The history of the study of acute appendicitis from antiquity to the present day.

Krylov Nikolai Nikolaevich Doctor of Medicine Professor of Department of Humanities, Institute of Social sciences The IM Sechenov First Moscow State Medical University 119571, Russia, Moscow, Leninsky Ave., 150 nnkrylov01@yandex.ru

The history of appendicitis includes examples of pronounced resistance to a change in the leading surgical paradigm, scrupulous but subsequently rejected results of early observations, emotional support for unconfirmed views, the importance of making general recommendations and, finally, the development of a highly satisfactory final solution.

Acute appendicitis (OA) is one of the most common acute surgical diseases known to mankind for a long time. It is assumed that the cause of death of a person embalmed in ancient Egypt around 2800 BC was right-sided delimited peritonitis, probably of appendicular origin ^[1]. The social significance of OA in the Russian Federation is currently determined by high morbidity and stable hospital mortality (142.3 and 0.215 cases per 100 thousand population, respectively) ^[2].

Anatomical studies.

Galen, who of all the ancients gave the most complete anatomical descriptions to date, did not find and did not describe the appendix, because he dissected only monkeys (mainly Pirinean macaques) who do not have an appendix. And what Galen did not establish, no one saw or quoted throughout the Middle Ages. And only in 1472 – Leonardo da Vinci depicted the appendix in drawings dedicated to human anatomy. However, they remained unknown for several centuries ^[3]. Then in 1522 Berengarius Carpus, professor of the Department of Human Anatomy at the University of Bologna (Italy), described the vermiform process as an independent organ. He found a kind of "appendage" of the colon empty inside, less than the width of the little finger on the hand and about three inches long. The appendix is clearly visible in the illustration of Andreas Vesalius' book De Humani Corporis Fabrica (1543), although it was not described in the text of the publication. Soon there was a terminological confusion due to the name of the appendix of the cecum in the works of Stephanus (1545) and Ambroise Pare (1582). It really had the form of a blind sac, while the true initial part of the colon, in their opinion, is just the junction of the appendix, ileum and colon ^[4,5].

Fallopius (1561) was the first to compare the shape of the appendix with a worm, and Bauhin (1579) hypothesized that the appendix in utero serves as a receptacle for feces. By the end of the eighteenth century, the general anatomy of the appendix was fairly well known. However, in 1847, Gerlach first drew attention to the fold of the mucous membrane, which can act as a valve closing the mouth of the appendix and which has since borne his name. Trietz in 1857 described the pericecal pits of the floating peritoneum, and Clado in 1892 attracted interest in the fold of the peritoneum running from the ovary to the mesoappendix and since then known as the "Klado fold". Subsequently, it was believed that it was in it that the lymphogenic path of infection spread from the appendages of the uterus to the appendix ^[6,7].

Autopsy data and pathogenesis

Many researchers of the history of appendicitis attribute Jean Fernel, the court physician of Catherine de' Medici, the first description of a postmortem diagnosis (1544).  This is claimed by the German surgeon Von Hilden (1652). A more vivid description of the destructive complicated appendicitis of the student of Boerhaave, Lorenz Heister (1711), who, after opening the body of a recently executed criminal, found a small abscess next to the blackened appendix. The Parisian surgeon Mestivier (1759), when opening the corpse of a 45-year-old man who died shortly after surgical drainage of an abscess in the lower right quadrant of the abdomen, explained the formation of an abscess by perforation of the appendix with a pin ^[8]. Since that time, there has been a fascination with the theory of the influence of foreign bodies as causes of obstruction and perforation of the appendix. In line with this theory was the observation of J. Parkinson (1812), who described a perforated appendix containing fecal matter and an unchanged cecum during the autopsy of a 5-year-old boy. Other post-mortem examinations found worms, pins, stones, fecal matter and other contents in his cavity ^[6]. This is where the definition of the vermiform process originates as "the trash bin of the abdominal cavity (digestive tract)". Already in 1839, Bright and Addison stated that the appendix is the cause of many or most of the inflammatory processes of the right iliac fossa ^[9]. Clinical observations and conservative therapy

 In the work "On epidemics", which is attributed to Hippocrates, there is a description of a clinical observation resembling the course of perforated appendicitis. "A woman who stayed at the house of Tisamenas had a painful attack of iliac pain (acute abdominal pain and bloating), severe vomiting; could not resist drinking; pain in the hypochondrium, as well as in the lower abdomen; there is no thirst; it became hot; limbs cold all over the body with nausea and insomnia; urine scanty and liquefied; the secretions are undigested, liquid, scanty. Nothing could do her any good. She died"^[10].

