EDITORIAL Adv Clin Exp Med 2004, 13, 5, 737–747 ISSN 1230−025X LESZEK PARADOWSKI, WOJCIECH BŁOŃSKI, RADOSŁAW KEMPIŃSKI 20 Years after Introducing Proton Pump Inhibitors. What Have We Achieved in Peptic Ulcer Disease Conventional Treatment? Co osiągnęliśmy w leczeniu zachowawczym choroby wrzodowej po 20 latach od wprowadzenia inhibitorów pompy protonowej? Department of Gastroenterology and Hepatology, Wroclaw Medical University, Poland Streszczenie Do połowy lat siedemdziesiątych XX w. pacjenci cierpiący na chorobę wrzodową byli skazani na stosowanie re− strykcyjnej diety, częstego odpoczynku i pobytów w szpitalu oraz niejednokrotnie byli operowani z powodu powi− kłań choroby. Wprowadzenie w 1976 r. antagonistów receptorów histaminowych H2 zmniejszyło znacznie liczbę powikłań i hospitalizacji. Obecnie podstawą leczenia antysekrecyjnego są inhibitory pompy protonowej (IPP) wprowadzone na rynek w 1984 r., ale ze względów finansowych leki działające antagonistycznie na receptory H2 są jednak nadal szeroko stosowane. Przełomem w leczeniu zachowawczym owrzodzeń trawiennych było opisanie w 1983 r. przez Warrena i Marschalla wpływu bakterii Helicobacter pylori na błonę śluzową żołądka i dwunastni− cy oraz wprowadzenie leczenia eradykacyjnego (Adv Clin Exp Med 2004, 13, 5, 737–747). Słowa kluczowe: choroba wrzodowa, Helicobacter pylori, antagoniści receptorów histaminowych H2, inhibitory pompy protonowej (IPP). Abstract Up to middle seventies patients with peptic ulcer were forced to use restrictive diet, long resting, hospitalization and often surgical procedures due to complications of the disease. Introducing of H2−antagonists in 1976 decreased dramatically the number of complications and hospital care of the disease. Nowadays the standard of antisecreto− ry treatment is the use of proton pump inhibitors introduced to the market in 1984 though due to the cost the H2− blokers are still widely prescribed. The breakthrough of peptic ulcer treatment was discovery of Helicobacter pylori influence on gastric and duodenal mucous by Warren and Marschall in 1983 and introduction of eradication treatment (Adv Clin Exp Med 2004, 13, 5, 737–747). Key words: peptic ulcer disease, Helicobacter pylori, H2−receptor antagonists, proton pump inhibitors (PPI). For the long time patients with peptic ulcer dis− scopic examination of stomach increased the prob− ease had been forced to restrictive lifestyle, fre− ability of confirming the active ulceration and eval− quent hospitalizations, often with gastric juice aspi− uation of its healing. From early 60s many ran− ration and long resting in bed. Diagnosis and treat− domized trials have been performed what com− ment of peptic ulcer had been mainly based on the pletely changed the clinical approach. Gradually intensity of clinical symptoms. Because of rather the specialist have been withdrawing from restric− vague correlation between clinical symptoms and tive diet and new drugs have been introduced [1]. peptic ulceration there had been no objective way to evaluate the effectiveness of different ways of History treatment. No randomized trials had been per− formed and the management of the disease had The symptoms that are caused by peptic ulcer been based on tradition and personal observations. were for the first time described by Diokles (350– The introduction of radiological and later endo− –325 BC) [2]. Gajus Plinius (23–79 AD) advised 738 L. PARADOWSKI, W. BŁOŃSKI, R. KEMPIŃSKI to the people with abdominal pains the consump− It is necessary to mention that those days the pep− tion of donkey or cow milk. He claimed that if the tic ulcer disease could only be diagnosed when ulcer grows in stomach, drinking of milk will heal bloody vomiting or tarry stools were reported – no it. Apart from that the knowledge about ulcer dis− radiological examinations with contrast were ease in ancient times and the Middle Ages was introduced into clinical practice and no random− limited. The studies on human anatomy performed ized trials were performed to evaluate the efficacy in the Renaisance led to better understanding of of different diet schemes in ulcer disease. Diet the structure of upper gastrointestinal tract [3]. The treatment was based on the theory that light meals first documented gastric ulcer was described by were less stimulating for gastric juice secretion Donatus in 1586. Donatus performed the post and that patients on long term diet were more often mortal examination of stomach and found the pain free [4, 5]. ulcer in distal part of stomach and pylorus. In 1772 In 1912 Bertram Sippy described the algo− John Hunter described the digestive properties of rithm of management in peptic ulcer disease. gastric juice. The term “peptic ulcer” was based on Sippy’s recommendations included: resting in bed, the theory that the lesion is caused by digestion. In complete starvation diet in the first 5 days fol− 1793 Matthew Ballie described the pathomorphol− lowed by every hour feeding with milk and cream ogy and clinical features of gastric ulcer. What is shifting with