Overview
Non-functionalAdrenal cortical carcinoma(Nonfunctional adrenocortical adenocarcinoma, NACC) is rare in clinical practice, and people are still unable to recognize the cause of the disease.
The early diagnosis rate of tumors is not high. Many patients have peripheral infiltration or distant metastasis at the time of treatment, and the progress rate is fast, which causes great difficulty for clinical treatment, and the prognosis is usually poor. With the improvement and popularization of imaging examination methods, adrenal cortical carcinoma is often found by chance during a physical examination or other diseases, accounting for 10% to 20% of adrenal incidents. Therefore, the actual incidence rate has increased in recent years. The age of onset varies from 1 to 80 years old, and is more common in adults or the elderly, with more men than women. It is more common to metastasize to lymph nodes, lungs, and liver, and to bones and brains.
symptom
The clinical symptoms of adrenocortical carcinoma are atypical, and can be divided into two types: endocrine disorders and endocrine disorders (no function). Clinically, some patients have mixed hormone secretion abnormalities, accounting for about 35% of patients with adrenocortical cancer.
Most patients with endocrine disorders showed that Cushing's syndrome combined with female masculinization was the most important manifestation, and abnormal sexual characteristics and primary aldosteronism were relatively rare. Mixed abnormal changes can occur in biochemical tests, both Cushing's syndrome and hypokalemia, and this hypokalemia often appears to be refractory, and conventional potassium supplementation is slow, which may be related to malignant tumors. Unrestricted growth and low degree of differentiation.
Non-functioning adrenocortical carcinoma, the onset is slow, the symptoms are different, often fatigue, weight loss, about 1/2 patients with intermittent hypothermia, and the absorption of necrotic tissue in the tumor. About 2/3 of the patients have pain in the side of the abdomen and lumbar pain. The larger the tumor, the pain is aggravated when the position changes, which may be caused by the tumor invading the capsule or twisting and shifting the kidney. At the time of physical examination, 1/3 of the cases can touch the abdominal mass, and in a few cases, the renal artery stenosis caused by the tumor can cause hypertension. Larger tumors can be associated with hypoglycemia. In patients with no functional disorders, there is often an increase in urine 17-KS.
Clinically, sometimes the initial manifestations are symptoms of distant metastasis, such as multiple lesions in the lungs, gynecological symptoms of vaginal metastasis, and hematuria in renal metastases. Gastrointestinal hemorrhage due to intestinal metastasis and symptoms such as bone, brain and eye metastasis.
diagnosis
1. Clinical features
The clinical symptoms of adrenocortical carcinoma are atypical, and can be divided into two types: endocrine disorders and endocrine disorders (no function).
2. Auxiliary inspection
(1) Laboratory inspection
All adrenal cortical tumors should be tested for adrenal function, especially non-functional adrenal cortical tumors. Sometimes, although there are no prominent clinical symptoms, it is not necessarily a non-functional tumor; and those with abnormal laboratory tests may not have corresponding clinical manifestations.
Examination of adrenal cortical secretion function, including plasma cortisol, 17-OHCS, 17-KS, CA, VMA and plasma aldosterone, renin activity, electrolytes, sex hormones (androgen, pregnane estrone) and glucose tolerance test, small doseDexamethasoneInhibition test, etc.
Non-functional adrenal cortical tumors have more normal blood and urinary cortisol. Because the tumor is too large and consumed too much, hypoproteinemia and hypoglycemia may occur. For example, bilateral large tumors may be associated with blood, urinary cortisol is lower than normal, aldosterone is more normal, and a small number of 17-ketocorticosteroids may have a slight increase.
(2) Imaging examination
Imaging studies such as B-ultrasound, CT or MRI are indispensable in the diagnosis of adrenal cortical cancer. In particular, non-functional asymptomatic adrenal tumors need to rely on imaging to confirm the diagnosis to determine whether the adrenal gland is abnormal, whether there is a tumor, to help locate and determine the adrenal properties. Many scholars believe that the vast majority of tumors in adrenocortical carcinoma are larger than 5 cm in diameter.
