181
Research article/Raziskovalni prispevek
PEPTIC ULCER HEMORRHAGE: COMPARISON OF
EFFICACY OF TWO METHODS OF ENDOSCOPIC
HEMOSTASIS – A PROSPECTIVE STUDY*
KRVAVEČA PEPTIČNA RAZJEDA: PRIMERJAVA UČINKOVITOSTI DVEH METOD
ENDOSKOPSKE HEMOSTAZE – PROSPEKTIVNA RAZISKAVA
Pavel Skok1, Marija Skok2
1 Dep. of Gastroenterology and Endoscopy, Clinical Department of Internal Medicine, General Hospital Maribor,
Ljubljanska ulica 5, 2000 Maribor
2 Health Centre Dr. A. Drolc Maribor, Ul. Talcev 5, 2000 Maribor
Arrived 2003-08-04, accepted 2003-11-21; ZDRAV VESTN 2004; 73: 181–6
Ključne besede: peptična razjeda; krvavitev; endoskopska
hemostaza; argonska plazemska koagulacija; injekcijsko skle-
rozacijsko zdravljenje; prospektivna raziskava
Izvleček – Izhodišča. Akutne krvavitve iz zgornje prebavne
cevi sodijo med pogosta nujna stanja, s katerimi se srečujemo
v urgentni medicini in gastroenterologiji. Peptična razjeda je
najpomembnejši vir krvavitev. V Sloveniji je letna incidenca
krvaveče peptične razjede 118 bolnikov/100.000 prebivalcev.
Bolezen je povezana s pomembno umrljivostjo, še zlasti pri
starejših bolnikih s pridruženimi obolenji. Po podatkih iz
literature so endoskopske hemostatske metode in zdravljenje
v usmerjenih intenzivnih enotah vplivale na zmanjšanje umr-
ljivosti pri teh bolnikih v zadnjem obdobju.
Namen raziskave. Namen raziskave je bil ovrednotiti učinko-
vitost in varnost argonske plazemske koagulacije v primerja-
vi z injekcijskim sklerozacijskim zdravljenjem pri krvaveči pep-
tični razjedi in ugotoviti umrljivost teh bolnikov v prospektiv-
ni, kontrolirani raziskavi.
Bolniki in metode. Raziskava vključuje 100 bolnikov s krva-
večo peptično razjedo, 63 moških in 37 žensk, povprečne sta-
rosti 57,1 leta, SD ± 16 let, v razponu od 26–80 let. Med njimi
je bilo 50 bolnikov z želodčno razjedo in 50 bolnikov z razje-
do dvanajstnika, zdravljenih zaradi krvavitve v naši ustano-
vi v obdobju od 1.januarja 1999 do 15. maja 2000. Vsi bolni-
ki so prvič zakrvaveli zaradi razjede. Ob nujni endoskopski
preiskavi je bila aktivnost krvaveče razjede ocenjena v skla-
du z Forrestovo klasifikacijo. Po randomizaciji smo pri 50
bolnikih opravili endoskopsko hemostazo z argonsko plazem-
sko koagulacijo (instrument ARCO 2000, skupina A), pri 50
bolnikih pa injekcijsko sklerozacijsko zdravljenje (z razred-
čenim adrenalinom v razmerju 1:10.000 in 1% polidokano-
lom, skupina B). Bolnike smo zdravili v enoti internistične
intenzivne medicine, kjer so bili hemodinamsko nadzorova-
ni. Prejemali so simptomatsko zdravljenje, vključno s transfu-
zijami. Skupini bolnikov se nista pomembneje razlikovali gle-
de na starost, spol, aktivnost krvavitve, uporabo nesteroidnih
protivnetnih zdravil in pogostost pridruženih obolenj.
Key words: peptic ulcer; hemorrhage; endoscopic hemosta-
sis; argon plasma coagulation; injection sclerotherapy; pro-
spective study
Abstract – Background. Interventional endoscopy has largely
reduced mortality in patients with peptic ulcer hemorrhage.
Study aims. To evaluate the efficacy and safety of endoscopic
hemostasis with argon plasma coagulation and injection scle-
rotherapy in bleeding peptic ulcer and determine the morta-
lity of patients in a prospective, controlled study.
Patients and methods. The study includes 100 patients with
peptic ulcer hemorrhage (male 63, female 37, av. age 57.1
years, SD ± 16, span 26–80; gastric ulcer 50 patients, duode-
nal ulcer 50 patients) in the period between 1 Jan. 1999 and
15 May 2000 treated in our institution. The bleeding activity
was determined according to Forrest classification. Fifty pa-
tients were randomized to receive argon plasma coagulation
(ARCO 2000 Electro Surgery unit, group A) and in fifty pa-
tients injection sclerotherapy (sclerosing with diluted adrena-
lin 1:10,000 plus polidocanol 1%, group B) was performed.
The groups did not differ with respect to age, sex, site, severity
of bleeding, use of NSAID and additional diseases.
Results. Clinically and endoscopically diagnosed reebleding
occured in 7/50 patients (14%) in group A and in 9/50 pa-
tients (18%) in group B; p = 0.78. The majority of reebleding
occured within 48 hours after endoscopic hemostasis, group
A 4/7 (57.1%), group B 7/9 (77.7%), p = 0.74. Repeated
endoscopic hemostasis did not prove successful in 8 patients
(group A 3/50, 6%, group B 5/50, 10%), p = 0.71. Seven pa-
tients were treated operatively. The total mortality rate was
9% (9/100 patients, group A 4/50, 8%, group B 5/50, 10%),
p > 0.05. Only one patient died due to peptic ulcer hemorrha-
ge, other 8 patients died due to concomitant diseases.
