Outcomes Following Colorectal Cancer Surgeries at the Basildon and Thurrock University Hospital.

Aim We reviewed surgical outcomes for patients with colorectal cancer resections in Basildon and Thurrock University Hospital between April 2019 and March 2020. Methods Clinical characteristics of 141 patients who underwent surgical resection for colorectal cancer at the district hospital were assessed and reported, including tumor site, disease stage, and type of surgical resection performed. We reviewed 30- and 90-day postoperative mortality, postoperative complications, return to the theater, and extended hospital stay data for these patients. The results of our review across measured outcomes were compared to the national average from the National Bowel Cancer Audit (NBOCA) Report. Results Clinical data and health outcomes for 141 patients with colorectal cancer resections within the index year were reviewed. The mean age at diagnosis was 68.9 (12.5) years. Among the patients, 61 (43.3%) were female, and 59 (41.8%) had Stage III and IV colorectal cancer. Around 95 (67.4%) had the colon as the primary tumor site, while 46 (32.6%) had the primary tumor site in the rectum. Of the patients, 17 (12.1%) had emergency surgeries, and 124 (87.9%) underwent laparoscopic surgery. Right hemicolectomy was the most common operation performed in 58 patients (41.1%). The average length of stay was 7.8 (6.6) days; the length of stay was similar for both colonic and rectal resections. Low 30-day and 90-day mortality rates of (1/141) 0.71% and (2/141) 1.4%, respectively, were observed compared to the 90-day United Kingdom (UK) national average mortality rate of 2.7% in 2019/20. Around 30 (21.3%) of the patients developed postoperative complications within 30 days of surgery. Only six out of 30 postoperative complications were classified as Clavien-Dindo Grade III. Conclusion Surgical outcomes for patients with colorectal cancer in our district general hospital are similar to or lower than the national averages estimated by NBOCA. To further strengthen surgical care delivery and improve patient outcomes in the United Kingdom, there is a need to improve surgical techniques and quality improvement processes.

Chronic Pain as a Complication in Open Inguinal Hernia Repair: A Retrospective Study of Consenting Practice in a Single Centre.

Introduction Inguinal hernia repair is one of the most commonly performed procedures in general surgery in the United Kingdom. Chronic pain as a long-term postoperative complication of this procedure has been extensively documented in the literature. However, this complication is often undisclosed during the consenting process. This omission impairs the patients' informed decision-making process. The Montgomery v Lanarkshire Health Board case, in 2015, changed the way in which patient consent is viewed legally. This has made proper consent practices more important to surgeons undertaking procedures. Aim The objective is to assess if there has been an improvement in consenting practices by comparing consent forms from 2015 (the year of the Montgomery ruling) and 2019, specifically in regard to the risk of chronic groin pain following open inguinal hernia repair with mesh. Methods This was a retrospective review of patients who underwent open inguinal hernia repair using a prosthetic mesh in 2015 and 2019. The medical records were retrieved on the trust's electronic medical record system using the patient's hospital number. The following parameters were obtained: patient demographics, preoperative clinic letters, operation notes and consent forms. The clinic letters and consent forms were systematically reviewed for any mention of chronic groin pain. Results In 2015 and 2019, 163 and 56 open inguinal hernia repairs with mesh were performed, respectively. The median age of patients was 63 (28-88) and 64.5 (19-88) in the respective years. Throughout both years there was a predominance in male patients, and the majority of cases were performed on an elective basis. Consent for chronic pain was present in 60.7% and 62.5% of cases in 2015 and 2019, respectively (p=0.055). Conclusion Despite the importance of adequate consenting practice, we found no significant improvement in consenting practice for chronic pain following open inguinal hernia repair in the four years following the Montgomery ruling.

Instituting a Green Zone for Elective Surgery During the Second Wave of COVID-19.

Objective Elective surgery came to a standstill during the first wave of COVID-19. The safe resumption of elective surgery with COVID-19 prevalent in the community remains a significant challenge. The aim of this study was to look into the outcomes of elective general surgery in a dedicated 'Green Zone (GZ)' during the second wave of COVID-19 in the United Kingdom. Method A 'Green Zone' pathway, meant to provide a COVID-free environment, was created. A retrospective review of prospectively collected data was done on consecutive patients who underwent an elective general surgical procedure at a single NHS trust over a six-month period (September 1, 2020, to February 28, 2021). The primary outcome was 30-day COVID-19 mortality. Secondary outcomes included 30-day non-COVID-19 mortality, readmissions, and complications. Results The study included 331 patients with a median age of 55 years (interquartile range, IQR, 41-67); 169 (51%) were females. The majority of the patients were American Society of Anaesthesiologists grade 2 (ASA 2; n=177, 53%) followed by ASA 3 (n=76, 23%). Forty-seven patients (14%) had been shielding earlier in the year. Most of the cases were day cases (n=224, 67%). There was no 30-day COVID-19 or non-COVID-19 mortality. One patient developed COVID-19 three weeks after the index operation. Thirty-day readmission and complication rate were 4% (n=14) and 6% (n=21). Most of the complications were Clavien-Dindo grade 2 (n=10, 3%) followed by an equal number of grades 1 and 3b (n=5, 1.5%). Conclusion This study has shown that a dedicated 'Green Zone' elective operating pathway is safe and feasible provided a balanced risk assessment approach is adopted.

