Epigenetic control of gene expression: Potential implications for cancer treatment.

Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. Gene expression is regulated at various levels and not only in response to DNA modifications. Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. Methylation of several tumor suppressor gene promoters is responsible for their silencing and thus potentially sustain cancerogenesis. Similarly, histone deacetylation can lead to oncogene activation. mi-RNA are small (18-20 nucleotides) non-coding RNA fragments capable of inhibiting other m-RNA, ultimately altering the balance in oncogene and tumor suppressor gene expression. It has been shown that growth of several tumor types can be stimulated by epigenetic changes in various phases of cancerogenesis, and drugs able to interfere with these mechanisms can have a positive impact on tumor progression. As matter of fact, epigenetic changes are dynamic and can be reversed by epigenetic inhibitors. Recently, methyltransferase and histone deacetylase inhibitors have attracted the attention of researchers and clinicians as they potentially provide alternative therapeutic options in some cancers. Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth. Epigenetic inhibitors work alone or in combination with other therapeutic agents. To date, a number of epigenetic inhibitors have been approved for cancer treatment. The main challenge in the field of epigenetic inhibitors is their lack of specificity. In this review article we describe their mechanisms of action and potential in cancer treatment.

"Fast track surgery" in the north-west of Italy: influence on the orientation of surgical practice.

Fast track surgery is a peri-operative management model, including different strategies to improve patients' convalescence, avoid metabolic alterations, reduce complications, and shorten hospital stay. Prerequisite is coordination between different practitioners (surgeon, anaesthetist, nurse, nutritionist, physiotherapist). The purpose of our investigation is to understand the level of fast track surgery application in Piedmont and to evidence analogies and differences among departments. We projected an investigation proposing, to every surgery department in Piedmont, a multiple-choice questionnaire evaluating the level of fast track surgery peri-operative interventions' application. Data analysis was conducted in two points of view: the transversal one with an overview of answer's percentages, the longitudinal one correlating data through Pearson's index (r). We collected answers by 78 % of balloted departments (38 on 49). Transversal analysis, including the evaluation of percentages of each question, shows that intra-operative period is the most influenced by fast track principles, and that only 12 departments of 38 apply complete protocols. Longitudinal analysis, estimating the whole of each department's answers, demonstrates the absence of statistical significance in the correlation between fast track surgery application and territorial (r = 0.18), economic (r = 0.31), or age (r = 0.06) variables. Influence of fast track surgery is significantly present in our territory, even though it is not fully concretized in protocols. The choice of fast track depends on the instruction, the environment and the sensibility of each surgeon. Knowledge of geographic distribution of departments applying this model can be useful to organize common protocols, starting from more experienced hospitals.

[Surgical treatment of internal duodenal diverticulum. Report of 2 clinical cases]. / Terapia chirurgica del diverticolo duodenale interno. Presentazione di due casi clinici.

Internal duodenal diverticulum is a rare disease. Nowadays, less than 100 cases are reported in Western literature. Even if it is a pathology of malformative origin, the first clinical manifestations occur quite always during the III decade. Main symptom is a violent, suddenly arisen, abdominal colic, often associated with meals and with spontaneous remission. Frequency of accesses is variable in time; in most serious cases, colics are so close to cause a considerable reduction of nutrition. Among diagnostical means, very useful are Rx enema (that offers pathognomonical images) and endoscopy, by which the formation can be visualized directly and its connection with papilla can be delineated. In some rare cases, differential diagnosis has to be made with cystic dilatations of bile duct, and particularly with type III according to Alonso-Lej classification or choledochocele. When such a distinction is not possible, differential diagnosis will be made on the basis of histological examination of the type of mucosa present in the internal aspect of the diverticulum. Therapy of symptomatic forms is surgery. The technique of choice is transduodenal diverticulectomy. Cannulation of bile duct is a useful means to found the papilla during intervention, to protect duodenal suture in the postoperative period and to control it radiologically. Two cases of internal duodenal diverticulum operated on in the last 2 years are described and diagnostical and therapeutical items are discussed.