Conclusions. Argon plasma coagulation seems to be an effec-
tive and safe alternative to injection sclerotherapy and other
hemostatic modalities in peptic ulcer hemorrhage.
ZDRAV VESTN 2004; 73: 181–6
* Data were in part presented at the 21st International Symposium on Intensive Care and Emergency medicine, Brussels, 20–23 March 2001 (abstract number 141–
S65). Podatki so bili delno predstavljeni na 21. International Symposium on Intensive Care and Emergency medicine, Bruselj, 20.–23. marec 2001 (izvleček številka
141-S65).
182 ZDRAV VESTN 2004; 73
Rezultati. Klinično in endoskopsko smo potrdili ponovitev kr-
vavitve pri 7/50 bolnikov (14%) v skupini A in pri 9/50 bolni-
kih pri skupini B (18%), p = 0,78. Večina ponovitev krvavitev
je bila v prvih 48 urah po endoskopski hemostazi, v skupini A
4/7 (57,1%), v skupini B 7/9 (77,7%), p = 0,74. S ponovljeno
endoskopsko hemostazo nismo bili učinkoviti pri 8 bolnikih
(skupina A 3/50, 6%, skupina B 5/50, 10%), p = 0,71. Zaradi
neuspešne endoskopske hemostaze smo 7 bolnikov zdravili
operativno. Skupna umrljivost vseh naših bolnikov je bila 9%
(9/100 bolnikov, skupina A 4/50, 8%, skupina B 5/50, 10%),
p > 0,05. Samo en bolnik je umrl zaradi krvaveče peptične
razjede, ostalih 8 bolnikov pa zaradi pridruženih bolezni.
Zaključki. Argonska plazemska koagulacija sodi med učinko-
vite, varne in cenovno dostopne metode endoskopske hemo-
staze pri akutnih krvavitvah iz prebavne cevi. Rezultati raz-
iskave potrjujejo, da je učinkovitost te metode pri krvaveči pep-
tični razjedi primerljiva z injekcijskim zdravljenjem, ki je v
Sloveniji med najpogosteje uporabljenimi tehnikami hemo-
staze. Umrljivost bolnikov s krvavečo peptično razjedo je pra-
viloma odvisna od pridruženih obolenj, ki vplivajo na razvoj
zapletov in neuspešnost endoskopskega in/ali operativnega
zdravljenja.
Introduction
Acute upper gastrointestinal hemorrhage is a frequent emer-
gency encountered in family practice, urgent medicine and
gastroenterology (1–3). This condition usually necessitates ho-
spital admission, often to an intensive care unit (ICU) for
fluid and blood resuscitation, hemodynamic monitoring and
urgent endoscopy. The most frequent causes of severe he-
morrhage are complications due to peptic ulcers of stomach
or duodenum and hemorrhagic, erosive mucosal changes of
the upper digestive tract (4, 5). Helicobacter pylori infection
and nonsteroidal antiinflammatory drugs (NSAIDs) account
for the majority of benign ulcerations (5). The importance of
NSAIDs as a major cause of peptic ulcer bleeding may de-
cline in the future, because the new class of NSAIDs, selective
cyclooxigenase-2 (COX-2) inhibitors, holds a great deal of pro-
mise in terms of reduced gastrointestinal toxicity. Various
statistics have confirmed that 20% of all peptic ulcer patients
have at least one incident of hemorrhage in their life. In
Slovenia, the incidence of peptic ulcer hemorrhage is 118/
100,000 inhabitants, with a significant mortality (5). At all ages
the incidence is higher in males, except in the age group over
80 years.
Emergency endoscopy is the most effective diagnostic and
therapeutic method in peptic ulcer hemorrhage (6–10). This
treatment modality has considerably reduced the number of
emergency operations, length of hospital stay and mortality
(4, 5, 7, 9). Different endoscopic techniques including elec-
trocoagulation, laser therapy, thermal probes, mechanical de-
vices, injection of fibrin/thrombin glue or injection of adre-
naline with or without a sclerosant or dessicant score a simi-
lar therapeutic success in peptic ulcer bleeding, but recurren-
ces of hemorrhage and the development of hemorrhagic
shock still represent alarming problems (3, 5, 6, 9–11). Argon
plasma coagulation (APC) is a special procedure of contact-
free electrocoagulation in which energy is transmitted to the
tissue through ionized and therefore conductive argon gas
(i.e. argon plasma) (11–19). APC through a flexible endoscope
provides a new technique for thermal devitalization or blood
coagulation which was introduced by Grund et al. in Tübin-
gen already in 1991 (11, 12).
The main objectives of this prospective study conducted at
our institution were to evaluate the efficacy and safety of
APC in comparison with injection sclerotherapy (IS) in bleed-
ing peptic ulcer and to evaluate the mortality of these pa-
tients.
