| disease | Kidney Cancer |
Kidney cancer, also known as renal cell carcinoma or renal adenocarcinoma, is the most common malignant tumor of the kidney parenchyma. Due to the extension of average life expectancy and advancements in medical imaging, the incidence of kidney cancer has increased compared to the past. Clinically, there are no obvious symptoms, and the number of kidney cancers incidentally discovered during physical examinations is increasing, reaching up to 1/2 to 1/5.
bubble_chart Pathological Changes
Kidney cancer is often unilateral and single-focal, with similar incidence rates on both the left and right sides. Most kidney cancers are round in shape and vary greatly in size. The tumor does not have a histological membrane, but there is a pseudo-membrane formed by compressed kidney parenchyma and fibrous tissue. A few are uniformly yellow or brown, while most have areas of hemorrhage, necrosis, and fibrous dissipating ecchymosis. Hemorrhage and necrosis can form cystic structures, and the tumor itself is a papillary cystadenocarcinoma. The tumor can destroy the entire kidney and may invade adjacent fat, muscle tissue, blood vessels, lymphatic vessels, etc. The renal fascia acts as a barrier to prevent local spread. Kidney cancer tends to extend into veins, forming tumor thrombi that can extend into the renal vein and inferior vena cava. Distant metastases commonly occur in the lungs, brain, bones, etc.
Electron microscopy reveals that most kidney cancer cells exhibit ultrastructural features of the proximal convoluted tubule to varying degrees, suggesting that kidney cancer originates from the proximal convoluted tubule. Most kidney cancers are clear cell carcinomas, but they can also be granular cell carcinomas, either concurrently or predominantly. These cells are spindle-shaped and sometimes resemble fleshy tumors. This more aggressive form of kidney cancer is referred to as undifferentiated carcinoma.
bubble_chart Clinical ManifestationsThe complaints and clinical manifestations of kidney cancer patients are varied and easily misdiagnosed as other diseases. The kidney is located in a concealed position, and its main connection with the outside is through urine. Therefore, hematuria is the most common symptom for detecting kidney cancer. However, hematuria can only occur after the tumor has invaded the renal pelvis, indicating that it is no longer an early symptom. For many years, hematuria, pain, and a mass have been referred to as the "triad" of kidney cancer. Most patients already have one to two symptoms when they seek medical attention, and only about 10% present with all three symptoms of the triad, making it rarely curable.
1. Hematuria: Hematuria is often painless, intermittent, and visible to the naked eye throughout the entire process. The interval between episodes shortens as the disease progresses. In cases of significant bleeding from kidney cancer, renal colicky pain may accompany hematuria, often caused by blood clots passing through the ureter. Blood clots from kidney cancer hematuria may form a strip-like shape as they pass through the ureter. The degree of hematuria is unrelated to the size of the kidney cancer. Sometimes, kidney cancer may present as persistent microscopic hematuria.
2. Lumbago: Lumbago is another common symptom of kidney cancer, usually presenting as a dull pain localized to the lower back. The pain is often caused by the growth of the mass stretching the renal capsule, or by blood clots passing through the ureter, as mentioned earlier. When the tumor invades surrounding organs and the lumbar muscles, the pain becomes more severe and persistent.
3. Mass: A mass is also a common symptom, with approximately one-third to one-fourth of kidney cancer patients presenting with an enlarged kidney upon medical examination. Due to the concealed location of the kidney, it is difficult to detect a mass until the kidney cancer has reached a considerable size. Generally, a palpable abdominal mass indicates an advanced stage of the disease.4. Pain: Pain is observed in about 50% of cases and is also a symptom of an advanced stage. It is caused by the stretching of the renal capsule or renal pelvis by the growing tumor, or by the tumor invading and compressing the retroperitoneal connective tissue, muscles, lumbar spine, or lumbar nerves, resulting in persistent pain in the affected side of the lower back.
5. Other symptoms: Unexplained fever, or metastasis at the time of initial detection, accompanied by symptoms such as lack of strength, weight loss, loss of appetite, anemia, cough, and expectoration of blood (indicating lung involvement). Additionally, the effects of renal adenocarcinoma are caused by the tumor's endocrine activity, including polycythemia, hypertension, hypotension, hypercalcemia, and fever syndrome. Although these systemic, toxic, and endocrine effects are non-specific, about 30% of patients initially present with a variety of mixed symptoms. These findings are valuable clues and are considered systemic effects of the tumor.
