In the early stage, late stage and recurrence of gastric cancer after treatment, a series of clinical manifestations not directly related to the lesion itself and its metastases often appear, which is called the syndrome of associated cancer. After surgery or chemotherapy or radiation treatment of gastric cancer lesions, the syndrome can be significantly relieved or disappeared. In recent years, the associated cancer syndrome of gastric cancer is gradually attracting clinical attention, which is undoubtedly helpful for the diagnosis, treatment, efficacy judgment and prognosis estimation of gastric cancer. The syndromes of gastric cancer with cancer are summarized as follows.
1.Cancerous non-metastatic neuromuscular syndrome
(1) Eaton_Lanbert syndrome It is reported that 70% of this syndrome is combined with tumors, and lung, ovarian and gastric tumors are the most common. The first symptom is muscle fatigue, weakness and abnormal pain in the lower limbs. The upper extremities are less frequently affected, and the typical manifestations of myasthenia gravis, such as droopy eyelids, impaired eye movement and diplopia, are rarely present. Most patients have thirst, decreased salivation and tear production, impaired pupillary regulation, impotence, abnormal sweating and other physiological abnormalities. The clinical examination shows a specific sign of muscle weakness that is spontaneously reduced by motor load on the lower extremities and is aggravated again when the muscle weakness is sustained. The electromyogram shows decreases in low frequency and increases in high frequency with repeated stimulation of peripheral nerves. The pathological changes are non-specific type II muscle fiber atrophy. The etiology of the disease is clearly defined as a presynaptic membrane lesion of the motor nerve terminal due to an abnormal autoimmune mechanism. Jiang Tao, Department of Oncology, Affiliated Hospital of Qingdao University
(2) Polymyositis and dermatomyositis The highest incidence of polymyositis is reported in China for gastric cancer and in Europe and the United States for breast cancer. The clinical features are.
(1) Most of the first symptoms occur 2 months to 48 months before the tumor symptoms become apparent.
(2) Combined tumors are positively correlated with age, especially in men.
The skin lesions are characterized by diffuse erythema of fiery red color, which can be faded by pressure on a slide, called malignant erythema.
④The symptoms cannot be relieved by high-dose corticosteroid treatment. The etiology of the disease is unknown, and the more consistent hypothesis is the autoimmune theory of tumor alienation products as allergens.
(3) Carcinomatous myopathy Lung, gastric and ovarian tumors are the most common, with the following clinical manifestations.
The clinical manifestations are: (1) low muscle strength of the scapular girdle, pelvic girdle and proximal extremities that cannot be explained by the malignant mass of the tumor patient, while the distal muscle strength is rarely involved.
②Weak or absent deep reflexes of the extremities.
(iii) Muscle atrophy. The pathological changes are non-specific, and most of them are a mixture of mild myogenic and neurogenic changes. The etiology is unknown and may be due to a single or multiple factors such as nutritional disorders, toxic effects, endocrine or immunological abnormalities in malignant tumors.
(4) Carcinomatous peripheral neuropathy is most common in oat cell carcinoma of the lung, followed by ovarian and gastric carcinomas. Two clinical types can be distinguished.
(1) Sensory neuropathy, which often occurs 2 to 3 months before the onset of symptoms in gastric cancer, with progressive limb sensory disorders as the main clinical manifestation, mostly consisting of symmetrical glove or garter-like pain, warmth, touch, tuning fork vibration, position, and other deep and superficial sensations. It is often accompanied by sensory ataxia.
(2) Sensorimotor neuropathy. Both sensory and motor dysfunction are present, but the symptoms of sensory dysfunction are relatively mild. The clinical signs are symmetrical muscle weakness, myasthenia, and diminished or absent deep reflexes in the extremities. This type is less common than the sensory type. According to the course of the disease, there are three types of peripheral neuropathy: advanced peripheral neuropathy, subacute sensory-muscular weakness peripheral neuropathy, and remitting-relapsing peripheral neuropathy.
2. Endocrine abnormalities [4-9]
(1) Ectopic TSH syndrome The literature reports that it is mostly seen in gastrointestinal tumors. Tumor tissues secrete thyrotropin-like substances, causing an increase in total T4, free T4, total T3 and plasma protein-bound iodine in plasma. Clinical features.