Patients and methods
The study includes 100 patients with an emergency hospital
admission due to peptic ulcer hemorrhage (male 63, female
37, av. age 57.1 years, SD ± 16, span 26–80; gastric ulcer 50
pts, duodenal ulcer 50 pts) in the period between 1 January
1999 and 15 May 2000. The study was approved in 1998 by
the Medical Ethics Committee of the Republic of Slovenia
(No. 90/09/98; The influence of Helicobacter pylori eradica-
tion on development of reflux disease of the esophagus in
patients with bleeding peptic ulcer) and carried out in accor-
dance with the principles of the Helsinki – Tokyo Declarati-
on and the Code of Ethics of Slovene health workers. At our
institution all patients with gastrointestinal hemorrhage are
treated at the Department of the Internal Medicine where the
only endoscopy unit is located, situated directly next to the
Intensive Care Unit (ICU). The organization of work ensures
the 24-hour presence of the endoscopy team. In all cases
urgent endoscopic investigations of the upper digestive tract
were carried out to determine the origin of hemorrhage
within two hours after admission. Prior to the procedure,
each patient was acquainted with the aim of the investigati-
on and he gave his written consent to the endoscopic proce-
dure. As premedication prior to the procedure, butylscopo-
lamine 20 mg/ml (Buscopan, Boehringer Ingelheim, Ger-
many) was administered in the iv. form, as well as local
anesthesia with 1% lidocaine spray (Xylocain, Astra), usually
1–2 insufflations. All investigations were carried out with an
Olympus GIF Q20 and GIF Q30 device (Olympus GmbH,
Hamburg) and the EVIS (Endoscopic Video Information Sys-
tem, CLV U20) with OTV-F3 OES TV system (Olympus Opti-
cal, Hamburg GmbH). Vigorous washing with the USW-1
water pump (Olympus Optical, Hamburg GmbH) was per-
formed to remove adherent clots from the ulcer floor to
better inspect the ulcer base. The bleeding activity was deter-
mined according to Forrest classification. In all patients en-
doscopic hemostasis was performed. During interventional
endoscopy patients were randomly allocated to either of
183
two groups by using sealed envelopes which has been distri-
buted to endoscopists. Fifty patients were randomized (gro-
up A) to receive Argon Plasma Coagulation (APC), and in
fifty patients (group B) injection sclerotherapy (IS) was per-
formed. The groups did not differ with respect to age, sex,
site and severity of bleeding, additional diseases or use of
nonsteroidal anti-inflammatory drugs (NSAIDs). APC was per-
formed with ARCO 2000 Electro Surgery unit (Söring Ltd,
Quickborn, Germany; the angle of the probe app. 45° in rela-
tion to tissue surface, distance from tissue app. 10 mm, po-
wer settings: 70 W, gas flow 2 l/min, using Argon gas of
99.99% purity). During endoscopic hemostasis, APC was first
performed around the bleeding source and if the vessel was
visible, also the vessel was coagulated. IS was performed
with diluted adrenalin 1:10,000 and 1% polidocanol (Sclero-
vein® preparation, Resinag AG, Schwyz). Injection treatment
consisted of diluted adrenaline which was administered in
aliquots of 1 ml close to the bleeding site (up to 6 ml) until
the hemorrhage stopped. Subsequently up to 3 ml of polido-
canol were injected closely around the bleeding lesion. After
endoscopic control of bleeding, patients were admitted to
the ICU. Blood pressure and heart rate were continously
monitored. Each patient received 40 mg omeprazole iv. (Lo-
sec® preparation, Astra, Södertälje, Sweden), which was follo-
wed by oral treatment with 20 mg omeprazole twice daily
after 3 days. Conventional supportive therapy including in-
travenous fluids and transfusions were given as required.
Transfusion of packed red cells was administered in order to
maintain the hemoglobin level at approximately 95–100 g/l.
In cases of clinically evident reebleding (hemodynamic in-
stability: systolic pressure < 100 mm Hg, heart rate > 100
beats/min, hematemesis or bloody aspirates after clear lava-
ges from nasogastric tube, passage of melena with a fall of
hemoglobin level of 20 g/l or an inadequate increase in
hemoglobin after transfusion) the patients were reendosco-
ped and the same hemostatic modality was repeated. In ca-
ses of second reebleding surgery was recommended to the
attending physician in the ICU. Each patient received anot-
her endoscopy four days later for Helicobacter pylori detec-
tion, biopsies were taken from antrum and corpus, rapid
urease test (Jatrox®-H. p.-Test, C. H. R Heim Arzneimittel
GmbH, Darmstadt, Germany) was performed and histologi-
cal examination in case of gastric ulcers to exclude mali-
gnancy. If Helicobacter pylori infection was confirmed, re-
commended antibiotic treatment (metronidazol 400 mg
twice daily, claritromycin 500 twice daily for the period of 7
days) was combined with proton pump inhibitor, omepra-
zol twice daily. Ulcer healing and Helicobacter pylori eradi-
cation (rapid urease test and histologic examination) was
registered 4 weeks after introduction the eradication the-
rapy. If first line eradication therapy failed, treatment was
given according to the antibiogramm.
The minimum observation time for the 91 patients who sur-
vived the bleeding or operation connected to hemorrhage
was 12 month. During the follow-up period patients were ma-
naged as outpatients. One year after inclusion in the study, 84
patients (84/91, 92.3%, group A: 42/46 patients, 91.3%, group
B: 42/45 patients, 93.3%) came to the gastroenterologic OPD
for a follow-up endoscopic investigation. Seven patients re-
fused the investigation.
Statistical analysis. The data were analyzed statistically
using the program SPSS for Windows (Version 8.0, SPSS Inc.,
1989–1997). The statistical data were expressed as arithmetic
mean and standard deviation. The Mann-Whitney U-test
was used for the analysis of nonparametric quantitative data
and the interaction of categorical data was determined
with χ 2 test. Conclusions were reached at a risk under 5%
(p < 0.05).
