Hereditary Neuroendocrine Tumor Syndromes

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Diagnosis of carotid arterial injury in major trauma using a modification of Memphis criteria

<p>Abstract</p> <p>Background</p> <p>Incidence of Blunt Cerebrovascular Injuries (BCVI) after head injury has been reported as 0.5-1% of all admissions for blunt trauma, with a high stroke and mortality rate. The purpose of this study is to evaluate if a modification of Memphis criteria could improve the rate of BCVI diagnosis.</p> <p>Methods</p> <p>Trauma patients consecutively admitted to Intensive Care Unit (ICU) from Jan 2008 to Oct 2009 were considered for the study. Memphis criteria comprehend: basilar skull fracture with involvement of the carotid canal, cervical spine fracture, neurological exam not explained by brain imaging, Horner's syndrome, LeFort II-III fractures, and neck soft tissue injury. As single criteria modification, we included all patients with petrous bone fracture, even without carotid canal involvement. In all patients at risk of BCVI, 64-slice angio-CT-scans was performed.</p> <p>Results</p> <p>During the study period, 266 patients were admitted to the ICU for blunt major trauma. Among them, 162 presented traumatic brain injury or cervical spine fracture. In accordance with the proposed modified-Memphis criteria, 53 patients showed risk factors for BCVI compared to 45 using the original Memphis criteria. Among the 53 patients, 6 resulted as having carotid lesions (2.2% of all blunt major traumas; one patient more than when using Memphis criteria). Anticoagulant therapy with low molecular weight heparin was administered in all patients. No stroke or hemorrhagic complications occurred. Clinical examination at 6-months showed no central neurological deficit.</p> <p>Conclusion</p> <p>A modification of a single criteria of Memphis screening protocol might permit the identification of a higher percentage of BCVI. Limited by sample size, this study needs to be validated.</p

Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients’ survival

IntroductionWe studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and p53 mutations in metastatic colorectal cancer (CRC) patients.Patients and methodsT2D was diagnosed according to the ADA criteria. HT was classified according to the ACC/AHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical and/or molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. P &lt; 0.05 were considered statistically significant.ResultsTwo-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) (P = 0.0246). DC, KRAS mutational status, T2D, BMI, and concomitant presence of T2D, BMI, and HT associated with survival (P &lt; 0.05). At multivariate analysis, age (≥65 vs. &lt;65 years), response to first-line chemotherapy (DC vs. no DC), and concomitant presence of T2D, BMI, and HT (HR: 4.56; 95% CI: 2.40–8.67; P = 0.0217) emerged as independent prognostic variables. P53 was mutated in 31/53 analyzed cases (60.4%). The most frequent gene variants were p.Arg175His and p.Cys135Tyr. High BMI (&gt;25 kg/m2) associated with occurrence of p53 mutations (P &lt; 0.0001). P53 mutated patients presented a worse prognosis compared to the wild-type ones (HR: 3.21; 95% CI: 1.43–7.23; P = 0.0047).ConclusionDiabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies. P53 mutations associate with prognosis and BMI unrevealing complex and unexplored connections between metabolism and cancer occurrence

Multifaceted Insights into Innovative Approaches to Treating Colorectal Cancer Metastasis: From Emerging Biological Factors to Radiomics

We extend our appreciation to the authors who have made substantial contributions to the Special Issue focusing on “Colorectal Cancer Metastasis” [...

Use of adjuvants for immunotherapy

Cancer vaccines are designed to stimulate the body's immune system to kill tumor cells. To improve their immunogenicity, vaccine antigens must be combined with adjuvants which are able to stimulate the innate immunity and potentiate the adaptive immune response. In the last years a new generation of adjuvants mimicking the natural microbial ligands have been developed. In particular, several TLR ligands have been extensively explored as vaccine adjuvants and many preclinical and clinical studies have been conducted. However, the road to approval of such adjuvants for clinical use is still to go

Systems Biology Approach for Cancer Vaccine Development and Evaluation

Therapeutic cancer vaccines do not hold promise yet as an effective anti-cancer treatment. Lack of efficacy or poor clinical outcomes are due to several antigenic and immunological aspects that need to be addressed in order to reverse such trends and significantly improve cancer vaccines’ efficacy. The newly developed high throughput technologies and computational tools are instrumental to this aim allowing the identification of more specific antigens and the comprehensive analysis of the innate and adaptive immunities. Here, we review the potentiality of systems biology in providing novel insights in the mechanisms of the action of vaccines to improve their design and effectiveness

Genetic regressive trajectories in colorectal cancer: A new hallmark of oligo-metastatic disease?

Colorectal cancer (CRC) originates as consequence of multiple genetic alterations. Some of the involved genes have been extensively studied (APC, TP53, KRAS, SMAD4, PIK3CA, MMR genes) in highly heterogeneous and poly-metastatic cohorts. However, about 10% of metastatic CRC patients presents with an indolent oligo-metastatic disease differently from other patients with poly-metastatic and aggressive clinical course. Which are the genetic dynamics underlying the differences between oligo- and poly-metastatic CRC? The understanding of the genetic trajectories (primary→metastatic) of CRC, in patients selected to represent homogenous clinical models, is crucial to make genotype/phenotype correlations and to identify the molecular events pushing the disease towards an increasing malignant phenotype. This information is crucial to plan innovative therapeutic strategies aimed to reverse or inhibit these phenomena. In the present study, we review the genetic evolution of CRC with the intent to give a developmental perspective on the border line between oligo- and poly-metastatic diseases

Animal models of medullary thyroid cancer: state of the art and view to the future

Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5-10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance

Current concepts of pheochromocytoma

AbstractPheochromocytoma (PCC), a rare neuroendocrine tumor, shows a prevalence ranging between 0.1% and 0.6% in individuals suffering from hypertension. To date, an increasing number of patients with hereditary forms or subclinical PCCs have been diagnosed. We reviewed the main controversies and the most recent updates, especially inheritance genetics and surgical management. According to the “rule of 10”, in 1/10 patients with pheochromocytoma it is malignant, in 1/10 of cases the tumor is bilateral, in 1/10 extra-adrenal and in 1/10 familial. Surgical resection, the only curative treatment, carries a high risk of hypertensive crises due to massive catecholamine release. Alpha 1 blocker therapy, alone or in combination with beta blockers, calcium antagonists, and plasma volume expansion, is the most commonly used preoperative treatment protocol. Minimally invasive adrenalectomy (laparoscopic and retro-peritoneoscopic) allows earlier mobilization and recovery, reducing the risk of pulmonary infections and thromb-oembolic complications, and is associated with lower morbidity and mortality rates than traditional surgery; it is currently considered the gold standard for the treatment of adrenal tumors ≤6 cm in diameter and weighing < 100 g. Genetic testing will increasingly be the key factor in estimating the life-long risk for development of recurrent disease, contralateral disease or malignant dedifferentiation, thus influencing follow-up protocols