Assessing the impact of rurality on oesophagogastric cancer survival in the North-East of Scotland- a prospective population cohort study.

INTRODUCTION: Despite advances in oncology therapies and surgical techniques, survival from oesophagogastric cancer remains low. Poorer cancer outcomes and survival for rural dwellers is documented worldwide and has been an area of focus in Scotland since 2007 when changes to suspected cancer national referral guidelines and governmental mandates on delivering remote and rural healthcare occurred. Whether these changes in clinical practice has impacted upon upper gastrointestinal cancer remains unclear. METHODS: A prospective, single-centre observation study was performed. Data from the regional oesophagogastric cancer MDT between 2013 and 2019 were included. The Scottish Index of Multiple Deprivation 2020 tool provided a rurality code (1 or 2) based on patient postcode at time of referral. Survival outcomes for urban and rural patients were compared across demographic factors, disease factors and stage at presentation. RESULTS: A total of 1038 patients were included in this study. There was no significant difference between rural and urban groups in terms of sex of patient, age at diagnosis, cancer location, or tumour stage. Furthermore, no difference was identified between those commenced on a radical therapy with other treatment plans. Despite this, rurality predicted for an improved outcome on survival analysis (p = 0.012) and this was independent of other factors on multivariable analysis (HR = 0.78, 95%CI 0.66-0.98; p = 0.032). DISCUSSION: The difference in survival demonstrated here between urban and rural groups is not easily explained but may represent improvements to rural access to healthcare delivered as a result of Scottish Government reports.

Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas.

BACKGROUND: Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy. METHODS: Tumour biopsies from patients (n=14) with TNM stage IB-IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations. RESULTS: We identified 520 genes with differential expression (Mann-Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin. CONCLUSIONS: In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma.

Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography (COGNATE): report of pragmatic randomised trial.

BACKGROUND: Endoscopic ultrasonography is recommended for staging gastro-oesophageal cancers, but has never been evaluated. OBJECTIVE: COGNATE (Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography) therefore aimed to evaluate whether adding 'endoscopic ultrasound' (EUS) to the usual staging algorithm changes treatment, improves (quality-adjusted) survival, and uses resources cost-effectively. DESIGN: Pragmatic parallel-group trial. Patients with gastro-oesophageal cancer received standard staging algorithms. Multidisciplinary teams chose provisional management plans from endoscopic mucosal resection, immediate surgery, surgery after chemotherapy, or chemotherapy and radiotherapy. We used dynamic randomisation to allocate consenting patients remotely by telephone in equal proportions between EUS and not. Thereafter we recorded changes in management plan, use of health-care resources, and three aspects of participant-reported quality of life: generic [measured by European Quality of Life - 5 Dimensions (EQ-5D)], cancer related [Functional Assessment of Cancer Therapy - General scale (FACT-G)] and condition-specific [FACT - Additional Concerns scale (FACT-AC)]. We followed participants regularly until death or the end of the trial - for between 1 and 4.5 years. We devised a quality assurance programme to maintain standards of endosonographic reporting. SETTING: Eight British hospitals, of which two - one Scottish teaching hospital and one English district general hospital - contributed 80% of participants; we combined the other six for analysis. PARTICIPANTS: Patients were eligible if they had a diagnosis of gastro-oesophageal cancer, had not started treatment, were free of metastatic disease, were fit for surgery (even if not planned) and had American Society of Anesthesiologists and World Health Organization grades of less than 3. INTERVENTIONS: Intervention group: standard staging algorithm plus EUS; control group: standard staging algorithm. MAIN OUTCOME MEASURES: Primary: quality-adjusted survival. Secondary: survival; health-related quality of life (EQ-5D, FACT-G and FACT-AC scales); changes in management plan; and complete resection rate. Although blinding participants was neither possible nor desirable, those responsible for analysis remained blind until the Trial Steering Committee had reviewed the definitive analysis. RESULTS: We randomised 223 patients, of whom 213 yielded enough data for primary analysis. EUS improved survival adjusted for generic quality of life with a hazard ratio of 0.705 [95% confidence interval (CI) 0.499 to 0.995], and crude survival with a hazard ratio of 0.706 (95% CI 0.501 to 0.996). The benefits of EUS were significantly greater for those with poor initial quality of life, but did not differ between centres. EUS reduced net use of health-care resources by £2860 (95% 'bootstrapped' CI from -£2200 to £8000). Combining benefits and savings shows that EUS is likely to be cost-effective, with 96% probability of achieving the National Institute for Health and Care Excellence criterion of costing of < £20,000 to gain a QALY. There were no serious adverse reactions attributable to EUS. EUS enhanced the management plan for many participants, increased the proportion of tumours completely resected from 80% (44 out of 55) to 91% (48 out of 53), and improved the survival of those who changed plan; although underpinning the significant differences in outcome, none of these process differences was itself significant. CONCLUSION: Endoscopic ultrasound significantly improves (quality-adjusted) survival, has the potential to reduce health-care resource use (not statistically significant) and is probably cost-effective (with 96% probability). We recommend research into the best time to evaluate new technologies. TRIAL REGISTRATION: ISRCTN1444215. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 39. See the HTA programme website for further project information.

Urgency of referral and its impact on outcome in patients with colorectal cancer.

