Isolated Limb Perfusion for Extremity Soft Tissue Sarcoma and Malignant Melanoma.

Isolated limb perfusion (ILP) is a regional chemotherapy technique used in the treatment of locally advanced or unresectable extremity soft tissue sarcoma (ESTS) or malignant melanoma (MM) of the limbs. It allows for high concentrations of chemotherapeutic agents to be perfused in the limb while minimising the risk of systemic side-effects. While the technique has been utilized for decades, the role of ILP has evolved as other treatment strategies have become available.

The effect of aging on short- and long-term results after esophagectomy: an international multicenter retrospective analysis.

The optimal treatment for esophageal cancer in elderly patients is still debated and data on postoperative results are limited. This retrospective international study aims to clarify the impact of age on clinical and oncological outcomes after esophagectomy. All patients that underwent esophagectomy for cancer between 2007 and 2016 at two European high-volume Centers have been included in the study.

Low local recurrence rates following marginal surgical resection of non-coelomic Atypical Lipomatous Tumours/Well-differentiated Liposarcomas.

Introduction: High rates of local recurrence (LR) have been reported following resection of extremity Atypical lipomatous tumours/Well-differentiated liposarcomas (ALTs). This retrospective study of patients who underwent resection of primary deep extremity and trunk ALTs at a specialist sarcoma centre aims to assess morbidity and factors associated with low local recurrence rates (LRR).

Methods: To review a homogeneous cohort of patients with low-grade disease, tumours with known high-risk histological features were excluded.

Adjuvant therapy following neoadjuvant chemotherapy and surgery for oesophageal adenocarcinoma in patients with clear resection margins.

Background: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy (NAC) and surgery is contentious. In UK practice, surgical resection margin status is often used to classify patients into receiving adjuvant treatment. This study aimed to assess any survival benefit of adjuvant therapy in patients with clear resection margins.

Regional chemotherapy by isolated limb perfusion prior to surgery compared with surgery and post-operative radiotherapy for primary, locally advanced extremity sarcoma: a comparison of matched cohorts.

Background: Induction chemotherapy by isolated limb perfusion (ILP) with melphalan and tumour necrosis factor-α is an effective strategy to facilitate limb-conserving surgery in locally advanced extremity sarcoma. In a comparison of cohorts matched for grade, size and surgical resectability, we compared the outcome of patients undergoing induction ILP prior to limb-conserving surgery and selective post-operative radiotherapy with patients undergoing limb-conserving surgery and routine post-operative radiotherapy.

Methods: Patients with primary, grade 2/3 sarcomas of the lower limbs over 10 cm in size were identified from prospectively maintained databases at 3 centres.

Genetically modified lentiviruses that preserve microvascular function protect against late radiation damage in normal tissues.

Improvements in cancer survival mean that long-term toxicities, which contribute to the morbidity of cancer survivorship, are being increasingly recognized. Late adverse effects (LAEs) in normal tissues after radiotherapy (RT) are characterized by vascular dysfunction and fibrosis causing volume loss and tissue contracture, for example, in the free flaps used for immediate breast reconstruction after mastectomy. We evaluated the efficacy of lentivirally delivered superoxide dismutase 2 (SOD2) overexpression and connective tissue growth factor (CTGF) knockdown by short hairpin RNA in reducing the severity of LAEs in an animal model of free flap LAEs.

Oncolytic vaccinia virus combined with radiotherapy induces apoptotic cell death in sarcoma cells by down-regulating the inhibitors of apoptosis.

Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion.

Enhanced cytotoxicity of reovirus and radiotherapy in melanoma cells is mediated through increased viral replication and mitochondrial apoptotic signalling.

Oncolytic viruses selectively target and replicate in cancer cells, providing us with a unique tool with which to target and kill tumour cells. These viruses come from a diverse range of viral families including reovirus type 3 Dearing (RT3D), a non-pathogenic human double-stranded RNA oncolytic virus, which has been shown to be an effective therapeutic agent, both as a mono-therapy and in combination with traditional chemotherapeutic drugs. This study investigated the interaction between RT3D and radiotherapy in melanoma cell lines with a BRAF mutant, Ras mutant or BRAF/Ras wild type genotype.

Isolated limb perfusion with biochemotherapy and oncolytic virotherapy combines with radiotherapy and surgery to overcome treatment resistance in an animal model of extremity soft tissue sarcoma.

The management of locally advanced or recurrent extremity sarcoma often necessitates multimodal therapy to preserve a limb, of which isolated limb perfusion (ILP) is a key component. However, with standard chemotherapeutic agents used in ILP, the duration of response is limited. Novel agents or treatment combinations are urgently needed to improve outcomes.

An atypical presentation of small bowel obstruction and perforation secondary to sporadic synchronous intra-abdominal desmoid tumours.

