Argon Plasma Coagulation Plus Injection Sclerotherapy Versus Injection Sclerotherapy Alone For The Prevention of Variceal Recurrence and Re Bleeding

Mansoura University
Faculty of Medicine
Internal Medicine Department
Argon Plasma Coagulation

Plus Injection Sclerotherapy Versus
Injection Sclerotherapy Alone For The
Prevention Of Variceal Recurrence And
Rebleeding
BY
Tarek Fouad El Sayed Mohamed
M.B.B.Ch.
Resident of internal medicine
Faculty of medicine, Mansoura university
Thesis
Submitted for Partial Fulfillment of the Master Degree
In Internal Medicine
Supervisors
Prof. Dr. Prof. Dr.

Magdy Hamed Abdel Fattah Ayman Nassem Mohamed
Menessy
Professor of internal medicine Professor of internal medicine
Faculty of medicine, Mansoura Faculty of medicine, Mansoura
university university
Dr. Mohamed Mahmoud Fahmy El-Saadany

Lecturer of internal medicine
Faculty of medicine, Mansoura university
2006
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ACKNOWLEDGEMENT
First and foremost, all thanks and gratefulness to "ALLAH", the

most beneficial and merciful.
I would like to express my deepest gratitude to Prof. Dr. Magdy

Hamed Abdel Fattah, Professor of Internal Medicine, Faculty of
Medicine, Mansoura University, for his continuous supervision, fruitful
guidance and generous support.
I would like also to express my sincere thanks to Prof. Dr. Ayman

Nassem Mohamed Menessy, Professor of Internal Medicine, Faculty of
Medicine, Mansoura University, for his endless effort, great help and
encouragement in this work.
I am deeply grateful and forever indebted to Dr. Mohamed

Mahmoud Fahmy El-Saadany, Lecturer of internal medicine, Faculty of
Medicine, Mansoura University, for his valuable effort, supervision and
guidance. Indeed, this work would not be accomplished without his
efforts and advices.
Last but not least, I would like to thank my colleagues, staff

members of the "Specialized Medical Hospital" endoscopy unit and my
patients for their help and patience in this work.
Tarek Fouad
2006
2006
CONTENTS
SUBJECT PAGE
INTRODUCTION AND AIM OF THE 1

WORK
REVIEW OF LITERATURE: 3
The Portal Venous System 3
Portal Hypertension 8
Management of esophageal varices 16

Argon Plasma Coagulation 27
PATIENTS AND METHODS 55
RESULTS 65
DISCUSSION 97
SUMMARY AND CONCLUSION 104
REFERENCES 108
ARABIC SUMMARY
LIST OF TABLES
Table Subject Page
Table (1) Setting of argon plasma coagulation (APC) 30

parameters.
Table (2) Conventional methods of haemostasis 33
compared with APC in different types of
haemorrhage.
Table (3) Scoring system for pathologic analysis of 45
argon plasma coagulation tissue effects on
esophageal and gastric tissue.
Table (4) Gastric tissue damage score for different 46
combinations of pulse duration and power.
Table (5) Esophageal tissue damage score for 1- and 3- 47
second pulse durations.
Table (6) Pugh's modification of Child's classification. 60
Table (7) Baseline demographic and clinical data of both 80
groups.
Table (8) Laboratory data and Child-Pugh score in both 81
groups at randomization and at the end of
treatment.
Table (9) Virological markers of the studied groups. 82
Table (10) Aetiology of liver cirrhosis in the studied 82
groups.
Table (11) Child-Pugh classification in the studied groups 82
at randomization.
Table (12) Initial Endoscopic Results . 83
Table (13) Data of variceal obliteration in both groups. 84
Table (14) Complications of sclerotherapy in both groups. 85
Table (15) Complications of argon plasma coagulation in 86
group I.
Table (16) Complications of APC in group I versus 87
complications of EST in group II.
Table (17) Data of variceal recurrence in both groups of 88
patients.
Table (18) Data of rebleeding in both groups of patients. 88
LIST OF FIGURES
Figure Subject Page
Figure (1) Schematic representation of the portal and 3

hepatic venous system.
Figure (2) Variation in origin of portal vein. 4
Figure (3) Regulation of vascular tone by endothelins and 14
nitric oxide.
Figure (4) Schematic representation of portosystemtic 15
collaterals.
Figure (5) The tissue effect of argon plasma coagulation 49
on esophageal mucosa.
Figure (6) Child-Pugh classification in the studied groups 89
at randomization.
Figure (7) Virological markers of the studied groups at 90
randomization.
Figure (8) Aetiology of liver cirrhosis in the studied 91
groups at randomization.
Figure (9) Initial Endoscopic Results (according to grade 92
of varices).
Figure (10) Kaplan-Meier analysis of the cumulative 93
recurrence-free curves.
Figure (11) Kaplan-Meier analysis of the cumulative 94
rebleeding-free curves.
Figure (12) Endoscopic application of argon plasma 95
coagulation.
Figure (13) Endoscopic appearance of the lower 95
esophageal mucosa at the end of an APC
session .
esophageal mucosa in the same patient one
month after the APC session.
esophageal mucosa in the same patient 6
months after the APC session.
List of Abbreviations and Acronyms
ACE Angiotensin converting enzyme
ALT Alanine aminotransferase
APC Argon plasma coagulation
AVM Arteriovenous malformations
c-GMP Cyclic guanosine monophosphate
DM Diabetes mellitus
ELISA Enzymes linked immunosorbent assay
EMR Endoscopic mucosal resection
EST Endoscopic sclerotherapy
ET-1 Endothelin-1
EVL Endoscopic variceal band ligation
GAVE Gastric antral vascular ectasia
GIT Gastrointestinal tract
H.&E. Hematoxylin and Eosin
HBsAg Hepatitis B surface antigen
HCV Hepatitis C virus
HF High frequency
HVPG Hepatic venous pressure gradient
INR International normalizing ratio
ISMN Isosorbide mononitrate
IVC Inferior vena cava
Nd/Yag Neodymium yttrium aluminum garnet
NO Nitric oxide
NOS Nitric oxide synthase
NSAIDs Non steroidal anti inflammatory drugs
NSBBs Nonselective beta-blockers
PHG Portal hypertensive gastropathy
PT Prothrombin time
TNF-αα Tumor necrosis factor alpha
TIPS Transjugular intrahepatic portosystemic shunt
W Watt
INTRODUCTION AND
AIM OF THE WORK
Introduction & Aim of the Work
INTRODUCTION
AND AIM OF THE WORK
Gastrointestinal bleeding is the most severe complication of portal

hypertension, and esophageal and gastric varices are by far the most
common sources of bleeding in these patients (D’Amico and Luca,
1999). After an initial variceal hemorrhage, the frequency of recurrent
bleeding ranges from 30% to 40% within the subsequent 6 weeks
(D'Amico et al., 1997).
Endoscopic injection sclerotherapy (EST) has long been the most

widely used technique to achieve variceal fibrosis (Kitano et al., 1990
and Narayanan and Patrick, 2006). Endoscopic injection sclerotherapy
involves injecting a sclerosant that subsequently results in variceal
thrombosis and fibrosis. It is usually performed every 10-14 days until the
varices are eradicated, which usually takes 5 or 6 sessions. After
obliteration, varices tend to recur over time in 50% to 70% of individuals
(Waked et al., 1997).
Argon plasma coagulation (APC) is a non-contact thermal coagulation

method in which high frequency current is applied to the target tissue
through an argon plasma jet (Consensus statement on therapeutic
endoscopy and bleeding ulcers, 1990). A distinctive feature characteristic
of argon plasma coagulation is safe, uniform and effective shallow
coagulation over extensive areas (Johanns et al., 1997).
In this study, argon plasma coagulation will be used to induce fibrosis

of the esophageal mucosa after eradication of esophageal varices with
injection sclerotherapy.
1
Introduction & Aim of the Work
Aim of the work:

The aim of the present clinical trial is to assess safety and efficacy of
endoscopic sclerotherapy (EST) plus Argon plasma coagulation (APC)
versus endoscopic sclerotherapy alone for the prevention of variceal
recurrence and rebleeding.
2
REVIEW OF
LITERATURE
Review of Literature
The Portal Venous System
The term ‘portal venous system’ is applied to a system that begins and
terminates in capillaries. In the abdomen, this system springs up as the
capillaries of the intestine, and ends in the hepatic sinusoids (Kapoor and
Sarin, 2002). A schematic representation of the main splanchnic venous
channels is shown in Fig (1).
Fig (1): Schematic representation of the portal and hepatic venous

system, SMV: superior mesenteric vein; IMV: inferior mesenteric vein;
SV: splenic vein; MPV, RPV, LPV: main, right and left portal vein;
LGV: left gastric vein, IVC: inferior vena cava; RHV, MHV, LHC,
right, middle and left hepatic vein (Kapoor and Sarin, 2002).
Anatomy of the portal venous system
The portal vein is formed behind the neck of the pancreas as the
superior mesenteric joins the splenic vein.
The portal trunk divides into 2 lobar veins. The right branch drains the
cystic vein, and the left branch receives the umbilical and paraumbilical
3
veins.
The portal vein is rarely variable. It often receives the left gastric vein,
and may also receive an accessory splenic, inferior phrenic branch,
pancreaticoduodenal, a pulmonary vein or right gastroepiploic vein
(Bergman et al., 1988) .Variation in origin of portal vein are shown in
figure (2).
Figure 2
Variation in origin of portal vein
(PV: portal vein, IM: inferior mesenteric, LG: left gastric, S: splenic, SM:
superior mesenteric).
(Bergman et al, 1988)
The portal vein itself is approximately 6-8 cm long and 1-1.2 cm in

diameter. It runs in the free edge of the lesser omentum from the pancreas
4
to the right end of the porta hepatis. The superior mesenteric vein forms
from the draining jejunal and ileal veins, its major tributaries being the
ileocolic, right colic and middle colic veins. The left and right gastric
veins and the gastroepiploic veins drain into the main portal vein. Two
major tributaries of importance in portal hypertension are: -
• Left gastric (coronary) vein.

• Inferior mesenteric vein. These enter the portal system close to the
splenic portal vein junction, the left gastric vein superiorly and the
inferior mesenteric vein inferiorly.
Portal vein flow in man is about 1000-1200 ml/ minute (Sherlock

and Dooley, 1997).
An important feature of this system is that a number of its tributaries

also communicate with the systemic circulation. These include the
intrinsic and extrinsic veins of the gastroesophageal junction;
hemorrhoidal veins of the anal canal; paraumbilical veins and the
recanalized falciform ligament; the splenic venous bed, the left renal vein;
and the retroperitoneum.
In portal hypertension, these venous collaterals dilate and allow portal

venous blood to return to the systemic circulation. Clinically, the most
significant collaterals are the intrinsic veins of the gastroesophageal
junction, which are located close to the mucosal surface. They are the
collaterals most likely to bleed when dilated because of increased blood
flow (Garcia-Tsao, 1999).
The other important surgical anatomy in portal hypertension is the

venous anatomy of the gastroesophageal junction, which has been
extensively studied by several investigators in the past two decades
(Vianna et al., 1987).
5
Angioarchitecture of the gastroesophageal junction:
The lower part of human osophagus has a characteristic vascular

structure (Vianna et al., 1987, Arakawa et al., 2002 and Obara, 2006):-
1- Gastric zone: it lies 2-3cm below the gastroesophageal
junction (junctional zone). Veins run longitudinally towards
esophagus rather than via an irregular network as seen in the rest
of the stomach.
2- Palisade zone: it lies 2-3 cm above the gastric zone extending
into lower esophagus. Evenly distributed longitudinal veins
correspond to major mucosal folds of the esophagus; there is no
perforating veins.
3- Perforating zone: it lies 2cm above the palisade zone. There
are large looping collaterals between internal and external
venous plexuses of the esophagus.
4- Truncal zone: it lies 8-10cm above the perforating zone.
There are 4-5 longitudinal veins in the lamina propria and
perforating veins from the submucosa to external venous plexus.
The veins of the gastroesophageal junction are classified as intrinsic,

extrinsic, and venae comitantes. The intrinsic veins form a subepithelial
and submucosal plexus starting at the gastric cardia (upper stomach) and
running the length of the esophagus. In healthy persons, these veins drain
into the extrinsic plexus through perforating veins 2 to 3 cm. above the
gastroesophageal junction. Flow through the perforating veins is
unidirectional toward the extrinsic plexus and systemic circulation. When
portal hypertension develops, however, the valves of the perforating veins
become incompetent and allow reversal of flow from the extrinsic to the
intrinsic system (Hegab et al., 2001).
6
It has been reported that bleeding from esophageal varices mostly

occurred in the caudal portion of the esophagus, but the reason was
unclear (Arakawa et al., 2002).
Normal physiology of portal circulation

Portal pressure (P) - like pressure in any vascular bed - is determined
by the product of portal venous inflow (Q) and the vascular resistance (R)
to this flow, that is:
P=Q×R
The normal hepatic blood flow is about 1.5 L/min of which

approximately four-fifths is contributed by the portal vein. The portal
vein pressure ranges from 5 to 8 mmHg and that of the hepatic veins as
well as the inferior vena cava is approximately 1-2 mmHg. The pressure
gradient between the portal venous and hepatic outflow venous system is
thus approximately 4 mmHg. The hepatic microcirculation is peculiar in
that the ratio of pre-to-post sinusoidal resistance is about 49: 1, in contrast
to that seen in skeletal muscle, where the pre- to post-capillary resistance
ratio is 4:1. The high ratio in hepatic bed which translates into a lack of
outflow resistance at the level of sinusoids, is in fact a protective
mechanism considering the fact that the hepatic endothelium is
discontinuous and the wide pores between endothelial cells would favour
the exudation of plasma proteins if the post-capillary sphincter pressure
were to be high (Laut and Greenway, 1987). Another peculiarity of the
hepatic macrocirculation is the interrelationship between hepatic artery
and portal vein blood flow. A decrease in portal venous blood flow or
sinusoidal pressure, reflexly increases the hepatic arterial flow, thus
maintaining adequate perfusion of the lobule. This response is possibly
mediated by adenosine, which has a vasodilatory action. Conversely, an
7
increase in sinusoidal pressure decreases the hepatic arterial flow. The

hepatic arterial flow however, lacks the potential to cause changes in
portal venous flow in response to physiological or metabolic stimuli
(Arakawa et al., 2002).
Portal Hypertension
Definition
The normal portal venous pressure is 5-8 mmHg (or 7-14 cm water).
Portal hypertension is defined as a hepatic venous pressure gradient
(HVPG) of greater than 6 mmHg. Alternatively, a splenic pulp pressure
of more than 15 mmHg or a direct portal vein pressure of greater than 21
mmHg (or 30 cm water) at surgery also constitutes portal hypertension
(PHT) (Kapoor and Sarin, 2002) .
Classification
The classification of portal hypertension is based on the site of
increased resistance to portal flow.
The possible sites are:
• Pre-sinusoidal - extrahepatic.
- intrahepatic.
• Sinusoidal.
• Post-sinusoidal - extrahepatic.
- intrahepatic
1)Presinusoidal
a) Extrahepatic
- Portal vein thrombosis
8
b) Intrahepatic
- Schistosomiasis.
- Idiopathic portal hypertension.
- Congenital hepatic fibrosis.
- Granulomatous diseases (e.g. sarcoidosis).
- Felty’s syndrome.
- Arsenic poisoning.
- Primary biliary cirrhosis.
2) Sinusoidal
- Alcoholic cirrhosis.
- Non-alcoholic cirrhosis.
- Vitamin A intoxication.
- Nodular regenerative hyperplasia : pathogenesis probably is
obliterative venopathy. The presence of nodules that press on the
portal system also has been postulated to play a role, although
nodularity is present in most cases without clinical evidence of
portal hypertension.
3)Postsinusoidal
a) Extrahepatic
- Inferior vena cava (IVC) obstruction.
- Right sided heart failure.
- Constrictive pericarditis .
- Tricuspid regurgitation.
- Budd Chiari syndrome.
- Congenital web.
b) Intrahepatic
- Veno-occlusive disease.
- Central hyaline sclerosis (alcoholic hepatitis).
As can be seen, a particular condition can contribute to portal
9
hypertension in more than one way and at more than one site. Apart from
the conditions enumerated, portal hypertension may rarely result from a
communication between a splanchnic artery to the portal venous system,
for example traumatic arterio venous fistula arising from splenic artery or
that between hepatic artery and portal vein (Kapoor and Sarin, 2002).
Pathophysiology and hemodynamics of portal

hypertension
From the equation P = Q × R, it is evident that the pathophysiology of
portal hypertension is dependent on two important factors :- vascular
resistance to portal blood flow (R) and blood flow in this bed (Q).
Changes in either (R) or (Q) affect the portal pressure. In most types of
portal hypertension, both the resistance to blood flow and the blood flow
are altered (Garcia-Tsao, 1999).
Hemodynamic factors in portal hypertension

