Perforated and bleeding peptic ulcer: WSES guidelines
穿孔和出血性消化性潰瘍：WSES 指南

Abstract  抽象

Background  背景

Peptic ulcer disease is common with a lifetime prevalence in the general population of 5–10% and an incidence of 0.1–0.3% per year. Despite a sharp reduction in incidence and rates of hospital admission and mortality over the past 30 years, complications are still encountered in 10–20% of these patients. Peptic ulcer disease remains a significant healthcare problem, which can consume considerable financial resources. Management may involve various subspecialties including surgeons, gastroenterologists, and radiologists. Successful management of patients with complicated peptic ulcer (CPU) involves prompt recognition, resuscitation when required, appropriate antibiotic therapy, and timely surgical/radiological treatment.
消化性潰瘍病很常見，普通人群的終生患病率為 5-10%，發病率為每年 0.1-0.3%。儘管在過去 30 年中，發病率、住院率和死亡率急劇下降，但這些患者中有 10-20% 仍然會出現併發症。消化性潰瘍病仍然是一個重大的醫療保健問題，會消耗大量財政資源。管理可能涉及各種亞專業，包括外科醫生、胃腸病學家和放射科醫生。複雜性消化性潰瘍 （CPU） 患者的成功管理包括及時識別、必要時復甦、適當的抗生素治療以及及時的手術/放射學治療。

Methods  方法

The present guidelines have been developed according to the GRADE methodology. To create these guidelines, a panel of experts was designed and charged by the board of the WSES to perform a systematic review of the available literature and to provide evidence-based statements with immediate practical application. All the statements were presented and discussed during the 5th WSES Congress, and for each statement, a consensus among the WSES panel of experts was reached.
本準則是根據 GRADE 方法制定的。為了制定這些準則，WSES 董事會設計並負責一個專家小組，對現有文獻進行系統審查，並提供可立即實際應用的循證陳述。所有發言均在第五屆 WSES 大會期間提出和討論，對於每項發言，WSES 專家小組都達成了共識。

Conclusions  結論

The population considered in these guidelines is adult patients with suspected complicated peptic ulcer disease. These guidelines present evidence-based international consensus statements on the management of complicated peptic ulcer from a collaboration of a panel of experts and are intended to improve the knowledge and the awareness of physicians around the world on this specific topic. We divided our work into the two main topics, bleeding and perforated peptic ulcer, and structured it into six main topics that cover the entire management process of patients with complicated peptic ulcer, from diagnosis at ED arrival to post-discharge antimicrobial therapy, to provide an up-to-date, easy-to-use tool that can help physicians and surgeons during the decision-making process.
這些指南考慮的人群是疑似複雜性消化性潰瘍病的成年患者。這些指南提出了專家小組合作的關於複雜消化性潰瘍治療的循證國際共識聲明，旨在提高世界各地醫生對這一特定主題的知識和認識。我們將工作分為出血和消化性潰瘍穿孔兩個主要主題，並將其分為六個主要主題，涵蓋複雜性消化性潰瘍患者的整個管理過程，從急診室到達時的診斷到出院后的抗菌治療，以提供最新、易於使用的工具，可以在決策過程中幫助醫生和外科醫生。

Introduction  介紹

Peptic ulcer disease is common with a lifetime prevalence in the general population of 5-10% and an incidence of 0.1–0.3% per year [1]. Peptic ulceration occurs due to acid peptic damage to the gastro-duodenal mucosa, resulting in mucosal erosion that exposes the underlying tissues to the digestive action of gastro-duodenal secretions. This pathology was traditionally related to a hypersecretory acid environment, dietary factors and stress. However, the increasing incidence of the Helicobacter pylori infection, the extensive use of NSAIDs, and the increase in alcohol and smoking abuse have changed the epidemiology of this disease. Despite a sharp reduction in incidence and rates of hospital admission and mortality over the past 30 years [2,3,4,5,6,7,8], complications are still encountered in 10–20% of these patients [9, 10]. Complications of peptic ulcer disease include perforation and bleeding and improvement in medical management has made obstruction from chronic fibrotic disease a rare event. A recent review on the epidemiology of complicated peptic ulcer disease [10] found that hemorrhage was by far the most common complication of peptic disease, with a reported annual incidence of hemorrhage in the general population ranging from 0.02 to 0.06%, with sample size-weighted average 30-day mortality of 8.6%. Reported annual incidence of perforation ranges from 0.004 to 0.014%, with sample size-weighted average 30-day mortality of 23.5%. Although perforation is less common, with a perforation:bleeding ratio of approximately 1:6, it is the most common indication for emergency operation and causes about 40% of all ulcer-related deaths [11].
消化性潰瘍病很常見，一般人群終生患病率為 5-10%，發病率為 0.1-0.3%/年[1]。消化性潰瘍是由於胃十二指腸黏膜的酸消化性損傷而發生的，導致黏膜糜爛，使下面的組織暴露於胃十二指腸分泌物的消化作用。這種病理傳統上與高分泌酸環境、飲食因素和壓力有關。然而， 幽門螺桿菌感染發病率的增加、非甾體抗炎藥的廣泛使用以及酗酒和吸煙的增加改變了這種疾病的流行病學。儘管過去 30 年來，發病率、住院率和死亡率均大幅下降[2,3,4,5,6,7,8]，但仍有 10-20% 的患者出現併發症[9,10]。 消化性潰瘍病的併發症包括穿孔和出血，醫療管理的改善使慢性纖維化疾病引起的梗阻成為一種罕見的事件。最近一項關於複雜性消化性潰瘍病流行病學的綜述[10]發現，出血是迄今為止消化性疾病最常見的併發症，據報導，一般人群的年出血發生率在 0.02%-0.06%之間，樣本量加權平均 30 日死亡率為 8.6%。報告的穿孔年發生率為 0.004%至 0.014%，樣本量加權平均 30 天死亡率為 23.5%。雖然穿孔較少見，穿孔出血比約為 1：6，但它是最常見的急診指征，約佔所有潰瘍相關死亡的 40%[11]。

Peptic ulcer disease remains a significant healthcare problem, which can consume considerable financial resources. Management may involve various subspecialties including surgeons, gastroenterologists, and radiologists. Successful management of patients with complicated peptic ulcer (CPU) involves prompt recognition, resuscitation when required, appropriate antibiotic therapy and timely surgical/radiological treatment.
消化性潰瘍病仍然是一個重大的醫療保健問題，會消耗大量財政資源。管理可能涉及各種亞專業，包括外科醫生、胃腸病學家和放射科醫生。複雜性消化性潰瘍 （CPU） 患者的成功管理包括及時識別、必要時復甦、適當的抗生素治療和及時的手術/放射治療。

Notes on the use of the guidelines: aims, targets, and limitations
關於使用準則的說明：目的、目標和限制

The Guidelines are aimed to present the state-of-the-art regarding diagnosis and therapeutic options for an optimal management of complicated peptic ulcer. These guidelines are thus intended to improve the knowledge and the awareness of physicians around the world on the specific topic of complicated peptic ulcer, providing an up-to-date tool that can help during the decision-making process. For this reason, the Guidelines are evidence-based and the grade of recommendation is provided to summarize the evidences present in literature. The population considered in these guidelines is adult patients with suspected complicated peptic ulcer disease. The practice Guidelines promulgated in this work do not represent a standard of practice. They are suggested plans of care, based on best available evidence and the consensus of experts but they do not exclude other approaches as being within the standard of practice. For example, they should not be used to compel adherence to a given method of medical management, which method should be finally determined after taking account of the conditions at the relevant medical institution (staff levels, experience, equipment, etc.) and the characteristics of the individual patient. However, responsibility for the results of treatment rests with those who are directly engaged therein, and not with the consensus group.
該指南旨在介紹複雜消化性潰瘍最佳管理的診斷和治療方案的最新技術。因此，這些指南旨在提高世界各地醫生對複雜消化性潰瘍特定主題的知識和認識，提供一種可以在決策過程中提供説明的最新工具。因此，該指南以證據為基礎，並提供推薦等級以總結文獻中存在的證據。這些指南考慮的人群是疑似複雜性消化性潰瘍病的成年患者。本工作中頒布的實踐指南並不代表實踐標準。它們是基於最佳現有證據和專家共識的建議護理計劃，但它們並不排除其他方法符合實踐標準。例如，不應使用它們來強迫遵守給定的醫療管理方法，應在考慮相關醫療機構的情況（人員級別、經驗、設備等）和個體患者的特徵后最終確定哪種方法。然而，治療結果的責任在於直接參與治療的人，而不是共識小組。

Methods  方法

These consensus guidelines are an update of the 2013 WSES position paper on this topic. To create these guidelines, a panel of experts was designed and charged by the board of the WSES to develop questions on six main topics that thoroughly cover the field of this pathology (diagnosis, resuscitation, nonoperative management, surgery, angiography-angioembolization, antimicrobial therapy). Then, leading specialists in the field were asked to perform a thorough search on each of these topics in different databanks (MEDLINE, SCOPUS, EMBASE) for relevant papers between 1985 and June 2018 and a systematic review of the available literature. They were asked to focus their search in order to provide evidence-based answers to every question with immediate practical application and to summarize them in statements. All the statements were presented and discussed during the 5^th WSES Congress held in Bertinoro, Italy in June 28th, 2018. For each statement, a consensus among the WSES panel of experts was reached. All the members contributed to the development of the manuscript; the manuscript was reviewed and approved by all the authors.
這些共識指南是 2013 年 WSES 關於該主題的立場檔的更新。為了制定這些指南，WSES 董事會設計並負責就六個主要主題提出問題，這些主題全面涵蓋了該病理學領域（診斷、復甦、非手術管理、手術、血管造影-血管栓塞術、抗菌治療）。然後，該領域的領先專家被要求在 1985 年至 2018 年 6 月期間的不同資料庫（MEDLINE、SCOPUS、EMBASE）中對這些主題中的每一個進行徹底檢索，以查找相關論文，並對現有文獻進行系統回顧。他們被要求集中搜索，以便為每個問題提供基於證據的答案並立即實際應用，並在陳述中總結它們。所有發言均於 2018 年 6 月 28 日在義大利貝爾蒂諾羅舉行的第五^屆 WSES 大會上發表和討論。對於每項發言，WSES 專家小組都達成了共識。所有成員都為手稿的開發做出了貢獻;稿件經過所有作者的審閱和批准。

The present guidelines have been developed according to the GRADE methodology [12, 13].
本指南是根據 GRADE 方法制定的 [12， 13]。

Topics and questions  主題和問題

For clarity, we report the six topics together with the questions dividend into each of them.
為清楚起見，我們將這六個主題連同每個主題的問題分紅一起報告。

Diagnosis  診斷

• 1. In patients with a suspected perforated  peptic ulcer, which are the appropriate biochemical and imaging investigations that should be requested?
  對於疑似消化性穿孔性潰瘍的患者，應要求進行哪些適當的生化和影像學檢查？

• 2. In patients with perforated peptic ulcer, what is the clinical value of risk scores such as Boey Score and Pulp score?
  在消化性潰瘍穿孔患者中，Boey 評分、Pulp 評分等風險評分的臨床價值是什麼？

• 3. In patients with suspected bleeding peptic ulcer, which biochemical and imaging investigations should be requested?
  對於疑似出血性消化性潰瘍的患者，應要求進行哪些生化和影像學檢查？

• 4. In patients with suspected bleeding peptic ulcer, what is the diagnostic role of endoscopy?
  在疑似出血性消化性潰瘍患者中，內鏡檢查的診斷作用是什麼？

• 5. In patients with bleeding peptic ulcer, are the endoscopic findings useful to determine the risk for rebleeding and how do they affect the clinical management?
  在出血性消化性潰瘍患者中，內鏡檢查結果是否有助於確定再出血的風險以及它們如何影響臨床管理？

Resuscitation  復甦

• 1. In patients with perforated peptic ulcer, which parameters should be evaluated ad ED referral?
  對於穿孔性消化性潰瘍患者，在急診轉診時應評估哪些參數？

• 2. In patients with perforated peptic ulcer, which are the appropriate targets for resuscitation (hemoglobin level, blood pressure/heart rate, lactates level, others)?
  對於穿孔性消化性潰瘍患者，哪些是合適的復甦目標（血紅蛋白水準、血壓/心率、乳酸水準等）？

• 3. In patients with bleeding peptic ulcer, which parameters should be evaluated at ED referral and which criteria should be adopted to define an unstable patient?
  對於出血性消化性潰瘍患者，在急診轉診時應評估哪些參數，以及應採用哪些標準來定義不穩定的患者？

• 4. In patients with bleeding peptic ulcer, which are the appropriate targets for resuscitation (hemoglobin level, blood pressure/heart rate, lactates level, others)?
  對於出血性消化性潰瘍患者，哪些是合適的復甦目標（血紅蛋白水準、血壓/心率、乳酸水準等）？

Non-operative management—endoscopic treatment
非手術治療——內鏡治療

• 1. In patients with perforated peptic ulcer, which are the indications for non-operative management?
  消化性潰瘍穿孔患者有哪些非手術治療指徵？

• 2. In patients with perforated peptic ulcer, is there a role for endoscopic treatment?
  在消化性潰瘍穿孔患者中，內鏡治療有作用嗎？

• 3. In patients with bleeding peptic ulcer, which are the indications for non-operative management?
  出血性消化性潰瘍患者有哪些非手術治療指徵？

• 4. In patients with bleeding peptic ulcer, which are the indications for endoscopic treatment?
  消化性潰瘍出血患者，內鏡治療的指征有哪些？

• 5. In patients with bleeding peptic ulcer, what is the appropriate pharmacological regimen (Erythromycin, PPI, terlipressin, others)?
  對於出血性消化性潰瘍患者，適當的藥物治療方案是什麼（紅黴素、PPI、特利加壓素等）？

• 6. In patients with recurrent bleeding from peptic ulcer, what is the role of non-operative management?
  在消化性潰瘍復發性出血患者中，非手術治療的作用是什麼？

Angiography–embolization
血管造影栓塞術

• 1. In patients with bleeding peptic ulcer, which are the indications for angiography?
  消化性潰瘍出血患者，血管造影的指征有哪些？

• 2. In patients with bleeding peptic ulcer, which are the indications for angioembolization?
  在出血性消化性潰瘍患者中，血管栓塞術的適應症有哪些？

• 3. Should embolization be considered for unstable patients with bleeding peptic ulcer?
  對於不穩定的出血性消化性潰瘍患者，是否應該考慮栓塞？

• 4. In patients with recurrent bleeding peptic ulcer, which are the indications for angioembolization?
  在復發性出血性消化性潰瘍患者中，血管栓塞術的適應症有哪些？

• 5. In patients who underwent angioembolization, which are the most appropriate embolization techniques and materials?
  在接受血管栓塞術的患者中，哪些栓塞技術和材料最合適？

• 6. In patients with bleeding peptic ulcer and non-evident bleeding during angiography is there a role for prophylactic embolization?
  對於出血、消化性潰瘍和血管造影過程中不明顯出血的患者，預防性栓塞是否有作用？

Surgery  手術

• 1. In patients with perforated peptic ulcer, which are the indications for surgical treatment and what is the appropriate timing for surgery?
  消化性潰瘍穿孔患者，手術治療的適應症有哪些，手術的合適時機是什麼時候？

• 2. In patients with perforated peptic ulcer what is the most appropriate surgical approach (open vs laparoscopy)?
  對於穿孔性消化性潰瘍患者，最合適的手術方法是什麼（開放式與腹腔鏡檢查）？

• 3. In patients with perforated peptic is there a role for sutureless repair?
  在消化性穿孔患者中，無縫修復有作用嗎？

• 4. In patients with perforated peptic ulcer and small perforation (< 2 cm), which surgical procedure should be adopted?
  消化性潰瘍穿孔、小穿孔（<2cm）患者應採用哪種手術？

• 5. In patients with perforated peptic ulcer and large perforation (≥ 2 cm), which surgical procedure should be adopted?
  消化性潰瘍穿孔、大穿孔（≥2cm）患者，應採用哪種手術？

• 6. In patients with perforated peptic ulcer, what is the role of damage control surgery?
  在消化性穿孔性潰瘍患者中，損傷控制手術的作用是什麼？

• 7. In patients with bleeding peptic ulcer, which are the indications for surgical treatment and which is the appropriate timing for surgery?
  對於出血性消化性潰瘍患者，哪些是手術治療的適應症，哪些手術時機是合適的？

• 8. In patients with bleeding peptic ulcer, what is the most appropriate surgical approach (open vs laparoscopy) and what are the most appropriate surgical procedures?
  對於出血性消化性潰瘍患者，最合適的手術方法是什麼（開腹與腹腔鏡）以及最合適的手術方法是什麼？

• 9. In patients with bleeding peptic ulcer, what is the role of damage control surgery?
  在出血性消化性潰瘍患者中，損傷控制手術的作用是什麼？

Antimicrobial therapy  抗菌治療

• 1. Should antibiotic therapy be prescribed and should anti-fungal therapy be administrated empirically in patients with perforated peptic ulcer?
  消化性潰瘍穿孔患者是否應開具抗生素治療，是否應憑經驗給予抗真菌治療？

• 2. In patients with perforated peptic ulcer, which antimicrobial regimen should be used and what is its correct duration?
  消化性潰瘍穿孔患者應採用哪種抗菌方案，正確的持續時間是多少？

• 3. In patients with bleeding peptic ulcer, which are the indications for antimicrobial therapy and for Helicobacter pylori testing?
  對於出血性消化性潰瘍患者，哪些適應症是抗菌治療和幽門螺桿菌檢測？

• 4. In patients with bleeding peptic ulcer and positive tests for H. pylori infection, which are the therapeutic options?
  對於出血性消化性潰瘍和幽門螺桿菌感染檢測呈陽性的患者，有哪些治療選擇？

Perforated peptic ulcer  穿孔性消化性潰瘍

Diagnosis  診斷

In patients with a suspected perforated peptic ulcer, which are the appropriate biochemical and imaging investigations that should be requested?
對於疑似消化性穿孔性潰瘍的患者，應要求進行哪些適當的生化和影像學檢查？

In patients with suspected gastroduodenal perforation, we recommend routine laboratory studies and arterial blood gas analysis (strong recommendation based on very low-quality evidences, 1D).
對於疑似胃十二指腸穿孔的患者，我們建議進行常規實驗室檢查和動脈血氣分析（基於極低品質證據的強烈推薦，1D）。

In patients with acute abdomen from suspected perforated peptic ulcer, we recommend a CT scan imaging (Strong recommendation based on low-quality evidences, 1C).
對於疑似消化性穿孔性消化性潰瘍引起的急腹症患者，我們建議進行 CT 掃描成像（基於低質量證據的強烈推薦，1C）。

In patients with acute abdomen from suspected perforated peptic ulcer, we recommend to perform chest/abdominal X-ray as the initial routine diagnostic assessment in case a CT scan is not promptly available (Strong recommendation based on low-quality evidences, 1C).
對於疑似消化性穿孔性消化性潰瘍引起的急腹症患者，我們建議進行胸部/腹部 X 線檢查作為初始常規診斷評估，以防無法及時進行 CT 掃描（基於低質量證據的強烈建議，1C）。

In patients with acute abdomen from suspected perforated peptic ulcer, when free air is not seen on imaging and there is ongoing suspicion of perforated peptic ulcer, we suggest performing imaging with the addition of water-soluble contrast either oral or via nasogastric tube (weak recommendation based on very low-quality evidences, 2D).
對於疑似消化性穿孔性潰瘍引起的急腹症患者，當影像學檢查未見遊離空氣且持續懷疑消化性穿孔性潰瘍時，我們建議進行影像學檢查，並添加水溶性造影劑，口服或通過鼻胃管（基於極低質量證據，2D）的弱推薦）。

