F. Roviello

Prospective study of peritoneal recurrence after curative surgery for gastric cancer

Peritoneal carcinomatosis is a common cause of failure after surgery for gastric cancer. The present longitudinal study was designed to evaluate the incidence and potential predictors of peritoneal recurrence after curative resection for gastric cancer.

A multicentric Western analysis of prognostic factors in advanced, node-negative gastric cancer patients

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.

The new TNM classification of lymph node metastasis minimises stage migration problems in gastric cancer patients

The present study aimed at investigating whether in gastric cancer patients stage migration occurs with extension of lymphadenectomy, when node metastases are staged according to the new pN classification (UICC 1997). The investigation involved 921 patients, who underwent R0 gastric resection for gastric cancer between 1988 and 1998 in three different Italian centres: Verona (n=236), Forlì (n=409), Siena (n=276). The relation among lymphadenectomy and pN category was assessed by Kendalls partial rank-order correlation coefficient, controlling for depth of tumour invasion. A direct evaluation of the Will Rogers phenomenon was accomplished in the Verona series, by comparing the number of positive nodes actually observed with the number of positive nodes which would have been retrieved by a less extended lymphadenectomy (D1). The number of positive nodes increased remarkably with the enlargement of lymphadenectomy, especially in pT2 patients (from 2.2±3.9 in D1 to 3.9±5.0 in D3) and in pT3/pT4 patients (from 5.1±5.9 in D1 to 11.3±12.6 in D3). Non-parametric statistics highlighted a weak (Kendalls partial T=0.128) but significant (P<0.001) correlation between pN category and extension of lymphadenectomy. In the direct analysis of the Verona series, 22 patients out of 230 (9.6%) migrated to a lower pN tier when ignoring positive nodes retrieved from the second and third level. This percentage increased to 39.1% (90 out of 230) when adopting the TNM 87 classification. In conclusion stage migration is of minor importance in gastric cancer patients, staged according to the new pN classification.

Super-extended (D3) lymphadenectomy in advanced gastric cancer

PURPOSE To analyze our experience with D3 lymphadenectomy in the treatment of advanced GC with specific reference to post-operative morbidity and mortality, incidence of para-aortic node (PAN) metastases, and long-term prognosis. METHODS Short- and long-term results of D3 lymphadenectomy were analyzed in 286 patients with advanced GC. RESULTS PAN metastases were demonstrated in 37 patients. PAN involvement was significantly higher in upper third tumours (29%) compared to middle and lower third (7%; P < 0.001). Eighty patients developed post-operative complications, being pulmonary disorders (6%), abdominal abscesses (4.5%) and pancreatic fistulas (3%) the most frequently observed. In-hospital mortality was 2%. Overall 5-year survival rate for R0 pT2-4 patients was 52%. When considering survival in relation to nodal involvement, both pN3 and non-regional lymph node metastases (M1a) patients showed a chance of long-term survival: 5-year survival was 31% for pN3 and 17% for M1a cases. Furthermore, the 5-year survival rate was remarkably high (about 60%) even in pN2 and pN3 subsets when no serosal invasion (pT2) was demonstrated. CONCLUSIONS D3 lymphadenectomy could be further explored in specialized centers for curative surgery of advanced GC, especially for upper third tumours, providing that an acceptable morbidity and no increase in mortality can be offered.

METACHRONOUS HEPATIC METASTASES FROM GASTRIC CARCINOMA: A MULTICENTRIC SURVEY.

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.

Changing clinical and pathological features of gastric cancer over time

The aim of the present multicentre observational study was to evaluate potential changes in clinical and pathological features of patients with gastric cancer (GC) treated in a 15‐year interval.

Gastric cancer in young patients with no alarm symptoms: focus on delay in diagnosis, stage of neoplasm and survival