1- Increased resistance to portal blood flow (‘initiator’)
a) Fixed component:
- Extrahepatic venous obstruction
- Intrahepatic fibrosis and ‘capillarization’ of sinusoids
- Vascular distortion by cirrhotic nodules, granulomas, etc.
b) Variable component:
- Hepatocyte swelling
- Stellate cell response (to endothelins, nitric oxide, endotoxins, etc)
- Stellate cell activation (alpha-actin levels and contractile state)
2 Increased portal blood flow (‘sustainer’)
- Nitric oxide synthase system
- Glucagon
10
- Prostaglandins
- Tumor necrosis factor-alpha
- Carbon monoxide
3 Collateral circulation.
1-Increased vascular resistance

As already mentioned, the major site of resistance within the portal
circulation is at the level of sinusoids. Increased resistance to portal
venous blood flow constitutes, the ‘backward’ component of portal
hypertension. This may result from a fixed component that is, distortion
of vascular anatomy by fibrotic septae separating cirrhotic nodules
(Popper et al., 1952) or by pericellular, perivenular fibrosis (Miyakawa et
al., 1985). Architectural derangements like ‘capillarization’ of sinusoids
(i.e. loss of fenestrae) and appearance of collagen in the Space of Disse
contribute to increased sinusoidal resistance (Orrego et al., 1981). More
significant however, are the variable factors which modulate the
intrahepatic vascular resistance. Portal flow may be obstructed by
compression of simusoids by swollen hepatocytes in alcoholics, even
before frank cirrhosis appears (Vidins et al., 1985). One of the important
reversible factors mediating vascular resistance may be endothelin-1 (ET-
1) (Stanley and Hayes, 1997). Two types of endothelin receptors have
been identified, ETA and ETB. The primary response mediated by ETA
is vasoconstriction (Rockey, 1997). Binding of endothelins to ETB
receptors on endothelial cells results in nitric oxide (NO) release and
smooth muscle relaxation, while action on ETB receptors on vascular
smooth muscle cells causes vasoconstriction. The production and actions
of endothelins in liver are diagrammatically represented in Fig (3). The
liver’s response to chronic injury of any kind is one of scarring and
fibrosis and the principal cell type responsible for fibrogenesis is the
11
stellate cell (Friedman, 1993). The stellate cells, when activated show
high expression of alfa actin and assume the shape of myofibroblasts. In
response to endothelins, these cells can contract and thus mediate
increased resistance to blood flow (Ballardini et al., 1988).
2-Increased portal blood flow and the hyperdynamic systemic

circulation:
Almost a decade ago, it was proposed that peripheral arterial
vasodilation was an important event contributing to the ‘maintenance’ of
portal hypertension. The increased splanchnic flow resulting from this
peripheral vasodilatation constitutes the ‘forward’ component of portal
hypertension. One of the first vasodilatory mediators studied in portal
hypertension was glucagon. It - however - became clear that it accounts
for only about 30% of the splanchnic vasodilation (Pak and Lee, 1994).
The production of prostacyclin is increased in experimental PHT and in
patients with chronic liver disease (Sitzmann et al., 1991).
Administration of the cyclo-oxygenase inhibitor indomethacin improves
the hyperdynamic circulation of cirrhosis, as well as improving the
vascular hyporesponsiveness of these subjects to vasoconstrictors like
nonrepinephrine. Treatment with indomethacin leads to a significant
decrease in superior mesenteric artery blood flow in cirrhotics (Roberts
and Kamath, 1999).
Recently, nitric oxide (NO) has received great attention as a peripheral

vasodilator agent in cirrhosis. The main factors favoring the role of NO
are:
i. Reduced vasopressor response to vasoconstrictors in cirrhotics is
reversed by inhibition of nitric oxide synthase (NOS) or endothelial
denudation (Claria et al., 1994).
12
ii. High concentration of cyclic guanosine monophosphate (c-GMP),

an intracellular mesenger of NO in aortic tissue from cirrhotic rats,
which is reduced by NOS inhibitors (Neiderberger et al., 1995).
iii. Normalization of arterial pressure, cardiac index and total systemic
vascular resistance that is, the hyperdynamicity of portal
hypertension on administration of NOS inhibitors.
Two types of NOS exist, the eNOS (endothelial or constitutive) and

the iNOS (inducible). The former is calcium dependent and membrane
associated and is rapidly activated by changes in local blood flow and
circulating hormones. Histochemical staining of liver shows increased
eNOS levels in portal hypertension, but it is not known with certainity
whether the increase is actually the result of increased splanchnic blood
flow and shear stress seen in portal hypertension (Shah et al., 1998). The
levels of eNOS are decreased by sepsis, while those of iNOS are
increased by lipopolysaccharide (LPS), interleukin-1 and tumor necrosis
factor alpha (TNF-α). Indeed, the iNOS levels are high even at the stage
of pre-ascitic cirrhosis and probably these cytokines are responsible for
this (Pierre-Yves et al., 1998). Increased NO levels in portal hypertension
are in part responsible for the hyporesponsiveness of mesenteric
vasculature to vasoconstrictive stimuli like alpha adrenergic agonists as
methoxamine. This is partly mediated by c-GMP as administration of
NOS inhibitors only partially restores this responsiveness. However, if
potassium channel blockers like tetraethylammonium are co-administered
with NOS inhibitors, this vasoconstrictor responsiveness is completely
restored (Atucha et al., 1998). It has also been recently shown that agents
which increase the entry of extracellular calcium into arterial smooth
muscle cells may decrease cirrhosis induced vasodilation and also reduce
the hyperdynamicity of portal hypertension (Moreau et al., 1998).
13
Studies have recently focused on carbon monoxide (CO) as a regulator of

stellate cell contractility and simusoidal blood flow. Carbon monoxide,
which is derived from degradation of heme by heme oxygenase, is not as
potent as NO in stimulating c-GMP synthesis and causing smooth muscle
relaxation. Also, CO may inhibit NO mediated c-GMP production, thus
countering the relaxing effect of NO.
Fig (3): Regulation of vascular tone by endothelins and nitric oxide.

Endothelin (ET) acts on vascular smooth muscle (VSM) ETA receptors to
induce smooth muscle contraction (left) and on endothelial cells (ETB) to
stimulate endothelial nitric oxide synthase (eNOS) which in turn leads to VSM
relaxation (right) through its second-messenger –cGMP. Inducible NOS is
stimulated by interferon gamma, lipopolysaccharide and TNF alpha- the stimuli
which inhibit eNOS (Kapoor and Sarin, 2002).
3- Collateral circulation:
Beyond a critical value of portal pressure, an attempt is made by the

body to dissipate further increase in the portal pressure, by formation of
portosystemic collaterals. In alcoholic cirrhosis, and HVPG of ≥ 12
mmHg appears to be necessary for the development of esophagogastric
varices (Garcia-Tsao et al., 1985).
14
Fig (4): Schematic representation of portosystemtic collaterals. Arrows reflect

the direction of blood flow which is reversed in the coronary vein (CV) and the
inferior mesenteric vein (IMV) leading to esophagogastric and anorectal
varices. There is resumption of flow in the obliterated paraumbilical vein
(PUV) which forms the abdominal “caput”. SMV, superior mesenteric vein,
SG, short gastric collaterals; LRA, leino-renal adrenal collaterals (Kapoor and
Sarin, 2002).
These collaterals (Fig 4) are, in fact, a system of resistance channels in

parallel with the portal venous system. The collaterals however, are not
passive conduits and respond reflexively and independently to various
hemodynamic and pharmacologic stimuli. The resistance to flow of blood
in these channels is governed by the Poiseuille’ Law:
R = 8η πr4
ηl/π
Where R = resistance, η = viscosity of fluid, l = length of the vessel

and r = radius of the vessel. As is evident, slight changes in the diameter
of the collateral can exquisitely alter the resistance to flow in the
collateral and this fundamental is made use of in managing portal
hypertension pharmacologically.
15
MANAGEMENT OF ESOPHAGEAL VARICES
Gastro-esophageal varices develop in 50% to 60% of cirrhotic patients

and approximately 30% of them will experience an episode of variceal
haemorrhage within 2 years of the diagnosis of the varices (Navarro et
al., 1969 and De Paulo et al., 2006).
Up to third to half of the patients with advanced liver disease and large
varices die after the first attack of variceal bleeding (Silverstein et al.,
1981).
Many factors contribute to the high mortality: torrential bleeding from
the varices causing blood loss and added hepatic ischaemia, compromised
hepatic functions, coagulopathy, infection and the time taken to control
the bleeding. Pharmacological therapy, endoscopic intervention, balloon
tamponade, surgical shunting and more recently, radiological treatment
have been part of the therapeutic protocol used to stop variceal bleeding
and to prevent recurrence and subsequent complications.
A multidisciplinary approach often depending on the patient's clinical
presentation and the optimal availability of the expertise and the
resources available decides the choice of treatment modalities.
Endoscopic management of variceal bleeding has unquestionably become
the main stay since its rapid evolution in the last two decades (De Paulo
et al., 2006).
Diagnosis of Varices
Endoscopy is the gold standard for the diagnosis of varices (LaBerge

et al., 1993).
Adequate air insufflations to the distal oesophagus are a must for
correct estimation of the variceal size.
16
Although esophageal varices are easy to detect, gastric varices may

some time pose difficulty in identification.
Linear array endoscopic ultrasound, contrast-enhanced computed
tomography scan, magnetic resonance angiography, transabdominal
ultrasound and examination have recently been added to the list of
investigation that has been used to locate the varices. Angiography can
also be used to identify varices. Angiography is usually performed when
severe upper gastrointestinal bleeding precludes adequate diagnostic
endoscopy (Woon Chang, 2006).
Treatment of esophageal varices
The treatment of esophageal varices includes the prevention of

variceal hemorrhage in patients who have never bled the treatment of the
acute bleeding episode and the prevention of rebleeding in patients who
had survived a bleeding episode from esophageal varices. An additional
scenario may come into practice: the ‘pre-primary’ prophylaxis or
treatment of compensated patients without varices in order to prevent the
development of varices (Woon Chang, 2006).
1. Pre-primery prophylaxis:
Studies to explore whether long-term therapy with nonselective beta-
blockers may prevent or delay the development of varices and other
complications of portal hypertension, such as ascites, in patients with
compensated cirrhosis have been prompted by the results of studies
showing that:
i. Development of portal systemic collaterals is significantly
lower in animals with experimental portal hypertension
treated chronically with beta-blockers than in controls (Sarin
et al., 1991).
17
ii. In patients with cirrhosis, varices decreased in size and may

eventually disappear when hepatic venous pressure gradient
(HVPG) is reduced below 12mmHg (Casado et al., 1998).
iii. The hepatic venous pressure gradient (HVPG) reduction
achieved by non-selective beta-blockers is significantly
greater in patients without varices than in those who already
have developed esophageal varices, and most achieve or
maintain a HVPG below 12mmHg (Abraldes and Bosch,
2002b).
2. Primary prevention
Continued propranolol or nadolol therapy markedly reduces the

bleeding risk, from 25% with non-active treatment to 15% with beta-
adrenergic blockers (D’Amico and Luca, 1997). Therapy with beta-
adrenergic blockers should be maintained indefinitely, because when
these are withdrawn the risk of variceal hemorrhage returns to what
would be expected in an untreated population. Moreover, it seems that
patients who discontinue beta-adrenergic blockers experience increased
mortality compared with an untreated population (Abraczinskas et al.,
2001). Variceal banding ligation is the only effective alternative for
primary prophylaxis, but its use should be restricted to patients with large
varices and intolerance or contraindications to beta-adrenergic blockers
(Garcia-Pagan, 2002).
Soliman (2003) concluded that endoscopic ligation of the varices is
safe and more effective than propranolol for the primary prophylaxis of
variceal bleeding in patients with cirrhosis complicated by esophageal
varices at high risk for bleeding.
Sarin S.K. et al., (1999) randomly assigned the two treatments to 89
patients with varices of more than 5 mm in diameter that were at high risk
18
for bleeding. 44 patients received propranolol at a dose sufficient to

reduce baseline heart rate by 25%; 45 patients had varices ligated until
they were either obliterated or too small to ligate. After 18 months, the
cumulative probability of variceal bleeding was 43% in the propranolol
group and 15% in the ligation group.
Endoscopic sclerotherapy is not indicated for the prevention of first

variceal haemorrhage in cirrhotic patients. More than 20 trials have
studied this issue enrolling in excess of 1000 patients. The trial protocols
were extremely heterogeneous, variceal size varied considerably, and
only one required a HVPG of greater than 12 mm Hg (Woon Chang,
2006).
Sclerotherapy technique also varied, with a variety of sclerosants in

different doses injected intravariceally or perivariceally or both. Although
some early trials showed a reduction in bleeding in the sclerotherapy
group, more recent and larger trials have shown either no value or a
deleterious effect of sclerotherapy (McCormick and Burroughs, 1992).
3. Treatment of acute variceal bleeding:
GENERAL MANAGEMENT
Large bore intravenous access is necessary to allow rapid transfusion

if required. Initial fluid resuscitation should be titrated to restore the
systolic blood pressure to 80 or 90 mm Hg, further fluid requirements
should aim to maintain haemoglobin at 100 g/I and urine output above 30
ml/hour. Overly aggressive fluid replacement should be avoided as
overfilling may increase portal pressure leading to rebleeding (Woon
Chan, 2006).
19
Drug therapy still improves the results of endoscopic treatment even if

started just after sclerotherapy or band ligation (Corley et al., 2001).
Terlipressin, somatostatin, octreotide or vapreotide are the drugs of
choice (Abraldes and Bosch, 2002a). If these drugs are not available,
vasopressin plus transdermal nitroglycerin is an acceptable option.
Pulmonary aspiration of blood or gastic secretions is common due to

the combination of encephalopathy and impaired consciousness due to
shock. In patients with significantly reduced conscious state early
endotracheal intubation is mandatory.
Bacterial infection complicates variceal haemorrhage in cirrhosis in up

to 66% of patients. A recent meta-analysis has demonstrated that short
term prophylactic antibiotics significantly reduces the incidence of
infection and increases short term survival (Bernard et al., 1999).
Prophylactic antibiotics therefore, should be routinely used in all patients
for seven days after admission for variceal haemorrhage.
ENDOSCOPIC MANAGEMENT
In the acute bleeding episode, either sclerotherapy or band ligation

may be used (De Franchis and Primignani, 1999).
Failures of medical therapy (drugs plus endoscopic therapy) should
undergo a second course of endoscopic therapy before proceeding to
transjugular intrahepatic portosystemic shunt (TIPS) or, in rare occasions,
to portosystemic shunt surgery. Administration of recombinant activated
factor VII may decrease the number of treatment failures among patients
with advanced liver failure (Child-Pugh class B and C) (Abraldes et al.,
2004).
20
4.Prevention of recurrent bleeding from esophageal varices
First-line treatments
Both pharmacological treatment and endoscopic therapy are
accepted first-line treatments to prevent rebleeding (Bosch et al., 2003).
a) Pharmacologic Therapy
1- Nonselective beta-blockers (NSBBs):

NSBBs (e.g. propranolol and nadolol) have been extensively
evaluated for the prevention of variceal bleeding in randomized
controlled trials. These agents decrease the splanchnic blood flow
by means of reduction of cardiac output and unopposed splanchnic
arterial vasoconstriction by blocking beta 2-receptors. They also
have a direct effect on portocollateral resistance, decreasing azygos
and gastroesophageal collateral blood flow. The effect of
propranolol on hepatic venous pressure gradient HVPG is moderate
(mean reduction, 12% to 16%), and is achieved in about one third
to one half of treated patients (El-Sayed et al., 1996 and Garcia-
Pagan et al., 1999).
2- Nitrates
Isosorbide dinitrate and, most commonly, isosorbide
mononitrate [ISMN] have been shown to reduce portal pressure by
selective venodilation in the splanchnic circulation, via promoting
reflex splanchnic vasoconstriction as a response to reduced mean
arterial and cardiac filling pressures, and also by reducing
intrahepatic resistance (Navasa et al., 1989, Hamed et al., 1998
and Abraldes et al., 2004). The latter effect may be mediated by
relaxation of myofibroblasts and activated stellate cells. However,
21
it is well known that patients with advanced cirrhosis have marked

vasodilatation and that the fall in arterial pressure and hepatic
blood flow, together with the reduction of preload and cardiac
output caused by nitrates, may have deleterious effects, including
the deterioration of renal function (Moreau and Lebrec, 1990).
Thus, nitrates should not be used on their own as therapy for portal
hypertension (Mela et al., 2003).
b) Endoscopic Therapy:
This treatment does not decrease portal pressure and therefore has no
effect on other complications of portal hypertension (Bosch et al., 2003).
1. Endoscopic sclerotherapy (EST):
EST was established during the past decade as a cornerstone treatment

for the prevention of recurrent esophageal variceal hemorrhage. EST
involves injecting a sclerosant material that subsequently results in
variceal thrombosis and scarring. It is performed every 10-14 days until
the varices are eradicated, which usually takes 5 or 6 sessions (El-
Ghawalby & Yassin, 1986; El-Zayadi et al., 1988 and El-Sayed et al.,
1996). After obliteration, varices tend to recur over time in 50% to 70%
of individuals. Such varices are at risk of rebleeding, and surveillance
endoscopy must be performed, initially at 6-month and later at 1-year
intervals (Waked and Korula, 1997).
Complications:
Each EST session can cause local or systemic complications. These
complications are greater with paravariceal than intravariceal injection.
Almost every patient will experience fever, dysphagia and chest pain.
This is usually transient. Bleeding is not usually from the puncture site
22
but from remaining varices or deep ulcers that have opened in

submucosal channels. Rebleeding takes place in about 30% of patients
before the varices have been obliterated (El-Sayed et al., 1996). Further
sclerotherapy is indicated if the haemorrhage comes from varices. If from
an ulcer, omeproazole is the drug of choice (Gimson et al., 1990).
Superficial ulcers resulting from tissue necrosis is the most common

complication (70% at 1 week), with stricture formation representing the
most significant long-term complication (Kahn et al., 1989). Esophageal
stricture may be related to chemical esophagitis, ulceration and acid
reflux. Esophageal dilatations are usually successful, but occasionally
surgery becomes necessary (Taibibian and Graham, 1987).
Perforation occurs in about 0-5% of cases and is usually delayed 5-7

days. It may be an extension of the ulcerative process (Pasricha et al.,
1994).
Pulmonary complications include chest pain, aspiration pneumonia

and mediastinitis (Badra, 1990 and Baydur and Korula, 1990).
Pleural effusions are found in 50% of cases (Azzam et al., 1990).

