According to the statistics of the Ministry of Health, cancer has become the number one killer in China. The tumors with the highest incidence rate for men are: lung cancer, stomach cancer, liver cancer, and for women: lung cancer, breast cancer, colorectal cancer, in that order. In recent years, with the promotion and application of various new treatment technologies, the survival rate of cancer patients has improved. According to the American Cancer Society (ACS), the number of cancer deaths in the United States has been decreasing for two consecutive years. The average 5-year survival rates for lung cancer, breast cancer, prostate cancer and colon cancer have reached 15%, 87%, 95% and 64% respectively. The incidence of distant metastases increases significantly as the survival of tumor patients increases. Bone is the third most common site of metastasis for malignant tumors, after lung and liver. Bone metastases are secondary tumors arising from malignant tumors originating in an organ, mostly carcinomas and a few sarcomas, that metastasize to the bone through the blood circulation or lymphatic system. Autopsy results show an overall incidence of 32.5%, and more than 90% of bone metastatic tumors originate from five tumor types: breast, prostate, lung, thyroid, and kidney cancer. The incidence of bone metastatic tumors is approximately 35-40 times higher than that of primary malignant bone tumors, thus bone oncologists are faced with a daunting task of diagnosis and treatment.
Clinical Characteristics
Without a history of primary malignant tumor, early diagnosis of bone metastatic cancer is very difficult. Therefore, clinicians should be familiar with the clinical, imaging and pathophysiological characteristics of bone metastatic cancer, always be alert to the cases of bone metastatic cancer in middle-aged and elderly orthopedic patients, and shorten the time from suspicion to definite bone metastatic cancer. At the same time, sarcoma, myeloma, lymphoma, senile osteoporosis and hyperparathyroidism should be carefully identified and excluded.
Bone metastasis cancer is more common in middle-aged and old people, with most cases occurring above the age of 40. The primary foci are often detected after the diagnosis of metastatic cancer, and some patients have a history of tumor surgery in their early years. Sometimes the primary tumor is so hidden that metastatic cancer may be the only clinical manifestation, and some patients are still unable to detect the primary tumor with modern instruments.
Bone metastases usually arise from hematogenous dissemination, mostly in flat bones, because red bone marrow, which still retains hematopoietic function in adulthood, can provide the proper conditions for tumor emboli to grow. The spine, pelvis and long bone epiphysis are the preferred sites. Trunk bones are more frequent than extremity bones, lower extremities are more frequent than upper extremities, knees and elbows are less common than distal bones. Bone metastases are often multiple and rarely single.
The population incidence of bone metastases is very high, but only about half of the patients show symptoms clinically. Common clinical manifestations include.
1. pain (50-90%).
2. pathological fractures (5%-40%)
3. hypercalcemia (10-20%)
4. spinal instability and spinal nerve root compression symptoms (<10%< span="">)
5. bone marrow suppression (<10%< span="">)
6, cachexia such as mental depression, wasting, weakness, anemia and low fever in advanced stage.
The spine is the site with the highest incidence of metastatic cancer, which has a special metastatic mechanism: the spinal venous system is located around the dura mater and the spine. Inherently without venous valves, it is both directly related to the upper and lower vena cava and can become an independent system. When the pressure increases in the thoracic abdominal cavity, there is slow, stagnant or reverse blood flow, creating opportunities for the passing cancer cells to stay and multiply. Patients with metastatic cancer of the spine often have pain as the main symptom, and once spinal cord and nerve root compression occurs it will seriously affect the quality of life. The incidence of metastatic cancer in the pelvic and sacral regions is also high, and the tumor may lead to many complications due to the surrounding adjacent vital organs. In addition, the difficulty and risk of surgery in this region are very high, and the preoperative evaluation and design of surgical plan are crucial. Long bone metastases of the extremities have insidious symptoms, and once pathological fractures occur patients’ quality of life is seriously impaired.
Hypercalcemia is a cause of death in bone metastatic cancer but is relatively uncommon in Asian populations. The causes of increased blood calcium include: (i) extreme debilitation of the patient, decreased protein, and increased free calcium in the blood. ② Fractures and tumor lesions can release calcium ions. ③Long-term 2 bedridden decalcification. ④The secretion of parathyroid hormone in the lesion is elevated and blood calcium can be increased. ⑤ Estrogen therapy for breast cancer can increase blood calcium. Malignant hypercalcemia can have abdominal pain, intractable vomiting, extreme debility, severe dehydration, rapid onset renal failure, and death by coma.
Characteristics of common primary tumors
The incidence of bone metastases in breast cancer is as high as 65%-75%, which is associated with a good prognosis for breast cancer, and patients still have a median survival of up to 2 years after the discovery of bone metastases, thus a relatively aggressive treatment strategy should be adopted for breast cancer patients. Similar to breast cancer, prostate cancer patients also have a high incidence of bone metastases which are mostly osteogenic and often precede visceral metastases. Prostate-specific antigen PSA is an important clinical parameter. When PSA >20ug/L, a whole-body bone scan should be routinely performed, and most early prostate cancers are hormone-dependent and thus have a good prognosis.
