ORCID Profile
0000-0002-2505-1643
Current Organisation
Basingstoke and North Hampshire Hospital
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Publisher: Wiley
Date: 08-05-2018
DOI: 10.1111/CODI.14106
Abstract: The current standard of care for locally advanced rectal cancer involves neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision. There is a spectrum of response to neoadjuvant therapy however, the prognostic value of tumour regression grade (TRG) in predicting disease-free survival (DFS) or overall survival (OS) is inconsistent in the literature. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was undertaken using Ovid MEDLINE, Embase and Google Scholar. Inclusion criteria were Stage II and III locally advanced rectal cancer treated with long-course CRT followed by radical surgery. The aim of the meta-analysis was to assess the prognostic implication of each TRG for rectal cancer following neoadjuvant CRT. Long-term prognosis was assessed. The main outcome measures were DFS and OS. A random effects model was performed to pool the hazard ratio (HR) from all included studies. There were 4875 patients from 17 studies, with 775 (15.9%) attaining a pathological complete response (pCR) and 719 (29.9%) with no response. A significant association with OS was identified from a pooled-estimated HR for pCR (HR = 0.47, P = 0.002) and nonresponding tumours (HR = 2.97 P < 0.001). Previously known tumour characteristics, such as ypN, lymphovascular invasion and perineural invasion, were also significantly associated with DFS and OS, with estimated pooled HRs of 2.2, 1.4 and 2.3, respectively. In conclusion, the degree of TRG was of prognostic value in predicting long-term outcomes. The current challenge is the development of a high-validity tests to predict pCR.
Publisher: Wiley
Date: 28-08-2020
DOI: 10.1111/ANS.16250
Publisher: Wiley
Date: 06-10-2022
DOI: 10.1111/ANS.18078
Abstract: The development of peritoneal metastases (PM) in patients with colorectal cancer (CRC) connotates a poor prognosis. Circulating tumour (ctDNA) is a promising tumour biomarker in the management CRC. This systematic review aimed to summarize the role of ctDNA in patients with CRC and PM. Following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines, a systematic review of the literature until June 2022 was performed. Studies reporting on the utility of ctDNA in colorectal PM were included. A total of eight eligible studies were identified including a total of 167 patients. The findings from this review suggest an evolving role for ctDNA in CRC with PM. ctDNA can be isolated from both plasma and peritoneal fluid, with peritoneal fluid preferred as the liquid biopsy of choice with higher mutation detection rates. Concordance rates between tissue and plasma eritoneal ctDNA mutation detection can vary, but is generally high. ctDNA has a potential role in monitoring anti‐EGFR treatment response and resistance, as well as in predicting future prognosis and recurrence. The detection of ctDNA in plasma of patients with isolated PM is also possibly suggestive of occult systemic disease, and patients exhibiting such ctDNA positivity may benefit from systemic treatment. Limitations to ctDNA mutation detection may include the size of peritoneal lesions, as well as the fact that PM poorly shed ctDNA. While these findings are promising, further large‐scale studies are needed to better evaluate the utility of ctDNA in this subset of patients.
Publisher: Oxford University Press (OUP)
Date: 25-09-2020
DOI: 10.1002/BJS.12050
Publisher: Springer Science and Business Media LLC
Date: 27-09-2021
Publisher: Medknow
Date: 2020
Publisher: Oxford University Press (OUP)
Date: 24-03-2021
DOI: 10.1093/BJS/ZNAB101
Abstract: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351 best case 196, worst case 816) or non-cancer surgery (733 best case 407, worst case 1664). Both exceeded the NNV in the general population (1840 best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
Publisher: Wiley
Date: 03-2021
DOI: 10.1111/CODI.15596
Publisher: Wiley
Date: 17-12-2020
DOI: 10.1111/CODI.15431
Abstract: This study aimed to describe the change in surgical practice and the impact of SARS‐CoV‐2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS‐CoV‐2 pandemic. This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS‐CoV‐2. Centres entered data from their first recorded case of COVID‐19 until 19 April 2020. The primary outcome was 30‐day mortality. Secondary outcomes included anastomotic leak, postoperative SARS‐CoV‐2 and a comparison with prepandemic European Society of Coloproctology cohort data. From 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty‐day mortality was 1.8% (38/2073), the incidence of postoperative SARS‐CoV‐2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS‐CoV‐2 (14/1601, 0.9%) and highest in patients with both a leak and SARS‐CoV‐2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58–14.06), postoperative SARS‐CoV‐2 (16.90, 7.86–36.38), male sex (2.46, 1.01–5.93), age years (2.87, 1.32–6.20) and advanced cancer stage (3.43, 1.16–10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%). Surgeons need to further mitigate against both SARS‐CoV‐2 and anastomotic leak when offering surgery during current and future COVID‐19 waves based on patient, operative and organizational risks.
