Gastroenterology Today Autumn 2015 by Media Publishing Company

Volume 25 No. 3

Autumn 2015

Gastroenterology Today In this issue Reflux Ruined My Teenage Years From GP Referral to Out-Patient Clinic Peritoneal Metastases in a Patient with Osteosarcoma

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CONTENTS

CONTENTS 5

EDITORS COMMENT

PAPER Reflux Ruined My Teenage Years

PAPER From GP Referral to Out-Patient Clinic

PAPER Randomized Placebo-Controlled Trial

CASE REPORT Retroperitoneal Gallstone Granuloma

CASE REPORT Peritoneal Metastases

ADVERTORIAL Dyspeptic Patients At Risk

ADVERTORIAL F aecal Haemoglobin Measurements

COVER STORY The burden of gastrointestinal disorders on healthcare systems is mounting. BIOHIT HealthCare is a Finnish biotechnology company that develops, manufactures and markets in vitro diagnostic tests to help tackle this universal problem. BIOHIT’s mission statement is “Innovating for Health” and under this responsibility we have launched a number of cutting edge and cost effective diagnostic tests to help guide Primary Care physicians when making referrals for those patients with the greatest need.

The increasing burden on endoscopic resources and low yield from diagnostic gastroscopies means there is an unmet need to better control the demand for gastroscopy. By pre-selecting patients in whom gastroscopy should be prioritised GastroPanel® offers the best risk classification strategy for patients with dyspepsia from a single blood sample.

This issue edited by: Dr M Goldman BSc, MBBS, MRCP, FFPM c/o Media Publishing Company Media House 48 High Street SWANLEY, Kent BR8 8BQ ADVERTISING & CIRCULATION: Media Publishing Company Media House, 48 High Street SWANLEY, Kent, BR8 8BQ Tel: 01322 660434 Fax: 01322 666539 E: info@mediapublishingcompany.com www.MediaPublishingCompany.com PUBLISHING DATES: February, June and October. COPYRIGHT: Media Publishing Company Media House 48 High Street SWANLEY, Kent, BR8 8BQ PUBLISHERS STATEMENT: The views and opinions expressed in this issue are not necessarily those of the Publisher, the Editors or Media Publishing Company. Next Issue Spring 2016 Subscription Information – Autumn 2015 Gastroenterology Today is a tri-annual publication currently sent free of charge to all senior qualified Gastroenterologists in the United Kingdom. It is also available by subscription to other interested individuals and institutions. UK: Other medical staff - £18.00 inc. postage Non-medical Individuals - £24.00 inc. postage Institutions Libraries Commercial Organisations - £48.00 inc. postage Rest of the World: Individuals - £48.00 inc. postage Institutions Libraries Commercial Organisations - £72.00 inc. postage We are also able to process your subscriptions via most major credit cards. Please ask for details.

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GASTROENTEROLOGY TODAY - AUTUMN 2015

BIOHIT’s GastroPanel® blood test is the latest patient prioritisation tool for individuals with dyspepsia and is recommended as the first-line diagnostic test for adults with stomach complaints and as a screening test for Atrophic Gastritis. In primary care GastroPanel® can be used to identify patients with an increased risk of Gastric Cancer by identifying the pre-neoplastic condition Atrophic Gastritis.

Gastroenterology Today

EDITORS COMMENT

EDITORS COMMENT Doctors as political pawns

Believe it or not, I was involved in the doctors’ work to rule 40 years ago. As I was in my first appointment, everyone involved in that incident should have retired by now, so there are no veterans of industrial action in the system today. The problem then was similar, in that the government wanted to limit overtime payments and also had the idea that junior hospital doctors might want to work their first four hours of overtime for no compensation. Devotion to duty is one thing, but being ordered to devote yourself is another. The action that occurred at that time was that non-urgent treatment was suspended and that was followed by a decision by most juniors to only work their core 40 hours per week. This was before the European working time directive, and working one night in three as well as the days was commonplace and one in two was relatively normal. Weekends could start on Friday morning and not complete until Monday evening. There were some positives to these arrangements in that all resident staff had their own free accommodation at the time and the potential benefit to patients was continuity of care. Admittedly things were simpler then with no governance, no 360/appraisal and lower expectations. The hospital I was working in was closed and staff and patients were transferred to another local hospital, where we worked our 40 hours/week in tandem with the existing staff. I remember that patients probably did suffer as a consequence as the system limped, distances from patients’ homes were increased, travelling times increased and continuity disappeared. Eventually the dispute was settled after about four to six weeks, but things were never the same: you cannot expunge the memory of industrial activity, and some activist juniors had their cards marked in perpetuity. In an ideal world, you should learn from history. The learning for me was that industrial action by trusted professionals removes that label. They are seen as higher earners and the public does not see them as a group in need of fair treatment, as they are people with a vocation. The other lesson learned is that if you want to conduct industrial action it has to have a real impact, not just nuisance value. That is tricky as no one wants to harm patients and there withdrawal of labour does not actually hurt the NHS/Government: it only allows the door to open for more draconian action. There are obviously areas that could be investigated where there would be significant public inconvenience without health risk, but would the public bring pressure to bear on government or would there be a Mexican standoff? Who blinks last wins. The danger is that this might be just the political scenario that a government of any flavour has been looking for. A way to limit the power and influence of licensed medical practitioners, and shift some of their roles and responsibilities on to cheaper and more compliant groups. A clinical decision taken away from doctors is one that can be controlled, regulated and made to cost less. One heretical conspiracy theory is that this is part of a strategy to make a degree in medicine less attractive so that cheaper healthcare workers become the dominant force, and the places at our excellent medical schools can be sold to the highest bidding non-EU undergraduates. So, junior doctors and consultants, be careful what you wish for.

GASTROENTEROLOGY TODAY - AUTUMN 2015

“In an ideal world, you should learn from history. The learning for me was that industrial action by trusted professionals removes that label. They are seen as higher earners and the public does not see them as a group in need of fair treatment, as they are people with a vocation.”

At the time of writing, there is a threat of industrial action by hospital doctors related to changes in their current contract of employment. It is a long time since I have worked in the NHS, but my understanding is that the new proposal for expanding patient access to doctors means that not only might they have to work more hours that were outside normal working hours, but they may not be compensated for this work in the same way, meaning that there is a possibility of earning less. That is my very simple way of expressing the idea that the employer will want terms of service that are disadvantageous for the doctor, but politically attractive for the employers. On the face of it, there is no simple solution as the NHS is cash limited and the resources (of manpower) are finite.

PAPER

“REFLUX RUINED MY TEENAGE YEARS” SUFFERING IS FINALLY OVER FOR TEENAGE GIRL THANKS TO REVOLUTIONARY PROCEDURE Sutton, 12 February 2015 – An 18 year-old girl who suffered

were a nightmare. I lost a lot of weight at a time when I should have

from horrific acid reflux for five years, resulting in her losing

been growing and at one point spent many nights in hospital, as they

a quarter of her body weight, has finally found relief thanks to

were so worried about the amount of weight I had lost. I can honestly

a revolutionary device that was fitted in a procedure that took

say that it ruined many years of my life.”

less than an hour. Kirsty Milne has sacrificed social occasions and lived in almost constant discomfort since the age of 13,

Robin, along with his wife Heather, endured years of frustration when

being unable to eat comfortably with her family or even go out

numerous medical professionals were unable to diagnose Kirsty’s

with her friends. With a weakened oesophageal muscle, Kirsty

condition. Having subscribed to a mailing list about private medical

found all food she tried to eat would regurgitate several times,

procedures, Robin one day happened upon a piece about Dr Dhiren

leaving her with no choice but to chew and swallow it repeatedly,

Nehra and the revolutionary LINX® procedure. He showed the piece

in an attempt to force it to stay in her stomach. Every meal took

to Kirsty and immediately contacted St Anthony’s Hospital in Surrey to

Kirsty over two hours to digest, leaving her feeling exhausted,

arrange a consultation. Robin says:

depressed and anxious. Thankfully, relief came in the form of an innovative device called the LINX® Reflux Management System,

“It was horrific seeing Kirsty suffer for so many years; we watched her

which comprises a small, flexible band of magnets enclosed in

withdraw into herself, which was heartbreaking as she used to be such

titanium beads which is implanted around the weak sphincter just

a bubbly, carefree and active girl. Understandably, the coping strategy

above the stomach. The magnetic attraction between the beads

Kirsty used was to withdraw socially, and while her friends were going

helps keep the weak oesophageal sphincter closed to prevent

out for meals and coffee, Kirsty would have to stay home. Eventually,

reflux. It is implanted via laparoscopic (keyhole) surgery and is

the horrendous impact of the condition, along with the anxiety Kirsty had

available on the NHS and privately.

around food, resulted in her losing a quarter of her body weight. She ended up in hospital for two weeks, some of it in intensive care. As a

Kirsty, who is now a first-year student of Modern Languages at Exeter

parent, watching your child suffer – foreseeing the long-term impact on

University, tried to deal with her symptoms with over-the-counter

their life, their health, their career – is truly horrific”

antacids. When these did not work, her parents, Robin and Heather, took her to her GP, who despite conducting numerous tests, could

At Kirsty’s consultation with Dr Nehra, several tests were conducted,

not ascertain what was wrong. By the time Kirsty was 17, she had

one which tested the strength of her oesophageal muscle. The test,

undergone numerous endoscopies and lost so much weight that she

called a manometry, records the contractions of the oesophageal

was kept in hospital as the doctors were too worried to allow her to go

muscle when eating or drinking. The manometry showed that Kirsty’s

home. Kirsty’s condition had a huge effect on her family and social life;

muscle was functioning at 0.1, the average and healthy range being

once an outgoing girl, Kirsty shied away from social occasions as she

18-20.

was paranoid that people would watch her eating and wonder what was wrong with her. Kirsty’s parents could see how introverted Kirsty

She explains:

was becoming and began to worry that she would have to deal with the GASTROENTEROLOGY TODAY - AUTUMN 2015

condition and its social and psychological effects for the rest of her life.

“I was 17 when Dr Nehra diagnosed me with a weak oesophageal

Kirsty says:

muscle. At the time I couldn’t have the procedure until I was 18, so had to wait a little while. Somehow, I knew that it would work. I applied

“Since my symptoms first appeared at age 13, I have undergone too

for university, having previously thought that I wouldn’t be able to go,

many tests to count! At first, the symptoms weren’t too bad; I would

knowing I would feel better by the time term began. I spent the time

swallow food and then it would come back up undigested, so I would

feeling like a light was finally shining at the end of a very long tunnel. The

swallow it again. It wasn’t like being sick; it was unpleasant but I was

procedure went really well; I had no adverse effects from it and now I

able to cope with it. However, it got worse over the years, to the point at

can pretty much eat what I want. My life has changed so much; I can go

which I would absolutely dread eating food. Food became my enemy.

out with my friends from university and not worry about eating in front of

Despite numerous tests and various medications, nobody seemed to

anyone. The anxiety has lifted and the illness that plagued me from such

know what was wrong. It was affecting my family; food has always been

a young age has finally been cured. It is a miracle.”

a big part of our family lifestyle, my mum would make everything from scratch and we would sit as a family and catch up with each other’s

Robin continues:

days. When my symptoms got really bad, mum would have to make me separate meals and take into consideration that I needed two hours

“The worst part was having to wait nine months until Kirsty turned 18;

after each meal to digest my food properly. It ruined my life, I was

I would have given anything to change that. Mr Nehra was so kind,

unable to go out socially, I was unable to go on days out and holidays

helpful and understanding; he reassured Kirsty throughout, drew

PAPER

diagrams explaining the procedure, and made sure she was comfortable and understood what was going to happen. Since the procedure Kirsty’s condition has improved immeasurably, she can now eat practically anything. Kirsty has gone off to university with confidence and is enjoying a fresh start . My daughter has her life back.” Mr Dhiren Nehra, General Surgeon with a special interest in laparoscopic and gastrointestinal surgery at St Anthony’s Hospital, says: “Kirsty and her parents came to see me as Kirsty had suffered with reflux and regurgitation for many years. The LINX® procedure was the ideal surgical option for Kirsty; LINX® is a safe and effective treatment which is inserted during a laparoscopic (keyhole) operation and prevents stomach acid leaking upwards, and the regurgitation of food and liquids. It has worked extremely well for Kirsty and we are delighted to have been able to help her, and essentially allow her to socialise and enjoy life again.” In 2014, a paper titled ‘Safety analysis of first 1000 patients treated with magnetic sphincter augmentation for gastroesophageal reflux disease’ published in Diseases of the Esophagus examined the safety profile of the first 1,000 patients implanted with LINX. The results showed event rates of 0.1% complications during and immediately after surgery, 1.3% hospital readmissions and 3.4% re-operations. The study concluded that LINX is a ‘safe therapeutic option for patients with chronic, uncomplicated GORD’. Another paper recently presented at the prestigious Annual Meeting of Thoracic Surgeons in Florida earlier this year, titled ‘Short-Term Outcomes Using Magnetic Sphincter Augmentation Versus Nissen Fundoplication for Medically Resistant Gastroesophageal Reflux Disease,’ compared the outcomes of people who underwent Magnetic Sphincter Augmentation, marketed as the LINX® Reflux Management System. Both groups of patients were interviewed 6 months’ post-surgery and the conclusion showed that both procedures controlled the symptoms of GORD but that the LINX® facilitates belching and creates less bloating. Reference the generally expected user experience outlined in the LINX clinical data on Torax’s website. The LINX device is restricted to sale and use by a licensed practitioner. Please contact an implanting physician to discuss suitability, risks, and side-effects with LINX. For more information please visit www.toraxmedical. co.uk/linx. For media enquiries please contact Kate Chaundy of Cacique PR

