Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience.

INTRODUCTION: The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic. METHODS: A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved. RESULTS: Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic. CONCLUSION: The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

Changing outlook for colorectal liver metastasis resection in the elderly.

BACKGROUND: This study sought to evaluate the impact of the advancements in clinical care, obtained over the last 20 years, for patients aged 70 and older undergoing liver resection for colorectal liver metastases (CRLM). METHODS: Consecutive patients age 70 or older who underwent liver resection for CRLM at Aintree University Hospital (Liverpool, UK) between May 2008 and May 2015 were compared to a dataset of consecutive patients, meeting the same criteria, between 1990 and 2007. An enhanced recovery programme after surgery (ERAS) combined with cardiopulmonary exercise testing (CPET) was introduced in January 2008. RESULTS: The proportion of patients over 70 years undergoing liver resection for CRLM increased over the study period (6% in 1990, 16.3% in 2000, 26.5% in 2005 and 25.8% in 2007). The patients in the later group were more often treated with neoadjuvant chemotherapy (58 vs 34, p = 0.006) and underwent parenchymal sparing surgery, resulting in fewer major hepatectomies (51 vs 111, p < 0.001) and less perioperative morbidity (49 vs 70, p = 0.043) and mortality (3 vs 9, p = 0.229). Although there was shorter disease free survival (DFS) in the later group (DFS at 1, 3 and 5 years was 52.1%, 31.6%, 29% vs. 71.8%, 49.1%, 44.0%)(p < 0.01), similar overall survival (OS) was achieved (OS at 1, 3 and 5 years was 85.4%, 51.6%, 32.8% vs. 81.7%, 42.1%, 27.3%)(p = 0.21). CONCLUSIONS: This study demonstrates that, with modern management (ERAS, CPET, neoadjuvant chemotherapy and parenchymal sparing surgery), a greater number of patients with CRLM, over the age of seventy, can undergo liver resection, with improved perioperative outcomes.

Role of a pre-operative radiological scoring system in determining resectability for potentially resectable hilar cholangiocarcinoma.

AIMS: Cholangiocarcinoma is a rare cancer arising from the biliary tree. Case series indicate that 25-40% of all borderline resectable primary tumours are potentially resectable. The Memorial Sloane Kettering System (MSKCC) stratifies patients for resectability by longitudinal and radial extension of the hilar tumour. The Bismuth-Corlette system describes the longitudinal extension of the tumour within the biliary duct system. We sought to validate and, if possible, augment these two scores within an independent validation cohort. METHODS: Patients diagnosed with hilar cholangiocarcinoma between January 2009 and December 2016 were analysed from a prospectively held database. Patients with distal cholangiocarcinoma, peripheral cholangiocarcinoma and gallbladder cancer were excluded. Comparison of surgical findings to pre-operative radiological imaging was undertaken at the time of surgery. RESULTS: The validation cohort was formed of 198 patients, of which, 55 (27.8%) patients underwent resection. Logistic regression analyses identified that BC score, MSKCC score, age at diagnosis and left artery involvement were all significant independent predictor's univariately. BC score explained 28% of the variability in resectability compared to 26% explained by MSKCC. In combination, the model consisting of BC score, age at diagnosis and left artery involvement explained 39% of variability in resectability compared to the 34% explained same model including MSKCC score instead of BC score. CONCLUSION: In this cohort an augmented BC score, incorporating left hepatic artery involvement, is more discriminative in predicting resectability than the current MSKCC system.

Surgical audit: are we not closing the loop?

PURPOSE: A clinical audit is a key component of the clinical governance framework. The rate of audit completion in general surgery has not been investigated. The purpose of this paper is to assess the rates of audit activity and completion and explore the barriers to successful audit completion. DESIGN/METHODOLOGY/APPROACH: This was a multi-centre study evaluating current surgical audit practice. A standardised audit proforma was designed. All clinical audits in general surgery during a two-year period were identified and retrospectively reviewed. Data held by the audit departments were collated, and individual audit teams were contacted to verify the data accuracy. Audit teams failing to complete the full audit cycle with a re-audit were asked to explain the underlying reasons behind this. FINDINGS: Of the six trusts approached, two refused to participate, and one failed to initiate the project. A total of 39 audits were registered across three surgical directorates. Only 15 out of 39 audits completed at least one audit cycle, with 4 deemed of no value to re-audit. Only seven audits were completed to re-audit. Achieving a publication or a presentation was the most cited reason for not completing the audit loop. ORIGINALITY/VALUE: This study demonstrates that the poor rates of audit completion rate found in other areas of clinical medicine pervade general surgery. Improved completion of an audit is essential and strategies to achieve this are urgently needed.

