the therapeutic control of gastric carcinoma has been achieved in the last 20 years. In this paper we present a review of controlled clinical trials on adjuvant chemotherapy and chemo-immunotherapy for gastric cancer and this topic is discussed in the light of our experience and that of the Gastrointestinal Group of the European Organization for Research and Treatment of Cancer. The results of adjuvant therapy are less satisfactory in Western countries than in Japan. The efficacy of the 5-fluorouracil + adriamycin + mitomycin C regimen in advanced gastric cancer has not been confirmed in an adjuvant setting. The therapeutic benefit reported in Japanese studies may be due to a chemotherapy started intraoperatively or during the immediate postoperative period and should also be considered in the light of a standardized surgical treatment. The new therapeutic trends, using recent chemotherapeutic associations tested in Phase I and II clinical trials or combining traditional chemotherapy with different types of immunostimulators, are discussed. Only when large-scale clinical studies have been made will it be possible to confirm their therapeutic efficacy.
- Published
- 1991
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.