Sclerotherapy is followed, one day later, by a restrictive defect in
respiratory function possibly due to sclerosant embolization in the lungs
(Samules et al., 1994).
Pyrexia is frequent and significant bacteremia may occur. Bacterial

peritonitis may follow injection sclerotherapy (Hamed et al., 1999 and
Sherlock & Dooley, 2002).
Portal vein thrombosis complicates 36% of the patients treated with

sclerotherapy. This may be important if subsequent shunt or liver
transplantation is required. Varices at other sites including the stomach,
ano-rectal area increase in size. Other recorded complications are cardiac
23
tamponade, pericarditis and brain abscess (Sherlock and Dolley, 2002).
2. Endoscopic variceal band ligation (EVL):
EVL is highly effective in obliterating varices. An elastic band is used

to strangulate the superficial varix, resulting in thrombosis,
inflammation, necrosis, and sloughing of the mucosa and mural scar
formation up to, but not including, the muscularis propria .Similarly to
sclerotherapy, ligation is performed every 10-14 days until the varices
are eradicated, which typically requires 3 or 4 sessions, i.e. fewer than
with sclerotherapy (Farag et al., 1998).
Complications
Endoscopic variceal band ligation is generally associated with fewer

complications than sclerotherapy. Minor complications such as transient
dysphagia and chest discomfort are not uncommon. Shallow ulcers at the
site of each ligation are the rule and rarely bleed (Stiegmann and
Yamamoto, 1992).
The most worrisome complication is bleeding due to untimely

sloughing of bands caused by inadvertent contact with the endosocpe
during follow-up endoscopy (Battaglia et al., 1996).
Second line treatments

Patients experiencing a significant episode of rebleeding while treated
with beta-adrenergic blockers ± isosorbide mononitrate (ISMN) or
endoscopic therapy should be considered for `rescue' derivative therapies.
Both TIPS and surgical shunts are very effective in preventing rebleeding
(Burroughs and Patch, 1999), but surgical shunts, preferably an H-graft
24
or a distal splenorenal shunt, should only be offered to patients with good

liver function (Child A class) in centers with qualified surgeons.
Liver transplantation is a definitive treatment for patients with

advanced liver disease who have bled and should be considered in all
such patients (Russel et al., 2003).
TIPS, unlike surgical shunts, does not seem to compromise

subsequent transplant surgery and has been used as bridging therapy to
liver transplantation in patients who have bled (Woon Chang, 2006).
Prevention consolidation therapy (mucosal-fibrosis

therapy) of esophageal varices using argon plasma
coagulation (APC)
Endoscopic injection sclerotherapy (EST) has been established as the
cornerstone for the prevention of recurrence of esophageal variceal and
rebleeding. It should be performed at 10-14 days intervals until the
varices are eradicated, which usually takes 5 or 6 sessions (El-Ghawalby
& Yassin, 1986; El-Zayadi et al., 1988 and El-Sayed et al., 1996).
However, recurrence of varices occurs in 41.7% of patients within one

year of obliteration, whereas rebleeding occurs in 15.6% of patients
within one year of obliteration (Krige, 2000 and Madonia et al., 2000).
In view of this unacceptably high rate of recurrence, the availability of
other supplemental prevention consolidation therapies has been earnestly
desired (Furukawa et al., 2002). Mucosal-fibrosis therapy has been
reported as being ideally suited for this purpose. There are several
different techniques for achieving mucosal fibrosis therapy, but the most
common are perivariceal injection of 1% polidocanol (Matsui et al.,
2004) and thermal coagulation of the esophageal mucosa using Nd/Yag
25
laser, high frequency coagulation, microwave coagulation (Obara et al.,

1994) or - recently- argon plasma coagulation.
Since argon plasma coagulation is theoretically well suited for

mucosal fibrosis therapy, it can be used for the complete elimination of
esophageal varices and for fibrosis of the distal esophageal mucosa
(Nakamura et al., 2001).
Watanabe et al. (2001) and Furukawa et al. (2002) demonstrated that

argon plasma coagulation is an effective prevention consolidation therapy
after endoscopic variceal band ligation (EVL) or sclerotherapy without
serious complications.
Matsui et al. (2004) compared argon plasma coagulation and

paravariceal injection sclerotherapy with 1% polidocanol as a mucosa-
fibrosing therapy for esophageal varices. They concluded that the one and
three-year cumulative recurrence-free rate in the APC group is higher
than those in the 1% polidocanol group.
26
Argon plasma coagulation (APC)
Introduction
The argon plasma coagulation (APC) is a non-contact method of
delivering high-frequency monopolar current through ionized and
electrically conductive argon gas, which is called argon plasma (Frank et
al., 2006). It was originally developed for use in open surgery (Brand et
al., 1990). It has also been used at laparoscopy (Daniell et al., 1993) and
thoracoscopy (Lewis et al., 1993).
APC was adapted for use in flexible endoscopy in 1991 and has many
potential applications in therapeutic endoscopy (Farin et al., 1994)
including ablative and palliative treatment of esophageal, gastric, and
colonic tumors, hemostatic electrocoagulation of angiodysplastic lesions
and peptic ulcers, and the mucosal ablation of Barrett's esophagus
(Sumiyama et al., 2006).
Argon gas is passed through a coagulation probe with an electrode at

its tip. The electrode is activated by means of a foot switch and
electrosurgery frequency current passes through the argon cloud, ionizing
it, enabling it to conduct a spark to the nearest point of contact with
tissue. The circuit is completed by means of a return electrode plate on
the patient.
Physical principle
APC is a noncontact electrocoagulation device that uses high-
frequency (HF) monopolar current conducted to target tissues through
ionized argon gas (argon plasma). Electrons flow through a channel of
electrically activated, ionized argon gas from the probe electrode to the
27
targeted tissue. Current density on arrival at the tissue surface causes

coagulation.
Coagulation depth is dependent on the generator power setting, flow
rate of the argon gas, duration of application, and distance of the probe tip
to the target tissue (Watson et al., 2000).
In contrast to other high frequency (HF) techniques, the HF current is
not conducted to the target tissue via monopolar, bipolar or multipolar
active electrodes in direct contact, but via ionized and thus electrically
conductive argon (which is called "argon plasma").
The argon arc contacts tissue closest to the electrode allowing for
en-face or tangential coagulation. With thermal coagulation of tissue, a
thin, superficial, electrically insulating zone of desiccation and a steam
layer (from the boiling of tissue) result, both contributing to limit
carbonization and depth of coagulation (Farin et al., 1994). The
insulating zone of desiccation produces increased electrical resistance in
the treated area. This prompts the current to move to another point on the
tissue surface where resistance is lower (Grund et al., 1998).
In addition, APC does not cause carbonization or vaporization and
therefore does not generate smoke, so it is well suited for endoscopic
application.
Equipment
Components of the APC equipment for endoscopy include a high-
frequency monopolar electrosurgical generator, argon gas source, gas
flow meter, flexible delivery catheters, foot activation switch, and
grounding pads.
The disposable probes consist of a Teflon tube coupled to a ceramic
nozzle housing a tungsten monopolar electrode. The probes are available
in two diameters (2.3 or 3.2 mm) and lengths (220 or 440 cm for the 2.3
28
mm probe, and 220 cm for the 3.2 mm probe). Nozzle orientation

includes a location at the tip of the catheter as well on the side of the
catheter tip, 90 degrees from the longitudinal axis of the probe.
The current generators can deliver between 5000 and 6500 V. Gas
flow settings can be adjusted between 0.5 L/min to 7 L/min. Power
adjustments can be made between 0 and 155 W.
Upon activation of the APC system via a foot switch that synchronizes
the delivery of the electrical current and argon gas, the argon becomes
ionized, thus allowing for current application to the target tissue. The
ionized argon gas contacts the tissue closest to the probe, which allows
for either en-face or tangential application.
Coagulation depth is a function of the power generator setting, the
distance from the target tissue, and the duration of the application
(Watson et al., 2000).
Generally, the zone of coagulation is 1 to 3 mm. The physical
properties of the incident tissue also may play a role in determining the
depth of tissue injury. By using fresh surgical specimens, Watson et al.,
(2000) found the depth of tissue injury in gastric tissue to be a function of
the power setting and pulse duration. In esophageal specimens, there was
only a marginal relationship between the depth of tissue injury with pulse
duration and no relationship to the power setting. Three zones of tissue
effect are encountered. The desiccation zone is located at the point of
current contact with the incident tissue; deeper layers of tissue effect
include a coagulation zone and devitalization zone.
Technique
The device settings used have varied by manufacturer, indications, and
study protocols. In vitro APC experiments demonstrated that depth and
diameter of the coagulation zone increased with duration of application
29
and increase in power settings. In general, low power and low argon flow
rates are used for hemostasis of superficial vascular lesions whereas
higher output settings are used for the tissue ablation.
Recommended dosages of APC energy in practice are shown in table
(1). The recommended values in the table refer to the standard equipment:
ICC 200 or ICC 350, APC 300 and flexible APC probes, all
manufactured by ERBE Electromedizin, Tuebingen, Germany (Grund et
al., 1999).
Table (1) Setting of argon plasma coagulation (APC) parameters

(Grund et al, 1999)
Power Activation time

Target tissue limitation(setting) (seconds)
(W)
Normal settings of oesophagus, 60 - 80 1-3
duodenum, small bowel and rectum
Stomach 60 - 80 1-3
Stent in / Overgrowth 60 3-5
Large tumour (diameter > 15 mm) 99 3-10
Medium sized tumour (diameter = 5-15 80 3-5
mm.)
Small tumours 60 1-5
Right colon 40 0.1-0.5
Remaining colon 40-50 1-3
Very high flow rates may result in prompt gaseous distention and
patient discomfort.
The operative distance between probe and tissue ranges from 2 to 8

mm. At low power settings, the probe tip must be close to - but not
touching - the tissue to allow the argon plasma to contact the targeted
tissue. The surface of the targeted tissue should be free of liquid
(including blood). If the surface is not clear, a coagulated film develops
leaving the tissue surface beneath inadequately treated. This limits use in
active hemorrhage. Surface fluids should be cleared by washing and
30
suctioning as necessary.
APC is performed with applications of 0.5 to 3 second duration
(Grund et al., 1994). A series of brief activations is superior to few
prolonged activations (Grund et al., 1999).
The probe tip can be directed to “paint” confluent or near-confluent
surface areas. A double channel endoscope allows concomitant aspiration
of the argon gas.
Precautions during endoscopic application of APC

- HF output power should be strictly limited according to the values
given in table (1)
- The ignition and electric arc must be properly tested outside the
endoscope before advancing the probe into the working channel.
- Tissue contact with the probe tip should be avoided during activation.
When the tip makes tissue contact, it functions as a contact monopolar
probe. Deep thermal injury will allow argon gas to flow into the
submucosa producing pneumatosis and even extraintestinal gas. The
dissected gas usually resorbes rapidly. However, this complication may
produce symptoms and may compromise the completeness of the
treatment session (Waye, 1999).
- When treating tissues in contact with metal implants such as stents,
current and/or power settings should be decreased accordingly.
- During application of APC to the target tissue, care should be taken to
avoid misdirection the plasma jet to the endoscope tip that could result
in damage to the video chip (Johanns et al., 1997).
- Aspiration should be done frequently during the procedure to avoid
overdistention with argon gas. In certain cases, such as treatment of
extensive GAVE, use of a double channel endoscope is helpful for
removal of the insufflated argon gas.
31
- Furthermore, care should be taken during application of APC in

patients with cardiac pacemakers since malfunction of those can occur,
as reported previously with conventional monopolar electrocoagulation
methods (Canard and Védrenne, 2001).
Clinical applications of argon plasma coagulation (APC)

The uses of the APC can be broadly categorized as hemostatic or ablative.
A. Hemostasis
Hemostasis represents one of the most important problems in
gastrointestinal endoscopy. Many different endoscopic methods have
been developed during the last 20 years (Soehandra et al., 1997),
resulting in revolution in treatment of different types of bleeding ( Table
2 ) (Grund et al., 1999) .No single method, however, covers all kinds and
sources of haemorrhage. All the currently used methods are insufficient
in the treatment of some difficult types of bleeding: diffuse bleeding
arising from large areas, bleeding as a result of coagulation disorders or
haemorrhage from a tumour which is diffuse and difficult to control (Lee
and Leiubermann, 1996).
To achieve hemostasis in these problematic lesions, argon plasma
coagulation (APC) was taken into consideration.
According to previous experience in open surgery, where APC has
proved to be an efficient method in the management of haemorrhage from
the liver, spleen or kidney, (Farin and Grund, 1994), the method was
modified to be applied in flexible endoscopy by developing flexible
probes and optimizing generators and gas sources (Grund et al., 1999).
32
Table (2) Conventional methods of haemostasis compared with argon

plasma coagulation (APC) in different types of haemorrhage
(Grund et al, 1999).
Rubber
Type of Clip Injection Heater Nd:YAG APC
band Sclerosants
bleeding techniques probe laser
ligation
Peptic ulcer
(visible vessel)
Spurting + - + - ? ? -
Oozing ? - + - + ? +
Varices - + + + - - ?
Tumour - - + - ? + +
Post- ? ? + - ? ? +
intervention
Inflammation - - - - - ? +
Post- - - - - - + +
irradiation
Angiodysplasia ? - + + ? ? +
Coagulation - - - - - ? +
disorders
1.Vascular ectasia
The APC has been used successfully to treat vascular ectasia of the
upper and lower digestive tract including gastric antral vascular ectasia
syndrome (GAVE) (Nakamura et al., 2006) , sporadic angiodysplasia,
hemorrhagic telangiectasia, and radiation-induced enteropathy and
proctopathy (Johanns et al., 1997 Wahab et al., 1997, Casey, 2006 and
Kwan et al., 2006) .
Watermelon stomach or gastric antral vascular ectasia (GAVE) is an
uncommon source of G.I. blood loss, which typically presents with an
iron deficiency anemia. In one study, 17 patients with GAVE were treated
successfully with APC, achieving eradication in 1 to 4 treatment sessions
(Probst et al., 2003). Over a mean follow-up of 30.4 months, recurrent
GAVE occurred in 5 patients requiring further treatment.
33
Five retrospective studies evaluated 78 patients with radiation

proctopathy treated with APC (Silva et al., 1999 and Tam et al., 2000).
Using various definitions of success, all but 5 patients (94%) improved
after treatment with 8 to 28 months' follow-up. Recurrence of significant
bleeding was reported in 3 patients. Three patients experienced self-
limited anorectal pain after treatment, 2 developed chronic rectal ulcers,
and 2 developed strictures requiring rectal dilatation.
Successful APC therapy leads to the disappearance of these vascular

structures (Shudo et al., 2001). Typically, two to 3 sessions are required
to achieve ablation, with an improvement in haemoglobin level and
obviation of transfusion requirements that is seen in up to 85.7% of
patients. Seventeen patients, 65% of whom exhibited iron deficiency
anemia, were treated with the APC for up to 4 sessions (Probst et al.,
2003).
Resolution of GAVE was seen in all patients, which was associated
with an improvement in the Hb from 7.8 to 11.5 gm/dL. Over a mean
follow-up of 30.4 months, GAVE recurred in 29.4% of patients, requiring
further therapy. In a retrospective case series, a mean of 2.6 treatment
sessions were used to treat GAVE, resulting in a loss of transfusion
dependency (Yussoff et al., 2002). Over a mean follow-up period of 20
months, a 40% recurrence rate was noted, which responded to further
APC therapy.
Arteriovenous malformations (AVM) of the stomach, the small bowel,
and the colon have been successfully treated .In a case series of 25
patients, the APC was successfully used to treat AVMs, with a significant
improvement in hemoglobin values and cessation of overt bleeding
(Rochalon et al., 2000). An eight percent recurrence rate of anemia was
noted over a 6-month follow-up period.
34
The combination of 1% polidocanol and the APC has been used to

successfully ablate gastric AVMs in a patient with Osler-Weber-Rendu
disease (Kitamura et al., 2001).
Asymptomatic accumulation of submucosal argon gas at the treatment
site also has been noted (Johanns et al., 1997).
Cecal perforation has been reported by Wahab et al., (1997). The
utility of obtaining a submucosal saline solution cushion before APC
therapy to prevent deep tissue injury has been demonstrated in a porcine
model (Norton et al., 2002a).
2. Treatment of bleeding peptic ulcers and the prevention of

recurrent esophageal varices :
In a small randomized controlled trial, the APC was compared with

the heat probe in 41 patients presenting with peptic ulcer disease with
major stigmata of recent hemorrhage, including active bleeding or a non-
bleeding visible vessel (Cipolletta et al., 1998).
The groups were well-matched for clinical criteria such as active
bleeding and hypotension. Both APC and heat probe were similar in
clinical outcomes such as initial hemostasis, recurrent bleeding, 30-day
mortality, and the need for emergency surgery. It must be emphasized
that a treatment difference may have been present but could not be
detected because of the small sample size (i.e. type II error).
Cipolletta et al., (2003) explored the utility of APC in the prevention of
recurrent esophageal varices after ablation with endoscopic band ligation.
In this interim analysis of an ongoing randomized controlled trial, patients
receiving APC exhibited a lower recurrence rate (0/14 APC vs. 6/16
controls). Transient fever, retrosternal pain, and dysphagia were seen in
the APC group.
35
Watanabe et al., (2001) and Furukawa et al., (2002) demonstrated

that argon plasma coagulation is an effective prevention consolidation
therapy after esophageal variceal ligation (EVL) or sclerotherapy with no
serious complications.
In a larger study, Nakamura et al., (2001) randomized 60 patients to

endoscopic variceal ligation (EVL) or EVL followed by APC (50-60 W,
1.5-2.0 L/min). Patients receiving argon plasma coagulation also were
treated with sodium alginate and thrombin granules. The cumulative
recurrence-free rate of variceal formation at 24 months was significantly
higher in the EVL/APC group than in patients receiving EVL
monotherapy (74.2% vs. 49.6%). The complication profiles were
equivalent except for significantly more episodes of post-treatment fever
in the group receiving combination therapy (63.3% vs. 33.3%).
3. Radiation proctopathy
Many case series have been published on the use of APC in the
treatment of radiation-induced proctopathy (Kaassis et al., 2000 and
Venkatesh et al., 2002). Power settings vary from 40 to 60 W, with gas
flows from 1 to 1.5 L/ min.
The majority of patients achieved symptomatic improvement after
approximately two treatment sessions. The number of treatment sessions
has been found to significantly correlate with the extent of the
proctopathy (Tjandra et al., 2001).
Relief from transfusion dependency was seen in 34 of 35 patients
(97.1%). No prospective comparative trials of the argon plasma
coagulation with other endoscopically directed treatment modalities exist,
nor is there any experience on the role of adjuvant medical therapy such
as the use of steroids, sucralfate or 5-aminosalicylic acid enemas between
APC sessions. Experience from the forementioned series indicates that
36
APC is a good “rescue” therapy in patients who have failed Nd:YAG

laser, multipolar coagulation, heat probe therapy, and endoscopic
formalin therapy (Silva et al., 1999 and Venkatesh et al., 2002).
APC should not be used in an inadequately evacuated colon for fear of
explosion (Soussan et al., 2003).
Villavincencio et al., (2002) compiled the most complete complication
profile of APC in treatment of radiation-induced proctopathy. Short-term
side effects occurred in 19% of patients and included tenesmus,
abdominal distention, and anisimus. A 19% long-term complication rate
included tenesmus, diarrhea, and rectal pain, which can persist for a
median of 2.5 months after argon plasma coagulation. Anismus may be
more common in patients who undergo treatment near the dentate line
(Silva et al., 1999). Transient urinary retention also has been reported
(Venkatesh et al., 2002). More serious reported complications include
rectovaginal fistula formation (Silva et al., 1999) and rectal strictures
requiring dilation (Tam et al., 2000). Gram negative bacteremia has been
reported in two patients with a myelodysplastic syndrome who did not
receive preprocedure antibiotics (Tam et al., 2000).
Kaassis et al., (2000) found that patients who were receiving
anticoagulation therapy may require more argon plasma coagulation
sessions but can achieve an equivalent clinical response as those who are
not on anticoagulation. Recurrent proctopathy has been reported and
responds to a second round of APC therapy.
4. Dieulafoy's lesions
Dieulafoy’s lesion is an uncommon cause of gastrointestinal bleeding

in which significant, and often recurrent, haemorrhage occurs from a
pinpoint non-ulcerated arterial lesion, usually high in the gastric fundus.
Similar lesions have also been identified in the distal esophagus, small
37
intestine, colon, and rectum. It has been identified more frequently in

recent years because of increased awareness of the condition (Al-Mishlab
et al., 1999).
Yoshino and his colleagues (2006) and Yarze (2006) successfully

used argon plasma coagulation in the management of gastrointestinal
bleeding originating from Dieulafoy lesions.
B. Ablation
1. Barrett's esophagus
Controversy surrounds endoscopic ablative therapy for Barrett's
epithelium. The possibility of residual nests of metaplastic cells
underneath the layer of neosquamous epithelium remains a concern.
As in other ablative modalities, variables to be considered in the
treatment of Barrett's esophagus include:
1. Length of the Barrett's segment.

2. Acid suppressive regimen—dosage and documentation of
success.
3. APC settings.
4. Treatment pattern.
5. Post-treatment surveillance.
The argon plasma coagulation wattage settings varied from 30 to 90

W. All the studies used acid suppression during the ablation interval, but
only two of them used 24-hour pH probe monitoring to document
efficacy of the treatment (Van Laethem et al., 1998, Basu et al., 2002
and Kenneth and Richard, 2006).
In a subset of 20 patients undergoing pH monitoring, Van Laethem et
al, (1998) did not find a significant difference in the eradication rates
38
between those with documented normalization of esophageal acid

exposure. When combining the case series, complete macroscopic
clearance of Barrett's epithelium was achieved in 82.6% of the patients.
However, microscopic foci of subepithelial Barrett's epithelium were
found in up to 50% of patients who achieved macroscopic clearance.
Transient complications included fever, odynophagia, and chest pain.
The data also suggests that it is more difficult to achieve complete

ablation in longer Barrett's (Mork et al., 1998 and Van Laethem et al.,
1998). Longer length Barrett's segments also were associated with a
significantly higher rate of complications (Pereira-Lima et al., 2000).
Four of the case series reported stricture formation that occurred in
4.3% to 10% of patients (Mork et al., 1998, Schulz et al., 2000 and
Tigges et al., 2001).
The development of intramucosal adenocarcinoma arising under
neosquamous epithelium has been documented despite achieving
macroscopic and apparent microscopic clearance (Van Laethem et al.,
2001).
Basu et al., (2002) treated 50 patients with a median Barrett's segment
length of 5.9 cm. In each case, a 24-hour pH probe was used to optimize
acid suppression. Thirty-four patients exhibited macroscopic clearance of
Barrett's epithelium. However 15 of these patients exhibited nests of
Barrett's epithelium underneath the neosquamous epithelial layer. Patients
with longer Barrett's segments were more likely to have residual
metaplastic epithelium after argon plasma coagulation therapy. Those
patients who reduced their dose of a proton pump inhibitor exhibited a
significantly greater rate of Barrett's recurrence. The post-treatment use of
acid suppression may be crucial in maintaining the “histologic remission”
of Barrett's epithelium (Mork et al., 1998).
39
Control of symptomatic reflux also may aid in the decrease in the

Barrett's surface area during APC ablation (Byrne et al., 1998).
Morino et al., (2003) performed laparoscopic Nissen fundoplication
followed by argon plasma coagulation therapy in 23 patients. A 24-hour
pH probe study 3 months after surgical intervention was used to
document normalization of acid exposure before APC treatment.
Complete macroscopic clearance was achieved in 20 (87%) patients. An
additional two patients were found to have islands of Barrett's epithelium
underneath the neosquamous epithelium. In one patient with an abnormal
postoperative 24-hour pH probe study, acid suppressive therapy with
omeprazole was used with APC therapy, resulting in complete squamous
re-epithelialization.
In a different study, 30 patients with Barrett's esophagus underwent
either a Nissen or Toupet fundoplication after APC ablation (Tigges et
al., 2001). In this series, 22 of the 30 patients had been followed for at
least 1 year. Two of 22 patients at 1 year exhibited histologically proven
short-segment Barrett's epithelium. Both of these patients had abnormal
pH and manometric studies, which suggested a failure of the
fundoplication. No subepithelial nests of metaplastic cells were identified
in the surveillance biopsy specimens.
The clinical outcomes of argon plasma coagulation in the treatment of

Barrett's esophagus with high-grade dysplasia or carcinoma in situ in
Barrett's esophagus are variable. Pereira-Lima et al., (2000) treated 14
patients with low-grade dysplasia and one with high-grade dysplasia by
using APC. After a mean follow-up of 10.6 months, there was no
microscopic recurrence of dysplastic lesions or progression to
malignancy. Another study evaluated APC treatment of high-grade
dysplasia or carcinoma in situ in 10 patients who were either not
40
candidates for surgery or refused operative intervention (Van Laethem et

al., 2001).Even though there was visual evidence of complete re-
epithelialization, 50% of patients had subepithelial nests of metaplastic
tissue. One patient exhibited a persistent focus of high-grade dysplasia,
and another patient with high-grade dysplasia developed invasive
adenocarcinoma.
2. Polyps and remnant adenomatous tissue after polypectomy

Two case series describe the use of APC for ablation of intestinal
polyps as well as for ablation of residual adenomatous tissue after gastric
and colonic polypectomy (Farin et al., 1994 and Fukami et al., 2006).
The utility of APC for the eradication of postpolypectomy residual

adenomatous tissue was described in a series of 30 patients with residual
adenomatous tissue after endoscopic polypectomy, 15 had complete
eradication after one APC session and all had complete eradication after
two sessions (Zlatanic et al., 1999).
3. Management of gastrointestinal malignancies :
a. Treatment of early gastric cancer:

In recent years, there has been an increasing number of cases of early
gastric cancer (T1, NX) with intramucosal invasion, which are untreatable
by surgical or endoscopic mucosal resection (EMR) because of their high
risk.
Sagawa et al., (2003) proved that argon plasma coagulation (APC) is
an effective and safe modality for treatment of early gastric cancer with
intramucosal invasion untreatable by surgical resection or EMR. They
used an argon gas flow of 2 L. /min. at a power setting of 60 W. and a
maximum irradiation time of 15 s/ sq.cm.
41
All lesions were irradiated easily, including difficult anatomical areas for
EMR such as the gastric cardia or the posterior wall of the upper gastric
body. In 26 of 27 patients (96%) there was no evidence of recurrence
during the follow up period (median 30 months).
b. Palliative debulking of obstructing G.I. malignancies

The APC has been used alone or in combination with other treatment
modalities in the palliation of esophageal, gastric, ampullary, and rectal
malignancies (Douglas and Todd, 2006).
Wahab et al., (1997) used the argon plasma coagulation in the
palliation of various obstructing G.I. malignancies. In 34 patients, APC
was used in concert with monopolar snare coagulation with or without
radiotherapy. The majority of the patients presented with malignancies of
the esophagus or gastric cardia. Savary dilation was used in some cases.
A mean of 3.5 sessions was used to achieve luminal patency of the
esophagus. The APC also was used successfully in one case of an
obstructing carcinoma of the ampulla of Vater and 7 patients with
obstructive and/or bleeding rectal carcinoma. There were no perforations
or uncontrollable hemorrhage. Repeat therapy was successfully used in
those with recurrent obstructive symptoms.
Akhtar et al., (2000) treated 18 patients with esophagogastric cancer
with obstructive symptoms or bleeding by using a 70 W. power setting
and 2 L. /min gas flow. Palliation was successful in 14 (78%) patients.
In the largest case series to date, 83 patients with malignant strictures
of the esophagus and gastric cardia were treated. In 53 patients, patency
was maintained until death, whereas 30 patients eventually required stent
placement. A perforation rate of 8% was noted (Heindorff et al., 1998).
In two case series of 20 patients with recurrent dysphagia caused by
tumor overgrowth of a previously placed endoprosthesis, the APC
42
exhibited an 80% success rate in restoring luminal patency (Robertson et

al., 1996).
A transient accumulation of air in the mediastinum and/or peritoneal
cavity has been reported in the palliation of esophagogastric malignancies
(Johanns et al., 1997).
C. Miscellaneous
- Argon plasma coagulation has also been used to ablate dysplastic
heterotopic mucosa, to recanalize occluded or overgrown metal stents or
cut displaced metal stents. (Schulz et al., 2000, Demarquay et al., 2001
and Sauve et al., 2001).
- Mulder et al., (1999) reported on extensive experience in treating
patients with Zenker's diverticulum endoscopically. In the hands of these
authors, the APC is a very useful effective tool for this indication (125
patients, mean number of sessions 1.8), although a number of patients
were also treated with additional endoscopic methods.
- APC has also been used in skin surgery. In preliminary clinical tests,
48 patients with common warts, senile hemangiomas and actinic
keratoses were treated with APC. In all cases, APC was highly effective
and easy to perform. No severe problems or complications were
observed. The skin lesions were destroyed with minimal or no scarring
and without damaging the surrounding tissue (Brand et al., 1998).
-Tonsillectomy with the argon-plasma-coagulation-raspatorium leads
to an almost bloodfree woundground and to a reduction of operation-time.
The often associated extensive post operative pain and uncontrolled
tissue- damage, known from electrical and lasersurgical techniques, was
not found in APC-tonsillectomy patients-group (Bergler et al., 2000 and
Skinner et al., 2006).
43
The tissue effect of argon plasma coagulation on

esophageal and gastric mucosa
The APC tissue effect was studied on the esophageal and gastric
samples at 40, 50, 60, 70, 80, 90, and 99 W at 90 degrees, 1 mm.
separation using pulse durations of 1 and 3 seconds. Each combination of
power and pulse duration was tested in triplicate for each type of tissue.
Each individual tissue sample was large enough for approximately 30
different pulses of argon plasma coagulation. Tissue samples were fixed
in formalin/saline, routinely embedded in paraffin sections, and stained
with H&E. Samples were coded and analyzed by the histopathologist
without knowledge of the coding. A scoring system for depth of tissue
destruction was created, with a high score indicating increased tissue
damage (gastric 0 to 5, esophageal 0 to 3, full scoring system in table 4
and table 5) (Watson et al., 2000).
Deep tissue damage that could lead to perforation was rare with argon
plasma coagulation. The depth of gastric mucosal damage increased with
increased pulse duration and increasing power settings, and although the
depth of esophageal mucosal damage was marginally related to pulse
duration, it was not related to the power setting.
Esophageal and gastric tissues were analyzed separately because a
different scoring system was used to assess tissue damage.
44
Table (3) Scoring system for pathologic analysis of argon plasma

coagulation tissue effects on esophageal and gastric tissue
Esophageal tissue
0 None or minimal
1 Mucosa only
2 Damage extending to submucosa
3 Damage extending into muscularis
propria
Gastric tissue
0 None or minimal
1 Foveolar layer only
2 Damage extending to pit
3 Specialized glands affected
4 Lamina propria
5 Damage extending into muscularis
propria
The histologic effect consisted of coagulation necrosis that varied

from superficial cell damage to wedge-shaped defects. This was
associated with coagulation of the stroma in the mucosa and deeper
within the submucosa. Submucosal blood vessels did not appear to be
affected.
Effect of argon plasma coagulation on gastric tissue
Table (4) shows the probability of obtaining a particular gastric tissue

damage score for each combination of power and pulse duration.
45
Table (4): Gastric tissue damage score for different combinations of

pulse duration and power (Watson et al, 2000)
Power One-second pulse Three-seconds pulse

