Temperature monitoring and lesion volume estimation during double-applicator laser-induced thermotherapy in ex vivo swine pancreas: a preliminary study

Tissue temperature distribution plays a crucial role in the outcome of laser-induced thermotherapy (LITT), a technique employed for neoplasias removal. Since recent studies proposed LITT for pancreatic tumors treatment, assessment of temperature and of its effects around the laser applicator could be useful to define optimal laser settings. The aims of this work are temperature monitoring and measurement of ablated tissue volume in an ex vivo porcine pancreas undergoing double-applicator LITT. A three-dimensional numerical model is implemented to predict temperature rise and volumes of ablated tissue in treated pancreas. Experiments are performed to validate the model, with two modalities: (1) 12-fiber Bragg grating sensors are adopted to monitor the heating and cooling during LITT at several distances from the applicators tip, and (2) 1.5-T MR imaging is used to estimate the ablated volume. Experimental data agree with theoretical ones: at 2 mm from both applicators tips, the maximum temperature increase is approximately 60 °C downward from the tips, while it increases of about 40 °C and 30 °C, respectively, at the level and upward from the tips. This behavior occurs also at other distances, proving that the tissue downward from the tip is mostly heated. Furthermore, the estimated volume with MRI agrees with theoretical one (i.d., 0.91?±?0.09 vs. 0.95 cm³). The encouraging results indicate that the model could be a suitable tool to choose the optimal laser settings, in order to control the volume of ablated tissue.     

Light-cured resin for post patterns.

A method of using light-cured acrylic resin as an alternative to the use of chemically-cured acrylic resins with elastomeric impressions for direct post patterns is presented. The GC Unifast LC acrylic resin is a powder/liquid type resin cured by exposure to visible light. The polymerization process has four stages before final curing: slurry, stringy, dough-like (plastic), and rubber-like (elastic). Advantages over current direct and indirect procedures include ease of manipulation of the material and no change in laboratory handling procedures. While in the dough-like state, the material can be contoured. In the rubber-like state, it is flexible to disengage from minor undercut areas.     

An evaluation of a strategy to improve the support of orthopaedic nurses through a team preceptorship programme

Transition to a new work area is often stressful for both experienced and new graduate nurses. It is essential that the new graduate be supported through this transition period to enable them to adjust to the environment itself, refine knowledge, and develop skills specific to their chosen clinical stream. In past years, several strategies have been designed with varying levels of success.This study evaluates an Australian transition support model, where the fundamental difference is that the management of the program is facilitated by a nurse possessing refined leadership, communication, clinical and organisational skills.The model has been evaluated on its effectiveness in meeting specific outcomes. The findings revealed that this coordinated team approach provided increased support for the new graduate, reduced the stress and workloads on the preceptors, whilst promoting confidence in the new starters and preventing conflict between preceptors and preceptees. The Coordinator’s role was shown to be an effective and crucial component in the Coordinated Team Preceptorship Model (CTPM) and findings illustrated that a team preceptorship model is not sustainable without a Coordinator.     

Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study

This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18–65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate-the equivalent of 900 mg aspirin- combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2-severe or moderate-to grade 1 or 0-mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.     

Ureteroscopic and extirpative treatment of upper urinary tract urothelial carcinoma: a 15‐year comprehensive review of 160 consecutive patients

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UTUC) have historically been treated with radical, extirpative surgery, primarily nephroureterectomy with bladder‐cuff excision. In general, there has been growing interest in renal preservation, as evidenced by the broadening application of nephron‐sparing surgery for renal parenchymal tumours. Beyond imperative reasons such as tumour in a solitary kidney, bilateral disease, or comorbidities preventing radical surgery, there is a growing role for endoscopic management of upper tract tumours. The aim has been to obtain similar oncological results to those of extirpative surgery, while preserving long‐term renal function. Properly selecting patients for these therapies, designing specific treatments based on a complex presentation, and general information with regard to outcomes and risks for patient counselling have been based historically on results from relatively small series without long‐term follow‐up. This study reflects all patients with UTUC treated by a single tertiary referral surgeon, accrued prospectively over 15 years using the same surgical techniques and treatment algorithms throughout the entire study period, with 10‐year survival data. The consecutively accrued nature and size of the study groups, uniformity in treatments, statistical review and long‐term follow‐up provide baseline oncological data that could help frame future study.