The clinical presentation of gastroduodenal perforation is usually sudden onset of abdominal pain. Localized or generalized peritonitis is typical of perforated peptic ulcer, but may be present in only two-thirds of the patients [14,15,16]. Thus, physical examination findings may be equivocal and peritonitis may be minimal or absent, particularly in patients with contained and / sealed leak. Laboratory tests are non-specific, although leukocytosis, metabolic acidosis and elevated serum amylase are usually associated with perforation [17]. The first diagnostic investigation is the radiograph of the abdomen and chest, to detect the presence of free abdominal air. Erect and left lateral decubitus X-rays have similar diagnostic accuracy, the latter being better tolerated by patients presenting with peritonitis. The presence of this radiological sign is highly variable across various studies present in literature and ranges between 30 and 85% of perforations. This high variability and the finding that a negative X-ray does not rule out a possible perforation led multiple authors to state that, in case of clear signs of peritonitis, an abdominal CT scan should be the first radiological examination to be performed. However, in the setting of a peripheral hospital without prompt access to a CT scan, the plain X-ray still has a diagnostic role and free air on X-ray associated with a clear history and signs of peritonitis on physical examination is sufficient to justify surgical exploration [9, 14, 15, 18]. An adjunct to plain X-ray could be the administration through a nasogastric tube (NGT) of water-soluble contrast that can detect the presence of a gastro-duodenal perforation. “Point-of-care” ultrasound could also detect free intra-peritoneal, when performed by a trained operator, with the demonstration of air under the abdominal fascia; anyway, its role in the diagnostic work-up of suspected perforated peptic ulcer still needs to be defined. Suspicious CT scan findings include unexplained intraperitoneal fluid, pneumoperitoneum, bowel wall thickening, mesenteric fat streaking, and presence of extraluminal water-soluble contrast. Indeed, CT scan is increasingly taking the main role in diagnosis of perforation, due to the greater sensitivity in detecting free air and to its ability to characterize the site and size of perforation and to exclude other possible causes [15, 18, 19]. However, up to 12% of patients with perforations may have a normal CT scan; in this scenario, the administration of oral water-soluble contrast or via nasogastric tube and performing triple contrast CT scan may improve diagnostic sensitivity and specificity [17].
胃十二指腸穿孔的臨床表現通常是突然發作的腹痛。局限性或全身性腹膜炎是穿孔性消化性潰瘍的典型表現，但可能僅見於 2/3 的患者[14,15,16]。 因此，體格檢查結果可能模棱兩可，腹膜炎可能很少或不存在，特別是在有封閉和/密封滲漏的患者中。實驗室檢查是非特異性的，但白細胞增多、代謝性酸中毒和血清澱粉酶升高通常與穿孔有關[17]。第一個診斷檢查是腹部和胸部的 X 光片，以檢測是否存在遊離腹部空氣。直立和左側臥位 X 線檢查具有相似的診斷準確性，後者對腹膜炎患者的耐受性更好。這種放射學體征的存在在文獻中存在的各種研究中差異很大，穿孔的範圍在 30% 到 85% 之間。這種高變異性和陰性 X 射線不能排除可能的穿孔的發現導致多位作者指出，如果出現明顯的腹膜炎跡象，腹部 CT 掃描應該是首先進行的放射學檢查。然而，在週邊醫院無法及時進行 CT 掃描的情況下，X 線平片仍具有診斷作用，X 線片上的自由空氣與體格檢查時腹膜炎病史和體征相關，足以證明手術探查是合理的[9,14,15,18]。 X 線平片的輔助手段可能是通過水溶性造影劑鼻胃管 （NGT） 給葯，可以檢測胃十二指腸穿孔的存在。 當由訓練有素的操作員進行時，「床旁」超聲還可以檢測遊離腹膜內，並在腹部筋膜下顯示空氣;無論如何，它在疑似穿孔性消化性潰瘍的診斷檢查中的作用仍需要確定。可疑的 CT 掃描結果包括不明原因的腹腔內積液、氣腹、腸壁增厚、腸系膜脂肪條紋和管腔外水溶性造影劑的存在。事實上，CT 掃描在穿孔診斷中越來越發揮著重要作用，因為它在檢測遊離空氣方面具有更高的靈敏度，並且能夠表徵穿孔的部位和大小並排除其他可能的原因[15,18,19]。 然而，高達 12% 的穿孔患者可能 CT 掃描正常;在這種情況下，口服水溶性造影劑或通過鼻胃管進行三重造影劑 CT 掃描可能會提高診斷敏感性和特異性[17]。

In patients with perforated peptic ulcer, what is the clinical value of risk scores such as Boey Score and Pulp score?
在消化性潰瘍穿孔患者中，Boey 評分、Pulp 評分等風險評分的臨床價值是什麼？

In patients with perforated peptic ulcer, we suggest to adopt scoring systems (including the Boey, PULP and ASA score) for risk-stratification of patients and to predict outcomes (weak recommendation, based on low-quality evidences, 2C).
對於消化性潰瘍穿孔患者，我們建議採用評分系統（包括 Boey、PULP 和 ASA 評分）對患者進行風險分層並預測結局（弱推薦，基於低質量證據，2C）。

Numerous scoring systems have been designed and validated with the aim of predicting mortality and morbidity in patients with perforated peptic ulcer [20,21,22]. The Boey score is the most used, followed by the ASA score and the PULP. Boey's score showed an elevated variability in accuracy across the different studies where it was tested. On the other hand, the PULP score is difficult to apply and has not yet been validated outside the initial center. The new PULP score and the ASA score predicted mortality equally well and better than the Boey score, but hypoalbuminemia still remains the strongest single predictor of mortality [20,21,22].
已經設計和驗證了許多評分系統，旨在預測消化性潰瘍穿孔患者的死亡率和發病率[20,21,22]。Boey 分數是最常用的，其次是 ASA 分數和 PULP。Boey 的分數顯示，在測試它的不同研究中，準確性的差異很大。另一方面，PULP 分數很難應用，並且尚未在初始中心之外得到驗證。新的 PULP 評分和 ASA 評分對死亡率的預測與 Boey 評分一樣好，但低白蛋白血症仍然是死亡率最強的單一預測因數[20,21,22]。

Resuscitation  復甦

In patients with perforated peptic ulcer, which parameters should be evaluated ad ED referral?
對於穿孔性消化性潰瘍患者，在急診轉診時應評估哪些參數？

We recommend prompt evaluation and early recognition of the patient with perforated peptic ulcer associated sepsis to prevent further organ failure and to reduce mortality (strong recommendation based on moderate-quality evidences, 1B).
我們建議對穿孔性消化性潰瘍相關膿毒症患者進行及時評估和早期識別，以防止進一步的器官衰竭並降低死亡率（基於中等品質證據的強烈建議，1B）。

We suggest adopting scoring systems (SOFA, qSOFA) to evaluate and assess the severity of the disease in patients with perforated peptic ulcer (Weak recommendation based on low-quality evidences, 2 C).
我們建議採用評分系統（SOFA、qSOFA）來評估和評估消化性潰瘍穿孔患者的疾病嚴重程度（基於低質量證據的弱推薦，2 C）。

Perforated peptic ulcer, with associated peritonitis and sepsis/septic shock, is a medical/surgical emergency requiring rapid evaluation and management [23]. It is crucial to identify parameters to assess the severity of the disease (i.e., to define if a patient is stable or unstable). The latest definition of sepsis/septic shock and related debates/controversies are beyond the scope of this manuscript but are covered in recent papers [24, 25]. The timely recognition of sepsis (i.e., before the occurrence of organ dysfunction) is a priority [25, 26]. During the ED evaluation of every septic patient, several elements should be considered to assess the clinical picture. Specifically, several symptoms (i.e., altered mental state, dyspnea), signs (i.e., tachycardia, tachypnea, reduced pulse pressure, decreased urine output) and laboratory findings (hyperlactatemia, arterial hypoxemia, increased creatinine, coagulation abnormalities) must be evaluated. It is important to keep in mind that these findings may be modified by preexisting disease or medications [27]; for this reason, the collection of clinical history needs to be performed carefully.
穿孔性消化性潰瘍伴有腹膜炎和膿毒症/膿毒性休克，是一種需要快速評估和處理的內科/外科急症[23]。確定評估疾病嚴重程度的參數（即確定患者是穩定還是不穩定）至關重要。膿毒症/膿毒性休克的最新定義和相關辯論/爭議超出了本稿的範圍，但在最近的論文中有所介紹[24,25]。 及時識別膿毒症（即在器官功能障礙發生之前）是當務之急[25,26]。 在對每位膿毒症患者進行急診評估時，應考慮幾個因素來評估臨床表現。具體來說，必須評估幾種癥狀（即精神狀態改變、呼吸困難）、體征（即心動過速、呼吸急促、脈壓降低、尿量減少）和實驗室檢查結果（高乳酸血症、動脈低氧血症、肌酐升高、凝血異常）。重要的是要記住，這些發現可能會因既往疾病或藥物而改變[27];因此，需要仔細收集臨床病史。

Scoring systems, i.e., the sequential organ failure assessment (SOFA) [28] or the quick SOFA (qSOFA) [29], with associated limitations [25, 30,31,32,33], are available to assess the severity of the disease.
評分系統，即序貫器官衰竭評估（sofa）[28]或快速 SOFA（qSOFA）[29]，但有相關局限性[25,30,31,32,33] 可用於評估疾病的嚴重程度。

In patients with perforated peptic ulcer, which are the appropriate targets for resuscitation (hemoglobin level, blood pressure/heart rate, lactates level, others)?
對於穿孔性消化性潰瘍患者，哪些是合適的復甦目標（血紅蛋白水準、血壓/心率、乳酸水準等）？

In unstable patients with perforated peptic ulcer, we recommend performing rapid resuscitation to reduce mortality (strong recommendation based on low quality evidences, 1C).
對於不穩定的消化性消化性潰瘍穿孔患者，我們建議進行快速復甦以降低死亡率（基於低質量證據的強烈建議，1C）。

In unstable patients with perforated peptic ulcer, we recommend restoring physiological parameters with a mean arterial pressure ≥ 65 mmHg, a urine output ≥ 0.5 ml/kg/h, and a lactate normalization) (strong recommendation based on low-quality evidences,1C).
對於不穩定的消化性消化性潰瘍穿孔患者，我們建議恢復生理參數，平均動脈壓≥ 65 mmHg，尿量≥ 0.5 ml/kg/h，乳酸正常化）（基於低品質證據的強烈推薦，1C）。

We suggest utlizing different types of hemodynamic monitoring (invasive or not) to optimize fluids/vasopressor therapy and to individualize the resuscitation strategy (strong recommendation based on low quality evidences, 1C).
我們建議利用不同類型的血流動力學監測（有創或非有創）來優化液體/血管加壓藥治療並個體化復甦策略（基於低品質證據的強烈推薦，1C）。

Unstable septic perforated peptic ulcer patients need appropriate and rapid (ideally within 1 h) resuscitation to reduce mortality [27, 29]; this must take place simultaneously with surgical consultation, microbiological cultures (blood and other), and antibiotic administration [24, 34]. Primarily, as in any emergency situation, a rapid ABC (airway, breathing, and circulation) evaluation should be done. Secondarily, appropriate targets for resuscitation (the same used for sepsis and septic shock [27, 35]) need to be considered. In general, the most important are:
不穩定的膿毒性穿孔性消化性潰瘍患者需要適當、快速（最好在 1 h 內）復甦以降低死亡率[27,29]; 這必須與外科會診、微生物培養（血液和其他）和抗生素給葯同時進行[24,34]。 首先，與任何緊急情況一樣，應進行快速 ABC（氣道、呼吸和迴圈）評估。其次，需要考慮適當的復甦目標（與膿毒症和膿毒性休克相同[27,35]）。 一般來說，最重要的是：

• Mean arterial pressure (MAP) ≥ 65 mmHg
  平均動脈壓 （MAP） ≥ 65 mmHg

• Urine output ≥ 0.5 ml/kg/h
  尿量≥0.5毫升/公斤/小時

• Lactate normalization  乳酸正常化

Several forms of hemodynamic monitoring (invasive or not) are available to optimize resuscitation and fluid/vasopressors administration. For a more comprehensive approach to sepsis and septic shock, we suggest referring to the last published guidelines of the “Surviving Sepsis Campaign” [35].
有幾種形式的血流動力學監測（有創或非侵入性）可用於優化復甦和液體/血管加壓藥的給葯。為了更全面地治療膿毒症和膿毒性休克，我們建議參考最近發表的“膿毒癥倖存運動”指南[35]。

Non-operative management—endoscopic treatment
非手術治療——內鏡治療

In patients with perforated peptic ulcer, which are the indications for non-operative management?
消化性潰瘍穿孔患者有哪些非手術治療指徵？

In patients with perforated peptic ulcer we suggest against a routinely use of non-operative management; non-operative management (NOM) could be considered in extremely selected cases where perforation has sealed as confirmed on water-soluble contrast study (weak recommendation based on low-quality evidences, 2C).
對於穿孔性消化性潰瘍患者，我們建議不要常規使用非手術治療;在水溶性造影劑研究證實穿孔已密封的極少數情況下，可以考慮非手術治療 （NOM）（基於低質量證據的弱推薦，2C）。

Non-operative management (NOM) of perforated peptic ulcer is attractive as it avoids surgery and its resultant morbidity, e.g., wound-related morbidity, postoperative adhesions, etc. The rationale of NOM is that, in the case of small perforations, the ulcer seals by omental adhesions and can then heal and the peritonitis does not need operation [36]. In 1989 Croft et al. conducted a prospective randomized trial [37] comparing emergency surgery and NOM in patients with a clinical diagnosis of perforated peptic ulcer: 83 patients were entered in the study over a period of 13 months and were randomly assigned to one the two study groups. In the NOM group, 11 patients (28 percent) had no clinical Improvement after 12 h and required an operation. The overall mortality rates in the two groups were similar (two deaths in each, 5%), and did not differ significantly in the morbidity rates (40% in the surgical group and 50% in the nonsurgical group). The hospital stay was 35% longer in the group treated conservatively and patients over 70 years old were less likely to respond to conservative treatment than younger patients (p < 0.05). Songne et al. in 2004 [38] conducted a prospective trial of 82 consecutive patients with diagnosis of perforated peptic ulcer; they initially underwent NOM and clinical improvement was achieved in 54% of patients after NOM. In multivariate analysis, the factors independently related to NOM failure were size of pneumoperitoneum, heart rate > 94 bpm, and abdominal meteorism (defined as distended bowel loops). In conclusion, the most important factors regarding the feasibility of NOM for perforated peptic ulcer are normal vital signs in a stable patient and whether the ulcer itself has sealed as confirmed by a water-soluble contrast study: if there is a free leak of contrast, surgery is needed. On the other hand, NOM could be considered if no contrast extravasation is present and the patient does not have signs of peritonitis or sepsis.
穿孔性消化性潰瘍的非手術治療 （NOM） 很有吸引力，因為它避免了手術及其由此產生的發病率，例如傷口相關發病率、術后粘連等。NOM 的基本原理是，在小穿孔的情況下，潰瘍通過大網膜粘連閉合，然後可以癒合，腹膜炎不需要手術[36]。1989 年，Croft 等人進行了一項前瞻性隨機試驗 [37]，比較了臨床診斷為消化性潰瘍穿孔患者的急診手術和 NOM：83 名患者在 13 個月內被納入研究，並被隨機分配到兩個研究組中的一個。在 NOM 組中，11 名患者 （28%） 在 12 小時後沒有臨床改善，需要手術。兩組的總體死亡率相似（各 2 人死亡，5%），發病率差異不顯著（手術組 40%，非手術組 50%）。保守治療組的住院時間延長了 35%，70 歲以上的患者對保守治療有反應的可能性低於年輕患者 （p < 0.05）。Songne 等[38]於 2004 年對 82 例連續診斷為消化性咽潰瘍穿孔的患者進行了前瞻性試驗;他們最初接受了 NOM，54% 的患者在 NOM 后取得了臨床改善。在多因素分析中，與 NOM 失敗獨立相關的因素是氣腹大小、心率 > 94 bpm 和腹部氣象（定義為擴張的腸袢）。 總之，關於 NOM 治療消化性潰瘍穿孔可行性的最重要因素是穩定患者的正常生命體征以及潰瘍本身是否已密封，經水溶性造影劑研究證實：如果造影劑有遊離洩漏，則需要手術。另一方面，如果不存在造影劑外滲並且患者沒有腹膜炎或敗血症的跡象，則可以考慮 NOM。

The essential pre-requisites and components of non-operative management of PPU can be grouped as “R”s [39]:
PPU 非手術治療的基本先決條件和組成部分可分為“R”[39]：

• Radiologically undetected leak
  放射學上未檢測到的洩漏

• Repeated clinical examination
  反覆臨床檢查

• Repeated blood investigations
  反覆血液檢查

• Respiratory and renal support
  呼吸和腎臟支援

• Resources for monitoring and
  用於監測和

• Readiness to operate  準備運營

NOM includes: nil by mouth; intravenous hydration; decompression via nasogastric tube; anti-secretory and PPI therapy; intravenous antibiotics; and follow-up endoscopy at 4–6 weeks. Mortality increases with every hour of delay to surgery, and hence, NOM must be carefully selected. Surapaneni et al. have shown nil mortality in patients who were operated within 24 h of onset of symptoms as compared to surgery beyond 48 h of onset of symptoms [40]. Buck et al. in 2688 Danish patients have shown that every hour of delay from admission to surgery was associated with an adjusted 2.4% decreased probability of survival compared with the previous hour [41]. Elderly patients may experience paradoxical higher mortality if non-operative management fails and caution is advised in patients > 70 years of age.
NOM 包括：口服無;靜脈補液;通過鼻胃管減壓;抗分泌和 PPI 治療;靜脈注射抗生素;4-6 周時進行隨訪內窺鏡檢查。死亡率隨著手術延遲一小時而增加，因此必須仔細選擇 NOM。Surapaneni 等研究顯示，與癥狀出現后 48 小時後手術相比，在癥狀出現后 24 h 內接受手術的患者死亡率為零[40]。Buck 等人在 2688 名丹麥患者中發現，與前一小時相比，從入院到手術的每延遲一小時，生存概率就會降低 2.4%[41]。如果非手術治療失敗，老年患者的死亡率可能會相反，並且建議 > 70 歲的患者謹慎行事。

In patients with perforated peptic ulcer is there a role for endoscopic treatment?
在消化性潰瘍穿孔患者中，內鏡治療有作用嗎？

In patients with perforated peptic ulcer, we suggest to avoid endoscopic treatment such clipping, fibrin glue sealing, or stenting (Weak recommendation based on low-quality evidences, 2C)
對於穿孔性消化性潰瘍患者，我們建議避免內鏡治療，如夾閉、纖維蛋白膠封閉或支架置入術（基於低質量證據的弱推薦，2C）

Closure of acute iatrogenic perforations with endoscopic clips is described [42, 43]; however, clips may not be effective in perforated ulcer cases due to fibrotic tissue with loss of compliance. Combined laparoscopic-endoscopic approaches for perforated ulcer closures have been described [44, 45]. Bergstrom et al. [46] present a case series of eight patients with perforated duodenal ulcers treated with covered self-expandable metal stents and the results indicate that, in very selected patients or in cases where surgical closure will be difficult, gastroscopy with stent placement could be performed during laparoscopy, followed by laparoscopic drain placement. In patients with severe co-morbidity or delayed diagnosis, gastroscopy and stent placement followed by radiologically guided drain placement could be an alternative to more standard treatment. Endoscopic snaring of omentum and pulling is also described as an effective adjunct along with duodenal plication. Furthermore, endoscopy also allows performing a biopsy and rule out gastric outlet obstruction in case of large perforations. In spite of these case series, all the above reported modalities are not recognized as standard approaches to perforated peptic ulcer and need further validation.
描述了使用內鏡夾閉合急性醫源性穿孔[42,43]; 然而，由於纖維化組織和失去順應性，夾子可能對穿孔性潰瘍病例無效。已經描述了腹腔鏡-內鏡聯合方法治療穿孔性潰瘍閉合術[44,45]。 Bergstrom 等[46]提出了一個病例系列，納入了 8 例十二指腸穿孔性潰瘍患者，接受覆蓋的自擴張金屬支架治療，結果表明，在非常選定的患者或難以手術閉合的情況下，可以在腹腔鏡檢查期間進行胃鏡檢查並放置支架，然後進行腹腔鏡引流管放置。對於患有嚴重合併症或延遲診斷的患者，胃鏡檢查和支架置入術，然後進行放射引導引流管放置可能是更標準治療的替代方法。內窺鏡下大網膜圈套和拉扯也被描述為十二指腸摺疊的有效輔助手段。此外，內窺鏡檢查還可以進行活檢，並在大穿孔的情況下排除胃出口梗阻。儘管有這些病例系列，但上述所有報告的模式均未被認為是消化性潰瘍穿孔的標準方法，需要進一步驗證。

