Synchronous hepatic metastasis and metachronous Krukenberg tumor from advanced colon cancer. A case report with an unexpected disease-free survival.

BACKGROUND: In the international literature we have never found a long survival in patients treated for a colon cancer with synchronous hepatic metastases and for a metachronous Krukenberg tumor. PRESENTATION OF CASE: A 46-year old woman for an advanced colon cancer with a synchronous hepatic metastases was subjected to a left hemicolectomy and a resection of liver segment V (R0 resection; T4N2bM1; stage IVa according AJCC 2010). After one year a CT of the abdomen revealed an expansive formation of the left ovary. The patient was subjected to a bilateral ovariectomy, hysterectomy and hiperthermic intraperitoneal chemotherapy (HIPEC). The patient, after several cycles of adjuvant chemotherapy, is disease-free 13 years after surgery. DISCUSSION: To our knowledge, in the literature there do not appear to be cases of such disease-free survival. The survival of patient despite the prognostic indexes is discussed. The authors discus the importance of an adequate surgical treatment especially for liver metastases simultaneously treated to colon cancer. The authors also focus on chemotherapy (FOLFOX and then FOLFIRI) performed in a pre-biological era. Furthermore, the degree to which the HIPEC may have had an impact is still unknown, although it seems to be the gold standard for the treatment of the microscopic peritoneal neoplastic remnant. CONCLUSION: The authors emphasize that the long term survival in colon cancer with hepatic and ovarian metastases is possible as long as it has an adequate surgical approach, a tailored chemotherapy and an intensive follow-up. Most likely new prognostic markers will have to be identified.

Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer.

Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib.

Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies.

Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1]) and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK]) the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma.

Paraneoplastic cerebellar degeneration associated with ovarian cancer.

Paraneoplastic cerebellar degeneration (PCD) is a rare neurological disorder characterized by a widespread loss of Purkinje cells associated with a progressive pancerebellar dysfunction. PCD often precedes the cancer diagnosis by months to years. Here, we report the case of a 64-year-old woman who developed PCD symptoms, associated with high levels of anti-Yo antibodies, one year after a previous diagnosis of ovarian cancer. Clinical features, pathogenesis and treatment of PCD associated with cancer are discussed according to previous studies.

Molecular targeted therapy in melanoma: a way to reverse resistance to conventional drugs.

Cutaneous melanoma is the most aggressive skin cancer. Beside surgery, it is treated with chemotherapy and immunotherapy. However, many patients relapse after adjuvant therapy. The recent identification of several key molecular pathways implicated in the pathogenesis of melanoma is spreading development of a number of new translational targeted therapies which could play an important role in overcoming or minimizing resistance to chemotherapeutic drugs and proapoptotic therapies. This review summarizes environmental factors and the most significant molecular events involved in melanoma pathogenesis, disclosing mechanisms responsible for drug resistance and pointing out the clinical view for emerging targeted therapies. Standard therapies and an update on the current clinical trials are also described.

'Genetic profiling' and ovarian cancer therapy (review).

High variability observed among ovarian cancer patients in response to the same therapy and the related toxicity may be correlated to gene polymorphisms and genetic alterations affecting the metabolism of drugs commonly used to treat this tumor. Recent studies have shown a correlation between the polymorphisms characterizing GSTM1-T1 detoxifying enzymes and poor outcome in advanced ovarian cancer patients treated with platinum/paclitaxel-based chemotherapy. Multidrug resistance 1 (mdr-1) polymorphisms were found to be associated with resistance to paclitaxel treatment. Polymorphisms of MRP2, a protein involved in methotrexate, cisplatin and irinotecan active metabolite glucuronide transport, negatively affect platinum-based chemotherapy response. A similar occurrence has been observed with CYP1A1 Ile462Val and ercc1 C118T polymorphisms while patients who were carriers of MTHFR C677T polymorphism had a better response to methotrexate therapy, but an elevated risk of toxicity. Biological therapy with Bevacizumab, the anti-vascular endothelial growth factor has been shown to be less efficient in ovarian cancer patients carrying the polymorphism of the Interleukin-8 gene. Instead, polymorphisms in the XPD gene (Lys751Gln and Asp312Asn), a member of the nucleotide excision repair pathway, positively affects the response to therapy with carboplatin/paclitaxel. Therefore, the study of 'genetic profiling' is crucial to improving the clinician's ability to tailor effective therapy to the molecular profile of the patient while minimizing toxicities. This review describes clinical applications of the above genetic polymorphisms in ovarian cancer patients treated with platinum/paclitaxel-based chemotherapy.

Extrahepatic disorders of HCV infection: a distinct entity of B-cell neoplasia?

Some infectious agents have been associated with B-cell lymphoma development. In the last decades, it has been demonstrated that patients infected by hepatitis C virus (HCV) are more likely to develop B-cell non-Hodgkin's lymphoma (NHL) than those uninfected. The prevalence of HCV-infection among NHL patients is reported in this review of all Italian studies on NHL and HCV infection, both case-control and case series. From 18 studies, the prevalence of anti-HCV antibodies in 2736 NHL patients was 19.7% (range: 8.3-37.1%). The association of HCV-infection with each NHL histotype in case-control studies is discussed. Molecular mechanisms by which HCV infection promotes B-cell NHL development is also explored and indicate that HCV-associated lymphomas may be a distinct entity. Clarification of these mechanisms may improve diagnosis, classification and therapy of this subset of NHL. Finally, treatment of HCV-positive patients with lymphoproliferative disorders are herein summarized and further support the notion that HCV infection contributes to the development of these pathologic conditions.