GASTROENTEROLOGY TODAY - AUTUMN 2015

the traditional surgical procedure or the minimally invasive

on 0207 250 4750 or kchaundy@caciquepr.com

PAPER

FROM GP REFERRAL TO OUT-PATIENT CLINIC: A COMPLEX PAPER TRAIL Raphael Cooper1, Adam Telford1, Steven Mann1 Department of Gastroenterology, Barnet Hospital, Herts, UK1 Corresponding Author: Dr Steven Mann, Barnet Hospital, Wellhouse Lane, Barnet, Herts EN5 3DJ Tel: 0208 216 4147 Email: steve.mann@nhs.net

Key words

The Modified Referral Process

Referral, Delays, Choose and book, Gastroenterology clinic

The current ‘modified referral system’ used by many Trusts is more complex than the traditional paper referral, relying on a referral management service (RMS) established by primary care doctors to reduce referrals into the hospital system. The RMS for our Trust is based in Holbrook House, Cockfosters. Their role is to filter referrals so that only appropriate patients are sent in to the Referral Management Team at the right institution. The unit is mainly comprised of administrative personnel, with a small amount of clinical input (GPSIs or consultants from the Trust) if needed.

Abstract The steps in the process from GP referral of a patient to Gastroenterology out-patient attendance are multiple and longwinded. Where it was once considered straightforward for a GP to refer to a named consultant or department, this has been converted to a complex paper trail. The two main routes for GPs to access the hospital system have been analysed and the delays at various stages have been compared. Choose and Book and the Modified referral system are both associated with delays, although the rate limiting step for both pathways is due to clinic capacity. This study highlights what happens behind the scenes to a GP letter from the point of referral to the hospital consultation episode.

Introduction Until a few years ago, primary care doctors would refer a patient to a hospital specialist by writing to a named doctor or specialty department. This letter would be received by the consultant’s secretary and would be triaged by the individual consultant as routine or urgent. The hospital appointment would then be made by the secretary or administration staff allocated to gastroenterology. However over the last few years, a straightforward system has been transformed into a complex paper trail.

GASTROENTEROLOGY TODAY - AUTUMN 2015

As part of our Student Selected Component (SSC) module in gastroenterology we reviewed the current process and pathways by which patient referrals are made to the Gastroenterology clinic. This is an aspect of daily administration that frontline clinicians are probably unaware of as it occurs behind the scenes and involves several layers of beaurocracy and algorithms. Our objective was to identify the steps in the process and to determine where delays can occur in receiving a hospital appointment.

Background A Traditional or “paper” referral has historically been the standard process to refer patients into Secondary Care. This involves a letter being sent from a GP to their requested service or named consultant and the patient then receives an appointment once the letter has been triaged by the consultant. In the current era, there are two main routes by which patients are referred into out-patient clinics by their GPs: 1. Modified Referral System 2. Choose & Book

1. A Barnet GP e-mails a referral letter to the RMS. 2. The RMS will triage the referral as to suitability for secondary care and the appropriate specialty. 3. RMS e-mails the referral letter to the Central Appointments Office (CAO), based at Chase Farm Hospital. The patient details are registered onto the Patient Administration System (PAS). 4. The following day, the referral is hand-delivered to the consultant for triage. Some specialty departments triage referrals on-line. 5. After the consultant has triaged the referral, the letter is handdelivered back to the CAO, where the booking staff make a “request” on the booking system for an appointment. The letter is scanned onto the electronic patient record (EPR) for review later, if necessary, and then shredded. 6. This “request” generates a letter (known as a Partial Booking 2 (PB2)), which is sent to the patient. The letter requests the patient to call the booking office to make an appointment. The patient has seven days in which to do this. 7. Patients are sent a confirmation letter for their appointment – this is automatically generated and sent to them when they book their appointment. If a mobile phone number has been ‘captured’, a text message is sent 7 days and 2 days prior to the appointment, reminding the patient of that appointment. 8. If a patient, having received their PB2 letter, contacts the booking office to book their appointment and there is no capacity in the system for an appointment, the patient is added to a “breach” list. This list is checked daily and discussed with the Business Manager who has a responsibility to ensure that these patients are seen within the optimal booking time, which is variable for each specialty. Ad hoc clinics are used to deal with these ‘breach’ patients. 9. If seven days elapse without hearing from the patient after the PB2 letter has been sent, a further letter (known as a PB3) is automatically generated and sent to the patient requesting them to call to book an appointment.

PAPER 10. If no response is received from the patient after another seven days, a PB5 letter is sent to the patient. This notifies them that they have been discharged from the clinic. The patient’s GP is not copied into this letter, at the request of the GPs who have been swamped with such letters. Should the patient still require review, they will have to return to their GP to restart the process.

We also analysed data using the PAS and EPR systems to identify

The Department of Health have set a target for patients to be treated

Data collected included :

consecutive new patients who had gastroenterology outpatient appointments over a 2-month period in 2013. Utilising a spreadsheet compiled by the gastroenterology administration staff, we identified 20 patients from the two main referral routes to track the time at each step in the process until the clinic appointment.

within 18 weeks of ‘referral’ (‘RTT’ pathway)1. The clock starts counting when the referral arrives in RMS – this is known as the ‘received date’. Our specialty has an optimal booking time of 12 weeks for the first appointment. If a GP posts a letter or faxes the CAO directly, new rules oblige the CAO to send the referral back to RMS for vetting (the clock

• Date of referral by GP • Date referral received at CAO • Date referral received by consultant

actually starts when the CAO received the initial referral under these

• Date referral sent back to CAO after triage

circumstances).

• Date appointment booked • Date of appointment

Choose & Book Referral Process The ‘Choose & Book’ system was introduced by the National Programme for IT as an e-booking software application in 20052. It allows the patient to choose the time and date of their appointment and preferred hospital whilst they are sitting in the GP surgery. The GP can then attach referral letters electronically, ideally removing any delays from posting and avoiding the loss of referral letters. The Choose and

Results Barnet and Chase Farm Hospitals serve a population of 500,000 in North West London on the border of Hertfordshire.The number of referrals into gastroenterology for 2012 were:

Book NHS website lists some of the advantages of the system which

• Modified Referral – 1302 (47%)

include fitting the appointment in with other commitments, choosing

• Choose & Book – 1484 (53%)

appointments that fit in with carers’ schedules, and allowing a change or cancellation easily over the phone or internet2.

The number of referrals rejected after triaging by Gastroenterology consultants in 2012 were:

1. GPs who wishes to use the Choose and Book System log on to the Choose & Book referral service. 2. The priority of appointment is selected (routine/urgent) 3. The type of service is selected e.g. gastroenterology 4. A list of appointments is displayed between 9 and 70 days from the log-on date, starting with first available. 5. Once a date and time is selected, a referral letter is attached electronically.

• Modified – 542 (42% of Modified referrals) • Choose & Book – 525 (35% of Choose & Book referrals) Rejections were made for several reasons which mainly include referral letter only being an advice request, allocation by CAO to wrong clinician, allocation by CAO to wrong specialty and triaging by consultants direct to endoscopy to expedite investigations. The mean time from referral to appointment was 86.6 days for modified

6. Data are checked by CAO the next day.

referrals and 71.1 days for Choose & Book representing a 15.5 day

7. Referrals are sent to consultant for triage. Currently, 75% of

delay for modified referrals to see the consultant. The mean time from

8. If accepted, the patient keeps their appointment. If it is rejected, CAO inform RMS who then inform the GP and the patient.

referral to receipt by the consultant was 3 days longer for modified referrals (19 days for modified referrals and 16 days for Choose & Book). Once booked, for either pathway, there was no difference in mean time to appointment (57.9 days).

The above process applies to referrals that are not “target” referrals, i.e. referrals that fall into the category of ‘2 week waits’ for suspected cancers. For these types of referrals, appointments can be chosen from

Conclusion

day 1 rather than day 9. Referral processes into secondary care are long winded and there

Methods

are many hold-ups before the patient even gets the appointment. In the ‘modified referral pathway’, the referral letter must pass through a minimum of five stages involving different personnel at each stage in

We spoke to several individuals involved in the out-patient bookings

order to make an appointment. In the Choose & Book pathway, there is

department and the ‘choose and book’ office to gain insight into the

no paper referral and the patient can make an appointment within days

referral process.

of referral.

GASTROENTEROLOGY TODAY - AUTUMN 2015

consultants in all specialties triage online.

PAPER The limitation of our audit is the small sample of only 20 patients which may not be sufficient in size to accurately reflect the differences between the two referral pathways. Nevertheless, this study provides us with insight into the referral process and can help us undertand what happens behind the scenes before the patient attends for their clinic consultation with the specialist. The delays of up to 2 weeks for the ‘modified referral process’ compared with Choose and Book referrals may be partly due to the higher rejection rate of referrals into the system. Consultants may be more reluctant to do this for Choose and Book patients once an appointment has already been allocated. We would be interested in assessing the waiting times for ‘rejected patients’ to see how much of an impact this has in patients who are reallocated to alternative clinics for example. However the RMS and CAO processes of the modified referral pathway appear to be the main factors leading to longer ‘referral to appointment times’ when compared with Choose & Book. There also appears to be a 2-3 week delay in the referral letter actually arriving in the consultant’s office. Once the appointment has been made the largest proportion of the total delay for both pathways is the wait for the clinic date which is always going to be limited by capacity issues and is the inevitable rate limiting step in these processes. These ‘improved’ systems appear to have led to a poorer service and more frustrations for patients who are waiting longer to hear about their appointment, compared with the historical letter from GP direct to consultant which would have taken the few days for a standard postal delivery. The desire to undertake this study was triggered by anecdotal reports of lengthy delays in the patient actually receiving their appointments and different personnel blaming different offices for those delays. As in all systems, the analysis has identified several areas where delays do occur, none of which would have happened with the traditional referral letter. The paper trail really is complex and difficult to follow for clinicians…is it all worthwhile?

Statement RC and AT contributed to the data collection, interpretation and writing the article, SM designed the study and supervised the project. None of the authors have any conflicts of interest. The project was not funded. GASTROENTEROLOGY TODAY - AUTUMN 2015

Acknowledgements: Erica Griffith, Gastroenterology Business Manager, for proof reading the paper and correcting any errors; Lisa Davis, Gastroenterology secretary, for use of her spreadsheet identifying consecutive patients for the study and her contacts in CAO for their help.

References 1. Referral to Treatment Consultant-led WaitingTimes Rules Suite. Department of Health, Jan 2012. 2. http://www.chooseandbook.nhs.uk/

GastroToday_Feb2015_29/01/2015 11:10

PAPER

RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF TRANSDERMAL RIVASTIGMINE FOR THE TREATMENT OF ENCEPHALOPATHY IN LIVER CIRRHOSIS (TREC TRIAL) Patrick P. Basu1,2, Niraj James Shah3, Mark M. Aloysius2, Robert S. Brown1 Columbia University College of Physicians & Surgeons, New York, USA, 2King’s County Hospital, New York, USA, 3James J. Peters VA Medical Center, New York, USA, Email: mark.aloysius5@gmail.com 1

Copyright © 2014 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

ABSTRACT

• Transdermal rivastigmine in combination with oral lactulose can

Objectives: Cognitive dysfunction in patients with hepatic

• Transdermal rivastigmine in combination with oral lactulose is

encephalopathy (HE) may be caused by alterations in cholinergic

be used safely in clinical practice.

efficacious in improving cognitive function in moderate HE (grade 2/3).

neurotransmission. The objective of the study was to evaluate the efficacy and safety of transdermal rivastigmine in improving cognitive

Further validation through large randomized clinical trials is

function in patients with overt HE.

required before this is adopted in universal clinical practice of treating HE.

