Paola Bertocchi

Targeting VEGF-VEGFR Pathway by Sunitinib in Peripheral Primitive Neuroectodermal Tumor, Paraganglioma and Epithelioid Hemangioendothelioma: Three Case Reports

Sunitinib malate (Sutent™; Pfizer Inc., New York, N.Y., USA) is a small molecule kinase inhibitor with activity against a number of tyrosine kinase receptors, including vascular endothelial growth factor receptors, stem-cell factor receptor, and platelet-derived growth factor receptors alpha and beta. Sunitinib, registered for the treatment of renal cell carcinoma and gastrointestinal stromal tumors, has recently been approved for the treatment of patients with advanced pancreatic neuroendocrine tumors. Peripheral primitive neuroectodermal tumor (pPNET), paraganglioma (PGL) and epithelioid hemangioendothelioma (EHE) are rare tumors in which there is an overexpression of pro-angiogenic factors and in which a high intratumoral microvessel density is a significant poor prognostic factor. On the basis of this preclinical rationale and the lack of effective treatments in pre-treated advanced stages of these rare diseases, we report our interesting experience of pPNET, PGL and EHE treatment with sunitinib.

Management of potentially resectable colorectal cancer liver metastases

Colorectal cancer is a very common malignancy worldwide and development of liver metastases, both synchronous or metachronous, is a common event. Of all patients with metastatic colorectal cancer, up to 77% have a liver-only disease and approximately 10%-20% of patients with colorectal liver metastases are considered resectable at the time of diagnosis. Surgical resection of liver metastases remains the best treatment option and it is associated with a survival plateau and a 20%-25% of long-term survivors. Perioperative chemotherapy for resectable liver metastases may improve resecability of liver metastases and disease free survival, but its impact on overall survival is still unclear and more studies are needed. Moreover, preoperative chemotherapy can increase postoperative complications. Further studies are needed to define the role of adjuvant chemotherapy after a R0 resection of liver metastases and to define the criteria for a better selection of patients candidate to hepatectomy. New strategies such as targeted therapies are emerging with promising results. Optimal management requires a multidisciplinary approach, local and systemic, but it is a still pending question. Colorectal liver metastases represent a major challenge for oncologists and surgeons. In this review will be analyzed available data about assessment and management of the patients with potentially resectable colorectal liver metastases.

Correlation among Streptococcus bovis, endocarditis and septicemia in a patient with advanced colon cancer: a case report

IntroductionOne of the bacterial agents that has been found to be associated with colorectal cancer is Streptococcus bovis, with 13% of infective endocarditis cases caused by this pathogenic species.Case presentationWe describe the case of a 57-year-old Caucasian man with infiltrating and ulcerating metastatic adenocarcinoma of the sigmoid colon. The patient was receiving second-line chemotherapy treatment and, on the eighth day of the second cycle, he developed a grade IV pancytopenia. We diagnosed a severe sepsis with positive blood cultures for Streptococcus bovis/gallolyticus with a secondary endocarditis.ConclusionsA recent study suggests that the majority of patients affected by colonic cancer have a Streptococcus bovis/gallolyticus colonization that becomes apparent as an overt infection only when immunosystem disorders or cardiac valve lesions occur. This correlation is important for involving more specialists in a correct and early diagnosis of this rare, but potentially fatal, complication.

The Emerging Role of NRAS Mutations in Colorectal Cancer Patients Selected for Anti-EGFR Therapies

Colorectal cancer (CRC) is one of the most common cancers worldwide. Despite the improvement in overall survival (OS) due to new treatments and targeted therapies alone or in combination with chemotherapy up-to-date, little is known about cellular mechanisms, both of primary and acquired resistance of CRC to anti-Epidermal Growth Factor Receptor (EGFR) antibodies. EGFR is characterized by tyrosine kinase activity and occupies a key-role in the control of cellular transduction pathways. Its activation triggers both the RAS-RAF and PIK3CA pathways and is required to promote cell growth, differentiation, proliferation, and invasion. Cetuximab and panitumumab are both monoclonal antibodies (MoAbs) directed against the extracellular domain of EGFR, thus leading to inhibition of the downstream signaling pathways. Mutations in oncogene Kirsten-RAS (KRAS) are frequently associated with resistance to anti-EGFR therapy. However, a significant number of KRAS wild-type (WT) tumors fail to obtain disease control with anti-EGFR agents. Therefore, additional biomarkers of response/resistance to these drugs such as BRAF, NRAS, PIK3CA and PTEN have been investigated. This review will point attention on Neuroblastoma-RAS (NRAS) status in metastatic CRC (mCRC) patients (pts) selected for anti-EGFR therapy.

Tyrosine Kinase Inhibitors in EGFR-Mutated Large-Cell Neuroendocrine Carcinoma of the Lung? A Case Report.

Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a high-grade carcinoma belonging to the neuroendocrine tumors of the lung and is different from typical lung large-cell carcinoma. It represents about 3% of all pulmonary malignancies and is characterized by neuroendocrine cytologic features. The treatment usually is platinum-based chemotherapy, however the outcome remains poor. Therefore new therapeutic options are needed. Tyrosine kinase inhibitors have demonstrated greater efficacy and better tolerability than standard chemotherapy in non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations. EGFR gene mutations were also rarely identified in LCNEC. We report a patient with lung LCNEC activating EGFR mutations who showed an impressive response to gefitinib.

Thyroid carcinoma showing thymus-like differentiation: Case presentation of a young man

Ectopic thymic tissue can be present in the thyroid gland and a carcinoma showing thymus-like differentiation (CASTLE) may arise from such tissue. We are reported the case of a 26-year-old man with CASTLE, with cervical subcutaneous nodules relapse, who showed a good response to treatment with surgery, chemotherapy and radiotherapy. The problematic aspect of this case was the diagnosis; only on review were we able to make a final diagnosis. CASTLE is a very rare neoplasm. It is important to differentiate this cancer from others tumors such as primary or metastatic squamous cell carcinoma of the head and neck or squamous cell thyroid carcinoma, because the therapy and prognosis are different. Diagnosis is complicated and requires careful histological analysis (CD5- and P63-positive with presence of Hassalls corpuscles); unfortunately there is no gold standard treatment so, in this case, we administered a sandwich of chemotherapy and radiotherapy.

Oxaliplatin-induced lung toxicity. Case report and review of the literature.

Rapidly developing pulmonary fibrosis associated with the use of the anti-cancer drug oxaliplatin has been reported mainly by Asiatic literature as isolate case reports. This rare but potentially fatal side effect has neither identified risk factors nor established treatment guideline. We report here a new clinical case concerning a patient with advanced gastric cancer treated with the oxaliplatin-based FOLFOX regimen along with a review of the literature as well as a discussion of emerging experimental treatment mainly based on imatinib.

Primary Osteosarcoma of the Breast: A Case Report

Introduction. Primary osteosarcoma of the breast is a rare soft-tissue form of osteosarcoma without involvement of the skeletal system. Due to the rarity of the disease, its clinical features and optimal treatment remain unclear. Case Presentation. This case report deals with a 62-year-old woman with pure osteosarcoma of the breast. Conclusions. The prognosis of primary osteosarcoma of the breast is poor. Recurrence is frequent, and it is often associated with haematogenous spread of the disease to the lung. Treatment follows the model of sarcomas affecting other locations and must be planned in a multidisciplinary fashion. Adjuvant chemotherapy should be considered for patients with tumors showing aggressive features.

Assessing cancer caregivers' needs for an early targeted psychosocial support project: The experience of the oncology department of the Poliambulanza Foundation.

OBJECTIVEnCaregivers play a key role in the management of patients with cancer. However, some studies have suggested that caregivers have even more unmet needs than the patients.nnnMETHODnTo better identify the needs and changes in the lifestyles of the caregivers in our practice and to plan a targeted support project to decrease caregiver burden, we administered the Caregivers QoL Index-Cancer (CQoLC) to 200 consecutive caregivers. This questionnaire assesses psychological well-being, the relationship with healthcare professionals, administration of finances, lifestyle disruption, and positive adaptation.nnnRESULTSnOur data showed that being a caregiver to a patient with metastatic disease negatively affected females mostly with regard to mental and emotional burden, while men complained more about their sexual life (42.3 vs. 33.6%), although this result was not significant. Some 93.5% of caregivers reported that they were pleased with their role, while 83.4% were concerned about financial difficulties.nnnSIGNIFICANCE OF RESULTSnWe strongly believe that early supportive care directed not only at patients but also to caregivers may improve the quality of life (QoL) in this population. We are currently developing a targeted support project to decrease caregiver burden.

Blind Snipers: Relevant Off Target Effects of Non-chemotherapeutic Agents in Oncology: Review of the Literature.

In recent years an increasing attention is focused on the potential effects of drugs on cancer incidence and/or cancer survival. Many medications of common use, developed for a variety of medical non-cancer situations, have been found to have potential anti- cancer effects. In this article, we performed an overview of the literature evidence for several commonly used non-cancer medications, such as aspirin, beta-blockers, metformin and other anti- diabetics, cardiac glycosides, anticoagulant heparin, statins, psychotropic drugs, vitamins, calcium and estrogens which have been shown to have anticancer effects, in observational and experimental studies. A huge amount of data supports the idea that a few of these commonly used medicines could decrease cancer death-rate, particularly aspirin, statins and metformin, crosswise different types of cancer. To date, no mature data are available from randomized and prospective trials; perhaps, the results of some studies underway will allow us to answer some questions on the possible use of these drugs in our clinical practice in primary and secondary prevention, or even in adjuvant setting.