Alfonso De Stefano

Prognostic significance of CEA, CA 19-9 and CA 72-4 preoperative serum levels in gastric carcinoma.

The prognostic value of preoperative serum levels of CEA, CA 19-9 and CA 72-4 tumor markers was investigated in 153 patients resected for gastric cancer. The positivity rates for CEA, CA 19-9 and CA 72-4 were 20.9, 34.6 and 28.1%, respectively. Multiple logistic regression analysis for positive levels of tumor markers indicates that CEA positivity is significantly related to the depth of invasion (p < 0.005) and the presence of distant metastasis (p < 0.05), CA 19-9 positivity is related to nodal involvement (p < 0.05) and the depth of invasion (p < 0.05), whereas CA 72-4 positivity is influenced by tumor size (p < 0.005) and noncurative surgery (p < 0.05). Positive levels of each tumor marker were associated with a worse prognosis if compared with negative cases using univariate analysis. Multivariate analysis of curatively resected cases identified depth in gastric wall (p < 0.0001), nodal status (p < 0.0005), and tumor location in the upper third (p < 0.05) as significant prognostic variables; CEA, CA 19-9 and CA 72-4 serum positivity did not reach statistical significance. However, when the positivity of the three markers was associated, a p value < 0.05 was observed. The analysis of survival curves stratified by tumor stage revealed that marker positivity significantly affects survival in stages I, II and IV (p < 0.05). The combined assay of CEA, CA 19-9 and CA 72-4 preoperative serum levels provides additional prognostic information in patients resected for gastric cancer; patients with preoperative positivity for one of these tumor markers should be considered at high risk of recurrence even in early stages of gastric carcinoma.

Prediction of Recurrence After Radical Surgery for Gastric Cancer: A Scoring System Obtained From a Prospective Multicenter Study

Objective:The aim of this prospective multicenter study was to define a scoring system for the prediction of tumor recurrence after potentially curative surgery for gastric cancer. Summary Background Data:The estimation of the risk of recurrence in individual patient may be relevant in clinical practice, to apply adjuvant therapies after surgery, and plan an adequate follow-up program. Only a few studies, most of which were retrospective or performed on a limited number of patients, have developed a prognostic score in patients with gastric cancer. Methods:A total of 536 patients who underwent UICC R0 resection between 1988 and 1998 at 3 surgical departments in Italy were considered. All patients were followed up using a standard protocol after discharge from the hospital. The mean follow-up period was 56 ± 44 months, and 94 ± 29 months for surviving patients. The scoring system was calculated on the basis of a logistic regression model, where the presence of the recurrence was the dependent variable, and clinicopathologic variables were the covariates. Results:Recurrence occurred in 272 of 536 patients (50.7%). The scoring system for the prediction of the risk in individual cases gave values ranging from 1.4 to 99.9; the model distributed most cases in the extremes of the range. The risk of recurrence increased remarkably with score values; it was only 5% in patients with a score below 10, up to 95.4% in patients with a score of 91 to 100. No recurrence was observed in 43 patients with a score below 4, whereas all of the 56 patients with a score over 97 presented a recurrence. The model correctly predicted recurrence in 227 of 272 patients (sensitivity, 83.5%), whereas the absence of recurrence was correctly predicted in 214 of 264 patients (specificity, 81.1%); the overall accuracy was 82.2%. Prognostic score was clearly superior to UICC tumor stage in predicting recurrence. The high effectiveness of the score was confirmed in preliminary data of a validation study. Conclusions:The scoring system obtained with a regression model on the basis of our follow-up data is useful for defining subgroups of patients at a very low or very high risk of tumor recurrence after radical surgery for gastric cancer. Final results of the validation study are essential for a clinical application of the model.

Different Patterns of Recurrence in Gastric Cancer Depending on Lauren’s Histological Type: Longitudinal Study

AbstractThe aim of this multicenter longitudinal study was to evaluate the pattern of recurrence in patients submitted to potentially curative surgery for intestinal-type and diffuse-type gastric cancer. The study included 412 patients surgically treated at three Italian surgical departments, subdivided into 273 intestinal-type cases (group A) and 139 diffuse-type cases (group B). Recurrence of disease was found in 41% of group A cases and 65% of group B cases (p <0.0001). The incidence of locoregional, hematogenous, and peritoneal recurrence was 20%, 19%, and 9% in group A, and 27%, 16%, and 34% in group B, respectively; the difference between the two groups was statistically significant for peritoneal recurrence (p <0.0001). Multivariate analysis identified as prognostic variables lymph node status, depth of invasion, extent of lymphadenectomy, advanced age, and male gender in group A; depth of invasion, extent of lymphadenectomy, tumor size, and lymph node status, in group B. Whereas in group A the incidence of peritoneal recurrence was limited in all subgroups examined, in group B very high rates were observed in cases with infiltration of the serosa, involvement of second-level lymph nodes, or large tumor size. The notable difference in the risk of peritoneal recurrence between the intestinal and diffuse types should be taken into consideration in the therapeutic approach to gastric cancer.

