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著者: 福田健介 大分大学医学部 消化器内科学講座

著者: 村上和成 大分大学医学部 消化器内科学講座

監修: 上村直実 国立健康危機管理研究機構(JIHS)国立国府台医療センター/東京医科大学消化器内視鏡センター

著者校正/監修レビュー済:2024/02/21
参考ガイドライン:
  1. 日本消化器病学会:消化性潰瘍診療ガイドライン 2020 改訂第3版
患者向け説明資料

改訂のポイント:
  1. 定期レビューを行い、消化性潰瘍に対する内視鏡治療について新たなエビデンスをもとに内容を変更・追記した。
  1. 消化性潰瘍に対する各種内視鏡止血術の効果を検討したシステマティックレビューでは、再出血率に関してクリップ法は単独でも局注法より優れていた。また、局注法は単独よりもクリップ法や凝固法を併用したほうが初回止血・再出血の予防に効果的であるとされた(Baracat F, et al. Surg Endosc. 2016 Jun;30(6):2155-68.)。

概要・推奨   

  1. 吐血(上部消化管出血)の原因は半数が胃・十二指腸潰瘍である(推奨度1)
  1. NSAIDs服用により、上部消化管出血のリスクは高まる(推奨度1)
  1. 低用量アスピリンを服用する患者は服用しない患者に比べ、上部消化管出血のリスクは高い(推奨度1)
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  1. 出血性消化性潰瘍患者の内視鏡的治療後にPPIおよびボノプラザン(VPZ)やH2RAを投与することで、治療成績が向上する(推奨度1)
  1. H. pylori除菌治療は胃潰瘍の治癒を促進する(推奨度1)
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病態・疫学・診察 

疫学情報・病態・注意事項  
  1. 吐血とは口腔より新鮮血やコーヒー残渣様吐物を排出することで、Treitz靱帯よりも口側の食道、胃、十二指腸などの上部消化管からの出血が原因である。
  1. 食道疾患では吐血は食道静脈瘤、逆流性食道炎、食道潰瘍、Mallory-Weiss 症候群などでみられる。食道からの吐血は胃酸と混合しないので赤色を呈する。
  1. 胃疾患では胃潰瘍、胃癌、悪性リンパ腫、急性胃粘膜病変(AGML)、吻合部潰瘍などで吐血がみられる。血液が胃酸と混合することで塩酸ヘマチンに変化するため、黒色を呈する。
  1. 十二指腸では十二指腸潰瘍、十二指腸びらんなどで吐血がみられる。胃を通過するため血液は胃酸の影響で黒色を呈する。
  1. H. pylori感染と低用量アスピリン(LDA)を含む非ステロイド抗炎症薬(NSAIDs)が消化性潰瘍の2大リスク因子であるが、近年前者は減少傾向、後者は増加傾向にある。
 
  1. 吐血(上部消化管出血)の原因は半数が胃・十二指腸潰瘍である(推奨度1)
  1. まとめ:吐血の原因の第1位は胃・十二指腸潰瘍であり、約50%以上を占める。
  1. 代表事例:山口ら[1]が2002年に上部消化管内視鏡時に何らかの止血術を実施した1,412例を検討しており、原因疾患は出血性胃潰瘍が626例(60%)、出血性十二指腸潰瘍が200例(19%)であった(参考画像<図表>)。他の報告および自験例[2][3]でも同様な結果であった。また欧米でも上部消化管出血の原因は消化性潰瘍が35~50%と報告されている[4]
  1. 結論:吐血の原因疾患は胃・十二指腸潰瘍が最も頻度が高い。
  1. 追記:胃・十二指腸潰瘍の次に頻度が高い疾患は食道静脈瘤破裂であり、他にMallory-Weiss症候群、逆流性食道炎などの頻度が高い。
 
吐血の原因疾患とその頻度

吐血の原因疾患は胃・十二指腸潰瘍が最も多く、次いで食道・胃静脈瘤が多い。
 
参考文献:
山口淳正、内園 均、谷口 保ほか:上部消化管出血の内科的治療 日本臨床内科医会雑誌2002;17:28-34 (改変あり)
長谷川申、高濱和也、平田一郎:消化管出血原因疾患の変遷と非手術的治療の意義、日腹救急医会誌2006;26:491-496 (改変あり)
小坂俊仁、芳野純治. 消化性疾患の主要な対症療法 吐血・下血. 消化器最新の治療 2009-2010. 菅野健太郎、上西紀夫、井廻道夫 編集.南江堂,東京, 2009;80-84

出典

小坂俊仁先生ご提供
問診・診察のポイント  
 
  1. 排出された血液の性状(新鮮血、コーヒー残渣様吐物、タール便、粘血便など)、出血量、持続期間、随伴症状を問診する。喀血した血液を飲み込み、それを嘔吐した場合に吐血と鑑別が難しいことがあり、咳嗽などの症状がないか確認する。

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文献 

山口淳正、内園 均、谷口 保ほか:上部消化管出血の内科的治療 日本臨床内科医会雑誌2002;17:28-34.
長谷川申、高濱和也、平田一郎:消化管出血原因疾患の変遷と非手術的治療の意義、日腹救急医会誌2006;26:491-496.
小坂俊仁、芳野純治. 消化性疾患の主要な対症療法 吐血・下血. 消化器最新の治療 2009-2010. 菅野健太郎、上西紀夫、井廻道夫 編集.南江堂, 2009;80-84.
British Society of Gastroenterology Endoscopy Committee
Non-variceal upper gastrointestinal haemorrhage: guidelines.
Gut. 2002 Oct;51 Suppl 4:iv1-6.
Abstract/Text
PMID 12208839
F Douglas Srygley, Charles J Gerardo, Tony Tran, Deborah A Fisher
Does this patient have a severe upper gastrointestinal bleed?
JAMA. 2012 Mar 14;307(10):1072-9. doi: 10.1001/jama.2012.253.
Abstract/Text CONTEXT: Emergency physicians must determine both the location and the severity of acute gastrointestinal bleeding (GIB) to optimize the diagnostic and therapeutic approaches.
OBJECTIVES: To identify the historical features, symptoms, signs, bedside maneuvers, and basic laboratory test results that distinguish acute upper GIB (UGIB) from acute lower GIB (LGIB) and to risk stratify those patients with a UGIB least likely to have severe bleeding that necessitates an urgent intervention.
DATA SOURCES: A structured search of MEDLINE (1966-September 2011) and reference lists from retrieved articles, review articles, and physical examination textbooks.
STUDY SELECTION: High-quality studies were included of adult patients who were either admitted with GIB or evaluated in emergency departments with bedside evaluations and/or routine laboratory tests, and studies that did not include endoscopic findings in prediction models. The initial search yielded 2628 citations, of which 8 were retained that tested methods of identifying a UGIB and 18 that identified methods of determining the severity of UGIB.
DATA EXTRACTION: One author abstracted the data (prevalence, sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality, with confirmation by another author. Data were combined using random effects measures.
DATA SYNTHESIS: The majority of patients (N = 1776) had an acute UGIB (prevalence, 63%; 95% CI, 51%-73%). Several clinical factors increase the likelihood that a patient has a UGIB, including a patient-reported history of melena (LR range, 5.1-5.9), melenic stool on examination (LR, 25; 95% CI, 4-174), a nasogastric lavage with blood or coffee grounds (LR, 9.6; 95% CI, 4.0-23.0), and a serum urea nitrogen:creatinine ratio of more than 30 (summary LR, 7.5; 95% CI, 2.8-12.0). Conversely, the presence of blood clots in stool (LR, 0.05; 95% CI, 0.01-0.38) decreases the likelihood of a UGIB. Of the patients clinically diagnosed with acute UGIB, 36% (95% CI, 29%-44%) had severe bleeding. A nasogastric lavage with red blood (summary LR, 3.1; 95% CI, 1.2-14.0), tachycardia (LR, 4.9; 95% CI, 3.2-7.6), or a hemoglobin level of less than 8 g/dL (LR range, 4.5-6.2) increase the likelihood of a severe UGIB requiring urgent intervention. A Blatchford score of 0 (summary LR, 0.02; 95% CI, 0-0.05) decreases the likelihood that a UGIB requires urgent intervention.
CONCLUSIONS: Melena, nasogastric lavage with blood or coffee grounds, or serum urea nitrogen:creatinine ratio of more than 30 increase the likelihood of a UGIB. Blood clots in the stool make a UGIB much less likely. The Blatchford clinical prediction score, which does not require nasogastric lavage, is very efficient for identifying patients who do not require urgent intervention.