antacid administration and control− worth mentioning that Ballie and his successors in ling the gastric juice secretion [6]. Sippy claimed XIX and XX century paid a lot of attention to gas− that: “gastric or duodenal ulcer would heal as tric ulcer – duodenal lesions were considered to quickly as any other ulcer if its surface was not appear rarely. exposed to acid digestion”. The aim of Sippy’s In XIX century French scientist Cruveilhier for therapy was preventing the ulceration from its the first time distinguished the gastric ulcer and digestive activity, what could be achieved by com− gastric cancer. The term “oval Cruveilhiera ulcer” plete neutralization of all acid when the stomach is describing the benign ulceration had been used in filled with food and the gastric juice is excreted literature till the end of XIX century. Englishman [7]. In 1915 Sippy modified his recommendations: John Abercrombie in his studies of peptic ulcer dis− the initial complete diet was liquidated and the ease noticed that in patients with duodenal ulcers amounts of milk and cream in the every hour the symptoms usually appear after 2–4 hours after meals were increased. The patient was resting in the meal. In the treatment Cruveilhier and bed for 3–4 weeks and every hour between 7 am Abercrombie prescribed the increased consump− and 7 pm he was receiving the combination of tion of milk. Abercrombie recommended light diet milk and cream. After 2–3 days the boiled eggs with small amounts of food per meal consisted gen− and precooked cereal products were introduced [6]. erally of milk and its products. In more advanced He also advised the consumption of neutralizing clinical cases he suggested occasional administra− mixtures (calcium carbonate, natrium carbonate, tion of bismuth oxide and calcium water. magnesium carbonate) between meals and every 30 minutes between 7 and 10 pm. Sippy was also performing gastric juice aspiration with Ewald Conventional Treatment catheter (3 times a week) to decrease the nocturnal of Peptic Ulcer Disease pains. The amount of aspirate was then measured to calculate the “free and total acid volume” [1]. In XIX and XX century the light diet was the Zankiewicz in 1948 performed the study of only treatment of peptic ulcer disease. In 1876 xenogenic blood infusions in 11 patients with gas− Leube recommended complete starvation diet. tric and duodenal ulcers [8]. The initial dose of 5 ml Gradually the recommendations were extended to caused the shock, then the 3–5 day interruption in milk, eggs, milk products and other light and not therapy was made depending on the extent of stimulating food. shock. Then the dose of blood was individually In 1901 during Internal Medicine Congress in modified even up to 20 ml. Each of 3 patients Wiesbaden Lenhartz proposed frequent and small received 5 blood infusions. In compared group in amount meals for patients suffering from peptic patients received: Extractum Belladonnae, Atro− ulcer. Diet had to be composed of food “not irri− pinum sulfuricum, Calcium bromatum i.v., Solutio tating” the ulceration and not stimulating the natrii hyposulfurosi i.v. and Phenobarbital. After secretion of gastric juice. In his own study treatment all patients were symptoms free and in Lenhartz showed that among 60 patients remain− 2 cases the healing of ulceration in radiological ing on his diet only 4 experienced the reoccurrence examination was confirmed. Zankiewicz also men− of hemorrhage from upper digestive tract what tioned the similar study by Mejerowicz and Blumin was far less than in patients on Leube diet (20%). who were treating 48 patients with blood infusions. Achievements in Peptic Ulcer Disease Conventional Treatment 739 In 1932 Winkelstein for the first time proposed 4 hours. In the first year after healing he advised the treatment of peptic ulcer with constant oral in− administration of naturalizing factors such as mag− fusion of milk. In 1933 he introduced milk with nesium trisilicate [10]. Doll and Pygott in their natrium bicarbonate. The infusion rate was 30 drops/ study also proved that hospitalization shortened /min (up to 3 liters par day) to the catheter placed the duration of peptic ulcer healing [11]. in duodenum. In 1942 Cornell et al. compared the In 1956 Doll et al. published the results of the effectiveness of different neutralizing mixtures. trial comparing the effectiveness of gastric milk He found the mixture of milk and calcium bicar− infusion in patients with gastric ulcer and in con− bonate to be the most effective. In 1947 trol group. Although the percentage of patients Douthwaite concluded that the most effective in with healed ulcer in both groups was similar, in neutralizing the acid is continuous 24−hour infu− patients receiving milk the pain withdrawal and sion infusion of 2.5 liters of milk through the weight gain was faster. Doll advised milk con− catheter placed in stomach. In 1950 Clark in his sumption as additional therapy when the pain was study proved the efficacy of 9−day intraoe− not reduced by resting in bed.