(1) Most commonly seen in men, manifesting as weakness, wasting, and neuropsychiatric symptoms.
② Lack of typical hyperthyroidism signs such as goiter and ophthalmoplegia.
(3) TSH release test is negative. In adult men with short-term hyperthyroidism, the possibility of gastric cancer should be considered.
(2) Ectopic insulin syndrome A small number of gastrointestinal tumors can cause hypoglycemia. The mechanisms are.
(1) Tumor tissues produce insulin-like growth factors _Ⅰ and II (IGF _Ⅰ, II) and growth interferon-A and C (SM-A, C), which promote glucose conversion and inhibit fat mobilization.
② Tumor growth consumes excess glucose. A sudden decrease in blood glucose can stimulate sympathetic nerves, resulting in excessive secretion of catecholamines from the adrenal medulla, which may manifest as sweating, palpitations, weakness or hunger. In severe cases, central nervous system hypoglycemia may occur, such as disorientation, convulsions, coma, etc. This type of hypoglycemia cannot be suppressed by glucagon and diazoxide.
(3) Ectopic ACTH syndrome 5%-10% of digestive tract tumors can develop Cushing’s syndrome. Clinical manifestations are atypical, mainly skin pigmentation, hypertension, edema, muscle weakness, hypokalemic alkalosis, and characteristic facial features and body shape are rare. Laboratory tests are characterized by.
① Plasma ACTH is significantly increased.
(2) Absence of circadian rhythm of plasma cortisol, no response to dexamethasone suppression test.
(4) Ectopic ADH syndrome is caused by abnormal secretion of ADH from gastric cancer cells. The main clinical manifestations are weakness, anorexia, thirst, drowsiness and painful muscle cramps caused by low blood sodium. In severe cases, water intoxication may occur, including confusion, disorientation, convulsions and coma. Laboratory tests are characterized by hyponatremia, increased urinary sodium, urinary osmolality greater than plasma osmolality and increased plasma ADH.
(5) Ectopic HCG syndrome It is reported that 24% of patients with gastric cancer have elevated HCG in blood. Clinical manifestations include breast development in men, but in women, it usually does not cause symptoms and may be accompanied by irregular uterine bleeding. Laboratory tests show that HCG is elevated in the blood and is not suppressed by testosterone or estradiol. Therefore, in adult men with unexplained breast development, gastric cancer should be excluded.
(6) Ectopic GH syndrome Gastrointestinal adenocarcinoma cells can secrete growth hormone-like substance and growth hormone-releasing factor, which can promote the release of GH from the anterior pituitary gland. The symptoms can be relieved by removing the tumor.
(7) Low T3 syndrome The incidence of this syndrome is second only to leukemia and malignant lymphoma in digestive tract tumors. The mechanism is unknown and may be related to chronic malnutrition and decreased 5′-deiodinase activity. The clinical features are decreased total T3 and normal total T4; increased rT3 and decreased T3/rT 3 ratio; patients do not show hypothyroidism.
(8) Low T3 and T4 syndrome is characterized by a decrease in total T3 and total T4, an increase in rT3 and a decrease in the T3/rT3 ratio. It is important to pay attention to this syndrome in patients with gastric cancer, which indicates poor prognosis and high mortality.
3.Metabolic abnormalities
(1) Hypercalcemia: The literature reports that hypercalcemia occurs in 3.3% of gastrointestinal tumors, with liver cancer being the most common and gastric cancer taking the fourth place. The mechanism is that tumors secrete parathyroid-like substances, which release bone calcium into the blood; tumor tissues secrete prostaglandin E and transforming growth factor alpha (TGFα), which cause bone resorption and increase blood calcium; and active vitamin D-like substances increase, which increase calcium absorption in the gastrointestinal tract. Early symptoms are not specific, but when the blood calcium concentration exceeds 3.8 mmo l/L, it can cause hypercalcemia and lead to death, and must be treated urgently to lower the blood calcium.