Publisher: Wiley
Date: 09-08-2021
DOI: 10.1111/ANAE.15560
Abstract: We aimed to determine the impact of pre‐operative isolation on postoperative pulmonary complications after elective surgery during the global SARS‐CoV‐2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre‐defined sub‐group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS‐CoV‐2 infection. Patients who isolated pre‐operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS‐CoV‐2 incidence and high‐income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre‐operative testing use of COVID‐19‐free pathways or community SARS‐CoV‐2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.
Publisher: AME Publishing Company
Date: 12-2019
Publisher: Springer Science and Business Media LLC
Date: 15-03-2018
Publisher: BMJ
Date: 31-03-2016
Publisher: Wiley
Date: 12-07-2021
DOI: 10.1111/CODI.15778
Abstract: Appendiceal pseudomyxoma peritonei (PMP) is a rare entity, with recurrence rates up to 26% despite optimal cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Evidence specific to PMP originating from non‐infiltrative appendiceal mucinous neoplasms (low grade ‐ LAMN and high grade ‐ HAMN) is lacking. The aim of this study was to identify patterns of recurrence and predictive factors for patients appropriate for iterative surgery. A bi‐institutional retrospective analysis was performed on patients undergoing complete cytoreduction and HIPEC for PMP derived from perforated LAMN or HAMN. Multivariate logistic regression was performed to identify independent predictors for re‐do CRS. Five‐year overall survival (OS) was stratified according to surgical intervention, and 5‐year disease‐free survival (DFS) was stratified according to histological PMP grade. Cox regression analysis was performed to identify independent predictors for OS and DFS. Sixty of 239 (25.1%) patients developed peritoneal recurrence between 2007 and 2020. The median time to recurrence was 20.7 months. The risk of disease recurrence was highest with high‐grade PMP ( P .001) and increasing PCI ( P .001). Patients with high‐grade histology from their index procedure and aged over 60 years were less likely to be offered iterative surgery on multivariate analysis. Patients who underwent iterative CRS and HIPEC had a 5‐year survival of 100%. Iterative CRS and HIPEC is feasible in selected patients with recurrent PMP, displaying good oncological outcomes. Age, index histology and level of abdominal quadrant involvement are predictive of proceeding to re‐do surgery.
Publisher: Springer Science and Business Media LLC
Date: 23-07-2018
DOI: 10.1245/S10434-018-6658-4
Abstract: In recent years, it has been demonstrated that immunotherapy is an effective strategy for the management of solid tumors. The origins of immunotherapy can be traced back to the work of William Coley, who elicited an immune response against sarcoma by injecting patients with a mixture of dead bacteria. Significant progress has been made since, with immune markers within the tumor now being used as predictors of cancer prognosis and manipulated to improve patient survival. While surgery remains central to the management of most patients with solid malignancies, it is important that surgeons consider the different immunotherapy strategies that can be employed to manage disease. Here, we highlight how the immune system influences tumorigenesis and bring attention to how current and future immunotherapies can serve as an adjunct to surgery.
Publisher: Wiley
Date: 24-08-2021
DOI: 10.1111/ANAE.15563
Abstract: SARS‐CoV‐2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri‐operative or prior SARS‐CoV‐2 were at further increased risk of venous thromboembolism. We conducted a planned sub‐study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS‐CoV‐2 diagnosis was defined as peri‐operative (7 days before to 30 days after surgery) recent (1–6 weeks before surgery) previous (≥7 weeks before surgery) or none. Information on prophylaxis regimens or pre‐operative anti‐coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS‐CoV‐2 2.2% (50/2317) in patients with peri‐operative SARS‐CoV‐2 1.6% (15/953) in patients with recent SARS‐CoV‐2 and 1.0% (11/1148) in patients with previous SARS‐CoV‐2. After adjustment for confounding factors, patients with peri‐operative (adjusted odds ratio 1.5 (95%CI 1.1–2.0)) and recent SARS‐CoV‐2 (1.9 (95%CI 1.2–3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS‐CoV‐2 (1.7 (95%CI 0.9–3.0)). Overall, venous thromboembolism was independently associated with 30‐day mortality (5.4 (95%CI 4.3–6.7)). In patients with SARS‐CoV‐2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri‐operative or recent SARS‐CoV‐2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS‐CoV‐2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
Publisher: Medknow
Date: 2019
Publisher: Wiley
Date: 13-08-2017
DOI: 10.1111/ANS.14141
Abstract: Colonoscopic surveillance in patients with a personal or family history of colorectal carcinoma or colonic polyps represents a significant workload for endoscopy services. Effective colonoscopic surveillance relies on quality endoscopic examination and appropriate surveillance interval. This review will discuss quality in colonoscopy and review guidelines for surveillance.
