Primary ovarian carcinoid syndrome

　　One, Etiology

　　It may be caused by the formation of benign teratomas from neuroendocrine cells in the respiratory and gastrointestinal epithelial components, therefore, 85% to 90% of ovarian carcinoids are components of teratomas.

　　Two, Pathogenesis

　　The gross appearance of ovarian carcinoid is a teratoma with yellow solid nodules, with a diameter of 3-15cm, averaging 9cm. Under the microscope, the tumor cells are of uniform size, and the carcinoid cells derived from the midgut are arranged in islet or nest-like patterns; those derived from the foregut and hindgut are arranged in small or ribbon-like patterns. Under the electron microscope, the neurosecretory granules of the islet carcinoid cells are irregularly dumbbell-shaped, while those of the small ribbon-like carcinoid are round or oval.

　　Primary ovarian adenoid carcinoid forms solid masses or nodules within the wall of teratoma or mucinous tumors. Under the microscope, there are two types of cells: goblet cells secreting mucus and argentophilic neuroendocrine cells. Immunocytochemical staining with CEA can distinguish these two types of cells. Under the microscope, the tumor cells are arranged in nests, strands, or acinar patterns, often with the formation of mucus pools.

　　The tumor cells of thyroid gland type are arranged in trabecular, islet, or mixed patterns. Carcinoid and thyroid tissue are mixed. Carcinoid cells have two types: argentaffin and argentophilic. Immunohistochemical staining of thyroglobulin and neuroendocrine cell markers are positive. Under the electron microscope, round or oval neuroendocrine granules can be found, with a diameter of 100-400nm.

　　The histological types of ovarian carcinoid can be divided into the following:

　　1, Islet (derived from the midgut).

　　2, Islet carcinoid associated with mature cystic teratoma.

　　3, Small bowel (derived from the foregut and hindgut).

　　4, Small bowel carcinoid associated with cystic teratoma.

　　5, Thyroid gland (derived from the endoderm with thyroid and c-cell differentiation).

　　6, Thyroid gland associated with mature cystic teratoma.

　　7, Mucinous carcinoid (goblet cell type or adenoid carcinoid).

　　8, Mixed type (combination of 2 or more simple types).

　　The most common complication of this disease is infection, with symptoms such as fever, abdominal pain, elevated white blood cells, and varying degrees of peritonitis. Infection should be actively controlled, and an elective operation should be scheduled for exploration. Secondly, although the disease belongs to benign lesions, there is also a possibility of malignant transformation if left untreated. Malignant transformation of primary ovarian carcinoid syndrome often occurs in older individuals, especially postmenopausal women, with rapid tumor growth in a short period of time, causing symptoms such as abdominal distension, loss of appetite,明显增大，固定，多有腹水。For those suspected of malignant transformation, timely surgical treatment should be sought.

　　Primary ovarian carcinoid syndrome is localized to one ovary in more than 90% of cases at the time of onset, generally does not metastasize, and the average range of ovarian involvement is 8cm. Among these, the solid carcinoid component accounts for 5% to 95% of the tumor volume.

　　Approximately one-third of patients with islet carcinoid develop carcinoid syndrome, while patients with small bowel carcinoid and thyroid gland carcinoid rarely develop carcinoid syndrome.

　　Carcinoid syndrome is not easily identified in the early stages, and it is often recognized only after histological diagnosis. Sometimes, it is not diagnosed until years after the appearance of metastases.

　　Facial erythema is a common early symptom of carcinoid syndrome, mainly identified based on medical history and the determination of 5-hydroxyindoleacetic acid (5-HIAA) in urine. Clinically, the 24-hour urine 5-HIAA content is measured, with a normal value of 2-8mg/24h. A positive result is indicated by a value exceeding 30mg/24h, and an elevated 5-HIAA level may be a sign of tumor secretion activity.

　　About 60% of patients with carcinoid syndrome have paroxysmal watery diarrhea with tenesmus, often occurring in the morning, and diarrhea often appears during the erythema faciei.

　　Cardiac involvement in carcinoid patients is common in the later stage of the disease, with an incidence rate of 69% to 72%, mainly affecting the heart valves, commonly tricuspid regurgitation or pulmonary stenosis, with a murmur heard in the corresponding auscultation area, leading to right heart failure in the end, and two-dimensional echocardiography can be used to confirm the diagnosis.

　　In recent years, there have been reports that patients with carcinoid tumors have severe defecation pain and pressure, which may be due to the tumor producing enterohormone peptide YY, which inhibits peristalsis.

