Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer

Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer

Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck

As the prognosis for squamous cell carcinoma of the head and neck remains unsatisfactory when compared to other malignancies, novel therapies targeting specific biomarkers are a critical emerging area of great promise. One particular class of drugs that has been developed to impede tumor angiogenesis is vascular endothelial growth factor-tyrosine kinase inhibitors. As current data is primarily limited to preclinical and phase I/II trials, this review summarizes the current and future prospects of these agents in squamous cell carcinoma of the head and neck. In particular, the combination of these agents with immunotherapy is an exciting area that may be a promising option for patients with recurrent or metastatic disease, evidenced in recent trials such as the combination immune checkpoint inhibitors with lenvatinib and cabozantinib. In addition, the use of such combination therapy preoperatively in locally advanced disease is another area of interest

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition

ACTH-Producing Neuroendocrine Carcinoma of the Liver with Cushing’s Syndrome

Paraneoplastic Cushing’s syndrome arises when neuroendocrine tumors cause excess glucocorticoid production. We report a case of ectopic ACTH-producing liver neuroendocrine tumor. A 71 y.o. female with a history of rectal squamous carcinoma presented with fatigue and diffuse swelling. Liver biopsy revealed metastatic neuroendocrine carcinoma. Workup revealed markedly elevated morning cortisol and ACTH. Overnight dexamethasone suppression testing and positive immunostaining for ACTH on biopsy suggested paraneoplastic Cushing’s syndrome secondary to neuroendocrine hepatic tumors with bony metastasis. This explained the patient’s persistent anasarca, hyperglycemia, and electrolyte abnormalities. Despite multiple interventions, the patient’s clinical status declined, and she expired

Gender differences in risk of stroke in patients with restless legs syndrome

Background Patients with Restless Legs Syndrome (RLS) have been recently reported to have a higher risk of stroke when compared to non-RLS patients, but the difference appears to be related to the duration of RLS. We hypothesize that diabetes mellitus, a condition that accelerates cardiovascular diseases, may enhance the risk of stroke more in RLS than in non-RLS patients. Methods and Results Patients diagnosed with RLS based on the International Restless Legs Syndrome Study Group criteria from a community-based sleep study center were compared to a 1:2 propensity matched non-RLS group. The association of diabetes and stroke in RLS and non-RLS patients in men and women were performed using Chi-Square and Cochran-Mantel-Haenszel Tests. Results Stroke was diagnosed in 29 out of 385 (7.5%) patients with RLS (mean age 55.1±0.7 years, 45% female) which was significantly higher than 32 out of 770 (4.2%; p=0.02) patients without RLS (mean age 54±0.5 years, 46% females). The presence of diabetes in the RLS group was associated with a 3 fold increased risk of stroke (OR 2.96, 95% Confidence Interval 1.05-8.37, p=0.03) compared to a 1.1 fold increased risk in non-RLS patients (OR: 1.08, 95% CI 0.44-2.65; p=0.87). This was significantly higher in female diabetics with RLS (18.2%) than in male diabetics (7.0%, p=0.03) or nondiabetics (5.7% in females vs 3.9% in males, p=0.52). Predictors of stroke in patients with RLS were the presence of hypertension, diabetes and female sex. Hypertension, diabetes and atrial fibrillation were predictors of stroke in non-RLS patients. Conclusions Gender differences exist in the risk of stroke in RLS patients with a 3.0 fold higher risk of stroke in diabetic women compared to diabetic men. In non-RLS patients, no significant difference in risk of stroke was found between women and men. Mechanisms underlying increased risk of stroke in RLS patients need to be defined and whether better diabetes control help reduce the stroke risk in RLS patients needs to be further investigated

Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer

Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer