John Ramage

Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs)

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices

Injection sclerotherapy of bleeding oesophageal varices is undoubtedly beneficial but it is associated with a substantial complication rate, and variceal rebleeding is common during the treatment period before variceal obliteration is achieved. We aimed to find out whether endoscopic variceal banding ligation is safer and more effective. The two methods were compared in a randomised controlled trial of 103 patients (54 assigned to banding ligation, and 49 to injection sclerotherapy) of whom 21 (39%) and 23 (47%), respectively, had active bleeding at index endoscopy. Both treatments were highly effective in controlling active haemorrhage (91% and 92% respectively). Variceal obliteration was not achieved for 22 patients in each group, but among those whose varices were eradicated, banding ligation achieved obliteration more quickly than did sclerotherapy (mean 39 [SD 4] vs 72 [7] days, p = 0.004) and in fewer endoscopy sessions (3.4 [2.2] vs 4.9 [3.5], p = 0.006). Rebleeding was less common in the banding ligation group than in the sclerotherapy group (16 [30%] vs 26 [53%], p < 0.05). There was no difference in outcome between the groups, but 14 sclerotherapy patients were withdrawn from the trial (7 for orthotopic liver transplantation) compared with only 5 (1 for liver transplantation) in the banding ligation group (p < 0.05). Complication rates were similar in the two groups. Variceal banding ligation is a safe and effective technique, which obliterates varices more quickly and with a lower rebleeding rate than injection sclerotherapy.

Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: Foregut, midgut, hindgut, and unknown primary

a DRK Kliniken Westend, Berlin , Germany; b UFR Bichat-Beaujon-Louis Mourier, Service de Chirurgie Digestive, Hopital Louis Mourier, Colombes , France; c Medicine and Surgery, General Surgery Section, MED/18 – General Surgery and d Department of Pathology, University of Verona, Verona , Italy; e Netherlands Cancer Centre, Amsterdam , and f Department of Nuclear Medicine, Erasmus University Medical Center, Rotterdam , The Netherlands;

Serum tumor markers for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis

BACKGROUND/AIMS The diagnosis of cholangiocarcinoma in primary sclerosing cholangitis (PSC), even with the use of current imaging techniques and brush cytology, is difficult and particularly important in patients being assessed for liver transplantation. This study investigated the accuracy of serum levels of a combination of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in the diagnosis of cholangiocarcinoma in patients with PSC. METHODS Seventy-four patients with PSC were studied. Fifteen patients had tumors (11 occult on imaging), 22 had severe PSC that necessitated transplantation (with explanted liver known to be free of tumor), and 37 patients had stable PSC. RESULTS An index of the two serum tumor markers [using the formula CA19-9 + (CEA x 40)] gave an accuracy of 86% in diagnosis of cholangiocarcinoma, with 10 of the 15 cases of cholangiocarcinoma having an increased value compared with none in a group of 22 comparable cases with no tumor. In addition, 6 of the 11 patients with occult tumors had abnormal values. Ultrasonography, computerized tomographic scanning, and endoscopic retrograde cholangiopancreatography were poor predictors of the presence of tumor. CONCLUSIONS A combination of serum tumor markers will identify most occult tumors and will improve selection of appropriate cases for orthotopic liver transplantation.

Gastrinoma (Duodenal and Pancreatic)

a Digestive Diseases Branch, NIH, Bethesda, Md. , USA; b Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; c Department of Hepatology and Gastroenterology, CHV A Pare Hospital, Boulogne , France; d Department of Gastroenterology, North Hampshire Hospital, Hampshire , UK; e Department of Surgery, Vivantes Humboldt Hospital, Berlin , Germany; f Department of Radiology, Royal Marsden Hospital, Sutton , UK; g Department of Pathology, Verona University, Verona , Italy; h Department of Radiology, Uppsala University, Uppsala , Sweden; i Department of Pathology, Universitatsspital Zurich, Zurich , Switzerland; j Department of Endocrinology and Metabolism, Hadassah University, Jerusalem , Israel; k Department of Oncology, Alexander Fleming Institute, Buenos Aires , Argentina; l Laboratory of Molecular Imaging and Experimental Radiotherapy, Universite Catholique de Louvain, Brussels , Belgium; m Department of Pathology, University Hospital of Kiel, Kiel , Germany

Enhanced liver fibrosis test can predict clinical outcomes in patients with chronic liver disease