Clinical utility of CEA, CA 19-9, and CA 72-4 in the follow-up of patients with resectable gastric cancer

BACKGROUND The aim of this longitudinal study was to evaluate the effectiveness of the serum tumor markers CEA, CA 19-9, and CA 72-4 in the early diagnosis of recurrence of gastric cancer. METHODS One hundred and thirty-three patients who had undergone potentially curative surgery were considered. Serum samples were obtained preoperatively, 1 week after surgery, and at every follow-up examination. Mean follow-up time for the entire patient population was 41 +/- 33 months, and 71 +/- 27 months for patients classified as disease-free. RESULTS Preoperative positivity was 16% for CEA, 35% for CA 19-9, and 20% for CA 72-4. Recurrence of disease was found in 75 patients (56%). Marker sensitivity in recurrent cases was 44% for CEA, 56% for CA 19-9, and 51% for CA 72-4; the combined use of the three markers increased sensitivity to 87%, which reached 100% in patients with positive preoperative levels. Marker specificity, evaluated in 58 disease-free patients, was 79% for CEA, 74% for CA 19-9, and 97% for CA 72-4. CONCLUSIONS The combined assay of CEA, CA 19-9, and CA 72-4 may be useful for early diagnosis of recurrence of gastric cancer; however, only CA 72-4 positivity should be considered a specific predictor of tumor recurrence.

Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: State of the art and future developments

Peritoneal carcinomatosis (PC) had long been regarded as a terminal disease, characterized by a very poor survival and worth treating with palliative therapy. A new strategy combining maximal surgery (cytoreductive surgery, CRS), with maximal regional chemotherapy (hyperthermic intraperitoneal chemotherapy, HIPEC), has been proposed to treat PC, resulting in long-term survival rates in selected patients. The emerging trend is to view localised peritoneal carcinomatosis, in the absence of other metastases, as a regional metastatic disease that is amenable to locoregional therapy. In spite of the need for more high quality studies, many international experts now agree that the use of this new strategy is a gold standard for treating selected patients with PC with the intent of curing. The best results are achieved in patients with limited disease who have completed macroscopic tumor removal. To offer a comprehensive review, we summarized the present status and possible future progress of this treatment modality, in particular outlining its rationale, current practice and general outcome.

Complications after Extended (D2) and Superextended (D3) Lymphadenectomy for Gastric Cancer: Analysis of Potential Risk Factors

BackgroundVery few studies from Western centers have compared D2 and D3 dissection in the surgical treatment of gastric cancer. The aim of the prospective observational study reported here was to analyze the postoperative outcome and potential risk factors for complications following D2 and D3 lymphadenectomy.MethodsA total of 330 consecutive patients, of which 251 submitted to D2 lymphadenectomy and 79 were treated by D3 lymphadenectomy, were enrolled in the study. Twenty potential risk factors for morbidity and mortality were studied by means of univariate and multivariate analysis.ResultsOverall morbidity and mortality rates were 34% (111 patients) and 4% (14 patients), respectively. Abdominal abscess, anastomotic leakage, pleuropulmonary diseases and pancreatitis were the most commonly observed complications. No differences in morbidity, surgical morbidity, mortality rates and mean hospital stay between D2 and D3 lymphadenectomy were found. Multivariate analysis revealed that American Society of Anesthesiologists’ (ASA) class II/III versus class I, perioperative blood transfusions, and low albumin serum levels were independent predictors of postoperative complications. Age, surgical radicality (R1/R2 vs. R0) and low albumin serum levels independently predicted mortality. Mortality rate was .5% in the 203 patients aged 75 years or younger who underwent curative surgery. Most of deaths were observed in patients older than 75 years with low albumin serum levels or treated by non-curative surgery.ConclusionsD2 lymphadenectomy represents a feasible procedure associated to acceptable morbidity and mortality rates. In specialized centers, D3 lymphadenectomy may be performed without increasing the risk of postoperative complications and associated deaths in carefully selected patients. These techniques should be avoided in subgroups of patients with a high risk of postoperative mortality.

