1. The document summarizes guidelines for the management of bleeding duodenal ulcers, including the etiology, risk factors, clinical assessment, endoscopic diagnosis and treatment options. 2. Key recommendations include performing early endoscopy within 24 hours, using the Forrest classification system to assess bleeding risk, and employing combination endoscopic therapy with epinephrine injection and thermal coagulation or clipping for high risk stigmata. 3. Doppler ultrasound may help guide endoscopic therapy by identifying persistent blood flow signals requiring further treatment to reduce rebleeding risk.

1. Bleeding Duodenal Ulcer
Dr B D Soni
SIDSS, SDMH

2. Ferguson CB, Mitchell RM: Nonvariceal upper gastrointestinal bleeding:Standard and new treatment.
Gastroenterol Clin North Am 34:607–621, 2005.

3. Introduction
• PUD represents the most frequent cause of upper GI
hemorrhage, accounting for approximately 40% of all cases.
• Approximately 10% to 15% of patients with PUD develop
bleeding at some point in the course of their disease.
• Bleeding is the most frequent indication for operation and the
principal cause for death in PUD.
• Incidence of bleeding peptic ulcer decreased over last decade
but despite changing treatment pattern mortality rate from
bleeding peptic ulcer have been relatively stable.

4. Introduction
• High incidences were noted in patients with
more advance age (6th decade)
• Incidence of emergency surgery has not
changed despite improved
medical/endoscopic treatment.

5. ETIOLOGY
• Bleeding peptic ulcers are almost always associated with H.
Pylori Or NSAIDs uses. (~96%)
• Risk of developing bleeding peptic ulcer with corticosteroids
use is debated while concomitant use of NSAIDs with steroids
raises the incidence of Hemorrhage by 10-fold.
• Alcohol
• Smoking

6. H.pylori
• Testing and diagnosis of Hp infection is essential for every patient
with UGI haemorrhage.
• The presence of the infection is usually underestimated in cases of
bleeding peptic ulcers.
• A rapid urease test (RUT), with or without histology, is usually the first
test performed during endoscopy.
• If the initial diagnostic test is negative, a delayed 13C-urea breath test
(UBT) or serology should be performed
• Once an infection is diagnosed, antibiotic treatment is advocated.
Ting-Chun Huang1,2 and Chia-Long Lee, Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 658108 (Review
article)

7. H. Pylori
• 60% - 70% of patients with a bleeding ulcer are H. pylori
positive
• Several studies and a large meta-analysis, have shown that H.
pylori treatment and eradication, in patients who test positive
for the infection, result in decreased rebleeding
• Importantly, once the H. pylori infection has been eradicated,
there is no need for long-term acid suppression and NO
increased risk of further bleeding with this approach.
Liu CC, Lee CL, Chan CC, et al: Maintenance treatment is not necessary after Helicobacter pylori
eradication and healing of bleeding peptic ulcer: A 5-year prospective, randomized, controlled
study. Arch Intern Med 163:2020–2024, 2003.

8. BLEED classification
five criteria:
1. Ongoing bleeding,
2. Systolic blood pressure less than 100 mm Hg,
3. Prothrombin time more than 1.2 times
control,
4. Altered mental status,
5. Unstable comorbid disease process that
would require ICU admission

9. • Any of these if present – model predicts approx 3-fold
increase in the risk of recurrent hemorrhage, need for surgical
management & death.
• Mortality rate is very high in pt with bleeding that develops in
the hospital primarily as a result of significant systemic
disease .

10. • Re-bleeding rates (~15-22%) and mortality (14-15%) in this
modern endoscopic era remained unchanged.
• Approximately 80-85% bleeding stops spontaneously
• Remaining 15-20% recurrent or continuous bleeding
• Re-bleeding increase mortality by 10 times

11. pathophysiology
• Bleeding develops as a consequence of peptic acid erosion of
the mucosal surface.
• chronic blood loss is common with any ulcer
• significant bleeding typically results when there is
involvement of an artery of the submucosa or, with
penetration of the ulcer, an even larger vessel.
• The most significant hemorrhage occurs when duodenal or
gastric ulcers penetrate into branches of the gastroduodenal
artery or left gastric artery, respectively.