　　Primary ovarian carcinosarcoma and its syndrome are difficult to diagnose before surgery and are also prone to misdiagnosis. Most cases need to be diagnosed by histology before they are recognized.

　　Carcinoid tumors are rare. The average age of primary ovarian carcinosarcoma patients at initial diagnosis is 55 years old, patients with islet carcinoid from the middle intestine are 30-70 years old, patients with reticularis pigmentosa are 20-50 years old, and patients with thyroid goiter are 30-60 years old. Generally, islet and thyroid goiter ovarian carcinoids related or unrelated to teratoma are the most common.

　　Prognosis

　　The 5-year survival rate of patients with non-metastatic carcinoid is 95%, with regional lymph node metastasis is 83%, and with distant metastasis is 38%. The 10-year survival rate of primary ovarian carcinosarcoma localized on one side is 100%, and the 15-year survival rate is 80%, with rare recurrence.

　　Patients with primary ovarian carcinosarcoma syndrome need the following examination items for diagnosis. 1. The content of 5-HIAA in 24-hour urine exceeding 30mg/24h is positive. 2. Tumor marker examination. 3. Laparoscopic examination, tissue pathological examination.

　　To effectively prevent a decrease in blood count, patients should supplement high-protein diet during chemotherapy, such as milk, soybeans, lean meat, pork feet, sea cucumber, fish, animal liver, and jujube, peanuts, walnuts, black fungus, carrots, and red beans, etc. Traditional Chinese medicine believes that 'black can enter the kidney', and the five black foods can tonify the kidney and fill the marrow, which is helpful for the improvement of blood count. Supplement high-nutrient liquid diet or porridge, such as lotus seed porridge, silver ear porridge, milk, soy milk, crucian carp soup, etc. Chemotherapy can damage the gastrointestinal mucosa, causing nausea, vomiting, upper abdominal pain, and decreased appetite. At this time, you can eat appetizing foods such as hawthorn, mung bean, yam, white radish, and mushrooms, and eat less and more frequently to avoid a feeling of fullness.

　　I. General treatment

　　1. Avoid inappropriate physical examinations and emotional fluctuations to prevent the increase of endogenous catecholamine release.

　　2. Discontinue adrenergic agonists, monoamine oxidase inhibitors, and ethanol.

　　Two, Drug Treatment

　　Indications: patients with mild early carcinoid syndrome symptoms

　　1. Combined use of H1 and H2 receptor antagonists

　　A. 5-HT antagonist mamidamide: 2mg, 1-3 times a day, taken orally.

　　B. 5-HT antagonist cyproheptadine: 2-8mg, taken orally every 4-6 hours.

　　C. Methyldopa: 250-500mg, 3-4 times a day. It can inhibit 5-HT synthesis.

　　2. Tryptophan hydroxylase inhibitors para-aminobenzoic acid

　　2-4g/d.

　　Can completely relieve diarrhea.

　　3. α-Adrenergic antagonist (phentolamine)

　　25-50mg, 1-3 times a day.

　　Treats skin flushing and inhibits the onset of carcinoid syndrome by antileukotriene and antiprostaglandin.

　　4. Somatostatin analogs such as octreotide

　　Twice a day.

　　Specifically inhibits the secretion of many endogenous peptides, controls diarrhea and flushing.

　　5. Interferon α

　　3 million U/d, for 5 consecutive days, then once a week on Monday, Wednesday, and Friday.

　　Three, Surgical Treatment

　　Surgical resection is the most ideal for primary carcinoid without metastasis, which can achieve the purpose of radical cure in the early stage.

　　1. Primary ovarian carcinoid:Ovarian and fallopian tube resection.

　　2. Complications

　　The use of anesthetic dosage during surgery and the compression of the tumor may cause carcinoid crisis - severe hypotension and tracheal spasm.

　　3. Precautions

　　Rescue items and relevant measures should be prepared before surgery.

　　4. Anesthesia:Sodium thiopental, pancuronium (pancuronium), and nitric oxide (NO

　　5. Antiserotonin drugs:Cyproheptadine.

　　During the operation, it should be avoided as much as possible to use drugs such as catecholamines.

　　Four, Chemotherapy

　　Used for the control of symptoms in primary carcinoid that cannot be removed in advanced cases.

　　1. Commonly Used Medications:Fluorouracil (5-Fu) 400mg/m2, plus streptozocin (streptozotocin) 500mg/m2, for 5 consecutive days, and then repeated after 6 weeks.

　　2. Precautions

　　For patients with carcinoid syndrome in the acute attack stage, the dose should be reduced and the administration time extended.