Publisher: Wiley
Date: 2023
DOI: 10.1111/ANS.18142
Publisher: Wiley
Date: 08-08-2023
DOI: 10.1111/ANS.18640
Publisher: Baishideng Publishing Group Inc.
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 18-10-2021
DOI: 10.1038/S41419-021-04141-5
Abstract: Anal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 2021
DOI: 10.1200/JCO.20.01933
Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9% adjusted odds ratio [aOR], 0.62 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6% aOR, 0.53 95% CI, 0.36 to 0.76). Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
Publisher: Wiley
Date: 06-03-2020
DOI: 10.1111/ANS.15810
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2019
DOI: 10.1097/DCR.0000000000001332
Abstract: There is increasing literature emerging on the significance of tumor-infiltrating lymphocytes in colorectal cancer. However, there have been inconsistent findings, secondary to small patient numbers and varied methods for identifying these lymphocytes. The aim of this study was to determine the prognostic and predictive power of tumor-infiltrating lymphocytes in colon, rectal (in neoadjuvant setting), and metastatic colorectal cancer. A comprehensive search of PubMed and Embase was undertaken from January 2006 to December 2016. The inclusion criteria included a description of the tumor-infiltrating lymphocyte subset(s) assessed with reporting of associated short- and long-term outcomes. The main outcome measures, were disease-free and overall survival. A total of 25 studies were included, 15 for primary colorectal cancer (4719 patients), 7 for locally advanced rectal cancer (727 patients), and 3 studies for metastatic colorectal cancer (418 patients). High CD3 + , CD8 + , FoxP3 + , and CD45RO + densities were associated with improved overall survival for primary colorectal cancer, with pooled estimated HRs of 0.88, 0.81, 0.70, and 0.63 (all p 0.001) respectively. Furthermore, in locally advanced rectal cancer, the levels of CD8 + cells were a significant predictor of good tumor regression grade after chemoradiotherapy. The retrospective nature of included studies and the significant interstudy heterogeneity were limitations. There is increasing evidence that tumor-infiltrating lymphocytes play an important role in predicting prognosis in colorectal cancer and tumor regression after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Clinical researchers are now in a unique position to build on this work to identify robust predictive markers to stratify patients not only to currently available therapies but also to immunotherapy, which has demonstrated success in improving patient outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2018
DOI: 10.1097/DCR.0000000000001010
Abstract: Anal squamous cell carcinoma is a rare cancer with a high cure rate, making research into the treatment of locoregional failure difficult. The purpose of this study was to examine factors related to local treatment failure and determine the outcomes of patients undergoing local salvage resection. This was a retrospective cohort study. This study was conducted at a quaternary referral center. Patients with anal squamous cell carcinoma treated with chemoradiotherapy between January 1983 and December 2015 were included. The influence of patient-, tumor-, and treatment-related factors on the primary outcome measures of locoregional failure, overall survival, and disease-free survival were investigated. Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had persistent disease and 36 (62%) developed locoregional recurrence. Multivariate analysis identified tumor stage (HR, 3.16 p 0.002) as an independent predictor of locoregional failure. Thirty abdominoperineal resections and 11 pelvic exenterations were undertaken with no surgical mortality. At a median follow-up of 20 months (range, 4–150 months), 5-year overall and disease-free survival for the salvage cohort was 51% and 47%. Margin positivity was an independent predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1 p = 0.027). Nineteen patients (48%) developed further relapse, which included all 10 patients with a positive resection margin, 3 of whom underwent re-resection. Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease. Limitations include the retrospective nature of the database, the prolonged time period of the study, and episodes of incomplete data. Advanced T stage is an independent predictor of local failure in anal squamous cell carcinoma. Most patients can be salvaged, with a positive resection margin being a strong predictor of further relapse and poor outcome. See Video Abstract at links.lww.com/DCR/A515.
Publisher: Springer Science and Business Media LLC
Date: 28-03-2017
DOI: 10.1038/NCOMMS14844
Abstract: TP53 , a critical tumour suppressor gene, is mutated in over half of all cancers resulting in mutant-p53 protein accumulation and poor patient survival. Therapeutic strategies to target mutant-p53 cancers are urgently needed. We show that accumulated mutant-p53 protein suppresses the expression of SLC7A11 , a component of the cystine/glutamate antiporter, system x C − , through binding to the master antioxidant transcription factor NRF2. This diminishes glutathione synthesis, rendering mutant-p53 tumours susceptible to oxidative damage. System x C − inhibitors specifically exploit this vulnerability to preferentially kill cancer cells with stabilized mutant-p53 protein. Moreover, we demonstrate that SLC7A11 expression is a novel and robust predictive biomarker for APR-246, a first-in-class mutant-p53 reactivator that also binds and depletes glutathione in tumours, triggering lipid peroxidative cell death. Importantly, system x C − antagonism strongly synergizes with APR-246 to induce apoptosis in mutant-p53 tumours. We propose a new paradigm for targeting cancers that accumulate mutant-p53 protein by inhibiting the SLC7A11–glutathione axis.
