Thyroid cancer _ thyroid cancer symptoms, treatment and prevention

Introduction:

Thyroid cancer (thyroid carcinoma) is the most common thyroid malignancy. It is a malignant tumor derived from thyroid epithelial cells. Most of the thyroid cancer originates from follicular epithelial cells. According to the pathological type, it can be divided into papillary carcinoma (60%) and follicles. Adenocarcinoma (20%), but the prognosis is better; follicular adenocarcinoma tumors grow faster, moderately malignant, and easy to undergo blood transfer; undifferentiated cancer has a poor prognosis, with an average survival time of 3 to 6 months. Papillary carcinoma is more common in thyroid cancer.

Cause:

(1) Causes of the disease

1. Iodine and thyroid cancer

Iodine is an essential trace element in the human body. It is generally believed that iodine deficiency is endemic goiter. Iodine deficiency leads to decreased thyroid hormone synthesis, increased thyroid stimulating hormone (TSH) levels, stimulation of thyroid follicular hyperplasia, thyroid enlargement, and thyroid gland. Hormones, the incidence of thyroid cancer is increased, the current opinion is still inconsistent, but most of them are follicular thyroid cancer, not the most common pathological type of thyroid cancer - papillary thyroid cancer, and in the endemic area of non-endemic goiter, thyroid papillary Cancer accounts for 85% of well-differentiated thyroid cancer. There is no significant change in the incidence of thyroid cancer before and after iodized salt prevention. The incidence of thyroid papillary carcinoma is increased after effective iodized salt prevention, and foods with high iodine intake are high. An iodine diet may increase the incidence of papillary thyroid cancer.

2. Radiation and thyroid cancer

X-ray irradiation of the thyroid gland of the experimental mouse can promote thyroid cancer in the animal, the nuclear deformation, the synthesis of thyroxine is greatly reduced, leading to cancer; on the other hand, the thyroid gland is destroyed and the endocrine hormone is not produced, thereby causing thyroid stimulating hormone ( TSH) a large amount of secretion can also promote thyroid cell cancer.

In clinical practice, many facts indicate that the occurrence of thyroid is related to the role of radiation. Children who have undergone upper mediastinal or cervical radiation therapy due to thymic enlargement or lymphoid adenoid proliferation during infancy are particularly susceptible to thyroid cancer. The cells of children and adolescents proliferate vigorously, and radiation is an additional stimulus that easily triggers the formation of tumors. The chances of developing thyroid cancer after receiving cervical radiation therapy in adults are rare.

3. Thyroid stimulating hormone chronic stimulation and thyroid cancer

Thyroid follicles are highly differentiated, with iodine and synthetic thyroglobulin. TSH also regulates the growth of thyroid follicular cells through cAMP-mediated signaling pathways, thyroid cancer may occur, serum TSH levels increase, and nodularity is induced. Goiter, thyroid follicular carcinoma can be induced by mutagen and TSH stimulation, and clinical studies have shown that TSH inhibition plays an important role in the treatment of differentiated thyroid cancer after surgery, but whether TSH stimulation is thyroid The pathogenic factors of cancer have yet to be confirmed.

4. The role of sex hormones and thyroid cancer

Because in the well-differentiated thyroid cancer patients, women are significantly more than men, so the relationship between sex hormones and thyroid cancer is valued. Clinically, the tumor size of well-differentiated thyroid cancer is found, usually young people have larger tumors than adults, young people Cervical lymph node metastasis or distant metastasis of thyroid cancer is also earlier than that of adults, but the prognosis is better than that of adults, but also with maternal, but the incidence of women after 10 years of age is significantly increased, it is possible that the secretion of estrogen is increased with thyroid cancer in young people. Related to the occurrence, so some people studied the sex hormone receptors in thyroid cancer tissue, and found that there are sex hormone receptors in the thyroid tissue: estrogen receptor (ER) and progesterone receptor (PR), and ER in thyroid cancer tissue. However, the impact of sex hormones on thyroid cancer is still inconclusive.

5. Glandular thyroid material and thyroid cancer

Animal experiments have confirmed that long-term use of raw thyroid material can induce thyroid cancer, can also hinder the synthesis of thyroid hormone, increase the secretion of TSH, stimulate thyroid follicular hyperplasia, may produce new thyroid organisms, accompanied by diffuse thyroid Swollen, causing thyroid tumors.

6. Other thyroid diseases and thyroid cancer

(1) Nodular goiter: thyroid cancer in nodular goiter has always been valued and is a risk factor associated with thyroid cancer. The incidence of thyroid cancer in nodular goiter can be as high as 4% to 17%. However, the relationship between nodular goiter and thyroid cancer has always been controversial, and the relationship between benign nodules and well-differentiated cancer progression is unclear.

The reason for the inconsistency between thyroid cancer and nodular goiter is that:

1Compared with the histological changes of nodular goiter and thyroid cancer, nodular goiter is a lesion of thyroid follicles, which is characterized by high expansion of follicles, flat cells of follicular walls, and expanded follicles. The nodules are filled with a large amount of colloid, and the fibrous envelope around the nodules is incomplete. But the most common thyroid cancer is not follicular thyroid cancer but papillary thyroid cancer.

2 comparing the age of onset of nodular goiter and thyroid cancer, found that the age of onset of thyroid cancer is significantly lower than the age of onset of nodular goiter, does not seem to support thyroid cancer secondary to nodular goiter.

3 compare the incidence of nodular goiter and thyroid cancer, nodular goiter in the population of 40,000 / 1 million, and thyroid cancer is only 40 / 1 million, far less than thyroid cancer in the nodular thyroid The incidence of swelling is 4% to 17%; the high incidence of thyroid cancer in nodular goiter is related to the selected cases of surgical treatment. In some cases, malignant thyroid disease is suspected in clinical practice, so it is not universal. significance.

Despite this, the presence of thyroid cancer in nodular goiter is still an indisputable fact. Nodular goiter is caused by TSH-induced follicular epithelial hyperplasia in different parts of the thyroid gland, resulting in papillary hyperplasia and angiogenesis, papillary Hyperplasia may occur in papillary thyroid cancer. After feeding rats or mice with drinking water and food in areas with iodine deficiency, serum TSH levels are increased, not only to induce nodular goiter, but also to produce thyroid gland in nodular goiter. Cancer, including papillary thyroid cancer and follicular thyroid cancer, has a prevalence of thyroid cancer of 15.6%, which is a risk factor for thyroid cancer.

(2) thyroid hyperplasia: the relationship between thyroid hyperplasia and thyroid cancer is not clear, it has been reported that congenital proliferative goiter has not been properly treated for a long time, and eventually thyroid cancer occurs, so congenital proliferative goiter is found in time, and It is very important to eliminate the long-term stimulation of TSH by thyroid hormone replacement therapy.

(3) thyroid adenoma: Most people think that thyroid cancer occurs with single thyroid adenoma. If thyroid cancer is secondary to thyroid adenoma, the type of thyroid cancer should be mainly follicular carcinoma, but the actual thyroid nipple Most of the cancers in the thyroid follicular carcinoma often have a history of adenomas, but it is difficult to confirm the relationship between them. Even with histological observation, it is difficult to confirm the relationship between them.

(4) Chronic lymphocytic thyroiditis (Hashimoto thyroiditis, HT): In recent years, more and more reports of thyroid cancer have been found in HT, the incidence rate is 4.3% to 24%, the difference is large, and because HT does not need more Surgical treatment, the actual incidence is more difficult to estimate, HT and thyroid cancer can be two unrelated diseases while coexisting in the gland of the thyroid gland, on the other hand, focal HT may also be the body's thyroid cancer Immune response, HT may lead to destruction of thyroid follicular cells, hypothyroidism, decreased thyroid hormone secretion, feedback caused by increased TSH, TSH continues to stimulate thyroid follicular cells, thyroid follicular cells hyperplasia and cancer; may also be TSH as a contributing factor Carcinogenesis occurs at the same time as thyroid oncogene overexpression; others believe that HT has a common background of autoimmune abnormalities with thyroid cancer.

(5) Hyperthyroidism: Because of the low level of serum TSH in patients with hyperthyroidism, it has been previously thought that thyroid cancer does not occur in patients with hyperthyroidism, or the incidence of thyroid cancer is consistent in patients with hyperthyroidism and the general population (0.6% to 1.6%). The incidence of thyroid cancer is 2.5% to 9.6%. In thyroid cancer, the incidence of hyperthyroidism can reach 3.3% to 19%, while patients with hyperthyroidism who are treated surgically are either due to large thyroid gland or because thyroid gland is already present. Section, so the actual incidence is unclear, and most of them are treated with drugs. Therefore, we should pay attention to the clinical situation of hyperthyroidism combined with thyroid cancer, and should be alert to the existence of thyroid cancer.

Thyroid cancer can be seen in a variety of causes of hyperthyroidism, including Graves disease, and the secretion of thyroid hormone by the tumor itself causes hyperthyroidism is rare, LATS), LATS is not stimulated by feedback inhibition of thyroid hormone to stimulate thyroid follicles, TSAb is a TSH receptor antibody (TSH Receptor Antibodies, TRAb), may induce thyroid cell malignant transformation, thyroid cancer, but has not been confirmed, but still controversial, whether it is Graves disease, or toxic nodular goiter, tumor lesions are small or For occultity, the incidence of metastasis is low, the prognosis is good, and it is similar to thyroid cancer in patients with non-hyperthyroidism.

7. Family factors and thyroid cancer Thyroid cancer is less common as an independent familial syndrome, but it can be used as part of familial syndrome or hereditary disease. A small number of families have a tendency to have multi-focal differentiated thyroid cancer, thyroid cancer. Familial colonic polyposis (such as Gardner syndrome), including colon adenomatous polyps with soft tissue, with fibromatosis most, with fibrosarcoma, is an autosomal dominant genetic disease, consisting of APC genes located on chromosomes 5q21 to q22 Due to mutation, the latter is a signaling protein involved in the regulation of cell proliferation, and a few people can develop cancer under TSH stimulation. Thyroid cancer.

(two) pathogenesis

1. Molecular biology Molecular biology research progress indicates that the conversion of human normal cells to malignant tumor cells has accumulated a variety of molecular biological changes, including initiation, resulting in cell growth independent of normal growth regulation, or The cells do not respond to normal regulation, and eventually malignant changes occur. Thyroid cancer has a variety of oncogenes and tumor suppressor gene abnormalities, and gene amplification and other pathways activate, causing normal cells to transform into uncontrolled malignant cells, and must have other In the participation of genes, cell malignant transformation usually has several expressions of these genes, or gene mutation and amplification occur simultaneously. This section discusses molecular biological changes in thyroid cancer.

(1) trk, trk, trk) is located in the q31 region of chromosome 1, encoding a cell surface receptor of a nerve growth factor belonging to a receptor tyrosine kinase, such as a Trk-T1 oncogene conjugated with TPP to activate . The expression of the trk oncogene can be found in papillary thyroid carcinoma.

The met(7q31) gene has 120 kb, including 21 exons separated by 20 introns, a transmembrane receptor tyrosine kinase, metephropathy in various cancerous tissues, but thyroid follicular The expression in cancer is only 25%.