Optimal perioperative care in peri-hilar cholangiocarcinoma resection.

Surgical resection remains the only proven curative treatment for peri-hilar cholangiocarcinoma. Despite recent advances in liver surgery techniques and perioperative care, resection for peri-hilar cholangiocarcinoma remains associated with significant morbidity and mortality. Considerable variation in the perioperative management of these patients exists. Optimal perioperative management has the potential to deliver improved outcomes. This article seeks to summarize the evidence underpinning best practice in the perioperative care of patients undergoing resection of peri-hilar cholangiocarcinoma. The authors also seek to identify areas where research efforts and future clinical trials should be targeted.

Hepatectomy for octogenarians with colorectal liver metastasis in the era of enhanced recovery.

BACKGROUND: Concern exists regarding the use of hepatectomy to treat colorectal liver metastasis (CRLM) in octogenarians due to prior studies suggesting elevated morbidity and mortality. Cardiopulmonary exercise testing (CPET) within pre-operative assessment and enhanced recovery after surgery (ERAS) have both been shown to be associated with low morbidity and mortality in patients undergoing hepatectomy. This study sought to compare the outcomes of octogenarians with patients aged 70-79 undergoing hepatectomy for CRLM, within a center utilizing both CPET and ERAS. METHODS: Consecutive patients age 70 or older who underwent hepatectomy for CRLM at Aintree University Hospital (Liverpool,UK), between May 2008 and May 2015 were identified from a prospectively maintained cancer database. Data were extracted and comparisons drawn. RESULTS: 127 patients aged 70-79 years and 34 octogenarians underwent respectively 137 and 35 hepatectomy for CRLM. There was no difference in hospital stay (6 days), morbidity and mortality between the groups. OS at 1, 3 and 5 years were 86.7%, 55% and 35.8% for those aged 70-79 compared to 79.4%, 37.3% and 20.4% for the octogenarians (p=0.127). DFS at 1,3 and 5 years was 52.5%, 31.7% and 31.7% for 70-79 group compared to 46.2%, 31.5% and 16.8% for the octogenarians (p=0.838). On multivariate analysis major hepatectomy was associated with an increased risk of post-operative complications, inferior OS and DFS. Chronological age was not a predictor of postoperative complications, poorer OS or DFS. CONCLUSIONS: Appropriately selected octogenarians can have similar postoperative outcomes to patients aged 70-79 when undergoing hepatectomy for CRLM using ERAS combined with CPET. This study advocates using CPET and ERAS in the selection and management of octogenarian patients with CRLM undergoing hepatectomy.

The risk of malignancy in ultrasound detected gallbladder polyps: A systematic review.

INTRODUCTION: Gallbladder polyps (GBPs) are a common incidental finding on ultrasound (US) examination. The malignant potential of GBPs is debated, and there is limited guidance on surveillance. This systematic review sought to assess the natural history of ultrasonographically diagnosed GBPs and their malignant potential. METHODS: The keywords: "Gallbladder" AND ("polyp" OR "polypoid lesion") were used to conduct a search in four reference libraries to identify studies which examined the natural history of GBPs diagnosed by US. Twelve studies were eligible for inclusion in this review. RESULTS: Of the 5482 GBPs reported, malignant GBPs had an incidence of just 0.57%. True GBPs had an incidence of 0.60%. Sixty four patients of adenomatous and malignant polyps were reported. Only in one patient was a malignant GBP reported to be <6mm. Risk factors associated with increased risk of malignancy were GBP >6mm, single GBPs, symptomatic GBPs, age >60 years, Indian ethnicity, gallstones and cholecystitis. CONCLUSION: With the reported incidence of GBP malignancy at just 0.57%, a management approach based on risk assessment, clear surveillance planning, and multi disciplinary team (MDT) discussion should be adopted. The utilization of endoscopic ultrasound(EUS) should be Only considered on the grounds of its greater sensitivity and specificity when compared to US scans.

