Renal cell carcinoma

　　What are the causes of renal cancer?

　　In addition to the three typical symptoms of hematuria, back pain, and tumor, renal cancer also has many non-urinary systemic extrarenal manifestations such as high fever, abnormal liver function, anemia, hypertension, polycythemia, and hypercalcemia. Whether it is open surgery or laparoscopic surgery for the treatment of renal cancer, the following complications may occur:

　　1. Hemorrhage.

　　2. Infection.

　　3. Perirenal organ injury (liver, spleen, pancreas, gastrointestinal tract).

　　4. Pleural injury.

　　5. Pulmonary embolism.

　　6. Renal failure.

　　7. Liver failure.

　　8. Urinary incontinence.

　　9. Other complications. Attention should be paid to prevention and appropriate treatment, and severe cases can lead to patient death. Before surgery, the risks and possible complications should be informed to the patient and family.

　　The complaints and clinical manifestations of renal cancer patients are variable, and they are prone to misdiagnosis as other diseases. The kidney is located in a concealed position, and its main contact with the outside world is urine, therefore, hematuria is the most common symptom for the detection of renal cancer. However, the occurrence of hematuria is only possible after the tumor invades the renal pelvis, so it is not an early symptom. For many years, hematuria, pain, and tumor have been called the 'triad' of renal cancer. Most patients have 1 to 2 symptoms when they visit the doctor, and those with all three symptoms account for about 10%, and there is little possibility of cure.

　　1. Hematuria:Hematuria is often painless, intermittent, and visible throughout the urine, with the interval shortening as the lesion progresses. Hematuria in renal cancer may be accompanied by renal colic, often caused by blood clots passing through the ureter. The blood clots in hematuria in renal cancer may form strips as they pass through the ureter, and the severity of hematuria is not related to the size of the renal cancer. Sometimes, renal cancer can manifest as persistent microscopic hematuria.

　　2. Back pain:Back pain is another common symptom of renal cancer, mostly dull pain, localized in the腰部. The pain is often caused by the growth and expansion of the kidney capsule due to the tumor, and blood clots passing through the ureter can also cause back pain, as mentioned earlier. When the tumor invades surrounding organs and lumbar muscles, the pain is more severe and persistent.

　　3. Tumor:Tumors are also a common symptom, and about 1/3 to 1/4 of renal cancer patients may find an enlarged kidney when they visit the doctor, as the kidney is located in a concealed position. It is difficult to detect a tumor in renal cancer before it reaches a relatively large size, and usually, when a tumor is felt in the abdomen, it is already a late symptom.

　　4. Pain:Pain is seen in about 50% of cases and is a late symptom, caused by the stretching of the renal capsule or pelvis by a gradually growing tumor, or due to the invasion and compression of the posterior abdominal wall connective tissue, muscle, lumbar vertebrae, or lumbar nerves by the tumor, resulting in persistent pain on the affected side of the腰部.

　　5. Other symptoms:Unexplained fever, or already metastasized when discovered, with fatigue, weight loss, loss of appetite, anemia, cough, and hemoptysis, and other pulmonary symptoms. Additionally, the effects of renal adenocarcinoma are caused by the endocrine activity of the tumor, including polycythemia, hypertension, hypotension, hypercalcemia, fever syndrome, although these systemic, toxic, and endocrine effects are non-specific, about 30% of patients initially have many mixed symptoms, which are valuable clues, and this finding is considered to be the systemic effect of the tumor.

　　Patients with renal cell carcinoma should consume foods that have the effect of decomposing carcinogens such as nitrosamines, such as carrots, green beans, gourds, pumpkins, sprouts, asparagus, etc., as well as foods that enhance the body's anti-cancer effect, such as mushrooms, shiitake mushrooms, water chestnuts, Job's tears, barley, soybeans, etc.

　　Hematuria is an important symptom of renal cell carcinoma, with polycythemia occurring in 3% to 4%; progressive anemia can also occur, with bilateral renal tumors, and the total renal function usually remains unchanged. Erythrocyte sedimentation rate increases. Some renal cell carcinoma patients may not have bone metastasis, but may have symptoms of hypercalcemia and increased serum calcium levels. Symptoms are quickly relieved after the removal of renal cell carcinoma, and blood calcium levels return to normal. Sometimes it can develop into liver dysfunction. If the tumor kidney is removed, it can be restored to normal.

　　Firstly,X-ray contrast techniques are the main means of diagnosing renal cell carcinoma.

　　1. X-ray films:X-ray films can show an enlargement of the renal outline and changes in contours. Occasionally, tumor calcification can be seen, as well as localized or widespread fluffy shadows within the tumor, or calcified lines, shells, around the tumor, especially in young patients with renal cell carcinoma.

