160例消化性溃疡合并上消化道出血的危险因素及治疗分析

目的 调查消化性溃疡(peptic ulcer, PU)合并上消化道出血的临床特征、危险因素,并对患者临床治疗方式进行探讨.方法 将2016-02/2017-12湖州市吴兴区人民医院接诊的160例PU合并上消化道出血患者设为观察组,将同期在我院就诊的160例PU患者设为对照组.分析PU合并上消化道出血的临床特征及危险因素.将160例PU合并上消化道出血患者按治疗方式不同分为两组, A组84例给予基础治疗+质子泵抑制剂三联疗法, B组76例患者行基础治疗+内镜下巴曲酶联合质子泵抑制剂三联疗法治疗,比较两组临床疗效、3 d后输血量、再出血率以及治疗期间不良反应发生率,并记录治疗30 d后幽门螺旋杆菌(Helicobacter pylori, H. pylori)根除率.结果 160例PU合并上消化道出血患者临床症状以黑便、呕血、黑便联合呕血常见,多伴随头晕;出血量以500mL为主;饮酒、吸烟、秋冬季发病、男性、应用非甾体抗炎药(non-steroidal anti-inflammatory drugs,NSAIDs)、胃溃疡、复合溃疡、溃疡病程≥6mo是PU合并上消化道出血的高危因素; A组总有效率、H.pylori根除率低于B组,再出血率、输血量高于B组,差异具有统计学意义(P0.05).结论 P U合并上消化道出血患者不良生活习惯、男性、应用NSAIDs、胃溃疡、复合溃疡、溃疡病程≥6mo是其发生高危因素,采用内镜介入治疗后联合质子泵抑制剂三联疗法治疗PU合并上消化道出血患者安全可靠.     

食管癌和环氧合酶-2关系的研究进展

环氧化酶是花生四烯酸代谢中的一种限速酶,其中的同工酶之一的环氧合酶-2,通过多种途径与诸多肿瘤的发生、发展和预后密切相关.食管癌具有高发病率和死亡率,近年来认为环氧合酶-2通过异型生物质(xenobiotic)代谢,抑制凋亡,参与慢性炎症、免疫抑制,上调血管生成因子的表达,以及促进肿瘤的浸润和转移在其致癌中起重要作用.实验证据表明利用选择性环氧合酶-2抑制剂抑制环氧合酶-2活性可以预防各种组织中肿瘤的形成,包括食管癌.本文就环氧合酶-2对食管癌的致癌作用及选择性环氧合酶-2抑制剂的预防和/或治疗作用作一综述.     

客观评价选择性环氧合酶-2抑制剂的全消化道安全性

自第一个选择性环氧合酶(COX)-2非甾体消炎药(NSAIDs)(亦称选择性COX-2抑制剂,简称选择性NSAIDs)塞来昔布于1998年问世以来,有关选择性NSAIDs与非选择性NSAIDs(亦称传统NSAIDs)的优劣之争就一直不断,其各自的大量的临床试验已经阐明这两类药物的优势[1].COX-1和COX-2均在健康人体组织发挥其生理作用.在炎症组织中COX-2起主导炎症反应的作用;而在胃肠道部位COX-1又起保护黏膜的主导作用.由此设计的选择性NSAIDs是既有抗炎镇痛效果,又能尽量避免损伤胃肠黏膜的新型NSAIDs[2].     

非甾体抗炎药相关性上消化道出血60例临床分析

回顾性分析60例非甾体抗炎药（NSAIDs）相关性上消化道出血患者临床资料。发现患者出血前1周内有服用NSAIDs类药物史,服药原因为心血管疾病、呼吸道感染、骨关节痛,前3种药物分别为阿司匹林、对乙酰氨基酚、扶他林。此类患者消化道症状不明显、Hp阳性率高;胃镜下见弥散性黏膜充血、水肿及多发性糜烂表浅溃疡;治疗效果好。提示NSAIDs是上消化道出血的重要病因,对需长期服药治疗者应用质子泵抑制剂和（或）前列腺素E衍生物预防,或改服选择性COX-2抑制剂,对有高危因素的患者应常规监测粪便隐血。     