Results
One hundred patients with active bleeding or stigmata of re-
cent bleeding from peptic ulcer were included in this study:
25 patients with spurting arterial bleeding (F1a), 25 patients
with oozing bleeding (F1b), 25 patients with visible vessel in
the ulcer (F2a) and 25 patients with adherent clot in the ulcer
(F2b). Patient characteristics are summarized in table 1. All
patients included in the study had their first episode of peptic
ulcer hemorrhage. After initial endoscopic hemostasis, clini-
cally and endoscopically diagnosed reebleding occured in
7/50 patients (14%) in group A and in 9/50 patients (18%) in
group B, p > 0.05. The reebleding rates of ulcers with diffe-
rent Forrest criteria are listed in table 2. If only clinically dia-
gnosed episodes were considered, the rate of recurrent he-
morrhage compared well between groups A and B, with 8%
(4/50) and 10% (5/50), p > 0.05. The majority of reebleding
occured within 48 hours, group A 4/7 (57.1%), group B 7/9
(77.7%). Reebleding ulcers were not significantly larger than
ulcers without further hemorrhage (1.55 cm vs. 1.45 cm, re-
spectively). The transfusion requirements were greater in
group A (1116 ± 216 ml vs. 1044 ± 144 ml, p = 0.05). Repeated
endoscopic hemostasis did not prove successful in 8 patients
(group A 3/50, 6%, group B 5/50, 10%), p > 0.05. After repeated
endoscopic interventions (21 in all, average 2.6, group A: 8
endoscopic interventions in three patients, group B: 13 en-
doscopic interventions in five patients), seven patients were
treated operatively. One patient refused operative treatment.
Apart from the bleeding peptic ulcer, every patient had at
least one coexisting disease. In three patients, the cause of
hemorrhage was a gastric ulcer and in four duodenal ulcer.
Regarding the type of operation, 4 patients were treated with
gastric resection according to the Billroth II method, three by
hemostatic suturing. During the postoperative period three
patients died (3/6, 50%, group A one patient, group B two
patients). Comparison of the outcome for patients in both
groups is listed in table 3. The total mortality rate was 9%
(9/100 patients), group A 8% (4/50), group B 10% (5/50), p >
0.05. Only one patient (1/100 patients, 1%) who refused ope-
rative treatment died directly due to peptic ulcer bleeding,
other 8 patients (8/100) patients, 8%, died due to concomi-
tant diseases, three among them (3/100 patients, 3%) after
emergency surgery. Causes of death included: respiratory
failure (2 patients), heart failure (2 patient), cerebral ischemia
(1 patient); among patients after surgery: multiorgan failure
(1 patient), heart failure (1 patient), pulmonary embolism
(1 patient).
At control endoscopic investigation, which was carried out
four weeks after introduction of eradication therapy, peptic
ulcer healing was confirmed in 42/46 patients, 91.3%, in
group A and in 39/45 patients, 86.7% in group B, p > 0.05. H.
pylori eradication treatment was efficient in 29/32 patients,
90.6% in group A (two patients with Helicobacter pylori in-
fection died, one after surgery, the other during hospitalisa-
tion) and in 29/33 patients, 87.9% in group B (two patients
with Helicobacter pylori infection died after surgery), p >
0.05. The results of the follow-up endoscopic investigation,
one year after inclusion in the study, are summarized in table
4. None of these 91 patients were treated for repeated hemo-
rrhage during this period.
Discussion
Significant advances have been made in understanding the
pathophysiology and management of peptic ulcer bleeding,
including improvements in endoscopic techniques, advances
in resuscitative measures and development of more potent
pharmacologic drugs (1, 2). The diagnosis and treatment of
SKOK P, SKOK M. PEPTIC ULCER HEMORRHAGE: COMPARISON OF EFFICACY OF TWO METHODS OF ENDOSCOPIC HEMOSTASIS
184 ZDRAV VESTN 2004; 73
peptic ulcer hemorrhage remains one of the most challeng-
ing and potentially rewarding parts of interventional endo-
scopy (3–10). In addition, emergency endoscopy can be use-
ful in predicting which patients are at higher risk for reebled-
ing. Although peptic ulcer bleeding is self limited in approxi-
mately 80% of cases, in the other 20% of patients who have
continued bleeding or reebleding during a hospitalisation,
mortality rates may be as high as 30% (1, 4, 5). In the last twen-
ty years, numerous effective methods of endoscopic hemo-
stasis were developed, making it possible to arrest most he-
morrhages from the peptic ulcer which did not stop spon-
taneously (1, 3, 4, 8, 9). During the last ten years, a large num-
ber of clinical trials have established that different modalities
of injection therapy (fibrin glue, thrombin, sclerosing agents,
ethanol, cyanoacrylate, cyanoacrylate glue, adrenaline), ther-
mal methods (electrocoagulation with monopolar or bipolar
probe, heater probe, laser photocoagulation, microwave) and
mechanical methods (hemoclips, rubber band ligation, endo-
Table 1. Patients characteristics.
Razpr. 1. Značilnosti bolnikov.
Group A (APC) Group B (IS) P value
Skupina A (APK) Skupina B (IS) P vrednost
Number of patients
Število bolnikov
50 50
Age (years, SD)
Starost (leta, SD)
56.7 ± 14.5 57.8 ± 14 ns (nz)
Sex (male/female)
Spol (moški/ženske)
32/18 31/19
Additional disease (%)
Pridružene bolezni (%)
46 48 ns (nz)
NSAID (%)
NSAR
32 30 ns (nz)
H. pylori (%) 68 70 ns (nz)
gastric ulcer
želodčna razjeda
64 64
dudenal ulcer
razjeda dvanajstnika
72 76
Hemoglobin (g/l)
Hemoglobin
103 ± 22 105 ± 20 ns (nz)
Ulcer location
Lokalizacija razjede
Gastric
Želodec
25 25
Duodenal
Dvanajstnik
25 25
Ulcer size (mm, SD)
Velikost razjede (mm, SD)
13 ± 3 13 ± 4 ns (nz)
Forrest classification
Forrestova klasifikacija
1a 12 12
1b 13 12
2a 12 13
2b 13 13
ns – not significant
nz – statistično neznačilno
Table 2. Reebleding rate of ulcers with different Forrest cri-
teria.