　　2. Intravenous urography:Intravenous urography is a routine examination method. Due to its inability to display tumors that have not caused deformation of the renal pelvis and calyces, and its difficulty in distinguishing whether a tumor is renal cell carcinoma, renal angiomyolipoma, or renal cyst, its importance has decreased. It is necessary to perform ultrasound or CT scans in conjunction to further differentiate. However, intravenous urography can understand the function of both kidneys, as well as the condition of the renal pelvis, calyces, ureters, and bladder, which is of important reference value for diagnosis.

　　3. Renal arteriography:Renal arteriography can detect tumors in the urinary system that are not deformed by contrast imaging, showing renal cell carcinoma with new blood vessels, arteriovenous fistulas, pooling of contrast agent with increased capsule blood vessels, and significant variations in angiographic patterns. Sometimes renal cell carcinoma may not be visible, such as in cases of tumor necrosis, cystic changes, or arterial embolism. In cases where renal arteriography is necessary, adrenaline can be injected into the renal artery to cause normal vessels to constrict while tumor vessels do not respond. In larger renal cell carcinomas, selective renal arteriography can also be followed by renal arteriography embolization to reduce bleeding during surgery. Renal cell carcinoma that cannot be surgically removed and has severe bleeding can be treated with renal arteriography embolization as palliative therapy.

　　2. Ultrasound scanning

　　Ultrasound examination is the simplest and least invasive examination method and can be part of routine physical examination. Renal masses larger than 1cm can be detected by ultrasound. It is important to differentiate whether the mass is renal cell carcinoma. Renal cell carcinoma is a solid mass, and due to possible hemorrhage, necrosis, or cystic change within, it usually has inhomogeneous echo, generally low echo. The boundary of renal cell carcinoma is not very clear, which is different from renal cysts. Intrarenal space-occupying lesions can cause deformation or rupture of renal pelvis, calyces, and renal sinus fat. Renal papillary cystadenocarcinoma resembles a cyst on ultrasound examination and may have calcification. When renal cell carcinoma and cysts are difficult to differentiate, biopsy can be performed. Biopsy under ultrasound guidance is relatively safe. The aspirate can be used for cytological examination and cystography. Cyst fluid is usually clear, without tumor cells, low in fat. Smooth cyst walls during contrast enhancement can confirm benign lesions. If the aspirate is bloody, it should be considered a tumor, and tumor cells may be found in the aspirate. If the cyst wall is not smooth during contrast enhancement, it can be diagnosed as malignant tumor. Renal angiomyolipoma is a solid renal tumor, with strong echo of fatty tissue, which is easy to differentiate from renal cell carcinoma. When renal cell carcinoma is found on ultrasound examination, attention should also be paid to whether the tumor has penetrated the capsule, whether there is enlargement of perirenal fat tissue, lymph nodes, renal vein, and whether there are cancer emboli in the inferior vena cava. It should also be noted whether there is metastasis to the liver.

　　3. CT scan:

　　CT plays an important role in the diagnosis of renal cell carcinoma, as it can detect renal cell carcinoma that has not caused changes in the renal pelvis and calyces, and is asymptomatic. It can accurately measure tumor density and can be performed on an outpatient basis. CT can accurately stage the disease. Some statistics show its diagnostic accuracy: invasion of renal vein 91%, perirenal spread 78%, lymph node metastasis 87%, involvement of nearby organs 96%. The CT scan of renal cell carcinoma shows a mass within the renal parenchyma, which can also protrude into the renal parenchyma. The mass is round, ovoid, or lobulated, with clear or blurred borders. On plain scan, it appears as a soft tissue mass with inhomogeneous density, CT value >20Hu, usually between 30-50Hu, slightly higher than normal renal parenchyma, but can also be similar or slightly lower. The inhomogeneity within the mass is due to hemorrhage, necrosis, or calcification. Sometimes, it can appear as a cystic CT value, but with soft tissue nodules on the cyst wall. After intravenous injection of contrast agent, the normal renal parenchyma CT value reaches about 120Hu. The tumor CT value also increases, but is significantly lower than normal renal parenchyma, making the tumor boundary clearer. If the mass CT value does not change after enhancement, it may be a cyst. Combining the CT values before and after contrast agent injection as liquid density can confirm the diagnosis. In cases of renal cell carcinoma with necrotic foci, renal cystadenocarcinoma, and renal artery embolism, the CT value does not increase after injection of contrast agent. Renal angiomyolipoma, due to its high fat content, often has a negative CT value, with inhomogeneous internal structure. After enhancement, the CT value increases, but still appears as fat density. Eosinophilic tumors have clear borders on CT examination and uniform internal density. After enhancement, the CT value increases significantly.