Surgery  手術

In patients with perforated peptic ulcer, which are the indications for surgical treatment and what is the appropriate timing for surgery?
消化性潰瘍穿孔患者，手術治療的適應症有哪些，手術的合適時機是什麼時候？

In patients with perforated peptic ulcer with significant pneumoperitoneum or extraluminal contrast extravasation or signs of peritonitis, we recommend operative treatment (Strong recommendation based on low-quality evidences, 1C)
對於有明顯氣腹或腔外造影劑外滲或腹膜炎體征的穿孔性消化性潰瘍患者，我們建議手術治療（基於低質量證據的強烈推薦，1C）

We recommend performing surgery as soon as possible, especially in patients with delayed presentation and patients older than 70   years old (strong recommendation based on moderate-quality evidences, 1B)
我們建議儘快進行手術，特別是對於延遲就診的患者和 70 歲以上的患者（基於中等質量證據的強烈推薦，1B）

The feasibility of NOM should be weighed with the evidence that an increase in surgical delay significantly impairs surgical outcome. In fact, a cohort study performed in 2013 from the Danish Clinical Register of Emergency Surgery [41] showed that, over the first 24 h after admission, each hour of surgical delay beyond hospital admission was associated with an adjusted 2.4% decreased probability of survival compared with the previous hour, over the entire observation period. Other studies highlighted the importance of a prompt surgical approach to PPU: a retrospective single-center study by Lunevicious et al. [47] showed an increase in the suture leakage rate after a delay in presentation > 9 h, while a recent prospective single-center study on 101 patients with peritonitis from peptic ulcer perforation who underwent laparotomy and simple closure with omental patch found that a perforation-to-surgery interval longer than 36 h was significantly associated with an increase in postoperative mortality [48]. Furthermore, a systematic review [49] performed in 2010 including fifty studies with 37 prognostic factors comprising a total of 29,782 patients provided strong evidence for an association of older age, comorbidity, and use of NSAIDs or steroids with mortality; shock upon admission, preoperative metabolic acidosis, tachycardia, acute renal failure, low serum albumin level, high ASA score, and preoperative delay > 24 h were also associated with poor prognosis. Limiting pre-operative delay thus seems to be of great importance.
應權衡 NOM 的可行性以及手術延遲增加顯著損害手術結果的證據。事實上，丹麥急診外科臨床註冊中心（Danish Clinical Register of Emergency Surgery）2013 年進行的一項佇列研究[41]顯示，在整個觀察期內，在入院后的前 24 小時內，入院后每延遲一小時的手術，與前一小時相比，調整后的生存概率降低 2.4%。其他研究強調了及時手術治療 PPU 的重要性：Lunevicious 等[47]的一項回顧性單中心研究顯示，在就診延遲> 9 h 後縫合線滲漏率增加，而最近一項前瞻性單中心研究對 101 例消化性潰瘍穿孔引起的腹膜炎患者進行了剖腹手術和大網膜貼片簡單閉合，發現穿孔到手術間隔超過 36 h 有顯著相關性術后死亡率增加[48]。此外，2010 年進行的一項系統評價[49]納入了 50 項研究，涉及 37 項預後因素，共 29,782 例患者，為高齡、合併症和使用 NSAIDs 或類固醇與死亡率的關聯提供了有力的證據;入院時休克、術前代謝性酸中毒、心動過速、急性腎功能衰竭、血清白蛋白水準低、ASA 評分高、術前延遲> 24 h 也與預後不良相關。因此，限制術前延誤似乎非常重要。

In patients with perforated peptic ulcer, which is the most appropriate surgical approach (open vs laparoscopy)?
對於穿孔性消化性潰瘍患者，哪種手術方法最合適（開放式與腹腔鏡檢查）？

In stable patients with perforated peptic ulcer, we suggest a laparoscopic approach. An open approach is recommended in the absence of appropriate laparoscopic skills and equipment (weak recommendation based on moderate-quality evidences, 2B).
對於患有穿孔性消化性潰瘍的穩定患者，我們建議採用腹腔鏡入路。在缺乏適當的腹腔鏡技能和設備的情況下，建議採用開放式方法（基於中等質量證據的弱推薦，2B）。

In unstable patients with perforated peptic ulcer, we recommend open surgery (strong recommendation based on very low-quality of evidences, 1D)
對於不穩定的消化性穿孔性潰瘍患者，我們推薦進行開放手術（基於極低質量的證據，1D，強烈推薦）

A recent meta-analysis from Cirocchi et al. [50] compared laparoscopic to open surgery for patients with perforated peptic ulcer: their search identified 8 RCTs for a total of 615 patients (307 patients undergoing laparoscopic repair and 308 patients undergoing open repair); however all the included studies were at high risk of bias. The comparison reported a significant advantage of laparoscopic repair with less postoperative pain in the first 24 h after surgery and less postoperative wound infections. No significant differences between laparoscopic and open surgery were found for overall postoperative mortality, leak of the suture repair, intra-abdominal abscesses and reoperation rate. This is the strongest evidence present so far the literature and suggests it is reasonable to pursue a laparoscopic approach for stable patients and in the presence of appropriate surgical skills.
Cirocchi 等[50]最近的一項 meta 分析比較了腹腔鏡手術和開放手術對消化性穿孔性潰瘍患者的治療：他們的檢索確定了 8 項隨機對照試驗，共 615 名患者（307 名患者接受腹腔鏡修復，308 名患者接受開放性修復）;然而，所有納入的研究都存在高偏倚風險。比較報告了腹腔鏡修復的顯著優勢，術后前 24 小時內術后疼痛更少，術后傷口感染更少。腹腔鏡手術和開放手術在術后總死亡率、縫合線修復滲漏、腹腔內膿腫和再手術率方面沒有發現顯著差異。這是迄今為止文獻中最有力的證據，表明在病情穩定且有適當手術技能的情況下採用腹腔鏡方法是合理的。

The effects of increased intra-abdominal pressure and hypercarbia due to CO2 insufflation during laparoscopy are well known (increased systemic vascular resistance, mean arterial pressure, afterload, heart rate, caval pressures, respiratory rate, peak airways pressure, PaCO2; reduced stroke volume, venous return, cardiac output, thoracic compliance, pH) [51] and preclude a laparoscopic approach to hemodynamically unstable patients or patients with severe cardiovascular or pulmonary comorbidity.
腹腔鏡檢查中 CO2 吹入導致腹內壓升高和高碳酸血症的影響是眾所周知的（全身血管阻力增加、平均動脈壓、后負荷、心率、腔靜脈壓、呼吸頻率、氣道峰值壓、PaCO2;每搏輸出量、靜脈迴流、心輸出量、胸腔順應性、pH 值降低）[51] 並排除對血流動力學不穩定患者或患有嚴重心血管或肺部合併症的患者進行腹腔鏡入路。

Is there a role for sutureless repair in patients with perforated peptic ulcer?
消化性潰瘍穿孔患者無縫修復有作用嗎？

Based on the available literature, no recommendation could be made about the sutureless repair.
根據現有文獻，無法對無縫縫合修復提出任何建議。

Sutureless repair was proposed with the rationale to shorten operative time and to simplify the surgical technique, making it easily performed by those who have limited experience with laparoscopic surgery. However, it has not gained a wide acceptance due to its high leakage rate compared to suture repair. A prospective study conducted from January 1992 to December 1998 included 374 patients with perforated peptic ulcer [52]; 219 patients were treated by open suture repair, 109 patients received laparoscopic fibrin glue repair and the remaining 46 patients were treated by laparoscopic suture repair. Laparoscopic fibrin glue repair was initially attempted in 149 patients but 40 required conversion to suture repair. The overall conversion rates for laparoscopic fibrin glue repair and laparoscopic suture repair were 27 and 15%, respectively. The main reasons for conversion were a large (1 cm or more) ulcer perforation and failure to locate the perforation site. The overall leak rates after laparoscopic glue repair and laparoscopic suture repair were 16 and 6% respectively and the reoperation rates for clinical leaks after laparoscopic glue repair and laparoscopic suture repair were 10 and 4% respectively. On the other hand, a retrospective cohort study performed from January 2008 to December 2012 found conflicting results [53]: 107 patients were included, 64 underwent laparoscopic repair with a sutureless on-lay omental patch, and 43 were treated by laparoscopic sutured omental patch. High-risk patients with Boey scores of 2 and 3 or those with perforations larger than 10 mm were excluded. The time to water intake was significantly shorter for patients who had repair with a sutureless omental patch (p = 0.007), as well as the mean hospital stay (p = 0.007). All patients in both groups survived to the end of the study and no patient experienced leakage after the operation. The evidences listed above are based on low quality studies and do not allow us to make a recommendation for its routine application.
提出無縫修復的理由是縮短手術時間並簡化手術技術，使腹腔鏡手術經驗有限的人可以輕鬆進行。然而，由於與縫合線修復相比，其洩漏率較高，因此並未獲得廣泛接受。一項前瞻性研究於 1992 年 1 月至 1998 年 12 月進行，納入了 374 例穿孔性消化性潰瘍患者[52];219 例患者接受開放縫合修復治療，109 例患者接受腹腔鏡纖維蛋白膠修復術治療，其餘 46 例患者接受腹腔鏡縫合修復治療。腹腔鏡纖維蛋白膠修復最初在 149 名患者中嘗試，但 40 名需要轉換為縫合修復。腹腔鏡纖維蛋白膠修復術和腹腔鏡縫合修復術的總體轉化率分別為 27%和 15%。轉換的主要原因是大（1 釐米或更大）潰瘍穿孔和未能定位穿孔部位。腹腔鏡膠修復術和腹腔鏡縫合線修復術后總滲漏率分別為 16%和 6%，腹腔鏡膠修復術和腹腔鏡縫合線修復術后臨床滲漏的再手術率分別為 10%和 4%。另一方面，2008 年 1 月至 2012 年 12 月進行的一項回顧性佇列研究發現結果相互矛盾[53]：納入 107 例患者，64 例接受腹腔鏡修復，使用無縫網膜貼片進行腹腔鏡修復，43 例接受腹腔鏡縫合大網膜補片治療。Boey 評分為 2 分和 3 分的高危患者或穿孔大於 10mm 的患者被排除在外。 使用未縫合網膜補片修復的患者飲水時間顯著縮短 （p = 0.007），平均住院時間 （p = 0.007）。兩組患者均存活至研究結束，術后無患者出現滲漏。上面列出的證據基於低品質研究，不允許我們對其常規應用提出建議。

In patients with perforated peptic ulcer and small perforation (< 2 cm), which surgical procedure should be adopted?
消化性潰瘍穿孔、小穿孔（<2cm）患者應採用哪種手術？

In patients with perforated peptic ulcer smaller than 2 cm, we suggest performing primary repair. No recommendation can be made whether the use of an omental patch can provide further protection of the repair (weak recommendation based on low-quality evidences, 2C)
對於小於 2 cm 的穿孔性消化性潰瘍患者，我們建議進行初步修復。無法推薦使用大網膜貼片是否可以為修復提供進一步的保護（基於低質量證據的弱推薦，2C）

Historically, repair with the adjunct of an omental patch was considered the “standard” laparoscopic procedure for perforated peptic ulcer repair. This belief is a now matter of debate as multiple studies showed the addition of an omental patch does  not add benefits to a simple suture repair, but it significantly increases the operation time.
從歷史上看，使用網膜補片進行修復被認為是穿孔消化性潰瘍修復的“標準”腹腔鏡手術。這種信念現在是一個有爭議的問題，因為多項研究表明，添加大網膜貼片不會增加簡單縫合修復的好處，但它會顯著增加手術時間。

Multiple retrospective single-center studies support these findings. Lin et al. [54] analyzed 118 patients with PPU who underwent laparoscopic repair with simple closure (n = 27) or omentopexy (n = 91) and found Three closure leakage: 1 after simple closure and 2 after omentopexy, but no patient died. After matching, the simple closure and omentopexy groups had comparable results regarding leakage rate. Comparison of the operating time in the 4.0- and 5.0–12-mm groups reported that the simple closure took less time than omentopexy for perforations smaller than 12 mm. Abd Ellatif and colleagues [55] enrolled 179 consecutive patients with PPU who were treated by laparoscopic repair; 108 patients with the omental patch technique and 71 with laparoscopic simple repair. Operative time was significantly shorter in the non-patch group and no patient was converted to laparotomy. There was no difference in age, gender, ASA score, surgical risk (Boey’s) score, and incidence of co-morbidities between two groups and both groups was comparable in terms of hospital stay, time to resume oral intake, postoperative complications and surgical outcomes. Lo et al. retrospectively identified 73 patients undergoing PPU laparoscopic repair, 26 received simple closure repair and 47 received simple closure plus omental patch. There was no difference in age, gender, ASA score, Boey risk score, incidence of co-morbidities, Mannheim Peritonitis index, median operation time or length of stay. Again, they stated that, in terms of leakage rate and surgical outcome, the maneuver to cover an omental patch on the repaired PPU did not show additional advantage compared to simple closure alone [56]. A multicenter non-randomized retrospective study [57] further strengthens these findings: between 2009 and 2013, 297 patients with PPU underwent a laparoscopic procedure in eight Romanian surgical centers. Primary suture repair was performed in 145 patients (48.8%), primary suture repair with omentopexy in 146 patients (49.2%) and the remaining 6 patients were converted to open surgery. The univariate complications rate analysis they performed found no significant association (p = 0.634; Fisher’s exact test) between the type of the repair and the rate of complications. A prospective non-randomized study by Ates et al. compared laparoscopic simple closure with conventional omental patch open repair for perforated peptic ulcer. Of the 35 patients enrolled, none experienced operative complications nor postoperative leak or residual intra-abdominal abscess [58]. On the other hand, multiple retrospective studies highlight low postoperative leak rates with the omental patch technique, even in case of perforations up to 2 cm in diameter [59]. Multiple authors suggest the adjunct of an omental patch in case of large ulcers with friable edges, to reduce the risk of the suture cutting through the edges of the ulcer [60].
多項回顧性單中心研究支持這些發現。Lin 等[54]分析了 118 例接受腹腔鏡簡單閉合術（n = 27）或大網膜固定術（n = 91）的 PPU 患者，發現 3 次閉合滲漏：1 例在簡單閉合后， 2 例在大網膜固定術后，但沒有患者死亡。匹配后，簡單閉合組和網膜固定術組在滲漏率方面的結果相當。比較 4.0-5.0-12mm 組的手術時間報告稱，對於小於 12mm 的穿孔，簡單閉合比網膜固定術花費的時間更短。Abd Ellatif 及其同事[55]連續招募了 179 例接受腹腔鏡修復治療的 PPU 患者;108 例患者採用大網膜貼片技術，71 例患者採用腹腔鏡簡單修復。非貼片組的手術時間明顯縮短，沒有患者轉為剖腹手術。兩組在年齡、性別、ASA 評分、手術風險（Boey』s）評分和合併症發生率方面無差異，兩組在住院時間、恢復口服時間、術后併發症和手術結局方面具有可比性。回顧性確定了 73 名接受 PPU 腹腔鏡修復的患者，其中 26 名接受了簡單閉合修復，47 名接受了簡單閉合加大網膜補片。年齡、性別、ASA 評分、Boey 風險評分、合併症發生率、曼海姆腹膜炎指數、中位手術時間或住院時間均無差異。他們再次指出，就滲漏率和手術結果而言，與單獨閉合相比，覆蓋修復後 PPU 上大網膜補片的作沒有顯示出額外的優勢[56]。 一項多中心非隨機回顧性研究[57]進一步強化了這些發現：2009 年至 2013 年間，297 名 PPU 患者在羅馬尼亞 8 個外科中心接受了腹腔鏡手術。145 例（48.8%）患者進行了初次縫合修復，146 例（49.2%）患者進行了大網膜固定術的初次縫合修復，其餘 6 例患者轉為開放手術。他們進行的單變數併發症發生率分析發現沒有顯著關聯（p = 0.634;費舍爾精確檢驗）介於修復類型和併發症發生率之間。Ates 等人的一項前瞻性非隨機研究比較了腹腔鏡簡單閉合術與傳統網膜補片開放修復術治療穿孔消化性潰瘍。在入組的 35 例患者中，均未出現手術併發症，也未出現術后滲漏或殘留腹腔內膿腫[58]。另一方面，多項回顧性研究強調，即使在直徑達 2cm 的穿孔的情況下，大網膜貼片技術的術后滲漏率也很低[59]。多位作者建議，對於邊緣易碎的大潰瘍，應加用大網膜補片，以降低縫合線切開潰瘍邊緣的風險[60]。

In light of the above, we cannot suggest the routine application of the omental patch because of the longer operative time, the need for advanced laparoscopic skills and the similar results after simple closure, but it could be considered a viable option in selected cases.
鑒於上述情況，我們不能建議常規應用大網膜貼片，因為手術時間較長，需要先進的腹腔鏡技術以及簡單閉合后的結果相似，但在某些情況下，它可以被認為是一個可行的選擇。

In patients with perforated peptic ulcer and large perforation (≥ 2 cm), which surgical procedure should be adopted?
消化性潰瘍穿孔、大穿孔（≥2cm）患者，應採用哪種手術？

We suggest a tailored approach based upon the location of the ulcer for the treatment of perforated peptic ulcer larger than 2 cm. In case of large gastric ulcers that raise the suspicion of malignancy, we suggest resection with contextual operative frozen pathologic examination whenever possible. In case of large duodenal ulcers, we suggest considering the need of resections or repair plus/minus pyloric exclusion/external bile drainage. We recommend duodenostomy only in extreme circumstances (weak recommendations based on very low-quality evidences, 2D).
我們建議根據潰瘍的位置採取量身定製的方法來治療大於 2 釐米的穿孔性消化性潰瘍。如果出現懷疑惡性腫瘤的大胃潰瘍，我們建議盡可能進行切除，並進行相關手術冷凍病理檢查。如果是大的十二指腸潰瘍，我們建議考慮是否需要切除或修復加/減幽門排除/膽汁外引流。我們建議僅在極端情況下進行十二指腸造口術（基於極低質量證據的薄弱建議，2D）。