Setting Tissue damage score
(W)
0 1/2 3/4/5 0 1/2 3/4/5
40 0.05 0.27 0.67 0.27 0.49 0.24
50 0.08 0.33 0.59 0.34 0.48 0.19
60 0.11 0.39 0.51 0.41 0.44 0.14
70 0.13 0.43 0.43 0.50 0.40 0.11
80 0.18 0.47 0.35 0.58 0.34 0.08
90 0.24 0.48 0.28 0.67 0.28 0.06
99 0.29 0.48 0.22 0.72 0.23 0.04
(For ease of interpretation, tissue damage scores 1 and 2 and damage

scores 3, 4, and 5 have been aggregated).
There was a significant increase in tissue damage with 3-second

compared with 1-second pulse durations (p = 0.003), and tissue damage
score also increased significantly with increases in the power setting (p =
0.031). However, only 2 of 42 gastric samples tested showed damage
extending into the muscularis propria (Watson et al., 2000).
Effect of argon plasma coagulation on esophageal tissue
The results suggested that the esophageal tissue damage score was
marginally related to pulse duration (p = 0.053) but not to the power
setting (p = 0.65). Table (5) shows the probability of obtaining a
particular esophageal damage score for 1- and 3-second pulses.
For esophageal tissue, using a 1-second pulse duration, the mean tissue
score was 0.72 (n = 21) and for 3 seconds it was 1.24 (n = 21). Only 1 of
46
42 esophageal samples tested showed damage extending into the

muscularis propria.
Table (5): Esophageal tissue damage score for 1- and 3-second pulse
durations (Watson et al, 2000)
Pulse Tissue damage
duration
0 1 2 3
1 second 0.48 (0.48) 0.33 (0.33) 0.18 (0.19) 0.01 (0.00)

3 seconds 0.23 (0.24) 0.34 (0.33) 0.39 (0.38) 0.04 (0.05)
Analysis of these data (Watson et al., 2000) revealed that the depth of
tissue damage increased with treatment pulse duration, whereas
increasing the power setting had a demonstrable effect on gastric but not
esophageal tissue. Different tissue damage scoring systems were used for
the two tissues because of their different, easily identifiable histologic
layers. The discordant findings on the effect of power settings may be
related to this.
Muscularis propria injury was only seen at pulse durations of 3
seconds and at power settings of 90 W. or more. In the in vitro study of
Johanns et al., (1997), there were no perforations in 640 lesions tested
from the stomach, small intestine, and colon; esophageal tissue was not
studied. The finding of deep tissue injury, even in a small proportion of
exposures, is of clinical relevance, particularly in the treatment of lesions
such as Barrett's esophagus, and may explain the development of
esophageal strictures in 2 patients treated by Van Laethem et al., (1998).
It is difficult to extrapolate precisely from in vitro studies to living tissue,
but theoretic considerations suggest that this in vitro model will give a
47
reasonably accurate indication of the acute effects of argon plasma

coagulation on living tissue. Electrical conductivity in freshly resected
specimens is likely to be similar to in vivo conductivity, and, although in
living tissue the effect of blood flow is to act as a heat sink, thereby
decreasing the observed temperature rise in any heated tissue, this effect
is only significant when pulse durations are far in excess of 3 seconds
(Welch et al., 1980 and Maciel et al., 1996).
Figure (5): The tissue effect of argon plasma coagulation on

esophageal mucosa. The effect of increasing the power setting (in
Watts) and time of activation (in seconds) on the surface area
affected and total energy deliverd to the target tissue.
48
The study of Watson et al., (2000) shows that, although muscularis

propria injury can occur in vitro in esophageal and gastric tissue during
argon plasma coagulation, it is infrequent and the clinical data thus far
compare favorably with previous experience with Nd/Yag laser therapy.
The observation that tissue damage in the esophageal samples treated for
3 seconds extended just through the mucosa into the submucosa supports
the case for using argon plasma coagulation in the ablative treatment of
Barrett's esophagus, as well as for other disorders in the upper GI tract.
Safety
As argon plasma coagulation is applied in monopolar mode, all the

safety principles of monopolar high-frequency electrosurgical procedures
apply, including the placement of a grounding-pad electrode.
Differences in adopted study methodologies, operator experience,
heterogeneous indications and patient populations, variable follow-up,
disparate definitions of complications, and probable publication bias all
limit the interpretation of safety data in the published experience to date.
Complications of APC
Although serious complications have been associated with surgical

applications of APC (Palmer et al., 1993), major complications appear to
be uncommon with endoscopic application (Grund et al., 1994 and
Boruchowicz et al., 2006).
Complications may be related to power setting, duration of

application, and distance of the probe tip to the target tissue (Watson et
al., 2000).
Reported complication rates range from 0% to 24% and include
49
gaseous distention by argon flow producing transient abdominal pain

(Grund et al., 1998), intestinal wall submucosal emphysema which may
as far as to become pneumatosis intestinalis (Wahab et al., 1997),
pneumoperitoneum, pneumomediastinum, subcutaneous emphysema,
pain at the treatment site, chronic ulceration, stricture formation,
fistulization, bleeding, transmural burn syndrome and transient fever
(Tan et al., 1995 and Johanns et al., 1997).
Pneumoperitoneum can occur from dissection of air through a tiny

perforation .Usually it is benign self limiting event and surgery is only
necessary if there is signs of peritonitis (Hoyer et al., 1998).
Watson et al., (2000) suggest that deep tissue destruction that could
lead to perforation is rare with APC and occurs mostly in very thin walled
structures or inadequate application. The reported frequency of
perforation with APC is 0.27%. This would support data from clinical
reports that perforation occurs only occasionally: Johanns et al., (1997)
report 2 cases of gas in the mediastinum and peritoneal cavity after
endoscopic application of argon plasma coagulation, and one case of
accumulation of submucosal gas in the caecum out of 66 patients studied.
In all three cases these effects were transitory, caused no symptoms, and
resolved spontaneously.
Grund et al., (1994) treated 102 patients in 189 sessions with a variety
of diagnoses and reported no perforations. These data compare favorably
with those in previous reports using Nd/Yag laser endoscopy, where
perforation rates were between 1.4% and 9% (Bown et al., 1987, Maciel
et al., 1996 and Canard and Védrenne, 2001).
Ulcers occur commonly following treatment of radiation proctitis

(Ravizza et al., 2003), most have a clinically benign course. To reduce the
50
risk of ulceration, spot treatments are preferable to extensive spray

painting of rectal mucosa following radiation therapy for prostate cancer.
Colonic thermal injury caused by argon plasma coagulation may

extend to the muscularis propria at recommended settings for argon
plasma coagulation. Protective arcing to nondesiccated tissue does not
appear to be significant in vivo. Submucosal injection of saline solution
protects against deep injury (Norton et al., 2002b).
The explanation for the discrepancy between the results of ex vivo

studies and the clinical experience remains unclear. However, repeated
coagulation at the same site (e.g., Barrett's esophagus) or excessive
distension of the wall of the bowel by air insufflation during colonoscopy
(e.g. in treatment of cecal angiodysplasia) may be adverse factors.
APC versus other electrocoagulative methods, especially

the Nd/Yag laser
Ideally, the endoscopic electrocoagulative treatment in the

gastrointestinal tract should fulfil the conditions of maximal efficacy
paired with minimal mechanical or thermal lesions of the unaffected
neighbouring tissue (Lee& Leiubermann, 1996). Not one of the
established methods can fulfil all these requirements (Morgan and
Clamp, 1988).
Conventional electrocoagulative techniques especially the

neodymium yttrium aluminum garnet (Nd/Yag) laser have the following
indisputable disadvantages (Karl et al., 1999):-
- A penetration depth cannot be estimated using visual control, and

hence a remarkable risk of perforation occurs.
51
- A high absorption of energy in liquid and/or coagulated blood,

leading to difficulty controlling the thermal effect.
- Difficult or impossible application in certain anatomical situations
demanding lateral application (caecum or esophagus) or inversion
(gastric cardia).
- The tip of the probe becomes easily encrusted, necessitating a
repeated pull out for cleaning.
- The absorption of energy depending on the colour of the tissue
(white tissues reflect 90% of the laser energy). The tissues,
however, changes its colour during activation.
On the other hand, argon plasma coagulation has a number of

advantages over (Nd/Yag) laser therapy (Karl et al., 1999):
- Laser containment facilities, such as eye protection or door

interlocks, are not required as it is electrosurgical and not laser
based.
- The machine is cheaper, less bulky, and more portable than laser
systems.
- APC is highly advantageous in difficult anatomical areas, for
stenotic tumours, in the colorectum, at high inversion angles in the
gastric cardia, and in the tracheobronchial system.
- The bright plasma jet is easily kept in view.
- The plasma jet can be used to pass brush-like over the tissues; thus
wide areas, diffuse haemorrhages are the special domaim of APC.
- The electrocoagulative effect may carry a lower risk of intestinal
perforation, as argon plasma coagulation is self-limiting, with the
previously treated, desiccated tissue being resistant to current
discharge. It might prove possible to cause ablation of the more
superficial mucosal layers while minimizing the risks of deeper
52
damage and perforation in the treatment of conditions such as

angiodysplasia and Barrett's esophagus.
Financial considerations
As a noncontact thermal device, its applications overlap with those of

endoscopic laser therapy. When compared with a laser, the APC is more
compact, mobile, and versatile, and is less costly. When compared with
contact thermal probes, the APC system is more complex and the APC
probes are more costly. However, the argon plasma coagulation generator
may be used with other monopolar and multipolar thermal devices.
The prices list of the ERBE APC 300 Plasma Coagulator system,
including the ICC 200 E/A generator and argon gas cylinder, and the
Con-med System 7500 ABC are both approximately $24,500. The unit
cost of APC disposable probes is $189 (ASGE. Technical review on
endoscopic hemostatic devices).
Future aspects
In summary, even a critical appraisal clearly shows that argon plasma

coagulation is not merely a new endoscopic technique but represents a
new, trendsetting development in gastrointestinal endoscopy.
It should be also remembered that argon plasma coagulation in general
is -at present- only in the initial stages of its development, and that APC
in its present form has taken only the first step in its clinical career.
Controlled, multicentre studies with large numbers of patients will be
needed to test argon plasma coagulation in different indications,
comparing the results with those of already established methods.
53
Further fundamental research in plasma physics is on the way to

elucidate the phenomenon of the interaction between plasma and tissues
(Karl et al., 1999) paving the way for wide-ranging future developments,
opening up the horizon of treatment of many previously challenging
conditions.
54
PATIENTS AND
METHODS
Patients & Methods
PATIENTS AND METHODS
This study was conducted on 100 patients who were admitted to G.I.
endoscopy unit at Mansoura University Emergency Hospital from
October 2004 to May 2006.
These patients were suffering from significant, recent first attack of

upper gastrointestinal bleeding which was confirmed endoscopically to be
due to bleeding esophageal varices (bleeding from esophageal varices
was defined as: when blood was directly seen by endoscopy to spurt or
ooze from an esophageal varix, or when red colour signs detected on
esophageal varices by endoscopy with no other identifiable potential
source of bleeding).
Exclusion criteria:
Patients were excluded if any of the following conditions was present:-
1- Severely decompensated liver (Child Pugh score>11), hepatocellular
carcinoma, portal vein thrombosis or other malignancies.
2- Isolated gastric varices.
3- Hepatic encephalopathy more than stage II.
4- Hepatorenal syndrome (Type I or type II with serum creatinine
exceeding 4 mg /dl).
5- History of shunt operation or previous injection sclerotherapy.
6- Bleeding tendency due to a hematological disorder.
7- Advanced cardiopulmonary disease.
8- Renal failure.
9- Non compliance of the patient.
55
Patients & Methods
Management of patients:
The initial control of acute variceal bleeding was done using the
standard resuscitation measures in G.I. endoscopy unit at Mansoura
University Emergency Hospital, which included:
1- Continuous close clinical observation.
2- Haemodynamic monitoring and intravenous fluids were started.
3- Blood transfusion was given to patients with haemoglobin (Hb)
level of less than or equal to 8 gm/dl avoiding over transfusion.
4- Systolic blood pressure was maintained at equal or more than 100
mmHg. Saline infusions were avoided.
5 - Parentral vitamin K1 was given to all patients.
6- Intravenous H2-receptor blocker, such as ranitidine, was given to
prevent development of stress ulcers.
7- Short term antibiotic prophylaxis was used in the form of
amoxicillin trihydrate 500 mg plus flucloxacillin monohydrate 500
mg intravenously every 8 hours.
8- Lactulose enemas were performed every 6 hours.
9- Emergency endoscopic sclerotherapy was performed within 24
hours of hospitalization.
After becoming haemodynamically stable and starting oral feeding,

informed consents were obtained from all participating patients.
All the participating patients were instructed not to use any portal
pressure lowering agents (e.g. beta blockers, nitrates, ACE
inhibitors…etc) during the whole duration of the study.
The participating patients were randomly divided into 2 groups:
56
Patients & Methods
1- Group I (combination therapy group):

- Included 50 patients, 40 males and 10 females.
- They were treated by regular endoscopic injection sclerotherapy, at 2
weeks intervals until complete variceal eradication. Then three sessions
of argon plasma coagulation therapy of the lower esophageal mucosa
were done at 2 – 4 weeks intervals until complete coagulation of the
mucosa in the distal esophagus was achieved.
- After each APC endoscopic session, patients were given omeprazole (20
mg/d) PO for one month to promote healing of the coagulated tissue.
- Follow up upper G.I. endoscopy was done one month after APC to
assess healing of the lower esophageal mucosa and then repeated at
monthly intervals to check for recurrence of esophageal varices.
- In case of endoscopic recurrence of esophageal varices, no endoscopic
intervention was done and follow up was continued.
- In case of recurrent esophageal hemorrhage, patients were instructed to
come back to Mansoura University Emergency Hospital for urgent
endoscopic therapy.
2- Group II (control group):

- Included 50 patients, 38 males and 12 females.
- They were treated by regular endoscopic injection sclerotherapy alone,
at 2 weeks intervals until complete variceal eradication. Then, follow up
upper G.I. endoscopy was done at monthly intervals to check for
recurrence of esophageal varices.
- During this study, variceal size was classified according to the North
Italian Endoscopic Club (NIEC) where F1 specifies varices which occupy
less than one third of the esophageal lumen, F2 denotes varices that
occupy one third of the lumen, and F3 marks varices that occupy more
57
Patients & Methods
than one third of the lumen (North Italian Endoscopic Club (NIEC),
1988).
- Eradication of esophageal varices is defined as complete disappearance
of varices or the presence of only trivial varices without red color
markings.
- Variceal recurrence is defined as the development of at least F1 varices
with red signs.
- Variceal rebleeding was defined as new episode of clinically
significant haematesis and/or melena from ruptured esophageal
varices according to Baveno III criteria (De Franchis, 2001).
All patients were subjected to:
1- Thorough history taking with special stress on:

- Presentation (haematemesis and / or melena).
- Precipitating factors for bleeding.
- Blood transfusion.
- Bilhariziasis and anti-bilharzial treatment.
- Upper GIT bleeding and endoscopy.
- Hepatic encephalopathy.
- History of surgery.
- Drug intake.
2- Clinical examination with special stress on:

- Vital signs, pallor, jaundice and other manifestations of liver
cell failure.
- Abdominal examination with stress on liver, spleen, ascites and
dilated veins.
- Chest, cardiac and neurological examination.
58
Patients & Methods
3- Laboratory investigations including:

