Carcinoid

Introduction to carcinoid Carcinoid, also known as carcinoid tumor, is a group of new organisms that occur in the gastrointestinal and other organ chromaffin cells. The clinical, histochemical and biochemical characteristics may vary depending on the site of occurrence. Tumors can secrete biologically active factors such as serotonin (serotonin), kinins, histamine, etc., causing vasomotor dysfunction, gastrointestinal symptoms, heart and lung lesions, etc., called carcinoid syndrome. basic knowledge The proportion of sickness: 0.01% Susceptible people: no specific population Mode of infection: non-infectious complication:

Carcinoid cause

The etiology of this disease has not yet been elucidated. Carcinoma is a tumor that produces small molecular peptides or peptide hormones, that is, APUD cell tumors, which can increase the activity of circulating adenine monophosphate through target cells, and can secrete strong physiological Active serotonin (serotonin), vasopressin and histamine, and some hormones that secrete other peptides, such as adrenocorticotropic hormone, catecholamine, growth hormone, parathyroid hormone, calcitonin, Anti-urea, gonadotropin, insulin, glucagon, prostaglandins, gastrin, motilin and other substances, the main substances producing carcinoid syndrome are serotonin and bradykinin, and histamine also participates in some functions.

Serotonin has a direct contraction effect on peripheral blood vessels and pulmonary blood vessels, and also has a strong contraction effect on the bronchus. It has a stimulating effect on the vagus nerve and ganglion cells of the gastrointestinal tract, and the gastrointestinal tract peristalsis is enhanced and the secretion is increased.

Bradykinin has a strong vasodilator effect. Some carcinoid tumors, especially gastric carcinoids, can produce a large amount of bradykinin, vasoactive substances such as histamine and cause skin flushing. Increased circulating serotonin can also cause endocardial fibers. Chemical.

Under normal circumstances, only about 2% of the tryptophan intake in food is used as a synthesis of serotonin (5-HT), 98% into the metabolic pathway of niacin and protein synthesis, but in patients with carcinoid syndrome. 60% of tryptophan can be taken up by tumor cells, resulting in increased 5-HT synthesis, reduced niacin synthesis, and 60% of tryptophan uptake of tumor cells by tryptophan hydroxylase to 5-hydroxytryptophan (5-HTP), which is then converted to 5-HT by dopa decarboxylase, partially stored in the secretory granules of the tumor cells, and the rest directly enters the blood. Most of the 5-HT free in the blood passes through the liver and lungs. Monoamine oxidase (MAO) in the brain is degraded into 5-hydroxyindoleacetic acid (5-HIAA) and excreted from the urine. The level of 5-HT in the serum of carcinoid patients originating from the midgut system is elevated, while 5-HIAA in the urine is discharged. Increase, this is a typical carcinoid syndrome, this accounted for more than 75% of cases of carcinoid syndrome, the foregut system carcinoid often lacks dopa decarboxylase, can not make 5-HTP into 5-HT, 5- HTP is directly released into the blood, so the 5-HTP level in the patient's serum is elevated, while the 5-HT is not elevated, and the patient's urine 5-HTP and 5-HT are discharged. Was added, while no significant increase in 5-HIAA, namely atypical carcinoid syndrome.

More than 90% of carcinoid tumors occur in the gastrointestinal tract, mainly in the appendix, terminal ileum and rectum, and a few occur in the colon, stomach, duodenum, Mckeel diverticulum and biliary tract, pancreatic duct, gonad, lung and bronchus, etc. Ethnic groups, the prevalence of carcinoids may be different, in the case of Japan in the stomach, duodenum and colon carcinoids are more than in Europe and the United States, small intestine carcinoids, it is speculated that this may be with Japan People and Europeans and Americans have different distributions of chromogranin cells in various organs.

Godwin comprehensively 2837 cases of carcinoid, 85.5% distributed in the gastrointestinal tract, the gastrointestinal tract outside the bronchial, lung, head, liver, pancreas, cervix, parotid gland, urethra, even testis or ovary, Orloff comprehensive literature 3000 cases The distribution of gastrointestinal carcinoids was 47.0% in the appendix, 27.5% in the ileum, 17.0% in the rectum, 2.5% in the stomach, 2.0% in the colon, 1.5% in the jejunum, 1.3% in the duodenum, 1.0% in the Meckel diverticulum, and 0.2% in the gallbladder. Most of them are seen in the appendix, and the appendix, ileum and rectum account for more than 90% of all gastrointestinal carcinoid tumors.