 The second aphorism of Hippocrates, "Suppuration with prolonged pain in the intestine is bad," led doctors of subsequent generations to believe that he knew and spoke about an abscess of the appendix. In addition, Peter Lowe (1612) claimed that Hippocrates really died of this disease. Obviously, most of these abscesses were indeed associated with the appendix, since stochastically it is most likely. The ancient Roman doctors Celsus and Galen observed patients with abdominal pain below the navel, more often on the right, which was prone to relapse. Subsequently, Areteus, Villanovanus, (1300) and Fernelius (1567) added little to the above observations ^[11].

In the early Christian era, the ancient tactic of "opening and draining" was used for abscesses in general and was sometimes used for accumulations of pus in the right iliac fossa. For example, Areteus in the II century opened an abscess in the right half of the abdomen, but it was next to the liver, and there are some doubts as to whether it was a perinephrine abscess or an abscess associated with the colon. In any case, surgical treatment was always postponed until the last possible moment, when the signs of an abscess became obvious. Ancient doctors preferred to allow the abscess to open on its own or allow the patient to die a peaceful death without subjecting him to torment due to the opening of the abscess. I.e., without exposing himself to the possible risk of being accused of murdering the patient and preferring that he die a natural death. This tactic persisted until the XIX century; only the waiting period varied: some doctors advocated only earlier removal of pus than others ^[8].

Oribasius (IV century) and Arab doctors - Razes and Avicenna (X-XI centuries) - encouraged the opening of an abscess in the abdomen, strengthening the skin covering it with astringents

The main method of treatment or supplement to it was bloodletting: immediate phlebotomy in the elbow bend, and in the presence of urinary retention - also from the subcutaneous vein on the ankle.  Emetics were prescribed if the pain was above the navel; laxatives - if it was localized below. In cases where there were signs of obvious inflammation, these remedies were not used, and bowel emptying was attempted with the help of volumetric and multiple enemas. The patient was prescribed to sit in a bath with hot oil in which various medications were dissolved ^[7].

The condition of such patients, as a rule, remained stable until a large abscess formed or complete intestinal obstruction with vomiting appeared, followed by a fatal outcome.  The cause of their illness was considered to be an incompetent ileocecal valve, and the lack of a detailed examination of the entrails during autopsy was because, for example, F. Hildanus (1620) claimed: "Most of these corpses smelled so terrible that he was not very attentive during examination" ^[12].

There were also rare cases of spontaneous recovery without treatment. For example, a Saracenus patient (1642) with a large abscess in the right groin, which opened on its own, forming a fecal fistula. In addition to the intestinal contents, 14 worms (ascaris?) emerged from this fistula at different times.

Sydenham (17th century) recommended in these cases to apply to the abdominal wall above the inflammatory infiltrate the cut body of a newly killed puppy. In cases where the pain recurred or when symptoms of abdominal discomfort persisted after an attack of pain in the iliac region, he recommended constant riding to shake out harmful substances from the caecum, where they were prone to accumulate. A.Pare in the sixteenth century insisted that many were cured of severe diseases of the ilium by drinking three pounds of mercury in hot water, "which even saved them from imminent death." It is curious that this practice, supported by the authority of the "father of modern surgery", persisted until 1830.

Some of the ancient doctors forced their patients to swallow lead pills (balls, bullets) in the hope that with their weight they would be able to overcome all obstacles and finally cause a full bowel movement. Helmont (1664) attributed all abdominal symptoms to bloating and suggested that all obstacles could be eliminated by swallowing lead bullets: "No one can die from inflammation of the ilium if only he swallows lead musket bullets, which by their excessive weight can move an obstacle located in the intestine." The larger these balls were and the more they were swallowed, the faster they should have had an effect, especially if the patient could stand on his feet and move in an upright position ^[13].

