Disappearing colorectal liver metastases in the era of state-of-the-art triple-modality diagnostic imaging.

INTRODUCTION: Systemic therapy can result in disappearance of colorectal liver metastases in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcome of patients with disappearing liver metastases (DLMs). METHODS: This was a retrospective study of consecutive patients treated for colorectal liver metastases at a high volume hepatobiliary centre between January 2013 and January 2015 after receiving induction or neoadjuvant systemic therapy. Main outcomes were use of imaging modalities, incidence, management and longterm outcome of patients with DLMs. RESULTS: Of 158 patients included, 32 (20%) had 110 DLMs. Most patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs was 10 mm (range 5-61). In the per lesion analysis, recurrence after "watch & wait" for DLMs occurred in 36%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (51 vs. 28 months, p < 0.05) and progression free survival (10 vs. 3 months, p = 0.003) were significantly longer for patients with DLMs. CONCLUSION: Even state-of-the-art imaging and restaging cannot solve problems associated with DLMs. Regrowth of these lesions occurs in approximately a third of the lesions. Patients with DLMs have better survival.

European Society of Surgical Oncology's strategy for clinical research: Paving the way for a culture of research in cancer surgery.

As part of its mission to promote the best surgical care for cancer patients, the European Society of Surgical Oncology (ESSO) has been developing multiple programmes for clinical research along with its educational portfolio. This position paper describes the different research activities of the Society over the past decade and an action plan for the upcoming five years to lead innovative and high quality surgical oncology research. ESSO proposes to consider pragmatic research methodologies as a complement to randomised clinical trials (RCT), advocates for increased funding and operational support in conducting research and aims to enable young surgeons to be active in research and establish partnerships for translational research activities.

Increased multimodality treatment options has improved survival for Hepatocellular carcinoma but poor survival for biliary tract cancers remains unchanged.

BACKGROUND: Primary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre. METHOD: Patients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data. RESULTS: A total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time. CONCLUSION: HCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers.

Impact of centralization of services on outcomes in a rare tumour: Retroperitoneal sarcomas.

BACKGROUND AND AIM: The retroperitoneal tumor (RPT) service in the North West costal region of England was centralized in May 2011 by the merger of the Merseyside, Cheshire and Lancashire, Cumbria sarcoma networks. Our aim was to analyze the impact of centralization of services on patient outcomes. METHODS: An analysis from 01/12/2004 to 30/11/2017 was undertaken from prospectively maintained database and electronic patient records; follow-up was until 30/04/2018. This time period encompassed 6.5 years before and after centralization of services took place. Survival analysis was done for Retroperitoneal Sarcomas (RPS) and also compared the impact of centralization. RESULTS: 72 patients (27 men), median age 69 (21-90) years) underwent 95 operations with an intention to excise RPS. Overall there were 52 (54.7%) multi-visceral resections (MVR). 91/95 (95.8%) patients with primary tumors had surgery with a curative (R0/1) intent. 30-day and 90-day operative mortality was 3.2% (n = 3) and 4.2% (n = 4) respectively. The 5-year survival for patients undergoing resection for RPTs was 51.3%. 79 (83.1%) of the resections in this series occurred in the 6.5-years post-centralization with an increase in MVR between the two time points (p < 0.0006). Despite the more radical nature of surgery post-centralization, there was no difference in 5-year survival for RPS patients when compared to pre-centralization, p = 0.575. However the 5-yr survival post-centralization compared favorability to national outcomes. CONCLUSION: Centralization in the management of RPS has resulted in an increase in resection rates and more complex MVRs, without compromising R0/1 resection rates; peri-operative mortality or overall survival.

Meta-analysis of prognostic factors for overall survival in patients with resected hilar cholangiocarcinoma.

