Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues.

Although biliary tract cancers are traditionally considered rare in Western countries, their incidence and mortality rates are rising worldwide. A better knowledge of the genomic landscape of these tumor types has broadened the number of molecular targeted therapies, including angiogenesis inhibitors. The role of immune checkpoint inhibitors (ICIs) could potentially change the first-line therapeutic approach, but monotherapy with ICIs has shown disappointing results in CCA.

Durvalumab in advanced cholangiocarcinoma: is someone knocking down the door?

Following the practice-changing results observed in several hematological and solid tumors, immunotherapy with immune checkpoint inhibitors (ICIs) has been tested in cholangiocarcinoma (CCA) patients. However, ICI monotherapy has had disappointing results in CCA, and phase I-III clinical trials have assessed whether combinatorial strategies including immunotherapy plus other anticancer agents may have a synergistic activity. The TOPAZ-1 trial has recently highlighted improved survival in CCA patients receiving first-line durvalumab plus gemcitabine-cisplatin compared with gemcitabine plus cisplatin alone, and several guidelines consider adding durvalumab to the reference doublet as standard of care.

Unexpected response to palliative radiotherapy for subcutaneous metastases of an advanced small cell pancreatic neuroendocrine carcinoma: a case report of two different radiation schedules.

Background: Skin metastases from pancreatic neuroendocrine carcinoma (PNEC) are rare and their palliative treatment is challenging. We report our experience in the multimodal management of one of the few reported cases of metastatic PNEC with multiple visceral and subcutaneous secondary lesions, focusing on the effectiveness of palliative radiotherapy for skin metastases.

Case Presentation: A 61-years old woman affected by a metastatic PNEC - with subcutaneous growing and bleeding secondary lesions (at the scalp, right scapular region and at the back of the left thoracic wall, respectively) - obtained a successful control of visceral metastases with the use of chemotherapy and an unexpected local response of her skin metastases with palliative radiotherapy.

Long-term survival in small cell lung cancer: a case report and review of the literature.

Small cell lung cancer (SCLC) represents approximately 13% of all newly diagnosed lung cancers. SCLC is a very aggressive disease characterized by early locoregional and distant metastases. The median survival is 14-16 months for patients with limited disease and 8-11 months for those with extensive disease, with 20-40% of patients with limited disease and 5% of patients with extensive disease alive at 2 years.

Circulating tumor cells: utopia or reality?

Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed.

B cells and HCV: an infection model of autoimmunity.

In addition to cause acute and chronic liver disease, hepatitis C virus (HCV) infection is frequently associated to autoimmune disorders, such as mixed cryoglobulinemia, primary glomerulonephritis, monoclonal gammopathy of undetermined significance and post-transplant proliferative disorders. Progression to malignant phenotype of B cells may be the consequence of additional genetic events or abnormal conditions resulting from modification of host cell genes involved in the control of oncogenes and oncoproteins. In this review, we will address the potential immune disregulatory mechanism(s) underlying HCV persistence.

Increased serum levels of the chemokine CXCL13 and up-regulation of its gene expression are distinctive features of HCV-related cryoglobulinemia and correlate with active cutaneous vasculitis.

Chemokine CXCL13, also known as BCA-1 (B cell-attracting chemokine-1) or BLC (B-lymphocyte chemoattractant), is a major regulator of B-cell trafficking. Hepatitis C virus (HCV) infection may be associated with B-cell dysfunction and lymphoproliferative disorders, including mixed cryoglobulinemia (MC). This study evaluates circulating levels of CXCL13 protein and specific mRNA expression in chronically HCV-infected patients with and without MC.

B-cell depletion in the treatment of mixed cryoglobulinemia.

A controlled study has been carried out to assess the efficacy of rituximab (RTX), a chimeric antibody that binds to the B-cell surface antigen CD20, in twenty patients with mixed cryoglobulinemia (MC) and HCV-positive chronic active liver disease, resistant to interferon-alpha (IFN-alpha) therapy. They received an intravenous infusion of 375 mg/m(2) RTX once a week for 4 consecutive weeks. Infusion of RTX had a good safety profile, and no severe side-effects were reported.

Clarithromycin-resistant genotypes and eradication of Helicobacter pylori.

Background: Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance.

Objective: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance.

Design: Post hoc subgroup study from a multicenter, randomized trial.