　　CT examination standards for determining the extent of renal cancer invasion

　　1, Mass limited within the renal capsule:The shape of the affected kidney is normal or locally protruding, or uniformly enlarged, with a smooth or slightly rough surface. If the mass is nodular and protrudes into the renal capsule, the surface is smooth, still considered to be limited within the renal capsule. The fat capsule is clear, and the perinephric fascia is not irregularly thickened. It cannot be judged whether the tumor is limited within the renal fascia based on the presence or absence of the fat capsule, especially in emaciated patients.

　　2, Limited invasion around the renal fascia within the fat capsule:The tumor protrudes and replaces the local normal renal parenchyma, with the renal surface rough and significant, the renal fascia irregularly thickened, and there are unclear soft tissue nodules in the fat capsule. Linear soft tissue shadows are not diagnosed.

　　3, Venous invasion:The renal vein thickens locally into a spindle-shaped bulge, with uneven density, abnormal increase or decrease, and density changes similar to tumor tissue. The standard for venous thickening is that the renal vein diameter is greater than 0.5 cm, and the diameter of the inferior vena cava in the upper abdomen is greater than 2.7 cm.

　　4, Lymph node invasion:The renal pedicle, abdominal aorta, inferior vena cava, and the circular soft tissue shadow between them have insignificant density changes after enhancement and can be considered as lymph nodes.

　　5, Invasion of adjacent organs:The boundary between the mass and adjacent organs disappears, and there are changes in the shape and density of adjacent organs. If it is simply the disappearance of the fat line between the tumor and adjacent organs, it is not diagnosed.

　　6, Renal pelvis invasion:The part of the tumor entering the renal pelvis has smooth and rounded edges in the shape of a crescent, forming an arc under compression. In delayed scanning, when the renal function is good, it can be seen that the contrast agent edge in the compressed renal pelvis and calyces is smooth and regular, which is considered to be simple compression of the renal pelvis and calyces. If the renal pelvis and calyces structure disappears or becomes occluded, or is completely occupied by the tumor, it indicates that the tumor has broken through the renal pelvis.

　　Four, Magnetic Resonance Imaging (MRI)

　　Magnetic Resonance Imaging (MRI) is a relatively ideal examination for the kidneys. The renal hilum and perinephric fat produce high signal intensity, the outer renal cortex is of high signal intensity, and the middle medulla is of low signal intensity. This difference may be due to the different osmotic pressure within the renal tissue, with a contrast difference of 50% between the two parts. This difference can be reduced with the extension of recovery time and hydration. There is no intraluminal signal in the renal arteries and veins, so they are of low intensity. The collecting system with urine is of low intensity. The MRI variation of renal cancer is large, determined by the tumor blood vessels, size, and presence or absence of necrosis. MRI does not well detect calcification foci due to their low proton density. MRI is easy to detect and investigate the extent of renal cancer invasion, surrounding tissue capsule, liver, mesentery, and lumbar muscle changes, especially when renal cancer appears with renal vein thrombus and metastasis in the inferior vena cava.

　　Patients with renal cell carcinoma should not have a biased diet and should not repeatedly eat the same kind of food. Avoid eating moldy, smoked, and unclean water, eat less hot food and salted food, and do not drink alcohol or smoke.

　　The main treatment for renal cell carcinoma is surgical resection. The effects of radiotherapy, chemotherapy, immunotherapy, etc., are not ideal and are not certain. There are statistics showing that the combination of radiotherapy and renal cell carcinoma has no effect on 5-year survival.

　　1. Renal cell carcinoma surgery:

　　It is divided into simple renal cell carcinoma resection and radical renal cell carcinoma resection. Currently, it is widely recognized that radical nephrectomy can improve survival rates. Radical nephrectomy includes the perirenal fascia and its contents: perirenal fat, kidney, and adrenal glands. There is still controversy about whether to perform local lymph node dissection in radical nephrectomy for renal cell carcinoma. Some believe that when lymph node metastasis occurs, it is often accompanied by hematogenous metastasis, and in cases with lymphatic metastasis, hematogenous metastasis eventually occurs; the distribution of lymph nodes is extensive and difficult to clean up thoroughly; however, some also believe that lymph node metastasis mainly occurs near the renal hilum and in the inferior vena cava and aortic region, which can be resected radically. But in cases where metastatic foci are found during radical lymph node dissection, very few patients survive for more than 5 years. It is advisable to ligate the renal artery and renal vein first during renal cell carcinoma surgery to reduce bleeding during surgery and the possible spread of the tumor.