BACKGROUND: Hilar cholangiocarcinoma is staged using the AJCC staging system. Numerous other prognostically important histopathological and demographic characteristics have been reported. The objective of this meta-analysis was to assess statistically the effect of postresectional tumour characteristics on overall survival of patients undergoing attempted radical curative resection for hilar cholangiocarcinoma. METHODS: Relevant studies were identified by searching the Ovid MEDLINE and PubMed databases. The search was limited to studies published between 2009 and 2017. Papers referring to intrahepatic or distal cholangiocarcinoma were excluded from review. Data extraction used standard Parmar modifications to determine pooled univariable hazard ratios (HRs). RESULTS: Twenty-four articles, containing 4599 patients, were assessed quantitatively. In pooled analyses, age (HR 1·16, 95 per cent c.i. 1·04 to 1·28), T category (HR 1·49, 1·30 to 1·70), lymph node involvement (HR 1·78, 1·65 to 1·93), microvascular invasion (HR 1·49, 1·34 to 1·68), perineural invasion (HR 1·54, 1·40 to 1·68) and tumour differentiation (HR 1·54, 1·38 to 1·72) were significant prognostic factors, with low heterogeneity. Portal vein resection (HR 1·54, 1·15 to 1·70) and resection margin status (HR 1·77, 1·57 to 1·99) had significant effects, but with high heterogeneity. Sex, tumour size and preoperative carbohydrate antigen 19-9 levels did not have a statistically significant effect on postoperative prognosis. CONCLUSION: Several tumour biological variables not included in the seventh edition of the AJCC classification affect overall survival. These require incorporation into prognostic models to ensure a personalized approach to prognostication and treatment.

The role of cetuximab in converting initially unresectable colorectal cancer liver metastases for resection.

In patients with metastatic colorectal cancer (mCRC) predominantly confined to the liver, whether a patient undergoes potentially curative resection of the liver lesions is a well-established principal determinant of long-term survival. There are a number of different agents, both chemotherapeutic and targeted biologic agents, which can aid in shrinking liver tumors, which would have otherwise been unresectable, allowing for potentially curative resection. The aim of this review article is to summarize the available evidence regarding optimal therapeutic strategies for converting initially unresectable metastases for potentially curative resection; we do not discuss patients who present with initially resectable disease. We have taken the approach to review trials that included R0 resection rates as one of the principal study endpoints and specifically enrolled patients with liver-limited disease. Primary tumor location has recently emerged as a putative prognostic and predictive factor in patients with mCRC; however, presently, there is a lack of resectability outcomes differentiating tumor location-defined subgroups, and several ongoing trials and retrospective analyses are anticipated to guide insights in the future. In conclusion, in patients with RAS wild-type mCRC, the data support preferential use of the anti-epidermal growth factor receptor monoclonal antibody cetuximab when combined with standard-of-care infusional doublet chemotherapy regimens (FOLFOX or FOLFIRI) for the conversion of initially unresectable metastases for potentially curative resection. Furthermore, we discuss data involving intensified chemotherapy regimens (i.e., 3-drug backbones such as FOLFOXIRI with or without a targeted biologic agent) to promote the conversion of initially unresectable metastases for potentially curative resection.

Long-term outcomes of patients with 10 or more colorectal liver metastases.

BACKGROUND: Although the number of colorectal liver metastases (CLM) is decreasingly considered as a contraindication to surgery, patients with 10 CLM or more are often denied liver surgery. This study aimed to evaluate the outcome after liver surgery and to identify prognostic factors of survival in such patients. METHODS: The study population consisted of a multicentre cohort of patients with CLM (N=12 406) operated on, with intention to resect, from January 2005-June 2013 and whose data were prospectively collected in the LiverMetSurvey registry. RESULTS: Overall, the group ⩾10 CLM (N=529, 4.3%) experienced a 5-year overall survival (OS) of 30%. A macroscopically complete (R0/R1) resection (72.8% of patients) was associated with a 3- and 5-year OS of 61% and 39% vs 29% and 5% for R2/no resection patients (P<0.0001). At multivariate analysis, R0/R1 resection emerged as the strongest favourable factor of OS (HR 0.35 (0.26-0.48)). Other independent favourable factors were as follows: maximal tumour size <40 mm (HR 0.67 (0.49-0.92)); age <60 years (HR 0.66 (0.50-0.88)); preoperative MRI (HR 0.65 (0.47-0.89)); and adjuvant chemotherapy (HR 0.73 (0.55-0.98)). The model showed that 5-year OS rates of 30% was possible provided R0/R1 resection associated with at least an additional favourable factor. CONCLUSIONS: Liver resection might provide long-term survival in patients with ⩾10 CLM staged with preoperative MRI, provided R0/R1 resection followed by adjuvant therapy. A validation of these results in another cohort is needed.

Precision surgery for colorectal liver metastases: Opportunities and challenges of omics-based decision making.

Precision surgery involves improving patient selection to ensure that surgical intervention that is proven to benefit on a population level is the optimal treatment for each individual patient. For patients with colorectal liver metastases (CRLM), existing prognostic scoring systems rely on well-recognised histopathological features such as size and number of lesions. Advances in preoperative imaging algorithms mean that increasingly low volume disease can be detected, improving assessment of these factors. In addition, novel imaging modalities mean that underlying tumour biology and metabolic behaviour during therapy can be assessed. Molecular analysis of tumours can provide crucial prognostic information, with the critical role of RAS/RAF mutations in prognosis well recognised. The optimal source of tissue for this level of analysis is debated, with good concordance between primary and metastatic lesions for some recognised prognostic factors but marked discrepancies for a variety of other relevant mutations. As well as mutational heterogeneity between primary and metastatic lesions, heterogeneity within tumours and dynamic changes in tumour biology over time present a significant challenge in assessing tumour for prognostic biomarkers. Circulating tumour cells offer one potential method of longitudinal tumour analysis, but are limited by current technologies. This review article summarises some of the key advances in prognostication for patients with resectable colorectal liver metastases, as well as highlighting the potential limitations of such an approach.

Role of staging laparoscopy in the stratification of patients with perihilar cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is a rare cancer with a poor prognosis. Radical surgical resection is the only option for curative treatment. Optimal determination of resectability is required so that patients can be stratified into operative or chemotherapeutic treatment cohorts in an accurate and time-efficient manner. Staging laparoscopy is utilized to determine the presence of radiologically occult disease that would preclude further surgical treatment. The aim of this study was to analyse the utility of staging laparoscopy in a contemporary cohort of patients with perihilar cholangiocarcinoma. METHODS: Patients diagnosed with potentially resectable perihilar cholangiocarcinoma between January 2010 and April 2015 were analysed retrospectively from a prospective database linked to UK Hospital Episode Statistics data. Patients with distal cholangiocarcinoma and gallbladder cancer were excluded from analysis. RESULTS: A total of 431 patients with perihilar cholangiocarcinoma were referred for assessment of potential resection at a supraregional referral centre. Some 116 patients with potentially resectable disease subsequently underwent surgical assessment. The cohort demonstrated an all-cause yield of staging laparoscopy for unresectable disease of 27·2 per cent (31 of 114). The sensitivity for detection of peritoneal disease was 71 per cent (15 of 21; P < 0·001). The accuracy for all-cause non-resection for staging laparoscopy was 66 per cent (31 of 47) with a positive predictive value of progress to resection of 81 per cent (69 of 85). Neither the Bismuth-Corlette nor the Memorial Sloan Kettering Cancer Center preoperative scoring system was contingent with cause of unresectability at staging laparoscopy (P = 0·462 and P = 0·280 respectively). CONCLUSION: In the present cohort, staging laparoscopy proved useful in determining the presence of radiologically occult metastatic disease in perihilar cholangiocarcinoma.

FOLFIRI plus cetuximab in patients with liver-limited or non-liver-limited RAS wild-type metastatic colorectal cancer: A retrospective subgroup analysis of the CRYSTAL study.