幽门螺杆菌阴性消化性溃疡

根据是否服用非甾体抗炎药（NSAIDs）可将幽门螺杆菌（H．pylor／）阴性消化性溃疡（PU）分为NSAIDs相关PU和非且pytori、非NSAIDs相关PU。NSAIDs相关PU病程较短，常无典型的腹痛，近50％为无痛性，症状与实际病变相关性差，内镜下常表现为多发溃疡，溃疡直径较小，多集中于胃窦部。对NSAIDs相关PU的治疗仍有争议．对高危人群和非高危人群应采用不同的治疗策略。非H. pylori、非NSAIDs相关PU发生的机制复杂．可能与高胃酸分泌、基础疾病致黏膜防御机制受损、少见病原体感染、某些药物以及其他因素如吸烟、心理因素、应激、饮食习惯等有关。由于发病因素较多且无法明确，非H.pylori、非NSAIDs相关PU的治疗效果常较差。     

归脾汤联合质子泵抑制剂三联疗法治疗消化性溃疡的远期疗效

[目的]研究归脾汤联合质子泵抑制剂三联疗法治疗消化性溃疡(PU)的远期疗效。[方法]将90例PU患者随机分为2组,治疗组45例应用归脾汤联合质子泵抑制剂三联疗法(奥美拉唑、阿莫西林及枸缘酸铋钾)治疗;对照组45例,应用质子泵抑制剂三联疗法治疗。[结果]治疗组临床总有效率95.6%,胃镜1年内复发率7.5%,胃镜2年内复发率12.5%,与对照组比较差异有统计学意义(P<0.05)。[结论]归脾汤联合质子泵抑制剂三联疗法治疗PU,有助于提高愈合率及降低复发率,巩固远期疗效。     

环氧合酶-2抑制剂增强食管癌放射敏感性的机制

食管癌是常见的消化系统恶性肿瘤,发病率较高,早期症状不典型,多数患者就诊时已属晚期.放射治疗是重要的晚期食管癌治疗方法.我们的前期研究已证实,食管鳞癌细胞株EC9706高表达环氧合酶-2(COX-2),COX-2选择性抑制剂NS398剂量-效应和时间-效应依赖地增加其放射敏感性[1],但确切机制尚不明确.     

非类固醇抗炎药对非消化系统肿瘤的作用

大量研究证明,环氧合酶抑制剂非类固醇抗炎药(NSAIDs)对食管癌、结直肠癌等多种肿瘤均可产生抑制作用,且在不同品种NSAIDs中结果也相当一致,具有肯定的抗肿瘤作用。本文介绍NSAIDs的抗肿瘤机制及其在非消化系肿瘤中的实验研究与应用。     

消化性溃疡并发症的外科诊治

20余年来，由于抗溃疡药物，如H2受体拮抗剂(H2RA)、质子泵抑制剂(PPI)和胃黏膜保护剂的应用，消化性溃疡(PU)的治愈率大为提高。幽门螺杆菌(H.pylori)的根除治疗又降低了溃疡的复发率，使需要外科治疗的PU患者明显减少，仅限于一些消化道大出血、溃疡穿孔和瘢痕性幽门梗阻等     

2型糖尿病伴发消化性溃疡愈合质量及其复发的临床评析

目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)伴发消化性溃疡(peptic ulcer,PU)愈合质量及复发的临床特点。方法随访观察72例T2DM伴发PU患者和74例同期诊断明确的非糖尿病PU患者,并进行对照分析。所有患者均为活动期溃疡合并幽门螺杆菌(Helicobacter pylori,H.pylori)感染,胃溃疡(gastric ulcer,GU)和复合性溃疡共96例患者接受8周奥美拉唑治疗,十二指肠球部溃疡(duodenal ulcer,DU)50例患者接受6周奥美拉唑治疗;同时加用克拉霉素、阿莫西林或甲硝唑抗H.pylori治疗2周。治疗结束后1个月和12个月分别进行胃镜检查和H.pylori检测。结果治疗结束后1个月随访,T2DM组Sc期溃疡愈合率低于非T2DM组(P0.01);H.pylori根除者溃疡高质量愈合率明显高于H.pylori未根除者(P0.01)。治疗结束后12个月随访,T2DM组的溃疡年复发率高于非T2DM组(P0.05);H.pylori根除者溃疡年复发率低于H.pylori未根除者(P0.01)。结论虽然H.pylori根除后溃疡可获得高质量愈合,且溃疡复发率显著降低,但T2DM伴发PU溃疡愈合质量差,溃疡年复发率高。应重视对T2DM伴发PU患者H.pylori和胃镜的随访和复查。     