PMID 22416103
Jia Qing Huang, Subbaramiah Sridhar, Richard H Hunt
Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis.
Lancet. 2002 Jan 5;359(9300):14-22. doi: 10.1016/S0140-6736(02)07273-2.
Abstract/Text BACKGROUND: The relation between H pylori infection and use of non-steroidal anti-inflammatory drugs (NSAIDs) in the pathogenesis of peptic-ulcer disease is controversial. We undertook a meta-analysis to address this issue.
METHODS: By computer and manually we sought observational studies on the prevalence of peptic-ulcer disease in adult NSAID takers or the prevalence of H pylori infection and NSAID use in patients with peptic-ulcer bleeding. Summary odds ratios were calculated from the raw data. Tests for homogeneity were done.
FINDINGS: Of 463 citations identified, 25 studies met inclusion criteria. In 16 studies of 1625 NSAID takers, uncomplicated peptic-ulcer disease was significantly more common in patients positive than in those negative for H pylori (341/817 [41.7%] vs 209/808 [25.9%]; odds ratio 2.12 [95% CI 1.68-2.67]). In five controlled studies, peptic-ulcer disease was significantly more common in NSAID takers (138/385 [35.8%]) than in controls (23/276 [8.3%]), irrespective of H pylori infection. Compared with H pylori negative individuals not taking NSAIDs, the risk of ulcer in H pylori infected NSAID takers was 61.1 (9.98-373). H pylori infection increased the risk of peptic-ulcer disease in NSAID takers 3.53-fold in addition to the risk associated with NSAID use (odds ratio 19.4). Similarly, in the presence of risk of peptic-ulcer disease associated with H pylori infection (18.1), use of NSAIDs increased the risk of peptic-ulcer disease 3.55-fold. H pylori infection and NSAID use increased the risk of ulcer bleeding 1.79-fold and 4.85-fold, respectively. However, the risk of ulcer bleeding increased to 6.13 when both factors were present.
INTERPRETATION: Both H pylori infection and NSAID use independently and significantly increase the risk of peptic ulcer and ulcer bleeding. There is synergism for the development of peptic ulcer and ulcer bleeding between H pylori infection and NSAID use. Peptic-ulcer disease is rare in H pylori negative non-NSAID takers.

PMID 11809181
Choitsu Sakamoto, Kentaro Sugano, Shinichi Ota, Nobuhiro Sakaki, Shin'ichi Takahashi, Yukio Yoshida, Taku Tsukui, Hiroyuki Osawa, Yukihiro Sakurai, Junji Yoshino, Yuji Mizokami, Tetsuya Mine, Tetsuo Arakawa, Hajime Kuwayama, Katsunori Saigenji, Koji Yakabi, Tsutomu Chiba, Tooru Shimosegawa, Jane E Sheehan, Susana Perez-Gutthann, Takuhiro Yamaguchi, David W Kaufman, Tsugumichi Sato, Kiyoshi Kubota, Akira Terano
Case-control study on the association of upper gastrointestinal bleeding and nonsteroidal anti-inflammatory drugs in Japan.
Eur J Clin Pharmacol. 2006 Sep;62(9):765-72. doi: 10.1007/s00228-006-0171-6. Epub 2006 Jul 4.
Abstract/Text OBJECTIVE: Studies in Western populations have shown the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and upper gastrointestinal bleeding (UGIB). The role of Helicobacter pylori infection in NSAIDs-related UGIB remains to be studied. We conducted a case-control study in Japan to investigate these related topics.
METHODS: Cases of UGIB due to duodenal or gastric ulcer, or gastritis were identified in 14 study hospitals in various areas of Japan. For each case, two controls were identified from population registries in the same district. Information on drugs and other risk factors was obtained from 175 cases and 347 controls by telephone interviews. Anti-H. pylori antibody in the urine was measured in a single laboratory for all the cases and 225 controls.
RESULTS: The odds ratio (OR) of UGIB was 5.5 for aspirin and 6.1 for other NSAIDs (NANSAIDs) (p<0.01). The OR for regular use was higher than for occasional use both for aspirin (7.7 vs 2.0) and NANSAIDs (7.3 vs 4.1). Loxoprofen (5.9), frequently used in Japan as a safe 'prodrug', was significantly associated with UGIB. The odds ratio for H. pylori infection was 4.9 and the relative excess risk due to the interaction between H. pylori and the use of NSAID was 1.2 (95% CI: -5.8-8.1).
CONCLUSION: NSAIDs including loxoprofen increase the risk of UGIB in Japan as in Western countries, with a similar magnitude of association. There was no evidence of biological interaction between NSAIDs and H. pylori infection.

PMID 16821007
Steven M Weisman, David Y Graham
Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events.
Arch Intern Med. 2002 Oct 28;162(19):2197-202.
Abstract/Text BACKGROUND: In spite of the clear evidence of benefit of aspirin in the secondary prevention of cerebrovascular and cardiovascular thrombotic events, its use in patients at high risk due to a previous event remains suboptimal. A possible explanation for this underuse is concern regarding the relative benefit in relation to the potential risk for serious gastrointestinal events.
OBJECTIVE: To compare the benefit and gastrointestinal risk of aspirin use for the secondary prevention of thromboembolic events.
DESIGN: A meta-analysis was conducted using 6 trials (6300 patients) meeting the inclusion requirement of use of low-dose aspirin (< or =325 mg/d) in approved secondary prevention indications.
RESULTS: Aspirin reduced all-cause mortality by 18%. In addition, aspirin use reduced the number of strokes by 20%, myocardial infarctions by 30%, and other "vascular events" by 30%. Alternately, patients who took aspirin were 2.5 times more likely than those in the placebo group to have gastrointestinal tract bleeding. The number needed to treat for aspirin to prevent 1 death from any cause of mortality was 67, while 100 needed to be treated to detect 1 nonfatal gastrointestinal tract bleeding.
CONCLUSION: Aspirin use for the secondary prevention of thromboembolic events has a favorable benefit-to-risk profile and should be encouraged in those at high risk.

PMID 12390062
S Derry, Y K Loke
Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis.
BMJ. 2000 Nov 11;321(7270):1183-7.
Abstract/Text OBJECTIVES: To assess the incidence of gastrointestinal haemorrhage associated with long term aspirin therapy and to determine the effect of dose reduction and formulation on the incidence of such haemorrhage.
DESIGN: Meta-analysis of 24 randomised controlled trials (almost 66 000 participants). Intervention: Aspirin compared with placebo or no treatment, for a minimum of one year.
MAIN OUTCOME MEASURES: Incidence of gastrointestinal haemorrhage.
RESULTS: Gastrointestinal haemorrhage occurred in 2.47% of patients taking aspirin compared with 1.42% taking placebo (odds ratio 1.68; 95% confidence interval 1.51 to 1.88); the number needed to harm was 106 (82 to 140) based on an average of 28 months' therapy. At doses below 163 mg/day, gastrointestinal haemorrhage occurred in 2.30% of patients taking aspirin compared with 1.45% taking placebo (1.59; 1.40 to 1.81). Meta-regression showed no relation between gastrointestinal haemorrhage and dose. For modified release formulations of aspirin the odds ratio was 1.93 (1.15 to 3.23).
CONCLUSIONS: Long term therapy with aspirin is associated with a significant increase in the incidence of gastrointestinal haemorrhage. No evidence exists that reducing the dose or using modified release formulations would reduce the incidence of gastrointestinal haemorrhage.

PMID 11073508
Kenneth R McQuaid, Loren Laine
Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials.
Am J Med. 2006 Aug;119(8):624-38. doi: 10.1016/j.amjmed.2005.10.039.
Abstract/Text PURPOSE: We performed a systematic review to define the relative and absolute risk of clinically relevant adverse events with the antiplatelet agents, aspirin and clopidogrel.
MATERIALS AND METHODS: Databases were searched for randomized controlled trials of low-dose aspirin (75-325 mg/day) or clopidogrel administered for cardiovascular prophylaxis. Relative risks (RR) were determined by meta-analysis of 22 trials for aspirin versus placebo and from single studies for aspirin versus clopidogrel, aspirin versus aspirin/clopidogrel, and clopidogrel versus aspirin/clopidogrel. Absolute risk increase was calculated by multiplying RR increase by the pooled weighted incidence of the control.
RESULTS: Aspirin increased the risk of major bleeding (RR=1.71; 95% confidence interval [CI], 1.41-2.08), major gastrointestinal (GI) bleeding (RR=2.07; 95% CI, 1.61-2.66), and intracranial bleeding (RR=1.65; 95% CI, 1.06-5.99) versus placebo. No difference between 75-162.5 mg/day and >162.5-325 mg/day aspirin versus placebo was seen. The absolute annual increases attributable to aspirin were major bleeding: 0.13% (95% CI, 0.08-0.20); major GI bleeding: 0.12% (95% CI, 0.07-0.19), intracranial bleeding: 0.03% (95% CI, 0.01-0.08). No study compared clopidogrel with placebo. One study showed increased major GI bleeding (but not non-GI bleeding endpoints) with aspirin versus clopidogrel (RR=1.45; 95% CI, 1.00-2.10). The absolute annual increase was 0.12% (95% CI, 0.00-0.28).
CONCLUSIONS: Low-dose aspirin increases the risk of major bleeding by approximately 70%, but the absolute increase is modest: 769 patients (95% CI, 500-1250) need to be treated with aspirin to cause one additional major bleeding episode annually. Compared with clopidogrel, aspirin increases the risk of GI bleeding but not other bleeding; however, 883 patients (95% CI, 357-infinity) would need to be treated with clopidogrel versus aspirin to prevent one major GI bleeding episode annually at a cost of over 1 million dollars.

PMID 16887404
金井尚之ほか:ショック.救急医学 2001;25:379-382.
[http://www.mhlw.go.jp/new-info/kobetu/iyaku/kenketsugo/5tekisei3b.html 厚生労働省医薬食品局血液対策課. 血液製剤の使用指針.改訂版.構成労働省(最終アクセス:2015年2月22日).
Loren Laine, Dennis M Jensen
Management of patients with ulcer bleeding.
Am J Gastroenterol. 2012 Mar;107(3):345-60; quiz 361. doi: 10.1038/ajg.2011.480. Epub 2012 Feb 7.
Abstract/Text This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1-3 days). Patients with idiopathic ulcers receive long-term anti-ulcer therapy.