1. General Examination: Hematuria is an important symptom, with polycythemia occurring in 3-4% of cases; progressive anemia may also occur. In cases of bilateral kidney tumors, overall kidney function usually remains unchanged, with an increased erythrocyte sedimentation rate. Some kidney cancer patients may exhibit symptoms of hypercalcemia and elevated serum calcium levels without bone metastasis. These symptoms rapidly resolve after kidney cancer removal, and calcium levels return to normal. Sometimes, liver dysfunction may develop, but normal function can be restored if the tumorous kidney is removed.
2. X-ray imaging is the primary diagnostic tool for kidney cancer.(1) X-ray plain film: X-ray plain films may reveal an enlarged kidney with altered contours, occasional tumor calcification, localized or extensive flocculent shadows within the tumor, or calcified lines around the tumor, often shell-like, especially common in younger kidney cancer patients.
(2) Intravenous urography: Intravenous urography is a conventional examination method. However, its importance has declined as it cannot display tumors that have not yet caused deformation of the renal pelvis and calyces, and it is difficult to distinguish whether the tumor is kidney cancer, renal angiomyolipoma, or renal cyst. Therefore, ultrasound or CT scans must be performed simultaneously for further differentiation. Nevertheless, intravenous urography provides valuable information about the function of both kidneys, as well as the condition of the renal pelvis, calyces, ureter, and bladder, which is crucial for diagnosis.
(3) Renal angiography: Renal angiography can detect tumors not visible on urography. Kidney cancer typically shows neovascularization, arteriovenous fistula, and pooling of contrast agents with increased membrane vascularity. Angiographic findings vary; sometimes kidney cancer may not be visible due to tumor necrosis, cystic changes, or angiographic embolization. If necessary, adrenaline can be injected during renal angiography, causing normal vessels to constrict while tumor vessels remain unresponsive.
In larger kidney cancers, selective renal angiography may be followed by renal artery embolization to reduce intraoperative bleeding. For kidney cancer patients who cannot undergo surgical resection and have severe bleeding, renal artery embolization can be performed as palliative treatment.
3. Ultrasound scanning: Ultrasound is the simplest and non-invasive examination method and can be part of routine physical examinations. Kidney masses larger than 1 cm can be detected by ultrasound. The key is to differentiate whether the mass is kidney cancer. Kidney cancer presents as a solid mass with heterogeneous echogenicity due to possible internal hemorrhage, necrosis, or cystic changes, typically showing low echogenicity. The boundaries of kidney cancer are often unclear, distinguishing it from renal cysts. Intrarenal masses and sexually transmitted diseases can cause deformation or rupture of the renal pelvis, calyces, or renal sinus fat. Renal papillary cystadenocarcinoma on ultrasound may resemble a cyst and may show calcification. When kidney cancer and cysts are difficult to differentiate, ultrasound-guided puncture is a relatively safe option. The aspirated fluid can be examined cytologically and used for cystography. Cyst fluid is usually clear, free of tumor cells, and low in fat. Smooth cyst walls on imaging confirm benign sexually transmitted diseases. If the aspirated fluid is bloody, malignancy should be suspected, and tumor cells may be found in the fluid. Irregular cyst walls on imaging indicate malignancy. Renal angiomyolipoma, a solid intrarenal tumor, shows strong echogenicity from fat tissue, making it easily distinguishable from kidney cancer. When kidney cancer is detected on ultrasound, attention should also be paid to whether the tumor has penetrated the membrane, perirenal fat tissue, the presence of enlarged lymph nodes, tumor thrombi in the renal vein or inferior vena cava, and liver metastasis.
4. CT Scan: CT plays an important role in the diagnosis of kidney cancer. It can detect kidney cancer 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 cancer. Some statistics show its diagnostic accuracy: invasion of the renal vein 91%, perirenal spread 78%, lymph node metastasis 87%, and involvement of adjacent organs 96%. On CT, kidney cancer appears as a mass within the kidney parenchyma, which may also protrude from the kidney parenchyma. The mass is round, oval, or lobulated, with clear or blurred boundaries. On plain scan, it appears as a heterogeneous soft tissue mass with a CT value >20Hu, usually between 30-50Hu, slightly higher than normal kidney parenchyma, or similar or slightly lower. The internal heterogeneity is due to hemorrhage, necrosis, or calcification. Sometimes it may appear as a cystic lesion with a CT value, but the cyst wall has soft tissue nodules. After intravenous injection of contrast, the CT value of normal kidney parenchyma reaches about 120Hu, and the CT value of the tumor also increases, but is significantly lower than that of normal kidney parenchyma, making the tumor boundaries clearer. If the CT value of the mass does not change after enhancement, it may be a cyst. Combining the CT values before and after contrast injection, a liquid density can confirm the diagnosis. In cases of necrosis within kidney cancer, renal cystic adenocarcinoma, and renal artery embolism, the CT value does not increase after contrast injection. Renal angiomyolipoma, due to its high fat content, often has a negative CT value, with internal heterogeneity. After enhancement, the CT value increases but still shows fat density. Oncocytoma on CT shows clear edges and uniform internal density, with a significant increase in CT value after enhancement.