Gastro-duodenal protection in an era of cyclo-oxygenase-2-selective nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective and necessary for the relief of pain and inflammation in patients with arthritis. NSAIDs are however also associated with an increased risk for ulceration in the stomach and in the duodenum, and many NSAID users experience bothersome dyspeptic symptoms during continued NSAID therapy. PPIs like omeprazole, have been shown to heal and to prevent ulcers and dyspeptic symptoms during continued NSAID therapy, and during continued NSAID therapy the prostaglandin analogue, misoprostol, has been shown to reduce the risk for ulcer complications. The COX-2 selective NSAID, rofecoxib, is in comparison with naproxen, a non-selective NSAID, associated with fewer clinically important upper gastrointestinal events. The incidence of myocardial infarctions seems, however, to be lower with naproxen than with rofecoxib, and this is expected to lead to low-dose aspirin use in rofecoxib users at risk for cardiovascular events. Co-administration of the COX-2 selective NSAID, celecoxib, and low-dose aspirin, is associated with the same risk for upper gastrointestinal ulcer complications alone and combined with symptomatic ulcers, as the non-selective NSAIDs, ibuprofen and diclofenac. A proton pump inhibitor (PPI) should be used for healing of NSAID-associated ulcers, and a PPI or misoprostol should be considered for prevention of ulceration in non-selective NSAID users at risk for ulceration. The experience with COX-2 selective NSAIDs is still limited, and it remains to be studied whether subpopulations of COX-2 selective NSAID users will benefit from gastro-duodenal protection.     

Prevention of NSAID-induced ulcers

Opinion statement Cyclooxygenase-2 (COX-2) selective inhibitors were developed as gastrointestinal (GI) safer alternatives to nonselective NSAIDs—providing equivalent analgesic and anti-inflammatory efficacy. Their GI sparing is impaired by concomitant aspirin use, and concerns regarding adverse cardiovascular effects have emerged. Risk factors for NSAID-related complications include a history of ulcer disease or bleeding, concomitant corticosteroid or anticoagulant therapy, use of high-dose or multiple NSAIDs (including low-dose aspirin), advanced age, and certain chronic diseases. If an NSAID must be used in a patient at risk, the lowest-risk NSAID should be used with, in many cases, cotherapy to reduce the risk for ulcers. COX-2 drugs have been associated with a significantly higher risk of vascular events than placebo or naproxen. This increase may be shared by nonselective NSAIDs and appears to be medication-and dose-dependent. Prostaglandin depletion is a central mechanism for NSAID ulcer development, and replacement therapy with misoprostol reduces NSAID toxicity; however, it is rarely used due to side effects. The acid suppression provided by traditional doses of histamine 2-receptor antagonists (H₂RAs) does not prevent most NSAID-related gastric ulcers. Despite a single study demonstrating that H₂RAs at double the dose may be effective, studies comparing such high doses with misoprostol or proton pump inhibitors (PPIs) for preventing NSAID ulcers are not available. PPIs are effective at single daily doses, do not demonstrate tachyphylaxis, and are superior to H₂RAs and misoprostol in reducing ulcers and NSAID-associated dyspepsia. NSAID choice should be predicated by an assessment of an individual’s cardiovascular and GI risk. For those with competing cardiovascular and GI risks, the tradeoffs between reducing adverse GI events (COX-2 inhibitor instead of a nonselective NSAID) must be explicitly weighed against concerns about cardiovascular side effects (naproxen instead of other agents). Considering cost is appropriate because it may not be feasible to recommend the “safest” regimen in every circumstance. The cost effectiveness of risk-reducing therapies is intimately tied to the patient’s underlying risk. For those at highest GI risk, using a PPI and a low-dose COX-2 inhibitor seems appropriate for those without high cardiovascular risk. For patients whose cardiovascular risk parallels or exceeds GI concerns, naproxen with a PPI is recommended when non-NSAID approaches fail.     