PMID 22310222
日本消化器病学会編:消化性潰瘍診療ガイドライン2015 改訂第2版、2015、南江堂.
Enric Brullet, Rafel Campo, Xavier Calvet, Merce Guell, Neus Garcia-Monforte, Joan Cabrol
A randomized study of the safety of outpatient care for patients with bleeding peptic ulcer treated by endoscopic injection.
Gastrointest Endosc. 2004 Jul;60(1):15-21.
Abstract/Text BACKGROUND: Outpatient management is safe for patients with non-variceal upper-GI bleeding who are at low risk of recurrent bleeding and death. However, outpatient care cannot be offered to many patients because of the presence of risk factors (severe comorbid disorders, major endoscopic stigmata of bleeding, significant hemorrhage). The present study assessed the safety of outpatient management for selected high-risk patients with bleeding peptic ulcer.
METHODS: Patients hospitalized with upper-GI bleeding because of peptic ulcer with a non-bleeding vessel were eligible for inclusion in the study. Inclusion criteria were the following: ulcer size less than 15 mm, absence of hypovolemia, no associated severe disease, and appropriate family support. After endoscopic therapy (injection of epinephrine and polidocanol), patients were randomized to outpatient or hospital care. Patients remained in the emergency ward for a minimum of 6 hours before discharge, during which time omeprazole was administered intravenously. Outpatients were contacted by telephone daily during the first 3 days; a 24-hour telephone hotline was provided for any queries. For both groups, outpatient visits were scheduled at 7 to 10 and 30 days after discharge.
RESULTS: A total of 82 patients were included: 40 were randomized to outpatient care and 42 to hospital care. Clinical and endoscopic variables were similar in both groups. The rate of recurrent bleeding was similar in both groups (4.8% outpatient, 5% hospital). There was no morbidity or mortality in either group at 30 days. Seven patients (17%) randomized to outpatient care received blood transfusion compared with 14 (38%) in the hospital care group (p=0.06). Mean cost of care per patient was significantly lower for the outpatient vs. the hospital group (970 US dollars vs. 1595 US dollars; p < 0.001).
CONCLUSIONS: Selected patients with bleeding peptic ulcer can be safely managed as outpatients after endoscopic therapy. This policy conserves health care resources without compromising standards of care.

PMID 15229419
水城 啓ほか:出血性胃潰瘍に対するクリニカルパス導入の検討. 日消誌2006;103:283-289.
山内宏哲ほか:胃潰瘍入院クリニカルパスの有用性について. 日消誌2003;100:844-851.
浅木 茂ほか:消化性潰瘍の発症時には,絶食の方が早く経過するのか?.治療 2006;88:1017-1019.
H S Sacks, T C Chalmers, A L Blum, J Berrier, D Pagano
Endoscopic hemostasis. An effective therapy for bleeding peptic ulcers.
JAMA. 1990 Jul 25;264(4):494-9.
Abstract/Text We performed a meta-analysis of 25 randomized control trials that compared endoscopic hemostasis with standard therapy for bleeding peptic ulcer. For recurrent or continued bleeding, the mean rate in control patients was 0.39, and the pooled rate difference, or reduction due to therapy, was 0.27 +/- 0.15 (95% confidence interval) (69% relative reduction). For emergency surgery, the mean rate in control patients was 0.26, and the pooled rate difference was 0.16 +/- 0.05 (62% relative reduction). Most important, for overall mortality, the mean rate in control patients was 0.10, and the pooled rate difference was 0.03 +/- 0.02 (30% relative reduction). The effects were greatest in patients with spurting or visible blood vessels and equivocal when the ulcer showed only signs of recent bleeding. We conclude that endoscopic hemostasis is clearly effective but that data were insufficient for direct comparisons between modalities. Randomized control trials to compare the different modes of endoscopic therapy should continue.

PMID 2142225
Alan N Barkun, Myriam Martel, Youssef Toubouti, Elham Rahme, Marc Bardou
Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses.
Gastrointest Endosc. 2009 Apr;69(4):786-99. doi: 10.1016/j.gie.2008.05.031. Epub 2009 Jan 18.
Abstract/Text BACKGROUND AND OBJECTIVE: Optimal endoscopic hemostasis remains undetermined. This was a systematic review of contemporary methods of endoscopic hemostasis for patients with bleeding ulcers that exhibited high-risk stigmata.
SETTING: Randomized trials that evaluated injection, thermocoagulation, clips, or combinations of these were evaluated from MEDLINE, EMBASE, and CENTRAL (1990-2006).
PATIENTS: A total of 4261 patients were evaluated.
OUTCOMES: Outcomes were rebleeding (primary), surgery, and mortality (secondary). Summary statistics were determined; publication bias and heterogeneity were sought by using funnel plots or by subgroup analyses and meta-regression.
RESULTS: Forty-one trials assessed 4261 patients. All endoscopic therapies decreased rebleeding versus pharmacotherapy alone, including sole intravenous (IV) proton pump inhibition (PPI) (OR 0.56 [95% CI, 0.34-0.92]); only one trial assessed high-dose IV PPI. Injection alone was inferior compared with other methods, except for thermal hemostasis (OR 1.02 [95% CI, 0.74-1.40]), with a strong trend of increased rebleeding if 1 injectate is used rather than 2 (OR 1.40 [95% CI, 0.95-2.05]). Injection followed by thermal therapy did not decrease rebleeding compared with clips (OR 0.82 [95% CI, 0.28-2.38]) or thermal therapy alone (OR 0.79 [95% CI, 0.24-2.62]). Subgroup analysis, however, suggested that injection followed by thermal therapy was superior to thermal therapy alone. Clips were superior to thermal therapy (OR 0.24 [95% CI, 0.06-0.95]) but, when followed by injection, were not superior to clips alone (OR 1.30 [95% CI, 0.36-4.76]). Surgery or mortality was not altered in most comparisons.
CONCLUSIONS: All endoscopic treatments are superior to pharmacotherapy alone; only 1 study assessed high-dose IV PPI. Optimal endoscopic therapies include thermal therapy or clips, either alone or in combination with other methods. Additional data are needed that compare injection followed by thermal therapy to clips alone or clips combined with another method.

PMID 19152905
O Blatchford, W R Murray, M Blatchford
A risk score to predict need for treatment for upper-gastrointestinal haemorrhage.
Lancet. 2000 Oct 14;356(9238):1318-21. doi: 10.1016/S0140-6736(00)02816-6.
Abstract/Text BACKGROUND: Current risk-stratification systems for patients with acute upper-gastrointestinal bleeding discriminate between patients at high or low risks of dying or rebleeding. We therefore developed and prospectively validated a risk score to identify a patient's need for treatment.
METHODS: Our first study used data from 1748 patients admitted for upper-gastrointestinal haemorrhage. By logistic regression, we derived a risk score that predicts patients' risks of needing blood transfusion or intervention to control bleeding, rebleeding, or dying. From this score, we developed a simplified fast-track screen for use at initial presentation. In a second study, we prospectively validated this score using receiver operating characteristic (ROC) curves--a measure of the validity of a scoring system--and chi2 goodness-of-fit testing with data from 197 patients. We also validated the quicker screening tool.
FINDINGS: We calculated risk scores from patients' admission haemoglobin, blood urea, pulse, and systolic blood pressure, as well as presentation with syncope or melaena, and evidence of hepatic disease or cardiac failure. The score discriminated well with a ROC curve area of 0.92 (95% CI 0.88-0.95). The score was well calibrated for patients needing treatment (p=0.84).
INTERPRETATION: Our score identified patients at low or high risk of needing treatment to manage their bleeding. This score should assist the clinical management of patients presenting with upper-gastrointestinal haemorrhage, but requires external validation.

PMID 11073021
日本消化器病学会編:消化性潰瘍診療ガイドライン2020 改訂第3版、2020、南江堂.
Felipe Baracat, Eduardo Moura, Wanderley Bernardo, Leonardo Zorron Pu, Ernesto Mendonça, Diogo Moura, Renato Baracat, Edson Ide
Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials.
Surg Endosc. 2016 Jun;30(6):2155-68. doi: 10.1007/s00464-015-4542-x. Epub 2015 Oct 20.
Abstract/Text BACKGROUND: Peptic ulcer represents the most common cause of upper gastrointestinal bleeding. Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this review is to compare the different modalities of endoscopic therapy.
METHODS: Studies were identified by searching electronic databases MEDLINE, Embase, Cochrane, LILACS, DARE, and CINAHL. We selected randomized clinical trials that assessed contemporary endoscopic hemostatic techniques. The outcomes evaluated were: initial hemostasis, rebleeding rate, need for surgery, and mortality. The possibility of publication bias was evaluated by funnel plots. An additional analysis was made, including only the higher-quality trials.
RESULTS: Twenty-eight trials involving 2988 patients were evaluated. Injection therapy alone was inferior to injection therapy with hemoclip and with thermal coagulation when evaluating rebleeding and the need for emergency surgery. Hemoclip was superior to injection therapy in terms of rebleeding; there were no statistically significant differences between hemoclip alone and hemoclip with injection therapy. There was considerable heterogeneity in the comparisons between hemoclip and thermal coagulation. There were no statistically significant differences between thermal coagulation and injection therapy, though their combination was superior, in terms of rebleeding, to thermal coagulation alone.
CONCLUSIONS: Injection therapy should not be used alone. Hemoclip is superior to injection therapy, and combining hemoclip with an injectate does not improve hemostatic efficacy above hemoclip alone. Thermal coagulation has similar efficacy as injection therapy; combining these appears to be superior to thermal coagulation alone. Therefore, we recommend the application of hemoclips or the combined use of injection therapy with thermal coagulation for the treatment of peptic ulcer bleeding.