CT scan criteria for determining the extent of kidney cancer invasion.
(1) The mass is confined within the renal capsule: The affected kidney has a normal shape or localized protrusion, or uniform enlargement. The protruding surface is smooth or grade I rough. If the mass protrudes nodularly into the renal capsule with a smooth surface, it is still considered confined within the renal capsule. The fat capsule is clear, and the perirenal fascia shows no irregular thickening. The presence of a fat capsule cannot be used to determine whether the tumor is confined within the renal fascia, especially in emaciated patients.
(2) Invasion confined within the perirenal fat capsule: The tumor protrudes and replaces local normal kidney parenchyma, with significant roughness on the kidney surface and irregular thickening of the renal fascia. There are poorly defined soft tissue nodules within the fat capsule, and linear soft tissue shadows are not diagnostic.
(3) Venous invasion: The renal vein thickens locally into a spindle-shaped bulge with uneven density, abnormally high or low, and the density change is consistent with the tumor tissue. The criteria for venous thickening are a renal vein diameter > .cm and an upper abdominal inferior vena cava diameter > 2.7cm.
(4) Lymph node invasion: Renal hilum, abdominal aorta, inferior vena cava, and round soft tissue shadows between them. If the density change after enhancement is not significant, it can be considered as a lymph node. Those <1cm are not diagnostic, and those ≧1cm are considered metastatic cancer.
(5) Invasion of adjacent organs: The boundary between the mass and adjacent organs disappears, with changes in the shape and density of the adjacent organs. If it only shows the disappearance of the fat line between the tumor and adjacent organs, it is not diagnostic.
(6) Renal pelvis invasion: The part of the tumor entering the renal pelvis has a smooth and rounded edge, forming a crescent or arc-shaped compression. Delayed scanning, when renal function is good, shows smooth and regular edges of the contrast agent in the compressed renal pelvis and calyces, which is considered simple compression of the renal pelvis and calyces. If the structure of the renal pelvis and calyces disappears or is occluded and completely occupied by the tumor, it suggests that the tumor has penetrated the renal pelvis.
5. Magnetic Resonance Imaging (MRI): MRI is ideal for examining the kidneys. The fat in the renal hilum and perirenal space produces high signal intensity. The outer renal cortex has high signal intensity, while the inner medulla has low signal intensity, possibly due to differences in osmotic pressure within the renal tissue, with a contrast difference of 50%. This difference can decrease with prolonged recovery time and hydration. The renal artery and vein have no intraluminal signal, so they appear as low intensity. The collecting system with urine appears as low intensity. MRI variations in kidney cancer are significant, determined by tumor vasculature, size, and the presence of necrosis. MRI does not detect calcifications well due to low proton density. MRI is effective in identifying the extent of kidney cancer invasion, surrounding tissue capsules, and changes in the liver, mesentery, and psoas muscle. It is particularly useful for detecting cancer thrombi in the renal vein and inferior vena cava, as well as lymph node metastases.
bubble_chart Treatment Measures
The primary treatment for kidney cancer is surgical resection, while the effects of radiotherapy, chemotherapy, and immunotherapy are not ideal or certain. Statistics show that combining kidney cancer with radiotherapy has no impact on 5-year survival rates.
1. Kidney cancer surgery is divided into simple kidney cancer resection and radical kidney cancer resection. Currently, it is widely accepted that radical kidney cancer resection can improve survival rates. Radical kidney cancer resection includes the perirenal fascia and its contents: perirenal fat, the kidney, and the adrenal gland. There is still controversy over whether radical kidney cancer resection should include local lymph node dissection. Some believe that lymph node metastasis often accompanies hematogenous metastasis, and cases with lymph node metastasis eventually develop hematogenous metastasis. Lymph nodes are widely distributed and difficult to completely remove. However, others argue that lymph node metastasis mainly occurs near the renal hilum, the inferior vena cava, and the main artery area, which can be radically resected. However, patients with metastatic lesions found during radical lymph node dissection rarely survive more than 5 years. During kidney cancer surgery, it is advisable to first ligate the renal artery and renal vein to reduce intraoperative bleeding and potential tumor spread.