Design: Randomized, controlled pilot study in which patients with grade 2 or 3 HE were treated with lactulose and randomized to receive either transdermal rivastigmine or placebo for 21 days. The modified encephalopathy scale (MES), object recognition test (ORT), trail test (TT), and serum ammonia were assessed at baseline weekly. Electroencephalography was performed at baseline and the final week of the study. Results: Patients were treated with lactulose (20 g/30 mL

Keywords Acetylcholinesterase, Cholinergic Function, Hepatic Encephalopathy, Rivastigmine

three times per day) and either transdermal rivastigmine (4.6 mg/d; n = 15) or placebo (n = 15). Transdermal rivastigmine significantly improved MES, ORT, and TT results compared with placebo (P ≤

1. Introduction

0.0001 at all 3 weeks for all 3 assessments). Serum ammonia improved in both treatment groups, although there was significantly greater

Hepatic encephalopathy (HE) is a neuropsychiatric complication of

improvement with placebo than rivastigmine after 2 weeks of treatment

acute and chronic liver disease [1] that contributes to the mortality of

(P < 0.03). There were no differences in electroencephalography results

patients with end-stage liver disease [2]. This potentially reversible

between treatment groups. Conclusions: Transdermal rivastigmine

condition [3] is characterized by a variety of symptoms, including

with concomitant lactulose significantly improved cognitive-function in

changes in consciousness and cognition [4]. The precise pathogenic

patients with overt HE.

mechanisms leading to HE are unknown but are primarily believed to involve the accumulation of ammonia and other gut-derived toxins

What is already known about this subject?

[5]. Such current approaches to the management of HE are primarily

• Current approaches to the management of HE are primarily designed

designed to reduce the levels of ammonia and other gut-derived toxins

to reduce the levels of ammonia and other gut-derived toxins.

disaccharides (to decrease bowel transit time) or rifamixin (nonabsorbable antibiotics to reduce ammoniogenic flora). • No transdermal cholinomimetic agents have been used with oral lactulose to date, in HE.

and non-systemic antibiotics (e.g., rifaximin) [6] . Accumulation of ammonia and gut-derived toxins can lead to a variety of pathogenic changes, including alterations in neurotransmitter signaling systems [3] [6]. While the changes in neurotransmitter systems may be complex and heterogenous, [7] upregulation of the inhibitory GABAergic and serotonergic pathways and impairment of the

What are the new findings?

excitatory glutamatergic and catecholaminergic pathways have been

• Transdermal rivastigmine is safe for use in patients with grade 2

hypothesized to be involved in the pathogenesis of HE [6]. Alterations

& 3 HE. • Transdermal rivastigmine in combination with oral lactulose in

in the cholinergic neurotransmitter system have also been observed in both animal models of HE [8]-[12] and in postmortem brain tissue

this study is far superior to lactulose alone in improving cognitive

samples from patients with HE [7] [8] [13]. For example, the level of

function.

acetylcholine (ACh) and the neurotransmitter of the cholinergic system, were reduced, and the activity of acetylcholinesterase (AChE), the

How might it impact on clinical practice in the foreseeable

enzyme that hydrolyzes ACh, was increased in brain extracts from rats

future?

with experimentally induced HE [8].

GASTROENTEROLOGY TODAY - AUTUMN 2015

• Traditional strategies for HE treatment have included non-absorbable

using therapies such as non-absorbable disaccharides (e.g., lactulose)

PAPER Similarly, the activity of AChE was higher in postmortem brain samples

was performed by electronic randomization. Dietary animal protein

from patients with HE compared with controls without cirrhosis [8].

intake was restricted to 50 g/d. The use of oral or intravenous antibiotics

Given the importance of cholinergic neurotransmission in cognitive

was prohibited during the 21 days of the study.

function and consciousness [14] alterations such as those, which disrupt cholinergic signaling, may explain the deficits in cognitive function and consciousness observed in patients with HE. Thus, therapies that may restore cholinergic balance may be useful in the treatment of patients with HE. Rivastigmine is a reversible AChE inhibitor used to treat dementia associated with Alzheimer’s disease (AD) and Parkinson’s disease [15]. Rivastigmine significantly improved learning in a rat model of HE [8], but, to date, there have been no reports of rivastigmine improving cognitive function in patients with HE. However, case reports of patients with HE treated with the AChE inhibitors neostigmine (with polyethylene glycol [PEG]) [16] [17] and physostigmine [18] have suggested that this class of drugs may be effective for the treatment of HE in humans. The objective of this randomized, placebo-controlled pilot study was to determine the efficacy and safety of transdermal rivastigmine for

2.3. Assessments Hepatic encephalopathy was assessed using the modified encephalopathy score (MES), a measure of memory loss, confusion, sleep disturbance, and comprehension with a minimum score of 4 (mild HE) and a maximum score of 12 (severe HE; Table 1). All questions for the MES were administered in the patient’s native language. Psychometric testing was performed using the trail test (TT) [21] and the object recognition test (ORT). The MES, TT, ORT, and serum ammonia levels were assessed at baseline and then weekly. Electroencephalography was performed at baseline and during the final week of the study. Safety was assessed.

2.4. Statistical Analysis

improving cognitive function in patients with grade 2 or 3 HE. T-test was used to compare transdermal rivastigmine to placebo by calculating p values for statistical significance (defined as P ≤ 0.05)

2. Methods

using SPSS version 20 for mac.

This was a randomized, placebo-controlled pilot study conducted

3. Results

between 2009 and 2010. The protocol was approved by the institutional review board at Finestein Institute. The study was performed in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Good Clinical Practice Guidelines, and applicable local laws and regulations. Signed informed consent was obtained for each patient before study enrollment.

3.1. Patients and Baseline Characteristics A total of 72 patients were screened (Figure 1). Of 12 who did not participate 8 did not meet the inclusion criteria and 4 declined to participate after signing the consent. Thirty patients were randomized; 15 received the transdermal rivastigmine patch and 15 received a

2.1. Patient Population Patients were eligible if they had grade 2 or 3 HE. Hepatic

placebo patch. Table 1 . Modified encephalopathy scoring systema.

encephalopathy grades were based on clinical and electroencephalographic criteria [19] [20]. Grade 2 HE was characterized by the presence of lethargy, inappropriate behavior, disorientation, asterixis, abnormal reflexes, and abnormalities on electroencephalogram (EEG) (i.e., slowing, triphasic waves). Patients with grade 3 HE exhibited somnolence (but were rousable), loss of GASTROENTEROLOGY TODAY - AUTUMN 2015

meaningful communication, asterixis, abnormal reflexes, and slowing, triphasic waves on EEG. Exclusion criteria included the recent or current use of antihistamines, metoclopramide, benzodiazepines, cannabinoids,

Variable

Mild (1 point)

Moderate (2 points)

Severe (3 points)

Memory loss

Past (30 days)

Recent past (7 days)

Recent (24 hours)

Confusion

Not confused

Mildly confused

Very confused

Sleep disturbance

Mild (changes in sleep pattern)

Moderate (fragmented sleep pattern)

Severe (less than 2 hours of sleep/night)

Comprehension

Well aware of surroundings

Impaired awareness of surroundings

Oblivious of surroundings

Patients are rated from 1 to 3 for each variable, and scores are added to calculate the modified encephalopathy score. Total score can range from 4 (mild) to 12 (severe).

or narcotics; acute gastrointestinal bleeding; sepsis; toxic metabolic syndrome; renal failure; and infection with human immunodeficiency virus. Urine was screened before the study and then weekly to detect the use of narcotics, benzodiazepines, and cannabinoids.

The demographics of the treatment groups were similar with respect to age, sex, and body mass index (Table 2). There were more black patients and fewer white and Hispanic patients in the transdermal rivastigmine group than in the placebo group. Baseline disease

2.2. Treatments

characteristics were similar between the treatment groups with respect to model for end-stage liver disease score, EEG, MES, and performance on the TT and ORT (Table 2). More patients in the placebo group

Eligible patients were treated with oral lactulose (20 g/30 mL three times

had alcoholic liver disease (40%) compared with the transdermal

daily) and randomized to receive either the transdermal rivastigmine

rivastigmine group (13%). Serum ammonia levels were slightly but

patch (Exelon® Patch; Novartis Pharmaceuticals Corporation, East

significantly higher in the transdermal rivastigmine group compared with

Hanover, NJ; 4.6 mg/d) or a placebo patch for 21 days. Randomization

the placebo group (P = 0.03).

PAPER Figure 1. Patient disposition.

seconds) approached normal (<60 seconds). In contrast, TT results in the placebo group only slightly improved from 158 seconds at baseline to 154, 134, and 146 seconds after 1, 2, and 3 weeks of treatment, respectively.

P. P

Table 2. Patient demographics and baseline disease characteristics.

Table 2. Patient demographics and baseline disease characteristics. Characteristic

56 (50 - 65)

Transdermal rivastigmine (n = 15) 56 (51 - 61)

10 (67)

9 (60)

Placebo (n = 15)

Mean age (range), y Male, n (%)

Table 2. Patient demographics and baseline disease characteristics.

Race, n (%) WhiteCharacteristic Black Mean age (range), y Hispanic

6 (40)

1 (7) 2 (13) 11 (73) 3 (20) 3 (20)

grade,score n (%) (range) MeanHE MELD

20 (18 - 22)

MeanSerum ORT ammonia, time, sc mol/L Mean MES

63 (20) (40) 61(40) (7) (33) 28 5(26 - 30) 2 (13) (7) 61(40) 1 (7) 5 (33) 9 2 (13) 6 1 (7) 9

239 6

MeanMean MESMELD score (range) d

Mean TT time, s Mean ORT time, sc EEG, n (%) Mean TT time, sd Normal GradeEEG, 1 n (%) GradeNormal 2 GradeGrade 3 1

respectively; P < 0.0001; Figure 2). Though the mean MES of both

9 (60)

28 (26 - 30)

MES compared with placebo within 1 week of treatment (7 vs 10,

10 (67)

Mean BMI (range) Race, n (%) Cirrhosis Whiteetiology, n (%) Alcohol Black Hispanic Hepatitis B Hepatitis MeanCBMI (range) Nonalcoholic steatohepatitis Cirrhosis etiology, n (%) OtherAlcohol Hepatitis B HE grade, n (%) Hepatitis C 2 Nonalcoholic steatohepatitis 3 Other a Serum 3 ammonia, mol/L

Transdermal rivastigmine resulted in a significantly lower mean

Transdermal rivastigmine 1 (7) (n = 15) 11 (73) 56 (51 - 61)

3 (20) 56 (50 - 65) 6 (40)

Male, n (%)

3.2. Modified Encephalopathy Score

6 (40) Placebo (n = 15)

20 (18 14- 22) 239 122

3 (20)

28 (26 - 30)

(47) 28 (26 7- 30) 1 (7)

2 (13) 2 (13) 3 (20) 7 (47) 8 1 (7) 2 (13) 7 20 (18 - 22) 8 b 7 245

20 (18 - 22) 14 245b125

122

125

158 9158 (60) 3 (20) 29 (60) (13) 31(20) (7)

P. P. Basu e

161

161 10 (67)

2 (13)

10 (67) 3 (20) 2 (13) 0 (0) Grade 2 2 (13) 3 (20) BMI, bodyGrade mass 3index; EEG, electroencephalogram; MELD, mod1 (7) HE, hepatic encephalopathy; 0 (0)

el for BMI, end-stage liverindex; disease; MES, modified encephalopathy score; ORT, object recognition body mass EEG, electroencephalogram; HE, hepatic encephalopathy; MELD, b d modrange, MES, 11 - 32 mol/L.encephalopathy P = 0.03. cNormal, <55 seconds. Normal, <60 test; TT, trailend-stage test. aNormal el for liver disease; modified score; ORT, object recognition a b c seconds. test; TT, trail test. Normal range, 11 - 32 mol/L. P = 0.03. Normal, <55 seconds. dNormal, <60 seconds.

treatment groups leveled off during weeks 2 and 3, the significant effect of transdermal rivastigmine compared with placebo on the mean MES was sustained at weeks 2 and 3 of the study (P < 0.0001 at both weeks). These results suggest that transdermal rivastigmine was significantly more effective than placebo at improving the degree of cognitive dysfunction in HE in patients receiving concomitant lactulose.

3.3. Psychometric Tests Patients who received transdermal rivastigmine had significantly better weeks 1 through 3 of the study compared with those who received placebo (P = 0.0001 at all 3 time points for both tests). In patients

Figure 2. Modified encephalopathy scores over the 3 weeks of treatment with placebo or transdermal rivastigmine. *P < 0.0001. MES, modified encephalopathy score.

