What’s new?

C Haemostatic forceps and endoscopic Doppler ultrasound in

gastrointestinal bleeding

C Endoscopic Submucosal Dissection (ESD) for upper and lower

GI lesions

C Radio-frequency ablation (RFA) in the management of Barrett’s

oesophagus

C Cholangioscopy in biliary tract disorders

NEW ADVANCES

Advances in therapeuticendoscopyRajvinder Singh

Swee Lin G Chen Yi Mei

Noriya Uedo

Ganesananthan Shanmuganathan

Krish Ragunath

AbstractThe field of gastrointestinal endoscopy has progressed significantly in the

last few decades. There has been a tremendous expansion leading not only

to improved diagnosis but treatment of gastrointestinal disorders, espe-

cially early neoplasia. Many gastrointestinal disorders originally requiring

surgical intervention are nowbeingmanaged using less andminimally inva-

sive means. In terms of the management of gastrointestinal bleeding, there

has been recent interest in the use of haemostatic forceps as well as endo-

scopic Doppler ultrasound. The application of Endoscopic Submucosal

Dissection has expanded from its initial role in gastric cancer to the treat-

ment of lesions in the oesophagus and colon. Therapy for Barrett’s oesoph-

agus is moving ahead rapidly with the new HALO system performing radio-

frequency ablation and the Spy-Glass is revolutionizing the management of

biliary disorders. Natural orifice transluminal endoscopic surgery (NOTES)

maybe thewayof the futurewith non-invasiveorminimally invasive surgery

potentially improving recovery times. This review will focus on all of these

recent developments in the field of therapeutic endoscopy.

Keywords endoscopic mucosal resection; endoscopic retrograde

cholangiopancreatography; gastrointestinal bleeding; luminal stenting;

radio-frequency ablation; submucosal dissection; therapeutic endoscopy

Rajvinder Singh MBBS MRCP MPhil FRACP AM FRCP is a Senior Consultant

Gastroenterologist at the Lyell McEwin Hospital and a Senior Clinical

Lecturer at the Department of Medicine, University of Adelaide,

Australia. Competing interests: none declared.

Swee Lin G Chen YiMei MBBS is an Advanced Gastroenterology Trainee at

the LyellMcEwinHospital, Australia. Competing interests: none declared.

Noriya Uedo MD PhD is a Senior Consultant Gastroenterologist and

Interventional Endoscopist at the Department of Gastrointestinal

Oncology, Osaka Medical Center for Cancer and Cardiovascular

Diseases, Osaka, Japan. Competing interests: none declared.

Ganesananthan Shanmuganathan KMN MD MRCP FRCP (Glasg. & Lon.) AM CMIA

is a Senior Consultant Physician and Gastroenterologist at the Pantai

Hospital, Kuala Lumpur, Malaysia. Competing interests: none declared.

Krish Ragunath DNB MPhil FRCP is an Associate Professor in Endoscopy

and Consultant Gastroenterologist at the Nottingham Digestive

Diseases Centre, Nottingham University Hospitals NHS Trust,

Nottingham, UK. Competing interests: none declared.

MEDICINE 39:5 284

Gastrointestinal bleeding

Endoscopic therapy has been shown to decrease morbidity in

patients presenting with gastrointestinal (GI) bleeding, provided

that patients have been resuscitated and stabilized before any

endoscopy is performed. The Rockall score is a clinical tool that

can be used to assess patients presenting with an acute upper GI

bleed. The risk of mortality can be predicted based on various

independent variables (age, shock, co-morbidity, endoscopy

findings) allowing patients to be stratified into high or low-risk

groups.1

A number of haemostatic endoscopic methods have been

developed to tackle non-variceal bleeding. Injection therapy

(adrenaline (epinephrine) 1:10,000 dilution), contact thermal

therapies (heater, bipolar and monopolar probes), non-contact

thermal therapy (argon plasma coagulation) and mechanical

modalities (haemoclip and haemostatic forceps) have all been

part of routine practice over the last decade. The amalgamation

of dual therapeutic modalities into a single device has the

potential to permit quicker haemostasis. This has been demon-

strated by the incorporation of a water jet channel into the heater

probe and the combination of an injection needle with the

bipolar cautery. However, studies showing the effect of this

approach on the final outcome (total length of hospital stay, need

for surgery and mortality) are lacking.

The introduction of two- and three-pronged clipping devices

has made it easier to grasp a bleeding vessel (Figure 1). Some

newer clips allow the endoscopist to open, close and rotate the

clip on demand to the desired axis, facilitating better placement

and reducing the number of clips needed to achieve haemostasis.

Argon plasma coagulation (APC) is especially effective in

ablating angiodysplastic lesions (Figure 2).2 High-frequency

monopolar current is applied in a non-contact manner with argon

acting as a conductor. This leads to coagulation of the superficial

vessels up to a depth of 3 mm. Haemostatic forceps, which are

routinely used to manage bleeding during endoscopic submu-

cosal dissection (see below), have been used in managing non-

variceal upper GI bleeding. Case reports describe its ability to

achieve haemostasis in the management of Dieulafoy lesions and

refractory bleeding ulcers.3 The bleeding point is pinched and

retracted by the haemostatic forceps before application of

a monopolar electrocurrent. However, excessive coagulation can

increase the risk of delayed perforation, and further appraisal of

this modality is required to determine its safety and use in the

management of both upper and lower GI bleeding.

� 2011 Elsevier Ltd. All rights reserved.

Figure 1 Haemoclip application. Bleeding visible vessel after adrenaline injection followed by application of three haemoclips.

NEW ADVANCES

Another novel modality, endoscopic Doppler ultrasound, has

been evaluated in patients presenting with upper GI haemor-

rhage secondary to peptic ulcer disease.4 This probe-based device

provides information on the presence or absence of blood flow as

sound that is received from a transceiver, which in turn is placed

on a target on an ulcer base. It can potentially be used to detect

the presence of a vessel underneath the ulcer, which can then be

treated prophylactically with the contact thermal therapies

described above.

Tissue glue, isobutyl-2-cyanoacrylate, mixed with lipiodol is

effective in treating bleeding from gastric varices that would

previously have required emergency salvage surgery or a trans-

jugular intrahepatic portosystemic shunt (TIPSS).5 Double-

channel therapeutic endoscopes have been introduced for better

management of upper GI bleeding. Advantages include the

ability to aspirate greater quantities of blood and to use two

devices simultaneously. In addition, these endoscopes have an

accessory irrigation channel that can provide a high-intensity

water jet when connected to an irrigation pump, thereby allow-

ing better visualization of a bleeding vessel.

Despite introduction of these novel devices, GI bleeding

cannot always be controlled endoscopically. Ten to 15% of

patients with a variceal bleed will continue to bleed despite initial

Figure 2 Argon plasma coagulation application to an angiodysplastic lesion in

MEDICINE 39:5 285

medical and endoscopic therapy. The Forrest Classification is

a helpful tool in stratifying the risk of ulcer re-bleeding based on

endoscopic appearance.6 Patients with a spurting artery or an

oozing vessel have a re-bleeding rate of up to 55e90%. In

refractory GI bleeding, it is especially important for the endo-

scopist to recognize the futility of further endoscopic therapy and

consider radiological or surgical approaches.

Endoscopic resection of early cancer

Endoscopic resection has increasingly come to the fore as a mini-

mally invasive procedure to manage dysplastic or superficial

neoplastic lesions of the gastrointestinal tract.7 It is particularly

useful in patientswho pose a high anaesthetic risk and are not fit for

surgery. It is also used increasingly to obtain a larger piece of tissue

for histological interpretation. Lesions deemed suitable for endo-

scopic mucosal resection (EMR) are lifted with submucosal injec-

tions of fluid to obtain a cushion that separates themucosa from the

muscularis layer. Resection can then be performed safely, using

either a snare fitted into a cap or a banding device. Lesions larger

than20mmaregenerally resectedpiecemeal.Toprevent recurrence

after incomplete removal of remnant premalignant lesions, endo-

scopic submucosal dissection (ESD) was recently introduced.8 ESD

the caecum.

� 2011 Elsevier Ltd. All rights reserved.

NEW ADVANCES

has been performed in the stomach and more recently in the

oesophagus, colon and rectum. It allows en bloc resection of large

lesions in a single piece, using various knives (needle, flex, hook,

insulated tip, triangular tip, flush) designed to allow the endoscopist

to perform dissection in a free-hand manner (Figure 3). Resected

specimens can be accurately staged and further management

tailored to the histology. The complications of this procedure

include perforation and bleeding (up to 5%), so they are generally

performed in ‘high-volume expert’ centres. At present, ESD is not

routinely available in the West as it requires specialized training.

This technique has been in the forefront of early luminal cancer

treatment in Japan where, following the implementation of routine

nationwide screening programmes more than two decades ago,

gastric cancer is generally detected early.

Ablative therapies

Advanced ablation technology, using radio-frequency ablation

(RFA) administered through a balloon catheter (HALO system),

has recently been shown to be highly effective for treatment of

high-grade dysplasia (HGD) and intramucosal cancer (IMC) in

Barrett’s oesophagus (BE).9 The most proximal margin of the BE

is measured from the incisors and a stiff guidewire is introduced

with removal of the endoscope. A balloon catheter is fed over the

guidewire and connected to an energy generator. The inner

oesophageal diameter is measured through inflation of the

balloon every 1 cm along the length of the BE to determine the

size of the ablation catheter. The balloon catheter is then

removed and the ablation catheter is fed over the guidewire,

Figure 3 Endoscopic submucosal dissection performed in a patient unfit for s

b Lesion more clearly demarcated with indigo carmine chromoendoscopy (Pari

e Specimen retrieved. f Histology revealed submucosal invasion.

MEDICINE 39:5 286

followed by the endoscope. Under direct vision, the balloon is

inflated and the electrode activated via a footswitch. Energy is

delivered for approximately 1.5 s, during which the balloon

deflates, and this is performed every 5e10 mm, moving distally

until completion. This procedure is repeated every 8e12 weeks

until all BE is eradicated.

This exciting new modality has overshadowed other ablative

techniques previously employed to remove residual HGD/IMC in

BE. The use of photodynamic therapy and APC were associated

with high rates of strictures and incomplete ablation, as well as

non-ablation of the remaining residual BE segment, which leaves

a fertile field with oncogenic aberrations that can increase the

risk of recurrent neoplasia.10 There was also the risk of foci of

intestinal metaplasia being buried under the neosquamous

mucosa after treatment. However, APC continues to be used for

the treatment of radiation proctopathy and palliation of GI

malignancy (Figure 2).2

Endoscopic retrograde cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) has

become the cornerstone of the management of pancreaticobiliary

disorders. It combines the use of endoscopy and fluoroscopy to

view the biliary and pancreatic ductal systems, and allows thera-

peutic intervention. A side-viewing duodenoscope provides the

best view of the ampulla. A sphincterotome-cannula (with or

without a guidewire) is then used to cannulate the bile or pancre-

atic duct and cholangiopancreatography is performed. ERCP is

commonly indicated for the management of biliary obstruction

urgery. a Flat depressed inconspicuous lesion on white light endoscopy.

s type IIaec). c Circumferential incision performed. d Base after resection.

� 2011 Elsevier Ltd. All rights reserved.

NEW ADVANCES

(benign or malignant) or treatment of choledocholithiasis, where

stones are extracted with a balloon or basket. Mechanical litho-

tripsy may be required if large stones require fragmentation.

Insertion of a plastic stent is used to manage benign strictures that

require stent change at least every 3 months to avoid infection. In

the case ofmalignant strictures, self-expanding permanentmetallic

stents are appropriate for palliation. Complications of ERCP

include pancreatitis, bleeding, infection and perforation.

The most recent innovation in ERCP is the ability to view the

biliary tree (cholangioscopy). Traditionally, standard cholangio-

scopy during ERCP requires two operators e the first holding the

duodenoscope and the second controlling the cholangioscope,

inserted through the working channel. The Spy-Glass system

provides a direct view of the biliary tree, using a fibre-optic probe

that can be inserted through the working channel of the duode-

noscope.11 The probe can be steered in four directions and is

designed to allow a single operator to perform both diagnostic

and therapeutic interventions. The recent introduction of a single

operator peroral cholangioscope has yielded promising results.12

Luminal stenting in advanced malignancy

The development of self-expanding metallic stents now allows

palliation of malignant strictures in patients with advanced cancer

unsuitable for surgery.13 These stents have been used in the

oesophagus, duodenum and colon with good effect. Reduction in

their diameter allows introduction within the delivery system and

facilitates placement across a stenosed region. After release, the

stent expands to reach its original shape. Covered stents have also

been introduced to prevent tumour ingrowth and for use in tra-

cheo-oesophageal fistulae. Complications of endoluminal stenting

include re-obstruction of tumour due to ingrowth and overgrowth,

stent migration, perforation and bleeding. Removable self-

expanding plastic stents, once considered an important advance in

the management of strictures due to benign disease, led to a high

(up to 80%) incidence of complications, in particular stent

migration,14 and are no longer recommended.

Natural orifice transluminal endoscopic surgery

Natural orifice transluminal endoscopic surgery (NOTES) is an

emerging experimental endoscopic alternative to conventional

laparoscopic or open surgery, which could revolutionize current

surgical practice.15 It re-defines the meaning of ‘non-invasive

surgery’, from the abdominal incisions of laparoscopic surgery

and, more recently, single-port surgery to ‘incision-free’ surgery.

NOTES involves insertion of a fibre-optic video endoscope

through a natural orifice, using a transgastric, transvaginal,

transcolonic or transrectal approach, and access to the abdominal

cavity via a visceral incision. Successful use of this technique has

been reported in cases of cholecystectomy and nephrectomy. The

potential advantages of ‘incision-free’ surgery are fewer wound-

related complications, less postoperative pain, a quicker recovery

time and an improved cosmetic result. However, residual chal-

lenges include control of abdominal peritoneal contamination,

adequacy of current instrumentation and adequate closure of the

visceral incision. The role of this technique in future surgical and

gastroenterology practice is yet to be defined.

MEDICINE 39:5 287

Conclusion

Over the last decade, innovations described abovehavepushed the

boundaries of gastrointestinal endoscopy further from a purely

diagnostic tool to a therapeutic one that is bothminimally invasive

and cost-effective. Further developments already on the horizon

include novel stapling and suturing devices, as well as endoscopic

devices for treatment of obesity.16 Interventional endoscopy is

destined to progress even further and will compete with surgical

procedures for an increasing range of indications. A

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� 2011 Elsevier Ltd. All rights reserved.