Background Clinicians use fibrosis in a liver biopsy to predict clinical outcomes of chronic liver disease. The performance of non-invasive tests has been evaluated against histological assessment of fibrosis but use of clinical outcomes as the reference standard would be ideal. The enhanced liver fibrosis (ELF) test was derived and validated in a large cohort of patients and shown to have high diagnostic accuracy (area under the curve (AUC)=0.80 95% CI 0.76 to 0.85) in identification of significant fibrosis on biopsy. Objective To evaluate ELF performance in predicting clinical outcomes by following up the original ELF cohort. Methods Patients recruited to the ELF study at seven English centres were followed up for liver morbidity and mortality by examination of clinical data. Defaulting/discharged patients were followed up by family practitioner questionnaires. Primary outcome measure was liver-related morbidity/liver-related death. Results 457 patients were followed up (median 7 years), with ascertainment of clinical status in 92%. There were 61 liver-related outcomes (39 deaths). Survival analysis showed that the ELF score predicts liver outcomes, with people having the highest ELF scores being significantly more likely to have clinical outcomes than those in lower-score groups. A Cox proportional hazards model showed fully adjusted HRs of 75 (ELF score 12.52–16.67), 20 (10.426–12.51) and 5 (8.34–10.425) compared with patients with ELF <8.34. A unit change in ELF is associated with a doubling of risk of liver-related outcome. Conclusions An ELF test can predict clinical outcomes in patients with chronic liver disease and may be a useful prognostic tool in clinical practice.

Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study

We intended to identify the prognostic factors and the results of interventions on patients with liver metastatic midgut carcinoids. Five institutions that are part of United Kingdom and Ireland neuroendocrine tumour (NET) group took part in this study. Patients were included if they had histology proven NET of midgut origin and liver metastases at the time of the study. Clinical and biochemical data were collected retrospectively from hospital charts, pathology reports, radiology reports and biochemistry records for each patient. Three hundred and sixty patients were included in the study. The median survival from date of diagnosis was 7.69 years (confidence interval (CI) 6.40-8.99) and 5.95 years (CI 5.02-6.88) from date of diagnosis of liver metastases. On univariate analysis, increasing age at diagnosis, increasing urinary hydroxyindole acetic acid levels, increasing plasma chromogranin A levels, high Ki67, high tumour volume and treatment with chemotherapy were identified as factors associated with a significantly poorer outcome. Resection of liver metastases, resection of small bowel primary, treatment with somatostatin analogue therapy and treatment with peptide receptor therapy were associated with improved prognosis. Multivariate analysis revealed that age at diagnosis (P=0.014), Ki67 level (P=0.039) and resection of primary (P=0.015) were independent predictors of survival. This is the largest study to our knowledge looking specifically at the prognosis and clinical course of patients with liver metastatic midgut NETs. For the first time, we have shown that Ki67 and resection of primary are independent predictors of survival for this group of patients.

Consensus guidelines for the management of patients with digestive neuroendocrine tumours: Well-differentiated colon and rectum tumour/carcinoma

a Department of Gastroenterology, North Hampshire Hospital, Basingstoke , UK; b Stadtisches Klinikum Neuss, Lukaskrankenhaus, Chirurgische Klinik I, Neuss , Germany; c Istituto di Radiologia, Policlinco GB Rossi, Verona , Italy; d Institute for Pathology, Kantonsspital, Baden , Switzerland; e Departments of Internal Medicine and Endocrinological and Metabolic Sciences, University of Genoa, Genoa , Italy; f II. Internal Medical Department, University Hospital Martin, Martin , Slovakia; g G. Genimatas Hospital, Athens , Greece; h Erciyes University Medical School, Department of Endocrinology and Metabolism, Kayseri , Turkey; i H. Lee Moffitt Cancer Center/ University of South Florida, Tampa, Fla. , USA; j Anatomie Pathologique, Hopital Edouard Herriot, Lyon , France;

Ribavirin therapy for hepatitis C infection following liver transplantation

Abstract  Hepatitis C infection following orthotopic liver transplantation may lead to progressive chronic graft dysfunction. In this study, seven liver transplant recipients with chronic allograft dysfunction due to hepatitis C infection (one acquired and six recurrent infections) were treated with oral ribavirin for 6 months. Symptoms of lethargy, nausea and anorexia improved in all patients within 2 weeks of starting the drug, with a fall in serum AST of at least 40 % by this time. Ribavirin‐induced haemolysis was clinically

Once daily MMX mesalazine for the treatment of mild-to-moderate ulcerative colitis: a phase II, dose-ranging study.

Background  SPD476 (MMX™ mesalazine), is a novel, once daily, high‐strength mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System™ (MMX) technology to delay and extend delivery of the active drug throughout the colon.