Analysis of the interactions between small pulmonary nodules, clinical factors and the risk of malignancy in the chest following diagnosis of head and neck cancer.

BACKGROUND: This study aims to investigate radiological and clinical factors which predict malignancy in indeterminate pulmonary nodules in patients with head and neck cancer (HNC). METHODS: Prospective data were collected in 424 patients who were reviewed in the NHS Lothian HNC multidisciplinary meeting from May 2016 to May 2018. Staging and follow-up CT chest imaging were reviewed to identify and assess pulmonary nodules in all patients. RESULTS: About 61.8% of patients had at least one pulmonary nodule at staging CT. In total, 25 patients developed malignancy in the chest. Metastatic disease in the chest was significantly associated with unknown or negative p16 status (p < .0005). Pleural indentation and spiculation were associated with indeterminate nodules, subsequently being shown to represent metastatic disease (p > .0005 and p = .046, respectively). CONCLUSION: Negative or unknown p16 status was associated with an increased propensity to develop metastatic disease in the chest in patients with HNC.

Cell therapy for advanced liver diseases: Repair or rebuild.

Advanced liver disease presents a significant worldwide health and economic burden and accounts for 3.5% of global mortality. When liver disease progresses to organ failure the only effective treatment is liver transplantation, which necessitates lifelong immunosuppression and carries associated risks. Furthermore, the shortage of suitable donor organs means patients may die waiting for a suitable transplant organ. Cell therapies have made their way from animal studies to a small number of early clinical trials. Herein, we review the current state of cell therapies for liver disease and the mechanisms underpinning their actions (to repair liver tissue or rebuild functional parenchyma). We also discuss cellular therapies that are on the clinical horizon and challenges that must be overcome before routine clinical use is a possibility.

Diaphragmatic hernia: a rare complication of hepatic ablation.

INTRODUCTION: Ablation has become an effective treatment for small hepatocellular carcinomas (HCC). Whilst ablation is a safe and effective technique, diaphragmatic injury is a rarely associated but significant complication.Case presentation: We present a case of a 67 year old patient who developed a diaphragmatic defect following microwave ablation (MWA) for HCC. The diaphragmatic defect progressed to herniation which was complicated by perforation of intrahernial large bowel. The patient was treated by emergency laparotomy and an extended right hemi-colectomy was performed. CONCLUSION: Our report adds to the current available knowledge on diaphragmatic injury following hepatic ablation and demonstrates the potential for life threatening consequences associated with this complication.

Impact of noncardiac findings in patients undergoing CT coronary angiography: a substudy of the Scottish computed tomography of the heart (SCOT-HEART) trial.

OBJECTIVES: Noncardiac findings are common on coronary computed tomography angiography (CCTA). We assessed the clinical impact of noncardiac findings, and potential changes to surveillance scans with the application of new lung nodule guidelines. METHODS: This substudy of the SCOT-HEART randomized controlled trial assessed noncardiac findings identified on CCTA. Clinically significant noncardiac findings were those causing symptoms or requiring further investigation, follow-up or treatment. Lung nodule follow-up was undertaken following the 2005 Fleischner guidelines. The potential impact of the 2015 British Thoracic Society (BTS) and the 2017 Fleischner guidelines was assessed. RESULTS: CCTA was performed in 1,778 patients and noncardiac findings were identified in 677 (38%). In 173 patients (10%) the abnormal findings were clinically significant and in 55 patients (3%) the findings were the cause of symptoms. Follow-up imaging was recommended in 136 patients (7.6%) and additional clinic consultations were organized in 46 patients (2.6%). Malignancy was diagnosed in 7 patients (0.4%). Application of the new lung nodule guidelines would have reduced the number of patients undergoing a follow-up CT scan: 68 fewer with the 2015 BTS guidelines and 78 fewer with the 2017 Fleischner guidelines; none of these patients subsequently developed malignancy. CONCLUSIONS: Clinically significant noncardiac findings are identified in 10% of patients undergoing CCTA. Application of new lung nodule guidelines will reduce the cost of surveillance, without the risk of missing malignancy. KEY POINTS: • Clinically significant noncardiac findings occur in 10% of patients undergoing CCTA. • Noncardiac findings may be an important treatable cause of chest pain • Further imaging investigations for noncardiac findings were recommended in 8% of patients after CCTA. • New lung nodule follow-up guidelines will result in cost savings.