- Liver function tests:
- Serum albumin level.
- Total and direct bilirubin levels.
- Alanine aminotransferase (ALT).
- Prothrombin time (PT), concentration and
international normalizing ratio (INR).
- Serum creatinine level.
- Complete blood count (CBC).
All these laboratory investigations were done at the beginning of the
study and after 12 weeks.
- Hepatitis C antibody (anti-HCV) by ELISA technique (Alter,
1992).
- Hepatitis B surface antigen (HbsAg)
4- Abdominal Ultrasonography (U.S.):

An abdominal ultrasonography scan was done using real-time
ultrasound equipment (Sono-Acc-Digital-GAIA) to inspect the
overall morphology of the liver, exclude presence of focal hepatic
lesions and to detect signs of portal hypertension (e.g.
splenomegally and collaterals).
Doppler evaluation of the main portal vein, the splenic vein

and the hepatic veins was done to evaluate portal vein patency and
direction of flow.
59
Patients & Methods
-The severity of liver disease was graded on the basis of Pugh's

modification of Child's classification (Pugh et al., 1973) as
follows :-
Table (6): Pugh's modification of Child's classification.
Variable 1 point 2 points 3 points
Encephalopathy None Stage 1 or 2 Stage 3 or 4

Ascites None Easily Poorly
controlled controlled
Bilirubin (mg/dl) <2 2–3 >3
Albumin (gm/dl) > 3.5 2.8 – 3.5 < 2.8
Prothrombintime (seconds) < 14 seconds 15-17 > 18 seconds
- Scores are summated to determine Child's class:

Child Class A = 5 – 6 points.
Child Class B = 7 – 9 points.
Child Class C = 10 – 15 points.
60
Patients & Methods
Endoscopic Injection Sclerotherapy
Endoscopic injection sclerotherapy was done for all patients in the

study at admission, within 24 hours from first attack, and at 2 weeks
interval using upper GIT endoscope (Pentax EG 3400 Japan).
Each session was done under light sedation by slow intravenous
injection of 5 mg. of midazolam (Dormicum) or diazepam (Neuril).
Sclerotherapy was performed using intravariceal injection, just above
the cardia. The sclerosant material used was ethanolamine oleate 5%.
Each varix was injected by about 4 – 6 ml of the sclerosant using flexible
needle (LDVI-23-MH Disposable variceal injector, Wilson-Cock Medical
Ind., Winston-Salem, North Carolina, USA). The first sclerotherapy
session was done at Mansoura University Emergency Hospital, then the
endoscopic follow up of the patients was done every 2 weeks in the
Specialized Medical Hospital Endoscopy unit, using the same technique
and equipments.
All the following endoscopic findings were recorded for all patients at
every session:
- Location of esophageal varices and their grading according to
the North Italian Endoscopic Club (NIEC) classification (North
Italian Endoscopic Club (NIEC), 1988).
- Risky signs of varices (red wheel marks, cherry-red spots and
hematocystic spots) (Hegab et al., 2001).
- Other esophageal findings (e.g. ulcer, stricture…etc)
- Portal hypertensive gastropathy (PHG) and its site (fundus,
body or antrum) (Bosch et al., 2003).
- Complications of sclerotherapy (e.g. postsclerotherapy ulcers).
- Obliteration of varices.
61
Patients & Methods
Argon Plasma Coagulation therapy
After complete variceal eradication in all patients, three sessions of

argon plasma coagulation therapy of the entire esophageal mucosa 5-7 cm
proximal to the esophagogastric junction were done in group I patients
(combination therapy group) at 2-4 weeks intervals until complete
coagulation of the distal esophageal mucosa was achieved.
Each session of APC was done under light sedation by slow
intravenous injection of 5mg of midazolam (Dormicum) or diazepam
(Neuril).
The APC equipment used in this study is ( ERBOTOM ICC 200 ) and
flexible APC probe (ERBE 2200 probe, Ref : 20132-049) 220 cm. in
length and 2.3 mm. in diameter with the (20132-046 fur APC 300)
connecting cable in between , all manufactured by ERBE Electromedizin,
Tuebingen, Germany.
The APC probe was introduced through upper GIT videoscope
(Pentax EG 3400 Japan).
The Power setting was adjusted to 60 W., gas flow at 1.5 to 2 liters per
minute and activation time ranging between 1 and 3 seconds.
The application technique used was to create longitudinal parallel
stripes of coagulation of the distal 5-7 cm. of the entire esophageal
mucosa.
Omeprzole 20 mg/d PO was given after each APC endoscopic session
for one month to promote healing of the coagulated tissue.
Follow up
Follow up upper G.I. endoscopy was performed for both groups
at monthly intervals to check for recurrence of esophageal varices.
62
Patients & Methods
• All patients were assessed for any rebleeding episodes which were
confirmed endoscopically.
• Patients who experienced rebleeding episodes before variceal
obliteration were excluded from the study after receiving the
appropriate treatment.
• All patients in group I were assessed for complications of argon
plasma coagulation therapy, whether early complications (e.g.
bleeding, chest pain, abdominal distension..etc) or delayed
complications (e.g. fever, dysphagia..etc).
• Follow up period in group I ranged between 78 and 84 weeks with a
mean of 80.08 ± 2.33 weeks, whereas in group II it ranged between 76
and 82 with a mean of 79.94 ± 2.01 weeks. There was no significant
statistical difference as regards the duration of follow up period
(P=0.64).
Statistical Analysis
• Data was analyzed using SPSS (Statistical Package for Social

Sciences), version 14 under Windows XP.
• The statistical significance of difference between mean values of two

groups (unpaired data) was calculated by Independant-Samples T test,
whereas the statistical significance of difference between mean values
of a single group (paired data) was calculated by Paired-Samples T
test.
• Study of association between caregorical variables was assessed using

Chi-Square test.
63
Patients & Methods
• Difference between both groups as regards data of recurrence and

rebleeding was analysed using Kaplan Miere test and Log Rank
equation.
• P ≤ 0.05 was considered to be statistically significant.
64
RESULTS
Results
RESULTS
The study was conducted on 122 patients at the start and only 100
patients completed the study because:
1. One patient developed secondary fundic varices.
2. Two patients developed hapatocellular carcinoma.
3. One patient developed variceal rebleeding before variceal

obliteration.
4. Uncompliance to treatment by 6 patients.
5. 12 patients lost follow up.
1- Baseline demographic and clinical data
Table (7) shows the baseline demographic and clinical data of both
groups at randomization.
a) Age and sex distribution:

Group I: included 50 patients, 40 males and 10 females, with the age
ranging between 41 and 66 years with the mean of 49.04 ± 6.45
years.
Group II: included 50 patients, 38 males and 12 females, with the age
ranging between 42 and 65 years with the mean of 50.28 ± 6.23
years.
- There was no statistically significant difference between both groups
as regards age and sex.
65
Results
b) Presentation:
Melena was the presentation in 32% of group I and in 26% of group II.
On the other hand, 68% of patients in group I and 74% of patients in
group II presented by both haematemesis and melena.
The difference between both groups as regard presentation was

statistically non significant.
c) Precipitating factors for bleeding:
- Ulcerogenic drugs as aspirin and other NSAIDs were the precipitating
factor in 22% of group I and 24% of group II, a statistically non

significant difference.
- Fever was the precipitating factor in 7% of both groups.
- Stress (physical or mental) was the precipitating factor in 12% of
group I and 16% of group II (statistically non significant).

- Combined factors were the precipitating in 1% of both groups.
- No history of a certain precipitating factor in 50% of group I and 42%
of group II.
d) Past history of anti-bilharzial treatment: was recorded in 32

patients (64%) of group I and 29 patients (58%) of group II (a statistically
non significant difference).
e) Concomitant medical diseases :

- Diabetes mellitus was found in 12 patients (24%) in group I
and in 14 patients (28%) in group II.
-There was no statistically significant difference between both
groups.
- Hypertension was found in 4 patient (8%) in group I whereas it
was found in 6 patient (12%) in group II.
66
Results

groups.
f) Initial bleeding episode:
The number of blood units transfused per initial bleeding episode

ranged from 0 to 5 blood units with the mean of 2.72 ± 1.46 in group I.
In group II, it ranged from 0 to 6 blood units with the mean of 2.5 ± 1.44
There was no statistically significant difference between both
groups as regards the number of blood units transfused per initial
bleeding episode. This means that the severity of initial bleeding
episode was almost similar in both groups.
g) Ascites:
Ascites was detected in 25 patients (50%) in group I whereas it
was found in 27 patients (24%) in group II.
groups.
h) Splenomegaly:
Splenomegaly was detected in 19 patients (38%) in group I
whereas it was found in 22 patients (44%) in group II.
groups.
2. Biochemical and haematological results
Table (8) shows the biochemical and haematological results and Child-
Pugh scoring of both groups at randomization and after the end of
treatment:
67
Results
1- Serum albumin:
Before treatment:
• Group I : serum albumin ranged between 2.4 to 4.4 with a mean of
3.14 ± 0.49 mg/dl
• Group II: serum albumin ranged between 2.3 and 4.5 with a mean
of was 3.09 ± 0.56mg/dl.
- Comparing both groups before treatment was statistically non
significant.
After treatment:
• Group I : serum albumin ranged between 2.3 to 4.4 with a mean of
3.02 ± 0.45mg/dl
• Group II: serum albumin ranged between 2.6 to 4.4 with a mean of
3.24 ± 0.5 mg/dl.
- Comparing serum albumin in group I before and after
treatment was statistically non significant.
- Comparing serum albumin in group II before and after

after treatment.
2-Total serum bilirubin:

Before treatment:
• Group I : total serum bilirubin ranged between 0.7 to 3.3 with a
mean of was 1.7 ± 0.74 mg/dl
• Group II : total serum bilirubin ranged between 0.7 to 3.2 with a
mean of was 1.73 ± 0.72mg/dl.

before treatment.
68
Results
After treatment:
• Group I: total serum bilirubin ranged between 0.8 and 3.2 with a
mean of 1.67 ± 0.76 mg/dl.
• Group II: total serum bilirubin ranged between 0.9 and 3.1 with a
mean of 1.77 ± 0.73mg/dl.
- Comparing total serum bilirubin in group I before and after
- Comparing total serum bilirubin in group II before and after
- There was no significant statistical difference between both groups
after treatment.
3 -Prothrombin time
Before treatment:
• Group I: prothrombin time ranged between 13 to 20 seconds with
a mean of 16.15 ± 1.94seconds.
• Group II: prothrombin time ranged between 14 to 21 seconds with
a mean of 16.28 ± 1.97seconds.
significant.
After treatment:
• Group I: prothrombin time ranged from 13 to 19 with a mean of
15.64 ± 1.63seconds.
• Group II: prothrombin time ranged from 14 to 20 with a mean of
was 16.18 ± 1.71seconds.
- Comparing prothrombin time in group I before and after
- Comparing prothrombin time in group II before and after
69
Results

after treatment.
4- Serum alanine aminotransferase (ALT):

Before treatment:
• Group I : serum ALT level ranged between 25 and 61 u/ml with a
mean of 40.48 ± 9.31u/ml.
• Group II: serum ALT level ranged between 21 and 58 u/ml with a
mean of 38.06 ± 10.76u/ml.
-There is no significant statistical difference between both groups before
treatment.
After treatment:
• Group I : serum ALT level ranged between 26 and 62 u/ml with a
mean of was 36.94 ± 8.79u/ml.
• Group II: serum ALT level ranged between 20 and 60 u/ml with a
mean of was 37.20 ± 9.6u/ml.
- Comparing serum ALT in group I before and after treatment
was statistically non significant.
- Comparing serum ALT in group II before and after treatment
was statistically non significant.
after treatment.
5-Serum creatinine:
Before treatment:
• Group I : serum creatinine ranged between 0.6 and 2 with a mean
of 1.16 ± 0.36mg/dl.
• Group II: serum creatinine ranged between 0.5 and 1.9 with a mean
of 1.14 ± 0.3mg/dl.
70
Results

significant.
After treatment:
• Group I : serum creatinine ranged between 0.7 and 1.6 with a mean
of 1.13 ± 0.26 mg/dl .
• Group II : serum creatinine ranged between 0.7 and 1.7 with a
mean of 1.11 ± 0.27 mg/dl .
- Comparing serum creatinine in group I before and after
- Comparing serum creatinine in group II before and after
after treatment.
6- Hemoglobin level:
Before treatment:
• Group I : hemoglobin level ranged between 7 and 10.8 gm% with a
mean of 8.81 ± 1.01gm%.
• Group II: hemoglobin level ranged between 7.1 and 12 gm% with a
mean of 8.96 ± 1.19gm%.
-There was no significant statistical difference between both groups
before treatment.
After treatment:
• Group I : hemoglobin level ranged between 6 and 11 gm% with a
mean of 9.06 ± 1.21gm%.
• Group II: hemoglobin level ranged between 7.1 and 12.5 gm%
with a mean of 8.78 ± 1.12gm%.
- Comparing hemoglobin level in group I before and after
71
Results
- Comparing hemoglobin level in group II before and after


after treatment.
7- White blood cells count

Before treatment:
• Group I : white blood cells count mean value was 5.74 ± 1.06 ×
103/m3
• Group II: white blood cells count mean value was 5.89 ± 1.25 ×
103/m3
significant.
After treatment:
• Group I : white blood cells count mean value was 5.85 ± 1.18 ×
103/m3.
• Group II: white blood cells count mean value was 6.2 ± 1.4 ×
103/m3.
- Comparing white blood cells count mean value in group I
before and after treatment was statistically non significant.
- Comparing white blood cells count mean value in group II
before and after treatment was statistically non significant.
groups after treatment.
8- Platelet count:
Before treatment:
• Group I : platelet count mean value was 125.68 ± 35.73 × 103/m3.
• Group II: platelet count mean value was 133.06 ± 33.33 × 103/m3.
72
Results
-There is no significant statistical difference between both groups

before treatment.
After treatment:
• Group I : platelet count was mean value 130.92 ± 35.03 × 103/m3.
• Group II: platelet count was mean value 121.84 ± 34.33 × 103/m3.
- Comparing platelet count was mean value in group I before
and after treatment was statistically non significant.
- Comparing platelet count was mean value in group II before
and after treatment was statistically non significant.
groups after treatment.
3- Results of other investigations
- Hepatitis virological markers:

Table (9) shows Hepatitis virological markers of both groups at
randomization.
There was 44 patients with positive anti HCV and 6 patients with
positive HbsAg in group I, while there was 47 patients with positive anti
HCV and 3 patients with positive HbsAg in group II.
There was a statistically significant difference between both groups as

regards virological markers.
4. Aetiology of liver disease
Table (10) shows aetiology of liver disease in both groups at

randomization.
As evidenced by abdominal ultrasonography and viral markers, There
was 20 patients (40%) suffering from post hepatitic cirrhosis and 30
patients (60%) suffering from mixed cirrhosis in
73
Results
group I, while in group II there was 17 patients (34%) suffering from post
hepatitic cirrhosis and 33 patients (66%) suffering from mixed cirrhosis.
There was no statistically significant difference between both groups
as regards the aetiology of liver disease.
5. Severity of liver disease
Table (11) shows severity of liver disease according to Child-Pugh

classification in the studied groups at randomization:
• Child-Pugh class A patients: were 20 (40%) in group I and 19
(38%) in group II.
• Child-Pugh class B patients: were 24 (48%) in group I and 26
(52%) in group II.
• Child-Pugh class C patients: were 6 (12%) in group I and 5 (10%)
in group II.

as regards the distribution of patients in each Child class.
Child-Pugh scoring in the two groups before and after treatment

(Table 8):
• Before treatment: It was 7.24 ± 1.72 points in group I and 7.26 ± 1.65
in group II. There was no statistically significant difference between
both groups.
• After treatment: It was 7.32 ± 1.67 in group I and 7.20 ± 1.67 in

group II. There was no statistically significant difference between both
groups.
- There was no statistically significant change of the score after
74
Results
treatment in either group of patients.
6. Endoscopic Results
I. Initial Endoscopic Results
Table (12) shows the endoscopic findings in the studied groups at

randomization:
a) Variceal size :
F1 varices were recorded in 5 patients (10%) in Group I and in 6

patients (12%) in group II


patients (92%) in group II.
b) Variceal number :
Two varices were recorded in 5 patients (10%) of group I and in

3 patients (6%) of group II.
Three varices were recorded in 19 patients (38%) of group I

and in 20 patients (40%) of group II.
Four varices were recorded in 23 patients (46%) of group I and

in 26 patients (52%) of group II.
Five varices were recorded in 3 patients (6%) of group I and in

one patient (2%) of group II.
75
Results

as regards endoscopic findings at randomization.
II. Results of endoscopic treatment:
A. Variceal obliteration
1- Time period to achieve variceal obliteration:
- It ranged between 6 to 12 weeks in group I with a mean of 6.05 ±

2.45 and from 6 to 14 weeks in group II with a mean of 7 ± 2.32.

as regards time needed to achieve variceal obliteration.
2-Number of sessions needed to achieve variceal obliteration:
It ranged between 3 to 6 sessions in group I with a mean of 4.14± 1.01

and from 3 to 7 sessions in group II with a mean of 4.28 ±1.14, a
statistically non significant difference.
3- Total amount of sclerosant material needed to achieve variceal

obliteration:
The mean of total amount of sclerosant material needed to achieve
variceal obliteration was 49.5 ± 15.77 c.c. in group I and 52.46 ± 17.37
c.c. in group II, a statistically non significant difference.
B. Complications of endoscopic injection sclerotherapy
Table (14) shows complications of sclerotherapy in both groups.
-Retrosternal pain occurred in 21 patients (42%) in group I and in 22

76
Results
-Abdominal distension occurred in 6 patients (12%) in each

group.
-Fever (>38 ºC.) occurred in 12 patients (24%) in group I and
13 patients (26%) in group II.
-Esophageal ulceration occurred in 6 patients (12%) in each
group.
-No cases of esophageal stricture, pleural effusion, pneumonia
were recorded in either group.

as regards complications of sclerotherapy.
C. Complications of Argon plasma coagulation therapy
- Three sessions of APC were performed in each patient of group I.

