Gastrointestinal bleeding: endoscopic treatment of peptic ulcer haemorrhage

2 Gastrointestinal bleeding: endoscopic treatment of peptic ulcer haemorrhage PAUL SWAIN If endoscopic haemostasis were highly effective it might offer the elderly high-risk patient with gastrointestinal (GI) bleeding a chance to avoid the mortality associated with an urgent laparotomy. It might also offer other advantages by reducing (a) the number of laparotomies required, (b) the rebleeding rate, (c) transfusion requirement, (d) the length of hospital stay, and (e) patient costs. The development of effective endoscopic haemostasis is also a prerequisite for the further development of endoscopic surgery. Striking advances have been made over the last 20 years in bioengineering, experimental and clinical studies. Despite its limitations, sometimes ignored by enthusiastic proponents, endoscopic haemostasis is the only method that has been consistently shown to be of value in the treatment of non-variceal haemorrhage. When compared with conventional methods of treatment of GI bleeding such as surgery, transfusion and drug therapy, endoscopic therapy has performed better in randomized controlled trials. Endoscopic haemostatic methods include thermal methods such as lasers, monopolar or bipolar diathermy and heater probes; the injection of vasoconstrictors, sclerosants and clotting factors; the topical application of materials for tamponade; and mechanical methods such as clips, metal coils, stapling and sewing machines. This chapter reviews the experimental and clinical evidence on the efficacy and safety of endoscopic methods of haemostasis. STIGMATA OF RECENT HAEMORRHAGE PREDICTION OF FURTHER BLEEDING

AND THE

Urgent endoscopy gives an exciting and often visually astonishing view of the nature of ulcer bleeding. In the early 197Os, with the advent of flexible endoscopes, active bleeding and the presence of blood in the stomach or duodenum were used to establish whether a lesion seen at endoscopy was in fact a source of bleeding (Forrest et al, 1974). Foster et al (1978) reported that stigmata of recent haemorrhage (SRH), i.e. blood adherent to or emanating from an ulcer, were of prognostic value, being associated with an increased chance that an individual patient might have further bleeding, 537

Baillidre’s Clinical GastroenterologyVol. 5, No. 3, September ISBN 0-7020-1543-l

1991

Copyright 0 1991, by Baillikre All rights of reproduction in any form

Tindall reserved

538

P. SWAIN

require urgent surgery or die. Griffiths et al (1979) stressed the importance of the finding of a visible vessel in the floor of an ulcer that has recently bled, suggesting in this retrospective series that 100% of such patients had further bleeding and that there was a very high mortality rate in this group. A prospective study by Storey et al (1981) suggested that the incidence of rebleeding from ulcers with visible vessels was lower (56%), but that if this feature was carefully sought with gentle endoscopic washing, the episodes of further bleeding and death were almost entirely confined to these patients. Ulcers without stigmata had a negligible incidence of further bleeding. The predictive value of the visible vessel for rebleeding has been confirmed by several series, many carried out in the course of trials of endoscopic therapy for peptic ulcer bleeding (Vallon et al, 1981; Papp, 1982; MacLeod et al, 1983; Bornman et al, 1985; Freitas et al, 1985; Swain et al, 1986a). The incidence of rebleeding in these studies ranged from 50 to 100%. One series by Wara (1985) reported a 32% rebleeding rate for ulcers with a visible vessel, and questioned the value of this observation. However, this series did confirm the low incidence of rebleeding (0%) in the absence of SRH and indicates a high rebleeding rate for visible vessels in ulcers in the duodenum (41%) and upper stomach (46%). Two other series (Krejs et al, 1987; Chang-Chien et al, 1988) have cast doubt on the predictive value of the visible vessel, reporting rebleeding rates of 13% and of 0% in duodenal ulcer, respectively. The difference in results in these series is probably due to differences of definition (some exclude patients with spurting arterial bleeding from their visible vessel group, which would tend to reduce the risk of further bleeding) and to difficulty in distinguishing clot adherent to a nonbleeding part of the ulcer crater from vessel wall proper or clot adherent to the eroded vessel at the true bleeding point. SRH seem a valuable and simple marker to select patients with peptic ulcer bleeding for close monitoring and for inclusion in trials. Other factors such as hypotension (Bornman et al, 1985), presence of arterial Doppler signal (Beckley and Casebow, 1986), spurting arterial haemorrhage (Swain et al, 1986b), ulcer size (Matthewson et al, 198S), ulcer site (Wara, 1985), and computer generated multivariate analysis of clinical data (de Dombal et al, 1986) may be useful to increase the prognostic value. The absence of SRH (Swain et al, 1986b) is perhaps an even more valuable observation than their presence, since such patients have an extremely low incidence of further haemorrhage and can therefore be managed with a short admission with minimal monitoring. ENDOSCOPIC

METHODS

TO CONTROL

GI BLEEDING

Lasers Argon laser

The argon laser is an example of an ion gas laser. The laser medium is ionized argon gas held in a tube sealed at each end by glass windows. A high current, constrained by a magnetic field and flowing between electrodes

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

HAEMORRHAGE

539

positioned within each end of the tube, ionizes the gas and excites the ions to high energy states. Transitions between high energy states and a lower energy level atomic system release photons in the blue-green part of the spectrum. The output of this laser is a beam of light made up of a number of spectral lines or wavelengths lying between 347 and 527 nm. Eighty per cent of the power is equally divided between two spectral bands, one at 488 nm and the other at 514.5 nm. Well-conducted studies of the argon laser in a standard canine model of bleeding gastric ulcers showed that low power (1 W) was ineffective, while high powers (5-7 W) were highly effective in stopping bleeding and that thermal tissue damage was limited (Silverstein et al, 1976). Vallon et al (1981) reported the first controlled trial of argon laser photocoagulation from Barcelona. Of 322 patients admitted with gastrointestinal bleeding, 136 had peptic ulcers. Of 28 with active bleeding at endoscopy, 10 out of 15 (67%) laser-treated patients stopped bleeding permanently, while only four out of 13 (31%) (P
540

P. SWAIN

Current status. Despite reasonably convincing evidence of its efficacy in randomized controlled trials, the argon laser is no longer widely used for treating bleeding peptic ulcers because the Nd : YAG laser has proved more effective and not as dangerous as was initially suspected. Gastroenterologists are also more likely to choose a Nd : YAG laser (if they can find the money) because of its superior performance in the treatment of obstructing GI tumours. The high power output (12 W) of the argon laser is more difficult to maintain than the output (100 W) of the relatively rugged Nd : YAG laser. A few units with both the argon and Nd : YAG laser prefer to use the argon laser to treat vascular malformations, especially in the colon, and multiple colonic polyps because of the argon laser’s greater margin of safety (Buchi and Brunetaud, 1987). Nd : YA G laser

The laser material of the Nd : YAG laser is a synthetic crystal rod of yttrium aluminium garnet (YAG) in which is held (‘doped’) a small concentration of neodymium (Nd) atoms. Blue-green light, emitted by a krypton lamp and focused into the rod by an elliptical reflector, excites or pumps the neodymium atoms into a band of high energy states which then decay. Lasing, predominantly at the near infrared 1064nm wavelength, results from transition of metastable higher energy states to lower energy states, which then decay rapidly via non-radiative transitions to the ground state. The laser cavity is completed by mirrors positioned at each end of the crystal rod. The output mirror is usually multicoated to allow only the desired wavelength to lase. Nath et al (1973) described the transmission of both argon and Nd : YAG laser radiation through a flexible fibreoptic transmission system within an endoscope. Studies in experimental bleeding ulcers demonstrated the efficacy of the high power Nd : YAG laser, though initially concerns were expressed about safety since at the most effective settings full thickness tissue damage was seen in two-thirds or more of the treated ulcers (Silverstein et al, 1979). In clinical practice, the depth of penetration is probably only important if perforation is produced. Dixonet al (1979) useda WNd : YAGlaserinstandardbleeding ulcers to study the perforation risk, and showed that full thickness tissue damage with the Nd : YAG laser did not lead to perforation providing the exposure time at 55 W was less than 9 s. Rutgeerts et al (1981) showed that short pulses of 60 W for 1 s or 70 W for 0.5 s caused less deep tissue injury than continuous 60 W irradiation, without loss of haemostatic efficacy. Kiefhaber et al (1977)) working with Nath, popularized the Nd : YAG laser as an endoscopic method for the treatment of bleeding peptic ulcer. By 1990 Kiefhaber, using the Nd: YAG laser, had reported the largest uncontrolled series of endoscopically treated patients with GI bleeding. A total of 996 out of 1058 (94%) active bleeding episodes were successfully treated, i.e. primary haemostasis was secured. Perforations in this series were less than 2%) occurring more commonly in acute than chronic ulcers. No group using any other modality has reported an experience of this size.