Publisher: Wiley
Date: 09-03-2021
DOI: 10.1111/ANAE.15458
Abstract: Peri‐operative SARS‐CoV‐2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS‐CoV‐2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre‐operative SARS‐CoV‐2 infection were compared with those without previous SARS‐CoV‐2 infection. The primary outcome measure was 30‐day postoperative mortality. Logistic regression models were used to calculate adjusted 30‐day mortality rates stratified by time from diagnosis of SARS‐CoV‐2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre‐operative SARS‐CoV‐2 diagnosis. Adjusted 30‐day mortality in patients without SARS‐CoV‐2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre‐operative SARS‐CoV‐2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3–4.8), 3.9 (2.6–5.1) and 3.6 (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARS‐CoV‐2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9–2.1)). After a ≥ 7 week delay in undertaking surgery following SARS‐CoV‐2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS‐CoV‐2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2018
DOI: 10.1200/PO.18.00075
Abstract: The presence of tumor-infiltrating lymphocytes (TILs) in tumors is superior to conventional pathologic staging in predicting patient outcome. However, their presence does not define TIL functionality. Here we developed an assay that tests TIL cytotoxicity in patients with locally advanced rectal cancer before definitive treatment, identifying those who will obtain a pathologic complete response (pCR). We also used the assay to demonstrate the rescue of TIL function after checkpoint inhibition blockade (CIB). Thirty-four consecutive patients were identified initially, with successful completion of the assay before surgery in those 17 patients who underwent full treatment. An in vitro cytotoxic assay of rectal cancer tumoroids cocultured with patient-matched TILs was established and validated. Newly diagnosed patients were recruited with pretreatment biopsy specimens processed within 1 month. Evaluation of TIL-mediated tumoroid lysis was performed by measuring the mean fluorescence intensity of cell death marker, propidium iodide. CIB (anti–programmed cell death protein 1 [anti–PD-1] antibody) response was also assessed in a subset of patient specimens. Six of the 17 patients achieved an objective pCR on final evaluation of the resected specimen after neoadjuvant chemoradiotherapy. Cytotoxic killing identified the pCR group with a higher mean fluorescence intensity (27,982 [95% CI, 25,340 to 30,625]) compared with the non-pCR cohort (12,428 [95% CI, 9,434 to 15,423] p .001). Assessment of the effectiveness of CIB revealed partial restoration of cytotoxicity in TILs with increased PD-1 expression with anti–PD-1 antibody exposure. Evaluating TIL function can be undertaken within weeks of the diagnostic biopsy, affording the potential to alter patient management decisions and refine selection for a watch-and-wait protocol. This cytotoxic assay also has the potential to serve as a platform to assist in the additional development of CIB.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
DOI: 10.1097/DCR.0000000000001026
Abstract: Rectal cancer outcomes have improved with the adoption of a multidisciplinary model of care. However, there is a spectrum of quality when viewed from a national perspective, as highlighted by the Consortium for Optimizing the Treatment of Rectal Cancer data on rectal cancer care in the United States. The aim of this study was to assess and identify predictors of circumferential resection margin involvement for rectal cancer across Australasia. A retrospective study from a prospectively maintained binational colorectal cancer database was interrogated. This study is based on a binational colorectal cancer audit database. Clinical information on all consecutive resected rectal cancer cases recorded in the registry from 2007 to 2016 was retrieved, collated, and analyzed. The primary outcome measure was positive circumferential resection margin, measured as a resection margin ≤1 mm. A total of 3367 patients were included, with 261 (7.5%) having a positive circumferential resection margin. After adjusting for hospital and surgeon volume, hierarchical logistic regression analysis identified a 6-variable model encompassing the independent predictors, including urgent operation, abdominoperineal resection, open technique, low rectal cancer, T3 to T4, and N1 to N2. The accuracy of the model was 92.3%, with an receiver operating characteristic of 0.783 ( p 0.0001). The quantitative risk associated with circumferential resection margin positivity ranged from % (no risk factors) to 43% (6 risk factors). This study was limited by the lack of recorded long-term outcomes associated with circumferential resection margin positivity. The rate of circumferential resection margin involvement in patients undergoing rectal cancer resection in Australasia is low and is influenced by a number of factors. Risk stratification of outcome is important with the increasing demand for publicly accessible quality data. See Video Abstract at links.lww.com/DCR/A512.
Publisher: Elsevier BV
Date: 10-2019
Publisher: Elsevier BV
Date: 11-2021
Publisher: Medknow
Date: 2020
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Glen R Guerra.