Luca Saragoni

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.

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.

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.

Fecal multiple molecular tests to detect colorectal cancer in stool.

BACKGROUND & AIMS Evaluation of molecular alterations in fecal DNA is a potential, noninvasive, alternative tool for the detection of colorectal cancer. We analyzed a large panel of molecular alterations involved in tumor transformation and progression to define their single diagnostic contribution in terms of sensitivity, cost, and time required to carry out the different tests. METHODS DNA was analyzed in stool from 38 healthy individuals and in paired stools and primary lesions from 56 patients with colorectal cancer. p53 exons 5-8, K-ras exons 1-2, four fragments of adenomatous polyposis coli (APC) exon 15, and 5 microsatellite loci were analyzed. Moreover, DNA amplification was evaluated for 4 exons of both p53 and APC. RESULTS K-ras (34%) and p53 (34%) mutations were the most frequent alterations in tumors, followed by microsatellite instability (13%) and APC mutations (13%). The most frequent event in stool was DNA amplification (51%), followed by alterations of K-ras (11%), p53 and microsatellite instability (6%), and APC (2%). K-ras and p53 gene mutations increased the capacity of DNA amplification to detect tumor cells by 8%. CONCLUSIONS K-ras and p53 gene mutations were the most frequent alterations observed in stool from patients with colorectal cancer, but DNA amplification was even more frequent, being present in more than half of patients. If these preliminary results are confirmed in a prospective study on a larger case series, this approach could be used for noninvasive colon cancer diagnosis in screening programs.

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.

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.

Lymph Node Micrometastases in Early Gastric Cancer and Their Impact on Prognosis

While the presence of lymph node metastases in early gastric cancer (EGC) is the most significant prognostic factor, the relevance of lymph node micrometastases remains uncertain. The authors studied 5400 lymph nodes dissected from 300 patients treated surgically for EGC between 1976 and 1999, all of whom were histologically pN0. Micrometastases were defined as single or small clusters of neoplastic cells identifiable only by immunohistochemical methods. Lymph node micrometastases were observed in 30 of the 300 patients (10%). No significant correlation was observed between micrometastases and other clinicopathological characteristics. Analysis of overall survival showed no significant difference between positive or negative micrometastasis groups. The results of our study show that the presence of lymph node micrometastases in EGC does not influence patient prognosis.

c-kit and SCF Expression in Normal and Tumor Breast Tissue

Several studies have shown a role of the tyrosine kinase receptor, c-kit, and its ligand, SCF, during organogenesis, normal cell development and growth of some tumor histotypes. In breast cancer, studies using different methodologies have shown conflicting results. In the present study we analyzed c-kit and SCF in 14 normal mammary epithelia samples, in 16 in situ and in 75 invasive breast cancers. The expression of c-kit and SCF protein was analyzed by immunohistochemistry and mRNA expression was evaluated by in situ hybridization and reverse-transcriptase polymerase chain reaction (RT-PCR). The different methodologies gave somewhat different results.Using immunohistochemistry and in situ hybridization, protein and mRNA expression of c-kit and SCF were high in normal mammary gland, significantly lower in in situ and almost completely undetectable in invasive breast cancer. Conversely, using RT-PCR, mRNA expression was observed in normal tissue and in all pathologic lesions of mammary gland, probably due to the high sensitivity of the methodology or to the positivity of elements other than tumor cells expressing the receptor and/or its ligand.These results suggest that the c-kit/SCF pathway plays an important role in the maintenance of normal growth of mammary epithelium and that the process of malignant transformation is accompanied by their progressive loss. Furthermore, we demonstrated that different results are attributable to different methodologies and that morphologic approaches are the most reliable for defining the cellular source of c-kit or SCF expression.

Lymph node micrometastases in patients with early gastric cancer: experience with 139 patients.

AbstractBackground:Although lymph node metastases in patients with early gastric cancer (EGC) is an important prognostic factor, the prognostic relevance of lymph node micrometastases is still uncertain. Methods:The authors studied 1488 lymph nodes, which were histologically confirmed as pN0, dissected from 139 patients who were treated for EGC between 1976–1994. Micrometastases were defined as a single or small cluster of neoplastic cells identifiable only by immunohistochemical methods. Results:Lymph node micrometastases was observed in 24 of the 139 patients (17%). No significant correlation was observed between micrometastases and other clinicopathological characteristics. Analysis of overall survival showed no significant difference between the micrometastases positive and negative groups. Conclusion:The results of our study show that the presence of lymph node micrometastases in EGC does not have an influence on patient prognosis.

Multiple Myeloma and Work in Agriculture: Results of a Case-Control Study in Forlì, Italy

Objectives: To evaluate the relation between the exposure to specific pesticides in agricultural work and the risk of multiple myeloma (MM).Methods: A case-control study was conducted in the province of Forlì, Italy. Forty-six cases of MM (20 females, 26 males; mean age 64 years, range 40 to 74) identified through the Romagna Cancer Registry in the years 1987-90, and 230 age- and gender-matched controls from the general population were interviewed in-person using a structured questionnaire focused on exposure to pesticides and other occupational and nonoccupational variables.Results: Among nonoccupational factors, the education level and the altitude of the place of residence were related inversely to MM risk. First-degree familiarity for hematolymphopoietic neoplasias and previous herpes zoster diagnosis were associated positively with the disease. A nonsignificant increase in MM risk was observed among workers in agriculture as a whole (odds ratio [OR] = 1.31, 95 percent confidence interval [CI] = 0.62-2.74). An increased risk was associated specifically with the cultivation of apples and pears (OR = 1.75, CI = 1.05-2.91). As regards pesticide exposure, only the chlorinated insecticides were related to an increase in the risk of MM.Conclusions: This study suggests that agricultural work and exposure to pesticides have a role in the etiology of MM. Cancer Causes and Control 1998, 9, 277-283