While the treatment of a small ulcer is relatively straightforward, the treatment of giant peptic ulcers (diameter > 2 cm) poses different challenges according to the anatomical location. Furthermore, large gastric ulcers should always raise the suspicion of malignancy [61]. The spontaneous perforation of gastric cancer is a rare complication, occurring in 1% of patients with gastric cancer, and it has been reported that about 10–16% of all gastric perforations are caused by gastric carcinoma [62]. Besides this, there are no specific surgical treatment recommendations since the site of perforation and the secondary effects on the surrounding anatomical structures must direct the necessary interventions. The gastric location is usually easier to treat when compared to the duodenal location and gastric resection and reconstruction should be the surgical choice for the treatment of perforated gastric ulcers larger than 2 cm. On the other hand, only the first portion of the duodenum can be resected easily without risk of injuring the bile duct or the pancreatic head. Antrectomy plus or minus D1–D2 resection with diversion is the classic and most commonly described intervention, if the ampullary region is not involved [63]. The proximity of the defect and its relation to the common bile duct and ampulla of Vater must also be thoroughly investigated and intraoperative cholangiography may even be necessary to verify common bile duct anatomy. Several different procedures, such as a jejunal serosal patch, Roux en-Y duodenojejunostomy, pyloric exclusion, and several variations of omental plugs [64] have been described for large duodenal defects when the defect is felt too large to perform a primary repair. In large ulcers, leak rates up to 12% have been reported from attempted closure with an omental patch procedure [65]. These patients also frequently present in septic shock when the amount of peritoneal spillage is large. This factor alone should significantly influence the choice of operative intervention, because a definitive resectional approach for ulcers involving the ampullary area (i.e., Whipple procedure or similar) is usually not recommended in patients with peritonitis, because of the high physiological impact of these procedures and the great risk of postoperative complications. In these cases, a damage control procedure (such as pyloric exclusion with gastric decompression via a nasogastric tube or a gastrostomy and an external biliary diversion via T-tube) will likely be the safest and most appropriate operation for the patient [66]. Duodenostomy (e.g., over Petzer tube) should be used only as a last resort, in the presence of giant ulcers with severe tissue inflammation and when mobilization of the duodenum is not possible and the patient is in severe septic shock with hemodynamic instability.
雖然小潰瘍的治療相對簡單，但巨大的消化性潰瘍（直徑 > 2 cm）的治療根據解剖位置提出了不同的挑戰。此外，大胃潰瘍應始終引起惡性腫瘤的懷疑[61]。胃癌的自發性穿孔是一種罕見的併發症，發生在 1%的胃癌患者中，據報導，大約 10-16%的胃穿孔是由胃癌引起的[62]。除此之外，沒有具體的手術治療建議，因為穿孔部位和對周圍解剖結構的次要影響必須指導必要的干預措施。與十二指腸位置相比，胃位置通常更容易治療，胃切除重建應是治療大於 2 cm 的穿孔性胃潰瘍的手術選擇。另一方面，只有十二指腸的第一部分可以輕鬆切除，而不會有損傷膽管或胰頭的風險。如果壺腹未累及壺腹區域，則前切除術加或減 D1-D2 切除術聯合分流是經典且最常見的干預措施[63]。還必須徹底調查缺損的接近程度及其與 Vater 膽總管和壺腹的關係，甚至可能需要術中膽管造影來驗證膽總管解剖結構。對於十二指腸大缺損，已經描述了幾種不同的手術，如空腸漿膜補片、Roux en-Y 十二指腸空腸吻合術、幽門排除術和幾種大網膜栓塞[64]，當感覺缺損太大而無法進行初次 修復時。 在大潰瘍中，嘗試使用大網膜貼片手術閉合的滲漏率高達 12%[65]。當腹膜溢出量較大時，這些患者也經常出現感染性休克。僅此因素就應該顯著影響手術干預的選擇，因為對於腹膜炎患者，通常不推薦對涉及壺腹區域的潰瘍進行最終切除方法（即 Whipple 手術或類似手術），因為這些手術對生理的影響很大，並且術后併發症的風險很大。在這些情況下，損傷控制作（如幽門排除，通過鼻胃管或胃造口術進行胃減壓，以及通過 T 型管進行膽道外改道）可能是患者最安全、最合適的手術[66]。十二指腸造口術（例如，在 Petzer 管上）只能作為最後的手段，在存在伴有嚴重組織炎症的巨大潰瘍的情況下，以及無法動員十二指腸並且患者處於嚴重感染性休克且血流動力學不穩定的情況下。

In patients with perforated peptic ulcer, what is the role of damage control surgery?
在消化性穿孔性潰瘍患者中，損傷控制手術的作用是什麼？

In patients with septic shock from a perforated peptic ulcer and signs of severe physiological derangement, we suggest a damage control strategy (Weak recommendation based on very low-quality of evidences, 2D)
對於因消化性潰瘍穿孔而發生感染性休克並有嚴重生理紊亂跡象的患者，我們建議採用損害控制策略（基於極低質量證據的弱推薦，2D）

In severe peritonitis, some patients may experience disease progression to severe sepsis and septic shock experiencing progressive organ dysfunction, hypotension, myocardial depression, and coagulopathy and a staged approach may be required. If the patient is not in a condition to undergo a definitive repair and/or abdominal wall closure, due to mandatory conditions requiring an open abdomen, the intervention should be abbreviated due to suboptimal local conditions for healing and global susceptibility to spiraling organ failure [67]. Such mandatory conditions include physical inability to close the abdominal fascia without tension, a decision to leave intra-abdominal packing, or a decision to leave blind bowel loops to expedite the procedure. Committing a patient to an open abdomen however has significant risks including the most feared enteroatmospheric fistula which has been reported to be more common in emergency general surgery patients than trauma patients. “Source control” of intra-abdominal contamination remains a discretionary reason to leave the abdomen open, recognizing that “inability to achieve source control” is a frequently quoted but poorly objectified concept in emergency general surgery. Although upper gastrointestinal perforations are often less catastrophic than lower gastrointestinal contaminations, when the patient responded with immunological activation and systemic sepsis, they are suffering from severe complicated intra-abdominal sepsis. If these conditions are met, then we suggest participation and potential enrollment in the COOL Trial [68,69,70] Closed or Open after Laparotomy (COOL) study (https://clinicaltrials.gov/ct2/show/NCT03163095) to help provide better guidance for clinicians in the future treating such challenging patients. In general, anastomoses should be avoided in the presence of hypotension or hemodynamic instability, especially if the patient requires vasopressors. After copious abdominal irrigation, a temporary abdominal closure device can be placed if there are mandatory factors dictating an OA or if the patient is randomized to this therapy in the COOL trial. The patient can then be resuscitated appropriately in the ICU. The surgeon can return to the OR for re-exploration, restoration of continuity and closure of the abdomen once the patient is hemodynamically stable. We refer you to the WSES guidelines on Open Abdomen management for further information [67].
在重度腹膜炎中，一些患者可能會出現疾病進展為重度膿毒症和感染性休克，並出現進行性器官功能障礙、低血壓、心肌抑制和凝血病，可能需要分階段入路。如果患者由於強制性條件需要開腹，無法進行根治性修復和/或腹壁封堵術，則由於局部癒合條件不理想，且整體易發生螺旋性器官衰竭，應縮短干預時間[67]。這些強制性條件包括身體無法在沒有張力的情況下關閉腹部筋膜、決定離開腹內填塞或決定留下盲腸袢以加快手術速度。然而，將患者置於開腹狀態存在重大風險，包括最令人恐懼的腸大氣瘺，據報導，這種瘺在急診普通外科患者中比創傷患者更常見。腹腔內污染的「源頭控制」仍然是保持腹部開放的自由裁量理由，因為認識到“無法實現源頭控制”是急診普通外科中經常被引用但客觀化不力的概念。儘管上消化道穿孔通常比下消化道污染的災難性更小，但當患者出現免疫啟動和全身性敗血症的反應時，他們患有嚴重的複雜腹腔內敗血症。 如果滿足這些條件，那麼我們建議參與並可能參加 COOL 試驗[68,69,70]剖腹手術後封閉式或開放式（COOL）研究（https://clinicaltrials.gov/ct2/show/NCT03163095），以説明臨床醫生在未來治療此類具有挑戰性的患者時提供更好的指導。 一般來說，在存在低血壓或血流動力學不穩定的情況下，應避免吻合，特別是當患者需要血管加壓藥時。在大量腹部沖洗后，如果存在強制性因素導致 OA 或患者在 COOL 試驗中隨機接受這種療法，則可以放置臨時腹部閉合裝置。然後患者可以在 ICU 中進行適當的復甦。一旦患者血流動力學穩定，外科醫生可以返回手術室進行重新探查、恢復連續性和腹部閉合。我們建議您參閱 WSES 關於開腹治療的指南[67]。

Antimicrobial therapy  抗菌治療

Should antibiotic therapy be prescribed and should anti-fungal therapy be administrated empirically in patients with perforated peptic ulcer?
消化性潰瘍穿孔患者是否應開具抗生素治療，是否應憑經驗給予抗真菌治療？

In patients with perforated peptic ulcer, we recommend the administration broad-spectrum antibiotics (strong recommendation based on low-quality evidences, 1C)
對於穿孔性消化性潰瘍患者，我們建議使用廣譜抗生素（基於低質量證據的強烈推薦，1C）

We recommend the collection of samples for microbiological analysis for both bacteria and fungi in all patients undergoing surgery with subsequent antibiotic therapy adjustment (strong recommendation based on low-quality evidences, 1C
我們建議收集樣本進行所有接受手術並隨後調整抗生素治療的患者的細菌和真菌微生物學分析（基於低品質證據的強烈建議，1C

We suggest not to administer antifungal agents as standard empiric therapy in patients with perforated peptic ulcer. Antifungal should be administrated in patients at high risk for fungal infection (e.g., immunocompromised, advanced age, comorbidities, prolonged ICU-stay, unresolved intra-abdominal infections) (weak recommendation based on low-quality evidences, 2C)
我們建議不要將抗真菌藥物作為消化性潰瘍穿孔患者的標準經驗性治療。真菌感染高風險患者（例如，免疫功能低下、高齡、合併症、ICU 住院時間延長、腹腔內感染未解決）應給予抗真菌藥物（基於低質量證據的弱推薦，2C）

The perforation of a peptic ulcer almost invariably leads to peritonitis due to the spillage of gastroduodenal content into the peritoneal cavity; this event brings a great burden of morbidity, which ranges from 17% to 63%, and is usually represented by pulmonary and wound infections [66]. Bacteria involved in peritoneal sepsis vary according to the etiology of the peritonitis, including the site of perforation. They are usually represented by gram-positive, gram-negative as well as anaerobic species [71]. Samples of peritoneal fluid should be collected in perforated patients because fungal infections after perforation are common and are associated with longer hospital stay, higher rate of surgical site infections (SSI), and increased mortality, as reported in a prospective study by Shan and coworkers [72]. In the same way, Prakash and coworkers [73] demonstrated in a prospective study on 84 patients undergoing surgery for perforation peritonitis that mortality was higher in patients having positive peritoneal fluid cultures (p < 0.001) compared with those with negative cultures, and in those subjects having mixed bacterial and fungal positive cultures compared with those with isolated bacterial cultures (p < 0.001).
消化性潰瘍的穿孔幾乎總是由於胃十二指腸內容物溢出到腹膜腔中而導致腹膜炎;這種事件帶來很大的發病負擔，發病率在 17%-63%之間，通常表現為肺部和傷口感染[66]。腹膜膿毒症的細菌因腹膜炎的病因而異，包括穿孔部位。它們通常以革蘭氏陽性、革蘭氏陰性和厭氧菌種為代表[71]。正如 Shan 及其同事的一項前瞻性研究報導的那樣，穿孔后的真菌感染很常見，並且與住院時間延長、手術部位感染率（SSI）升高和死亡率增加有關，因此應採集穿孔患者的腹膜液樣本[72]。同樣，Prakash 及其同事[73]在一項針對 84 例接受穿孔性腹膜炎手術的患者的前瞻性研究中證明，與陰性培養的患者相比，腹膜液培養陽性的患者死亡率更高（p < 0.001），細菌和真菌混合培養陽性的受試者與分離細菌培養的患者相比（p < 0.001）。

Notwithstanding positive peritoneal fungal culture is a significant risk factor for adverse outcome in patients with PPU [72, 73], the addition of an antifungal therapy to a broad-spectrum antibiotic therapy is still a matter of debate [74]. While antifungal therapy is recommended for hospital-acquired infections and in patients critically ill or severely immunocompromised [75], in case of community-acquired fungal infection, it has been suggested that antifungal therapy should be reserved for only clinically severe cases [76].
儘管腹膜真菌培養陽性是 PPU 患者不良結局的重要危險因素[72,73]，但在廣譜抗生素治療中加入抗真菌治療仍存在爭議[74]。雖然推薦對醫院獲得性感染以及危重症患者或重度免疫功能低下患者進行抗真菌治療[75]，但對於社區獲得性真菌感染，有人建議僅對臨床重症病例進行抗真菌治療[76]。

In a retrospective analysis of 133 patients admitted to the emergency department for abdominal pain due peptic perforation, Li and coworkers [74] demonstrated that there was not a statistically significant difference in survival rate between patients who received antifungal therapy and those who did not and that, on a multivariate analysis, only shock on admission and an APACHE score higher than 20 were independent risk factors for a poor outcome. According to this evidence, antifungal therapy does not benefit patients suffering from PPU peritonitis with Candida spp. isolated from peritoneal fluid cultures in general, and antifungal therapy should be reserved for patients who are critically ill and/or severely immunocompromised.
在一項回顧性分析中，133 例因消化性穿孔引起的腹痛而入院的急診患者，Li 及其同事[74]發現，接受抗真菌治療的患者和未接受抗真菌治療的患者之間的生存率沒有統計學上的顯著差異，並且在多變數分析中，只有入院時休克和 APACHE 評分高於 20 是預後不良的獨立危險因素。根據該證據，抗真菌治療對從腹膜液培養物中分離的念珠菌屬 PPU 腹膜炎患者無益，抗真菌治療應僅用於危重和/或嚴重免疫功能低下的患者。

In patients with perforated peptic ulcer, which antimicrobial regimen should be used and what is its correct duration?
消化性潰瘍穿孔患者應採用哪種抗菌方案，正確的持續時間是多少？

In patients with perforated peptic ulcer, we recommend to start as soon as possible an empiric broad-spectrum antibiotic regimen against a mixture of Gram-negative, Gram-positive, and anaerobic bacteria, possibly after peritoneal fluid has been collected (Strong recommendation based on low-quality evidences, 1C)
對於穿孔性消化性潰瘍患者，我們建議在收集腹膜液后儘快開始針對革蘭氏陰性菌、革蘭氏陽性菌和厭氧菌混合物的經驗性廣譜抗生素方案（基於低質量證據的強烈推薦，1C）

In patients with perforated peptic ulcer, we suggest a short-course (3–5 days or until inflammatory markers normalize) antibiotic therapy (weak recommendation based on low-quality evidences, 2C).
對於穿孔性消化性潰瘍患者，我們建議短期（3-5 天或直到炎症標誌物恢復正常）抗生素治療（基於低質量證據的弱推薦，2C）。

Perforated peptic ulcer peritonitis is by definition poly-microbial. Gram-negative and Gram-positive as well as anaerobic bacteria and yeasts can be isolated from peritoneal fluid cultures. Antimicrobial therapy, together with adequate source control, plays a pivotal role in the management of patients with peritonitis, especially in those who are immunocompromised. As stated in a previous published paper [71], an empiric broad-spectrum antimicrobial therapy should be started as soon as possible, and possibly after peritoneal fluid sample collection, irrespective of the presence of severe sepsis or septic shock. In these patients, a de-escalation approach is warranted, to avoid the onset of microbial resistances and to promptly treat eventual sepsis. The empiric antimicrobial regimen should be single or combined, according to the range requirements of antimicrobial coverage and the risk factors for major resistance patterns [76].
穿孔性消化性潰瘍性腹膜炎根據定義是多菌性。革蘭氏陰性菌和革蘭氏陽性菌以及厭氧菌和酵母菌可以從腹膜液培養物中分離出來。抗菌治療以及充分的源頭控制在腹膜炎患者的管理中起著關鍵作用，尤其是免疫功能低下的患者。如先前發表的一篇論文[71]所述，無論是否存在嚴重膿毒症或膿毒性休克，都應儘快 開始經驗性廣譜抗菌治療，並可能在腹膜液樣本採集后開始。對於這些患者，需要採取降級方法，以避免微生物耐葯性的發生並及時治療最終的膿毒癥。經驗性抗菌藥物治療方案應為單一或聯合，根據抗菌藥物覆蓋範圍要求和主要耐葯模式的危險因素[76]。

Modification of the drug regimen becomes possible when cultures are available, and clinical status can be better assessed. If inflammatory markers do not improve, it is mandatory to rule out other extra-abdominal sources of infections or different pathogens [71]. As widely accepted [71], a beta-lactam/beta-lactamase inhibitor can be used as first-line therapy in case of intra-abdominal infections, due to its vigorous in vitro activity against gram-positive, gram-negative, and anaerobic bacteria [77]. The principles of empiric antibiotic treatment should be defined according to the most frequently isolated bacteria, always taking into consideration the local trend of antibiotic resistance. In this era of prevalent drug-resistant microorganisms, the threat of resistance is a source of major concern that cannot be ignored. In the past 20 years, incidence of healthcare-associated IAIs caused by MDROs has risen dramatically [78], probably in correlation with escalating levels of antibiotic exposure and increasing frequency of patients with one or more predisposing conditions, including elevated severity of illness, advanced age, degree of organ dysfunction, low albumin levels, poor nutritional status, immunosuppression, presence of malignancy, and other comorbidities. The first step in determining potential resistance patterns of a given infection is by establishing whether the infection is community-acquired or healthcare-associated (nosocomial). The spectrum of microorganisms involved in nosocomial infections is significantly broader than in community-acquired infections.
當培養物可用時，可以修改藥物方案，並且可以更好地評估臨床狀態。如果炎症標誌物沒有改善，則必須排除其他腹外感染源或不同病原體[71]。正如廣泛接受的[71]，β-內醯胺類/β-內醯胺酶抑製劑可作為腹腔內感染的一線治療，因為它對革蘭氏陽性菌、革蘭氏陰性菌和厭氧菌具有強烈的體外活性[77]。經驗性抗生素治療的原則應根據最常分離的細菌來定義，並始終考慮當地抗生素耐藥性的趨勢。在這個耐葯微生物盛行的時代，耐藥性的威脅是一個不容忽視的重大關注來源。在過去 20 年中，MDROs 引起的醫療保健相關 IAIs 的發病率急劇上升[78]，這可能與抗生素暴露水準的上升和患有一種或多種易感疾病的患者頻率增加有關，包括疾病嚴重程度升高、高齡、器官功能障礙程度、白蛋白水準低、營養狀況不佳、免疫抑制、惡性腫瘤、 和其他合併症。確定特定感染的潛在耐葯模式的第一步是確定感染是社區獲得性感染還是醫療保健相關（院內感染）。院內感染涉及的微生物範圍明顯廣泛於社區獲得性感染。

Quinolone resistance, prevalence of ESBL-producing bacteria, prevalence and mechanisms of carbapenem resistance in the local environment, and the place of recent traveling should be always taken into account when an antibiotic therapy is administered empirically. Generally, the most important factors in predicting the presence of resistant pathogens in intra-abdominal infections are acquisition in a healthcare setting (particularly if the patient becomes infected in the ICU or has been hospitalized for more than 1 week), corticosteroid use, organ transplantation, baseline pulmonary or hepatic disease, and previous antimicrobial therapy [78]. In patients with IAIs, when patients are not severely ill and when source control is complete, a short course (3–5 days) of postoperative therapy is suggested. In 2015, a prospective study on appropriate duration of antimicrobial therapy was published [79]: the study randomized 518 patients with IAIs and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4 ± 1 calendar days. In patients with intra-abdominal infections who had undergone an adequate source control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. In this study, most patients were not severely ill.
在經驗上進行抗生素治療時，應始終考慮喹諾酮類耐藥性、產生 ESBL 的細菌的流行率、碳青黴烯類耐藥性在當地環境中的患病率和機制以及最近旅行的地點。一般來說，預測腹腔內感染中是否存在耐葯病原體的最重要因素是醫療環境中的感染（特別是患者在 ICU 感染或住院超過 1 周）、皮質類固醇的使用、器官移植、基線肺或肝臟疾病以及既往抗菌治療[78].對於 IAI 患者，當患者病情不嚴重且源控制完成時，建議進行短期（3-5 天）術后治療。2015 年，發表了一項關於適當持續時間的前瞻性研究[79]：該研究將 518 例 IAIs 和充分來源控制的患者隨機分配至發熱、白細胞增多和腸梗阻消退后 2 天接受抗生素治療，最多治療 10 天（對照組），或接受固定療程的抗生素治療（實驗組）4±1 個日曆日。在接受充分源控制程式的腹腔內感染患者中，固定持續時間抗生素治療（約 4 天）後的結局與延長至生理異常消退後的較長療程（約 8 天）后的結局相似。在這項研究中，大多數患者病情並不嚴重。