GASTROENTEROLOGY TODAY - AUTUMN 2015

performance on both the ORT (Figure 3(a)) and TT (Figure 3(b)) during

Figure 2. Modified encephalopathy scores over the 3 weeks of treatment with placebo or * transdermal P treatment, < 0.0001. respectively. MES, modified encephalopathy score. seconds after 1, 2,rivastigmine. and 3 weeks of treated with transdermal rivastigmine, ORT results (45 seconds) were

3.4. Clinical Tests

normal (<55 seconds) within 1 week of treatment with transdermal 3.4. Clinical Tests

seconds after 1, 2, and 3 weeks of treatment, respectively.

rivastigmine. The improvement in the ORT with transdermal rivastigmine

For patients in patients both treatment groups, serum groups, ammoniaserum levels were progressively lower each of the 3 weeks For in both treatment ammonia levels were was sustained as scores remained normal during weeks 2 and of 3.4.3 Clinical Tests progressively lower each of the 3 weeks of the study compared with treatment (35 and 30 seconds, respectively). In contrast, in patients who in both treatment groups, serum ammonia levels were progressively lower each of the 3 For patients baseline (Table 3). However, transdermal rivastigmine did not have a received placebo, ORT results only slightly improved from 125 seconds 259 than placebo. In fact, patients greater effect on serum ammonia levels at baseline to 98 seconds after 1 week and actually worsened during

weeks 2 and 3 of the study (101 and 109 seconds, respectively).

who received placebo had slightly but significantly greater reductions in

Results of the TT were also substantially improved in patients who

rivastigmine after 2 weeks of treatment (P = 0.03). However, by the third

received transdermal rivastigmine, decreasing from a baseline score

serum ammonia levels compared with 259 those who received transdermal

week of treatment, thereduction in serum ammonia was not significantly

of 161 seconds to 90 seconds and 92 seconds after 1 and 2 weeks of

different between the 2 groups. There were no differences in EEG

treatment, respectively. By the third week of treatment, TT results (65

results between the 2 treatment groups.

PAPER

su et al.

improves cognitive function compared with placebo in patients with grade 2 or 3 HE who were receiving concomitant lactulose. These results support those of earlier case reports in which hepatic coma resolved in 3 patients with HE who were treated with other AChE inhibitors [16] -[18]. In 2 of the patients, treatment with neostigmine and PEG electrolyte solution to improve gastric motility and bowel cleansing, respectively, resulted in the resolution of hepatic coma after 2 days [16] [17]. The third patient was treated with physostigmine and immediately regained consciousness after administration of the AChE inhibitor [18]. The observation that inhibition of AChE enhances cognitive function is not unique to HE. Rivastigmine is also used to treat AD and Parkinson’s

(a)

disease dementia. The AChE inhibitors galantamine and donepezil are also used for the treatment of AD. Inhibition of AChE may improve cognitive function in patients with HE, AD, or Parkinson’s disease dementia by increasing levels of ACh in the brain and prolonging ACh activity at neural synapses [15]. However, there is mounting evidence that AChE inhibitors may have an antiinflammatory effect [22] which has been observed in patients with AD [23]. Such a mechanism may be relevant to patients with HE because cerebral inflammation has been directly implicated in the pathogenesis of HE in a rat model of acute liver failure, [24] and systemic inflammation has been implicated in the pathogenesis of HE [25] and the impairment of neuropsychologic function [26] in patients with liver disease. In patients with HE, AChE inhibitors may also increase gastrointestinal motility and thereby

(b)

Figure 3. Psychometric tests. Scores for (a) object recognition test and (b) trail test over the 3 weeks of treatment with placebo or transdermal rivastigmine. Normal scores for object recognition test and trail testare less than 55 seconds and less than 60 seconds, respectively.*P = 0.0001.

enhance the effect of intestinal cathartics such as lactulose and PEG, which were used concomitantly in this study and the previously described case reports, respectively [16] -[18].

the study compared with baseline (Table 3). However, transdermal rivastigmine did not have a While greaterrivastigmine effect on is available in oral and transdermal formulations, serum ammonia levels than placebo. In fact, patients who received placebo had slightly but significantly greater the transdermal formulation may be more favorable in general and reductions in serum ammonia levels compared with those who received transdermal rivastigmine after 2 weeks for patients of treatment (P = 0.03). However, by the third week of treatment, thereduction in serum ammonia was not with sig- HE. First, transdermal rivastigmine generally offers Overall, transdermal rivastigmine no reactions nificantly different between the 2 groups. Therewas werewell no tolerated, differencesand in EEG results betweenimproved the 2 treatment tolerability compared with the oral formulation, particularly with were reported at the patch-application site. In the transdermal groups. respect to gastrointestinal adverse events such as nausea and vomiting rivastigmine group, 1 patient (7%) reported diarrhea and 1 (7%) reported [15] [27]. This may be because of the more gradual and smoother 3.5. Safety dry mouth. In the placebo group, 2 patients (13%) reported diarrhea, 1 increase in absorption of transdermal rivastigmine compared with oral Overall, transdermal rivastigmine was well tolerated, no reactions reported at the (7%) reported dry mouth, and 1 (7%) and reported urinarywere retention (Table 4).patch-application site. rivastigmine In the transdermal rivastigmine group, 1 patient (7%) reported diarrhea and 1 (7%) reported dry mouth. In [15]. the Second, the ease of dosing of the transdermal patch compared with placebo group, 2 patients (13%) reported diarrhea, 1 (7%) reported dry mouth, and 1 (7%) reported urinary re-oral formulations may be advantageous in patients with tention (Table 4). HE, particularly those with higher grades of HE who may be unable

3.5. Safety

4. Discussion

to easily ingest tablets or oral solutions. Lastly, oral rivastigmine is The results of this randomized, placebo-controlled pilot study suggest administered twice daily [28] while the patch is applied only once daily The results ofthat this transdermal randomized, placebo-controlled pilot study suggestcognitive that transdermal rivastigmine significantly rivastigmine significantly improves function [29]. This dosing schedule may provide less interference with daily improves cognitive function compared with placebo in patients with grade 2 or 3 HE who were receiving concompared with placebo in patients with grade 2 or 3 HE who were life. Overall, the advantages of transdermal delivery of rivastigmine receiving conmay increase P. patient and satisfaction for patients and P. Basucompliance et al.

4. Discussion

GASTROENTEROLOGY TODAY - AUTUMN 2015

caregivers. Indeed, caregivers of patients with

Table 3. Serum ammonia levels.

260

AD preferred the transdermal rivastigmine patch compared with the oral capsule in a large (n =

Mean change from baseline, mol/L

Treatment week

Placebo (n = 15)

Transdermal rivastigmine (n = 15)

–92

–91

–113

–107

0.03

–137

–131

0.05

P value

NS = not significant.

1059 caregivers) 24-week study comparing the transdermal and oral formulations of rivastigmine in patients with AD [30]. One limitation to this study is that it was performed using a small population of patients (N = 30). Furthermore, patients in both

Table 4. Side events. Side Event

Placebo (n = 15)

Transdermal rivastigmine (n = 15)

Diarrhea

Dry mouth

Urinary Retention

treatment groups were receiving concomitant lactulose. The finding in this study that there was improvement of MES in the placebo group (albeit to a significantly lesser degree than the

improves cognitive function compared with placebo in patients with grade 2 or 3 HE who were receiving concomitant lactulose. These results support those of earlier case reports in which hepatic coma resolved in 3 patients with HE who were treated with other AChE inhibitors [16]-[18]. In 2 of the patients, treatment with neostigmine and PEG electrolyte solution to improve gastric motility and bowel cleansing, respectively, resulted in the resolution of hepatic coma after 2 days [16] [17]. The third patient was treated with physostigmine and im-

PAPER transdermal rivastigmine group) suggests that lactulose may have contributed to the improvement in MES observed in this study. However, patients who received placebo did not experience any substantial or sustained benefit in cognitive function as assessed using the TT and ORT. This suggests that transdermal rivastigmine had an independent effect on cognitive function in patients with grade 2 or 3 HE. Interestingly, despite the improvement in cognitive function with transdermal rivastigmine, there was no improvement in serum ammonia levels with the AChE inhibitor compared with placebo. In fact, after 2 weeks of treatment, serum ammonia levels were reduced to a slightly but significantly greater degree in patients who received placebo compared with those who received transdermal rivastigmine. This suggests that reductions in serum ammonia levels are not clinically relevant in the context of improving the results of psychometric tests such as the TT and ORT. It is notable that serum ammonia levels can be influenced by several factors, including the conditions leading to HE (i.e., precipitating factors), mild exertion by the patient before phlebotomy (including fist clenching), prolonged tourniquet application, and blood-sample drawing technique andstorage [1] [6] [31]-[33]. Thus, results may not be comparable among patients or even between samples taken at different times from an individual patient. In this study, transdermal rivastigmine with lactulose was safe and well tolerated. Diarrhea, a common adverse event associated with lactulose treatment, [6] was reported by 1 patient who received transdermal rivastigmine and 2 patients who received placebo. Adverse events associated with AChE-inhibitor use were only reported by 1 patient in the transdermal rivastigmine group (dry mouth) and by 2 patients in the placebo group (dry mouth, urinary retention). Further, no skin irritation at the patch-attachment site was reported in this study. The favorable safety and tolerability profile reported here for transdermal rivastigmine in patients with HE is comparable to that reported in patients with AD, although a small percentage of patients with AD did develop some skin irritation [27].

5. Conclusion In conclusion, although performed with a small number of patients, this randomized, placebo-controlled pilot study demonstrates that transdermal rivastigmine used offlabel with concomitant lactuloseis is safe and effective for improving cognitive function in patients with HE. of transdermal rivastigmine in patients with HE. Because of the benefit of transdermal rivastigmine on cognitive function shown here, these trials should be conducted not only in patients with overt HE (grade ≥ 1) but also in patients with minimal HE (grade 0) in which the only symptom is cognitive dysfunction measurable only by psychometric or neurophysiologic testing [6].

References

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CASE REPORT RETROPERITONEAL GALLSTONE GRANULOMA CAUSING HYDRONEPHROSIS AND ATROPHY OF THE IPSILATERAL KIDNEY; A UNIQUE COMPLICATION OF LOST GALLSTONES DURING LAPAROSCOPIC CHOLECYSTECTOMY: A CASE REPORT AND LITERATURE REVIEW Afridi FG, French JJ, HPB and Transplant Surgery, Freeman Hospital, Freeman Road. Newcastle upon Tyne, United Kingdom.

Abstract

Case:

Gallstone spillage is relatively common during Laparoscopic

A 48-year-old lady underwent a laparoscopic cholecystectomy at a

Cholecystectomy (LC). Delayed presentation with complications can

non-specialist centre for symptomatic gallstones. She presented 7

occur if these stones are not retrieved. 6-40% gallstone spillage and

months later to the same non-specialist centre with persistent right loin

13-32% cases of lost stones have been reported in the literature. 0.1-

pain. All bloods tests including renal function and inflammatory markers

6% post operative morbidity has been reported and diagnosis can

were normal. An US scan showed a dilated right-sided renal collecting

prove difficult in the cases which do present with complications.

system and atrophied right kidney. A CT performed at this point showed a number of additional findings; a 7cm soft tissue retroperitoneal mass

The case of a 48 year old lady is presented who developed

extending inferiorly from the around the pelvic-ureteric junction, enlarged

a retroperitoneal mass causing outflow obstruction with

mesenteric and retroperitoneal nodes, and a small amount of ascites.

hydronephrosis and atrophy of the right kidney after a LC.

She was referred to the specialist centre (Urology Department) for

Histopathological analysis of the mass after a hand assisted

further management. Following a Urology MDT a differential diagnosis

laparoscopic biopsy revealed xanthogranulomatous inflammation

of this atypical mass was constructed. This was (i) a local inflammatory

related to bile extravasation with associated foreign body giant cell

mass (possibility due to the recently performed procedure or secondary

reaction to calculus debris pointing to a spilled gallstone as the most

to Crohn’s disease), (ii) a retrocaecal appendix or (iii) a retroperitoneal

likely source of this mass. To the authors’ knowledge this is the first

sarcoma (iv) TCC. A ureteric stent was placed and further investigation

case of its nature being reported.

with a colonoscopy (normal) was performed. Referral was then made to the supra-regional specialist Sarcoma unit

Introduction

located at the same hospital. Following Sarcoma MDT discussion, further investigations were performed. Serum CA125, Ca19-9, CEA,

Laparoscopic Cholecystectomy (LC) is the gold standard current

fasting gut hormones (Chromogranin A, Pancreatic polypeptide,

treatment option for symptomatic gallstone disease. Gallstone

Neurokinin A, insulin, glucagon and VIP) and 24 hour urinary 5HIAA

spillage during LC is a relatively common occurrence1. It is more

were normal. DMSA renogram showing very poor right kidney function

common in cases of gallbladder perforation during surgery; the

(left kidney >90% function, right kidney <10%). A repeat CT (Image

reported incidence of perforations is 6-40% 2 and in about a third of

2) showed a persistent mass. The aetiology of this mass was still

these cases, the spilled stones are not retrieved leading to possible

uncertain. To obtain a biopsy a laparoscopic hand assisted biopsy was

delayed presentation with 0.08-0.8% complications

performed 6 weeks after presentation to our specialist centre. Histologic

3-6

. Initially it

report of the biopsy showed appearances of xanthogranulomatous

the peritoneum7 but the increasing number of reports of delayed

inflammation most likely secondary to bile extravasation with associated

complications attributable to these stones has brought this

foreign body giant cell reaction to calculous debris. There was no

hypothesis into question. There is a higher rate of complications

evidence of malignancy.

following intra-peritoneal spillage during LCs than in open cholecystectomy, likely due easier retrieval during open surgery via

A conservative management strategy was adopted. . Surgical excision

either (i) direct removal (ii) copious irrigation or gauze mopping.

was not embarked upon due to the benign pathology of the lesion, the

Difficulty in visualising these stones at LC may be a contributory

extent and relationship of the mass to adjacent structures (in contact/

factor .

infiltrating the IVC, right ureter and renal pelvis, duodenum, small bowel,

right psoas and loop of sigmoid colon), the magnitude of the procedure We present the first report of a symptomatic granulomatous mass

that would be needed to clear the mass and sub-optimal patient fitness.

around a spilled gall-stone during LC arising in the retroperitoneum

An interval CT was arranged. This was performed 8 months later and

causing right-sided ureteric obstruction and hydronephrosis and

showed that the soft tissue retroperitoneal mass was slightly smaller

atrophy of the right kidney. To the author’s knowledge, there are

in size. The patient is undergoing continued follow-up, CT scan at 13

only three cases of gallstone granuloma formation reported thus

months and the most recent CT, performed 25 months post LC shows

far; two intra-peritoneal

static appearances.