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

541

HAEMORRHAGE

Table 1. Results of a randomized trial of Nd : YAG laser photocoagulation for bleeding peptic ulcer (Swain et al, 1986b).

Laser Number of patients Rebleeding Surgery Death

70 7* 7s It

Control 68 27 24 8

* P
Several groups have reported results of randomized controlled trials. Several of these have produced reasonably convincing evidence of efficacy; for example, the results of our own group (Swain et al, 1986b) are given in Table 1. The majority of such studies have shown significant benefit in laser-treated patients when compared with a control group. Some studies have not shown significant benefit, but in all studies trends can be discerned which favour laser treatment. Meta-analysis of these trials shows significant benefit for all endpoints, i.e. rebleeding incidence (continued or recurrent bleeding), requirement for urgent surgery and mortality rate. Although the Nd : YAG laser frequently produces full thickness damage in the canine stomach (which perhaps surprisingly is a little thicker than the human stomach) and presumably also does this commonly in the human stomach, perforation rates have been remarkably low in clinical studies. Only one perforation occurred in the eleven trials of Nd : YAG laser treatment which have been reported (Table 2). The battles to provide evidence of the efficacy of endoscopic treatment of bleeding peptic ulcer were fought over the Nd : YAG laser trials. It is worth assessing them critically, partly because current ideas on trial design, techniques of treatment and an improved understanding of the pathogenesis of ulcer bleeding have emerged from them, but also because some workers feel that the evidence for the efficacy of endoscopic treatment of bleeding peptic ulcer is now so good that it is no longer necessary or ethical to include a control group in such studies. Instead they prefer to compare new methods with ones which have previously been shown to have significant benefit. A meta-analysis of the trials of laser photocoagulation for bleeding ulcers has been performed by Henry and White (1988). Eight trials of laser photocoagulation randomized 448 patients to laser treatment and 458 patients to no endoscopic treatment. The overall results favoured laser photocoagulation for all endpoints at a high level of statistical significance (rebleeding P~O.025, surgery P
Monopolar

electrocoagulation

Radiofrequency current has been used for surgical haemostasis for 80 years as diathermy, with a generator, a point or forceps coagulator and a large

et al, 1988

Buset

(67) (36)

(83)

(33)

(42)

(20)

(10.5)

(n)

Total

VV VV

(86)

in GU in DU

Total (174) Active bleed

(42) (46)

(32)

Total (138) Spurting (29) vv (50) Minor SRH and clot

vf7

VViclot

Arterial bleed Spots (25)

Active VVklot

Total

(25)

bleed

subgroup

of randomized

(59)

trials

42

41 32

20 33

40 80 48 16

40

32

100 0

20*

15* 33

22 29

lo* 20* 14” 3

11*

18

25* 0

5* 21

29

17 38 32

42

59

Treatment group

(%)

of the Nd : YAG

38

57

Control group

Rebleeding

controlled

32

15 20

35

26

100 0

13 23

15

38

41

Control group

20

14 18

lo*

5

13’ 0

3 14

26

42

13*

Treatment group

(%)

in the treatment

Surgery

laser

2

1 0

12

33

8

25 0

16 14

15

15

27

Control group

Death

of bleeding

9

1 0

0*

11”

0

0 0

16 14

14

17

24

did not.

ulcer.

Treatment group

(%)

peptic

W = visible vessel; SRH = stigmata of recent haemorrhage; GU = gastric ulcer; DU = duodenal ulcer. * P
et al, 1990

et al, 1987

Krejs

Matthewson

et al. 1986b

et al, 1985$

et al, 1985

Swain

Trudeau

Homer

et al, 1983

1982

Rutgeerts,

MacLeod

et al, 1981t

Escourrou

Total

Active

et al, 1981

et al, 1980

Rhode

Ihre

Total

2. Results

Reference

Table

1 perforation 2 bleeds

2 bleeds

0

0

0

0

1 bleed

0

Complications

is

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

HAEMORRHAGE

543

electrical plate attached to the patient to complete the circuit. Heat is developed around the small point of electrical contact, the electrical current passing through the patient’s body to the large surface area of the plate. Monopolar diathermy has been used for snare polypectomy through flexible endoscopes for 17 years and for sphincterotomy for 15 years. Monopolar electrocoagulation for ulcer haemostasis uses metal balltipped probes, most having a channel for irrigation. These can be used with direct metal to tissue contact (dry monopolar electrocoagulation) or an electrically conductive fluid can be used to transmit the current to the tissue without metal contact in order to reduce tissue adherence (liquid monopolar electrocoagulation). The results of three randomized controlled trials of monopolar electrocoagulation in the treatment of bleeding peptic ulcer are given in Table 3. No perforations occurred in these trials. However, Koch et al (1973) reported three perforations and one death in an early series, but this was probably due to using too powerful a radiofrequency generator setting. Anxieties about the unpredictability of tissue damage caused by monopolar electrocoagulation in experimental studies led to the examination of other modalities such as lasers and the development of bipolar electrocoagulation and heater probe methods. Bipolar electrocoagulation Uncontrolled studies. Reports using bipolar electrocoagulation in uncontrolled trials were generally favourable (Gilbert et al, 1982; Jessen, 1983; Winkler et al, 1983; Hajiro et al, 1984; Jensen et al, 1986b). In these reports active bleeding from a variety of non-variceal bleeding lesions was stopped in 81 to 100% of patients, but bleeding recurred in 0 to 29% (mean 25%). No perforations were observed, but occasionally (O-9%) brisk bleeding occurred when the probe was applied to non-bleeding visible vessels. Controlled trials. Two early controlled trials of bipolar electrocoagulation did not show benefit. Goudie et al (1984) studied 46 patients with peptic ulcer and SRH, and Kernohan et al (1984) studied 45 patients with peptic ulcers or erosions with active bleeding or SRH. No differences in mortality, rebleeding rate or transfusion requirement were observed. O’Brien et al (1986) reported a trial randomizing 204 patients with peptic ulcer bleeding with either active bleeding, non-bleeding visible vessel or adherent clot to bipolar electrocoagulation (small diameter 7 French probe) or control, i.e. no endoscopic treatment. In this trial bipolar-treated ulcers had significantly less further bleeding (treated group 17 out of 101 vs control group 34 out of 103, P< 0.05). A significant reduction in further bleeding was seen in the subgroups with visible vessels whether actively bleeding (six out of 40 vs 13 out of 21, P< 0.05) or not (seven out of 43 vs 16 out of 43, P-CO.05). Laine (1987) randomly treated 44 patients with active upper GI bleeding from an ulcer, Mallory-Weiss tear or vascular malformation. Bipolar electrocoagulation treated patients had significantly better haemostasis

a significantly

= duodenal

Dry

Liquid

Liquid

ulcer;

GU/DU

GU

GWDU

Type of ulcer

controlled

average

VV = visible

lower

of randomized

Type of monopolar coagulation

3. Results

GU = gastric ulcer; DU * P-ZO.05. t This trial also reported

1982t

et al, 1987

Moreto

Papp,

et al, 1985

Freitas

Reference

Table

hospital

vessel;

trials

(VV) (AB) (SRH) (total)

stay (18.5

AB = active

1116”

1116*

3/14* 2/11 O/11 5/36

Monopolar group

13116

11/21

9117 6110 2115 17142

Control group

vs 8.3 days)

hospital

= stigmata

l/16*

costs

of bleeding

($5709

O/16

l/16

l/36

Death

ulcer.