If yeast are isolated in the peritoneal fluid culture, the antifungal regimen should be selected according to the clinical and immunological status of the patient, severity of disease, prior exposure to other antifungal therapies, and type of infection (community-acquired vs. hospital-acquired) [80]. The duration of hospital stay is a concern, because prolonged stay is associated with antifungal resistance of Candida strains [81]. Moreover, biofilm formation of fungi usually goes along with significant changes in virulence and resistance because, once embedded into biofilm, fungi become more protected against the fungicidal/fungistatic effect of drugs.
如果在腹膜液培養中分離出酵母菌，應根據患者的臨床和免疫學狀態、疾病嚴重程度、既往接受過其他抗真菌治療的經歷以及感染類型（社區獲得性 vs. 醫院獲得性）來選擇抗真菌治療方案[80]。住院時間長短是一個問題，因為住院時間延長與念珠菌菌株的抗真菌耐藥性有關[81]。此外，真菌的生物膜形成通常伴隨著毒力和耐藥性的顯著變化，因為一旦嵌入生物膜中，真菌就會更好地抵禦藥物的殺菌/抑菌作用。

Four classes of antifungal drugs are available [82]:
抗真菌藥物有 4 類[82]：

• 1) Azoles (fluconazole, itraconazole, voroconazole, and posaconazole), with fungistatic action against most Candida spp.;
  唑類藥物（氟康唑、伊曲康唑、伏羅康唑和泊沙康唑），對大多數念珠菌屬具有抑菌作用;

• 2) Echinocandins (caspofungin, micafungin, anidulafungin), with fungicidal effect;
  棘白菌素（卡泊芬凈、米卡芬凈、阿尼杜拉芬凈），具有殺菌作用;

• 3) Polyenes (deoxycholate and liposomal formulations of amphotericin B), with fungicidal effect but moderate peritoneal penetration;
  多烯類（兩性黴素 B 的去氧膽酸鹽和脂質體制劑），具有殺菌作用，但腹膜滲透性適中;

• 4) Flucytosine, only used in combination with another antifungal agent in difficult-to-treat cases, because of the high risk of resistance.
  氟胞嘧啶，僅在難以治療的病例中與另一種抗真菌藥物聯合使用，因為耐葯風險高。

Fungistatic drugs should be used in critically ill patients at low-risk for invasive Candida infections, without prior exposure to azoles, and the therapy should be administered for 7-10 days or until definitive negative fluid cultures. In high-risk patients with or without prior exposure to azoles, echinocandins should be preferred. The duration of treatment depends on the extent of organ involvement. If candidemia is detected, the administration should be prolonged at least 14 days after the end of episode [82].
侵襲性念珠菌感染風險低的危重患者應使用抑菌藥物，且事先未接觸過唑類藥物，治療應持續 7-10 天或直至液體培養最終陰性。對於有或沒有既往接觸過唑類藥物的高危患者，應首選棘白菌素。治療的持續時間取決於器官受累的程度。如果檢測到念珠菌血症，應在發作結束后至少延長給葯 14 日[82]。

Following we report the suggested antibiotic regimens according to WSES guidelines on intra-abdominal infections.
接下來，我們根據 WSES 關於腹腔內感染的指南報告了建議的抗生素治療方案。

Community-acquired  社區獲得

1) Empiric antibiotic regimens for non-critically ill patients with IAIs and normal renal function:
1） IAIs 且腎功能正常的非危重患者經驗性抗生素治療方案：

• Amoxicillin/clavulanate 1.2-2.2 g 6-hourly or ceftriaxone 2 g 24-hourly + metronidazole 500 mg 6-hourly or cefotaxime 2 g 8-hourly + metronidazole 500 mg 6-hourly
  阿莫西林/克拉維酸鹽 1.2-2.2 g，每次 6 小時或頭孢曲松 2 g，每 24 小時 + 甲硝唑 500 mg，每 6 小時或頭孢噻肟 2 g，每 8 小時 + 甲硝唑 500 mg，每 6 小時一次

• In patients with beta-lactam allergy: ciprofloxacin 400 mg 8-hourly + metronidazole 500 mg 6-hourly
  β-內醯胺類過敏患者：環丙沙星 400 毫克，每次 8 小時 + 甲硝唑 500 毫克，每次 6 小時

• Patients at risk for infection with community-acquired ESBL-producing Enterobacteriacea: ertapenem 1 g 24 hourly or tigecycline 100 mg initial dose, then 50 mg 12-hourly
  有感染社區獲得性 ESBL 腸桿菌感染風險的患者：厄他培南 1 g 24 小時或替加環素 100 mg 初始劑量，然後 50 mg 12 小時

2) Empiric antibiotic regimens for critically ill patients with IAIs and Normal renal function:
2） IAIs 危重患者腎功能正常的經驗性抗生素治療方案：

• Piperacillin/tazobactam 4.5 g 6-hourly or cefepime 2 g 8-hourly + metronidazole 500 mg 6-hourly
  哌拉西林/他唑巴坦 4.5 克，每次 6 小時或頭孢吡肟 2 克，每次 8 小時 + 甲硝唑 500 毫克，每次 6 小時

• patients at risk for infection with community-acquired ESBL-producing Enterobacteriacea: meropenem 1 g 8-hourly or doripenem 500 mg 8-hourly or imipenem/cilastatin 1 g 8-hourly
  有感染社區獲得性 ESBL 腸桿菌菌感染風險的患者：美羅培南 1 g 8 小時或多立培南 500 mg 8 小時或亞胺培南/西司他汀 1 g 8 小時

3) If antifungal therapy is indicated:
3） 如果需要抗真菌治療：

• Fluconazole (LD 12 mg/kg BW-800 mg; MD 6 mg/kg/day) should be given in critically ill patients, with community-acquired Candida peritonitis, no prior azole exposure, low-risk for infections with fluconazole-resistant Candida spp., as prophylaxis to prevent invasive infections
  氟康唑（LD 12 mg/kg BW-800 mg;MD 6 mg/kg/天）應用於社區獲得性念珠菌腹膜炎、既往未接觸過唑類藥物、氟康唑耐藥念珠菌屬感染風險低的危重患者，作為預防侵襲性感染的預防

• Echinocandin antifungals are recommended as first-line therapy for invasive infections, and candidemia in non-neutropenic critically ill patients
  棘白菌素抗真菌葯被推薦作為非中性粒細胞減少性危重患者侵襲性感染和念珠菌血症的一線治療

• Amphotericin B (3–5 mg/day) should be considered if alternative therapy is not available or in case of intolerance to echinocandin or azoles
  如果無法替代療法或對棘白菌素或唑類藥物不耐受，應考慮兩性黴素 B（3-5 mg/天）

Healthcare-associated  醫療保健相關

1) Empiric antimicrobial regimens for non-critically ill patients with IAIs and normal renal function:
1） IAIs 且腎功能正常的非危重患者經驗性抗菌方案：

• Piperacillin/tazobactam 4.5 g 6-hourly
  哌拉西林/他唑巴坦 4.5 克，每次 6 小時

•  In patients at higher risk for infection with MDROs including recent antibiotic exposure, patient living in a nursing home or long-stay care with an indwelling catheter or postoperative infections
  在感染 MDRO 風險較高的患者中，包括最近接觸過抗生素、住在療養院或留置導管的長期護理或術后感染的患者

  ○ Meropenem 1 g 8-hourly +/− ampicillin 2 g 6-hourly or
  ○ 美羅培南 1 克，每 8 小時一次 +/- 氨苄青黴素 2 克，每 6 小時一次或

  ○ Doripenem 500 mg 8-hourly +/− ampicillin 2 g 6-hourly or
  ○ 多利培南 500 mg，每 8 小時一次 +/- 氨苄青黴素 2 g，每 6 小時一次或

  ○ Imipenem/Cilastatin 1 g 8-hourly or
  ○ 亞胺培南/西司他丁 1 克，每 8 小時一次或

  ○ As a carbapenem-sparing regimen piperacillin/tazobactam 4.5 g 6-hourly + tigecycline 100 mg initial dose, then 50 mg 12-hourly
  ○ 作為碳青霉烯類保留方案，哌拉西林/他唑巴坦 4.5 g 6 小時 + 替加環素 100 mg 初始劑量，然後 50 mg 12 小時

2) Empiric antimicrobial regimens for critically ill patients with IAIs normal renal function
2） IAI 腎功能正常危重患者的經驗性抗菌方案

• Meropenem 1 g 8-hourly or
  美羅培南 1 克，每次 8 小時或

• Doripenem 500 mg 8-hourly or
  多利培南 500 毫克，每 8 小時一次或

• Imipenem/cilastatin 1 g 8-hourly
  亞胺培南/西司他丁 1 克，每 8 小時一次

+

• Vancomycin 25–30 mg/kg loading dose then 15–20 mg/kg/dose 8-hourly or
  萬古黴素 25–30 mg/kg 負荷劑量，然後 15–20 mg/kg/劑量，每 8 小時一次或

• Teicoplanin 12 mg/kg 12-hourly times 3 loading dose then 12 mg/kg 24-hourly
  替考拉寧 12 mg/kg 12 小時乘以 3 負荷劑量，然後 12 mg/kg 24 小時

3) In patients at risk for infection with vancomycin-resistant Enterococci (VRE) including patients with previous enterococcal infection or colonization, immunocompromised patients, patients with long ICU stay, or recent vancomycin exposure:
3） 有感染萬古黴素耐葯腸球菌 （VRE） 風險的患者，包括既往感染過腸球菌或定植的患者、免疫功能低下的患者、長期入住 ICU 的患者或近期接觸過萬古黴素的患者：

• Linezolid 600 mg 12-hourly or
  利奈唑胺 600 mg，每 12 小時一次或

• Daptomycin 6 mg/kg 24-hourly
  達托黴素 6 mg/kg，24 小時

Bleeding peptic ulcer  出血性消化性潰瘍

Diagnosis  診斷

In patients with suspected bleeding peptic ulcer, which biochemical and imaging investigations should be requested?
對於疑似出血性消化性潰瘍的患者，應要求進行哪些生化和影像學檢查？

In patients with suspected bleeding peptic ulcer, we recommend blood-typing, determinations of hemoglobin, hematocrit and electrolytes, and coagulation assessment (strong recommendation based on very low-quality evidences, 1D).
對於疑似出血性消化性潰瘍的患者，我們建議進行血型分析、血紅蛋白、血細胞比容和電解質測定以及凝血評估（基於極低質量證據的強烈推薦，1D）。

In patients with suspected bleeding peptic ulcer, when endoscopy is not available, we suggest performing contrast-enhanced CT scan (weak recommendation based on very low-quality evidences, 2D)
對於疑似出血性消化性潰瘍的患者，當無法進行內鏡檢查時，我們建議進行對比增強 CT 掃描（基於極低質量證據的弱推薦，2D）

Peptic ulcer is still the primary cause of non-variceal upper gastrointestinal bleeding and hypovolemic shock or its consequences is a major cause of mortality in acute upper gastrointestinal bleeding [1, 83]. In the acute setting, with the suspicion of bleeding peptic ulcer, blood tests that include blood-typing and cross-matching with determinations of hemoglobin, hematocrit, electrolytes, and coagulation assessment should be performed in all patients. Alteration of coagulation with INR greater than 1.5 is associated with an increased risk of mortality [84].
消化性潰瘍仍然是非靜脈曲張性上消化道出血和低血容量性休克的主要原因，其後果是急性上消化道出血死亡的主要原因[1,83]。 在急性情況下，如果懷疑消化性潰瘍出血，應對所有患者進行血液檢查，包括血型和交叉配血，以測定血紅蛋白、血細胞比容、電解質和凝血評估。INR 大於 1.5 時凝血改變與死亡風險增加相關[84]。

Data are limited in the literature on the use of CT-scan in the evaluation of gastrointestinal bleeding. Given the assumption that gastroscopy is the first diagnostic step, in patients where it is negative or not feasible, CT-scan may be a valuable tool to detect the site and the degree of the bleeding. Otherwise, CT angiography is the first-line investigation of choice for undifferentiated major gastrointestinal hemorrhage (being particularly useful for the localization of small and large intestinal acute hemorrhage). There are increasing data to suggest that CT-scan should be the “next step” investigative procedure in cases of active GI hemorrhage [85, 86].
關於使用 CT 掃描評估消化道出血的文獻中的數據有限。假設胃鏡檢查是第一個診斷步驟，對於陰性或不可行的患者，CT 掃描可能是檢測出血部位和程度的寶貴工具。否則，CT 血管造影是未分化大消化道出血的首選一線檢查（對小腸和大腸急性出血的定位特別有用）。越來越多的數據表明，對於活動性胃腸道出血，CT 掃描應該是“下一步”的檢查程式[85,86]。

In patients with suspected bleeding peptic ulcer, what is the diagnostic role of endoscopy?
在疑似出血性消化性潰瘍患者中，內鏡檢查的診斷作用是什麼？

In patients with suspected bleeding peptic, ulcer, we recommend performing endoscopy as soon as possible, especially in high-risk patients (Strong recommendation based on low-quality evidences, 1C)
對於疑似出血性消化性、潰瘍的患者，我們建議儘快進行內鏡檢查，尤其是高危患者（基於低品質證據的強烈推薦，1C）

Gastroscopy must take place as soon as possible. Many studies, including a meta-analysis of randomized controlled trials [87], have shown the role of gastroscopy in reducing rebleeding, need for surgery, and mortality. Early endoscopy done within 24 h provides both an effective therapy of the bleeding and prognostic information based on endoscopic stigmata [88, 89].
胃鏡檢查必須儘快進行。許多研究，包括一項 meta 分析，包括一項隨機對照試驗[87]，都表明胃鏡檢查在減少再出血、手術需求和死亡率方面的作用。在 24 h 內進行的早期內鏡檢查既能有效治療出血，又能根據內鏡柱頭提供預後資訊[88,89]。

In patients with bleeding peptic ulcer, are the endoscopic findings useful to determine the risk for rebleeding and how do they affect the clinical management?
在出血性消化性潰瘍患者中，內鏡檢查結果是否有助於確定再出血的風險以及它們如何影響臨床管理？

We suggest guiding management decisions according to stigmata of recent hemorrhage during endoscopy because they can predict the risk of further bleeding (strong recommendation based on low-quality evidences, 1C)
我們建議根據內鏡檢查期間近期出血的恥辱來指導治療決策，因為它們可以預測進一步出血的風險（基於低品質證據的強烈推薦，1C）

The gastroscopy findings can be classified using the modified Forrest classification. With the identification of lesions with high-risk stigmata, it is possible to stratify the risk of rebleeding, the need for intervention, and mortality [89, 90]. Furthermore, gastroscopy is essential in identifying patients with a low risk that may be discharged early [87, 88]. Numerous scores have been tested to predict the need for surgery and gastroscopy, the Glasgow-Blatchford Score (GBS), the Rockall score, and the AIMS65 being the most widely evaluated and adopted. Risk stratification should identify high-risk patients for early intervention and reduce the duration of hospital stay for low-risk patients [91, 92].
胃鏡檢查結果可以使用改良的 Forrest 分類進行分類。通過識別具有高危柱頭的病變，可以對再出血的風險、干預的必要性和死亡率進行分層[89,90]。 此外，胃鏡檢查對於識別可能提前出院的低風險患者至關重要[87,88]。 已經測試了許多分數來預測手術和胃鏡檢查的必要性，格拉斯哥-布拉奇福德評分 （GBS）、Rockall 評分和 AIMS65 是最廣泛評估和採用的。風險分層應識別高危患者進行早期干預，並縮短低危患者的住院時間[91,92]。

Resuscitation  復甦

In patients with bleeding peptic ulcer, which parameters should be evaluated at ED referral and which criteria should be adopted to define an unstable patient?
對於出血性消化性潰瘍患者，在急診轉診時應評估哪些參數，以及應採用哪些標準來定義不穩定的患者？

We recommend a rapid and careful surgical/medical evaluation of bleeding peptic ulcer disease patients to prevent further bleeding and to reduce mortality (strong recommendation based on very low-quality evidences, 1D)
我們建議對出血性消化性潰瘍病患者進行快速、仔細的手術/醫學評估，以防止進一步出血並降低死亡率（基於極低質量證據的強烈建議，1D）

We recommend evaluating several elements (symptoms, signs, and laboratory findings) to assess the stability/instability of patients with bleeding peptic ulcer at ED referral (strong recommendation based on low quality evidences, 1C)
我們建議評估幾個因素（癥狀、體征和實驗室檢查結果），以評估出血性消化性潰瘍患者在急診轉診時的穩定性/不穩定性（基於低質量證據的強烈建議，1C）

In patients with bleeding peptic ulcer, we suggest evaluating patients according to Rockall and Glasgow-Blatchford scoring systems to assess the severity of the disease and to guide therapy (weak recommendation based on low-quality evidences, 1C).
對於出血性消化性潰瘍患者，我們建議根據 Rockall 和 Glasgow-Blatchford 評分系統評估患者，以評估疾病的嚴重程度並指導治療（基於低質量證據的弱推薦，1C）。

Bleeding peptic ulcer disease is a clinical emergency requiring a rapid surgical/medical evaluation to assess the stability of the clinical picture; the approach is similar to the bleeding trauma patient [93]. In this regard, we suggest referring to the last edition of the European guideline on management of major bleeding and coagulopathy following trauma [94]. The parameters that should be assessed at ER referral are the same as reported in the American College of Surgeons Advanced Trauma Life Support (ATLS) (American College of Surgeons Committee on Trauma. ATLS® Student Manual 10th Edition; 2018) classification of blood loss (heart rate, blood pressure, pulse pressure, respiratory rate, urine output, Glasgow Coma Scale score, and base deficit). Moreover, it is very important to take an accurate medical history [93] especially regarding:
出血性消化性潰瘍病是一種臨床急症，需要快速手術/醫學評估以評估臨床表現的穩定性;該方法與出血創傷患者類似[93]。對此，我們建議參考歐洲創傷后大出血和凝血病管理指南的最新版本[94]。急診轉診時應評估的參數與美國外科醫師學會高級創傷生命支援 （ATLS）（美國外科醫師學會創傷委員會）中報告的參數相同。ATLS® 學生手冊第 10 版;2018）失血量分類（心率、血壓、脈壓、呼吸頻率、尿量、格拉斯哥昏迷量表評分和鹼基缺陷）。此外，記錄準確的病史非常重要[93]，特別是關於：

• Drugs and diseases that may affect the coagulation status (i.e., antiplatelets, anticoagulants, hepatic failure)
  可能影響凝血狀態的藥物和疾病（即抗血小板、抗凝、肝功能衰竭）

• Cardiac (i.e., coronary artery disease) and pulmonary diseases that may make patients more susceptible to adverse effects of anemia
  心臟（即冠狀動脈疾病）和肺部疾病可能使患者更容易受到貧血不良影響

• Neurological diseases (i.e., dementia) that may predispose patients to pulmonary aspiration of gastric contents.
  可能使患者易患胃內容物肺誤吸的神經系統疾病（即失智）。

Several scoring systems are available for the evaluation of patients with upper gastrointestinal bleeding. The Rockall score [95] can be utilized to identify patients at risk of adverse outcomes where the Glasgow-Blatchford bleeding score [96] identifies patients needing interventions such as blood transfusions or endoscopy.
有幾種評分系統可用於評估上消化道出血患者。Rockall 評分[95]可用於識別有不良結局風險的患者，而 Glasgow-Blatchford 出血評分[96]可識別需要輸血或內鏡檢查等干預措施的患者。

In patients with bleeding peptic ulcer, which are the appropriate targets for resuscitation (hemoglobin level, blood pressure/heart rate, lactates level, others)?
對於出血性消化性潰瘍患者，哪些是合適的復甦目標（血紅蛋白水準、血壓/心率、乳酸水準等）？