(3) Nuclear medicine examination
Adenomas can show uniform radioactivity concentration, while adenocarcinomas exhibit uneven radioactivity concentration. In recent years, positron emission tomography (PET) technology has also been applied to the diagnosis of adrenal malignancies. Becher et al. used 18 fluorinated deoxyglucose (18F-FDG) positron emission tomography to scan 10 patients with adrenocortical carcinoma, and found that the uptake of FDG in all primary and metastatic lesions was significantly enhanced, and the wing sensitivity and specificity were 100. % and 97%. Barzon et al. used 75Se-labeled methylnorcholic acid for adrenal scanning. All non-functioning adenocarcinomas and 70% of functional adenocarcinomas were free of nuclides, and all normal adrenal tissues were absorbed, indicating that radionuclide scanning is in the diagnosis of adrenal gland. There is a certain value in cortical cancer.
treatment
1. Dichlorodichloroethane treatment plan
Dichlorobenzene dichloroethane (O, P-DDD) can alter the metabolism of adrenal cortex hormones and androgen, inhibit the secretion of corticosteroids, destroy the adrenal cortex, and shrink the tumor. It is suitable for palliative treatment for patients who cannot be operated, postoperative tumor residual, and metastatic lesions. Long-term treatment is only available for patients who initially have a therapeutic effect. It has been reported in the literature that a good therapeutic effect may be obtained with a concentration of >10 μg/ml or >14 μg/ml of dichlorophenyldichloroethane. However, recent studies have suggested that there is no necessary relationship between concentration and efficacy. The main side effect is neuromuscular toxicity, which is related to the dose used.
Modern imaging technology can more accurately determine the therapeutic effect of chlorhexidine. It can be divided into:
(1) complete effect, no tumor survival for at least 4 weeks;
(2) partial effect, tumor volume reduction >50% for at least 4 weeks;
(3) Micro-effect, the tumor volume is reduced by 25% to 50%. The therapeutic effect of dichlorophenyldichloroethane has been controversial, and most scholars believe that oral treatment with diclofenac in advanced patients is beneficial to the prognosis and prolong survival. For patients who do not respond to treatment, try to combine chlorhexidine with multi-drug chemotherapy. Other steroid synthesis inhibitors such as ketoconazole, aminoglutethimide and other therapeutic effects, there is currently insufficient clinical research evidence.
The drug of dichlorobenzene dichloroethane is slow, at least for more than 8 weeks, and the starting dose is small. 500mg daily, if there is no adverse reaction, 4 times a day, then increase 500mg every 3 days, the maximum 12g / d, should pay attention to side effects such as nausea, vomiting, lethargy, blurred vision and salivation, reduce or stop depending on the severity . Prednisone is required to prevent adrenal insufficiency. It has also been reported that CTX can be used alone or in combination after radiotherapy.VincristineAnd fluorouracil for immediate effect.
2. Chemotherapy
Adrenal cortical carcinoma can express multidrug resistance gene (MDR) 21, leading to the secretion of P2 glycoprotein and accelerating the cytotoxic drug failure. Dichlorobenzene dichloroethane can interfere with the function of MDR21 and P2 glycoproteins and antagonize its drug resistance. Therefore, the clinical use of chemotherapeutic drugs and chlorhexidine dichloride is currently used in combination. Commonly used drugs include doxorubicin,Cyclophosphamide, fluorouracil, cisplatin, etoposide and the like. The standard for judging the effect of chemotherapy was the same as that of bischlorobenzene dichloride, Berruti et al., and 28 patients with cortical cancer treated with etoposide, doxorubicin, cisplatin and dichlorodichloroethane. 54% had therapeutic effects (completely Effects of the ten-part effect), the most common side effects include gastrointestinal and nervous system reactions. BonacCl and other studies treated 18 patients with cortical carcinoma with etoposide, cisplatin and dichlorodichloroethane, and 33% had therapeutic effects. Multi-drug chemotherapy is also only palliative treatment. Due to the low incidence of cortical cancer, the clinical research, especially the clinical trials of chemotherapy drugs, has a small sample size, and the tumor discovery is more advanced, the progress is faster, and the survival time is shorter. Therefore, the efficacy of combined chemotherapy is still Not sure.
For those who are not surgically treated, the use of chlorhexidine alone or in combination with cytotoxic drugs is the most effective treatment. In order to achieve the best results, the amount of the drug is 14 to 20 μg / ml is strictly required. For patients with worsening conditions, the most promising alternative treatments are:Etoposide(etoposide), daunorubicin, cisplatin+Mitotane(mitotane) and streptozotocin + mitotane, these drugs are currently being used in international phase clinical trials. After the tumor is completely removed (for example, by mitoxantrone radiation therapy), adjuvant therapy is necessary because only 35% of the disease-free survivors within 5 years after surgery, but no effective adjuvant treatment has yet been developed. National registries, international cooperation and trials not only provide patients with important new therapeutic instruments, but also facilitate researchers to systematically study the treatment of adrenocortical cancer. However, future treatments for adrenocortical carcinoma will depend to a large extent on a deeper understanding of the pathogenesis of tumor molecules, which also contributes to the development of modern cancer treatments (eg tyrosine kinase inhibitor treatment). ).
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