Background: The test and treat strategy for Helicobacter pylori infection has raised some concern since young gastric cancer patients may have no alarm symptoms. In this study the frequency of alarm symptoms was assessed in a series of young gastric cancer patients, as well as the impact of absence of alarm symptoms on delay in diagnosis and stage of gastric cancer at diagnosis and survival. Methods: A retrospective study was carried out on 92 gastric cancer patients ≤ 45 years of age identified from databases in four hospitals between January 1985 and December 2001. Characteristics analysed included duration and features of dyspeptic symptoms, presence of alarm symptoms, time interval from the onset of symptoms to diagnosis, pTNM stage and survival. Results: Of the 92 patients, 54 (58.7%) presented uncomplicated dyspepsia and 38 (41.3%) alarm symptoms. In those with uncomplicated dyspepsia, epigastric pain was the most common complaint (64.1%) followed by vomiting (30.4%), heartburn and nausea. Weight loss was the most common alarm symptom (30.4%), followed by anorexia (10.9%), dysphagia or anaemia (7.6%). The mean delay from first symptoms to final diagnosis was 16.8 ± 13.9 weeks in patients with alarm symptoms and 29.3 ± 39.9 weeks in patients without alarm symptoms (P:ns). Patients without alarm symptoms showed significantly less aggressive gastric cancer compared to patients with alarm symptoms in relation to TNM stage and survival (cumulative 5‐year survival rate: 76% versus 49% P: 0.01). The survival rate, at 5 years, of patients without alarm symptoms, and with a history of dyspepsia of more than 24 weeks, was higher than that in patients with early diagnosis (93.4% versus 66.5%; P: 0.05). Conclusions: A large proportion of young gastric cancer patients present without alarm symptoms. Despite the delay in diagnosis, these patients have a better outcome than those with alarm symptoms. Thus the delay in diagnosis of patients without alarm symptoms does not affect survival.

Breast Cancer Local Recurrence: Risk Factors and Prognostic Relevance of Early Time to Recurrence

BackgroundLocal recurrence occurs in 10%–20% of patients treated with breast-conserving surgery for stage I–II breast cancer. The aim of the present study was to investigate breast cancer local recurrence, potential risk factors, and prognostic impact.MethodsA total of 503 patients treated with breast-conserving surgery were included in the study. All patients underwent axillary dissection and postoperative radiotherapy, and all patients had negative margins at pathological examination. Median follow-up was 82 months. Local recurrence was classified as early when it occurred within 2 years from surgery. The risk factors for local recurrence and overall survival were estimated by univariate and multivariate analyses.ResultsForty-six cases (9.1%) of local recurrence were observed, 11 of which occurred within 24 months of surgery; the other 35, sometime later. Statistically significant risk factors for local recurrence were premenopausal status, peritumoral vascular invasion, multifocality, and absence of estrogen receptors. Independent negative prognostic factors for overall survival at 5 and 10 years were N stage, absence of estrogen receptors, and early time to recurrence. Overall survival at 10 years was 10.0% for patients with early recurrence, 87.5% for patients with late recurrence, and 87.9% for patients without recurrence.ConclusionsNone of the studied clinicopathological characteristics alone is a determinant for the choice of surgical treatment. Younger patients treated with breast-conserving surgery should receive aggressive postsurgical treatment and should be followed with an intensive follow-up program when metastatic axillary lymph nodes, negative estrogen receptors, or peritumoral vascular invasion are present.

Prognostic relevance of proliferative activity evaluated by Mib-1 immunostaining in node negative breast cancer.

AIM The purpose of this prospective observational study was to analyze the role of Mib-1 immunostaining as a proliferation index in breast cancer. Correlations between Mib-1 expression and clinico-pathological characteristics as well as its prognostic value have been studied in a series of 432 node negative breast cancers. METHODS Mib-1 expression was evaluated by immunohistochemistry. Tumor sections from highly cellular invasive areas of cancer were stained by monoclonal antibody Mib-1 (Dako) and cells whose nuclei stained positive were counted in 10 randomly chosen HPFs and expressed as percentages of all epithelial cells. A minimum of 400 cells were counted. Correlation between Mib-1 staining and clinico-pathological factors was investigated by means of univariate and multivariate analyses. The prognostic impact on actuarial disease free (DFS) and overall survival (OS) was evaluated by univariate analysis using the log-rank test and by multivariate analysis using Cox regression model. RESULTS Tumors were considered as positive for Mib-1 expression when more than 15% of cells counted were stained. Mib-1 positivity was found in 190/432 cases and resulted in being significantly related to tumor grade, tumor size and absence of estrogen receptors at multivariate analysis. With a median follow-up of 66 months, Mib-1 positivity resulted in being the only independent predictor of OS (RR 2.92), and an independent predictor of DFS (RR 2.01) together with absence of estrogen receptors (RR 2.15). CONCLUSIONS Mib-1 index of proliferative activity correlates well to other established prognostic factors of breast cancer. Mib-1 index may improve the tailoring of adjuvant therapy in early breast cancer, and our experience adds evidence to its effectiveness as prognostic factor. Efforts to reach uniformity in the methodology and in the scoring system should be done to warrant a standardized procedure and make Mib-1 determination definitively reliable in the current clinical practice.

Vitamin E serum levels and gastric cancer : results from a cohort of patients in tuscany, italy

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