Razpr. 2. Ponovitve krvavitev pri različnih razjedah glede na
Forrestove kriterije.
Forrest classification
Group A Group B P
(N, %) (N, %) value
Forrestova klasifikacija
Skupina A Skupina B P vred-
(štev., %) (štev., %) nost
1a – spurting arterial bleeding
2/12 (16.7) 2/12 (16.7) ns (nz)brizgajoča arterijska krvavitev
1b – oozing arterial bleeding
1/13 (7.7) 3/12 (25) ns (nz)mezeča arterijska krvavitev
2a – visible vessel in the ulcer
2/12 (16.7) 2/13 (15.4) ns (nz)viden krn žile v dnu razjede
2b – adherent clot in the ulcer
2/13 (15.4) 2/13 (15.4) ns (nz)krvni strdek v dnu razjede
Av. reebleding rate (%)
Povprečna ponovitev krvavitve (%)
14% 18% p = 0.78
ns – not significant
nz – statistično neznačilno
Table 3. Comparison of the outcome for patients in both
groups.
Razpr. 3. Primerjava učinkovitosti zdravljenja bolnikov v obeh
skupinah.
Group A Group B P
(N, %) (N, %) value
Skupina A Skupina B P vred-
(štev., %) (štev., %) nost
Failure of endoscopic hemostasis
Neuspešna endoskopska
3/50 (6) 5/50 (10) ns (nz)
hemostaza
Surgery
Operativno zdravljenje
3/50 (6) 4/50 (8)* ns (nz)
Mortality – after surgery
Umrli – po op. posegu
1/3 (33.3) 2/4 (50) ns (nz)
Total
Skupaj
4/50 (8) 5/50 (10) ns (nz)
ns – not significant
nz – statistično neznačilno
* – one patient refused operative treatment
– bolnik je odklonil operativno zdravljenje
Table 4. The results of follow-up endoscopic investigations in
84 patients one year after inclusion in the study (seven pa-
tients refused endoscopy).
Razpr. 4. Rezultati kontrolne endoskopske preiskave pri 84 bol-
nikih leto dni po vključitvi v raziskavo (sedem bolnikov je
preiskavo zavrnilo).
Group A Group B P
(N, %) (N, %) value
Skupina A Skupina B P vred-
(štev., %) (štev., %) nost
Number of patients
42/46 (91.3) 42/45 (93.3) ns (nz)Število bolnikov
Peptic ulcer (recurrence)
Ponovitev peptične razjede
gastric
želodčna
– –
duodenal (1)
dvanajstnika
1/42 (2.4) 1/42 (2.4) ns(nz)
Peptic ulcer bleeding
Krvaveča peptična razjeda
– –
H. pylori (re)infection
Ponovna okužba s H. pylori
gastric ulcer (2)
želodčna razjeda
1/42 (2.4) – ns (nz)
duodenal ulcer (3)
razjeda dvanajstnika
1/42 (2.4) 2/42 (4.8) ns (nz)
(1) Both patients were using preparations of acetilsalycilic acid in the last week
before endoscopic investigation and were H. pylori negative.
Oba bolnika sta uporabljala pripravke acetilsalicilne kisline v zadnjem te-
dnu pred endoskopijo, okužbe s H. pylori nismo potrdili.
(2) The patient had H. pylori infection at inclusion at the study.
Bolnik je imel okužbo s H. pylori ob vključitvi v raziskavo.
(3) The patient from group A had H. pylori infection at inclusion at the study,
from group B one patient had also H. pylori at inclusion at the study.
Bolnik iz skupine A je imel okužbo s H. pylori ob vključitvi v raziskavo, iz
skupine B pa je imel okužbo s H. pylori ob vključitvi v raziskavo samo en
bolnik.
185
loop, endoscopic sewing) control active bleeding from peptic
ulceration and decrease the risk of rebleeding (3, 6, 8, 9, 17–
20). Their success is similar, to a great extent the success de-
pends on personal training, experience of the investigator and
the quality of instruments for interventional endoscopy (3,
6). Injection therapy is widely used, because effective hemo-
stasis can be accomplished with injection of various solutions,
including vasoconstrictors such as adrenaline, sclerosants such
as 1% polidocanol, ethanolamine, hypertonic saline and 98%
alcohol (3, 4). In Slovenia, sclerotherapy with polidocanol is
the method which has been used most frequently in the last
fifteen years (1–3). This method is still considered effective,
safe and economical. In clinical trials the amount of sclero-
sants is usually limited, because of the risk of ulcer extension
or perforation with larger volumes of injection. Serious com-
plications of endoscopic sclerotherapy are unusual and only
sporadicaly reported: extensive necrosis of gastric mucosa,
gastric ulcer, cholestasis and duodenal hematoma (3, 4, 8, 9).
Potential adverse effects of injecting adrenaline include syste-
mic absorption, which is rarely clinically significant (3).