Gastric Electrical Stimulation with the Enterra System: A Systematic Review.

Background. Gastric electrical stimulation (GES) is a surgically implanted treatment option for refractory gastroparesis. Aim. To systematically appraise the current evidence for the use of gastric electrical stimulation and suggest a method of standardisation of assessment and follow-up in these patients. Methods. A systematic review of PubMed, Web of Science, DISCOVER, and Cochrane Library was conducted using the keywords including gastric electrical stimulation, gastroparesis, nausea, and vomiting and neuromodulation, stomach, central nervous system, gastric pacing, electrical stimulation, and gastrointestinal. Results. 1139 potentially relevant articles were identified, of which 21 met the inclusion criteria and were included. The quality of studies was variable. There was a variation in outcome measures and follow-up methodology. Included studies suggested significant reductions in symptom severity reporting over the study period, but improvements in gastric emptying time were variable and rarely correlated with symptom improvement. Conclusion. The evidence in support of gastric electrical stimulation is limited and heterogeneous in quality. While current evidence has shown a degree of efficacy in these patients, high-quality, large clinical trials are needed to establish the efficacy of this therapy and to identify the patients for whom this therapy is inappropriate. A consensus view on essential preoperative assessment and postoperative measurement is needed.

The role of hepatectomy in the management of metastatic gastric adenocarcinoma: a systematic review.

BACKGROUND: Gastric cancer has a high mortality, with many patients presenting with advanced disease. Many patients who undergo curative gastrectomy will subsequently develop metastatic disease. Hepatectomy has an established place in treating metastases from a variety of cancers but its role in gastric cancer is not clear. This review sought to systematically appraise the literature to establish the role of hepatectomy in treating gastric cancer metastases. METHOD: Medline and EMBASE were searched for all papers publishing data on survival of patients with metastatic gastric adenocarcinoma who underwent hepatectomy. RESULTS: Seventeen studies with 438 patients were included. There were no randomised controlled trials. Perioperative mortality was 2%, with morbidity between 17 and 60%. Patients with solitary metastases appeared to have better survival. Other favourable survival characteristics included unilobar disease, and metachronous presentation. No advantage was demonstrated with either adjuvant or neoadjuvant chemotherapy. DISCUSSION: Few patients with hepatic metastases from gastric cancer are suitable for hepatectomy, but for those suitable there appears to be survival benefit. Patients with synchronous, multiple or bilobar metastases have worse survival. CONCLUSION: The evidence supporting the role of hepatectomy in the treatment of hepatic metastases from gastric cancer is weak. However in a selected group there appears to be a survival advantage; patients with solitary metastases had better survival outcomes than those with multiple metastases and metachronous presentation was associated with a better prognosis than synchronous presentation. Hepatectomy should be considered in these patients in the setting of a randomised trial.

Cardiopulmonary exercise testing before liver surgery.

BACKGROUND: Cardiopulmonary exercise testing (CPET) assessed "poorer" fitness correlates with poorer outcomes in blinded studies. Whether this correlation will persist when CPET is utilized to stratify care as part of a multi-modal enhanced recovery after surgery (ERAS) program is unclear. This study examined whether CPET variables were associated with postoperative morbidity in patients undergoing hepatectomy within an ERAS program. OBJECTIVES AND METHODS: Data were prospectively collected on patients undergoing elective hepatectomy between October 2009 and April 2011. The relationships between CPET derived variables; postoperative complications and length of stay were investigated. RESULTS: Of 267 patients undergoing surgery, 197 had undergone standard cycle ergometer CPET. The relative oxygen uptake [VO2 (ml kg(-1) min(-1))] and ventilatory equivalent of CO2 (VE/VCO2) at the anaerobic threshold (AT) were not associated with complications or length of stay. Greater absolute oxygen uptake at AT [VO2 at AT (L min(-1) )] was associated with early hospital discharge [OR 2.16 (95% CI 1.18-3.96), P = 0.013] on multivariable analysis. CONCLUSIONS: When CPET is used to delineate perioperative management a low relative oxygen uptake [VO2 (ml kg(-1) min(-1) )] at the AT does not place patients at significantly higher risk of postoperative complications. This suggests CPET assessed "poor" fitness should not be used as a barrier to surgical intervention.