The incidence of bone metastasis from lung cancer is 30%-40%, and some data show that the primary tumor with the highest incidence of bone metastasis in the country is lung cancer. Adenocarcinoma has the highest incidence and early onset, followed by small cell lung cancer and squamous carcinoma. The most common site is the spine, especially the thoracic spine. The prognosis of patients is poor, with a 1-year survival rate of about 5%.
Bone metastases from kidney cancer are found in up to 25% of cases. There is ample evidence that metastatic lesions tend to heal spontaneously in some cases after resection of the primary tumor of the kidney, so a proactive approach to prophylactic internal fixation of renal cancer bone metastases should be taken.
Bone metastases from thyroid cancer are also more common, and the degree of osteolytic destruction of metastases is often very severe, with a high incidence of pathological fractures. Prophylactic internal fixation can effectively prevent the occurrence of fractures, and can be combined with 131I internal irradiation or radiotherapy after surgery, with a good prognosis.
Other bone metastases such as neuroblastoma, the most common bone metastases in children, are very similar to Ewing sarcoma and need to be differentiated. The incidence of bone metastases from digestive system tumors is in the following order: esophageal cancer, gastric cancer, colorectal cancer, liver cancer and pancreatic cancer. Nasopharyngeal cancer has a high incidence in South China, and also has a high rate of bone metastasis, with osteolytic destruction predominating, and treatment is mainly based on radiotherapy and prophylactic internal fixation. Bone metastases from bladder cancer, cervical cancer, seminomatous cell tumor and malignant melanoma are also not uncommon. Imaging
The imaging manifestations of metastatic bone tumors can be divided into osteolytic, osteogenic and mixed. The former is the most common, forming worm-like or map-like bone defects with indistinct boundaries and irregular margins without sclerosis around them. Residual bone trabeculae and bone cortex can be seen in the osteolytic area without periosteal reaction. In a few cases, there is cortical swelling. Most of the bone metastases have no soft tissue shadow. Osteogenic destruction imaging can be seen as speckled or lamellar dense shadow, even ivory-like, with disorganized, thickened and rough bone trabeculae, and the volume of affected bone can be increased. Mixed bone metastases have both osteogenic and osteolytic shadows. Nuclear scan is very important for the diagnosis of bone metastasis and can be used for early screening of systemic lesions, but false positives must be excluded. Bone metastases from kidney cancer and multiple myeloma often appear as cold areas on a nuclide scan. CT and MRI can clearly show the size and extent of the lesion and its adjacent relationship with the surrounding tissues and organs, and PET, as an emerging technology, is playing a more important role in the diagnosis of bone metastases.
Bone metastases from prostate cancer, bladder cancer and some breast cancers are osteogenic destruction. The cells of these epithelial tumors have osteogenic ability, and the fibrous stroma around the tumor produces osteoblast-stimulating factor, which provides the matrix for ossification; in addition, the cancer tumor can stimulate the endosteal bone trabeculae to produce new bone, which is a response to the tumor, and this bone bearing ability is poor. Most bone metastases are osteolytic destruction, which is accomplished by the participation of osteoclasts. Osteoclast activating factor is produced by tumor cells and leukocytes around the tumor; in addition, tumor cells can rapidly and directly resorb bone, or directly destroy bone through the secretion of bone degrading enzymes.
Metastases of thyroid cancer and kidney cancer can form more obvious soft tissue masses along with osteolytic destruction, which need to be differentiated from primary malignant bone tumors.
For lesions with abundant blood flow, such as renal cell carcinoma and myeloma, preoperative angiography can be performed and vascular embolization can be performed on the day of surgery, which can reduce intraoperative bleeding.
Factors of poor patient prognosis
1.Tumor type: non-small cell lung cancer, liver cancer and other highly malignant tumors.
2. the short time between the diagnosis of the tumor and the occurrence of bone metastases.
3, presence of visceral metastases.
4. multiple bone metastases.
Comprehensive treatment
1.Systemic therapy (systemic chemotherapy and molecular targeted therapy).
2.Surgical treatment.
3.Radiotherapy.
4.Diphosphonate drug therapy.
5.Nucleotide therapy.
6, pain treatment.
7.Immunotherapy.
8. nutritional support therapy.
Principles and indications of preoperative biopsy.
1. If the patient has a clear history of malignancy and multiple bone destruction is found throughout the body at the same time (long bones, vertebrae, pelvis), preoperative biopsy is not a mandatory operation.
2.Patients with clear history of malignant tumor and single bone destruction, biopsy should be performed to clarify the diagnosis before making surgery plan.
3.Patients with no history of tumor but suspected metastatic cancer of bone must have preoperative biopsy except for lymphoma, myeloma and sarcoma, and if metastatic cancer is diagnosed, the primary tumor should be searched under the guidance of pathological results.
For sarcoma of long bone, once intracapsular scraping is chosen, it will cause serious contamination of surrounding tissues, and internal fixation such as plate or intramedullary needle will make limb preservation surgery impossible, these situations will be disastrous and must be given enough attention by orthopedic surgeons.