9,10

and one epigastric1.

GASTROENTEROLOGY TODAY - AUTUMN 2015

was thought that these spilled stones are gradually absorbed by

CASE REPORT Investigations: At presentation bloods tests including renal function and inflammatory markers were normal. Radiological investigation with ultrasound showed right kidney hydronephrosis and atrophied right kidney; a CT showed a 7 cm retroperitoneal mass extending inferiorly from the around the pelvic-ureteric junction (with significant adjacent structure involvement), enlarged mesenteric /retroperitoneal nodes and ascites. Investigations were then performed to rule out malignancy. These included serum CA125, Ca19-9, CEA, fasting gut hormones (Chromogranin A, Pancreatic polypeptide, Neurokinin A, insulin, glucagon and VIP) and 24 hour urinary 5HIAA). All these tests were normal. DMSA renogram was performed showing <10% function on the right side. Laparoscopic hand assisted biopsy of the retroperitoneal mass which showed xanthogranulomatous inflammation secondary to bile extravasation with associated foreign body giant cell reaction to calculus debris. Reassuringly no evidence of malignancy was seen. Repeat interval follow-up CT scans (up to 25 months post presentation) have showed the mass to be reducing in size.

procedure do unfortunately occur. Spillage and importantly loss of gallstones is one such complication. Studies report a 6-40% incidence of gallstone spillage with 13-32% cases of ‘lost’ stones 11-14

with a reported post-operative morbidity of 0.1-6% 15. Spillage

can occur secondary to GB perforation during dissection (42%75%), traction (15-51%), extraction through a narrow trocar opening (5-10%), slippage of the cystic duct clip (14-21%)

3, 16-18

. It is

difficult to determine the real incidence of complications due to lost gallstones as most evidence is either retrospective with none/short follow-up periods or, isolated case reports 4. Complications are however more likely in elderly patients 19, spillage of pigment stones with concurrent spillage of infected bile (92% bilirubinate stones may contain viable bacterial micro-colonies

20, 21

). The reported

complication rate of lost gallstones following LC varies from 0.080.3% 4, 5 to 0.08-0.8%

3-6

(Table 1).

Examining cases with gallbladder perforation alone the complication rate can be 2.4%

rising to 7% in clearly documented

cases of spilled stones; with a range of 1.4-12%

3, 4, 23, 26.

The time to presentation with complications varies, most patients present within a few months following LC (peak incidence at 16

Differential diagnoses: There are a number of differential diagnoses that should be considered. These are abscess, malignancy (including cystadenoma/ cystadenocarcinoma, Mesothelioma, Cystic teratoma, Paraganglioma, Schwannoma), a retrocaecal appendix mass, a retroperitoneal sarcoma/lymphoma/fibrosis/hemorrhage/ adenopathy, a local inflammatory mass (possibility due to the recently performed operation or secondary to Crohn’s disease), a transitional cell carcinoma of renal pelvis/ureter, actinomycosis, endometriosis, pseudomyxoma retroperitonei, a developmental lesion (Müllerian cyst/ Epidermoid cyst/ Bronchogenic cyst), pseudocyst, urinoma and a lymphocele.

to 27 weeks years

27, 28

) but delayed presentation of 10 years

and 20

have also been reported. As in our case, an incorrect

but understandable initial diagnosis of malignancy can be made resulting in patient distress and extensive investigations 2. The mode of presentation following spillage and non-retrieval of gallstones also varies. Gallstones may remain in the peritoneal cavity or travel to distant sites causing varied and seemingly unlikely complications. Zehetner et al

reviewed 111 case

reports and studies reporting complications of lost gallstones. The most commonly occurring complications are: abdominal wall abscess (16 case reports/studies), intra-abdominal abscess (15 publications), subhepatic abscess (10 studies), sub-phrenic abscess (9 studies). Also mentioned is cutaneous, vaginal and urinary bladder fistula formation and stone expectoration via the

Subsequent followup:

upper respiratory tract in 4 cases. Gynaecological, urological and

After initial extensive investigations (as summarised above)

Diagnosis of complications arising due to spilled gallstones can be

including a hand assisted laparoscopic biopsy to ascertain the nature of this retro-peritoneal mass, the patient is under GASTROENTEROLOGY TODAY - AUTUMN 2015

conservative management with regular clinical follow-up, blood tests and interval CT imaging. Her renal function post ureteric stent insertion stays normal despite the fact that her right kidney remains atrophic. All interval CT images (at 6 months, 1 year and 2 years) showed the mass decreasing in size (to 3 cms at last imaging). The management plan is regular clinical review, CT imaging and ureteric stent management. Resection of the mass may be considered if the current conservative approach fails with return of clinical symptoms or worsening biochemistry.

systemic complications are the most infrequent (Table 2).

challenging. Imaging modalities that can be employed are US, CT and MRI. The choice modality which is non-invasive and associated with minimal patient morbidity is US

98, 99

especially in diagnosing

stones within an abscess cavity. Radiologic findings can however be misleading and may mimic hydatid disease, appendicitis 97

, actinomycosis 98, endometriosis 63, simple abscesses

malignancy

78, 98, 99

and

; especially if a non-opaque calculus is in a site

difficult to visualize. Our patient was also extensively investigated. Once a confirmed diagnosis of benign nature of the mass was made, the MDT decision was to manage this lesion conservatively. This decision

Discussion and Literature Review:

was based upon a number of factors - post-ureteric stent normal renal function, established renal atrophy and reduced right renal function (10% right, 90% left renogram), intimate involvement of

LC is the treatment of choice for patients with symptomatic

adjacent viscera to the mass which would necessitate an extensive

gallstone disease. Complications of this minimally invasive

resection if surgery was considered and a patient with multiple

CASE REPORT significant co-morbidities (hypertensive, hypothyroid, asthmatic,

a minimally invasive technique

high BMI, previous 2 C-Sections). If diagnosis of malignancy was

indicated

made, clearly an alternative management strategy would have been

in cases of perforation of an acutely inflamed GB with spillage of

adopted, including assessment for resectional surgery.

visibly infected bile 31. Cystoscopic excision has been employed to

19, 22

104

or open laparotomy may be

. The use of therapeutic antibiotics is only indicated

remove gall stone granulomas from the bladder 85. In less morbid Due to the morphology of the mass, its retroperitoneal location

states, a careful wait and watch policy may be all that is needed.

and the fact that as the patient did not present in the immediate

Clear documentation aiding future diagnoses is by far the most

post-operative period, while a complication of LC was included, a

important aspect of management

2, 3, 17

long list of differential diagnosis was considered. If however, there was clear documentation of spilled GS at surgery, this would have

One aim of this report is to encourage clear documentation of

alerted the authors to the likely aetiology of the mass sooner. This

spillage of gall stones per-op and promote patient awareness.

in turn could have reduced investigation time and time to reach the

Practicing surgeons need to be aware of the risks associated with

management plan although the authors feel a tissue diagnosis was

GS spillage and bear this differential in mind when dealing with

mandatory before embarking on definitive treatment. The authors

intra-abdominal masses especially in the post-cholecystectomy

also comment that a complication following LC should always been

setting.

considered in such cases despite the time lapse in presentation since LC and in the absence of documentation of spilled GS.

Learning points:

A sound surgical technique to avoid stone spillage, good dissection

1. Complications due to intra-operative gallstone spillage are a

along anatomical planes, aspiration of a distended GB and using

rare but important occurrence in surgical practice leading to

retrieval bags to remove GB via ports can all be useful. If however

both immediate as well as delayed post-operative morbidity. A

stone spillage does occur meticulous retrieval and copious

safe and careful surgical approach is fundamental to avoiding

irrigation may help minimize complications. Routinely converting to

this complication.

an open procedure at the time of LC following spillage of stones is not universally indicated as the morbidity risk of an open procedure

2. There is no clear evidence supporting the routine conversion

probably outweighs the morbidity risk of retained stones. In some

to open surgery if spillage occurs, however a careful search

large series the conversion rate from a LC to an open procedure

and retrieval of all lost stones should be carried out followed by

is reported at 6%

copious peritoneal lavage.

4, 25

. In 2.1-2.5% of these conversions the reason

documented was spillage of gallstones

7, 100, 101

Management of

complications depends on the extent of morbidity and organ

3. Clear documentation with patient and clinician awareness is of

involved. Drainage of superficial abscesses and sinuses facilitates

paramount importance to facilitate early diagnosis in cases who

resolution

do present with complications.

102, 103

. For deep intra-abdominal abscesses either

Table 1: Reported incidence of spilled stones and post-operative complications (n= number of laparoscopic cholecystectomies) Series

Incidence of spilled

Incidence of

gallstones

complications

Schafer 4 et al (n=10174)

5.7 % (n=581)

0.08% (n=8)

Diez 22 et al (n=3686)

6.9% (n=254)

0.32% (n=12)

Sarli16 et al (n=1127)

11.6% (n=131)

n/a

Rice 23 et al (n=1059)

9.7% (n=103)

0.28% (n=3)

Memon 24 et al (n=856)

12.3% (n=106)

0.58% (n=5)

GASTROENTEROLOGY TODAY - AUTUMN 2015

CASE REPORT Table 2

All possible complications Abscess/collection:

Distant stone expression:

Abdominal wall abscess

24, 32-34

Posterior rectus fat necrosis

Pelvic stones

Intra-abdominal abscesses

18, 22, 34, 37-39

40 36, 41

Peritoneal abscess Pelvic abscess

Port site stones

22,79,80

Stones in hernial sac

42-44

81,82

77,78,83 22,46

Retro-hepatic abscess

Retro-peritoneal abscess Right flank abscess

Malignancy: 48-50

Implantation malignancy

6, 33

Paraumbilical tumor

Subhepatic abscess

36,51-54

Subphrenic abscess

24,55-59

Transdiaphragmatic abscess Umbilical wound abscess

Granuloma formation: 60

Gallstone granuloma

22,24,61

Vesical granuloma

1,9,10

Mycoses:

Infection/ inflammation: 24,48,51,62

Thoracoabdominal mycosis

Retro-peritoneal actinomycosis Cellulitis

Obstruction:

Granulomatous peritonitis

Mimicking acute appendicitis Peritonitis

Stones in ovary/ fallopian tubes (tubolithiasis)

Port site abscesses

Fever

41,77,78

Stones in gastro-colic omentum

Paracolic abscess

12,64,74-

Gluteal abscess Liver abscess

Bronchiolithiasis with stone expectoration

22,87,88

Ileus with bowel obstruction 64

Small bowel obstruction

89,90

Incarcerated hernia with stone

32,91

Pleural empyema, fluid collections GASTROENTEROLOGY TODAY - AUTUMN 2015

55,56,66

Pneumonia

OTHER 51,67

Jaundice

Recurrent staphylococcal bacteremia

38,69,92

Middle colic artery thrombosis

Septicemia and death secondary to

Spontaneous liver bleeding

septic shock secondary to intra-

Adhesions

peritoneal gallstones

Fistulation /Sinus formation Erosion to back

47,64,70

Fistula formation

13,51,71-73

Non-infectious intra-abdominal collections

Chronic pelvic pain, Infertility and Dysmenorrhea 78,96,97

Dyspareunia

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Vadlamudi G, Graebe R, Khoo M, Schinella R. Gallstones implanting in the ovary. A complication of laparoscopic cholecystectomy. Arch Pathol Lab Med. 1997; 121:155-8.

