Is there still a role for abatacept in the treatment of lupus?

Introduction: The quest for safer and more effective treatments for systemic lupus erythematosus (SLE) has led to the development of many new biologic therapies. Abatacept is the first drug targeting co-stimulation between T cells and antigen presenting cells, with abundant pre-clinical evidence to support its use in SLE.

Areas covered: This review will present the relevant aspects of lupus pathophysiology pertaining to the mechanism of action of abatacept, a summary of murine studies and the latest human clinical trials.

Expert opinion: Abatacept has demonstrated efficacy in both rheumatoid arthritis and psoriatic arthritis, and earlier studies have suggested tantalising evidence of efficacy in SLE. However, the latest randomised double-blinded study showed disappointingly negative results, much like the case of rituximab in SLE. Currently, abatacept remains a possible therapeutic option as an off-label therapy, and it is a part of our therapeutic armamentarium in difficult cases. The need to find appropriate definitions of response and optimal study design continues to be paramount in the field of lupus therapies.     

Is there still a role for sucralfate in the treatment of gastritis?

The endoscopic diagnosis of gastritis is usually made when a patient develops symptoms and undergoes an upper gastrointestinal endoscopy. There are often obvious aetiological causes such as smoking, alcohol Helicobacter pylori infection or drug treatment. Lifestyle changes can sometimes improve symptoms but often patients will be treated with a proton pump inhibitor. The stomach mucosa produces a protective mucous to prevent damage cause by gastric acid and exogenous agents can disrupt this layer. Repair of this protective layer can be enhanced by reduction in gastric acid secretion using H2 receptor antagonist or proton pump inhibitors or by cytoprotective drugs such as misoprostol, sucralfate, aluminium ions or bismuth subsalts. Sucralfate is a complex polymer which at a low pH changes its chemical configuration and binds to serum protein to form a protective layer protecting the mucosa against further injury. Cytoprotective drugs were the first line treatment for peptic disease including gastritis for many years but since the launch of cimetidine in 1976 and the subsequent launch of omeprazole in 1988, their use has slowly declined. First line treatment for patients with symptomatic gastritis after removal of potential causative factors is likely to be a proton pump inhibitor in 2019. This is despite the fact that there is some evidence that sucralfate is superior than a H2 receptor antagonist in the endoscopic healing rates in patients with gastritis. The logical treatment choice in patients with resistance symptoms is a combination of a proton pump inhibitor and sucralfate but evidence is lacking. Until such evidence is available In the meantime, we would suggest that there is a role for sucralfate in the treatment of intransigent gastritis and that mucosal protection should be considered even ahead of acid suppression given its favourable safety and toxicity profile.     

Contrast-enhanced ultrasound in planning thermal ablation of liver metastases: Should the hypervascular halo be included in the ablation volume?

Introduction

Liver metastases often exhibit a hypervascular halo during the arterial phase of contrast-enhanced ultrasonography (CEUS). This finding has no correlates on baseline gray-scale imaging, and it has never been characterized. The aim of this study was to identify the features of this halo and determine whether it should be included in the ablation volume during thermal ablation procedures.

Materials and methods

We prospectively enrolled 25 patients referred to our department for thermal ablation of liver metastases. Before treatment all patients underwent CEUS, and the maximum diameter of the metastatic lesion was measured before administration of the ultrasound contrast agent and during the arterial and portal venous phases of the contrast contrast-enhanced study. Maximum diameters in the different vascular phases were compared with the Turkey–Kramer test. Two biopsies were obtained from each lesion with a 21-gauge needle: 1) one from the center of the metastasis to confirm the diagnosis and 2) one from the hypervascular peripheral halo identified in the arterial phase at CEUS.

Results

The mean (±standard deviation) maximum lesion diameter was 2.67 ± 1.2 cm before contrast agent injection, 3.50 ± 1.4 cm during the arterial phase, and 2.71 ± 1.2 cm during the venous phase. The difference between maximum diameters measured before contrast enhancement and in the arterial phase was highly significant (mean: 0.84 ± 0.45 cm, p < 0.0001). Histological examination of halo specimens revealed inflammatory infiltrates with no evidence of tumor infiltration in 24/25 (96%) cases and normal hepatic parenchymal tissue in the 25th specimen.

Discussion

The hypervascular halo surrounding liver metastases during the arterial phase of CEUS represents a chronic inflammatory infiltrate, not tumor infiltration. However, since chronic inflammation appears to promote neovascularization and the production of tumoral growth factors, it seems wise to include the hypervascular halo in the intended-to-treat volume when planning the ablation procedure.     

Is there a role for liver transplantation in the treatment of hepatocellular carcinoma in non-cirrhotic liver?