We recommend several resuscitation targets, similar to those of damage control resuscitation in the bleeding trauma patient (weak recommendation based on low-quality evidences, 1C).
我們推薦幾個復甦目標，類似於出血創傷患者的損傷控制復甦目標（基於低質量證據的弱推薦，1C）。

In patients with bleeding peptic ulcer, we recommend to maintain an Hb level of at least > 7 g/dl during the resuscitation phase (strong recommendation based on moderate-quality evidences, 1B).
對於出血性消化性潰瘍患者，我們建議在復甦階段將 Hb 水平維持在至少 > 7 g/dl（基於中等質量證據的強烈建議，1B）。

Early resuscitation of patients with upper gastrointestinal bleeding is of paramount importance to reduce mortality; this must proceed simultaneously with endoscopic and surgical procedures [97]. A rapid ABC (airway, breathing, and circulation) evaluation should be done immediately. Appropriate targets for resuscitation in bleeding peptic ulcer patients can be considered the same used in bleeding trauma patients (systolic blood pressure of 90–100 mmHg until major bleeding has been stopped; normalization of lactate and base deficit; hemoglobin 7–9 g/dl; correction/prevention of coagulopathy); for this reason, we refer to the abovementioned guideline [94]. Regarding hemoglobin level, a randomized controlled trial comparing the efficacy and safety of a restrictive transfusion strategy (transfusion with an Hb > 7 g/dl) with those of a liberal transfusion strategy (transfusion with an Hb > 9 g/dl) in severe acute gastrointestinal bleeding has been performed [98]. The restrictive strategy, compared with the liberal strategy, has been significantly associated with a better outcome.
上消化道出血患者的早期復甦對於降低死亡率至關重要;這必須與內鏡和外科手術同時進行[97]。應立即進行快速 ABC（氣道、呼吸和迴圈）評估。出血性消化性潰瘍患者的適當復甦目標可認為與出血性創傷患者相同（收縮壓為 90-100 mmHg 直至大出血停止;乳酸和鹼缺乏正常化;血紅蛋白 7-9 g/dl;糾正/預防凝血病）;因此，我們參考了上述指南[94]。關於血紅蛋白水準，一項隨機對照試驗比較了限制性輸血策略（輸注 Hb > 7g/dl）與自由輸血策略（輸注 Hb > 9g/dl）治療嚴重急性消化道出血的療效和安全性[98]。與自由主義策略相比，限制性策略與更好的結果顯著相關。

Non-operative management—endoscopic treatment
非手術治療——內鏡治療

In patients with bleeding peptic ulcer, which are the indications for non-operative management?
出血性消化性潰瘍患者有哪些非手術治療指徵？

In patients with bleeding peptic ulcer, we recommend non-operative management as the first line of management after endoscopy (strong recommendation based on low-quality evidences, 1C).
對於出血性消化性潰瘍患者，我們建議將非手術治療作為內鏡檢查后的一線治療（基於低品質證據的強烈建議，1C）。

Non-operative management of bleeding peptic ulcer incorporates principles of ABCDE [99]:
出血性消化性潰瘍的非手術治療採用 ABCDE 原則[99]：

• Airway control  氣道控制

• Breathing—ventilation and oxygenation
  呼吸——通氣和氧合

• Circulation—fluid resuscitation and control of bleeding
  迴圈——液體復甦和控制出血

• Drugs—pharmacotherapy with PPIs, prokinetics, etc.
  藥物——PPI、促動力藥等藥物治療。

• Endoscopy (diagnostic and therapeutic) or embolization (therapeutic)
  內窺鏡檢查（診斷和治療）或栓塞（治療）

A meta-analysis from Barkun et al. [100] that included forty-one randomized trials showed that all endoscopic therapies decreased rebleeding versus pharmacotherapy alone. Endoscopy is indicated to establish diagnosis and institute therapy for bleeding peptic ulcer [101]. In acutely bleeding ulcers, endoscopy is a part of resuscitation.
Barkun 等[100]的一項 meta 分析納入了 41 項隨機試驗，結果顯示，與單獨的藥物治療相比，所有內鏡治療都能減少再出血。內鏡檢查可用於確定消化性潰瘍出血的診斷和治療[101]。在急性出血性潰瘍中，內窺鏡檢查是復甦的一部分。

In patients with bleeding peptic ulcer, which are the indications for endoscopic treatment?
消化性潰瘍出血患者，內鏡治療的指征有哪些？

In patients with bleeding peptic ulcer, we recommend endoscopic treatment to achieve hemostasis and reduce re-bleeding, the need for surgery, and mortality (strong recommendation based on low-quality evidences, 1C).
對於出血性消化性潰瘍患者，我們建議進行內鏡治療以實現止血並減少再出血、手術需求和死亡率（基於低質量證據的強烈推薦，1C）。

We suggest stratifying patients based on the Blatchford score and adopting a risk-stratified management (weak recommendation based on very low-quality evidences, 2D):
我們建議根據 Blatchford 評分對患者進行分層，並採用風險分層管理（基於極低質量證據的弱推薦，2D）：

• In the very low-risk group, we suggest outpatient endoscopy (weak recommendation based on low-quality evidences, 2C)
  在極低風險組，我們建議門診內鏡檢查（基於低質量證據的弱推薦，2C）

• In the low-risk group, we recommend early inpatient endoscopy (≤ 24 h of admission) (strong recommendation based on low-quality evidences, 1C).
  在低風險組中，我們建議早期住院內鏡檢查（入院后≤24 h）（基於低品質證據的強烈推薦，1C）。

• In the high-risk group, we recommend urgent inpatient endoscopy (≤ 12 h of admission) (strong recommendation based on low-quality evidences, 1C).
  在高危人群中，我們建議緊急住院內鏡檢查（入院后≤12 h）（基於低品質證據的強烈建議，1C）。

In patients with spurting ulcer (Forrest 1a), oozing ulcer (Forrest 1b), and ulcer with non-bleeding visible vessel (Forrest 2a), endoscopic hemostasis is recommended (strong recommendation based on low-quality evidences, 1C)
對於噴出性潰瘍（Forrest 1a）、滲出性潰瘍（Forrest 1b）和伴有非出血可見血管的潰瘍（Forrest 2a）的患者，建議進行內鏡下止血（基於低質量證據的強烈推薦，1C）

In patients with bleeding peptic ulcer, we suggest dual modality for endoscopic hemostasis (weak recommendation based on moderate-quality evidences, 2B)
對於出血性消化性潰瘍患者，我們建議採用雙重內鏡止血方式（基於中等質量證據的弱推薦，2B）

In patients with bleeding peptic ulcer, we suggest considering Doppler probe–guided endoscopic hemostasis if expertise is available (weak recommendation based on very low-quality evidences, 2D).
對於出血性消化性潰瘍患者，如果有專業知識，我們建議考慮多普勒探頭引導下內鏡下止血（基於極低質量證據的弱推薦，2D）。

Endoscopy not only establishes the diagnosis but also treats the bleeding. WSES advocates patients’ risk determination by using Blatchford score, Forrest classification, and clinical judgment. Three levels of risk stratification are proposed:
內窺鏡檢查不僅可以確定診斷，還可以治療出血。WSES 宣導使用 Blatchford 評分、Forrest 分類和臨床判斷來確定患者的風險。提出了三個級別的風險分層：

• Very low risk—safe for outpatient management, low risk of death
  極低風險 — 門診治療安全，死亡風險低

• Low risk—need for admission and early endoscopy
  低風險——需要入院和早期內鏡檢查

• High risk—need for resuscitation and urgent endoscopy
  高風險 - 需要復甦和緊急內窺鏡檢查

Risk stratification is based on many risk prediction models and Blatchford score is one of the most validated tools. In an international multicenter prospective study including 3012 patients, Stanley et al. [102] has shown that Blatchford score of 1 or less (very low-risk group) had a sensitivity of 98.6%, specificity of 34.6%, positive predictive value of 96.6%, and a negative predictive value of 56.0% for non-intervention and survival both as the combined endpoint. They also reported that a threshold Blatchford score of 7 or more (high-risk group) was best at predicting endoscopic treatment, with a sensitivity of 80.4%, specificity of 57.4%, positive predictive value of 31.3%, and negative predictive value of 92.4%. Endoscopy reassures a safe and early discharge in low-risk patients and assists therapy in high-risk patients. While the timing of endoscopy is determined by local protocols and resources, the sooner the better, WSES advocates to perform endoscopy at the earliest available opportunity regardless of the risk profile and the only limitation would be resources and expertise. Endoscopy by the “clock” is mere guidance, and if endoscopy could be done earlier, then a clinician should do it. Endoscopy is a part of the resuscitative strategy and blood transfusion should not replace early hemostasis. Dual modality of endoscopic hemostasis is advocated in preference to single modality. Marmo et al. has conducted a meta-analysis [103] including 20 randomized controlled trials and 2472 patients comparing dual therapy versus monotherapy in endoscopic treatment of high-risk bleeding ulcers and concluded that dual endoscopic therapy was superior to epinephrine injection alone in improving outcomes of patients with high-risk bleeding ulcers. In a Cochrane review including 19 randomized studies and 2033 patients, Vergara et al. [104] has shown that additional endoscopic treatment after epinephrine injection reduces further bleeding and the need for surgery in patients with high-risk bleeding peptic ulcer; however, they cannot conclude that a particular form of dual-modality treatment is equal or superior to another. Shi et al. have performed a network meta-analysis on dual therapy choices [105] and shown that the addition of mechanical therapy after epinephrine injection significantly reduced the probability of rebleeding (OR 0.19, 95% CI 0.07–0.52) and surgery (OR 0.10, 95% CI 0.01–0.50). Epinephrine with thermal therapy was shown to reduce the rebleeding rate (OR 0.30, 95% CI 0.10–0.91) but not the need for surgical intervention (OR 0.47, 95% CI 0.16–1.20). Hence, it appears that mechanical therapy along with epinephrine injection is adequate. In patients with adherent clot (Forrest 2b), WSES advocates non-aggressive clot irrigation-flushing attempts rather than mechanical dislodgment. The Asia-Pacific Working Group consensus advocates vigorous target irrigation for at least 5 min and dual-modality hemostasis for patients with adherent clots [106]. We advocate a cautious approach for dislodging the adherent clots. If expertise is available, a vigorous approach could be adopted [107]. The individual endoscopist should be at the liberty to make decisions and we propose individual judgment until further evidence is available to support that clot dislodgment improves outcomes. In the event of bleeding, therapy is strongly advocated. Newer modalities such as over the scope clips (OTSC), hemospray, EUS-guided ultrasound angiography, RFA, Endoclot, endoscopic band ligation, cryotherapy, Ankaferd blood stopper, and endoscopic suturing devices are available. Their role needs to be defined. There are six studies that have investigated the role of over the scope clips either as first-line or as second-line therapy for refractory bleeding [108,109,110,111,112,113]. Doppler probe–guided lesion assessment is more accurate than endoscopic scoring of predicting rebleeding risk. In a prospective cohort study including 163 patients, Jensen et al. showed spurting (Forrest 1a), visible vessel (Forrest 2a), and adherent clot (Forrest 2b) have a higher Doppler flow compared with oozing (Forrest 1b); Doppler assessment improved risk stratification [114]. It is important to note that rebleeding risk prediction is superior to Forrest classification system, i.e., Forrest 1b has low risk of rebleeding compared with Forrest 2a and Forrest 2b lesions. Doppler probe–guided lesion management is shown to reduce rebleeding and further intervention. In a single blinded randomized controlled study including 148 patients with 125 ulcers, Jensen et al. has shown that Doppler probe–guided endoscopic hemostasis significantly reduced 30-day rates of rebleeding compared with standard, visually guided hemostasis with the number needed to treat of 7 [115].
風險分層基於許多風險預測模型，而 Blatchford 評分是最經過驗證的工具之一。在一項納入 3012 例患者的國際多中心前瞻性研究中，Stanley 等[102]表明，Blatchford 評分為 1 分或更低（極低危組）的敏感性為 98.6%，特異度為 34.6%，陽性預測值為 96.6%，陰性預測值為 56.0%，均為聯合終點。他們還報告說，閾值 Blatchford 評分為 7 分或更高（高危組）最能預測內窺鏡治療，靈敏度為 80.4%，特異性為 57.4%，陽性預測值為 31.3%，陰性預測值為 92.4%。內窺鏡檢查可確保低風險患者的安全和早期出院，並協助高危患者的治療。雖然內窺鏡檢查的時間取決於當地的協議和資源，但越早越好，但 WSES 主張儘早進行內窺鏡檢查，無論風險狀況如何，唯一的限制是資源和專業知識。按“時鐘”進行內窺鏡檢查只是指導，如果內窺鏡檢查可以更早進行，那麼臨床醫生就應該這樣做。內窺鏡檢查是復甦策略的一部分，輸血不應取代早期止血。主張雙重內窺鏡止血方式而不是單一方式。Marmo 等進行了一項 meta 分析[103]，納入了 20 項隨機對照試驗和 2472 例患者，比較了內鏡下治療高危出血性潰瘍的雙重治療與單藥治療，得出的結論是，內鏡雙重治療在改善高危出血性潰瘍患者的預後方面優於單獨注射腎上腺素。 在一項包含 19 項隨機研究和 2033 名患者的 Cochrane 綜述中，Vergara 等[104]表明，腎上腺素注射后額外的內鏡治療可減少高危出血性消化性潰瘍患者的進一步出血和手術需求;然而，他們不能得出結論，一種特定形式的雙模式治療等於或優於另一種。Shi 等對雙重治療選擇進行了網路 meta 分析[105]，結果表明，注射腎上腺素后加用機械治療可顯著降低再出血（OR 0.19,95%CI 0.07-0.52）和手術（OR 0.10,95%CI 0.01-0.50）的概率。腎上腺素聯合熱療顯示可降低再出血率（OR 0.30,95% CI 0.10-0.91），但不需要手術干預（OR 0.47,95% CI 0.16-1.20）。因此，機械治療和腎上腺素注射似乎是足夠的。對於粘連凝塊 （Forrest 2b） 患者，WSES 提倡非侵襲性凝塊沖洗沖洗嘗試，而不是機械移位。亞太工作組一致認為，對於粘附血栓患者，應進行至少 5min 的強力目標沖洗和雙模式止血[106]。我們主張採取謹慎的方法去除粘附的凝塊。如果有專業知識，可以採取積極的方法[107]。個別內窺鏡醫師應該有自由做出決定，我們建議個人判斷，直到有進一步的證據支援凝塊移位可改善結局。如果發生出血，強烈建議進行治療。 可以使用較新的方式，例如內窺鏡夾 （OTSC）、血液噴霧劑、EUS 引導超聲血管造影、RFA、內膜囊、內窺鏡帶結紮術、冷凍療法、Ankaferd 止血器和內窺鏡縫合裝置。需要定義它們的作用。有 6 項研究探討了內窺鏡夾作為難治性出血一線或二線治療的作用[108,109,110,111,112,113]。 多普勒探頭引導下的病變評估比內窺鏡評分更準確，可以預測再出血風險。在一項包括 163 名患者的前瞻性佇列研究中，Jensen 等人顯示，與滲出 （Forrest 1b） 相比，噴出 （Forrest 1a）、可見血管 （Forrest 2a） 和粘附凝塊 （Forrest 2b） 具有更高的多普勒流量;多普勒評估改善了風險分層[114]。需要注意的是，再出血風險預測優於 Forrest 分類系統，即與 Forrest 2a 和 Forrest 2b 病灶相比，Forrest 1b 的再出血風險較低。多普勒探頭引導的病變管理被證明可以減少再出血和進一步干預。在一項納入 148 例 125 個潰瘍的單盲隨機對照研究中，Jensen 等發現，與標準的目視引導下止血相比，多普勒探頭引導下內鏡下止血可顯著降低 30 天再出血率，治療所需次數為 7 例[115]。

In patients with bleeding peptic ulcer, what is the appropriate pharmacological regimen (erythromycin, PPI, terlipressin, others)?
消化性潰瘍出血患者，合適的藥理方案（紅黴素、PPI、特利加壓素等）是什麼？

In patients with bleeding peptic ulcer, we suggest administering pre-endoscopy erythromycin (weak recommendation based on moderate-quality evidences, 2B).
對於出血性消化性潰瘍患者，我們建議在內鏡檢查前給予紅黴素（基於中等質量證據的弱推薦，2B）。

In patients with bleeding peptic ulcer, we suggest starting PPI therapy as soon as possible (weak recommendation based on moderate-quality evidences, 2B),
對於出血性消化性潰瘍患者，我們建議儘快開始 PPI 治療（基於中等質量證據的弱推薦，2B），

In patients with bleeding peptic ulcer, after successful endoscopic hemostasis, we suggest administration of high-dose PPI as continuous infusion for the first 72 h (weak recommendation based on moderate-quality evidences, 2B).
對於出血性消化性潰瘍患者，在內鏡止血成功后，我們建議在前 72 小時內連續輸注大劑量 PPI（基於中等質量證據的弱推薦，2B）。

In patients with bleeding peptic ulcer, we recommend PPI for 6–8 weeks following endoscopic treatment. Long-term PPI is not recommended unless the patient has ongoing NSAID use (strong recommendation based on moderate-quality evidences, 1B)
對於出血性消化性潰瘍患者，我們建議在內鏡治療后 6-8 周進行 PPI。除非患者持續使用 NSAID，否則不建議長期使用 PPI（基於中等質量證據的強烈推薦，1B）

The role of acid suppression in the treatment of peptic ulcer and its complications is well known [116], but the dosage and the duration of PPI administration for the treatment of bleeding peptic ulcer are still a matter of debate. Multiple studies highlighted that high-dose regimens of PPI [117] reduce rebleeding, surgical intervention, and mortality following endoscopic hemostasis. In a randomized placebo-controlled trial of 767 patients with peptic ulcer bleeding treated with endoscopic therapy because of high-risk stigmata, high-dose intravenous PPIs (80 mg of esomeprazole bolus plus 8 mg/h of continuous infusion for 72 h) significantly reduced rebleeding (5.9% vs. 10.3%, p = 0.03) and the need for endoscopic retreatment [118]. Similar results were found by meta-analysis; high-dose intravenous PPIs after endoscopic therapy significantly reduced rebleeding, need for surgery, and mortality compared with placebo/no therapy [119]. On the other hand, a Cochrane review [120] focusing on this topic and including twenty-two RCTs found insufficient evidence to conclude superiority, inferiority, or equivalence of high-dose PPI treatment over lower doses in peptic ulcer bleeding. Another systematic review from the Cochrane Collaboration [121] included six RCTs comprising 2223 patients and showed that PPI treatment initiated before endoscopy for upper gastrointestinal bleeding might reduce the proportion of patients with stigmata of recent bleeding at index endoscopy and significantly reduces the requirement for endoscopic therapy during index endoscopy. However, this study found no evidence that PPI treatment affects clinically important outcomes, namely mortality, rebleeding, or need for surgery. In the light of the above, the administration of high-dose PPI, starting prior to endoscopy and continuing for the first 72 h, seems reasonable and could be suggested, even though further studies are needed to give a strong recommendation. However, the use of proton-pump inhibitors should not replace urgent endoscopy in patients with active bleeding.
抑酸在消化性潰瘍及其併發症治療中的作用是眾所周知的[116]，但 PPI 治療出血性消化性潰瘍的劑量和持續時間仍存在爭議。多項研究強調，高劑量 PPI 方案[117]可減少內鏡止血后的再出血、手術干預和死亡率。一項隨機安慰劑對照試驗納入了 767 例因高危柱頭而接受內鏡治療的消化性潰瘍出血患者，結果顯示，大劑量靜脈注射 PPI（80mg 埃索美拉唑推注加 8mg/h 連續輸注 72h）可顯著減少再出血（5.9% vs. 10.3%，p = 0.03）和內鏡再治療的需要[118].薈萃分析也發現了類似的結果;與安慰劑/不治療相比，內鏡治療后大劑量靜脈注射 PPI 可顯著降低再出血、手術需求和死亡率[119]。另一方面，一項聚焦該主題並納入 22 項 RCT 的 Cochrane 綜述[120]發現，沒有足夠的證據得出大劑量 PPI 治療優於低劑量 PPI 治療消化性潰瘍出血的優劣性或等效性。Cochrane 協作[121]的另一項系統評價納入了 6 項 RCT，涉及 2223 名患者，結果表明，在內鏡檢查前開始 PPI 治療上消化道出血可能會降低指標內鏡檢查時近期出血恥辱的患者比例，並顯著降低指標內鏡檢查期間對內鏡治療的需求。然而，這項研究沒有發現任何證據表明 PPI 治療會影響臨床上重要的結果，即死亡率、再出血或手術需求。 鑒於上述情況，在內鏡檢查前開始並持續前 72 小時給予大劑量 PPI 似乎是合理的，並且可以建議，儘管需要進一步的研究才能給出強烈的建議。然而，質子泵抑製劑的使用不應取代活動性出血患者的緊急內鏡檢查。

