Enrico Basso

Focus on genetic and epigenetic events of colorectal cancer pathogenesis: implications for molecular diagnosis

Originally, colorectal cancer (CRC) tumorigenesis was understood as a multistep process that involved accumulation of tumor suppressor genes and oncogenes mutations, such as APC, TP53 and KRAS. However, this assumption proposed a relatively limited repertoire of genetic alterations. In the last decade, there have been major advances in knowledge of multiple molecular pathways involved in CRC pathogenesis, particularly regarding cytogenetic and epigenetic events. Microsatellite instability, chromosomal instability and CpG island methylator phenotype are the most analyzed cytogenetic changes, while DNA methylation, modifications in histone proteins and microRNAs (miRNAs) were analyzed in the field of epigenetic alterations. Therefore, CRC development results from interactions at many levels between genetic and epigenetic amendments. Furthermore, hereditary cancer syndrome and individual or environmental risk factors should not be ignored. The difficulties in this setting are addressed to understand the molecular basis of individual susceptibility to CRC and to determine the roles of genetic and epigenetic alterations, in order to yield more effective prevention strategies in CRC patients and directing their treatment. This review summarizes the most investigated biomolecular pathways involved in CRC pathogenesis, their role as biomarkers for early CRC diagnosis and their possible use to stratify susceptible patients into appropriate screening or surveillance programs.

Efficacy and safety analysis of once per cycle pegfilgrastim and daily lenograstim in patients with breast cancer receiving adjuvant myelosuppressive chemotherapy FEC 100: a pilot study.

Background Neutropenia is a common toxicity in patients receiving myelosuppressive chemotherapy. In this prospective pilot study, we compared the efficacy and safety profiles of pegfilgrastim administered subcutaneously once per cycle and lenograstim administered subcutaneously daily six times per cycle, for primary neutropenia prophylaxis in women with breast cancer receiving adjuvant anthracycline-based chemotherapy. Materials and methods Twenty women were enrolled. All patients received epirubicin 100 mg/m2 with 5-fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and every 21 days thereafter, according to the FEC 100 chemotherapy regimen. Eight patients received a single dose of pegfilgrastim on day 2, while 12 patients were treated with daily administration of lenograstim from days five to ten. Absolute neutrophil count and duration of grade 3–4 neutropenia were monitored using seriated blood samples. The incidence of bone pain was evaluated using the visual analog scale (VAS). Results The incidence of grade 3–4 neutropenia was 75% in patients who received pegfilgrastim, and 25% in patients who received lenograstim. One case of febrile neutropenia was shown in pegfilgrastim patients. The mean duration of grade 3–4 neutropenia was 2 days in pegfilgrastim group versus 1.4 days in the lenograstim group. Bone pain was present in 37.5% of pegfilgrastim patients versus 58.3% of lenograstim patients. The mean duration of bone pain in the pegfilgrastim group was 4 days versus 6 days in the lenograstim group. Conclusion In our experience, a single injection of pegfilgrastim was less effective for controlling neutropenia than six daily injections of lenograstim. The safety profiles of pegfilgrastim and lenograstim were similar with a lower incidence of bone pain in patients treated with pegfilgrastim.

Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC)

Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features.

A 68-year-old Caucasian man presenting with urinary bladder lymphoepithelioma: a case report

IntroductionLymphoepithelioma is a very rare form of malignant tumor originating from epithelial line cells. Its occurrence has potential clinical, therapeutic and prognostic implications. In the present report we describe an unusual case of bladder cancer with two different histological varieties: transition cell carcinoma and lymphoepithelioma-like carcinoma. Lymphoepithelioma-like carcinoma of the bladder has only been rarely reported in the literature to date.Case presentationWe present the case of a 68-year-old Caucasian man who, after occurrence of hematuria, underwent transurethral resection of a bladder tumor. The results of a histological examination confirmed a high-grade non-muscle-invasive pT1 lymphoepithelioma-like carcinoma of the urinary bladder, associated with a concurrent high-grade transition cell carcinoma. After analyzing the histological features, our patient was subjected to treatment with intra-vesical instillations of bacillus Calmette-Guérin. Our work stresses that diagnosis and therapeutic approaches can be difficult and controversial, especially in the early stages of this rare carcinoma.ConclusionsThis report emphasizes the importance of extending our knowledge and experiences regarding this uncommon carcinoma. Further studies are needed to better understand this rare disease and define more accurate diagnostic and therapeutic strategies.

382 Efficacy, Safety Profiles and Cost-effectiveness Analysis of Pegfilgrastim and Lenograstim in Patients with Non Metastatic Breast Cancer Receiving Adjuvant Myelosuppressive Chemotherapy

Background: This occupational therapy doctoral research presentation reports on life with lymphoedema post-breast cancer treatment, particularly in relation to women’s self-perceived imposition of restrictions associated with conservative treatment protocols and the implications of this for compliance with treatment regimens. Material and Methods: A longitudinal narrative approach was used to examine the lived experience of breast cancer from the perspectives of seven Irish women over a three year period. In-depth semi-structured interviews were recorded and transcribed verbatim and then analysed using Interpretative Phenomenological Analysis (IPA) in order to explore the participants’ own sense-making of their experiences. Results: These indicate that compliance with conservative treatments prescribed for lymphoedema of the upper arm associated with breast cancer treatment is partial, because of perceived conflict with the performance of valued roles and activities (occupations) that have subjective preferential status and a higher priority for participants. Results are supported with and illustrated by the use of verbatim quotes from participants. Conclusion: Rehabilitation professionals need to seek out the likely factors that will influence risky choice-making behaviours in relation to lymphoedema self-management and to further include targeted prospective advice on predictable and anticipated factors such as performance of valued roles and important activities, in order to assist breast cancer survivors affected by lymphoedema to more fully comply with conservative treatment regimens. Such an anticipatory approach can prevent exacerbation of lymphoedema of the affected upper limb by promoting prospective problem-solving by women prior to engagement in their meaningful activities of daily living.