BACKGROUND: Adding cetuximab to first-line FOLFIRI in the phase 3 CRYSTAL trial significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients with KRAS wild-type (wt) or RAS wt metastatic colorectal cancer (mCRC). In this retrospective subgroup analysis of CRYSTAL, we investigated benefit of treatment in patients with KRAS wt or RAS wt tumors according to whether patients had liver-limited disease (LLD) or non-LLD, including assessing the role of cetuximab in downsizing metastases and conversion rates from initially unresectable to resectable disease. METHODS: PFS, OS, ORR, and R0 resection rates were analyzed according to treatment arm for the LLD and non-LLD subgroups. RESULTS: Of the 367 patients with RAS wt tumors, 89 (24%) had LLD and 278 (76%) had non-LLD. Within the RAS wt LLD and non-LLD subpopulations, demographic and baseline characteristics were comparable between treatment arms. In patients with RAS wt LLD, adding cetuximab to FOLFIRI significantly improved PFS (hazard ratio [HR][95% CI] = 0.21[0.09-0.49]) and ORR (odds ratio [OR][95% CI] = 8.99[3.17-25.52]), and numerically improved OS (HR[95% CI] = 0.65[0.38-1.10]) and R0 resection rate (OR[95% CI] = 2.68[0.63-11.43]) relative to FOLFIRI alone. In patients with RAS wt non-LLD, adding cetuximab to FOLFIRI significantly improved PFS (HR[95% CI] = 0.65[0.46-0.93]), OS (HR[95% CI] = 0.71[0.54-0.93]), ORR (OR[95% CI] = 2.44[1.49-3.98]), and-numerically-R0 resection rate (OR[95% CI] = 5.94[0.79-44.88]). Similar results were obtained from the KRAS wt population. CONCLUSIONS: Adding cetuximab to first-line FOLFIRI appears to improve clinical outcomes and R0 resection rates in KRAS wt and RAS wt mCRC patients with LLD as well as in those with non-LLD.

PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer.

PURPOSE: Perioperative chemotherapy confers a 3-year progression free survival advantage following resection of colorectal liver metastases (CRLM), but is associated with significant toxicity. Chemoembolisation using drug eluting PVA microspheres loaded with irinotecan (DEBIRI) allows sustained delivery of drug directly to tumour, maximising response whilst minimising systemic exposure. This phase II single arm study examined the safety and feasibility of DEBIRI before resection of CRLM. METHODS: Patients with resectable CRLM received lobar DEBIRI 1 month prior to surgery, with a radiological endpoint of near stasis. The trial had a primary end-point of tumour resectability (R0 resection). Secondary end-points included safety, pathologic tumour response and overall survival. RESULTS: 40 patients received DEBIRI, with a median dose of 103 mg irinotecan (range 64-175 mg). Morbidity was low (2.5%, CTCAE grade 2) with no evidence of systemic chemotoxicity. All patients proceeded to surgery, with 38 undergoing resection (95%, R0 resection rate 74%). 30-day post-operative mortality was 5% (n = 2), with neither death TACE related. 66 lesions were resected, with histologic major or complete pathologic response seen in 77.3% of targeted lesions. At median follow up of 40.6 months, 12 patients (34.3%) had died of recurrent disease with a median overall survival of 50.9 months. Nominal 1, 3 and 5-year OS was 93, 78 & 49% respectively. CONCLUSIONS: Resection after neoadjuvant DEBIRI for CRLM is feasible and safe. Single treatment with DEBIRI resulted in tumour pathologic response and median overall survival comparable to that seen after systemic neoadjuvant chemotherapy. Registered at clinicaltrials.gov (NCT00844233).

Adherence to early mobilisation: Key for successful enhanced recovery after liver resection.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) has been proven effective in liver surgery. Adherence to the ERAS pathway is variable. This study seeks to evaluate adherence to key components of an ERAS protocol in liver resection, and identify the components associated with successful clinical outcomes. METHOD: All patients undergoing liver resections for two consecutive years were included in our ERAS pathway. Six key components of ERAS included preoperative assessment, nutrition and gastrointestinal function, postoperative analgesia, mobilisation and discharges. Successful accomplishment of ERAS was defined as hospital discharge by postop day (POD) 6. Adherences of these elements were compared between the successful and un-successful groups. RESULTS: During the studied period, 223 patients underwent liver resections, among which 103 had major hepatectomies. N = 147 patients (66%) were discharged within our ERAS protocol target (6 days). On multivariable analysis, sitting out of bed by POD 1 (p < 0.03), walking by POD 3 (p = 0.03), removal of urinary catheter by POD 3 (p < 0.01), and avoiding major complications (p < 0.01) were factors associated with successful completion to our ERAS protocol; whereas advanced age (p = 0.34) and discontinuation of PCA/epidural by POD 3 (p = 0.50) were not significant parameters. There was a significant difference in the length of stay (p < 0.01) following major and minor liver resection, of which the indications for surgery also varied significantly. There was no difference in hospital re-admission rate, and morbidity and mortality between major and minor liver resection. CONCLUSIONS: Facilitating early mobilisation and reducing postoperative complications are keys to successful outcomes of ERAS in liver resection.

