Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)

Oncotarget. 2017 Aug 16;8(44):76961-76973. doi: 10.18632/oncotarget.20290. eCollection 2017 Sep 29.

Background: The glyoxalase-1 gene (GLO1) is a hotspot for copy-number variation (CNV) in human genomes. Increased GLO1 copy-number is associated with multidrug resistance in tumour chemotherapy, but prevalence of GLO1 CNV in gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) is unknown.

Conclusions: GLO1 copy-number was increased in a large percentage of patients with GEP- NET and correlated positively with increased Glo1 protein in tumour tissue. Analysis of GLO1 copy-number variation particularly in patients with midgut NET could be a novel prognostic marker for tumour progression.

UHCW Research: Kaltsas G, James S, Gopalakrishnan K, Fisk A, Dimitriadis GK, Grammatopoulos DK and Weickert MO

Screening for malnutrition in patients with gastro-entero-pancreatic neuroendocrine tumours: a cross-sectional study

BMJ Open. 2016 May 4;6(5):e010765. doi: 10.1136/bmjopen-2015-010765.

OBJECTIVES: To investigate whether screening for malnutrition using the validated malnutrition universal screening tool (MUST) identifies specific characteristics of patients at risk, in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET).

CONCLUSIONS: Given the frequency of patients identified at malnutrition risk using MUST in our relatively large and diverse GEP-NET cohort and the clinical implications of detecting malnutrition early, we recommend routine use of malnutrition screening in all patients with GEP-NET, and particularly in patients who are treated with long-acting somatostatin analogues.

UHCW Research: Qureshi SA, Burch N, Hattersley JG, Khan S, Gopalakrishnan K, Darby C, Wong JL, Davies L, Fletcher S, Shatwell W, Sothi S, Randeva HS, Dimitriadis GK and Weickert MO.

The effect of non-steroidal anti-inflammatory drugs on severity of acute pancreatitis and pancreatic necrosis

RCS Annals: https://doi.org/10.1308/rcsann.2017.0205

Acute pancreatitis (AP) is a common emergency presentation and can be disabling. There is significant morbidity and mortality associated with AP, and it places a considerable burden on the healthcare system. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have a protective effect in some elective contexts. This retrospective study aimed to evaluate the effect of NSAIDs on the course of AP and the severity of the disease.

UHCW Research: G Marangoni

Tumour diameter is not reliable for management of non-secreting pancreatic neuroendocrine tumours

doi: 10.1530/EC-17-0293 Endocr Connect 2017 vol. 6 no. 8 876-885 

Small non-functioning pancreatic NETs (pNETs) ≤2 cm can pose a management dilemma in terms of surveillance or resection. There is evidence to suggest that a surveillance approach can be considered since there are no significant radiological changes observed in lesions during long-term follow-up. However, other studies have suggested loco-regional spread can be present in ≤2 cm pNETs. The aim of this study was to characterise the prevalence of malignant features and identify any useful predictive variables in a surgically resected cohort of pNETs. 418 patients with pNETs were identified from 5 NET centres. Of these 227 were included for main analysis of tumour characteristics. Mean age of patients was 57 years, 47% were female. The median follow-up was 48.2 months. Malignant features were identified in 38% of ≤2 cm pNETs. ROC analysis showed that the current cut-off of 20 mm had a sensitivity of 84% for malignancy. The rate of malignant features is in keeping with other surgical series and challenges the belief that small pNETs have a low malignant potential. This study does not support a 20 mm size cut-off as being a solitary safe parameter to exclude malignancy in pNETs.

UHCW Research: Saboor Khan, Martin O. Weickert

Warning over surgery delays for thousands of patients

A leading surgeon was warned thousands of patients are not being prioritised for gallbladder surgery after pancreatitis – despite the risk of the condition returning that in some cases could kill them.

To obtain this article please send a request to libraryw@uhcw.nhs.uk

Non-invasive Diagnosis of Pancreatic Cancer Through Detection of Volatile Organic Compounds in Urine

Gastroenterology, 2017, doi.org/10.1053/j.gastro.2017.09.054.

UHCW Research: Ramesh Arasaradnam

Volixibat for non-alcoholic steatohepatitis (NASH)

Currently, there are no approved therapies for the treatment of NASH, but doctors recommend dietary changes and exercise to prevent or slow disease progression. Volixibat is a new experimental once-daily oral tablet that may improve NASH by targeting and blocking a protein (apical sodium-dependent bile acid transporter) found in the liver. This is thought to improve liver function by reducing the amount of cholesterol (fatty substance) in this organ. If licensed, volixibat has the potential to establish itself as a single-agent and the first treatment specifically for NASH.


From the NIHR Innovation Observatory

A4250 for progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a rare, inherited condition that usually begins in infancy. The condition affects the liver, hindering or stopping the flow of bile from the liver. Bile flow is needed for fats, nutrients and vitamins to be absorbed into the body, and also to help the body get rid of toxins. Problems absorbing fats and nutrients can lead to poor weight gain and slower growth, and excess toxins in the body can lead to jaundice and itching, which can have a large impact on the quality of life of the patient and their family. There is no cure for this condition, and current treatments can only reduce the symptoms and slow down damage to the liver. It is not known how many people have this condition, but around 35 genetic tests are carried out each year for this condition.
The drug A4250 works in a new way that directly targets the part of the gut that allows bile to flow into the liver. By stopping bile from coming into the liver, bile levels are reduced, slowing down damage to the liver and reducing the symptoms of jaundice and itching. Because the drug acts directly on the gut, it has the potential to reduce the side-effects that occur with current medicines, such as problems with vitamin absorption. The drug is taken by mouth as a capsule.