12. Clinical Assessment
Class I Class II Class III Class IV
Blood loss 0-15% 15-30% 30-40% >40%
PR (Bts/Min) <100 >100 >120 >140
BP Normal Normal BUT
postural Hypo
Pulse pressure N
RR 14-20 20-30 30-35 35-40
Urine Output >30 20-30 5-15 Negligible
Fluid used crystalloids Crystalloids Crystalloids
+ colloids
Crystalloids
+ colloids
SABISTON TEXTBOOK OF SURGERY, 19th Edition

13. Assessment
• In patients without shock, postural changes should be elicited
by allowing the patient to sit up with his or her legs dangling
for 5 minutes. A fall in blood pressure of more than 10 mm Hg
or an elevation of the pulse of more than 20 beats/min again
reflects at least a 20% blood loss.
• Obtain CBC, electrolytes, BUN/Cr, PT INR/ APTT, blood type,
and cross-match.

14. Resuscitation
• Initiate resuscitation with crystalloid intravenous fluids with the use
of “ LARGE BORE(green/Gray)” IV-access catheters
• PRBC
– If tachycardia or hypotension is present
– If the hemoglobin level is less than 10 g per deciliter. Patients
who received transfusion within 12 h of presentation had a twofold
increased rate of re-bleeding (OR 2.26; 95% CI 1.76–2.90) and a 28%
increase in mortality (OR 1.28; 95% CI 0.94–1.74) compared to those not
early transfused.
• Oxygen
• Consideration of intubation if airway protection is indicated
• correction of coagulopathy (deranged LFT)
Hearnshaw SA, Logan RF, Palmer KR, Card TR, Travis SP, Murphy MF.Aliment Pharmacol
Ther. 2010 Jul;32(2):215-24.

15. NG tube aspirate
American Society For Gastrointestinal Endoscopy

16. Pharmacotherapy Prior to Endoscopy
• Consider initiating treatment with an IV PPI (80-mg
bolus dose plus continuous infusion at 8 mg/hr)
while awaiting early endoscopy
– Down-staging of endoscopic lesions by stabilizing clot with decrease
need for endoscopic therapy (19 % vs. 28% p value 0.007)
– Not have an effect on outcomes (mortality , re-bleeding , transfusion
requirement )
• No role for H2 blocker
• ?Octretide

17. Clinical Predictors of Poor Outcomes
• Older age (>60years)
• Severe co-morbidity
• Active bleeding
• Hypotension or shock
• RBC transfusion6 unit
• Inpatient bleeding
• Severe coagulopathy
Adler DG et al. Gastrointest Endosc 2004; 60:497-504

18. Risk-Stratification Tools for Upper
Gastrointestinal Hemorrhage

19. ?Timing of endoscopy
• Should be performed within 24 hours for all patient
who present with F/o UGI bleed (Index-endoscopy)
• Improve certain outcomes
– the number of units of blood transfused
– the length of the hospital stay
• Treatment recommendations have focused on the
first 72 hours after presentation and endoscopic
evaluation and therapy, since this is the period
when the risk of rebleeding is greatest (90 %)

20. ?Timimg
Soon after initial resuscitation and initiation of
medical therapy, urgent endoscopy is the
preferred procedure for diagnosis and
treatment because of its high accuracy and
low complication rate.
Gastrointest Endosc Clin N Am. 2011 October ; 21(4): . doi:10.1016/j.giec.2011.07.012.

21. Role of Endoscopy
• Diagnosis : 90-95% sensitive at locating bleeding site
• Prognosis : likelihood of persistent or recurrent
bleeding can be predicted
• Therapy : provide therapeutic options
( inject , burn ,clip )

23. Endoscopic risk assessment

24. Forrest grade Ia Forrest grade Ib
Forrest classification
Forrest grade IIa

25. Forrest grade IIc Forrest grade III
Forrest classification
Forrest grade
IIb

26. Role of IV Erythromycin
• May improve the quality of endoscopic exams in patients with
UGI hemorrhage by promoting the emptying of intragastric
blood
• cost-effectiveness study confirmed that giving intravenous (IV)
erythromycin prior to endoscopy for acute UGI bleeding
resulted in cost savings and an increase in quality-adjusted
life-years
• IV erythromycin is strongly recommended prior to endoscopy
in patients with severe UGI haemorrhage, when clots or blood
are anticipated and may obscure the bleeding site.
Winstead NS, Wilcox CM. Erythromycin prior to endoscopy for acute upper
gastrointestinal hemorrhage: a cost-effectiveness analysis. Aliment Pharmacol Ther. 2007;
26:1371–1377.

