Thoracic surgical management of colorectal lung metastases: a questionnaire survey of members of the Society for Cardiothoracic Surgery in great Britain and Ireland

Introduction

Distant metastases to liver and lung are not uncommon in colorectal cancer. Resection of metastases is accepted widely as the standard of care. However, there is no firm evidence base for this. This questionnaire survey was carried out to assess the current practice preferences of cardiothoracic surgeons in Great Britain and Ireland.

Methods

An online questionnaire survey was emailed to cardiothoracic surgeons in Great Britain and Ireland. The survey was live for 12 weeks. Responses were collated with SurveyMonkey^®.

Results

Overall, there were 75 respondents. The majority (83%) indicated thoracic surgery as a specialist interest. Almost all (99%) used thoracic computed tomography (CT) for staging; 70% added liver CT and 51% added pelvic CT. Fluorodeoxyglucose positron emission tomography was used by 86%. The most frequent indication for pulmonary resection (97%) was solitary lung metastasis without extrathoracic disease. Video assisted thoracoscopic surgery (VATS) was used by 85%. In addition, thoracotomy was used by 96%. A third (33%) used radiofrequency ablation. Synchronous liver and lung resection was contraindicated for 83% of respondents. Over three-quarters (77%) thought that scientific equipoise exists presently for lung resection for colorectal lung metastases but only 21% supported a moratorium on this type of surgery until further evidence becomes available.

Conclusions

The results confirm that the majority of respondents use conventional cross-sectional imaging and either VATS or formal thoracotomy for resection. The results emphasise the continuing need for formal randomised trials to provide evidence of any survival benefit from pulmonary metastasectomy for colorectal lung metastases.     

Amelioration of coxsackievirus B3-mediated myocarditis by inhibition of tissue inhibitors of matrix metalloproteinase-1

Coxsackievirus B3 (CVB3) is a major cause of acute myocarditis, a serious condition that is refractory to treatment. Myocardial damage results in tissue remodeling that, if too extensive, may contribute to disease. Remodeling is achieved by extracellular proteolysis mediated by the matrix metalloproteinases (MMPs), and MMP activity is counterbalanced by tissue inhibitors of MMPs (TIMPs). We show herein that TIMP-1 expression is induced in the myocardium by CVB3 infection. Surprisingly, TIMP-1 knockout mice exhibited a profound attenuation of myocarditis, with increased survival. The amelioration of disease in TIMP-1 knockout mice was not attributable to either an altered T-cell response to the virus or to reduced viral replication. These data led us to propose a novel function for TIMP-1: its highly localized up-regulation might arrest the MMP-dependent migration of inflammatory cells at sites of infection, thereby anatomically focusing the adaptive immune response. The benefits of TIMP-1 blockade in treating viral myocarditis were confirmed by administering, to wild-type animals, TIMP-1-specific siRNA or polyclonal antisera, both of which diminished CVB3-induced myocarditis. These unexpected findings indicate that increased TIMP-1 expression exacerbates, rather than ameliorates, CVB3-induced myocarditis and, thus, that TIMP-1 may represent a target for the treatment of virus-induced heart disease.     

A nine-year review of medicolegal claims in neurosurgery

Introduction

Neurosurgery remains among the highest malpractice risk specialties. This study aimed to identify areas in neurosurgery associated with litigation, attendant causes and costs.

Methods

Retrospective analysis was conducted of 42 closed litigation cases treated by neurosurgeons at one hospital between March 2004 and March 2013. Data included clinical event, timing and reason for claim, operative course and legal outcome.

Results

Twenty-nine claims were defended out of court and twelve were settled out of court. One case required court attendance and was defended. Of the 42 claims, 28, 13 and 1 related to spinal (0.3% of caseload), cranial (0.1% of caseload) and peripheral nerve (0.07% of caseload) surgery respectively. The most common causes of claims were faulty surgical technique (43%), delayed diagnosis/misdiagnosis (17%), lack of information (14%) and delayed treatment (12%), with a likelihood of success of 39%, 29%, 17% and 20% respectively. The highest median payouts were for claims against faulty surgical technique (£230,000) and delayed diagnosis/misdiagnosis (£212,650). The mean delay between clinical event and claim was 664 days.