Objective assessment of trainee operative experience in a tertiary hepatobiliary unit.

INTRODUCTION: Indicative numbers for completion of training (CCT) in the UK requires 35 upper Gastrointestinal/Hepatobiliary resections and 110 (50 non HPB trainees) cholecystectomies. We aim to identify whether the training experience in our centre meets the CCT requirements for hepatobiliary surgery and compare training opportunities to those in international fellowships. METHODS: We retrospectively reviewed our hospital's operating theatre database for all patients undergoing a liver or gallbladder resection between January 2008 and July 2015 using corresponding procedural codes and consultant name. The cohort was categorized based on case and primary operating surgeon. The training grade of the surgeon was split into junior registrar (ST3/5), senior registrar (ST6/8) and senior fellow (post-CCT). RESULTS: Over a 7.5 year period we performed 2301 hepatobiliary procedures. The senior fellows and senior registrars performed a median of 42 liver resections (range 15-94) and 77 (range 35-110) cholecystectomies as the primary operator in any given 12 month period. The academic output for the unit was 104 over this period, with a median publication rate of 1.34 papers/trainee in any given 12 months. 15/16 senior fellow/senior registrars went on to secure substantive hepatobiliary consultant posts. CONCLUSIONS: Our centre delivers in excess of the required operative volume and clinical competencies for CCT in Hepatobiliary surgery in a 12 month period and exposure of trainees to operative experience is commensurate to the best performing international fellowships.

Management of disappearing colorectal liver metastases.

The development of new potent systemic treatment modalities has led to a significant increase in survival of patients with colorectal liver metastases. In the neo-adjuvant setting, these modalities can be used for patient selection, down staging, and conversion from non-resectable to resectable liver metastases. In addition, complete radiological disappearance of metastases can occur, the phenomenon of disappearing liver metastases. Because only a small percentage of these patients (0-8%) have a complete radiological response of all liver metastases, most patients will undergo surgery. At laparotomy, local residual disease at the site of the disappeared metastasis is still found in 11-67%, which highlights the influence of the imaging modalities used at (re)staging. When the region of the disappeared liver metastasis was resected, microscopically residual disease was found in up to 80% of the specimens. Alternatively, conservative management of radiologically disappeared liver metastases resulted in 19-74% local recurrence, mostly within two years. Obviously, these studies are highly dependent on the quality of the imaging modalities utilised. Most studies employed CT as the modality of choice, while MRI and PET was only used in selective series. Overall, the phenomenon of disappearing liver metastases seems to be a radiological rather than an actual biological occurrence, because the rates of macroscopic and microscopic residual disease are high as well as the local recurrence rates. Therefore, the disappeared metastases still require an aggressive surgical approach and standard (re)staging imaging modalities should include at least CT and MRI.

Common variables in European pancreatic cancer registries: The introduction of the EURECCA pancreatic cancer project.

BACKGROUND: Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer Care, is a platform aiming to harmonize cancer data collection and improve cancer care by feedback. After the prior launch of the projects on colorectal, breast and upper GI cancer, EURECCA's newest project is collecting data on pancreatic cancer in several European countries. METHODS: National cancer registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between different national registries and will enable data comparison on a larger scale. Additionally, first data was requested from the participating countries. RESULTS: Over 24 countries have been approached and 11 confirmed participation: Austria, Belgium, Bulgaria, Denmark, Germany, The Netherlands, Slovenia, Spain, Sweden, Ukraine and United Kingdom. The number of collected data items varied between 16 and 285. This led to a shared items list of 25 variables divided into five categories: patient characteristics, preoperative diagnostics, treatment, staging and survival. Eight countries shared their first data. CONCLUSIONS: A list of 25 shared items on pancreatic cancer coming from eleven participating registries was created, providing a basis for future prospective data collection in pancreatic cancer treatment internationally.

