Outcomes of hyperbaric oxygen treatment for central and branch retinal artery occlusion at a major Australian referral hospital.

Introduction: This study analysed the treatment outcomes of patients that received hyperbaric oxygen treatment (HBOT) for retinal artery occlusion (RAO) at the Royal Brisbane and Women's Hospital in Brisbane, Australia between 2015 and 2021. Methods: Retrospective study from patient records including 22 eyes from 22 patients that received HBOT for either central RAO (17 patients) or branch RAO (five patients). Patients received the Royal Brisbane and Women's Hospital RAO protocol for their HBOT. Analysis included best corrected visual acuity pre- and post-treatment, subjective improvements, side effects and patient risk factors were also recorded. Results: Improvement in best corrected visual acuity was LogMAR -0.2 for central RAO on average with 8/17 (47%) experiencing objective improvement, 5/17 (29%) experienced no change and 4/22 (24%) experienced a reduction in best corrected visual acuity. Subjective improvement (colour perception or visual fields) was reported in an additional 4/17 patients, resulting in 12/17 (71%) reporting improvement either in visual acuity or subjectively. There was no improvement in the best corrected visual acuity of any of the five patients suffering from branch RAO. Cardiovascular risk factors present in the cohort included hypertension, hypercholesterolaemia, previous cardiovascular events, cardiac disease and smoking. Limited side effects were experienced by this patient cohort with no recorded irreversible side effects. Conclusions: Hyperbaric oxygen treatment appears a safe, beneficial treatment for central RAO. No benefit was demonstrated in branch RAO although numbers were small. Increased awareness of HBOT for RAO resulting in streamlined referrals and transfers and greater uptake of this intervention may further improve patient outcomes.

Delay to elective colorectal cancer surgery and implications for survival: a systematic review and meta-analysis.

AIM: The Covid-19 pandemic has delayed elective colorectal cancer (CRC) surgery. The aim of this study was to see whether or not this may affect overall survival (OS) and disease-free survival (DFS). METHOD: A systematic review was carried out according to PRISMA guidelines (PROSPERO ID: CRD42020189158). Medline, EMBASE and Scopus were interrogated. Patients aged over 18 years with a diagnosis of colon or rectal cancer who received elective surgery as their primary treatment were included. Delay to elective surgery was defined as the period between CRC diagnosis and the day of surgery. Meta-analysis of the outcomes OS and DFS were conducted. Forest plots, funnel plots and tests of heterogeneity were produced. An estimated number needed to harm (NNH) was calculated for statistically significant pooled hazard ratios (HRs). RESULTS: Of 3753 articles identified, seven met the inclusion criteria. Encompassing 314 560 patients, three of the seven studies showed that a delay to elective resection is associated with poorer OS or DFS. OS was assessed at a 1 month delay, the HR for six datasets was 1.13 (95% CI 1.02-1.26, p = 0.020) and at 3 months the pooled HR for three datasets was 1.57 (95% CI 1.16-2.12, p = 0.004). The estimated NNH for a delay at 1 month and 3 months was 35 and 10 respectively. Delay was nonsignificantly negatively associated with DFS on meta-analysis. CONCLUSION: This review recommends that elective surgery for CRC patients is not postponed longer than 4 weeks, as available evidence suggests extended delays from diagnosis are associated with poorer outcomes. Focused research is essential so patient groups can be prioritized based on risk factors in future delays or pandemics.

Elective Repair of Abdominal Aortic Aneurysm and the Risk of Colonic Ischaemia: Systematic Review and Meta-Analysis.

INTRODUCTION: Colon ischaemia (CI) is a significant complication of open (OR) and endovascular (EVAR) repair of abdominal aortic aneurysm (AAA). With a rapid increase in EVAR uptake, contemporary data demonstrating the differing rates and outcomes of CI between EVAR and OR, particularly in the elective setting, are lacking. The aim was to characterise the risk and consequences of CI in elective AAA repair comparing EVAR with OR. METHODS: A systematic review and meta-analysis of the literature was performed using the Cochrane collaboration protocol and reported according to the PRISMA guidelines. PubMed, MedLine, and EMBASE were searched for studies reporting CI rates after elective AAA repair. Ruptured AAAs were excluded from analysis. RESULTS: Thirteen studies reporting specific outcomes of CI after elective AAA repair, containing 162,750 evaluable patients (78,151 EVAR and 84,599 OR) were included. All studies found a higher risk of CI with OR than with EVAR. Three studies performed confounder adjustment with CI rates of 0.5-1% versus 2.1-3.6% (EVAR vs. OR) and combined odds ratio of 2.7 (2.0-3.5) for the development of CI with OR versus EVAR. The majority of cases of CI occurred within 30 days and were associated with variable mortality (0-73%) and re-intervention rates (27-54%). GRADE assessment of evidence strength was very low for all outcomes. There was a high degree of heterogeneity between studies both methodologically and in terms of CI rates, re-intervention, mortality, and time to development of CI. CONCLUSIONS: EVAR is associated with a reduced incidence of CI compared with OR.

DNA hypermethylation as a predictor of extramural vascular invasion (EMVI) in rectal cancer.