Kidney cancer is a highly vascular tumor, often with large collateral veins, making surgery prone to bleeding and difficult to control. Therefore, for larger tumors, selective renal artery embolization can be performed preoperatively, although it may cause severe pain, fever, intestinal paralysis, infection, etc., and should not be routinely applied.
Special issues in kidney cancer treatment:
(1) Kidney-sparing surgery for kidney cancer: Kidney-sparing surgery is considered for bilateral kidney cancer or solitary kidney cancer, as well as cases with poor contralateral kidney function, such as renal vascular hypertension, kidney stones, renal subcutaneous nodules, or ureteropelvic junction stenosis. Kidney cancer smaller than 3 cm in diameter and located at the kidney's edge may also be considered for kidney-sparing surgery, which involves partial nephrectomy or tumor enucleation.
(2) Inferior vena cava tumor thrombus: Kidney cancer is prone to developing tumor thrombi in the renal vein and inferior vena cava. Recent studies suggest that if no local or distant spread is detected, radical kidney cancer resection can include the removal of venous tumor thrombi or extraction of inferior vena cava tumor thrombi, with a still favorable prognosis. During surgery, the inferior vena cava should be blocked above the thrombus level to avoid fatal pulmonary embolism. If the thrombus extends to the heart, the inferior vena cava can be blocked within the pericardium, and the thrombus can be removed by incising the inferior vena cava.
(3) Local spread of kidney cancer invading adjacent tissues and organs: This is a challenging issue in kidney cancer treatment. Complete surgical resection of the tumor and affected tissues is the only curative method, with a 5-year survival rate of only about 5% for such patients. Local spread of kidney cancer may be accompanied by pain due to tumor invasion of the posterior abdominal wall, sacrospinal muscles, and nerve roots. Direct liver invasion by kidney cancer is rare, with liver metastases being more common than direct invasion. Involvement of the duodenum and pancreas is almost impossible to cure. Even with distant metastases, if surgery is feasible, the primary kidney tumor can often be removed, and metastatic lesions may still achieve a considerable survival rate. Removal of the diseased kidney also eliminates hematuria and pain, making it worthwhile.
2. Immunotherapy: Over the years, it has been proven that lymphocytes in human solid tumors have an immune response to their tumor cells. However, the cytotoxic effect of these tumor-infiltrating lymphocytes (TIL) on autologous tumors 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 effects on autologous tumors. Normal human lymphocytes cultured with interleukin-2 (IL-2) can produce effector cells known as lymphokine-activated killer (LAK) cells. A group of 57 kidney cancer patients were treated with LAK cells and IL-2: 36 with LAK cells + IL-2 and 21 with IL-2 alone. In the LAK cells + IL-2 group, 4 patients achieved complete remission (CR), 8 achieved partial remission (PR), with an effective rate of 12/36 (33%). In the IL-2 alone group, only 1/21 patients achieved CR.
Tumor-infiltrating lymphocytes, or TIL cells, can also be expanded in vitro with IL-2. Animal experiments have found that this adoptive transfer of TIL is 50 to 100 times more effective than LAK cells and can destroy metastatic lesions in the lungs and liver. The potential for its clinical application is still under investigation.
3. Chemotherapy: The efficacy of chemotherapy for kidney cancer is poor, and the effect of single-drug treatment is even worse. Experts have evaluated 37 chemotherapy drugs for single-drug treatment of kidney cancer, among which alkylating agents showed relatively better results. The more effective combinations in combination chemotherapy include: Madagascar periwinkle herb alkaloid + methotrexate + bleomycin + Tamoxifen; vincristine + doxorubicin + BCG + medroxyprogesterone acetate; Madagascar periwinkle herb alkaloid + doxorubicin + hydroxyurea + MA. Overall, multi-drug treatment is superior to single-drug treatment.
4. Combination of immunotherapy and chemotherapy: A group of 957 cases of metastatic or recurrent kidney cancer were treated with interferon alpha-2a. The response rate was 12% when used alone, but increased to 24% when combined with Madagascar periwinkle herb alkaloid. Among responders, the 2-year survival rate was 50-70%, while non-responders had a survival rate of 10-15%. The ideal dose is 1.8 million units of interferon administered subcutaneously or intramuscularly three times a week, and 0.1 mg/kg of Madagascar periwinkle herb alkaloid intravenously every three weeks.
The survival factors for kidney cancer have been discussed previously. Generally, the 5-year survival rate after nephrectomy for kidney cancer is 35-40%, and the 10-year survival rate is 17-30%. The prognosis of kidney cancer can sometimes be difficult to predict, as metastatic lesions may appear 20 years, 30 years, or even longer after the surgical removal of kidney cancer.