(total)

Monopolar group

peptic

vs $3157).

haemorrhage.

9116

8121

1.5142

8117

Control grow

of recent

(total)

6/36 O/16*

(VV)

2/14*

Surgery

in the treatment

Monopolar group

and total

SRH

electrocoagulation

bleeding;

Rebleeding

of monopolar

0116

3121

4142

Control group

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

545

HAEMORRHAGE

(90% vs 13%, P
Control (n = 32)

Haemostasis (active) Further bleeding Surgery Transfusion (units) Mortality

20% 72% 41% 3.5 9%

Bipolar electrocoagulation (n=30) 90%* 44% 33% 3.7 3%

Heater probe (n = 32) 93%* 22%* 3%* 1.3 3%

*P
In a subsequent study of power levels and tissue effect with the bipolar electrode, Jensen et al (1989) found new optimal settings and have suggested that clinical results are improved at such settings (using 10-14 s pulses at a setting of 5); they reported no further bleeding in eight out of nine patients treated with this method. Complications. Perforations have been rare with bipolar electrocoagulation. Three have been reported (Brearley et al, 1987; Rutgeerts et al, 1987; Laine, 1990). Bleeding precipitated by treatment of a non-bleeding visible vessel is not uncommon, occurring in about one-third of Laine’s patients (1990), most stopping with further treatment. Heater probe (heat probe)

The heater probe is a metal-tipped

(brass) probe within which there is an

546

P. SWAIN

avalanche diode (chip). The resistance of this diode varies with temperature, and this property allows remote electronic control of the temperature of the brass tip of the probe. By this means the temperature is raised to and held at 250°C until a preset amount of energy is delivered to the tissue in contact with the probe by thermal conduction. To reduce sticking the brass probe has a silicone non-stick coating. To protect the delicate internal parts of the probe, the irrigation ports are proximal to the probe tip, allowing effective irrigation during probe contact. Non-randomized studies by Storey (1983), Shorvon et al (1985), Johnston et al (1985) and Jensen et al (1986b) suggested that this device was safe and effective. Four controlled trials of the heater probe versus no endoscopic therapy have been reported. Two (Avgerinos et al, 1989; Matthewson et al, 1990; Table 12) did not demonstrate significant benefit. Controlled trial evidence for efficacy has been reported by Fullarton et al (1989). A total of 43 patients with peptic ulcer and major SRH were included. No patient treated with the heater probe had further bleeding, surgery or death. There was a statistically significant reduction in the rebleeding rate when compared with a sham-treated group. Jensen et al (1988,1989) sh owed a significant reduction in further bleeding and requirement for urgent surgery in a heater probe treated group when compared with control patients (see Table 4). Meta-analysis

of thermal probe methods

The meta-analysis of randomized controlled trials of thermal probe methods (monopolar, bipolar and heater probe) published by Henry and White (1988) suggested a significant reduction in rebleeding and requirement for urgent surgery, but not as yet a reduction in mortality. Injection

treatment

The apparent efficacy of injection sclerotherapy in variceal haemorrhage led some investigators to try this in ulcer haemostasis. The advantages of cheapness and the wide availability of the necessary materials and expertise make this an attractive method. Injection cannula

Most commercially available injection needles have an outer diameter of 0.5mm and a shorter bevel than on conventional needles for intravenous use. These are joined to an inner sleeve, usually made of Teflon, through which the injection material is forced. There is an outer sheath sometimes made of wound wire and sometimes of Teflon. The needle length should not be longer than 7 mm to reduce the risk of perforating the bowel. The patency and length of the injection needle should be checked before use. The use of disposable endoscopic injection needles should reduce the chance of cross-infection but will increase the cost of this relatively inexpensive treatment.

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

547

HAEMORRHAGE

Materials for injection Adrenaline (1 :lOOOO). Adrenaline (epinephrine USP) may act by causing local vasoconstriction (Chung et al, 1988b) but it also has effects on platelet aggregation and some clotting factors. The volumes injected range from 1.5 to 10ml. Chung et al (1988a) reported a controlled trial in which 68 patients with active bleeding were randomized to injection treatment (34 patients) or no endoscopic treatment (34 patients). Endoscopy was repeated 24 h later and further treatment given if active bleeding was seen again. Emergency surgery was significantly decreased in the patients treated with adrenaline injections (five out of 38 [15a/]o vs 14 out of 38 [41%], P
Adrenalineplus

Adrenaline plus sodium tetradecyl sulphate. A randomized study comparing

adrenaline

alone with adrenaline

Table 5. A trial comparing endoscopy treatment.

and the sclerosant sodium tetradecyl

injection

of adrenaline

Injection Number of patients Major recurrent haemorrhage Minor recurrent haemorrhage Rebleeding overall Urgent surgery Deaths Transfusion (units) Hospital stay (days) * P
therapy

3 & 12(12%) 15 (S%)t 3 (5%)" 2 (4%) 0.42 (+ l.l)* 11.7 (ts.l)f

and

polidocanol

No endoscopic

with therapy

58 25 (43%) 14(24%) 39(27%) 20(34%) 4 (7%) 2.77 (23.3) 16.3 (+ 11.3)

no

548

P. SWAIN Table 6. A further trial comparing injection of adrenaline and polidocanol with no endoscopy treatment.

Number of patients Rebleeding Surgery Death Transfusion (units)

Injection therapy

No endoscopic treatment

36 7 (19%)” 7 (19%) 1 (3%) 1.63*

36 15 (42%) 12 (33%) 1 (3%) 2.86

* P
sulphate (3%, 1 ml) by Chung et al (1990) did not show a significant advantage in patients treated with the additional sclerosant, though a small trend towards a lower rebleeding rate was observed. Alcohol. Absolute alcohol is thought to produce haemostasis by desiccating vascular structures and adjacent tissues (Asaki et al, 1983; Sugawa et al, 1986; Nakagawa et al, 1989; Randall et al, 1989). This method requires the injection of small volumes (O.i-O.2ml) of 98% dehydrated alcohol (total volume 0.6-l .2 ml) at about four sites l-2 mm from the bleeding vessel. A tuberculin syringe is used to control the small injection volumes, and one investigator recommends a wire-wound injection needle (e.g. the Olympus NMl-K) because its stiff shaft gives greater control (Sugawa, 1990). Nakagawa et al (1989) reported treating 147 patients with alcohol injections, resulting in 11 rebleeds (8%), urgent surgery in eight (5%) and death in 11 (8%). Although no truly randomized controlled trials of alcohol injection have been reported, a Romanian study examined the effect on mortality in a unit where one endoscopist working on Tuesdays, Wednesdays and Saturdays treated bleeding peptic ulcers with alcohol injection, while another working Mondays, Thursdays and Fridays did not (Pascu et al, 1989) (Table 7). Table 7. A study comparing injection of alcohol with no endoscopy treatment. Number of patients Urgent surgery Death

Alcohol injection

No endoscopic treatment

65 2 (3%)* 1 (1.5%)*

78 10 (13%) 17 (22%)

NB Rebleeding rates were not clearly reported. * PCO.05.

Thrombin and thrombin-fibrinogen mixtures. Fuchs et al (1986) injected 100 iu of thrombin in 3 ml of normal saline into bleeding vessels, using a total of about 10-15 ml, in a group of 47 patients. The bleeding was stopped in 80% without complications. Friedrichs et al (1989) injected thrombin and fibrinogen through a double lumen endoscopic injection needle around the bleeding vessel in order to form a coagulum of fibrinogen. He reported promising results in a group of 200 patients.