Randomized clinical trial of prehabilitation before planned liver resection.

BACKGROUND: Patients with low fitness as assessed by cardiopulmonary exercise testing (CPET) have higher mortality and morbidity after surgery. Preoperative exercise intervention, or prehabilitation, has been suggested as a method to improve CPET values and outcomes. This trial sought to assess the capacity of a 4-week supervised exercise programme to improve fitness before liver resection for colorectal liver metastasis. METHODS: This was a randomized clinical trial assessing the effect of a 4-week (12 sessions) high-intensity cycle, interval training programme in patients undergoing elective liver resection for colorectal liver metastases. The primary endpoint was oxygen uptake at the anaerobic threshold. Secondary endpoints included other CPET values and preoperative quality of life (QoL) assessed using the SF-36®. RESULTS: Thirty-eight patients were randomized (20 to prehabilitation, 18 to standard care), and 35 (25 men and 10 women) completed both preoperative assessments and were analysed. The median age was 62 (i.q.r. 54-69) years, and there were no differences in baseline characteristics between the two groups. Prehabilitation led to improvements in preoperative oxygen uptake at anaerobic threshold (+1·5 (95 per cent c.i. 0·2 to 2·9) ml per kg per min) and peak exercise (+2·0 (0·0 to 4·0) ml per kg per min). The oxygen pulse (oxygen uptake per heart beat) at the anaerobic threshold improved (+0·9 (0·0 to 1·8) ml/beat), and a higher peak work rate (+13 (4 to 22) W) was achieved. This was associated with improved preoperative QoL, with the overall SF-36® score increasing by 11 (95 per cent c.i. 1 to 21) (P = 0·028) and the overall SF-36® mental health score by 11 (1 to 22) (P = 0·037). CONCLUSION: A 4-week prehabilitation programme can deliver improvements in CPET scores and QoL before liver resection. This may impact on perioperative outcome. REGISTRATION NUMBER: NCT01523353 (https://clinicaltrials.gov).

Rectal cancer with synchronous liver metastases: Do we have a clear direction?

Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms.

Variation in Cardiac Screening and Management of Carcinoid Heart Disease in the UK and Republic of Ireland.

AIMS: Screening for carcinoid heart disease is an important, yet frequently neglected aspect of the management of patients with neuroendocrine tumours (NETs). Screening is advocated in international guidelines, although recommendations on the modality and frequency are poorly defined. We mapped current practice for the screening and management of carcinoid heart disease in specialist NET centres throughout the UK and Republic of Ireland. MATERIALS AND METHODS: Thirty-five NET centres were invited to complete an online questionnaire outlining the size of NET service, patient selection criteria for carcinoid heart disease screening and the modality and frequency of screening. RESULTS: Twenty-eight centres responded (80%), representing over 5500 patients. Eleven per cent of centres screen all patients with any NET, 14% screen only patients with midgut NETs, 32% screen all patients with liver metastases and/or carcinoid syndrome and 43% screen all patients with evidence of syndrome or raised urinary/serum/plasma 5-hydroxyindoleacetic acid (5HIAA). The mode of screening included clinical examination, echocardiography and biomarker measurement: 89% of centres carry out echocardiography, ranging from at initial presentation only (24%), periodically without clearly defined intervals (28%), annually (36%) or less than annually (12%); three centres use a scoring system to report their echocardiograms. Fifty per cent of centres utilise biomarkers for screening (chromogranins, plasma/urinary 5HIAA or most commonly N-terminal pro-brain natriuretic peptide) at varying time intervals. CONCLUSION: There is considerable heterogeneity across the UK and Ireland in multiple aspects of screening and management of carcinoid heart disease.