Lightweight versus heavyweight mesh in laparoscopic inguinal hernia repair: a meta-analysis.

BACKGROUND: Reinforcement of inguinal hernia repair with prosthetic mesh is standard practice but can cause considerable pain and stiffness around the groin and affect physical functioning. This has led to various types of mesh being engineered, with a growing interest in lighter-weight mesh. Minimally invasive approaches have also significantly reduced postoperative recovery from inguinal hernia repair. The aim of this systematic review was to compare the outcomes after laparoscopic inguinal repair using new lightweight or traditional heavyweight mesh in published randomised controlled trials. METHODS: Medline, Embase, trial registries, conference proceedings, and reference lists were searched for controlled trials of heavyweight versus lightweight mesh for laparoscopic repair of inguinal hernias. The primary outcomes were recurrence and chronic pain. Secondary outcomes were visual analogue pain score at 7 days postoperatively, seroma formation, and time to return to work. Risk differences were calculated for categorical outcomes and standardised mean differences for continuous outcomes. RESULTS: Eight trials were included in the analysis of 1,667 hernias in 1,592 patients. Mean study follow-up was between 2 and 60 months. There was no effect on recurrence [pooled analysis risk difference 0.00 (95% CI -0.01 to 0.01), p = 0.86] or chronic pain [pooled analysis risk difference -0.02 (95% CI -0.04 to 0.00); p = 0.1]. Lightweight and heavyweight mesh repair had similar outcomes with regard to postoperative pain, seroma development, and time to return to work. CONCLUSION: Both mesh options appear to result in similar long- and short-term postoperative outcomes. Further long-term analysis may guide surgeon selection of mesh weight for laparoscopic inguinal hernia repair.

The role of ABCG2 in modulating responses to anti-cancer photodynamic therapy.

The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) transmembrane protein transporter is known for conferring resistance to treatment in cancers. Photodynamic therapy (PDT) is a promising anti-cancer method involving the use of light-activated photosensitisers to precisely induce oxidative stress and cell death in cancers. ABCG2 can efflux photosensitisers from out of cells, reducing the capacity of PDT and limiting the efficacy of treatment. Many studies have attempted to elucidate the relationship between the expression of ABCG2 in cancers, its effect on the cellular retention of photosensitisers and its impact on PDT. This review looks at the studies which investigate the effect of ABCG2 on a range of different photosensitisers in different pre-clinical models of cancer. This work also evaluates the approaches that are being investigated to address the role of ABCG2 in PDT with an outlook on potential clinical validation.

Characterising a PDMS based 3D cell culturing microfluidic platform for screening chemotherapeutic drug cytotoxic activity.

Three-dimensional (3D) spheroidal cell cultures are now recognised as better models of cancers as compared to traditional cell cultures. However, established 3D cell culturing protocols and techniques are time-consuming, manually laborious and often expensive due to the excessive consumption of reagents. Microfluidics allows for traditional laboratory-based biological experiments to be scaled down into miniature custom fabricated devices, where cost-effective experiments can be performed through the manipulation and flow of small volumes of fluid. In this study, we characterise a 3D cell culturing microfluidic device fabricated from a 3D printed master. HT29 cells were seeded into the device and 3D spheroids were generated and cultured through the perfusion of cell media. Spheroids were treated with 5-Fluorouracil for five days through continuous perfusion and cell viability was analysed on-chip at different time points using fluorescence microscopy and Lactate dehydrogenase (LDH) assay on the supernatant. Increasing cell death was observed in the HT29 spheroids over the five-day period. The 3D cell culturing microfluidic device described in this study, permits on-chip anti-cancer treatment and viability analysis, and forms the basis of an effective platform for the high-throughput screening of anti-cancer drugs in 3D tumour spheroids.

A Review on the Scope of Photothermal Therapy-Based Nanomedicines in Preclinical Models of Colorectal Cancer.

Oncologic thermal ablation involves the use of hyperthermic temperatures to damage and treat solid cancers. Thermal ablation is being investigated as a method of treatment in colorectal cancers and has the potential to complement conventional anticancer treatments in managing local recurrence and metastatic disease. Photothermal therapy utilizes photosensitive agents to generate local heat and induce thermal ablation. There is growing interest in developing nanotechnology platforms to deliver such photosensitive agents. An advantage of nanomedicines is their multifunctionality, with the capability to deliver combinations of chemotherapeutics and cancer-imaging agents. To date, there have been no clinical studies evaluating photothermal therapy-based nanomedicines in colorectal cancers. This review presents the current scope of preclinical studies, investigating nanomedicines that have been developed for delivering multimodal photothermal therapy to colorectal cancers, with an emphasis on potential clinical applications.

Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer.

BACKGROUND: Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids. METHODS: Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0-200 nM) for 16 h. Cultures were irradiated with light (1 J/cm2) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 µM Ko143, on cytotoxicity following Hypericin-PDT was evaluated. RESULTS: Hypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01). CONCLUSIONS: Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition.

Faecal calprotectin in patients with suspected colorectal cancer: a diagnostic accuracy study.

BACKGROUND: NICE guidance exists for the use of faecal calprotectin (FC) when irritable bowel syndrome or inflammatory bowel disease are suspected. Often, however, colorectal cancer is considered within the differential. Should FC have a high diagnostic accuracy for colorectal cancer, it may be applicable as a primary care screening test for all patients with lower gastrointestinal symptoms. AIM: To determine the negative and positive predictive value (NPV/PPV) of FC in patients referred from primary care with suspected colorectal cancer. DESIGN AND SETTING: A diagnostic accuracy study conducted at a single secondary care site METHOD: Consenting patients referred with suspected colorectal cancer within the '2-week wait' pathway provided a stool sample for FC prior to investigation. FC levels were reconciled with end diagnoses: cancer, adenomatous polyps ≥10 mm, and all enteric organic disease. RESULTS: A total of 654 patients completed the evaluation; median age 69 years, female 56%. The NPV for colorectal cancer was 98.6% and 97.2% when including polyps ≥10 mm. The PPV for all organic enteric disease was 32.7%. The diagnostic yield for cancer based on clinical suspicion was 6.3%. By altering the FC cut-off to fix the NPV at 97.0%, the PPV for cancer increased from 8.7% to 13.3%. CONCLUSION: FC has a high NPV for colorectal cancer and significant polyps in patients with suspected cancer. In total, 27.8% of patients had a normal FC and could safely have been spared a '2-week wait' referral. The addition of FC testing into the current symptom-based assessment has the potential to increase colorectal cancer detection rate yet be clinically and cost effective.