Table (15): shows complications of argon plasma coagulation in
group I .
-Retrosternal pain occurred in 21 patients (42%) .

-Abdominal distension occurred in 8 patients (16%).
-Fever (>38 ºC.) occurred in 23 patients (46%).
-Esophageal ulceration occurred in 2 patients (4%).
-No cases of esophageal stricture, pleural effusion, pneumonia
were recorded in either group.
Table (16): shows complications of the performed endoscopic

procedures in both groups (EST plus APC in group I and EST alone in
group II): By comparing the overall complications in both groups, the
incidence of fever was significantly higher in group I which received
argon plasma coagulation therapy while the incidence of retrosternal
77
Results
chest pain, dysphagia and esophageal ulceration was not different

between the two groups.
D. Variceal recurrence
Table (17) shows the data of variceal recurrence in both groups of
patients.
1- Rate of variceal recurrence:

Variceal recurrence was recorded in 7 patients (14%) in
group I and 19 patients (38%) in group II.
By comparing both groups, the recurrence rate is significantly

decreased in group I patients.
2- Time between obliteration and recurrence:

In group I , it ranged between 19 and 38 weeks with a mean of
29.57± 6.29 weeks while in group II it ranged between 7 and 35 weeks
with a mean of 20.68± 6.84 weeks.
There is a significant prolongation in the time period between
obliteration and recurrence in group I patients.
E. Rebleeding
Table (18) shows data of rebleeding in both groups of patients.
- No mortality occurred in either group due to rebleeding.
1- Rate of variceal rebleeding:

- rebleeding was recorded in one patient (2%) in group I
and 7 patients (14%) in group II.
2- Time between obliteration and rebleeding:
78
Results
- One patient in group I rebled, rebleeding occurred at the 27th

week, while in group II the time between obliteration and rebleeding
ranged between 16 and 35 weeks with a mean of 25.37 ± 7.92 weeks.
3- Source of rebleeding:
- The source of rebleeding in both groups was endoscopically
confirmed to be due to rupture of esophageal varices.
79
Results
Table (7): Baseline demographic and clinical data of both groups.

P
Variable Group I Group II
value
Total number of patients 50(100%) 50(100%)
Age (years)
- Range (41 – 66) (42 – 65)
0.13
- Mean ± SD 49.04 ± 50.28 ±
6.45 6.23
Sex (male/female) 40/10 38/12 0.63
Presentation (No & %)
- Melena 16 (32%) 13 (26%) 0.7
- Both haematemesis and melena 34(68%) 37(74%)
Past history of anti-bilharzial treatment
(No & %) 32(64%) 29(58%) 0.54
Diabetes mellitus (No & %)

12(24%) 14(28%) 0.64
Hypertension (No & %) 4(8%) 6(12%) 0.50

Precipitating factors for bleeding :
1- Ulcerogenic drugs 11(22%) 12(24%)
2- Fever 7(14%) 7(14%)
0.96
3- Stress 6(12%) 8(16%)
4- Combined 1(2%) 1(2%)
5- No history 25(50%) 21(42%)
Number of blood units transfused per initial
bleeding episode
- Range (0-5) (0-6)
0.42
- Mean ± SD 2.72 ± 1.46 2.5 ± 1.44
Ascites (No & %)
25(50%) 27(54%) 0.69
Splenomegaly (No & %)

19(38%) 22(44%) 0.54
80
Results
Table (8): Laboratory data and Child-Pugh score in both groups at

randomization and at the end of treatment.
Comparison
Group I Group II
between both
(n = 50) (n = 50)
Variable groups
Before After
Before After After
P Before P treatment treatment
treatment treatment treatment treatment
P value P value
Serum
Albumin 3.14 ± 0.49 3.02 ± 0.45 0.22 3.09 ± 0.56 3.24 ± 0.5 0.08 0.62 0.06
(mg/dl)
Total serum
bilirubin 1.7 ± 0.74 1.67 ± 0.76 0.83 1.73 ± 0.72 1.77 ± 0.73 0.8 0.81 0.49
(mg/dl)
Prothrombin 16.15 ± 15.64 ± 16.28 ± 16.18 ±
0.14 0.79 0.74 0.11
time (seconds) 1.94 1.63 1.97 1.71
ALT u/ml 40.48 ± 36.94 ± 38.06 ±
0.07 37.20 ± 9.6 0.55 0.23 0.88
9.31 8.79 10.76
Serum
creatinine 1.16 ± 0.36 1.13 ± 0.26 0.61 1.14 ± 0.3 1.11 ± 0.27 0.65 0.74 0.71
(mg/dl)
Hemoglobin
8.81 ± 1.01 9.06 ± 1.21 0.22 8.96 ± 1.19 8.78 ± 1.12 0.45 0.5 0.24
level (gm %)
Total white
5.74 ± 1.06 5.85 ± 1.18 5.89 ± 1.25 6.2 ± 1.4 x
blood cells 3 3 3 3 0.59 3 3 0.25 0.5 0.17
x 10 /m x 10 /m x 10 /m 103/m3
count
Platelet count 125.68 ± 130.92 ± 133.06 ± 121.84 ±
3 3 0.44 0.08 0.28 0.19
(x 10 /m ) 35.73 35.03 33.33 34.33
Pugh Child
score 7.24 ± 1.72 7.32 ± 1.7 7.26 ± 1.65 7.20 ± 1.67
0.1 0.08 0.95 0.72
(points)
81
Results
Table (9): Virological markers of the studied groups.

Group I Group II
Variable (n = 50) (n = 50) P value
No % No %
HBsAg positive
6 12% 3 6% 0.29
patients
Anti-HCV positive
44 88% 47 94% 0.29
patients
Table (10): Aetiology of liver cirrhosis in the studied groups.

Group I Group II
No % No %
Post hepatitic cirrhosis
20 40% 17 34%
0.53
Mixed ( bilharzial & post
30 60% 33 66%
hepatitic) cirrhosis
Table (11): Child-Pugh classification in the studied groups at

randomization.
Group I Group II
Variable P value
(n = 50) (n = 50)
Child-Pugh class A 20 (40%) 19 (38%)

( No & % )
Child-Pugh class B 24 (48%) 26 (52%)

( No & % ) 0.91
Child-Pugh class C 6 (12%) 5 (10%)

( No & % )
82
Results
Table (12): Initial Endoscopic Results

Group I Group II
No % No %
According to grade
- Patients with F1 5 10% 6 12% 0.75

varices
- Patients with F2 22 44% 19 38% 0.54
varices
- Patients with F3 43 86 % 46 92% 0.34
varices
According to number
of varices
- Two varices 5 10% 3 6%

- Three varices 19 38% 20 40% 0.63
- Four varices 23 46% 26 52%
- Five varices 3 6% 1 2%
83
Results
Table (13): Data of variceal obliteration in both groups.
Group I Group II
Variable P value
(n = 50) (n = 50)
Time needed for variceal

obliteration (weeks)
Mean ± SD 6.05 ± 2.45 7 ± 2.32 0.28
Range (6 – 12) (6 – 14)
Number of sessions needed to
achieve variceal obliteration
0.13
Mean ± SD 4.14 ± 1.01 4.28 ±1.14
Range (3 – 6) (3 – 7)
Total amount of sclerosant
material needed to achieve 49.5 ± 52.46 ±
0.24
variceal obliteration (c.c.) 15.77 17.37
84
Results
Table (14): Complications of sclerotherapy in both groups.

Group I Group II
P
Variable (n = 50) (n = 50)
value
No % No %
Early Complications
Retrosternal chest pain 21 42% 22 44% 0.84
Abdominal distension 6 12% 6 12% 1.0
Perforation 0 0% 0 0% 1.0
Delayed Complications
Dysphagia 17 34% 16 32% 0.83
Esophageal ulcer 6 12% 6 12% 1.0
Fever (>38 ºC.) 12 24% 13 26% 0.82
Esophageal stricture ( confirmed

0 0% 0 0% 1.0
by endoscopy )
Pleural effusion 0 0% 0 0% 1.0
Pneumonia 0 0% 0 0% 1.0
Combined complications 0 0% 0 0% 1.0
Mediastinitis 0 0% 0 0% 1.0
Death 0 0% 0 0% 1.0
85
Results
Table (15): Complications of argon plasma coagulation in group I.
Variable No %
Early Complications
Retrosternal chest pain 21 42%
Abdominal distension 8 16%
Submucosal emphysema 0 0%
Perforation 0 0%
Dysphagia 16 32%
Fever (>38 ºC.) 23 46%
Esophageal ulcer 2 4%
Pneumonia 0 0%
Pleural effusion 0 0%
Oesophageal stricture ( confirmed by
0 0%
endoscopy )
Combined complications 0 0%
Mediastinitis 0 0%
Death 0 0%
86
Results
Table (16): Complications of APC in group I versus complications of

EST in group II:
Group I (EST plus Group II (EST
APC) alone) P
Variable
(n = 50) (n = 50) value
No % No %
Early Complications
Retrosternal chest 21 42% 22 44% 0.84
pain
Abdominal distension 0.56
8 16% 6 12%
Submucosal
0 0% 0 0% 1.0
emphysema
Perforation 0 0% 0 0% 1.0
Dysphagia 16 32% 16 32% 1.0
Fever (>38 ºC.) 23 46% 13 26% 0.03
Esophageal stricture
(confirmed by 0 0% 0 0% 1.0
endoscopy )
Esophageal ulcer 2 4% 6 12% 0.14
Pleural effusion 0 0% 0 0% 1.0
Mediastinitis 0 0% 0 0% 1.0
Pneumonia 0 0% 0 0% 1.0
Combined
0 0% 0 0% 1.0
complications
Death 0 0% 0 0% 1.0
87
Results
Table (17): Data of variceal recurrence in both groups of patients.
Group I Group II
Variable P value
(n = 50) (n = 50)
Total number of patients with

variceal recurrence
7 (14%) 19 (38%) 0.006
Time between obliteration and

recurrence (weeks)
29.57± 6.29 20.68± 6.84 0.003
Mean ± SD (Log Rank
(19-38) (7-35) test)
Range
Table (18): Data of rebleeding in both groups of patients.
Group I Group II
Variable P value
(n = 50) (n = 50)
Total number of patients who

rebled from ruptured esophageal 1 7 0.027
varices (2%) (14%)
Time between obliteration and

rebleeding (weeks) Rebleeding 0.006
Mean ± SD occurred at the (25.37 ± 7.92) (Log Rank
th
Range 27 week 16-35 test)
88
Results
Figure (6)
Child-Pugh classification in the studied groups

at randomization
89
Results
Figure (7)
Virological markers of the studied groups at

randomization
90
Results
Figure (8)
Aetiology of liver cirrhosis in the studied groups

at randomization
91
Results
Figure (9)
Initial Endoscopic Results

(According to the grade of varices)
92
Results
Figure (10)
Kaplan-Meier analysis of the cumulative

recurrence-free curves. The cumulative
recurrence-free rate was significantly higher in
group I
93
Results
Figure(11)
Kaplan-Meier analysis of the cumulative

rebleeding-free curves. The cumulative
recurrence-free rate was significantly higher in
group I
94
Results
Figure (12): Endoscopic application of argon plasma

coagulation. The APC probe appears creating a longitudinal
stripe of coagulation of the distal esophageal mucosa.
Figure (13): Endoscopic appearance of the lower esophageal

mucosa at the end of an APC session.
95
Results
Figure (14): Endoscopic appearance of the lower

esophageal mucosa in the same patient one month after the APC
session.
Figure (15): Endoscopic appearance of the lower

esophageal mucosa in the same patient 6 months after the APC
session.
96
DISCUSSION
Discussion
DISCUSSION
Bleeding from ruptured esophageal varices is a major cause of

morbidity and mortality in cirrhotic patients (Graham and Smith, 1981
and Narayanan and Patrick, 2006), as well as in patients with
hepatosplenic schistosomiasis (Corderio, 1990). It is also the most
common cause of upper gastrointestinal bleeding in Egypt (Sheir et al.,
1980).
Endoscopic injection sclerotherapy is a widely used method for

treatment of haemorrhage from ruptured esophageal varices, both for
haemostasis and for prevention of rebleeding (Menessy, 1988,
Hashizume et al., 1992, and Narayanan and Patrick, 2006). For
prevention of recurrent variceal bleeding, endoscopic injection
sclerotherapy is performed on a repeated basis until varices in the distal
esophageal mucosa are obliterated (Hashizume et al., 1992 and El -
Sayed et al., 1996). However, recurrence of varices occurs in 41.7% of
patients within one year of obliteration, whereas rebleeding occurs in
15.6% of patients within one year of obliteration (Garrett et al, 1988,
Krige, 2000 and Madonia et al., 2000).
In view of this unacceptably high rate of recurrence, the availability of

other pharmacological, endoscopic and radiological therapies for the
prevention of variceal recurrence and rebleeding has been earnestly
desired (Furukawa et al., 2002). Prevention consolidation therapy
(mucosa-fibrosing therapy) has been reported as being ideally suited for
this purpose (Obara, 2006). There are several different techniques for
performing mucosal fibrosis therapy, but the most common are
97
Discussion
perivariceal injection of 1% polidocanol (Matsui et al., 2004) and thermal

coagulation of the esophageal mucosa using Nd/Yag laser, high
frequency coagulation, microwave coagulation (Obara et al., 1994),
however, these consolidation therapies had disastrous complications (e.g.
esophageal stricture and mediastinitis) (Furukawa et al., 2002).
Prevention consolidation therapy using argon plasma coagulation is a

recent, trendsetting endoscopic technique where argon plasma
coagulation - a non contact, monopolar thermal method - is used for
induction of fibrosis of the distal esophageal mucosa after variceal
obliteration to minimize the rate of variceal recurrence and rebleeding
(Nakamura et al., 2001 and Watanabe et al., 2001). The distinguishing
characteristic of APC is that shallow coagulation can be achieved over
extensive tissue areas within a short period of time, making it ideal for
mucosal fibrosis therapy. APC has proven to be an effective prevention
consolidation therapy that may be used after esophageal variceal ligation
(EVL) or sclerotherapy with no serious complications (Furukawa et al.,
2002).
The present clinical randomized trial was specifically designed to

assess the efficacy and safety of argon plasma coagulation as a prevention
consolidation therapy after endoscopic injection sclerotherapy for the
prevention of variceal recurrence and rebleeding. So two groups of
patients were studied, the first group included 50 patients treated by
endoscopic injection sclerotherapy followed by argon plasma coagulation
therapy. The second group included 50 patients treated by endoscopic
injection sclerotherapy alone.
In our study, variceal bleeding was much more encountered in males