PMID 26487199
Kelvin K F Tsoi, Heyson C H Chan, Philip W Y Chiu, Carol Y Y Pau, James Y W Lau, Joseph J Y Sung
Second-look endoscopy with thermal coagulation or injections for peptic ulcer bleeding: a meta-analysis.
J Gastroenterol Hepatol. 2010 Jan;25(1):8-13. doi: 10.1111/j.1440-1746.2009.06129.x.
Abstract/Text BACKGROUND AND AIMS: In the management of peptic ulcer bleeding, the benefits of second-look endoscopic treatment with thermal coagulation or injections in controlling recurrent bleeding is unsure. This study set out to compare efficacy of routine second-look endoscopy with treatment using either thermal coagulation or injections versus single endoscopy by pooling data from published work.
METHODS: Full publications in the English-language published work as well as abstracts in major international conferences were searched over the past 10 years, and six trials fulfilling the search criteria were found. Outcome measurements included: (i) recurrent bleeding; (ii) requirement of surgical intervention; and (iii) mortality. We examined heterogeneity of trials and pooled the effects by meta-analysis. The quality of studies was graded according to the prospective randomization, methods of patient allocation, the list of exclusion criteria, outcome definitions and the predefined salvage procedures for uncontrolled bleeding.
RESULTS: Among 998 patients recruited in these five randomized trials, 119 received routine second-look endoscopy with thermal coagulation, and 374 received second-look with endoscopic injection and 505 had single endoscopic therapy. Less recurrent bleeding was reported after thermal coagulation (4.2%) than single endoscopy (15.7%) (relative risk [RR] = 0.29; 95% confidence interval [CI] = 0.11-0.73), but no reduction was reported for the requirement of surgical intervention and all-cause mortality. Injection therapy did not reduce re-bleeding (17.6%) when compared to single endoscopy (20.8%; RR = 0.85; 95% CI = 0.63-1.14), requirement for surgery and mortality.
CONCLUSION: Routine second-look endoscopy with thermal coagulation, but not injection therapy, reduced recurrent peptic ulcer bleeding. There is no proven benefit in reducing surgical intervention and overall mortality.

PMID 20136971
S K H Wong, L-M Yu, J Y W Lau, Y-H Lam, A C W Chan, E K W Ng, J J Y Sung, S C S Chung
Prediction of therapeutic failure after adrenaline injection plus heater probe treatment in patients with bleeding peptic ulcer.
Gut. 2002 Mar;50(3):322-5.
Abstract/Text BACKGROUND: Continued or recurrent bleeding after endoscopic treatment for bleeding ulcer is a major adverse prognostic factor. Identification of such ulcers may allow for alternate treatments.
AIM: To determine factors predicting treatment failure with combined adrenaline injection and heater probe thermocoagulation. Methods: Consecutive patients with bleeding peptic ulcers who received endoscopic therapy between January 1995 and March 1998 were studied. Data on clinical presentation, endoscopic findings, and treatment outcomes were collected prospectively. Multiple logistic regression analysis was used to identify independent risk factors for treatment failure.
RESULTS: During the study period, 3386 patients were admitted with bleeding peptic ulcers: 1144 (796 men, 348 women) with a mean age of 62.5 (SD 17.6) years required endoscopic treatment. There were 666 duodenal ulcers (58.2%), 425 gastric ulcers (37.2%), and 53 anastomotic ulcers (4.6%). Initial haemostasis was successful in 1128 patients (98.6%). Among them, 94 (8.2%) rebled in a median time of 48 hours (range 3-480). Overall failure rate was 9.6%. Mortality rate was 5% (57/1144). Multiple logistic regression analysis revealed that hypotension (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.40-3.48), haemoglobin level less that 10 g/dl (OR 1.87, 95% CI 1.18-2.96), fresh blood in the stomach (OR 2.15, 95% CI 1.40-3.31), ulcer with active bleeding (OR 1.65, 95% CI 1.07-2.56), and large ulcers (OR 1.80, 95% CI 1.15-2.83) were independent factors predicting rebleeding.
CONCLUSIONS: Larger ulcers with severe bleeding at presentation predict failure of endoscopic therapy.

PMID 11839708
B Joseph Elmunzer, Scott D Young, John M Inadomi, Philip Schoenfeld, Loren Laine
Systematic review of the predictors of recurrent hemorrhage after endoscopic hemostatic therapy for bleeding peptic ulcers.
Am J Gastroenterol. 2008 Oct;103(10):2625-32; quiz 2633. doi: 10.1111/j.1572-0241.2008.02070.x. Epub 2008 Aug 5.
Abstract/Text BACKGROUND: An increased knowledge regarding the predictors of rebleeding after endoscopic therapy for bleeding ulcers should improve clinical management and outcomes. The aim of this systematic review was to identify the strongest and most consistent predictors of rebleeding to assist in the development of tools to stratify and appropriately manage patients after endoscopic therapy.
METHODS: Bibliographic database searches for prospective studies assessing rebleeding after endoscopic therapy for bleeding ulcers were performed. Relevant studies were identified, and data were abstracted in a duplicate and independent fashion. The primary outcomes sought were significant independent predictors of rebleeding by multivariable analyses in > or =2 studies.
RESULTS: Ten articles met the prespecified inclusion criteria. The pooled rate of rebleeding after endoscopic therapy was 16.4%. The independent pre-endoscopic predictors of rebleeding were hemodynamic instability (significant in 5 of 5 studies; summary odds ratio [OR] 2.75, 95% confidence interval [CI] 1.99-3.51) and comorbid illness (significant in 2 of 7 studies; insufficient data to calculate summary OR or report OR range). The independent endoscopic predictors of rebleeding were active bleeding at endoscopy (significant in 5 of 8 studies; summary OR 1.93, 95% CI 1.30-2.55), large ulcer size (significant in 4 of 5 studies; summary OR 2.01, 95% CI 1.21-2.80), posterior duodenal ulcer (significant in 2 of 3 studies; insufficient data to calculate summary OR or report OR range), and lesser gastric curvature ulcer (significant in 2 of 2 studies; insufficient data to calculate summary OR or report OR range).
CONCLUSIONS: The independent predictors of recurrent hemorrhage after endoscopic therapy, particularly those that are the strongest and most consistent in the literature, may be used to select patients who are most likely to benefit from aggressive post-hemostasis care, including intensive care unit (ICU) observation and second-look endoscopy. Prospective studies designed to formally assess the relative utilities of these factors in predicting rebleeding and dictating management are needed.

PMID 18684171
T A Rockall, R F Logan, H B Devlin, T C Northfield
Risk assessment after acute upper gastrointestinal haemorrhage.
Gut. 1996 Mar;38(3):316-21.
Abstract/Text The aim of this study was to establish the relative importance of risk factors for mortality after acute upper gastrointestinal haemorrhage, and to formulate a simple numerical scoring system that categorizes patients by risk. A prospective, unselected, multicentre, population based study was undertaken using standardised questionnaires in two phases one year apart. A total of 4185 cases of acute upper gastrointestinal haemorrhage over the age of 16 identified over a four month period in 1993 and 1625 cases identified subsequently over a three month period in 1994 were included in the study. It was found that age, shock, comorbidity, diagnosis, major stigmata of recent haemorrhage, and rebleeding are all independent predictors of mortality when assessed using multiple logistic regression. A numerical score using these parameters has been developed that closely follows the predictions generated by logistical regression equations. Haemoglobin, sex, presentation (other than shock), and drug therapy (non-steroidal anti-inflammatory drugs and anticoagulants) are not represented in the final model. When tested for general applicability in a second population, the scoring system was found to reproducibly predict mortality in each risk category. In conclusion, a simple numerical score can be used to categorize patients presenting with acute upper gastrointestinal haemorrhage by risk of death. This score can be used to determine case mix when comparing outcomes in audit and research and to calculate risk standardised mortality. In addition, this risk score can identify 15% of all cases with acute upper gastrointestinal haemorrhage at the time of presentation and 26% of cases after endoscopy who are at low risk of rebleeding and negligible risk of death and who might therefore be considered for early discharge or outpatient treatment with consequent resource savings.

PMID 8675081
G I Leontiadis, V K Sharma, C W Howden
Systematic review and meta-analysis: proton-pump inhibitor treatment for ulcer bleeding reduces transfusion requirements and hospital stay--results from the Cochrane Collaboration.
Aliment Pharmacol Ther. 2005 Aug 1;22(3):169-74. doi: 10.1111/j.1365-2036.2005.02546.x.
Abstract/Text BACKGROUND: Proton-pump inhibitors reduce re-bleeding and surgical intervention, but not mortality, after ulcer bleeding.
AIM: To examine the effects of proton-pump inhibitor treatment on transfusion requirements and length of hospital stay in patients with ulcer bleeding.
METHODS: For the Cochrane Collaboration meta-analysis of randomized-controlled trials of proton-pump inhibitor therapy for ulcer bleeding, outcomes of transfusion requirements and hospital stay were summarized, respectively, as mean (+/-s.d.) units transfused and hospital days. We calculated weighted mean difference with 95% confidence interval. We also performed subgroup analyses according to geographical origin of the randomized-controlled trials.
RESULTS: There was significant heterogeneity among randomized-controlled trials for either outcome. Overall, proton-pump inhibitor treatment marginally reduced transfusion requirements (WMD = -0.6 units; 95% CI: -1.1 to 0; P = 0.05) and length of hospitalization (WMD = -1.1 days; 95% CI: -1.5 to -0.7; P < 0.0001). Most of the randomized-controlled trials did not state precise criteria for administering blood transfusion and discharging patients, thereby limiting the strength of conclusions on the pooled effects.
CONCLUSIONS: Proton-pump inhibitor treatment for ulcer bleeding produces small, but potentially important, reductions in transfusion requirements and length of hospitalization.