The original recognition of the ret proto-oncogene is due to its ability to efficiently transform cultured NIH3T3 fibroblasts. It is a dominant transforming oncogene that plays a role in the development of medullary thyroid carcinoma and papillary thyroid carcinoma, including 20 The phenotype, about 30 kb in length, encodes a transmembrane tyrosine kinase receptor, and is expressed by the extracellular ligand binding region, the neural crest cells, and the genitourinary system. The system, which regulates neural crest cell proliferation, MEN) type 2, is activated by gene rearrangement in papillary thyroid carcinoma.

In 1987, Fusco found that 25% of thyroid papillary carcinomas and their metastatic lymph nodes have conversion sequences in DNA transfection experiments, which are considered to be new oncogenes and named PTC (representing thyroid papillary carcinoma), resulting in coding The ret gene of the tyrosine kinase is produced by juxtaposition with the 5' end sequence of one of the various unrelated genes, so it is called ret/PTC oncogene. According to the difference of the collocated sequence, at least 7 ret/ have been identified. PTC oncogenes, such as ret proto-oncogenes, D10S170 (H4) gene rearrangement (ret/PTC1) on the same chromosome, ret proto-oncogene and RIα gene rearrangement on chromosome 17 (ret/PTC2), ret primary cancer The rearrangement of the gene and the RFG/ELE1 gene located in the same chromosomal region (ret/PTC3) is the most common mode of activation. It was found that the ELE1 gene and the ret proto-oncogene tyrosine kinase coding region are linked to the 5' end of other genes. The encoded protein exhibits phosphorylation activity and is activated by the formation of a dimer with its physiological ligand GDNF.

Ret/PTC gene-encoded dimeric protein-mediated ret kinase activation, ret/PTC oncogene also has a transforming effect on cultured thyroid cells, indicating that ret gene mutation is associated with tumorigenesis initiation, ret/PTC oncogene The expression is almost exclusively in papillary thyroid carcinoma, the incidence rate is 5% to 44%, and the ret/PTC positive expression rate of thyroid papillary carcinoma in children associated with the Chernobyl nuclear accident is as high as 67% to 87%, and Mostly RET/PTC3. Differences in incidence may reflect geography.

There is no significant difference in the pathological features of thyroid papillary carcinoma or trk oncogene expressing ret/PTC oncogene. It is possible that trk functions similarly to ret/PTC, but not in ret/PTC and TRK. In typical papillary thyroid carcinoma, it may be that other receptor tyrosine kinases or their downstream signaling molecules cause corresponding nuclear changes, and patients with multiple mucosal neuroma have almost the 918th retinoin gene. Sub-mutation, in the sporadic MTC, the incidence of codon mutation at position 918 of the ret proto-oncogene can reach 33% to 67%, but not in the DNA of normal cells, which may occur just in the receptor tyrosine. The catalytically active site of the acid kinase. A mutation in codon 918 of the ret proto-oncogene may indicate a poor prognosis.

(2) ras gene: The name of the ras gene is derived from the prefix of rat sarcoma, which was isolated from the retrovirus of rat sarcoma in 1964 and located in Kirstern of the short arm of chromosome 12 (12p). K)-ras and neuroblastoma(N)-ras located on the short arm of chromosome 1 (1p1), which are composed of 4 exons and 5 introns respectively. The encoded proteins are 21kD protein p21ras. It consists of 188-189 amino acid residues, is immobilized on the inner side of the cell membrane, has GTPase (GTPase) activity, and is a member of the large family of G proteins. Although it is a small molecule, it is different from the G protein with a trimer structure. It has the function of regulating cell growth and differentiation, is an intracellular signal transduction, and transmits growth signals to cells. When p21ras binds to GTP, it is activated. After GTP hydrolysis, p21ras binds to GDP in an inactive state.

The ras oncogene passes through the 12th, changes the GTP binding or GTPase activity of the p21 protein, and isolates the H-ras oncogene with dominant activation. The 12th codon of H-ras changes from normal -GGC-(glycine) -GTC-(valine), the mutant H-ras is exactly the same as the oncogene VH-ras in Harveg sarcoma virus. This amino acid change affects the spatial conformation of p21ras, which reduces the GTPase activity by 1000-fold, while the p21ras protein is at The activation state combined with GTP causes cell malignant transformation, so the normal product becomes a carcinogenic product. Mutations in the ras oncogene are found in a variety of human malignancies.

The role of ras protein in the signal transduction process of normal thyroid follicular cell proliferation is still unclear. Whether it is a benign thyroid adenoma or a malignant differentiated or undifferentiated carcinoma, there is a point mutation in the ras oncogene, indicating that The ras oncogene mutation occurs in the early stage of thyroid follicular cell tumor formation. The mutant ras interacts with other oncogenes to transform normal adult thyroid follicular cells, stop differentiation, proliferate, reduce iodine, and express thyroid gland. Oxidase, even in human tissue culture, forms cell clones similar to thyroid tumors. Mutations in the ras gene are associated with thyroid follicular carcinoma. The mutation rate of ras gene detected in radiation-related thyroid tumors can reach 60%.

(3) myc gene: members of the myc gene family include c-myc, a nuclear transcription factor protooncogene, a protein encoding 439 amino acid residues, the product of which is a protein of 456 amino acid residues, and the encoded product is 364 amino acids. The protein of the residue is a nuclear transcriptional regulator. The myc protein can be structurally divided into a transcriptional activation region, a non-specific DNA binding region, a nuclear target sequence, an alkaline region, a helix-loop-helix and a leucine zipper region, and a base. The sex region follows the spiral-loop-helix and can be combined with special chromosomal DNA sequences to regulate the transcription process, regulate cell growth, and have the chromosomal gene translocation of myc gene in the body tumor, which is regulated by various substances. The regulatable gene is also a gene that allows cells to proliferate indefinitely and promote cell division. The c-myc gene is also involved in apoptosis.

High levels of c-myc mRNA can be found in differentiated thyroid cancer and thyroid undifferentiated carcinoma, which is 3 to 11 times higher than normal thyroid tissue, and c-myc specific antisense oligodeoxynucleotide blocks c- Myc protein synthesis can also significantly reduce the growth rate of adenocarcinoma cells.

(4) TSH receptor and gsp gene: highly differentiated thyroid follicular cells have polyiodine, TSH-thyroid follicular cell membrane TSH receptor-G protein-cAMP, which produces a cascade-like cascade of regulation, and G protein has at least There are 20 subtypes, and the α subunit Gαi protein of the inhibitory G protein reduces cAMP.

TSH receptor gene mutation or gsp gene mutation has been found in benign and malignant thyroid tumors. TSH receptor gene mutation or gsp gene mutation is closely related to thyroid hyperfunction adenoma, resulting in TSH-like effect in thyroid follicular cells. , Gαs gene codon 201 mutation, CGT (arginine) → TGT (cysteine), decreased endogenous GTPase activity, adenylate cyclase activity, equivalent to TSH chronic stimulation, mutant TSH The receptor gene or gsp gene itself does not cause tumors. The pathological stimulation caused by the mutation may inhibit the regulation of normal cell proliferation, but it needs to cooperate with other gene mutations, especially the differentiated thyroid carcinoma with higher basal adenylate cyclase activity. Such as thyroid cancer with hyperthyroidism. The role of mutant TSH receptors and gsp genes in the development of thyroid cancer remains to be further explored.

(5) RB gene: RB gene belongs to tumor suppressor gene and is a susceptibility gene of retinoblastoma. It is located in the 13q14 region of chromosome 13 and has 27 exons and 26 introns. The DNA is about 200kb long. The gene-encoded phosphorylated protein product Rb protein, with a molecular weight of about 110kD, regulates the cell cycle, inhibits excessive cell proliferation, and the Rb protein is non-phosphorylated. Once the cell enters proliferation (G2, S, M phase), the Rb protein is mainly Phosphorylated form exists, inhibits cell proliferation, is involved in Cyclin D1 (CD1), and the main variant of RB gene abnormality is deletion. Mutated RB protein loses the function of binding to homonuclear ligands, cell differentiation The response of the signal is blocked, resulting in unrestricted cell growth and tumor formation in the body.

In thyroid papillary carcinoma and thyroid follicular carcinoma, the incidence of abnormalities such as RB gene deletion or mutation can reach 54%, while the incidence of RB gene deletion or mutation in thyroid undifferentiated cancer can reach 60%. 4 to 5 times.

(6) p53 gene: p53 gene is one of the most important tumor suppressor genes. The incidence of p53 point mutation in thyroid undifferentiated carcinoma is high. It is thought that p53 protein which causes tumor formation or cell transformation is a product of p53 gene mutation. It is a tumor-promoting factor that eliminates the function of normal wild-type p53. Mutant p53 protein plays an important role in tumor formation. It is about 20 kb in length and consists of 11 exons and 10 introns and is transcribed into 2.5 kb mRNA. The encoded product is composed of 393 amino acid residues, a nuclear phosphoprotein p53 with a molecular weight of 53 kD, and a basic region of amino acid residues 319 to 393 at the C-terminus. The normal p53 protein is easily hydrolyzed in cells, and the half-life is 20 min. The mutant p53 protein has a half-life of 1.4 to 7 hours. The biological function is a checkpoint for DNA damage in the G1 phase. It is involved in the regulation of cell growth, monitoring and maintaining the integrity of the genome of the cell. If the DNA is destroyed, the p53 protein accumulates and makes the cell The cycle is paused in the late G1, but not in the S phase, thus avoiding the replication of damaged DNA, and there is enough time for the damaged DNA to be repaired, then p53 can pass programmed cell death or "apoptosis" triggers cell suicide, removes damaged cells, prevents the production of cells with cancerous mutations, and when cells are exposed to external environmental carcinogens, DNA damage cannot be repaired, genetic instability, mutation accumulation, and weight Accelerated platoons promoted the transformation of cells into cancer cells, with 175 different types of tumors with different types of mutations.

In thyroid cancer, the major altered form of p53 gene is a little mutated, the incidence of p53 gene abnormalities can reach 25%, and the incidence of p53 gene alteration in thyroid undifferentiated cancer can be as high as 86%.

(7) p16 gene: p16 gene, also known as multiple tumor suppressor 1 (MTS1), located on chromosome 9 9p21, consisting of two introns and three exons, encoding a protein with a molecular weight of 16kD (p16), located in the nucleus, is one of the key enzymes acting on the cell division cycle, directly involved in the regulation of the cell cycle, negatively regulates cell proliferation and division, inhibits cell growth and division, and prevents cancer from occurring. Inhibiting the catalytic activity of CDK4, thereby inhibiting cells from G1 into S phase, inhibiting cell growth and division, and causing loss of function such as mutation, can not inhibit CDK4, and finally cause cells to enter malignant proliferation and accelerate tumorigenesis.

Studies have found that the presence of p16 gene deletion in thyroid cancer cell lines, the expression of p16 protein in thyroid cancer tissue is significantly lower than that of thyroid tumor, and the expression of p16 protein decreases with the increase of malignant degree of thyroid cancer, suggesting that p16 protein can be used as clinical Determining the prognosis of thyroid cancer, the deletion of p16 gene in thyroid cancer is not a frequent event.