27. Risk of re-bleeding acc. To SRH

28. High risk lesions

29. Indication of endoscopic therapy
Stigmata Endoscopic therapy
Active bleeding Yes
Non-bleeding visible vessel Yes
Adherent clot Yes
Flat spot No
Clean base No

30. Risk stratification by ‘EDUP’
• Endoscopic Doppler ultrasound probe (EDUP)
technology has been used to interrogate
nonvariceal and variceal bleeding lesions
• DUP uses a small (2 mm diameter), flexible
pulsed-wave, 16 or 20-MHz probe that is
passed through the endoscope’s biopsy
channel directly onto the bleeding lesion

31. EDUP

32. EDUP
• The output signal is expressed as an audible signal
• Based on EDUP signal, scanning depths, and DUP placement on the
lesion, this technology permits evaluation of arterial or venous
blood flow, depth of the blood vessel and position of the blood
vessel
• Use of DUP has shown that most NBVVs demonstrate an arterial
signal while some ulcers with a clean base or pigmented spot also
show an underlying arterial signals
• Persistence of a positive Doppler signal after endoscopic treatment
correlates with the potential for rebleeding. Therefore, endoscopic
DUP may be a useful guide to the completion of hemostasis
• If endoscopic treatment is continued until the underlying blood
flow signal is extinguished the rebleeding rate of NVGIB is very low

33. Research on EDUP
• A prospective study in a group of severely
bleeding ulcer patients with active arterial
bleeding, NBVV and adherent clot, showed
that EDUP–Guided endoscopic treatment
provided a significantly reduced rate of
recurrent hemorrhage at 30 days than
standard therapy based on endoscopic
stigmata alone
Jensen DM, Ohning GV, Singh B, et al. For severe UGI hemorrhage Doppler ultrasound
probe is more accurate and helpful for complete endoscopic hemostasis than lesion
stigmata alone Gastrointest Endosc. 2008; 67:AB81.

34. Research on EDUP
• A decision-analysis comparing EDUP of acute
ulcer hemorrhage with standard treatment,
demonstrated an average cost savings ranging
from $560 to $1160 per patient in the EDUP-
directed group
Chen V, Wong RCK. Endoscopic Doppler Ultrasound versus Endoscopic Stigmata –
directed management of acute peptic ulcer hemorrhage: a multimodel cost analysis.
Dig Dis Sciences. 2007; 52:149–160.

35. Summary: EDUP
1. There is a close correlation between a
positive signal and endoscopic stigmata
2. EDUP-positive ulcers are more likely to
rebleed than EDUP-negative ulcers
3. persistence of a EDUP-positive signal in ulcers
after endoscopic coagulation results in an
increased risk of ulcer rebleeding.

36. Endoscopic therapy
Ideal Endoscopic hemostasis technique -
1. Reproducible effectiveness
2. Easy & rapid application
3. Low complication rates
4. Low cost
5. Portability to bedside
6. Widespread availability

37. Injection therapy
• Epinephrine (1:10000 or 1:20000 in saline)
• provides local tamponade, vasoconstriction, and improved
platelet aggregation to promote hemostasis
• Other injectables- alcohol, ETHn, polidocanol, tissue glue, fibrin
glue, CYN- Not recommended (not evaluated for use)
• The technique involves injection through a sclerotherapy
catheter with a 25-gauge retractable needle in 4 quadrants
around actively bleeding point or non-bleeding vessel
• Dilute epinephrine/saline solution (1:10,000 – 1:20,000) is
injected in 0.5–1.5 ml increments up to a total of 25 – 30 ml.

38. Injection therapy
• Large-volume injection (>13 mL) is associated
with better hemostasis, suggesting that the
endoscopic injection works in part by
compressing the bleeding vessel and inducing
tamponade
Lin HJ, Hsieh YH, Tseng GY, et al: A prospective, randomized trial of large- versus small-volume
endoscopic injection of epinephrine for peptic ulcer bleeding. Gastrointest Endosc 55:615
619, 2002
• Should not use alone

39. Endoscopic Electrocoagulation
• Monopolar, bipolar and MPEC
• In bipolar/MPEC current flow in between two or more electrodes
separated by 1 to 2 mm at the probe tip
• Current flow is concentrated closer to the tip than with a monopolar
probe, providing less depth of tissue injury and lesser potential for
perforation
• Coaptive coagulation directly gives pressure on the stigmata
temporarily interrupts blood flow through the underlying vessel,
reduces the heat sink effect, and with application of heat can
coaptively seal arteries up to 2 mm in diameter
• MPEC coagulation is effective for treatment of actively bleeding
ulcers, NBVV or adherent clot and prevention of rebleeding by
coaptively coagulating the artery underlying these SRH

40. Mechanical Hemostasis
• Metallic clips (endoclips), endoloops, and rubber band ligation
• Grasp into the submucosa, seal the underlying patent blood vessels,
and/or approximates the sides of lesions during endoscopy
• The clips can produce hemostasis similar to surgical ligation, if
properly applied
• Placement of 2 additional clips to ligate proximally and distally from
the bleeding point to occlude the underlying artery is recommended
• Endoclipping may be limited by the vessel size (> 2 mm in diameter),
difficulty in accessing ulcers (such as proximal lesser curve of the
stomach, posterior wall gastric body and posterior duodenal bulb),
fibrotic lesions and single clip deployment

41. Combined therapy
• The technique involves dilute epinephrine injection into four
quadrants around stigmata in the ulcer base followed by thermal
coagulation with heater probe or multipolar probe, or deployment
of endoclips
• Combination therapy has become the standard treatment for
actively bleeding ulcers and non-bleeding adherent clot
• Results of meta-analysis reported that dual therapy achieved
significantly better outcomes than epinephrine injection alone
Marmo R, Rotondano G, Piscopo R, et al. Dual therapy versus monotherapy in the endoscopic
treatment of high-risk bleeding ulcers: a meta-analysis of controlled trials. Am J Gastroenterol. 2007;
102:279–289

42. RECOMMENDATIONS FOR ENDOSCOPIC THERAPY
• Combination therapy with
epinephrine injection
(1:10,000 or 1:20,000 in
saline) and thermal
coagulation (multipolar or
heater probe) or
hemoclipping is
recommended
• Successful endoscopic
hemostasis occurs in
nearly 100% of lesions

43. RECOMMENDATIONS FOR ENDOSCOPIC THERAPY
• If oozing from an ulcer
base persists despite
irrigation and
observation,
monotherapy with
thermal probes or
hemoclipping is
effective
• Rebleeding rates are
less than 5%

44. RECOMMENDATIONS FOR ENDOSCOPIC THERAPY
• Monotherapy with
thermal coagulation
(heater or multipolar
probe) is effective if
coaptive coagulation is
done
• Hemostasis of NBVV with
hemoclips provides
similar beneficial
outcomes as thermal
therapy

45. RECOMMENDATIONS FOR ENDOSCOPIC THERAPY
• Combination therapy
Four-quadrant dilute epinephrine injection
close to the attachment of the clot, in the
ulcer base
A rotatable polypectomy snare is used to
shave down the clot
Thermal coaptive coagulation or
hemoclipping to treat the residual clot or
NBVV
Rebleeding rate for adherent non bleeding
clots was less than 5% (CURE Trial)

46. RECOMMENDATIONS FOR ENDOSCOPIC THERAPY
No benefit from endoscopic hemostasis, since
patients with these endoscopic findings have a
very low rebleeding rate – 7% and 3 % respectively
on medical therapy alone

47. Limitation of endoscopic therapy
challenging lesions
• Large ulcer defect more than 2cm
• Visible vessel more than 2 mm
• Inaccessible lesions
• Challenging positions ( posterior wall stomach
,lesser curve , posterior bulbar wall)
• Fibrotic base for hemoclip

48. Outcome of Endoscopic Management
• Hemostasis>95%
• Recurrent bleeding<15%
• Death 6-8% (irrespective of any optimal
endoscopic & medical treatment)
Barkun A et al. Ann Intern Med 2003; 139:843-5,
Cipolletta L et al. Endoscopy 2007; 39:7-10
Treat the patient and Not just the
source of bleeding