Postoperative Complications and Functional Results After Subtotal Gastrectomy with Billroth II Reconstruction for Primary Gastric Cancer

Subtotal gastrectomy is considered the preferred treatment for gastric cancer with antral location. The aim of this study was to assess the incidence of early postoperative complications and late functional results in patients who underwent subtotal gastrectomy with Billroth II reconstruction for primary gastric adenocarcinoma. The results of 310 patients were analyzed with regard to postoperative complications and death rates. Functional results as they relate to the gastric resection were evaluated in 195 disease-free patients. Of the 310 patients, 77 developed postoperative general and surgical complications (24.8%) and 13 consequently died (in-hospital mortality: 4.2%). Although infrequent (6 cases, 1.9%), anastomotic leak was the most serious complication (4 cases died during the postoperative phase). Considering functional results, weight loss continued for the first trimester after surgery, after which it stabilized. Loss of appetite was rarely observed; early after the operation the majority of patients were consuming a normal diet and regularly consumed less than five meals per day (83.6%). Dumping syndrome was uncommon and usually resolved within one year (12.3% at three months, 9.5% after one year, 5.2% after two years). On the other hand, postprandial abdominal fullness was frequently observed (43.1% at three months, 36.1% after one year, 21.3% after three years, and 16.5% after five years). Billroth II reconstruction after subtotal gastrectomy is associated with a limited risk of anastomotic complications. Anastomotic leak, although infrequent, is a life-threatening complaint and requires prompt recognition and aggressive surgical treatment. The incidence of late complications was low and the majority of patients recovered from them within one year after surgery, although the occurrence of postprandial abdominal fullness was not completely irrelevant.

Prognostic Value of Extracapsular Extension of Axillary Lymph Node Metastases in T1 to T3 Breast Cancer

BackgroundThe importance of extracapsular extension (ECE) of axillary metastases as a risk factor for either local or distant recurrence and poorer survival in breast cancer has been suggested, but its prognostic value has not been uniformly confirmed.MethodsFrom a prospective database including 1142 breast cancer patients operated on at the Department of General Surgery and Surgical Oncology of the University of Siena, we selected 376 cases with pT1 to pT3 node-positive breast cancer. The prognostic significance of ECE of axillary metastases was evaluated with respect to disease-free survival, overall survival, and the patterns of disease recurrence. Such prognostic significance was then compared with that of other clinical and pathologic factors.ResultsWith a median follow-up of 103 months, factors with independent prognostic value for disease-free survival by multivariate analysis included absence of estrogen receptors (P < .0005), pN category (P < .01), presence of lymphovascular invasion (LVI; P < .005), and ECE (P < .0001). An independent negative prognostic effect on overall survival was observed for absence of estrogen and progesterone receptors (P < .05), pN category (P < .05), and presence of LVI (P < .005) and ECE (P < .0001). The presence of ECE was significantly related to an increased risk of regional (13.4% vs. 6.6%; P = .037) and distant (43% vs. 16.2%; P < .001) recurrences.ConclusionsECE demonstrated a stronger statistical significance in predicting prognosis than the pN category and was also related to an increased risk of distant recurrences. We suggest that the decision on adjuvant therapy should consider the presence of ECE of axillary metastases and peritumoral LVI as indicators of high biological aggressiveness.

p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

AbstractBackground: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer. Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis. Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression. Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.

High Incidence of Familial Gastric Cancer in Tuscany, a Region in Italy

Objectives: Only 1% of diffuse gastric cancers occur in families with autosomal dominant gastric cancer susceptibility. Germline mutations in the E-cadherin gene account for the hereditary diffuse gastric cancer (HDGC) syndrome. We studied a large cohort of gastric cancer patients from Tuscany, a region in Italy, to evaluate the presence of familial clustering of gastric cancer. Methods: 238 pedigrees were retrospectively studied by structured interviews. All probands with diagnosed gastric cancer were contacted in-person or by phone and tumor types were assessed in first- and second-degree relatives. Familial aggregation was investigated in order to search for families with suspected HDGC. Results: Familial aggregation for gastric cancer was observed in 79 of 238 cases (33.2%). Among these, there were 64 families (81%) with one gastric cancer other than the proband, 10 families with two gastric cancers (12.7%) and 5 families with three gastric cancers (6.3%). Fourteen families fulfilled the HDGC clinical criteria, one of them presenting with a pathogenic germline mutation in the E-cadherin gene (7.1%). Conclusions: The prevalence of familial HDGC appears extremely high. Since only one pathogenic germline mutation was noted in a family fulfilling the HDGC clinical criteria, factors other than E-cadherin gene mutations may contribute to the familial clustering of HDGC.