79. Zamir G, Lyass S, Pertsemlidis D, Katz B. The fate of the dropped gallstones during laparoscopic cholecystectomy. Surg Endosc 1999; 13:68 –70. 80. Ok E, Sozuer E. Intra-abdominal gallstone spillage detected during umbilical trocar site hernia repair after laparoscopic cholecystectomy: report of a case. Surg Today 2000; 30: 1046–8. 81. Rosin D, Korianski Y, Yudich A, Ayalon A. Lost gallstones found in a hernial sac. J Laparoendosc Surg 1995; 5: 409 –11. 82. Aspelund G, Halldorsdottir BA, Isaksson HJ, Moller PH. Gallstone in a hernia sac. Surg Endosc 2003; 17: 657.

84. Karwasra RK, Yadav V, Garg P, et al. Implantation malignancy after laparoscopic cholecystectomy. Indian J Gastroenterol 2001; 20:36. 85. Famulari C, Pirrone G, Macrì A et al. The vesical granuloma: rare and late complication of laparoscopic cholecystectomy. Surg Laparosc Endosc Percutan Tech. 2001 Dec; 11(6):368–371. 86. Ramia JM, Mansilla A, Villar J, et al. Retroperitoneal actinomycosis due to dropped gallstones. Surg Endosc 2004; 18:345–9. 87. Wills VL, Smith RC. Gallstone ileus: post cholecystectomy. Aust N Z J Surg 1994; 64: 650 –2. 88. Habib E, Khoury R, Elhadad A, et al. [Digestive complications of biliary gallstone lost during laparoscopic cholecystectomy]. Gastroenterol Clin Biol 2002; 26: 930–4.

90. Tekin A. Mechanical small bowel obstruction secondary to spilled stones. J Laparoendosc Adv Surg Tech A 1998; 8: 157–9. 91. Bebawi M, Wassef S, Ramcharan A, Bapat K. Incarcerated indirect inguinal hernia: a complication of spilled gallstones. JSLS 2000; 4: 267–9. 92. Stevens S, Rivas H, Cacchione RN, et al. Jaundice due to extrabiliary gallstones. JSLS 2003; 7: 277–9. 93. AlSamkari R, Hassan M. Middle colic artery thrombosis as a result of retained intraperitoneal gallstone after laparoscopic cholecystectomy. Surg Laparosc Endosc Percutan Tech 2004; 14: 85– 6. 94. Jost CJ, Smith JL, Smith RS. Spontaneous hepatic hemorrhage secondary to retained intraperitoneal gallstones. Am Surg. 2000; 66: 1059-60. 95. Tschmelitsch J, Glaser K, Klingler A, Klingler P, Bodner E. Late complication caused by stone spillage during laparoscopic cholecystectomy. Lancet. 1993; 342: 369. 96. Targarona EM, Balagué C, Cifuentes A at al. The spilled stone. A potential danger after laparoscopic cholecystectomy. Surg Endosc. 1995; 9: 768-73. 97. Makanjuola D, Murshid K, Al Rashid R et al. Peritoneal lithiasis and cliptomas following laparoscopic cholecystectomy. Eur J Radiol. 1996; 23: 121-5. 98. Morrin MM, Kruskal JB, Hochman MG et al. Radiologic features of complications arising from dropped gallstones in laparoscopic cholecystectomy patients. AJR Am J Roentgenol. 2000; 174: 1441-5 99. Atri M, Bonifacio A, Ryan M et al. Dropped gallstones post laparoscopic cholecystectomy mimicking peritoneal seeding: CT and ultrasound features. J Comput Assist Tomogr. 2002; 26:10005. 100. The Southern Surgeons Club. A prospective analysis of 1518 laparoscopic cholecystectomies. N Engl J Med. 1991; 324:1073-8. 101. Simopoulos C, Botaitis S, Polychronidis A et al. Risk factors for conversion of laparoscopic cholecystectomy to open cholecystectomy. Surg Endosc. 2005; 19: 905-9. 102. Cacdac RG, Lakra YP. Abdominal wall sinus tract secondary to gallstones: a complication of laparoscopic cholecystectomy. J Laparoendosc Surg. 1993 Oct; 3 (5):509–511. 103. Yao CC, Wong HH, Yang CC, Lin CS. Abdominal wall abscess secondary to spilled gallstones: late complication of laparoscopic cholecystectomy and preventive measures. J Laparoendosc Adv Surg Tech A. 2001 Feb; 11(1):47–51. 104. Albrecht Roxie M, Eghtestad Bijan, Gibel Lawrence et al. Percutaneous removal of spilled gallstones in a subhepatic abscess. Am Surg. 2002 Feb; 68(2):193–195.

GASTROENTEROLOGY TODAY - AUTUMN 2015

83. Gosselink-Jongen SJ, Bongers KJ, Westerveld BD, Rethmeier HB. “Tubalithiasis”; a late complication of laparoscopic cholecystectomy with stone spillage. Eur J Surg 1999; 165:169 –70.

89. Dittrich K, Weiss H. [Ileus of the small intestine caused by a lost gallstone! A late complication of laparoscopic cholecystectomy.] Chirurg 1995; 66:443–5.

CASE REPORT

PERITONEAL METASTASES IN A PATIENT WITH OSTEOSARCOMA - A RARE CASE K. Edwards, M. Baldwin & I. Salam1 Department of 1gastroenterology medicine, Hywel Dda University Health Board

Summary A 65 year-old man diagnosed with high-grade osteosarcoma of the right proximal humerus, treated with surgery and adjuvant chemotherapy presented seventeen months later with spread of osteosarcoma to the left lower limb. Further resection was undertaken and adjuvant chemotherapy was given. A Computerised Tomography (CT) scan showed progression of pulmonary metastases and the possibility of small peritoneal metastases. Two months later he further presented with right leg pain and swelling. Repeat CT scan demonstrated a large peritoneal metastasis with no abdominal symptoms. This case report demonstrates a rare case of peritoneal metastasis in osteosarcoma. A review of current literature and pathological mechanisms for tumour spread to unusual sites are discussed.

Introduction

was made. The patient returned to primary care two months later with worsening pain of the right humerus. Radiological examination showed a pathological fracture with a bony mass of the right proximal humerus. Further CT imaging reported an “osteolytic lesion of the right proximal humerus with potential pulmonary metastases”. Biopsy of the humeral mass confirmed a diagnosis of high-grade sarcoma. In March 2014 the patient underwent proximal humerus endoprosthetic reconstruction followed by three cycles of cisplatin and doxorubicin adjuvant chemotherapy. Follow up CT imaging in August 2014 showed regression of the pulmonary nodules and no evidence of abdominal spread concluding that the disease was in remission. However CT scan in December 2014, fourteen months after initial diagnosis, revealed an osteolytic lesion in the eighth rib, progression of the pulmonary nodules and a peritoneal metastasis measuring 4.6cm in the ileocaecal region. No further therapy was given at this point. Seventeen months after diagnosis, in March 2015, the patient developed left knee pain and swelling. Magnetic Resonance Imaging

GASTROENTEROLOGY TODAY - AUTUMN 2015

Osteosarcoma is a primary malignant bone tumour characterised

(MRI) of the left knee revealed sarcomatous spread to the posterior

typically by the production of osteoid, or immature bone.1,2,3 Overall,

soft tissues of the left knee. This was subsequently resected with clear

osteosarcoma is very rare accounting for just 0.2 percent of all cancers4

margins followed by a further three cycles of gemcitabine and docetaxel

with 124–150 cases per year in England and Wales.5

adjuvant chemotherapy.

Despite its rarity, osteosarcoma is the second commonest primary bone

Two months later the patient further developed a right calf pain and

associated tumour after multiple myeloma.6 Osteosarcoma is more

swelling. Doppler ultrasound imaging excluded a deep vein thrombosis.

common in children and adolescents representing four percent of all

A repeat CT scan revealed rapid progression of metastatic tumour

malignancies in children aged up to 14 years.4 Only ten percent of all

disease in the peritoneum. The largest pelvic metastasis measured

osteosarcomas are found in patients over the age of 60 years7 and are

23cm longitudinally extending into the mid abdomen causing left

associated more with risk factors such as previous radiation therapy

hydronephrosis and infiltrated into the left iliac muscle (Figure1).

or benign bone conditions such as Paget’s disease.8 Osteosarcoma is

Progression of the pulmonary metastases was also noted along with

thought to arise from a mesenchymal stem-cell within the metaphysis

pathological rib and thoracic vertebral fractures. Despite this large

of long bones which is capable of transforming into bone, cartilage or

abdominal metastasis the patient did not complain of any abdominal

fibrous tissue.9 The most common sites of involvement are: distal femur,

discomfort or any gastro-intestinal symptoms.

proximal tibia, proximal humerus, middle and proximal femur.10 At present the patient is receiving a course of Pazopanib, a form of Between ten and twenty per-cent of patients have metastatic disease

tyrosine-kinase inhibitor; the outcome of this treatment is yet to be seen.

at the time of diagnosis11 the majority of which involve the lungs (80%) or bone.12 Transmission is via haematological spread primarily.13 Recurrence rates vary between 30 – 50%.14,15,16 Here we report a rare case of osteosarcoma of the right proximal humerus presenting later with pulmonary, bone and peritoneal spread.

Case report

Discussion Osteosarcoma is an uncommon form of bony tumour and very rarely metastasises to the peritoneal cavity. This is the first report of such condition in this age group. Despite osteosarcoma being a rare cancer, ongoing advances in its management have improved patient outcomes. With the advent of

A 65-year-old male presented to his general practitioner in August

adjuvant chemotherapy in combination with limb sparing surgery the

2013 with discomfort of the right humerus and reduced range of

five year survival rate for patients without metastatic disease on initial

movement of the shoulder joint. The diagnosis of adhesive capsulitis

presentation now exceeds 60%.17, 18

CASE REPORT References

Figure 1. CT imaging of the peritoneal metastases

Nonetheless there is a recurrence rate of over 30% in such patients.19, 20, 21 Relapses have been reported to develop at unusual anatomical sites including the heart, brain and skin. The patient reported in our case developed a first relapse, pulmonary and peritoneal metastases, after a disease free interval (DFI) of 14 months. Review of similar cases show a comparable DFI of 11.5 to 21 months14, 16. The DFI between this patients first and second relapse, in which he had sarcoma involving the left knee, was only three months - well below the mean interval of six months as suggested by Bacci et al.16 Metastasis of osteosarcoma to the peritoneum is very rare. One study conducted over a 13 year period by Kebudi Rejin at al revealed that only two patients out of 94 who were diagnosed with osteosarcoma went on to develop peritoneal metastases. These developed between three and four years after primary diagnosis, with a median survival time of four months.22 Only ten percent of all osteosarcomas are found in patients over the age of 60 years, the majority of which are thought to be directly linked to benign bone conditions such as Paget’s disease. It is therefore of no surprise that the case studies presented in literature are primarily inclusive of children or young adults. No case study has yet been found detailing osteosarcoma with peritoneal metastases in the older age group.

Conclusion Peritoneal metastases from osteosarcoma are extremely rare, with only a handful of cases being reported. Osteosarcoma is mainly a disease of the young, with the older populations being relatively spared. Here we report a unique case of osteosarcoma presenting with peritoneal metastasis in a man of 65 years. This discussion highlights the importance of regular follow-up imaging to detect early disease spread as it suggests poor prognosis of such patients once peritoneal metastases have been diagnosed.

GASTROENTEROLOGY TODAY - AUTUMN 2015

The most common site for disease spread after initial surgery and chemotherapy is to the lungs19, accounting for 87% of first relapse metastasis.16 A minority of patients present with unusual extra-pulmonary metastases after initial chemotherapy, as in our reported case. Many authors have suggested this to be linked directly with the initial chemotherapy received. Many hypotheses exist regarding regulation of tumour cell specificity at distant organ sites. The most well recognised theory to this was put forward by Stephen Paget in 1889;23 the ‘seed and soil’ theory proposed that cells could only proliferate at a distant site if they were fully compatible with a particular environment provided by a specific organ. Further, if a tumour is made up of a heterogeneous cell population it is proposed that chemotherapy may select certain cell populations within the tumour.24 In keeping with Paget’s ‘seed and soil’ theory this increase in selection pressure on tumour cell populations after initial chemotherapy would subsequently allow an altered tumour cell phenotype to metastasise to more unusual sites, as in this patients case.