(8) nm23 gene: tumor infiltration, including tumor cells detached from the primary tumor, into the extracellular matrix, tumor metastasis is related to the transfer gene activation or metastasis suppressor gene inactivation, is a combination of a variety of metastasis-related genes and metastasis-inhibiting genes As a result of the action, the expression of the nm23 gene was decreased in the highly metastatic tumor, and the expression intensity in the low metastatic cell line was 10-fold higher than that in the high metastatic cell line, indicating that the product encoded by nm23 has a function of inhibiting tumor metastasis.

There are two nm23 genes in the human genome, namely nm23-H1, and nm23-H2, all of which are located at 17q21.3, encoding a 17kD protein consisting of 152 amino acids, nm23 protein and nucleoside diphosphate kinase (NDDK). The amino acid sequence is highly homologous, the homology of nm23-H1 is 89%, and the homology of nm23-H2 is 97%. NDPK is widely present, which transfers the phosphate group of 5' NTP to 5'NDP. Protein activation, which is involved in the polymerization of functional microtubules and G-protein-mediated signaling, on the one hand may cause abnormal microtubule polymerization and cause spindle abnormalities during meiosis, resulting in the formation of chromosome aneuploidy in cancer cells, Promote the development of tumors, on the other hand, may affect the cytoskeleton and cause cell movement, thus participating in the invasion and metastasis process and development process, regulated by two independent regulatory systems, wherein the level of nm23-H1 mRNA is related to cancer cell metastasis More closely, it is currently believed that although nm23 is not necessarily a transcriptional stimulator of myc, it is at least an important regulatory gene of myc, nm23 can induce the expression of myc, and the loss of nm23-H1 contributes to the permanent survival of cells.

Studies have found that the intensity of nm23-H1 immunohistochemical staining is irrelevant to the age of onset of papillary thyroid carcinoma, but the immunological activity of nm23-H1 significantly affects distant metastasis and survival in patients with thyroid follicular carcinoma. Curve, therefore, nm23-H1 can be considered as a prognostic factor for thyroid follicular carcinoma.

(9) Fas/FasL gene: Fas/FasL gene is a superfamily member of apoptosis-related gene, TNF) receptor. TNF is a kind of cytokine mainly produced by activated macrophages, which is cytotoxic. The partial composition: signal peptide, FasL) is a 40kD protein. FasL binds to Fas to initiate death signal, leading to apoptosis, which is a three-dimensional symmetrical structure perpendicular to the cell membrane. The structurally complementary binding of the two leads to the intracellular delivery of Fas. The key to the death signal is the Fas/FasL-mediated apoptosis.

Fas and FasL are expressed in various subtypes of thyroid cancer, and are significantly higher than thyroid adenoma and nodular goiter. Therefore, the expression of Fas and FasL genes may be related to the occurrence and development of thyroid cancer.

(10) bcl-2 gene: bcl-2 gene is opposite to TNF family. Bcl-2 gene can prevent cells from entering apoptosis process. It has been found that many proteins belong to bcl-2 family and can be divided into two types, one class. It is an anti-apoptotic bcl-2 family, mainly Bcl-2, mainly including Bax.

Bcl-2 protein expression may be associated with the occurrence of thyroid tumors. Both benign and malignant tumors of the thyroid have high levels of bcl-2 expression, while normal tissues express less bcl-2, along with the clinical stage of thyroid cancer. The progress of infiltration, the positive rate of bcl-2 was significantly decreased, and the positive rate of bcl-2 in undifferentiated carcinoma was significantly lower than that in differentiated type.

(11) Angiogenesis factor: The growth of tumor is divided into a slow growth phase without blood vessels and a rapid proliferation phase with blood vessels. Angiogenesis is a key link to promote tumor growth. Tumor invasion and metastasis is a complex multi-stage process, and angiogenesis is In the multi-step process of tumor invasion and metastasis, they play an important role, such as primary tumor proliferation, metastatic cancer, and so on.

The process of angiogenesis involves a series of morphological and biochemical changes associated with regulation between angiogenic factors and angiogenesis inhibitors, with at least 15 angiogenesis inhibitors. Angiogenic factors include vascular endothelial growth factor (VPF/VEGF).

Fibroblast growth factor is a mitogen and chemokine that has strong effects on vascular endothelial cells. The level of bFGF in blood of tumor patients can be maintained at a high level, and it is related to the degree of malignancy of thyroid cancer. The expression of bFGF is not thyroid cancer. Events that occur frequently.

(12) MMPs and FAK: During the infiltration and metastasis of tumor cells, the degradation of extracellular matrix (ECM) plays an important role. MMPs) are a group of zinc ion-dependent endopeptidases, of which MMP- 2 The selective degradation of intercellular matrix components and the degradation of the main component of the basement membrane type IV collagen, FAK) is a key enzyme in the process of integrin-mediated signal transduction, can induce the expression of MMPs gene, in normal cells It may promote cell adhesion and inhibit the growth of anchored cells. Overexpression of FAK can cause cells to surpass this growth inhibition and cause cancer cells to lose growth inhibition and proliferate.

The expression of MMP-2 and FAK may be associated with papillary thyroid carcinoma. The positive expression rate and positive intensity of MMP-2 and FAK in papillary thyroid carcinoma are significantly higher than those in adjacent tissues of thyroid cancer.

(13) Sodium/iodine symporter: Sodium iodide symporter (NIS) is a transmembrane glycoprotein, NIS protein consists of 643 amino acids, molecular weight 70-90kDa, later NIS of human thyroid gland It has also been successfully cloned, such as salivary gland, NIS protein promotes the transport of iodine into thyroid cells, NIS protein increases in thyroid tissue of Graves disease, TSH increases thyroid cells expressing NIS protein, 61.6% expresses NIS protein, while undifferentiated carcinoma does not. The expression of NIS protein indicates that NIS expression is inversely proportional to the degree of differentiation of thyroid cancer. It occurs in differentiated thyroid cancer in children and adolescents. When NIS expression is high, the tumor recurrence rate is low. Inducing thyroid cancer tissue to express NIS, radioactive iodine can be used. Radiation Therapy.

(14) Pax8-PPARγ1: Pax is a paired-type homeobox, which belongs to the homeobox gene in vertebrates. It has been successfully screened to isolate 9 different mouse Pax genes ( Paxl-9), a homologous box protein that is closely related to the development of the nervous system, acts as a peroxisome proliferator activater receptor gamma 1, PPARγ1, a subtype of nuclear transcription factor It has various regulatory effects such as regulation of cytokine production and promotion of epithelial cell growth. The thyroid follicular carcinoma has a chromosomal translocation in which the DNA-binding domain of Pax8 gene and the A to F domain of PPARγ1 gene fuse with each other, encoding a fusion oncoprotein. Pax8-PPARγ1, the detection of PPARγ1 mRNA or PPARγ1 protein contributes to the diagnosis of thyroid follicular carcinoma, and can reduce the need to remove benign thyroid tumors to exclude malignant lesions, although the detection rate of PPARγ1 protein is in thyroid follicular carcinoma. It is 35% to 63%, but it is also 55% in follicular thyroid tumors. Therefore, the significance of Pax8-PPARγ1 in the diagnosis of thyroid follicular carcinoma still needs further confirmation.

(15) Telomerase: There are telomeres at the end of the chromosome of human normal somatic cells. The length of telomeres is repeated with each chromosome, and the telomere is shortened to a certain extent. The cells stop dividing and go to death, which can be changed continuously. Short telomeres act as a repair to complement telomere deletions due to chromosomal replication, maintain telomere integrity, and extend cell life.

In addition to protecting telomeres, telomerase in organisms is also closely related to cancer. The incidence of telomerase and undifferentiated carcinoma is higher than that of thyroid papillary carcinoma. Analysis of telomerase activity to distinguish thyroid nodules Malignant, limited value in the diagnosis of thyroid cancer, and found that the expression of human telomerase reverse transcriptase (hTERT) is related to thyroid cancer, and is positively correlated with the degree of malignancy and infiltration of thyroid cancer. Pre-FNAC detection of hTERT expression is of added value in the diagnosis of thyroid cancer and contributes to the choice of surgical treatment.

In conclusion, early changes in papillary or follicular carcinoma of thyroid follicular epithelial cells may be caused by mutations in the ret or ras gene, and abnormalities in one or more of the mechanisms of cell cycle regulation may play an important role in tumor development. Role, and the occurrence of p53 mutation is closely related to the transformation of differentiated cancer to undifferentiated carcinoma, and ret, and how to interact, is a problem to be clarified.

2. Pathology According to the histopathological features of thyroid cancer, it is generally divided into four types.

(1) papillary carcinoma: a malignant tumor originating from the thyroid gland, accounting for 50% to 89%. It is the first peak before or after 20 or 30 years old. Bilateral nodules, hard texture, irregular borders, poor mobility, no obvious discomfort, so the average duration of treatment has reached 5 years, even more than 10 years, small diameter can be less than 1cm, hard Sometimes it can not be touched, often due to metastasis to the cervical lymph nodes, even at the time of autopsy, pathological sections can be confirmed as thyroid cancer, often due to long course of disease, cystic changes, resulting in difficulty in swallowing, puncture can extract yellow liquid, easily misdiagnosed as Cysts, late metastasis, easy to invade lymphatic vessels, so early cervical lymph node metastasis, especially in children, mainly in bilateral cervical lymph nodes, swollen lymph nodes can not be found for many years. Late stage can also be transferred to the upper mediastinum or axillary lymph nodes. Lump puncture and lymph node biopsy help to establish the diagnosis.

Under the microscope, the tumor tissue is mostly composed of papillary nodes, the size of the nipple, the branch is more than 3 grades, and the outer layer is a single layer or a plurality of layers of square cancer cells, which are evenly distributed and resemble a ground glass.

(2) Follicular carcinoma: refers to thyroid cancer with follicular differentiation and no papillary structure. Its malignancy is higher than that of papillary carcinoma, accounting for about 20% of thyroid cancer, second only to papillary Cancer ranks second, especially in women over 40 years old, mostly solid, can undergo degenerative changes, including hemorrhage, often similar to benign follicular adenoma, and is not easy to distinguish, even in pathological frozen sections, diagnosis There are certain difficulties, diversity changes, similar to normal thyroid tissue, can also be a poorly differentiated change of follicles and gel-like substances, with envelope and vascular invasion, such as eosinophils, can be diagnosed as Eosinophilic adenocarcinoma, which is a clear cell carcinoma, is more easily infiltrated into the periphery and is moderately malignant. The main metastatic route is the transfer of blood to the lungs and bones.

(3) medullary carcinoma: originated from thyroid C cells (ie, parafficular cells), is a moderate malignant tumor, accounting for 3% to 8% of thyroid malignant tumors, but in the same cancer The cancer cells in the nest have the same shape, no nipple and follicular structure, and their classification is mainly from the European Cancer Research and Treatment Organization (EORTC), the National Thyroid Cancer Treatment Collaborative Research Group (NTCTCS) and thyroid cancer surveillance. %, the average age is about 50 years old, the cancer is often single, mostly confined to one side of the thyroid, the texture is hard, the edge is clear, the length of the disease is long (several months to more than 10 years), the lymph node metastasis, the often metastatic part is Cervical lymph nodes can produce compression symptoms and metastatic masses. They can reappear when recurrence and metastasis. Family members can be screened by CT. People have used ret gene mutation analysis to diagnose the disease and screen high-risk subjects in family members.

