Circulating tumor cells count predicts survival in colorectal cancer patients.

BACKGROUND AND AIMS: Data on the potential of circulating tumor cells (CTC) count in predicting overall survival (OS) in patients with colorectal cancer are timely and worthy of interest. This study aimed to evaluate the prognostic role of CTC count in both localized and metastatic colorectal cancer patients. METHODS: Consecutive patients with histological diagnosis of colorectal cancer were enrolled. CTC count was performed, by using a quantitative immunofluorescence method, at baseline (T0) and 1 month following start of chemotherapy (T1). A CTC count <2 was considered negative, whilst a CTC level >/= 2 was positive. Overall survival was calculated accordingly. RESULTS: A total of 75 colorectal cancer patients were enrolled, including 54 stages I-III and 21 stage IV patients. Overall, 21 (28%) patients had a positive CTC count at baseline, and it was significantly associated with a worse prognosis as compared to a negative status (OS: 36.2 vs. 61.6 months; P = 0.002). CTC count remained positive after chemotherapy in 22.4% of the patients and it was an independent prognostic factor of OS (P = 0.03; Hazard Ratio: 3.55; 95% CI: 1.1-11.5). CONCLUSIONS: This study found that the presence of CTCs is associated with a reduced survival in colorectal cancer patients. Further studies aimed at testing such a predictive value in early stage colorectal cancer are awaited.

Metronomic chemotherapy for cancer treatment: a decade of clinical studies.

PURPOSE: Over the past few years, more and more new selective molecules directed against specific cellular targets have become available for cancer therapy, leading to impressive improvements. In this evolving scenario, a new way of delivering older cytotoxic drugs has also been developing. Many studies demonstrated that several cytotoxic drugs have antiangiogenic properties if administered frequently and at lower doses compared with standard schedules containing maximal tolerated doses (MTD). Such a new strategy, named metronomic chemotherapy, focuses on a different target: the slowly proliferating tumour endothelial cells. About 10 years ago, metronomic chemotherapy was firstly enunciated and hereafter many clinical experiences were published related to almost any cancer disease. This review analyses available studies dealing with metronomic chemotherapy and its combination with several targeted agents in solid tumours. METHODS: A computerized literature search of MEDLINE was performed using the following search terms: metronomic OR "continuous low dose" AND chemotherapy AND cancer OR solid tumours. RESULTS: Satisfactory results have been achieved in diverse tumour types, such as breast and prostate cancer or paediatric sarcomas. Moreover, many studies have reported that metronomic chemotherapy determined minimal toxicity compared to MTD chemotherapy. Overall, published series on metronomic schedules are very heterogeneous often reporting on retrospective data, while only very few studies were randomized trials. These limitations still prevent to draw definitive conclusions in diverse tumour types. CONCLUSIONS: Large well-designed studies are eagerly awaited for confirming the promises of metronomic schedules and their combinations with targeted molecules.

Tumors of ampulla of Vater: A case series and review of chemotherapy options.

Carcinomas of the Ampulla of Vater are rare tumors, accounting for 0.2% of gastrointestinal cancers. Compared with other biliary tract neoplasms, these tumors have a relatively favorable prognosis after surgical resection. Based on their epithelium of origin, two subtypes of ampullary carcinoma have been recently distinguished: intestinal and pancreatobiliary. This study evaluates histopathological features and outcomes of ampullary carcinoma and to compares the survival of these tumors to that of other biliary tract tumors. The chemotherapic options available for ampullary cancer are also reviewed. We analyzed data from 20 consecutive patients with ampullary carcinomas and 26 patients with other biliary tract carcinomas, observed in our Institution. Statistical analysis was performed by using either Fisher's exact test or χ(2) test for categorical variables. Median time of survival was calculated and compared using the Log-Rank test. Similar distribution of demographic characteristics and stage between ampullary and other biliary tract cancers was observed. Patients with ampullary cancer underwent surgery more frequently than other biliary cancers while chemotherapy and radiotherapy were used equally. In accordance with the literature, a longer median survival was observed in the group of ampullary carcinomas.

Chemotherapy for the biliary tract cancers: moving toward improved survival time.

BACKGROUND: The biliary tract carcinomas rank fifth in incidence among all gastrointestinal tumours. This group of tumours includes both cholangiocarcinoma and gallbladder carcinoma. Although surgery represents the main therapeutic option for these patients, both radiotherapy and chemotherapy could be used in a multidisciplinary approach. Several studies are currently available on the use of chemotherapy, including 5-fluorouracil, mitomycin C, methotrexate, doxorubicin and cisplatin or newer anticancer molecules, such as gemcitabine, capecitabine, oxaliplatin and irinotecan. However, the small sample size of most of these studies prevents generalization. DISCUSSION: We reviewed the available data on both chemotherapy and targeted therapies for biliary carcinoma. By using conventional chemotherapy, a response rate ranging from 10% to 40% has been reported. Although encouraging data emerged with the use of targeted therapies, further efforts are needed to improve treatment options for patients with biliary tract cancer.

Somatostatin receptor subtype 2 A (SSTR2A) and HER2 expression in gastric adenocarcinoma.

