Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance.

Introduction: Neoadjuvant radiotherapy is successfully used in rectal cancer to improve overall survival. However, treatment response is both unpredictable and variable. There is strong evidence to show that the phenomenon of tumour hypoxia is associated with radioresistance, however the mechanism(s) behind this are poorly understood. Consequently, there have only been a small number of studies evaluating methods targeting hypoxia-induced radioresistance. The purpose of this systematic review is to evaluate the potential effectiveness of targeting hypoxia-induced radioresistance in rectal cancer and provide recommendations for future research in this area. Methods: A comprehensive literature search was performed following the PRISMA guidelines. This study was registered on the Prospero database (CRD42023441983). Results: Eight articles met the inclusion criteria. All studies identified were in vitro or in vivo studies, there were no clinical trials. Of the 8 studies identified, 5 assessed the efficacy of drugs which directly or indirectly targeted hypoxia and three that identified potential targets. There was conflicting in vivo evidence for the use of metformin to overcome hypoxia induced radioresistance. Vorinostat, atovaquone, and evofosfamide showed promising preclinical evidence that they can overcome hypoxia-induced radioresistance. Discussion: The importance of investigating hypoxia-induced radioresistance in rectal cancer is crucial. However, to date, only a small number of preclinical studies exist evaluating this phenomenon. This systematic review highlights the importance of further research to fully understand the mechanism behind this radioresistance. There are promising targets identified in this systematic review however, substantially more pre-clinical and clinical research as a priority for future research is needed.

Smoking is associated with a higher complication and failure rate in arteriovenous grafts for haemodialysis: A multi-centre experience.

INTRODUCTION: Arteriovenous grafts (AVG) for haemodialysis (HD) access are recommended as a second line modality due to higher morbidity and mortality rates than arteriovenous fistulae (AVF). Smoking is already established as a risk factor in lower extremity bypass graft failure used for peripheral vascular disease, but its effect on AVGs remains unclear. We aimed to investigate the relationship of smoking on AVG outcomes. METHODS: A 3 year (01/08/2015-01/08/2018) multi-centre retrospective study was carried out on patients receiving an AVG for HD. Data included patient demographics, medical history, operation, type of graft, postoperative course and primary and secondary patency rates. Statistical analyses performed were Kaplan-Meier curves and Cox's proportional hazard regression. RESULTS: Fifty-five AVGs were performed (1052 AVF performed) in this period. The most common complication was thrombosis (38.9%). Primary patency at 6, 12 and 24 months were 55%, 45% and 44% respectively. Secondary patency at 6, 12 and 24 months were 63%, 56% and 54% respectively. Smoking was found to be a poor prognostic factor for primary (HR 3.734 (1.818-7.668 95% CI) p < 0.001) and secondary patency (HR 6.238 (2.729-14.257) p < 0.001). Smoking was also significantly associated with graft thrombosis (HR 5.741 (2.380-13.848 95% CI) p < 0.001). DISCUSSION: Primary patency rates are lower than previous reports whilst secondary patency is equivalent. Smoking results in a greater risk of thrombosis and poorer primary and secondary patency. This is recognised in vascular surgical grafts, but has not been previously described in AVGs for HD access. Smoking is a modifiable risk factor and as AVGs are typically used for end-stage vascular access patients. Pre-operative strategies to promote smoking cessation, including patient education and prehabilitation should be employed to improve outcomes.

The predictive significance of neutrophil-to-lymphocyte ratio in cholecystitis: a systematic review and meta-analysis.

PURPOSE: The aim of this review was to examine whether neutrophil-to-lymphocyte ratio (NLR) can predict the presence of cholecystitis and distinguish between simple and severe cholecystitis. METHODS: A systematic literature search was performed. Risk of bias was assessed using the Newcastle-Ottawa Scale. Random effects model was used to calculate mean difference (MD) in two situations: (a) no cholecystitis versus cholecystitis and (b) simple versus severe cholecystitis. Receiver operating characteristic (ROC) curve analysis was performed to determine cut-off values of NLR for the above situations. RESULTS: Ten retrospective studies comprising of 2827 patients were included. Three hundred twenty-seven had no cholecystitis, 2100 had simple cholecystitis and the remaining 400 had severe cholecystitis. NLR was significantly higher in acute cholecystitis compared to "no cholecystitis" (MD = 8.05 (95% CI 7.71-8.38), p < 0.01) and in severe cholecystitis when compared with simple cholecystitis (MD = 3.14 (95% CI 1.26-5.02), p < 0.01). For patients with cholecystitis compared to those without cholecystitis, an NLR cut-off value of 2.98 was identified (AUC = 0.90). Logistic regression analysis confirmed an NLR > 2.9 was an independent predictor of cholecystitis (OR 36.0, p = 0.006). In simple versus severe cholecystitis, an NLR cut-off value of 8.5 was identified (AUC = 0.73). Binary logistic regression analysis suggested an NLR > 8.5 was not an independent predictor of severe cholecystitis (OR 6.5 p = 0.090). CONCLUSION: NLR is significantly higher in patients with cholecystitis of any severity compared to patients without cholecystitis. Moreover, NLR can predict acute cholecystitis. However, NLR cannot predict the severity of disease due to inadequately powered studies. Future research is required.

Totally extra-peritoneal repair versus trans-abdominal pre-peritoneal repair for the laparoscopic surgical management of sportsman's hernia: A systematic review and meta-analysis.