APC is a recently introduced treatment in gastrointestinal en-
doscopy. This coagulation method is a special procedure
which transfers high-frequency current to tissue in a non-
contact manner via ionized and therefore conductive argon
gas (i. e. argon plasma) (11–17). The argon gas is ionised in
the high-frequency electric field between the electrode of the
applicator and the tissue. This method of endoscopic hemo-
stasis was introduced in our department in 1998 and replaced
the use of Nd-Yag laser in different hemorrhagic lesions and
gastrointestinal tumors (17). Argon is a colour- and odour-
less, non toxic, inert gas. It illuminates in ionised conditions,
which makes the use of the high-frequent alternating current
under visual-endoscopic control possible. In the past, this
method has been successfully used for hemostasis and de-
vitalisation in open surgery. Liver transplant surgeons use a
similar device to treat the bleeding surface of the diaphragm
and the liver following blunt dissection. Over the last decade
this method was also introduced into laparoscopic surgery
(11, 12). The development of special probes, which can be
handled via flexible endoscopes, has made this method
applicable for interventional endoscopy as well. From the
beginning, APC was used for the treatment of benign and
malignant tumors of the gastrointestinal tract and endosco-
pic hemostasis in hemorrhagic lesions (11, 12, 17–19). APC is
becoming increasingly popular also for treatment of Barrett’s
esophagus. The method proved to be highly effective and
easily used. The advantages of this technique are particularly
evident in difficult hemostasis situations, i. e. over large sur-
face areas, profuse hemorrhaging, in instances of difficult lo-
calization or critical wall characteristics (11, 12, 17). Due to
shallow penetration depth, this method reduces damage to
adjacent or submucosal tissues and also reduces the risk of
perforation (1, 12, 15, 19). Depending on instrument settings,
power settings, argon gas flow and the type of application
(axial, radial, retrograde), the penetration depths remains
between 0.5 and 3 mm and is therefore particularly suitable
for endoscopic hemostasis also in the duodenum and thin-
walled colon (11, 12). According to the results published, APC
is suitable in angiodysplasia, watermelon stomach, radiation
proctitis, bleeding peptic ulcers, obstructed stents, multiple
polyps and residues after polypectomy or mucosectomy (12,
17–19). When compared with laser treatment, APC has a
better advantage-risk ratio. Ease of learning, low cost and mo-
bility of the equipment are additional arguments for choosing
APC rather than laser. However, the extensive gas production
and related painful distension of the intestinal wall and risk
of perforation must not be underestimated. The results of our
study indicate that APC is a safe and effective alternative of
endoscopic hemostasis in peptic ulcer hemorrhage. No per-
forations, uncontrollable bleeding or other serious complica-
tions were seen in treatment of any of this patients. Although
no significant differences in efficacy were found comparing
two hemostatic methods, in the group of patients treated with
APC, lower rebleeding rates and lower mortality were obser-
ved. Another advantage of this method compared to IS might
be that repetition is harmless. In our patients no serious com-
plications developed after retreatment. The results of our
trial also confirmed that only one patient (1%) died directly
due to peptic ulcer bleeding, other seven patients died due to
concomitant diseases.
There is no doubt, that due to development of interventional
endoscopy and hemostatic therapy, allowing a successful
arrest of hemorrhage in as many as 90–97%, the mortality from
peptic ulcer hemorrhage has decreased (4, 6, 18–25). The
association between continued or recurrent bleeding and high
mortality in patients with peptic ulcer hemorrhage has been
already recognized in the past. According to various authors,
the mortality rate is still 5–14% (4, 5, 18–20). In our group of
patients it was 9%. There are several clinical and endoscopic
risk factors (different risk scoring systems: APACHE – Acute
Physiology and Chronic Health Evaluation scoring system,
Rockall risk scoring system, ASA – American Society of Anae-
sthesiology classification, Baylor bleeding score) that have
been suggested as predictive of an adverse outcome in these
patients (1, 4, 5, 17, 18, 24–26). Development of clinical pre-
dictive scoring systems has the potential to provide rational
and scientifically based criteria for diagnostic and manage-
ment decisions such as triage to an ICU, repeated attempts of
endosopic hemostasis, elective versus emergency surgery and
early discharge from ICU (19, 27, 28). The demographics of
patients with peptic ulcer hemorrhage suggest that this po-
pulation is older and includes many patients with significant
medical conditions which increase mortality (3, 4, 6, 21, 26).
Reebleding is considered one of the most important risk fac-
tors for mortality and occurs in 10–30% of those successfully
treated, although there is still considerable disagreement about
what the most important prognostic factors are (1, 5, 6, 26–
30). Many factors independently predict the risk of rebleeding.
According to some authors, the activity of bleeding at the
time of evaluation is a key prognostic factor (1, 19, 24, 27, 31–
35). The risk of reebleding from gastric or duodenal ulcers
can be estimated on the basis of endoscopic signs and diffe-
rent other criteria (36–41). Endoscopic stigmata of recent
bleeding – including the presence of an active spurting
vessel, a visible vessel or a fresh clot – are predictors of an
increased risk of bleeding. Ulcers on the proximal lesser
curve of the stomach and on the posterior surface of duode-
num generally have a higher chance of rebleeding because of
their proximity to the left gastric and gastroduodenal arteries
(42, 43). Patients with bleeding gastric ulcer develop recurrent
hemorrhage more often than do those with bleeding duodenal
ulcer. Other important independent predictors of rebleeding
are mainly shock at admission, age older than 65 years, ulcer
size (diameter greater than 2 cm) and comorbidity (36, 38,
39).
In treating a patient with peptic ulcer hemorrhage, it is vital to
strive for definitive endoscopic hemostasis. If continued
bleeding cannot be stopped, a timely decision regarding
other therapeutic options must be made (30, 38–40). Mini-
mally invasive surgery, as well as radiological techniques, par-
ticulary arterial embolisation, are valid alternatives to repeated
attempts of endoscopic hemostasis (43). A surgeon should
be notified immediately after interventional endoscopy if
endoscopic hemostasis was unsuccessful or if an ulcer at high
risk of rebleeding was diagnosed. The combination of endo-
scopic stigmata and clinical risk factors should guide our punc-
tual clinical decisions and increase the accuracy of predicting
individual risk in patients with peptic ulcer hemorrhage (34,
SKOK P, SKOK M. PEPTIC ULCER HEMORRHAGE: COMPARISON OF EFFICACY OF TWO METHODS OF ENDOSCOPIC HEMOSTASIS
186 ZDRAV VESTN 2004; 73
39, 44–49). Optimization of diagnostic and therapeutic mana-
gement may help decrease the mortality from peptic ulcer
bleeding in the future (50, 51).