Typical gastrointestinal carcinoid, tumor is often a small yellow or gray submucosal nodular mass, single or multiple, mucosal surface more complete, its shape is different, nodular, polypoid or ring A few tumors can form ulcers on the surface, which looks like adenocarcinoma, often invading the muscle layer and serosal layer. Some patients may have multiple-type carcinoid tumors. The ileal carcinoid is often multiple, the tumor is small, and the diameter is 3.5. Below cm, mostly in 1.5cm, a group of 78 cases in China, rectal carcinoid sites are in the rectum below 10cm, the tumor size is about 0.2 ~ 2.5cm, more than 1.0cm, shaped like polyps, but no pedicle, cut face view It is gray or grayish yellow, hard and has a clear boundary.

The cancer-like cells are square, columnar, polygonal or circular under the microscope, the nucleus is uniform, there is very little nuclear fission phase, and the cytoplasm contains eosinophilic particles. According to electron microscopy, the cytoplasm of various parts of the gastrointestinal tract is intracytoplasmic. The morphology of the particles and histochemistry are different. The small intestine cancer cells contain large and polymorphic particles. The silver staining reaction is positive, so it is pro-silver. The particles of gastric cancer cells are round. When silver staining reaction, it must be Adding an exogenous reducing agent is a positive reaction, so it is argyrophilic. The rectal cancer cells are large, round, uniform, and the staining reactions of both silver and silver are negative, so they are non-reactive.

The histological structure of carcinoid tumors is characterized by a variety of arrangement of tumor cells, and Soga et al. are classified into 5 types according to the arrangement.

Type A cancer cells accumulate in solid nodular nests. The cells are roughly circular, irregularly arranged, and infiltrated around the cord. They are more common in carcinoids of the midgut system and are the most typical type.

B-type tumor cells have a small structure, arranged in a layer, such as a shell, the nucleus in the peripheral part, arranged neatly like a grid or strip, more common in carcinoid originating from the foregut system.

Type C square cells are arranged in a glandular shape, but there are no cavities or rosettes.

D-type tumor cells are irregular in shape and irregularly arranged, forming a large myeloid structure. Types C and D are more common in carcinoid originating from the hindgut system.

The E type is various hybrid types of the above four types.

The atypical hyperplasia and mitotic phase of carcinoid are not obvious. It is generally difficult to judge the degree of malignancy from the cell morphology. For reference, the size of a type 1 cancer, comprehensive 843 surgical data, the maximum diameter of 1cm or less, 90%~ 100% manifested as a benign course, between 1 and 2cm, 30% to 50% have metastasis, diameter >2cm, 80% to 100% have metastasis, 2 degree of infiltration, according to statistics have invaded the gastrointestinal muscle layer Cancer, 90% of metastasis, 3 growth sites, appendix carcinoids are almost benign, even if it has infiltrated into the serosa, metastasis is still rare (<2%).

The metastasis rate of small intestine carcinoid is 30%, and the colon is 38%. The malignant carcinoid of duodenum and stomach is rarer than the small intestine.

Carcinoid metastasis can directly infiltrate and grow, penetrate the serosa to the surrounding tissues, lymphatic metastasis or hematogenous metastasis, no local lymph node metastasis and direct hematogenous metastasis. Occasionally, there are reports of hematogenous metastasis. It can also be transferred to bone, lung and brain. Other rare metastatic sites are reported: ovary, epididymis, skin, bone marrow, posterior peritoneum, eyelid, adrenal gland, spleen, pancreas, kidney, thyroid gland, bladder, prostate, child The cervix also reports of metastasis into the breast, and its clinical signs are very similar to those of the primary breast cancer.