BACKGROUND: Open and laparoscopic modalities are employed for treatment of sportsman's hernia with totally extra-peritoneal (TEP) and trans-abdominal pre-peritoneal (TAPP) laparoscopic approaches both currently being utilised. At present, neither subtype has demonstrated a beneficial superiority for sportsman's hernia repair, as concluded in the most recent systematic review comparing the outcomes of each technique. The aim of this review was to evaluate current evidence to ascertain whether there was a difference in laparoscopic techniques following sportsman's hernia repair. METHODS: A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Databases searched included PubMed, Scopus and Web of Science to identify all randomised controlled trials (RCTs) and observational studies Risk of bias was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale for RCTs and observational studies, respectively.The assessed outcomes included median time to return to sporting activity, complications and the degree of postoperative pain reduction within three months. Random effects model was used to calculate pooled proportion data where feasible. Subgroup analyses were also performed. RESULTS: 28 studies were identified including 2 RCTs and 26 observational studies. No significant differences were observed between techniques in the primary or secondary outcomes. Significant heterogeneity was observed in all outcomes. This was more pronounced for return to sporting activity meaning that meta-analysis was not feasible in this domain. Median time to return to sporting activity was 28 days for both techniques. CONCLUSIONS: There is no observed difference in the primary and secondary outcomes in either technique. An RCT comparing TEP and TAPP repair is needed to provide definitive data on this matter.

Elevation of High-sensitive Troponin T Predicts Mortality After Open Pancreaticoduodenectomy.

BACKGROUND: Open pancreaticoduodenectomy has a high complication and measurable mortality rate. Recent reports (based across multiple surgical disciplines) demonstrate that elevated postoperative high sensitivity troponin T (hsTnT) predicts adverse outcomes in non-cardiac surgery. The aim of this study was to evaluate postoperative hsTnT as a prognostic marker of mortality, major adverse cardiovascular events (MACE), post-operative non-cardiac complications and length of stay (including intensive care stay) in open pancreaticoduodenectomy. METHODS: A retrospective review of open pancreaticoduodenectomy patients was undertaken from 01/10/2017-31/03/2019. Receiver operating characteristic (ROC) curves were calculated to identify ideal cut-off values for hsTnT. Univariate and multivariate analyses were performed to scrutinize the relationship between mean hsTnT and 30-day, 90-day mortality, MACE, post-operative non-cardiac complications and length of stay. RESULTS: One hundred and nine patients were identified. ROC curves demonstrated a strong correlation between elevated mean hsTnT and 30-day, 90-day mortality and MACE (AUC = 0.937, AUC = 0.852, AUC = 0.779, respectively). Multivariate analysis showed mean hsTnT > 21 ng/l was significantly associated with 90-day mortality (OR 43.928, p = 0.004) and MACE (OR 8.177, p = 0.048). CONCLUSIONS: HsTnT is predictive of mortality and MACE in the context of open pancreaticoduodenectomy. Association between hsTnT and prolonged critical care stay was less significant. Non-cardiac complications and length of stay show no significant association with hsTnT.

Total endoscopic-assisted linea alba reconstruction (TESLAR) for treatment of umbilical/paraumbilical hernia and rectus abdominus diastasis is associated with unacceptable persistent seroma formation: a single centre experience.

PURPOSE: Umbilical hernia with concomitant rectus abdominus diastasis (RAD) is potentially associated with higher recurrence. Open and laparoscopic techniques have already been described, however, recent endoscopic methods show great promise. Therefore, our aim was to establish the risks and benefits of performing total endoscopic-assisted linea alba reconstruction (TESLAR). METHODS: A retrospective review from 28/03/2018 to 01/05/2019 of TESLAR patients was undertaken. Data collected included medical history, operative notes and postoperative course. Statistical analyses were performed using univariate analysis. Operative technique began with a subcutaneous dissection from the lateral borders of anterior rectus sheath, lower costal margin, and pubic bone. The defect was defined and subsequently reduced. Anterior rectus sheath was subsequently plicated and if a mesh was inserted, an on-lay mesh was placed. RESULTS: 21 patients were identified with an 8:13 male to female ratio. Mean age and BMI were 53.1 and 29.7, respectively. 19/21 patients reported post-operative complications requiring reintervention. 17/21 patients had a seroma, all requiring draining with a minority (5/21) requiring formal excision. Univariate analysis showed age (p < 0.001), BMI (p < 0.001) and female gender (p = 0.022) were significantly associated with repeated number of seroma aspirations. CONCLUSION: TESLAR is associated with high rates of seroma and reintervention, including revisional surgery. Open repair should be considered as an alternative strategy for hernia and RAD repair.

Rheumatoid nodule on the anterior mitral valve leaflet.

Symptomatic cardiac rheumatoid nodules are a rare but recognized manifestation of rheumatoid arthritis. We describe the surgical management of a rheumatic nodule involving the anterior leaflet of the mitral valve.

Vermiform appendix within incisional hernia.

The vermiform appendix (whether inflamed or not) within a hernia is very rare occurrence. We present the unprecedented case of a normal appendix found within a Pfannenstiel incisional hernia. A diagnostic laparoscopy was performed as appendicitis was suspected. However, the tip of a normal appendix was visualised within a previous Pfannenstiel incision. Laparoscopic appendicectomy was carried successfully and the patient was discharged. The patient later returned for a successful elective laparoscopic incisional hernia repair.

Bilateral ureteric stones: an unusual cause of acute kidney injury.

A 49-year-old man presented to the accident and emergency department, with a short history of vague abdominal pain, abdominal distension and two episodes of frank haematuria. A plain chest film showed dilated loops of large bowel and blood results on admission showed an acute kidney injury (stage 3). A diagnosis of bowel obstruction was made initially but a CT scan of the abdomen showed bilateral obstructing calculi. After initial resuscitation, the patient had bilateral ultrasound-guided nephrostomies and haemofiltration. He later underwent bilateral antegrade ureteric stenting. A decision will later be made on whether or not he is fit enough to undergo ureteroscopy and laser stone fragmentation.