Continuous wound infusion with ropivacaine alone provides adequate analgesia following laparotomy.

BACKGROUND: Although continuous wound infusion (CWI) with local anaesthetic has been used as an adjunct for pain relief following laparotomy, its use as the main modality has not been studied. This approach negates side effects related to intravenous opioid administration, therefore promoting enhanced recovery from surgery. We conducted this study to investigate the feasibility and efficacy of CWI following laparotomy. METHODS: Consecutive patients who underwent laparotomy from June 2016 to December 2019 were analysed. All patients were given CWI with only oral supplementation. Pain was assessed based on the numeric rating scale (NRS). RESULTS: One hundred and three patients were analysed. Mean age was 61.1 (standard deviation 16.7). 47.6% of patients were operated for intestinal obstruction. Large bowel resection was the most common operation performed (49.5%). 69.9% of patients underwent emergency surgery, whilst 51.5% of patients had surgery for cancer. On postoperative day 0, NRS was 3.2 (standard deviation (sd) 2.6) which decreased to 1.5 (sd 1.9) on day 3, and 1.1 (sd 1.8) on day 5. Mean time to flatus was 2.3 (sd 1.4) days, whilst mean time to first bowel movement was 3.1 (sd 1.7) days. Patients were able to commence ambulation by 2.5 (sd 1.8) days. Patients could tolerate a normal diet on day 3.9 (sd 3.3), and IV drip was removed on day 3.5 (sd 3.0). Mean length of stay was 9.1 (sd 6.9) days. Only two patients suffered from respiratory depression (1.9%) whilst five patients suffered from hypotension (4.9%). No patients had pruritus. 23.3% of patients had nausea or vomiting. Only one patient had a catheter-related complication which was easily addressed. CONCLUSION: CWI provides adequate pain relief as the principle modality of analgesia after surgery, without opioid side effects.

Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: role in driving cancer progression.

Colorectal cancer is a global disease with increasing incidence. Mortality is largely attributed to metastatic spread and therefore, a mechanistic dissection of the signals which influence tumor progression is needed. Cancer stroma plays a critical role in tumor proliferation, invasion and chemoresistance. Here, we sought to identify and characterize exosomal microRNAs as mediators of stromal-tumor signaling. In vitro, we demonstrated that fibroblast exosomes are transferred to colorectal cancer cells, with a resultant increase in cellular microRNA levels, impacting proliferation and chemoresistance. To probe this further, exosomal microRNAs were profiled from paired patient-derived normal and cancer-associated fibroblasts, from an ongoing prospective biomarker study. An exosomal cancer-associated fibroblast signature consisting of microRNAs 329, 181a, 199b, 382, 215 and 21 was identified. Of these, miR-21 had highest abundance and was enriched in exosomes. Orthotopic xenografts established with miR-21-overexpressing fibroblasts and CRC cells led to increased liver metastases compared to those established with control fibroblasts. Our data provide a novel stromal exosome signature in colorectal cancer, which has potential for biomarker validation. Furthermore, we confirmed the importance of stromal miR-21 in colorectal cancer progression using an orthotopic model, and propose that exosomes are a vehicle for miR-21 transfer between stromal fibroblasts and cancer cells.

Profiling the MicroRNA Payload of Exosomes Derived from Ex Vivo Primary Colorectal Fibroblasts.

The tumor microenvironment is a heterogeneous and dynamic network that exists between cancer and stroma, playing a critical role in cancer progression. Certain tumorigenic signals such as microRNAs are derived from the stroma and conveyed to cancer cells (and vice versa) in nanoparticles called exosomes. Their identification and characterization is an important step in better understanding cellular cross talk and its consequences. To this end we describe how to culture primary ex vivo derived fibroblasts from colorectal tissue, isolate their exosomes, extract exosomal RNA and perform microRNA profiling.

Towards low carbon society in Iskandar Malaysia: Implementation and feasibility of community organic waste composting.

Rapid population growth and urbanisation have generated large amount of municipal solid waste (MSW) in many cities. Up to 40-60% of Malaysia's MSW is reported to be food waste where such waste is highly putrescible and can cause bad odour and public health issue if its disposal is delayed. In this study, the implementation of community composting in a village within Iskandar Malaysia is presented as a case study to showcase effective MSW management and mitigation of GHG emission. The selected village, Felda Taib Andak (FTA), is located within a palm oil plantation and a crude palm oil processing mill. This project showcases a community-composting prototype to compost food and oil palm wastes into high quality compost. The objective of this article is to highlight the economic and environment impacts of a community-based composting project to the key stakeholders in the community, including residents, oil palm plantation owners and palm oil mill operators by comparing three different scenarios, through a life cycle approach, in terms of the greenhouse gas emission and cost benefit analysis. First scenario is the baseline case, where all the domestic waste is sent to landfill site. In the second scenario, a small-scale centralised composting project was implemented. In the third scenario, the data obtained from Scenario 2 was used to do a projection on the GHG emission and costing analysis for a pilot-scale centralised composting plant. The study showed a reduction potential of 71.64% on GHG emission through the diversion of food waste from landfill, compost utilisation and significant revenue from the compost sale in Scenario 3. This thus provided better insight into the feasibility and desirability in implementing a pilot-scale centralised composting plant for a sub-urban community in Malaysia to achieve a low carbon and self-sustainable society, in terms of environment and economic aspects.

A top-down view of the tumor microenvironment: structure, cells and signaling.

It is well established that the tumor microenvironment (TME) contributes to cancer progression. Stromal cells can be divided into mesenchymal, vascular, and immune. Signaling molecules secreted by the tumor corrupts these cells to create "activated" stroma. Equally, the extracellular matrix (ECM) contributes to tumor development and invasion by forming a biologically active scaffold. In this review we describe the key structural, cellular and signaling components of the TME with a perspective on stromal soluble factors and microRNAs (miRNAs).