Carcinoid cells originate from the enterochromaffin cells (also known as kulchitsky cells) in the APUD cell system. These cells are derived from embryonic neural crests and are widely distributed in the digestive tract. They have chromophore-pro-silver particles and can produce a variety of peptide amines. Hormones, in recent years, with the advancement of immunohistochemical techniques, a variety of hormones have been confirmed in tissue sections. Carcinoid syndrome is a metabolite formed by the serotonin and various vasoactive substances through the liver, and enters the lungs through the blood. The heart, the pulmonary artery and subendocardial fibrous tissue hyperplasia, about half of the cases with right heart valve disease, including pulmonary valve and tricuspid valve thickening, shortening, stiffness, adhesion, endocardial and chordae can be fiber thickening , causing pulmonary stenosis, tricuspid atresia, etc., the left subendocardial elastic fiber has focal or diffuse fibrous hyperplasia and other heart disease, especially bronchial carcinogenesis, left heart, pulmonary artery, tricuspid valve, Aortic valve fibrosis is more common.

Carcinoid prevention

As the cause of this disease has not yet been fully elucidated, it is important to pay attention to some dietary and environmental risk factors that cause cancer.

Carcinoid complications Complication

The disease can be complicated by complications of various systems, and the specific performance varies with the lesion.

Cancer-like symptoms Common symptoms Similar to urticaria skin... Nausea abdominal pain Low blood pressure Diarrhea Systemic weight loss bowel bloating Hepatomegaly Weight loss

Lack of special signs of carcinoid tumors, diagnosis is quite difficult, clinically often overlooked or misdiagnosed as appendicitis, Crohn's disease, intestinal cancer and other diseases, when carcinoid tumors appear carcinoid syndrome, the diagnosis is easier, typical manifested as skin Flushing, diarrhea, abdominal pain, asthma, right heart valve disease and hepatomegaly, increased serum 5-HT content and increased 5-HIAA excretion in urine, which is meaningful for diagnosis. If it exceeds 261.5-523mol/24h, the diagnosis can be established. The histological examination of the tumor can be confirmed.

The primary site of carcinoid and whether there is a transfer, you need to choose the following according to the condition:

1 digestive tract endoscopy and biopsy;

2 bronchoscopy can determine the carcinoid located in the bronchus;

3 selective angiography is helpful for intestinal carcinoid;

4B ultra or CT examination can understand the liver metastasis of carcinoid;

5 digital rectal examination and proctoscopy are helpful in the diagnosis of rectal carcinoid. The symptoms of carcinoid tumors are not obvious or only local symptoms, while carcinoid syndrome often has obvious systemic symptoms. Rectal carcinoids are often used at the time of census. The accident was discovered.

(a) local symptoms of carcinoid tumors

1. Right lower quadrant pain The appendix carcinoid can cause luminal obstruction, which often leads to appendicitis, which is characterized by right lower abdominal pain.

2. Intestinal obstruction symptoms Small intestine carcinoid and its metastatic mass can cause intestinal obstruction, abdominal pain, abdominal distension, bowel, nausea, vomiting and other symptoms.

3. Abdominal masses A small number of carcinoids can occur in the abdominal mass, malignant carcinoids invade the surrounding tissue or metastasis, often appear abdominal mass.

4. Gastrointestinal hemorrhage Gastric or duodenal carcinoid can cause upper gastrointestinal bleeding; intestinal carcinoid can also have blood in the stool or hidden bleeding, and can cause anemia.

5. Respiratory symptoms The most common manifestations of bronchial carcinoids are respiratory symptoms such as cough, cough, hemoptysis, chest pain and so on.

(B) the systemic symptoms of carcinoid syndrome are mostly caused by liver metastasis of malignant small intestine carcinoid, and can also be caused by carcinoids in the bronchus, stomach, pancreas, thyroid, ovary, etc.

1. Skin flushing 63% ~ 94% of patients can have this symptom, mostly in the upper body, mainly in the face and neck, the skin is a bright red seizure change, gastric cancer may be due to the secretion of histamine, so similar Urticaria skin flushing plaques, flushing may be accompanied by fever, tears, palpitations, hypotension, facial and eyelid edema, seizures and duration, most of which last about 1 to 5 minutes, after a long time It lasts for several hours, starts in a few days or weeks, and can be increased to several times a day. It can be stimulated during emotional, physical activity, drinking, eating foods high in tyramine, injecting calcium, catecholamines, etc. Symptoms, after many years of onset, the skin capillaries and venules can be chronically constricted, resulting in a fixed skin blue-purple change, mostly in the face, nose and lip, similar to patients with long-term mitral stenosis.