Whether liver transplantation (LT) plays a role in the treatment of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver (NCL) is a matter of debate. The recommendations for LT in this setting are extremely fragile and less well-defined than for cirrhosis-associated HCC. All reports of LT for NCL-HCC revealed that long-term outcomes of these patients are poor, and these dismal figures are justified by the advanced tumor stage at the time of LT, suggesting the presence of systemic micrometastatic disease. The decision-making regarding LT for NCL-HCC is difficult, since specific selection criteria are scarce, and basically the potential candidates are those with unresectable only-liver tumor at admission, or unresectable intrahepatic recurrence post-resection. Besides the surgical aspects regarding the tumor resectability, other phenotypic and genetic characteristics of the tumor should be considered for the indication of LT in this scenario. The present minireview aims to discuss and analyze the last series of LT for NCL-HCC, in order to help clinicians in the decision-making process regarding the role of LT in NCL-HCC treatment.     

Is meta-analysis clinically useful for perianesthesia nurses?

Meta-analyses can provide clinicians with the evidence-based information necessary to effect change in patient care delivery. Meta-analysis, the application of statistical techniques to condense data from a group of individual studies, is the most sophisticated summary of research evidence. An example meta-analysis study of inadvertent surgical hypothermia is used in this article to describe how nurses can locate, evaluate, and apply synthesized research data for perianesthesia clinical practice. Without data to support decisions, nurses will increasingly be faced with decisions made by others based on cost-cutting measures alone. Although meta-analysis may resolve a controversy or solve a clinical problem, it will not provide simple statistical answers for complex problems or obviate the need for sound and compassionate clinical judgment.     

Radiofrequency ablation of neuroendocrine liver metastases—the Middlesex experience

Background Current treatment options for neuroendocrine liver metastases are not widely applicable or not that effective. Image-guided thermal ablation offers the possibility of a minimally invasive, albeit palliative, treatment that decreases tumor volume, preserves most of the normal liver, and can be repeated several times. We report our experience with image-guided thermal ablation in 25 patients with unresectable liver metastases.Methods Since 1990 we have treated 189 tumors at 66 treatment sessions in 25 patients (12 female, 13 male; median age, 56 years; age range, 26–78 years). Thirty treatments were performed with a solid-state laser, and 36 treatments were performed with radiofrequency ablation. All but one treatment was performed percutaneously under image guidance. Sixteen patients had metastases from carcinoid primaries, three from gastrinoma, two from insulinoma, and four from miscellaneous causes. Fourteen of 25 had symptoms from hormone secretion.Results Imaging follow-up was available in 19 patients at a median of 21 months (range, 4–75 months). There was a complete response in six patients, a partial response in seven, and stable disease in one; hence, tumor load was controlled in 14 of 19 patients (74%). Relief of hormone-related symptoms was achieved in nine of 14 patients (69%). The median survival period from the diagnosis of liver metastases was 53 months. One patient with end-stage cardiac disease died after a carcinoid crisis. There were eight (12%) complications: five local and three distant, four major and four minor.Conclusions As a minimally invasive, readily repeatable procedure that can be used to ablate small tumors, preferably before patients become severely symptomatic, radiofrequency ablation can provide effective control of liver tumor volume in most patients over many years.     

Three-dimensional ultrasound volumetric measurements: Is the largest number of image planes necessary for outlining the region-of-interest?

Volumetric measurement is useful in the clinical practice as it can accurately assess the size of organs and lesions, which aids diagnosis and monitoring of treatment response. This in vitro study was undertaken to evaluate and compare the accuracy of three-dimensional ultrasound (3D-US) volumetric measurements using different numbers of image planes for outlining the region-of-interest. A total of 20 tissue phantoms (10 with regular and 10 with irregular tissue specimens) with known volume (2.2 - 14.7 ml) were constructed. The tissue phantoms were scanned with a commercially-available ultrasound machine in conjunction with a 3D add-on system and the volume of the tissue specimen of the phantoms was measured by manual outlining of the boundaries using different numbers of image plane (16, eight, four and two image planes). Results showed that there was a high accuracy in 3D-US volumetric measurements, when 16 and eight image planes were used (best-fit slope between measured and true volume: 0.9224-0.9761 and 0.9099-0.956, respectively). Results also showed that there was no significant difference in the volume measured with 16 and eight image planes for both phantoms with regular- and irregular-shaped tissue specimens (p > 0.05). The measurement differences between 16 and eight image planes ranged from -0.07 to 0.14 ml for phantoms with regular-shaped tissue and from -0.24 to 0.1 ml for phantoms with irregular-shaped tissue. 3D-US has a high accuracy in volumetric measurements of regular- and irregular-shaped structures. Although highest accuracy in volume measurements was found when 16 image planes were used, similar level of accuracy can be achieved with eight image planes but the measurement time can be reduced by 50%. Therefore, in 3D-US volumetric measurements, the largest number of image planes may not be necessary for outlining the region-of-interest.     

Activities of daily living. Old-fashioned or still useful?

1 The Index of Activities of Daily Living (ADL) is used by many nurses to assess function in older adults, but there is debate regarding the scoring, wording of questions, and validity in diverse populations. 2 Older adults may give inaccurate answers to ADL questions because they misunderstand the questions, have personal reasons for underreporting or overreporting difficulty in ADL, or fail to recognize difficulty because they have adapted to changes in function. 3 Physical performance tests, especially of the lower extremities, may be an alternative method of assessing function, especially in high-functioning older adults who report no difficulty in ADL.