AIM: Primary care referral for patients with bowel symptoms is triaged by general practitioners to urgent or routine based on the clinical suspicion of malignancy. Triage directly influences time to assessment and investigation. This study aimed to establish whether urgency of referral of patients with large bowel malignancy has any effect on management. METHOD: An analysis was undertaken of all patients with colorectal cancer referred by primary care and discussed at the regional colorectal multi-disciplinary team (MDT) meetings from January 2009 to December 2010. Demographics and tumour data were collated prospectively from MDT records, and operation and investigation reports. RESULTS: Of 369 primary case referrals with colorectal cancer, 303 (82.1%) were urgent and 66 (17.9%) routine. Patient characteristics (age, sex, American Society of Anesthesiologists grade) and resection rates were similar in both groups and no significant difference in tumour location was observed. The time from referral to diagnosis was significantly longer in the routine group (mean 73.7 days vs 30.2 days; P = 0.001). Dukes stage was less advanced for the routine referral group, (P = 0.002). CONCLUSION: Urgency of referral decreased the time to diagnosis. This did not influence resection rates. Dukes stage was higher for urgent referrals. Long-term follow-up is required to determine any impact on survival.

The impact of operative approach for oesophageal cancer on outcome: the transhiatal approach may influence circumferential margin involvement.

AIM: Surgery for oesophageal cancer remains the only means of cure for invasive tumours. It is claimed that the surgical approach for these cancers impacts on morbidity and may influence the ability to achieve tumour clearance and therefore survival, however there is no conclusive evidence to support one approach over another. This study aims to determine the impact of operative approach on tumour margin involvement and survival. METHODS: Data were extracted from the Scottish Audit of Gastric and Oesophageal Cancer (SAGOC), a prospective population-based audit of all oesophageal and gastric cancers in Scotland between 1997 and 1999 with a minimum of five-year follow up. Analysis focused on the three commonest approaches (Ivor Lewis n = 140, transhiatal n = 68, left thoraco-laparotomy n = 142) for oesophageal cancer. RESULTS: Operative approach had no significant impact on post-operative morbidity, mortality, overall margin involvement and survival. Transhiatal approach resulted in significantly more circumferential margin involvement (p = 0.019), and the presence of circumferential margin involvement significantly reduced five-year survival (median survival 13 months) compared to no margin involvement (median survival 25 months, p = 0.001). CONCLUSION: Surgical approach for oesophageal cancer had no significant effect on morbidity, post-operative mortality and five-year survival. Non-selective use of the transhiatal approach is associated with a significantly greater circumferential margin involvement, with positive circumferential margin impacting adversely on 5-year survival.

Bile vomiting in paediatrics: what do we really know?

Bile vomiting is clinically significant in neonates and children, indicating intestinal obstruction until proven otherwise. The aim of this study was to assess whether nursing staff within a children's hospital were able to accurately identify bilious vomiting and if a deficiency existed, whether educational posters could rectify this problem. A primary audit was conducted in the Royal Aberdeen Children's Hospital evaluating the ability of nursing staff to identify bile vomit and its significance. Educational posters were distributed and a secondary audit was conducted after six months to complete the audit cycle. The second audit also compared the knowledge of different medical professionals. In the primary audit, 41% of nurses selected the colour yellow, compared with 18% of nurses in the second audit with approximately 70% selecting dark-green. Thirty-three percent of nurses in the primary audit confirmed intestinal obstruction as the cause of bile vomiting, compared with 64% of nurses in the secondary audit. In conclusion, this study identified a deficiency in the recognition of bile vomiting among nurses, but demonstrates that the use of educational posters can significantly improve knowledge. This can be beneficial in the early recognition of this potential surgical emergency.

Morbidity and mortality rates following gastric cancer surgery and contiguous organ removal, a population based study.

BACKGROUND: Complete surgical (R0) resection remains the only potentially curative intervention for patients with localised gastric cancer. To achieve a curative resection, patients may require complex operations with resection of contiguous organs. The aim of this study was to assess how the extent of surgical resection influenced morbidity, mortality and survival in an aged non-selected population with significant comorbid disease. PATIENTS AND METHODS: Data were extracted from the Scottish Audit of Gastric and Oesophageal Cancer (SAGOC), a prospective population-based audit of all oesophageal and gastric cancers in Scotland between 1997 and 1999 with a minimum of 1-year follow-up. RESULTS: A total of 646 patients underwent surgical exploration for gastric cancer. A significantly higher incidence of chest infections (18.5 vs 11%, p< 0.05) and anastomotic leaks (14.3 vs 2.2%, p< 0.05) were associated with total gastrectomy (n=168) when compared to distal gastrectomy (n=272) resections. A 9.2% mortality rate and a 60% 1-year survival were associated with gastric resection alone. Removal of the spleen (n=131), pancreas (n=30) or liver resection (n=5) was associated with a significantly higher mortality rates, 18.3, 23.3 and 40%, respectively (p< 0.05), and significantly lower 1-year survival rates, 50.9, 39.1 and 20%, respectively (p< 0.05). CONCLUSIONS: The risk of more extensive resection is not balanced by improved survival in this population based series. Extending gastric resection to involve contiguous organs should be confined to highly selected cases.

Congenital funnel anus: investigation and novel management strategy.

Congenital funnel anus is a rare and poorly documented condition in which treatment strategies are still evolving. The authors present 2 cases and describe the findings after magnetic resonance imaging along with the treatment regime used successfully in these children.

Laparoscopic excision of a triple gallbladder.

Triplication of the gallbladder is a rare congenital anomaly of the biliary tract; there are only nine reported cases to date. We report a case in which laparoscopic cholecystectomy was performed in a patient with biliary colic and choledocholithiasis. Preoperative assessment with ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) failed to reveal the eventual findings of a triple gallbladder. Successful excision of the triple gallbladder was carried out laparoscopically, and the final diagnosis was confirmed by the pathologist. The patient made an uneventful postoperative recovery and was free of gastrointestinal symptoms at follow-up. This case report describes the first laparoscopic excision of a triple gallbladder and highlights the importance of pre-/perioperative imaging to allow for the safe dissection of rare anomalies of the biliary tract via the laparoscopic approach.