A prokinetic drug given before endoscopy helps to empty stomach contents and improves viewing at endoscopy. Only five randomized trials and their pooled analyses have been published: three with the use of erythromycin and two with metoclopramide [122]. Pre-endoscopy erythromycin has been extensively studied and shown to enhance the visualization as well as reduce the need for second endoscopy [123, 124]. However, such practice has not shown to reduce the need for surgical intervention or impact mortality [125].
內窺鏡檢查前給予的促動力藥物有助於排空胃內容物並改善內窺鏡檢查時的視力。目前僅發表了 5 項隨機試驗及其匯總分析：3 項使用紅黴素，2 項使用甲氧氯普胺[122]。內鏡檢查前紅黴素已被廣泛研究，並證明可以增強可視化並減少第二次內鏡檢查的需要[123,124]。 然而，這種做法並未顯示出可以減少手術干預的需要或影響死亡率[125]。

After initial hemostasis, the risk of rebleeding must be minimized by adjunct therapies. In patients who have PPU complicated by bleeding, there is a 33% risk of rebleeding in 1–2 years. Furthermore, there is a 40–50% rebleeding risk over the subsequent 10 years following the initial episode of bleeding [126]. PPIs are recommended for 6–8 weeks following endoscopic treatment of peptic ulcer bleeding to allow mucosal healing [127]. Once mucosal healing has been achieved, how long PPIs should be continued is still controversial. Randomized prospective trials have demonstrated a benefit to long-term acid-suppression therapy in two settings: chronic NSAID users and H. pylori-infected patients [128]. Testing for H. pylori is recommended in all patients with BPU. This should be followed by eradication therapy for those who are H. pylori positive, with subsequent assessment of the effect of this therapy, and renewed treatment in those in whom eradication fails.
初始止血后，必須通過輔助治療將再出血的風險降至最低。對於 PPU 併發出血的患者，1-2 年內再出血的風險為 33%。此外，在首次出血發作后的 10 年內，再出血風險為 40-50%[126]。消化性潰瘍出血的內鏡治療后，建議在 6-8 周內使用 PPI，以促進黏膜癒合[127]。一旦實現粘膜癒合，PPI 應該持續多長時間仍存在爭議。隨機前瞻性試驗表明，長期抑酸治療在兩種情況下獲益：長期 NSAID 消費者和幽門螺桿菌感染患者[128]。建議對所有 BPU 患者進行幽門螺桿菌檢測。隨後，應對幽門螺桿菌陽性患者進行根除治療，隨後評估該療法的效果，並對根除失敗的患者進行重新治療。

In patients with recurrent bleeding from peptic ulcer, what is the role of non-operative management?
在消化性潰瘍復發性出血患者中，非手術治療的作用是什麼？

In patients with recurrent bleeding from peptic ulcer, we recommend endoscopy as a first-line treatment (strong recommendation based on low-quality evidences, 1C).
對於消化性潰瘍復發性出血的患者，我們推薦將內鏡檢查作為一線治療（基於低質量證據的強烈推薦，1C）。

In patients with recurrent bleeding, we suggest transcatheter angioembolization as an alternative option where resources are available (weak recommendation based on very low-quality evidences, 2D).
對於反覆出血的患者，我們建議在資源可用的情況下將經導管血管栓塞術作為替代選擇（基於極低質量證據的弱推薦，2D）。

Emergency endoscopy is the first-line management for rebleeding peptic ulcer [129]. Such endoscopy must be done at the earliest available opportunity. In patients who are hemodynamically stable, angioembolization of the bleeding vessel is an option. However, this should be carefully balanced for its inherent risks of patient transfer, contrast nephropathy, pancreatitis, or cholecystitis risk due to embolization material and risks associated with vascular access.
急診內鏡檢查是再出血性消化性潰瘍的一線治療[129]。必須儘早進行此類內窺鏡檢查。對於血流動力學穩定的患者，出血血管血管栓塞是一種選擇。然而，應仔細權衡其患者轉移、造影劑腎病、胰腺炎或栓塞材料導致的膽囊炎風險以及與血管通路相關的風險。

Angiography, embolization
血管造影、栓塞

In patients with bleeding peptic ulcer, which are the indications for angiography?
消化性潰瘍出血患者，血管造影的指征有哪些？

In patients with bleeding peptic ulcer, we suggest considering angiography for diagnostic purposes as a second-line investigation after a negative endoscopy (weak recommendation based on low-quality evidences, 2C).
對於出血性消化性潰瘍患者，我們建議考慮將血管造影作為內鏡檢查陰性后的二線檢查（基於低質量證據的弱推薦，2C）。

No recommendation can be made regarding the role of provocation angiography.
無法就激發血管造影的作用提出建議。

Angiography may assist both the diagnosis and the treatment of hemorrhage associated with peptic ulcer disease. However, endoscopy remains the first-line investigation of choice for an undifferentiated upper gastrointestinal hemorrhage [130]. Similarly, endoscopy is the first-line diagnostic modality for patients with suspected upper gastrointestinal hemorrhage from ulcer disease [130].
血管造影可能有助於診斷和治療消化性潰瘍病相關出血。然而，內鏡檢查仍然是未分化上消化道出血的首選一線檢查[130]。同樣，內鏡檢查是疑似潰瘍性上消化道出血患者的一線診斷方式[130]。

Angiography for diagnostic purposes is a second-line investigation and angiography before endoscopy results in unacceptable rates of negative investigations and is not warranted given the invasive nature of an angiogram. Angiography is useful for the confirmation and localization of the point of hemorrhage and allows treatment by embolization. On occasion, provocation angiography with the use of anticoagulants may be indicated. An inter-specialty consensus should guide this investigation on a case by case basis. Only case reports, case series, and expert opinion are available to guide this decision-making.
用於診斷目的的血管造影是二線檢查，內鏡檢查前的血管造影會導致不可接受的陰性檢查率，並且考慮到血管造影的侵入性，沒有必要。血管造影可用於確認和定位出血點，並允許通過栓塞進行治療。有時，可能需要使用抗凝劑進行激發血管造影。專業間共識應根據具體情況指導這項調查。只有病例報告、病例系列和專家意見可用於指導這一決策。

In patients with bleeding peptic ulcer, which are the indications for angioembolization?
在出血性消化性潰瘍患者中，血管栓塞術的適應症有哪些？

In hemodinamically stable bleeding peptic ulcer patients, where endoscopic hemostasis fails twice or is not possible/feasible, we suggest angiography with angioembolization where technical skills and equipment are available (weak recommendation based on very low-quality evidences, 2D)
對於血液病性穩定的出血性消化性潰瘍患者，內鏡止血兩次失敗或不可能/不可行，我們建議在有技術技能和設備的情況下進行血管造影和血管栓塞術（基於極低質量證據的弱推薦，2D）

Endoscopy is the established first-line therapy for the management of hemorrhage associated with peptic ulcer disease. It is appropriate (high-level evidence), to also conduct a second endoscopic examination with therapeutic intent, in cases of recurrent hemorrhage. However, where this also fails, surgery has been traditionally indicated. These operations are reported to be associated with mortality rates as high as 40% [129, 131]. Because of this high postoperative mortality, other strategies have been sought and angioembolization has become increasingly described during the past two decades.
內窺鏡檢查是治療消化性潰瘍病相關出血的既定一線療法。在反覆出血的情況下，出於治療目的進行第二次內鏡檢查也是適當的（高級證據）。然而，如果這也失敗了，傳統上需要手術。據報導，這些手術的死亡率高達 40% [129， 131]。由於術后死亡率很高，人們一直在尋求其他策略，並且在過去二十年中越來越多地描述血管栓塞術。

High-risk surgical patients have been suggested and recommended as the ideal candidates for angioembolization [130, 132]. However, no specific data exist investigating or defining the definition of “high risk.” Interdisciplinary consensus (surgery, gastroenterology, intensive care, anesthesia) is required to guide this decision-making. Low-risk surgical patients are likely to benefit from an operative strategy due to the likely reduced mortality in this group. No specific studies exist to validate this claim.
高危手術患者已被推薦為血管栓塞術的理想候選者[130,132]。 然而，目前尚無具體數據調查或定義「高風險」的定義。需要跨學科共識（外科、胃腸病學、重症監護、麻醉）來指導這一決策。由於該組的死亡率可能降低，低風險手術患者可能會從手術策略中受益。沒有具體的研究來驗證這一說法。

Furthermore, according to the physiology behind wound repair, it is possible that angioembolization could complicate a subsequent surgical intervention because of the reduction in the blood flow of the operative field, but no specific data exists to validate this claim.
此外，根據傷口修復背後的生理學，血管栓塞可能會因為手術野血流量減少而使後續手術干預複雜化，但沒有具體數據來驗證這一說法。

Should embolization be considered for unstable patients with bleeding peptic ulcer?
對於不穩定的出血性消化性潰瘍患者，是否應該考慮栓塞？

We suggest against a routinely use of angioembolization unstable patients. Angioembolization in unstable patients could be s considered  only in selected cases and in selected facilities (weak recommendation based on very low-quality evidences, 2D).
我們建議不要常規使用血管栓塞不穩定的患者。不穩定患者的血管栓塞術只能在選定的病例和選定的設施中考慮（基於極低質量證據的弱推薦，2D）。

There are no specific data to address the relative safety of angioembolization compared with surgery in hemodynamically unstable patients. Variable definitions of hemodynamic stability between studies further complicate meaningful recommendations in this field. Successful reports of angioembolization in patients with hemorrhagic shock are described. A recent retrospective case series describing super-selective angioembolization in 51 patients with active gastrointestinal hemorrhage (with 57% of these upper gastrointestinal in nature), demonstrated the possibility of this approach in patients with physiological shock (defined in this study as a systolic blood pressure of < 90 mmHg) [133].
沒有具體數據可以解決血管栓塞術與手術相比血流動力學不穩定患者的相對安全性。研究之間血流動力學穩定性的定義不同，使該領域的有意義的建議更加複雜。描述了失血性休克患者血管栓塞術的成功報告。最近的一項回顧性病例系列描述了 51 例活動性消化道出血患者（其中 57%為上消化道出血）的超選擇性血管栓塞術，證明瞭這種方法在生理性休克患者（本研究定義為收縮壓為< 90mmHg）患者中的可能性[133]。

The appropriateness of angioembolization in hemodynamically unstable patients depends on a number of factors, including the timely availability and skills of the angioembolization service, the quality of the initial and ongoing resuscitation, the quality of the peri-procedural and post-procedural intensive care, and patient variables. Furthermore, the presence of a hybrid OR or strict proximity of OR and the angioembolization facility is mandatory for the angiographic approach to unstable patients. A coordinated, interdisciplinary approach (surgery, interventional radiology, gastroenterology, intensive care, and anesthesia) is likely to benefit these critically ill patients, although there are no specific data to validate this hypothesis.
血管栓塞術對血流動力學不穩定患者是否適用取決於許多因素，包括血管栓塞服務的及時可用性和技能、初始和持續復甦的品質、圍手術期和術后重症監護的品質以及患者變數。此外，對於不穩定患者的血管造影方法，必須存在混合手術室或手術室和血管栓塞設施的嚴格接近。協調的跨學科方法（手術、介入放射學、胃腸病學、重症監護和麻醉）可能會使這些危重患者受益，儘管沒有具體數據來驗證這一假設。

In patients with recurrent bleeding peptic ulcer, which are the indications for angioembolization?
在復發性出血性消化性潰瘍患者中，血管栓塞術的適應症有哪些？

In patients with rebleeding peptic ulcer, we suggest angioembolization as a feasible option (weak recommendation based on low-quality evidences, 2C).
對於再出血性消化性潰瘍患者，我們建議血管栓塞作為可行的選擇（基於低質量證據的弱推薦，2C）。

For recurrent bleeding (defined as re-bleeding after 2 endoscopic therapeutic attempts), angioembolization and surgical options should be considered. Multiple reports and case series of successful angioembolization of hemorrhage from gastroduodenal ulcer disease are reported [134]. However, no high-level studies comparing the outcomes for angioembolization with surgery exist. One prospective and multiple retrospective cohort studies comparing outcomes between patients undergoing angioembolization with those undergoing surgery for rebleeding after failed endoscopic control are available. These studies were summarized in three meta-analysis [135,136,137]. Kyaw et al. summarized 6 retrospective cohort studies: surgery was found to significantly reduce the likelihood of further (post-intervention) hemorrhage, and was associated with a trend towards a reduced need for further intervention. However, surgery was also associated with a trend to increased mortality. Beggs et al. included 9 cohort studies (8 retrospective and 1 prospective), and similarly concluded that surgery was associated with a significantly lower risk of rebleeding, and only a marginal trend towards increased mortality. Subsequent to these first two meta-analyses, a case-control study comparing angioembolization with surgery [138] reported a trend to higher rebleeding rates following angioembolization, and a trend towards higher mortality after surgery was seen. A significantly lower rate of post-procedural complications was reported in the angioembolization cohort. The latest meta-analysis [137] found similar results, but interestingly found a slight drift toward a lower mortality for the angioembolization group.
對於復發性出血（定義為 2 次內鏡治療嘗試后再次出血），應考慮血管栓塞術和手術選擇。有多篇成功血管栓塞治療胃十二指腸潰瘍出血的報導和病例系列報導[134]。然而，尚無比較血管栓塞術與手術結果的高級研究。一項前瞻性和多項回顧性佇列研究比較了接受血管栓塞術的患者與在內窺鏡控制失敗后接受再出血手術的患者之間的結果。這些研究總結在 3 項 meta 分析中[135,136,137]。Kyaw 等總結了 6 項回顧性佇列研究：發現手術可顯著降低進一步（干預后）出血的可能性，並與進一步干預需求減少的趨勢相關。然而，手術也與死亡率增加的趨勢有關。Beggs 等人納入了 9 項佇列研究（8 項回顧性和 1 項前瞻性），並同樣得出結論，手術與顯著降低的再出血風險相關，並且死亡率增加的趨勢很小。繼前兩項 meta 分析之後，一項比較血管栓塞術與手術的病例對照研究[138]報告了血管栓塞術后再出血率升高的趨勢，並且觀察到手術后死亡率升高的趨勢。據報導，血管栓塞術佇列中的術后併發症發生率顯著降低。最新的薈萃分析[137]發現了類似的結果，但有趣的是，血管栓塞組的死亡率略有下降。

In patients with bleeding peptic ulcer who underwent angioembolization, which are the most appropriate embolization techniques and materials?
在接受血管栓塞術的出血性消化性潰瘍患者中，哪些栓塞技術和材料最合適？

Varied techniques and materials exist for the use in the embolization of bleeding duodenal ulcer disease. A tailored approach, guided by the multidisciplinary team, incorporating patient, pathology, and environmental factors is suggested (weak recommendation based on low-quality evidences, 2C).
存在用於栓塞出血性十二指腸潰瘍病的各種技術和材料。建議採用由多學科團隊指導的量身定製的方法，結合患者、病理學和環境因素（基於低質量證據的弱推薦，2C）。

Successful embolization of gastric and duodenal arteries is complicated by the rich collateral blood supply. Several technical points are raised in various case reports, series, and review articles in this field. There are no high-level articles to guide these technical considerations. Pre-procedural endoscopic localization of the point of hemorrhage could assist guidance of the selective and super-selective angiography and the angiogram can be further guided by the placement of an endoscopic clip at the ulcer if this has been identified. Diagnostic angiography usually commences with a selective coeliac axis and superior mesenteric artery catheterization and angiogram. Where no extravasation is seen, a super-selective approach normally follows. Imaging from both aspects of the bleeding point is ideally obtained (both sides need to be approached).
胃動脈和十二指腸動脈的成功栓塞因豐富的側支血液供應而變得複雜。該領域的各種病例報告、系列和評論文章提出了幾個技術觀點。沒有高級文章來指導這些技術注意事項。術前內窺鏡定位出血點可以幫助指導選擇性和超選擇性血管造影，如果已確定，可以通過在潰瘍處放置內窺鏡夾來進一步指導血管造影。診斷性血管造影通常從選擇性乳糜動脈軸和腸系膜上動脈導管插入術和血管造影開始。如果沒有觀察到外滲，通常會採用超選擇性方法。理想情況下，從出血點的兩個方面進行成像（需要接近兩側）。

In patients with bleeding peptic ulcer and non-evident bleeding during angiography, is there a role for prophylactic embolization?
對於消化性潰瘍出血且血管造影時出血不明顯的患者，預防性栓塞是否起作用？

No recommendation can be made on the role of prophylactic embolization.
不能對預防性栓塞的作用提出建議。

Prophylactic embolization may be considered in two situations
在兩種情況下可以考慮預防性栓塞

• Empirically, at the time of a negative angiogram: Several authors have suggested a role for blind embolization for upper gastrointestinal hemorrhage, noting that these patients had similar outcomes to patients who underwent embolization after the demonstration of a point of hemorrhage [134, 139, 140]. A variation on this uses the endoscopic information to guide the area for embolization [141, 142]. However, these approaches are based on retrospective cohorts. There are insufficient high-level data to draw firm conclusions.
  根據經驗，在血管造影陰性時：幾位作者提出了盲栓塞治療上消化道出血的作用，並指出這些患者與在出現出血點后接受栓塞的患者具有相似的結局[134,139,140]。 另一種變體是利用內鏡信息來引導栓塞區域[141,142]。 然而，這些方法基於回顧性佇列。沒有足夠的高層次數據來得出確切的結論。

• As a planned intervention, in association with endoscopic control: The addition of prophylactic embolization in addition to endoscopic hemostasis has been investigated by several authors, including most recently with two randomized controlled trials [143, 144]. Laursen et al. demonstrated a trend toward improved outcomes in patients who underwent additional prophylactic embolization. However, the second RCT by Lau et al. failed to confirm this observation. This approach was also supported by a retrospective series by Mille et al. [145].
  作為一項計劃干預措施，與內鏡控制相關：幾位作者研究了在內鏡止血之外增加預防性栓塞，包括最近的兩項隨機對照試驗[143,144]。 Laursen 等人在接受額外預防性栓塞術的患者中表現出改善預後的趨勢。然而，Lau 等人的第二次隨機對照試驗未能證實這一觀察結果。這種方法也得到了 Mille 等[145]的回顧性系列支援。

At present, the evidences available in the literature appear to be insufficient to routinely recommend this approach.
目前，文獻中可用的證據似乎不足以常規推薦這種方法。

Surgery  手術

In patients with bleeding peptic ulcer, which are the indications for surgical treatment and which is the appropriate timing for surgery?
對於出血性消化性潰瘍患者，哪些是手術治療的適應症，哪些手術時機是合適的？