The European authority G. Burgave in "Aphorisms" (1709) warned against such stupidity with a warning that is not without its value today: "As long as this disease continues in its inflammatory stage, it often affects unwary people with colicky pain, which is attributed to cold, wind and flatulence and, accordingly, she is poorly treated with carminative and intoxicating medicines, and with fatal consequences." The complex therapy of such cases according to Burgava included the following treatment:

1. Large and repeated bloodletting.

2. Laxative and cooling enemas 3-4 times a day and more often.

3. Cooling drinks with "reasonable addition of opiates".

4. Abscesses of the abdominal wall are opened by inflicting a wound (primarily in young subjects).

 5. Avoid anything warming.

6. Continue the same course until a complete cure is provided, that is, until all symptoms disappear within three days ^[8].

 However, the treatment with bullets continued for at least another century, as evidenced by the case of Herlin (1768), who published the results of an autopsy of a man who died of inflammation in the right wing of the ilium. He was forced to swallow three large lead balls (in the hope of overcoming the obstruction). At autopsy, they were found in the appendix, which was expanded to the size of the rest of the intestine.

In 1705, D. Morgagni described in great detail the clinical and anatomical parallels (complaints, anamnesis, data from an objective study and dynamics of clinical symptoms over several days and the results of an autopsy of the body of the deceased) with destructive complicated appendicitis and published his observations in the classic work "De sedibus et causis morborum per anatomen indagatis libri V" (1761).

        The "gold standard" of treatment of the inflammatory process caused by inflammation of the process, in 1830-1880, was the appointment of large doses of opium. Although, apparently, the antiperistaltic effect of the drug allowed the inflammatory process to be localized to some extent, the principal advantage of such treatment was, most likely, the comfortable death of the patient in an unconscious state ^[11,14].

Surgical treatment

The world's first appendectomy was performed by the chief surgeon of Queen Anne, as well as Kings George I and George II Claudius Amyand in 1735 at the St.George is in London . The removal of the process was "forced" because he operated on an 11-year-old boy for an inguinal hernia complicated by a fecal fistula. In the hernial sac, Amyand found a perforation of the apex of the vermiform process. The surgeon decided on appendectomy (ligature method) and herniation with a favorable outcome ^[15].

            Frenchman Francois Melier (1827) first described the clinical picture of acute appendicitis and confirmed his lifetime diagnosis during a sectional study of 6 corpses of patients who died from this disease. He suggested that it was the vermiform process, and not the cecum, that was the cause of ileocecal infiltrates, ulcers and peritonitis, and also for the first time unequivocally spoke in favor of the possibility of surgical removal of the appendix.  This point of view was ignored in Europe due to the influence of the opinion of Baron G. Dupuytren, a leading surgeon in Paris ^[16,17], who did not recognize the appendix as the cause of inflammation in the lower right quadrant of the abdomen.

The explicit or implicit rejection of the appendicular theory of the genesis of inflammation in the right iliac fossa and the refusal of surgical removal of the process can presumably be explained by the lack of ideas about the tactics and technique of such intervention in the absence of general anesthesia (which appeared only in the middle of the nineteenth century) and the doctrine of antiseptics by D. Lister (1867).

          In the 1840s-1880s, the main method of surgical treatment of acute appendicitis in the world was the opening and drainage of paraappendicular abscesses. At the same time, in the middle of the XIX century, disputes arose as to where the true cause of inflammatory processes of the right iliac fossa lies. Terms such as "stercoral typhitis", "simple typhitis", "perithiphilitis", "chronic typhilitis", "apophysitis", "epithelitis", "pericecitis" and others flooded the specialized literature of that time ^[18].

           In 1848, H.Hancock performed laparotomy for the first time in a patient with acute peritonitis lasting several days, drained the abdominal cavity in the lower right quadrant of the abdomen, but did not remove the inflamed appendix. Two weeks later, fecal matter left the drained abdominal cavity and the patient recovered. He suggested such treatment before the appearance of softening and fluctuation over the infiltrate, as well as before the formation of dense adhesions in the abdominal cavity. The optimal time for such an operation, in his opinion, took a period of time from the fifth to the seventh and from the eleventh to the fourteenth day of the course of the disease ^[19].