Girelli summarized the medical records of 78 cases of medullary thyroid carcinoma from 1969 to 1986 in Italy. The results were: ages 15 to 89 years, mean 45 years old, male to female ratio: 1:2.9, 3 cases were family type non-MEN type, 3 cases were MEN2A type, 2 cases of MEN2B type, 34 cases of death (4 cases died of other diseases unrelated to this disease), 22 cases of survivors survived for 10 to 24 years, the length of survival is mainly related to tumor The stage is closely related to the age at the time of treatment. The early treatment has a good effect, while the abnormal one has recurred in different periods after surgery. The higher the blood CT level, the earlier the recurrence. However, 30% of patients have only elevated blood CT (individually 15 years) without recurrence of lesions.

(4) Undifferentiated carcinoma: clinically including giant cell carcinoma and small cells and other types of malignant thyroid cancer (squamous cell carcinoma), which is the most malignant thyroid tumor, and the disease progresses. Rapid, early local lymph node metastasis, or invasion of the recurrent laryngeal nerve, trachea or esophagus, and often through the blood to the lungs, accounting for about 5% of thyroid cancer, but in a short period of time, the mass rapidly increased, and rapid local infiltration , forming a bilateral diffuse thyroid mass, the mass is large and hard, the boundary is unclear, and it is fixed with the surrounding tissue, accompanied by tenderness, and is also easy to spread to the distant blood.

(1) Causes of the disease

1. Iodine and thyroid cancer

2. Radiation and thyroid cancer

3. Thyroid stimulating hormone chronic stimulation and thyroid cancer

4. The role of sex hormones and thyroid cancer

5. Glandular thyroid material and thyroid cancer

6. Other thyroid diseases and thyroid cancer

The reason for the inconsistency between thyroid cancer and nodular goiter is that:

(two) pathogenesis

2. Pathology According to the histopathological features of thyroid cancer, it is generally divided into four types.

symptom:

The early clinical manifestations of thyroid cancer are not obvious. Patients or family members and doctors accidentally found that the thyroid gland has a hard and uneven mass, and there are many unconscious symptoms. The neck mass is often an asymmetric lumps, and the thyroid nodule mass can be gradually increased. With swallowing up and down activities, and can be invaded by the trachea and fixed, the mass is easy to produce compression symptoms earlier, such as accompanied by hoarseness, poor breathing, difficulty swallowing, or local tenderness and other compression symptoms, when the jugular vein is compressed, can occur Signs of lateral venous engorgement and facial edema are one of the characteristics of thyroid cancer, such as lung metastasis and bone metastasis, and even pathological fractures, while the neck should be carefully examined for thyroid gland.

Papillary thyroid carcinoma

Papillary thyroid carcinoma is generally small, and the development changes slowly, but there may be metastasis in the early stage. The lesions that are often found first may be metastases. The benign masses are more common before the age of 40, and may not progress in 20 to 30 years. Patients over 50 to 60 years of age progress faster.

Papillary thyroid carcinoma is a low-grade malignant tumor, the most common pathological type of thyroid cancer, accounting for 60% to 70% of thyroid cancer in adults and 70% of thyroid cancer in children, especially in children, about 2 /3 cases of papillary thyroid carcinoma are actually mixed tumors, and different proportions of follicular carcinomas can be found in their lesions. The natural course of these patients is similar to papillary carcinoma, and the current classification criteria will Some patients are classified as papillary carcinoma.

(1) Characteristics of the onset: The peak age of onset is 30 to 50 years old, and the female patient is 3 times that of male patients. Among the thyroid cancer caused by external rays, 85% is papillary carcinoma, and the course of coexistence of human and cancer can be long. After several years to a dozen years, even after lung metastasis, you can still carry tumors to survive.

(2) Clinical manifestations: Papillary thyroid carcinoma is a progressively enlarged neck mass. The mass is painless and may be inadvertently discovered by the patient or physician. Therefore, the time of treatment is usually late, and it is easily misdiagnosed as benign lesions. There may be varying degrees of hoarseness, and patients with papillary thyroid carcinoma have no changes in thyroid function, but some patients may develop hyperthyroidism.

In the neck examination, the characteristic manifestation is an asymmetrical mass in the thyroid gland. The texture is hard, the edges are more fuzzy, and the surface of the tumor is uneven. The mass can be swallowed. If the tumor invades the trachea or surrounding tissue, The mass is more fixed.

(3) Metastatic characteristics: When lymph node metastasis occurs in papillary thyroid carcinoma, it is mostly confined to the thyroid region. On the clavicle, a few cases may have axillary lymph node metastasis. In some cases, sentinel lymph node enlargement above the thyroid isthmus may occur. Regional lymph node metastasis occurred in % of patients.

A small number of cases are metastasized through the blood line, mainly for pulmonary metastasis. Several tumor nodules can be formed in the lungs or the whole lungs can be snowflake-shaped. The patient can maintain relatively normal lung function for 10 to 30 years and become a thyroid gland. The only source of thyroxine in the body after resection, leading to obstructive and restrictive lung disease. Distant metastasis can also occur at bones and the like.

2. Thyroid follicular carcinoma

The development of follicular carcinoma is also slow, characterized by rapid dissemination of blood, more distant metastasis, and can reach bone tissue and lung. Because its tissue cytology approximates thyroid follicular structure, it can have iodine absorption function. Therefore, a small number of patients can The performance is hyperthyroidism, the rate of 131I is increased, and when the advanced tumor develops, the superior vena cava compression syndrome can also be caused. The reliable indicators for diagnosing thyroid follicular carcinoma are vascular and capsule invasion, and distant metastasis. The case of complete resection of the lesion is approximately 1/2 to 2/3.

(1) Characteristics of the disease: It can occur at any age, but there are more middle-aged and elderly people. The peak age of the disease is 40-60 years old. There is obvious lymph node metastasis or distant metastasis, even when the biopsy of distant bone metastasis is performed. Get a diagnosis.

(2) Clinical manifestations: The first manifestation of most patients is a thyroid mass, the tumor grows slowly, the texture of the mass is medium, the boundary is unclear, the surface is not smooth, the thyroid activity is better, and the tumor invades the tissue adjacent to the thyroid. After the fixation, the performance is hoarse, some patients may have metastatic symptoms, such as the femur.

(3) Metastatic characteristics: Because thyroid follicular carcinoma invades blood vessels more, local invasion and distant metastasis can occur. Compared with papillary thyroid carcinoma, lymph node metastasis occurs in the neck and mediastinum. 8% to 13%, other organs, such as the brain, bladder and skin can also be involved, less osteogenic changes, can be used after oral radionuclide iodine, radiotherapy by internal irradiation, and even excessive secretion of thyroid hormone.

3. Thyroid medullary carcinoma

Thyroid C cells originate from neural crests, and adrenal medulla cells, known as amine precursor uptake and decarboxylation cells. Most medullary thyroid carcinomas are associated with the RET oncogene located on chromosome 10, q11.2.

(1) Characteristics and classification of the disease: The disease is highly malignant and can be metastasized through the bloodstream. The medullary thyroid carcinoma can be divided into four types.

1 scattered hair: 70% to 80%, non-genetic, no similar diseases in the family, will not be passed on to the offspring, no other endocrine gland lesions, the ratio of male to female incidence is about 2:3, and there is Codon mutations have a poor prognosis.

2 Familial type: refers to patients with a family genetic predisposition, but not accompanied by other endocrine glands, the age of high incidence is 40 to 50 years old. Its gene mutation pattern is the same as MEN2A.

3MEN2A: MEN is multiple endocrine neoplasia syndrome (MEN), which is related to medullary thyroid carcinoma is MEN2A and MEN2B, including bilateral medullary thyroid carcinoma or C cell hyperplasia, so the incidence of men and women is similar, high incidence The age is 30 to 40 years old and involves 609 of exon 10 and 11 of the RET gene.

4MEN2B: including bilateral medullary thyroid carcinoma, and is malignant), but rarely involving the parathyroid glands, the incidence rate of men and women is similar, the high-risk age is 30 to 40 years old. Mutations in the 918th codon in exon 16 of the RET gene were found in almost all cases.

(2) Clinical manifestations: Most patients in the first visit, the main manifestations are painless hard solid nodules of the thyroid, local lymphadenopathy, and sometimes lymphadenopathy becomes the first symptom, such as with heterologous ACTH, can produce different Symptoms, serum calcitonin levels are significantly increased, which is the biggest feature of the disease, so calcitonin becomes a diagnostic marker, more than 0.6ng / ml, should consider C cell proliferation or medullary carcinoma, due to calcitonin The regulation of blood calcium levels is far less powerful than that of parathyroid hormone, as well as ganglionoma or mucosal neuroma, which is MEN.

At the time of physical examination, the thyroid mass is solid, the boundary is unclear, and the surface is not smooth. The family and MEN2 patients can be bilateral thyroid masses, and the masses have better activity. After the late invasion of adjacent tissues, they are more fixed, such as hoarseness.

(3) metastatic characteristics: the early stage of medullary thyroid carcinoma invades the lymphatic vessels of the thyroid gland, and quickly metastasizes to other parts of the gland and lymph nodes in the neck. It can also metastasize to the lungs through distant metastasis and transfer to the lungs. It is associated with the lack of capsules in medullary carcinoma.

4. Undifferentiated thyroid cancer

(1) Characteristics of the disease: Undifferentiated thyroid cancer is a highly malignant tumor, accounting for 2% to 3% of thyroid cancer. It is also reported that 5% to 14%, the age of onset is more than 65 years old, and young people are less common. The thyroid undifferentiated carcinoma of follicular cells can also be divided into giant cells, which are mostly giant cells and spindle cells. Differentiated and undifferentiated carcinomas, including follicular adenomas, can also be present in the same case. Metastatic cancer of the biceps muscle, although cervical lymph node dissection and biceps resection, lung metastasis still died.

(2) Clinical manifestations: Most patients showed progressive neck masses, accounting for 64% to 80%, but there was no thyroid enlargement before the onset, the mass was hard and rapidly increased; 2 thyroid enlargement, may be accompanied There is a distant metastasis; 3 has a history of thyroid mass for many years, but the thyroid mass suddenly increases rapidly and becomes hard as a stone; 4 there is untreated DTC, which increases rapidly after a period of time, accompanied by Regional lymph nodes are enlarged.

(3) Metastatic characteristics: Due to the high degree of malignancy of thyroid undifferentiated carcinoma, the disease develops very rapidly, invading surrounding tissues and organs, such as the trachea, and even forming a mass in the trachea and esophagus, leading to respiratory and swallowing disorders. 90% of patients with cervical lymph node metastasis, 25% of patients with tracheal involvement, and 50% of patients who have undergone lung metastasis through the bloodstream.