Conclusions

Spinal surgery carries the highest litigation risk versus cranial and peripheral nerve surgery. Claims are most commonly against faulty surgical technique and delayed diagnosis/misdiagnosis, which have the highest success rates and payouts. In spinal surgery, the most common cause of claims is faulty surgical technique. In cranial surgery, the most common cause is lack of information. Claims may occur years after the clinical event, necessitating thorough contemporaneous documentation for adequate future defence. We emphasise thorough patient consultation and meticulous surgical technique to minimise litigation in neurosurgical practice.     

Adiposity and Fat Metabolism in Lactating and Fasting Northern Elephant Seals

Several taxa of animals fast completely from food and water during energy-intensive periods such as lactation, breeding, and development. In elephant seals, these behaviors are sustained by high adiposity, high rates of fat mobilization, and reduced oxidation of carbohydrates and proteins. Adiposity and the regulation of lipolysis directly affect lactation energetics, milk composition, and mating success. Long-term fasting induces changes in regulation of lipolysis and lipid metabolism that influence fatty acid (FA) availability and the onset of insulin resistance. Hypoinsulinemia and elevated circulating FAs are also associated with several unique features of carbohydrate metabolism, including elevated plasma glucose, gluconeogenesis, and Cori cycle activity as well as high rates of pyruvate and tricarboxylic acid cycling. Glucose-lactate pools and triacylglycerol-FA cycles may be linked via glyceroneogenesis and this may be an important pathway influencing both fat and carbohydrate metabolism. Together, these features allow a sustained, high intensity, fat-based metabolism without substantial accumulation of ketoacids.     

Atorvastatin inhibits CXCR7 induction to reduce macrophage migration

We have recently reported that CXCR7, the alternate high affinity SDF-1 receptor, is induced during monocyte-to-macrophage differentiation, leading to increased macrophage phagocytosis linked to atherosclerosis. Statins, the most widely used medications for atherosclerosis, were shown to have pleiotropic beneficial effects independent of their cholesterol-lowering activity. This study aimed to determine whether induction of CXCR7 during macrophage differentiation is inhibited by statins and its significance on macrophage physiology. Here we show for the first time that atorvastatin dose-dependently inhibited CXCR7 mRNA and protein expression in THP-1 macrophages, without affecting the other SDF-1 receptor, CXCR4. Pharmacotherapy relevant dose of atorvastatin affected neither cell viability nor macrophage differentiation. Suppression of CXCR7 expression was completely reversed by supplementation with mevalonate. Inhibition of squalene synthase, the enzyme committed to cholesterol biosynthesis, also decreased CXCR7 induction, albeit not as efficacious as atorvastatin. However, the geranylgeranyl transferase inhibitor, GGTI-286, the farnesyl transferase inhibitor, FTI-276, and the Rho kinase inhibitor, Y-27632, all failed to mimic the effect of atorvastatin, suggesting that the protein prenylation pathways are not critical for atorvastatin inhibition of CXCR7 induction. Interestingly, the dramatic effect of atorvastatin was only partially mimicked by other statins including pravastatin, fluvastatin, mevastatin, and simvastatin. Furthermore, activation of CXCR7 by SDF-1, TC14012, or I-TAC all prompted macrophage migration, which was significantly suppressed by atorvastatin treatment, but not by the CXCR4 antagonist. We conclude that atorvastatin modulates macrophage migration by down-regulating CXCR7 expression, suggesting a new CXCR7-dependent mechanism of atorvastatin to benefit atherosclerosis treatment beyond its lipid lowering effect.     

"Stem cell" origin of the hematopoietic defect in dyskeratosis congenita

We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse.