The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts' knowledge taking in consideration the relevant stakeholders' opinions and complying with the international methodology standards.
Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1%. With little improvement in survival rates observed in the past 40 years, there is a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically. We have previously demonstrated the benefit of combined chemo-sonodynamic therapy (SDT), delivered using oxygen carrying microbubbles (OMB), as a targeted treatment for pancreatic cancer in a murine model of the disease. In this manuscript, we report the preparation of a biotin functionalised Gem ligand for attachment to OMBs (OMB-Gem). We demonstrate the effectiveness of chemo-sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD) of the OMB-Gem and a Rose Bengal loaded OMB (OMB-RB) as a targeted treatment for pancreatic cancer. Specifically, UTMD using the OMB-Gem and OMB-RB conjugates reduced the viability of MIA PaCa-2, PANC-1, BxPC3 and T110299 pancreatic cancer cells by >60% (p < 0.001) and provided significant tumour growth delay (>80%, p < 0.001) compared to untreated animals when human xenograft MIA PaCa-2 tumours were treated in SCID mice. The toxicity of the OMB-Gem conjugate was also determined in healthy non-tumour bearing MF1 mice and revealed no evidence of renal or hepatic damage. Therefore, the results presented in this manuscript suggest that chemo-sonodynamic therapy using the OMB-Gem and OMB-RB conjugates, is potentially an effective targeted and safe treatment modality for pancreatic cancer.
Photodynamic therapy (PDT) is a clinically approved anti-cancer treatment that involves the activation of an otherwise inactive sensitiser drug with light, which in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS). As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge. In this manuscript, we have prepared a CaO nanoparticle (NP) formulation coated with a pH-sensitive polymer to enable the controlled generation of molecular oxygen as a function of pH. The polymer coat was designed to protect the particles from decomposition while in circulation but enable their activation at lower pH values in hypoxic regions of solid tumours. The oxygen generating capability of the polymer coated NPs was demonstrated in aqueous solution with minimal oxygen produced at pH7.4, whereas it increased significantly when the pH was reduced to 6.2. The polymer coated CaO NPs were also observed to significantly increase tumour pO levels (p<0.05) in mice bearing ectopic human xenograft MIA PaCa-2 pancreatic tumours with an average increase in tumour pO of 6.5mmHg in the period 10-30min following administration. A statistically significant improvement in PDT mediated efficacy (p<0.001) was also observed when the particles were administered to mice bearing the same tumours 20min prior to PDT treatment. These results suggest that the polymer coated CaO NP formulation offers significant potential as an in situ method for oxygen generation to enhance the efficacy of treatments that depend on the presence of oxygen to elicit a cytotoxic effect.
Open bile duct surgery seems superior to ERCP in achieving common bile duct stone clearance based on the evidence available from the early endoscopy era. There is no significant difference in the mortality and morbidity between laparoscopic bile duct clearance and the endoscopic options. There is no significant reduction in the number of retained stones and failure rates in the laparoscopy groups compared with the pre-operative and intra-operative ERCP groups. There is no significant difference in the mortality, morbidity, retained stones, and failure rates between the single-stage laparoscopic bile duct clearance and two-stage endoscopic management. More randomised clinical trials without risks of systematic and random errors are necessary to confirm these findings.
BACKGROUND: Depressive symptoms are an independent risk factor for outcome in patients with cardiac disease, but their effect on outcome among patients undergoing coronary artery bypass grafting is not well understood. OBJECTIVES: To determine whether or not clinical variables including length of stay, readmission rates, and mortality are related to patients' level of depressive symptoms before and after coronary artery bypass grafting. METHODS: An observational, longitudinal design was used. The Medical Outcomes Study 36-item short-form health survey was used to collect data on depressive symptoms in 416 patients undergoing coronary artery bypass grafting. The distribution of depressive symptoms was correlated with length of stay after the procedure, readmission, and mortality. RESULTS: The level of depressive symptoms before coronary artery bypass grafting correlated with the level of depressive symptoms at 6 weeks follow-up, both for the individual items "feeling down in the dumps" (r = 0.24, P = .009) and "feeling downhearted" (r = 0.36, P < .001) and for the overall score on the Mental Health scale (r = 0.40, P < .001). Feeling down in the dumps (P = .007) and overall scores on the Mental Health scale (P = .02) were significantly related to readmission within 6 months. CONCLUSIONS: Higher levels of depressive symptoms before coronary artery bypass grafting are related to higher hospital readmission rates 6 months after the procedure. Nurses can play a pivotal role in determining which patients require evaluation, educating patients, and initiating effective treatment, which may prevent readmission related to depressive symptoms.
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