Efficacy of the specific endothelin a receptor antagonist zibotentan (ZD4054) in colorectal cancer: a preclinical study.

Endothelin 1 (ET-1) is overexpressed in cancer, contributing to disease progression. We previously showed that ET-1 stimulated proliferative, migratory, and contractile tumorigenic effects via the ET(A) receptor. Here, for the first time, we evaluate zibotentan, a specific ET(A) receptor antagonist, in the setting of colorectal cancer, in cellular models. Pharmacologic characteristics were further determined in patient tissues. Colorectal cancer lines (n = 4) and fibroblast strains (n = 6), isolated from uninvolved areas of colorectal cancer specimens, were exposed to ET-1 and/or ET(A)/(B) receptor antagonists. Proliferation (methylene blue), migration (scratch wounds), and contraction (gel lattices) were assessed. Receptor distribution and binding characteristics (K(d), B(max)) were determined using autoradiography on tissue sections and homogenates and cytospun cells, supported by immunohistochemistry. Proliferation was inhibited by ET(A) (zibotentan > BQ123; P < 0.05), migration by ET(B) > ET(A), and contraction by combined ET(A) and ET(B) antagonism. Intense ET-1 stromal binding correlated with fibroblasts and endothelial cells. Colorectal cancer lines and fibroblasts revealed high density and affinity ET-1 binding (B(max) = 2.435 fmol/1 × 10(6) cells, K(d) = 367.7 pmol/L; B(max) = 3.03 fmol/1 × 10(6) cells, K(d) = 213.6 pmol/L). In cancer tissues, ET(A) receptor antagonists (zibotentan; BQ123) reduced ET-1 binding more effectively (IC(50): 0.1-10 µmol/L) than ET(B) receptor antagonist BQ788 (∼IC(50), 1 mmol/L). ET-1 stimulated cancer-contributory processes. Its localization to tumor stroma, with greatest binding/affinity to fibroblasts, implicates these cells in tumor progression. ET(A) receptor upregulation in cancer tissues and its role in tumorigenic processes show the receptor's importance in therapeutic targeting. Zibotentan, the most specific ET(A) receptor antagonist available, showed the greatest inhibition of ET-1 binding. With its known safety profile, we provide evidence for zibotentan's potential role as adjuvant therapy in colorectal cancer.

Biologics against cancer-specific receptors - challenges to personalised medicine from early trial results.

Understanding molecular mechanisms of tumourigenesis underlies new therapeutic strategies that specifically target tumours. This has led to the evolution of personalised therapy that was first used in breast cancer when hormone receptor status was determined. More recently in colorectal cancer treatment the Epidermal Growth Factor receptor and its tumourigenic role has led to its targeting by using Cetuximab and Panitumumab. Addition of these drugs to existing drug regimes (FOLFOX and FOLFIRI) showed improved respectability rates in patients with liver metastasis. Most recently the Endothelin receptor has been implicated in multiple tumourigenic processes. Interest has grown in using Endothelin A receptor antagonists as adjuvant or combination therapy as suggested by the FOLFERA and FOLFIRI trials currently on-going.

Endothelin-1 stimulates colon cancer adjacent fibroblasts.

Endothelin-1 (ET-1) is produced by and stimulates colorectal cancer cells. Fibroblasts produce tumour stroma required for cancer development. We investigated whether ET-1 stimulated processes involved in tumour stroma production by colonic fibroblasts. Primary human fibroblasts, isolated from normal tissues adjacent to colon cancers, were cultured with or without ET-1 and its antagonists. Cellular proliferation, migration and contraction were measured. Expression of enzymes involved in tumour stroma development and alterations in gene transcription were determined by Western blotting and genome microarrays. ET-1 stimulated proliferation, contraction and migration (p < 0.01 v control) and the expression of matrix degrading enzymes TIMP-1 and MMP-2, but not MMP-3. ET-1 upregulated genes for profibrotic growth factors and receptors, signalling molecules, actin modulators and extracellular matrix components. ET-1 stimulated colonic fibroblast cellular processes in vitro that are involved in developing tumour stroma. Upregulated genes were consistent with these processes. By acting as a strong stimulus for tumour stroma creation, ET-1 is proposed as a target for adjuvant cancer therapy.