Outcomes Post Beyond Total Mesorectal Excision Plane Resections Following Setting up Complex Colorectal Cancer Service in a District General Hospital.

Background: This study aims to validate the feasibility of a hub-and-spoke model for pelvic exenteration (PE) surgery while upholding favorable patient outcomes. Methods: A retrospective analysis of patients undergoing PE at our trust October 2017 and December 2023 was conducted. Descriptive statistics and Kaplan-Meier survival analysis were employed. Results: Sixty-seven patients underwent PE during the study period, mainly for locally advanced colorectal cancer (n=61, 91.04%). Minimally invasive surgery was performed in 16 cases (Robotic 3, 4.47% / Laparoscopic 13, 19.40) while the rest of patients 51 had open surgery (75.11%). Median hospital stay was 12 days (range:8-20). While 24 patients (35.82%) developed major complications (CD III-IV) post-surgery, there were no mortalities associated with pelvic exenteration in this study. Of the 67 patients undergoing surgery with curative intent, negative margins (R0 resection) were achieved in 57 patients (85.12%). This is comparable to outcomes reported by the PelvEx collaborative (85.07% versus 79.8%). At a median follow-up of 22 months, 15 patient (22.38%) recurred with 10.44% local recurrence rate. The 2 years overall and disease-free survival were 85.31% and 77.0.36%, respectively. Conclusion: Our study suggests that a nascent PE service, supported by specialist expertise and resources, can achieve good surgical outcomes within a district general hospital.

UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) with oxaliplatin for colorectal cancer peritoneal metastases (NCT03868228).

Objectives: This is the first UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for colorectal cancer peritoneal metastases. This trial aimed to assess the impact of PIPAC in combination with standard of care systemic treatment on: progression free survival (PFS); quality of life (QoL); and short-term complications. In addition, this trial set out to demonstrate that PIPAC can be performed safely in operating theatres within a National Health Service (NHS) setting. Methods: Single-centre clinical trial with prospective data collection for patients undergoing 8-weekly PIPAC with oxaliplatin at 92 mg/m2 from January 2019 till January 2022. Progression free survival was assessed using peritoneal carcinomatosis index (PCI) by CT scans and laparoscopy. Quality of life was assessed by EORTC QLQ-C30 questionnaire. Adverse events were recorded using CTCAE. Results: Five patients underwent a total of ten PIPAC administrations (median 2, range 1-4). Median PFS was 6.0 months. QoL was maintained across repeat PIPAC procedures but a decrease in social functioning and increased fatigue were evident. Three incidences of grade 3 adverse events occurred but PIPAC was well tolerated. Conclusions: The presented data demonstrates that PIPAC is feasible and can be safely delivered within the NHS for patients with colorectal cancer peritoneal metastases, but caution must also be exercised given a risk of adverse events. Systemic chemotherapy can be safely administered at a different unit to the PIPAC procedure if both groups have clear lines of communication and timely data sharing.

Cast Tube Assay: A 3-D in vitro assay for visualization and quantification of horizontal chemotaxis and cellular invasion.

Directed cell motility, as controlled by soluble factors, is crucial for many biological processes, including development, cancer progression, and wound healing. The use of directed cell motility also shows promise for applications in regenerative medicine such as therapeutic angiogenesis. Unfortunately, current in vitro 3-D migration and invasion models limit our understanding and application of these processes. Here, we present a novel and cost-effective 3-D chemotaxis assay for assessing the invasive response of cells to a chemoattractant extracellular matrix (ECM). Our system takes advantage of a custom-casting chamber to set two gels in contact with each other along a defined front, one containing a suitable chemoattractant and the other the cells. Rotation of the chamber allows easy visualization of invasion across the interface. The effectiveness of the assay was demonstrated by studying the invasion of both human dermal fibroblasts (FBs) and smooth muscle cells (SMCs) into a polyethylene glycol (PEG) hydrogel containing basic fibroblast growth factor (bFGF). Incorporation of bFGF resulted in significantly increased and directional invasion for both cell groups.

Simultaneous isolation of enriched myoblasts and fibroblasts for migration analysis within a novel co-culture assay.

Skeletal muscle injury elicits the activation of satellite cells and their migration to the wound area for subsequent terminal differentiation and tissue integration. However, interstitial fibroblasts recruited to the site of injury promote deposition of fibrotic tissue, which hampers myoblast-mediated muscle regeneration. Currently, analysis of myoblast migration in vitro can be accomplished using chemotactic, cell-exclusion, or wound healing assays. Yet, to investigate cell motility following skeletal muscle damage more accurately, migration assays need to better simulate the repair process. Here we present a protocol for the simultaneous isolation of myoblasts and fibroblasts from the same muscle tissue, ensuring the consistent generation of enriched, purified, and matched cell populations at a low passage number. We then describe a wound assay that uses a novel approach to the co-culture of myoblasts and fibroblasts to mimic the injured environment more closely than other established methods. Using this assay, we demonstrate that fibroblasts are able to increase myoblast migration significantly, validating our new in vitro method. As the observed effect on migration is most likely mediated by secreted factors, our assay could easily be extended to include antibody-based protein analysis of secreted factors in animal or human systems.

Coacervate Delivery of Growth Factors Combined with a Degradable Hydrogel Preserves Heart Function after Myocardial Infarction.

Regenerative therapies to improve prognosis after heart attack and mitigate the onset of heart failure are urgently needed. To this end, we developed a bioactive therapy of sustained release of the morphogen Sonic hedgehog (Shh) and the anti-inflammatory cytokine interleukin-10 (IL-10) from a coacervate delivery vehicle. This is combined with a structural therapy consisting of a biodegradable polyethylene glycol (PEG) hydrogel, harnessing the benefits of both components. Upon injection into the hearts of rats after heart attack, we found that each component synergistically improved the benefit of the other. Furthermore, their combination was critical to preserve heart function. These findings indicate that, when combined, growth factor delivery and an injectable hydrogel represent a promising therapeutic approach for treatment after heart attack.

Traumatic orbital compartment syndrome: importance of prompt recognition and management.

The orbit is a cone-shaped structure formed by rigid bony walls within which the globe and retrobulbar contents are encased. Anteriorly, the orbital septum and eyelids form another relatively inflexible boundary. The medial and lateral canthal tendons attach the eyelids to the orbital rim and also limit any anterior displacement of the globe. Although small increases in orbital volume can be compensated for by forward displacement of the globe and prolapse of fat, a rapid rise in intraorbital pressure normally ensues. This increase in pressure within the confined space of the orbit causes decreased perfusion with associated ischaemic damage not unlike that seen in other compartment syndromes. We report a case of traumatic orbital compartment syndrome successfully decompressed by means of a lateral canthotomy.