Alberto Di Leo

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.

Survival benefit of extended D2 lymphadenectomy in gastric cancer with involvement of second level lymph nodes: A longitudinal multicenter study

BackgroundThe survival benefit of extended lymphadenectomy in the surgical treatment of gastric cancer is still being debated. The aim of this longitudinal multicenter study was to evaluate long-term survival in a group of patients with involvement of second level lymph nodes, which would not have been removed in the case of a limited lymphadenectomy. Results were compared with those in patients with involvement of first level lymph nodes.MethodsBetween 1991 and 1997, 451 patients with primary gastric cancer underwent curative resection with extended lymphadenectomy at three surgical departments in Italy according to the rules of the Japanese Research Society for Gastric Cancer.ResultsIn 451 cases treated by extended lymphadenectomy, morbidity and mortality rates were 17.1% and 2%, respectively. In 126 patients (27.9%) (group A), metastases were found in lymph node stations 7 to 12; 109 patients (24.2%) had metastases confined to the first level (group B). Lymph node stations 7 and 8 showed the highest incidence of metastases in the second level (17.1% and 12.4%, respectively). A significant difference in 5-year survival was observed between group A and group B (32% vs. 54%;P=.0005). This difference disappeared when cases were stratified according to the number of positive lymph nodes. By multivariate analysis, only the number of positive lymph nodes (relative risk, 1.8;P<.0001) and the depth of invasion (relative risk. 2.1;P<.0001), but not the level of involved nodes, showed to be independent predictors of poor prognosis.ConclusionsJapanese-type extended lymphadenectomy yields low morbidity and mortality rates if performed in specialized centers. This procedure could provide a good probability of long-term survival, even for patients with involvement of regional lymph nodes.

Results of surgical treatment of adenocarcinoma of the gastric cardia

BACKGROUND Comparison among different studies regarding adenocarcinoma of the cardia has been difficult since the Siewert classification was introduced. This study analyzed the experience of a single institution in the treatment of gastric cardia cancer with the aim of assessing principal prognostic factors and long-term outcome. METHODS The results of 96 patients who underwent resection with curative intent for gastric cardia cancer at the First Division of General Surgery, University of Verona, from January 1988 to February 2000, were analyzed statistically with special reference to Siewert type. RESULTS Despite a high number of curative resections (85.4%), the 5-year survival rate was poor (24%) for all Siewert types (p = 0.8), and for early tumors (51%) also. Chance of cure was limited to pN0 and pN1 patients. Multivariate analysis showed that microscopic or macroscopic residual tumor and pN-positive categories had a significantly higher risk of death (risk ratio, 2.18 and 2.68, respectively) and the pN2 and pN3 category had the most negative prognostic factor (risk ratio, 7.6). CONCLUSIONS The long-term prognosis for gastric cardia cancer remains poor and is independent of Siewert type, with cure limited to pN0 and pN1 patients.

Lymph Node Involvement in Gastric Cancer for Different Tumor Sites and T Stage

BackgroundThe aim of lymphadenectomy is to clear all the metastatic nodes achieving a complete removal of the tumor; nevertheless, its role in gastric cancer has been very much debated.Materials and methodsThe frequency of node metastasis in each lymphatic station according to the International Gastric Cancer Association, was studied in 545 patients who underwent D2 or D3 lymphadenectomy from June 1988 to December 2002.ResultsUpper third early cancers have shown an involvement of N2 celiac nodes in 25%. In advanced cancers, there was a high frequency of metastasis in the right gastroepiploic (from 10% in T2 to 50% in T4) and in the paraaortic nodes (26% in T2, 32% in T3, 38 % in T4). N3 left paracardial nodes involvement was observed in an important share of middle third tumors (17% in T3, 36% in T4). Splenic hilum nodes metastasis were common in T3 and T4 cancers located in the upper (39%) and middle (17%) stomach. N2 nodal involvement was frequent in lower third advanced cancers. Metastasis in M left paracardial and short gastric nodes were observed in a small percentage of cases.ConclusionGiven the nodal diffusion in our gastric cancer patients, extended lymphadenectomy is still a rationale to obtain radical resection.

Classification of lymph node metastases from carcinoma of the stomach: Comparison of the old (1987) and new (1997) TNM systems

Abstract. The pN classification of gastric cancer is currently based on the distance of metastatic nodes from the primary tumor (TNM—1987). The UICC (Union Internationale Contre le Cancer) has recently proposed a new classification system based on the number of the involved nodes (TNM—1997). The present prospective study is aimed at verifying whether the two classifications (1) assign approximately a similar rank to individual patients and (2) give comparable prognostic information. The Cox regression model was used to evaluate the prognostic significance of either the distance or the number of positive nodes, controlling for sex, age, site, histology and depth of tumor invasion, in a group of 175 patients who underwent curative surgery for gastric cancer from March 1988 to October 1997. Among the patients classified as N1 and N2 according to TNM—1987, 81.8% (36/44) and 35.8% (19/53), respectively, were coded as N1 and N2 by the new classification. The survival probabilities of N1 and N2 categories were similar in both classifications. The N2 category of TNM—1987 comprised also 10 cases with >15 positive nodes (N3 category of TNM—1997), who presented a large excess mortality (RR = 35.14 with respect to N0). When the site and number of positive nodes are combined in a new variable, both appear to be important from a prognostic point of view. Both anatomic location and number of nodes with metastasis are important predictors of survival in gastric cancer patients. Caution should be used when replacing the old classification with the new one, as they group patients in a different way.