Patient-Centered Access to IBD Care: A Qualitative Study.

Background: Canada has the highest global age-adjusted incidence and prevalence rates of inflammatory bowel disease (IBD). Due to IBD patient volumes and limited resources, challenges to timely access to specialty care have emerged. To address this gap, the aim of this paper was to understand the experiences and perspectives of persons living with IBD with a focus on accessing health care. Methods: Using a qualitative descriptive approach, patients diagnosed with IBD (≥18 years of age) were purposively sampled from rural and urban gastroenterology clinics and communities across Canada. Co-facilitated by a researcher and patient research partner, 14 focus groups were recorded, transcribed, and coded for themes. Thematic analysis was used to ascertain the congruence or discordance of IBD specialty care access experiences. Results: A total of 63 individuals participated in the study. The majority of participants were female (41/63, 65%) and from urban/suburban regions (33/63, 52%), with a mean age of 48.39 (range 16-77 years). The analysis generated three main themes: (1) need for patient to be partner, (2) adapting IBD care access to individual context, and (3) patient-defined care priorities should guide access to IBD care. Conclusions: The complexity of specialty care access for IBD patients cannot be underestimated. It is vital to possess a robust understanding of healthcare system structures, processes, and the impact of these factors on accessing care. Using a patient-centered exploration of barriers and facilitators, IBD specialty care access in Canada can be better understood and improved on provincial and national levels.

Stakeholder Perspectives on Access to IBD Care: Proceedings From a National IBD Access Summit.

Background: Canada has among the highest incidence and prevalence rates of inflammatory bowel disease (IBD) in the world. While access to IBD specialty care can have a direct impact on health-related outcomes, the complexity of accessing IBD specialty care within Canada is not well understood and presents a barrier to implementation and evaluation of IBD specialty care. Aim: The IBD Summit was held in partnership with Crohn's & Colitis Canada to identify barriers and facilitators of IBD specialty care by exploring the perceptions and experiences of key stakeholders of IBD care across Canada. Results: A total of 20 key stakeholders attended, including gastroenterologists, patients, researchers and policymakers. Perceptions and experiences of stakeholders were transcribed, coded and thematically analyzed. Three key categories relating to access to IBD care arose: (1) inadequate system structure, (2) process inefficiencies and (3) using outcomes to guide system change. The IBD Summit identified similar perceptions and experiences among stakeholders and across provinces, highlighting common barriers and facilitators that transcended provincial and health care system boundaries. Conclusions: Key suggestions identify the clinical importance of comprehensive integrated multidisciplinary care approaches with enhanced communication between patient and health care providers, greater information sharing among team members, streamlined referral and triage processes, and improved incorporation of best practice into clinical care. Stakeholders across Canada and in other countries may benefit from the suggestions presented herein, as well as the successful use of collaborative and inclusive methods of gathering the perceptions and experiences of key stakeholders from diverse backgrounds.

Senolytic treatment preserves biliary regenerative capacity lost through cellular senescence during cold storage.

Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by the progressive loss of biliary tract architecture) continue to occur after liver transplantation, negatively affecting liver function and frequently leading to graft loss and retransplantation. To study the biological effects of organ preservation before liver transplantation, we generated murine models that recapitulate liver procurement and static cold storage. In these models, we explored the response of cholangiocytes and hepatocytes to cold storage, focusing on responses that affect liver regeneration, including DNA damage, apoptosis, and cellular senescence. We show that biliary senescence was induced during organ retrieval and exacerbated during static cold storage, resulting in impaired biliary regeneration. We identified decoy receptor 2 (DCR2)-dependent responses in cholangiocytes and hepatocytes, which differentially affected the outcome of those populations during cold storage. Moreover, CRISPR-mediated DCR2 knockdown in vitro increased cholangiocyte proliferation and decreased cellular senescence but had the opposite effect in hepatocytes. Using the p21KO model to inhibit senescence onset, we showed that biliary tract architecture was better preserved during cold storage. Similar results were achieved by administering senolytic ABT737 to mice before procurement. Last, we perfused senolytics into discarded human donor livers and showed that biliary architecture and regenerative capacities were better preserved. Our results indicate that cholangiocytes are susceptible to senescence and identify the use of senolytics and the combination of senotherapies and machine-perfusion preservation to prevent this phenotype and reduce the incidence of biliary injury after transplantation.

Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease.

Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have therefore purified human biliary epithelial cells (hBECs) from human livers that were not used for liver transplantation. hBECs were tested as a cell therapy in a mouse model of biliary disease in which the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures, and fibrosis. hBECs are expandable and phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease.

Study protocol: a multicentre, open-label, parallel-group, phase 2, randomised controlled trial of autologous macrophage therapy for liver cirrhosis (MATCH).

INTRODUCTION: Liver cirrhosis is a growing global healthcare challenge. Cirrhosis is characterised by severe liver fibrosis, organ dysfunction and complications related to portal hypertension. There are no licensed antifibrotic or proregenerative medicines and liver transplantation is a scarce resource. Hepatic macrophages can promote both liver fibrogenesis and fibrosis regression. The safety and feasibility of peripheral infusion of ex vivo matured autologous monocyte-derived macrophages in patients with compensated cirrhosis has been demonstrated. METHODS AND ANALYSIS: The efficacy of autologous macrophage therapy, compared with standard medical care, will be investigated in a cohort of adult patients with compensated cirrhosis in a multicentre, open-label, parallel-group, phase 2, randomised controlled trial. The primary outcome is the change in Model for End-Stage Liver Disease score at 90 days. The trial will provide the first high-quality examination of the efficacy of autologous macrophage therapy in improving liver function, non-invasive fibrosis markers and other clinical outcomes in patients with compensated cirrhosis. ETHICS AND DISSEMINATION: The trial will be conducted according to the ethical principles of the Declaration of Helsinki 2013 and has been approved by Scotland A Research Ethics Committee (reference 15/SS/0121), National Health Service Lothian Research and Development department and the Medicine and Health Care Regulatory Agency-UK. Final results will be presented in peer-reviewed journals and at relevant conferences. TRIAL REGISTRATION NUMBERS: ISRCTN10368050 and EudraCT; reference 2015-000963-15.

Canadian Association of Gastroenterology Communique: After-Hours Endoscopy Cart.

BACKGROUND: Endoscopic procedures performed after-hours often require therapeutic interventions that are technically demanding for the endoscopist. The aim of this position paper is to provide guidance on the minimum standard of equipment that should be available on a mobile endoscopy cart for provision of a safe and effective after-hours emergency endoscopy service. The guidance is based on consensus among academic and community gastroenterologists in Canada. METHODS: A modified Delphi process was used to establish consensus among 9 participants. A list of statements was prepared by an expert panel of endoscopists. The statements were divided into three broad sections for what should be on an after-hours endoscopy cart including medications, nonendoscopic tools and therapeutic/diagnostic equipment. Consensus for being on the endoscopy cart was achieved when 75% or more of voting members indicated 'agree'. RESULTS: For nonendoscopic tools, there was agreement for having sterile saline, sterile water, endoscope lubricant, various syringes, bite blocks (paediatric and adult size), a water pump with foot peddle, formalin jars for biopsy specimens, digital photo and printing capability and an overtube. For medications, there was agreement for having hyoscine butylbromide and epinephrine on the cart. For therapeutic/diagnostic tools, there was agreement for having biopsy forceps (standard and jumbo), polypectomy snares, sclerotherapy needles and agent (for a variceal bleed), band ligation kit, multipolar electrocautery probes, heater probe catheter, endoscopic clips, hemostatic powder and retrieval devices. INTERPRETATION: This position paper provides guidance on the minimum standard of items that should be on an after-hours endoscopy cart. Standardization of equipment may help improve safety and quality of after-hours endoscopic procedures.