PURPOSE: DNA hypermethylation in gene promoter regions (CpG islands) is emerging as an important pathway in colorectal cancer tumourigenesis. Whilst genetic mutations have been associated with extramural vascular invasion (EMVI) in rectal cancer, no such association has yet been made with epigenetic factors. METHODS: 100 consecutive neoadjuvant-naïve patients undergoing curative surgery for rectal were classified according to the presence or absence of EMVI on histopathological examination. DNA was extracted from tumours and subjected to bisulfite conversion and methylation-specific PCR to determine CIMP status (high, intermediate, or low; according to a validated panel of 8 genes). CIMP status was correlated with EMVI status, histopathological, clinical, and demographic variables, in addition to overall (OS) and disease free (DFS) survival. RESULTS: 51 patients were characterised as CIMP-low, 48 CIMP-intermediate, and one patient CIMP-high. EMVI-positivity was associated with CIMP-intermediate epigenotype (p < 0.001). Patients with EMVI-positive tumours were found to have significantly more advanced disease by pT, pN, and pAJCC categorisation (p = 0.002, p < 0.001, and = p < 0.001, respectively). EMVI-positivity was significantly associated with the requirement for adjuvant chemotherapy (p < 0.001), and worse DFS but not OS (p = 0.012 and p = 0.052). CONCLUSIONS: Given the association between CIMP-intermediate epigenotype and EMVI-positivity, and the subsequent disadvantage in pathological stage, requirement for adjuvant therapy and worse survival, tumour epigenotyping could potentially play an important role in personalising patients' cancer care. Further work is required to understand the mechanisms that underlie the observed effect, with the hope that they may provide novel opportunities for intervention and inform treatment decisions in rectal cancer.

Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype.

AIM: To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer. METHODS: Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined upon histological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed. RESULTS: There were 160 patients analysed with a median follow-up time of 46.4 mo. Twenty-one (13%) patients demonstrated high levels of CIMP methylation (CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion (EMVI) compared with CIMP-L [8/21 (38%) vs 15/99 (15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival (P < 0.001). Intermediate CIMP status was significantly associated with KRAS mutation (P = 0.01). There were 14 (9%) patients with a pathological complete response (pCR) compared to 116 (73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pCR had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant (P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced "T" stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence. CONCLUSION: We report a novel association of pre-treatment characterisation of CIMP-H with EMVI status which has prognostic implications and is not readily detectable on pre-treatment histological examination.

Review of the development of DNA methylation as a marker of response to neoadjuvant therapy and outcomes in rectal cancer.

There is much debate around the preoperative treatment of colorectal cancer and, in particular, neoadjuvant chemoradiotherapy in locally advanced rectal cancer. This treatment carries a significant risk of harmful side effects and has a highly variable response rate. Predictive biomarkers have been the subject of a great deal of study with the aim of pretreatment risk stratification in order to more accurately determine which patients will derive the most benefit and least harm from these treatments. The study of epigenetics in colorectal cancer is relatively recent, and distinct patterns of aberrant DNA methylation, in particular the cytosine-phosphate-guanine (CpG) island methylator phenotype (CIMP), have been demonstrated in colorectal cancer, and their characterisation and significance are under debate, particularly in rectal cancer. These patterns of DNA methylation have been associated with differences in response to therapy and treatment outcomes and therefore have the potential to be used as biomarkers in tailored therapy regimes for patients with rectal cancer. This review aims to summarise the current state of the art in rectal cancer, with particular regard to the determination of DNA methylation patterns, the CpG island methylator phenotype and its potential as a novel biomarker in rectal cancer treatment and prediction of outcomes and response after neoadjuvant chemoradiotherapy.

Patients with non-diagnostic hyperamylasaemia must be investigated and managed as per acute pancreatitis.

OBJECTIVES: The identification of hyperamylasaemia insufficient to confidently diagnose acute pancreatitis in patients with epigastric pain poses a clinical dilemma. The aim of this study was to identify a cohort of such patients and review their presentation, investigation and outcome. DESIGN: Patients admitted through the emergency surgical intake during a 12-month period with serum amylase levels of 100-400 IU/L were identified and case notes reviewed to confirm those presenting with upper abdominal pain. Subsequent radiological and biochemical investigations were recorded. PARTICIPANTS: A total of 25 patients with non-diagnostic hyperamylasaemia. SETTING: Ward patients in a University Hospital. MAIN OUTCOME MEASURES: Amylase level, eventual diagnosis, drug history. RESULTS: Twenty-five patients were identified with a mean age of 46.7 years. The median serum amylase level was 230 IU/L (range 102-358 IU/L). Twenty-two patients underwent transabdominal ultrasound at presentation, with gallstones identified in nine cases. The remaining three had documented gallstones and were awaiting elective cholecystectomy. Of the 13 patients with no evidence of cholelithiasis, six were taking medications known to cause pancreatitis, seven patients underwent computed tomography (CT) scans that identified chronic pancreatitis in three, and were non-diagnostic in four cases. These four patients underwent endoscopic ultrasound (EUS) evaluation of the biliary tree identifying microlithiasis in one but no pathology in the remaining three cases. CONCLUSIONS: Patients with hyperamylasaemia not diagnostic of pancreatitis should be carefully investigated, as gallstones will be identified in at least 50%. An accurate drug history is also invaluable.