Conclusions
During the past twenty years, endoscopy has developed as
the modality of choice for determining diagnosis, prognosis
and therapy for peptic ulcer bleeding. Clinical trials have con-
firmed that different methods of endoscopic hemostasis in-
cluding injection therapy, thermal coagulation, hemoclips and
other modalities are effective in decreasing bleeding from this
type of gastrointestinal hemorrhagic lesion. The method used
for the individual patient depends on available resources and
the experience of the endoscopist. Argon plasma coagulation
seems to be an effective and safe alternative to other hemo-
static modalities in peptic ulcer hemorrhage. No serious com-
plications were related to application of this hemostatic me-
thod in our study. Further prospective studies should be di-
rected towards refining our understanding of which ulcers
will rebleed and why, and optimizing therapy on selected high-
risk patients to improve their outcome.
Acknowledgement
The authors thank all participating in the study.
References
1. Skok P. Incidenca krvavitev iz zgornje prebavne cevi – petletna prospektiv-
na študija. Zdrav Vestn 2000; 69: 727–31.
2. Skok P. The epidemiology of hemorrhage from the upper gastrointestinal
tract in the mid-nineties – has anything changed? Hepatogastroenterology
1998; 24: 2228–33.
3. Skok P. How efficient is endoscopic injection sclerotherapy in peptic ulcer
hemorrhage? Hepatogastroenterology 1997; 15: 861–5.
4. Friedmann L, Martin P. The problem of gastrointestinal bleeding. Gastro
Clin North Am 1993; 22: 717–21.
5. Skok P. Peptična razjeda – najpogostejši vzrok krvavitve iz prebavne cevi.
Zdrav Vestn 1999; 68: 415–9.
6. Cook DJ, Guyatt GH, Salena BJ et al. Endoscopic therapy for acute non
variceal upper gastrointestinal haemorrhage: A meta-analysis. Gastroente-
rology 1992; 102: 139–48.
7. O’Connor KW, Robinson M, Boyce G et al. The role of endoscopy in the
management of non variceal acute upper gastrointestinal bleeding. Gastro-
intest Endosc 1992; 38: 760–4.
8. Steffes C, Sugawa C. Endoscopic management of non variceal gastrointesti-
nal bleeeding. World J Sur 1992; 16: 1025–33.
9. Kohler BJ, Riemann F. Upper gastrointestinal bleeding value and conse-
quences of emergency endoscopy and endoscopic treatment. Hepatogastro-
enterology 1994; 38: 198–200.
10. Gupta PK, Fleischer D. Endoscopic hemostasis in non-variceal bleeding.
Endoscopy 1994; 26: 48–54.
11. Grund KE, Storek D, Farin G. Endoscopic argon plasma coagulation (APC).
First clinical experiences in flexible endoscopy. End Surg 1994; 2: 42–6.
12. Grund KE, Zindel C, Farin G. Argon plasma coagulation through a flexible
endoscope. Evaluation of a new therapeutic method after 1606 uses. Dtsch
Med Wochenschr 1997; 122: 432–8.
13. Wahab PJ, Mulder CJJ, den Hartog G, Thies JE. Argon plasma coagulation in
flexible gastrointestinal endoscopy. Pilot experiences. Endoscopy 1997; 29:
176–81.
14. Johanns W, Luis W, Janssen J, Kahl S, Greiner L. Argon plasma coagulation
(APC) in gastroenterology: experimental and clinical experiences. Eur J Ga-
stroenterol Hepatol 1997; 9: 581–7.
15. Conio M, Gostout CJ. Argon plasma coagulation (APC) in gastroenterology:
experimental and clinical experiences. Gastrointest Endosc 1998; 48: 109–
10.
16. Skok P, Pocajt M. Argon plasma coagulation in giant antral polyp, causing
intermittent gastric outlet obstruction – case report. Endosk Heute 1999; 12:
20–2.
17. Palmer KR. Ulcers and nonvariceal bleeding. Endoscopy 2000; 32: 118–23.
18. Aabakken L. Nonvariceal gastrointestinal bleeding. Endoscopy 2001; 33:
16–23.
19. Kohler B, Riemann JF. The endoscopic Doppler: Its value in evaluating ga-
stroduodenal ulcers after hemorrhage and as an instrument of control of
endoscopic injection therapy. Scand J Gastroenterol 1991; 26: 471–6.
20. Hepworth CC, Kadirkamathan SS, Swain CP, Gong F. Comparison of endo-
scopic mechanical and injection methods of hemostasis on mesenteric ves-
sels. Gut 1994; 36: Suppl: S35–S9.
21. Skok P. Endoscopic hemostasis in exulceratio simplex – Dieulafoy’s
disease hemorrhage: a review of 25 cases. Endoscopy 1998; 30: 590–4.
22. Rockall TA, Logan RFA, Devlin HB, Northfield TC. Incidence of and morta-
lity from upper gastrointestinal haemorrhage in the United Kingdom. BMJ
1995; 311: 226–30.
23. Katz J. The clinical course of peptic ulcer disease. Med Clin North Am 1991;
75: 831–40.