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

HAEMORRHAGE

549

saline plus adrenaline. Hirao et al (1985) injected 3 ml of 3.6% saline and adrenaline (1: 20 000) in three or four sites close to a bleeding vessel. For bleeding lesions with severe fibrosis 1 ml of a 7.2% saline and 1: 20 000 adrenaline solution were also injected. Permanent haemostasis was reported in 93% of 158 patients. No randomized clinical trial has been reported. However, hypertonic saline at 3.6 and 7.2% performed poorly, showing no haemostatic effect, in studies of coagulation of canine gut arteries and was significantly inferior when compared with alcohol, TES (1% tetradecyl sulphate, 32% ethanol and 0.3% normal saline) or polidocanal (Randall et al, 1989). Hypertonic

Complications

of injection therapy

Perforation has been reported with absolute alcohol in one out of 84 patients (1%) by Asakiet al (1983) andtwo out of 147patients (1.5%) by Nakagawaet al (1989) in a continuation of Asaki’s series. Fuchs et al (1986) reported two perforations (1%) with polidocanol plus adrenaline injections. Rutgeerts et al (1987) reported two perforations in a studyin which adrenaline was used as a pretreatment for Nd : YAG or bipolar electrocoagulation. One perforation occurred in each treatment group of 50 patients. The injection material can be inadvertently sprayed over the patient or endoscopy staff and goggles should be worn as eye damage can occur (Herlihy and Bozymski, 1982). Reservations about injection treatment

Injection methods are at present rather fashionable in the treatment of peptic ulcer bleeding. However, I have some anxieties about the security of the haemostasis achieved by injection methods. They all perform poorly in experiments conducted on standard bleeding experimental ulcers and isolated mesenteric and serosal vessels. Some can reduce bleeding rates but none terminate such bleeding (Randall et al, 1989; Rutgeerts et al, 1989). It is difficult to conceive how an injection of adrenaline could alter the outcome of bleeding from a patient with a significant hole in a large artery such as the gastroduodenal artery. Indeed, one experienced proponent (Soehendra et al, 1985) advises against injection treatment of major bleeding in the posterior bulb position. Topical therapy

Topical therapy, if it worked, would be an attractive method for endoscopic haemostasis. It could be used to arrest bleeding or in combination with other methods to prevent recurrent bleeding. The available agents produce little or no tissue damage, unlike thermal or injection methods, and the treatment would be cheap and portable. Agents that have been studied include microcrystalline collagen haemostat (MCH), clotting factors, cyanoacrylate tissue glues and ferromagnetic tamponade. MCH is made of bovine collagen. It activates the intrinsic clotting system,

550

P. SWAIN

attracts platelets and swells on contact with blood to form a patch which may seal small blood vessels. Klein et al (1982) reported that MCH decreased bleeding by 75% in a canine gastric ulcer model, and that bleeding stopped in eight out of nine patients with bleeding ulcers. Clotting factors (e.g. cryoprecipitate/thrombin spray) applied topically did not produce reliable haemostasis in animal experimental bleeding ulcers (Matek and Demling, 1986). Linscheer and Fazio (1979) treated six patients with bleeding who had required an average of 12 units of blood prior to endoscopic treatment with the cryoprecipitate spray and reported no further bleeding in these patients. The use of clotting factors derived from pools of human plasma might carry a small hepatitis risk. Trifluoroisopropyl cyanoacrylate was shown to decrease bleeding from chronic canine ulcers (Martin and Silvis, 1977) but not from standard bleeding ulcers (Protell et al, 1978). Martin and Silvis (1977) suggested that treatment with cyanoacrylate was successful in 12 out of 14 patients in whom it could be successfully applied in a group of 18 patients. Peura et al (1982) has carried out the only randomized controlled trial in this field (Table 8). Table scopic

8. Randomized controlled therapy in bleeding peptic

trial of cyanoacrylate ulcer.

Cyanoacrylate Number of patients Rebleeding Surgery

versus

No endoscopic

24 6 6

no endotreatment

28 4 3

Smith (1980) suggested that the application of a strong magnetic field to hold a slurry of thrombin and iron filings applied topically to a bleeding ulcer might stop bleeding. A randomized controlled trial reported by Birns (see Peura, 1990) in five patients resulted in one out of two control patients and two out of three patients treated with ferromagnetic tamponade rebleeding and requiring surgery. This study was abandoned because the thick ferromagnetic slurry was difficult to apply and the immobilization required for successful administration was poorly tolerated by the patients. Topical treatment for bleeding is out of fashion at present. It performed less well in animal experiments than thermal methods at a time when some groups were performing animal studies of outstanding quality. The technical problems of delivery were never completely solved. It lacked an enthusiastic proponent with a large clinical case load to test the hypothesis that it might be an effective treatment. The idea remains attractive and shares many of the advantages and drawbacks of injection treatment. If injection methods are found to be reliable in clinical studies it is likely that a reappraisal of topical methods will follow. Mechanical

methods of endoscopic haemostasis

Mechanical haemostasis using clips, staples, elastic bands or tied thread is known to surgeons to be more secure than thermal, injection or topical

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

HAEMORRHAGE

551

methods, especially for large bleeding vessels. Some atternpts to apply these methods using flexible endoscopy have been made. Clips

The Sakura J clip designed in the mid 1970s by Hayashi et al (1975) and modified by Hachisu (1988) is elegantly designed to pass through the biopsy channel (2.8 mm) of a conventional endoscope. The clip is opened and then closed tight on the bleeding point by pulling the proximal loop of a compressible metal clip into a metal ring so that the clip closes in to adopt the figure 8 (Hayashi, 1984). This was reported to be effective in controlling 22 out of 24 gastric ulcers and three out of four duodenal ulcers. Dislodgement is not infrequent (28%) and further bleeding was reported in 23% of patients. Balloon

tamponade

Balloon tamponade has been tried for the treatment of bleeding duodenal ulcer (Taylor, 1988). A balloon is inserted over an endoscope and inflated to 2.5cm in the duodenal bulb. The endoscope is withdrawn, leaving the balloon impacted in the duodenal bulb. Three patients with bleeding from chronic duodenal ulcers were treated with this device; one rebled and one died. Sutures and staples

Our group have reported the development of an endoscopic sewing machine (Swain and Mills, 1986) and stapling device (Swain et al, 1989). These devices work by sucking tissue into a cavity within the machine and then either pass a needle and thread through the tissue to form a stitch, or close a row of staples into a B conformation like an office stapler. These devices can achieve more secure haemostasis of large vessels than thermal methods in animal models and in experiments on isolated arteries. A corkscrew-like device designed to be driven into bleeding ulcers by a torque transmitting cable which passes through the biopsy channel of an endoscope has been reported by Escourrou (1990). This was used to terminate bleeding in two patients with bleeding gastric ulcer. These devices which use mechanical means to achieve haemostasis are still at an early developmental stage and several of them are not yet easy to use with precision. COMPARISONS OF DIFFERENT PEPTIC ULCER HAEMOSTASIS

ENDOSCOPIC

METHODS

OF

The difficulties of comparing any method with a non-treated control group when studying the treatment of peptic ulcer bleeding are considerable. The difficulties of comparing one treatment with another are probably greater.

P. SWAIN

Experience with one modality is likely to be greater, introducing bias since the operator cannot be blinded. If both treatments are more effective than no endoscopic treatment, then the number of patients with bleeding ulcer required to give a significant answer is likely to be very large. Nevertheless, several comparative studies have been undertaken, though few have included a control group. Comparisons of injection with thermal endoscopic methods Lin et al (1988) performed a randomized study of patients with major stigmata to compare heater probe treatment with injection of alcohol. In this study the heater probe was significantly superior to injection of alcohol (Table 9). Chung and Leung (1989) conducted a randomized study of active ulcer bleeding comparing injection of adrenaline to heater probe treatment, with Table 9. A trial comparing injection heater probe treatment.

Number of patients Initial haemostasis Rebleeding Successful retreatment Permanent haemostasis

of alcohol with

Injection

Heater probe

36 80.6% 22.2% 40% 70.6%

42 loo%* 12.2% 75% 95.1%*

* P
Table 10. A trial comparing injection of adrenaline with heater probe treatment.

Number of patients Initial haemostasis Difficult endoscopic haemostasis Repeat treatment Emergency surgery Mean units transfused Median hospital days Mortality

Injection

Heater probe

64 95%* 6% 8% 22% 4.7 5 3.1%

58 85% 12% 5% 19% 3.7 6 6.9%

* P
11.

A trial comparing injection of alcohol with bipolar electrocoagulation. Bipolar electrocoagulation

Number of patients Further bleeding Blood transfusions (units) Urgent surgery Hospital stay (days) Hospital cost (dollars) Mortality

31 6% 1.8 6% 5.8 7160 3%

Injection therapy 29 10% 1.3 7% 7.2 8520 3%

553

ENDOSCOPIC TREATMENT OF PEPTIC ULCER HAEMORRHAGE

little difference between the two methods (Table 10). Laine (1990) randomized 60 patients with a bleeding peptic ulcer to treatment with bipolar electrocoagulation or sclerotherapy. His results (Table 11) also showed the techniques to be comparable in effectiveness. Comparisons

of thermal methods

Rutgeerts et al (1987) reported a randomized comparison of Nd : YAG laser and 3.2mm (10 French) bipolar probe in 100 patients presenting at endoscopy with a peptic ulcer and a spurting or oozing vessel or a nonbleeding visible vessel. All were pretreated with an injection of 4-8ml of 1: 10000 adrenaline. Twenty patients had a second treatment because of recurrent bleeding. There were no significant differences between these two groups. Johnston et al (1985) reported a non-randomized study which contrasted his initial (somewhat unfavourable) experience with Nd : YAG laser with his subsequent experience with the heater probe, for which he has become an enthusiastic proponent. He reported that he used much more energy (mean 4798 J vs. 347 J) with the laser than with the heater probe, the treatment took longer and more frequently required general anaesthesia or endotracheal intubation. Neither method caused perforation, but the laser caused bleeding in 10 out of 35 patients, which did not occur with the heater probe. Matthewson et al (1990) reported a randomized controlled trial comparing Nd : YAG laser, heater probe and no endoscopic therapy. In total 143 consecutive patients with SRH accessible to laser therapy were included in the trial. Rebleeding was significantly reduced (P < 0.05) in the laser-treated group compared with the control group. Although there was a trend suggesting that the heater probe had a lower incidence of rebleeding when compared with control, this was not statistically significant (Table 12). These results suggested that heater probe and control treatment are inferior to laser treatment. Table 12. A trial comparing endoscopy therapy. Number of patients Rebleeding Death

Nd: YAG

laser, heater probe, and no

Nd : YAG laser

Heater probe

Control

44 9 (20%)* 1 (2%)

57 16 (28%) 6 (10%)

42 18 (42%) 4 (9%)

* P
SOME OBSERVATIONS ON THE PROBLEMS WITH RANDOMIZED CONTROLLED TRIALS IN PEPTIC ULCER BLEEDING

Careful reading of the results of all the controlled trials in this field gives the impression that a majority of studies show benefit for patients with bleeding

554

P. SWAIN

peptic ulcer treated with thermal or injection methods. This impression is confirmed for thermal methods by published meta-analysis (Henry and White, 1988). However, several trials have not shown benefit. Negative trials should be taken seriously, particularly because it may be harder for such trials to achieve publication. It is also fair to criticize meta-analysis on the grounds that it is a poor substitute for an effectively designed study randomizing sufficient numbers of patients to provide a convincing answer to a hypothesis. Meta-analysis is particularly hard to do in this subject since there is considerable heterogeneity in the design of endoscopic treatment trials. It is possible that there is no real difference between the negative and positive trials, and that the different trends shown occur simply by chance. Technical differences could explain several negative trials. For example, early trials with Nd : YAG laser may have been less successful than subsequent trials because the laser used gave a maximum power output of 50 W and the real power output could not be measured because of the absence of a power meter. Animal studies have shown that the optimal power level for effective and safe haemostasis is 70-80 W. Thus the advent of the 100 W Nd : YAG laser with a built-in power meter may have altered the outcome. Similarly, several studies of bipolar electrocoagulation used a small diameter 2.8mm probe with a 25 W generator. Animal studies have shown that the larger diameter 3.2 mm probe with a 50 W generator is more effective. The value of the visible vessel as a predictor of further bleeding and as a target for endoscopic haemostasis was not initially recognized in trial design. Indeed, this knowledge really emerged as a result of some of these early trials. The trials that have focused on this finding have, in general, been more likely to give a result favouring endoscopic therapy. Over all the trials hangs the statistical problem that has bedevilled studies of GI bleeding: 75-85% of patients with bleeding ulcers will stop bleeding spontaneously so that large numbers of patients need to be randomized in order to show any therapeutic difference and to reduce the chance of a l3 (or type II) error, i.e. the failure to show a significant difference when one exists. Thus it became important to select from these large numbers of patients with ulcer bleeding well-matched subsets who had a similar high risk of further bleeding, urgent surgery and death. Most well-designed trials now study prospectively stratified subgroups of patients with endoscopic evidence of active arterial (spurting) bleeding (5% prevalence, 80% chance of continued or recurrent bleeding) and non-bleeding visible vessels (20% prevalence, 45% risk of further bleeding). SOME TIPS ON THE ENDOSCOPY GI BLEEDING

OF PATIENTS

WITH

Patients requiring endoscopy following a GI bleed are a little more difficult to endoscope than routine, non-bleeding patients. They are generally sicker and often more restless and frightened. Engaging their confidence is essential before starting endoscopy. I prefer to use minimal or no sedation in

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

HAEMORRHAGE

555

elderly or ill patients who are bleeding. I sometimes use opiates in restless young patients with a high alcohol intake who may become disinhibited with benzodiazepine sedation. Since the stomach may not be empty, a lateral position with head down is even more essential than with conventional endoscopy. Gently seeking a succussion splash before starting can diminish the chance of unexpectedly encountering a stomach full of blood. I do not lavage the stomach before endoscopy since lavage tubes can cause erosions and diagnostic confusion. If there is a large volume of blood in the stomach when the endoscope is passed, it may be helpful to encourage the patient not to retch and to move the endoscope quickly but gently through the oesophagus, inspecting it for varices and Mallory-Weiss tears, to enter the fundus with the finger holding the air inflation button. As the stomach inflates, the blood will fall away into the distended fundus and this manoeuvre will tend to lift a posterior high lesser curve ulcer out of the pool of blood. It is less common to find significant bleeding ulcers in the fundus or high on the greater curve where this pool tends to collect. Even if the stomach is filled with a stomach-sized clot cast, it is usually possible to slide along the lesser curve and enter the duodenum. If the blood is fresher in the fundus than in the duodenum this may hint at a high gastric lesion missed on the way down. However, because of the head-down position of the patient, blood will tend to run in a cephalad direction, and fresh blood high in the stomach still may have come from the duodenum. A clot prolapsing through the pylorus and obscuring it usually indicates duodenal ulceration. If there is partial duodenal stenosis and bleeding, the ulceration is usually distal to the stenosis. There are two common sites associated with severe bleeding from peptic ulcers: the first is a high posterior position on the lesser curve and the second is posteroinferiorly in the proximal duodenal bulb. There are some catches in endoscoping bleeding patients. Antral ulcers can be mistaken for a major bleeding source when the true bleeding lesion is a duodenal ulcer, as small antral ulcers are common in the presence of duodenal ulceration. Multiple ulcers high on the lesser curve can cause problems; the most proximal and usually the largest, ulcer is most likely the source of major bleeding. There are also problems diagnosing active bleeding. Spurting often stops spontaneously. A jet of blood can look like a string of blood clot. Pulsatile movement of blood can be caused by cardiac or respiratory movements moving pools of blood rhythmically. Bleeding can be caused by the endoscope touching mucosa or granulation tissue. Therefore, it is wise to be critical of the diagnosis of active spontaneous bleeding in lesions which were missed or seen not to bleed as the endoscope passed them but appeared to be bleeding on pulling the endoscope back. The diagnosis of oozing is especially subjective, requires a careful washing technique and may not be of spontaneous origin in ulcers that were not touched by the endoscope. In addition, the diagnosis of non-bleeding visible vessels can cause difficulty. If I am in doubt about a possible visible vessel, I ask myself whether the spot in question within the ulcer crater is the only point from which the bleeding is likely to have come and I move the endoscope to check

556

P. SWAIN

that the spot is raised. Gentle washing, to try and clear loose debris from the ulcer, is particularly helpful and in my experience is a safe procedure that does not provoke bleeding. The motorized washing facility that is a feature of heater probe, bipolar electrocoagulation and liquid electrode units is very useful for clearing blood and debris to improve vision and for demonstrating the presence or absence of active bleeding. The features which increase the chance of rebleeding when a visible vessel is seen include the presence of: spurting, visible pulsation, a loud arterial Doppler signal, large ulcer size, low haemoglobin or shock on admission. Endoscopes get blocked more frequently during use in bleeding patients than in normal usage. Although fresh blood can occasionally be effectively aspirated through a large channel endoscope, if there are lumps of clot it is usually unwise to try suction which can block the endoscope and cause loss of vision. In general it is better to limit suction and to use washing as a method of improving vision. Blood absorbs light and the view may become dark when endoscoping bleeding patients, especially with videoendoscopes. It is easier to see erosions with a large diameter endoscope and a bright light source. Severely anaemic patients may have very pale mucosa and colour contrast between normal mucosa and an ulcer may be lost. Changing to a larger diameter instrument, waiting until the stomach has been emptied of blood and transfusing the patient can reveal lesions missed at the first endoscopy. The following tips may be helpful to those beginning to practice therapeutic endoscopy for GI bleeding. The use of a test firing of the probe or laser on the mucosa at the edge of the ulcer may be helpful in allowing a biological test of any thermal method. At effective coagulation powers, a single pulse should produce a ring of blanched mucosa but should not break the surface. It can be hard to place each pulse of laser energy or the probes or needles precisely, especially high on the lesser curve because the target moves. This movement can be controlled to some degree by giving Buscopan (hyoscine butylbromide) or glucagon judiciously if peristalsis is a problem. Asking the patient to hold his breath at a critical moment in treatment may assist if respiration is interfering with the aim. Major bleeding from ulcers is common at two sites: the posterior aspect of the high lesser curve and the posteroinferior aspect of the duodenal bulb. Both these sites can be difficult to treat and are usually approached at acute angles of between 0 and 45” using forward-viewing endoscopes. On the high lesser curve, access can sometimes be improved by curving the endoscope with a J manoeuvre, and rotation of the endoscope with its eccentrically placed biopsy channel may sometimes give a different and more useful angle of approach. Because a relatively small volume of blood (20-30ml) can quickly fill the duodenal bulb (but not the stomach), active bleeding and bleeding induced by treatment is harder to treat in the duodenum. It is helpful to be prepared for such bleeding by being in a position to deliver several pulses of treatment to different sites around the vessel fairly quickly if bleeding starts. The endoscopic magnification and the proximity of the view often makes active bleeding seem dramatic. However, most bleeding episodes will tend to slow in a short time, the view may improve and treatment can proceed.

ENDOSCOPIC TREATMENT OF PEPTIC ULCER HAEMORRHAGE

557

SUMMARY The development and study of haemostatic methods that can be used through flexible endoscopes has been one area of gastroenterology in which major advances have been made over the last 15 years. Bioengineering research with lasers and thermal probes as well as the study and application of simple injection techniques has given the endoscopist a range of tools with which to stop bleeding. Randomized controlled trials have provided fairly convincing evidence that these methods can be of value in the treatment of human peptic ulcer bleeding. REFERENCES Asaki S, Nishimura T, Satoh A & Goto Y (1983) Endoscopic control of gastrointestinal haemorrhage by local injection of absolute ethanol-a basic assessment of the procedure. Tohoku Journal of Experimental Medicine 140: 339-352. Avgerinos A, Rekoumis G, Argirakis G, Gouma P, Papadimitriou N & Karamanolis D (1989) Randomized comparison of endoscopic heater probe electrocoagulation, injection of adrenaline and no endoscopic therapy for bleeding peptic ulcers. Gastroenterology 98: AlS(abstract). Balanzo .I, Sainz S, Such J et al (1988) Endosc.rpic hemostasis by local injection of epinephrine and polidocanol in bleeding ulcer. A prospective randomized trial. Endoscopy 20: 289291. Beckley DE & Casebow MP (1986) Prediction of rebleeding from peptic ulcer: experience with an endoscopic Doppler device. Gut 27: 96-99. Bornman PC, Theodorou NA, Shuttleworth RD, Essel HP & Marks IN (1985) Importance of hypovolaemic shock and endoscopic signs in predicting recurrent haemorrhage from peptic ulceration: a prospective evaluation. British Medical Journal 291: 245-257. Brearley S, Hawker PC, Dykes PW & Keighley MR (1987) Per-endoscopic bipolar diathermy coagulation of visible vessel using a 3.2 mm probe-a randomized clinical trial. Endoscopy 19: 160-163. Buchi KN & Brunetaud JM (1987) Endoscopic laser therapy. In Dixon JA (ed.) Surgical Application of Lasers, pp 95-118. Chicago: Year Book Medical. Buset M, Des Marez B, Vandermeeren A et al (1988) Laser therapy for non bleeding visible vessels in peptic ulcer hemorrhage: a prospective randomized study. Gastrointestinal Endoscopy 34: 173. Chang-Chien C, Wu C, Chen P et al (1988) Differential implications of stigmata of recent hemorrhage in gastric and duodenal ulcers. Digestive Diseases and Sciences 33: 4OWO4. Chung S & Leung J (1989) Heat probe or epinephrine injection for actively bleeding ulcers: a randomised comparison. Gastrointestinal Endoscopy 35: 152(abstract). Chung SCS, Leung JWC, Steele RJC et al (1988a) Endoscopic injection of adrenaline for actively bleeding ulcers: a randomized trial. British Medical Journal 34: 1631-1633. Chung SCS, Leung FW & Leung JWC (1988b) Is vasoconstriction the mechanism of hemostasis in bleeding ulcers injected with epinephrine? A study using reflectance spectrophotometry. Gastrointestinal Endoscopy 34: 174(abstract). Chung SCS, Leung JWC, Leong HT, Lo KK, Griffin SM & Li AKC (1990) Does adding a sclerosant improve the results of endoscopic epinephrine injection in actively bleeding ulcers? Interim report of a randomized trial. Gastrointestinal Endoscopy 36: 194. de Dombal FT, Clarke JR, Clamp SE, Malizia G, Kotwal MR & Morgan AG (1986) Prognostic factors in upper gastrointestinal bleeding. Endoscopy lS(supplement 2): 6-10. Dixon JA, Berenson MM & McCloskey DW (1979) Nerodymium-YAG laser treatment of experimental canine gastric bleeding. Acute and chronic studies of photocoagulation, penetration and perforation. Gustroenterology 77: 647-651. Escourrou J (1990) First clinical evaluation and experimental study of a new mechanical suture device for endoscopic hemostasis. Gastrointestinal Endoscopy 36: 494-497.

558

P. SWAIN

Escourrou J, Frexinos J, Bommelaer G et al (1981) Prospective randomized study of YAG photocoagulation in gastrointestinal bleeding. In Atsumi K & Nimsakul N (eds) Proceedings ofLaser, Tokyo 1981, pp 5-30. Fleischer D & Bown SG (1990) Endoscopic Nd: YAG laser therapy for acute upper gastrointestinal bleeding. In Jensen DM & Brunetaud JM (eds) Medical Laser Endoscopy, pp 149-162. Dordrecht: Kluwer Academic. Forrest JAH, Findlayson NDC & Shearman DLC (1974) Endoscopy in gastrointestinal bleeding. Lancet ii: 394-396. Foster DN, Miloszewski KJA & Losowsky MS (1978) Stigmata of recent haemorrhage in diagnosis and prognosis of upper gastrointestinal bleeding. British Medical Journal i: 1173-1177. Freitas D, Donato A & Monteiro JG (1985) Controlled trial of liquid monopolar electrocoagulation in bleeding peptic ulcers. American Journal of Gastroenterology 80: 8X-857. Friedrichs 0, Papen J & Beccu L (1989) Endoscopic submucosal injection of fibrin adhesive in peptic ulcer bleeding. Gut 30: A1462(abstract). Fuchs KH, Wirtz HJ, Schaube H & Elfeldt R (1986) Initial experience with thrombin as injection agent for bleeding gastroduodenal lesions. Endoscopy 18: 146148. Fullarton G, Birnie CC, Macdonald A et al (1988) Controlled study of heater probe (H.P.) in bleeding peptic ulcers. Gastroenterology 94: A138. Fullarton GM, Birnie GG, MacDonald A & Murray WR (1989) Controlled trial of heater probe treatment in bleeding peptic ulcers. British Journal of Surgery 76: 541-544. Gilbert PA, Verhoeven J, Jessen K et al (1982) A multicentre clinical trial of the Bicap probe for upper gastrointestinal bleeding. Gastrointestinal Endoscopy 29: 150A. Goudie BM, Mitchell KG, Birnie GG & Mackay C (1984) Controlled trial of endoscopic bipolar electrocoagulation in the treatment of bleeding peptic ulcers. Gut 25: 1185A. Griffiths WJ, Neumann DA & Welsh JD (1979) The visible vessel as an indicator of uncontrolled or recurrent hemorrhage. New England Journal of Medicine 300: 1411-1413. Hachisu T (1988) Evaluation of endoscopic hemostasis using an improved clipping apparatus. Surgical Endoscopy 2: 13-17. Hajiro K, Yamamoto H, Matsui H et al (1984) Endoscopic bipolar electrocoagulation in upper gastrointestinal bleeding. Endoscopy 16: 69. Hayashi J (1984) The study of endoscopic staunching clips for bleeding of the exposed vessel end of the ulcer. In Okabe M, HondaT & Oshiba S (eds) Endoscopic Surgery, pp 117-124. New York: Elsevier. Hayashi T, Yonezawa M, Kuwabara T & Kudoh I (1975) The study on staunch clips for treatment by endoscopy. Gastrointestinal Endoscapy 17: 92-101. Henrv DA & White I (1988) Endosconic coagulation for gastrointestinal bleeding. New J&gland Journal of kedicine 318: 186187. Herlihy KJ & Bozymski EM (1982) Sclerotherapist’s eye. Gastrointestinal Endoscopy 28: 42-43. Hirao M, Kobayashi T, Masuda K et al (1982) Endoscopic local injection of hypertonic saline-epinephrine solution to arrest haemorrhage from the upper digestive tract. II. Clinical application and hemostatic effect. Gastroenterological Endoscopy of Japan 24: 234-241. Hirao M, Kobayashi T, Masuda K et al (1985) Endoscopic local injection of hypertonic saline-epinephrine solution to arrest hemorrhage from the upper digestive tract. Gustrointestinal Endoscopy 31: 313-317. Homer AC, Powell S & Vicary FR (1985) Is Nd-YAG laser treatment for upper gastrointestinal bleeds of benefit in a district general hospital? Postgraduate Medical Journal 61: 19-22. Ihre T, Johansson C, Seligson U et al (1981) Endoscopic YAG-laser treatment in massive gastrointestinal bleeding. Scandinavian Journal of Gastroenterology 16: 633-640. Jensen DM (1990) Heat probe for hemostasis of bleeding peptic ulcers: techniques and results of randomized controlled trials. Proceedings of the Consensus Conference on Therapeutic Endoscopy in Bleeding Peptic Ulcers. Gastrointestinal Endoscopy 30: S42-49. Jensen DM. Machicado GA. Tania JL & Elkashoff J (1984) Controlled trial of endoscooic argon laser for severe ulcer hemorrhage. Gastroenterology 86: 1125(abstract). _ Jensen D, Machicado GA, Reedy TE et al (1986a) Bleeding UGI angioma: endoscopic coagulation and outcome. Gastrointestinal Endoscopy 32: 142A. Jensen D, Machicado GA, Silpa Met al (1986b) Bicap vs heater probe for hemostasis of severe ulcer bleeding. Gastrointestinal Endoscopy 32: 143A.

ENDOSCOPIC

TREATMENT

OF PEPTIC

ULCER

HAEMORRHAGE

559

Jensen DM, Machicado GA, Kovacs TOG et al (1988) Controlled randomized study of heater probe and BICAP for hemostasis of severe ulcer bleeding. Gastroenterology 94: AZOg(abstract). Jensen D, Hirabayashi K & CURE Hemostasis Research Group (1989) A study of coagulation depths with BICAP and heater probe to improve endoscopic hemostasis of bleeding peptic ulcers. Gastrointestinal Endoscopy 35: 18l(abstract). Jessen K (1983) Bicap control of UGI bleeding. Gastroenterology 21: 68A. Johnston JH, Sones JQ, Long BW & Posey EL (1985) Comparison of the heater probe and YAG laser in endoscopic treatment of major bleeding from peptic ulcers. Gastrointestinal Endoscopy 31: 175-181. Kernohan RM, Anderson JR, McKelvey ST & Kennedy TL (1984) A controlled trial of bipolar electrocoagulation in patients with upper gastrointestinal bleeding. British Journal of Surgery 71: 889-891. Kiefhaber P, Nath G & Moritz K (1977) Endoscopical control of massive gastrointestinal haemorrhage by irradiation with a high power neodymium-YAG laser. Progress in Surgery 15: 14@155. Kiefhaber P, Kiefhaber K, Huber F & Nath G (1990) Ten years endoscopic neodymium-YAG laser coagulation in gastrointestinal hemorrhage. In Jensen DM & Brunetaud JM (eds) Medical Laser Endoscopy, pp 109-118. Dordrecht: Kluwer Academic. Klein FA, Drueck C, Breuer RI et al (1982) Control of upper gastrointestinal bleeding with a microcrystalline collagen hemostat. Digestive Diseases and Sciences 27: 981-985. Koch H, Pesche HJ, Bauerle H et al (1973) Experimentelle Untersuchung und klinische Erfahrung zur Electrokoagulation blutender Lasionen im oberen Gastrointestinaltrakt. Fortschritte

Endoscokop

4: 69-71.

Kortan P, Haber G & Marcon N (1987) Endoscopic injection therapy for nonvariceal bleeding lesions of the upper gastrointestinal tract. Gastrointestinal Endoscopy 33: 199-202. Krejs GJ, Little KH, Westergaard H et al (1987) Laser photocoagulation for the treatment of acute peptic ulcer bleeding. New England Journal of Medicine 316: 1618-1621. Laine L (1987) Multipolar electrocoagulation in the treatment of active upper gastrointestinal tract haemorrhage. A prospective controlled trial. New England Journal of Medicine 316: 1613-1617. Laine L (1988) Multipolar electrocoagulation (MEPC) for the treatment of ulcers with nonbleeding visible vessels (VV): a prospective, controlled trial. Gastroenterology 94: A246. Laine L (1989) Multipolar electrocoagulation in the treatment of ulcers with non-bleeding visible vessels: a prospective, controlled trial. Annals of Internal Medicine 110: 510-514. Laine L (1990) Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers. Gastroenterology 99: 1303-1306. Lin HJ, Tsai VT, Lee DS et al (1988) A prospectively randomized trial of heat probe thermocoagulation versus pure alcohol injection in non-variceal peptic ulcer hemorrhage. American

Journal

of Gastroenterology

83: 283-286.

Linscheer WG & Fazio TL (1979) Control of upper gastrointestinal hemorrhage by spraying of clotting factors. Gastroenterology 77: 642-646. MacLeod I, Mills PR, Mackenzie JF et al (1983) Neodymium yttrium aluminium garnet laser photocoagulation for major haemorrhage from peptic ulcers and single vessels. British Medical

Journal

286: 345-358.

Martin TR & Silvis SE (1977) The endoscopic control of GI blood loss with a tissue adhesive (MBR 4197). Gastroenterology 72: 1098. Matek W & Demling L (1986) Hemostasis-therapeutic alternatives to the laser. Endoscopy 18: 17-20.

Matthewson K, Pugh S & Northfield TC (1988) Which peptic ulcer patients bleed? Gut 29: 70-74. Matthewson K, Swain CP, Bland M, Kirkham JS, Bown SG & Northfield TC (1990) Randomized comparison of Nd YAG laser, heater probe and no endoscopic therapy for bleeding peptic ulcers. Gastroenterology 98: 1239-1244. Moreto M, Zaballa M, Ibanez S, Setiem F & Figa M (1987) Efficacy of monopolar electrocoagulation in the treatment of bleeding gastric ulcer: a controlled trial. Endoscopy 19: 54-56. Nakagawa K, Asaki S & Sato T (1989) Endoscopic treatment of bleeding peptic ulcers. World Journal

of Surgery

13: 154-157.

560

P. SWAIN

Nath G, Gorisch W & Kiefhaber P (1973) First laser endoscopy via a fiberoptic transmission system. Endoscopy 5: 213-215. O’Brien JD, Day SJ & Burnham WR (1986) Controlled trial of small bipolar probe in bleeding peptic ulcers. Lancet i: 4611-468. Panes J, Viver J, Forne M et al (1987) Controlled trial of endoscopic sclerosis in bleeding peptic ulcer. Lancet ii: 1292-1294. Papp JP (1982) Endoscopic electrocoagulation in the management of upper gastrointestinal tract bleeding. Surgical Clinics of North America 62: 797-806. Pascu 0, Draghici A & Acalovachi 1(1989) The effect of endoscopic hemostasis with alcohol on the mortality rate of nonvariceal upper gastrointestinal hemorrhage: a randomised prospective study. Endoscopy 21: 53-55. Peura DA (1990) Topical therapy for control of gastrointestinal bleeding. Gastrointestinal Endoscopy 36: S53-55. Peura DA, Johnson LF, Burkhalter FL et al (1982) Use of trifluoroisopropyl cyanoacrylate polymer (MBR 4197) in patients with bleeding peptic ulcers of the stomach and duodenum: a randomized controlled study. Journal of Clinical Gastroenterology 4: 325328. Protell RL, Silverstein FE, Gulacsik C et al (1978) Failure of cyanoacrylate tissue glue (flucrylate, MBR 4197) to stop bleeding from experimental canine gastric ulcers. Digestive Diseases and Sciences 23: 903-908. Randall GM, Jensen DM, Hirabayashi K & Machicado GA (1989) Controlled study of different sclerosing agents for coagulation of canine gut arteries. Gastroenterology 96: 1274-1281. Rhode H, Thon K, Fischer M et al (1980) Results of a defined concept of endoscopic neodymium-YAG laser therapy in patients with upper gastrointestinal bleeding. British Journal of Surgery 67: 360. Rutgeerts P, Vantrappen G, Geboes K & Broeckaert L (1981) Safety and efficacy of neodymium-Yag laser photocoagulation: an experimental study in dogs. Gut 22: 38-44. Rutgeerts P, Vantrappen G, Broeckhaert L et al (1982) Controlled trial of YAG laser treatment of upper digestive hemorrhage. Gastroenterology 83: 410-416. Rutgeerts P, Vantrappen G, Van Hootegem P et al (1987) Neodymium-YAG laser photocoagulation versus multipolar electrocoagulation for treatment of bleeding ulcers: a randomized comparison. Gastrointestinal Endoscopy 33: 199202. Rutgeerts P, Geboes K & Vantrappen G (1989) Experimental studies of injection therapy for severe nonvariceal bleeding in dogs. Gastroenterology 97: 610-621. Shorvon P, Leung JWC, Cotton PB et al (1985) Preliminary clinical experience with the heat probe at endoscopy in acute upper gastrointestinal bleeding. Gastrointestinal Endoscopy 311: 364-366.

Silverstein FE, Auth DC, Rubin CE & Protell RL (1976) High power argon laser treatment via standard endoscopes. 1. A preliminary study of efficacy in control of experimental erosive bleeding. Gastroenterology 71: 558-563. Silverstein FE, Protell RL, Gilbert DA et al (1979) Argon vs neodymium-YAG laser photocoagulation of experimental canine ulcers. Gastroenterology 77: 491-496. Smith FW, Hemonen LA, Peterson EC et al (1980) The use of a strong magnetic field in the control of gastrointestinal bleeding. Gastroenterology 78: 1264. Soehendra N & Werner B (1976) New techniques for endoscopic treatment of bleeding gastric ulcer. Endoscopy 8: 85-87. Soehendra N, Grimm H & Tietze B (1984) Gastrointestinale Blutung-Therapeutische Sklerosierung. Zeitschrift fir Gustroenterologie 22: 102-108. Soehendra N, Grimm H & Stenzel M (1985) Injection of non-variceal bleeding lesions of the upper gastrointstinal tract. Endoscopy 17: 129-132. Storey D (1983) Endoscopic control of peptic ulcer haemorrhage using the ‘heater probe’. Gut 24: 967-968A. Storey DW, Bown SG, Swain CP, Salmon PR, Kirkham JS & Northfield TC (1981) Endoscopic prediction of recurrent bleeding in peptic ulcers. New England Journal of Medicine 305: 915-916. Sugawa C (1990) Injection therapy for the control of bleeding ulcers. Gastrointestinal Endoscopy 36: SSO-52. Sugawa C, Fujita Y, Ikeda T & Walt AG (1986) Endoscopic hemostasis of bleeding of the

ENDOSCOPIC

TREATMENT

upper gastrointestinal Gynecology

and Obstetrics

OF PEPTIC

ULCER

HAEMORRHAGE

tract by local injection

of 98% dehydrated

561 ethanol. Surgery,

162: 159-163.

Swain CP (1986) Forrest 11 bleeding: indications for treatment and results of laser therapy. Endoscopy

18(supplement

1): 14-16.

Swain CP & Mills TN (1986) An endoscopic sewing machine. Gastrointestinal Endoscopy 32: 36-37. Swain CP, Bown SG, Storey DW, Kirkham JS, Salmon PR & Northfield TC (1981) Controlled trial of argon laser photocoagulation in bleeding peptic ulcer. Lancet ii: 1313-1316. Swain CP. Storev DW. Bown SG et al (1986a) Nature of the bleeding vessel in recurrentlv bleeding gastric ulcers. Gastroenterdlogy 9b: 595-606. Swain CP, Salmon PR, Kirkham JS et al (1986b) Controlled trial of Nd: YAG laser photocoagulation in bleeding peptic ulcers. Lancet i: 1113-1117. Swain CP, Brown G & Mills TN (1989) An endoscopic stapling device: development of a new flexible endoscopically controlled device for placing multiple transmural staples in gastrointestinal tissue. Gastrointestinal Endoscopy 35: 338-339. Taylor TV (1988) Isolated duodenal tamponade for treatment of bleeding duodenal ulcer. Lancet i: 911-912. Trudeau W, Siepler JK, Ross K, Cornish D & Prindiville T (1985) Endoscopic Nd : YAG laser photocoagulation of bleeding ulcers with visible vessels. Gastrointestinal Endoscopy 31: 138. Vallon AG, Cotton PB, Laurence BH, Armengol-Miro JR & Salord-Oses JC (1981) Randomised trial of endoscopic argon laser photocoagulation in bleeding peptic ulcers. Gut 22: 228-233.

Wara P (1985) Endoscopic prediction of major rebleeding-a prospective study of stigmata of haemorrhage in bleeding ulcer. Gastroenterology 88: 1209-1214. Winkler W et al (1983) Initial experience with Bicap multipolar electrocautery in the control of upper gastrointestinal hemorrhage. Gastrointestinal Endoscopy 29: 169A.