5. Rare thyroid cancer

(1) thyroid lymphoma: the incidence of thyroid lymphoma is low, accounting for less than 5% of primary thyroid tumors, mainly non-Hodgkin's lymphoma, the ratio of male to female patients is (2 ~ 3): 1, in addition to rapid increase In addition to large thyroid masses, the disease is often accompanied by obvious local symptoms such as hoarseness, difficulty breathing, and difficulty swallowing. Non-Hodgkin's lymphoma is a multicentric tumor that grows in the reticuloendothelial system, so the incidence of liver is from 0 to 60%. 30% to 70% of patients have HT.

(2) Thyroid metastasis: The malignant tumors in other parts of the body can be transferred to the thyroid gland, such as breast cancer, including 3 cases of lung cancer, which have obvious primary tumor symptoms.

(3) thyroid squamous cell carcinoma: thyroid squamous cell carcinoma is rare, accounting for about 1% of thyroid malignant tumors, and the incidence rate in the population is about 2% to 3%, mainly from Japan, or it can be a widespread thyroid papillary carcinoma. Can also be derived from the thyroid gut tube or cleft palate, part of the primary thyroid squamous cell carcinoma with carcinoma showing thymus-like element (CASTLE), from ectopic thymus or cleft palate sac residual tissue, The prognosis is good, the age of onset is more than 50 years old, no obvious gender difference, early symptoms of invasion and compression of surrounding organs, that is, hoarseness, late invasion of both sides of the leaves, hard texture, fixed, unclear border, accompanied by trachea Compression, cervical lymphadenopathy, poor prognosis, the current treatment is to remove the tumor as much as possible plus radical surgery or radiation therapy.

diagnosis:

Thyroid mass grows faster, there are metastases, and there are obvious compression symptoms, hypothyroidism, thyroid scans, cold nodules, or abnormal thyroid CT scans and MRI images. The final diagnosis should be based on pathological biopsy. Papillary thyroid carcinoma.

1. Diagnostic points When there is a goiter in the clinic, the age of the patient should be combined. The following manifestations should consider thyroid cancer.

(1) General information: Special attention should be paid to gender. Therefore, special attention should be paid to understanding the iodine intake of patients, especially if there is a history of long-term iodine deficiency.

(2) Medical history:

1 Current medical history: 50% of childhood thyroid nodules are malignant, and single male nodules in young men should also be alert to the possibility of malignancy. Pay special attention to the location of the mass or nodule, whether it will increase rapidly in a short period of time, whether it is accompanied by swallowing. Difficulties, whether accompanied by flushing of the face, the occurrence of tracheal compression caused by breathing difficulties, the possibility of malignancy is large.

Through the current medical history investigation, an overall assessment of the patient's thyroid function status should be made. It is necessary to know in detail whether there is an increase in food intake, and should also pay attention to the systemic symptoms of tumor metastasis (such as headache).

2 Past history: Whether you have had a head or neck due to other diseases.

Have you ever had a thyroid disease (such as chronic lymphocytic thyroiditis).

3 Personal History: Whether there is an environmental history of exposure to nuclear radiation pollution. Whether the occupations involved have important radioactive sources and personal protection.

4 Family history: medullary carcinoma has a family genetic predisposition, and similar patients in the family can provide diagnostic clues.

(3) Physical examination: a thyroid mass or nodule can be found, and a skilled palpation of the neck can provide useful diagnostic data, which is fixed when the quality is hard or swallowed, and the lesion is fixed on the same side, such as lymph node puncture. Grass yellow clear liquid, mostly lymph node metastasis of thyroid metastasis.

Most of the thyroid cancers are single nodules. The nodules can be round or elliptical. Some nodules are irregular in shape, hard and have no obvious tenderness. They often adhere to the surrounding tissues and cause limited or fixed activity, often accompanied by neck. In the lower part, a single nodule of the thyroid gland is more than a multiple nodule, but multiple nodules, and there may be tenderness.

1 oppression and invasive signs: thyroid cancer can compress and invade surrounding tissues and organs when it is large, often have difficulty breathing, and may have corresponding clinical manifestations.

2 type of cancer syndrome: medullary thyroid carcinoma can have hyperthyroidism.

(4) Auxiliary examination: In clinical practice, benign or malignant tumors of the thyroid gland are characterized as "thyroid nodules", except for most "hot" nodules, other types of nodules or imaging findings "Unexpected nodules (accidental tumors)" should think of the possibility of thyroid tumors; some thyroid cancers can also secrete TH independently, so they can also be expressed as "hot nodules", so in fact, all thyroid nodules should be excluded first. Thyroid tumors (sometimes, thyroid cancer can only be diagnosed under the microscope), no lymph nodes around or enlarged; 3 lung or bone with metastases with unknown primary lesions; 4 elevated serum calcitonin, greater than 600μg / L.

2. Classification and staging of thyroid cancer staging, the most common international and domestic is TNM staging, UICC) and the American Joint Committee on Cancer (AJCC) fifth revised TNM staging criteria affecting thyroid cancer staging The relevant factors are first of all pathological types. The size of the tumor and the degree of invasion of the lymph nodes are also related to the stage. The age has an important influence on the staging of differentiated thyroid cancer, and the stage is the largest tumor.

(1) Definition of TNM:

1 primary tumor (T):

TX: Unable to estimate the primary tumor.

T0: No primary tumor was found.

T1: The tumor is confined to the thyroid gland with a maximum diameter of ≤ 1 cm.

T2: The tumor is confined to the thyroid gland, 1 cm < maximum diameter ≤ 4 cm.

T3: The tumor is confined to the thyroid gland with a maximum diameter of >4 cm.

T4: Tumors, regardless of size, are outside the thyroid capsule.

2 regional lymph nodes (N): regional lymph nodes refer to the lymph nodes of the neck and upper mediastinum.

NX: Unable to estimate regional lymph node conditions.

N0: No regional lymph node metastasis was found.

N1: regional lymph node metastasis, can be divided into N1a ipsilateral cervical lymph node metastasis, N1b bilateral or contralateral cervical lymph nodes.

3 distant transfer (M):

MX: Can't make an estimate of whether there is a distant transfer.

M0: No distant transfer.

M1: There is a distant transfer.

(2) Staging standards:

1 staging criteria for papillary thyroid carcinoma and follicular carcinoma.

2 thyroid medullary carcinoma staging criteria.

3 thyroid undifferentiated cancer staging criteria, all cases are stage IV.

Identification

The key to diagnosing thyroid nodules is to identify the nature of the nodules. Before diagnosing thyroid cancer, the following diseases should be identified:

Nodular goiter

Generally there is the basis of iodine deficiency, middle-aged women are more common, the medical history is longer, the lesions often involve bilateral thyroid, multiple nodules, nodules vary in size, smooth, soft, no abnormal symptoms of nodules, partial nodules Cystic changes occur, the gland can be reduced in symmetry, the thyroid mass rapidly increases and the surrounding tissue infiltrates, the mass is firm, the activity is poor, and then the deep cervical lymph nodes and the supraclavicular lymph node metastasis.

2. Thyroiditis

Various types of thyroiditis may be misdiagnosed as thyroid cancer, such as increased symmetry of the thyroid gland, nodular shape, adhesion and fixation with surrounding tissues, but different performance under light microscopy.

(1) Subacute thyroiditis: often secondary to upper respiratory tract infection, destruction of thyroid follicles, release of colloids, elevated body temperature, goiter, one side of the thyroid hardened, accompanied by mild tenderness, after a few weeks Involved in the other side of the thyroid; some cases can be repeated within a few months, serum T3, but the thyroid 131I absorption rate is significantly reduced, this separation has diagnostic value. The treatment with adrenocortical hormone and thyroxine is better. Most cases can be diagnosed based on typical clinical findings.

(2) Chronic lymphocytic thyroiditis: more than 40 years old women, bilateral thyroid chronic, rubber-like hardness, nodules on the surface, generally no adhesion or fixation with surrounding tissues, no swelling of the cervical lymph nodes, and part of the thyroid gland Coexisting cancer, such as mucinous edema, thyroid antibody is significantly elevated.

(3) sclerosing thyroiditis (Riedel's disease): also known as fibrotic thyroiditis, is a local manifestation of chronic fibroproliferative diseases, with an average of 2 to 3 years, basal metabolism is normal or slightly higher, hard as wood, but keep The original shape of the thyroid gland is often fixed with surrounding tissues and presents with compression symptoms. It is characterized by tight breathing and difficulty in distinguishing from thyroid cancer.

3. Multiple endocrine neoplasia

(1) MEN 2A type: unilateral or bilateral adrenal pheochromocytoma, patients have a family history, in the C cell proliferation stage can be considered medullary carcinoma, and then pheochromocytoma occurs, and catecholamines are secreted, When catecholamines are abnormally elevated, palpitations may occur, which may occur before medullary thyroid carcinoma, and pathological examination of local lesions may be observed. There is amyloid deposition between the epidermis and the dermis, and the cause is unknown, which may indicate medullary carcinoma.

(2) MEN 2B type: for medullary thyroid carcinoma, including sublingual or subconjunctival mucosal neuroma, Marfanoid body type (slim body, poor muscle development, intestinal obstruction or diarrhea, early metastasis, lesions may have expanded Outside the neck, but only a few are malignant, such as diarrhea, often bilateral, and often due to sudden death of chromaffin cells, should be treated with pheochromocytoma, postoperative elective resection of medullary thyroid carcinoma, should be treated first Medullary thyroid carcinoma, hypercortisolism can be alleviated, the prognosis is poor, MEN 2A is better, and the loose hair is in the middle.

complication:

The tumor rapidly enlarges, compresses the trachea, infiltrates the esophagus and recurrent laryngeal nerve and causes difficulty in breathing.

treatment:

Non-surgical treatment

Thyroid cancer is the most effective, and a variety of non-surgical adjuvant treatments have a long-term survival rate and recurrence rate, especially in high-risk groups. Some thyroid cancers that cannot be completely removed, such as local fixation, or unresectable Thyroid cancer with a high degree of malignancy, such as invasive gland in vitro tissue, and tumors that have distant metastasis or local recurrence and unresectable, non-surgical adjuvant therapy has the effect of relieving symptoms and prolonging life.

(1) Thyrotropin inhibition therapy for differentiated thyroid cancer: Correct use of thyrotropin (TSH) inhibition therapy after DTC can achieve good results in most patients, and the local recurrence rate and distant metastasis rate are significantly reduced. The 30-year survival rate has also increased significantly.

Mechanism of 1TSH Inhibition Therapy: Although many factors that stimulate thyroid growth and genes associated with thyroid tumors, such as epidermal growth factor (EGF) and its receptor (EGFr), have been found, TSH is most important to stimulate thyroid follicles. Iodine and promote the organicization of iodine, and increase the intracellular cyclic adenosine monophosphate (cAMP) by adenylate cyclase, which leads to phosphorylation of cytoplasmic proteins and increased nuclear replication. Thereby accelerating the deterioration of the tumor, the adenylate cyclase has been increased, and the reactivity is reduced when the TSH is inhibited. The TSH inhibition therapy has no therapeutic effect on the formed cancer, but can delay its development, and only the primary is removed. Suppression, inhibition therapy may have a better effect.