In patients with bleeding peptic ulcer, we suggest surgical hemostasis (or angiographic embolization if immediately available and with appropriate skills) after failure of repeated endoscopy. In patients with hypotension and/or hemodynamic instability and/or ulcer larger than 2 cm at first endoscopy, we suggest surgical intervention without repeated endoscopy (strong recommendation based on very low-quality evidences, 1D).
對於出血性消化性潰瘍患者，我們建議在重複內鏡檢查失敗後進行手術止血（或血管造影栓塞，如果可以立即進行並具有適當的技能）。對於首次內鏡檢查時出現低血壓和/或血流動力學不穩定和/或潰瘍大於 2 cm 的患者，我們建議手術干預而不重複內鏡檢查（基於極低質量證據的強烈建議，1D）。

A renowned RCT conducted in 1999 [129] compared endoscopic retreatment with surgery for peptic ulcer rebleeding after initial endoscopy. Over a 40-month period, 92 patients with recurrent bleeding were enrolled: 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term control of bleeding. Thirteen underwent salvage surgery, 11 because retreatment failed, and 2 because of perforations resulting from thermocoagulation. Five patients in the endoscopy group died within 30 days, as compared with eight patients in the surgery group (p = 0.37). Seven patients in the endoscopy group had complications, as compared with 16 in the surgery group (p = 0.03). Duration of hospitalization, need for ICU admission, ICU length of stay, and the number of blood transfusions were similar in the two groups. In multivariate analysis, hypotension at randomization (p = 0.01) and an ulcer size of at least 2 cm (p = 0.03) were independent factors predictive of the failure of endoscopic retreatment. According to these data, repeated endoscopy is indicated for stable patients with ulcers smaller than 2 cm in diameter, while for patients with a larger ulcer and heavier bleeding, surgery may be taken into account as a first-line therapy.
1999 年進行的一項著名隨機對照試驗[129]比較了內鏡再治療與手術治療初次內鏡檢查后消化性潰瘍再出血。在 40 個月的時間里，招募了 92 名復發性出血患者：48 名患者被隨機分配接受立即內窺鏡再治療，44 名患者被分配接受手術。在分配接受內窺鏡再治療的 48 名患者中，35 名出血得到長期控制。13 人接受了挽救手術，11 人因為再治療失敗，2 人因為熱凝導致穿孔。內窺鏡檢查組有 5 名患者在 30 天內死亡，而手術組有 8 名患者死亡 （p = 0.37）。內鏡檢查組有 7 名患者出現併發症，而手術組為 16 名 （p = 0.03）。兩組住院時間、入住 ICU 需求、ICU 住院時間、輸血次數相近。在多變數分析中，隨機分組時的低血壓 （p = 0.01） 和至少 2 cm 的潰瘍大小 （p = 0.03） 是預測內窺鏡再治療失敗的獨立因素。根據這些數據，對於直徑小於 2 釐米的穩定潰瘍患者，需要重複內窺鏡檢查，而對於潰瘍較大、出血較多的患者，可以考慮手術作為一線治療。

No evidence is available regarding the impact on clinical outcome of time before surgery for bleeding peptic ulcer. We suggest immediate surgery for unstable patients with bleeding peptic ulcer refractory to endoscopy/angioembolization.
沒有證據表明消化性潰瘍出血術前時間對臨床結果的影響。對於內鏡檢查/血管栓塞術難治性消化性潰瘍出血性不穩定的患者，我們建議立即進行手術。

In patients with bleeding peptic ulcer, what is the most appropriate surgical approach (open vs laparoscopy) and what are the most appropriate surgical procedures?
對於出血性消化性潰瘍患者，最合適的手術方法是什麼（開腹與腹腔鏡）以及最合適的手術方法是什麼？

In patients with refractory bleeding peptic ulcer, we suggest surgical intervention with open surgery (weak recommendation based on very low-quality evidences, 2D).
對於難治性出血性消化性潰瘍患者，我們建議進行手術干預和開放手術（基於極低質量證據的弱推薦，2D）。

In patients operated for bleeding peptic ulcer, we suggest intra-operative endoscopy to facilitate the localization of the bleeding site (weak recommendation based on very low-quality evidences, 2D).
對於因消化性潰瘍出血而接受手術的患者，我們建議術中進行內鏡檢查以促進出血部位的定位（基於極低質量證據的弱推薦，2D）。

We suggest choosing the surgical procedure according to the location and extension of the ulcer and the characteristics of the bleeding vessel (weak recommendation based on low-quality evidences, 2C)
我們建議根據潰瘍的位置和擴展以及出血血管的特徵來選擇手術方式（基於低質量證據的弱推薦，2C）

An immediate or delayed biopsy is recommended (weak recommendation based on low-quality evidences, 2C)
建議立即或延遲活檢（基於低質量證據的弱推薦，2C）

A refractory bleeding peptic ulcer is defined as an ulcer still bleeding after repeated endoscopy/angioembolization. Open surgery is recommended when endoscopic treatments have failed and there is evidence of ongoing bleeding, plus or minus hemodynamic instability. The choice of the appropriate surgical procedure for bleeding peptic ulcer should be made on the basis of the location and extension of the ulcer and the characteristics of the bleeding vessel. Surgical approach involves ulcer oversew or resection. Bleeding gastric ulcers should be resected or at least biopsied for the possibility of neoplasms. Conversely, most duodenal ulcers requiring surgery for persistent bleeding are usually large and posterior lesions, and the bleeding is often from the gastro-duodenal artery. A recent prospective cohort study conducted in Denmark [146] compared the outcomes of duodenal and gastric bleeding peptic ulcers and found a significantly higher 90-day mortality and reoperation rate for the duodenal location, confirming the greater complexity of surgical management of this ulcer. Via duodenotomy, the bleeding vessel can be seen on the floor of the ulcer and can be rapidly oversewn. It is critical to perform triple-loop suturing of bleeding of the GDA due to the collateral blood supply to the transverse pancreatic arteries. The surgeon may not know preoperatively where the bleeding originates and intraoperative endoscopic guidance may be helpful. For patients with intractable ulcer bleeding, Schroeder et al. [147] from the analysis of a large database (ACS-NSQIP) have found that the surgical procedure of vagotomy/drainage is associated with significantly lower mortality than simply simple local ulcer oversew. They further suggest that vagotomy/drainage is preferred to local procedures alone for the surgical management of patients with bleeding peptic ulcer disease requiring emergency operation for intractable bleeding ulcers.
難治性出血性消化性潰瘍定義為重複內窺鏡檢查/血管栓塞術后仍在出血的潰瘍。當內鏡治療失敗且有持續出血的證據，加上或減少血流動力學不穩定時，建議進行開放手術。消化性潰瘍出血性潰瘍的手術方案應根據潰瘍的位置和延伸以及出血血管的特點來選擇合適的手術方法。手術方法包括潰瘍覆蓋或切除。出血性胃潰瘍應切除或至少進行活檢以排除腫瘤的可能性。相反，大多數因持續性出血而需要手術的十二指腸潰瘍通常是大的後部病變，出血通常來自胃十二指腸動脈。最近在丹麥進行的一項前瞻性佇列研究[146]比較了十二指腸和胃出血性消化性潰瘍的結果，發現十二指腸位置的 90 天死亡率和再手術率顯著更高，證實了這種潰瘍手術治療的複雜性更大。通過十二指腸切開術，可以在潰瘍的底部看到出血血管，並且可以迅速縫合。由於胰橫動脈的側支血液供應，對 GDA 出血進行三環縫合至關重要。外科醫生在術前可能不知道出血的來源，術中內窺鏡引導可能會有所説明。對於頑固性潰瘍出血患者，Schroeder 等[147]通過對大型資料庫（ACS-NSQIP）的分析發現，迷走神經切開術/引流手術的死亡率明顯低於簡單的局部潰瘍過度縫合。 他們進一步建議，對於需要對頑固性出血性潰瘍進行緊急手術的出血性消化性潰瘍患者的手術治療，迷走神經切開術/引流術比單獨局部手術更可取。

In patients with bleeding peptic ulcer, what is the role of damage control surgery?
在出血性消化性潰瘍患者中，損傷控制手術的作用是什麼？

We suggest considering damage control surgery for patients with hemorrhagic shock and signs of severe physiological derangement, in order to quickly resolve the bleeding and allow a prompt ICU admission (weak recommendation based on very low-quality evidences, 2D).
我們建議考慮對失血性休克和嚴重生理紊亂體徵的患者進行損傷控制手術，以快速解決出血並允許及時入住 ICU（基於極低質量證據的弱推薦，2D）。

Indications for damage control surgery in bleeding peptic ulcer are similar to those for perforated peptic ulcer and are reported in the WSES guidelines on Open Abdomen management in non-trauma patients [67].
消化性潰瘍出血性損傷控制手術的指徵與消化性潰瘍穿孔的指征相似，WSES 關於非創傷患者開腹治療的指南中都有報導[67]。

Antimicrobial therapy  抗菌治療

In patients with bleeding peptic ulcer, which are the indications for antimicrobial therapy and for Helicobacter pylori testing?
對於出血性消化性潰瘍患者，哪些適應症是抗菌治療和幽門螺桿菌檢測 ？

In patients with bleeding peptic ulcer, empirical antimicrobial therapy is not recommended (strong recommendation based on low-quality evidences, 1C)
對於出血性消化性潰瘍患者，不推薦經驗性抗菌治療（基於低質量證據的強烈推薦，1C）

We recommend performing Helicobacter pylori testing in all patients with bleeding peptic ulcer (strong recommendation based on low-quality evidences, 1C).
我們建議對所有出血性消化性潰瘍患者進行幽門螺桿菌檢測（基於低品質證據的強烈建議，1C）。

Bleeding peptic ulcer accounts for 75% of patients admitted to ED for peptic ulcer disease [148] and has different etiologies (ulcerogenic medications such as acetylsalicylic acid and NSAIDs, H. pylori infection, etc). H. pylori infection has a variable prevalence of 20–50% among patients with bleeding peptic ulcer in various countries, but its eradication is associated with a significant reduction in ulcer recurrence rate and rebleeding [66, 149,150,151]. In a systematic review, Gisbert et al. showed a 26% rebleeding rate among patients with H. pylori infection–associated bleeding ulcers who did not receive eradication therapy [150]. Conflicting results are reported about appropriate timing to start eradication therapy. Empirical eradication therapy immediately after re-feeding has been suggested as the most cost-effective strategy [151], but its real effectiveness can vary by regional prevalence of the bacteria. Therefore, confirming the result of H. pylori test and initiating eradication therapy in H. pylori-positive patients prior to discharge would appear to be a more appropriate strategy than to apply empirical therapy to all patients with BPU [66, 152].
消化性潰瘍出血佔因消化性潰瘍病而入住急診室的患者中的 75%[148]，並且有不同的病因（乙醯水楊酸和 NSAIDs 等致潰瘍藥物、 幽門螺桿菌感染等）。幽門螺桿菌感染在各國消化性潰瘍出血患者中的患病率各不相同，為 20-50%，但根除幽門螺桿菌可顯著降低潰瘍復發率和再出血[66,149,150,151]。 在一項系統評價中，Gisbert 等顯示，未接受根除治療的幽門螺桿菌感染相關出血性潰瘍患者的再出血率為 26%[150]。關於開始根除治療的適當時間，報告了相互矛盾的結果。重新餵養后立即進行經驗性根除治療被認為是最具成本效益的策略[151]，但其實際效果可能因細菌的地區流行情況而異。因此，在幽門螺桿菌陽性患者出院前確認幽門螺桿菌檢測結果並開始根除治療似乎比對所有 BPU 患者進行經驗性治療更合適[66,152]。

For this reason, all patients having BPU should undergo H. Pylori testing. Different tests are available to confirm H. pylori infection. The urea breath test (UBT) and stool antigen testing are acceptable non-invasive tests with a sensitivity of 88–95% for UBT and 94% for stool antigen testing, respectively. Specificity is 95–100% for UBT and 92% for stool antigen testing, respectively [151]. In cases of bleeding peptic ulcer, H. pylori testing on endoscopic tissue biopsy may be available [151].
因此，所有患有 BPU 的患者都應接受幽門螺桿菌檢測。有不同的測試可用於確認幽門螺桿菌感染。尿素呼氣試驗 （UBT） 和糞便抗原檢測是可接受的無創檢測，UBT 的靈敏度分別為 88-95% 和糞便抗原檢測的靈敏度為 94%。UBT 的特異性分別為 95-100%和糞便抗原檢測的 92%[151]。對於出血性消化性潰瘍，可進行幽門螺桿菌內鏡組織活檢[151]。

In patients with bleeding peptic ulcer and positive tests for HP infection, which are the therapeutic options?
對於出血性消化性潰瘍和 HP 感染檢測呈陽性的患者，有哪些治療選擇？

In H. pylori-positive BPU patients, eradication therapy is recommended to avoid recurrent bleeding (strong recommendation based on low-quality evidences, 1C)
對於幽門螺桿菌陽性 BPU 患者，建議根除治療以避免復發性出血（基於低質量證據的強烈推薦，1C）

In patients with HP positive tests, standard triple therapy (amoxicillin, clarithromycin, and PPI) regimen is recommended as first-line therapy if low clarithromycin resistance is present (strong recommendation based on moderate-quality evidences, 1B)
對於 HP 檢測呈陽性的患者，如果克拉黴素耐藥性較低，建議將標準三聯治療（阿莫西林、克拉黴素和 PPI）方案作為一線治療（基於中等質量證據的強烈推薦，1B）

10 days of sequential therapy with four drugs (amoxicillin, clarythromicin, metronidazole, and PPI) is recommended in selected cases, if compliance to the scheduled regimen can be maintained, and if clarithromycin high resistance is detected (strong recommendation based on low-quality evidences, 1C).
在特定病例中，如果可以保持對預定方案的依從性，並且如果檢測到克拉黴素高耐藥性，則建議使用四種藥物（阿莫西林、克拉尼曲黴素、甲硝唑和 PPI）進行 10 天的序貫治療（基於低質量證據的強烈推薦，1C）。

In patients with HP positive tests, a 10-day levofloxacin-amoxicillin triple therapy is recommended as second-line therapy if first-line therapy failed (strong recommendation based on moderate-quality evidences, 1B).
對於 HP 檢測呈陽性的患者，如果一線治療失敗，建議將 10 天左氧氟沙星-阿莫西林三聯療法作為二線治療（基於中等質量證據的強烈推薦，1B）。

We recommend to start standard triple therapy (STT) after 72–96 h of intravenous administration of PPI and to administer it for 14 days (strong recommendation based on low-quality evidences, 1C)
我們建議在靜脈注射 PPI72-96 小時后開始標準三聯療法（STT），並給葯 14 天（基於低質量證據，1C 的強烈推薦）

The worldwide prevalence of H. pylori infections is approximately 50%, with the highest being in developing countries [153]. Standard treatments for H. pylori infections have been endorsed by Western scientific societies, and by regulatory authorities relying on clarithromycin, metronidazole, or amoxicillin in conjunction with PPI [154].
幽門螺桿菌感染的全球患病率約為 50%，其中發展中國家最高[153]。 幽門螺桿菌感染的標準治療已得到西方科學學會的認可，監管機構也認可了克拉黴素、甲硝唑或阿莫西林聯合 PPI[154]。

As the response to eradication therapy is significantly related to the prevalence of primary resistance in the population, the choice of treatment regimen should be based on the knowledge of the underlying prevalence of resistant strains in the community [151,152,153,154].
由於根除治療的反應與人群中原發性耐葯的患病率顯著相關，因此治療方案的選擇應基於對社區耐葯菌株潛在患病率的瞭解[151,152,153,154]。

Several international guidelines [151, 152] and available meta-analysis [153, 154] recommend that standard triple therapy (amoxicillin, clarithromycin, and PPI) regimen should be used as first-line therapy if low clarithromycin resistance is present. The suggested doses are:
一些國際指南[151,152]和現有的 meta 分析[153,154]建議，如果克拉黴素耐藥性較低，則應使用標準的三聯治療方案（阿莫西林、克拉黴素和 PPI）方案作為一線治療。 建議劑量為：

• PPI standard dose twice a day;
  PPI 標準劑量，每天兩次;

• Clarithromycin 500 mg twice a day;
  克拉黴素 500 毫克，每天兩次;

• Amoxicillin 1000 mg twice a day, or
  阿莫西林 1000 毫克，每天兩次，或

• Metronidazole 500 mg twice a day.
  甲硝唑 500 毫克，每天兩次。

Sequential therapy with four drugs (amoxicillin, clarithromycin, metronidazole, and PPI) should be considered in selected cases, if compliance to the scheduled regimen can be maintained, and if clarithromycin high resistance is detected. It is defined as the use of one PPI and amoxicillin for the first 5 days followed by PPI plus clarithromycin and metronidazole for the next 5 days [155]. Recommended doses are as follows:
在某些病例中，如果可以維持對預定方案的依從性，並且如果檢測到克拉黴素高耐藥性，則應考慮使用四種藥物（阿莫西林、克拉黴素、甲硝唑和 PPI）進行序貫治療。其定義為前 5 日使用一種 PPI 和阿莫西林，隨後 5 日使用 PPI 加克拉黴素和甲硝唑[155]。推薦劑量如下：

• PPI standard dose twice a day;
  PPI 標準劑量，每天兩次;

• Amoxicilllin 1000 mg twice a day;
  阿莫西林 1000 毫克，每天兩次;

• Clarithromycin 500 mg twice a day;
  克拉黴素 500 毫克，每天兩次;

• Metronidazole 500 mg twice a day.
  甲硝唑 500 毫克，每天兩次。

If any of these regimens failed, a second-line therapy is represented by a 10-day levofloxacin-amoxicillin triple therapy. The suggested doses are:
如果這些方案中的任何一個失敗，則以 10 天左氧氟沙星-阿莫西林三聯療法為二線治療。建議劑量為：

• PPI standard dose twice a day;
  PPI 標準劑量，每天兩次;

• Levofloxacin 500 mg once a day or 250 twice a day;
  左氧氟沙星 500 毫克，每天一次或 250 毫克，每天兩次;

• Amoxicillin 1000 mg twice a day.
  阿莫西林 1000 毫克，每天兩次。

Conclusions  結論

Peptic ulcer disease is still common among the world population and its incidence pattern is evolving in relation to the rise of new risk factors, i.e., the increasing incidence of the Helicobacter pylori infection, the extensive use of NSAIDs and the increase in alcohol and smoking abuse. Despite the tremendous improvement in preventive therapies, the rate of complication of this disease is still high and is burdened by high morbidity and mortality. Prompt recognition and treatment of the complications lead invariably to a better outcome, especially in elderly and frail patients. For this reason, these guidelines present evidence-based international consensus statements on the management of complicated peptic ulcer from a collaboration of a panel of experts and are intended to improve the knowledge and the awareness of physicians around the world on this specific topic. We divided our work into two main topics, bleeding and perforated peptic ulcer, and structured it into six main topics that cover the entire management process of patients with complicated peptic ulcer, from diagnosis at ED arrival to post-discharge antimicrobial therapy, to provide an up-to-date and easy-to-use tool that can help physicians and surgeons during the decision-making process.
消化性潰瘍病在世界人群中仍然很常見，其發病模式正在隨著新危險因素的增加而演變，即幽門螺桿菌感染的發病率增加、非甾體抗炎藥的廣泛使用以及酗酒和吸煙的增加。儘管預防性治療有了巨大的進步，但這種疾病的併發症發生率仍然很高，並且受到高發病率和死亡率的負擔。及時識別和治療併發症總是會帶來更好的結果，特別是對於老年和體弱的患者。出於這個原因，這些指南提出了由專家小組合作的關於複雜消化性潰瘍治療的循證國際共識聲明，旨在提高世界各地醫生對這一特定主題的了解和認識。我們將工作分為出血和消化性潰瘍穿孔兩個主要主題，並將其結構為六個主要主題，涵蓋複雜性消化性潰瘍患者的整個管理過程，從急診到達時的診斷到出院后的抗菌治療，以提供最新 且易於使用的工具，可以在決策過程中幫助醫生和外科醫生。