2. Gastrointestinal symptoms are mainly caused by hyperactivity of the intestines, which can cause episodes of abdominal cramps and bowel sounds. It can have diarrhea from soft stools to episodes of watery stools, and sensation after urgency. The gastrointestinal symptoms are seen in 68%-84. Most of the patients have skin flushing at the same time. Only 15% of the patients have no flushing symptoms, and a few patients may have malabsorption syndrome, which causes obvious poor nutritional status.

3. Respiratory symptoms can occur small bronchospasm, causing paroxysmal asthma, seen in 8% to 25% of patients, this symptom can sometimes be earlier than other symptoms, resulting in misdiagnosis as an allergic disease, like skin flushing, can also be affected Emotional, physical activity, etc.

4. Cardiovascular symptoms are seen in 11% to 53% of cases. After long-term illness, subendocardial fibrosis can occur, affecting the valve part. The right heart is obvious, the left heart is light, and half of the cases can be detected in the late clinical stage. Heart valve disease, tricuspid atresia and pulmonary stenosis are more common, can cause right heart failure, endocardial fibrosis may be caused by serotonin released by carcinoid, lung contains more monoamine oxidase It can be inactivated, so the left heart is only susceptible to the right-to-left shunt and bronchial carcinoid. If it occurs in the left ventricle, it is mainly mitral valve disease, similar to rheumatic heart disease, heart Most of the lesions are the main cause of death in carcinoid patients.

5. Other patients with more than 90% of the patients have liver metastases, often with signs of hepatomegaly. In some cases, skin brown pigmentation and hyperkeratosis may occur in the later stage, which may be rough-skinned and may also cause myopathy. For type I and type II muscle fiber atrophy, arthrosis, manifested as joint stiffness, pain during activity, X-ray visible inter-articular joint erosion, most cyst-like translucent areas in the phalanx, interphalangeal joints and metacarpophalangeal joints near the joint area Osteoporosis.

Clinically, patients with carcinoid tumors should be considered if:

1 right abdomen mass, long-term weight loss, history of diarrhea, suspected and small intestinal carcinoid may;

2 intermittent diarrhea can not be explained by other reasons, facial telangiectasia, paroxysmal flushing, asthma or mental symptoms, suggesting the existence of carcinoid syndrome, such as with hepatomegaly, should consider the possibility of this disease;

3 chronic low intestinal obstruction accompanied by blood in the stool, the course of disease is relatively long, the general situation is still good, should consider the possibility of colon carcinoid tumor;

4 young patients have no history of smoking, lung mass, long-term survival, and can exclude other lesions, suggesting that bronchopulmonary carcinoid tumor may be.

(C) classification of carcinoid tumors Williams according to the different parts of the carcinoid origin have different characteristics, the carcinoid tumors are divided into three types, the three in cytology, histochemistry, biochemistry and clinical manifestations are different, There are also differences in treatment.

Carcinoid examination

(A) 5-HT determination of serum 5-HT levels in patients with carcinoid syndrome often increased significantly, mostly 83 ~ 510mol / 24h (normally 11 ~ 51mol / 24h).

(B) 5-HIAA determination of urinary 5-HIAA excretion in patients with carcinoid syndrome, often more than 78.5mol / 24h, generally 156.9 ~ 3138mol / 24h (normal value <47.1mol / 24h).

(3) Skin flushing test

1 10 ml of ethanol was added orally to 15 ml of orange juice. After 3 to 5 minutes, about 1/3 of the patients developed skin flushing.

2 intravenous injection of norepinephrine 15 ~ 20g, adrenaline 5 ~ 10g, these two stimulation tests are helpful for diagnosis, but there are arrhythmia, heart failure, asthma history should be cautious.

Carcinoma diagnosis

Differential diagnosis

1. Appendice carcinoid should be differentiated from appendicitis or Crohn's disease. Gastrointestinal barium meal and 5-HT, 5-HIAA determination can help identify.

2. Small intestine carcinoid should be differentiated from other small intestine tumors, small bowel barium meal, enteroscopy and 5-HT, 5-HIAA determination, etc., can be identified.

3. Rectal carcinoid should be differentiated from rectal adenoma or adenocarcinoma, relying on proctoscopy and biopsy, has a diagnostic value.

4. Carcinoid syndrome should be differentiated from systemic tissue basophilia, the latter skin flushing lasts 20 to 30 minutes or longer, often accompanied by itching and pigmented urticaria, bone marrow smear can be found tissue hoard Alkaline cells are abnormally proliferating.

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