H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amoxicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.
The immunogenicity of malignant melanomas has been recognized by the observed recruitment of tumor-specific cytotoxic T-cells (CTL), leading to the identification of several melanoma associated antigen (MAA). However, numerous strategies to treat melanoma with immunotherapy have resulted in only partial success. In this editorial, we discuss recent data related to the ability of tumors to elude immune responses. We therefore discuss different strategies to induce a clinically effective immune response. These approaches include 1) immunostimulation: including peptide/protein based vaccines, dendritic cell vaccines, and adoptive cell transfer; and 2) overcoming immunosuppression, including targeting of checkpoint molecules such as CTLA-4, circumventing the activity of Tregs, and assuring antigen expression by tumor cells (thwarting antigen silencing). Finally, we discuss recent advances in gene therapy, including adoptive therapy with engineered T cell receptors (TCRs). These issues lead to the conclusion that successful immunotherapy in malignant melanoma requires a combination of strategies aimed at both inducing immunostimulation and blocking immunosuppression.Melanoma, a highly malignant tumor of the pigmented cells, is a significant worldwide health concern. The 5-year survival for patients with involvement of regional lymph nodes is 35%, with fewer than 2% of patients with visceral metastatic disease alive at 5 years. Therapy with interferon alpha-2b (IFNalpha-2b), the only agent approved in the United States for adjuvant use in high-risk melanoma patients, has not shown consistent overall survival benefit in randomized trials and is associated with considerable toxicity. Conventional chemotherapy for unresectable metastatic disease does not improve survival, while patients with completely resected metastatic disease have a median survival of <20 months. Since there is clearly a need for more effective therapies in these high-risk patients and because steps towards new effective therapies against melanoma are currently being taken, we will focus on melanoma therapies to highlight the new immunotherapy strategies.While there is good reason to question the effectiveness of the host response against spontaneously arising tumors, there is clear evidence that specific immune cells are recruited to tumor sites. In fact, lymphocytic infiltration of tumors was first observed by Rudolf Virchow in 1863, before
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