than females, which is similar to findings reported previously by Menessy
98
Discussion
(1988) and El-Sayed et al. (1996). This can be possibly explained by the
fact that males have higher incidence of hepatitis and bilharzial infection
and more liable for exposure to physical and mental stress (Mousa and
El-Gendy, 1962).
In the present study, the mean age of patients was found to be about 49
years which is nearly similar to studies reported by Al-Karawi and
Mohamed (1988) and El-Sayed et al. (1996). This observation can be
explained by the fact that, during this period of life, maximum activity in
work with increased mental and physical stress could be found (Mousa
and El-Gendy, 1962).
Ulcerogenic drugs, mental or physical stress, fever were the

precipitating factors for rupture of esophageal varices in 23%, 14% and
14% respectively. These results are in agreement with the findings of
Menessy et al., (1988).
Franco (1977) explained the effect of stress by the excessive
catecholamine release leading to splenic contraction and constriction of
hepatic venous sphincters leading to rise of portal pressure.
Ulcerogenic drugs are also major precipitating factors for bleeding in

our study. This can be attributed to inhibition of prostaglandin synthesis
in the gastric mucosa (Mirouze et al., 1983).
Amer et al., (1970) explained the effect of fever by the fact that fever
induces hyperdynamic circulation and hepatotoxic effect, both leading to
rise in portal pressure.
99
Discussion
In the present study, about two thirds of patients suffered from mixed
schistosomal and post-hepatitic cirrhosis, while only one third of patients
suffered from pure post-hepatitic cirrhosis. This finding is in accordance
with that of Deiab (2003).
In our study, the incidence of anti-HCV positive patients was 88% in

group I and 94% in group II. Whereas the incidence of HBsAg positive
patients was 12% in group I and 6% in group II. This low incidence of
HBsAg positive patients is not consistent with the findings of El Sayed et
al. (1996) who reported that 63% of patients are HBsAg positive. This
may be attributed to the fact that coinfection of hepatitis B patients with
HCV suppresses HBV replication causing underestimation of HBV
prevalence as reflected by HBsAg (Sheen et al., 1992).
In the current study, Child-Pugh class A and B patients represents the

majority of cases (40% and 48% respectively in group I and 38% and
52% respectively in group II) .This is in agreement with that reported by
El-Askalany (1993), Abd El-Mageed (2001) and Deiab (2003). This can
be explained by the fact that patients with schistosomal liver disease have
the advantage of relatively well preserved liver function, as the lesion is
primarily a mesenchymal affection, sparing parenchyma until late
advanced stage of the disease (Ramos et al., 1964).
Initially, both groups of patients of the present study were well

matched as regards age, sex, baseline biochemical and haematological
data, etiology of liver disease, severity of underlying liver disease (Child-
Pugh scoring) and endoscopic data.
In our study, obliteration of esophageal varices using repeated

injection sclerotherapy was performed in both groups with almost similar
100
Discussion
results: the time needed for variceal obliteration (in weeks) was 6.05 ±
2.45 in group I and 7 ± 2.32 in group II ( P = 0.28 ) , number of sessions
needed to achieve variceal obliteration was 4.14 ± 1.01 in group I and
4.28 ±1.14 in group II ( P = 0.13 ), total amount of sclerosant material
needed to achieve variceal obliteration was 49.5 ± 15.77 in group I and
52.46 ± 17.37 in group II ( P = 0.24 ), these figures are consistent with
results of sclerotherapy obliteration of esophageal varices reported by
Hamed et al. (1998) .
After complete variceal obliteration in both groups, APC was
performed in all patients of group I producing fibrosis of the distal 5-7cm.
of the whole circumference of esophageal mucosa. Three APC sessions
were required to ablate the distal esophageal mucosa .The APC
equipment adjustment and technique used in our study were similar to
those adopted by Nakamura et al. (2001) and Cipoletta et al. (2003).
To determine the therapeutic outcome, all patients were followed up
by upper G.I. endoscopy at monthly intervals to check for variceal
recurrence. The cumulative recurrence-free rate at the end of follow up
period was significantly better in group I (the combination therapy group)
than group II (control group) . Recurrence was recorded in 7 patients
(14%) of group I and in 19 patients (38%) of group II, also time interval
between obliteration and recurrence was longer in group I ranging from
19 to 38 weeks with a mean of 29.57± 6.29 weeks while in group II it
ranges between 7 and 35 weeks with a mean of 20.68± 6.84 weeks. APC
definitely enhanced mucosal fibrosis and improved the recurrence-free
rate .
The total number of patients who rebled was one patient (2%) in group
I and 7 patients (14%) in group II. There was significant reduction in the
101
Discussion
rebleeding rate in group I. Bleeding esophageal varices were the source of

rebleeding in all patients who experienced rebleeding episodes.
The results of our study can be put in accordance with the findings
of Nakamura et al., (2001) who studied the efficacy and safety of argon
plasma coagulation as a prevention consolidation therapy after
endoscopic variceal ligation (EVL). They performed their study on two
patient groups each consists of 30 patients. The first group received
combined EVL plus APC therapy while the other group received EVL
only. They concluded that endoscopic ligation of esophageal varices
combined with APC is superior to ligation alone in prevention of variceal
recurrence and rebleeding. Our results also come in accordance with a
similar study performed by Cipoletta and his colleagues (2003) .In their
study, thirty patients with cirrhosis, a history of acute esophageal variceal
bleeding, and eradication of varices by endoscopic variceal ligation were
randomized to argon plasma coagulation group (16 patients) or
observation group (14 patients). They concluded that argon plasma
coagulation of the distal esophageal mucosa after eradication of
esophageal varices by endoscopic variceal ligation is safe and effective
for reducing the rate of variceal recurrence.
Complications of sclerotherapy are mainly dependent on the technique

(intravariceal or paravariceal), type of sclerosant material, interval
between sessions and usage of overtube or balloon compression after
sclerotherapy (Madonia et al., 1990). In the present study, retrosternal
chest pain was recorded in 21 patients (42%) of group I and 22 patients
(44%) in group II. This is probably attributed to esophageal spasm after
sclerotherapy (Shocunt et al., 1986).
In our study, esophageal ulceration was recorded in 6 patients (12%)
in each group, this come in agreement with Laine et al. (1993) who
reported incidence rate of about 15% , but comes in contrast to Shocunt
102
Discussion
et al. (1986) who reported incidence rate of 20%-60% of esophageal

ulceration following sclerotherapy. These ulcerations required treatment
with 8-weeks course of omeprazole (40 mg daily), this is in agreement
with the study of Gimson et al. (1990). Dysphagia was reported in 34%
and 32% in group I and group II respectively and usually occurred in
association with esophageal ulceration and subsided within few days.
Fever was reported in 24% and 26% in group I and group II
respectively, it improved within 24 hours after sclerotherapy without
affecting the final outcome.
In our study, no major complications of sclerotherapy were recorded
(No esophageal srticture, pleural effusion, mediastinitis or death).
As regards complications of argon plasma coagulation therapy in the
combined therapy group, these were generally mild, transient and
required no treatment. Retrosternal chest pain occurred in 42% of
patients, dysphagia in 32% it was mild and subsided within few days.
Fever was reported in 24% of patients; it ranged between 38 and 39 ºC.
and was rapidly alleviated by antipyretic medications (paracetamol
500mg. every 8 hours).
No esophageal srticture, pleural effusion, esophageal ulceration
mediastinitis or deaths were recorded in the combined therapy group.
By comparing the overall complications in both groups, the incidence
of fever was significantly higher in group I (P = 0.03) which received
argon plasma coagulation therapy while the incidence of retrosternal
chest pain, dysphagia was not different between the two groups (Table
16). This complications profile of APC is almost similar to that concluded
by Nakamura et al. (2001), Cipolletta et al., (2002) and Boruchowicz et
al., (2006).
In our study, no early hemorrhage was observed in either group, no
patients died during treatment or follow up period.
103
SUMMARY AND
CONCLUSION
Summary & Conclusion
Summary and Conclusions
Endoscopic injection sclerotherapy is widely used for treatment of

bleeding esophageal varices. Repititive injections result in the eradication
of varices, but the high incidence of variceal recurrence and rebleeding –
may be as high as 50% – still represents a major clinical problem (De
Paulo et al., 2006).
The argon plasma coagulation (APC) technique is a non-contact

electrocoagulation method that utilizes a high frequency electric current
led by the flow of ionized gas, which is delivered to the target tissue to
form a coagulation zone. APC has been used over the last two decades in
laparoscopic and thoracoscopic operations, it was used in flexible
endoscopy for the first time in 1991 (Grund et al., 1998). A distinctive
feature characteristic of APC is effective shallow, uniform coagulation
over extensive areas, thus it can be used to induce fibrosis of the target
tissues.
In this study, argon plasma coagulation was used as a prevention

consolidation therapy (mucosa-fibrosing therapy) by inducing fibrosis of
the distal esophageal mucosa after eradication of esophageal varices with
(EST).
The aim of this prospective randomized study is to evaluate the safety

and efficacy of argon plasma coagulation when added to sclerotherapy for
prevention of variceal recurrence and rebleeding compared to
sclerotherapy alone.
This study was conducted from October 2004 to May 2006 on 100
patients who were admitted to Mansoura Emergency Hospital with a
104
clinically significant, recent and first attack of upper gastro-intestinal

bleeding which was confirmed endoscopically to originate from
esophageal varices.
Immediately after admission to the hospital, initial control of acute

variceal bleeding was done using the standard resuscitation measures and
patients were then treated by urgent endoscopic sclerotherapy within 12
hours of admission. All patients were subjected to thorough history
taking, full clinical examination, liver and kidney function tests, complete
blood picture, hepatitis B and C markers, abdominal ultrasonography.
Randomization was carried out after bleeding has been controlled and
the patients were divided into 2 groups:
- Group I: treated by regular endoscopic sclerotherapy at 2 weeks
interval until complete variceal eradication. Then argon plasma
coagulation therapy of the lower esophageal mucosa was done at 2 – 4
weeks intervals until complete coagulation of the mucosa in the distal
esophagus was achieved. It included 50 patients, 40 males and 10 females
with mean age of 49.04 ± 6.45 years.
- Group II: treated by endoscopic sclerotherapy alone at 2 weeks
intervals until complete variceal eradication. It included 50 patients, 38
males and 12 females with mean age of 50.28 ± 6.23 years.
All patients were followed-up by upper G.I. endoscopy at monthly

intervals to check for recurrence of esophageal varices. Changes in
biochemical parameters were reassessed after 12 weeks. Rebleeding
episodes were recorded and the source of rebleeding was endoscopically
confirmed.
Initially, the 2 groups were matched for age, sex, etiology of liver
disease, severity of liver disease (Child-Pugh scoring), biochemical,
105
haematological and endoscopic data at randomization.

At the end of the follow up period, the following results were
recorded:
1- No changes in the biochemical and haematological data in both
groups.
2-Variceal obliteration was achieved in both groups with no
significant statistical differences as regards the time needed for
variceal obliteration, number of sessions needed for variceal
obliteration or total amount of sclerosant material needed for
variceal obliteration.
3- The cumulative recurrence-free rate was significantly better in
group I than group II.
Variceal recurrence was recorded in 7 patients (14%) of group I
and in 19 patients (38%) of group II.
The time interval between obliteration and recurrence was longer in
group I ranging from 19 to 38 weeks with a mean of 29.57± 6.29
weeks while in group II it ranges between 7 and 35 weeks with a mean
of 20.68± 6.84 weeks ( P value by Log Rank test = 0.003 ).
4- Variceal rebleeding was significantly reduced in group I
compared to group II (P value = 0.027). The total number of
patients who rebled was one patient (2%) in group I and 7
patients (14%) in group II. Bleeding esophageal varices were the
source of rebleeding in all patients who experienced rebleeding
episodes.
5- Complications of sclerotherapy were almost similar in both
groups; these were mild and transient in the form of fever,
retrosternal pain and superficial esophageal ulceration.
6- Complications of argon plasma coagulation therapy in the
combined therapy group were generally mild, transient.
106
retrosternal chest pain occurred in 42%, abdominal distension in

16% dysphagia in 32% and fever in 46% of group I patients.
7- Comparing the overall complications in both groups, the
incidence of fever was significantly higher (P = 0.03) in group I
which received argon plasma coagulation therapy while the
incidence of retrosternal chest pain, abdominal distension,
esophageal ulceration and dysphagia was not different between
the two groups.
8- No esophageal stricture, pleural effusion, pneumonia or
mediastinitis were recorded in both groups.
9- No deaths were recorded in both groups during treatment or
follow up period.
Conclusion and Recommendations
1- Combination of endoscopic injection sclerotherapy and argon

plasma coagulation - as a mucosal fibrosis therapy - is superior
to sclerotherapy alone in decreasing the incidence of variceal
recurrence and rebleeding.
2- Argon plasma coagulation is an effective prevention
consolidation therapy that has minimal complications and well
tolerated by patients.
3- Further controlled, multicentre studies, on larger number of
patients and for longer duration should be done for better
assessment of the long-term efficacy and safety of argon plasma
coagulation as a prevention consolidation therapy.
107
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Argon Plasma Coagulation Plus Injection Sclerotherapy Versus Injection Sclerotherapy Alone For The Prevention of Variceal Recurrence and Re Bleeding

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Argon Plasma Coagulation Plus Injection Sclerotherapy Versus Injection Sclerotherapy Alone For The Prevention of Variceal Recurrence and Re Bleeding

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Mansoura University

Argon Plasma Coagulation

Prof. Dr. Prof. Dr.

Dr. Mohamed Mahmoud Fahmy El-Saadany

PDF processed with CutePDF evaluation edition www.CutePDF.com

‫إ‪)*+,‬ام ﺕ‪ ./0‬ا@رﺝ=ن ;‪:‬ز‪ 67 87‬اﻝ‪234‬‬

First and foremost, all thanks and gratefulness to "ALLAH", the

I would like to express my deepest gratitude to Prof. Dr. Magdy

I would like also to express my sincere thanks to Prof. Dr. Ayman

I am deeply grateful and forever indebted to Dr. Mohamed

Last but not least, I would like to thank my colleagues, staff

INTRODUCTION AND AIM OF THE 1

The Portal Venous System 3

Management of esophageal varices 16

SUMMARY AND CONCLUSION 104

Table Subject Page

Table (1) Setting of argon plasma coagulation (APC) 30

Figure Subject Page

Figure (1) Schematic representation of the portal and 3

Gastrointestinal bleeding is the most severe complication of portal

Endoscopic injection sclerotherapy (EST) has long been the most

Argon plasma coagulation (APC) is a non-contact thermal coagulation

In this study, argon plasma coagulation will be used to induce fibrosis

Aim of the work:

The Portal Venous System

Fig (1): Schematic representation of the portal and hepatic venous

Anatomy of the portal venous system

(Bergman et al, 1988)

The portal vein itself is approximately 6-8 cm long and 1-1.2 cm in

• Left gastric (coronary) vein.

Portal vein flow in man is about 1000-1200 ml/ minute (Sherlock

An important feature of this system is that a number of its tributaries

In portal hypertension, these venous collaterals dilate and allow portal

The other important surgical anatomy in portal hypertension is the

Angioarchitecture of the gastroesophageal junction:

The lower part of human osophagus has a characteristic vascular

The veins of the gastroesophageal junction are classified as intrinsic,

It has been reported that bleeding from esophageal varices mostly

Normal physiology of portal circulation

The normal hepatic blood flow is about 1.5 L/min of which

increase in sinusoidal pressure decreases the hepatic arterial flow. The

Pathophysiology and hemodynamics of portal

Hemodynamic factors in portal hypertension

1-Increased vascular resistance

2-Increased portal blood flow and the hyperdynamic systemic

Recently, nitric oxide (NO) has received great attention as a peripheral

ii. High concentration of cyclic guanosine monophosphate (c-GMP),

Two types of NOS exist, the eNOS (endothelial or constitutive) and

Studies have recently focused on carbon monoxide (CO) as a regulator of

Fig (3): Regulation of vascular tone by endothelins and nitric oxide.

Beyond a critical value of portal pressure, an attempt is made by the

Fig (4): Schematic representation of portosystemtic collaterals. Arrows reflect

These collaterals (Fig 4) are, in fact, a system of resistance channels in

Where R = resistance, η = viscosity of fluid, l = length of the vessel

MANAGEMENT OF ESOPHAGEAL VARICES

Gastro-esophageal varices develop in 50% to 60% of cirrhotic patients

Endoscopy is the gold standard for the diagnosis of varices (LaBerge

Although esophageal varices are easy to detect, gastric varices may

Treatment of esophageal varices

The treatment of esophageal varices includes the prevention of

ii. In patients with cirrhosis, varices decreased in size and may

Continued propranolol or nadolol therapy markedly reduces the

for bleeding. 44 patients received propranolol at a dose sufficient to