Enrico Maria Pasqual

Tamoxifen and its main metabolites serum and tissue concentrations in breast cancer women.

Because of a possible relationship between tamoxifen (T) concentrations and clinical effects, we initiated a preliminary investigation on serum and tissue concentrations of T and its main active metabolites, and 4-hydroxytamoxifen, in women with positive breast cancer estrogen receptor. One hundred forty-eight patients were studied: 80 were admitted for monitoring of therapeutic serum drug concentrations, 22 had tissue concentrations taken at surgery, and 46 patients had uterine mucosa levels measured at diagnostic hysteroscopy. Steady-state serum concentrations were reached after 1 month of continuous treatment, with desmethyltamoxifen being the highest represented derivative from the third week onward. There was no relationship between dose (in mg/kg body weight) and steady-state serum concentrations during therapeutic drug monitoring of patients. The highest tissue concentrations were observed in breast lymph-nodes, cancer tissue, and uterine mucosa. On the basis of these data, we speculate that T and its active metabolites may exert both a defensive role (ie, an obstacle to the diffusion of malignant cells through the local lymphatic system) and a harmful one (induction of uterine malignancies).

Surgical Treatment and Survival in Patients with Liver Metastases from Neuroendocrine Tumors: A Meta-Analysis of Observational Studies

Introduction. The role of hepatic resection in patients with liver metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is still poorly defined. Therefore, we examined the results obtained with surgical resection and other locoregional or systemic therapies by reviewing the recent literature on this topic. We performed the meta-analysis for comparing surgical resection of hepatic metastases with other treatments. Materials and Methods. In this systematic review and meta-analysis of observational studies, the literature search was undertaken between 1990 and 2012 looking for studies evaluating the different survivals between patients treated with surgical resection of hepatic metastases and with other surgical or nonsurgical therapies. The studies were evaluated for quality, publication bias, and heterogeneity. Pooled hazard ratio (HR) estimates and 95% confidence intervals (CI.95) were calculated using fixed-effects model. Results. We selected six studies in the review, five of which were suitable for meta-analysis. We found a significant longer survival in patients treated with hepatic resection than embolisation HR 0.34 (CI.95 0.21–0.55) or all other nonsurgical treatments HR 0.45 (CI.95 0.34–0.60). Only one study compared surgical resection with liver transplantation and meta-analysis was not feasible. Conclusions. Our meta-analysis provides evidence supporting the hypothesis that hepatic resection increases overall survival in patients with liver metastases from GEP-NETs. Further randomized clinical trials are needed to confirm these findings and it would be desirable to identify new markers to properly select patients for surgical treatment.

Curative versus palliative surgical resection of liver metastases in patients with neuroendocrine tumors: a meta-analysis of observational studies

BACKGROUND The role of surgical therapy in patients with liver metastases from neuroendocrine tumors (NETs) is unclear. In this study, the results obtained with curative or palliative resection, by reviewing recent literature and performing a meta-analysis, were examined. MATERIALS AND METHODS A systematic review and meta-analysis of observational studies published between January 1990 and October 2013 were performed. Studies that evaluated the different survival between patients treated by curative or palliative surgical resection of hepatic metastases from NETs were considered. The collected studies were evaluated for heterogeneity, publication bias, and quality. To calculate the pooled hazard ratio (HR) estimate and the 95% confidence interval (95% CI), a fixed-effects model was applied. RESULTS After the literature search, 2,546 studies were found and, among 38 potentially eligible studies, 3 were considered. We did not find a significant longer survival in patients treated with curative surgical resection of hepatic metastases when compared to palliative hepatic resection HR 0.40 (95% CI: 0.14-1.11). In one study, palliative resection of hepatic metastases significantly increased survival when compared to embolization. CONCLUSIONS Curative and also palliative surgery of NETs liver metastases may improve survival outcome. However, further randomized clinical trials are needed to elucidate this argument.

Microscopic peritoneal carcinomatosis in gastric cancer: Prevalence, prognosis and predictive factors

Peritoneal carcinomatosis (PC) is typically identified in advanced stage gastric cancer and is frequently considered to be an incurable disease. Along with macroscopic PC, microscopic PC may be diagnosed through pathological examination of tissue specimens and is not detectable during surgical intervention. The present study aimed to analyse the prevalence, prognostic value and predictive factors for microscopic PC. In the present retrospective study, data from patients with epithelial gastric cancer that were treated with curative intent surgery were examined. Patients with macroscopic PC were excluded. Additionally, the study population was divided into two groups based on the presence or absence of microscopic PC. The prevalence of microscopic PC was 5.5%. Microscopic PC exhibited a significant negative effect on overall survival. In addition, multivariate analyses revealed that the significant predictive factors for the presence of microscopic PC were adenocarcinoma of a diffuse type, lymphatic and vascular invasion, cancer location at the site of previous gastric surgery and a tumour extent >T2. In particular, the presence of lymphatic and vascular invasion was the most significant predictive factor. These results indicate that ≥5.5% of patients with gastric cancer who undergo surgery with a curative intent may benefit from more aggressive loco-regional treatment against microscopic PC at the time of surgery.

Surgical Indications, Timing, and Strategy in Non-colorectal Liver Metastases

Taking into consideration all primary solid tumors, the liver represents the most common site involved in distant metastasization, also due to its important blood reception from the majority of digestive organs. Despite the abundant literature and guidelines about colorectal liver metastases, there is still great debate about the treatment strategy in the case of non-colorectal ones. Therefore, in this chapter, we reviewed the treatment strategy and surgical indications for the most frequent non-colorectal liver metastases. In the case of neuroendocrine hepatic secondaries, the literature suggests that surgery should be always considered for patients with resectable hepatic disease, as this treatment results more likely to offer the best long-term outcome. For what concerns liver metastases from gastric cancer, surgical approach should always be undertaken if indications are appropriate, after a multidisciplinary discussion to plan an adequate multidisciplinary adjuvant treatment, a proper patient selection, and the exclusion of additional secondary tumors or extrahepatic metastases. Taking into consideration liver secondaries from breast cancer and their chemosensitivity, in the absence of brain and lung lesions, it can be considered a space for liver surgery, especially in the case of single lesions or a maximum of two lesions with dimensions within 3 cm. However, as the number of cancer survivors is progressively increasing and, with it, the number of patients affected by non-colorectal liver metastases, further randomized controlled trials are required in order to better define the benefit of hepatic surgery in these kinds of patients.