The etiology and pathogenesis of carcinoid

Etiology of carcinoid, as well as with other malignancies, remains unclear.
The tumor, not complicated carcinoid syndrome, often over a long period of time causes no clinical manifestations. The latter arise in any localization of carcinoid if the tumor process captures the regional lymph nodes and mesentery or penetrates into the mucous membrane. This rarely happens when carcinoid Appendix and is very often seen in cases of destruction of the bowel. With the spread of this invasive tumor and the growth is massive education connective tissue at the nearby tissues, which gradually leads to active puckering and scar rebirth of the mesentery in the relevant sections of the gastro-intestinal tract. Such violations contribute to the emergence of intestinal obstruction, often by type of intussusception or inversion.
Only in the last decade were obtained new data on the clinical picture and the pathogenesis of the so-called "carcinoid syndrome". Initial ideas about the nature of the latter is closely connected with the discovery and study of serotonin and modern views on violations of its currency in various pathological conditions.
Recent studies Penttila and Lempinen (1968), held on bioptic material using conventional colors and the method of fluorescence, found that enterochromaffin cells throughout the gastrointestinal tract is rich in serotonin - 5-hydroxytryptamine (5-GOTH).
Until recently, most researchers have carcinoid syndrome" as a result of an intermittent increased revenues in the blood serotonin produced enterochromaffin cells. Indeed, carcinoids have the ability to convert tryptophan to serotonin, and half of dietary amino acids consumed tumor cells that creates real prerequisites for the emergence of endogenous deficiency of nicotinic acid, for education which tryptophan is also necessary.
Grahame-Smith (1964) in vitro after incubation slices of carcinoid tryptophan, labeled with radioactive carbon - 14, in the presence of inhibitors decarboxylase observed the formation of 5-hydroxytryptophan, is the precursor of serotonin.
When functioning carcinoids some researchers found in the blood increase serotonin content above 0.1 to 0.3 mg/ml, and in the urine of a significant increase in the concentration of 5-hydroxyindole-acetic acid (5-GOIC), reaching 50 - 500 mg at the rate of 2-10 mg (Pernow and Walnenstrom, 1954, 1957; Uden-friend, 1955; Jones and others, 1968). However Lembeek (1953) have long warned against excessive hobby serotonin theory of origin "carcinoid syndrome" and has expressed an opinion about a possible value of other biologically active substances produced by the tumor.
Clinical observations testified that, as a rule, at the height of spontaneous seizures redness in the blood were observed increase of concentration of serotonin. Intravenous administration of serotonin was not accompanied by typical episodes of redness. The decarboxylase inhibitor, reduces the synthesis of serotonin, and direct antagonists actions last (cyproheptadine at and metisergid) has been very little effective means of struggle with bouts of redness (Sjoerdsma and Melman, 1964).
Intravenous injection of epinephrine in patients with carcinoid was accompanied by typical episodes of redness, that has allowed to carry adrenaline test to the number of diagnostic tests.
Trying to explain the mechanism of action of adrenaline in such cases, Oates and Sjoerdsma (1962) remembered observations Hilton and Lewis (1956), which showed that catecholamines released from perefuterovan salivary gland kinin-peptides. They suggested that adrenaline in similar ways can affect carcinoid tumors. Kinin-peptides are related to highly active biological substances that cause expansion of blood vessels, bronchial spasm, hyperperistaltic intestines. To endogenous peptides of this type are lysyl-bradykinin and bradykinin, formed by the action of proteolytic enzymes (callicrein) on protein substrate - kininogen belonging to A2-globulin, which are synthesized in the liver and enter the bloodstream.
Kallickreina normal form of glandular elements of the pancreas, intestines, salivary glands and sweat glands. It turned out that when intravenous bradikinina arise typical episodes of redness and enzyme (kallickrein), which can form bradykinin of A2-globulin, was isolated from metastases carcinoma in the liver (Melman and others, 1965; Werle, etc., 1966).
This enzyme is chemically different from plasma kallikrein and released into the blood stream during spontaneous and adrenaline and alcohol episodes of redness. In many patients there was a correlation between the occurrence of attacks of redness and increased content in the blood of kinins, and increased venous tone and accelerate blood circulation. However, some patients with carcinoid syndrome" level of kinins plasma did not differ from the norm. Perhaps modern methods of study of kinins are not sensitive enough to detect out of focus, but pharmacologically significant changes in their concentrations in the blood.
Most researchers believe that kinini determine the occurrence of episodes of redness; as for the other symptoms of carcinoid syndrome, the role of kinins in them remains unclear. Kinini like serotonin may stimulate the growth of fibrous tissue, cause bronhospazm, and also to enhance the motor activity of the bowel, but Melman (1968) warns against erroneous claims that kinini are the only mediators carcinoid syndrome".
Recently, the researchers ' attention was attracted by a prostaglandin, a group of naturally formed gidroxizina acids with strong biological activity (Bergstrom and Weeks, 1965; Carlson, 1966; Pickles, 1967; Euler and Elliason, 1967). Intravenous administration of large doses of prostaglandins people were led to episodes of redness. It is possible that in cases "carcinoid syndrome", where the level of kinins did not differ from the norm, episodes of redness were due to increased allocation of prostaglandins (Sandler, 1968).
Now suggest that localization of carcinoids and their embryonic origin in a specific way affect the features of carcinoid syndrome in different groups of patients. One of them are carcinoids bronchus, stomach, and pancreas diseases originating from the front of the colon (the foregut), the other - carcinoids of the small intestine, emerging from the mid-gut (mitgut).
Embryological classification Williams and Sandler (1963) was recently modified Pariente et al. (1967) and presented on the table. 6.

Presents the literary data clearly indicate that carcinoids are multicuturalism tumors, which explains polimerplast clinical picture "carcinoid syndrome". The leading role of serotonin in the development of the latter currently under revision, and, obviously, this hormone causes only some pathological symptoms (diarrhea, intestinal hyperperistaltic, change the endocardium), while other biologically active substances (kinini, histamine, prostaglandins, antidiuretic hormone and others) take an active part in vasomotor and hemodynamic disorders (episodes of redness, hypotension, cardiac failure and other).
One should agree with the opinion Sjoerdsma and Melman (1964), "carcinoid syndrome" with the expansion of our ideas becomes "carcinoid spectrum.