24. Kreiss C, Blum AL. Epidemiology and risk factors of gastroduodenal ulcer.
Chirurg 1996; 67: 7–13.
25. Sonnenberg A, Everhart JE. Health impact of peptic ulcer in the United
States. Am J Gastroenterol 1997; 92: 614–20.
26. Fock KM. Peptic ulcer disease in the 1990s: an Asian perspective. J Gastro-
enterol Hepatol 1997; 12: S23–8.
27. Segal WN, Cello JP. Hemorrhage in the upper gastrointestinal tract in the
older patient. Am J Gastroenterol 1997; 92: 42–6.
28. Brullet E, Calvet X, Campo R, Rue M, Catot L, Donoso L. Factors predicting
failure of endoscopic injection therapy in bleeding duodenal ulcer. Gastro-
intest Endosc 1996; 43: 111–6.
29. Kohler B, Maier M, Benz C, Riemann JF. Acute ulcer bleeding. A prospective
randomized trial to compare Doppler and Forrest classifications in endo-
scopic diagnosis and therapy. Dig Dis Sci 1997; 42: 1370–4.
30. Imhof M, Ohmann C, Hartwig A, Thon KP, Hengels KJ, Roher HD.Which
peptic ulcers bleed? Results of a case-control study. DUSUK Study Group.
Scand J Gastroenterol 1997; 32: 131–8.
31. Laine L, Peterson WL. Bleeding peptic ulcer. N Engl J Med 1994; 331: 717–
21.
32. Meier R, Wettstein AR. Treatment of acute nonvariceal upper gastrointesti-
nal hemorrhage. Digestion 1999; 60: Suppl: 47–52.
33. Rollhauser C, Fleischer DE. Upper gastrointestinal nonvariceal bleeding: A
review covering the years 1996–97. Endoscopy 1998; 30: 114–25.
34. Skok P, Sinkovič A, Čeranič D, Pocajt M. Peptic ulcer bleeding in Intensive
Care Unit (ICU): a prospective, controlled, randomized study. Critical Care
2001; 5: Suppl 1: S 65–5.
35. Skok P, Križman I, Skok M. Krvaveča peptična razjeda, nesteroidna proti-
vnetna zdravila in okužba s Helicobacter pylori – prospektivna, kontrolira-
na, randomizirana raziskava. Zdrav Vestn 2002; 71: 357–62.
36. Kovacs TO, Jensen DM. Recent advances in the endoscopic diagnosis and
therapy of upper gastrointestinal, small intestinal and colonic bleeding. Med
Clin North Am 2002; 86: 1319–56.
37. Repici A, Ferrari A, De-Angelis C. Adrenaline plus cyanoacrylate injection
for treatment of bleeding peptic ulcers after failure of conventional endo-
scopic haemostasis. Dig Liver Dis 2002; 34: 349–55.
38. Rockall, Logan RFA, Devlin HB et al. Risk assessment after upper gastro-
intestinal hemorrhage. Gut 1996; 38: 316–22.
39. Vreeburg EM, Terwee CB, Snel P et al. Validation of the Rockall risk scoring
system in upper gastrointestinal bleeding. Gut 1999; 44: 331–5.
40. Lee JG, Liebermann DA. Complications related to endoscopic hemostasis
techniques. Gastrointest Endosc Clin N Am 1996; 6: 305–21.
41. Cash BD. Evidence-based medicine as it applies to acid suppression in the
hospitalized patient. Crit Care Med 2002; 30: Suppl 6: S373–8.
42. Rollhauser C, Fleischer DE. Nonvariceal upper gastrointestinal bleeding.
Endoscopy 2002; 34: 111–8.
43. Monig SP, Lubke T, Baldus SE, Schafer H, Holscher AH. Early elective sur-
gery for bleeding ulcer in the posterior duodenal bulb. Own results and
review of the literature. Hepatogastroenterology 2002; 49: 416–8.
44. Freeman ML. Training endoscopists to recognize the stigmata of hemorrha-
ge in bleeding ulcers. Endoscopy 1995; 27: 90–2.
45. Lau JYW, Sung JY, Lau JFT et al. Stigmata of recent hemorrhage in peptic
ulcer bleeding: is there inter-observer agreement among international ex-
perts? Digestive Disease Week, San Diego, 14–17 May 1995, Abstract No.
1703.
46. Mondardini A, Barletti C, Rocca G et al. Non variceal upper gastrointestinal
bleeding and Forrest’s classification: Diagnostic agreement between en-
doscopists from the same area. Endoscopy 1998; 30: 508–12.
47. Swain P. Perception and interpretation: The problem of the visible vessel.
Endoscopy 1998; 30: 570–4.
48. Villanueva C, Balanzo J, Espinos JC et al. Prediction of therapeutic failure in
patients with bleeding peptic ulcer treated with endoscopic injection. Dig
Dis Sci 1993; 38: 2062–70.
49. Zimmerman J, Siguencia J, Tsvang E et al. Predictors of mortality in patients
admitted to hospital for acute upper gastrointestinal hemorrhage. Scand J
Gastroenterol 1995; 30: 327–31.
50. Skok P. Peptic ulcer hemorrhage: Evaluation of risk factors of mortality. In:
Bismuth H, Galmiche JP, Huguier M, Jaeck D eds. 8th World Congress of the
International Gastro-Surgical Club; Strassburg/France; April 15–18, 1998. Bo-
logna: Monduzzi Editore S.p.a., 1998: 97–100.
51. Saeed ZA, Cole RA, Ramirez FC et al. Endoscopic retreatment after sucessful
initial hemostasis prevents ulcer rebleeding: A prospective randomized tri-
al. Endoscopy 1996; 28: 288–94.