49. COMPLICATIONS
• perforation or precipitation of bleeding from a NBVV
• In a meta-analysis pooled rates for complications
associated with endoscopic treatment were 0.8%
• perforations occurred significantly more frequently in
patients receiving combination treatment, such as injection
plus thermal coagulation or dual injection (epinephrine
followed by a sclerosant) than single therapy
• Perforations were more frequent after endoscopic
retreatment with thermal coagulation

50. Hemospray

51. Hemospray
• Hemospray, a novel modality, is a inorganic
powder, has recently been approved in Canada
for the management of nonvariceal upper
gastrointestinal bleeding (UGIB)
It achieves hemostasis by adhering to the bleeding
site, which leads to mechanical tamponade and,
by concentrating and activating platelets and
coagulation factors, promotes thrombus
formation

52. Hemospray
95% acute hemostasis
Sung JJ Endoscopy. 2011 Apr;43(4):291-5. Epub 2011 Mar 31.

53. Hemospray
• conventional endoscopic therapies may not be feasible in patients
with active multifocal bleeding sites, particularly those with
challenging anatomy and coagulopathy, in which contact
coagulation efforts may be hampered by further tissue damage and
induction of more bleeding . In contrast, Hemospray can quickly
cover large areas and does not require en face view or direct
contact with the bleeding lesion
• Hemospray appears to allow safe control of acute bleeding and may
be used in high-risk cases as a temporary measure or a bridge
toward more definitive therapy
AHL Yau, G Ou, C Galorport, et al. Safety and efficacy of Hemospray® in upper
gastrointestinal bleeding. Can J Gastroenterol Hepatol 2014;28(2):72-76.

54. surgery
• Despite significant advances in endoscopic therapy,
approximately 10% of patients with bleeding ulcers still
require surgical intervention for effective hemostasis
• Ulcers larger than 2 cm, posterior duodenal ulcers, and
gastric ulcers have a significantly higher risk of rebleeding
• Patients with these characteristics need closer monitoring
and possibly earlier surgical intervention
• Essentially all patient with bleeding peptic ulcer should
undergo UGIE prior to the consideration of surgical therapy
Shackelford’s SURGERY of the ALIMENTARY TRACT

55. Indication
1. Hemodynamic instability despite vigorous
resuscitation (>6 U transfusion)
2. Failure of endoscopic techniques to arrest
hemorrhage
3. Recurrent hemorrhage (with up to two attempts
at obtaining endoscopic hemostasis)
4. Shock associated with recurrent hemorrhage
5. Continued slow bleeding with a transfusion
requirement >3 U /day
Shackelford’s SURGERY of the ALIMENTARY TRACT

56. Relative Indication
• Rare blood type or difficult crossmatch,
• Refusal of transfusion
• Shock on presentation
• Advanced age
• Severe comorbid disease
• A bleeding chronic gastric ulcer for which
malignancy is a concern.
Shackelford’s SURGERY of the ALIMENTARY TRACT

57. AIM
• First priority at operation should be control of
the hemorrhage
• A decision must be made regarding the need
for a definitive acid-reducing procedure
• ?H. Pylori treatment
Shackelford’s SURGERY of the ALIMENTARY TRACT

58. Surgery for Bleeding DU
• A pyloroduodenotomy is necessary to inspect the duodenal bulb
and gastric antrum. The gastroduodenal artery is the usual source
of bleeding, which should be controlled by placement of suture
ligatures
• Once the bleeding has been addressed, a definitive acid-reducing
operation may be performed. With the identification of H. pylori,
the utility of a vagotomy has been questioned.
• The data, however, suggest that, even in the era of H. pylori and our
ability to eradicate it, a TV perhaps should be performed in those
patients with a bleeding duodenal ulcer.
Shackelford’s SURGERY of the ALIMENTARY TRACT

59. ?TV
• 1. Only 40% to 70% of patients with a bleeding duodenal
ulcer are positive for H. pylori.
• 2. H. pylori testing in the setting of an acute hemorrhage is
less reliable, with the CLO (Campylobacter-like organism)
test having a false-negative rate of 18% versus 1% in those
not actively bleeding.
• 3. If an acid-reducing procedure is not performed, up to
50% of patients are at risk of recurrent bleeding.
• 4. Conflicting evidence that H. pylori treatment changes the
risk of recurrent bleeding
Shackelford’s SURGERY of the ALIMENTARY TRACT