OBJECTIVE

• ? To present long‐term oncological outcomes of all patients treated surgically for upper urinary tract urothelial carcinoma (UTUC) over a 15‐year period.

PATIENTS AND METHODS

• ? All patients (N= 160) treated from January 1996 to August 2011 were prospectively studied and placed into three distinct groups after initial diagnostic ureteroscopy (URS): Group 1: low grade lesions treated with URS (n= 66); Group 2: high grade lesions palliatively treated with URS (n= 16); and Group 3: extirpative surgery (nephroureterectomy [NU]; n= 80).
• ? Statistical analysis was performed using Kaplan–Meier methodology to calculate overall (OS), cancer‐specific (CSS) and metastasis‐free survival (MFS).

RESULTS

• ? The median patient age at presentation was 73 years, and the mean (range) follow‐up time was 38.2 (1–185) months. At initial diagnostic URS, 71 (44.4%) patients presented with high grade and 89 (55.6%) patients presented with low grade disease.
• ? The 2‐, 5‐ and 10‐year CSS rates were 98, 87 and 81% for patients with low grade disease, and 97, 87 and 78% for patients treated with URS (Group 1), not significantly different from those patients with low grade disease treated with NU (Group 3), (P= 0.54).
• ? Of the patients treated with URS for low grade disease, 10 (15.2%) progressed to high grade disease at a mean time of 38.5 months.
• ? Patients with high grade disease treated with NU had a 2‐, 5‐, and 10‐year CSS of 70, 53 and 38%, with a MFS of 55, 45 and 35%.
• ? Median survival of patients with high grade disease treated with palliative URS was 29.2 months with a 2‐year OS of 54%.
• ? On multivariate analysis only high grade lesion on initial presentation was found to be a significant factor (P < 0.001; hazard ratio = 7.27).

CONCLUSIONS

• ? Grade is the most significant predictor of OS and CSS in those with UTUC, regardless of treatment method.
• ? Ureteroscopic and extirpative therapy are acceptable options for those with low grade disease showing excellent long‐term CSS.
• ? Extirpative therapy was found to result in relatively poor long‐term CSS in patients with high grade disease, underscoring the need for adjuvant or neoadjuvant therapies.

     

MUTYH mediates the toxicity of combined DNA 6-thioguanine and UVA radiation

The therapeutic thiopurines, including the immunosuppressant azathioprine (Aza) cause the accumulation of the UVA photosensitizer 6-thioguanine (6-TG) in the DNA of the patients'' cells. DNA 6-TG and UVA are synergistically cytotoxic and their interaction causes oxidative damage. The MUTYH DNA glycosylase participates in the base excision repair of oxidized DNA bases. Using Mutyh-nullmouse fibroblasts (MEFs) we examined whether MUTYH provides protection against the lethal effects of combined DNA 6-TG/UVA. Surprisingly, Mutyh-null MEFs were more resistant than wild-type MEFs, despite accumulating higher levels of DNA 8-oxo-7,8-dihydroguanine (8-oxoG). Their enhanced 6-TG/UVA resistance reflected the absence of the MUTYH protein and MEFs expressing enzymatically-dead human variants were as sensitive as wild-type cells. Consistent with their enhanced resistance, Mutyh-null cells sustained fewer DNA strand breaks and lower levels of chromosomal damage after 6-TG/UVA. Although 6-TG/UVA treatment caused early checkpoint activation irrespective of the MUTYH status, Mutyh-null cells failed to arrest in S-phase at late time points. MUTYH-dependent toxicity was also apparent in vivo. Mutyh^−/−mice survived better than wild-type during a 12-month chronicexposure to Aza/UVA treatments that significantly increased levels of skin DNA 8-oxoG. Two squamous cell skin carcinomas arose in Aza/UVA treated Mutyh^−/− mice whereas similarly treated wild-type animals remained tumor-free.