Nodal abdominal spread in adenocarcinoma of the cardia. Results of a multicenter prospective study

Background. Precise knowledge of the abdominal nodal spread of cardia adenocarcinoma in relation to the depth of invasion of the tumor and its longitudinal extension may be very important for the surgeon as a guide in choosing the type of resection and lymphadenectomy. Methods. The frequency of node metastases in each abdominal station of the first and second tier was prospectively studied in 101 patients with type II and III cardia cancer (defined as approved by the consensus conference held during the second International Gastric Cancer Conference in Munich in April, 1997) who underwent total gastrectomy with D2 lymphadenectomy during the period January 1994 to April 1998. Lymph nodes were retrieved immediately after operation by the surgeon and assigned to the appropriate station according to the classification of the Japanese Research Society for Gastric Cancer. Results. In early gastric cancer, of both type II and type III, lymph node involvement was limited to the perigastric nodes of the upper half of the stomach and to the lymph node station of the celiac trunk. In advanced cancers, whether of type II or type III, there was a fairly high frequency of metastases to the perigastric nodes of the lower half of the stomach; there was also high frequency of metastases at N2 stations, without differences in frequency between pT2 and pT3 tumors (staged according to the classification of the Japanese Research Society for Gastric Cancer). Conclusions. The results of our study provide evidence for the need to perform a total gastrectomy with D2 lymphadenectomy in all patients with advanced cardia cancer type II or type III. In early cancers, a less extensive resection (proximal gastrectomy) with D2 lymphadenectomy may be indicated.

Multivisceral Resection for Locally Advanced Gastric Cancer: An Italian Multicenter Observational Study

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.

Subtotal versus total gastrectomy for T3 adenocarcinoma of the antrum

BackgroundThe role of subtotal or total gastrectomy in the treatment of advanced gastric cancer of the antrum with serosal invasion was investigated.MethodsThe investigation involved 117 patients with a cancer of the lower third of the stomach invading the serosa (pT3) who underwent R0 resection with at least D2 lymphadenectomy between 1988 and 1998 at three different Italian centers. The choice of surgical procedure (40 total gastrectomies and 77 subtotal gastrectomies) was based on the preference of the surgeon; none of the patients underwent splenectomy. The Cox regression model was used to evaluate the prognostic significance of the type of surgery (subtotal versus total gastrectomy), controlling for age, sex, histology, nodal involvement, and surgical center.ResultsThe morbidity and mortality rates did not vary significantly according to the type of surgery. Patients undergoing subtotal gastrectomy presented a better disease-related survival than patients undergoing total gastrectomy (P = 0.011): the median survival times were, respectively, 38 months and 23 months, and the overall cumulative 5-year survival rates (95% confidence intervals [CI]) were, respectively, 36% (22%–50%) and 22% (11%–37%). On univariate analysis, the relative risk (RR) of disease-related death was 1.84 (1.14–2.97) after total gastrectomy, with respect to subtotal gastrectomy. This difference was blunted on multivariate analysis (RR, 1.66; 0.99–2.78): in the final model, only nodal metastasis was a significant prognostic factor, while type of surgery had a borderline significance (P = 0.057).ConclusionsSurvival after subtotal gastrectomy is not lower than that after total gastrectomy in patients with tumor of the antrum invading the serosa.

Surgical Site Infections in an Italian Surgical Ward: A Prospective Study

BACKGROUND Surgical site infection (SSI) remains a major cause of morbidity and death. This study analyzed the results of surveillance to evaluate the incidence, risk factors, and characteristics of SSI in patients who underwent an operation in a typical Italian surgical ward. METHODS A group of 1,281 patients operated on from August 2005 to December 2007 underwent prospective and direct observation of incisions by a surgeon according to the U.S. Centers for Disease Control and Prevention (CDC) National Nosocomial Infections Surveillance (NNIS) method. The minimum follow-up was 30 days. A locally-modified risk index score (LRI) based on the NNIS was calculated for each patient, using as a cut point the 75(th) percentile of the duration of surgery (in minutes) for that particular procedure. RESULTS Seventy-six patients were affected by incision site infection, and the SSI rate was 5.9%. Thirty-four (2.6% of the series) were superficial incisional, 32 (2.5%) deep incisional, and 10 (0.8%) organ/space SSIs. An increasing value of the LRI was significantly (p < 0.05) related to an increasing risk of infection. The SSI rates were 0.6%, 3.7%, 7.3%, and 26.8% for LRI value of M = - 1, 0, 1, and >or=2, respectively. Obesity (body mass index >30 kg/m(2)), diabetes mellitus, and emergency surgery were associated with a higher risk of infection by multivariable analysis independent of the LRI. CONCLUSIONS The NNIS method can be useful for SSI surveillance and monitoring in single surgical wards. Longer operations, diabetes mellitus, and obesity increase the risk of SSI, as does performance of surgery in an emergency situation.