Non-steroidal anti-inflammatory agents with selective inhibitory activity on cyclooxygenase-2. Interest and future prospects

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the production of primary prostanoids by blocking the access of arachidonic acid to the active site of the cyclooxygenases (COXs). Because the prostanoids produced by COX-1 appear to play a physiological role (protection of the gastric mucosa, platelet aggregation, vascular homeostasis, maintenance of renal sodium-water balance) while those produced by COX-2 seem mainly to intervene in the inflammatory response and in certain processes associated with cell proliferation, the hypothesis has been put forward that the NSAIDs that are selective COX-2 inhibitors should theoretically be capable of maintaining NSAID therapeutic properties but also have fewer adverse side effects due to the maintenance of prostaglandin production at normal physiological levels. CURRENT KNOWLEDGE AND KEY POINTS: The hypothesis of COX isoenzyme selectivity has led to a proposed classification for COX inhibitors: 1) COX-1 selective inhibitors (low-dosage aspirin); 2) COX non-selective inhibitors (the majority of classified NSAIDs, which when administered over the long term, e.g., in cases of rheumatoid arthritis, cause duodenal ulcers in 20% of cases and gastric hemorrhage in 1-4% of cases/year); 3) COX-2 preferential inhibitors (meloxicam and nimesulide, which have fewer gastric side effects than standard NSAIDs, but which are not risk-free at high doses); 4) COX-2 selective inhibitors (celecoxib and rofecoxib). Preliminary clinical studies have shown that COX-2 selective inhibitors are as efficient as standard NSAIDs and have fewer adverse digestive side effects, thereby confirming the interest of this proposed classification. In the UK, the aforementioned studies have led to the commercialization of rofecoxib for the treatment of pain and osteoarthritis, while celecoxib has been introduced in medical practice in the USA and other countries for the treatment of rheumatoid arthritis and osteoarthritis. FUTURE PROSPECTS AND PROJECTS: Various epidemiological and laboratory studies have indicated that NSAIDs may be able to reduce the risk of cancer (colorectal cancer in particular) and Alzheimer's disease due to their inhibitory activity on COXs, especially COX-2. The therapeutic contribution of COX-2 specific inhibitors has to be more fully evaluated, particularly as these agents could delay the healing of duodenal ulcers and interfere with several COX-2-induced physiological functions. It is therefore suggested that until further information becomes available, this new class of NSAIDs should be used with caution in certain patient populations.     

Role of acid suppressants in prophylaxis of NSAID damage

Gastric acid contributes to the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced ulceration via several mechanisms, including conversion of superficial to deeper injury, impairment of haemostasis, and interference with ulcer healing. The suppression of acid secretion has been shown to reduce the severity of NSAID-induced mucosal damage in experimental models and clinical studies. Current evidence indicates that proton pump inhibitors (PPIs) are the preferred treatment for the healing of gastric ulcers when NSAIDs cannot be discontinued. PPIs are superior to standard-dose H(2)-receptor antagonists and equivalent to low-dose misoprostol in preventing NSAID-induced gastric ulcers. Whether there is any significant advantage of PPIs over higher doses of H(2)-receptor antagonists or misoprostol is unknown. The efficacy of PPIs is enhanced in the presence of H. Pylori infection. Omeprazole has been shown to be effective for the secondary prevention of ulcer bleeding in H. pylori -infected NSAID users. The efficacy of PPIs for the prevention of ulcer complications in H. pylori-negative NSAID users remains uncertain.     

The role of proton pump inhibitors in NSAID-associated gastropathy and upper gastrointestinal symptoms

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in the United States. Ulcers are found with an endoscopy in 15%-30% of patients who are using NSAIDs regularly, and the annual incidence of upper gastrointestinal (GI) clinical events is 2.5%-4.5% among those who use NSAIDs regularly. Upper GI symptoms, such as dyspepsia, also occur in up to 60% of patients taking NSAIDs. H2-receptor antagonists when used at standard doses are not effective at preventing gastric ulcers resulting from the use of NSAIDs. Misoprostol effectively decreases NSAID-induced ulcers and GI complications, but issues of compliance (multiple daily doses) and side effects (eg, diarrhea and dyspepsia) may limit its use. Once-daily therapy with proton pump inhibitors has been documented to significantly decrease the development of NSAID-associated ulcers in endoscopic studies, reduce the rate of NSAID-related ulcer complications, and reduce upper GI symptoms in NSAID users.     

Management of nonsteroidal anti-inflammatory drug-induced gastroduodenal disease by acid suppression.

