Molecular biology of sporadic gastric cancer: prognostic indicators and novel therapeutic approaches

Both the availability of multiple treatment modalities and novel therapeutic targets make the correct prognostic stratification and the identification of truly predictive factors an issue of major debate in gastric cancer. Along with "classic" prognostic factors such as those related to the diffusion of the tumour at diagnosis (i.e., depth of gastric wall infiltration, locoregional lymph nodes or distant metastases) or those concerning the pathologic characteristics of the tumour, other, innovative, factors should be considered if a better definition of the characteristics of the tumour is to be given. These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR). Some of those putative prognostic indicators can also be considered predictive of response to therapy as they are a molecular target either to chemotherapeutics (i.e., thymidilate synthase that is targeted by 5FU) or to a new class of antineoplastic molecules (i.e., c-erb B-2 targeted by trastuzumab, COX-2 by NSAIDs, matrix metalloproteinases, EGFR and VEGFR by specific inhibitors).     

Increasing trends of cervical adenocarcinoma incidence in Central Italy despite Extensive Screening Programme, 1985-2000

Incidence rates of adenocarcinoma of the uterine cervix have been reported to be increasing in several countries, but not in Italy. The aim of the present study was to analyse trends in cervical cancer incidence by histological type in two districts of Central Italy (Florence and Prato), covered by the Tuscany Cancer Registry (RTT), where cytological screening had been available since the 1970s. Incident cervical cancers during 1985-2000 were 1012. Estimated Annual Percent Change (EAPC) by age-groups and histological type were computed. Incidence increased for adenocarcinoma (EAPC = +5.7%; 95% confidence interval (CI)+2.8; +8.6); whereas, it decreased for squamous cancer (EAPC = -1.9%; 95% CI-3.8; 0) and for other or not specified types (EAPC = -4.4%; 95% CI-10.0; +1.5). Adenocarcinoma increased significantly among younger women (<55 years) but not among older ones, whereas squamous cell cancer decreased among older women only. The burden of cervical cancers might increase in the future if no specific preventive strategies for adenocarcinoma are implemented.     

Immunodeficiency in different histotypes of radically operable gastrointestinal cancers

Cell-mediated immunodeficiency, with Total and T lymphocytes count decrease, is well established in cancer patients and it predicts a poor prognosis and poor survival rates. Furthermore, major surgery induces a transient immunodeficiency, too. Nevertheless, cell-mediated immunity in pancreatic cancer, which has a very poor prognosis, has not been completely outlined. Aim of this study is to evaluate the cell-mediated IL-2 dependent immune status in operable pancreatic cancer patients and to compare it with other gastrointestinal tumors. One hundred and twenty-one cancer patients (22 pancreatic, 48 gastric and 51 colorectal), with a median age of 66 years (range 42-83), 55 males and 66 females, were enrolled. Total lymphocyte count and lymphocytes subset (T helper count - CD4+) were assessed preoperatively and on the 14th and 50th postoperative day. Results obtained were compared between the groups and related to nodal involvement (N0 versus N+). Colorectal and gastric cancer patients showed quantitative lymphocyte deficiency at baseline in 29% and 41% of cases, respectively. Fourteen days after surgery values below normal range were found in 44% and 54% (Total) and 53% and 67% (T helper), respectively. Recovery of postoperative surgery-related lymphocytopenia occurred late only in patients with normal count at baseline. According to regional nodal involvement (pN0/N+) T helper deficiency was significantly more frequent in patients with nodal involvement than in patients without. In pancreatic cancer, percentage of immunodepressed patients at baseline was higher compared to the other two groups (71%). Lymphocyte count was significantly different between pancreatic and gastric/colorectal cancer, reaching a statistical significance at baseline and on the 14th and 50th postoperative day. No differences of T helper deficiency were noted according to nodal involvement (N0 versus N+) neither at baseline nor in the postoperative period. In conclusion, the degree of immunosuppression varies among different tumor types: since initial stages of disease, immunodepression was significantly greater in pancreatic cancer which should be considered always a systemic disease even in early stages and indipendently from the nodal involvement and from tumor load.     

Radiation therapy of breast cancer. Reasoned approach to a clinical case

The case of a patient undergoing quadrantectomy of lower quandrants of the right breast and ipsilateral axillary lymph node dissection for breast cancer followed by adjuvant radiotherapy is discussed. The stage of the disease and prognostic factors are analyzed for prognosis. Comorbidities ruled out chemotherapy. Radiation therapy was planned followed by clinicoinstrumental controls. After the second control ipsilateral costal bone metastases were observed; radiation therapy for palliation was prescribed.     

Sil overexpression in lung cancer characterizes tumors with increased mitotic activity

Sil (SCL interrupting locus) was cloned from the most common chromosomal rearrangement in T-cell acute lymphoblastic leukemia. It is an immediate early gene whose expression is associated with cell proliferation. Sil protein levels are tightly regulated during the cell cycle, reaching peak levels in mitosis and disappearing on transition to G1. A recent study found Sil to be one of 17 genes whose overexpression in primary adenocarcinomas predicts metastatic spread. We hypothesized that Sil might have a role in carcinogenesis. To address this question, we utilized several approaches. Using a multitumor tissue array, we found that Sil protein expression was increased mostly in lung cancer, but also at lower levels, in a subset of other tumors. Microarray gene expression analysis and immunohistochemistry of lung cancer samples verified these observations. Sil gene expression in lung cancer correlated with the expression of several kinetochore check-point genes and with the histopathologic mitotic index. These observations suggest that overexpression of the Sil gene characterizes tumors with increased mitotic activity.     

The epidemiology of fatty liver

There are insufficient data available on the epidemiology of fatty liver to design a complete and correct view of the prevalence, incidence and natural history of this disorder. This article, mainly based on the revision of recently published papers in this field, attempts to give an overview of the current findings on the epidemiology of fatty liver worldwide. The possible factors involved in the development of fat accumulation in the liver, and their potential role in the progression of the disorder will be also addressed.