Enhanced recovery in the resection of colorectal liver metastases.

BACKGROUND: There is limited evidence for the use of enhanced recovery after surgery (ERAS) in patients undergoing hepatectomy, and the impact of the evolution of ERAS over time has not been examined. This study sought to evaluate the effect of an evolving ERAS program in patients undergoing hepatectomy for colorectal liver metastases (CRLM). METHODS: A multimodal ERAS program was introduced in 2/2008. Consecutive patients undergoing hepatectomy for CRLM between 2/2008 and 9/2012 were included in the study. Data were collected prospectively. Retrospective analysis compared an early ERAS cohort (2/2008-4/2010) with a later cohort with a matured ERAS program (5/2010-8/2012). RESULTS: Length of stay reduced as experience of ERAS increased (Log-rank χ(2) = 10.43, P = 0.001). Although median length of stay remained unchanged (6 days), the probability of hospitalization beyond 10 days was 25% in the early cohort compared with 7% in the later cohort. Critical care utilization reduced over time (75.5% vs. 54.7%, P < 0.0001). Complications occurred in 38.2%, with no difference in between cohorts. One postoperative death occurred in the early cohort (<0.3%). CONCLUSIONS: This study suggests that as experience of ERAS evolves, there is a progressive reduction in hospitalization and critical care admission. This is without any increase in morbidity and mortality.

Optimal imaging sequence for staging in colorectal liver metastases: analysis of three hypothetical imaging strategies.

BACKGROUND: Computed tomography (CT), positron emission tomography CT (PET-CT) and magnetic resonance imaging (MRI) all play a role in the management of colorectal liver metastases (CRLM), but inappropriate over investigation can lead to delays in treatment and additional cost. This study aimed to determine the optimal sequence for pre-operative imaging pathway to minimise delays to treatment and healthcare costs. METHODS: All patients with colorectal liver metastases referred to a single tertiary liver specialist multidisciplinary team (MDT) between 2008 and 2011 were examined. Primary data of clinical and radiological outcomes of all patients were analysed. These data were used to construct and test 3 hypothetical imaging strategies - 'Upfront', 'Sequential' and 'Hybrid' models. RESULTS: Six hundred and forty four consecutive patients were included. One hundred and sixty five patients were excluded for curative resection following the initial CT review. Subsequently 167/433 patients did not proceed to hepatectomies. Eighty (47.9%) of these patients had extra-hepatic disease identified on PET-CT, and 29 were due to the exclusion by MRI liver. A resectable pattern of liver disease on initial CT did not exclude patients with occult disease on PET-CT. Based on cost analysis, assessment of initial CT, followed by MDT with subsequent PET-CT and MRI imaging thereafter (Hybrid model), was associated with the shortest time-to-decision and lowest cost. CONCLUSIONS: Resectable pattern of liver metastases should not solely be used to determine the application of PET-CT for staging. Hybrid model is associated with the lowest cost and shortest time-to-treatment.

Surgical management of colorectal liver metastases: a European perspective.

The treatment of colorectal cancer metastatic to the liver is increasingly complex as a result of changes in the patient population, advances in preoperative staging, changing definitions of resectability, advances in surgical technique and the expanding chemotherapeutic armamentarium. Management of these patients within a multidisciplinary team is increasingly important and associated with better outcomes. In patients with irresectable hepatic metastases, high secondary resection rates can be achieved with multiagent chemotherapy when managed in conjunction with a liver specialist. Perioperative mortality rates are reducing but morbidity remains high, and enhanced recovery could help reduce morbidity. Despite the advancing age and comorbidity of the patient population, multimodal management is likely to lead to further improvements in perioperative and long-term outcomes.

Metal stents: a bridge to surgery in hilar cholangiocarcinoma.