Incidental Non-cardiac Findings in Cardiovascular Imaging.

Improvements in imaging techniques have led to an expansion in the number of cross-sectional cardiac studies being performed. This means that incidental non-cardiac findings (INCF) identified on cardiac imaging have become an important clinical concern. The majority of INCF are not clinically significant. However, some INCF will require follow-up or changes in management. Differentiating clinically significant from non-significant INCF can be challenging, particularly given the breadth of potential findings and the range of organ systems involved. Following up INCF also has economic implications. Recent changes to the lung nodule follow-up guidelines will reduce the cost of following up incidental lung nodules. In this manuscript, we discuss the common and important INCF which may be identified in cardiovascular imaging and explore potential implications of these findings.

Analysis of the incidence and factors predictive of outcome in patients with head and neck cancer with pulmonary nodules.

BACKGROUND: The management of pulmonary nodules is challenging; unfortunately, little is known about the incidence and significance of pulmonary nodules in patients with head and neck cancer. METHODS: A review was conducted of 400 consecutive patients with head and neck cancer. Imaging was reviewed to identify the incidence of nodules and patient, tumor, and radiological factors associated with the risk of malignancy. RESULTS: Nodules were found in 58% of patients, with a malignant rate of 6%. Age was the only predictor of having a nodule and advanced-stage III + IV was a predictor of malignancy (P = .023; odds ratio [OR] 10.64; confidence interval 1.33-84.98). CONCLUSION: Patients presenting with head and neck cancer have a higher incidence of pulmonary nodules and a higher risk of malignancy. In contrast to the British Thoracic Society (BTS) guidelines, which use size to guide the need for serial scans, we would recommend follow-up imaging in all patients with head and neck cancer with nodules, irrespective of size.

Transitioning to highly effective therapies for the treatment of chronic hepatitis C virus infection: a policy statement and implementation guideline.

Chronic hepatitis C virus (HCV) infection increases all-cause mortality, rates of cirrhosis, hepatocellular carcinoma, liver transplantation and overall health care utilization. Morbidity and mortality disproportionately affect individuals born between 1945 and 1975. The recent development of well-tolerated and highly effective therapies for chronic HCV infection represents a unique opportunity to dramatically reduce rates of HCV-related complications and their costs. Critical to the introduction of such therapies will be well-designed provincial programming to ensure immediate treatment access to individuals at highest risk for complication, and well-defined strategies to address the global treatment needs of traditionally high-risk and marginalized populations. HCV practitioners in New Brunswick created a provincial strategy that stratifies treatment according to those at highest need, measures clinical impact, and creates evaluation strategies to demonstrate the significant direct and indirect cost savings anticipated with curative treatments.

The relationships between body composition and the systemic inflammatory response in patients with primary operable colorectal cancer.

BACKGROUND: Weight loss is recognised as a marker of poor prognosis in patients with cancer but the aetiology of cancer cachexia remains unclear. The aim of the present study was to examine the relationships between CT measured parameters of body composition and the systemic inflammatory response in patients with primary operable colorectal cancer. PATIENT AND METHODS: 174 patients with primary operable colorectal cancer who underwent resection with curative intent (2003-2010). Image analysis of CT scans was used to measure total fat index (cm(2)/m(2)), subcutaneous fat index (cm(2)/m(2)), visceral fat index (cm(2)/m(2)) and skeletal muscle index (cm(2)/m(2)). Systemic inflammatory response was measured by serum white cell count (WCC), neutrophil:lymphocyte ratio (NLR) and the Glasgow Prognostic Score (mGPS). RESULTS: There were no relationships between any parameter of body composition and serum WCC or NLR. There was a significant relationship between low skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p = 0.001). This was confirmed by linear relationships between skeletal muscle index and both C-reactive protein (r = -0.21, p = 0.005) and albumin (r = 0.31, p<0.001). There was no association between skeletal muscle index and tumour stage. CONCLUSIONS: The present study highlights a direct relationship between low levels of skeletal muscle and the presence of a systemic inflammatory response in patients with primary operable colorectal cancer.