One major cause of peptic ulceration is the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The precise mechanisms through which NSAIDs cause peptic ulceration are unknown, but the discovery that they reduce the production of 'cytoprotective' prostaglandins led to the hypothesis that coadministration of exogenous prostaglandins heals and prevents NSAID-induced gastroduodenal ulcers and other mucosal lesions. Studies using high doses of misoprostol have shown that it does have a protective effect; however, gastrointestinal intolerance of this prostaglandin E2 analogue is common. Early indications that acid suppression was effective in the management of NSAID-related peptic ulcers came from studies showing that gastric ulcers could be healed by omeprazole in patients who continued to take NSAIDs. Other studies suggested that acid suppression reduces the incidence of mucosal lesions but that standard dose ranitidine protects only against duodenal lesions. Subsequent studies reported that higher dose H2 receptor antagonist therapy can protect against both gastric and duodenal ulcers during continued NSAID therapy. An ideal therapeutic strategy would heal NSAID-related ulcers and prevent the development of new NSAID-related lesions and complications in patients who are unable to discontinue NSAID therapy. A number of recent studies indicate that effective acid-suppressive treatment with the proton pump inhibitor omeprazole can achieve these aims. Overall, data from recent studies show that acid suppression with the proton pump inhibitor omeprazole at a dose of 20 mg daily is the most effective means of healing NSAID-associated gastroduodenal lesions and that it is the most effective prophylactic therapy. In the long run, the role of omeprazole will have to be evaluated with respect to its cost effectiveness compared with other strategies and with respect to the development of less damaging NSAIDs.     

Nonsteroidal anti-inflammatory drugs, aspirin, and gastrointestinal prophylaxis: an ounce of prevention

Because of the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs), NSAID-related gastrointestinal (GI) complications are recognized as the most prevalent drug toxicity in the United States. The withdrawal of 2 selective cyclooxygenase-2 (COX-2) inhibitors (agents specifically developed to reduce ulcer complications) from the US market owing to adverse cardiovascular events has made reducing ulcer risk more important than ever for patients receiving NSAID treatment. In addition, the impact of aspirin, implicated by itself as a cause of serious adverse GI events and in combination with NSAIDs as a source of incremental risk, remains under-appreciated. Balancing the cardiovascular risks of selective COX-2 inhibitors with the higher GI risks associated with conventional NSAIDs remains a major clinical challenge. Gastro-protective therapy, such as with a proton pump inhibitor, is beneficial in patients receiving NSAIDs, but despite current treatment recommendations, this "ounce of prevention" remains substantially underused for patients at risk.     

NSAID-induced gastroduodenal damage: strategies for prevention

The improved knowledge of the mechanism by which NSAIDs work and damage the gastrointestinal (GI) mucosal suggested a series of measures for the prevention of NSAIDs-induced GI lesions, apart from the use of those proved to be less toxic. PPI have now been definitively shown to be more effective in the relief of symptoms and in the healing and prevention of ulcers/erosions than H2-antagonists and also better tolerated than misoprostol. Other more innovative approaches include selective and highly selective COX-2 inhibitors, NSAIDs containing NO or stimulating the gastric endogenous biosynthesis of NO, and chiral NSAIDs. Clinical usefulness of other compounds, including NSAIDs associated with zwitterionic phospholipids or fibroblast growth factor, is still under investigation.     

Nonsteroidal anti-inflammatory drugs, low-dose aspirin, and potential ways of reducing the risk of complications.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an annual incidence of 1-2% of gastrointestinal (GI) complications, which may be fatal in some cases. Low-dose aspirin is also associated with an increased risk of upper GI bleeding, but the increase is about three times lower than that found with common NSAIDs. Misoprostol (600-800 microg/day) reduces the incidence of complications in non-aspirin NSAID users. Co-therapy with antisecretory drugs (proton pump inhibitors, PPIs) also reduces the risk of GI bleeding in high-risk patients taking NSAIDs and/or low-dose aspirin. Another way of reducing the incidence of GI complications is to use the highly selective cyclo-oxygenase 2 (COX-2) inhibitors. The GI safety of nitric oxide NSAIDs (NO-NSAIDs) has been demonstrated extensively in experimental conditions and preliminary clinical studies. Epidemiological studies have also shown that nitric oxide donor drugs reduce the risk of upper GI bleeding, which might be important in patients receiving low-dose aspirin.