BACKGROUND: A possible anticancer role for somatostatin has been suggested. This study assessed the presence of somatostatin receptor subtype 2A (SSTR2A) in gastric cancer, correlating its expression with histological type, grade, human epidermal growth factor receptor 2 (HER2) expression, and disease outcome. MATERIALS AND METHODS: Gastric cancer tissues of 51 consecutive patients were collected for immunohistochemical assessment of both SSTR2A and HER2 expression. RESULTS: SSTR2A expression was observed in 38 (74.5%) cases. Prevalence of SSTR2A expression was significantly higher in well to moderately (G1-2) differentiated gastric cancer as compared to poorly (G3) differentiated tumors (96% vs. 52%; p<0.01), as well as in intestinal- than in diffuse-type cancer (97% vs. 20%; p<0.001). HER2 expression was positive in 18 (35%) patients, and it was associated with SSTR2A expression (r=0.50, p<0.001), being co-expressed in 17 (95%) out of 18 positive cases. RFS was significantly lower in patients with diffuse HER2 expression. CONCLUSION: This study demonstrated a co-localization between SSTR2A and HER2, potentially opening new therapeutic strategies for patients with gastric cancer.

Gastric mucosa alterations in first-degree relatives of gastric cancer patients.

BACKGROUND: First-degree relatives of gastric cancer patients have an increased risk of developing such neoplasia, and several alterations in gastric mucosa of these subjects have been described. On the other hand, both gastric cell hyperproliferation and abnormalities of adhesion molecules have been involved in gastric carcinogenesis. We studied gastric mucosa alterations in first-degree relatives of gastric cancer patients. PATIENTS AND METHODS: This prospective, case-controlled study enrolled 39 first-degree relatives of gastric cancer patients and 39 matched controls. Biopsy specimens obtained at endoscopy were used to assess epithelial cell proliferation plus E-cadherin and beta-catenin expression by immunohistochemical methods. H. pylori infection was assessed by histology and a rapid urease test. RESULTS: Gastric epithelial cell proliferation values were not significantly different between the patient and control groups. H. pylori infection significantly increased cell proliferation values both in patients and in controls, without a significant difference between the two groups. Moreover, cell proliferation values were significantly higher in cases harboring intestinal metaplasia than in those without it. Alterations of the adhesion molecules were described exclusively in those patients harboring intestinal metaplasia. In detail, a reduction of both E-cadherin and beta-catenin expression was observed in 8 (67%) out of 12 first-degree relatives and in 6 (67%) out of 9 controls with intestinal metaplasia (p = 0.4). These alterations were similarly distributed between H. pylori infected and uninfected cases. CONCLUSION: Our data showed that a family history of gastric cancer itself is not associated with gastric cell hyperproliferation. However, both cell hyperproliferation and alterations of adhesion molecules have been detected in those patients with intestinal metaplasia.

Relationship between beta-catenin expression and epithelial cell proliferation in gastric mucosa with intestinal metaplasia.

AIM: To investigate beta-catenin expression in patients with intestinal metaplasia, and to look for a possible relationship between beta-catenin expression and either epithelial proliferation values or Helicobacter pylori (H pylori) infection. METHODS: Twenty patients with complete type intestinal metaplasia were studied. beta-Catenin expression and epithelial cell proliferation in antral mucosa were assessed using an immunohistochemical analysis. H pylori infection was detected by histology and a rapid urease test. RESULTS: Reduced beta-catenin expression on the surface of metaplastic cells was detected in 13 (65%) out of 20 patients. Moreover, in eight (40%) patients intranuclear expression of beta-catenin was found. When patients were analyzed according to H pylori infection, the prevalence of both beta-catenin reduction at the cell surface and its intranuclear localization did not significantly differ between infected and uninfected patients. Cell proliferation was higher in patients with intranuclear beta-catenin expression as compared to the remaining patients, although the difference failed to reach the statistical significance (36+/-8.9 vs 27.2+/-11.4, P = 0.06). On the contrary, a similar cell proliferation value was observed between patients with reduced expression of beta-catenin on cell surface and those with a normal expression (28.1+/-11.8 vs 26.1+/-8.8, P = 0.7). H pylori infection significantly increased cell proliferation (33.3+/-10.2% vs 24.6+/-7.4%, respectively, P = 0.04). CONCLUSION: Both cell surface reduction and intranuclear accumulation of beta-catenin were detected in intestinal metaplasia. The intranuclear localization of beta-catenin increases cell proliferation. H pylori infection does not seem to play a direct role in beta-catenin alterations, whilst it significantly increases cell proliferation.

Alteration of E-cadherin expression in gastric mucosa: role of intestinal metaplasia and Helicobacter pylori infection.

BACKGROUND: Although E-cadherins have been involved in gastric carcinogenesis, their role in precancerous lesions, such as intestinal metaplasia, is still unclear. This study aimed to assess the role of both intestinal metaplasia and H. pylori infection on E-cadherin expression in gastric mucosa. PATIENTS AND METHODS: Twenty-one consecutive patients with intestinal metaplasia were enrolled to assess E-cadherin expression in metaplastic areas. Twenty further patients without intestinal metaplasia, with and without H. pylori, were enrolled to evaluate the role of the infection on E-cadherin expression. All patients underwent upper endoscopy and gastric biopsies were taken for histological and immunohistochemical assessment. RESULTS: A substantial reduction of E-cadherin expression in metaplastic areas was observed in 14 (67%) of the 21 patients, similarly in H. pylori-infected and uninfected patients (64% vs 71%, p=0.3). In the group without intestinal metaplasia, no reduction in E-cadherin expression was detected either in infected patients or in those without H. pylori infection. CONCLUSION: The data showed that intestinal metaplasia is associated with E-cadherin down-regulation, whereas H. pylori infection does not seem to play a direct role in this process.