1. Huvos A. Bone Tumors: Diagnosis, treatment, and prognosis. 2nd edition. WB Saunders, Philadelphia 1991. 2. Sissons HA. The WHO classification of bone tumors. Recent Results Cancer Res 1976; 104. 3. McKenna R, Schwinn C, Soong K, et al. Sarcomas of the osteogenic series (osteosarcoma, chondrosarcoma, parosteal osteogenic sarcoma, and sarcomata arising in abnormal bone): an analysis of 552 cases. J Bone Joint Surg Am 1966; 48(1). 4. National cancer intelligence network. Bone Sarcomas: incidence and survival rates in England - NCIN Data Briefing. Public health England. September 2010. 5. National Institute for Health and Clinical Excellence (NICE), “Guidance on Cancer Services—Improving Outcomes for People with Sarcoma: the Manual. 2006. 6. Resnick D, Greenway GD. Tumors and tumor-like lesions of bone: imaging and pathology of specific lesions. In: Resnick D, editor. Bone and Joint Imaging. 2nd edn. Philadelphia, PA: W.B. Saunders; 1996. pp. 991–1065. 7. American Cancer Society. Osteosarcoma- detailed guide. 2014. Updated 01.06.2015 8. Fuchs B, Ptitchard DJ. Etiology of osteosarcoma. Clin Orthop Relat Res. Apr 2002;397(1):40-52. 9. Rosenburg AE, Cleton-Jansen A-M, de Pinieux G, et al. Conventional osteosarcoma. In: WHO classification of tumours of soft tissue and bone, 4th, Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. (Eds), IARC, Lyon 2013. p.282. 10. Meyers PA, Gorlick R. Osteosarcoma. Pediatr Clin North Am. Aug 1997;44(4):973-89. 11. Marina N, Prat C, Rao B et al. Improved prognosis of children with osteosarcoma metastatic to the lung(s) at the time of diagnosis. Cancer. Dec 1992;70(11):2722-7. 12. Ferguson WS, Goorin AM. Current treatment of osteosarcoma. Cancer Invest. 2001;19(3):292-315. 13. Nouyrigat P, Berdah J, Roullet B, Olivier J. Osteosarcoma with calcified regional lymph nodes. Pediatr Radiol. 1993;23(1):74-5. 14. Tabone M, Kalifa C, Rodary C et al. Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy. J Clin Oncol. Dec 1994;12(12):2614-20. 15. Meyer W, Schnell M, Kumar A et al. Thoracotomy for pulmonary metastatic osteosarcoma: An analysis of rognostic indicators for survival. Cancer. 1987; 59(2):374-9. 16. Bacci G, Avella M, Picci P et al. Metastatic patterns in osteosarcoma. Tumori. Aug 1988;74(4):421-7. 17. Davis A, Bell R, Goodwin P. Prognostic factors in osteosarcoma: A critical review. J Clin Oncol. Feb 1994;12(2):423-31. 18. Bramwell V, Burgers M, Sneath R et al. A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: The first study of the European Osteosarcoma Intergroup. J Clin Oncol. 1992;10(10):1579-91. 19. Jeffree GM, Price HG, Sisson HA. The metastatic patterns of osteosarcoma. Br J Cancer. July 1975; 32(1):87-107. 20. Jaffe N, Smith E, Abelson HT, Frei E 3rd. Osteogenic sarcoma: alterations in the pattern of pulmonary metastases with adjuvant chemotherapy. J Clin Oncol. Apr 1983;1(4):251-4. 21. Pratt C, Shanks E, Hustu O, Rivera G, Smith J, Kumar AP. Adjuvant multiple drug chemotherapy for osteosarcoma of the extremity. Cancer. Jan 1977;39(1):51-7. 22. Kebudi Rejin, Özgüven A. Aykan, Görgün Ömer, et al. Intra-Abdominal Metastasis in Osteosarcoma: Survey and Literature Review. Pediatr Hematol Oncol. Oct 2011;28(7):609-15. 23. Paget S. The distribution of secondary growths in cancer of the breast. Lancet. Aug 1989;8(2):98-101. 24. Westra A, Schrijvers D, Somville J et al. Late peritoneal metastasis in a patient with osteosarcoma. Ann Oncol. Aug 1998;9(8):907-11.

ADVERTORIAL

DYSPEPTIC PATIENTS AT RISK IDENTIFIED BY A SIMPLE BLOOD TEST Gastric Cancer (GCa) is diagnosed in more than 7,000 people each year in the UK with a 5 year survival rate of 19%.1 The UK National Screening Committee does not recommend systematic population screening for GCa because there is insufficient evidence demonstrating effective outcomes from GCa screening where there is low incidence of disease.2 SECONDARY prevention strategies for screening where cancer is the endpoint could benefit from a paradigm shift towards PRIMARY prevention by implementing a more effective pathway to identify those individuals who belong to GCa Risk Groups, particularly in low incidence areas such as the UK.

Patients at risk It is well documented that alarm symptoms are poor indicators of disease and that predictive values are poor, whilst some significant gastric conditions are asymptomatic and often missed. Atrophic Gastritis (AG) is a high-risk, chronic inflammatory condition of the gastric mucosa that is caused by Helicobacter pylori infection or autoimmune disease. Often asymptomatic, it is the most important risk factor and precursor to intestinal GCa. AG can develop at any time, and severity and prevalence increase with age. It is estimated that 4% of >40 year olds suffer from atrophic corpus gastritis, but the prevalence in people >70 year olds can reach 8%.3

GASTROENTEROLOGY TODAY - AUTUMN 2015

Individuals with Chronic Atrophic Gastritis are at increased risk of developing GCa through a series of progressive stages defined by Correa’s cascade of carcinogenesis.4 In 2002 Whiting et al reported that 18% of AG cases progressed to cancer.5 AG is therefore a useful endpoint for Primary prevention by identifying patients at risk of GCa at an early, preventive stage.

GastroPanel® blood test • Categorise patients by Cancer risk • Diagnose Atrophic Gastritis • Identify patients requiring gastroscopy • Identify patients with achlorhydria and hypochlorhydria

GastroPanel® reports the following risks: • Peptic and duodenal ulcers • Gastric cancer • Vitamin B12 and other micronutrient deficiencies

GastroPanel® makes evidence based recommendations: • Gastroscopy and biopsy • Helicobacter eradication • Investigation of anaemia and malabsorption

Non-invasive identification of patients at risk GastroPanel® is a low cost and straight forward blood test that accurately detects AG6 and as such resides in the domain of primary prevention. The measurement of plasma Pepsinogen I and II and their ratio is a well-established non-invasive tool for diagnosing advanced corpus AG in high- and low- GCa incidence areas. Additionally, Gastrin-17 is a specific biomarker that is useful for revealing the morphological and functional status of the antrum mucosa.

1. CRUK 2. http://legacy.screening.nhs.uk/stomachcancer 3. Telaranta-Keerie A. et al. Prevalence of undiagnosed advanced atrophic corpus gastritis in Finland: an observational study among 4,256 volunteers without specific complaints. Scand J Gastroenterol 2010;45(9):1036-41. 4. Correa P. A Human Model of Gastric Carcinogenesis. Cancer Res 1988;48:3554-3560. 5. Whiting J. et al. The long term results of endoscopic surveillance of premalignant gastric lesions. Gut 2002;50:378–381. 6. Vaananen H. et al. Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicenter study. Eur J Gastroenterol Hepatol. 2003;15(8):885-91.

ADVERTORIAL In 2010 a consensus was formed that the measurement of pepsinogen I, pepsinogen II and Helicobacter pylori IgG antibodies from a plasma sample are the best non-invasive tests to identify GCa risk groups.7 In January 2015 this was reinforced by a 92 percent expert consensus vote advocating that Serological tests (pepsinogen I and II and H. pylori antibody) are useful for identifying individuals with an increased risk of GCa.8 By measuring a combination of Pepsinogen I, Pepsinogen II, Gastrin-17 and Helicobacter pylori IgG GastroPanel® provides an accurate and rapid indication of stomach health and reports on the structure and function of the gastric mucosa. The GastroPanel® blood test is especially useful because the test provides doctors with extensively validated and objective information to support their clinical decisionmaking and categorises patients into to risk groups:

GastroPanel ® is low cost, easy to adopt, and can be diffused rapidly throughout healthcare systems by fitting into the existing infrastructure. The GastroPanel® blood test is manufactured by BIOHIT HealthCare, a Finnish company that specialises in the screening, diagnosis and monitoring of GI diseases. Learn more at www.gastropanel.com

7. Malfertheiner P. et al. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut 2012;61:646-64.

GASTROENTEROLOGY TODAY - AUTUMN 2015

GastroPanel® is recommended as the first-line diagnostic tool for adult patients suffering from dyspepsia in Primary Care, and as a screening test for AG. In primary care GastroPanel® can be used to identify patients with increased risk of GCa by identifying AG. With the increasing burden on endoscopic resources and low yield from diagnostic gastroscopies, GastroPanel® can select patients in whom gastroscopy should by recommended using a well-defined, effective risk classification strategy. In turn this can help manage the demand for gastroscopy and improve the 5-year survival of GCa.

8. Kentaro S et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015;64:9 1353-1367.

ADVERTORIAL

FAECAL HAEMOGLOBIN MEASUREMENTS: A NEW PARADIGM IN INVESTIGATION OF PATIENTS PRESENTING IN PRIMARY CARE WITH LOWER ABDOMINAL SYMPTOMS Callum G Fraser, Centre for Cancer Prevention and Screening, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY Scotland Email: callum.fraser@nhs.net

Key words Adenoma; Colorectal cancer; Colorectal disease; Diagnostic

The prediction, according to the University of Birmingham

accuracy; Faecal haemoglobin; Faecal immunochemical test;

produced report, is that more than 750,000 extra endoscopies will

Faecal occult blood test; Inflammatory Bowel Disease

need to be performed each year in the UK by 2020, about a 44% rise from current demands: the increase will be due to the ageing and growing population, meaning more people with symptoms will

Abstract A recent report highlights the current problems with ever increasing demands for lower gastrointestinal endoscopy arising from referrals from primary care. Enhancing facilities and staffing would undoubtedly have some merits, but introduction of quantitative faecal immunochemical tests (FIT), which measure faecal haemoglobin concentration (f-Hb), would have undoubted benefits. Traditional guaiac FOBT (gFOBT) have many disadvantages and their use in assessment of the symptomatic has been widely deprecated. However, these have been superseded by FIT. Recent publications prove that f-Hb has very high sensitivity for colorectal cancer (CRC) and therefore has potential as a rule-in test, with a positive test result requiring rapid referral. However, it is important to also consider detection of higher-risk adenomas and inflammatory bowel disease: f-Hb has very high negative predictive value for these as well as CRC. A negative test result provides considerable reassurance that significant colorectal disease is absent and endoscopy might not be required. GASTROENTEROLOGY TODAY - AUTUMN 2015

Abdominal symptoms are common but significant colorectal disease is rarer. Use of f-Hb could rationalise the ever-growing referrals for endoscopy in those presenting to primary care with such symptoms, all of which have low positive predictive value. Measurement of f-Hb is now a mature investigation worthy of ubiquitous introduction.

need testing, as well as changes potentially being made to the NHS Bowel Cancer Screening Programme (BCSP) [1]. The report makes eleven cogent recommendations, including increased investment in diagnostic services and solution of workforce issues to cope with increasing pressures. Additionally, it recommends that innovative ways to meet rising demand, including alternative pathways and processes that would help speed up diagnosis, should be considered: the example given is â&#x20AC;&#x153;straight to test accessâ&#x20AC;? to endoscopy through telephone triage/ pre-assessment. The final recommendation considers the proposed replacement of the traditional guaiac-based faecal occult blood test (gFOBT) currently used as the initial investigation in the NHS BCSP with the faecal immunochemical test for haemoglobin (FIT) and documents concerns that this will increase demand on endoscopy services. However, the report does not consider the innovative use of measurements of faecal haemoglobin concentration (f-Hb) in assessment of patients with lower abdominal symptoms presenting in primary care. The clinical dilemma for primary care is whom to refer for endoscopy. The Rule of Sixths derived from the extensive literature shows that, of the patients being referred for lower gastrointestinal tract endoscopy from primary care, only 1/6 have serious colorectal disease, 2/6 (1/3) have less serious bowel disease (diverticular

1. A Major Current Problem

disease, haemorrhoids, hyperplastic and small polyps) and 3/6 (1/2) have no detectable abnormality (see: https://scpnblog. wordpress.com/2015/06/12/investigating-bowel-symptoms-

According to a new report commissioned by Cancer Research UK,

remember-the-rule-of-sixths/). Considerable evidence now supports

NHS services for diagnosing cancer are underfunded, understaffed

the thesis that measurement of f-Hb is a valuable tool to assist in

and key waiting time targets are being missed [1]. The report

the assessment of patients and can play a major role in deciding

highlights the growing pressures on endoscopy services,

who would merit referral so that the scarce endoscopy resource is

particularly regarding colorectal cancer (CRC).

directed to those who would benefit most.