PMID 16091053
N M Selby, A K Kubba, C J Hawkey
Acid suppression in peptic ulcer haemorrhage: a 'meta-analysis'.
Aliment Pharmacol Ther. 2000 Sep;14(9):1119-26.
Abstract/Text BACKGROUND: The use of acid-decreasing agents in the management of peptic ulcer haemorrhage continues to be controversial. Most clinical trials examining the efficacy of these drugs contain small numbers of patients, making it difficult to draw conclusions about their efficacy.
METHODS: We report a meta-analysis that examined the effect of these drugs in the management of peptic ulcer haemorrhage. Included studies were located using a search of the Medline database between 1980 and 1999. Studies were published in English, randomized and controlled by a placebo group. Mantel-Haenszel and blinded random models were used in conducting the statistical processing of this meta-analysis.
RESULTS: Twenty-one randomized placebo-controlled trials were included. The total number of patients was 3566 and the mean study size was 170 (range 20-1005). Seventeen of the papers assessed the efficacy of H2-antagonists, three assessed proton pump inhibitors and one was concerned with antacid therapy. The meta-analysis showed a significant reduction in re-bleeding rates (odds ratio, OR 0.727, 0.618-0.855, P < 0.001) and surgery rates (OR 0.707, 0.582-0.859, P < 0.001) when acid decreasing agents are used for acute peptic ulcer haemorrhage. Mortality rates appear to be unaffected (OR 1.140, 0.818-1.588, P=0. 49).
CONCLUSIONS: This meta-analysis demonstrates a significant beneficial effect of acid-decreasing agents in lowering re-bleeding and surgery rates, but demonstrated no effect upon mortality.

PMID 10971227
Showkat Ali Zargar, Gul Javid, Bashir Ahmad Khan, Ghulam Nabi Yattoo, Altaf Hussain Shah, Ghulam Mohammad Gulzar, Jaswinder Singh Sodhi, Sheikh Abdul Mujeeb, Mushtaq Ahmad Khan, Nisar Ahmad Shah, Hakim Mohamad Shafi
Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial.
J Gastroenterol Hepatol. 2006 Apr;21(4):716-21. doi: 10.1111/j.1440-1746.2006.04292.x.
Abstract/Text BACKGROUND AND AIM: Following successful endoscopic therapy in patients with peptic ulcer bleeding, rebleeding occurs in 20% of patients. Rebleeding remains the most important determinant of poor prognosis. We investigated whether or not administration of pantoprazole infusion would improve the outcome in ulcer bleeding following successful endoscopic therapy.
METHODS: In this double-blind, placebo-controlled, prospective trial, patients who had gastric or duodenal ulcers with active bleeding or non-bleeding visible vessel received combined endoscopy therapy with injection of epinephrine and heater probe application. Patients who achieved hemostasis were randomly assigned to receive pantoprazole (80 mg intravenous bolus followed by an infusion at a rate of 8 mg per hour) or placebo for 72 h. The primary end-point was the rate of rebleeding.
RESULTS: Rebleeding was lower in the pantoprazole group (8 of 102 patients, 7.8%) than in the placebo group (20 of 101 patients, 19.8%; P = 0.01). Patients in the pantoprazole group required significantly fewer transfusions (1 +/- 2.5 vs 2 +/- 3.3; P = 0.003) and days of hospitalization (5.6 +/- 5.3 vs 7.7 +/- 7.3; P = 0.0003). Rescue therapies were needed more frequently in the placebo group (7.8% vs 19.8%; P = 0.01). Three (2.9%) patients in the pantoprazole group and eight (7.9%) in the placebo group required surgery to control their bleeding (P = 0.12). Two patients in the pantoprazole group and four in the placebo group died (P = 0.45).
CONCLUSION: In patients with bleeding peptic ulcers, the use of high dose pantoprazole infusion following successful endoscopic therapy is effective in reducing rebleeding, transfusion requirements and hospital stay.

PMID 16677158
O B Schaffalitzky de Muckadell, T Havelund, H Harling, S Boesby, P Snel, E M Vreeburg, S Eriksson, P Fernström, G Hasselgren
Effect of omeprazole on the outcome of endoscopically treated bleeding peptic ulcers. Randomized double-blind placebo-controlled multicentre study.
Scand J Gastroenterol. 1997 Apr;32(4):320-7.
Abstract/Text BACKGROUND: Haemostasis is highly pH-dependent and severely impaired at low pH. However, there is no clear evidence that acid-suppressing drugs have beneficial effects in peptic ulcer haemorrhage. Endoscopic haemostatic treatment provides important reduction in morbidity and may be more efficient when a neutral intragastric pH is maintained.
METHODS: We conducted a double-blind, placebo-controlled multicentre study of intravenous infusion of omeprazole (80 mg as bolus, followed by 8 mg/h) or placebo for 72 h. All patients received 20 mg omeprazole orally from day 3 until follow-up on day 21. Only patients with ulcer haemorrhage, endoscoped within 12 h after admission, and with a history or signs of circulatory failure and spurting bleeding, oozing bleeding, visible vessel, or clot, were included. Endoscopic intervention was aimed at when spurting bleeding, oozing bleeding, or a visible vessel was observed. The primary efficacy measure was the worst ranking on an overall outcome scale (5 = death, 4 = surgery, 3 = additional endoscopic treatment, 2 = more than 3 units of blood, and 1 = no more than 3 units of blood transfused). Base-line prognostic factors of treatment success by day 3 and of other binary outcomes were considered in a logistic regression model.
RESULTS: Two hundred and seventy-four patients were randomly assigned to omeprazole (134 patients) or placebo (140 patients). The number of patients included in the 'intention-to-treat' analysis was 130 in the omeprazole group and 135 in the placebo group. The primary variable, the overall outcome at 72 h, showed a difference (P = 0.004) between the two treatments in favour of omeprazole. Treatment success by 72 h defined as no death, no operation, or no additional endoscopic treatment was 91.0% in the omeprazole group and 79.7% in the placebo group (therapeutic gain, 11.3 percentage units; 95% confidence interval, 2.3 to 20.4 percentage units). Significant differences in favour of omeprazole were also found for secondary variables such as number of blood transfusions, duration and degree of bleeding, and the need for surgery and additional endoscopic treatments on day 3 and day 21. However, the numbers of deaths by day 3, 21, or 35 were very similar.
CONCLUSIONS: We found a beneficial effect of intravenous omeprazole in severe ulcer haemorrhage, with a reduction in the number of operations, in endoscopic treatments, and in the duration and severity of bleeding.

PMID 9140153
Christopher N Andrews, Adrian Levy, Martin Fishman, Michael Hahn, Kenneth Atkinson, Peter Kwan, Robert Enns
Intravenous proton pump inhibitors before endoscopy in bleeding peptic ulcer with high-risk stigmata: a multicentre comparative study.
Can J Gastroenterol. 2005 Nov;19(11):667-71.
Abstract/Text BACKGROUND: It is not clear if starting intravenous proton pump inhibitors (IV PPI) before endoscopic therapy provides additional benefit over starting it afterward in patients with high-risk ulcer stigmata of peptic ulcer disease.
METHODS: All patients who received IV pantoprazole bolus and infusion and underwent endoscopy in six Canadian hospitals over 20 months were reviewed. Only patients with high-risk ulcer stigmata (arterial bleeding, oozing, nonbleeding visible vessel or adherent clot) were included. Patients receiving IV PPI before endoscopy (before group) were compared with those who received it after endoscopy (after group) with respect to endoscopic findings and, secondarily, to patient demographics and clinical outcomes.
RESULTS: The demographics and baseline characteristics of the before group (n=57) and the after group (n=109) were similar. The before group was more likely to have had IV PPI started outside of daytime hours, and median time to endoscopy in patients admitted with upper gastrointestinal bleeding was 24 h (interquartile range 9.5 to 35) in the before group and 11.3 h (interquartile range 3.7 to 17.2) in the after group (P<0.0001). At the time of endoscopy, 33% of patients in the before group had actively bleeding lesions (Forrest 1a or 1b) compared with 54% in the after group (P=0.01), but there were no significant differences in rebleeding, surgical rates, intensive care unit admission or death between the groups.
CONCLUSION: IV PPI infusions before endoscopy may lower the proportion of actively bleeding peptic ulcer lesions at endoscopy, but this finding does not appear to affect rates of rebleeding, surgery or death.