(2) Hypolipidemia It is reported that most patients with gastric cancer have significantly lower blood cholesterol and triglyceride than healthy people. Lipids may increase after surgery and then decrease when recurrence occurs. The median survival of patients with gastric cancer in the hypolipidemic group was shorter than that of patients with gastric cancer in the hyperlipidemic group, suggesting a poor prognosis. The etiology may be related to the inhibition of lipoprotein synthesis and increase of lipolysis in tumor patients, the decrease of digestive tract absorption function, and insufficient lipid intake.
（The mechanism is that the tumor cell differentiation is impaired and the cell maturation stays, so that the cell restores its original function of producing AFP. Clinically, if primary liver cancer and chronic liver disease are excluded, gastric cancer should be considered as a possibility. A few gastric cancers with liver metastasis may also show AFP positivity.
4.Skin lesions
(1) Acanthosis nigricans The incidence of malignant tumors with acanthosis nigricans is the highest in gastric cancer. The clinical manifestations are progressive generalized skin pigmentation, roughness, reduced elasticity, irregular dense dotted black warts and papilloma-like proliferation. It may occur before, after, or simultaneously with gastric cancer. The pathological changes are hyperkeratosis of the epidermis and thickening of the spiny cell layer.
(2) Paraneoplastic acanthosis: It is rare and mainly seen in men with upper gastrointestinal tumors. Clinical manifestations: hyperkeratotic psoriatic plaques on the skin of the hands, feet, nose and ears, and extensive hyperkeratosis on the palmoplantar area, with thickened and brittle nails. Facial skin resembles eczema or lupus erythematosus.
(3) Leser-Tre’let sign: It is a sign of malignant tumor of internal organs, commonly seen in patients with gastric cancer. The clinical manifestation is sudden onset of multiple pruritic seborrheic keratosis skin lesions. It may disappear after tumor removal or treatment, and may reappear in case of recurrence.
5.Hematological system diseases
(1) Anemia: When there is no bone marrow metastasis in gastric cancer, it is often accompanied by anemia. The main reasons are bleeding, malnutrition and excessive destruction of red blood cells due to autoimmune reaction caused by tumor. Most of the laboratory tests are positive pigment anemia, reticulocytes do not increase, leukocytes often increase, platelets are mostly reduced, and total iron binding capacity is normal or slightly decreased. Iron, vitamin B12 and folic acid are generally ineffective in this type of anemia. After tumor removal or treatment, the anemia can be reduced or even disappeared.
(2) Agranulocytosis: The white blood cell count of patients with gastric cancer may increase significantly, mainly neutrophils. Clinical symptoms are usually absent, but occasionally leukemia-like reactions may occur.
(3) Thrombocytopenia: The main cause of thrombocytopenia is an increase in platelet surface binding immunoglobulin and accelerated platelet destruction due to abnormal immune function. The clinical manifestations are more aggressive, and the disease can rapidly worsen within a short period of time. Treatment of the primary focus with corticosteroids may improve symptoms. Laboratory tests may reveal an increase in platelet-associated IgG and IgM and an increase in bone marrow megakaryocytes.
(4) The concentration of coagulation factors in the blood of patients with DIC digestive tract tumors (especially mucinous adenocarcinoma) is commonly increased. The mucin secreted by the tumor tissue and the necrotic tissue can cause the blood to be in a hypercoagulable state. In addition, patients with gastric cancer have higher serum levels of fibrin degradation products than normal, which can lead to secondary hyperfibrinolysis. These factors may induce DIC.
6. Nephrotic syndrome is reported to be caused by malignant tumor in 15.7% of a group of nephrotic syndrome patients over 60 years old. It may occur before, after or simultaneously with gastric cancer. It presents with swelling, proteinuria, A/G inversion, and increased blood cholesterol. The etiology of the syndrome is still unclear, but it may be due to the deposition of antigen-antibody immune complexes in the glomerulus caused by tumor-associated antigens, carcinoembryonic antigens, tumor virus antigens, etc. The nephrotic syndrome can be relieved after tumor eradication. One case was admitted to our hospital with nephrotic syndrome, and after the diagnosis of gastric sinus adenocarcinoma, radical surgery of gastric cancer was performed, and the nephrotic syndrome disappeared after surgery.