ADVERTORIAL 2. Tests for the Presence of Blood in Faeces

3. FOBT in Assessment of the Symptomatic

Tests for the presence of haemoglobin in faeces, often called

For some time, the widely-held view has been that traditional gFOBT,

faecal occult blood tests (FOBT), have been used for many years.

while perhaps of value in screening programmes [5], have no role in

Traditionally, the guaiac-based FOBT (gFOBT) was applied in a

assessment of patients with symptoms. Older guidelines such as those

variety of clinical settings in addition to in asymptomatic population-

from the National Institute for Health and Clinical Excellence (NICE) [6],

based screening programmes. These have well-documented

the Scottish Intercollegiate Guidelines Network (SIGN) [7] and the British

disadvantages, including that two samples from each of three faeces

Society of Gastroenterology (BSG) [8] were unequivocal in stating that

are recommended, sampling must be directly onto the test card, the

FOBT should not influence decision making in symptomatic patients

cards must be dry before development, the detection of the haem

and are of no benefit in the investigation of iron deficiency anaemia.

moiety of haemoglobin (Hb) through its peroxidase activity means that the false positive results can be generated through dietary

Significant controversy has been raised, however, by the recently

constituents and the stability of haem means that bleeding from

issued guidance (NG12) from the National Institute for Health and Care

any part of the gastrointestinal tract can give positive test results [2]

Excellence (NICE) which state that, in possible CRC, patients who

[3]. In contrast, the newer FIT, which detect epitopes on the globin

do not meet criteria for suspected cancer referral should be offered

moiety of Hb, have many merits in that only one faecal sample is

FOBT [9]. The guideline is to offer FOBT to assess for CRC in adults

generally required, sampling is with hygienic, user-friendly specimen

without rectal bleeding who are aged 50 and over with unexplained

collection devices, there is no interference from dietary constituents

abdominal pain or weight loss, or are aged under 60 with changes

because the antibodies used are directed to human Hb and, since

in their bowel habit or iron-deficiency anaemia, or are aged 60 and

Hb is rather unstable in the gut, only bleeding from the colorectum

over and have anaemia even in the absence of iron deficiency. These

is detected. FIT are now the test of choice in CRC screening

recommendations were subject to a barrage of criticism during the

programmes everywhere [4] [5]. FIT come in two types, qualitative

consultation phase as well as after publication of the final guideline [10],

tests using immunochromatography similar in format to the very

largely because the evidence was based on publications concerning

widely used pregnancy tests [4] and, of higher utility, qualitative tests

the use of gFOBT in primary care: as above, these have many well-

using automated immunoturbidimetry in which the actual f-Hb can be

documented disadvantages and are considered to be obsolete [11] and Our New Senior

measured with good performance characteristics, allowing the cut-off f-Hb to be selected according to the clinical purpose [5].

are, as recognised by NICE, Team unavailable generally having been deleted Management from the repertoires of most laboratories in the UK.

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GASTROENTEROLOGY TODAY - AUTUMN 2015

EMIS Health has the tools you need to enable you to easily manage your patients with gastrointestinal disease. We can import data from your previous system to ensure continuity of the patient record.

ADVERTORIAL However, if NICE had recommended use of f-Hb as a tool to aid

208 symptomatic patients had f-Hb measured: undetectable f-Hb

in the investigation of patients presenting in primary care, then

ruled out 96.6% of advanced colorectal neoplasia (ACRN = CRC +

the guideline would have been both up to date and relevant.

HRA). It was concluded that undetectable FIT is a good strategy to

Unfortunately, the now large evidence-base supporting this clinical

rule-out ACRN in symptomatic patients [17].

application was mainly generated only during the gestation of NG12 and, simply because of timing, a golden opportunity to revolutionise current practice with the use of f-Hb measurements was unexploited.

5. Conclusions Recent peer-reviewed studies on the use of f-Hb, with a low cut-off,

4. Faecal Haemoglobin Concentration (f-Hb) Measurements: Evidence for a New Paradigm

in assessment of those presenting with lower abdominal symptoms have shown very high clinical specificity (often 100%) for CRC, so that a positive test result should stimulate rapid referral for colonoscopy. Moreover and, probably more importantly, f-Hb in

A study done in Scotland reported that f-Hb was measured on

this context has very high negative predictive value for detection

single samples from 280 patients referred for lower gastrointestinal

of significant colorectal diseases well worthy of detection, namely,

tract endoscopy from primary care in NHS Tayside, who then

CRC plus HRA plus IBD. In consequence, a negative test result

underwent endoscopy. Using a cut-off f-Hb of 10 µg Hb/g faeces,

provides considerable reassurance that colonoscopy is not

negative predictive values of 100%, 94.4%, and 93.9% were

required urgently or even at all. While detailed algorithms for the

found for CRC, higher-risk adenoma (HRA) and inflammatory

introduction of f-Hb measurements require further local exploration,

bowel disease (IBD), respectively. It was concluded that f-Hb

there is no doubt that f-Hb measurements have considerable

measurements have considerable potential to contribute to

potential to contribute to reducing unnecessary colonoscopy for the

reducing unnecessary endoscopy for the majority of symptomatic

majority of symptomatic patients. It is considered that this simple

patients [12]. In a much larger study in the same NHS Board, 1043

and inexpensive investigation, with easy to collect single faecal

patients returned samples for f-Hb measurement and negative

samples, should become widely used in everyday practice.

predictive values for CRC, HRA and IBD were 100%, 97.8% and 98.4%, respectively, using a cut-off of any detectable f-Hb. It was concluded that, in primary care, undetectable f-Hb is a good ruleout test for significant colorectal disease and could guide who requires further endoscopic investigation [13]. A further very recent study from another NHS Board in Scotland, Lanarkshire, involving 484 patients referred for endoscopy, concluded that potential exists for using f-Hb measurements to investigate symptomatic patients and guide the use of colonoscopy resources since, using a f-Hb cut-off of 10 µg Hb/g faeces, for the group with CRC or HRA or IBD, the negative predictive value was 96.2% [14]. It is understood that the two Scottish NHS Boards in which these studies were done are already progressing the introduction of f-Hb in primary care as a necessary prerequisite for referrals to endoscopy, from which the f-Hb and clinical symptoms will be assessed and decisions made. Three studies from different regions of Spain provide considerable additional evidence that f-Hb is a most useful investigation. Firstly, GASTROENTEROLOGY TODAY - AUTUMN 2015

the diagnostic accuracy of f-Hb for CRC at a cut-off of 20 µg Hb/g faeces was compared with NICE [7] and SIGN [6] referral criteria. In 787 symptomatic patients, f-Hb had a higher sensitivity for CRC

References 1. Health Services Management Centre of the University of Birmingham and Midlands and Lancashire Commissioning Support Unit. Scoping the future: evaluation of endoscopy capacity across the NHS in England, 2015. See: http://www. cancerresearchuk.org/about-us/cancer-news/press-release/201509-06-tests-to-diagnose-cancer-underfunded-and-staffoverstretched 2. Fraser CG. A future for faecal haemoglobin measurements in the medical laboratory. Annals of Clinical Biochemistry 2012;49:518-26. 3. Carroll MR, Seaman HE, Halloran SP. Tests and investigations for colorectal cancer screening. Clinical Biochemistry 2014:47:921-39. 4. Allison JE, Fraser CG, Halloran SP, Young GP. Population screening for colorectal cancer means getting FIT: the past, present, and future

detection (87.6%) than NICE (61.9%) or SIGN criteria (82.5%)

of colorectal cancer screening using the fecal immunochemical test

and it was suggested that f-Hb is more accurate for the detection

for hemoglobin (FIT). Gut Liver 2014;8:117-30.

of CRC than the NICE and SIGN referral criteria for referral of symptomatic patients for colonoscopy [15]. Secondly, in 1054

5. Young GP, Symonds EL, Allison JE, Cole SR, Fraser CG, et al.

symptomatic patients referred for a colonoscopy, the usefulness

Advances in fecal occult blood tests: the FIT revolution. Digestive

of f-Hb and SIGN and NICE guidelines for urgent referral were

Diseases Science 2015;60:609-22.

compared for their efficacy in the detection of CRC and advanced neoplasia (AN = CRC + HRA): it was found that the guidelines detected 46.7% and 43.3% of cases of CRC while f-Hb ≥15 μg Hb/g

6. Scottish Intercollegiate Guidelines Network. SIGN. Management of Colorectal Cancer. SIGN, 2003. See www.sign.ac.uk/pdf/sign67.pdf

faeces detected 96.7% of cases. The detection of AN was also better using f-Hb than the guidelines and it was stated that a f-Hb

7. National Institute for Health and Clinical Excellence. NICE. Clinical

based strategy performs better than high-risk symptoms based

Guideline 27. Referral for Suspected Cancer, 2005. See www. nice.

strategies for fast-tracking referrals [16]. Finally, samples from

org.uk/nicemedia/pdf/cg027niceguideline.pdf

ADVERTORIAL 8. Goddard AF, James MW, McIntyre AS, Scott BB; British Society

14. Godber IG, Todd LM, Fraser CG, MacDonald LR, Ben Younes H.

of Gastroenterology. Guidelines for the management of iron

Use of a faecal immunochemical test for haemoglobin can aid

deficiency anaemia. Gut 2011;60:1309-16.

in the investigation of patients with lower abdominal symptoms. Clinical Chemistry and Laboratory Medicine 2015; in press.

9. National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. (NG12.) 2015. See; www.nice. org.uk/guidance/ng12.

15. Cubiella J, Salve M, Díaz-Ondina M, Vega P, Alves MT, et al, Diagnostic accuracy of the faecal immunochemical test for colorectal cancer in symptomatic patients: comparison

10. Steele R, Forgacs I, McCreanor G, Benton S, Machesney M, et al. Use of faecal occult blood tests in symptomatic patients.

with NICE and SIGN referral criteria. Colorectal Disease 2014;16:O273-82.

British Medical Journal 2015;351:h4256. 16. Rodríguez-Alonso L, Rodríguez-Moranta F, Ruiz-Cerulla A, 11. Young GP, Fraser CG, Halloran SP, Cole SR. Guaiac based

Lobatón T, Arajol C, et al. An urgent referral strategy for

faecal occult blood testing for colorectal cancer screening: an

symptomatic patients with suspected colorectal cancer

obsolete strategy? Gut 2012;61:959-60.

based on a quantitative immunochemical faecal occult blood test. Digestive and Liver Disease 2015 May 15. pii: S1590-

12. McDonald PJ, Digby J, Innes C, Strachan JA, Carey FA, et al. Low faecal haemoglobin concentration potentially

8658(15)00310-2. doi: 10.1016/j.dld.2015.05.004. [Epub ahead of print].

rules out significant colorectal disease. Colorectal Disease 2013;15:e151-9.

17. Auge JM, Fraser CG, Rodriguez C, Roset A, Lopez-Ceron M, et al. Clinical utility of one versus two faecal immunochemical

13. Mowat C, Digby J, Strachan JA, Wilson R, Carey FA, et al.

test samples in the detection of advanced colorectal neoplasia

Faecal haemoglobin and faecal calprotectin as indicators

in symptomatic patients. Clinical Chemistry and Laboratory

of bowel disease in patients presenting to primary care with

Medicine 2015 Jun 27. pii: /j/cclm.ahead-of-print/cclm-2015-

bowel symptoms. Gut Published Online First: 20 August 2015

0388/cclm-2015-0388.xml. doi: 10.1515/cclm-2015-0388. [Epub

doi:10.1136/gutjnl-2015-309579.

ahead of print].

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Why You Should Consider Alternative EWD Chemistries The alternative EWD chemistries project was started nearly two years ago. The Project partners were Audere Medical Services Ltd, Amity International, and the project leader was Peskett Solutions Ltd (Ruhof UK) We are pleased to announce that the project was a resounding success and we are now in a position to offer our services to all hospitals using EWD’s During the EWD project the following questions were raised: Will the Trust save money changing to alternative EWD Chemistries? • We have saved our project Hospital £56,000 per annum on their EWD detergent, disinfectant.

Are there any other added benefits with using alternative chemistries? • Our alternative EWD project has been running for nearly two years. The customer has been monitoring the chemical effects to the EWD’s and Endoscopes. • The endoscope manufacturer has reported a 23% reduction in scope damage from the cleaning and disinfectant chemistries. • The customer has reported an impressive increase of 41% up time. This has been contributed to the alternative chemistries and improved servicing and parts.

How do you deal with Type Testing? • The type testing for the chemistries is performed by the validation company on site. The alternative chemistries were selected to chemically match the chemistries supplied by the EWD manufacturer. This decision was based on ensuring EWD and Endoscope compatibility.

What about Patient safety? • To offer alternative chemistries we needed to ensure that all the required EWD validation testing was carried out to current relevant standards. The endoscopes over the last 2 years have shown no significant signs of deterioration. We are confident that this will continue and there should be no impact on Patient Safety.

Please contact Matthew to discuss the alternative EWD chemistries project further. Tel: 01323 511038 Email: support@peskettsolutions.com