Case Report Bilateral Breast Metastases from Vulvar Carcinoma: A Case Report and Literature Review

Vulvar carcinoma is a rare disease that accounts for 3-5% of all gynecologic malignancies. Breast represents an unusual site of metastasis and only a few cases are reported. We describe the first case of bilateral metastatic breast carcinoma of vulvar origin, at an 80-year-old female patient. Six months after treatment of her primary disease, she presented with bilateral metastatic squamous cell breast carcinoma. Diagnosis was based on clinical, radiological, and histological facts. Breast although rare is another potential site of metastasis in vulvar cancer and thus mammary gland examination should be considered in the follow-up of these patients. Differential diagnosis between primary and metastatic lesions is of utmost importance for appropriate management

Anti-CTLA4 monoclonal antibodies: the past and the future in clinical application

Recently, two studies using ipilimumab, an anti-CTLA-4 monoclonal antibody (mab) demonstrated improvements in overall survival in the treatment of advanced melanoma. These studies utilized two different schedules of treatment in different patient categories (first and second line of treatment). However, the results were quite similar despite of different dosage used and the combination with dacarbazine in the first line treatment. We reviewed the result of randomized phase II-III clinical studies testing anti-CTLA-4 antibodies (ipilimumab and tremelimumab) for the treatment of melanoma to focus on practical or scientific questions related to the broad utilization of these products in the clinics. These analyses raised some considerations about the future of these compounds, their potential application, dosage, the importance of the schedule (induction/manteinance compared to induction alone) and their role as adjuvants. Anti-CTLA-4 antibody therapy represents the start of a new era in the treatment of advanced melanoma but we are on the steep slope of the learning curve toward the optimization of their utilization either a single agents or in combination

ICOS regulates the generation and function of human CD4+ Treg in a CTLA-4 dependent manner

Inducible co-stimulator (ICOS) is a member of CD28/Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) family and broadly expressed in activated CD4+ T cells and induced regulatory CD4+ T cells (CD4+ iTreg). ICOS-related signal pathway could be activated by the interaction between ICOS and its ligand (ICOSL). In our previous work, we established a cost-effective system to generate a novel human allo-antigen specific CD4hi Treg by co-culturing their naïve precursors with allogeneic CD40-activated B cells in vitro. Here we investigate the role of ICOS in the generation and function of CD4hi Treg by interrupting ICOS-ICOSL interaction with ICOS-Ig. It is found that blockade of ICOS-ICOSL interaction impairs the induction and expansion of CD4hi Treg induced by allogeneic CD40-activated B cells. More importantly, CD4hi Treg induced with the addition of ICOS-Ig exhibits decreased suppressive capacity on alloantigen-specific responses. Dysfunction of CD4hi Treg induced with ICOS-Ig is accompanied with its decreased exocytosis and surface CTLA-4 expression. Through inhibiting endocytosis with E64 and pepstatin A, surface CTLA-4 expression and suppressive functions of induced CD4hi Treg could be partly reversed. Conclusively, our results demonstrate the beneficial role of ICOS-ICOSL signal pathway in the generation and function of CD4hi Treg and uncover a novel relationship between ICOS and CTLA-4. © 2013 zheng et al.published_or_final_versio

Current and Emerging Treatment Options for Castration-Resistant Prostate Cancer: A Focus on Immunotherapy

BACKGROUND: Castration-resistant prostate cancer is a disease with limited treatment options. However, the ongoing elucidation of the mechanisms underlying this disease continues to support the development of not only novel agents, but also innovative approaches. Among these therapies, immunotherapy has emerged as a promising strategy. DESIGN: This review article summarizes the most recent data from investigations of immunotherapies in castration-resistant prostate cancer (literature and congress searches current as of August 2011). RESULTS: Immunotherapeutic strategies such as passive immunization, vaccines, and particularly checkpoint blockade have demonstrated some efficacy as single agents. Elucidation of effective combinations of agents and drug regimens is ongoing but will require continued careful investigation, including the standardization of surrogate endpoints in clinical trials. CONCLUSIONS: It is hypothesized that the combination of immunotherapeutic agents with traditional and novel chemotherapeutics will potentiate the efficacy of the chemotherapeutics while maintaining manageable toxicity

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer

Systemic mastocytosis as a cause of severe osteoporosis in a young woman

We report a case of a 46-year-old woman suffering from 5 years of premenopausal osteoporosis due to systemic mastocytosis (SM). The only clinical symptom was severe back pain and restricted spinal movements resulting from the existing vertebral compression fractures. There were no skin lesions. Because of the severity of the case, nonresponse to the administered treatment, and the premenopausal initiation of her osteoporosis, a further investigation for an underlying cause was accomplished. Laboratory evaluations excluded metabolic or endocrinologic abnormalities. Serum tryptase was slightly elevated while urinary excretion of histamine was highly increased. A diagnostic bone marrow biopsy specimen was done and the patient fulfilled the diagnostic criteria for SM. SM should be included in the differential diagnosis in cases of unusually presented osteoporosis due to its significant morbidity and the existing treatment options. Copyright © 2010 by Lippincott Williams & Wilkins

Telemedicine in Shipping Made Easy - Shipping eHealth Solutions

This research study aims to highlight the main weak and strong points of existing telemedicine technologies as well as to propose the creation of a new, innovative and financially efficient system of telemedicine which can be used in the maritime industry. In addition to main applications and details of the new system, the article describes and expounds on necessary equipment as well as personnel training. © 2020, Springer Nature Switzerland AG

Bilateral Breast Metastases from Vulvar Carcinoma: A Case Report and Literature Review

Vulvar carcinoma is a rare disease that accounts for 3–5% of all gynecologic malignancies. Breast represents an unusual site of metastasis and only a few cases are reported. We describe the first case of bilateral metastatic breast carcinoma of vulvar origin, at an 80-year-old female patient. Six months after treatment of her primary disease, she presented with bilateral metastatic squamous cell breast carcinoma. Diagnosis was based on clinical, radiological, and histological facts. Breast although rare is another potential site of metastasis in vulvar cancer and thus mammary gland examination should be considered in the follow-up of these patients. Differential diagnosis between primary and metastatic lesions is of utmost importance for appropriate management

Timing of laparoscopic cholecystectomy for acute cholecystitis: A prospective non randomized study

AIM: To study the timing of laparoscopic cholecystectomy for patients with acute cholecystitis. METHODS: Between January 2002 and December 2005, all American Society of Anesthesiologists classification (ASA) I, II and III patients with acute cholecystitis were treated laparoscopically during the urgent (index) admission. The patients were divided into three groups according to the timing of surgery: (1) within the first 3 cl, (2) between 4 and 7 d and (3) beyond 7 d from the onset of symptoms. The impact of timing on the conversion rate, morbidity and postoperative hospital stay was studied. RESULTS: One hundred and twenty-nine patients underwent laparoscopic cholecystectomy for acute cholecystitis during the index admission. Thirty six were assigned to group 1, 58 to group 2, and 35 to group 3. The conversion rate and morbidity for the whole cohort of patients were 4.6% and 10.8%, respectively. There was no significant difference in the conversion rate, morbidity and postoperative hospital stay between the three groups. CONCLUSION: Laparoscopic cholecystectomy for acute cholecystitis during the index admission is safe, regardless of the time elapsed from the onset of symptoms. This policy can result in an overall shorter hospitalization. (C) 2006 The WJG Press. All rights reserved