The first operation in Russia for an abscess in the right iliac cavity (opening of the abscess) was performed by Prof. P. Y. Nemmert in 1843 to his colleague Prof. V. E. Ekk. N. I. Pirogov summarized the principles of treatment of ulcers in the right iliac region in Russia in 1852. In the journal "Friend of Health" he published an article "On abscesses of the iliac cavity" and described extraperitoneal access ("Pirogov access") for opening a paraappendicular abscess. P. Platonov (under the guidance of N. I. Pirogov) defended his doctoral dissertation "On abscesses of the iliac cavity" (1854). In 1861, at the St. Petersburg Medical and Surgical Academy, Tula physician G. Shakhtinger defended his doctoral dissertation on the topic "On inflammation of the cecum, its vermiform process and surrounding fiber". However, the works of Russian surgeons did not mention either the early symptoms of OA or the nature of pathological changes in the process ^[20].

             In 1880, L.Tait (England) apparently performed the first appendectomy for gangrenous appendicitis. But later he avoided the operations of removing the appendage and was an ardent opponent of "listerism" ^[8] Seal A. Appendicitis: a historical review. Can J Surg 1981; 24:427-433. Information about this and other "pioneer" operations was revealed retrospectively after many years. For example, operation A.Groves in 1883^[21].

 The first appendectomies were sporadic and had intermittent success. Thus, patients Mikulicz (1884) and Kronlein (1885) did not survive the operation, and Charter-Symonds (1885) successfully removed both the process and the free-lying fecolitis out of the peritoneum. R.Hall (1886) operated on a 17-year-old patient for an inguinal hernia, the contents of which was a perforated process. Appendectomy and drainage of the pelvic abscess led to the recovery of this patient ^[15]. In the USA, it is believed that T.Morton performed the first correct preoperative diagnosis and targeted appendectomy after laparotomy in 1887. Unfortunately, he lost from the natural course of the unoperated  OA of both brother and son ^[8].

Already by 1882, the most important question began to be discussed: "How to treat frequent cases of perforation of the vermiform process, in which there is no limited accumulation of pus (abscessing)?". Extreme points of view on this problem have appeared. Byrd: "I have not been able to find a single recorded case in which this procedure (laparatomy) has been attempted with success. No matter how plausible and important this operation may actually be, the difficulty of making an accurate diagnosis will become an almost insurmountable obstacle to its implementation. Medicine is useless in these cases, except for euthanasia, and surgery can't even do that."  However, Mikulicz was full of optimism: "It would be much better if we could remove the appendix as soon as the diagnosis of its inflammation was sufficiently reliable, and remove from the abdominal cavity any concretions or decomposing tissues that could be the cause of inflammation." These words represent the end of the preceliotomy period of the period of preceliotomy in the history of the appendix, when a simple incision and removal of pus were recognized as appropriate surgical treatment.  The actual removal of the appendix has now become the focus of the surgical world, and the modern era of medical surgery was about to begin ^[22,23,24].

To introduce a new paradigm in the treatment of OA and clarify the nomenclature of the disease was able in the USA, when on June 18, 1886, a professor at Harvard University (USA) pathologist.Fitz read a report on perforated appendicitis, its early diagnosis and treatment ^[25]. He proved that most of the inflammatory diseases of the right lower quadrant begin in the appendix, scrupulously described the clinical features of appendicitis and, most surprisingly, insisted on the speedy surgical removal of the appendix.

He showed that in 209 cases of typhlitis or perityphlitis, the clinical symptoms were identical to those observed in 257 cases of appendix perforation, and convinced the medical world that with any inflammation of the right iliac fossa, "fons et origo mali" ("root and source of evil") is the vermiform process of the cecum. He also established a mortality rate in the treatment of acute appendicitis – 67%. In addition, Fitz used the term "appendicitis" for the first time. Subsequently, this term was criticized because it consists of a Greek suffix with a Latin root. Nevertheless, he soon entered the professional thesaurus and became generally accepted.

In 1889, Charles McBurney (USA) described the cardinal, which have become "classic", symptoms of acute appendicitis, formulated indications for early laparotomy in this disease, justified oblique variable access to the appendix in the right iliac region ^[26]

Since 1890, the historiography of appendicitis has become a history of improving techniques and diagnostics. At the same time, as a rule, it was a question of a variant of laparotomic access and a method of processing the stump of the process.