It has been confirmed that TSH receptors are present in follicular cell-derived DTC. In vitro experiments have also found that this receptor responds to TSH stimulation. Tyrosin can inhibit thyroid tumor production by inhibiting TSH, and TSH can stimulate phosphatidylinositol phosphate. The kinase-dylinositol phophokinase C (PKC) system, especially in the absence of iodine, promotes the formation of thyroid nodules.

Dunhill (1937) first proposed the use of TSH to treat thyroid cancer, and is widely used in existing DTCs and to prevent recurrence of resected tumors.

Thyroxine has a negative feedback effect on TSH and is the basis for the implementation of inhibition therapy, but the physiological function is equivalent to 3 to 5 times that of T4, mainly from the liver, 80% of papillary thyroid carcinoma and follicular carcinoma. Good curative effect can cause many hazards. In addition, the use of long-lived preparations such as thyroid powder (tablets), some scholars oppose inhibition treatment, but compared with 30-year survival rate, the inhibition therapy group is significantly higher than the control group, such as Signing, paying attention to and avoiding various adverse reactions, inhibition therapy does have a positive value.

Implementation of 2TSH inhibition therapy:

A. Treatment indications: Because the prognosis of DTC in high-risk group is not as low as that in low-risk group, and thyroxine increases oxygen consumption in the heart and causes osteoporosis, the best indication for inhibition therapy is age <65 years old, especially high-risk group. And women before menopause.

Secondly, DTC should also use inhibition therapy after total thyroidectomy, especially in the 5 years after recurrence, it must be individualized according to the possibility of local recurrence or systemic metastasis, when there are some poor prognosis factors. Inhibition therapy should be given, such as thyroid cancer without iodine, invasion of the capsule.

B. Selection of preparations: The current commonly used preparation is levothyroxine sodium (1 evothyroxine, L-T4), with a long half-life of about 7 days, while the half-life of liothyronine (T3) is only 24 hours. The high-risk group of patients is beneficial to shorten the time before the test, and timely scan.

The levothyroxine sodium (L-T4) preparation is pure, the content of thyroxine is accurate, and there is no allergic reaction, but the price is expensive. Although the biological preparation thyroid powder (tablet) has a rough preparation, it is still valuable because of its low cost. It is also convenient to exchange thyroid powder (tablet) with levothyroxine sodium (L-T4). The equivalent dose exchanged between the two is about 40 mg of thyroid powder (tablet) equivalent to 100 μg of levothyroxine sodium (L-T4). The half-life of the two is similar.

C. Mastery of dose: TSH (S-TSH) concentration and T3 should be measured according to high sensitivity immunoassay, and T3, usually <0.3μU/ml, or even <0.01μU/ml, often at 0.3~ 1.0 μU/ml (normal reference value of S-TSH is 0.3 to 6.3 μU/ml).

The recommendations of the American Society of Clinical Endocrinology and the American Thyroid Association are for patients in the low-risk group (Tables 4 and 5), ie, the MACIS score is <6.0, which makes the TSH less than the normal low value; for the intermediate-risk group, the MACIS score is 6.0-6.9. However, clinical hyperthyroidism should not occur; for patients with high-risk groups, the MACISS score is >7.0, but the complications should be closely monitored, especially in postmenopausal women.

In addition, the dose of thyroxine must be reduced with age to avoid osteoporosis and increased myocardial oxygen consumption. However, the dose must be increased when: a. gastrointestinal malabsorption: such as cirrhosis. b. Take some drugs that block T4 absorption: such as aluminum hydroxide. c. Take some drugs that block T3 to T4 peripheral transformation: such as amiodarone (ethylamine iodine). d. Take medications that inhibit non-deiodinated T4 clearance: such as pethidine. e. Selenium deficiency. f. Pregnancy.

The treatment of patients with early or high-risk thyroid cancer should be treated with total inhibition. The daily effective dose of levothyroxine sodium (L-T4) is <60 years old: 2.2 μg/kg; >60 years old: 1.5-1.8 μg/kg. The dose must be adjusted with the measured value of thyroid function. Patients in the low-risk group need only partial inhibition therapy.

D. Treatment time limit: When the postoperative administration has not been unified, regardless of unilateral or bilateral thyroidectomy, the serum thyroxine level is basically within the normal range within 3 weeks after surgery, and there is no clinical manifestation of hypothyroidism. It is more common in unilateral resection, and T4 and FT4 are not significantly reduced about 5 days after operation. Early administration of exogenous hormone may further increase hormone levels in the body, aggravating the above symptoms, and some patients will have S-TSH in the short term after surgery. In the state of transient inhibition, it is not appropriate to take the drug from the perspective of inhibition. It should be stopped after the effect of releasing hormones in the operation disappears. The patient who has unilateral thyroidectomy is 3 times after the operation, and the upper limit of the normal range is doubled. Therefore, it is recommended to give inhibition therapy 2 weeks after bilateral thyroidectomy from 2 to 3 weeks after surgery, that is, 3 weeks after unilateral thyroidectomy.

As for the duration of use, patients in the high-risk group are best taken for life, while the low-risk group is eligible for recurrence in the first 5 years after surgery, and can be treated with total inhibition within 5 years after surgery. Close follow-up and regular pathological examination, 5 years After partial inhibition or no treatment, or after radionuclide iodine ablation, all residual thyroid has been destroyed, monitoring serum TG levels at follow-up is extremely meaningful, TG should not increase, serum TG increased> 5ng/ml, must be alert to tumor recurrence or metastasis, serum TG level is more sensitive than radionuclide scanning, even if the radionuclide scan is negative, can not completely exclude cancer metastasis, Duren and other TG sensitivity and specificity of 91% and 99 %, because TG is stimulated by TSH to stimulate thyroid follicles, any disease that increases thyroid function can be increased, such as nodular goiter. When there is functional thyroid follicle, TG increase does not mean malignant tumor .

3 adverse reactions of inhibition therapy: as long as the dose of thyroxine is appropriate, most of them have no adverse reactions and must be prevented.

A. Hyperthyroidism (hyperthyroidism) or subclinical hyperthyroidism: As long as the thyroid function is reviewed regularly, T3 can avoid this adverse reaction.

B. Osteoporosis: manifested as bone pain, decreased serum parathyroid hormone, especially in the lack of calcium.

C. Increased myocardial oxygen consumption, angina pectoris, and even myocardial infarction, must be used with caution or abandonment of inhibition therapy for coronary heart disease with atrial fibrillation.

4 The efficacy of inhibition therapy: Inhibition therapy reduces the recurrence rate of thyroid papillary and follicular adenocarcinoma and the mortality associated with thyroid cancer, even in elderly patients with advanced disease, suggesting that no matter for III, showing postoperative The cumulative recurrence rate was 17% in patients treated with levothyroxine sodium (L-T4), compared with 34% in the control group. Although there was no significant difference in 10-year survival between the inhibitory group and the control group, the 30-year survival rate showed inhibition. The therapy group was significantly better than the control group.

(2) Nuclide iodine treatment: radionuclide iodine (131I, both detectable by γ-camera, tissue absorption of γ-rays is minimal, and the destruction of thyroid follicles or cancer is high energy and range Only 0.5 cm of beta radiation.

After oral iodine iodine, the upper digestive tract can be quickly absorbed, reaches the certain tissues through the blood circulation and is concentrated, and expressed by functional sodium-iodine transport (NIS), and finally by urine, the more follicles of the diseased tissue More, the curative effect is also the best, the curative effect is the best, papillary adenocarcinoma is better in iodine, and the curative effect is better; medullary cancer has little or no iodine, so the curative effect is worse; because the undifferentiated cancer does not take iodine Therefore, almost no treatment with nuclear iodine.

1 Nuclide iodine treatment of differentiated thyroid cancer: Some DTCs, such as papillary, have good curative effect, but they must be used at least after unloading surgery, that is, they can only be used as adjuvant therapy for DTC. .

Because of the adverse reactions of nuclide iodine, it is still controversial whether or not DTC should be treated with radionuclide. The 10-year survival rate is quite high, and Crile (1988) considers the efficacy and nuclides of inhibition therapy. Iodine was similar, and it was found that 6.4% of patients with postoperative nuclides and iodine plus inhibition therapy, 13.1% of those who used inhibition therapy alone, 40% of the two treatments, and 100% of the radionuclide treatment group after surgery. The control group was only 33.3%.

In recent years, more and more scholars have paid attention to the treatment of radionuclide iodine, but because of its poor efficacy on poorly differentiated and undifferentiated thyroid cancer, it is less used.

According to the purpose of treatment, the treatment of nuclide iodine can be divided into ablation therapy after thyroidectomy, and internal irradiation therapy which can be transferred without reoperation.

A. Ablation therapy: Ablation therapy is performed after DTC for thyroidectomy. The residual normal thyroid is destroyed by radionuclide and the total thyroidectomy is achieved. There are many complications of thyroidectomy, such as parathyroid gland. Dysfunction, no need to take additional nuclides and other preparations, usually can be found in a small dose of 2mCi 131I diagnostic scan can not detect the lesions, can be found 24% to 39% intraoperative and chest radiographs can not be found in the metastases Therefore, it has the effect of further diagnosis of metastases.

The dose of nuclide iodine used in ablation therapy is large, so it is still controversial whether this therapy is necessary after surgery. This therapy does not improve long-term survival rate and tumor recurrence rate. It is found that the ablation group is compared with the control group, II. It is considered that if the 30-year survival rate is required, postoperative ablation therapy should be considered. As long as the initial scope of surgery is appropriate, postoperative ablation therapy is of little significance in low-risk patients, especially in patients with papillary carcinoma. Postoperative permanent parathyroidism is found. The incidence of hypogonadism was 2%, the incidence of permanent recurrent laryngeal nerve damage was 1%, and the 30-year recurrence rate was only 19.1%, while the postoperative ablation group also had 16.6% (P=0.89). There was no significant difference ( P=0.43), follicular, especially Hurthle cell thyroid cancer, should be treated with postoperative ablation to achieve early detection of metastases and prolong life. After complete ablation, serum TG increases, especially when TSH increases. Considering the possibility of metastasis, it should be treated early. In recent years, postoperative ablation therapy has been widely accepted under the control of appropriate doses.

The significance of using ablation therapy is: a. The thyroid itself is multifocal. According to the continuous pathological section of the total thyroidectomy specimen, the incidence of recessive cancer in the contralateral gland is as high as 10% to 25% or even 80%. You can choose to ablate the residual gland after thyroidectomy by radionuclide iodine, which can achieve the purpose of total resection, eliminate all glandular recessive lesions, and have many complications of total thyroidectomy. It can also achieve early diagnosis. It is difficult to find metastatic lesions and further treatment as early as possible. If ablation is used after surgery, the possibility of such transformation can be reduced.

a. Indications: II, and the partial thyroid remains in the initial surgery, as a preparation for further radionuclide therapy.

b. Ablation time: usually 2 to 3 weeks after surgery is most appropriate, TSH increased by up to 30μU / ml, at this time, localized metastases or residual lesions have the strongest iodine ability, >50μU / ml, but inhibit the nucleus Absorption of iodine.

c. The successful index of ablation dose ablation is: iodine content <1% at 48h; thyroid scan after ablation is not developed.