From the NIHR Innovation Observatory

Paclitaxel as albumin-bound nanoparticles with gemcitabine for untreated metastatic pancreatic cancer [TA476]

Evidence-based recommendations on paclitaxel as albumin-bound nanoparticles (nab-paclitaxel; Abraxane) for untreated metastatic pancreatic cancer in adults.

Paclitaxel as albumin-bound nanoparticles (nab‑paclitaxel) with gemcitabine is recommended as an option for untreated metastatic adenocarcinoma of the pancreas in adults, only if:

• other combination chemotherapies are unsuitable and they would otherwise have gemcitabine monotherapy and
• the company provides nab‑paclitaxel with the discount agreed in the patient access scheme.

This recommendation is not intended to affect treatment with nab‑paclitaxel that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Pancreatic cancer patients to have routine access to life extending drug after new deal

NICE has recommended nab-paclitaxel for routine NHS use after the company agreed a confidential price discount and provided more evidence on its effectiveness.

Irreversible electroporation for treating pancreatic cancer

New NICE Interventional Procedures Guidance on using irreversible electroporation for treating pancreatic cancer. This involves inserting special needles into the tumour in the pancreas. Short electrical pulses of a high voltage current are then passed through the needles. The aim is to destroy the cancer cells.

NICE says pancreatic cancer drug is not cost effective for routine NHS use

Pegylated liposomal irinotecan is used for treating metastatic pancreatic cancer that has progressed after being treated by a different therapy.

NICE says that for metastatic pancreatic cancer the drug is not beneficial enough to justify its high cost for routine NHS use

Endoscopic transluminal pancreatic necrosectomy

New NICE interventional Procedure Guidance on endoscopic transluminal pancreatic necrosectomy in adults. This involves removing dead tissue from the pancreas.

Molecular Imaging of Late Somatostatin Receptor–Positive Metastases of Renal Cell Carcinoma in the Pancreas by Radiolabeled 111In SRS Octreotide Scan: A Rare Differential Diagnosis to Multiple Primary Pancreatic Neuroendocrine Tumors

Abstracts of the 13th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease. March 9-11, 2016, Barcelona, Spain.  Abstract I9

Somatostatin-Receptor Scintigraphy (SRS) has a sensitivity and specificity for pancreatic NETs (pNETs) of 90 and 80% respectively. SRS is indicated as first staging procedure and one of the
most sensitive imaging modalities for well-differentiated neuroendocrine tumors, based on imaging of somatostatin receptors (SSRTs).  The aim was to report 111In SRS scan ability in detecting lesions of RCC origin.

UHCW Research: Dimitriadis G., Davies L., Randeva H.S., Weickert M.O.

NICE says pancreatic cancer treatment considered not cost effective for routine NHS use

The drug pegylated liposomal irinotecan, was not clinically effective enough in treating pancreatic cancer, to justify its high cost, NICE says a statement.

Johanson-Blizzard syndrome

Update on Johanson-Blizzard Syndrome (JBS) from Orphanet, the portal for rare diseases and orphan drugs.

Johanson-Blizzard syndrome (JBS) is a multiple congenital anomaly characterized by exocrine pancreatic insufficiency, hypoplasia/aplasia of the nasal alae, hypodontia, sensorineural hearing loss, growth retardation, anal and urogenital malformations, and variable intellectual disability.

Treat the Cause: A review of the quality of care provided to patients treated for acute pancreatitis

This NCEPOD report examines the quality of care received by patients admitted to hospital with a primary diagnosis of acute pancreatitis during the first 6 months of 2014. My first impression was that this report was a good news story, since a sizeable proportion of these patients received good care during a time when our daily press had started to regularly identify stories about how badly the NHS is handling patients, due to reduced resources. However, as with most NCEPOD reports, more detailed scrutiny reveals that the true picture is more complex and as a result my second impression is that there are many aspects of care in which we could be doing better. Our report has been able to identify these and make some practical recommendations to improve the situation.

Cellvizio confocal endomicroscopy system for characterising pancreatic cysts

New NICE  medtech innovation briefing (MIB) on the Cellvizio confocal endomicroscopy system for characterising pancreatic cysts.

Cellvizio is a confocal laser endomicroscopy (CLE) system with a fibre-optic probe for real-time imaging of tissues. It is designed for use as an adjunct to the standard endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) procedure, to characterise pancreatic cysts and provide additional information to help guide therapeutic decisions. The evidence summarised in this briefing comes from 2 feasibility and 3 pilot studies with a total of 138 adult patients. The diagnostic accuracy for Cellvizio was reported to be between 71% and 87% in 3 studies compared with histopathology, EUS-FNA or a committee consensus. In 2 studies, images were successfully obtained in all patients. In another study, images were successfully obtained in most (17 of 18) patients. The device was used to identify and validate new diagnostic criteria for pancreatic cyst types in 4 studies. The numbers of safety incidents in 2 Cellvizio studies were higher than reported in a previous EUS-FNA-only study. The main capital component of the Cellvizio system costs £79,000 with installation, commissioning and initial training costs of £2,145. Each fibre-optic miniprobe (AQ-Flex 19) can be used up to 10 times and costs £4,000. All costs are excluding VAT.