Metastatic Gastric Adenocarcinoma Presenting as a Solitary Plaque on the Palm

Cutaneous metastases from gastric adenocarcinoma are extremely rare. When present, metastasis typically signifies disseminated disease with a poor prognosis. We report a case of an 80-year-old male with gastric cancer who presented with a single, erythematous plaque on the left palm, a very rare site for skin metastasis. Results of a skin biopsy demonstrated that the cutaneous metastasis originated from the stomach. This report emphasized the need for appropriate investigation into newly appearing, unusual, or persistent skin lesions

Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX). DATA SOURCES: The following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs. METHODS: Network meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained. RESULTS: Sixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX. CONCLUSIONS: bDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission). STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003386. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Head and neck chondrosarcoma: Analysis of 16 cases

Objective: Head and neck chondrosarcomas are rare, accounting for less than 12% of all chondrosarcomas. Few studies with larger series approach the clinicopathological characteristics of these tumours. The aim of this study was describe clinical findings, management and outcome of 16 cases of head and neck chondrosarcoma from a single institution. Study design: The files of the Cancer Hospital A. C. Camargo were reviewed, and data from patients with head and neck chondrosarcoma were collected. Results: Mean age was 36 years, with slight male predilection. The most common site affected was maxilla (43%). Surgery was the main modality treatment performed in 10 patients. Overall 5-year survival rate was 56.4%. Although it was not statistically significant, the most important factor affecting overall survival was tumour size. Conclusion: Early diagnosis and adequate surgical resection are important to get better survival rates. (C) 2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.47755555

Prognostic factors in head and neck adenoid cystic carcinoma

The aim of this study was to analyse the clinical, histological and immunohistochemical prognostic factors of a large series of adenoid cystic carcinoma, using univariate and multivariate survival analyses. All cases of head and neck ACC (n = 129) treated in a single institution in Brazil, between 1955 and 1997, were selected for the study. Univariate survival analysis revealed that age older than 45 years (p = 0.04), period of complaints inferior to 18 months (p = 0.007), presence of paresthesia (p = 0.04), T stage (p = 0.01), N stage (p = 0.04), M stage (p < 0.001), clinical stage (p = 0.003), solid histological type (p < 0.001), presence of residual tumor (p < 0.001) and expression of p53 (p = 0.08) correlated with a poor prognosis. In the multivariate survival analyses, clinical stage, solid histological subtype and increased expression of p53 were independent significant prognostic factors. According to our findings, clinical stage, solid growth pattern and expression of p53 were the most important prognostic factors in patients with ACC. (c) 2005 Elsevier Ltd. All rights reserved.42213914

ErbB2 and fatty acid synthase (FAS) expression in 102 squamous cell carcinomas of the tongue: Correlation with clinical outcomes

The oncoprotein ErbB2 (HER-2/neu) is a tyrosine kinase cell surface receptor overexpressed in several human malignancies, including oral squamous cell carcinoma (OSCC). ErbB2 was recently shown to regulate the expression of fatty acid synthase (FAS), a multifunctional enzyme complex responsible for the de novo biosynthesis of saturated fatty acids. Here we evaluated the relationship between the immunohistochemical expression of ErbB2, FAS, and Ki-67 with the clinicopathologic characteristics of tongue squamous cell carcinoma (SCC). One hundred and two patients with tongue SCC treated from 1990 to 1995 were studied. Clinical and treatment data were obtained from the medical records and histo pathological features revised. Paraffin-embedded tissues were submitted to standard immunohistochemical reactions for ErbB2, FAS and Ki-67. A strong positive correlation between ErbB2 labeling at the cell membrane and FAS expression was found in the tongue SCC samples (p < 0.0001). The intracytoplasmatic expression of ErbB2 as well as Ki-67 nuclear staining were significantly associated with a high risk of recurrence by predicting both disease free survival (log-rank test, p = 0.0096 and p = 0.0047, respectively) and overall survival (log-rank test, p = 0.0029 and p = 0.0001, respectively). Taken together, our results suggest that the immunolocalization of ErbB2 at the cell surface of malignant oral keratinocytes is linked to FAS expression whereas the intracytoplasmatic ErbB2 or Ki-67 staining predict high risk of recurrence of tongue SCC. (c) 2007 Elsevier Ltd. All rights reserved.44548449

Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Overexpression of fatty acid synthase (FASN) and ErbB2 has been described in oral squamous cell carcinomas (OSCC). FASN is the key lipogenic enzyme responsible for the endogenous synthesis of fatty acids and its expression can be regulated by ErbB2. The deubiquitinating enzyme (DUB) ubiquitin-specific protease 2a (USP2a) plays a critical role in prostate cancer cell survival by stabilizing the FASN protein. This study investigates whether the gene expression and the immunohistochemical status of FASN, ErbB2, and USP2a correlate with the clinicopathological characteristics of OSCC cases. A strong positive correlation among ErbB2, FASN, and USP2a expression (p = 0.001) was observed by qRT-PCR in laser capture micro-dissected OSCC samples. Perineural infiltration was associated with ErbB2 mRNA expression (p = 0.046). The presence of metastatic cervical lymph nodes was associated with FASN (p = 0.002), ErbB2 (p = 0.001), and USP2a (p = 0.006) mRNA levels. ErbB2 staining at the cell membranes was stronger in well-differentiated lesions while a cytoplasmic positivity was found in poorly differentiated tumors. Most of the OSCC (97.06%) that showed a high positivity for FASN were also labeled for ErbB2 at the cell membranes (p = 0.001). FASN and ErbB2 positivity was associated with tumor thickness and lymphatic embolization (p = 0.006 and p = 0.035, p = 0.006 and p = 0.024 respectively). The membrane expression of ErbB2 as well as FASN and Ki-67 staining were significantly associated with a high risk of recurrence by predicting both disease free survival (log-rank test, p = 0.0056, p = 0.0011, and p = 0.0004, respectively) and overall survival (log-rank test, p = 0.0005, p = 0.0062, and p = 0.0001, respectively). Taken together, the results presented here suggest a molecular connection among FASN, ErbB2, and USP2a in OSCC since their mRNA and protein levels were associated with tumor progression and poor prognosis. (C) 2009 Elsevier Ltd. All rights reserved.4510E134E139Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [02/08030-1, 04/06398-7]FAPESP [9814335