Within a certain range, the dose of nuclide iodine is positively correlated with the effective rate of ablation. The dose of 100-150 mCi is 85%-95%. The excessive dose does not increase the curative effect. The higher the initial dose, the higher the ablation efficiency. The number of treatments is reduced. Balc et al suggest that the appropriate dose of initial application of radionuclide should be ≥30mCi. Beieraltes believes that when taking 1 to 5mCi of iodine iodine, a diagnostic scan can not show occult metastases, especially preoperative iodine. When the rate is <4%, 100~149mCi high-dose radionuclide iodine should be applied. For the initial treatment, it is better to use a safer dose. If necessary, add 75-100mCi or fractionation after 6-12 months of initial nuclear iodine treatment. Ablation therapy for safety and effectiveness.

B. Unresectable primary tumor, or cervical lymph node metastasis, should be the first choice for re-surgery, or with the liver, as well as the inoperable primary lesion, as long as local iodine can be treated with radionuclide iodine, and then Treatment with a larger dose of nuclides, the dose depends on the clinical manifestations, the maximum dose is 800 ~ 1000mCi, but the side effects are extremely large.

Radionuclide iodine treatment is effective for recurrence, especially in about 70% of thyroid follicular carcinoma. In children with thyroid papillary carcinoma with iodine function, the 10-year survival rate can be reached after treatment with nuclides. 74%, and only 6% of patients without iodine function, with DTC with bone, 5 to 10 years of survival rate in the iodine iodine treatment of iodine function is 79%, but not iodine only 55%.

The iodine intake rate of thyroid cancer significantly affects the efficacy of iodine iodine. The iodine uptake rate of younger thyroid cancer is higher than that of the elderly. The metastases with mild hypothyroidism often have thyroid function and easily absorb iodine, 30~ 50μU/ml is the best, and >50μU/ml is inversely proportional to the iodine uptake rate, which can inhibit the release of iodine from the thyroid without changing the iodine uptake function, thus increasing the efficacy of iodine iodine.

In addition, the efficacy of radionuclide iodine is related to the following factors: a. Non-invasive and lymph node metastasis, the effect of radionuclide iodine is better, while DTC with surrounding tissue infiltration ability of nuclear iodine is less effective, but The small-scale lung metastasis detected by radionuclide scanning is better, which can reduce the mortality rate by 50%. The lung metastases found by other imaging findings have a mortality rate of 6 times that of the small-scale lung metastasis. The curative effect is even worse, the cure rate is only 7%, and the improvement rate is only 36%, and the curative effect is also poor. The nerve damage caused by edema can be prevented by using adrenal cortical hormone or recombinant human thyrotropin (rhTSH) to prevent serious consequences. .

2 nucleus iodine treatment of medullary carcinoma: familial medullary thyroid carcinoma type IIA (MENIIA) has a better prognosis, sporadic 55%, 10-year survival rate of only 50%, and thyroidectomy, 10 The annual survival rate is over 95%. If there is an extraglandular invasion at the time of initial surgery.

It is generally believed that medullary carcinoma does not take up iodine, and nuclides iodine has no therapeutic effect. When the residual gland cancer recurs, although the C cells that cause medullary carcinoma do not take iodine, the normal thyroid follicles have iodine function. By irradiating nearby C cells, the so-called bystander effect achieves a certain therapeutic effect. However, some people have objections to this effect.

If the initial surgery found that the tumor was confined to the gland, no thyroidectomy was performed and the serum calcitonin increased after surgery, indicating that there may be hidden lesions in the residual gland. Nuclide iodine can still be used as valuable adjuvant therapy, and most of them Can prolong the survival period, the residual focal lesions with 150mCi of nuclides iodine treatment, but the effect is not reliable, such as bone, radionuclide iodine treatment is not applicable, because only metastatic C-cells do not take iodine cancer cells, There is no normal thyroid follicle with iodine function.

3 complications of nuclides iodine treatment:

A. Early complications: Within three weeks after taking the drug, small doses (<30mCi) of riboside iodine treatment rarely occur. The incidence increases when the dose is >150 to 200 mCi.

a. Acute radiation sickness: the incidence rate is <1%, which occurs within 12 hours after taking the drug. The performance is weak.

b. Salivary gland inflammation: The incidence rate is about 5% to 10%, which can occur immediately or several days after taking the drug. In severe cases, there may be parotid glands, and the taste change may last for weeks or months.

c. Transient radiation gastritis: very rare, produced within 1/2 to 1 hour after oral administration, showing nausea.

d. Radiation cystitis: manifested as bladder irritation, keep emptying the bladder once every 2 to 3 hours. If the drinking water is not enough within 24 hours, or if the bladder is not evacuated in time, radiation cystitis may occur.

e. Abdominal discomfort and mild diarrhea: occur on the first 1-2 days after taking the drug.

f. Neck edema: Commonly after ablation therapy, it occurs in the residual thyroid gland, and when the iodine is good, it shows a neck edema similar to vascular nerve.

g. Transient hyperthyroidism: Nuclide iodine causes massive destruction of the thyroid gland, and rapid release of thyroxine can cause transient hyperthyroidism, when the tumor subsides.

h. Myelosuppression: Almost all occur, especially when the dose is too large, can lead to severe bone marrow suppression.

i. Temporary recurrent laryngeal nerve palsy: produced during radionuclide ablation after thyroidectomy.

k. Tumor metastasis hemorrhage can also cause fatal brain edema. Adrenal cortex hormone prevention should be used before the application of radionuclide iodine in brain metastasis.

B. Late complications: Complications that occur after 3 months of treatment are late complications.

a. Radiation pneumonitis and pulmonary fibrosis: occur in patients with extensive lung metastases with good iodine intake, especially when the dose is too large. The preventive methods are: the dose of nuclide iodine within 48h is controlled within 80mCi; the application of adrenocortical hormone before treatment.

b. Persistent myelosuppression: Very rare. Only occurs when the dose of nuclide iodine in bone transfer applications is too large.

c. Leukemia: rare, the incidence rate <2%, especially in the elderly over 50 years old. The best prevention method is to extend the treatment period of iodine iodine for 6 to 12 months.

d. Fine (oval) reduction or no functional disorder: occurs in patients under 20 years of age, long-term follow-up can be found 12% infertility. It is therefore recommended that pregnancy should be given only 6 months after treatment.

f. Bladder cancer: rarely occurs, very large dose (>800mCi).

g. Differentiated thyroid cancer is transformed into undifferentiated carcinoma: most of them believe that the cancer itself is transformed, not caused by nuclear iodine.

(3) Radiation therapy: Radiation therapy (ie, external beam therapy) has a certain effect on controlling residual lesions of thyroid cancer and some metastases, especially for some lesions that do not take up ribo-iodine, such as spindle cells and giant cell carcinoma. It is an ideal treatment method, which can be combined with radionuclide iodine therapy. It can be treated with radiation or external radiation.

1 indication: the best indication for radiation therapy is surgery, but residual iodine-free lesions, but the effect of completely inoperable lesions is poor.

The following conditions are commonly used indications for radiation therapy: A. The middle part of the neck that does not ingest nuclear iodine, regardless of whether the lesion is iodine or not, the effect of radiation therapy is better; E. Brain metastasis and other liver metastasis ineffective; F In order to reduce the fatal symptoms caused by soft tissue compression, such as the vena cava compression syndrome; G. some preoperative treatment to increase the resection rate and improve the efficacy of some giant thyroid cancer; H. as a sequential or combined chemotherapy Part of it, such as thyroid lymphoma, especially thyroid undifferentiated cancer.

2 Therapeutic dose and course of treatment: The radiation dose for thyroid lymphoma is 45Gy within 4 to 5 weeks, and the therapeutic dose for other thyroid cancers is relatively large, and more than 70Gy is applied within 7.5 weeks.

3 efficacy: the efficacy of radiation therapy is related to the type of pathology.

A. Differentiated thyroid cancer: The prognosis of DTC is better. Mayo Hospital reported no distant metastasis at the time of diagnosis. The 25-year survival rate was 94.5%; and 197 cases of follicular carcinoma were 75.2%. These patients did not need radiation after surgery. treatment.

Because DTC usually can take iodine, the indication of radiation therapy is only the recurrence and metastasis of iodine. The radiotherapy should not be performed before the radionuclide treatment, because it will damage the efficacy of iodine iodine.

Farahati reported that DTC 99 cases of stage IV were treated with radionuclide iodine ablation after total thyroidectomy, and then treated with TSH inhibition therapy, including thyroid, with an dose of 1.8 to 2.0 Gy per dose, and a total amount of 7 to 8 weeks. 65 to 70 Gy, but not effective for lymphatic metastasis (P = 0.27), regional or distant metastasis rate (P = 0.0003), the tumor significantly reduced or disappeared, and the survival period was 25 years.

Tubiana reported radiation therapy for 97 patients with DTC residual disease, with 15 and 25 years survival rates of 57% and 40%, respectively, while the 15-year survival rate of the control group was only 39%; 15 years of local recurrence significantly decreased (11% vs 23 %), but the 15-year survival rate is very different (7% vs 39%), indicating that radiotherapy has a certain effect.

B. Medullary carcinoma: The efficacy of local radiotherapy for medullary carcinoma is still controversial. The 10-year local recurrence-free tumor-free survival rate is 86.5%. It is only effective for bone and radiation therapy, and can prolong the survival of 75% of patients. In the period, 5 cases were reduced by >50%, one case was completely relieved, the survival period was 6 years, the other case was 4 years, and 5 cases died after 3 years. Radiation therapy has a certain alleviation effect on pain caused by bone metastasis and symptoms caused by regional metastasis.

C. Undifferentiated cancer: The prognosis of thyroid undifferentiated carcinoma is very poor. The 1-year survival rate is only 0-20%. The efficacy of radiotherapy alone is not satisfactory. The median survival time is about 3 to 7 months, and some cases are even 6 The application of 60Gy in the week is still ineffective, and the 1-year survival rate is only 6% to maintain airway patency during treatment. There are reports of prolonged survival for several years, but the complications of treatment are numerous and can be surgically removed, especially non-invasive. And thyroid capsules, can significantly prolong the survival period, the undifferentiated cancer confined to the gland is still mainly surgery, radiation as an adjuvant treatment, does not prolong the survival period.

D. Primary thyroid lymphoma: Primary thyroid lymphoma is rare, accounting for only 4% to 8% of thyroid tumors, accounting for 1.3% of lymphoma, almost all B-cell lymphoma, often with chronic lymphoid Thyroiditis, early surgery should be supplemented with radiation therapy, total dose of 40 ~ 50Gy within 4 to 5 weeks, can control local lesions, good efficacy, combined with chemotherapy to enhance local efficacy and prevent distant metastasis.

Mayo Hospital with 40Gy for neck or for mediastinal radiation therapy, the 5-year disease-free survival rate is 57%, and is related to the residual amount of the disease, the 5-year survival rate is 59%, which is limited to 75% in the gland 85%, low-grade malignant people can reach 90%, and those who invade the gland are only 35% to 59%.