PMID 16292361
A Lanas, A Artal, J M Blás, M T Arroyo, J Lopez-Zaborras, R Sáinz
Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer.
J Clin Gastroenterol. 1995 Sep;21(2):103-6.
Abstract/Text The pharmacotherapy of bleeding peptic ulcer is directed at attempting to keep the gastric pH above the proteolytic range for pepsin. In this randomized, prospective, open clinical trial we have compared the effects and outcome of omeprazole versus ranitidine in patients with bleeding peptic ulcer. Of 219 consecutive patients with upper gastrointestinal bleeding, 51 (23.2%) had an ulcer with endoscopic predictors of rebleeding at the time of diagnosis. These 51 patients were selected at random to receive either omeprazole (80 mg bolus and 40 mg/12 h i.v.) or ranitidine (50 mg/4 h i.v.). No endoscopic therapy was performed at the time of diagnosis. Twenty of these patients with duodenal ulcer (n = 10 omeprazole, n = 10 ranitidine) underwent 24-h gastric pH monitoring. Both groups were homogeneous in all clinical and endoscopic parameters. No differences in blood transfusion units, time of hospitalization, the lowest hematocrit measured, and mortality rates were observed between the groups. However, omeprazole reduced the number of rebleeding episodes (p = 0.1) and the need for surgery (3.8% vs. 22.7%; p = 0.05). Omeprazole also reduced the amount of time the gastric pH was < 6 (15.3 +/- 5.9% vs. 61.8 +/- 5.6%, p < 0.0001). We conclude that parenteral omeprazole is much more effective than ranitidine in keeping the gastric pH above the proteolytic range for pepsin in bleeders and that this might explain a better outcome in a subset of patients with bleeding peptic ulcers treated with parenteral omeprazole.

PMID 8583073
C P Dekkers, J A Beker, B Thjodleifsson, A Gabryelewicz, N E Bell, T J Humphries
Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of active gastric ulcer--a European multicentre study. The European Rabeprazole Study Group.
Aliment Pharmacol Ther. 1998 Aug;12(8):789-95.
Abstract/Text BACKGROUND: Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active, benign gastric ulcers.
METHODS: In this randomized, double-blind, multicentre study, conducted at 25 European sites, rabeprazole and omeprazole were compared in patients with active gastric ulcers. Two hundred and twenty-seven patients with active benign gastric ulcer were randomized to receive either rabeprazole 20 mg (n = 113) or omeprazole 20 mg (n = 114) once daily for 3 or 6 weeks, with healing monitored by endoscopy.
RESULTS: After 3 weeks, complete healing (ITT analysis) was documented in 58% of patients given rabeprazole and 61% in patients given omeprazole (N.S.). After 6 weeks the healing rates were identical in both groups at 91%. Rabeprazole-treated patients had numerically greater symptom relief at all 12 points of comparison. The differences significantly favoured rabeprazole at week 3 for daytime pain improvement (P = 0.023) and at week 6 for pain frequency (P = 0.006) and complete resolution of night pain (P = 0.022). Both drugs were well-tolerated over the 6-week treatment course. Mean changes from baseline to end-point in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen.
CONCLUSION: In this study, rabeprazole produced healing rates comparable to omeprazole at weeks 3 and 6, but provided more consistent and occasionally significantly superior symptom improvement. Both treatments were well-tolerated.

PMID 9726393
L Barbara, R Corinaldesi, G Dobrilla, G De Pretis, G Bianchi Porro, A Prada, R Carratù, P Paoluzi, G Mazzacca, F Sabbatini
Ranitidine vs cimetidine: short-term treatment of gastric ulcer.
Hepatogastroenterology. 1983 Aug;30(4):151-3.
Abstract/Text We compared the clinical effectiveness and endoscopic results of ranitidine and cimetidine treatment; 71 outpatients, all affected with benign gastric ulcer, were selected for the study (43 type I, 7 type II and 21 type III, according to Johnson's classification). The patients were treated randomly for 4 weeks with ranitidine (300 mg daily) or cimetidine (1 g daily). An endoscopic examination was repeated within 3 days after the end of the treatment. Clinical checks were performed weekly in order to monitor the clinical course of pain and antacid consumption, according to the patient's needs. The patients who did not demonstrate complete healing on endoscopic examination were treated for an additional 4 week period. At the end of this 4 week period, another endoscopic examination was done. Thirty-six patients treated with ranitidine and 33 with cimetidine completed the first period of therapy. The two groups were homogeneous with regard to sex, age, duration of disease, smoking habits, alcohol consumption, and type and size of ulcer. Ranitidine and cimetidine treatments did not demonstrate any significant difference with regard to ulcer healing after the 4th or the 8th week of therapy. Both ranitidine and cimetidine were less effective in healing type I than type II and III G.U., at the 4th week of treatment. No significant differences between the two groups were noted with regard to pain or weekly antacid consumption. No significant side effects were reported.

PMID 6313502
H Miwa, N Uedo, J Watari, Y Mori, Y Sakurai, Y Takanami, A Nishimura, T Tatsumi, N Sakaki
Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers - results from two phase 3, non-inferiority randomised controlled trials.
Aliment Pharmacol Ther. 2017 Jan;45(2):240-252. doi: 10.1111/apt.13876. Epub 2016 Nov 27.
Abstract/Text BACKGROUND: Vonoprazan is a new potassium-competitive acid blocker for treatment of acid-related diseases.
AIM: To conduct two randomised-controlled trials, to evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU).
METHODS: Patients aged ≥20 years with ≥1 endoscopically-confirmed GU or DU (≥5 mm white coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU.
RESULTS: For GU, 93.5% (216/231) of vonoprazan-treated patients and 93.8% (211/225) of lansoprazole-treated patients achieved healed GU; non-inferiority of vonoprazan to lansoprazole was confirmed [difference = -0.3% (95% CI -4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan-treated patients and 98.3% (177/180) of lansoprazole-treated patients achieved healed DU; non-inferiority to lansoprazole was not confirmed [difference = -2.8% (95% CI -6.400, 0.745); P = 0.0654]. The incidences of treatment-emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan-treated vs. lansoprazole-treated patients; levels returned to baseline after treatment in both groups.
CONCLUSIONS: Vonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non-inferior with respect to GU healing and has similar efficacy for DU healing.

© 2016 Takeda Pharmaceutical Company, Ltd. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
PMID 27891632
Alexander C Ford, Brendan C Delaney, David Forman, Paul Moayyedi
Eradication therapy in Helicobacter pylori positive peptic ulcer disease: systematic review and economic analysis.
Am J Gastroenterol. 2004 Sep;99(9):1833-55. doi: 10.1111/j.1572-0241.2004.40014.x.
Abstract/Text BACKGROUND AND AIM: We conducted a systematic review and economic analysis to ascertain the efficacy of eradication therapy in the treatment of H. pylori positive peptic ulcer disease.
METHODS: Comprehensive search of electronic databases, bibliographies of retrieved articles, contact with pharmaceutical companies, and experts in the field to identify published and unpublished literature from 1966 to the present. The data were incorporated into a Monte Carlo simulation Markov model that incorporated all the uncertainty in the estimates to evaluate cost-effectiveness.
RESULTS: Fifty-two trials were included in the final metaanalysis. In duodenal ulcer healing, H. pylori eradication therapy was superior to ulcer healing drug (relative risk (RR) of ulcer persisting = 0.66; 95% confidence interval (CI) = 0.58 to 0.76) and no treatment (RR = 0.37; 95% CI 0.26 to 0.53). In gastric ulcer healing, H. pylori eradication therapy was not statistically superior to ulcer healing drug (RR = 1.32; 95% CI = 0.92 to 1.90). In preventing duodenal ulcer recurrence, H. pylori eradication therapy was not statistically superior to maintenance therapy with ulcer healing drug (RR of ulcer recurring = 0.73; 95% CI = 0.42 to 1.25), but was superior to no treatment (RR = 0.19; 95% CI = 0.15 to 0.26). In preventing gastric ulcer recurrence, H. pylori eradication was superior to no treatment (RR = 0.31; 95% CI 0.19 to 0.48). The Markov model suggested H. pylori eradication is cost-effective for duodenal ulcer over 1 year and gastric ulcer over 2 years with over 95% confidence despite the uncertainty in the data.
CONCLUSIONS: H. pylori eradication therapy reduces the recurrence of peptic ulcer disease and is cost-effective.

PMID 15330927
A Ford, B Delaney, D Forman, P Moayyedi
Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients.
Cochrane Database Syst Rev. 2003;(4):CD003840. doi: 10.1002/14651858.CD003840.
Abstract/Text BACKGROUND: Peptic ulcer disease is the cause for dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain.
OBJECTIVES: The primary outcomes were the proportion of peptic ulcers healed initially and proportion of patients free from relapse following successful healing. Eradication therapy was compared to placebo or pharmacological therapies in H. pylori positive patients. Secondary aims included symptom relief and adverse effects.
SEARCH STRATEGY: A search was undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group module using CCTR, MEDLINE, EMBASE and CINAHL databases. Experts in the field and pharmaceutical companies were contacted. Abstract books between 1994 and 2002 were hand-searched.
SELECTION CRITERIA: Randomised controlled trials of short and long-term treatment of peptic ulcer disease in H. pylori positive adults were analysed. Patients received at least one week of H pylori eradication compared with ulcer healing drug, placebo or not treatment. Trials were included if they reported assessment from 2 weeks onwards.
DATA COLLECTION AND ANALYSIS: Data were collected on ulcer healing, recurrence, relief of symptoms and adverse effects.
MAIN RESULTS: 59 trials were eligible. Data extraction was not possible in 7 trials, and 52 trials were included. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95% confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients, RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant differences were detected between eradication therapy and UHD (13 trials, 1469 patients, RR = 1.32; 95% CI = 0.92, 1.90). In preventing duodenal ulcer recurrence no significant differences were detected between eradication therapy and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was superior to no treatment (26 trials 2434 patients, RR = 0.19; 95% CI = 0.15, 0.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (9 trials, 774 patients, RR = 0.31; 95% CI 0.19, 0.48).
REVIEWER'S CONCLUSIONS: A 1 to 2 weeks course of H. pylori eradication therapy is an effective treatment for H. pylori positive peptic ulcer disease.