　　Renal cell carcinoma is a highly vascular tumor, often with large tributary veins, making surgery prone to bleeding and difficult to control. Therefore, in the surgery of larger tumors, selective renal artery embolization can be performed before surgery, which can cause severe pain, fever, intestinal paralysis, infection, and should not be used routinely.

　　Special issues in the treatment of renal cell carcinoma:

　　1. Surgical resection of renal cell carcinoma that retains renal tissue:Surgical resection of renal cell carcinoma that retains renal tissue, such as bilateral renal cell carcinoma or solitary renal renal cell carcinoma, and poor contralateral renal function such as renal vascular hypertension, renal calculi, renal tuberculosis, and stricture at the renal pelvis and ureter. Renal cell carcinoma with a small size, i.e., less than 3 cm in diameter and located at the edge of the kidney, can also be considered for surgery to retain renal tissue, with the surgical method being partial nephrectomy, or the tumor can also be punctured out.

　　2. Inferior vena cava thrombus:Renal cell carcinoma is prone to develop thrombi in the renal vein and inferior vena cava. In recent years, it has been considered that if there is no local or distant spread, the thrombi in the veins can be resected or removed from the inferior vena cava at the time of radical nephrectomy, and the prognosis is still good. The inferior vena cava should be blocked above the level of the thrombus during surgery to avoid fatal pulmonary embolism. If the thrombus extends to the heart, the inferior vena cava can be blocked within the pericardium, and then the inferior vena cava can be cut open to remove the thrombus.

　　3. Local spread of renal cell carcinoma invades adjacent tissues and organs:This is a difficult problem in renal cell carcinoma treatment. The only method that can cure the disease is the complete resection of the tumor and its involved tissues, and the survival rate of such patients is only 5% after 5 years. Local spread of renal cell carcinoma can be accompanied by pain, due to the invasion of the posterior abdominal wall, sacrospinalis muscle, and nerve roots. Direct invasion of the liver by renal cell carcinoma is rare, with more metastases within the liver than direct invasion. There is almost no possibility of cure when the duodenum and pancreas are involved. Although there may be distant metastases, most patients can still have the primary renal tumor removed if surgery is possible, and the lesions of the metastases still have the possibility of obtaining a relatively long survival rate. After the diseased kidney is removed, hematuria and pain are also eliminated, making it worthwhile.

　　Two, Immunotherapy

　　For many years, it has been proven that human solid tumor-infiltrating lymphocytes have an immune response to their own tumor cells, but the cytotoxic effect of this tumor infiltrating lymphocyte (TIL) on autologous tumor cells is often low due to inhibitory mechanisms within the tumor. These TIL cells need to be stimulated and expanded in vitro to fully exert their cytotoxic effect on autologous tumors. Normal human lymphocytes and interleukin-2 (IL-2) culture can produce effector cells called lymphokine-activated killer cells (LAK). A group of 57 patients with renal cell carcinoma were treated with LAK cells and IL-2; LAK cells + IL-2 in 36 cases, IL-2 alone in 21 cases, LAK cells + IL-2 in 4 cases with complete remission (CR), 8 cases with partial remission (PR), and an efficacy rate of 12/36 (33%). The IL-2 group had only 1/21 cases with CR.

　　Tumor infiltrating lymphocytes (TIL) can also be expanded in vitro with IL-2, and animal experiments have found that this adoptive transfer of TIL has a therapeutic effect 50 to 100 times stronger than LAK cells, and can destroy its lung and liver metastases. The possibility of its clinical application is still under discussion.

　　Three, Chemotherapy

　　The efficacy of chemotherapy for renal cell carcinoma is not good, and the efficacy of monotherapy is even worse. Some experts have statistics that among 37 chemotherapy drugs used alone to treat renal cell carcinoma, alkylating agents have a better effect. The combination of chemotherapy with better efficacy is: vinblastine + methotrexate + bleomycin + Tamoxifen testicle; vincristine + doxorubicin + BCG + methylprednisolone; vinblastine + doxorubicin + hydroxyurea + MA. In summary, multi-drug therapy is better than monotherapy.

　　Four, Combined Immunotherapy and Chemotherapy

　　A group of 957 patients with renal cell carcinoma metastasis ± recurrence were treated with interferon alpha-2A, with an efficacy rate of 12% when used alone. If combined with vinblastine, the efficacy rate is 24%. Effective patients may have a survival rate of 50% to 70% in 2 years, while ineffective patients have a survival rate of 10% to 15%. The ideal dose is interferon 1.8 million units subcutaneous or intramuscular injection, three times a week, and vinblastine 0.1mg/kg intravenous injection, once every 3 weeks.