BACKGROUND: Obstructive jaundice in patients with hilar cholangiocarcinoma is a known risk factor for hepatic failure after liver resection. Plastic stents are most widely used for preoperative drainage. However, plastic stents are known to have limited patency time and therefore, in palliative settings, the self-expanding metal stent (SEMS) is used. This type of stent has been shown to be superior because it allows for rapid biliary decompression and a reduced complication rate after insertion. This study explores the use of the SEMS for biliary decompression in patients with operable hilar cholangiocarcinoma. METHODS: A retrospective evaluation of a prospectively maintained database at a tertiary hepatobiliary referral centre was carried out. All patients with resectable cholangiocarcinoma were recorded. RESULTS: Of 260 patients referred to this unit with cholangiocarcinoma between January 2008 and April 2012, 50 patients presented with operable cholangiocarcinoma and 27 of these had obstructive jaundice requiring stenting. Ten patients were initially treated with SEMSs; no stent failure occurred in these patients. Seventeen patients initially received plastic stents, seven of which failed in the interval between stent placement and laparotomy. These stents were replaced by SEMSs in four patients and by plastic stents in three patients. Median time to laparotomy was 45 days and 68 days in patients with SEMSs and plastic stents, respectively. CONCLUSIONS: Self-expanding metal stents provide adequate and rapid biliary drainage in patients with obstruction caused by hilar cholangiocarcinoma. No re-interventions were required. This probably reflects the relatively short interval between stent placement and laparotomy.

Segmental and lobar administration of drug-eluting beads delivering irinotecan leads to tumour destruction: a case-control series.

BACKGROUND: Irinotecan-loaded drug-eluting beads represent a novel drug delivery method that allows for the locoregional delivery of irinotecan to colorectal liver metastases (CRLM). The method has shown impressive response rates. However, the pathological response to this treatment has not previously been demonstrated. METHODS: Patients with easily resectable CRLM were treated with drug-eluting beads delivering irinotecan (DEBIRI) 4 weeks prior to resection. Pathological tumour response was graded using a validated system. The intraoperative detection of previously unidentified disease allowed for the assessment of pathological responses directly attributable to bead treatment. RESULTS: In Patient 1, segmental embolization of the target lesion in segment VIII resulted in 100% necrosis (0% viability). An untreated lesion in segment IV was found to be 30% viable. In Patient 2, subsegmental embolization of the target lesion in segment VI resulted in 60% necrosis and 40% fibrosis (0% viability). An untreated lesion in segment VI remained 60% viable. In Patient 3, lobar embolization of the target lesion in segment II resulted in 0% viability. Two further lesions within the treated hemiliver, both with 0% viability, and one lesion in the untreated hemiliver with 45% viability were discovered at laparotomy. CONCLUSIONS: This series demonstrates the effectiveness of DEBIRI in the treatment of CRLM. High rates of tumour destruction are possible, even with the proximal lobar administration of DEBIRI. Lobar administration appears to be an appropriate method of delivery for integration into future therapeutic regimens.

Microwave ablation of ex vivo human liver and colorectal liver metastases with a novel 14.5 GHz generator.

PURPOSE: This study assessed the relationship between time, power and ablation size using a novel high-frequency 14.5 GHz microwave applicator in ex vivo human hepatic parenchyma and colorectal liver metastases. Previous examination has demonstrated structurally normal but non-viable cells within the ablation zone. This study aimed to further investigate how ablation affects these cells, and to confirm non-viability. MATERIALS AND METHODS: Ablations were performed in ex vivo human hepatic parenchyma and tumour for a variety of time (10-180 s) and power (10-50 W) settings. Histological examination was performed to assess cellular anatomy, whilst enzyme histochemistry was used to confirm cellular non-viability. Transmission electron microscopy was used to investigate the subcellular structural effects of ablation within these fixed cells. Preliminary proteomic analysis was also performed to explore the mechanism of microwave cell death. RESULTS: Increasing time and power settings led to a predictable and reproducible increase in size of ablation. At 50 W and 180 s application, a maximum ablation diameter of 38.8 mm (±1.3) was produced. Ablations were produced rapidly, and at all time and power settings ablations remained spherical (longest:shortest diameter <1.2). Routine histological analysis using haematoxylin-eosin (H&E) confirmed well preserved cellular anatomy despite ablation. Transmission electron microscopy demonstrated marked subcellular damage. Enzyme histochemistry showed complete absence of viability in ablated tissue. CONCLUSIONS: Large spherical ablation zones can be rapidly and reproducibly achieved in ex vivo human hepatic parenchyma and colorectal liver metastases using a 14.5 GHz microwave generator. Despite well preserved cellular appearance, ablated tissue is non-viable.