PMID 14583996
J P Gisbert, S Khorrami, F Carballo, X Calvet, E Gene, E Dominguez-Muñoz
Meta-analysis: Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer.
Aliment Pharmacol Ther. 2004 Mar 15;19(6):617-29. doi: 10.1111/j.1365-2036.2004.01898.x.
Abstract/Text AIM: To perform a meta-analysis comparing the efficacy of Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer.
METHODS: A search was made of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and several congresses for controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of peptic ulcer re-bleeding. Studies with all patients taking non-steroidal anti-inflammatory drugs were excluded. Extraction and quality assessment of the studies were performed by two reviewers.
RESULTS: In the first meta-analysis, the mean percentage of re-bleeding in the H. pylori eradication therapy group was 4.5%, compared with 23.7% in the non-eradication therapy group without long-term antisecretory therapy [odds ratio, 0.18; 95% confidence interval (CI), 0.09-0.37; 'number needed to treat' (NNT), 5; 95% CI, 4-8]. In the second meta-analysis, the re-bleeding rate in the H. pylori eradication therapy group was 1.6%, compared with 5.6% in the non-eradication therapy group with maintenance antisecretory therapy (odds ratio, 0.25; 95% CI, 0.08-0.76; NNT, 20; 95% CI, 12-100). When only patients with successful H. pylori eradication were included, the re-bleeding rate was 1%.
CONCLUSIONS: The treatment of H. pylori infection is more effective than antisecretory non-eradication therapy (with or without long-term maintenance antisecretory treatment) in the prevention of recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori, and eradication therapy should be prescribed to infected patients.

PMID 15023164
日本消化器内視鏡学会:抗血栓薬服用者に対する消化器内視鏡診療ガイドライン 直接経口抗凝固薬(DOAC)を含めた抗凝固薬に関する追補 2017;59、1547-1552、Gasroenterol Endosc、2017.
Antonio Tarasconi, Gian Luca Baiocchi, Vittoria Pattonieri, Gennaro Perrone, Hariscine Keng Abongwa, Sarah Molfino, Nazario Portolani, Massimo Sartelli, Salomone Di Saverio, Arianna Heyer, Luca Ansaloni, Federico Coccolini, Fausto Catena
Transcatheter arterial embolization versus surgery for refractory non-variceal upper gastrointestinal bleeding: a meta-analysis.
World J Emerg Surg. 2019;14:3. doi: 10.1186/s13017-019-0223-8. Epub 2019 Feb 1.
Abstract/Text Background: Nowadays, very few patients with non-variceal upper gastrointestinal bleeding fail endoscopic hemostasis (refractory NVUGIB). This subset of patients poses a clinical dilemma: should they be operated on or referred to transcatheter arterial embolization (TAE)?
Objectives: To carry out a systematic review of the literature and to perform a meta-analysis of studies that directly compare TAE and surgery in patients with refractory NVUGIB.
Materials and methods: We searched PubMed, Ovid MEDLINE, and Embase. A combination of the MeSH terms "gastrointestinal bleeding"; "gastrointestinal hemorrhage"; "embolization"; "embolization, therapeutic"; and "surgery" were used (("gastrointestinal bleeding" or "gastrointestinal hemorrhage") and ("embolization" or "embolization, therapeutic") and "surgery")). The search was performed in June 2018. Studies were retrieved and relevant studies were identified after reading the study title and abstract. Bibliographies of the selected studies were also examined. Statistical analysis was performed using RevMan software. Outcomes considered were all-cause mortality, rebleeding rate, complication rate, and the need for further intervention.
Results: Eight hundred fifty-six abstracts were found. Only 13 studies were included for a total of 1077 patients (TAE group 427, surgery group 650). All selected papers were non-randomized studies: ten were single-center and two were double-center retrospective comparative studies, while only one was a multicenter prospective cohort study. No comparative randomized clinical trial is reported in the literature.Mortality. Pooled data (1077 patients) showed a tendency toward improved mortality rates after TAE, but this trend was not statistically significant (OD = 0.77; 95% CI 0.50, 1.18; P = 0.05; I2 = 43% [random effects]). Significant heterogeneity was found among the studies.Rebleeding rate. Pooled data (865 patients, 211 events) showed that the incidence of rebleeding was significantly higher for patients undergoing TAE (OD = 2.44; 95% CI 1.77, 3.36; P = 0.41; I2 = 4% [fixed effects]).Complication rate. Pooling of the data (487 patients, 206 events) showed a sharp reduction of complications after TAE when compared with surgery (OD = 0.45; 95% CI 0.30, 0.47; P = 0.24; I2 = 26% [fixed effects]).Need for further intervention. Pooled data (698 patients, 165 events) revealed a significant reduction of further intervention in the surgery group (OD = 2.13; 95% CI 1.21, 3.77; P = 0.02; I2 = 56% [random effects]). A great degree of heterogeneity was found among the studies.
Conclusions: The present study shows that TAE is a safe and effective procedure; when compared to surgery, TAE exhibits a higher rebleeding rate, but this tendency does not affect the clinical outcome as shown by the comparison of mortality rates (slight drift toward lower mortality for patients undergoing TAE). The present study suggests that TAE could be a viable option for the first-line therapy of refractory NVUGIB and sets the foundation for the design of future randomized clinical trials.
Limitations: The retrospective nature of the majority of included studies leads to selection bias. Furthermore, the decision of whether to proceed with surgery or refer to TAE was made on a case-by-case basis by each attending surgeon. Thus, external validity is low. Another limitation involves the variability in etiology of the refractory bleeding. TAE techniques and surgical procedure also differ consistently between different studies. Frame time for mortality detection differs between the studies. These limitations do not impair the power of the present study that represents the largest and most recent meta-analysis currently available.

PMID 30733822
Moe Kyaw, Yee Tse, Daphne Ang, Tiing Leong Ang, James Lau
Embolization versus surgery for peptic ulcer bleeding after failed endoscopic hemostasis: a meta-analysis.
Endosc Int Open. 2014 Mar;2(1):E6-E14. doi: 10.1055/s-0034-1365235. Epub 2014 Mar 7.
Abstract/Text BACKGROUND AND STUDY AIMS: A meta-analysis was conducted to assess the efficacy of transcatheter arterial embolization (TAE) compared with surgery in the management of patients with recurrent nonvariceal upper gastrointestinal bleeding (NVUGIB) after failure of endoscopic hemostasis.
PATIENTS AND METHODS: Publications in English and non-English literatures (OVID, MEDLINE, and EMBASE) and abstracts from major international conferences were searched for studies comparing TAE with surgery for treatment of NVUGIB after endoscopic hemostasis failure. Outcome measures included rebleeding rate, all-cause mortality rate, and need for additional interventions to secure hemostasis.
RESULTS: From 1234 citations, 6 retrospective comparative studies were included that involved 423 patients (TAE, 182, 56 % male; surgery, 241, 68 % male). TAE patients were older (mean age, TAE 75, surgery, 68). The risk of rebleeding was significantly higher in TAE patients compared with surgically treated patients (relative risk [RR] 1.82, 95 % confidence interval [95 %CI] 1.23 - 2.67), with no statistically significant heterogeneity among the included studies (P = 0.66, I (2) = 0.0 %). After sensitivity analysis excluding studies with a large age difference between the two groups, a higher risk of bleeding remained in the TAE group (RR 2.64, 95 %CI] 1.48 - 4.71). No significant difference in mortality (RR 0.87, 95 %CI 0.59 - 1.29) or requirement for additional interventions (RR 1.67, 95 %CI 0.75 - 3.70) was shown between the two groups.
CONCLUSION: A higher rebleeding rate was observed after TAE, suggesting surgery more definitively secured hemostasis, with no significant difference in mortality rate or requirement of additional interventions. The TAE patients were older and in poorer health, thus future randomized studies are needed for accurate comparison of the two modalities.

PMID 26134614
D L Morris, P C Hawker, S Brearley, M Simms, P W Dykes, M R Keighley
Optimal timing of operation for bleeding peptic ulcer: prospective randomised trial.
Br Med J (Clin Res Ed). 1984 Apr 28;288(6426):1277-80.
Abstract/Text From October 1980 to September 1983 all patients with upper gastrointestinal bleeding were admitted to a centralised unit and investigated by early endoscopy. A total of 142 patients with a proved duodenal or gastric ulcer were randomised after stratification for age and site of ulcer to early (aggressive) surgical management or a delayed (conservative) policy. Significantly more operations (n = 42; 60%) were performed in the early than in the delayed (n = 9; 20%) groups (p less than 0.01). There were no deaths among the 42 patients under 60. The overall mortality in the 100 patients aged over 60 was 10% and when analysed on an "intention to treat" basis there was no difference between early and delayed surgery. When, however, an unrelated death from a bleeding colonic polyp was excluded and the data analysed on "treatment received" the mortality was only 2% in the early group compared with 13% in the delayed group (p less than 0.05). When analysis was confined to gastric ulcer the difference between early (0%) and delayed (24%) treatment was even greater. The results of this trial indicate that for patients over 60 an aggressive surgical policy is associated with a significant reduction in mortality.

PMID 6424827
W B Greiser, B W Bruner, J M Shamoun, G J Jurkovich, J J Ferrara
Factors affecting mortality in patients operated upon for complications of peptic ulcer disease.
Am Surg. 1989 Jan;55(1):7-11.
Abstract/Text Surgical treatment of complicated peptic ulcer disease (PUD) is associated with a high mortality in selected, high-risk patients. The authors reviewed their operative experience for PUD over a five year period beginning in July 1982. One hundred and sixty-two operative procedures were performed on 160 patients. The indications for surgery were intractability (18); perforation (50); hemorrhage (81); and obstruction (13). The average ages of the survivors and those who died was 49.0 and 65.7 years respectively. Partial gastric resection (PGR), with or without vagotomy, was the most commonly performed procedure (54% of cases) while vagotomy and drainage (V & D) was used in 31 per cent of patients. The overall mortality in this series was 8 per cent; it was highest in the hemorrhage group (10%). Pre-operative transfusion requirements in this population were greater in those who died versus those who survived (12.1 and 7.3 units respectively, P less than 0.005). In addition, 75 per cent of the deaths were over 60 years of age. In elderly patients operated upon for hemorrhage, the procedure-related mortality for V & D and PGR was 24 per cent and 13 per cent respectively. (These groups were similar with regard to co-morbidity, hemodynamic stability, and transfusion requirements). It is the authors contention that PGR may be safely used for the treatment of bleeding peptic ulcer disease (particularly GU) in selected elderly, high-risk patients.

PMID 2913910
P J Zed, P S Loewen, R S Slavik, C A Marra
Meta-analysis of proton pump inhibitors in treatment of bleeding peptic ulcers.
Ann Pharmacother. 2001 Dec;35(12):1528-34.
Abstract/Text OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) compared with placebo and histamine receptor antagonists (H2RAs) for reducing the incidence of rebleeding, surgery, and death in acute gastrointestinal bleeding (GIB) associated with peptic ulcer disease.
DATA SOURCES: A systematic search of the English-language literature was performed using MEDLINE, EMBASE, and Pre-MEDLINE (from 1966 to September 2000) and a manual search of references.
STUDY SELECTION: Randomized, controlled trials evaluating any PPI for acute GIB in adults with the end points of rebleeding, surgery of death.
DATA SYNTHESIS: Nine trials (1829 pts.) were included. The relative odds of rebleeding indicated a 50% reduction in the PPI-treated group (OR 0.50, 95% CI 0.33 to 0.77; p = 0.002, NNTB 9; 95% CI NNTB 6 to 13). The relative odds of surgery indicated a 53% reduction in the PPI-treated group (OR 0.47, 95% CI 0.29 to 0.77; p = 0.003; NNTB 17, 95% CI 12 to 35). The relative odds for mortality indicated a nonsignificant 8% decrease in the odds of death in the PPI-treated group (OR 0.92, 95% CI 0.46 to 1.83, p = 0.81; NNTB 323, 95% CI NNTB 47 to infinity to NNTH 33).
CONCLUSIONS: PPIs are superior to H2RAs and placebo in preventing rebleeding and the need for surgery in patients with GIB, although they do not appear to reduce mortality.

PMID 11793613
J Olejnik, P Labas, V Zahradnik
Possible risks in combining endoscopic and surgical therapy of bleeding peptic ulcers.
Hepatogastroenterology. 2003 Jul-Aug;50(52):1169-72.
Abstract/Text BACKGROUND/AIMS: Today's therapy of bleeding peptic ulcers consists of pharmacological hemostasis, endoscopic therapy and surgery in chronological order. The aim of this study was to objectively assess the contribution of the contemporary algorithm of therapy with the use of endoscopic and surgical hemostasis techniques for the therapy of bleeding peptic ulcers.
METHODOLOGY: This study is a retrospective analysis and comparison of two randomized groups A/B with 427/388 patients with endoscopically verified bleeding from peptic ulcer lesions Forrest I-IIb. Patients in group A (1990-1993) were treated without endoscopic intervention, compared with group B patients (1998-2001) who were treated with endoscopic intervention. In both groups we have statistically scored and compared: quantitative operative therapy share, time interval from the beginning of therapy until surgery, APACHE II score of patients at the beginning of therapy and on the day of surgery, complications requiring re-operation and mortality.
RESULTS: In groups A/B surgical hemostasis was required in 15.0/10.6% cases, from which 90.6/61.0% operations were resections and bionomic operations. Data evaluation of APACHE II scores from both groups at the beginning of treatment showed no significant difference, but at the time of operative therapy the APACHE II scores were significantly higher in group B (11.83 +/- 6.49/15.00 +/- 4.36). The length of unstable intervals of bleeding in group B compared to group A was quantitatively lengthened (A = 55.6 +/- 19.8/B = 68.6 +/- 37.0 h). Significant differences were also noted in the number of re-operations 7.8/9.8% and mortality 15.6/24.3% between groups A/B.
CONCLUSIONS: The contemporary accepted sequence of hemostatic therapy is accompanied by the risks of limited selection of optimal methods of endoscopic therapy, protracting the interval of bleeding with unfavorable rise in APACHE II score, and hesitancy in indication for surgery in intractable bleeding after non-surgical therapy.

PMID 12846007
P Kujath, O Schwandner, H-P Bruch
Morbidity and mortality of perforated peptic gastroduodenal ulcer following emergency surgery.
Langenbecks Arch Surg. 2002 Nov;387(7-8):298-302. doi: 10.1007/s00423-002-0331-9. Epub 2002 Nov 8.
Abstract/Text BACKGROUND: This study assessed the surgical concept and prognosis of perforated gastroduodenal ulcers.
PATIENTS AND METHODS: Data from 102 patients who underwent emergency surgery for peptic ulcer perforation were recorded prospectively. To evaluate morbidity and mortality ulcer perforation was classified into three types: type A, solitary peripyloric ulcer located anteriorly in which laparoscopic closure by suture with omentoplasty was treatment of choice and postoperative endoscopic biopsy was mandatory; type B, perforated ulcer with large defect in which excision and suture was necessary; type C, complicated perforated ulcer with destruction of proximal duodenum and penetration into adjacent organs in which resectional surgery was indicated.
RESULTS: Morbidity and mortality were significantly lower in type A (9%, 4%, respectively) than types B (22%, 20%) and C (34%, 17%). Closure of type A perforation was managed laparoscopically in all cases. Billroth II resection was performed in 75% of type C cases. Age, ASA status, and time of surgery were independent prognostic factors by multivariate analysis, with increased mortality in patients older than 65 years, ASA III and IV, and surgery after 24 h following onset of symptoms.
CONCLUSIONS: Prognosis of perforated ulcer disease is highly correlated with age, comorbid conditions (ASA status), and time of surgery. The proposed classification system helps to determine patients at risk of mortality.

PMID 12447556
Mario Testini, Piero Portincasa, Giuseppe Piccinni, Germana Lissidini, Fabio Pellegrini, Luigi Greco
Significant factors associated with fatal outcome in emergency open surgery for perforated peptic ulcer.
World J Gastroenterol. 2003 Oct;9(10):2338-40.
Abstract/Text AIM: To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city.
METHODS: One hundred and forty-nine consecutive patients (M:F ratio=110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings.
RESULTS: The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (chi2) with increased mortality in patients undergoing surgery (0.0001CONCLUSION: Factors such as concomitant diseases, shock on admission, delayed surgery, and postoperative abdominal and wound infections are significantly associated with fatal outcomes and need careful evaluation within the general workup of patients admitted for perforated peptic ulcer.

PMID 14562406
T J Crofts, K G Park, R J Steele, S S Chung, A K Li
A randomized trial of nonoperative treatment for perforated peptic ulcer.
N Engl J Med. 1989 Apr 13;320(15):970-3. doi: 10.1056/NEJM198904133201504.
Abstract/Text To determine whether surgery could be avoided in some patients with perforated peptic ulcer, we conducted a prospective randomized trial comparing the outcome of nonoperative treatment with that of emergency surgery in patients with a clinical diagnosis of perforated peptic ulcer. Of the 83 patients entered in the study over a 13-month period, 40 were randomly assigned to conservative treatment, which consisted of resuscitation with intravenous fluids, institution of nasogastric suction, and intravenous administration of antibiotics (cefuroxime, ampicillin, and metronidazole) and ranitidine. Eleven of these patients (28 percent) had no clinical improvement after 12 hours and required an operation. Two of the 11 had a perforated gastric carcinoma, and 1 had a perforated sigmoid carcinoma. The other 43 patients were assigned to immediate laparotomy and repair of the perforation. One of these patients was found to have a perforated gastric carcinoma. The overall mortality rates in the two groups were similar (two deaths in each, 5 percent), and did not differ significantly in the morbidity (infection, cardiac failure, or renal failure) rates (40 percent in the surgical group and 50 percent in the nonsurgical group). The hospital stay was 35 percent longer in the group treated conservatively. Patients over 70 years old were less likely to respond to conservative treatment than younger patients (P less than 0.05). We conclude that in patients with perforated peptic ulcer, an initial period of nonoperative treatment with careful observation may be safely allowed except in patients over 70 years old, and that the use of such an observation period can obviate the need for emergency surgery in more than 70 percent of patients.

PMID 2927479
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、渡邉裕次、井ノ口岳洋、梅田将光および日本医科大学多摩永山病院 副薬剤部長 林太祐による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
福田健介 : 特に申告事項無し[2025年]
村上和成 : 特に申告事項無し[2025年]
監修:上村直実 : 講演料(武田薬品工業(株),カイゲンファーマ(株))[2025年]

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