The contribution of Russian surgeons should be noted.  In 1888, K.P.Dombrovsky tied a vermiform process at its base with an appendicular abscess in a three-year-old child.  In 1889, A.A.Bobrov resected part of the process from the appendicular infiltrate. And in 1890, A.A.Troyanov performed the first appendectomy in Russia at the Obukhov Hospital.P.I.Diakonov in 1894 performed the first appendectomy in Russia in a child, and in 1901 he proposed peritonization of the ligated stump of the appendix with a pouch suture; he also for the first time performed immersion of the unbound stump of the appendix into the cecum with a pouch suture ^[20].

  By the beginning of the twentieth century, the number of appendectomies performed by individual surgeons was already in the thousands ^[27]. Moreover, about 23 of them were "interval" - some time after the acute attack was stopped, already in the "cold" period ^[28].

       The slow accumulation of quantitative successes in the treatment of OA changed qualitatively after the introduction of antibiotic therapy into clinical medicine in the 1940s and 1950s. Surgeons were able to prevent and treat vital septic complications ^[29].

There are several cases of a doctor performing an "open" (laparotomy) appendectomy to himself: in 1961 - Leonid Rogozov during an Antarctic expedition; in 1976 - Sergey Pakhomov on a nuclear missile submarine (then he was awarded the Order of the Red Banner of Battle) ^[20]. 

A qualitative change in the technique of appendectomy surgery occurred in the second half of the twentieth century after the introduction of laparoscopic technology and equipping the operating room with special dissecting soft tissues and stitching equipment. So in 1977, Dekok performed an endoscopic appendectomy for the first time, but removed the appendage through an additional mini-laparotomy. Already in 1988 K.Semm (Germany) performed a “passing” laparoscopic appendectomy for chronic appendicitis during gynecological surgery, and in 1987 J.Schrieber (Germany) performed the first laparoscopic appendectomy for acute appendicitis ^[20].Currently, the frequency of laparoscopic appendectomy in the Russian Federation varies by district from 9.85 to 53.1%, averaging 25.1% across the country ^[2].

Possible influence on the course of history

     31/XII, 1882, the famous politician and statesman, the Prime Minister of France, Gambetta L.M., died; the cause of death was retrocecal gangrenous appendicitis masked by the clinic of acute food toxicoinfection. Only the famous Parisian surgeon O.M. Lannelongue insisted on the operation, firmly settling on the diagnosis of retrocecal appendicitis and retroperitoneal abscess. But other surgeons disagreed with his diagnosis.  "My assumptions were rejected," Lannelongue wrote bitterly, "the people surrounding Gambetta stopped trusting me"^[16]. DeMoulin D. Historical notes on appendicitis. Arch Chir Neerl 1975; 27:97-102.

           On June 26, 1902, the coronation of Edward VII (Great Britain) was scheduled, but on June 23, symptoms of acute appendicitis appeared and began to progress rapidly. Dr. F.Treves recommended immediate surgery. The future king asked to postpone the operation and perform it after the coronation. Then F. Treves uttered the famous phrase: "In this case, your corpse will be crowned" ^[30]. Courtney J.F. The celebrated appendix of Edward VII. Med Times 1976; 104:176-181. The coronation was postponed, the patient was operated on with recovery. F. Treves recalled that he did not leave the patient for seven days and nights. For services to the king, he allowed himself to resign in 1908, and Edward VI ruled the British Empire for eight years.         F. Treves was not a supporter of early surgery for acute appendicitis and subsequently lost his daughter from it ^[30,31]. Stevenson RS. Famous Illnesses in history. London: Eyre & Spottiswoode,1962; 23-43. Courtney JF. The celebrated appendix of Edward VII. Med Times 1976; 104:176-181.

