Optimising the management of dysplastic lesions in the oesophagus with photodynamic therapy

The outcome of patients suffering from adeno and squamous carcinoma of the oesophagus remains poor. In the west, the incidence of adenocarcinoma has increased dramatically, with most cases occurring in association with Barrett's oesophagus (BE). Both adeno and squamous carcinoma are believed to progress through worsening degrees of dysplasia. This thesis assesses the role of Elastic Scattering Spectroscopy (ESS) as an objective diagnostic test for dysplasia and Photodynamic Therapy (PDT) with 5-aminolevulinic acid (ALA) as a less invasive treatment option. It also looks for a better understanding of the factors influencing mucosal healing after PDT. Using ESS, the sensitivity and specificity was 83% for distinguishing HGD/cancer from LGD/non dysplastic BE. Low dose ALA (30mg/kg) PDT eradicated 38% of HGD in BE compared with 67% eradication with a higher dose (60mg/kg). The higher dose also decreased the length of BE. In a study comparing red with green light (fixed light doses) for treating HGD, at 30 mg/kg ALA, 63% and 13 % of patients were clear of HGD with red and green laser respectively. At 60 mg/kg, the corresponding figures were 78% and 33% for the same light dose. 5 of 5 patients with LGD in BE and 4 of 5 patients with HGD in squamous mucosa had their dysplasia eradicated with ALA PDT. Successful PDT involves healing by regeneration of normal squamous mucosa. My in vitro studies created a PDT wound model using malignant oesophageal cell lines to assess the role of different cytokines in healing. Keratinocyte Growth Factor (KGF) was found to promote wound healing after PDT and significantly encouraged (p 0.001) the development of squamous cell lines. In conclusion: 1. ESS can differentiate dysplasia and early cancer from non-dysplastic and normal mucosa (sensitivity and specificity 83%). 2. PDT using high dose (60mg/kg) ALA (but not low dose) is effective in eradicating HGD in BE using red light. 3. The cytokine, KGF may promote healing with squamous mucosa after PDT. 4. Larger scale clinical trials are now required to confirm these results

Efficacy of Ketamine in Improving Pain after Tonsillectomy in Children: Meta-Analysis

<div><p>Background and objectives</p><p>The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children.</p><p>Subjects and Methods</p><p>Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0–24 hours after leaving the operation room were included in the analysis.</p><p>Results</p><p>The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics.</p><p>Conclusion</p><p>Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study.</p></div

Preoperative ketamine versus control or opioids.

<p>Odd ratio of the incidence of analgesic requirements (A, B), standard mean difference of amounts of analgesic requirements (C, D), time to first analgesic administration (E, F), and time of first oral intake (G, H) (total : number of participants per group).</p

Subgroup analysis of the effects of administration routes of ketamine on the postoperative pain.

<p>Subgroup analysis of the effects of administration routes of ketamine on the postoperative pain.</p

Preoperative ketamine versus control.

<p>Standard mean difference of amounts of antiemesis requirements (A) and odd ratio of the incidence of postoperative nausea and vomitting (B) (total : number of participants per group).</p

Diagram of selection of studies.

<p>Diagram of selection of studies.</p

Subgroup analysis of the effects of administration routes of ketamine on the consumption of analgesics.

<p>Subgroup analysis of the effects of administration routes of ketamine on the consumption of analgesics.</p

Turbinate size-related changes in immunophenotypic characteristics.

<p>hTMSCs in the hypertrophic turbinate (A) and the contralateral turbinate (B) were negative for CD14, CD19, CD34, and HLA-DR, and positive for CD29, CD73, CD90, a phenotype characteristic of mesenchymal stem cells. The hTMSCs in the two groups expressed a comparable proportion of specific surface markers.</p

Effect of turbinate size on the osteogenic differentiation potential of hTMSCs.

<p>Cells were cultured in osteogenic induction medium. RT-PCR analysis of bone sialoprotein (BSP), runt-related transcription factor 2 (Runx2), bone morphogenetic protein-2 (BMP-2), osterix (Osx), osteocalcin (OC), and type I collagen (Col1) mRNA in osteogenically differentiated hTMSCs during 2 weeks of culture. The experiment was repeated in triplicate for each sample. No significant difference between the groups was identified by unpaired t-test (<i>p</i><0.05).</p

Data of patients with nasal septal deviation showing their cellular count and viabilty of hTMSCs.

<p>Data of patients with nasal septal deviation showing their cellular count and viabilty of hTMSCs.</p