Introduction: Desmoid tumours (DTs) are rare, soft tissue tumours which account for 0.03% of all neoplasms. They are characteristically locally invasive but do not metastasize.

Prevalence and correlates of cell phone use among Texas drivers.

Introduction: Cell phone use while driving restricts peripheral awareness and impairs reaction time. This study assessed the 3-year prevalence of cell phone use (CPU) of drivers and characteristics associated with its use in six cities across Texas, 2011-2013.

Methods: CPU and driver characteristics were observed among motor vehicles (n = 1280) stopped at major intersections in medical and academic campuses.

Adenovirally delivered enzyme prodrug therapy with herpes simplex virus-thymidine kinase in composite tissue free flaps shows therapeutic efficacy in rat models of glioma.

Introduction: Free flap gene therapy exploits a novel therapeutic window when viral vectors can be delivered into a flap ex vivo. The authors investigated the therapeutic potential of an adenovirally-delivered thymidine kinase/ganciclovir prodrug system expressed following vector delivery into a free flap.

Methods: The authors demonstrated direct in vitro cytotoxicity by treating a panel of malignant cell lines with the thymidine kinase/ganciclovir system and demonstrated significant cell kill proportional to the multiplicity of infection of adenoviral vector expressing thymidine kinase.

BRAF- and MEK-Targeted Small Molecule Inhibitors Exert Enhanced Antimelanoma Effects in Combination With Oncolytic Reovirus Through ER Stress.

Reovirus type 3 (Dearing) (RT3D) infection is selective for cells harboring a mutated/activated RAS pathway. Therefore, in a panel of melanoma cell lines (including RAS mutant, BRAF mutant and RAS/BRAF wild-type), we assessed therapeutic combinations that enhance/suppress ERK1/2 signaling through use of BRAF/MEK inhibitors. In RAS mutant cells, the combination of RT3D with the BRAF inhibitor PLX4720 (paradoxically increasing ERK1/2 signaling in this context) did not enhance reoviral cytotoxicity.

Physician weight recommendations for overweight and obese firefighters, United States, 2011-2012.

Introduction: National guidelines state that health care professionals (HCPs) should advise patients on the importance of maintaining a healthy weight. Firefighters have high rates of obesity, and cardiovascular events are the leading cause of line-of-duty deaths in firefighters. This study assessed the association of age and body mass index (BMI) with HCP weight recommendations among male firefighters.

Isolated limb perfusion with melphalan, tumour necrosis factor-alpha and oncolytic vaccinia virus improves tumour targeting and prolongs survival in a rat model of advanced extremity sarcoma.

Isolated limb perfusion (ILP) is a treatment for advanced extremity sarcoma and in-transit melanoma. Advancing this procedure by investigating the addition of novel agents, such as cancer-selective oncolytic viruses, may improve both the therapeutic efficacy of ILP and the tumour-targeted delivery of oncolytic virotherapy. Standard in vitro assays were used to characterise single agent and combinatorial activities of melphalan, tumour necrosis factor-alpha (TNF-α) and Lister strain vaccinia virus (GLV-1h68) against BN175 rat sarcoma cells.

Adiposity predicts self-reported frequency of poor health days among male firefighters.

Objective: Quantify the association between adiposity and frequency of self-reported poor health days among male firefighters.

Methods: Measures were taken for body mass index, waist circumference, and percentage of body fat. Firefighters self-reported the outcome of the number of poor health days in the past 30 days.

Surgical outcomes following resection for sporadic abdominal wall fibromatosis.

Background: Fibromatosis can be classified according to site of origin, namely, extraabdominal, abdominal wall, or intraabdominal. This study reports on the surgical management and long-term outcomes from a single center in the management of sporadic abdominal wall fibromatosis.

Methods: Patients who underwent surgery for abdominal wall fibromatosis between 1998 and 2013 were identified from a prospectively maintained database.

Role of thoracotomy and metastatectomy in gestational trophoblastic neoplasia: a single center experience.

Gestational trophoblastic neoplasia (GTN) is a rare collection of malignancies which are usually curable with modern chemotherapy. Lung metastasis is a relatively common feature of these malignancies and is not considered an adverse prognostic feature. Occasionally, however, the management of these patients necessitates adjuvant thoracic surgery, either to establish the diagnosis or to potentially provide a curative resection of drug-resistant foci of disease.

Increased haemoglobin A2 percentage in HIV infection: disease or treatment?

An elevated haemoglobin A2 percentage has been reported in HIV-infected patients, possibly attributable to therapy. In cross-sectional and cohort studies we have established that A2 is often elevated in untreated patients; a further rise during treatment is attributable specifically to zidovudine. The haemoglobin A2 may be high enough to lead to a misdiagnosis of beta thalassemia trait if there is a lack of awareness of this unexpected effect of HIV infection and its treatment.