In May 1921, the surgeon of the Kremlin Medical Department, N.N.Rozanov, operated on a member of the Politburo and the Organizational Bureau of the Central Committee, and then (from April 1922) and the General Secretary of the Central Committee of the CPSU (b), I.V. Stalin, about gangrenous appendicitis: "The operation was very difficult, in addition to removing the appendix, a very wide resection of the cecum had to be done and it was difficult to vouch for the outcome of the operation" (from the memoirs of V.N. Rozanov). "We decided to operate under local anesthesia because of the weakness of the patient. But the pain forced to stop the operation, they gave chloroform… Then he lay thin and pale as death, transparent, with the imprint of terrible weakness." (F. Alliluyev). V.I. Lenin called Rozanov twice a day, inquiring about the health of the "wonderful Georgian", and a week later (!) the patient had his stitches removed, and ten days later he was discharged!

One can only imagine how the history of Russia would have developed in the event of a premature death of a patient?

On February 26, 1939, the USSR celebrated Krupskaya's birthday, and collectives and individual citizens sent congratulations from all over the country to Ilyich's faithful colleague and girlfriend. And at this time , the doctors recorded the state of the culprit of the celebration: "The patient is still in a state close to unconsciousness. Significant bruising. Cold limbs. Sticky sweat. The pulse is arrhythmic... The general condition remains extremely serious, which does not exclude the possibility of a near sad outcome."

        On the morning of February 27, 1939, N.K. Krupskaya died. In a note to Stalin and Molotov, Professors S. Spasokukotsky, A. Ochkin, V. Vinogradov and the head of the Kremlin Medical Department A. Busalov wrote that "surgical intervention... with a deep lesion of all internal organs and at the age of 70 it was absolutely unacceptable." Officially, the cause of death was "acute appendicitis, peritonitis." I.V. Stalin personally carried the urn with Krupskaya's ashes ^[20].

Conclusion

It is impossible to cite all publications related to OA and which have now become history, since by 1889 there were about 2,500 of them, and by 1950 more than 13,000 ^[32]. Surely, this list is incomplete. Therefore, we stopped at mentioning only fundamental and fundamentally significant works.

Guided by the nature of surgical interventions adopted at different times and the evolution of indications for them, the history of the doctrine of appendicitis can be divided into several periods ^[20].

The first period lasted for several centuries until 1884. At that time, few patients with periappendicular abscesses were subjected to surgical treatment. Indications for surgery were given only when the abdominal wall was involved in the suppurative process. Often such ulcers were opened independently. Patients with peritonitis were not operated at all.

The second period (1884-1909) is significant in that the process began to be removed in the acute period of the disease, but only with diffuse or delimited peritonitis. In addition, appendectomy was performed in the “cold period” in case of the effectiveness of conservative therapy in order to prevent relapses of the disease. Mortality in peritonitis reached 80-90%, and in abscesses – up to 30%.

The third period in Russia lasted about 20 years (1909-1926). Appendectomy was performed only within 24-48 hours after the patient was admitted to the hospital in the absence of a positive effect from conservative therapy and the appearance of symptoms of destructive appendicitis. Such tactics were justified by the fact that the clinical symptoms of appendicitis, especially in the first hours of the disease, do not correspond to pathoanatomic changes in the process, and it is not always possible to predict the outcome of the disease. And after 48 hours, the inflammatory process either subsides or is limited. The use of early surgery in the first 48 hours allowed to reduce the overall mortality rate to 2.8%, but with advanced forms it remained high (more than 20%).

The fourth period (late 1920s - 1960s) is the period of emergency operations for acute appendicitis, regardless of the timing and form of the disease. A patient with suspected acute appendicitis was operated on within 6 hours from the moment of admission to the hospital, if this diagnosis cannot be excluded.

The number of appendectomies has increased enormously. The overall mortality rate decreased to 0.1-0.2%, and in destructive forms – to 1.5-2.1%.However, the number of unjustified appendectomies has sharply increased (on average 15-40%).

The fifth period (late 1960s–1970s) is a wait-and–see tactic. In the absence of an increase in acute phenomena, patients were monitored during the day. However, emergency intervention remained the leading principle in most institutions.

The new period (1980s – present) is the period of refined preoperative diagnosis of acute appendicitis. Radiation (CT, ultrasound) and video endoscopic (laparoscopy) methods allow to confirm the clinical diagnosis before surgery, reduce the frequency of unjustified laparotomies and appendectomies to 1-3%. Laparoscopic appendectomy is being developed, improved and widely used.