60. • TV with pyloroplasty is the most frequently
used operation for bleeding duodenal ulcer
• In most cases the bleeding will have been
localized to the first part of the duodenum
and the bleeding vessel can be controlled
Shackelford’s SURGERY of the ALIMENTARY TRACT

61. procedure
• Upper midline laparotomy, entering the
peritoneal cavity
• A Kocher manoeuvre is then performed to
mobilize the duodenum. This gives better
exposure and relieves any tension on the
subsequent suture line
• The pyloric vein of Mayo is virtually always
present on the anterior surface of the inferior
pylorus
• Two 3-0 silk traction sutures are placed astride
the anterior pylorus and parallel to each other

62. Fischer's mastery of surgery 6th edn

63. • While lifting up on the traction sutures, a
longitudinal incision is made through the
pyloric muscles and extended 2 to 3 cm
proximally into stomach and distally into
duodenum
• The duodenal mucosa is inspected for any
evidence of active bleeding, ulceration, or
induration
• If active bleeding is encountered, this is
controlled by digital pressure
• The bleeding vessel is then ligated.

64. • This vessel is often the gastroduodenal artery
• This vessel at the level of the posterior
duodenal wall has a T or three-vessel junction.

65. • It is important to suture ligate the gastroduodenal
artery superiorly and inferiorly, followed by
ligation of the medial transverse pancreatic
branches using a U-stitch
• Care should be taken to avoid injury to the
common bile duct during suture placement
• After gaining control of the bleeding, the
pyloroplasty is performed. Most often this is done
as a Heineke- Mikulicz pyloroplasty
• If the duodenum is soft, pliable, and minimally
deformed, a running closure of the inside layer is
done using absorbable suture in an inverting
fashion

66. • An outside Lembert layer of 4-0 silk sutures in
an interrupted fashion completes the
procedure
• Some prefer a single-layer closure because of
the potential risk of obstruction associated
with a two-layer closure and the possibility of
inverting an excess amount of mucosa
• The procedure is then completed by
performing a TV

68. ?HSV
• In experienced hands, HSV may represent the best
therapy for a bleeding duodenal ulcer
• Several reports have shown that even in the setting of
an acute hemorrhage this procedure can be done
safely with good long-term results if surgeon has
significant experience with the operation
• As a result, more traditional expedient operation with
proven efficacy such as TV with pyloroplasty is
recommended over HSV

69. Vagotomies

71. Shackelford’s SURGERY of the ALIMENTARY TRACT

72. If D1 is completely shattered by large duodenal
ulcer
Billroth I gastroduodenal
anastomosis might be
needed.
World Journal of Emergency Surgery Di Saverio
et al. 2014, 9:45

73. Re-bleeding after Surgery
• Several authors have advocated STAE as a
viable alternative to operative treatment for
ulcer bleeding after surgery
• Data from two large series suggest that TAE
can achieve long-term hemostasis in roughly
75% of patients with recurrent bleeding after
duodentomy and ulcer oversewing
Eriksson LG, Ljungdahl M, Sundbom M, et al. Transcatheter arterial embolization versus surgery
in the treatment of upper gastrointestinal bleeding after therapeutic endoscopy failure. J Vasc
Interv Radiol. 2008; 19(10):1413–1418. [PubMed: 18755604]
Holme JB, Nielsen DT, Funch-Jensen P, et al. Transcatheter arterial embolization in patients with
bleeding duodenal ulcer: an alternative to surgery. Acta Radiol. 2006; 47(3):244–247. [PubMed:
16613304]

74. Re-bleeding after Surgery
• Despite the best surgical efforts, re-bleeding
after surgery occurs in between 6–17% of cases
• Endoscopic therapy- not recommended after Sx
• Two options- reoperation or STAE
• Reoperation when considered in past it was
ulcer excision+ Billroth I GDA
Millat B, Hay JM, Valleur P, et al. Emergency surgical treatment for bleeding duodenal ulcer:
oversewing plus vagotomy versus gastric resection, a controlled randomized trial. French
Associations for Surgical Research. World J Surg. 1993; 17(5):568–573. discussion 574.
[PubMed: 8273376]
Poxon VA, Keighley MR, Dykes PW, et al. Comparison of minimal and conventional surgery in
patients with bleeding peptic ulcer: a multicentre trial. Br J Surg. 1991; 78(11):1344–1345.
[PubMed: 1760699]

75. Thanks