(4) Chemotherapy: The sensitivity and efficacy of thyroid cancer to chemotherapy is inferior to that of radionuclide iodine and radiation therapy. Most of them can only have local remission, and the efficacy of monotherapy is worse, especially for radionuclide iodine and radiation therapy. Sensitive, can be used for comprehensive palliative treatment of thyroid cancer. Cyclophosphamide can be tested for advanced thyroid cancer or undifferentiated cancer.

Manumycin is a famesyl-protein transferase inhibitor, often used alone or in combination with other drugs (such as paclitaxel) for the treatment of undifferentiated thyroid cancer.

Targeted therapy of monoclonal antibodies, which has been in trial use in recent years, may be a new approach to the treatment of thyroid cancer (mainly medullary carcinoma) (eg anti-CEA radiolabeled antibodies).

Some people have tried somatostatin analogues and interferon to treat medullary thyroid carcinoma. It has a certain effect. The combination of chemotherapy drugs and immunomodulatory drugs can improve the body's immunity and strengthen the anticancer effect.

1 Chemotherapy of differentiated thyroid cancer: insensitive to radionuclide iodine and radiation therapy, or advanced DTC with surgical indications, especially with lung, chemotherapy has certain curative effect, treatment with heart failure, effective rate is 17 %, but none of them was markedly effective, and the effective rate was 26%, of which 11.6% was markedly effective, and the survival rate was more than 10% for more than 2 years. 5% of patients survived after stopping the drug.

Burgess et al (1978) used doxorubicin (doxorubicin) alone in the treatment of 53 cases of thyroid cancer, 2 / 3 effective, stable or reduced mass, prolonged survival, especially differentiated and medullary carcinoma, undifferentiated cancer The efficacy was poor, with a median effective period of 8 months and a survival period of 17 months to avoid serious complications.

2 Chemotherapy of medullary carcinoma: Most medullary thyroid carcinoma has a good prognosis, but about 20% of patients have rapid progression, distant metastasis, and poor prognosis, ie, APUD (amine precursor uptake and decarboxy) tumors, such as The effect of doxorubicin (doxorubicin), especially doxorubicin (doxorubicin), can reach 15% to 30%. The efficacy of monotherapy is less than that of combination therapy, and liver.

Used by WuVincristine(1.4mg/m2), qd×2 intravenous infusion, every 3 to 4 weeks for 1 course of treatment with lung, 4 cases were effective, 2 cases of serum calcitonin and mass were significantly decreased and reduced, lasting 14~ At 19 months, the effective rate was 57%, of which 28% was markedly effective, with only mild to moderate gastrointestinal symptoms, and a small number (2/7) of moderate blood loss.

Petursson treated a 20-year-old medullary carcinoma with lungs, with streptozocin (streptomycin), first with streptavidin (streptozotocin) (500mg/m2) qd × 5, doxorubicin (Amylon (60mg/m2) intravenously every 3 weeks, every 6 weeks of treatment, after the control of lung metastasis, switch to dacarbazine (azepine) (250mg / m2) and fluorouracil (5-Fu) (450mg /m2)qd×5, 75% later, every 4 weeks for 1 course of treatment, the tumor shrinks for 10 months, and 21 months after treatment, it eventually died due to recurrence of lung lesions.

3 Chemotherapy of thyroid undifferentiated carcinoma: The prognosis of thyroid undifferentiated carcinoma is very poor. Although it has poor curative effect on chemotherapy, it still has a certain reaction, the reaction rate is 33%, and the use of doxorubicin alone The response rate is only 5%, the average age is 68 years old, and 2 cases survive more than two years (28, therefore, the development of undifferentiated cancer, which is lack of treatment, is not possible when radiotherapy is ineffective or inappropriate. effective method.

4 chemotherapy for primary thyroid lymphoma: chemotherapy for primary thyroid lymphoma is similar to lymphoma, with an 8-year survival rate of 100%.

(5) Biological preparation therapy for medullary carcinoma: medullary thyroid carcinoma is developed from parafollicular cells, which is a neuroendocrine tumor, CEA), which secretes other peptides, such as serotonin and substance P. Certain clinical symptoms specific to cancerous diseases are treated with biological agents against these peptides and have a symptomatic treatment effect.

Somatostatin inhibits the secretion of several growth factors and hormones in tumor cells, and 50% of medullary carcinomas have somatostatin receptors. Somatostatin can cause symptoms caused by these hormones, such as diarrhea. Somatostatin is less likely to shrink tumors. It has also been reported that somatostatin can stabilize tumors for several months. IFN) also has some effects on existing metastatic APUD tumors, which can block tumor cells in G0-G1. Period of division, and can activate the immune regulatory system, interferon (rIFN-α-2A) in the treatment of neuroendocrine tumors, the main symptom improvement rate of 64%.

1 Somatostatin: The half-life of natural somatostatin is only 3 min, and the curative effect is short. It must be continuously and continuously used to maintain an effective blood concentration, so it is difficult to promote it clinically.

2 somatostatin derivatives: currently used somatostatin derivatives are octreotide (Octreotide), their half-life is significantly prolonged, has been used in clinical.

The mechanism by which somatostatin derivatives inhibit tumor growth is: A. inhibiting the mediators that promote tumor growth; B. inhibiting tumor angiogenesis; C. regulating immune activity; D. blocking tumor cells by tumor cell somatostatin receptors The mitosis.

Octapeptide octreotide can improve the symptoms of medullary thyroid carcinoma and reduce serum calcitonin and CEA, but the anti-tumor effect is poor, diarrhea, and serum calcitonin decreases in all cases, octreotide can only improve weakness, serum drop Calcium decreased in only 4 cases, only 1 case had anti-tumor effect, and the efficacy of octapeptide octreotide alone was not very satisfactory.

3 octreotide combined with interferon: Joensuu (1992) combined applicationOctreotideAnd interferon (recombinant interferon alpha-2b) in the treatment of end-stage metastatic carcinoid, found that serum tumor markers decreased, or even normal, suggesting that it may be effective in the treatment of other neuroendocrine tumors, 8 cases of sporadic thyroid marrow The cancer has a metastasis that has not been resectable (mediastinum, and has a somatostatin receptor confirmed by 111In-DTPA, 300 μg/d subcutaneous injection for 6 months, interferon (r-IFN-α-2b) 5 million U/d Intramuscular injection, 3 times a week for 12 months, of which 5 cases of flushing, 6 cases of serum calcitonin and CEA decreased, the original 32% ~ 88%, suggesting that the tumor is inhibited, but metastases It has not been reduced, and it has been found that with stable lesions and lowering serum calcitonin and CEA, it is necessary to inject octreotide daily, which is expensive.

4 combination of sustained-release octreotide and interferon: Lanreotide is a novel cyclic octapeptide somatostatin derivative, which has a long extension of half-life after chelation with a sustained-release agent, and can be injected once every 10 to 14 days. Maintain effective blood concentration, intramuscular injection of sustained-release octreotide 30mg/2 weeks, 6 months later, intramuscular injection of sustained-release octreotide 30mg every 10 to 14 days, and then use 6 months, start interferon (r -IFN-α-2b) 5 million U intramuscular injection, 3 times a week, sharing slow release octreotide for 12 months, r-IFN-α-2b 11 months, the effect is obvious, 2 of which small metastases disappear, 3 The tumor was stable, and most (6/7) symptoms were significantly improved.

In conclusion, the combination of somatostatin derivatives and interferon (recombinant interferon) can alleviate the symptoms caused by the secretion of peptide hormones in tumors, reduce the level of serum tumor markers, and suggest tumor suppression, but the control effect on tumor itself is still weak. .

(6) Percutaneous ethanol injection therapy: mainly used for the treatment of solid small to moderate nodules. After finding the most abundant area in the nodules, the ethanol was injected with a 21-22 needle. TSH should be followed before and after treatment. This method can have a cure rate of about 60%.

Ethanol injection is mainly used to treat non-functional thyroid nodules, especially those with metastatic and local compression symptoms. Ethanol injection therapy is not preferred.

(7) Symptomatic treatment: When there is hypoparathyroidism after thyroid cancer surgery, calcium and vitamin D can be added, and cyproheptadine can be used to relieve symptoms.

(8) Comprehensive treatment of thyroid cancer: In addition to surgery, there are many non-surgical treatments for thyroid cancer. The use of various therapies alone has limitations, and the efficacy is sometimes unsatisfactory, and in some cases, combined application, It can achieve twice the result with half the effort, but it must be properly grasped, otherwise it will cause half the effort.

1 comprehensive treatment of differentiated thyroid cancer:

A. Radionuclide iodine ablation combined with TSH inhibition therapy: Mazzaferri et al believe that DTC with age >40 years old and tumor >1.5cm is combined with radionuclide iodine ablation after a large range of surgery (near total thyroidectomy) Gland and TSH inhibition therapy can effectively improve the 30-year survival rate and reduce the recurrence rate. The median follow-up period was 15.7 years. It was found that the efficacy of TSH inhibition therapy was less than that of nuclear iodine ablation. The recurrence rate of the latter was reduced. /3, and no combination of the two after surgery died of thyroid cancer.

Because TSH affects the intake of nuclide iodine, the best time for the treatment of radionuclide with serum TSH at 30-50 μU/ml, TSH is significantly increased within 2 to 3 weeks after thyroidectomy, so it should be 2 to 3 weeks after surgery. After monitoring serum TSH, it can be used as a whole body small dose of radionuclide iodine (1 ~ 5mCi) scan to understand the ability to take iodine, can be used as inhibition therapy, if you can take iodine, you can initially understand the presence or absence of metastasis, then apply nuclear iodine Therapeutic dose; if there is no metastasis, the ablation dose can be used as a radionuclide iodine ablation treatment to understand whether there is a recessive metastases that are not shown by low-dose radionuclide iodine. The therapeutic dose should be added, and then the inhibitory therapy should be used to enhance the curative effect. Do not apply a therapeutic dose of radionuclide again.

B. Nuclide iodine combined with radiotherapy: The main indication is that DTC with certain iodine intake ability but not enough, or with surgical anti-indication, combined with radiotherapy can improve long-term survival rate.

The above content is for reference only, please consult the relevant physician or relevant medical institution if necessary.

prevention:

1. Try to avoid X-rays of head and neck in childhood.

2. Maintaining a happy spirit and preventing emotional internal injuries is an important aspect of preventing the occurrence of this disease.

3. For water and soil factors, pay attention to diet adjustment, and often eat kelp, in fact, it may also be another predisposing factor for certain types of thyroid cancer.

4. Patients with thyroid cancer should eat nutritious food and fresh vegetables to avoid fatty.

5. Avoid the use of estrogen, because it plays a role in the development of thyroid cancer.

6. For thyroid proliferative diseases and benign tumors should go to the hospital for positive.

7. Postoperative thyroid cancer, active use of Chinese and Western medicine prevention and treatment is an effective way to improve the efficacy. 8. Actively exercise and improve disease resistance.

Introduction to thyroid cancer

Published by on February 1, 2019February 1, 2019